5 Minute Urology Consult, The - Gomella, Leonard G. (SRG) PDF

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LWBK1391-FM LWBK1391-Gomella September 26, 2014 11:32
The
5-Minute
Urology
Consult
Editor-in-Chief
3RD EDITION Leonard G. Gomella, MD, FACS
The Bernard W. Godwin Professor of Prostate Cancer
Chairman
Department of Urology
Sidney Kimmel Medical College
Associate Director, Jefferson Sidney Kimmel Cancer Center
Clinical Director, Jefferson Sidney Kimmel Cancer Network
Thomas Jefferson University
Philadelphia, Pennsylvania
Associate Editors
Gerald L. Andriole, MD, FACS
Arthur L. Burnett, II, MD, MBA, FACS
Robert C. Flanigan, MD, FACS
Thomas E. Keane, MB, ChB, FRCSI, FACS
Harry P. Koo, MD, FAAP, FACS
Judd W. Moul, MD, FACS
Raju Thomas, MD, MHA, FACS
i
Acquisitions Editor: Keith Donnellan

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Third Edition
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Second Edition c 2010 by Lippincott Williams & Wilkins, a Wolters Kluwer business
First Edition
c 2000 by Lippincott Williams & Wilkins
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The 5-minute urology consult / editor-in-chief, Leonard G. Gomella ; associate editors, Gerald Andriole [and
six others]. – Third edition.
p. ; cm.
Five minute urology consult
Includes bibliographical references and index.
ISBN 978-1-4511-8998-8 (alk. paper)
I. Gomella, Leonard G., editor. II. Title: Five minute urology consult.
[DNLM: 1. Urologic Diseases–Handbooks. WJ 39]
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This work is no substitute for individual patient assessment based upon healthcare professionals’
examination of each patient and consideration of, among other things, age, weight, gender, current or prior
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does not provide medical advice or guidance and this work is merely a reference tool. Healthcare
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Given continuous, rapid advances in medical science and health information, independent professional
verification of medical diagnoses, indications, appropriate pharmaceutical selections and dosages, and
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prescribing medication, healthcare professionals are advised to consult the product information sheet (the
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warnings and side effects and identify any changes in dosage schedule or contradictions, particularly if the
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ii
To Tricia, Leonard, Patrick, Andrew, and

Michael, for their understanding and
encouragement, and with appreciation
for their individual accomplishments.
“En tierra de los ciegos el tuerto es rey.”

SPANISH PROVERB
iii
iv
PREFACE
I
am very pleased to present the third edition of The 5-Minute ally any topic can be searched for on the Internet, the ability to sort
Urology Consult. The first edition was released almost 15 years through the information presented, confirm the validity, and rapidly
ago, with the second edition published in 2010. The continuing find the specific information needed is often very time-consuming
advances in urology lead to this much-needed 2015 update. The and can be prone to error. Multiple studies have shown that many
goal of this book is to provide the reader with useful information in websites can contain erroneous, misleading, or out-of-date infor-
a quick reference format to help with the everyday care of patients mation. Readers of this book can be assured that the information
with urologic problems. This third edition has undergone extensive presented is held to the highest standards possible, as it is writ-
editing and updating to reflect the most current data possible at ten, reviewed, and further edited primarily by academic urologists
the time of publication. and other academic specialists. Every effort is made to present the
Urologic diseases and conditions are common problems seen by most up-to-date standards of care at the time of publication.
all health care providers. Almost one-third of all congenital disorders This book, a member of the popular “5-Minute Consult’’ series
involve the genitourinary system, and the urinary tract accounts for published by Wolters Kluwer Health, generally follows the organi-
almost 25% of all solid tumors in adults. While this book is written zational formatting of the other books in the series. However, there
primarily for urologists, any health care practitioner who deals with are notable exceptions, as this book is focused on a primarily surgi-
urologic complaints and conditions should find the book a useful cal subspecialty. Section I: Urologic Diseases and Conditions
resource. Students of urology, residents and fellows preparing for provides information on more than 300 major topics in the field of
oral and written in-service examination, and practicing urologists urology. The style of this section, while similar to the other books
preparing for certification examinations will find the book a use- in the series, focuses more attention on the surgical management,
ful study aid. While primarily written for practitioners in the United where appropriate. Furthermore, evidence-based medicine refer-
States, the table of contents has been reviewed by our international ences, standard fare in the “5-Minute Consult’’ series, are included
editorial board, which represent more than three dozen countries, in in this urology edition. This is representative of the trend in the field
an attempt to capture as many diseases and conditions as possible of medicine to assign “levels of evidence’’ to treatment recommen-
for international readers. dations (see page ix for a further discussion). A challenge with any
The broad array of topics addressed in this book is based on surgical discipline is that, when reviewing published literature, this
reviews of published literature, major textbooks, grand rounds case type of information is not as well represented as in other medi-
presentations, validated Internet resources, and actual patient con- cal disciplines. The reader will note that in this edition, the use of
sultations. Topics are meant to represent “real-world’’ clinical ques- evidence-based medicine is identified in chapters as appropriate.
tions from very broad to very specific topics. Some of the topics Many topics are further supported by algorithms and the enhnaced
may appear redundant, such as Section I topics “Scrotum and tes- image library available in the ebook version provided along with the
ticle, mass’’ and “Testis, tumor and mass, adult, general consid- print version. Both ICD-9 and preliminary high level ICD-10 codes
erations.’’ There is a deliberate reason for this, namely, to frame have been incorporated in preparation for the rollout of ICD-10 in
the thought process to differentiate scrotal masses from testicular late 2015.
masses when the presenting problem is not clear. If it is clearly Section II: Short Topics: A to Z consists of more than 1,300
a testicular mass, then the one topic deals effectively with that diseases, conditions, presenting complaints, or key concepts in the
setting. If it is not a clear mass in the testicle, the reader can ap- field that the practitioner must be aware of but may not be worthy
proach the problem more broadly in terms of a mass within the of a complete 2-page chapter. Section III has been greatly ex-
scrotum that may or may not involve the testicle. Coverage in- panded and now features nearly 90 visual algorithms to enhance
cludes adult and pediatric urology, as well as subspecialty areas many more clinically relevant topics. Section IV is dedicated ex-
of urology such as urologic oncology, endourology, female urology, clusively to a core discipline in our field, Urinalysis and Urine
neurourology, andrology, infectious diseases, and renal transplan- Studies. Section V: Alternative and Complementary Uro-
tation. It represents a core of essential “must-know’’ and practical logic Therapies is a focused review that is of interest to both
information specifically written for the field of urology. While some patients and caregivers alike. Section VI: Urologic Drug Ref-
surgical techniques are discussed, this is not meant to be a compre- erence is a very unique collection of information on hundreds of
hensive urologic surgical text. Numerous high-quality publications drugs used in urologic practice in the United States as well as some
address the finer points of urologic surgery. This book addresses traditionally nonurologic medications that are clinically significant
pre and post operative care as well as some intra-operative tech- to the urologic practitioner. Additional urologic applications not of-
niques; however the focus is on more global patient management ten found on the package insert for “off-label’’ use in daily care are
issues. included for many medications. These “off-label’’ applications are
I am often surprised when asked why medical books such as noted on the basis of published literature with additional input and
this are even necessary as a reference in the modern world be- the personal observations of the authors and editors. Finally, Sec-
cause there is so much information readily available on devices tion VII: Reference Tables is a collection of useful reference
such as smartphones via the Internet. While the reality is that virtu- information and forms. A media and image collection is available in
v
vi r r r Preface
the ebook version of this book. Please see information inside front opportunity to work with. My personal interactions with the company
cover on how to access this content. and their willingness to discuss any and all issues relating to the
In any project of this magnitude, there are numerous individuals book are testimony to their corporate philosophy in respecting the
responsible for its success. I would like to thank the following in- authors’ opinions to develop the best educational products possible
dividuals who provided the initial guidance in 1996 to develop the in the field of medicine. Brian Brown, Keith Donnellan, and Bren-
first urology version of the 5-Minute Consult: Lippincott Williams & dan Huffman are the best partners a medical author could hope
Wilkins editors Carroll Cann and Craig Percy, and an early pioneer to work with. In the final production stages, David Saltzberg and
of the 5-Minute Consult concept, Dr. Mark Dambro. Thanks to my Harish Kumar kept everything moving to stay on schedule. Spe-
administrative assistants Denise Tropea and Barbara Devine, who cial thanks to Philadelphia-based friend and professional photog-
provided key support to keep the contributors and this edition or- rapher Robert Neroni, who captured the spirit of urology in our cover
ganized. A special thanks to the more than 370 authors and editors photo.
who took the time to contribute to this edition and the numerous Our children, Leonard, Patrick, Andrew, and Michael, deserve
contributors to the previous editions that laid a strong foundation credit for their encouragement and patience over the many years
for this third update. To my colleagues who served as Associate, of my time spent working on this project. In this edition, i am very
Consulting, Specialty and International Editors, my most sincere proud that a few of the boys were actually able to make tangible
gratitude and appreciation for the time you took to recruit authors, professional contributions.
create and review content. It is also with great sadness that one of Most importantly, I would like to thank my wife, Tricia, with
our international editors and an icon in the field of Urology, Pro- the usual and customary accolades that authors share about their
fessor John Fitzpatrick passed away during the completion of this spouses in acknowledging the love and support provided. However,
book. He will be missed by all but his numerous contributions to her attention to detail as a behind-the-scenes editorial partner and
our field will live on. skilled reviewer for final content of this book added a degree of
Residents from the Department of Urology of Thomas Jefferson accuracy that I could never have accomplished alone.
University and from the University of West Virginia deserve special Please contact me if you have corrections or suggestions on
acknowledgement. They supported the content of both Section II ways to improve future editions of the book. I hope that The 5-
“Short Topics” and Section III “Algorithms.” Their names appear in Minute Urology Consult will provide useful information to allow all
the contributor listing as having been authors but are not specifically of us to care for our urology patients in the best way possible.
recognized for their work in these sections. Now however, they are. LEONARD G. GOMELLA, MD
The editorial and production staff at Wolters Kluwer Health have leonard.gomella@jefferson.edu
distinguished themselves as the best publishing team I have had the www.urologyquestion.com
EVIDENCE-BASED MEDICINE
E
vidence-based medicine (EBM) is generally defined as the ommendations can be found. However, we recognize that in a pri-
use of current best medical evidence to aid in making deci- marily surgical-based specialty such as urology, this area is not
sions about the care of an individual patient. While the ultimate yet as well defined as in more general areas of medical practice.
decision-making process for or against a given treatment must be As an illustrative example in a chapter on hypertension, the EBM
made between the patient and the health care provider, EBM seeks recommendation might read:
to assess the quality of evidence that a specific course of action
is based on. The underlying principle is the evaluation of medical “Use thiazide diuretics as a first-line agent for the
interventions and the literature that supports these interventions in treatment of essential hypertension, as it has the great-
a systematic and organized fashion. Since its introduction as a con- est efficacy in preventing the vascular complications
cept in the modern medicine over 30 years ago, there has been in- of hypertension (5)[A].’’
creased emphasis on this concept in daily patient care. While there
are currently many different systems of EBM, we have adopted the The A designation, as noted in the algorithm later, implies this
5-Minute Clinical Consult standard of the “SORT Taxonomy’’ from recommendation is based on the highest-quality, patient-oriented
the American Academy of Family Physicians. The key components evidence, and should be followed. The number 5 refers to the
are summarized later. A full review of this article can be viewed source, which would be listed under the “References’’ heading
at http://www.aafp.org/afp/20040201/548.html. Throughout this as reference #5. Recommendations that are level A evidence are
edition of The 5-Minute Urology Consult, these evidence-based rec- shaded blue in the text.
Strength of recommendation Definition

A Recommendation based on consistent and good-quality patient-oriented evidence.
r Highest-quality resource, such as a systematic review. This is a summary of the medical literature on a given topic
that uses strict, explicit methods to perform a thorough search of the literature and then provides a critical appraisal of
the individual studies concluding in a recommendation. The Cochrane reviews are considered by many to be the most
prestigious collection of systematic reviews (www.cochrane.org).
B Recommendation based on inconsistent or limited-quality patient-oriented evidence.

r This implies that the data referenced are derived from high-quality randomized controlled trials that were performed to
minimize bias in their outcome. Bias is anything that may interfere with the truth; in the medical literature, it is often
unintentional but is more common than we appreciate. In short, always assume that some degree of bias exists in any
research endeavor.
C Recommendation based on consensus, usual practice, opinion, disease-oriented evidence, or case series
for studies of diagnosis, treatment, prevention, or screening.
r This implies that the reference used does not meet het “A’’ or “B’’ requirements; these are often treatments recommended
by consensus groups (such as the American Cancer Society). In some cases, they may be the standard of care. But
implicit in a group’s recommendations is the bias of the group or author that supports the reference.
Modified from Domino FJ, ed. The 5-Minute Clinical Consult 2010. Philadelphia: Lippincott Williams & Wilkins; 2009.
vii
viii
EDITORS
EDITOR-IN-CHIEF Judd W. Moul, MD, FACS

James H. Semans, MD Professor of Surgery
Leonard G. Gomella, MD, FACS Division of Urologic Surgery
The Bernard W. Godwin Professor of Prostate Cancer Duke University Medical Center
Chairman Durham, North Carolina
Sidney Kimmel Medical College Raju Thomas, MD, MHA, FACS
Associate Director, Jefferson Sidney Kimmel Cancer Professor and Chairman
Center Department of Urology
Clinical Director Jefferson Sidney Kimmel Cancer Network Tulane University School of Medicine
Thomas Jefferson University New Orleans, Louisiana
SECTION EDITORS
ASSOCIATE EDITORS T. Ernesto Figueroa, MD, FAAP, FACS
Clinical Associate Professor
Gerald L. Andriole, MD, FACS Sidney Kimmel Medical College
Robert K. Royce Distinguished Professor Chief, Division of Pediatric Urology
Chief of Urologic Surgery Nemours/Alfred I. DuPont Hospital for Children
Division of Urologic Surgery Wilmington, Delaware
Washington University Uropharmacology, Pediatric
St. Louis, Missouri
Deborah Tova Glassman, MD
Arthur L. Burnett, II, MD, MBA, FACS Clinical Assistant Professor
Patrick C. Walsh Professor of Urology Department of Urology
Department of Urology Sidney Kimmel Medical College
The James Buchanan Brady Urological Institute Thomas Jefferson University
Baltimore, Maryland Philadelphia, Pennsylvania
Short Topics
Albert J. Jr. and Claire R. Speh Professor Kevin R. Loughlin, MD, MBA, FACS
Chair, Department of Urology Professor of Surgery (Urology)
Loyola University Stritch School of Medicine Division of Urology
Chicago (Maywood), Illinois Brigham & Women’s Hospital
Boston, Massachusetts
Thomas E. Keane, MB, ChB, Uropharmacology
FRCSI, FACS Franklin C. Lowe, MD, MPH
Professor and Chairman Professor of Clinical Urology
Department of Urology Columbia University College of Physicians & Surgeons
The Medical University of South Carolina New York, New York
Charleston, South Carolina Alternative & Complementary Urologic Therapies
Harry P. Koo, MD, FAAP, FACS J. Ryan Mark, MD
Chief of Pediatric Medicine Chief
Department of Urology Department of Urology
Joseph M. Sanzari Children’s Hospital Thomas Jefferson University
Hackensack University Medical Center Philadelphia, Pennsylvania
Hackensack, New Jersey Video Editor
ix
x r r r Editors
Alana M. Murphy, MD Michael L. Blute, Sr., MD, FACS

Assistant Professor Walter S. Kerr, Jr. Professor of Surgery
Department of Urology Chief
Sidney Kimmel Medical College Department of Urology
Thomas Jefferson University Massachusetts General Hospital
Philadelphia, Pennsylvania Boston, Massachusetts
Short Topics
Culley C. Carson, III, MD, FACS
Jack H. Mydlo, MD Rhodes Distinguished Professor
Professor and Chairman Department of Urology
Department of Urology University of North Carolina at Chapel Hill
Temple University Chapel Hill, North Carolina
Uropharmacology
E. David Crawford, MD, FACS
Andrew A. Gomella, BS Professor of Surgery/Urology/Radiation
Oncology
Class of 2018
University of Colorado, Denver
Denver, Colorado
Graphics James F. Donovan, Jr., MD
Professor of Surgery (Urology)
Sven Wenske, MD Director
Assistant Professor Division of Urology
Department of Urology Department of Surgery
Columbia University College of University of Cincinnati College of Medicine
Physicians & Surgeons Cincinnati, Ohio
New York, New York
Alternative & Complementary Urologic Michael J. Droller, MD
Therapies Katherine and Clifford Goldsmith Professor of
Urology
Stanley Zaslau, MD, MBA, FACS Professor of Oncology
Professor and Chief Department of Urology
Urology Residency Program Director The Mount Sinai Medical Center
Division of Urology Pelham, New York
West Virginia University
Morgantown, West Virginia Michael J. Erhard, MD
Algorithms Medical Director
Division of Pediatric Urology
CONSULTING EDITORS Nemours Children’s Clinic
Jacksonville, Florida
Arie Belldegrun, MD, FACS
Professor & Chief of Urologic Oncology Gabriel P. Haas, MD, FACS
Roy & Carol Doumani Chair in Urologic Medical Director
Oncology Astellas Pharma Gobal Development
Department of Urology Deerfield, Illinois
David Geffen School of Medicine at UCLA
Los Angeles, California Ethan J. Halpern, MD
Professor of Radiology and Urology
David A. Bloom, MD, FACS Vice Chairman of Radiology Research
The Jack Lapides Professor and Chair Department of Radiology
Department of Urology Sidney Kimmel Medical College
University of Michigan Medical School Thomas Jefferson University
Ann Arbor, Michigan Philadelphia, Pennsylvania
Editors r r r xi
Thomas Jarrett, MD Richard J. Macchia, MD, FACS

Professor and Chairman SUNY Distinguished Teaching Professor &
Department of Urology Chairman Emeritus
George Washington University Affiliate Professor of Biomedical Science
Washington, DC Charles E. Schmidt College of Medicine
Florida Atlantic University
Karen E. Knudsen, PhD Department of Urology
Vice Provost for Research Thomas Jefferson University Fort Lauderdale, Florida
Deputy Director for Basic Science and Leader Prostate
Program Sidney Kimmel Cancer Center Edward M. Messing, MD, FACS
Hilary Koprowski Endowed Professor Departments of Professor of Oncology & Pathology
Cancer Biology, Urology, Radiation Oncology, & Medical Chairman
Oncology Sidney Kimmel Medical College Department of Urology
Thomas Jefferson University Philadelphia, Pennsylvania University of Rochester Medical School
Rochester, New York
Paul H, Lange, MD
Professor of Urology Joel B. Nelson, MD
Director Frederic N. Schwentker Professor and Chairman
Prostate Cancer Research Institute Department of Urology
Department of Urology University of Pittsburgh School of Medicine
University of Washington Pittsburgh, Pennsylvania
Seattle, Washington
Nick A. Pavona, MD
Herbert Lepor, MD, FACS Professor, Department of Surgery
Professor and Martin Spatz Chairman Division of Urology
Urologist In Chief Benjamin Franklin University Medical Center
NYU Langone Medical Center Chadds Ford, Pennsylvania
New York University School of Medicine Steven P. Petrou, MD
New York, New York Consultant
Seth P. Lerner, MD, FACS Professor of Urology
Professor of Urology Mayo Medical School
Beth and Dave Swalm Chair in Urologic Oncology Mayo Clinic
Department of Urology Jacksonville, Florida
Baylor College of Medicine
Houston, Texas Daniel P. Petrylak, MD
Professor of Medicine (Medical Oncology) and Urology
John A. Libertino, MD, FACS Co-Director, Signal Transduction Research Program
Chairman of Institute of Urology Yale Cancer Center
Lahey Hospital and Medical Center Yale School of Medicine
Burlington, Massachusetts New Haven, Connecticut
W. Marston Linehan, MD James S. Rosoff, MD

Chief, Urologic Oncology Branch Assistant Professor
National Cancer Institute Department of Urology
National Institute of Health Yale School of Medicine
Bethesda, Maryland New Haven, Connecticut
John H. Lynch, MD, FACS Howard M. Sandler, MD, MS, FASTRO

Professor and Chairman Chair, Radiation Oncology
Department of Urology Ronald H. Bloom Family Chair in Cancer Therapeutics
Medstar Georgetown University Hospital Cedars-Sinai Medical Center
Washington, DC Los Angeles, California
xii r r r Editors
Ihor S. Sawczuk, MD, FACS Laurence S. Baskin, MD, FACS, FAAP

Chair Urology Chief Pediatric Urology
Co-Chief Urologic Oncology Division Children’s Hospital and Research Center, Oakland
John Theurer Cancer Center Professor of Urology
Chief Medical Officer University of California, San Francisco
Hackensack University Medical Center San Francisco, California
Hackensack, New Jersey Fetal Urology
Dolores Shupp-Byrne, PhD Ruth C. Birbe, MD

Research Assistant Professor Assistant Professor, Quality Assurance Director
Editorial Director Pathology, Anatomy and Cell Biology
Department of Urology Thomas Jefferson University
Thomas Jefferson University Philadelphia, Pennsylvania
Philadelphia, Pennsylvania Pathology
Dan Theodorescu, MD, PhD, FACS Gennady Bratslavsky, MD

Paul A. Bunn Chair in Cancer Research Professor & Chair
Professor of Surgery and Pharmacology Department of Urology
Director SUNY Upstate Medical University
University of Colorado Cancer Center Syracuse, New York
Aurora, Colorado Molecular Genetics
J. Brantley Thrasher, MD, FACS James A. Brown, MD, FACS

Professor and William L. Valk Chair Professor
University of Kansas Medical Center University of Iowa
Kansas City, Kansas Iowa City, Iowa
Laparoscopy
J. Stuart Wolf, Jr., MD, FACS
The David A. Bloom Professor of Urology Brett S. Carver, MD
Associate Chair for Clinical Operations Assistant Attending
Head, Division of Endourology Department of Surgery
Department of Urology Division of Urology
University of Michigan Memorial Sloan Kettering Cancer Center
Ann Arbor, Michigan New York, New York
Urologic Oncology/Testis Cancer
SPECIALTY EDITORS
Joseph Y. Cheung, MD, PhD
Anthony Atala, MD, FACS Chair, Department of Medicine
William Boyce Professor and Chairman Professor of Medicine
Department of Urology Temple University School of Medicine
Wake Forest School of Medicine Philadelphia, Pennsylvania
Winston-Salem, North Carolina Nephrology
Pediatric Urology
Michael S. Cookson, MD, FACS
John M. Barry, MD, FACS Chairman and Professor, Donald D. Albers Endowed
Director, Living Donor Kidney Transplantation Chair
Professor of Urology, Professor Emeritus of Surgery Department of Urology
Department of Urology University of Oklahoma Health Sciences
Oregon Health & Science University Center
Portland, Oregon Oklahoma City, Oklahoma
Renal Transplantation Guidelines
Editors r r r xiii
Scott E. Eggener, MD Costas D. Lallas, MD, FACS

Associate Professor of Surgery - Urologic Oncology Associate Professor
Department of Surgery Director of Robotic Surgery
University of Chicago Sidney Kimmel Medical College
Chicago, Illinois Department of Urology
Urotechnology Thomas Jefferson University
Tricia Lacy Gomella, MD Robotic Surgery and Surgical Simulation
Part Time Assistant Professor
Department of Pediatrics
The Johns Hopkins University School of Medicine Viraj Master, MD, FACS
Baltimore, Maryland Associate Professor
Neonatology Associate Chair of Clinical Affairs and Quality
Tomas L. Griebling, MD, MPH, FACS Emory University
John P. Wolf 33-Degree Masonic Distinguished Professor Atlanta, Georgia
and Vice Chair of Urology and Faculty Associate - The Clinical Trials
Landon Center on Aging
The University of Kansas Surena F. Matin, MD, FACS
Kansas City, Kansas Associate Professor
Geriatric Urology Director, Minimally Invasive New Technology in Oncologic
Surgery (MINTOS)
J. Stephen Jones, MD, FACS Department of Urology
Chief of Surgical Operations, Fairview Hospital, A University of Texas, MD Anderson Cancer Center
Cleveland Clinic Hospital Houston, Texas
Professor of Surgery (Urology) Cleveland Clinic Lerner Urologic Oncology/Bladder Cancer
College of Medicine at CWRU
Cleveland Clinic Martin M. Miner, MD
Cleveland, Ohio Clinical Associate Professor of Family Medicine and
Ambulatory Urology Urology
Co-Director Men’s Health Center
Dennis G. Karounos, MD Warren Alpert School of Medicine
Chief, Endocrinology Section Brown University
VA Medical Center Providence, Rhode Island
Associate Professor in Internal Medicine Men’s Health
Division of Endocrinology & Molecular
University of Kentucky
Lexington, Kentucky Robert M. Moldwin, MD, FACS
Endocrinology Professor of Urology
North Shore-LIJ Hofstra University School of
Wm. Kevin Kelly, DO Medicine
Professor, Medical Oncology and Urology and Director, Pelvic Pain Center, North Shore-LIJ Healthcare
Director, Division of Solid Tumor Oncology System
Department of Medical Oncology Arthur Smith Institute for Urology
Sidney Kimmel Medical College Long Island Jewish Medical Center
Thomas Jefferson University New Hyde Park, New York
Philadelphia, Pennsylvania Infection and Inflammatory Diseases
Medical Oncology
Eric A. Klein, MD, FACS Allen F. Morey, MD, FACS

Chair, Glickman Urologic & Kidney Institute Professor, Paul C. Peters Chair in Urology
Cleveland Clinic UT Southwestern Medical Center
Cleveland, Ohio Dallas, Texas
Urologic Oncology/Prostate Cancer Urotrauma
LWBK1391-FM LWBK1391-Gomella October 6, 2014 15:9
xiv r r r Editors
John Patrick Mulhall, MBBCh, FACS, FECSM Philippe E. Spiess, MD

Director Associate Member
Sexual and Reproductive Medicine Program Department of Genitourinary
Division of Urology Oncology
Memorial Sloan Kettering Cancer Center Moffitt Cancer Center
New York, New York Tampa, Florida
Erectile Dysfunction Urologic Oncology/Penile Cancer
Stephen Nakada, MD, FACS Edouard J. Trabulsi, MD, FACS

The David T. Uehling Professor and Chairman Associate Professor
University of Wisconsin Sidney Kimmel Medical College
Madison, Wisconsin Sidney Kimmel Cancer Center
Endourology & Urolithiasis Thomas Jefferson University
Craig S. Niederberger, MD, FACS Uroradiology
Professor and Department Head
Department of Urology Robert G. Uzzo, MD, FACS
University of Illinois at Chicago Professor and Chairman
Chicago, Illinois Department of Surgical Oncology
Infertility Fox Chase Cancer Center
David F. Penson, MD, MPH Urologic Oncology/Kidney Cancer
Hamilton and Howd Chair in Urologic Oncology
Chair, Department of Urologic Surgery Richard Valicenti, MA, MD
Professor of Urologic Surgery, Medicine and Health Policy Professor and Chair
Vanderbilt University Medical Center Department of Radiation Oncology
Nashville, Tennessee UC Davis School of Medicine
Epidemiology and Health Related Quality of Life Sacramento, California
Radiation Oncology
Michael A. Pontari, MD
Professor of Urology Sandip P. Vasavada. MD, FACS
Department of Urology Urologic Director
Temple University Center for Female Pelvic Medicine & Reconstructive
Philadelphia, Pennsylvania Surgery
Sexually Transmitted Infections Cleveland Clinic Lerner College of Medicine
Cleveland, Ohio
Ganesh V. Raj, MD, PhD, FACS Female Urology
Associate Professor of Urology
University of Texas Southwestern Medical
Hunter Wessels, MD, FACS
Professor and Nelson Chair in Urology
Center
Dallas, Texas
University of Washington
Precision Medicine
Seattle, Washington
Reconstructive Urology
Patrick J. Shenot, MD, FACS
Associate Professor
Deputy Chair and Residency Program INTERNATIONAL EDITORIAL BOARD
Director
Department of Urology Taha Abo-Almagd Abdel-Meguid, MD
Sidney Kimmel Medical College Professor
Thomas Jefferson University Department of Urology
Philadelphia, Pennsylvania King Abdulaziz University Hospital
Neurourology Jeddah, Saudi Arabia
Editors r r r xv
Abrahamsson Per-Anders, MD, PhD Magdy El-Akkad, MD

Chairman and Professor Professor of Urology
Department of Urology Assiut University Hospital
Skane University Hospital Assiut, Egypt
Malmo, Sweden
John M. Fitzpatrick, Mch, FRCSI, FEBU, FC
Atif Akdas, MD Urol (SA), FRCS GLAS, FRCS
Professor of Urology Professor of Surgery
Uro-Tip University College Dublin
Istanbul, Turkey Head of Research, Irish Cancer Society
Department of Surgery
Christiaan Huibert Bangma, MD University College Dublin
Professor and Chairman Dublin, Ireland
Erasmus University Medical Center Neil E. Fleshner, MD, MPH,
Rotterdam, The Netherlands FRCSC
Martin Barkin Professor and Chair of Urology
Allen Chiura, MD Department of Surgery (Urology)
Consultant Urological Surgeon University of Toronto
Parirenyatwa Government Hospital Toronto, Ontario, Canada
Teaching Hospital for University of Zimbabwe Avondale
Harare, Zimbabwe Peter J. Gilling, MD, FRACS
Associate Professor of Surgery
Yew Lam Chong, MBBS, MRCS, Head of the Bay of Plenty Clinical School
Mmed, FAMS Bay of Plenty District Health Board
Head of Department of Urology University of Auckland
Adjunct Assistant Professor Tauranga, New Zealand
Tan Tock Seng Hospital Narmada P. Gupta, MD, MCh
Singapore Chairman, Academic & Research
Marius C. Conradie, MD Medanta The Medicity, Gurgaon, Delhi
Staff Urologist
Haryana, India
Netcare Waterfall City Hospital
Midrand, South Africa Hubert John, MD
Formerly Professor Dr. Med.
Head of Urology Department of Urology
Pietermaritzburg Metropolitan Hospital Chefarzt Klinik für Urologie
Department of Urology Zürich, Switzerland
Nelson R Mandela School of Medicine
Wandsbeck, South Africa Francis Xavier Keeley, Jr., MD, FRCS
Consultant Urologist
Anthony J. Costello, MD, FRACS, FRCSI(hon), Bristol Urological Institute
MBBS Bristol, England
Professorial Fellow & Head Department of Urology, The
Royal Aihua Li, MD, PhD
Melbourne Hospital Chairman, Chief Urologist and Professor
Parkville, VIC, Australia Department of Urology
Yangpu District Central Hospital of Shanghai
Bob Djavan, MD, PhD Shanghai, China
Professor of Urology
Department of Urology Evangelos Liatsikos, MD, PhD
New York University and University of Vienna Associate Professor of Urology
Chairman, Regional Office of the European Association of Department of Urology
Urology University of Patras
Vienna, Austria Rio-Patras, Greece
xvi r r r Editors
Atsushi Mizokami, MD, PhD Arnulf Stenzl, MD

Lecturer Professor and Chairman
Department of Integrative Cancer Therapy & Urology Department of Urology
Kanazawa University Graduate School of Medical Sciences Eberhard-Karls University
Kanazawa, Japan Tuebingen, Germany
Francesco Montorsi, MD Teuvo L.J. Tammela, MD, PhD

Professor and Chairman Professor of Urology and Chairman
Director, Urological Research Institute Department of Surgery
Department of Urology Tampere University Hospital
Universita Vita Salute San Raffaele Tampere, Finland
Milan, Italy
Claudio Teloken, MD, PhD
Guillermo Montoya, MD Professor of Urology
Professor of Urology Chairman, Residency Program of Urology at
Department of Urology UFCSPA
Hospital de Especialdades Department of Urology
Mexico City, Mexico UCSPA-Federal University of Medical Sciences
Porto Alegre, Brazil
Alejandro Ramon Nolazco, MD
Especialista Consultor En Urologia Olivier Traxer, MD, PhD
Hospital Britanico De Buenos Aires and Professor of Urology
Hospital Universitario Austral Director of the Minimally Invasive
Buenos Aires, Argentina Surgery
Juliano Z. K. Panganiban, MD, FPCS, FPUA, University of Pierre et Marie Curie
MBAH Paris, France
Urologic Surgeon/Consultant Urologist
Institute of Urology Levent N. Türkeri, MD, PhD
St. Luke’s Medical Center Professor of Urology
Quezon City, Philippines Department of Urology
Marmara University School of
Dmitry Pushkar, MD Medicine
Professor and Chairman Istanbul, Turkey
General Scientific Secretary, Russian Society of Urology
Urologist General of Urology Hendrik Van Poppel, MD, PhD
Department of Urology Chairman, Department of Urology
Moscow State University of Medicine & Dentistry University Hospitals Leuven
Moscow, Russia Leuven, Belgium
Jacob Ramon, MD Dr. Huberto Villavicencio

Professor and Chairman Director del servicio de Urologia
Department of Urology Fundació n Puigvert
Sheba Medical Center Barcelona, Spain
Tel-Hashomer, Tel Aviv University
Tel Aviv, Israel
CONTRIBUTORS
Divya Ajay, MD Angela M. Arlen, MD Nima Baradaran, MD

Resident Fellow Urology Resident
Department of Urology Department of Urology Department of Urology Urology
Duke University Medical Center Emory University School of Medicine Medical University of South Carolina
Durham, North Carolina Atlanta, Georgia Charleston, South Carolina
Osama Al-Omar, MD Anthony Atala, MD, FACS John M. Barry, MD, FACS
Assistant Professor W.H. Boyce Professor Director
Director Pediatric Urology Chair-Department of Urology Living Donor Kidney Transplantation
Division of Urology Department of Urology Professor of Urology
West Virginia University Director Professor Emeritus of Surgery
Morgantown, West Virginia Wake Forest Institute for Regenerative Department of Urology
Medicine Oregon Health & Science University
Michael J. Amirian, MD Wake Forest School of Medicine Portland, Oregon
Resident Winston-Salem, North Carolina
Department of Urology Julia S. Barthold, MD, FAAP
Timothy D. Averch, MD, FACS Professor of Urology and Pediatrics
Professor and Vice Chair for Quality Sidney Kimmel Medical College
Director of Endourology Associate Chief, Nemours Division of
Christopher Amling, MD, FACS Department of Urology Urology
Professor and Chair University of Pittsburgh Medical Center Nemours/Alfred DuPont Hospital for
Department of Urology Pittsburgh, Pennsylvania Children
Oregon Health & Science University Luigi Avolio, MD Wilmington, Delaware
Portland, Oregon Department of Pediatric Surgery
Laurence S. Baskin, MD, FACS, FAAP
Mark R. Anderson, MD, MSc IRCCS Policlinico San Matteo Foundation
Chief Pediatric Urology
Resident in Urology University of Pavia
Children’s Hospital and Research
Division of Urology Pavia, Italy
Center, Oakland
Duke University Medical Center Demetrius H. Bagley, MD, FACS Professor of Urology
Apex, North Carolina The Nathan Lewis Hatfield Professor of University of California, San Francisco
Gerald L. Andriole, MD, FACS Urology and Professor of Radiology San Francisco, California
Robert K. Royce Distinguished Professor Department of Urology
Nelson Bennett, Jr., MD
Chief of Urologic Surgery Sidney Kimmel Medical College
Director of Sexual Medicine and Surgery
Washington University in St. Louis Thomas Jefferson University
Institute of Urology
Barnes-Jewish Hospital and Siteman Philadelphia, Pennsylvania
Lahey Hospital and Medical Center
Cancer Center Sonia Bahlani, MD
Burlington, Massachusetts
St. Louis, Missouri Fellow
Department of Urology Brian M. Benway, MD
James B. Angel, MD Assistant Professor of Urologic Surgery
The Arthur Smith Institute for Urology
Resident Washington University in St. Louis
North Shore LIJ Healthcare System
Division of Urology St. Louis, Missouri
New York, New York
Department of Surgery
Mark W. Ball, MD Boback M. Berookhim, MD, MBA
University of Kentucky
Resident Fellow
Lexington, Kentucky
James Buchanan Brady Urologic Institute Male Sexual and Reproductive Medicine
Jodi A. Antonelli, MD Johns Hopkins Medical Institutions Urology Service
Endourology Fellow Baltimore, Maryland Department of Surgery
Department of Urology Ahmad H. Bani-Hani, MD, FAAP Memorial Sloan-Kettering Cancer Center
UT Southwestern Medical Center Assistant Professor, Department of New York, New York
Dallas, Texas Urology Fernando J. Bianco, Jr., MD
Margarita M. Aponte, MD Sidney Kimmel Medical College Assistant Professor of Urology
Fellow Division of Urology Columbia University
New York University Langone Medical Nemours/Alfred I. DuPont Hospital for CEO
Center Children Urological Research Network
New York, New York Wilmington, Delaware Miami, Florida
xvii
xviii r r r Contributors
Megan T. Bing, MD Erin M. Burns, MD Kai-Wen Chuang, MD

Resident Resident Chief Resident
Department of Urology Medical University of South Carolina Arthur Smith Institute for Urology
University of Iowa Hospitals and Clinics Charleston, South Carolina North Shore-Long Island Jewish Health
Iowa City, Iowa System
Lysanne Campeau, MD, CM, PhD, Manhasset, New York
Trinity J. Bivalacqua, MD, PhD FRCSC
Associate Professor of Urology and Clinical Fellow Ryan Christopher Cleary, MD
Oncology Department of Urology Resident
James Buchanan Brady Urologic New York University Langone Medical Department of Urology
Institute Center Thomas Jefferson University
Johns Hopkins Medical Institutions New York, New York Philadelphia, Pennsylvania
Baltimore, Maryland Jonathan Cloutier, MD
Douglas A. Canning, MD, FACS Fellow in Endourology
Robert H. Blackwell, MD Professor of Urology in Surgery
Resident Department of Urology
University of Pennsylvania Tenon Hospital
Department of Urology Director, Pediatric Urology
Loyola University Health System University of Pierre et Marie Curie
The Children’s Hospital of Philadelphia Paris, France
Brookfield, Illinois Philadelphia, Pennsylvania
Michael S. Cookson, MD
Aaron G. Boonjindasup, MD, MPH
Daniel J. Canter, MD Chairman and Professor
Resident
Associate Member Donald D. Albers Endowed Chair
Fox Chase Cancer Center Department of Urology
Tulane University School of Medicine
Vice Chairman University of Oklahoma Health Sciences
New Orleans, Louisiana
Urologic Institute of Southeastern Center
Daniel Box, MD Pennsylvania Oklahoma City, Oklahoma
Resident Philadelphia, Pennsylvania Christopher S. Cooper, MD, FAAP,
Department of Surgery FACS
Division of Urology Christina Carpenter, MD
Resident Professor of Pediatric Urology
University of Cincinnati College of Associate Dean
Medicine Department of Surgery
Division of Urology Student Affairs & Curriculum
Cincinnati, Ohio University of Iowa Carver College of
Rutgers University–New Jersey
Sam J. Brancato, MD Medical School Medicine
Urologic Oncology Fellow Newark, New Jersey Iowa City, Iowa
National Cancer Institute Anthony T. Corcoran, MD
North Bethesda, Maryland Brett S. Carver, MD Urologic Oncology Fellow
Assistant Attending Fox Chase Cancer Center
Gennady Bratslavsky, MD Department of Surgery Philadelphia, Pennsylvania
Professor and Chair Division of Urology
Department of Urology Nicholas G. Cost, MD
Memorial Sloan-Kettering Cancer
SUNY Upstate Medical University Assistant Professor
Center
Syracuse, New York Department of Surgery
New York, New York
Division of Urology
James A. Brown, MD, FACS Pasquale Casale, MD, FACS University of Colorado School of Medicine
Professor Joan and Irene Given Professor of Aurora, Colorado
Department of Urology Urology Nicholas Cowan, MD
University of Iowa Columbia University Resident
Iowa City, Iowa Chief Department of Urology
Timothy E. Bunchman, MD Pediatric Urology Morgan Stanley Oregon Health & Science University
Professor & Director, Pediatric Children’s Hospital of New York Portland, Oregon
Nephrology Presbyterian
Nick Cowan, MD
Virginia Commonwealth University Division of Pediatric Urology
Richmond, Virginia Columbia University Medical Center
Oregon Health & Science University
New York, New York
Arthur L. Burnett, II, MD, MBA, FACS Portland, Oregon
Patrick C. Walsh Professor of Urology Jed-Sian Cheng, MD, MPH Brian Cox, MD
Department of Urology Chief Resident Chief Resident
The James Buchanan Brady Urological Department of Urology Department of Urology
Institute SUNY Upstate Medical University Oregon Health & Science University
Baltimore, Maryland Syracuse, New York Portland, Oregon
Contributors r r r xix
Bic N. Cung, MD Mary Ellen T. Dolat, MD Ahmer V. Farooq, DO

Resident Resident Assistant Professor
Department of Urology Division of Urology in the Department of Department of Urology
Temple University School of Medicine Surgery Loyola University Medical Center and
Philadelphia, Pennsylvania Virginia Commonwealth University Stritch School of Medicine
Akhil Das, MD, FACS Richmond, Virginia Maywood, Illinois
Assistant Professor of Urology Steve Dong, MD Brad Figler, MD
Department of Urology Clinical Instructor Assistant Professor of Urology
Sidney Kimmel Medical College Department of Urology Sidney Kimmel Medical College
Thomas Jefferson University University of Southern California Thomas Jefferson University
Philadelphia, Pennsylvania West Hollywood, California Philadelphia, Pennsylvania
Michel Daudon, PhD Philip J. Dorsey, Jr., MD, MPH T. Ernesto Figueroa, MD, FAAP, FACS
Service des Explorations Founctionnelles Resident Clinical Associate Professor
Tenon Hospital Department of Urology Sidney Kimmel Medical College
University of Pierre et Marie Curie Tulane University School of Medicine Chief, Division of Pediatric Urology
Paris, France New Orleans, Louisiana Nemours/Alfred I. DuPont Hospital for
Ross M. Decter, MD, FRCS Elizabeth V. Dray, MD Children
Professor and Chief Resident Wilmington, Delaware
Division of Urology Department of Urology
Surgery Jason C. Fisher, MD
Loyola University Medical Center
MS Hershey Medical Center Assistant Professor of Surgery
Maywood, Illinois
The Pennsylvania State University Division of Pediatric Surgery
College of Medicine Daniel Dugi, III, MD Joseph M. Sanzari Children’s Hospital
Hershey, Pennsylvania Assistant Professor Hackensack, New Jersey
Jessica M. DeLong, MD Sallyanne M. Fisher, MSN, FNP-BC,
Oregon Health & Science University
Fellow, Adult & Pediatric Reconstructive CUNP
Portland, Oregon
Urology Urology Nurse Practitioner
Urology John B. Eifler, MD Department of Veteran’s Affairs Medical
Eastern Virginia Medical School Clinical Instructor Center
Virginia Beach, Virginia Department of Urologic Surgery Wilmington, Delaware
Joan C. Delto, MD Vanderbilt University Medical Center
Urology Resident Nashville, Tennessee Carrie L. Fitzgerald, DO, MPH
Mount Sinai Medical Center Fellow
Justin D. Ellett, MD, PhD Department of Urology
Miami Beach, Florida
Resident University of Iowa Hospitals and Clinics
Robert B. Den, MD Medical University of South Carolina Iowa City, Iowa
Assistant Professor of Radiation Charleston, South Carolina
Oncology and Cancer Biology Robert C. Flanigan, MD, FACS
Chandy Ellimoottil, MD
Radiation Oncology Albert J. Jr. and Claire R. Speh Professor
Resident
Kimmel Cancer Center and Chair
Thomas Jefferson University Loyola University Stritch School of
Maywood, Illinois
Philadelphia, Pennsylvania Medicine
Adam P. Dicker, MD, PhD Leigh Mark Ettinger, MD, MS Chicago (Maywood), Illinois
Professor and Chair Clinical Assistant at the Hackensack
University Medical Center Drew A. Freilich, MD
Radiation Oncology
Assistant Professor of Pediatrics at the Resident
University of Medicine & Dentistry of Department of Urology
Sidney Kimmel Cancer Center
New Jersey New York Medical College
Department of Pediatrics White Plains, New York
Hackensack University Medical Center
Roger R. Dmochowski, MD, MMHC, Debra L. Fromer, MD
Hackensack, New Jersey
FACS Chief
Professor of Urology Thomas M. Facelle, MD Female Pelvic Medicine & Reconstructive
Vice Chair Section of Surgical Sciences Resident Medicine
Department of Urology Division of Urology Department of Urology
Vanderbilt University Medical Center Rutgers New Jersey Medical School Hackensack University Medical Center
Nashville, Tennessee Newark, New Jersey Hackensack, New Jersey
xx r r r Contributors
Nilay M. Gandhi, MD Tomas L. Griebling, MD, MPH, FACS Jennifer E. Heckman, MD, MPH
Resident John P. Wolf 33-Degree Masonic Resident in Urology
James Buchanan Brady Urologic Distinguished Professor and Department of Urology
Institute Vice Chair of Urology and Faculty University of Wisconsin
Johns Hopkins Medical Institutions Associate Madison, Wisconsin
Baltimore, Maryland The Landon Center on Aging
Jason C. Hedges, MD, PhD
Francisco Gelpi-Hammerschmidt, MD Assistant Professor
The University of Kansas
Chief Resident Department of Urology
Kansas City, Kansas
Department of Urology Oregon Health & Science
Thomas Jefferson University Jennifer A. Hagerty, DO University
Philadelphia, Pennsylvania Assistant Professor Portland, Oregon
Kristin A. Greco, MD Departments of Urology and Pediatrics Lauren N. Hendrix, MD
Resident Sidney Kimmel Medical College Resident
Department of Urology Division of Urology Division of Urology
Loyola University Medical Center Nemours/Alfred I. DuPont Hospital for Department of Surgery
Maywood, Illinois Children University of Kentucky
Wilmington, Delaware Lexington, Kentucky
Bradley C. Gill, MD, MS
Resident in Urology Sang Won Han, MD Amin S. Herati, MD
Department of Urology Professor of Urology Resident
Cleveland Clinic Department of Urology Department of Urology
Cleveland, Ohio Yonsei University College of Smith Institute for Urology Hofstra North
Medicine Schore – LIJ School of Medicine
Leonard G. Gomella, MD, FACS
Seoul, Korea Briarwood, New York
The Bernard W. Godwin Professor of
Prostate Cancer Won K. Han, MD Duane R. Hickling, MD
Chairman Associate Professor Female Pelvic Medicine and
Department of Urology Department of Medicine Reconstructive Surgery Fellow
Sidney Kimmel Medical College Division of Nephrology NYU School of Medicine
Associate Director, Jefferson Sidney Sidney Kimmel Medical College New York, New York
Kimmel Cancer Center Thomas Jefferson University
Clinical Director, Jefferson Sidney Irvin H. Hirsch, MD
Philadelphia, Pennsylvania Clinical Professor
Kimmel Cancer Network
Misop Han, MD Department of Urology
Associate Professor of Urology and Thomas Jefferson University
Oncology Philadelphia, Pennsylvania
Tricia Lacy Gomella, MD Department of Urology
Part Time Assistant Professor Steve J. Hodges, MD
Brady Institute of Urology Associate Professor
Department of Pediatrics Johns Hopkins Medical Institutions
The Johns Hopkins University School of Department of Urology
Baltimore, Maryland Wake Forest School of Medicine
Medicine
Baltimore, Maryland Jessica H. Hannick, MD Winston-Salem, North Carolina
Resident Jean Hoffman-Censits, MD
Patrick T. Gomella, MD, MPH
Loyola University Medical Center and Assistant Professor
Resident
Stritch School of Medicine Department of Medical Oncology
Maywood, Illinois Sidney Kimmel Medical College
George Washington University
Washington, DC Thomas Jefferson University
Samuel Haywood, MD
Michael A. Gorin, MD Resident
Resident Glickman Urologic and Kidney James M. Hotaling, MD, MS
James Buchanan Brady Urologic Institute Andrology Fellow
Institute Cleveland Clinic Foundation Department of Urology
Johns Hopkins Medical Institutions Cleveland, Ohio University of Illinois at Chicago
Towson, Maryland Chicago, Illinois
Kelly A. Healy, MD
Shaun G.S. Grewal, MD Assistant Professor Wayland Hsiao, MD
Chief Resident Department of Urology Assistant Professor
Division of Urologic Surgery Sidney Kimmel Medical College Department of Urology
Washington University Thomas Jefferson University Emory University School of Medicine
Tulsa, Oklahoma Philadelphia, Pennsylvania Atlanta, Georgia
Contributors r r r xxi
Jonathan H. Huang, MD Mark L. Jordan, MD, FACS Tariq A. Khemees, MD

Resident Chief of Urology Resident
Department of Urology VA Long Beach Health Care System Department of Urology
Emory University School of Medicine Clinical Professor The Ohio State University Wexner
Atlanta, Georgia Department of Urology Medical Center
University of California Columbus, Ohio
Scott G. Hubosky, MD
Assistant Professor Irvine, California Arjun Khosla, MD
Vice Chair for Quality and Safety Chief Resident
Adam O. Kadlec, MD
Resident
Sidney Kimmel Medical College Thomas Jefferson University
Jefferson Medical College Philadelphia, Pennsylvania
Philadelphia, Pennsylvania Maywood, Illinois Kiranpreet K. Khurana, MD
Chad P. Hubsher, MD Resident
Resident in Urology Jonathan S. Karpelowsky, MD, PhD Department of Urology
Division of Urology Senior Lecturer/Staff Specialist Glickman Urological and Kidney Institute
West Virginia University Pediatric Surgery Cleveland Clinic
Morgantown, West Virginia Children’s Hospital at Westmead & Cleveland, Ohio
University of Sydney Kathleen Kieran, MD, FAAP, FACS
Mark Hurwitz, MD Westmead, New South Wales, Australia Assistant Professor of Urology
Professor and Director of Thermal
Sanjay S. Kasturi, MD University of Iowa Hospitals and Clinics
Oncology
CR Bard Fellow in Endourology and University of Iowa Carver College of
Department of Radiation Oncology
Minimally Invasive Surgery Medicine
Department of Urology Iowa City, Iowa
Sidney Kimmel Cancer Center
Thomas Jefferson University Sidney Kimmel Medical College Igor I. Kislinger, MD
Philadelphia, Pennsylvania Thomas Jefferson University Resident
Philadelphia, Pennsylvania Department of Surgery
Youngjae Im, MD
University of Miami
Assistant Professor in Urology James Kearns, MD Miami, Florida
Department of Urology Resident
Yonsei University College of Medicine Eric A. Klein, MD, FACS
Section of Urology
Seoul, Korea Chair, Glickman Urologic & Kidney
University of Chicago
Institute
Mohamed T. Ismail, MD Chicago, Illinois
Cleveland Clinic
Assistant Professor Cleveland, Ohio
Christopher E. Keel, DO
Resident Joseph C. Klink, MD
Department of Urology Fellow in Urologic Oncology
Tulane University School of Medicine Center for Urologic Oncology
New Orleans, Louisiana Glickman Urological and Kidney Institute
Chief of Urology
Wilmington VA Medical Center Cleveland, Ohio
Francis Xavier Keeley, Jr., MD, FRCS
Wilmington, Delaware Consultant Urologist Michael O. Koch, MD, FACS
Mohamed S. Ismail, MBChB, MRCS, Bristol Urological Institute John P. Donohue Professor of Urology
PhD Bristol, England Chairman, Department of Urology
Specialist Registrar in Urology Department of Urology
Douglas C. Kelly, MD Indiana University School of Medicine
Chief Resident Indianapolis, Indiana
Southmead Hospital
South Gloucestershire, England Harry P. Koo, MD, FAAP, FACS
Emma F.P. Jacobs, MD Philadelphia, Pennsylvania Chief of Pediatric Medicine
Department of Urology Wm. Kevin Kelly, DO Joseph M. Sanzari Children’s Hospital
Indiana University Professor of Medical Oncology and Hackensack University Medical Center
Indianapolis, Indiana Urology Hackensack, New Jersey
Director
Robert Janssen, MD Division of Solid Tumor Oncology Jayram Krishnan, DO, MBA
Resident Department of Medical Oncology Fellow
Division of Urology Sidney Kimmel Medical College University of Dentistry and Medicine of
West Virginia University Thomas Jefferson University New Jersey
Morgantown, West Virginia Philadelphia, Pennsylvania Cherry Hill, New Jersey
xxii r r r Contributors
Chandan R. Kundavaram, MD Michael C. Large, MD Xiaolong Shawn Liu, MD

Chief Resident Fellow Chief Resident
Department of Urology Urologic Oncology Department of Urology
Thomas Jefferson University Department of Urology Thomas Jefferson University
Philadelphia, Pennsylvania University of Chicago Philadelphia, Pennsylvania
Chicago, Illinois
Nicholas J. Kuntz, MD Megan M. Lo, MD
Resident in Urologic Surgery Benjamin R. Lee, MD, FACS Assistant Professor
Division of Urology Professor of Urology & Medicine Children’s Hospital of Richmond at VCU
Duke University Medical Center (Oncology) Richmond, Virginia
Durham, North Carolina Department of Urology
Christopher J. Long, MD
Tulane University School of Medicine
Adonteng A. Kwakye, MD Pediatric Urology
New Orleans, Louisiana
Resident Fellow Surgery
Medical University of South Carolina Hyeyoung Lee, MD, MS Division of Urology
Charleston, South Carolina Clinical Assistant Professor of Urology The Children’s Hospital of Philadelphia
Department of Urology Philadelphia, Pennsylvania
Lydia T. Laboccetta, MD Yonsei University College of Medicine
Resident Franklin C. Lowe, MD, MPH, FACS
Seodaemungu, Seoul, Korea
Medical University of South Carolina Professor of Clinical Urology
Charleston, South Carolina Yong Seung Lee, MD Department of Urology
Clinical Research Assistant Professor Columbia University, College of
John M. Lacy, MD Department of Urology Physicians & Surgeons
Resident Yonsei University College of Medicine New York, New York
Department of Surgery Seodaemungu, Seoul, Korea
Adam M. Luchey, MD
Division of Urology
Ryan S. Levey, MD Resident
University of Kentucky College of
Resident Division of Urology
Medicine
Medical University of South Carolina West Virginia University
Lexington, Kentucky
Charleston, South Carolina Morgantown, West Virginia
H. Henry Lai, MD, FACS Garjae Levien, MD Alosh Madala, MD
Assistant Professor of Urologic Resident Resident
Surgery Division of Urology Department of Urology
Washington University in St. Louis Department of Surgery Upstate Medical University
St. Louis, Missouri University of Maryland School of Medicine Syracuse, New York
Costas D. Lallas, MD, FACS Baltimore, Maryland Ramiro J. Madden-Fuentes, MD
Associate Professor Patricia Lewandoski, MD Resident
Director, Robotic Surgery Resident Duke University Medical Center
Department of Urology Department of Urology Durham, North Carolina
Sidney Kimmel Medical College Thomas Jefferson University S. Bruce Malkowicz, MD, FACS
Thomas Jefferson University Philadelphia, Pennsylvania Associate Professor of Surgery and
Philadelphia, Pennsylvania Urology
Kenneth Lieberman, MD
Sarah M. Lambert, MD Chief Co-Director
Assistant Professor Section of Pediatric Nephology Urologic Oncology
Division of Pediatric Urology Professor, Pediatrics Division of Urology
Columbia University Medical Center Department of Pediatrics University of Pennsylvania
Morgan Stanley Children’s Hospital of Hackensack University Medical Center Philadelphia, Pennsylvania
New York Hackensack, New Jersey J. Ryan Mark, MD
Presbyterian, New York, New York Jianqing Lin, MD Chief Resident
Eric Langewisch, MD Assistant Professor Department of Urology
Assistant Professor Department of Medical Oncology Thomas Jefferson University
Division of Nephrology Sidney Kimmel Medical College Philadelphia, Pennsylvania
Oregon Health & Science University Thomas Jefferson University Viraj A. Master, MD, PhD, FACS
Portland, Oregon Philadelphia, Pennsylvania Associate Professor
Dawud Lankford, MD, MPH Mark C. Lindgren, MD Associate Chair of Clinical Affairs and
Resident Resident Quality
Department of Urology Department of Urology Department of Urology
New York Medical College University of Illinois at Chicago Emory University School of Medicine
Valhalla, New York Chicago, Illinois Atlanta, Georgia
Contributors r r r xxiii
Surena F. Matin, MD, FACS Allen F. Morey, MD, FACS Samuel Walker Nickles, MD
Associate Professor Paul C. Peters Chair in Urology Resident
Director Professor Medical University of South Carolina
Minimally Invasive New Technology in Department of Urology Charleston, South Carolina
Oncologic Surgery UT Southwestern Medical Center
Craig S. Niederberger, MD, FACS
Department of Urology Dallas, Texas
Professor and Department Head
The University of Texas MD Anderson Judd W. Moul, MD, FACS Department of Urology
Cancer Center James H. Semans, MD Professor of University of Illinois at Chicago
Houston, Texas Surgery Chicago, Illinois
Derek Matoka, MD Division of Urologic Surgery
Assistant Professor Duke University Medical Center Dmitriy Nikolavsky, MD
Department of Urology Durham, North Carolina Assistant Professor
Loyola University Medical Center Department of Urology
John Patrick Mulhall, MBBCh, FACS,
Stritch School of Medicine SUNY Upstate Medical University
FECSM
Maywood, Illinois Syracuse, New York
Director
Kurt A. McCammon, MD, FACS Sexual and Reproductive Medicine Victor W. Nitti, MD, FACS
Associate Professor Program Professor of Urology and Obstetrics &
Urology Division of Urology Gynecology
Eastern Virginia Medical School Memorial Sloan Kettering Cancer Center Vice Chair
Virginia Beach, Virginia New York, New York Department of Urology
Alana M. Murphy, MD Director
Monica M. Metzdorf, MD
Assistant Professor Female Pelvic Medicine and
Pediatric Urologist
Department of Urology Reconstructive Surgery
Kaiser Permanente
Los Angeles, California
Thomas Jefferson University New York University Langone Medical
Reza Mehrazin, MD Philadelphia, Pennsylvania Center
Fellow New York, New York
Fellow, Urologic Oncology Katie S. Murray, DO
Fox Chase Cancer Center Chief Resident Paul H. Noh, MD, FACS, FAAP
Philadelphia, Pennsylvania Department of Urology Director of Minimally Invasive Surgery
The University of Kansas Associate Professor
Matthew A. Meissner, MD Kansas City, Kansas Division of Urology
Resident Cincinnati Children’s Hospital Medical
Jack H. Mydlo, MD
Department of Urology Center
Professor and Chair
UT Southwestern Medical Cincinnati, Ohio
Center
Temple University School of
Dallas, Texas Samuel Ohlander, MD
Medicine
Urology Resident
Vani S. Menon, MD Philadelphia, Pennsylvania
Resident Stephen Y. Nakada, MD, FACS University of Illinois at Chicago
Department of Urology The David T. Uehling Professor and Chicago, Illinois
Loyola University Medical Center Chairman
Maywood, Illinois Department of Urology Tara K. Ortiz, MD
University of Wisconsin Urology Resident
Megan M. Merrill, DO
Madison, Wisconsin Department of Surgery
Urologic Oncology Fellow
Division of Urology
Department of Urology Michael J. Naslund, MD
Duke University Medical Center
The University of Texas MD Anderson Professor and Chief
Durham, North Carolina
Cancer Center Division of Urology
Houston, Texas Department of Surgery John J. Pahira, MD
Director Professor of Urology
Robert M. Moldwin, MD, FACS
Maryland Prostate Center Department of Urology
Professor of Urology
University of Maryland School of Georgetown University Hospital
North Shore-LIJ Hofstra University
Medicine Washington DC
School of Medicine
Baltimore, Maryland
Director, Pelvic Pain Center, North Daniel C. Parker, MD
Shore-LIJ Healthcare System Frank M. Nezu, MD Resident in Urology
Arthur Smith Institute for Urology Urology Division Chief Department of Urology
Long Island Jewish Medical Center Howard County General Hospital Temple University
New Hyde Park, New York Clarksville, Maryland Philadelphia, Pennsylvania
LWBK1391-FM LWBK1391-Gomella October 6, 2014 15:9
xxiv r r r Contributors
Neal Patel, MD Sandip M. Prasad, MD, MPhil W. Stuart Reynolds, MD, MPH
Resident Assistant Professor of Urology and Assistant Professor
Division of Urology Associate Director of the Urology Department of Urologic Surgery
Department of Surgery Residency Program Vanderbilt University Medical Center
Rutgers-Robert Wood Johnson Medical Medical University of South Carolina Nashville, Tennessee
School Charleston, South Carolina
Kyle A. Richards, MD
New Brunswick, New Jersey Raj S. Pruthi, MD, FACS Urologic Oncology Fellow
Elizabeth K. Peacock, MD Professor and Chief of Urology Surgery
Chief Resident Department of Surgery The University of Chicago Medical Center
Medical University of South Carolina University of North Carolina School of Chicago, Illinois
Charleston, South Carolina Medicine
Julie M. Riley, MD
Chapel Hill, North Carolina
Margaret S. Pearle, MD, PhD, FACS Assistant Professor
Professor of Urology Marcus L. Quek, MD, FACS Director of Endourology
Professor of Internal Medicine Associate Professor Division of Urology
Department of Urology Department of Urology University of New Mexico
UT Southwestern Medical Center Loyola University Medical Center and Albuquerque, New Mexico
Dallas, Texas Stritch School of Medicine
Chad R. Ritch, MD, MBA
Maywood, Illinois
David F. Penson, MD, MPH Clinical Instructor
Hamilton and Howd Chair in Urologic Ganesh V. Raj, MD, FACS Urologic Surgery
Oncology Associate Professor of Urology Vanderbilt University Medical Center
Chair, Department of Urologic Surgery Department of Urology Nashville, Tennessee
Professor of Urologic Surgery, Medicine UT Southwestern Medical Center
Nathan R. Roberts, MD
and Health Policy Dallas, Texas
Resident
Vanderbilt University Medical Center Pravin Rao, MD Department of Urology
Nashville, Tennessee Assistant Professor of Urology Thomas Jefferson University
Michael Perrotti, MD Director of Reproductive Medicine and Philadelphia, Pennsylvania
Albany Urologic Oncology Surgery James S. Rosoff, MD
Albany, New York James Buchanan Brady Urological
Assistant Professor
Institute Department of Urology
John L. Phillips, MD, FACS Johns Hopkins University
Urology Program Director Yale School of Medicine
Baltimore, Maryland New Haven, Connecticut
New York Medical College Amar J. Raval, MD Sherry S. Ross, MD
Sleepy Hollow, New York Resident
Assistant Professor of Surgery and
Michael A. Poch, MD Pediatrics
Thomas Jefferson University Department of Surgery
Assistant Professor Philadelphia, Pennsylvania
Genitourinary Oncology Division of Urology
Moffitt Cancer Center Mathew C. Raynor, MD Duke University Medical Center
University of South Florida Assistant Professor Durham, North Carolina
Tampa, Florida Division of Urologic Surgery
Joshua D. Roth, MD
The University of North Carolina School
Dana Point, MD Resident
of Medicine
Chapel Hill, North Carolina
Division of Urology Indiana University School of Medicine
West Virginia University Nathaniel Readal, MD Indianapolis, Indiana
Morgantown, West Virginia Urology Resident
Eric S. Rovner, MD, FACS
James Buchanan Brady Urology Institute
Michael A. Pontari, MD Professor of Urology
Baltimore, Maryland
Professor and Vice-Chairperson Medical University of South Carolina
Department of Urology Jeremy N. Reese, MD, MPH Charleston, South Carolina
Temple University School of Medicine Resident
Edmund S. Sabanegh, Jr., MD
Philadelphia, Pennsylvania Department of Urology
Chairman
University of Pittsburgh Medical Center
Mary K. Powers, MD Department of Urology
Pittsburgh, Pennsylvania
Resident Professor of Surgery (Urology)
Department of Urology Matthew J. Resnick, MD Cleveland Clinic
Tulane University School of Assistant Professor of Urologic Surgery Lerner College of Medicine at Case
Medicine Vanderbilt University Medical Center Western Reserve University
New Orleans, Louisiana Nashville, Tennessee Cleveland, Ohio
Contributors r r r xxv
Daniel D. Sackett, MD Arpeet Shah, MD Zachary L. Smith, MD

Chief Resident Resident Resident
Department of Urology Department of Urology Division of Urology
Thomas Jefferson University Loyola University Medical Center University of Pennsylvania
Philadelphia, Pennsylvania Chicago, Illinois Philadelphia, Pennsylvania
Gurdarshan S. Sandhu, MD Ellen Shapiro, MD, FACS
Philippe E. Spiess, MD
Urologic Oncology Fellow Professor of Urology Associate Member
Surgery Director
Department of Genitourinary Oncology
Washington University School of Pediatric Urology
Moffitt Cancer Center
Medicine Department of Urology
Tampa, Florida
St. Louis, Missouri New York University School of Medicine
Bruce J. Schlomer, MD New York, New York Christopher L. Starks, MD
Assistant Professor of Pediatric Urology Oleg Shapiro, MD, FACS Fellow
Urology Assistant Professor Center for Male Fertility
Baylor College of Medicine and Texas Department of Urology Department of Urology
Children’s Hospital Upstate Medical University Glickman Urological and Kidney
Houston, Texas Syracuse, New York Institute
The Cleveland Clinic Foundation
Kymora Scotland, MD, PhD Patrick J. Shenot, MD, FACS
Shaker Heights, Ohio
Resident Associate Professor and Deputy Chair
Department of Urology Department of Urology Gillian Stearns, MD
Thomas Jefferson University Hospital Sidney Kimmel Medical College Resident
Philadelphia, Pennsylvania Thomas Jefferson University Department of Urology
Philadelphia, Pennsylvania Upstate Medical University
Allen D. Seftel, MD, FACS
Professor of Urology Yaniv Shilo, MD Syracuse, New York
Cooper Medical School of Rowan Resident
Department of Urology Douglas W. Storm, MD, FAAP, FACS
University
University of Pittsburgh Medical Center Assistant Professor of Pediatric
Chief
Pittsburgh, Pennsylvania Urology
Division of Urology
Cooper University Medical Center Abhinav Sidana, MD University of Iowa
Camden, New Jersey Resident Carver College of Medicine
Robert L. Segal, MD, FRCS (c) Department of Surgery Iowa City, Iowa
Fellow Division of Urology
Sexual Medicine University of Cincinnati College of Medicine Andrew D. Strine, MD
Urology Cincinnati, Ohio Resident
James Buchanan Brady Urological Jay Simhan, MD Department of Urology
Institute Chief Resident Indiana University School of Medicine
Johns Hopkins Medical Institutions Department of Urology Indianapolis, Indiana
Pikesville, Maryland Temple University
Stephen E. Strup, MD, FACS
Casey Allison Seideman, MD Philadelphia, Pennsylvania
James F. Glenn Professor and Chief of
Resident Angela B. Smith, MD Urology
Department of Urology Assistant Professor Department of Surgery
UT Southwestern Medical Center Department of Urology University of Kentucky College of
Dallas, Texas UNC School of Medicine Medicine
Ahmad Shabsigh, MD, FACS Chapel Hill, North Carolina Lexington, Kentucky
Assistant Professor of Urology Paul H. Smith III, MD
Department of Urology Debasish Sundi, MD
Resident
The Ohio State University Wexner Chief Resident
Division of Urology
Medical Center Brady Institute of Urology
Penn State Milton S. Hershey Medical
Columbus, Ohio Johns Hopkins Medical Institutions
Center
Baltimore, Maryland
Anish K. Shah, MD Hershey, Pennsylvania
Chief Resident Grahame H.H. Smith, MBBS Gregory E. Tasian, MD, MSc
Department of Surgery Head of Urology Staff Urologist
Division of Urology Department of Urology Clinical Instructor of Urology in Surgery
University of Cincinnati College of The Sydney Children’s Hospital Network Surgery, Division of Urology
Medicine (Westmead) The Children’s Hospital of Philadelphia
Cincinnati, Ohio Westmead, New South Wales, Australia Philadelphia, Pennsylvania
xxvi r r r Contributors
Raju Thomas, MD, MHA, FACS Evalynn Vasquez, MD, MBA Michael E. Woods, MD
Professor and Chairman Resident Associate Professor of Urology
Department of Urology Department of Urology Department of Urology
Tulane University School of Loyola University Medical Center University of North Carolina School of
Medicine Maywood, Illinois Medicine
New Orleans, Louisiana Taylor B. Vaughan, MD Chapel Hill, North Carolina
Adeep B. Thumar, MD Department of Urology
Christopher Wright, MD
Chief Resident Medical University of South Carolina
Urology Resident
Department of Urology Charleston, South Carolina
Rutgers-New Jersey Medical School
Thomas Jefferson University Bryan Voelzke, MD, MS Totowa, New Jersey
Philadelphia, Pennsylvania Assistant Professor
Department of Urology Blake A. Wynia, MD, MPH
Jeffrey J. Tomaszewski, MD Resident
Harborview Medical Center at the
Fellow Department of Urology
University of Washington
Urologic Oncology New York University
Seattle, Washington
Fox Chase Cancer Center New York, New York
Philadelphia, Pennsylvania Srinivas Vourganti, MD
Clinical Fellow National Institutes of Rafael E. Yanes, MD
Edouard J. Trabulsi, MD, FACS Health Resident
Associate Professor National Cancer Institute Department of Urology
Department of Urology Urologic Oncology Branch Mount Sinai Medical Center
Sidney Kimmel Medical College Washington, DC Bay Harbor Island, Florida
Thomas Jefferson University Nikhil Waingankar, MD
Philadelphia, Pennsylvania Resident Shilo Yaniv, MD
Anthony J. Tracey, MD, MPH The Arthur Smith Institute for Urology Clinical Instructor in Urology
Resident North Shore-Long Island Jewish Health Department of Urology
Department of Urology System University of Pittsburgh Medical
Tulane University School of Long Island City, New York Center
Medicine Pittsburgh, Pennsylvania
Dana A. Weiss, MD
New Orleans, Louisiana Pediatric Urology Fellow Matthew A. Young, MD
Matthew A. Uhlman, MD, MBA Surgery, Division of Urology Resident
Resident The Children’s Hospital of Medical University of South Carolina
Department of Urology Philadelphia Charleston, South Carolina
University of Iowa Hospitals and Philadelphia, Pennsylvania
Sven Wenske, MD Austin R. Younger, MD
Clinics
Assistant Professor Resident
Iowa City, Iowa
Department of Urology Medical University of South Carolina
Robert G. Uzzo, MD, FACS Columbia University College of Charleston, South Carolina
Chairman Physicians & Surgeons
Department of Surgical Oncology Lee C. Zhao, MD, MS
New York, New York Assistant Instructor
Fox Chase Cancer Center
Hunter Wessells, MD, FACS UT Southwestern Medical Center
Professor and Nelson Chair in Urology Dallas, Texas
Vladimir A. Valera, MD, PhD Department of Urology
Resident University of Washington Philip T. Zhao, MD
Department of Urology Seattle, Washington Chief Resident
New York Medical College Division of Urology, Department of
Jessica Wetterlin, MD
Valhalla, New York Surgery
Resident
Rutgers-Robert Wood Johnson Medical
Sandip P. Vasavada, MD, FACS Department of Urology
School
Urologic Director Loyola University Medical Center
New Brunswick, New Jersey
Center for Female Pelvic Medicine & Maywood, Illinois
Reconstructive Surgery Daniel A. Wollin, MD Jack Matthew Zuckerman, MD
Cleveland Clinic Lerner College of Resident Resident
Medicine Department of Urology Department of Urology
Glickman Urological Institute New York University Eastern Virginia Medical School
Cleveland, Ohio New York, New York Norfolk, Virginia
CONTENTS
Preface v Hematuria, Adult 846

Evidence-Based Medicine vii Hematuria, Macroscopic (Gross) Pediatric 847
Editor-in-Chief ix Hematuria, Pediatric Microscopic Isolated
Associate Editors ix Asymptomatic 848
Section Editors ix Hematuria, Traumatic 849
Consulting Editors x Hyperaldosteronism, Primary (Aldosteronism,
Conn Syndrome) 850
Specialty Editors xii
Hypercalcemia 851
International Editorial Board xiv
Hyperkalemia 852
Contributors xvii
Hypernatremia 853
Alphabetical Topic Index xxviii
Hypertension and Elevated Blood Pressure,
SECTION I: Urologic Diseases and Conditions 1 Treatment 854
SECTION II: Short Topics: A to Z 641 Hypocalcemia 855
Hypokalemia 856
SECTION III: Algorithms 821
Hypomagnesemia 857
Abdominal Pain, Lower 822 Hyponatremia 858
Acid Phosphatase Elevation 823 Hypospadias 859
Acute Scrotum 824 Incontinence, Female 860
Addison Disease (Adrenocortical Insufficiency) 825 Incontinence, Male 861
Adrenal Mass, Solid 826 Incontinence, Pediatric 862
Alkaline Phosphatase Elevation 827 Infertility 863
Anuria or Oliguria 828 Infertility, Male Abnormal Semen 864
Bladder Trauma 829 Infertility, Male, Low Semen Volume 865
Bladder Tumor 830 Lower Urinary Tract Symptoms (LUTS),
Candiduria 831 Male 866
Cushing Syndrome 832 Lymphadenopathy 867
Cystocele and/or Enterocele 833 Metabolic Acidosis 868
Delayed Puberty 834 Metabolic Syndrome, Treatment 869
Disorders of Sexual Development (DSD) 835 Nephrotic Syndrome 870
Dyspareunia 836 Nocturia 871
Dysuria 837 Parathyroid Hormone, Elevated Serum 872
Ejaculation, Premature 838 Pelvic Pain, Female 873
Enuresis 839 Penis, Squamous Cell Carcinoma 874
Erectile Dysfunction 840 Penis, Trauma 875
Fecal Incontinence 841 Polyuria 876
Foley Catheter Problem (Difficult Placement, Male) 842 Precocious Puberty 877
Genital Ulcers 843 Priapism 878
Groin and Hip Pain 844 Prostate Cancer, Castration Resistant 879
Gynecomastia 845 Prostatitis 880
xxvii
xxviii r r r Contents
Proteinuria 881 Anticoagulation and Antiplatelet Therapy in

PSA 882 Urologic Practice 982
Pulmonary Embolism, Diagnosis 883 AUA Symptom Index/International Prostate
Symptom Score (I-PSS) 984
Pulmonary Embolism, Treatment 884
Catheter Guide 985
Pyuria 885
Contrast Agents, Genitourinary 986
Rectal Injury 886
International Index of Erectile Function (IIEF) 987
Rectocele and Enterocele 887
Male Sexual Health Questionnaire (MSHQ)
Renal Colic Management 888 Short Form 989
Renal Failure, Acute 889 National Institutes of Health (NIH) Chronic
Renal Mass 890 Prostatitis Symptom Index (CPSI) 990
Renal Mass, Intraoperative Consult 891 Prostate Cancer Screening Guidelines 991
Renal Trauma, Hemodynamically Stable 892 Sexual Health Inventory for Men IIEF-5 992
Scrotum and Testicle, Mass 893 TNM Classification: Cervix Cancer 993
Scrotum and Testicle, Trauma 894 TNM Classification: Colon Cancer 994
Testis Cancer, Nonseminoma 895 TNM Classification: Kidney Cancer 995
Testis Cancer, Seminoma 896 TNM Classification: Penis Cancer 996
Testosterone Deficiency (Hypogonadism) 897 TNM Classification: Prostate Cancer 997
Undescended Testicle (Cryptorchidism) 898 TNM Classification: Rectal Cancer 998
Uremia 899 TNM Classification: Renal Pelvis and Ureter Cancer 999
Urethral Discharge 900 TNM Classification: Testis Cancer 1000
Urinary Retention, Male 901 TNM Classification: Urethral Cancer 1001
Urine Leak From Vagina 902 TNM Classification: Urinary Bladder Cancer 1002
Urolithiasis 903 Uroradiology Signs (See also Section II:
Urolithiasis, Ureteral Calculi 904 “Uroradiology Signs”) 1003
UTI, Adult Female 905 Voiding Diary 1006
UTI, Pediatric 906 Index 1007
Vaginal Bleeding, Abnormal 907 Alphabetical Topical Index (Section I and II)
Vaginal Discharge 908
11β-Hydroxylase (CYP11B1) Deficiency 642
Vas Deferens, Congenital Absence 909
2,8-Dihydroxyadenine (2,8-DHA) Urolithiasis 642
Vitamin D Deficiency 910
21-Hydroxylase (CYP21A2) Deficiency 642
SECTION IV: Urinalysis and Urine Studies 911 5α-Reductase Deficiency 642
I. Urine Analysis 912 Aarskog Syndrome (Faciodigitogenital Syndrome) 642
II. Spot or Random Urine Studies 913 Abdominal Mass, Adult, Urologic Considerations 2
III. Creatinine Clearance and Glomerular Abdominal Mass, Newborn/Child, Urologic
Filtration Rate 913 Considerations 4
IV. 24-hr Urine Studies 914 Abdominoperineal Resection (APR), Urologic
Considerations 642
SECTION V: Alternative and Complementary
Urologic Therapies 915 Abrams–Griffiths Nomogram 642
Acetaminophen Abuse, Urologic Considerations 642
SECTION VI: Urologic Drug Reference 921
Acquired Renal Cystic Disease 643
SECTION VII: Reference Tables 977 Acrosome Reaction Assay 643
Aging Male Survey (AMS) 978 Actinomycosis, Renal 643
Antibiotic Prophylaxis: AUA Guidelines 979 Acute Kidney Injury (AKI), Definitions 643
Contents r r r xxix
Acute Kidney Injury, Adult (Renal Failure, Acute) 6 Ammonium Chloride Loading Test 647
Acute Kidney Injury, Pediatric (Renal Failure, Acute) 8 Ammonium Urate Urolithiasis 647
Acute Scrotum 10 Amsterdam and Bethesda Criteria for Lynch Syndrome 647
Acute Tubular Necrosis 12 Amyloidosis, Genitourinary 26
Addison Disease 14 Anal Sphincter Tone and Sensation, Urologic
Adenofibroma, Metanephric, Pediatric 643 Considerations 647
Adenomatoid Tumors, Testicular and Paratesticular 16 Anderson-Hynes Pyeloplasty 647
Adrenal Adenoma 18 Andrews Procedure (Hydrocele) 648
Adrenal Angiomyolipoma 643 Androgen Deficiency in the Aging Male (ADAM)
and ADAM Questionnaire 648
Adrenal Calcifications 643
Androgen Deprivation Syndrome (ADS)/Metabolic
Adrenal Cortical Carcinoma 20
Syndrome 648
Adrenal Cysts and Pseudocysts 644
Androgen Insensitivity Syndrome (AIS; or Androgen
Adrenal Cytomegaly 644 Resistance Syndrome), Complete (CAIS) and
Adrenal Hemorrhage 644 Partial (PAIS) 648
Adrenal Hypoplasia 644 Androgen/Anabolic Steroid Abuse 649
Adrenal Incidentalomas 644 Andropause (Late-Onset Hypogonadism) 28
Adrenal Insufficiency, Acute (Adrenal Crisis) 22 Angiokeratoma of Fordyce (Penile and Scrotal
Adrenal Mass 24 Angiokeratomas) 649
Adrenal Metastases 644 Angiolymphoid Hyperplasia, Penile 649
Adrenal Myelolipoma (Adrenal Myolipoma) 644 Angiomyxoma, Perineal 649
Adrenal Oncocytoma 644 Angiosarcoma, Genitourinary 649
Adrenalitis 645 Anogenital Intraepithelial Neoplasia 649
Adrenocortical Disease, Primary Pigmented Anorectal Malformations: Imperforate Anus, Cloaca,
Nodular 645 and Urogenital Sinus Anomalies 30
Adrenogenital Syndrome 645 Anorgasmia, Female 649
Adrenoleukodystrophy 645 Anorgasmia, Male 32
Aging Male Survey 645 Anterior Urethral Valves 649
Al Ghorab Corporal Shunt 645 Antiandrogen Withdrawal Syndrome (Flutamide
Withdrawal Syndrome) 649
Al Ghorab Corporal Shunt with Burnett “Snake”
Maneuver 645 Antisperm Antibodies 650
Alagille Syndrome 646 Anuria and Oliguria, Adult 34
Alkaline Phosphatase, Urologic Considerations 646 Anuria and Oliguria, Pediatric 36
Alkaptonuria 646 Aphthous Ulcer, External Genitalia 650
Allopurinol Hypersensitivity Syndrome (AHS) 646 Appendix Testis and Appendix Epididymis, Torsion 650
Alopecia Genitalium 646 Aristolochic Acid (Fang Chi) 650
α-(Alpha) Fetoprotein 646 Arteriovenous Fistula (AVF), Renal (or Arteriovenous
Malformation [AVM]) 650
Alport Disease/Syndrome 646
Artificial Insemination (AI) 651
Alström–Edwards Syndrome 646
Ask-Upmark Kidney 651
Alzheimer Disease, Urologic Considerations 646
Asopa Hypospadias Repair 651
Ambiguous Genitalia 646
Aspergillosis, Genitourinary 651
American Association for the Surgery of Trauma
(AAST) Organ Severity Scales: Genitourinary Aspermia 651
Injuries 647 Assisted Reproductive Technology (ART) 651
Aminoaciduria 647 Asthenospermia 651
xxx r r r Contents
Athletic Hematuria 652 Bites to Penis, Animal, and Human 656

Atopic Dermatitis (Eczema), Urologic Considerations 652 BK Virus, Urologic Considerations 656
Attentive Digital Rectal Exam 652 Black-Water Fever 656
Atypical Adenomatous Hyperplasia of the Prostate Bladder Agenesis 656
(Adenosis) 652 Bladder Areflexia (Detrusor Areflexia) 46
Atypical Small Acinar Proliferation, Prostate (ASAP) 652 Bladder Augmentation 656
AUA (American Urologic Association) Symptom Bladder Calculi (Vesical Calculi) 48
Index for BPH 652 Bladder Cancer, Adenocarcinoma 50
Autonomic Dysreflexia 38 Bladder Cancer, General 52
Azoospermia 652 Bladder Cancer, Intravesical Agents 656
Back Pain, Urologic Considerations 653 Bladder Cancer, Non-Muscle-Invasive Bladder
Bacteriuria and Pyuria 40 Cancer (Ta, T1) (NMIBC) 54
Balanitis and Balanoposthitis 42 Bladder Cancer, Squamous Cell Carcinoma 56
Balanitis Xerotica Obliterans/Lichen Sclerosis et Bladder Cancer, Urothelial, Metastatic (Clinical
Atrophicus 653 and Pathologic N+, M+) 58
Balanitis, Zoon (Plasma Cell Balanitis) 653 Bladder Cancer, Urothelial, Micropapillary 657
Balkan Nephropathy 653 Bladder Cancer, Urothelial, Muscle Invasive
Banff Classification, Transplant Rejection 653 (Clinical and Pathologic T2/T3/T4) (MIBC) 60
Barcat-Redman Hypospadias Repair 653 Bladder Cancer, Urothelial, Muscle Invasive
(Clinical and Pathologic T2/T3/T4) (MIBC)
Bariatric Surgery, Urologic Considerations 653 Neoadjuvant Therapy 62
Bartter Syndrome 653 Bladder Cancer, Urothelial, Superficial Carcinoma
Bashful Bladder (Paruresis, Shy Bladder Syndrome, In Situ (CIS) (NMIBC) 64
“Pee-Shy”) 654 Bladder Choriocarcinoma 657
BCG Refractory Transitional Cell Carcinoma (TCC) 654 Bladder Contractility Index (BCI) 657
BCG Sepsis/BCG-Osis 44 Bladder Diverticulum 657
BCL-2, Urologic Considerations 654 Bladder Ears 657
Beckwith–Wiedemann Syndrome 654 Bladder Filling Defects 658
Beer Nephroureterectomy 654 Bladder Hemangioma 658
Beer Potomania 654 Bladder Hernia 658
Behçet Disease 654 Bladder Hypoplasia 658
Bellini Duct Carcinoma (Collecting Duct Carcinoma) 654 Bladder Injury, Intraoperative 66
Belt Procedure 654 Bladder, Inflammatory Pseudotumor 658
Benchekroun Ileal Valve 655 Bladder Leiomyoma 658
Berger Disease (IgA Nephropathy) 655 Bladder, Lymphoma 658
Bergman Sign 655 Bladder Mass, Differential Diagnosis 658
β-hCG (Human Chorionic Gonadotropin) 655 Bladder, Metastasis To 658
Bethanechol Supersensitivity Test 655 Bladder Neck Contracture 659
Bezoars (Fungus Balls) 655 Bladder Neck Hypertrophy 659
Bifid Renal Pelvis 655 Bladder, Neurofibroma 659
Bifid Scrotum 655 Bladder Outlet Obstruction (BOO) 68
Biofeedback, Urologic Considerations 655 Bladder Outlet Obstruction Index (BOOI) 659
Biofilm, Urologic Considerations 655 Bladder Pain/Interstitial Cystitis Symptom
Biothesiometry, Penile 656 Score (BPIC-SS) 659
Birt–Hogg–Dubé Syndrome 656 Bladder, Paraganglioma 659
Contents r r r xxxi
Bladder, Pheochromocytoma 659 Bulbocavernosus Reflex 664

Bladder Sarcoma (Leiomyosarcoma/ Bulking Agents, Injectable 664
Rhabdomyosarcoma) 659 Bullous Pemphigoid 664
Bladder Small Cell Carcinoma (Oat Cell, Signet Ring) 660 BUN (Blood Urea Nitrogen),
Bladder, Teardrop 660 Increased/Decreased 665
Bladder Trabeculation and Cellules 660 Burch Colposuspension 665
Bladder Trauma 70 Burns, External Genitalia and Perineum 76
Bladder Tumors, Benign and Malignant, General Buschke-Lowenstein Tumor 665
Considerations 72 Byar Flaps 665
Bladder, Villous Adenoma 660 Calcifications, Abdominal and Pelvic 665
Bladder Wall Calcification, Differential Diagnosis 660 Calcifications, Bladder 665
Bladder Wall Thickening, Differential Diagnosis 660 Calcifications, Prostate 665
Blastomycosis, Genitourinary 660 Calcifications, Renal 665
Bleomycin Toxicity 661 Calcinosis, Idiopathic Scrotal 665
Blue Diaper Syndrome 661 Calciphylaxis 665
Blue Dot Sign 661 Calcium Load and Fast Studies 666
Blue Nevus (Melanosis), Urologic Considerations 661 Calcium Supplementation and Urolithiasis 666
Boari-Ockerblad Flap 661 Calyceal Diverticula 78
Body Mass Index (BMI), Urologic Considerations 661 Camey I and II Orthotopic Urinary Diversion 666
Bone Marrow/Stem Cell Transplantation, Urologic Canal of Nuck Hydrocele and Cyst (Female
Considerations 661 Hydrocele) 666
Bone Metastasis, Urologic Considerations 661 Candidiasis—Cutaneous, External Genitalia 666
Bone Mineral Density, Urologic Considerations 662 Captopril Test 666
Bone Scan, Urologic Considerations 662 Carcinoid Tumors, Genitourinary 666
Bonney Test (Marshall Test) 662 Carcinosarcoma, Bladder 666
Bors-Comarr Classification of Voiding Dysfunction 662 Carcinosarcoma, Prostate 667
Bosniak Classification of Renal Cysts 662 Carney Syndrome (Carney Complex) 667
Bourne Test 662 Carney Triad 667
Bowen Disease and Erythroplasia of Queyrat 74 Caruncle, Urethral 667
Bowenoid Papulosis 662 Casale Procedure 667
Boyarsky Guidelines for BPH 663 Cat-Eye Syndrome 667
Boyce Nephrotomy (Anatrophic Catheterizable Stoma Problems 80
Nephrolithotomy) 663 Cauda Equina Syndrome 667
Brachytherapy Seed Embolus 663 Caudal Regression Syndrome 667
Brain Metastasis, Urologic Considerations 663 Cavernosography 667
Brenner Tumors 663 Cavernosometry 668
Bricker Ureteral Anastomosis 663 Cecil Urethral Stricture Repair 668
Brigham Sling (Urethropexy) 663 Cecoureterocele 668
Brink Score 663 Cello Scrotum 668
British Testicular Tumor Classification 663 Cerebral Palsy, Urologic Considerations 668
Bronchogenic Cyst, Retroperitoneal 663 Cervical Cancer, Urologic Considerations 668
Brunn Buds and Nests (Von Brunn Nests) 663 Chancroid 668
Brushite (Calcium Monohydrogen Phosphate) 664 Charcot-Boettcher Crystals and Filaments 668
BTA Testing (BTA and BTA Stat Urine Test) 664 Charge Association 668
xxxii r r r Contents
Chemotherapy Toxicity, Urologic Considerations 668 Contact Dermatitis, Urologic Considerations 673
Chlamydia Sexually Transmitted Disease 669 Contrast Allergy and Reactions 98
Chordee 82 Contrast-Induced Nephropathy (CIN) 674
Christmas Tree Bladder 669 Cordonnier and Nesbit Ureteral Anastomosis 674
Chronic Kidney Disease (CKD) 669 Corpora Amylacea (CA) 674
Chronic Kidney Disease, Adult (Renal Failure, Cortical Necrosis, Acute (Renal Cortical Necrosis) 674
Chronic) 84 Costovertebral Angle Tenderness 674
Chronic Kidney Disease, Pediatric (Renal Failure, Cough Stress Test 674
Chronic) 86 Cowper Duct Cyst 674
Chronic Pelvic Pain Syndrome/Chronic Prostatitis
Cowper Gland Carcinoma 675
(CPPS/CP) in Males 669
Cowperitis (Inflammation of Bulbourethral Gland) 675
Chronic Pelvic Pain Syndrome (CPPS) in Females 669
Creatinine, Serum, Increased/Decreased 675
Chronic Prostatitis Symptom Index (CPSI)/NIH-CPSI
(National Institutes of Health CPSI) 670 Credé Maneuver 675
Churg-Strauss Syndrome 670 Cremasteric Reflex 675
Chylocele 670 Cribriform Clear Cell Hyperplasia of the Prostate 675
Chylous Ascites 88 Cryptococcus, Genitourinary 675
Chyluria Crystal-Induced Acute Kidney Injury
90
(Acute Renal Failure) 675
Circumcision, Adult Considerations 92
CT Scan, Urologic Considerations 675
Circumcision, Female 670
Culp-Deweerd Pyeloplasty 676
Circumcision, Pediatric Considerations 94
Cunningham Clamp 676
Cisplatin Toxicity 670
Cushing Disease and Syndrome 100
Clitoral Length 671
Cyclophosphamide (Cytoxan) Toxicity 676
Clitoral Priapism 671
Cystadenocarcinoma, Genitourinary 676
Clitoromegaly 671
Cystadenoma, Genitourinary 676
Clonidine Suppression Test 671
Cystadenoma/Cystadenocarcinoma, Retroperitoneal 676
Clostridium Difficile Colitis, Urologic Considerations 671
Cystatin C 676
Clot Retention 671
Cystic Fibrosis, Urologic Considerations 676
Cobb Collar 671
Cystinosis 677
Cobra Head Sign 671
Cystitis Cystica 677
Coccidiomycosis, Genitourinary 671
Cystitis, Emphysematous 677
Cohen (“Cross-Trigonal”) Ureteral Reimplantation 672
Cystitis, Eosinophilic 677
Coital Incontinence (Coital leakage/Intercourse
Cystitis Follicularis 677
Incontinence) 672
Cystitis Glandularis and Cystitis Glandularis of
Collecting System Duplication, Complete 672
Intestinal Type 677
Colon and Rectal Cancer, Urologic Considerations 672 Cystitis, General Considerations 102
Column of Bertin, Hypertrophied 672 Cystitis, Granulomatous 677
Compartment Syndrome, Urologic Considerations 672 Cystitis, Hemorrhagic (Infectious, Noninfectious,
Compulsive Masterbation 672 Radiation) 104
Condyloma Acuminata (Veneral Warts) 96 Cystitis, Polypoid and Papillary 677
Condylomata Lata 672 Cystitis, Radiation 677
Congenital Adrenal Hyperplasia (CAH) 672 Cystitis, Viral 678
Congenital Nephrosis/Nephrotic Syndrome 673 Cystocele Grading: Baden–Walker, Pelvic Organ
Constipation, Urologic Considerations 673 Prolapse Quantification (POP-Q) 678
Contents r r r xxxiii
Cystocele 106 Dysfunctional Voiding 682

Cystogram, Indications and Technique 678 Dysgerminoma 682
Cystometrogram 678 Dysorgasmia 682
Cystosarcoma Phyllodes, Prostate 678 Dysorgasmia (Painful Orgasm), Male 120
Cystoscope Processing 678 Dyspareunia, Female 122
Cytokeratin Staining 679 Dyspareunia, Male (Partner Dyspareunia,
Cytology, Prostate 679 Hispareunia) 682
Cytology, Urinary Dysraphism, Spinal 683
679
Cytomegalovirus (CMV), Urologic Considerations Dysthyroidism (Hypo/Hyperthyroidism) Urologic
679
Considerations 683
Davis Intubated Ureterotomy 679
Dysuria 124
Daytime Frequency Syndrome (Pollakiuria) 679
Ecchymosis, Flank 683
Deep Venous Thromboembolism (DVT) Prophylaxis:
Aua Guidelines Echinococcus, Renal 683
679
Edema, External Genitalia (Lymphadema,
Deep Venous Thrombosis and Pulmonary Embolus,
Peno-Scrotal Edema) 126
Urologic Considerations 108
Edema, Lower Extremity, Urologic
Dehydroepiandrosterone (DHEA) and DHEA Sulfate
Considerations 683
(DHEA-S) Blood Test 680
Edward Syndrome 683
Delayed Nephrogram 680
Ejaculation, Female 683
Dementia and Voiding Dysfunction 680
Ejaculation, Painful 683
Dent Disease 680
Ejaculation, Premature (Premature Ejaculation) 128
Denys-Drash Syndrome (DDS), Urologic
Considerations 680 Ejaculatory Anhedonia 684
Dermatitis Herpetiformis 680 Ejaculatory Disturbances (Delayed, Decreased,
Absent) 130
Dermatophyte, External Genitalia 680
Ejaculatory Duct Obstruction (EDO) 684
Dermoid Cyst, Testicular 680
Electroejaculation 684
Desmoplastic Small Round Cell Tumor 681
Electromyography, External Sphincter 684
De Toni-Fanconi-Debre Syndrome 681
Elejalde Syndrome 684
Detrusor Overactivity 110, 681
Elephantiasis, Scrotum (Elephantiasis Scroti) 684
Detrusor Sphincter Dyssynergia (DSD) 112
Encopresis, Urologic Considerations 684
Dexamethasone Suppression Test 681
Encrusted Cystitis and Pyelitis 684
Diabetes Insipidus (DI), Urologic Considerations 681
Encrusted Ureteral stent 685
Diabetes Mellitus, Urologic Considerations 114
Endocarditis (SBE) Prophylaxis, Urologic
Dietl Crisis 681 Considerations 685
Dimercaptosuccinic Acid (DMSA) Renal Scan 681 Endocervicosis, Bladder 685
Disorders of Sexual Development (DSD) 116 Endometriosis, Genitourinary 685
Diuretic Renogram 681 Enuresis, Adult 132
Doppler, Penile 682 Enuresis, Pediatric 134
Down Syndrome, Urologic Considerations 682 EPCA-2 (Early Prostate Cancer Antigen) 685
Dribbling, Postvoid 682 Epididymal Cyst 685
Dromedary Hump 682 Epidermoid Cyst, Testicle 685
Drooping Lily Sign 682 Epididymal Cystadenoma/Papillary
Drop Metastases 682 Cystadenoma 685
Drug Eruption, Fixed 682 Epididymis, Mass (Epididymal Tumors and Cysts) 136
Dysfunctional Elimination Syndrome 118 Epididymis, Metastasis To 685
xxxiv r r r Contents
Epididymis, Obstruction 686 Fine-Needle Aspiration (FNA) of Prostate 689

Epididymitis 138 FISH: Urinary Fluorescent In Situ Hybridization
Epispadias 140 (UroVysion Test) 689
Epitheloid Hemangioma, Penis and Scrotum 686 Fistula, Enterovesical 690
Erectile Dysfunction Inventory of Treatment Survey Fistula, Rectourethral 690
(EDITS) 686 Fistula, Ureteroarterial 690
Erectile Dysfunction, Following Pelvic Surgery Fistula, Vesicocutaneous 690
or Radiation 142 Fistula, Vesicouterine 690
Erectile Dysfunction/Impotence, General Fistula, Vesicovaginal and Ureterovaginal 690
Considerations 144
Fitz–Hugh–Curtis Syndrome 691
Erection Hardness Score (EHS) for ED 686
Flank Hernia Following Nephrectomy 691
Erysipelas, External Genitalia 686
Flank Pain, General 154
Erythema Multiforme (EM), External Genitalia 686
Fluorescent (Blue Light) Cystoscopy 691
Erythrasma 686
Foley Catheter Problems (Insertion and Removal) 156
Excretory Urogram, Intraoperative (“On Table
IVP”/“Single-Shot IVP”) 686 Foley Y-V Pyeloplasty 691
Expressed Prostatic Secretions (EPS) 686 Fordyce Spots (Ectopic Sebaceous Glands), Penis 691
Exstrophy, Bladder (Classic Exstrophy) 146 Foreign Body, Bladder and Urethra 691
Exstrophy, Cloacal 148 Formalin Instillation, Indications and Technique 691
Exstrophy–Epispadias Complex (EEC) 687 Fossa Navicularis Diverticulum 691
Extragonadal Germ Cell Tumors (EGCT) 687 Fournier Gangrene 158
Extramammary Paget Disease, Urologic Fowler Syndrome (Primary Disorder of Urethral
Considerations 687 Sphincter Relaxation) 692
Extramedullary Hematopoesis, Renal 687 Fowler–Stephens Orchiopexy 692
Extravasation During Urologic Surgery 687 Fracture Risk Associated with Prostate Cancer and
Fabry Disease/Syndrome Androgen Deprivation Therapy 692
687
Familial Testotoxicosis Fragile X Syndrome 692
687
Fanconi Syndrome Fraley Syndrome 692
687
Fatty Casts 688 French Catheter Scale 692, 985
Fecal Incontinence, Urologic Considerations 688 Frequency, Urinary 692
Fecaluria 688 Frequency–Dysuria Syndrome 692
Female Hypoactive Sexual Desire Disorder 688 Fuhrman Nuclear Grading Classification, Renal Cell
Carcinoma (RCC) 693
Female Sex Function Index (FSFI) 688
Fungal Infections, Genitourinary 160
Feminizing Genitoplasty 688
Funguria 693
Fertile Eunuch Disease/Syndrome 688
Funiculitis 693
Fertility and Cancer Therapy, Urologic
Considerations 150 Gamete Intrafallopian Transfer (GIFT) 693
Fibroepithelial Polyp, Genitourinary 688 Ganglioneuroblastoma, Adrenal 693
Fibroepithelial Polyp, Penis 689 Ganglioneuroma, Adrenal 693
Fibrous Hamartoma of Infancy 689 Gartner Duct Cyst 693
Fibrous Pseudotumor of Testicular Tunic 689 Genital Arousal Disorder (Persistent) 693
Fiducial Markers 689 Genital Piercing, Urologic Considerations 694
Filariasis, Urologic Considerations 689 Genital Skin Loss 694
Filling Defect, Upper Urinary Tract (Renal Pelvis Genital Ulcers 694
and Ureter) 152 Genitourinary Pain Index (GUPI) 694
Contents r r r xxxv
Genomic Testing, Prostate Cancer 694 Growing Teratoma Syndrome 699

Germ Cell Aplasia (Sertoli Cell Only Syndrome) 694 Guillain–Barré (Transverse Myelitis) Syndrome:
Gestational Age Assessment, Urologic Urologic Considerations 699
Considerations 695 Gun Shot Wound, External Genitalia 699
Gibbon Classification of Voiding Dysfunction 695 Gun Shot Wound, Kidney 699
Gibson Incision 695 Gynecomastia 170
Giggle Incontinence (Enuresis Risoria) 695 Hailey–Hailey Disease (Benign Familial Pemphigoid) 699
Gil-Vernet Extended Pyelolithotomy 695 Hald–Bradley Classification of Voiding Dysfunction 699
Gil-Vernet Orthotopic Urinary Diversion 695 Hand Foot Syndrome 699
Gil-Vernet Ureteral Reimplantation 695 Hautmann Pouch 699
Gitelman Syndrome 695 Heikel–Parkkulainen Reflux Classification System 699
Gittes Needle Urethropexy 695 Hematocele 700
Gleason Grade, Tertiary Pattern 695 Hematospermia 172
Gleason Grading/Scoring System 695 Hematuria, Athletic (Runners’ Hematuria) 700
Gleason Grading System, Modified 696 Hematuria, Gross and Microscopic, Adult 174
Glenn-Anderson Ureteroneocystostomy 696 Hematuria, Gross and Microscopic, Pediatric 178
Glomerulocystic Kidney Disease Hematuria–Dysuria Syndrome 700
(Cortical Microcystic Disease) 696 Hematuria–Loin Pain Syndrome 700
Glomerulonephritis, Acute 162 Hemizona Assay 700
Glomerulonephritis, Chronic 164 Hemorrhage Following TURP or TURBT 180
Glomerulosclerosis 696
Hemorrhage, Postoperative, Urologic Considerations 700
Glucagon Stimulation Test 696
Hemorrhage, Retroperitoneal and Perinephric 700
Glycosuria, Renal 696
Hemosiderin, Urinary 700
Goldstein Test 697
Henoch–Schönlein Purpura (HSP) 700
Goldston Syndrome 697
Hepatitis A & B (HAV/HBV), Urologic
Gonadal Dysgenesis, Mixed 697 Considerations 701
Gonadal Dysgenesis, Pure 697 Hepatorenal Syndrome 701
Gonadoblastoma 697 Hereditary Leiomyoma Renal Cell Carcinoma
Gonorrhea 166 (HLRCC) Syndrome 701
Goodpasture Syndrome 697 Hereditary Papillary Renal Cell Carcinoma (HPRCC) 701
Goodwin Ureteral Anastomosis 697 Hernia Uterine Inguinale 701
Gorlin Syndrome 697 Herpes Simplex, Genital 182
Gout, Urologic Considerations 698 Herpes Zoster, Genitourinary 701
Gouverneur Syndrome 698 Hesitancy and Intermittency 184
Granuloma Inguinale (Donovanosis) 698 Hidradenitis Suppurativa (Acne Inversa), Urologic
Granulosa Cell Tumors 698 Considerations 701
Grapefruit and Grapefruit Juice, Interaction with Hinman Syndrome (Hinman–Allen syndrome)
Urologic Medications 698 (Nonneurogenic Neurogenic Bladder) (Occult
Gratification Disorder Neuropathic Bladder) 701
698
Griess Test Hispareunia (Male Dyspareunia) 702
698
Griss Sex Function Index (Golombok–Rust Histoplasmosis, Genitourinary 702
Inventory of Sexual Satisfaction) 698 HIV Nephropathy 702
Groin Hernia, Pediatric 698 HIV/AIDS, Urologic Considerations 186
Groin/Inguinal Mass, Male and Female 168 Hodgkin Disease, Urologic Considerations 702
xxxvi r r r Contents
Hodgson Types I, II, III Hypospadias Repair 702 Hypokalemia, Urologic Considerations 707
Honeymoon Cystitis 702 Hypomagnesemia, Urologic Considerations 707
Horseshoe Kidney 702 Hyponatremia, Urologic Considerations 707
Horton-Devine “Flip-Flap” Hypospadias Repair 702 Hypophosphatemia, Urologic Considerations 707
Hot Flushes/Vasomotor Instability in Males 188 Hypospadias, Free Graft Repair 707
Hounsfield Units 702 Hypospadias, Tubularized Incised Plate (TIP) Repair 707
HPC-1 (Hereditary Prostate Cancer 1 Locus) 703 Hypospadias, 2-Stage Repair 708
HPV (Human Papilloma Virus), Urologic Hypospadias, Urethral Advancement for Subglanular
Considerations 703 and Midshaft Defects 708
Human Growth Hormone (hGH), Urologic Hypospadias 204
Considerations 703 Hysterectomy, Urologic Considerations 708
Hunner Ulcer 703 IC (Interstitial Cystitis) Symptom Index 708
Hutch Diverticulum 703 Ice Water Test 708
Hydatid Cyst (Hydatid Disease) 703 ICIQ-MLUTS (International Consultation on
Hydrocalycosis 703 Incontinence Questionnaire-Male Lower Urinary
Tract Symptoms) 708
Hydrocele of the Spermatic Cord 703
IIEF (International Index of Erectile Function) 708, 987
Hydrocele, Adult & Pediatric 190
Immunocompromised Patients, Urologic
Hydrocolpos and Hydrometrocolpos, Pediatric 192 Considerations 206
Hydronephrosis/Hydroureteronephrosis Immunohistochemical Staining, Urologic
(Dilated Ureter/Renal Pelvis), Adult 194 Considerations 709
Hydronephrosis/Hydroureteronephrosis Imperforate Hymen 709
(Dilated Ureter/Renal Pelvis), Pediatric 196
In Vitro Fertilization (IVF) and Embryo Transfer 709
Hydronephrosis/hydroureteronephrosis
Incontinence Clamps 709
(Dilated Ureter/Renal Pelvis), Prenatal 198
Incontinence Impact Questionnaire (IIQ-7) 709
Hymenal Skin Tags 703
Incontinence (Urinary) with Orgasm (Climacturia) 710
Hyperaldosteronism, Primary (Aldosteronism, Conn
Syndrome) 200 Incontinence, Urinary, Adult Female 210
Hyperbaric Oxygen, Urologic Considerations 703 Incontinence, Urinary, Adult Male 212
Hypercalcemia, Urologic Considerations 704 Incontinence, Urinary, Following Radical
Prostatectomy 214
Hypercalciuria (Absorptive, Renal, and Resorptive) 704
Incontinence, Urinary, Pediatric 216
Hypercarbia During Laparoscopy 704
Indevus Urgency Severity Scale (IUSS) 710
Hypercontinence 705
Indiana Pouch 710
Hyperkalemia, Urologic Considerations 705
Infertile Male Syndrome 710
Hypermagnesemia, Urologic Considerations 705
Infertility, Urologic Considerations 218
Hypernatremia, Urologic Considerations 705
Inflammatory Bowel Disease, Urologic
Hyperoxaluria, Urologic Considerations 705 Considerations 710
Hyperparathyroidism, Urologic Considerations 706 Inflammatory Pseudotumor (Pseudosarcomatous
Hyperphosphatemia, Urologic Considerations 706 Fibromyxoid Tumor) 710
Hyperprolactinemia, Urologic Considerations 202 Infundibular Stenosis 710
Hyperspermia and Hypospermia 706 Infundibulopelvic Dysgenesis 710
Hypertension, Urologic Considerations 706 Inguinal Hernia, Adult, Urologic Considerations 710
Hyperuricosuria 706 Inguinal Hernia, Pediatric, Urologic Considerations 710
Hypocitraturia 706 Injection Therapy for Vesicoureteral Reflux 711
Hypogonadism, Society Definitions 706 Insect Bite, Penis and Scrotum 711
Contents r r r xxxvii
Intermittent Hormonal Therapy (IHT)/Intermittent Lactate Dehydrogenase (LDH), Urologic

Androgen Deprivation (IAD) 711 Considerations 716
International Children’s Continence Society (ICCS), Lapides Classification of Voiding Dysfunction 716
Terminology 711 Laser Technologies and Urologic Applications 716
International Germ Cell Cancer Collaborative Latex Allergy, Urologic Considerations 222
Group (IGCCCG) 711 Laurence–Moon–Bardet–Biedl Syndrome 716
International Prostate Symptom Score (I-PSS) 712, 984 Lazy Bladder Syndrome (Nurse’s Bladder) 716
Interstitial Cystitis (IC)/Painful Bladder
Leadbetter–Clarke Ureteral Anastomosis 717
Syndrome (PBS) 220
Leadbetter–Politano Ureteroneocystostomy 717
Interstitial Nephritis 712
Leak Point Pressure (LPP)/Abdominal Leak Point
Intracytoplasmic Sperm Injection (ICSI) 712 Pressure (ALPP) 717
Intraoperative Floppy Iris Syndrome (IFIS) 712 LeBag Neobladder 717
Intrauterine Insemination (IUI) 712 LeDuc Ureteral Anastomosis 717
Intrinsic Sphincter Deficiency (ISD) 712 Leiomyomatosis, Hereditary 717
Inverted Papilloma, Bladder 712 Leopard Syndrome 717
Inverted Papilloma, Ureter and Renal Pelvis 712 Leriche Syndrome 717
IRS (Intergroup Rhabdomyosarcoma Study)
Lesch–Nyhan Syndrome 717
Clinical Classification 713
Leukemia, Urologic Considerations 717
Jaboulay/Winkelman Procedure (Hydrocelectomy) 713
Leukoplakia, Penis 718
Jack Stones 713
Leukorrhea 718
Jarisch–Herxheimer Reaction 713
Libido, Diminished, Female 224
Jejunal–Ileal Bypass, Urologic Considerations 713
Libido, Diminished, Male 226
Jeune Syndrome (Asphyxiating
Thoracic Dysplasia) 713 Lichen Nitidus, Penis 718
Joint Replacement, Urologic Considerations 713 Lichen Planus, Penis 718
Juvenile Gangrenous Vasculitis, Scrotal Lichen Sclerosis Et Atrophicus 718
(Pyoderma Gangrenosum) 714 Lichen Simplex Chronicus (Lichen Simplex Complex) 718
Juxtaglomerular Cell Tumor, Kidney 714 Lich–Gregoir Ureteral Reimplantation 718
Kallmann Syndrome 714 Liddle’s Syndrome 718
Kaposi Sarcoma, Urologic Considerations 714 Life Expectancy, Urologic Considerations 719
Kartagener Syndrome (Immotile Cilia Syndrome) 714 Lipoma, Bladder 719
Kegel Exercises 714 Lipoma, Spermatic Cord 719
Kelami Classification System (Modified) 714 Lipomatosis, Pelvic 719
Kelly Plication 714 Lipomeningocele, Urologic Considerations 719
Kerr Kinks 714 Liver Metastasis, Urologic Considerations 719
Ketamine Abuse, Urologic Considerations 714 Lobar Nephronia 719
Kibrick Test 715 Lord Procedure (Hydrocelectomy) 719
Kidney, Metastasis To 715 Lowe Syndrome 720
Kidney, Supernumerary 715 Lower Urinary Tract Symptoms 228
Klinefelter Syndrome 715 Lub Syndrome 720
Klippel–Trenaunay–Weber Syndrome 715 Lyme Disease, Urologic Considerations 720
Kock Pouch and Hemi-Kock Neobladder 715 Lymphadenopathy, Inguinal 230
Koyle Stent 715 Lymphadenopathy, Pelvic and Retroperitoneal 232
Kruger Strict Sperm Morphology 715 Lymphangiogram, Pedal 720
Labial Adhesions and Fusion 716 Lymphangioma, Bladder 720
xxxviii r r r Contents
Lymphangioma, Renal 720 Megacystis, Congenital 724

Lymphangioma, Retroperitoneal 720 Megacystis-Megaureter Syndrome 725
Lymphangioma, Scrotal 720 Megalourethra 725
Lymphatic Ascites 720 Megaureter, Congenital 240
Lymphocele, Pelvic 234 Melanoma, Adrenal 725
Lymphogranuloma Venereum 720 Melanoma, Genitourinary 725
Lymphoma, Urologic Considerations 721 Melanoma, Urethral 725
Lymphoreticular Malignant Neoplasm, Penis 721 Menkes Syndrome (Menkes Kinky Hair Disease) 725
Lymphovascular Invasion (LVI), Urologic Menopause, Urologic Considerations 725
Considerations 721 Mesoblastic Nephroma, Congenital (Bolande
Lynch Syndrome 721 Disease) 242
MACE (Malone Antegrade Continence Enema) 721 Mesothelioma, Benign, Testicular Tunic 725
Macro-Orchidism (MO) 721 Mesothelioma, Malignant, Testicular Tunic 726
MAG 3 Renal Scan 721 Metabolic Stone Evaluation (24-hr Urine Studies) 726
MAGPI Hypospadias Repair 721 Metabolic Syndrome, Urologic Considerations 726
Mainz I, II, III Pouch Urinary Diversion 722 Metanephric Adenofibroma, Kidney (Nephrogenic
Malacoplakia, Genitourinary Adenofibroma) 727
722
Malaria (Black Water Fever), Urologic Considerations 722 Metanephric Adenoma 727
Male Sexual Function Scale Metapyrone Test 727
722
Male Sexual Health Questionnaire (MSHQ) and the Meyer–Weigert Law 727
MSHQ Short Form 722 MIBG Scan 727
Malrotated Kidney/Renal Malrotation 722 Michaelis–Gutmann Bodies 727
Marshall–Marchetti–Krantz (MMK) Cystourethropexy 722 Microcystic/Nested Variant Urothelial Carcinoma 727
Martius Graft 722 Microlithiasis, Testis 727
Mathieu Hypospadias Repair 722 Micropapillary Bladder Cancer 727
Maturation Arrest 722 Micropenis (Microphallus) 244
Maximum Androgen Blockade (MAB)/Combined Micturition Syncope 728
Hormonal Therapy (CHT) 723 Milk of Calcium, Urinary Tract 728
Mayer–Rokitansky–Kuster–Hauser Syndrome Milk–Alkali Syndrome 728
(Rokitansky—Kuster–Hauser Syndrome) 723 Mitrofanoff Principle 728
Mayo Clinic Grading System for Prostate Cancer 723 Mixed Epithelial Stromal Tumor of the Kidney
McCune–Albright Syndrome 723 (MESTK) 728
McGuire Urinal 723 Molluscum Contagiosum 728
Meatal Stenosis, Urethral, Female 723 Mondor Disease 728
Meatal Stenosis, Urethral, Male 723 Monfort Technique 728
Meckel–Gruber Syndrome (Meckel Syndrome) 723 Monti Procedure 728
Median Bar 723 Morris Syndrome 729
Median Raphe Cyst 723 Moskowitz Vaginal Prolapse Repair 729
Medications That Can Impact Voiding Function 724 Mostofi (WHO) Grading System, Prostate Cancer 729
Medullary Cystic Kidney 724 Mowat–Wilson Syndrome 729
Medullary Cystic Kidney Disease (MCKD) 236 Mucormycosis, Genitourinary 729
Medullary Sponge Kidney (MSK) 238 Mucosuria (Mucinuria) 729
Megaprepuce (Congenital Mega Prepuce) 724 Muir–Torre Syndrome 729
Megacalycosis 724 Mulberry Stones 729
Contents r r r xxxix
Mulcahy Protocol 729 Nephropathy, Obstructive 733

Müllerian Duct Remnants and Syndrome (PMDS) 730 Nephropathy, Urate (Urate Nephropathy) 733
Multicystic Dysplastic Kidney 246 Nephroptosis 734
Multilocular Cystic Nephroma (Cystic Nephroma, Nephrotic Syndrome 256
Multilocular Cyst) 730 Nesbit Chordee Repair 734
Multiple Endocrine Neoplasia (MEN I, MEN II) 730 Neuroblastoma 258
Multiple Myeloma, Urologic Considerations 730 Neuroendocrine Tumors, Genitourinary 734
Multiple Sclerosis, Urologic Considerations 248 Neurofibromatosis, Urologic Considerations 734
Mumps Orchitis 730 Neurogenic Bladder, General Considerations 260
MURCS Association (Müllerian Duct, Renal, and Neurogenic Detrusor Overactivity (NDO) 734
Cervical Vertebral Defects) 730
Neuromodulation, Urologic Considerations 734
Muscle Flap Types, Urologic Considerations 730
Neves–Zincke Classification 734
Mustardé Hypospadias Repair 730
NMP-22 Testing 735
Myasthenia Gravis, Urologic Considerations 250
Nocturia 262
Mycoplasma Genitalium Infection 731
Nocturnal Erections, Normal and Abnormal 735
Mycoplasma Hominis, Urinary Tract Infection 731
Nocturnal Penile Tumescence (NPT) Testing 735
Myelodysplasia (Spinal Dysraphism), Urologic
Considerations Nocturnal Polyuria (NP) 735
252
Myocutaneous Flaps Nomograms, Urologic 735
731
Myofascial Pain, Urologic Considerations Nonarteritic Anterior Ischemic Optic Neuropathy
731
(NAION) 735
Myofascial Pelvic Pain Syndrome (MPPS) 731
Nonsacral Neuromodulation 735
Myoglobin Nephrotoxicity 731
Noonan Syndrome 735
Myoglobinuria 731
N-Telopeptide, Urinary (NTX) 735
Nagamatsu Incision 731
Nutcracker Syndrome 735
National Comprehensive Cancer Network (NCCN)
Guidelines 732 Obesity, Urologic Considerations 736
National Institutes of Health (NIH) Obturator Nerve Injury, Intraoperative 736
Chronic Prostatitis Symptom Index (CPSI) 732, 990 Obturator Reflex, Urologic Considerations 736
Necrospermia 732 O’Leary–Sant Scores (O’Leary–Sant Interstitial
Nelson Syndrome 732 Cystitis Symptom Index [ICSI]) 736
Nephritis, Radiation 732 Oligoasthenoteratospermia 736
Nephrocalcinosis, Adult 254 Oligospermia 736
Nephrocalcinosis, Neonatal 732 Omphalocele-Exstrophy of the Bladder—Imperforate
Anus-Spina Bifida Defects (OEIS) Complex 736
Nephrogenic Adenoma (NA) and Metaplasia 732
Opioid-Induced Hypogonadism 736
Nephrogenic Syndrome of Inappropriate Antidiuresis 732
Opitz–Frias Syndrome 737
Nephrogenic Systemic Fibrosis/Fibrosing
Dermatopathy (NSF/NFD) 732 Oral–Facial–Digital (OFD) Syndrome 737
Nephrometry Scoring Systems (PADUA, C-Index, Orchitis, General Considerations 264
RENAL) 732 Orchitis, Granulomatous 737
Nephronophthisis (Juvenile, Infantile, Orgasmic Pain (Painful Ejaculation) 737
and Adolescent) 733 Ortho-Phthalaldehyde (OPA) Chemical Disinfectant 737
Nephropathy, Analgesic 733 Ossifying Renal Tumor of Infancy 737
Nephropathy, Ischemic 733 Osteitis Pubis, Urologic Considerations 266
Nephropathy, Membranous 733 Osteonecrosis of the Jaw (ONJ), Urologic
Nephropathy, Minimal Change 733 Considerations 737
xl r r r Contents
Osteoporosis and Osteopenia, Urologic Pelvic Fracture, Urologic Considerations 742

Considerations 737 Pelvic Liposarcoma 742
Osteotomy, Urologic Considerations 738 Pelvic Organ Prolapse (Cystocele and Enterocele) 276
Ovarian Cancer, Urologic Considerations 738 Pelvic Organ Prolapse Quantification System
Ovarian Remnant Syndrome 738 (POP-Q) 743
Ovarian Vein Syndrome 738 Pelvic Pain and Urgency/Frequency (PUF) Patient
Overactive Bladder (OAB) 268 Symptom Scale 743
Oxalate-Associated Renal Disease 738 Pelvic Pain, Female 278
Oxalate, Dietary 738 Pelvic Pain, Male 743
p53, Urologic Considerations 738 Pelvis, Bifid, Renal 743
Pad Testing 738 Pelvis, Extrarenal 743
Pagano Ureteral Anastomosis 739 Pemphigus Foliaceus and Vulgaris 743
Page Kidney 739 Penile and Corporal Body Mass 743
Paget Disease, Anogenital/Extramammary 739 Penile Brachial Pressure Index (PBI) 743
Paget Disease, Bone 739 Penile Doppler Ultrasound Indications and
Painful Bladder Syndrome (PBS) 739 Parameters 743
Palliative Radiation, Urologic Considerations 739 Penile Enhancement and Lengthening 743
Pancreatitis, Autoimmune Urologic Considerations 739 Penile Intraepithelial Neoplasia 744
Paneth Cell-Like Change, Prostate 739 Penile Necrosis (Gangrene) Non-Fournier
Gangrene 744
Papillary Necrosis, Renal 270
Penile Pain Syndrome 744
Papillary Urothelial Neoplasm of Low Malignant
Potential (PUNLMP) 740 Penile Prosthesis Problems
(Infection/Extrusion/Malfunction) 280
Papilloma, Bladder 740
Penile Prosthesis, Models and Descriptions 744
Papilloma, Renal Pelvis 740
Penile Rehabilitation 744
Papillorenal Syndrome 740
Penile Shortening 744
Paquin Ureteral Reimplantation 740
Penile Skin Bridges (Penile Bands) 745
Paraphilias, Urologic Considerations 740
Penile, Mass (Noncutaneous) 745
Parastomal Hernia 740
Penis, Agenesis (Aphallia) 745
Paratesticular Rhabdomyosarcoma 741
Penis, Angiosarcoma 745
Paratesticular Tumors 272
Paraurethral and Vaginal Wall Masses Penis, Artificial Nodules (Tancho Nodules, Bulletus,
741
Fang Muk, Chagan Balls) 745
Parkinson Disease, Urologic Considerations 274
Penis, Basal Cell Carcinoma 745
Partin Tables 741
Penis, Bowenoid Papulosis 745
Patau Syndrome 741
Penis, Buried (Concealed/Hidden/Trapped) 745
Patient Perception of Bladder Condition (PPBC) 741
Penis, Cancer, General Considerations 282
Patient Perception of Intensity of Urgency
Scale (PPIUS) Penis, Cancer, Lymphadenopathy 284
741
PCA3 (Prostate Cancer Gene 3 Urine Assay) 741 Penis, Curvature, and/or Pain 286
Pearly Papules of Penis 742 Penis, Cutaneous Horn 745
Pediatric-Modified Risk Injury Failure Loss Penis, Cutaneous Lesion 288
End-Stage Renal Disease (pRIFLE) 742 Penis, Cysts 746
Pediculosis Pubis (Crab Lice/Pubic Lice) 742 Penis, Duplication (Diphallus) 746
Peliosis Hepatis 742 Penis, Fixed Drug Eruptions 746
Pelvic Floor Dysfunction 742 Penis, Hemangioma (Cavernous Hemangioma) 746
Contents r r r xli
Penis, Hirsute Papilloma (Pearly Penile Papules, Phosphate Nephropathy, Acute 750
Coronal Papillae) 746 Pinworms, Urologic Considerations 750
Penis, Hypoplasia 746 Pipe Stem Urethra 750
Penis, Kaposi Sarcoma 746 PI-RADS Prostate MRI Scoring System 750
Penis, Leiomyoma 746 PLAP (Placental Alkaline Phosphatase) 751
Penis, Leiomyosarcoma 746 Plasmacytoid Urothelial Carcinoma 751
Penis, Length, Normal 746 Plasmacytoma, Bladder 751
Penis, Leukoplakia 747 Plasmacytoma, Testicular 751
Penis, Malignant Fibrous Histiocytoma (MFH) 747 Ploidy Analysis, Bladder Cancer 751
Penis, Melanoma 747 Ploidy Analysis, Prostate Cancer 751
Penis, Metastasis To 747 Pneumaturia (Gas in Urine) 300
Penis, Neurilemoma (Schwannoma) 747 Pneumoretroperitoneum 751
Penis, Neurofibrosarcoma Pneumoscrotum 751
(Malignant Schwannoma) 747
Polyarteritis Nodosa (PAN), Urologic
Penis, Sclerosing Lipogranuloma (Paraffinoma) 747 Considerations 751
Penis, Sclerosing Nonvenereal Lymphangitis 747 Polycystic Kidney Disease, Autosomal Dominant 302
Penis, Squamous Cell Carcinoma 290 Polycystic Kidney Disease, Autosomal Recessive 304
Penis, Strangulation 747 Polyembryoma 752
Penis, Syringoma 748 Polyhydramnios/Oligohydramnios 306
Penis, Thrombosis of Dorsal Vein 748 Polyoma Virus (BK, JC), Urologic
Penis, Torsion 748 Considerations 308, 752
Penis, Trauma 292 Polyorchidism 752
Penis, Verrucous Carcinoma 748 Polythelia, Urologic Considerations 752
Penis, Webbed 748 Polyuria 752
Penn Pouch 748 Positron Emission Tomography (PET) Imaging,
Pereyra Urethropexy 748 Choline C 11 752
Perineal Grooves 748 Positron Emission Tomography (PET) Imaging,
Perineal Mass Urologic Considerations 752
748
Perineal Pain, Differential Diagnosis Post Micturition Symptoms 752
749
Perineal Trauma (Straddle Injury) Postorgasmic Illness Syndrome (POIS) 752
749
Perinephric Mass Postatrophic Hyperplasia of the Prostate 753
749
Perinephric Stranding 749 Postcoital Prophylactic Antibiotics 753
Perineural Invasion, Urologic Considerations 749 Postcoital Test 753
Peripheral Neuropathy, Urologic Considerations 749 Posterior Tibial Nerve Stimulation (PTNS) 753
Periureteritis 750 Posterior Urethral Valves 310
Periurethral Abscess 750 Postobstructive Diuresis 312
Perlman Syndrome 750 Postoperative Spindle Cell Nodule, Bladder 753
Peyronie Disease 294 Posttransplant Lymphoproliferative Disorder 753
Pfannenstiel Incision 750 Postvoid Dribbling 753
Pheochromocytoma 296 Potassium Sensitivity Testing 753
phi (Prostate Health Index) (See Section II: Potter Syndrome/Potter Sequence 754
“Prostate Health Index (phi) and [-2] proPSA”) 750 Pouchitis 754
Phimosis and Paraphimosis 298 Prader–Willi Syndrome 754
Phimosis, Clitoral 750 Precocious Puberty 754
xlii r r r Contents
Pregnancy, Bacteriuria, Pyuria, and Urinary Tract Prostate Cancer, Locally Advanced
Infection 754 (Pathologic T3, T4) 332
Pregnancy, Hematuria 754 Prostate Cancer, Metastatic (Clinical and
Pregnancy, Radiologic Considerations 754 Pathologic N+, M+) 334
Pregnancy, Renal Transplantation 754 Prostate Cancer, Mucinous Adenocarcinoma 758
Pregnancy, Urinary Diversion 755 Prostate Cancer, Positive Margin Following Radical
Prostatectomy 336
Pregnancy, Urinary Tract Obstruction 755
Prostate Cancer, Prevention (Chemoprevention) 758
Pregnancy, Urolithiasis 314
Prostate Cancer, Rising PSA Following Androgen
Pregnancy, Urologic Malignancy 755
Ablation (Castration-Resistant Prostate Cancer,
Pregnancy, Urologic Medications 755 CRPC and mCRPC) 338
Prehn Sign 755 Prostate Cancer Risk Calculators 758
Prentiss Maneuver 755 Prostate Cancer, Risk Stratification (D’Amico
Preputial Stones 755 Classification) 759
Pressure–Flow Studies 755 Prostate Cancer, Secondary Hormonal Therapy 759
Priapism, Stuttering (Intermittent Priapism) 755 Prostate Cancer, Small Cell (Neuroendocrine) 759
Priapism 316 Prostate Cancer, Squamous and Adenosquamous 759
Primitive Neuroectodermal Tumors (PNET) Prostate Cancer, Urothelial 340
(Extraskeletal Ewing Sarcoma) 756 Prostate Cancer, Very Low Risk and Active
Princeton III Consensus Recommendations: Surveillance 342
Erectile Dysfunction (ED) and Cardiovascular Prostate Health Index (PHI) and [–2] proPSA 759
Disease 756
Prostate Urethral Angle 760
Prolactin, Serum Level 756
Prostate, Abscess 344
Prolapse, Staging Systems 756
Prostate, Basal Cell Hyperplasia 760
Propantheline Stimulation Test 756
Prostate, Benign Enlargement (Benign Prostate
Prophylactic Antibiotics, AUA Guidelines 756, 979 Enlargement [BPE]) 760
Prostascint Scan 756 Prostate, Benign Hyperplasia/Hypertrophy (BPH) 346
Prostate Biopsy, Infections and Complications 318 Prostate, Benign Obstruction (Benign Prostatic
Prostate Cancer Screening Guidelines 756, 991 Obstruction [BPO]) 760
Prostate Cancer, Active Surveillance and Prostate, Calculi 348, 760
Watchful Waiting 757 Prostate, Female 760
Prostate Cancer, Basal Cell Carcinoma 757 Prostate, Hematuria 760
Prostate Cancer, Biochemical Recurrence
Prostate, Infarction 760
(Elevated PSA) Following Cryotherapy 320
Prostate, Massage 760
Prostate Cancer, Biochemical Recurrence
(Elevated PSA) Following Radiation Therapy 322 Prostate, Nodule 350
Prostate Cancer, Biochemical Recurrence Prostate Stents (Urolume and Spanner) 761
(Elevated PSA) Following Radical Prostatectomy 324 Prostatic Acid Phosphatase (PAP) 761
Prostate Cancer, Circulating Tumor Cells (CTC’s) 757 Prostatic Intraepithelial Neoplasia (PIN) 352
Prostate Cancer, Ductal Adenocarcinoma 757 Prostatic Urethral Polyps 761
Prostate Cancer, Familial 758 Prostatic Utricle Anomalies 761
Prostate Cancer, General 326 Prostatic Utricle Calcification 761
Prostate Cancer, Leiomyosarcoma, and Other Prostatitis, Acute, Bacterial (NIH I) 354
Uncommon Sarcomas 758 Prostatitis, Asymptomatic Inflammatory (NIH IV) 761
Prostate Cancer, Localized (T1, T2) 328 Prostatitis, Chronic Nonbacterial, Inflammatory and
Prostate Cancer, Locally Advanced (Clinical T3, T4) 330 Noninflammatory (NIH CP/CPPS III A and B) 356
Contents r r r xliii
Prostatitis, Chronic, Bacterial (NIH II) 358 Pyelitis Cystica 766

Prostatitis, General 360 Pyelitis Glandularis 766
Prostatitis, Granulomatous 362 Pyelogenic Cyst 767
Prostatitis, Mycotic (Fungal Prostatitis) 761 Pyelonephritis, Acute, Adult 374
Prostatitis, NIH Classification System 762 Pyelonephritis, Acute, Pediatric 376
Prostatitis, Stress 762 Pyelonephritis, Chronic 378
Prostatitis, Tuberculous 762 Pyelonephritis, Emphysematous 380
Prostatodynia 762 Pyelonephritis, Xanthogranulomatous 382
Prosthesis, Infected Penile 762 Pyocystis 767
Proteinuria 364 Pyonephrosis 384, 767
Prune Belly (Eagle–Barrett or Triad) Syndrome 366 Pyospermia 767
Pruritus, External Genitalia, Male 762 Pyuria 386
PSA, Age-Adjusted (See Section II “PSA, General Q-Tip Test 767
Considerations”) 763
Quakel Corporal Shunt 767
PSA Bounce (See Section II “PSA, General
Considerations”) Radiation Exposure Guidelines 767
763
PSA Complexed (See Section II “PSA, General Radiation, Pelvic, Urologic Considerations 767
Considerations”) 763 Radiation Proctitis, Urologic Considerations 768
PSA Density (PSAD) (See Section II “PSA, General Radiation, Renal and Retroperitoneal, Urologic
Considerations”) 763 Considerations 768
PSA Elevation Following Negative Prostate Biopsy 368 Radiopharmaceuticals, Urologic Considerations
PSA Elevation, General Considerations 370 (Strontium89 , Samarium153 , Radium223 ) 768
PSA Failure, ASTRO and Phoenix Definitions Rapid Plasma Reagin (RPR) Blood Test 768
(See Section II “PSA, General Considerations”) 763 Raz Bladder Neck Suspension (Urethropexy) 768
PSA, Free and Total (See Section II “PSA, General Raz Vaginal Wall Sling 768
Considerations”) 763 Reactive Arthritis/Reactive Arthritis Triad
PSA, General Considerations and PSA Derivatives 763 (Formerly Reiter Syndrome) 768
PSA, Race-Adjusted (See Section II “PSA, General Rectal Injury During Radical Prostatectomy or
Considerations and PSA Derivatives”) 765 Radical Cystectomy 388
PSA, RT-PCR 765 Rectocele, Urologic Considerations 769
PSA Velocity (PSAV) and PSA Doubling Time Red Scrotum Syndrome 769
(PSADT) (See Section II “PSA, General
Reed Syndrome 769
Considerations and PSA Derivatives”) 765
Reflux Nephropathy 769
Pseudodyssynergia (Hinman Syndrome) 765
Reifenstein Syndrome 769
Pseudohermaphroditism, Male (XY DSD) and
Female (XX DSD) 372 Reinke Crystals 769
Pseudomyxoma Ovarii-Like Posttherapeutic Renal Adenoma (Papillary Adenoma) 769
Alteration in Prostate Adenocarcinoma 765 Renal Agenesis (Bilateral and Unilateral) 769
PSMA (Prostate-Specific Membrane Antigen) 765 Renal Anatomy, Normal Radiographic Findings
Psoas Abscess, Urologic Considerations 765 (Sizes, Calyces) 769
Psoas Hitch Procedure 766 Renal and Perirenal Abscess 390
Psoriasis, External Genitalia 766 Renal Angiomyolipoma 392
Psychogenic Polydipsia 766 Renal Artery Aneurysm 770
Pudendal Nerve Entrapment/Pudendal Neuropathy 766 Renal Artery Fibromuscular Dysplasia 770
Pulmonary Metastasis, Urologic Considerations 766 Renal Artery Stenosis/Renovascular Hypertension 394
Purple Urine Bag Syndrome 766 Renal Capsular Neoplasms 396
xliv r r r Contents
Renal Carcinoid Tumor 770 Renal Tubular Acidosis 434

Renal Cell Carcinoma with Tumor Thrombus 398 Renal Tumors, WHO 2004 Classification 774
Renal Cell Carcinoma, Chromophobe 770 Renal Vein Thrombosis, Adult and Pediatric 436
Renal Cell Carcinoma, Clear Cell 770 Renal Vein, Leiomyosarcoma 774
Renal Cell Carcinoma, Familial 770 Renal–Retinal Syndrome 774
Renal Cell Carcinoma, General 400 Renin, Plasma and Renal Vein 774
Renal Cell Carcinoma, Localized (T1–T2) 402 Reninoma (Renin-Secreting Juxtaglomerular
Renal Cell Carcinoma, Locally Advanced (T3–T4) 404 Cell Tumor) 775
Renal Cell Carcinoma, Metastatic (N+, M+) 406 Reno-Alimentary Fistula 775
Renal Cell Carcinoma, Papillary Types 1 and 2 Reno-Bronchial Fistula 775
771
Renal Cell Carcinoma, Pediatric Renomedullary Interstitial Cell Tumor
408
(Medullary Fibroma, Renal Hamartoma) 775
Renal Cell Carcinoma, Sarcomatoid 771
Reperfusion Injury, Renal (Renal Ischemia and
Renal Cell Carcinoma, Tubulocystic 771 Reperfusion Injury) 775
Renal Cell Carcinoma, Unclassified 771 Residual Urine (Postvoid Residual [PVR]) 775
Renal Cell Carcinoma, Xp11.2;TFE3 Translocations 771 Resistive Indices (RI) 775
Renal Cholesterol Embolism Syndrome 771 Rete Testis, Adenocarcinoma 775
Renal Colic 410 Rete Testis, Tubular Ectasia and Cystic Dysplasia 776
Renal Cortical Adenoma 772 Retrocaval/Circumcaval Ureter 776
Renal Cysts (Intrarenal, Peripelvic, and Parapelvic) 412 Retrograde Ejaculation 438
Renal Dysplasia, Hypodysplasia, and Hypoplasia 414 Retrograde Urethrogram (RUG), Technique 776
Renal Ectopia 416 Retroperitoneal Abscess 440
Renal Fusion Anomalies 418 Retroperitoneal Fibrosis (RPF, Ormond Disease) 442
Renal Hemangioma 772 Retroperitoneal Hematoma 776
Renal Hemangiopericytoma 772 Retroperitoneal Liposarcoma 776
Renal Infarction 420 Retroperitoneal Lymphoma 776
Renal Leiomyoma 772 Retroperitoneal Masses, Fluid, and Cysts 444
Renal Leiomyosarcoma 772 Retroperitoneal Rheumatoid Nodules 776
Renal Lymphangiectasia 772 Retroperitoneal Sarcoma 777
Renal Malrotation 772 Retroperitoneum, Fat Necrosis 777
Renal Mass 422 Rhabdoid Tumor, Malignant 777
Renal Mass, Indeterminate 772 Rhabdomyolysis 446
Renal Mass, Intraoperative Consultation 424 Rhabdomyosarcoma, Pediatric (Sarcoma
Renal Medullary Carcinoma 773 Botryoides) 448
Renal Oncocytoma 426 Rieger Syndrome 777
Renal Osteodystrophy 773 Rifle Criterion for Acute Renal Injury 777
Renal Pseudotumor 773 Rim Sign (Rim Nephrogram) 777
Renal Sarcoma, Adult and Pediatric 428 Robinow Syndrome 777
Renal Sinus Abnormalities 773 Robson Staging System 777
Renal Transplant Types (Standard/Extended/Donor Rokitansky–Kuster–Hauser Syndrome 778
After Death) 773 Rosewater Syndrome 778
Renal Transplantation and Neoplasia 773 Rovsing Polycystic Kidney Operation 778
Renal Trauma, Adult 430 Rovsing Syndrome 778
Renal Trauma, Pediatric 432 Sacral Agenesis, Urologic Consideration 450
Contents r r r xlv
Sacral Neuromodulation 778 Seminal Vesicle, Cysts and Masses 460

SANI Score 778 Seminal Vesicle, Cysts 783
Sarcoidosis, Urologic Considerations 452 Seminal Vesiculitis 783
Sarcoma, Clear Cell of the Kidney 778 Seminoma with High Mitotic Rate (Seminoma,
Saw Palmetto 778 Anaplastic) 783
Scabies, Urologic Considerations 778 Seminoma, Classic 783
Scardino-Prince Pyeloplasty 779 Seminoma, Spermatocytic 783
Schaefer Obstruction Grading System 779 Sex Reversal Syndrome (XX Male) 783
Schiller-Duval Bodies 779 Sex-Hormone Binding Globulin (SHBG) 783
Schistosomiasis, Urologic Considerations 779 Sexsomnia 783
Schwannoma, Renal 779 Sexual Abuse, Pediatric 462
Scleroderma, Urologic Considerations 779 Sexual Anhedonia/Ejaculatory Anhedonia 783
Sclerosing Adenosis of the Prostate 779 Sexual Dysfunction, Female 464
Scrotal Pain Syndrome (Chronic Scrotal Pain Sexual Function Survey (SFS) (International
Syndrome [CSPS]) 779 Index of Erectile Function [IIEF]) 784, 988
Scrotal Pearls (Scrotoliths) 779 Sexual Health Inventory for Men (SHIM) Score 784, 992
Scrotal Skin Lesions 779 Sexually Transmitted Infections (STIs)
Scrotal Tongue 780 (Sexually Transmitted Diseases [STDs]), General 466
Scrotal Varices 780 Shy Drager Syndrome, Urologic Considerations 784
Scrotum and Testicle, Mass 454 Sickle Cell Disease, Urologic Considerations 468
Scrotum and Testicle, Trauma 456 Signet Ring Carcinoma, Prostate 784
Scrotum, Accessory and Ectopic 780 Silber Vasoepididymostomy 784
Scrotum, Bifid 780 Skene (Paraurethral) Gland Adenocarcinoma 784
Scrotum, Engulfment (Penoscrotal Transposition) 780 Skene (Paraurethral) Gland,
Inflammation/Adenitis 784
Scrotum, Epidermal Inclusion Cyst 780
Skin Tags, External Genitalia (Acrochordon,
Scrotum, Fat Necrosis 781
Pedunculated Papilloma) 784
Scrotum, Giant Neurolemmoma 781
Sleep Apnea, Urologic Considerations 784
Scrotum, Hemangioma 781
Sling Materials 785
Scrotum, Hypoplasia 781
Smegma 785
Scrotum, Idiopathic Calcinosis 781
Smith–Lemli–Opitz Syndrome 785
Scrotum, Squamous Cell Carcinoma 458
Smoking, Urologic Considerations 785
SEAPI Incontinence Classification System 781
Snodgrass Hypospadias Repair 785
Seborrheic Dermatitis 781
Soap-Bubble Nephrogram 785
Semen Analysis, Abnormal Findings and
Terminology Sodium Cyanide Nitroprusside Test 785
781
Semen Analysis, Technique, Normal Values 782 Solitary Fibrous Tumor, Renal 785
Semen Leukocytes 782 Sperm Granuloma 785
Seminal Plasma Hypersensitivity (Seminal Plasma Sperm Penetration Assay (SPA, Hamster Test) 786
Allergy) and Hypersensitivity to Human Semen Sperm Vitality 786
(HHS) 782 Spermatic Cord Mass and Tumors 470
Seminal Vesicle Agenesis 782 Spermatic Cord, Liposarcoma 786
Seminal Vesicle, Amyloidosis 782 Spermatocele 472
Seminal Vesicle Calculi and Calcifications 782 Spina Bifida/Spina Bifida Occulta, Urologic
Seminal Vesicle, Carcinoma 782 Considerations 786
xlvi r r r Contents
Spinal Cord Compression, Urologic Considerations 786 Testis Cancer, Embryonal Carcinoma 490
Spinal Cord Injury, Urologic Considerations 474 Testis Cancer, Endodermal Sinus Tumors
Spinal Shock 786 (Yolk Sac Tumors) 492
Spindle Cell Neoplasm, Urologic Considerations 786 Testis Cancer, Nonseminomatous Germ Cell
Tumors, General 494
Spinning Top Urethra 787
Testis Cancer, Pediatric, General Considerations 496
Splenic Injury During Radical Nephrectomy 787
Testis Cancer, Seminoma 498
Splenogonadal Fusion 787
Testis, Carcinoid 790
Splenule/Splenosis, Urologic Considerations 787
Testis, Carcinoma In Situ (CIS)/Intratubular Germ
Sports Hernia (Athletic Pubalgia, Sportsman’s
Cell Neoplasia (ITGCN) 791
Hernia) 787
Testis, Cystic Lymphangiomas 791
Squamous Metaplasia, Genitourinary 787
Testis, Cysts 791
Stamey Procedure (Urethropexy) 787
Testis, Dermoid Cyst 791
Stamey Test (3-Glass Test, 4-Glass Test,
Meares–Stamey Test) 788 Testis, Hemangioma 791
Stauffer Syndrome 788 Testis, Leukemia 791
Steinstrasse 788 Testis, Leydig Cell Tumor 500
STING Procedure 788 Testis, Lymphoma 792
Stranguria 788 Testis, Metastasis To 792
Streak Gonad 788 Testis, Microlithiasis 792
Stress Urinary Incontinence, Female 476 Testis, Normal Size 792
Stress Urinary Incontinence, Male 478 Testis, Pain (Orchalgia) 502
Strickler Ureteral Anastomosis 788 Testis, Retractile 792
Stroke (CVA), Urologic Considerations 480 Testis, Sertoli Cell Tumor 504
Struvite 788 Testis, Sex Cord Stromal Tumors 792
Studer Pouch 789 Testis, Teratoma, Extragonadal 792
Superficial Inguinal Pouch of Denis-Browne 789 Testis, Teratoma, Mature and Immature 506
Supernumerary Kidney 789 Testis, Tumor and Mass, Adult, General
Supine Stress Test 789 Considerations 508
Suprapubic Pain, General Considerations 482 Testis, Tumor and Mass, Pediatric, General
Considerations 510
Swyer Syndrome (XY Sex Reversal) 789
Testis, Vasocongestion From Sexual Arousal
Syndrome of Inappropriate Antidiuretic Hormone
Without Ejaculation (“Blue Balls”) 792
(SIADH) 789
Testosterone (Free and Total) Serum 792
Syphilis 484
Testosterone Replacement Following Localized
Systemic Lupus, Urologic Considerations 789 Prostate Cancer Therapy 793
Tabes Dorsalis 789 Testosterone Replacement Therapy, General
Taghaandan 790 Principles 512
Takayasu Arteritis, Urologic Considerations 790 Testosterone Replacement Therapy, Prostate
Tanner Stages/Classification of Sexual Maturity 790 Cancer Risk 793
Teratoma, Sacrococcygeal, Urologic Considerations 790 Testosterone, Decreased (Hypogonadism) 514
Testicular Feminization Syndrome 790 Tethered Cord 793
Testicular Prosthesis 790 Tethered Cord Syndrome 793
Testis Biopsy, Indications 790 Thiersch-Duplay Hypospadias Repair 793
Testis Cancer, Adult General Considerations 486 Thompson Pyeloplasty 793
Testis Cancer, Choriocarcinoma 488 Thoracic Kidney 794
Contents r r r xlvii
Tinea Cruris (Jock Itch) 794 Umbilical Abnormalities, Urologic Considerations 532
TMPRSS2-ERG Gene Fusion, Prostate Cancer 794 Underactive Bladder (Detrusor Underactivity) 534
Toileting Programs 794 Undervirilized Male Syndrome (Mild Androgen
Torsion, Testis or Testicular/Epididymal Appendages 518 Insensitivity) 797
Transesophageal Echocardiogram (TEE), Urologic Undescended Testes (Cryptorchidism) 536
Considerations 794 Uninhibited Detrusor Contraction 797
Transureteroureterostomy, Technique and Urachal Abnormalities 797
Indications 794 Urachal Carcinoma 538
Transplant Rejection, Renal 520 Urachal Carcinoma Staging Systems 798
Transsexualism, Urologic Considerations 794 Urate, Dietary 798
Transurethral Resection (TUR) Syndrome 522 Ureaplasma Urealyticum 798
Tri-Mix 794 Ureter and Renal Pelvic Tumors, General
Trichomoniasis 795 Considerations 540
Trichotemnomania, Pubic 795 Ureter and Renal Pelvis, Squamous Cell
Trichotillomania, Pubic Carcinoma 542
795
Trigonitis Ureter and Renal Pelvis, Urothelial Carcinoma 544
795
Ureter, Agenesis/Atresia 798
Trisomy 4 P 795
Ureter, Deviation 798
Trisomy 8 795
Ureter, Diverticulum 798
Trisomy 9 795
Ureter, Duplicated and Bifid 798
Trisomy 9 P 795
Ureter, Ectopic (Ureteral Ectopia) 799
Trisomy 10 Q 795
Ureter, Fibroepithelial Polyps 799
Trisomy 11 Q 795
Ureter, Fish Hook (Reverse J) 799
Trisomy 13 795
Ureter, Hemangioma 799
Trisomy 18 (Edwards Syndrome) 795
Ureter, Intraoperative Injury 546
Trisomy 20 P 796
Ureter, J Hooking 799
Trisomy 21 796
Ureter, Leiomyoma 799
Trisomy 22 796
Ureter, Leiomyosarcoma 799
Trisomy Syndrome 796
Ureter, Metastasis To 799
Trocar Injury During Laparoscopy 524
Ureter, Nephrogenic Adenoma (NA) 799
True Hermaphroditism (OVO-Testicular Disorder of
Sexual Differentiation [OVO-DSD]) 796 Ureter, Neurofibroma 799
Tuberculosis, Bladder and Urethra 796 Ureter, Obstruction 548
Tuberculosis, Genitourinary, General Considerations 526 Ureter, Pipe-Stem 800
Tuberculosis, Kidney and Ureter 528 Ureter, Radiation Injury To 800
Tuberculosis, Male External Genitalia 796 Ureter, Retrocaval (Circumcaval, Postcaval) 800
Tuberculosis, Prostate and Epididymis 796 Ureter, Shepherd’s Crook 800
Tuberous Sclerosis 796 Ureter, Spiral (Corkscrew) 800
Tumor Lysis Syndrome (TLS) 796 Ureter, Stone Passage Statistics 800
Tunica Albuginea/Paratesticular Tumors and Cysts 530 Ureter, Stricture 800
Tunica Vaginalis Tumors 797 Ureter, Trauma 550
Turner Syndrome (XO Syndrome) 797 Ureter, Valves 800
Turner–Warwick Inlay Urethroplasty 797 Ureteral Jets 801
UISS-UCLA International Kidney Cancer Staging Ureteral Stricture Following Urinary Diversion 801
System 797 Ureteritis 801
xlviii r r r Contents
Ureteritis Cystica 801 Urethritis, Acute 805

Ureterocele 552 Urethritis, Chronic, Female 805
Ureteroenteric Anastomotic Stricture 554 Urethritis, Gonococcal and Nongonococcal 576
Ureteroneocystostomy, Techniques and Indications 801 Urethritis, Polypoid 805
Ureteropelvic Junction Obstruction 556 Urethritis, Senile 805
Urethra, Abscess (Periurethral Abscess) 558 Urethrocele 805
Urethra, Adenocarcinoma of Accessory Glands 801 Urethrorrhagia, Idiopathic 805
Urethra, Adenomatous Polyps 801 Urge Incontinence/Urge Urinary
Urethra, Bleeding (Blood at Meatus) 801 Incontinence (UUI) 805
Urethra, Calculi 802 Urgency Perception Score (UPS) 806
Urethra, Condyloma (Warts) Urgency, Urinary (Frequency & Urgency) 578
802
Urethra, Diverticular Carcinoma Uric Acid Nephropathy 806
802
Urethra, Diverticulum, Male Urinary Ascites (Uroperitoneum) 806
802
Urethra, Duplication Urinary Diversion, Electrolyte, and Other
802
Abnormalities 806
Urethra, Foreign Body 802
Urinary Diversion, Risk of Malignancy 806
Urethra, Hemangioma 802
Urinary Flow Rate (Uroflowmetry) 806
Urethra, Leiomyoma 802
Urinary Residual Volume (Postvoid Residual) 807
Urethra, Leiomyosarcoma 803
Urinary Retention after Stress Urinary
Urethra, Leukoplakia 803 Incontinence Surgery in Females 580
Urethra, Lymphoma 803 Urinary Retention Following Brachytherapy 807
Urethra, Malacoplakia 803 Urinary Retention, Adult Female 582
Urethra, Malignant Melanoma 803 Urinary Retention, Adult Male 584
Urethra, Meatus, Normal Caliber 803 Urinary Retention, Pediatric 586
Urethra, Metastasis To 803 Urinary Retention, Postoperative 807
Urethra, Nephrogenic Metaplasia (Adenoma) 803 Urinary Tract Infection (UTI), Adult Female 588
Urethra, Obstruction 803 Urinary Tract Infection (UTI), Adult Male 590
Urethra, Polyps (Fibroepithelial, Adenomatous, Urinary Tract Infection (UTI), Catheter-
Inflammatory) 804 Associated (CAUTI, CA-UTI) 592, 807
Urethra, Prolapse (Female) 804 Urinary Tract Infection (UTI), Complicated, Adult 594
Urethra, Villous Adenoma 804 Urinary Tract Infection (UTI) Complicated,
Urethral Carcinoma, General Considerations 560 Pediatric 596
Urethral Caruncle 562 Urinary Tract Infection (UTI), Pediatric 598
Urethral Discharge 564 Urine, Abnormal Color 807
Urethral Diverticula, Female 566 Urine, Cytology 807
Urethral Hypermobility 804 Urine, Foaming 807
Urethral Mass 568 Urine, Odor 808
Urethral Pressure Profile (UPP) 804 Urine, Particles In 808
Urethral Sling, Indications and Anatomic Positions 804 Urinoma (Perinephric Pseudocyst) 808
Urethral Squamous-cell Carcinoma 570 Urinothorax 808
Urethra, Stenosis/Stricture, Female 804 Urodynamics, Indications and Normal Values 808
Urethral Stricture, Male 572 Urogenital Distress Inventory (UDI-6) 809
Urethral Syndrome 804 Urolithiasis, Adult, General 600
Urethral Trauma (Anterior and Posterior) 574 Urolithiasis, Calcium Oxalate/Phosphate 602
Contents r r r xlix
Urolithiasis, Cystine, and Cystinuria (Hypercystinuria) 604 Vasography, Technique and Indications 812
Urolithiasis, Drug Induced 809 Venous Leak Syndrome 812
Urolithiasis, Indinavir and Other Protease Inhibitors 809 Vesicoureteral Reflux, Adult 632
Urolithiasis, Infectious (Struvite) 809 Vesicoureteral Reflux, Pediatric 634
Urolithiasis, Matrix 809 Vesiculobullous Lesions, External Genitalia 813
Urolithiasis, Melamine 809 Videourodynamics 813
Urolithiasis, Methotrexate 809 Villous Adenoma, Bladder/Urethra 813
Urolithiasis, Pediatric, General Considerations 606 Vimentin, Staining 813
Urolithiasis, Renal 608 Vincent Curtsy 813
Urolithiasis, Staghorn 610 Vitiligo, Urologic Considerations 813
Urolithiasis, Triamterene 810 Voiding Diary Frequency Volume Chart (FVC) 814
Urolithiasis Ureteral 612 Voiding Symptoms, Definitions (ICS Definitions) 814
Urolithiasis, Uric Acid 614 Von Hippel–Lindau Disease/Syndrome 636
Urolithiasis, Xanthine 810 Vulvar Malignancy, Urologic Considerations 814
Uroradiology Signs 810 Vulvodynia 814
Urosepsis 616 VURD Syndrome 814
Urostomy Problems 618 WAGR Syndrome (Wilms Tumor-Aniridia-Genital
Anomaly Retardation) 814
Urothelial Dysplasia 810
Wallace Ureteral Anastomosis 814
Vacterl/Vater Association 810
Walter Reed Staging System, Testis Cancer 814
Vaginal Agenesis 810
Waterhouse Urethral Stricture Repair 814
Vaginal Atrophy/Vulvovaginal Atrophy, Urologic
Considerations 810 Waterhouse–Friderichsen Syndrome 815
Vaginal Discharge, Urologic Considerations 810 Weddellite 815
Vaginal Duplication 810 Wegener Granulomatosis, Urologic Considerations 815
Vaginal Fusion Weiss Criterion 815
811
Vaginal Mass, Newborn Whewellite 815
811
Vaginal Mesh Erosion Whitaker Test 815
620
Vaginal Pessaries, Urologic Considerations Whitlockite 815
811
Vaginal Prolapse WHO 2004 Histologic Classification of Tumors of
811
the Urinary Tract 815
Vaginitis/Vulvovaginitis 622
WHO/ISUP Consensus Classification of Urothelial
Vaginosis 811 Neoplasms (1998, 2004, and 2010) 815
Valsalva Maneuver 811 Wilms Tumor (Nephroblastoma) 638
Vanderbilt Cystectomy Index (VCI) 811 Wilms Tumor Staging System, International Society
Vanishing Testis Syndrome 811 of Pediatric Oncology (SIOP) 816
Varicocele, Adult 624 Wilms Tumor Staging System, National (NWTS) 816
Varicocele, Pediatric 626 Winter Corporal Shunt 816
Vas Deferens, Calcification (CVD) 812 Wolffian Duct Remnants 816
Vas Deferens, Congenital Absence 628 Wound Dehiscence, Urologic Considerations 817
Vas Deferens, Obstruction 812 Wound Infection, Postoperative, Urologic
Vasculitis, Urologic Considerations 812 Considerations 817
Vasectomy and Postvasectomy Pain Syndrome 630 Wunderlich Syndrome 817
Vasectomy Reversal, General Considerations Xanthogranulomatosis (Erdheim–Chester Disease) 817
(Vasovasostomy) 812 Xanthoma, Bladder 817
l r r r Contents
X-linked Spinal and Bulbar Atrophy Syndrome Yolk Sac Tumor, Prostate 818
(Kennedy Syndrome) 817 Young Classification of Posterior Urethral Valves 818
XX Gonadal Dysgenesis (46, XX) 817 Young-Dees-Leadbetter Bladder Reconstruction 818
XX Male Reversal Syndrome (XX Male) 817 Young Syndrome 818
XXX Syndrome (Triple X Syndrome, Triplo-X) 817 Zellweger Syndrome (Cerebrohepatorenal Syndrome) 818
XXXY Syndrome 817 Zinner Syndrome 818
XXY Syndrome (Klinefelter Syndrome) 818 Zipper Entrapment 818
Yolk Sac Tumor, Bladder 818 Zona Pellucida Binding Assay 819
LWBK1391-SEC-A LWBK1391-Gomella ch001.xml September 19, 2014 17:56
SECTION I
Urologic Diseases and Conditions
Section Editor: Leonard G. Gomella, MD, FACS
1
ABDOMINAL MASS, ADULT, UROLOGIC CONSIDERATIONS

Brian M. Benway, MD
r Renal abscesses: Usually follow insufficient DIAGNOSTIC TESTS & INTERPRETATION

BASICS treatment of lobar nephronia; needle aspiration may Lab
be needed to make a diagnosis r CBC, complete metabolic panel
DESCRIPTION r TB can cause cold abscess formation. Pus r Urinalysis and culture
r Urologic masses are usually retroperitoneal in
developing from a renal source may track alongside r Adrenal metabolic workup if adrenal mass is
adults psoas muscle and appears in the groin, where it suspected – see Section I “Adrenal Adenoma”
– May arise from several sites must be distinguished from hernia. r Tumor markers
◦ Renal (malignant and benign) r Perinephric abscess: Usually arises as a result of
◦ Adrenal – Testis – AFP, β-HCG, LDH
pre-existing renal factors such as renal calculi, ◦ AFP – may be elevated in embryonal,
◦ Germ cell (retroperitoneal lymphadenopathy) ureteral calculi, hydronephrotic changes, renal cystic
◦ Metastatic teratocarcinoma, yolk sac, but never in pure
disease, or infected carcinoma choriocarcinoma or pure seminoma
◦ Other (retroperitoneal fibrosis [RPF], hematoma, r Hematomas: May be caused by a ruptured kidney or ◦ LDH may indicate retroperitoneal involvement,
abscess, lymphocele, lymphoma, urinary ureteral avulsion. Blood in the retroperitoneal space
retention) but not specific to testis
may track to the corresponding iliac fossa r Pregnancy testing where appropriate
EPIDEMIOLOGY r Renal cysts
r Bladder-related: Retention, tumors and urachal Imaging
Incidence r Ultrasound
r Renal cell carcinoma: 55,000 new cases per year. abnormality, or cancer
r Metastatic tumors to the adrenal glands and kidney – Good for detecting cystic lesions, but not optimum
Incidence is rising (1) for calcified masses or smaller stones. Quality is
r Testis cancer: 8,000 new cases per year
ASSOCIATED CONDITIONS operator-dependent.
Prevalence r Hydronephrosis, renal insufficiency (malignant r Computed tomography (CT)
Varies with disease type obstruction) – Good for detecting solid abdominal masses,
r Aortitis, aortic aneurysm (RPF) metastatic lesions, and stone.
RISK FACTORS
r Cancer (renal, adrenal, testis) r Stauffer syndrome (RCC) – CT angiography can evaluate renal vasculature.
r Prior surgery (lymphocele) – PET-CT approved for diagnosis of RCC metastases.
GENERAL PREVENTION r Magnetic resonance imaging (MRI)
r Infection (abscess, RPF) N/A
r Trauma (hematoma, urinoma) – Good for evaluating adrenal masses and
indeterminate renal lesions.
r Urinary retention
DIAGNOSIS – Can be used in patients with iodine allergies and
Genetics renal insufficiency, though caution should be
r Renal lesions have some known genetic alterations: HISTORY exercised in the latter.
r Weight loss, cachexia, night sweats (malignancy or r 131 l-metaiodobenzylguanidine (MIBG)
– von Hipple Lindau (VHL)
– Hereditary papillary renal cell chronic septic disease) – Only role for evaluating pheochromocytoma.
– Birt–Hogg–Dubé r Spiking fevers, flank pain (infectious) r Intravenous pyelogram/excretory urogram
– Hereditary leiomyomatosis r Recent trauma with or without hematuria – Largely historical, replaced by CT or MR urography.
– Tuberous sclerosis r History of testis mass
Diagnostic Procedures/Surgery
r Classic triad for renal cell carcinoma (hematuria, r Fine-needle aspiration or core biopsy of mass
PATHOPHYSIOLOGY
r Various urologic pathologic conditions may present flank pain, palpable mass) is relatively uncommon in – Renal biopsy sensitivity enhanced by use of
with a mass: modern era coaxial core biopsy techniques (2)
r Primary renal neoplasms: PHYSICAL EXAM Pathologic Findings
– Malignant: Renal cell carcinoma (RCC), renal r Abdominal wall masses such as lipomas, Varies depending upon type and location of mass
sarcoma, adult Wilms tumor, urothelial carcinoma, hematomas, lymph nodes, and hernias can be
lymphoma readily determined by physical exam
– Benign: Renal cortical adenoma, renal r Palpable abdominal mass
oncocytoma, renal hamartoma (angiomyolipoma) – Location, tenderness
fibroma r Any mucoid drainage from the umbilicus
r Primary adrenal neoplasms: Adrenal cortical r Hypertension
carcinoma, pheochromocytoma, adrenal adenoma, r Lymphadenopathy
paraganglioma r Lower extremity edema
r Hydronephrosis
r Lower extremity pulses
r Primary and metastatic germ cell tumor (GCT): Are
r Varicocele (more common on right)
composed of seminoma, embryonal cell carcinoma,
yolk sac tumor, teratoma, and choriocarcinoma – Left side consider renal mass with occlusion of
r Primary extragonadal GCTs can occur renal vein
r Scrotal exam
intraperitoneally
– Metastatic GCTs are associated with
retroperitoneal lymphadenopathy
2
ABDOMINAL MASS, ADULT, UROLOGIC CONSIDERATIONS

A
DIFFERENTIAL DIAGNOSIS See Also (Topic, Algorithm, Media)
r Adrenal mass: See Section I “Adrenal Mass” ONGOING CARE r Abdominal Mass, Adult, Urologic Considerations
r Distended bladder Image
r GI tract: PROGNOSIS r Abdominal Mass, Newborn, Child, Urologic
– Hepatomegaly, splenomegaly, pancreatitis, Prognosis depends upon clinical diagnosis and staging Considerations
pancreatic mass, tumors, volvulus, constipation COMPLICATIONS r Hydronephrosis
r Gynecologic: See associated chapters regarding disease-specific r Renal Masses
– Pregnancy, uterine fibroids, ovarian cysts, interventions r Renal Cell Carcinoma
malignancy r Retroperitoneal Masses, Fluid, and Cysts
FOLLOW-UP
– Hydronephrosis r Retroperitoneal Fibrosis
r Other: Intra-abdominal abscess, ascites Patient Monitoring r Testis Cancer
r Renal mass: See Section I “Renal Mass” Depends upon clinical diagnosis and management.
r Retroperitoneal mass: See Section I ”Retroperitoneal See associated chapters regarding specific disease
processes.
Masses, Fluid, and Cysts” CODES
r Ruptured abdominal aortic aneurysm Patient Resources
r Urachal abnormality N/A
ICD9
r 189.0 Malignant neoplasm of kidney, except pelvis
REFERENCES r 194.0 Malignant neoplasm of adrenal gland
TREATMENT r 789.30 Abdominal or pelvic swelling, mass, or lump,
1. Chow WH, Devesa SS, Warren JL, et al. Rising unspecified site
GENERAL MEASURES incidence of renal cell carcinoma in the United
r Varies by underlying ailment
States. JAMA. 1999;281:1628–1631. ICD10
– Renal malignancy – radical or partial 2. Maturen KE, Nghiem HV, Caoili EM. Renal mass r C64.9 Malignant neoplasm of unsp kidney, except
nephrectomy, ablation, observation (3) core biopsy: Accuracy and impact on clinical renal pelvis
– Adrenal malignancy – adrenalectomy management. AJR AM J Roentgenol. 2007;188: r C74.90 Malignant neoplasm of unsp part of
– Adrenal adenoma – excision or observation 563–570. unspecified adrenal gland
– Testis cancer – retroperitoneal lymph node r R19.00 Intra-abd and pelvic swelling, mass and
3. Kunkle DA, Kutikov A, Uzzo RG. Management of
dissection, chemotherapy, radiation
small renal masses. Semin Ultrasound CT MR. lump, unsp site
– Renal abscess, xanthogranulomatous
2009;30:352–358.
pyelonephritis – antibiotics, drainage,
nephrectomy CLINICAL/SURGICAL
– Cysts – observation, decortication, drainage and
sclerosis
ADDITIONAL READING PEARLS
– Retention – placement of Foley catheter r Glockner JF, Vrtiska TJ. Renal MR and CT r Abdominal masses in the adult can arise from
– Hydronephrosis – double-J stent placement or angiography: Current concepts. Abdom Imaging. several different processes.
percutaneous nephrostomy tube placement 2007;32:407–420. r Radiographic information is often essential to
r Hussain HK, Korobkin M. MR imaging of the adrenal
MEDICATION diagnosis.
First Line glands. Magn Reson Imaging Clin N Am. 2004;12: r Management varies upon disease type.
r Antibiotics for abscess or obstruction 515–544, vii.
r Corticosteroids, tamoxifen for RPF r Johns Putra L, Lawrentschuk N, Ballok Z. et al.
18F-fluorodeoxyglucose positron emission
Second Line tomography in evaluation of germ cell tumor after
Mycophenolate mofetil, azathioprine for RPF chemotherapy. Urology. 2004;64:1202–1207.
SURGERY/OTHER PROCEDURES r Schoder H, Larson SM. Positron emission
Depends upon clinical diagnosis tomography for prostate, bladder, and renal cancer.
Semin Nucl Med. 2004;34:274–292.
ADDITIONAL TREATMENT
Radiation Therapy
r Limited utility for renal cell carcinoma
r Used for seminomatous germ cell tumors
Additional Therapies
Depends upon clinical diagnosis
Complementary & Alternative
Therapies
N/A
3
ABDOMINAL MASS, NEWBORN/CHILD, UROLOGIC CONSIDERATIONS

Yong Seung Lee, MD
Sang Won Han, MD
r CT:
BASICS DIAGNOSIS – Used to enhance findings on US or solid mass on
US
DESCRIPTION HISTORY – Good anatomic detail
r Traditional presentation was palpable mass in the r Prenatal ultrasound (1)
– Useful in older children and suspected
newborn/child abdomen – Oligohydramnios: Associated with PUV, bilateral malignancies
r Current presentation is usually by prenatal UPJ, urethral atresia, polycystic or multicystic – Limitation: High sensitivity of pediatric patients to
ultrasound dysplastic kidneys, renal agenesis radiation exposure, may require sedation
r Most masses are nonsurgical; 87% of surgical – Polyhydramnios: Associated with high GI r MRI:
lesions are benign obstructions – Good for vascular involvement, adrenal origin
r Almost 2/3 of infantile abdominal masses arise from r Postnatal history
– Good anatomic detail
kidneys, followed by GI tract (12%), female genital – Initial discovery – May gather functional and quantitative
system (10%), retroperitoneum (9%) – Duration from detection of mass information
– Rapidity of growth – Limitation: May require sedation/anesthesia
EPIDEMIOLOGY – Constitutional symptoms: Fever, pain, weight loss, r Radionuclide scans:
Incidence UTI, dysuria, hematuria, melena, anorexia, bilious – Renal scans: Used to determine renal function,
Abdominal mass in 1 per 1,000 live births vomiting scarring, infection, and obstruction
Prevalence PHYSICAL EXAM – Biliary scans: Evaluate for choledochal cysts
Varies with disease type r Perform thorough abdominal exam (2): – Liver–spleen scans: Used for diagnosis of liver
– Size and location tumors or splenic enlargement
RISK FACTORS r VCUG:
– Solid or cystic
Genetics – Tender or nontender – Used to rule out lower urinary tract pathology
r Disease specific
– Smooth, irregular, indurated, or soft
r Neuroblastoma Diagnostic Procedures/Surgery
– Fixed or mobile N/A
– Chromosome 1p deletion – Auscultation, percussion, and transillumination
– Allelic loss of 11q r Additional exam: Pathologic Findings
– Gain of copies of 17q correlate with more – Nasogastric tube for intestinal decompression Disease specific
aggressive tumor – Foley catheter for urinary decompression
– N-MYC oncogene amplification
DIFFERENTIAL DIAGNOSIS
– Rectal/introital exam r Hydronephrosis: Most common cause of neonatal
r Polycystic kidney disease, autosomal recessive
DIAGNOSTIC TESTS & INTERPRETATION abdominal mass (1):
(ARPKD) – UPJ obstruction: Most common cause of
– Gene locus at chromosome 6p21 Lab
r Rhabdomyosarcoma (RMS) r Labs should be tailored to clinical suspicion hydronephrotic abdominal mass
r CBC: – Other causes: UVJ obstruction, PUV, VUR,
– Mutation of TP53 gene found in tumors of megaureter, and ureteroceles
patients with Li–Fraumeni syndrome – Anemia, neutropenia, thrombocytopenia may – <15% of neonates present with mass
– Alveolar RMS is associated with translocation suggest bone marrow involvement – Later presentation: UTI, flank pain, hematuria
between chromosomes 1 or 2 and 13 – Leukocytosis suggests possible infection/ after trauma
– Embryonal RMS demonstrates LOH on obstruction r Multicystic dysplastic kidney:
chromosome 11p15.5 r BUN/creatinine/electrolytes
r Wilms tumor – 2nd most common cause; together with UPJ
– Elevated BUN/creatinine suggests renal constitute 40% of all neonatal abdominal masses
– WT1 (11p13): Denys–Drash and WAGR (Wilms compromise, dehydration – Unilateral flank mass; more common on left, and
tumor, aniridia, genitourinary problems, r Urinalysis:
in boys
retardation) – Hematuria seen in Wilms tumor, renal vein – US shows multiple noncommunicating cysts of
– WT2 (11p15): Beckwith–Wiedemann thrombosis, UPJ obstruction after trauma various sizes; nuclear scan shows nonfunction on
– WTX (Xq11.1): Inactivated in up to 1/3 of Wilms r 24-hr urine
affected side
tumors – Elevated homovanillic acid and vanillylmandelic r Multilocular cystic nephroma:
– FWT1 (17q), FWT2 (19q): Familial acid seen in neuroblastoma or pheochromocytoma – Spectrum from benign cyst to cystic Wilms tumor
– LOH at 1p and 16q is associated with an r Serum β-hCG and α-fetoprotein:
– Present in males <5 yr and females >30 yr
increased risk of tumor relapse and death – Used in tumors such as teratoma, liver, and – Diagnosis by surgical excision
PATHOPHYSIOLOGY germ-cell tumors r Renal vein thrombosis:
Disease specific, related to organ of origin Imaging – Most common cause of neonatal hematuria; 65%
r Plain abdominal x-rays: occur in neonatal period, 30% after age 1; male
ASSOCIATED CONDITIONS
– Check for obstruction/ileus; air–fluid levels on predominance
Disease specific
upright and lateral; absence of air in rectum – Classic features: Flank mass, hematuria,
GENERAL PREVENTION – Calcifications can suggest neuroblastoma, thrombocytopenia
N/A teratoma, hepatoblastoma, meconium peritonitis, – Occurs in conditions associated with dehydration,
urinary, or biliary stones maternal diabetes, sepsis, diarrhea, or sickle cell
r Abdominal US: disease
– Primarily evaluation modality r Polycystic kidney disease:
– Used to establish location, size, organ of origin, – Autosomal recessive; diagnosed in neonatal
internal architecture, and vascular supply period; 50% die in 1st few hours or days usually
– Can determine cystic vs. solid from respiratory failure; of survivors, 86% alive at
– Inexpensive and noninvasive; rarely requires 1 yr and 67% at 15 yr
sedation
4
ABDOMINAL MASS, NEWBORN/CHILD, UROLOGIC CONSIDERATIONS

A
r Congenital mesoblastic nephroma: r Hepatobiliary masses: FOLLOW-UP
– Most common renal tumor diagnosed on – Primary liver tumors are 3rd most common solid Patient Monitoring
antenatal US abdominal mass in childhood (15% total) Disease specific
– Most common renal neoplasm of infancy – Benign lesions: 1/3 (hemangioendothelioma,
– Mean age 3.5 mo mesenchymal hamartoma, adenoma, focal Patient Resources
– Surgery is usually curative nodular hyperplasia, congenital cysts) N/A
r Wilms tumor: – Malignant: 2/3 (hepatoblastoma most common
– Most common childhood abdominal malignancy; <5 yr; hepatocellular carcinoma present ages REFERENCES
most common malignant renal neoplasm in 12–15)
children r Splenic masses: 1. Becker AM. Postnatal evaluation of infants with an
– Usually presents as smooth, nontender, unilateral – Congenital splenic cysts abnormal antenatal renal sonogram. Curr Opin
abdominal mass – Congenital hemolytic anemias: Pediatr. 2009;21:207–213.
– Rare >10 yr and <6 mo; median age 3.5 yr Hemoglobinopathies, thalassemias, hereditary 2. Golden CB, Feusner JH. Malignant abdominal
– 80% of cases occur in age <5 yr spherocytosis masses in children: Quick guide to evaluation and
– Increased frequency in WAGR, r Lymphoma: Common in boys >5 yr diagnosis. Pediatr Clin N Am. 2002;49:1369–1392.
Beckwith–Wiedemann, and Denys–Drash – 60% non-Hodgkin; 1/3 involve abdomen; can 3. Miller RJ, Breech LL. Surgical correction of vaginal
syndromes present as intussusception anomalies. Clin Obstet Gynecol. 2008;51:223–236.
– Combination surgery, chemotherapy, and
radiation yields success rates >90% in favorable
histology; lower in unfavorable histology TREATMENT ADDITIONAL READING
r Neuroblastoma:
– Most common solid neonatal abdominal mass GENERAL MEASURES Isaacs H. Fetal and neonatal hepatic tumors. J Pediatr
– Most common malignancy of newborn Stabilize patient as necessary. Treatment is based on Surg. 2007;42:1797–1803.
– 50% of all malignant tumors in children; 50% diagnosis.
See Also (Topic, Algorithm, Media)
before age 2 MEDICATION r Abdominal Mass, Newborn, Child, Urologic
– Fixed, painful, irregular mass that often crosses First Line Considerations Image
midline r Neuroblastoma r Hydrocolpos and Hydrometrocolpos
– Fever, malaise, weight loss; ill-appearing – Chemotherapy is a part of a multidisciplinary r Hydronephrosis/hydroureteronephrosis
compared to Wilms tumor approach including surgery, and bone or stem cell r Multicystic Dysplastic Kidney
– 90% have catecholamine excess transplantation r Neuroblastoma
r Adrenal hemorrhage:
– Treatment schema based on INSS stage, age, r Polycystic Kidney Disease
– 1–2% of healthy infants N-MYC amplification, DNA ploidy, and Shimada r Rhabdomyosarcoma, Pediatric
– Predisposing factors: Birth trauma, large birth histopathology
r RMS r Ureteropelvic Junction Obstruction
weight, perinatal asphyxia, sepsis, and
coagulopathy r Wilms Tumor (Nephroblastoma)
– Chemotherapy is 1st line prior to radiation or
– Supportive care, rare intervention surgical resection in all cases except those
r Genital mass – Hydrocolpos and hydrometrocolpos
amenable to immediate partial cystectomy
(3): r Wilms tumor CODES
– Hydrocolpos: Gross distension of the vagina – Adjuvant chemotherapy is based on NWTSG
– Hydrometrocolpos: Gross distension of the vaginal recommendations ICD9
and uterus – SIOP studies favor preop chemotherapy r 753.14 Polycystic kidney, autosomal recessive
– Due to obstruction from vaginal atresia or r 789.3 Abdominal or pelvic swelling, mass, or lump
stenosis, imperforate hymen, or cloacal anomaly Second Line r 789.30 Abdominal or pelvic swelling, mass, or lump,
– Pelvic midline mass; US shows fluid-filled mass N/A
unspecified site
between bladder and rectum SURGERY/OTHER PROCEDURES
r Genital mass – Ovarian cyst: Surgery is specific to disease process. In general, ICD10
– 1:3,000 girls tumors, obstructive/infection problems will need r C64.9 Malignant neoplasm of unsp kidney, except
– Most common cause of abdominal cystic tumor in surgery. renal pelvis
female fetus r C74.90 Malignant neoplasm of unsp part of
– Presents as large mobile midabdominal mass
unspecified adrenal gland
– Cysts and tumors: 17% neonatal to age 4; 28% Radiation Therapy r Q61.19 Other polycystic kidney, infantile type
r RMS: Part of a multidisciplinary approach to curative
from 5–9 yr; 55% 9–18 yr
– Prepuberty 50% are malignant, teratoma most therapy including surgical excision and
common chemotherapy CLINICAL/SURGICAL
r Genital mass – RMS: r Wilms tumor: For higher stage favorable histology,
or for patients with focal or diffuse anaplasia
PEARLS
– 15–20% arise from genitourinary system:
Prostate, bladder, paratesticular, vulvar/vaginal, r Determining the age (neonates vs. children) can
uterine Neuroblastoma: Multidisciplinary approach may differentiate between likely etiologies. In general,
– 2 major subtypes: Embryonal (most common), include bone or stem cell transplantation older children are more at risk of developing
alveolar (worse prognosis) malignant masses compared with neonates and
r GI masses: Complementary & Alternative
young children.
Therapies r Two most common entities causing neonatal
– 12% of neonatal abdominal masses N/A
– Intestinal duplication: abdominal mass (UPJ obstruction and MCDK), can
◦ Common; congenital cystic abnormalities, with be differentiated by renal scan. The renal scan
ileum most common, followed by esophagus, ONGOING CARE usually shows some function in the hydronephrotic
duodenum kidney and nonfunction MCDK.
– Hypertrophic pyloric stenosis PROGNOSIS r Concerning malignant masses, neuroblastoma, and
– Intestinal cysts: Meconium, omental, duplication, Disease specific hepatoblastoma are more likely in children <2;
mesenteric COMPLICATIONS older children are more susceptible to Wilms,
Treatment specific hepatocellular carcinoma, genitourinary tract
tumors, and germ-line tumor.
5
ACUTE KIDNEY INJURY, ADULT (RENAL FAILURE, ACUTE)

Joan C. Delto, MD
Fernando J. Bianco, Jr., MD
ASSOCIATED CONDITIONS r Neck vein distention, lung rales

BASICS r Dehydration r Abdominal exam
r Trauma – Bruits
DESCRIPTION r Burns – Palpable mass
r The term acute kidney injury (AKI) has replaced the r Sepsis – Distention, palpable bladder
older descriptor of acute renal failure (ARF) r Urinary tract infection – Costovertebral angle tenderness
– Rapid decline in renal function characterized by r Chronic renal insufficiency r Digital rectal exam—prostate size/nodularity
progressive azotemia, with or without oliguria r Hypertension r Patency of urinary catheters, stents
(<500 mL/d) r Peripheral edema, rash
r Congestive heart failure
– Decreased glomerular filtration rate
r Attempts to standardize the definition of AKI have r Liver disease, cirrhosis DIAGNOSTIC TESTS & INTERPRETATION
been proposed by different groups as noted below. r Nephrolithiasis Lab
However, their utility in daily clinical care has not r BPH r CBC, BUN, creatinine, electrolytes (including
been confirmed (1) r Advanced prostate or bladder cancer, malignancy Ca/Mg/Phos), consider arterial blood gases (ABGs)
– Acute dialysis quality initiative (ADQI) group RIFLE r Malignant hypertension r AKI
criteria – Rise in serum creatinine (SCr) of at least
– Acute kidney injury network (AKIN) GENERAL PREVENTION 0.3 mg/dL over a 48-hr period
r Hydration
– Kidney Disease/Improving Global Outcomes – Over 1.5 times the baseline SCr value within the
(KDIGO) Clinical Practice Guidelines r Proper renal dosing of medication; daily dosing of
7 previous days
aminoglycosides r Common lab abnormalities in AKI:
EPIDEMIOLOGY r Avoidance of nephrotoxic agents
Incidence – Increased: K+, phosphate, Mg, uric acid
r Adequate voiding (timed, double voiding)
r 5% of hospital admissions – Decreased: Hematocrit (Hct), Na, Ca
r Risk of contrast-induced AKI may be reduced by r NephroCheckTM detects the presence of insulin-like
r 30% of ICU admissions
r 25% of hospital patients develop AKI N-acetylcysteine 600 mg PO BID on day prior to and growth-factor binding protein 7 (IGFBP7) and tissue
day of contrast and isotonic NaHCO3 3 mL/kg/h × 1 inhibitor of metalloproteinases (TIMP-2) in the urine
– 50% are iatrogenic hr before and 1 mL/kg/h × 6 hr after contrast (both AKI associated); the test provides a risk score
RISK FACTORS administration of developing AKI within 12 hrs
r Preoperative risk factors for development of AKI: r Creatinine kinase (rhabdomyolysis)
– Age >56 ALERT r Immune antibodies (vasculitis)
– Male Determine if the patient is on any nephrotoxic r Urine
– Emergency surgery medication? Has there been recent contrast
– Urinalysis: Blood, protein, cells, casts, crystals
– Intraperitoneal surgery injection? Is the foley draining? ◦ Transparent hyaline casts—prerenal etiology;
– Diabetes mellitus pigmented granular/muddy brown casts—ATN;
– Active CHF WBC casts—acute interstitial nephritis; RBC
– Ascites DIAGNOSIS casts—glomerulonephritis
– Hypertension – Urine eosinophils: ≥1% eosinophils by Hansel’s
r HISTORY
– Preoperative renal insufficiency stain suggestive of acute interstitial nephritis
– Urination history—frequency, urgency, strength of
Genetics stream, hematuria (sensitivity, 67%; specificity, 83%)
No genetic association – Fever, chills – Urine electrolytes (Urine Na; UNa )
– Nausea, vomiting, diarrhea – Urine osmolality (Uosm )
PATHOPHYSIOLOGY
r Pre-renal – Flank or abdominal pain – Fractional excretion of sodium (FENA)
r Prerenal
– Transient renal hypoperfusion (reversible) – Recent strenuous activity
– Stimulation of sympathetic nervous system and – Review medications—nephrotoxic agents, – FENA <1%; BUN/Cr >20
RAS causing renal vasoconstriction and sodium diuretics – UNa <10; Uosm >500
r Intrarenal
reabsorption; stimulation of antidiuretic hormone – Comorbidities
– Water reabsorption, low urine output, ◦ Renal disease – FENA >2%; BUN/Cr <15
concentrated urine ◦ Diabetes – UNa >20; Uosm <350
r Intrarenal ◦ Hypertension r Postrenal
– Acute tubular necrosis (ATN) ◦ Liver disease – FENA >4%; BUN/Cr >15
◦ Renal ischemia – Infections – UNa >40; Uosm <350
◦ Depletion of ATP – Nephrolithiasis Imaging
◦ Dysfunction of plasma membrane – BPH r Renal/bladder ultrasound
◦ Reperfusion injury – Malignancies, metastatic disease – Hydronephrosis
◦ Oxidative stress leading to tubular cell damage – Previous abdominal or pelvic surgeries – Stones
◦ Rhabdomyolysis and hemolysis – Radiation – Bladder volume, post void residual
r Postrenal (obstruction) – Chemotherapy – Prostatic size
– Intrinsic obstruction – Prior ureteroscopy or endoscopy – Bladder masses causing obstruction
r Social History
– Extrinsic compression – Ureteral jets, resistive indices
r Iatrogenic (urinary extravasation, fistula) – Smoking r Abdominal x-ray (KUB)
– Reabsorption of BUN, Cr – Alcohol – Calcifications
– Drug use – Stent location
PHYSICAL EXAM r CT abdomen/pelvis
r Vital signs: Blood pressure, heart rate, orthostatic – Obstructing stones
changes – Obstructing masses
r Volume status, body weight r Renal scan
r Urinary output, drain output – Obstruction
– Kidney function
6
ACUTE KIDNEY INJURY, ADULT (RENAL FAILURE, ACUTE)

A
Diagnostic Procedures/Surgery r Control of urinary extravasation r If question of stent migration, obtain KUB or US
r Cystoscopy with retrograde pyelography r Dietary considerations r Ureteral stents will need to eventually be exchanged
r Renal biopsy (acute glomerular nephritis) – Maintain carbohydrate and protein intake or removed
– Restrict: Phosphorus, potassium, sodium r Consideration of internalization of percutaneous
Pathologic Findings
r Acute interstitial nephritis MEDICATION nephrostomy tubes
– Interstitial edema, marked interstitial infiltrate of T First Line Patient Resources
cells and monocytes See above National Kidney Foundation: www.kidney.org
– Eosinophilic plasma cells
– PMN cells Second Line
– Granulomata N/A REFERENCES
DIFFERENTIAL DIAGNOSIS (4) SURGERY/OTHER PROCEDURES 1. Lameire N, Van Biesen W, Vanholder R. Acute renal
r Prerenal (∼55%): Hypotension; volume depletion r Postrenal
failure. Lancet. 2005;365:417–430.
(GI losses, excessive sweating, dehydration, – If cannot drain bladder per urethra, consider 2. Pannu N, Klarenbach S, Wiebe N, et al. Renal
hemorrhage); renal artery stenosis/embolism; burns; suprapubic tube replacement therapy in patients with acute renal
heart failure; liver failure – Ureteral stent failure: A systematic review. JAMA. 2008;299:
r Intrarenal (∼40%): ATN (from prolonged prerenal – Percutaneous nephrostomy 793–805.
insufficiency, radiographic contrast material, – If clot retention, removal of clots. May require
3. Weisberg LS. Management of severe hyperkalemia.
aminoglycosides, NSAIDs, or other nephrotoxic cystoscopy, clot evacuation
Crit Care Med. 2008;36:3246–3251
substances); glomerulonephritis; acute interstitial – If BPH, consideration for outpatient TURP
r Indications for dialysis (called renal replacement 4. White HF, Kurland JM. Acute kidney injury. In:
nephritis (drug-induced); arteriolar insults; vasculitis; Domino FJ, ed. The Five Minute Clinical Consult.
accelerated hypertension; cholesterol embolization therapy can be hemo or peritoneal dialysis: For these
Philadelphia, PA: Wolters Kluwer; 2014.
(common after arterial procedures); intrarenal urgent and potentially life-threatening indications:
deposition/sludging (uric acid nephropathy and – Metabolic disturbances refractory to medical
management such as hyperkalemia, metabolic
multiple myeloma [Bence Jones proteins])
r Postrenal (∼5%): Extrinsic compression (eg, BPH, acidosis, hypo/hypercalcemia, hyperphosphatemia
ADDITIONAL READING
– Pericarditis or pleuritis r Duty BD, Kavoussi LR. Assessment and Management
carcinoma, pregnancy); intrinsic obstruction (eg,
calculus, tumor, clot, stricture, sloughed papillae); – Uremic encephalopathy of Incidentally Detected Unilateral Hydronephrosis in
decreased function (eg, neurogenic bladder) – Uremia-related bleeding diathesis Adults. AUA Update Series. 2012;31:30.
r Pseudo-AKI: Endogenous chromogens (eg, bilirubin, – Volume overload refractory to diuretics r Van Wert R, Friedrich JO, Scales DC, et al. High-dose
– Severe refractory hypertension renal replacement therapy for acute kidney injury:
ascorbic acid, uric acid) and exogenous chromogens
(eg, cephalosporins, trimethoprim, cimetidine) may Systematic review and meta-analysis. Crit Care Med.
interfere with the creatinine assay and cause falsely ONGOING CARE 2010;38:1360–1369.
elevated results See Also (Topic, Algorithm, Media)
PROGNOSIS r Acute Kidney Injury, Pediatric (Renal Failure, Acute)
r Prerenal
r Acute Glomerulonephritis
TREATMENT – Good if renal function improvement within r Acute Tubular Necrosis
24–72 hr after fluid repletion r Contrast-Induced Nephropathy (CIN)
GENERAL MEASURES r ATN
r AKI requires close management of fluid, acid–base, r Postobstructive Diuresis
and electrolyte balance and the removal of uremic – Mortality rate of ATN generally 50%
toxins – Mortality rate of ATN in ICU 75%
r Fenoldopam, a dopamine agonist, may decrease – Of those who survive ATN, 50% have complete
resolution of renal function CODES
dialysis and mortality in AKI (4)
r Furosemide is ineffective in preventing and treating – 5% of AKI patients will require chronic renal
replacement therapy ICD9
AKI r Postrenal r 584.5 Acute kidney failure with lesion of tubular
r Prerenal
– Great recovery once obstruction and insult are necrosis
– Restoration of renal perfusion; isotonic fluid resolved r 584.9 Acute kidney failure, unspecified
r Intrarenal r 593.81 Vascular disorders of kidney
– Cessation of nephrotoxic drugs COMPLICATIONS
r Postobstructive diuresis
– Renal dosing of medications ICD10
r Postrenal r Sepsis post relief of obstruction with instrumentation r N17.0 Acute kidney failure with tubular necrosis
– Foley or suprapubic tube drainage r Stent inflammation, crusting, and pain r N17.9 Acute kidney failure, unspecified
– Ensure patency of drains r Chronic renal failure r N28.0 Ischemia and infarction of kidney
◦ Ensure proper placement within bladder
◦ Rule out catheter obstruction (mucus, clot) FOLLOW-UP
– Percutaneous nephrostomy tube Patient Monitoring CLINICAL/SURGICAL
r Treatment of hyperkalemia (3) r Blood pressure control
r Monitoring of creatinine, potassium, calcium, and PEARLS
– Monitor EKG when K+ >6 mmol/L
◦ IV calcium phosphorus r Maximize urinary drainage.
◦ Sodium bicarbonate (if acidotic) r Repeat imaging (US) to re-evaluate hydronephrosis r Avoid nephrotoxic agents.
◦ Insulin and glucose r Upper tract obstructive uropathy should be acutely
◦ Kayexalate managed by stent vs. percutaneous nephrostomy.
◦ Hemodialysis for severe hyperkalemia or
refractory to treatment
7
ACUTE KIDNEY INJURY, PEDIATRIC (RENAL FAILURE, ACUTE)

Leigh Mark Ettinger, MD, MS
Kenneth Lieberman, MD
PATHOPHYSIOLOGY
BASICS r Prerenal and intrinsic renal injury disrupt the DIAGNOSIS
regional perfusion of, and subsequent oxygen
DESCRIPTION delivery to, the kidney (3) HISTORY
r A sudden or recently acquired functional impairment r Evaluate for shock, sepsis, bleeding, dehydration,
– The natural arterial gradient of oxygen tension
of the kidney relative to physiologic demands with from cortex to medulla makes the kidney highly gastrointestinal losses
or without actual kidney injury (1) r Assess recent medication exposure, including
susceptible to hypoxic and oxidative injury during
r Causes mild to potentially life-threatening ischemia and reperfusion natural products
alterations in fluid, electrolyte, acid–base and – Poorly perfused glomerular endothelial cells r History of urologic surgery, anatomic problems, or
hormonal homeostasis release vasoactive substances, proteases, reactive kidney transplantation
r Terminology evolving from acute tubular necrosis oxygen species, and nitric oxide and activate the r Family history of ESRD, HUS
(ATN) to acute renal failure (ARF) to acute kidney coagulation cascade and complement pathways r Recent trauma, crush injury
injury (AKI) of varying grades to standardize – Even well-perfused kidneys can develop AKI r Seek signs of CKD, such as growth delay
reporting, clinical care, and research during sepsis from circulating cytokines, r Review recent blood tests to determine baseline
r Diagnosed by the Pediatric Modified Risk Injury lymphocytes, T cells, and other factors serum creatinine (SCr) and onset of AKI
Failure Loss End Stage Renal Disease (pRIFLE) – When found in the presence of cardiac,
criteria based on the estimated creatinine clearance pulmonary, or hepatic failure it is likely due to PHYSICAL EXAM
endothelial activation and circulatory aberrations r Assess hydration status, blood pressure, heart rate,
(eCCl, based on Schwartz formula) and urine output
(UOP) (2) – Nephrotoxic agents each have their own and temperature
mechanism of damage, eg, by forming crystals in r Lungs for rales
– Risk: eCCl decrease by 25% and/or UOP
the microstructures of the kidney r Abdomen for masses
<0.5 mL/kg/h for 8 hr
– Injury: eCCl decrease by 50% and/or UOP – Rhabdomyolysis causes intrarenal
vasoconstriction, direct ischemic tubule injury, and DIAGNOSTIC TESTS & INTERPRETATION
<0.5 mL/kg/h for 16 hr
tubular obstruction in acidic urine Lab
– Failure: eCCl decrease by 75% or eCCl r SCr and blood urea nitrogen will be elevated
r Postrenal injury is due to antegrade urine flow
<35 mL/min/1.73 m2 and/or UOP <0.3 mL/kg/h r May have hyperkalemia, acidosis
for 24 hr or anuric for 12 hr disruption from the kidney
– Must be bilateral to cause pRIFLE findings but can r Hemoglobin will be low if bleeding
– Loss: Persistent failure >4 wk
be unilateral if only one kidney is present due to r HUS causes thrombocytopenia, increased lactate
– End stage renal disease (ESRD): Persistent failure
>3 mo congenital absence, prior nephrectomy, or kidney dehydrogenase
r No standardized definition for neonatal AKI transplant r When muscular damage is the cause creatinine
r Etiology may be multifactorial, especially in the ICU kinase will be elevated and urinary myoglobin will
EPIDEMIOLOGY setting be positive
Incidence r Urinalysis to detect red blood cells, proteinuria
r A difficult assessment since, until recently, there was ASSOCIATED CONDITIONS r Urine eosinophils indicate interstitial nephritis
no unifying criteria to make the diagnosis CKD increases the risk for AKI
r Strict UOP monitoring to assess AKI stage and
– Recent meta-analysis showed reported incidences GENERAL PREVENTION
r Prerenal progression
in hospitalized pediatric population from 1–82% r Atypical-AKI
(3) – Prevent volume depletion (1)[B] – Clinical AKI fails to meet the definition
Prevalence – Maintain cardiac output and oxygenation with ◦ SCr falsely lowered by dilution due to large
Unknown vasopressors and blood transfusions as needed volume fluid resuscitation or transfusions,
RISK FACTORS (1)[C] thereby reflecting the blood donors’ kidney
r Chronic kidney disease (CKD) increases the risk for r Intrinsic renal function
AKI – Careful dosing and therapeutic drug level ◦ SCr falsely lowered by muscle wasting or
r Hospitalization, especially in the ICU monitoring of aminoglycosides or avoidance reduced muscle mass due to quadriplegia,
r Exposure to potentially nephrotoxic agents, such as altogether cerebral palsy, or other neuromuscular disorders
– Use lipid formulation of amphotericin B or another ◦ SCr falsely lowered during sepsis by decreased
nonsteroidal anti-inflammatories (NSAIDs), contrast,
antifungal alternative muscle perfusion
aminoglycosides r Real-time markers of AKI are being sought
r Recent surgery, solid organ or marrow transplant, – Contrast-induced AKI
◦ Avoid the use of contrast – Candidates include serum cystatin C, kidney injury
cardiopulmonary bypass
◦ Use either iso- or low-osmolar iodinated molecule-1, interleukin-18, liver fatty acid–binding
Genetics contrast media protein, neutrophil gelatinase-associated lipocalin
r If recurrent rhabdomyolysis, consider an underlying
◦ Intravenous fluid expansion for those patients at Imaging
defect in muscle metabolism risk r Renal ultrasound with Doppler analysis of the renal
r If recurrent hemolytic uremic syndrome (HUS)
– Avoid NSAIDs artery and veins
consider a defect in the complement cascade – Animal models have shown the potential benefit – Hydronephrosis indicates obstruction
r If AKI in the presence of CKD then consider inherited of vasodilators, growth factors, antioxidants, and – Increased echogenicity consistent with medical
forms of ESRD, such as autosomal recessive anti-inflammatory drugs in preventing AKI renal disease
polycystic kidney disease r A single dose of theophylline given to neonates with
– Thrombosis of renal artery or vein
severe perinatal asphyxia has been shown to – Small echogenic kidneys, cystic kidneys indicate
significantly reduce the risk of AKI CKD
r Bladder ultrasound
– Trabeculated, thick-walled bladder may indicate
lower urinary tract abnormality such as a
neurogenic bladder or obstruction
r Technetium-99m MAG3 renal scan can be used in
prolonged AKI to differentiate prolonged ATN from
permanent cortical necrosis
8
ACUTE KIDNEY INJURY, PEDIATRIC (RENAL FAILURE, ACUTE)

A
Diagnostic Procedures/Surgery r Discontinue potentially nephrotoxic drugs FOLLOW-UP
Kidney biopsy rarely necessary but may be indicated to r Medications with renal clearance require Patient Monitoring
diagnosis prolonged AKI without a clear etiology dosing/timing adjustments/drug level monitoring, Monitor SCr, blood pressure, somatic growth,
Pathologic Findings when available, to reduce the risk of toxicity urinalysis for signs of CKD after resolution of AKI
r Nutritional research is limited to observational
Kidney biopsy may reveal ATN, interstitial disease, Patient Resources
thrombotic microangiopathy, medication-induced studies r American Society of Pediatric Nephrology
crystal formation, glomerulonephritis – Critically ill children should receive 100–130% of – www.aspneph.com/parentpatient.asp
their basal energy needs r Kidney & Urology Foundation of America
r Prerenal MEDICATION – www.kidneyurology.org/
– Intravascular volume depletion First Line r National Kidney Foundation
◦ Dehydration, hemorrhage, gastrointestinal r Diuretics to convert oliguric AKI to nonoliguric AKI – www.kidney.org/patients/index.cfm
losses, burns, pancreatitis, peritonitis have not been shown to affect outcomes (1)[C]
◦ Congestive heart failure, sequestration in r IV sodium bicarbonate has been administered to
interstitial spaces, shock, anaphylaxis correct the acidosis of AKI but has not been studied REFERENCES
r Intrinsic renal with randomized controlled trials 1. Kidney Disease: Improving Global Outcomes
– ATN, hypoxic/ischemic insults, sepsis/toxin r Emerging treatments include apoptosis inhibitors,
(KDIGO) Acute Kidney Injury Work Group. KDIGO
mediated, multiple organ dysfunction syndrome, iron chelators, anti-inflammatory agents, repair Clinical Practice Guideline for Acute Kidney Injury.
interstitial nephritis, tumor lysis syndrome, agents (eg, stem cells) Kidney Inter., Suppl. 2012;2:1–138.
glomerulonephritis, vascular thrombosis, cortical
Second Line 2. Akcan-Arikan A, Zappitelli M, Loftis LL, et al.
necrosis, HUS, cortical dysplasia or hypoplasia,
N/A Modified RIFLE criteria in critically ill children with
rhabdomyolysis
acute kidney injury. Kidney Inter. 2007;71:
– Potentially nephrotoxic agents such as SURGERY/OTHER PROCEDURES 1028–1035.
aminoglycoside antibiotics, NSAIDs, radio-opaque r Central venous access may be needed for renal
contrast, antivirals, antifungals, chemotherapeutic replacement therapy (CRRT or hemodialysis) 3. Basu RK, Devarajan P, Wong H, et al. An update
agents r Postrenal AKI may require decompression surgery, and review of acute kidney injury in pediatrics.
– Chinese herb nephropathy is an acute to chronic Pediatr Crit Care Med. 2011;12:339–347.
nephrostomy tube, or ureteral stent
interstitial fibrosis caused by Aristolochia fangchi, r Nephrolithiasis may respond to extracorporeal shock 4. Perazella M. Nephrogenic Systemic Fibrosis, kidney
an herb still available in natural products ordered disease, and gadolinium: Is there a link? Clin J Am
wave lithotripsy, endoscopic surgery, or surgery
online Soc Nephrol. 2007;2:200–202.
(open, laparoscopic, robotically assisted)
r Postrenal
– Obstruction in the ureter(s) or urethra ADDITIONAL TREATMENT
– Bilateral nephrolithiasis due to cystinuria has been Radiation Therapy ADDITIONAL READING
reported as a cause of pediatric AKI N/A
N/A
r Pseudo-AKI Additional Therapies
– Always interpret lab data in clinical context to N/A See Also (Topic, Algorithm, Media)
r Acute Kidney Injury, Adult (Renal Failure, Acute)
avoid overdiagnosis of AKI
◦ Endogenous chromogens (eg, bilirubin, ascorbic Complementary & Alternative r Chronic Kidney Disease, Pediatric (Renal Failure,
Therapies Chronic)
acid, uric acid) and exogenous chromogens (eg,
N/A r Pediatric Modified Risk Injury Failure Loss End Stage
cephalosporins, trimethoprim, cimetidine) may
interfere with the creatinine assay and cause Renal Disease (pRIFLE)
falsely elevated results ONGOING CARE
◦ Weight-based determination of UOP may falsely
cause the obese patient to fulfill the criteria PROGNOSIS CODES
r With multisystem organ failure the addition of AKI
without actual AKI
increases mortality from 10–57%
r A 3–5-yr follow-up study after resolution of AKI ICD9
r 584.5 Acute kidney failure with lesion of tubular
TREATMENT showed that 40–50% of pediatric patients showed necrosis
signs of CKD (3) r 584.9 Acute kidney failure, unspecified
GENERAL MEASURES
r Reduce risk of dehydration or fluid overload by only COMPLICATIONS r 728.88 Rhabdomyolysis
replacing calculated insensible fluid losses and r Hyperkalemia, fluid overload, pulmonary edema,
measured UOP hypertension, acidosis, reduced drug excretion, and ICD10
r M62.82 Rhabdomyolysis
– Intravenous fluid should have no potassium uremic symptoms
r Maintain renal perfusion and oxygenation (1)[C] – Overcorrection of any of the above r N17.0 Acute kidney failure with tubular necrosis
– Renal dilators (dopamine, fenoldopam) have not r Nephrogenic systemic fibrosis (NSF) is a rare but r N17.9 Acute kidney failure, unspecified
been shown to improve pediatric AKI potentially lethal fibrosing disorder of the skin, liver,
– No studies relating fluid type used in pediatric heart, lungs, diaphragm, and skeletal muscle
resuscitation on AKI incidence or outcome observed in patients with AKI or CKD who were CLINICAL/SURGICAL
r Continuous renal replacement therapy (CRRT) has exposed to gadolinium used in MRI (4) PEARLS
not been shown to improve kidney function or – 335 cases in the NSF International Registry at the
r AKI is often multifactorial.
mortality, although there is controversy about the time of writing; some were children
– Gadolinium should be avoided in AKI r Seek prerenal, intrinsic renal, and postrenal causes
timing of initiation, dose, route, and duration (1)[C]
r Hemodialysis or peritoneal dialysis may play a role in r Patients exposed to the Aristolochia fangchi herb of the AKI.
are at increased risk for urothelial malignancies r Stage AKI with pRIFLE criteria.
supportive care of the patient with AKI
r Avoid potentially nephrotoxic drugs and gadolinium
during AKI.
9
ACUTE SCROTUM
r Appendix torsion is a result of vascular compromise PHYSICAL EXAM

BASICS may be related to pedunculated anatomy of the r General
appendage – Vital signs; low-grade fever with torsion, fever
DESCRIPTION – Appendix testis 95% of appendix torsions with UTI
r Acute pain and swelling in the scrotum is typically – Appendix epididymis torsion is less common – Presence of inguinal hernia
related to testicular pathology and is usually referred r Epididymitis – Abdominal and flank tenderness
to as “acute scrotum” in the absence of obvious – Can present as acute or chronic epididymitis r GU exam
trauma. ◦ Acute: Severe swelling, tenderness, rigors, high – Assess cremasteric reflex (2):
r Occasionally pain from ureteral colic can be referred fevers ◦ Stroke or pinch the skin of the upper thigh
to the testicle but swelling is usually absent. – Infectious causes ◦ Normal reflex is contraction of the cremaster
r Chronic testicular pain is referred to orchalgia. ◦ In men >35 yr of age, Chlamydia trachomatis muscle with elevation of the testis.
r Testicular torsion is a major cause of the acute and Neisseria gonorrhoeae (sexually transmitted ◦ Absent reflex may aid in distinguishing testicular
scrotum particularly in children and requires timely infections) are the most common pathogens torsion from epididymitis/other causes of an
diagnosis and treatment to avoid testicular loss. ◦ In men >35 yr of age coliforms most common acute scrotum where reflex is present
r In adults acute epididymo-orchitis is the most ◦ Less common pathogens: Ureaplasma, TB, ◦ Phren sign (pain relief with elevation of testicle)
common cause of an acute scrotum. Brucella species; with HIV infection, is no longer considered accurate for diagnosis of
r In children torsion of a testicular appendix or testicle Cytomegalovirus and Cryptococcus torsion
– Less frequent causes include autoimmune r Testicular torsion
are most common causes.
diseases, vasculitis, trauma – Testicle may be high riding
EPIDEMIOLOGY – In a prepubertal boy epididymitis is almost always – Very tender and may assume a transverse lie due
Incidence associated with a urinary tract anomaly to twisting of the cord
r Testicular torsion occurs most commonly in neonates – The spermatic cord will not usually be palpable
and postpubertal boys and is more common on the r Torsion – May be scrotal wall erythema and swelling
left – Cremasteric reflex often absent
– Bell clapper deformity: 10–15% of males r Torsion appendix
– However in 1 series 39% of patients were
– Cryptorchidism
reported to be in men >21 yr of age (1) r Epididymitis – Pain may be localized to upper pole of testicle
r Torsion of an appendix more common in prepubertal – Cremasteric reflex usually present
– Other sexually transmitted infections
boys – Blue dot sign: Rare, more likely in prepubertal
r Approximately 600,000 cases of epididymitis/yr in – Prostatic hypertrophy
boys;
US GENERAL PREVENTION ◦ Tender nodule with blue discoloration on the
r Torsion: Reduce testicular loss risk by upper pole of the testis and more easily seen in
Prevalence
– Early diagnosis and treatment light-skinned individuals
Testicular torsion: 1:4,000 males <25 yr old
– Community awareness about testis pain – In late findings scrotal swelling and reactive
RISK FACTORS – Elective bilateral orchidopexy for intermittent pain hydrocele may be present
r Testicular torsion or contralateral orchidopexy at surgery for an r Epididymitis
– Cryptorchidism episode of acute torsion – Cremasteric reflex usually present
– Bell clapper deformity r Epididymitis – Acute epididymitis may have significant swelling
r Epididymitis – Safe sex practices and tenderness; with chronic epididymitis there is
– Unprotected sex in younger men tenderness but usually no scrotal swelling
– Prostate disorders in older men
– Urinary tract instrumentation DIAGNOSIS DIAGNOSTIC TESTS & INTERPRETATION
– Anal insertive intercourse Lab
HISTORY r Urinalysis
Genetics r Rule out any traumatic insult to the groin area
– White cells and positive leukocyte esterase
Testicular torsion reported in 10% of family members; – Some patients report minor trauma before ◦ Suspect epididymitis or UTI
may be autosomal or X-linked recessive; no specific presentation of torsion – Red blood cells suggest renal or ureteral source of
genetic defects identified r Sexual practice history
pain (eg, stone)
r Recent urinary tract instrumentation – In cases of torsion UA usually negative
PATHOPHYSIOLOGY
r Testicular torsion can be either intravaginal or r Testicular torsion r Urine culture if epididymitis or UTI suspected
extravaginal – The classic presentation is sudden hemiscrotal r Consider urethral swab if urethral discharge present:
– Intravaginal testicular torsion is twisting of the pain often awakening the patient from sleep Culture and nucleic acid amplification testing for
spermatic cord within the tunica vaginalis – Pain can radiate to the groin chlamydia and gonorrhea
◦ Usually due to a so-called “bell clapper – Nausea and/or vomiting can be present
– Movement tends to worsen the pain Imaging
deformity”: A failure of normal posterior r Scrotal US with Doppler
anchoring of the gubernaculum, epididymis and – A history of intermittent testicular discomfort may
be present suggesting past torsion and detorsion – Intravaginal testicular torsion findings
testis. Leaves the testis free to rotate within the
r Appendix torsion – Usually shows decreased or absent arterial flow
tunica vaginalis of the scrotum much like the
but may be normal
clapper inside of a bell (present in 12% of – Symptoms are similar to testicular torsion but not r Appendix torsion findings
males) as severe
– Extravaginal testicular torsion is twisting of both r Epididymitis – Normal exam most common
the spermatic cord and tunica vaginalis – Supratesticular complex mass without vascular
– Can present with acute: Fever, chills, rigors, or as
r Perinatal: Extravaginal testicular torsion is usually flow may be present
chronic testicular/scrotal discomfort r Epididymitis
the cause – More likely to be associated with voiding
complaints than torsion – Enlarged epididymis reported as “epididymitis”
often present
– Doppler flow normal or increased
10
ACUTE SCROTUM
A
Diagnostic Procedures/Surgery r Epididymitis: Chronic FOLLOW-UP
In cases of testicular torsion, surgical exploration is – Scrotal elevation, avoid sexual and athletic Patient Monitoring
usually diagnostic and therapeutic activity, warm baths, and NSAIDs Epididymitis due to culture-proven C. trachomatis or
r Appendix torsion: Ibuprofen to reduce inflammation N. gonorrhoeae: refer sex partners for evaluation and
Pathologic Findings
N/A and discomfort treatment disease
r Testis torsion: Pain control may require opioids
DIFFERENTIAL DIAGNOSIS Patient Resources
r Abscess or other infection such as Fournier gangrene Second Line MedlinePlus: Testicular torsion http://www.nlm.
r Appendix torsion (appendix testis or epididymis N/A nih.gov/medlineplus/ency/article/000517.htm
testis) SURGERY/OTHER PROCEDURES
– Most commonly seen in prepubertal boys r Urgent scrotal exploration, bilateral fixation for REFERENCES
– Most common cause of acute scrotum in this age extravaginal testicular torsion to avoid asynchronous
group contralateral torsion 1. Cummings JM, Boullier JA, Sekhon D, et al. Adult
r Epididymitis due to UTI or STD: Rare or uncommon r Manual detorsion: Use only if surgery is delayed testicular torsion. J Urol. 2002;167(5):2109–2110.
in pediatric age group; more likely in adult >2 hr 2. Rabinowitz R. The importance of the cremasteric
r Fat necrosis of scrotal wall – Testicle most often rotates medially during torsion reflex in acute scrotal swelling in children. J Urol.
r Henoch–Schönlein purpura – Manual detorsion is accomplished by attempting 1984;132(1):89–90.
– Rash usually present to rotate the testicle laterally toward the thigh
r Incarcerated inguinal hernia – The twisting can range from 180–720 degrees
r Orchitis: With the exception of mumps orchitis, such that multiple detorsion twists may be ADDITIONAL READING
isolated orchitis without epididymitis in adults is rare required
Yu KJ, Wang TM, Chen HW, et al. The dilemma in the
r Referred pain: Urolithiasis or intra-abdominal – However in up to 1/3 of cases, the torsion rotation
diagnosis of acute scrotum: Clinical clues for
process such as appendicitis can be lateral
differentiating between testicular torsion and
r Testicular infarction due to spermatic cord injury or – Successful detorsion still requires operative
epididymo-orchitis. Chang Gung Med J. 2012;
intervention and orchidopexy
thrombosis 35(1):38–45.
r Testicular torsion: Most common in peripubertal – Hallmarks of successful manual detorsion include
pain relief, testicle assuming a lower position in See Also (Topic, Algorithm, Media)
boys but can occur at any age; less common than the scrotum, reorientation of the testicle from r Acute Scrotum Algorithm
appendix torsion transverse lie to vertical positioning, restoration of r Acute Scrotum Image
r Testicular tumor: Usually painless but may have
Doppler blood flow r Appendix Testis and Appendix Epididymis, Torsion
tenderness with trauma r Epididymitis
r Trauma and possible testicular rupture: History ADDITIONAL TREATMENT
r Torsion, Testis, or Testicular/Epididymal Appendages
suggestive; hematocele usually present Radiation Therapy
r Orchalgia; consider voiding dysfunction N/A
N/A CODES
TREATMENT
Complementary & Alternative ICD9
Therapies r 604.90 Orchitis and epididymitis, unspecified
ALERT N/A r 608.9 Unspecified disorder of male genital organs
Testicular torsion is a surgical emergency because r 608.20 Torsion of testis, unspecified
the likelihood of testicular salvage diminishes with
the duration of torsion. ONGOING CARE
ICD10
PROGNOSIS r N44.00 Torsion of testis, unspecified
GENERAL MEASURES r In cases of testicular torsion 12 hr is considered the r N45.3 Epididymo-orchitis
r Clinical history, exam, and diagnostic studies
point at which the testis suffers irreversible damage r N50.9 Disorder of male genital organs, unspecified
(urinalysis, Color Doppler Ultrasound) have a high r Torsion surgery outcomes appear better in children
degree of accuracy in making the diagnosis
r Emergent exploration indicated if evaluation than in adults
– Salvage rates in males <21 yr was 70% vs. those CLINICAL/SURGICAL
suggests intravaginal testicular torsion or diagnosis
>21 yr who had a salvage rate of 41% (3) PEARLS
is equivocal ◦ Potential explanations: Time to presentation
r If torsion is present and surgery cannot be r Color Doppler ultrasonography is the preferred
impacted salvage and patients over 21 yr of age
performed in a reasonable amount of time, manual had a greater degree of cord twisting than the imaging technique for evaluating the acute scrotum.
detorsion should be considered younger patients r Cremasteric reflex is usually absent in testicular
r Most cases of epididymitis can be treated on an
COMPLICATIONS torsion.
outpatient basis
r Testicular torsion
MEDICATION – Testicular loss and or atrophy
First Line – Infertility
r Epididymitis: Acute r Appendix testis/epididymis torsion
– Ice, scrotal elevation, and NSAIDs with antipyretic – Usually none long term
for high temperature r Epididymitis
– Younger male: Ceftriaxone (250 mg IM) with – Scrotal abscess
doxycycline (100 mg PO BID × 10 days). – Urosepsis
– Older males: Ceftriaxone (250 mg IM) along with – Chronic orchalgia
a 10-day course of fluoroquinolone for enteric
organisms (ofloxacin 300 mg PO BID or
levofloxacin (500 mg PO BID)
11
ACUTE TUBULAR NECROSIS

Costas D. Lallas, MD, FACS
ASSOCIATED CONDITIONS r Urine tests

BASICS r Sepsis – Urinalysis: Muddy brown granular and epithelial
r Hemorrhage (operative, obstetric, trauma) cell casts and free epithelial cells secondary to
DESCRIPTION r Pre-existing renal insufficiency (diabetes, sloughing of the tubular epithelium vs.
r Acute tubular necrosis is the most common type of near-normal in prerenal disease
hypertension)
intrarenal acute renal injury (AKI) r Edematous states such as CHF – The classic sediment of ATN includes pigmented
– Usually due to prolonged ischemia or (muddy brown) granular casts and renal tubular
administration of nephrotoxins GENERAL PREVENTION epithelial cells, which may be seen in nearly 80%
r A syndrome of intrinsic renal failure secondary to r Avoid prolonged renal ischemia by timely
of cases of oliguric ARF
ischemic or toxic insults management of hemorrhage, dehydration and other – Urine sodium concentration: High >40 mEq/L due
r Histopathologic findings of ATN variable causes of renal hypoperfusion to tubular injury vs. <20 mEq/L in prerenal
r Decreased urine output: r Avoidance of contrast agents in the setting of renal disease in an attempt to conserve sodium
– Can be nonoliguric, oliguric >500 mL/d, or insufficiency (contrast-induced nephropathy) – Fractional excretion of sodium (FENa): Above 2%
r Appropriate management of potentially nephrotoxic in ATN while <1% in prerenal disease, measured
anuric. Mortality increases from 20–60% to 80%
if the patient is oliguric or anuric. medications as urine Na divided by plasma Na times plasma
r Signs of underlying disorder: CR divided by urine CR, although causes of ATN
associated with a low FENa are that due to
– Signs of sepsis or of hypotensive events secondary DIAGNOSIS intravenous contrast material, rhabdomyolysis,
to trauma, cardiac disease, surgery with excessive
blood loss, or interruption of blood supply to HISTORY sepsis, and multisystem organ failure
kidneys r Specific attention to: – Urine osmolality: Urine osmolality <450 mOsm/kg
– Hypotensive episodes, blood transfusions, in ATN secondary to loss of concentrating ability;
EPIDEMIOLOGY >500 mOsm/kg in prerenal disease
intravenous contrast exposure r Urine creatinine concentration divided by plasma
Incidence r Meticulous listing of medications to include dosage
r ARF is present in 209 per million population. creatinine concentration: Ratio is <20 in ATN while
r ARF may affect 2–5% of patients in a tertiary care to assure appropriate dosing for level of renal
function >40 in prerenal disease, reflecting loss of tubular
hospital, and the incidence of ARF in the surgical or r Make sure other medications which depend on renal water reabsorption
medical ICU may exceed 20–30% Imaging
r Breakdown of ARF: ATN, 45%; prerenal causes, metabolism are also given at appropriate doses to
avoid side effects r Renal ultrasonography
21%; acute or chronic renal failure, 13%; urinary – Sensitive test to determine obstruction. Doppler
tract obstruction, 10%; glomerulonephritis or PHYSICAL EXAM can detect gross blood flow in renal vein and
r Vital signs and hemodynamic parameters should be
vasculitis, 4%; acute interstitial nephritis, 2%; artery
atheroembolism, 1% critically assessed. r Plain abdominal film
r A patient’s weight is helpful information, and its
RISK FACTORS – Identifies the presence or location of renal calculi
r Decreased renal perfusion from: daily measurement is important in the diagnosis and and is particularly helpful to discern the proper
management of ARF. position of stents and drains
– Prolonged hypotension, surgical interruption of r Evaluate the volume status of the patient.
blood flow, NSAIDs, ACE inhibitors, cyclosporine r Functional studies
r Nephrotoxic agents: r Evaluate neck veins and auscultation of heart and
– Nuclear scans can determine perfusion or tubular
– Radiocontrast media (low osmolality is possibly lungs; assess extremities and the presacral area for secretion; MRI can give some functional
safer), aminoglycosides, cisplatin, amphotericin, edema. information while providing anatomic information
r General exam
drug intoxications with acetaminophen or Diagnostic Procedures/Surgery
r Evaluate for bladder distention and assess for signs
ethylene glycol N/A
– The most commonly seen nephrotoxins in the of vasculitis or cutaneous rashes.
hospitalized patient include radiographic contrast Pathologic Findings
DIAGNOSTIC TESTS & INTERPRETATION r Tubule cell injury (2):
material, antibiotics (especially aminoglycosides
Lab – Tubular epithelial cells are particularly sensitive to
and amphotericin B), chemotherapeutic agents, r Serum tests (2)
NSAIDs, and ACE inhibitors ischemia and are also vulnerable to toxins. The
– BUN/plasma creatinine ratio: The ratio is normal structural changes include those of reversible
Genetics at 10 to 15:1 in ATN, but >20:1 in prerenal injury (such as cellular swelling, loss of brush
N/A disease due to the increase in passive border and polarity, blebbing, and cell
PATHOPHYSIOLOGY (1) reabsorption of urea, the ratio may also be detachment) and those associated with lethal
r Acute tubular injury increased with GI bleed, muscle breakdown, and injury (necrosis and apoptosis)
r Renal hypoperfusion and renal ischemia are the administration of corticosteroids or tetracycline r Disturbances in blood flow:
– Rate of rise of plasma creatinine: Rise of – Intrarenal vasoconstriction results in both reduced
most common causes of ATN
r The ischemic form is due to the reductions in >0.3–0.5 mg/dL in ATN vs. slower rise with glomerular blood flow and reduced oxygen
fluctuations with prerenal disease delivery to the functionally important tubules in
glomerular filtration rate (GFR) are secondary to
vascular and tubular factors the outer medulla (thick ascending limb and
– Ischemia from reductions in GFR from decreased straight segment of the proximal tubule)
renal plasma flow or dilatation of the efferent DIFFERENTIAL DIAGNOSIS
arteriole. After return of normal blood flow, ATN r Prerenal azotemia
persists secondary to tubular changes r Postrenal azotemia
– In addition, both exogenous and endogenous r Other forms of renal azotemia
nephrotoxic compounds exist. r Glomerulonephritis, disseminated intravascular
r Tubular factors: Backleak and tubular obstruction.
coagulopathy, arterial or venous obstruction,
Tubular obstruction secondary to a sloughed brush intrarenal precipitation
border, cellular debris, Tamm–Horsfall protein, and
decreased filtration pressure contribute to
obstruction and maintenance of ATN
12
ACUTE TUBULAR NECROSIS

A
REFERENCES
TREATMENT ONGOING CARE
1. Goldfarb DA, Poggio ED. Etiology, pathogenesis,
GENERAL MEASURES PROGNOSIS and management of renal failure. In: Wein AJ,
r Define and treat the underlying cause. r Slight improvements in survival in those patients Kavoussi LR, Novick AC, Partin AW, Peters CA, eds.
r Discontinue any nephrotoxic agents. with ATN requiring dialysis in an ICU setting Campbell-Walsh Urology, 10th ed. Philadelphia,
r Prophylaxis and treatment of complications of ARF. – The Mayo Clinic compared 1977–1979 with PA: WB Saunders, 2012.
r Early nephrology consultation. 1991–1992 showed high survival both in hospital 2. Erdbruegger U, Okusa, MD. Etiology and diagnosis
r Management of fluid disturbances. (52% vs. 32%) and at 1 yr (30% vs. 21%) of prerenal disease and acute tubular necrosis in
r Maintain a euvolemic state by restricting total fluids – Higher mortality rates are seen in elderly patients acute kidney injury (acute renal failure). UpToDate.
and in patients with respiratory failure, multiple Accessed August 4, 2014
to no more than urine output plus insensible losses. organ failure, pre-existing chronic diseases, and
MEDICATION systemic hypotension
r Major causes of death are infection and underlying
First Line ADDITIONAL READING
r High-dose loop diuretics (1–3 g/d) may convert disease, not renal failure
oliguric to nonoliguric ATN in some patients; it has – Patients at risk are generally very ill, with evidence Belcher JM, Parikh CR. Is it time to evolve past the
not been determined that this conversion decreases of multiple organ dysfunction prerenal azotemia versus acute tubular necrosis
r Of patients who survive ATN, nearly half will have a classification? Clin J Am Soc Nephrol. 2011;6:
the duration of ATN or mortality. Dopamine may
increase urine output, but its benefit is in question. complete recovery of renal function and a majority 2332–2334.
– Studies suggest that patients who respond to of the remainder have an incomplete recovery. Only See Also (Topic, Algorithm, Media)
mannitol, furosemide, or dopamine with an about 5% of all ARF patients require chronic r Acute Kidney Injury, Adult (Renal Failure, Acute)
increased urine output have better outcomes than maintenance dialysis r Acute Kidney Injury, Pediatric (Renal Failure, Acute)
nonresponders. COMPLICATIONS r Contrast Induced Nephropathy (CIN)
r Management of electrolyte disturbances r Fluid overload, electrolyte disturbances, metabolic
– Electrolyte disturbances can be minimized by acidosis
prophylactic institution of a low-potassium, – Hypertension, edema, acute pulmonary edema, CODES
low-protein diet accompanied by fluid restriction hyponatremia, hyperkalemia, hypermagnesemia,
and oral phosphate binders. hypercalcemia, hyperphosphatemia,
r Hyperkalemia is the most common and most ICD9
hyperuricemia 584.5 Acute kidney failure with lesion of tubular
dangerous abnormality and should be treated – Uremic signs and symptoms necrosis
aggressively with calcium supplementation until r GI: Nausea, vomiting, GI bleed; neurologic:
potassium levels can be reduced with combinations Encephalopathy, coma, seizures, peripheral ICD10
of insulin and glucose or potassium-binding resins. neuropathy; cardiac: Pericarditis uremic N17.0 Acute kidney failure with tubular necrosis
Second Line pneumonitis; hematologic: Bleeding, anemia;
N/A immunologic: Impaired granulocyte/lymphocyte
function
CLINICAL/SURGICAL
SURGERY/OTHER PROCEDURES
r Hemodialysis (HD), peritoneal dialysis (PD), and
PEARLS
FOLLOW-UP
continuous arteriovenous hemofiltration (CAVH) Patient Monitoring r High-dose loop diuretics (1–3 g/d) may convert
– CAVH: Need ICU, limited mobility, need r Duration oliguric to nonoliguric ATN in some patients; it has
anticoagulation, removes fluid well but slow – Renal failure phase usually lasts 7–21 days if the not been determined that this conversion decreases
correction of electrolyte abnormalities primary insult (ischemia, nephrotoxin) can be the duration of ATN or mortality.
– PD: No anticoagulation needed but slower corrected. Recovery is usually heralded by a r Of patients who survive ATN, nearly half will have a
correction of electrolyte abnormalities progressive increase in urine output and a return complete recovery of renal function and a majority
– HD: Expensive, anticoagulation necessary, of BUN and CR to the previous baseline. of the remainder have an incomplete recovery. Only
vascular access necessary but allow rapid r Recovery of renal function about 5% of all ARF patients require chronic
correction of fluid and electrolyte abnormalities – Irreversible loss of renal function can occur if the maintenance dialysis.
combination of pre-existing renal disease and r A patient’s weight is helpful information, and its
prolonged ARF secondary to repeat ischemic daily measurement is important in the diagnosis and
Radiation Therapy insults and/or nephrotoxin administration management of ARF.
N/A – If the patient survives, baseline CR is usually only
Additional Therapies 1–2 mg/dL above baseline.
N/A r Those patients that need dialysis and have
Complementary & Alternative bioincompatibility with the dialysis membrane or
Therapies have repeat episodes of hypotension have a worse
N/A prognosis.
Patient Resources
N/A
13
ADDISON DISEASE
Shaun G.S. Grewal, MD
r APS type 2
BASICS – Adrenal insufficiency, Thyroid disease, Type I DM DIAGNOSIS
– HLA-DR3, CTLA-4
DESCRIPTION r APS type 4 HISTORY
r Primary adrenal insufficiency r Vague symptoms; requires high index of suspicion
– Other autoimmune diseases
r Inadequate production of glucocorticoid and r Congenital adrenal hyperplasia – Fatigue, weight loss, anorexia, vomiting, GI
mineralocorticoid complaints, abdominal pain, diarrhea, muscle
– 21β-hydroxylase (CYP21 mutation)
– Differentiated from secondary (pituitary) and aches, salt craving, hypotension, behavioral
– 11β-hydroxylase (CYP 11B1 mutation)
tertiary (hypothalamic) causes of adrenal causes of changes, headaches, sweating, depression,
– 17∂-hydroxylase (CYP17 mutation)
adrenocorticoid insufficiency in which r Adrenoleukodystrophy (ALD) decreased libido, lethargy
mineralocorticoids are normally spared – Acute adrenal insufficiency: Life-threatening
– Demyelination of CNS hypotension, acute abdominal pain, vomiting,
r Triple A syndrome (Allgrove)
ALERT fevers
– Alacrima, achalasia, neurologic impairment
Acute adrenal insufficiency (Addisonian crisis): PHYSICAL EXAM
r Life-threatening hypotensive shock. PATHOPHYSIOLOGY r Vitals: Orthostatic hypotension
r Autoimmune disorders are the most common cause r Weight loss
r Most common cause is acute withdrawal of
in developed nations (80–90%) r Hyperpigmentation
chronic steroid. r Partial or complete T-cell mediated destruction of
r Acute stress (ie, surgery) without an adequate r Pigmented buccal mucosa and nail beds
adrenal cells r Loss of axillary and pubic hair
stress dose of steroids. – 90% of adrenal gland must be destroyed to cause r Vitiligo
insufficiency
r Goiter
EPIDEMIOLOGY – Decreased production of cortisol, aldosterone, and
Incidence adrenal androgens DIAGNOSTIC TESTS & INTERPRETATION
r 4.7–6.2 per million in Western populations (1) – Hypovolemia and prerenal azotemia cause
Lab
r Females more frequently affected than males orthostatic hypotension, dizziness, and lethargy r Electrolyte disturbances
– TB most common cause in underdeveloped – Adrenal crisis mostly attributable to
– Classic triad: Hyponatremia, hyperkalemia,
nations mineralocorticoid deficiency
azotemia
– Autoimmune disorders most common cause in – Pituitary compensation with increased ACTH
– Hypercalcemia
developed nations (90%) – ACTH and proopiomelanocortin-related peptides
– Lymphocytosis
stimulate melanocytes causing hyperpigmentation
Prevalence r Adrenal dysgenesis or hypoplasia – Hypoglycemia
r 93–140 per million (1) – Metabolic acidosis
– AHC or Triple A syndrome r Screening test
– Mortality 0.3 per 100,000 r Adrenal destruction
– Measure cortisol, ACTH
RISK FACTORS – APS1, APS2, APS4, ALD ◦ Low cortisol (<165 nmol/L)
r Tuberculosis – Infectious ◦ Elevated ACTH (>45 pmol/L)
r Autoimmune disease ◦ TB, HIV, CMV, histoplasmosis, cryptococcus, r Confirmation of abnormal screening test
r AIDS coccidioidomycosis
– Short corticotropin test
r Immunosuppression – Adrenal hemorrhage ◦ 250 μg ACTH
r Bilateral adrenal hemorrhage ◦ Sepsis
◦ Serum cortisol at 0, 30, and 60 min
r Bilateral adrenalectomy ◦ Disseminated intravascular coagulation
◦ Peak cortisol <550 nmol/L diagnostic (2)
◦ Anticoagulant therapy
r Drug induced
– Bilateral adrenalectomy Imaging
– Mitotane, aminoglutethimide, etomidate, r Adrenal infiltration r Routine imaging not recommended in cases of
ketoconazole, suramin, mifepristone definite autoimmune adrenalitis
– Adrenal metastasis, primary adrenallymphoma,
Genetics sarcoidosis, amyloidosis, hemochromatosis r CT or MRI in cases of suspected infection,
r 40% of patients with a 1st-/2nd-degree relative r CAH (see Genetics) malignancy, infiltration, hemorrhage
with an associated disorder r Calcifications present in up to 50% with TB
r Isolated autoimmune adrenalitis ASSOCIATED CONDITIONS
r Autoimmune endocrine disorders
– HLA-DR3, CTLA 4 r Thyroid disorder (17%)
r APS type 1
r Diabetes mellitus (12%)
– Adrenal insufficiency, hypoparathyroidism, chronic
r Gonadal dysfunction (12%)
mucocutaneous candidiasis
– AIRE gene (21q22) GENERAL PREVENTION
No general prevention guidelines exist for prevention
of primary hypoaldosteronism.
14
ADDISON DISEASE
A
Diagnostic Procedures/Surgery SURGERY/OTHER PROCEDURES FOLLOW-UP
No specific diagnostic procedures Stress dose steroids: 25–150 mg hydrocortisone or Patient Monitoring
5–30 mg methylprednisolone IV day of the procedure r Medic-alert bracelet to be worn at all times
Pathologic Findings
Atrophic adrenals in autoimmune adrenalitis in addition to maintenance therapy; taper to the usual r Instruct patients on proper use of emergency
dose over 1–2 days. hydrocortisone injections
DIFFERENTIAL DIAGNOSIS r Monitor for signs of appropriate glucocorticoid and
r Primary adrenal insufficiency (Addison disease) ADDITIONAL TREATMENT
r Secondary adrenal insufficiency (pituitary failure) Radiation Therapy mineralocorticoid replacement
– No hyperpigmentation (lack of ACTH elevation) N/A Patient Resources
r www.addisonsdisease.net
– Etiologies include chronic steroids, Additional Therapies
panhypopituitarism, Sheehan syndrome r Salt loading prior to major stress recommended by r www.addisonssupport.com
(postpartum necrosis), brain trauma, pituitary some
apoplexy, pituitary surgery r Future advances using long-acting hydrocortisone
r Tertiary adrenocortical insufficiency preparations to better mimic physiologic state
REFERENCES
Complementary & Alternative 1. Arlt W, Allolio B. Adrenal Insufficiency. Lancet.
Therapies 2003;361:1881–1893.
TREATMENT
No established alternative therapies 2. Lvås K, Husebye E. Addison’s disease. Lancet.
GENERAL MEASURES 2005;365:2058–2061.
r Acute adrenal insufficiency (addisonian crisis) 3. Reisch N. Fine tuning for quality of life: 21st
– 5 S’s: ONGOING CARE century approach to treatment of Addison’s
◦ Salt disease. Endocrinol Metab Clin North Am. 2009;
PROGNOSIS
◦ Sugar r Adrenal crisis may be lethal. 38:407–418.
◦ Steroids r Recommended dosages for glucocorticoid and
◦ Support
mineralocorticoid replacement rarely cause
◦ Search for precipitating cause
significant side effects; close monitoring is essential
ADDITIONAL READING
MEDICATION to prevent excess treatment. Chakera AJ. Addison disease in adults: Diagnosis and
First Line COMPLICATIONS management. Am J Med. 2010;123:409–413.
r Corticosteroid replacement: r Side effects of excess steroid replacement:
– Hydrocortisone 15–25 mg/d See Also (Topic, Algorithm, Media)
– Weight gain, high BP, hyperglycemia, growth r Addison Disease (Adrenocortical Insufficiency)
◦ BID dosing: 20 mg, 10 mg
◦ TID dosing: 10 mg, 5 mg, 5 mg
retardation, bruising, cardiovascular risks, gastric Algorithm
ulcers, poor wound healing, skin striae, r Waterhouse–Friderichsen Syndrome
◦ Monitor body weight and signs/symptoms of osteoporosis
over/under replacement r Side effects of excess mineralocorticoid:
r Mineralocorticoid replacement:
– Hypertension, bradycardia, hypernatremia, CODES
– Fludrocortisone 0.05–0.20 mg/d congestive heart failure, suppressed renin levels,
– Monitor blood pressure, peripheral edema, serum growth retardation
sodium, and potassium r Acute withdrawal of chronic steroid replacement ICD9
r Major stress: Surgery, trauma, sepsis: 255.41 Glucocorticoid deficiency
may precipitate acute adrenal crisis
– IV hydrocortisone 100–300 mg/d (TID dosing) r Must rule out or treat glucocorticoid deficiency prior ICD10
then taper to initiation of thyroxine for hypothyroidism, as this E27.1 Primary adrenocortical insufficiency
r Minor stress
may precipitate adrenal crisis.
– Increase steroid dose 2–3-fold then taper over
several days CLINICAL/SURGICAL
Second Line PEARLS
r Dehydroepiandrosterone (DHEA) replacement
r Addisonian crisis: Is acute, life-threatening shock.
– 25–50 mg/d r 5 S’s for treatment of addisonian crisis
– Impacts mood/feeling of well-being (3)
– Salt; Sugar; Steroids; Support; Search for
precipitating cause.
r Classic triad: Hyponatremia, Hyperkalemia,
Azotemia.
r Use “stress dose” steroids for patients with Addison
disease undergoing surgical procedures.
15
ADENOMATOID TUMORS, TESTICULAR AND PARATESTICULAR

Ramiro J. Madden-Fuentes, MD
BASICS DIAGNOSIS r Excision via inguinal approach
r Frozen section for pathology – proceed to
DESCRIPTION HISTORY orchiectomy with high cord ligation if malignant
r Adenomatoid tumors are benign lesions of the male r Duration of lesion and size
testicular adnexa. r Interval growth Pathologic Findings
r Associated pain, dysuria, tenderness – epididymitis r Gross
r Usually ∼1 cm in size (range 0.5–7.5 cm) (1)[C]
r Most often asymptomatic r Prior malignancy or scrotal pathology – Small (1 cm), well circumscribed without fibrous
r Mesenchymal origin (2)[C] r Exposure to tuberculosis (TB) capsule
– Tan-white, homogeneous
r History of sarcoidosis, histoplasmosis r Microscopic
EPIDEMIOLOGY r History of urinary tract infection or sexually
Incidence – Adenomatoid cells within fibrous stroma
r The majority of patients present within the 3rd–5th transmitted infection – Occasional cystic dilation
r Recent GU manipulation – bacillus Calmette–Guérin – Irregular, somewhat branched-appearing tubular
decades of life (3)[C].
r Adenomatoid tumors are the most common (BCG) instillation structures appear within the tumor, a coalescence
neoplastic processes involving the testicular adnexal PHYSICAL EXAM of the cellular vacuoles, which form a false lumen
and spermatic cord structures (3)[C]. r Scrotal exam (4)[C]
r Adenomatoid tumors in females occur in uterus > – Identify location of mass – single or multiple DIFFERENTIAL DIAGNOSIS
fallopian tubes > ovary (1)[C]. – Evaluate for varicocele or hydrocele r Benign tumors of epididymis:
– Compare with contralateral scrotal contents – Leiomyoma
Prevalence – Evaluate if fixed, mobile, indurated, or
Not well defined – Papillary cystadenoma (associated with von
encroaching on other structures Hippel–Lindau syndrome)
RISK FACTORS – Evaluate for spermatic cord involvement – Lipomas
None described – Transillumination – to identify if fluid filled – Hamartomas
Genetics (spermatocele, hydrocele) – Adrenal cortical adenomas
r Inguinal exam r Malignant tumors of the epididymis:
N/A
– Evaluate for lymphadenopathy – Sarcoma (rhabdomyosarcoma, leiomyosarcoma,
PATHOPHYSIOLOGY – Hernia fibrosarcoma, liposarcoma)
r Mesothelial origin is most accepted theory (3)[C]
DIAGNOSTIC TESTS & INTERPRETATION – Melanotic neuroectodermal tumor of the
r Benign with no reported cases of metastasis
epididymis
r Capable of local invasion Lab r Extension of primary testicular tumor
r Tumor markers if concern for testicular mass –
r Epididymis, tunica vaginalis, spermatic cord are most r Metastatic tumor to epididymis:
α-fetoprotein (AFP),
common sites – Urologic (prostate, kidney)
– β-human chorionic gonadotropin (β-HCG)
ASSOCIATED CONDITIONS – Lactate dehydrogenase (LDH) – GI (stomach, colon, carcinoid, pancreas)
◦ Purified protein derivative (PPD) if TB suspected r Other lesions of the epididymis
N/A
◦ No specific labs to diagnose adenomatoid – Granuloma (sperm, TB, sarcoidosis)
GENERAL PREVENTION – Spermatocele
r Routine self-exam for identification of scrotal tumors
– Epididymitis
content masses Imaging – Epidermoid inclusion cyst
r Routine genital exam by physician r Scrotal ultrasound
– Epididymal abscess
– Solid vs. cystic
– Location – testicular or paratesticular
◦ If located in the tunica albuginea can grow into
the testicular parenchyma and resemble a
testicular malignancy
– Vascular or avascular
16
ADENOMATOID TUMORS, TESTICULAR AND PARATESTICULAR

A
REFERENCES r Spermatocele
TREATMENT r Testis, Tumor and Mass, Adult, General
1. Wachter DL, Wünsch PH, Hartmann A, et al. r Testis, Tumor and Mass, Pediatric, General
GENERAL MEASURES Adenomatoid tumors of the female and male Considerations
r Excision via inguinal approach – for benign lesions genital tract. A comparative clinicopathologic and r Von Hippel–Lindau Disease
r Epididymitis – consider sexually transmitted infection immunohistochemical analysis of 47 cases
as source in young men and treat accordingly (see emphasizing their site-specific morphologic
Sexually Transmitted Infections section) diversity. Virchows Arch. 2011;458(5):593–602.
2. Delahunt B, Eble JN, King D, et al.
CODES
MEDICATION Immunohistochemical evidence for mesothelial
First Line origin of paratesticular adenomatoid tumor. ICD9
N/A r 222.0 Benign neoplasm of testis
Histopathology. 2000;36:109–115.
r 222.3 Benign neoplasm of epididymis
Second Line 3. Montgomery JS, Blood DA. The diagnosis and
r 222.8 Benign neoplasm of other specified sites of
N/A management of scrotal masses. Med Clin North
Am. 2011;95(1):235–244. male genital organs
r Excision of suspicious lesion via inguinal approach 4. Amin MB. Selected other problematic testicular and ICD10
paratesticular lesions: Rete testis neoplasms and r D29.8 Benign neoplasm of other specified male
with proximal vascular control
r Frozen section pseudotumors, mesothelial lesions and secondary genital organs
r If positive for malignancy, radical orchiectomy tumors. Mod Path. 2005;18:S131–S145. r D29.20 Benign neoplasm of unspecified testis
r Further surgical therapy guided by pathology but r D29.30 Benign neoplasm of unspecified epididymis
may include retroperitoneal lymph node dissection if ADDITIONAL READING
rhabdomyosarcoma
r Centers for Disease Control and Prevention. Sexually CLINICAL/SURGICAL
ADDITIONAL TREATMENT Transmitted Diseases Treatment Guidelines, 2010. PEARLS
Radiation Therapy MMWR. 2010;59 (No. RR-12)
N/A r Montgomery JS, Blood DA. The diagnosis and r Adenomatoid tumors are benign with no reported
Additional Therapies management of scrotal masses. Med Clin North Am. metastasis.
r Excision via inguinal approach with proximal
N/A 2011;95(1):235–244.
r Rubenstein RA, Dogra VS, Seftel AD, et al. Benign vascular control preferred.
Complementary & Alternative r Treatment for epididymitis is guided by risk of
Therapies intrascrotal lesions. J Urol. 2004;171:1765–1772.
sexually transmitted infections as a source.
N/A See Also (Topic, Algorithm, Media) r Ultrasound is important to delineate a testicular vs.
r Adenomatoid Tumors, Testicular and Paratesticular
paratesticular origin of the mass.
ONGOING CARE Image
r Epididymis, Cystadenoma
PROGNOSIS r Epididymis, Metastasis to
Adenomatoid tumors are uniformly benign with no r Epididymitis
well-documented cases of true invasion, metastasis, or r Paratesticular Tumors, General
recurrence after excision (3)[C] r Sexually Transmitted Infections
COMPLICATIONS
Scrotal hematoma, pain, infection
FOLLOW-UP
Patient Monitoring
r Oncologic follow-up if malignant disease
r Patient testicular self-exam
Patient Resources
http://www.aafp.org/afp/1998/0215/p685.html
17
ADRENAL ADENOMA
Aaron G. Boonjindasup, MD, MPH
DIAGNOSTIC TESTS & INTERPRETATION r SCS is an indication for adrenalectomy.

BASICS Lab r Patients are at risk for postoperative adrenal
r Extent of endocrine evaluation in patients with
insufficiency (AI).
DESCRIPTION adrenal adenoma is controversial. Basic screening r Pheochromocytoma:
r Adrenal adenoma is a benign cortical neoplasm that
evaluation consists of:
may or may not have endocrine activity (functioning) – If screening: Stop tricyclic antidepressants,
– Basic metabolic panel (BMP)
r Up to 80% are nonfunctioning and benign; the ◦ If elevated K+ and patient also hypertensive phenoxybenzamine before testing
other 20% need further evaluation may be aldosterone-secreting lesion – Screening tests
– Generally <4 cm and discovered incidentally – Plasma metanephrines: Most sensitive test for – Plasma-free metanephrines
pheochromocytoma ◦ Stop acetaminophen 5 days prior
EPIDEMIOLOGY ◦ Draw sample in supine position
– 24-hr urine cortisol
Incidence – 24-hr fractionated urinary metanephrines
– Low-dose dexamethasone suppression test to R/O
∼1% if <30 yr old and 7% if >70 yr old ◦ Verify normal renal function before testing
SCS if suspected clinically
Prevalence r Complete endocrine evaluation should be performed r See pheochromocytoma section for details.
r Found in 1.8–8.7% of autopsies
if findings on examination and history suggest
r Incidental adrenal masses found on 0.5–5% of excess of specific hormone or if positive findings Imaging
abdominal CTs (82% nonfunctional, 5% Cushing, found on screening examination r Adrenal adenoma: Small, well defined,
5% pheochromocytoma, 1% Conn) r Primary hyperaldosteronism (Conn syndrome)
homogeneous
– Usually between 20 and 60 yr old – Basic metabolic profile r Size criteria important
RISK FACTORS ◦ Hypokalemia, alkalosis, HTN
– ≤5 cm usually benign
Slightly more common in females – Aldosterone: Renin ratio – ≥6 cm – 25% malignant
◦ Values that define a positive screen subject to r May see atrophy of contralateral adrenal
Genetics lab variability but >30 suggested by NIH as
More common in multiple endocrine neoplasia (MEN) r CT (triphasic adrenal scan)
cutoff for positive aldosterone to renin ratio and
type I, Beckwith–Wiedemann syndrome, and the indicates need for confirmatory testing – CT Adenoma characteristics: Sharp margin,
Carney complex – Confirmatory testing for hyperaldosteronism smooth and homogeneous, lipid rich, <10 HU
◦ 3-day oral sodium-loading test—high sodium density on noncontrasted images, density reduces
PATHOPHYSIOLOGY by 60% on initial contrast density at scan delayed
r Primary hyperaldosteronism (Conn syndrome) diet for 3 days followed by 24-hr urine
measurements of aldosterone, sodium, and 15 min
– Excess production of aldosterone (Zona
creatinine – <10 HU on noncontrast CT
Glomerulosa): Hypokalemia, Alkalosis, HTN ◦ 71% sensitive, 98% specific for adenoma
r Cushing syndrome ◦ + test = 24-hr aldosterone > 12 mg/d
◦ Captopril suppression test may be used for – >60% washout at 15 min
– Excess production of cortisol (Zona Fasciculata): ◦ 100% sensitive/100%specific for adenoma
Suppresses ACTH from pituitary patients with cardiac and renal disease which
prohibit sodium loading – Adrenal myelolipoma – low HU, but never below
ASSOCIATED CONDITIONS r Cushing syndrome 20 HU
r Hypertension r MRI
– 24-hr urine cortisol >100 mg
r Glucose intolerance – Both carcinoma and pheochromocytomas are
– If equivocal, perform low-dose dexamethasone
r MEN1 syndrome suppression test hyperintense on T2 images (ie, they “light up” as
r Subclinical Cushing syndrome (SCS) (obesity, ◦ 1 mg dexamethasone at 11 PM they go from T1 to T2)
hypertension, type 2 diabetes, hypercholesterolemia) ◦ Plasma cortisol between 8 AM and 9 AM – Signal from cortical adenomas drops out in
◦ Normal: Cortisol <5 ng/mL opposed phase
◦ Cushing syndrome: Inability to suppress cortisol ◦ Loss of signal between in- and out-of-phase
DIAGNOSIS production images (microscopic fat-sensitive sequence)
– Rule out ACTH-dependent cause (ectopic or suggest adenoma
HISTORY ◦ MRI T2 intensity <0.8 compared to liver
r Determine history of hypertension, obesity, and pituitary hypersecretion of ACTH)
◦ 80% sensitive/80% specific for adenoma
– Measure late-afternoon ACTH
glucose intolerance
– >15 pg/mL – ACTH dependent Diagnostic Procedures/Surgery
– Suggestive of Cushing syndrome or adrenocortical r Adrenal biopsy or fine needle aspiration may be
– <15 pg/mL – ACTH independent (adrenal)
carcinoma
r Hypertension and history of hypokalemia – Adrenal venous sampling may be indicated if performed in select cases
bilateral adrenal lesions present to establish – Reserved for differentiation of metastatic disease
– Aldosterone-producing adenoma lateralization of aldosterone secretion in surgical and benign lesion
r History of malignancy
candidates – May not be able to differentiate between benign
r Patient medications (“polypharmacy” for
from malignant adrenocortical tumor
hypertension) ALERT r Rule out pheochromocytoma with plasma
r Family history Subclinical Cushing syndrome (SCS can occur where
metanephrine screening before performing biopsy
abnormalities of the hypothalamic–pituitary– on an adrenal mass
PHYSICAL EXAM adrenal axis exists in the absence of overt signs and
r Blood pressure and heart rate Pathologic Findings
r Look for stigmata of Cushing syndrome symptoms of Cushing syndrome. r Aldosterone-producing adenoma
r May occur in 5–24% of patients with incidentally
– Hirsutism, oligomenorrhea, easy bruising, – Spironolactone bodies – eosinophilic laminated
excessive acne, muscle weakness, truncal obesity, discovered adrenal tumors. cytoplasmic inclusions
r May not be clinically evident following standard ◦ Found after treatment with spironolactone
buffalo hump, purple striae
screening for cortisol hypersecretion. – Cortisol-producing adenoma
r 1 mg overnight dexamethasone suppression test – Vacuolated neoplastic cells
most sensitive for SCS. – Intracytoplasmic lipid
r Should be performed in ALL patients with adrenal r Bilateral adrenal adenomas
mass and metabolic syndrome. – Fungal, TB, histoplasmosis
18
ADRENAL ADENOMA
A
DIFFERENTIAL DIAGNOSIS r Steroid supplementation will be needed after COMPLICATIONS
r Adrenal cortical carcinoma (up to 80% functional) adrenalectomy for cortisol-producing tumors until r Hypertension
r Adrenal hemorrhage suppressed HPA recovers (median of 15 mo) r Diabetes mellitus
– Bilateral lesions – Postoperatively (POD 2): Hydrocortisone 20 mg PO r Atherosclerosis
r Adrenal hyperplasia (pituitary hypersecretion of qAM, 10 mg qPM r Poor wound healing
ACTH) – Hydrocortisone slowly tapered over 3 mo to r Nephrolithiasis
r Adrenal myelolipoma 10 mg daily
– 15% of patients with Cushing syndrome – due to
r Lymphoma – AM cortisol should be measured and repeated
hypercalciuria
r Metastatic lesion until >10 ng/dL r Adrenal insufficiency (Addison disease)
– Confirm recovery of HPA with cosyntropin test
– Melanoma, lung, breast, kidney r Monitor for electrolyte disturbances with BMP and
r Neuroblastoma FOLLOW-UP
r Nonfunctioning adenoma postoperative AI in patients with hormonally active Patient Monitoring
tumors and/or SCS r Nonfunctioning benign adrenal mass can be
r Pheochromocytoma r Acute AI (addisonian state) followed with physical and radiologic examinations
r TB, or other infectious cause
– 5–20% show enlargement >1 cm
ALERT – No guideline on growth velocity on surgical
This is a life-threating condition often preceded by treatment
TREATMENT hypotension unresponsive to fluid resuscitation.
GENERAL MEASURES r May occur in the postoperative state in the setting
r Based on functional status and size of lesion of cortisol-secreting lesion with downregulated
REFERENCES
r Correct hypertension and electrolyte abnormalities. contralateral adrenal function, and in patients 1. Kapoor A, Morris T, Rebello R. Guidelines for the
MEDICATION with previous contralateral adrenal resection or management of the incidentally discovered adrenal
due to concurrent illness or infection. mass. Can Urol Assoc J. 2011;5(4):241–247.
First Line r Other nonspecific symptoms may include
r For hormonally active adenomas in patients who 2. Gill IS. The case for laparoscopic adrenalectomy.
refuse surgery or have contraindications to surgery abdominal pain, salt craving, nausea, vomiting, J Urol. 2001;166:429–436.
r Conn syndrome fatigue, and fever. 3. Bittner JG, Brunt LM. Evaluation and management
r Electrolyte abnormalities such as hypernatremia or of adrenal incidentaloma. J Surg Onc. 2012;106:
– Spironolactone, eplerenone
◦ Aldosterone receptor antagonists in the distal hyperkalemia and other laboratory anomalies such 557–564.
convoluted tubule (DCT). as anemia, lymphocytosis, or eosinophilia may 4. Mandevillle J, Moinzadeh A. Adrenal
– 2nd line – Amiloride, triamterene also be found. incidentalomas: AUA Update Series. 2010;29:
◦ Inhibitors of DCT aldosterone sensitive sodium r Prolonged use of etomidate may increase risk of 33–39.
channels postoperative adrenal insufficiency. See Also (Topic, Algorithm, Media)
r Cushing syndrome r May begin steroid replacement if high clinical r Adrenal Adenoma Image
– Aminoglutethimide index of suspicion. r Adrenal Cortical Carcinoma
◦ Blocks the 1st step in cortisol synthesis r Diagnosis Obtain AM serum cortisol and ACTH r Adrenal Cysts and Pseudocysts
(cholesterol to pregnenolone) r Adrenal Hemorrhage
level:
– Metapyrone r Adrenal Incidentaloma
◦ Blocks the final step in cortisol synthesis – Normal >10 ng/dL, low–normal
(3.4–10 ng/dL), AI <3.4 ng/dL r Adrenal Mass
(11-deoxycortisol to cortisol)
– Confirmatory testing with evaluation of r Adrenal Mass, Algorithm
– Ketoconazole
◦ Inhibits 1st step and to a lesser extent the last response to ACTH stimulation (cosyntropin test) r Adrenal Mass Image
step in cortisol synthesis ◦ Measure serum cortisol at baseline r Adrenal Metastasis
◦ Give cosyntropin 0.25 mg IV × 1 r Adrenal Myelolipoma
Second Line ◦ Measure serum cortisol 60 min after dose r Adrenal Myelolipoma (Adrenal Myolipoma)
N/A
◦ Adequate response: Cortisol >18 μg/dL
SURGERY/OTHER PROCEDURES r If acute AI is highly suspected, don’t wait for
r Surgical indications
– Hormonally active masses
result before treating: CODES
– Give 2–3 L D5 NS quickly and 4 mg
– Any masses ≥5 cm (25% of masses >6 cm are dexamethasone IV
assumed to be adrenal cortical carcinomas) ICD9
– Use dexamethasone because IV cortisol will r 227.0 Benign neoplasm of adrenal gland
– Masses with suspicious imaging characteristics of
interfere with the diagnosis later during r 255.0 Cushing’s syndrome
carcinoma
◦ Homogeneous, irregular borders, HU >20 hospitalization r 255.12 Conn’s syndrome
r Laparoscopic and robotic approaches described, but r Maintenance therapy:
may have limitations with larger lesions – Hydrocortisone 30 mg/d ICD10
r D35.00 Benign neoplasm of unspecified adrenal
r Retroperitoneal approach possible for both open – Fluorohydrocortisone 0.05–0.1 μg/d
gland
and laparoscopic surgery; may reduce ileus r E24.0 Pituitary-dependent Cushing’s disease
r Perioperative stress dose steroids indicated during
ONGOING CARE r E26.01 Conn’s syndrome
unilateral adrenalectomy for cortisol-producing
adenomas and may be indicated for patients with PROGNOSIS
SCS r Untreated Cushing syndrome can be fatal due to CLINICAL/SURGICAL
r Preoperatively: 50 mg hydrocortisone IV q8h postop
day 1
cardiovascular, thromboembolic, or hypertensive PEARLS
complications or infection
r Surgical removal of hormonally active adenomas is r Adrenal lesions should be surgically treated if
usually curative ≥5 cm or if functional/active.
r No guideline on normal growth velocity for adrenal
lesions.
r Melanoma, lung, breast, colon, and renal cell
cancers have metastatic predilection to adrenal
gland.
19
ADRENAL CORTICAL CARCINOMA

John M. Lacy, MD, FACS
Imaging
BASICS DIAGNOSIS r CT of abdomen is preferred initial study in patients
adrenal lesion:
DESCRIPTION HISTORY – Benign tumors
r Most common symptoms are related to excess
Adrenal cortical carcinoma is a primary malignancy ◦ Homogeneous appearance with well-delineated
arising in the adrenal cortex cortisol production (Cushing’s syndrome) in margins
50–60%, then virilization (20%), or mixed ◦ Generally <4–6 cm, smooth and round or oval
EPIDEMIOLOGY syndromes (20–30%) contour
Incidence r History of onset of symptoms <12 mo is suspicious ◦ <10 HFU or rapid washout of contrast <15 min
r Rare: 0.5–2 cases per million people per year
for ACC – Primary ACCs:
r Bimodal occurrence: r Constitutional symptoms: ◦ Nonhomogeneous internal architecture
– Initial peak in children <5 yr old; – Weight loss, malaise, weakness, nausea, or ◦ Irregular contour, invasion of surrounding
– 2nd peak in adults in 4th and 5th decades of life vomiting usually associated with poor prognosis structures
r Female:male ratio ∼1.5:1 r In children, suggested by generalized weight gain ◦ >10 HFU or delayed washout of contrast
r ∼80–130 cases in USA annually and delayed linear growth >15 min
r <5% of all adrenal incidentalomas, with correlation r Nonfunctional tumors may be larger and present r MRI not proven to be more sensitive in
between size of tumor and likelihood of ACC with mass effect differentiating malignant from benign tumors:
– 2% of lesions <4 cm – Painful or palpable mass – Preferred imaging modality for evaluation of vena
– 6% of lesions 4–6 cm – Lower extremity edema caval involvement
– 25% of lesions >6 cm – Urinary obstruction – ACCs generally isodense to the liver on
Prevalence – Budd–Chiari syndrome T1-weighted images; intermediate to high signal
Mirrors incidence, as prognosis is poor – GI symptoms intensity (brighter white) on T2-weighted images
r Hyperaldosteronism (rare): (less bright than pheochromocytoma).
RISK FACTORS – Hypertension r FDG-PET potentially useful in radiologically
Genetic associations (see below) – Hypokalemic alkalosis indeterminate lesions.
Genetics r Feminization (rare) r Bone scan if suspicious of skeletal metastases.
r Sporadic cases r Incidental finding during imaging workup for other
– Inactivation of p53 on 17q13 morbidities r Role of percutaneous biopsy limited
– Alterations at 11p15 locus, site of IGF-2 – Difficult to distinguish between benign and
– Activation of β-catenin gene PHYSICAL EXAM
r Familial syndromes r Palpable abdominal mass malignant tissue
r Signs of Cushing’s syndrome (functional ACCs): – Concern for seeding biopsy tract
– Li–Fraumeni syndrome
– Beckwith–Wiedemann syndrome Violaceous striae, moon facies, truncal obesity, Pathologic Findings
buffalo hump, glucose intolerance, r Macroscopic:
– Multiple endocrine neoplasia (MEN) 1
– Congenital adrenal hyperplasia hyperpigmentation – Lobulated, orange tumor with necrotic areas,
r Signs of virilization (oligomenorrhea, hirsutism, calcifications, intratumoral hemorrhages
– Adenomatous polyposis coli
cystic acne, excessive muscle mass, voice deepening, r Microscopic:
PATHOPHYSIOLOGY temporal balding, clitoromegaly) – Weiss criteria for malignancy includes ≥3 of the
r Difficult to distinguish benign from malignant r Gynecomastia following:
adrenal tumors in absence of metastatic disease. ◦ High nuclear grade
r Pathologic features such as mitotic activity, grade, DIAGNOSTIC TESTS & INTERPRETATION ◦ Mitotic rate > 5/50/hpf
vascular invasion, various architectural features, and Lab ◦ Atypical mitotic fevers
tumor size have not consistently correlated with r Tests for glucocorticoid excess (minimum 3 out of ◦ Eosinophilic tumor cell cytoplasm
prognosis. 4 tests) ◦ Diffuse architecture in >33% of tumor
r Most (60–70%) ACCs are functioning, although this – Dexamethasone suppression test ◦ Necrosis
is related to the extent of workup. – 24-hr urinary free cortisol ◦ Vascular invasion
– Basal cortisol (serum) ◦ Sinusoidal invasion
ASSOCIATED CONDITIONS – Basal ACTH (plasma)
r Cushing’s syndrome secondary to functional tumors ◦ Capsular invasion
r Sexual steroids and steroid precursors r Antigen Ki-67 is a promising new
r Familial syndromes (see above)
– DHEA-S (serum) immunohistochemical marker
GENERAL PREVENTION – 17-OH-progesterone (serum) – Marker of proliferative activity
No recommendations – Testosterone (serum) – Low-risk ACC – expressed in <10% of cells
– 17-β-estradiol – High-risk ACC – expressed in >10% of cells
– 24-hr urine steroid metabolite exam
r Mineralocorticoid excess DIFFERENTIAL DIAGNOSIS
r Functioning adrenal masses:
– Potassium (serum)
– Aldosterone/renin ratio – Adenoma, aldosteronoma, pheochromocytoma
r Nonfunctioning adrenal masses:
◦ Only used in patients with arterial hypertension
and/or hypokalemia – Hemorrhage, cyst, metastatic tumor,
r Catecholamine excess to exclude neuroblastoma
r Other: Renal cell carcinoma
pheochromocytoma
– Meta- and normetanephrines (plasma)
– Catecholamines or metanephrine excretion
(24-hr urine)
20
ADRENAL CORTICAL CARCINOMA

A
ADDITIONAL TREATMENT REFERENCES
TREATMENT Radiation Therapy
r ACCs formerly considered radioresistant 1. Carnaille B. Adrenocortical Carcinoma: Which
GENERAL MEASURES r Now radiation used in 2 scenarios: surgical approach? Langenbecks Arch Surg.
Complete surgical excision is treatment of choice in – Adjuvant therapy in patients with high risk for 2012;397(2):195–199.
resectable stage I or II tumors and children recurrence 2. Reibenantz J, Jurowich C, Erdogan I, et al. Impact
– Palliative control of local symptomatic metastases of lymphadenectomy on the oncologic outcome of
MEDICATION
to bone, brain, or vena cava obstruction (3) patients with adrenocortical carcinoma. Ann Surg.
First Line 2012;255:363–369.
r Mitotane is the treatment of choice for metastatic Additional Therapies
r Inhibitors of steroid synthesis may be useful in 3. Polat B, Fassnacht M, Pfreunder L, et al.
ACC Radiotherapy in adrenocortical carcinoma. Cancer.
– Objective regression in tumor size in 35% controlling symptoms of glucocorticoid excess 2009;115:2816–2823.
– Dosage escalated to tolerance, which is limited – Metyrapone
– Significant toxicity – GI, CNS, endocrine – Aminoglutethimide
– Must monitor serum levels closely – Ketoconazole
– Strong inhibitor of steroidogenesis – Etomidate
ADDITIONAL READING
◦ Both glucocorticoid and mineralocorticoid r Baudin E, Leboulleux S, Al Ghuzlan A, et al.
replacement necessary ALERT Therapeutic Management of advanced
r Mitotane monotherapy may be used in patients with Hydrocortisone must be administered during surgery adrenocortical carcinoma: What do we know in
low tumor burden or indolent disease and postoperatively if patients with glucocorticoid 2011? Horm Cancer. 2011;6:363–371.
r Polychemotherapy indicated with high tumor burden excess. r Berruti A, Baudin E, Gelderblom H, et al. Adrenal
or rapidly progressive disease cancer: ESMO Clinical Practice Guidelines for
– Cytotoxic chemotherapy under investigation Complementary & Alternative
diagnosis, treatment and follow-up. Ann Oncol.
◦ Etoposide, doxorubicin, cisplatin, and mitotane Therapies 2012;23(suppl 7):vii131–8.
r Locoregional therapy may be indicated in cases of
◦ Streptozotocin and mitotane r Carnaille B. Adrenocortical carcinoma: Which
progression despite mitotane
Second Line surgical approach? Langenbecks Arch Surg.
r If failed mitotane monotherapy, add cytotoxic – Arterial chemoembolization
2012;397(2):195–199.
– Radiofrequency ablation
chemotherapy See Also (Topic, Algorithm, Media)
r If failed initial polychemotherapy regimen, may try r Adrenal Adenoma
whichever regimen was not used ONGOING CARE r Adrenal Cortical Carcinoma Image
r Clinical trials underway for targeted therapies r Adrenal Mass
PROGNOSIS
– IGF-1 receptor inhibitors r Overall prognosis is poor, with overall 5-yr survival r Adrenal Mass Algorithm
– Multi-tyrosine-kinase inhibitors
ranging from 15–60% based on stage
SURGERY/OTHER PROCEDURES r Overall recurrence rate 17–85%
r Indications for surgery (1) – 23% in R0 patients CODES
– Hormonally active mass – 51% for R1 and R2 patients
– Size >5–6 cm r Stage at diagnosis is the most important prognostic ICD9
r Open approaches variable r 194.0 Malignant neoplasm of adrenal gland
– Anterior approach (chevron or subcostal incision) r ∼70% of patients present with advanced disease r V84.09 Genetic susceptibility to other malignant
for the rare low-stage ACC (stage III or IV) neoplasm
– For more advanced ACCs, a thoracoabdominal
incision provides optimal exposure COMPLICATIONS ICD10
r Fever due to tumor necrosis r C74.00 Malignant neoplasm of cortex of unspecified
– Avoid risk of port side seeding associated with
r Anemia from hemorrhage into the tumor
laparoscopy adrenal gland
r Laparoscopy r Adrenal crisis in patients who undergo surgery for r C74.02 Malignant neoplasm of cortex of left
– Feasible in stage I and stage II tumors <10 cm in functioning tumors without adequate steroid prep adrenal gland
size r Z15.09 Genetic susceptibility to other malignant
FOLLOW-UP
– Many studies report equivalent oncologic neoplasm
Patient Monitoring
outcomes (1) r Close follow-up is critical
– Postoperative advantages r Abdominal CT or MRI and chest CT recommended
◦ Less analgesic requirement CLINICAL/SURGICAL
◦ Lower blood loss every 3 mo for a minimum of 2 yr
r Serum and urinary steroid levels should also be PEARLS
◦ Shorter postop fasting period
◦ Reduced length of hospital stay monitored, though they are less sensitive for r Rapid development of symptoms is key to
r Advanced local disease may require resection of detection of recurrence than imaging distinguishing ACC from Cushing’s syndrome.
r Follow-up should be long-term, since late recurrence r Lymphadenectomy provides improved staging and
adjacent visceral organs, portions of vena cava
and/or tumor thrombus of ACC (after ≥10 yr) is not uncommon may lead to favorable oncologic outcomes.
r Surgery may also play a role in the setting of Patient Resources r Radiation therapy useful as adjuvant therapy in
metastatic disease r www.adrenalcancerhope.org high-risk patients and for local palliation.
– Primary tumor represents the bulk of disease r www.adrenocorticalcarcinoma.org r Laparoscopic adrenalectomy feasible in experienced
– Complete resection is feasible surgeon’s hands if mass <8–10 cm.
– Tumor objectively responds to medical treatment r Close follow-up is critical, as late recurrence is
or stabilizes over period of 6 mo reported.
r Lymphadenectomy provides improved staging and
may lead to favorable oncologic outcomes (2)
21
ADRENAL INSUFFICIENCY, ACUTE (ADRENAL CRISIS)

Debasish Sundi, MD
Misop Han, MD
Genetics r Acute adrenal crisis usually presents acutely with

BASICS r Hereditary factors may influence development of hypotension or hypotensive shock:
autoimmune adrenal insufficiency. – Clinical picture is more complex as a result of a
DESCRIPTION r Familial glucocorticoid insufficiency may be mixture of preceding slow-onset symptoms and
r Acute adrenal insufficiency (Sometimes called associated with a recessive gene pattern. signs including abdominal pain, sepsis, pituitary or
r Addison disease has been associated with a variety adrenal hemorrhage, surgery, or trauma
Addisonian crisis) symptoms are attributable to
of autoimmune diseases. – Acute adrenal insufficiency should be considered
mineralocorticoid deficiency—there are many
in patients presenting in the emergency room with
etiologies (1)[A]. PATHOPHYSIOLOGY
r The adrenal cortex produces 3 classes of steroid abdominal pain, nausea, diarrhea, hypotension,
r Adrenal crisis is a subtype of acute adrenal
and fever
insufficiency; it is a rapid and intensive process hormones: Mineralocorticoids (aldosterone), – The etiology of hypotension is profound
triggered by a stressor such as surgery or sepsis. glucocorticoids (cortisol), and androgens. hypovolemia
r Symptoms of the Addison disease (chronic adrenal r Cortisol deficiency is primarily responsible for the
– Hypotension may be one of the last signs
insufficiency) are difficult to recognize; often the manifestations of the crisis. (preterminal) because mineralocorticoid secretion
diagnosis of Addison disease is made when patients r Primary adrenal insufficiency is due to failure of the is usually somewhat preserved in patients on
present with an acute crisis. adrenal cortex. chronic glucocorticoid replacement.
r Patient may present in hemodynamic compromise r Secondary adrenal insufficiency is caused by failure
PHYSICAL EXAM
secondary to sodium and plasma volume depletion. of ACTH stimulation of the adrenal cortex. r Check blood pressure: Extreme hypotension and/or
r Addisonian crisis should be treated immediately; r Chronic steroid administrations result in suppression
shock refractory to fluids and vasopressors suggests
treatment should not be delayed pending diagnostic of ACTH production via feedback inhibition acute adrenal crisis.
test results. r Vitiligo often coexists with Addison disease:
r The disease usually results from bilateral adrenal ASSOCIATED CONDITIONS
Nearly 50% of patients with adrenalitis have some Hyperpigmentation along palmar creases, buccal
cortex destruction: Destruction of the adrenal cortex form of autoimmune disease: Hypoparathyroidism, mucosa, pressure points, perianal mucosa, and
causes a combined deficiency of glucocorticoids, gonadal collapse, diabetes mellitus type I, nipple areolas.
mineralocorticoids, and adrenal androgens. hypothyroidism (Hashimoto thyroiditis), or r Check for signs of generalized weakness and
hyperthyroidism (Grave disease). specifically muscle weakness.
ALERT r Check for loss of axillary hair in females.
Hypotension and shock refractory to resuscitation GENERAL PREVENTION r In adrenal crisis, patients may be hyper- or
with fluids and vasopressors should be considered r Perioperative stress dose steroid replacement when
hypothermic.
Addisonian crisis and treated with intravenous indicated (3)[B].
steroids. r Low threshold to intervene with IV glucocorticoid DIAGNOSTIC TESTS & INTERPRETATION
replacement at early signs of fluid refractory Lab
EPIDEMIOLOGY r Plasma cortisol: Early AM levels <3 μg/dL
hypotension
Incidence (80 nmol/L) suggests diagnosis
r Addison disease incidence: 0.6/100,000 per year r Serum ACTH:
r Up to 0.7% of patients undergoing major surgery DIAGNOSIS – If low in the setting of low cortisol, patient has
may experience adrenal insufficiency pituitary/hypothalamic disease
HISTORY – If high in the setting of low cortisol, primary
Prevalence r Prior steroid use:
r Addison disease prevalence: 4–11/100,000 adrenal insufficiency exists
– Risk increases with minimum 20 mg/d prednisone r Electrolyte abnormalities: Decreased sodium and
r >75% of patients with septic shock manifest or equivalent for at least 5 days within the past chloride levels, increased potassium levels and an
adrenal insufficiency 12 mo increased BUN/Cr ratio (reflecting hypovolemia)
RISK FACTORS – Patients receiving normal physiologic levels require r Hypercalcemia may be seen during adrenal crisis
r Neonates: Bilateral adrenal hemorrhage from birth about 1 mo to recover normal adrenal function. r Hypocalcemia may be seen with associated
trauma – Extensive topical use of high-potency steroids or
high-dose inhaled steroids over prolonged periods polyglandular failure and hypoparathyroidism
r Children: Pseudomonal or meningococcal septicemia r Excess proopiomelanocortin and melanocyte-
can also be a factor
leading to acute hemorrhagic destruction of both r Lapse in steroid therapy in a patient on chronic stimulating hormone levels may be found
adrenal glands (Waterhouse–Friderichsen syndrome)
r Adults: Adrenal crisis after surgical or septic stress; therapy
r Severe physiologic stress such as burn, surgery, or ALERT
bilateral adrenal hemorrhage from systemic Labs are used only in the setting of nonemergent
anticoagulation or coagulation disorder severe bacterial infection
r Bleeding diathesis or anticoagulant use adrenal insufficiency and have no role in the acute
r Special at-risk populations: Pregnant women,
r Worsening or possibly intractable nausea, vomiting, management of adrenal crisis.
patients with idiopathic adrenal vein thrombosis,
patients who have undergone venography or and abdominal pain Imaging
r Fever may be severe or completely absent r Abdominal x-rays may show adrenal calcifications if
vascular embolization of adrenal adenoma
r Most common cause: Rapid withdrawal of steroids r Primary or secondary adrenal insufficiency usually
adrenocortical insufficiency is secondary to fungal or
from patients with adrenal atrophy secondary to present insidiously with nonspecific symptoms of TB infection.
chronic steroid use chronic fatigue, weakness and lethargy, anorexia, r Abdominal CT may show enlarged adrenal glands
r Medications: Ketoconazole, aminoglutethimide, weight loss, postural hypotension, and somnolence with TB infection or malignant mass.
dronabinol, mitotane, phenytoin, rifampin r Adrenals may be small secondary to idiopathic
atrophy, autoimmune adrenalitis, or advanced TB.
r Adrenal gland hemorrhage or thrombosis may be
seen.
22
ADRENAL INSUFFICIENCY, ACUTE (ADRENAL CRISIS)

A
Diagnostic Procedures/Surgery r Pregnancy considerations FOLLOW-UP
r Rapid ACTH stimulation (cosyntropin, a synthetic – During labor and delivery, IV normal saline 0.9% Patient Monitoring
derivative of ACTH) test: and 25 mg of IV hydrocortisone should be given r Consider increase in steroid dosing when the patient
– Following collection of baseline serum cortisol, q8h with quick tapering after delivery has an episode of minor fever, infection, trauma, or
250 μg of synthetic ACTH is administered IM or IV. – Considered compatible with lactation: Infant must physical stress.
– Plasma cortisol response is reassessed at 60 min. be monitored for adverse effects including r Monitor blood pressure, weight, serum electrolytes,
– Those with no response have primary adrenal hypoadrenalism and blood glucose levels.
failure; if the cortisol levels increase following
SURGERY/OTHER PROCEDURES r Monitor growth in pediatric patients.
synthetic ACTH injection, the adrenal insufficiency r Perioperative management during routine urologic r Bone density, ophthalmologic exams.
is secondary to pituitary dysfunction.
surgery Patient Resources
Pathologic Findings – Consultation with the preoperative physician for
r Autoimmune adrenal cortical infiltrate National Library of Medicine: http://www.nlm.nih.gov/
medical clearance and the procedural medlineplus/ency/article/000378.htm
r Adrenal cortical infarction/necrosis, with or without anesthesiologist is advised.
hemorrhage – Many patients taking low-dose prednisone (such
r Metastatic carcinoma in adrenal gland
as for autoimmune inflammatory disorder) are REFERENCES
r Tuberculous granuloma of adrenal able to undergo major surgery without any
r Radiation effect 1. Oelkers W. Adrenal insufficiency. N Engl J Med.
endocrine morbidity even without administration 1996;335:1206–1212.
of intraoperative stress-dose steroids (3)[B].
DIFFERENTIAL DIAGNOSIS 2. Annane D, Sébille V, Charpentier C, et al. Effect of
Incident fluid-refractory hypotension in this
r Acute insufficiency (addisonian crisis) (1)[A] treatment with low doses of hydrocortisone and
group should be promptly treated with IV
– Shock (septic, cardiogenic, or hemorrhagic) fludrocortisone on mortality in patients with septic
hydrocortisone.
– Acute abdomen shock. JAMA. 2002;288(7):862–871.
– Patients with chronic adrenal failure and complete 3. Marik PE, Varon J. Requirement of perioperative
r Chronic insufficiency (Addison disease) physiologic steroid replacement do generally stress doses of corticosteroids. Arch Surg.
– Secondary adrenocortical insufficiency require procedural stress-dose steroids. 2008;143(12):1222–1226.
– Celiac disease – Individualization of stress-doses and postoperative
– Syndrome of inappropriate ADH secretion taper regimens is recommended.
– Lead exposure ADDITIONAL READING
– Severe nutritional deficiencies ADDITIONAL TREATMENT
– Neurofibromatosis Radiation Therapy Williams GH, Dluhy RG. Disorders of the Adrenal
– Peutz–Jeghers syndrome N/A Cortex. In: Harrison’s Principles of Internal Medicine,
– Porphyria cutanea tarda Additional Therapies 16th ed. New York, NY: McGraw-Hill, 2004.
– Salt-depletion nephritis r Maintenance doses of steroids:
– Bronchogenic carcinoma See Also (Topic, Algorithm, Media)
– Hydrocortisone (oral): 15–20 mg qAM and r Adrenal Calcifications
– Anorexia nervosa, depression 5–10 mg qPM r Addison Disease
– Prednisone (oral): 5 mg AM and 2.5 mg PM r Addison Disease (Adrenocortical Insufficiency
– Fludrocortisone (oral): 0.05–0.2 mg/d
TREATMENT Algorithm )
Complementary & Alternative r Adrenal Hemorrhage
GENERAL MEASURES Therapies r Adrenal Hypoplasia
r In critically ill and decompensating patients, N/A
maintain airway, and ensure adequate ventilation.
r Treatment instituted with IV fluid and
dexamethasone or hydrocortisone should not be
ONGOING CARE CODES
delayed in suspected adrenal crisis. Start treatment PROGNOSIS
and perform more extensive tests once patient is r There is a high risk of morbidity and mortality ICD9
stabilized. associated with unrecognized acute crisis. May 255.41 Glucocorticoid deficiency
MEDICATION result in cardiovascular collapse if not recognized. ICD10

r Excellent long-term prognosis following immediate r E27.2 Addisonian crisis
First Line r E27.40 Unspecified adrenocortical insufficiency
r IV fluids: 0.9% NS or 5% dextrose in NS management of acute crisis and long-term
maintenance therapy.
r Hydrocortisone: 100 mg IV bolus immediately;
followed by either 100 mg q6h or 10 mg/h COMPLICATIONS CLINICAL/SURGICAL
r Abdominal distention, peptic ulcer
continuous infusion for 2–3 days (2)[A]. r Edema, glaucoma, increased intraocular pressure PEARLS
r Dexamethasone: 2–8 mg as a single dose; this may
r Hyperglycemia, hypertension
be repeated as necessary Preoperative anesthesia consultation for perioperative
r Immunosuppression stress dose steroid replacement is recommended for
Second Line r Mood changes, weight gain, hirsutism any patient on steroid therapy.
r Pediatric considerations
– Hydrocortisone: 1–2 mg/kg/dose bolus
immediately; followed by 25–150 mg/d given in
divided doses q6–8h (infants and young children)
r Geriatric considerations
– Start dosage on the low end of the dosing range
due to greater frequency of impaired cardiac and
renal function
– Increased susceptibility to adverse effects such as
glaucoma, diabetes, and osteoporosis with
long-term therapy
23
ADRENAL MASS
Kyle A. Richards, MD
PATHOPHYSIOLOGY – Primary hyperaldosteronism

BASICS r Adrenal glands consist of an outer cortex and inner ◦ Nocturia/polyuria (due to hypokalemia)
medulla and are part of endocrine system ◦ Muscle cramps and palpitations
DESCRIPTION r Aberrant secretion of hormones = symptoms – Adrenocortical carcinoma
r An adrenal mass is generally considered to be an r Adrenal cortex ◦ Abdominal/back pain
adrenal lesion >1 cm – Zona glomerulosa ◦ Cushing’s syndrome (see above)
r Often found after abdominal imaging and often ◦ Produces mineralocorticoid aldosterone ◦ Altered reproductive or sexual function
termed “adrenal incidentaloma” ◦ Regulates sodium and fluid homeostasis ◦ Hyperaldosteronism (see above)
r Rarely presents with acute or chronic symptoms ◦ Promotes exchange of potassium for sodium in – Sex steroid-secreting tumor
distal tubule of nephron ◦ Altered reproductive or sexual function
EPIDEMIOLOGY – Metastatic cancer
◦ Excess aldosterone = Conn’s syndrome
Incidence – Zona fasciculata ◦ History of extra-adrenal cancer
r Incidental adrenal mass (1,2)[A] ◦ Produces glucocorticoid cortisol r Medical history
– Peak incidence at age 50–70 ◦ Regulates cellular and glucose metabolism, – Malignancy or syndromes
– 50–60% right side, 30–40% left side, 10–15% immune processes, and other regulatory r Medications such as exogenous steroids
bilateral functions r Family history: See “Genetics”
r Female:Male 1.2–1.5:1 ◦ Excess cortisol = Cushing’s syndrome
– Zona reticularis PHYSICAL EXAM
r Nonsecretory adenoma 75% r Blood pressure and heart rate
r Cortisol-producing 8% ◦ Produces adrenal androgens
r Focus on signs suggestive of adrenal hyperfunction
◦ Excess androgens = virilization
r Pheochromocytoma 5% r Adrenal medulla or malignant disease
r Adrenocortical carcinoma 5% (3)[A] – Produces catecholamines – Cushing’s syndrome
◦ Hypertension
– Bimodal age distribution: Age <5 and 40–50 – Excess catecholamines = pheochromocytoma
r Addison’s disease = adrenal insufficiency ◦ Central adiposity
– 1–2 per million persons per year
◦ Facial rounding and plethora
– 2–6% bilateral – Usually not caused by adrenal masses ◦ Supraclavicular and upper back fat pads
– Slightly higher incidence on left side
ASSOCIATED CONDITIONS ◦ Thin skin, purple striae, and acne
r Metastases 2% r See “Genetics” ◦ Hirsutism
r Aldosteronoma 1% r Hypertension (paroxysmal or sustained) – Pheochromocytoma
Prevalence r Osteoporosis/osteopenia (cortisol excess) ◦ Hypertension, orthostasis, tachycardia
r 4% in patients undergoing CT scan r Diabetes mellitus (cortisol excess) ◦ Fever, pallor, tremor
r 6% in autopsy series r Hypokalemia (aldosterone excess) ◦ Retinopathy
r Hyperlipidemia (cortisol excess) – Primary hyperaldosteronism
r Increases with age (2)[A] ◦ Edema, paresthesias, weakness, tremors
r Pheochromocytomas
– 0.2% age 20–29; 7% age ≥70 – Adrenocortical carcinoma
– Multiple endocrine neoplasia IIa or IIb ◦ Abdominal mass
RISK FACTORS – Neurofibromatosis type 1 ◦ Cushing’s syndrome signs (see above)
r Sex (1)[A] – Von Hippel–Lindau syndrome ◦ Gynecomastia
– Malignant adrenal mass: Male > female (2:1) – Tuberous sclerosis – Sex steroid-secreting tumor
– Benign adrenal mass: Female > male (1.7:1) – Sturge–Weber syndrome ◦ Gynecomastia or testicular atrophy
r Aging – Carney triad
r Adrenocortical carcinoma DIAGNOSTIC TESTS & INTERPRETATION
r Prior history of cancer especially melanoma, lung,
– Multiple endocrine neoplasia 1 Lab
breast, or kidney
– Li–Fraumeni syndrome r Assess all for biochemical function (2)[A]
– 50% of these adrenal masses are metastases
– Carney complex r Cushing’s syndrome
Genetics – Beckwith–Wiedemann
r Rare genetic syndromes may predispose to adrenal – Hyperkalemic, hyperglycemic
GENERAL PREVENTION
masses (1,4)[B] – 24-hr urinary free cortisol (5)[A]
None ◦ <80 μg/24 h excludes diagnosis
– Beckwith–Wiedemann
◦ Overexpression of insulin-like growth factor II – Cortisol suppression testing
gene DIAGNOSIS ◦ 1 mg dexamethasone at 11 PM and measure
◦ Adrenocortical carcinoma serum cortisol at 8 AM next day
HISTORY ◦ Serum cortisol > 5 μg/dL is diagnostic
– Li–Fraumeni r Focus on symptoms suggestive of adrenal
◦ Mutations in p53 tumor suppressor gene ◦ 97% specificity
◦ 10–20% have adrenocortical carcinoma hyperfunction or malignant disease r Pheochromocytoma
– Cushing’s syndrome
– Multiple endocrine neoplasia 1 ◦ Weight gain – Plasma metanephrines
◦ 40% have adrenal masses ◦ 96–100% sensitivity, 85–89% specificity
◦ Easy bruising
◦ Adenoma and adrenocortical carcinoma – 24-hr urine fractionated metanephrines
◦ Poor wound healing
– Multiple endocrine neoplasia 2 ◦ Proximal muscle weakness ◦ 91–98% sensitivity and specificity
◦ RET-2 proto-oncogene abnormalities r Primary hyperaldosteronism
◦ Emotional and cognitive changes
associated with pheochromocytoma ◦ Opportunistic and fungal infections – Hypokalemia, mild hypernatremia, alkalosis
◦ 40–50% have adrenal masses – 40% normokalemic
◦ Altered reproductive function
– Carney complex – Aldosterone-to-renin ratio (morning)
◦ 30% have adrenal hypercortisolism – Pheochromocytoma
◦ Episodic symptoms ◦ Patients must stop spironolactone, eplerenone,
– McCune–Albright syndromes ◦ Forceful heartbeat, pallor, tremor, headache, or amiloride
◦ Associated with adrenal hypercortisolism ◦ Cutoff for + result is lab dependent
and diaphoresis
– Von Hippel–Lindau disease ◦ Spontaneous or precipitated by postural change, – Confirmatory testing
◦ 10–20% have pheochromocytoma ◦ Saline infusion test
anxiety, meds, and Valsalva
– Neurofibromatosis type 1 ◦ 24-hr urinary aldosterone excretion test while
◦ Up to 5% have pheochromocytoma patient maintains high sodium diet
24
ADRENAL MASS
A
r Adrenocortical carcinoma (3)[A] REFERENCES
– Most commonly cortisol secreting TREATMENT
– Serum dehydroepiandrosterone (DHEA) 1. Barzon L, Sonino N, Fallo F, et al. Prevalence and
r Sex steroid-secreting tumor GENERAL MEASURES natural history of adrenal incidentalomas. Eur J
r Observation, resection, or medical therapy Endocrinol. 2003;149:273–285.
– Serum testosterone and 17β-estradiol in women r Depends on size of lesion, functionality, malignant 2. Young WF. The incidentally discovered adrenal
with virilization or men with feminization mass. N Engl J Med. 2007;356:601–610.
potential, and overall health of patient
Imaging 3. Ng L, Libertino JM. Adrenocortical carcinoma:
MEDICATION
r CT scan (2)[A] Diagnosis, evaluation, and treatment. J Urol.
First Line 2003;169:5–11.
– Benign adrenal adenoma r Cushing’s syndrome (5)[C]
◦ Usually <3 cm and homogeneous 4. Aron D, Terzolo M, Cawood TJ. Adrenal
– Aminoglutethimide, metyrapone, ketoconazole
◦ Density <10 HU with >50% washout of r Pheochromocytoma incidentalomas. Best Pract Res Clin Endocrinol
contrast at 10 min Metab. 2012;26:69–82.
– Phenoxybenzamine, propranolol 5. Mandeville J, Moinzadeh A. Adrenal incidentaloma.
– Adrenocortical carcinoma or adrenal mets r Primary hyperaldosteronism: Spironolactone
◦ Usually >4 cm, heterogeneous, calcifications, AUA Update Series. 2010;29:34–39.
r Adrenocortical carcinoma: Mitotane
necrosis
◦ Density >25 HU and <50% washout of Second Line
contrast at 10 min r Adrenocortical carcinoma ADDITIONAL READING
r MRI – Cisplatin, etoposide, 5-flurouracil, doxorubicin,
vincristine Taffel M, Haji-Momenian S, Nikolaidis P, et al. Adrenal
– Benign adrenal adenoma imaging: A comprehensive review. Radiol Clin N Am.
◦ Rapid contrast washout and high lipid content;
SURGERY/OTHER PROCEDURES 2012;50:219–243.
isointense with liver on T2 r Should remove all functional adrenal masses
– Adrenocortical carcinoma or adrenal mets r Open surgery if large or locally advanced; evaluate See Also (Topic, Algorithm, Media)
◦ Hyperintense with liver on T2 imaging r Addison Disease
for vein thrombus or adjacent organ invasion r Adrenal Adenoma and Cortical Carcinoma
– Pheochromocytoma r Minimally invasive surgery is now accepted
◦ “Light bulb” sign: see very high signal intensity r Adrenal Angiomyelolipoma
r Remove masses >5 cm; high malignancy risk
on T2-weighted imaging r Adrenal Calcifications
r Metaiodobenzylguanidine (MIBG) scan r Consider partial adrenalectomy for solitary adrenals,
r Adrenal Cysts and Pseudocysts
– Useful for extra-adrenal pheochromocytoma bilateral disease, familial syndromes r Adrenal Hemorrhage
Diagnostic Procedures/Surgery ADDITIONAL TREATMENT r Adrenal Incidentaloma
r Primary hyperaldosteronism Radiation Therapy r Adrenal Mass Algorithm
– Adrenal vein sampling for lateralization of Only for palliation of bone metastases from adrenal r Adrenal Mass Image
aldosterone production, if unclear by imaging cortical carcinoma r Adrenal Metastasis
r Biopsy r Adrenal Myelolipoma
– Rule out pheochromocytoma prior to biopsy N/A r Adrenal Oncocytoma
– Helpful if concern for metastases or infection r Cushing’s Disease and Syndrome
Pathologic Findings Therapies r Pheochromocytoma
See “Differential Diagnosis” N/A
r Adrenal cortical tumors (4)[A] ONGOING CARE CODES
– Adenoma
– Carcinoma PROGNOSIS ICD9
r Adrenalectomy cures hypertension in 33–72% of r 194.0 Malignant neoplasm of adrenal gland
– Nodular hyperplasia
r Adrenal medullary tumors r 227.0 Benign neoplasm of adrenal gland
patients with primary hyperaldosteronism (5)[B]
r 10–15% recurrence rate after resection of r 255.9 Unspecified disorder of adrenal glands
– Pheochromocytoma
– Ganglioneuroma/neuroblastoma pheochromocytoma ICD10
r Other adrenal tumors r Adrenocortical carcinoma has poor prognosis r C74.90 Malignant neoplasm of unsp part of
– Myelolipoma, lipoma, hemangioma – Mean survival 18 mo (4)[B] unspecified adrenal gland
– Metastases r D35.00 Benign neoplasm of unspecified adrenal
– Hamartoma, teratoma – 5-yr survival 15–47%
r Infectious or inflammatory gland
COMPLICATIONS r E27.9 Disorder of adrenal gland, unspecified
– Abscess or fungal infection r Adrenal insufficiency post adrenalectomy
– Amyloidosis, sarcoidosis r Unrecognized malignancy/pheochromocytoma
– Cytomegalovirus
FOLLOW-UP
CLINICAL/SURGICAL
– Cysts (pseudocysts, parasitic, epithelial- and
endothelial-lined cysts) Patient Monitoring PEARLS
r Congenital adrenal hyperplasia r Conservative management principles (2)[B] r Assess all for biochemical function.
r Hemorrhage r Remove all adrenal masses >5 cm.
– Repeat imaging at 6, 12, and 24 mo
r Pseudoadrenal masses – Repeat hormonal testing annually for 4 yr r Do not biopsy pheochromocytoma.
– Splenic, pancreatic, renal lesions – If growth ≥1 cm or autonomous hormonal
– Vascular lesions or technical artifacts secretion, consider surgery
Patient Resources
r www.pheochromocytoma.org
r www.cancer.gov/cancertopics/types/adrenocortical
25
AMYLOIDOSIS, GENITOURINARY
Christopher Wright, MD
Mark L. Jordan, MD, FACS
ASSOCIATED CONDITIONS DIAGNOSTIC TESTS & INTERPRETATION

BASICS r End-stage renal disease (ESRD) requiring dialysis r Proteinuria in 50–80%
r Nephrotic syndrome r Renal failure in 50%
DESCRIPTION r Diabetes r Elevated liver function tests (cholestatic pattern)
r Heterogeneous group of disorders with extracellular r Multiple myeloma r Diagnosis of AL amyloidosis requires evidence of a
deposition of protein in abnormal fibrillar form: r Familial Mediterranean fever (FMF) monoclonal proliferative disorder
– Can involve any organ system – Serum or urine monoclonal (M) protein can be
– Hereditary inflammatory disorder characterized by
– Kidney, ureters, seminal vesicles, prostate, penis, detected
severe attacks of abdominal pain in 95% of
and testis can be involved
patients Imaging
– >50% of genitourinary (GU) tract cases involve
– AA amyloidosis with renal failure is common r CT or ultrasound (US) may demonstrate
the bladder
complication hydronephrosis secondary to obstruction (ureteral
– Commonly forms “pseudotumors” in bladder,
ureter, or renal pelvis GENERAL PREVENTION amyloid)
r 25 structurally unrelated proteins known to cause N/A r Magnetic resonance imaging (MRI):
amyloidosis – T2-weighted images are suggestive of amyloid
r May be primary, secondary, or hereditary deposition. Can be confused with prostate cancer
r May be organ limited or systemic DIAGNOSIS invading into seminal vesicles on MRI for prostate
r Clinical presentation depends on the number and Diagnostic Procedures/Surgery
EPIDEMIOLOGY r Cystoscopy for hematuria
nature of the organs affected
Incidence r Even in patients with multiple-organ involvement, it – Lesions are difficult to distinguish from transitional
r Uncommon disorder and exact worldwide incidence
is usually possible to identify 1 organ as the cell carcinoma (TCC) without biopsy or resection
is unknown r Ureteroscopy or retrograde pyelogram for ureteral
– In the United States appears to be stable at “dominant” site of involvement
involvement
6–10 cases per million person-years HISTORY r Biopsy
r Age-specific incidence rates increase in each decade r Nonspecific symptoms such as fatigue and weight
– Abdominal fat pad aspirate or bone marrow
over age 40 loss are common biopsy have high success rates and are preferred
– Median age at diagnosis is 64 yr and <5% of r Patient on dialysis
sites of biopsy
patients are under age 40 (1) r Family history of amyloidosis
– Renal biopsy performed if former is negative with
r Chronic disease or inflammation high suspicion
RISK FACTORS
r Chronic and recurrent mucosal and submucosal r Cardiac: ◦ Will be positive in >90% of cases
inflammation – 60% of patients Pathologic Findings
r Hemodialysis patients develop deposits in kidneys – Signs/symptoms of heart failure r Diagnosis requires histologic demonstration of
r Chronic inflammatory disorders r Neurologic:
amyloid deposits:
– 20% with mixed sensory and peripheral – Congo red stain
Genetics neuropathy
r Familial or hereditary amyloidosis exists ◦ Orange under light microscope
r Dozens of specific variations described – Carpal tunnel syndrome ◦ Green birefringence under polarized light
r Liver:
r Familial forms often do not present until adulthood – Electron microscopy can be used to identify
– 70% will have hepatomegaly microfibrils
r Patients with immunoglobulin light chain (AL) r Bladder: – Immunohistochemical analysis assists in typing:
amyloidosis frequently have chromosomal – Painless hematuria in 75% ◦ Diagnosis of transthyretin-type amyloidosis
abnormalities but there is no single chromosome – Irritative symptoms (urgency, frequency) limits need for further evaluation as it identifies
change that is diagnostic – Clinically similar to bladder cancer the amyloidosis as inherited
PATHOPHYSIOLOGY r Ureter: r Seminal vesicle amyloidosis can be seen in radical
r More than 20 distinct low–molecular-weight – Flank pain if obstruction prostatectomy specimens but the significance is
proteins are recognized to form amyloid fibrils, the – Anuria if bilateral amyloidosis unknown
2 most common being (2): – Hematuria
r Prostate: DIFFERENTIAL DIAGNOSIS
– AL, formerly referred to as primary amyloidosis r Bladder
◦ Fibrils composed of fragments of monoclonal – Hematuria – Difficult to distinguish from TCC without biopsy
light chains – Bladder outlet obstruction may be present r Ureter
◦ Affected patients may have amyloidosis alone or
in association with other plasma cell dyscrasias PHYSICAL EXAM – May be confused with stones or other causes of
r Peripheral edema (nephritic syndrome) obstruction (eg, strictures)
(eg, multiple myeloma) r Hepatosplenomegaly r Nephrotic syndrome and glomerulonephritis
– AA amyloidosis
◦ Fibrils composed of fragments of the acute r Generally no specific physical exam findings
phase reactant serum amyloid A
◦ Typically reactive (secondary) to chronic
inflammation
r Thought to be a misfolding event; misfolded variants
are prone to self-aggregation
– These become insoluble complexes that
accumulate in tissues
r Renal amyloid is often a glomerular deposition
leading to proteinuria
26
AMYLOIDOSIS, GENITOURINARY
A
ADDITIONAL READING
TREATMENT ONGOING CARE r Javed A, Canales BK, Maclennan GT. Bladder
GENERAL MEASURES PROGNOSIS amyloidosis. J Urol. 2010;183:2388–2389.
r In AL amyloidosis treatment is aimed at reducing the r Single institution experience of 421 patients who r Mangera A, Linton KD, Fernando M, et al. What is
production of monoclonal light chain precursor with received high-dose melphalan with stem cell the evidence for the management of urethral
chemotherapy or, occasional, radiotherapy or transplant shows event-free survival and overall amyloidosis? A systematic review of the literature.
surgery of a localized amyloidogenic plasmacytoma survival of 2.6 and 6.3 yr, respectively (4) BJU Int. 2012;109:1858–1861.
r In AA amyloidosis treatment is generally supportive r Long-term survival in those who develop renal
with therapy directed at primary cause if identified failure remains poor r Amyloidosis Image
– Ranges from 12–24 mo r Bladder Tumors, Benign and Malignant, General
MEDICATION r AA amyloidosis has better prognosis
First Line Considerations
r High-dose melphalan chemotherapy followed by COMPLICATIONS r Bladder Mass, Differential Diagnosis
autologous blood stem cell transplantation (2) See above r Filling Defect, Upper Urinary Tract (Renal Pelvis and
– 25–67% complete hematologic response seen in FOLLOW-UP Ureter)
single and multicenter trials Patient Monitoring
– Response far exceeds cyclic oral melphalan and r Bladder or urethra
prednisone (see 2nd line) – Repeat periodic surveillance cystoscopies CODES
r Colchicine can be used in FMF to prevent proteinuria
– Recurrence rates >50%
Second Line r Ureters ICD9
r Low-dose oral melphalan with prednisone in a r 277.30 Amyloidosis, unspecified
– US or CT to monitor hydronephrosis
cyclical fashion r 277.39 Other amyloidosis
Patient Resources r 583.81 Nephritis and nephropathy, not specified as
– Rarely results in complete hematologic response Amyloidosis foundation (www.amyloidosis.org)
or reversal of amyloid-related organ dysfunction acute or chronic, in diseases classified elsewhere
SURGERY/OTHER PROCEDURES ICD10
r Renal transplant REFERENCES r E85.3 Secondary systemic amyloidosis
– Graft survival similar to matched controls without 1. Kyle RA, Linos A, Beard CM, et al. Incidence and r E85.8 Other amyloidosis
amyloidosis natural history of primary systemic amyloidosis in r N08 Glomerular disorders in diseases classified
– Recurs in graft in 20–33% due to continued Olmsted County, Minnesota, 1950 through 1989 elsewhere
activity of underlying disease [see comments]. Blood. 1992;79:1817–1822.
r TUR of bladder lesion with fulguration
2. Sanchorawala V, Jacobson DR, Seldin JC, Buxbaum
– Adjuvant intravesical DMSO has shown success in JN. The Amyloidoses. In: Lichtman MA, Kipps TJ, CLINICAL/SURGICAL
preventing recurrence (3) Seligsohn U, Kaushansky K, Prchal JT, eds. Williams PEARLS
ADDITIONAL TREATMENT Hematology, 8th ed. New York, NY: McGraw-Hill; r Both surgically and radiologically, genitourinary
Radiation Therapy 2010.
3. McCammon KA, Lentzner AN, Moriarty RP, et al. amyloidosis may mimic TCC in GU tract, therefore
Only rarely used for localized amyloidogenic biopsy is needed.
plasmacytoma Intravesical dimethyl sulfoxide for primary r Abdominal fat pad aspirate is preferred location to
amyloidosis of the bladder. Urology. 1998;52:
Additional Therapies 1136–1138. obtain biopsy, followed by bone marrow and finally
r Supportive care kidney.
4. Cibeira MT, Sanchorawala V, Seldin DC, et al.
– Management of heart failure
Outcome of AL amyloidosis after high-dose
– Salt restriction, diuretics, and treatment of
melphalan and autologous stem cell
secondary hyperlipidemia for nephrotic syndrome
transplantation: Long-term results in a series of
– Analgesics for neuropathic pain
421 patients. Blood. 2011;118:4346–4352.
Therapies
N/A
27
ANDROPAUSE (LATE-ONSET HYPOGONADISM)

Katie S. Murray, DO
Tomas L. Griebling, MD, MPH, FACS
r Blood glucose to screen for diabetes mellitus

BASICS DIAGNOSIS r PSA for prostate cancer screening
r Monitoring while on testosterone replacement
DESCRIPTION HISTORY
r Hypogonadism is a reduction in serum testosterone r Patients often complain of: therapy (TRT)
– CBC to monitor hematocrit (risk of polycythemia)
and other circulating androgens – Frailty-decreased grip strength, diminished gait
– PSA
– Primary hypogonadism: Arises directly from speed, easy fatigue and exhaustion, unintentional
– Liver function tests
testicular causes weight loss, and low levels for physical activity
– Secondary hypogonadism is where changes occur – Decreased energy Imaging
in hypothalamic–pituitary–testicular axis – Decreased mentation Bone density scan to evaluate for osteopenia or
– Late-onset hypogonadism is a gradual reduction – Diminution in muscle mass and strength osteoporosis
in serum testosterone levels in elderly men; often – Decreased libido Diagnostic Procedures/Surgery
referred to as “andropause.” – Erectile dysfunction Prostate biopsy if PSA and DRE are suspicious for
– Loss of morning erections prostate cancer
EPIDEMIOLOGY – Increased visceral fat
r Estimates suggest more than 4.5 million elderly Pathologic Findings
– Decrease in bone mineral density (osteoporosis
American men may be affected and osteopenia) N/A
r 80% of men report moderate or severe scores – Sleep disturbances DIFFERENTIAL DIAGNOSIS
consistent with hypogonadism on surveys (1)[B] – Depression r Acute critical illness (surgery, head trauma)
r Thought to be underreported and underdiagnosed in – Metabolic syndrome r Age-related decline (“Andropause”)
elderly males
– Poor glycemic control and diabetes mellitus r Alcoholism
– Coronary/CV disease r Chronic illness (liver failure, chronic renal failure,
RISK FACTORS
PHYSICAL EXAM hypertension, hypothyroidism, diabetes, sleep
Decreases in serum testosterone occur naturally as r Overall energy, muscle mass, and disposition apnea, obesity, anorexia nervosa, depression, HIV)
part of the aging process r Psychological evaluation r Hematologic (sickle cell disease, thalassemia)
Genetics – Screen for clinical depression r Hemochromatosis of the pituitary, Leydig cells
r Attenuated action of androgen receptor (AR) may r Include complete GU exam r Hypopituitarism (hypothalamic/pituitary)
contribute – Testis (size, consistency), digital rectal exam r Kallmann syndrome (congenital absence of GnRH)
r Those with longer AR CAG repeat polymorphism r Klinefelter syndrome
DIAGNOSTIC TESTS & INTERPRETATION
are at higher risk of andropausal symptoms (2)[B] r Medications: LHRH analogs/antagonists,
Lab
PATHOPHYSIOLOGY r TT: Diurnal variations so most accurate specimens glucocorticoids, androgens, estrogens, progestins
r Testosterone age-related declines vary by reported are obtained in the morning (prior to 10:00 AM) (eg, megestrol), chronic opioids, marijuana
study: – General accepted values although there is no clear (controversial)
– Testosterone declined approximately 100 ng/dL lab definition of hypogonadism r Noonan syndrome
(3.5 nmol/L) from age 20–80 yr – <300 ng/dL with symptoms r Pituitary infections, infiltration, trauma, radiation
– European Male Aging Study (EMAS) total – <200 ng/dL without symptoms (decreased LH/FSH production)
testosterone (TT) fell 0.4% a year and the free – FDA research trial definition: <300 ng/dL r Pituitary tumors, macroadenomas,
testosterone fell 1.3% from age 40–79 yr r Free testosterone hyperprolactinemia
r As age increases, there is: – <50 pg/mL r Prader–Willi syndrome
– Decreased number of Leydig cells within the r SHBG (sex hormone binding globulin) r Sertoli-cell-only syndrome
testicle (site of testosterone production) – Increases with aging, which leaves a greater r Testicular failure (primary): Congenital or acquired
– Decreased testicular responsiveness to LH percentage of protein-bound testosterone and anorchia, cryptorchidism, mumps orchitis, radiation
– Dampening in the amplitude of circadian release lower levels of circulating free testosterone therapy, chemotherapy
of T r Estradiol: Increased aromatization of testosterone to r Testicular tumors
– Increased serum sex hormone binding globulin estradiol in adipose tissue
(SHBG) r If abnormal TT levels, then check LH and prolactin
◦ binds T, therefore less bioavailable (functionally
active) T
r Relationship with cardiovascular (CV) disease is
thought to be multifactorial
– Nitric oxide (NO) is an important mediator in both
CV health and erectile function
r Metabolic syndrome
r Diabetes mellitus
r Hypertension
r Tobacco abuse
r Sleep apnea
r Psychological disorders
r Social stress
GENERAL PREVENTION
None
28
ANDROPAUSE (LATE-ONSET HYPOGONADISM)

A
ADDITIONAL READING
TREATMENT ONGOING CARE r Bhasin S, Cunningham GR, Hayes FJ, et al.
GENERAL MEASURES PROGNOSIS Testosterone therapy in men with androgen
r Can treat ED with phosphodiesterase-5 inhibitors if r TRT is associated with improved responses in many deficiency syndromes: An Endocrine Society clinical
no contraindications areas practice guideline. J Clin Endocrinol Metabol.
– Avanafil – Quality of life 2010;95:2536–2539.
– Sildenafil – Mood and affect r Petak SM, Nankin HR, Spark RF, et al. American
– Tadalafil – Sexual function and libido Association of Clinical Endocrinologists Medical
– Vardenafil – Cognitive function Guidelines for clinical practice for the evaluation and
– Start at lowest dose and titrate up for efficacy – Glycemic control treatment of hypogonadism in adult male
COMPLICATIONS patients–2002 Update. Endocr Pract. 2002;8:
MEDICATION
r Prostate cancer diagnosis or progression of disease 440–456.
First Line r Polycythemia
r TRT (3)[B] See Also (Topic, Algorithm, Media)
– Potential for cardiac and cerebral vascular events r Beers Criterion
– Intramuscular, transdermal (patches and gels), r Erectile Dysfunction/Impotence, General
and buccal preparations. See Section I FOLLOW-UP
Considerations
“Testosterone Replacement Therapy, General Patient Monitoring r Hypogonadism, Society Definitions
Principles” for specifics on TRT agents r Hemoglobin and hematocrit
r Bone mineral density r Testis, Normal Size
– Selection is dependent on patient/physician
r DRE and PSA for prostate cancer screening r Testosterone (Free and Total) Lab Testing
preference and feasibility
– Considerations in the older male: The American r Continued monitoring of testosterone levels r Testosterone Replacement Following Localized
Geriatrics Society (AGS) lists testosterone in the r Overall men’s health issues Prostate Cancer Therapy
Beers Criteria as a medication to generally avoid r Testosterone Replacement Therapy, General
– Blood glucose
in older adults because of potential for cardiac – Serum lipids Principles
problems and men with personal history of r Testosterone, Decreased (Hypogonadism)
– Overall cardiovascular health
prostate cancer (4)[A]
– The choice of TRT should be individualized on Patient Resources
specific clinical needs Urology Care Foundation AUA www.urologyhealth.
org/urology/index.cfm?article=132
CODES
– Absolute contraindications: Personal history of
breast cancer or untreated prostate cancer
– Relative contraindications: Polycythemia, BPH
ICD9
causing urinary retention, treated prostate cancer
REFERENCES r 253.4 Other anterior pituitary disorders
r 257.2 Other testicular hypofunction
Second Line 1. Trinick TR, Feneley MR, Welford, et al. International
N/A web survey shows high prevalence of symptomatic ICD10
testosterone deficiency in men. Aging Male. 2011; r E23.0 Hypopituitarism
SURGERY/OTHER PROCEDURES 14:10–15. r E29.1 Testicular hypofunction
Men with primary erectile dysfunction complaints can 2. Liu CC, Lee YC, Wang CJ, et al. The impact of
discuss surgical placement of penile prostheses, use of androgen receptor CAG repeat polymorphism on
vacuum erection devices, or vasoactive intracavernosal andropausal symptoms in different serum CLINICAL/SURGICAL
injection therapy testosterone levels. J Sex Med. 2012;9:2429–2437 PEARLS
ADDITIONAL TREATMENT 3. Bhattacharya RK, Khera M, Blick G, et al.
Radiation Therapy Testosterone replacement therapy among elderly Treatment is based upon symptomatology more than
N/A males: The Testim Registry in the US (TRiUS). Clin lab values.
Interv Aging. 2012;7:321–330.
N/A 4. American Geriatric Society 2012 Beers Criteria
Update Expert Panel. American Geriatrics Society
Complementary & Alternative updated Beers Criteria for potentially inappropriate
Therapies medication use in older adults. J Am Geriatr Soc.
r Increased weight-bearing exercise 2012;15:22–27.
r Diet and exercise
r Weight loss
r Phytotherapies: Limited research on safety and
efficacy of herbal medications
– Limited data on ability of any OTC supplement to
influence T levels
29
ANORECTAL MALFORMATIONS: IMPERFORATE ANUS, CLOACA, AND

UROGENITAL SINUS ANOMALIES
Youngjae Im, MD
Sang Won Han, MD
ASSOCIATED CONDITIONS PHYSICAL EXAM

BASICS r About 50–67% of all ARM are associated with r Thoroughly examine the perineum to determine
other anomalies number and position of orifices:
DESCRIPTION – In general, the higher the ARM, the more likely – Perineum flattened in higher-level ARM
r Anorectal malformations (ARMs) are a spectrum of there are associated abnormalities r Inspect the genitalia: Rule out hypospadias,
congenital anomalies involving the anorectal and r Can occur as an isolated abnormality or as part of a cryptorchidism, clitoromegaly
urogenital systems, such that the anus and distal syndrome: r Assess vertebrae: Look for sacral abnormalities
rectum are often absent – VACTERL: Vertebral, anorectal, cardiac, r Palpate for an abdominal mass that may represent a
– Imperforate anus: Absence of an anus, typically tracheoesophageal fistula, renal, limb distended bladder or hydrometrocolpos
with a fistula between rectum and lower urinary abnormalities r Rule out associated pathologies:
tract r Spinal and bony abnormalities are present in
– Cardiac auscultation for murmur
– Persistent urogenital sinus (UGS) is seen in 4 33–50% of ARM: – Insert nasogastric tube for tracheoesophageal
entities (1): – Tethered cord in 20–30%
◦ Genital ambiguity state: Most common being fistula
– Sacral agenesis, the most common vertebral – Skeletal/limb assessment
congenital adrenal hyperplasia (CAH) anomaly r Once the diagnosis of an imperforate anus is made,
◦ Pure UGS: With normal external genitalia r Genitourinary abnormalities ranges from 33% to
◦ Cloaca: In females, a common channel between assess for the presence of a fistula
almost 50% of ARM: – It may take up to 24 hr for signs of fistula to be
lower urinary tract, vagina, and rectum – VUR present in 14–56% of ARM
◦ Female exstrophy evident
– Renal agenesis: 12–30%
EPIDEMIOLOGY – Neurogenic bladder: 4–25% DIAGNOSTIC TESTS & INTERPRETATION
Incidence – Renal anomalies: Horseshoe kidney, ectopic Lab
r ARM: 1 in 4,000–5,000 live births: kidney, multicystic dysplastic kidney 4–12% r Renal profile
r Cloaca: 1 in 40,000–50,000 live births – Cryptorchidism/hypospadias: 4–6% r Urinalysis: Abnormal if fistula to urinary tract
r UGS: 1 in 500 live births r Gynecologic problems are common in ARM, but r 17-hydroxy-progesterone in UGS with virilization to
r Incidence of ARM in the setting of genetic disease is most may not be diagnosed until puberty or rule out CAH
adulthood r Karyotype if ambiguous genitalia
about 5–10%
– Duplicated vaginas with septum
Prevalence Imaging
– Absent vagina; vaginal atresia r Studies to determine level of ARM:
N/A – Bicornuate uterus
– Prone, cross-table lateral plain film
RISK FACTORS – Clitoromegaly in UGS associated with CAH ◦ Should be performed at 24 hr after birth to
r Proposed association with in utero vascular r Cardiovascular abnormalities are present in
allow enteric gas to reach the most distal area
accidents, maternal diabetes and obesity, maternal 10–30% of ARM: of the colon
ingestion of thalidomide, phenytoin, and – Atrial septal defects and ventricular septal defects ◦ Distance between rectal gas shadow and
trimethadione and maternal exposure to smoking are most common perineal opening measured
r Tracheoesophageal fistula (TEF) and esophageal r Abdominal US: Evaluate bilateral kidneys, bladder,
and caffeine
r Some degree of heritability, as incidence of atresia (EA) occur in 5–10% with ARM ± müllerian structures
subsequent children having ARM is 1% GENERAL PREVENTION r Voiding cystourethrogram (VCUG)/cloaca
Genetics International Consortium on Anorectal Malformations gram/genitogram: Evaluate presence of VUR as well
r ARM found in certain congenital syndromes with aims to identify genetic and environmental risk factors as relation of urinary tract to rectum (and to
associated genetic abnormalities (2) in ARM. No prevention reduction strategies are müllerian structures)
– Trisomy 21: Imperforate anus without fistula currently available. r Colostogram: Distal to mucous fistula and proximal
– Microdeletion of chromosome 22q11.2 to colostomy to evaluate colon and its relation to
– Familial inheritance pattern: ARM with a other pelvic structures prior to definitive surgery
rectovestibular or rectoperineal fistula, almost DIAGNOSIS r Spinal imaging:
15% had a positive family history for an ARM HISTORY – Spinal US prior to 6 mo of age
– Currarino triad: ARM, sacral agenesis, presacral r Prenatal diagnosis: Low sensitivity/specificity – Spinal MRI after 6 mo of age
mass (or meningocele); autosomal dominant – Dilated colon, oligohydramnios, and distended Diagnostic Procedures/Surgery
– Townes–Brocks syndrome: ARM, external ear vagina on prenatal US may be signs of ARM r Echocardiogram and ECG: Rule out cardiac
abnormalities, hearing loss, polydactyly, renal – Antenatal findings suggestive of cloacal anomaly: anomalies
anomalies; autosomal dominant ◦ Transient fetal ascites with bilobed or trilobed r Urodynamic study : Especially in cases of UTI, VUR,
– Cat eye syndrome: ARM, coloboma, preauricular pelvic cystic structures
tag, heart defect, urinary tract abnormalities, urinary incontinence, spinal anomalies
◦ Bilateral hydronephrosis or oligohydramnios – The most common finding on UDS is an upper
mental retardation r Lower-level ARM and UGS may go undiagnosed in motor neuron lesion with an overactive detrusor
PATHOPHYSIOLOGY newborn until later symptoms develop: and/or detrusor sphincter dyssynergia (DSD)
r Classic theory: The urorectal septum (mesoderm), – Constipation, abdominal distension in rectal r Exam under anesthesia/endoscopy: Helps delineate
fails to grow caudally to meet the lateral Rathke atresia, anorectal stenosis relationships between structures and measure
folds to divide the cloacal membrane (endoderm – Urinary incontinence and/or retention in UGS length of common channel and proximity of
and ectoderm) into the anterior urogenital – Amenorrhea and abdominal distension due to fistula/confluence to bladder neck
membrane and the posterior anal membrane. hydrometrocolpos or hematocolpos at puberty in
r Alternative theory: A mesenchymal mass displaces UGS Pathologic Findings
N/A
the dorsal cloacal membrane anteriorly, preventing
its joining with the hind gut.
30
ANORECTAL MALFORMATIONS: IMPERFORATE ANUS, CLOACA, AND UROGENITAL SINUS ANOMALIES

A
r Definitive surgery at age 2–24 mo:
r Classification systems for ARM (3)
REFERENCES
– Lower lesions: Approached through a PSARP
– Wingspread classification: Traditional “low,” – Higher lesions: Laparotomy as well as PSARP 1. Rink RC, Kaefer M. Surgical management of
“intermediate,” or “high” ARM – In cloaca with a long common channel, when disorders of sexual differentiation, cloacal
– Pena classification: Based on the presence and vagina will not reach perineum, can interpose a malformation, and other abnormalities of the
position of the fistula section of bowel between vagina and perineum genitalia in girls. In: Wein AJ, et al., eds.
– Krickenbeck anatomic classification: An anatomic – Genitoplasty in cases of virilized genitalia Campbell-Walsh Urology. 10th ed. Philadelphia,
description of ARM, type of surgical procedure r Colostomy take-down a few months after definitive PA: Saunders Elsevier; 2012.
performed, and postop assessment of bowel reconstruction, once anal dilations satisfactory 2. Marcelis C, de Blaauw I, Brunner H. Chromosomal
movements, constipation, and soiling r Further urologic surgery later as indicated (ureteral anomalies in the etiology of anorectal
r Lesions in the male: Classifying patients (ie, into reimplantation for VUR, bladder neck reconstruction malformations: A review. Am J Med Genet A.
low-lying or higher lesions) have important clinical for incontinence, augmentation for small capacity, 2011;155:2692–2704.
implications with regard to their treatment and poorly compliant bladder) 3. Nah SA, Ong CC, Lakshmi NK, et al. Anomalies
prognosis associated with anorectal malformations according
– Imperforate anus without fistula, rectal atresia, ADDITIONAL TREATMENT to the Krickenbeck anatomic classification. J Ped
rectoperineal fistula Radiation Therapy Surg. 2012;47:2273–2278.
– Recto bulbar urethral fistula N/A 4. Peña A, Hong A. Advances in the management of
– Recto posterior urethral fistula Additional Therapies anorectal malformations. Am J Surg. 2000;180:
– Rectovesical fistula Clean intermittent catheterization may be necessary in 370–376.
r Lesions in the female: cases of neurogenic bladder 5. Ganesan I, Rajah S. Urological anomalies and
– Imperforate anus without fistula, rectal atresia, chronic kidney disease in children with anorectal
rectoperineal fistua malformations. Pediatr Nephrol. 2012;27:
Therapies
– Rectovestibular fistula: Most common defect 1125–1130.
N/A
– Cloaca: Further subdivided into length of common
channels:
◦ Short (<3 cm): Good prognosis ONGOING CARE ADDITIONAL READING
◦ Long (>3 cm): More complicated and worse
prognosis PROGNOSIS r Grano C, Aminoff D, Lucidi F, et al. Long-term
r Bowel function (4):
– UGS: disease-specific quality of life in children and
◦ Some associated with virilization, as in CAH – Voluntary bowel movements in 75% of ARM after adolescent patients with ARM. J Ped Surg.
◦ Some not associated with virilization definitive repair 2012;47:1317–1322.
◦ Can be result of congenital cloaca following – Fecal soiling occurs in about half of patients with r Herman RS, Teitelbaum DH. Anorectal
isolated repair of the rectum voluntary bowel movements malformations. Clin Perinatol. 2012;39:403–422.
– Total fecal continence (voluntary bowel
movements, no soiling) in 37% of ARM; the lower See Also (Topic, Algorithm, Media)
r Anorectal Malformations: Imperforate Anus, Cloaca
TREATMENT the ARM, the chance of fecal continence
– Constipation in 48% of ARM; the lower the ARM, and Urogenital Sinus Anomalies Images
GENERAL MEASURES the more likely to have constipation r Disorders of Sexual Differentiation
r Newborn should not be given any enteric intake and r Positive prognostic factors for fecal continence: r Exstrophy, Cloacal
should have nasogastric suction Good perineal raphe, well-defined anal dimple,
r Hydrometrocolpos (present in 50% of cloaca) and
normal spine, brisk muscle reflex
urinary retention in newborn period managed with r Urinary incontinence (4): CODES
catheter drainage until operative intervention – Present overall in 9% of ARM
MEDICATION – Highest probability in cloaca (19% if common ICD9
channel <3 cm, 69% if >3 cm) r 255.2 Adrenogenital disorders
First Line r Renal failure (CKD): 1–6% (5)
r IV antibiotics neonatally and perioperatively r 751.2 Atresia and stenosis of large intestine,
r Prophylactic antibiotics continued at least until VUR rectum, and anal canal
COMPLICATIONS r 751.5 Other anomalies of intestine
is ruled out r Ongoing problems usually due to underlying
r Eventual fecal incontinence may be treated with congenital abnormality, not iatrogenic causes
r NGB in many ARM, but rarely due to surgery ICD10
combination of enemas and antimotility agents r E25.0 Congenital adrenogenital disorders assoc w
r Eventual constipation may be treated with
FOLLOW-UP enzyme deficiency
combination of enemas and laxatives r Q42.3 Congenital absence, atresia and stenosis of
r Anticholinergics may be necessary for neurogenic Patient Monitoring
r Close follow-up needed to manage long-term anus without fistula
bladder r Q43.9 Congenital malformation of intestine,
problems like fecal and urinary incontinence and
Second Line associated urologic abnormalities unspecified
N/A r Should follow through puberty and child-bearing
SURGERY/OTHER PROCEDURES age due to potential for hydrometrocolpos/
r Newborn: hematocolpos, infertility, ectopic pregnancy, delivery CLINICAL/SURGICAL
– Diverting colostomy with mucous fistula needed in issues PEARLS
all but the lowest of ARM: Patient Resources ARM usually requires neonatal surgical interventions
◦ Level of colostomy should be distal on http://www.pullthrough.org/anorectal-malformation- and follow-up to obtain and maintain fecal and
descending colon; distance between stomas treatment/ urinary continence.
should be wide to minimize the length of bowel
that could potentially be in contact with urine in
cases of fistula
– Neonatal posterior sagittal anorectoplasty
(PSARP) in low ARM
– In cases of hydrometrocolpos, vaginotomy may be
necessary as newborn
– In cases of urinary retention, cutaneous
vesicostomy may be necessary as newborn
31
ANORGASMIA, MALE
Robert L. Segal, MD, FRCS(C)
Genetics PHYSICAL EXAM

BASICS N/A r Genital exam to verify the presence and normalcy of
testicles and epididymides bilaterally
DESCRIPTION PATHOPHYSIOLOGY r Secondary sexual characteristics and hair distribution
r Anorgasmia is defined as the complete inability to r Unless a specific organic cause is noted (see Risk
r Neurologic exam to assess genital sensation
achieve an orgasm (the physical and emotional Factors), anorgasmia is associated with underlying
r May not be contributory
sensation experienced at the peak of sexual psychological factors
excitation) (1) – Fear, anxiety, hostility, and relationship difficulties DIAGNOSTIC TESTS & INTERPRETATION
– In males, orgasm is typically associated with – It has been suggested to relate to orthodoxy of
Lab
ejaculation (antegrade semen passage through religious belief (ie, it is sinful to experience r Serum morning testosterone level
the urethra) orgasm/sexual pleasure) r As indicated
– There is more robust literature in the female – “Performance anxiety” may be a common cause
r May relate to men deriving greater – Semen analysis
population with anorgasmia – Semen culture
– Also described in some references as orgasmic arousal/enjoyment from masturbation than
– Urine culture
disorder, orgasmic dysfunction, or orgasmic intercourse (2)
– Urine cytology
inhibition – Masturbatory frequency/style may be predisposing
– Thyroid screen
r Anorgasmia is often associated with factors, as men with coital anorgasmia may report
high levels of masturbation (2) Imaging
delayed/inhibited ejaculation or anejaculation, r Alcohol may transiently cause anorgasmia Scrotal/transrectal ultrasound if indicated
although orgasm and ejaculation are separate
phenomena ASSOCIATED CONDITIONS Diagnostic Procedures/Surgery
– Orgasm is a cerebrally mediated event, whereas r Anejaculation None
ejaculation is localized to the genitourinary tract r Delayed/inhibited ejaculation Pathologic Findings
r Must result in personal distress or interpersonal r Depression N/A
difficulty according to definitions by the DSM-IV-TR r Infertility
and the World Health Organization Second DIFFERENTIAL DIAGNOSIS
r Psychiatric distress (anxiety, depression)
Consultation on Sexual Dysfunction (2) GENERAL PREVENTION
r May be lifelong or acquired; may be global (every r Retrograde ejaculation
N/A
r Anejaculation
sexual encounter), intermittent or situational (in a
r Delayed ejaculation
certain environment, with a particular partner) DIAGNOSIS r Reduced ejaculation
EPIDEMIOLOGY r Penile hypnoanesthesia
HISTORY
Incidence r Is the problem lifelong or acquired?
N/A r Sexual history
Prevalence – Establish the conditions (if any) where the patient
r Difficult to clearly report, as there is no clear
is able to experience orgasm
definition of normal ejaculatory latency time r Assess the presence of life stressors or other
r In general, DE is reported at low rates in the
psychological factors, the quality of the patient’s
literature, rarely exceeding 3% (3,4), but has been nonsexual relationship with the partner
reported in up to 25% of clinical cohorts (2) r Medication use
RISK FACTORS – SSRIs and gabapentin have been implicated
r Advancing age
r Endocrinopathies (hypothyroidism, hypogonadism)
r Pelvic trauma/surgery (radical prostatectomy,
proctocolectomy, bilateral sympathectomy)
r Pelvic radiation therapy
r Neuropathy (multiple sclerosis, diabetes mellitus,
spinal cord injury)
r Secondary to medication (thiazide diuretics, tricyclic
and selective serotonin reuptake inhibitor [SSRI]
antidepressants, alcohol, gabapentin)
32
ANORGASMIA, MALE
A
ONGOING CARE r Ejaculatory Disturbances (Delayed, Decreased, or
TREATMENT
Absent)
GENERAL MEASURES PROGNOSIS r Erectile Dysfunction, Following Pelvic Surgery or
r Treatment should be etiology specific r Continued support/psychotherapy may be required
Radiation
r May include patient/couple psychoeducation and/or r Anorgasmia related to trauma/surgery, radiation
psychosexual therapy [C] therapy, and neuropathies may not be reversible
r Pharmacologic treatment has met limited success (2)
COMPLICATIONS CODES
MEDICATION None
ICD9
First Line FOLLOW-UP r 302.74 Male orgasmic disorder
None currently FDA approved Patient Monitoring r 608.89 Other specified disorders of male genital
Second Line N/A organs
r No drugs are specifically approved for treatment of
Patient Resources
anorgasmia, so any treatment is off-label (2) N/A ICD10
r F52.32 Male orgasmic disorder
– Cyproheptadine (increases cerebral serotonin
levels) r N53.11 Retarded ejaculation
– Amantadine (stimulant of dopaminergic nerves) REFERENCES
– Bupropion, buspirone, and yohimbine have been
anecdotally employed to reverse SSRI-induced 1. Mulhall JP, Nelson CJ. Male orgasmic disorder: CLINICAL/SURGICAL
What do we know? Contemp Urol. 2007;Feb 1.
anorgasmia PEARLS
2. McMahon CG, Jannini E, Waldinger M, et al.
SURGERY/OTHER PROCEDURES Standard operating procedures in the disorders of r Anorgasmia is often associated with ejaculatory
None orgasm and ejaculation. J Sex Med. 2013;10: disorders.
ADDITIONAL TREATMENT 204–229. r Unless a specific organic cause is noted, anorgasmia
Radiation Therapy 3. Rowland D, McMahon CG, Abdo C, et al. Disorders is associated with underlying psychological factors.
of orgasm and ejaculation in men. J Sex Med. r Anorgasmia related to trauma/surgery, radiation
N/A
2010;7(4 Pt 2):1668–1686. therapy, and neuropathies may not be reversible.
Additional Therapies 4. McMahon CG, Abdo C, Incrocci L, et al. Disorders r There are no approved pharmacologic treatments
r Psychotherapy
of orgasm and ejaculation in men. J Sex Med. for anorgasmia.
r Masturbation retraining
2004;1:58–65.
r Education on revised sexual techniques which
maximize arousal
Complementary & Alternative ADDITIONAL READING
Therapies r Perloff MD, Thaler DE, Otis JA. Anorgasmia with
Yohimbine has utility in anecdotal reports gabapentinxs may be common in older patients. Am
J Geriatr Pharmacother. 2011;9(3):199–203.
r Segraves RT. Considerations for a better definition of
male orgasmic disorder in DSM V. J Sex Med.
2010;7(2 Pt 1):690–695.
33
ANURIA AND OLIGURIA, ADULT

Won K. Han, MD
r Intrarenal: PHYSICAL EXAM

BASICS – Associated with structural renal damage r Signs of intravascular depletion
◦ Vascular (renal infarction, renal artery stenosis, – Orthostatic hypotension
DESCRIPTION renal vein thrombosis, etc.) – Tachycardia
r Anuria: No urine output or <50 mL/d ◦ Tubular (ischemia, nephrotoxin) – Decreased skin turgor
r Oliguria: Urine output of 500 mL/d or <0.5 mL/kg/h ◦ Glomerular (acute glomerulonephritis, vasculitis, – Dry mucous membrane
r Often the earliest sign of impaired renal function thrombotic microangiopathy) r Signs of heart failure
r Associated with a severe decrease in the glomerular ◦ Interstitium (interstitial nephritis, tumor – Jugular venous distension
filtration rate (GFR) compromising kidney’s main infiltration) – Rales or crackles in lung exam
r Postrenal (obstructive uropathy): – Dyspnea, orthopnea
functions
– Maintenance of body composition (such as fluid, – Mechanical or functional obstruction of the flow – Gallop rhythm
acid–base, electrolyte content, and concentration) of urine r Signs of volume overload
– Excretion of metabolic end products and foreign ◦ Intraureteral obstruction (stones, crystals, clots, – Generalized edema
substances (urea, toxins, and drugs) tumor) – Ascites
◦ Extraureteral obstruction (tumor, retroperitoneal – Dyspnea
EPIDEMIOLOGY fibrosis) – Paroxysmal nocturnal dyspnea
Incidence ◦ Prostatic hypertrophy r Signs of abdominal compartment syndrome
r Frequency depends on various clinical settings: ◦ Neurogenic bladder – Abdominal distension
– 1% at admission – Abdominal tenderness
– 2–5% during hospitalization ASSOCIATED CONDITIONS
r Chronic kidney disease r Signs of postrenal obstruction
– 4–15% after cardiopulmonary bypass
r Nephrolithiasis – Bladder distention
Prevalence r Diabetes mellitus – Enlarged prostate on rectal exam
N/A r Peripheral vascular disease – Signs of urethral trauma
RISK FACTORS r Bladder outlet obstruction – Pelvic mass
r Chronic kidney disease r Pelvic and abdominal tumors – Patients with indwelling catheters should be
r Congestive heart failure irrigated to rule out blockage
r Diabetes mellitus GENERAL PREVENTION DIAGNOSTIC TESTS & INTERPRETATION
r Avoid nephrotoxic medications (NSAIDs, ARBs
r Hypertension Lab
r Myeloma (angiotensin receptor blockers), ACEIs r Serum electrolytes
r Nephrotoxic medications (angiotensin-converting-enzyme inhibitors), – Acute kidney injury (AKI)
radiographic contrast) especially in the setting of ◦ Rise in serum creatinine (SCr) of at least
Genetics impaired renal function 0.3 mg/dL over a 48-hr period
N/A r Avoid hypotension (keep mean arterial pressure
◦ Over 1.5 times the baseline SCr value within the
[MAP] >60 mmHg) 7 previous days
PATHOPHYSIOLOGY r Adequate hydration
r Oligoanuria may result from 3 broad – Electrolyte and acid–base disorders
pathophysiologic processes: Prerenal, intrarenal, ◦ Metabolic acidosis
and postrenal causes ◦ Hyponatremia
r Prerenal: DIAGNOSIS ◦ Hyperkalemia
– Physiologic responses that lead to decreased GFR HISTORY ◦ Hyperphosphatemia
r Age, gender r Urinalysis with microscopic exam
– Maintain GFR by afferent arterial dilatation and
efferent arteriolar constriction (mediated by r Duration of symptoms – Prerenal: High specific gravity, normal, or hyaline
angiotensin II) r Chronic kidney disease casts
– Enhanced tubular reabsorption of salt and water r Diabetes mellitus – Intrarenal:
– Prolonged renal hypoperfusion can lead to acute r Hypertension ◦ Acute tubular necrosis (ATN): Low specific
tubular injury r Cardiac disease gravity, granular casts, muddy brown cast,
◦ True volume depletion: Hemorrhage, tubular epithelial cells
r Liver disease ◦ Glomerulonephritis: Proteinuria, hematuria, red
gastrointestinal loss (vomiting, diarrhea,
r Organ transplantation blood cell casts
bleeding), renal loss (diuretics, osmotic diuresis),
skin or respiratory loss (insensible loses, burns), r Episode of hypotension (MAP <60 mmHg) ◦ Interstitial nephritis: White blood cells (WBCs),
3rd spacing (pancreatitis, crush injury, or r Fluid losses WBC casts, eosinophils, hematuria
skeletal fracture) – Vomiting, diarrhea ◦ Vascular disorders: Normal or hematuria
◦ Decrease in effective circulating blood volume: – Diuretics – Postrenal: Normal or hematuria. WBCs, occasional
Sepsis, heart failure, hepatic failure, nephrotic – Burns, trauma, surgery granular casts
syndrome, anaphylaxis r Exposure to nephrotoxic medications r Urine indices
◦ Drugs affecting glomerular hemodynamics: – ACEIs, ARBs, NSAIDs – Prerenal: Fractional excretion of sodium (FeNa)
Afferent arteriolar dilatation (nonsteroidal – CNIs (cyclosporine, tacrolimus) <1%, serum Bun/Cr ratio >20:1
anti-inflammatory drugs [NSAIDs] or calcineurin – Aminoglycosides, cephalosporins amphotericin B, – Intrarenal: FeNa >1%, serum Bun/Cr ratio <20:1
inhibitors [CNIs]), efferent arteriolar constriction radiographic contrast – Postrenal: FeNa variable, serum Bun/Cr ratio
(angiotensin-converting enzyme inhibitors – Acyclovir, sulfonamides, indinavir (can precipitate >20:1
[ACEIs] or angiotensin II receptor blockers within the tubular lumen)
[ARBs]) – Anticholinergics
– Chemo agents (cisplatin, methotrexate,
5-fluorouracil, interleukin-2, etc.)
r Symptoms of urinary tract obstruction
– Anuria or oliguria
– Urinary urgency, hesitancy
– Intermittent polyuria
– History of kidney stones
– Gross hematuria
34
ANURIA AND OLIGURIA, ADULT

A
Imaging MEDICATION FOLLOW-UP
r Renal/bladder ultrasonography: 1st line in imaging,
First Line Patient Monitoring
noninvasive, no radiation exposure r Prerenal causes: Usually rapidly reversed following r Serial renal function testing for resolution
– Hydronephrosis and hydroureter restoring renal perfusion r Subsequent renal imaging study to confirm the
– Kidney stones – Replace fluid with intravenous hydration or blood resolution of postrenal obstruction
– Pelvic/retroperitoneal masses product transfusion
r Duplex Doppler ultrasound: To evaluate the patency – Discontinue the nephrotoxic medications (NSAIDs,
of renal artery and vein ARBs, ACEIs) REFERENCES
r Voiding cystourethrogram: To evaluate – Optimize cardiac output and volume status
vesicoureteral reflux r Intrarenal causes: ATN is the most common cause 1. Han WK. Biomarkers for early detection of acute
r Nuclear renal scans (such as technetium 99 m kidney injury. Current Biomarker Findings.
– There is no single or sequence of interventions 2012;2:77–85.
mercaptoacetyltriglycine [MAC3]): To assess the that will significantly improve renal function after
adequacy of renal perfusion and obstructive 2. Metha RL, Pascual MT, Soroko S, et al. Diuretics,
onset of ATN (1)[A] mortality, and nonrecovery of renal function in
uropathy
r Intravenous urography or intravascular contrast dye – Use of diuretics and low-dose dopamine acute renal failure. JAMA. 2002;288:2547–2553.
generally does not indicate as it may exacerbate ◦ Increasing urine output does not shorten the 3. Ho KM, Power BM. Benefits and risks of furosemide
renal injury duration of renal failure, decrease the in acute kidney injury. Anaesthesia. 2010;65:
requirement for dialysis or improve survival in 283–293.
Diagnostic Procedures/Surgery patients with established oliguric AKI (2,3)[A] 4. Lameire N, Van Biesen W, Vanholder R. Acute renal
r Foley catheter placement: To rule out lower urinary
◦ Diuretics may be given for a short length of time failure. Lancet. 2005;365:417–430.
tract obstruction
r Retrograde pyelography with cystoscopy: To define for volume control
the site and cause of obstruction ◦ Low-dose dopamine (1–3 μg/kg/min, ADDITIONAL READING
r Urodynamic study: To evaluate functional intravenously) does not reduce mortality or
abnormality of the bladder (neurogenic bladder) promote the recovery of renal function (4)[A] r Devarajan P. Oliguria. Medscape 2014: http://
r Renal biopsy: To determine intrarenal etiology emedicine.medscape.com/article/983156-overview;
r Obstructive uropathy: Usually responds to release of Accessed July 28, 2014.
Pathologic Findings r Klahr S, Miller SB. Acute oliguria. N Engl J Med.
N/A the obstruction and type of procedure is depending
on level of obstruction 1998;338:671–675.
DIFFERENTIAL DIAGNOSIS – Nephrostomy tube
r Prerenal causes of AKI See Also (Topic, Algorithm, Media)
– Ureteral stent r Acute Kidney Injury, Adult (Renal Failure, Acute)
– Gastrointestinal loss – Foley catheter r Acute Kidney Injury, Pediatric (Renal Failure, Acute)
– Renal loss r Thrombotic microangiopathies and dysproteinemias r Acute Tubular Necrosis (ATN)
– Heart failure
(intrarenal causes) r Anuria or Oliguria Algorithm
– Hepatic failure
– Plasmapheresis/or plasma exchange
– Nephrotic syndrome
– Medications affecting renal hemodynamics
r Intrarenal causes of AKI ONGOING CARE CODES
– Renal ischemia
– Nephrotoxins PROGNOSIS ICD9
r Mortality rate depends on the underlying cause and r 593.9 Unspecified disorder of kidney and ureter
– Acute glomerulonephritis
– Interstitial nephritis associated medical condition r 599.60 Urinary obstruction, unspecified
– Vascular complication r In most clinical situations, acute oliguria is reversible r 788.5 Oliguria and anuria
r Postrenal causes of AKI and does not result in permanent renal impairment
– Intraureteral obstruction r Identification and timely treatment of reversible ICD10
– Extraureteral obstruction causes are crucial because the therapeutic window r N13.9 Obstructive and reflux uropathy, unspecified
– Bladder outlet obstruction may be small r N28.9 Disorder of kidney and ureter, unspecified
r R34 Anuria and oliguria
COMPLICATIONS
r Inability to manage electrolytes and fluid balance
TREATMENT
resulting in various complications CLINICAL/SURGICAL
GENERAL MEASURES – Cardiovascular
r Prompt diagnosis of cause for oliguria/anuria to ◦ Arrhythmias PEARLS
guide treatment ◦ Congestive heart failure r Oliguria is often the earliest sign of impaired renal
r All patients with oliguria/anuria should have a Foley – Gastrointestinal
◦ Nausea and vomiting function.
catheter placed to monitor accurate urine output r Prompt diagnosis and timely treatment of reversible
and eliminate lower urinary tract obstruction causes ◦ Ileus
r Appropriate medical managements for acid–base ◦ Bleeding causes are crucial because the therapeutic window
– Neurologic may be small.
disorder, fluid imbalance, electrolyte imbalance r Diuretics and low-dose dopamine do not reduce
(such as hyperkalemia, hyperphosphatemia, ◦ Confusion
◦ Asterixis mortality or promote the recovery of renal function.
hypocalcemia)
r Renal replacement therapy: If supportive medical ◦ Seizures
managements are not successful – Infection
r Requirement of renal replacement therapy
– Refractory hyperkalemia
– Refractory volume overload
– Refractory acidosis
– Uremic pericarditis
35
ANURIA AND OLIGURIA, PEDIATRIC

Jennifer A. Hagerty, DO
BASICS DIAGNOSIS r Prerenal
– Burns
DESCRIPTION HISTORY – Dehydration
r Typically 1st sign of impaired renal function r Age, sex
– Drugs
r Anuria: No urine output r Duration of symptoms
– GI losses
r Oliguria: Significantly reduced urine volume r Pre-existing renal disease – Heart disease
– <1 mL/kg/h in infants r Medications – Hemorrhage
– <0.5 mL/kg/h in children r Symptoms of urinary tract obstruction – Respiratory distress syndrome
r Antenatal history – Shock/sepsis
EPIDEMIOLOGY r Family history r Intrinsic renal disease
Incidence – Acute tubular necrosis
r 10% of newborns in the NICU (1)[C] PHYSICAL EXAM – Exposure to nephrotoxins (drugs, myoglobin, uric
r 2–5% of children in the ICU (1)[C] r Signs of hypovolemia
acid)
r 10–30% of children undergoing cardiac surgery – Tachycardia – Congenital kidney disease
(1)[C] – Hypotension – Renal vascular abnormalities
– Decreased skin turgor – Glomerulonephritis
Prevalence – Dry mucous membranes r Urinary tract obstruction
N/A r Signs of hypervolemia
– Neurogenic bladder
RISK FACTORS – Edema – Posterior urethral valves
r Hypovolemia r Signs of obstructive uropathy – Meatal stenosis
r Intrinsic renal disease – Palpable bladder or kidney – Bilateral UPJ or ureteral obstruction or unilateral
r Urinary tract obstruction – Meatal stenosis in a solitary kidney
r Glomerulonephritis – Bilateral obstructing calculi
r Nephrotoxic medications
Lab
Genetics r Urinalysis
TREATMENT
Dependent on diagnosis – Protein, red cells, casts: Possible
PATHOPHYSIOLOGY
glomerulonephritis GENERAL MEASURES
r Prerenal failure – Low specific gravity: Possible acute interstitial r Treatment of the underlying cause
nephritis or intrinsic renal disease r Appropriate medical managements for acid–base
– Most common cause of oliguria
– High specific gravity: Possible prerenal cause disorder, fluid imbalance, electrolyte imbalance
– Hypoperfusion in otherwise normal kidneys
– Nitrate: Suggests infection (such as hyperkalemia, hyperphosphatemia,
– Administration of nephrotoxic agents can r Basic metabolic panel
precipitate oliguria when reduced renal perfusion hypocalcemia)
– BUN/Cr ratio: >20 suggests prerenal cause r Strict volume monitoring of input and output
is present
r Intrinsic renal failure – Evaluate renal function and electrolyte balance r Avoidance of nephrotoxic agents (NSAIDs, ARBs
– Associated with structural kidney damage Imaging (angiotensin receptor blockers), ACEIs
including acute tubular necrosis (ischemia, drugs, r Renal and bladder ultrasound for hydronephrosis (angiotensin-converting-enzyme inhibitors))
or toxins), primary glomerular diseases, or vascular and bladder distention and thickening of the wall MEDICATION
lesions r VCUG for suspected bladder outlet obstruction
r Nuclear renal scan for function, dysplasia, and First Line
– Altered tubule cell metabolism leads to ischemia,
Hydration to optimize cardiac output and volume
then altered metabolism and subsequently cell drainage status
death
r Postrenal failure Diagnostic Procedures/Surgery Second Line
Placement of a urethral catheter r Diuretics considered if adequate intravascular
– Obstructive uropathy
– Usually reversible with relief of the obstruction Pathologic Findings volume status and patient remains oliguric
Dependent on diagnosis r Hemodialysis or peritoneal dialysis to be considered
ASSOCIATED CONDITIONS if severe electrolyte abnormalities or volume
r Pre-existing renal disease
overload
r Obstructive uropathy
GENERAL PREVENTION
r Maintain adequate hydration
r Avoid nephrotoxic agents in children with
underlying renal disease
36
ANURIA AND OLIGURIA, PEDIATRIC

A
SURGERY/OTHER PROCEDURES Patient Resources r Chronic Kidney Disease, Pediatric
Relief of obstruction with urethral catheter, ureteral r American Society of Pediatric Nephrology: r Posterior Urethral Valves
stenting, or nephrostomy tube www.aspneph.com r Ureteropelvic Junction Obstruction
r National Kidney Foundation: www.kidney.org r Urinary Retention, Pediatric
Radiation Therapy
N/A REFERENCES CODES
N/A 1. Schneider J, Khemani R, Grushkin C, et al. Serum
creatinine as stratified in the RIFLE score for acute ICD9
Complementary & Alternative kidney injury is associated with mortality and r 276.52 Hypovolemia
Therapies length of stay for children in the pediatric intensive r 599.60 Urinary obstruction, unspecified
None care unit. Crit Care Med. 2010;38:933–939. r 788.5 Oliguria and anuria
2. Askenazi DJ, Feig DI, Graham NM, et al. 3–5 year
ONGOING CARE longitudinal follow-up of pediatric patients after ICD10
r E86.1 Hypovolemia
acute renal failure. Kidney Int. 2006;69:184–189.
PROGNOSIS r N13.9 Obstructive and reflux uropathy, unspecified
r Acute oliguria is often completely reversible if r R34 Anuria and oliguria
recognized and treated promptly ADDITIONAL READING
r Small increases in serum creatinine can be indicative
r Daniels RC, Bunchman TE. Renal Complications and CLINICAL/SURGICAL
of worsening outcome (2)[C]
therapy in the PICU: Hypertension, CKD, AKI, and PEARLS
COMPLICATIONS RRT. Crit Care Clin. 2013;29:279–299.
r Progression to permanent renal injury r Fortenberry JD, Paden ML, Goldstein SL. Acute r Prerenal oliguria is typically reversible with complete
r Infections secondary to uremia leading to impaired
Kidney Injury in Children. Pediatr Clin North Am. return of renal function within 24–72 hr.
defenses 2013;60:669–688. r Avoid nephrotoxic agents in patients with
r Cardiovascular complications secondary to fluid
See Also (Topic, Algorithm, Media) underlying intrinsic renal failure.
overload and electrolyte abnormalities r Acute Kidney Injury, Adult (Renal Failure, Acute)
r Neurologic changes: Confusion, lethargy, and
r Acute Kidney Injury, Pediatric
seizures r Acute Tubular Necrosis
r Gastrointestinal effects: Anorexia, nausea, and
r Anuria and Oliguria, Adult
vomiting
FOLLOW-UP
Patient Monitoring
r Serial renal function testing until resolution of
anuria/oliguria
r Imaging based on diagnosis
– Monitor renal/bladder ultrasound for obstructive
uropathy
37
AUTONOMIC DYSREFLEXIA
Michael J. Amirian, MD
BASICS DIAGNOSIS TREATMENT

DESCRIPTION HISTORY GENERAL MEASURES
r Autonomic dysreflexia (AD) occurs in patients with r SCI or transverse myelitis at T6 or above r Removal of triggering stimulus is the 1st step
spinal cord lesions at and above the 6th thoracic r Screen for urologic causes
– Minimize noxious stimuli below level of injury
level (T6) – Bladder distention – Bladder drainage or bowel decompression
r Potentially life-threatening condition in response to – Recent instrumentation – If present, consider gentle Foley catheter irrigation
noxious stimuli – Indwelling urethral or suprapubic tube with no more than 10–20 mL saline to make sure
– Genitourinary cause is the most common trigger – Urinary tract infection that the catheter is patent
for AD – Renal, ureteral, or bladder calculi r Monitor BP closely during acute episodes
– Bladder distention, instrumentation of the urinary – Epididymitis or orchitis – BP >150 mmHg requires urgent management to
tract, and UTI are the most common causes to – Ejaculation avoid severe complications
trigger AD – Urodynamic testing r Sitting the patient upright might reduce BP
r Rapid, extreme BP elevation, bradycardia, headache, r Nonurologic causes
diaphoresis, sweating, nausea, and piloerection – Bowel distention ALERT
– Pressure sores Left untreated consequences of autonomic
EPIDEMIOLOGY – Tight clothing
Incidence dysreflexia can cause seizures, intracranial bleeds,
– Ingrown toenails
Unknown hypertensive encephalopathy, and death.
– Sexual intercourse
Prevalence – Pregnancy and labor MEDICATION
r ∼85% of quadriplegic and high paraplegic r Symptoms may include blurred vision, nasal
First Line
individuals prone to AD in response to noxious congestion, anxiety r Acute episodes managed with nitrates or arterial
stimuli PHYSICAL EXAM dilators under closely monitored conditions
r More common in men than women r BP often severely elevated and often accompanied – Nitrates: Sub lingual nitroglycerine, apply 1”, 2%
– Due to increased bladder outlet resistance by bradycardia nitro paste
RISK FACTORS – Consider that the resting BP is decreased after SCI ◦ Nitrates should be avoided in patients who may
r Male (ie, 90/60) be using PDE-5 inhibitors (sildenafil vardenafil,
r High spinal cord injury (SCI) – A normal BP of 120/80 may actually represent tadalafil) for erectile dysfunction
HTN in this patient population – Nifedipine 10 mg PO immediate release form
Genetics – A BP 20–40 mmHg above the patients baseline ◦ “Bite and swallow” technique
None may be a sign of AD – Captopril 25 mg SL
r Flushing and profuse sweating above level of injury – Hydralazine or labetalol 10 mg IV
PATHOPHYSIOLOGY
r Activation of sympathetic neurons in lateral horn of r Piloerection (“goose bumps” with cold or clammy r Chronic treatment with α-blockers may improve
spinal cord causing unopposed reflex sympathetic skin below the level of the SCI) some symptoms of AD (1)[B]
activity r Evaluate for noxious stimuli below level of SCI
– Doxazosin 2–8 mg PO QD
– Stimuli (bladder or bowel distention and pain) – Skin – Terazosin 2–5 mg PO QD-BID
cause activation ◦ Infection, pressure sores – Tamsulosin 0.4 mg PO QD
r Vasoconstriction and subsequent hypertension ◦ Ingrown nails – Alfuzosin 10 mg PO QD
(HTN) ◦ Burns r Appropriate antibiotics if UTI suspected
– In response, vagal nerve triggers bradycardia ◦ Tight-fitting clothing
r Vagal nerve is able to vasodilate above injury Second Line
DIAGNOSTIC TESTS & INTERPRETATION r Phenoxybenzamine 10 mg PO BID
(flushing in face), but vessels below injury remain
vasoconstricted
Lab r Botulinum toxin injection into the detrusor
r Urinalysis and urine culture
r Other symptoms of sympathetic activation – For patients on intermittent catheterization to
– Evaluate for infection decrease bladder pressure
– Diaphoresis and piloerection – UTI can be a trigger for AD r Botulinum toxin injection into external sphincter
ASSOCIATED CONDITIONS Imaging – For patients who void reflexively to decrease
SCI r CT of abdomen and pelvis voiding pressures
GENERAL PREVENTION – Evaluate for urolithiasis if cause not apparent
r Avoid rapid or prolonged bladder distention
r Maintain regular schedule of bowel emptying r Urodynamic tests to:
r Monitor for pressure sores – Evaluate bladder compliance
– Rule out persistently elevated bladder pressures
Pathologic Findings
N/A
r Brain stem tumors
r Paroxysmal HTN
r Pheochromocytoma
r Preeclampsia
38
AUTONOMIC DYSREFLEXIA
A
SURGERY/OTHER PROCEDURES Patient Resources See Also (Topic, Algorithm, Media)
r Sphincterotomy or sphincter stent prosthesis Christopher & Dana Reeve Foundation Paralysis r Autonomic Dysreflexia Image
Resource Center. Autonomic Dysreflexia.http://www. r Detrusor-Sphincter Dyssynergia
– Allows reflex voiding with low-pressure bladder
emptying into a condom catheter (2)[A]. paralysis.org/site/c.erJMJUOxFmH/b.1338071/ r Spinal Cord Injury
r Bladder augmentation k.5E45/Autonomic Dysreflexia.htm
– Only in patients with ability to catheterize
r Sacral rhizotomy REFERENCES CODES
– For severe cases (3)[B] 1. Vaidyanathan S, Soni BM, Sett P, et al. ICD9
ADDITIONAL TREATMENT Pathophysiology of autonomic dysreflexia: r 337.3 Autonomic dysreflexia
Radiation Therapy Long-term treatment with terazosin in adult and r 596.89 Other specified disorders of bladder
N/A pediatric spinal cord injury patients manifesting r 599.0 Urinary tract infection, site not specified
recurrent dysreflexic episodes. Spinal Cord.
Additional Therapies 1998;36:761–770. ICD10
N/A 2. Chancellor M, Gajewski J, Ackmain CF, et al. r G90.4 Autonomic dysreflexia
Complementary & Alternative Long-term follow-up of the North American r N32.89 Other specified disorders of bladder
Therapies Multicenter UroLume Trial for the treatment of r N39.0 Urinary tract infection, site not specified
N/A external detrusor-sphincter dyssynergia. J Urol.
1999;161:1545–1550.
3. Hohenfellner M, Pannek J, Bötel U, et al. Sacral CLINICAL/SURGICAL
ONGOING CARE bladder denervation for treatment of detrusor PEARLS
PROGNOSIS hyperreflexia and autonomic dysreflexia. Urology.
2001;58:28–32. r Most common triggers are from the genitourinary
Managed effectively will have little impact on patient
system such as bladder distention or
COMPLICATIONS instrumentation.
Intracerebral and subarachnoid hemorrhage ADDITIONAL READING r AD occurs at and above level of T6.
FOLLOW-UP r Chronic treatment with α-blockers may improve
Consortium for Spinal Cord Medicine. Acute
Patient Monitoring some symptoms of AD.
r Clean intermittent catheterization management of autonomic dysreflexia: Individuals r Sphincterotomy or sphincter stent prosthesis allows
with spinal cord injury presenting to health-care
– Frequent (at least 4 times daily) facilities, 2nd ed. Available at http://www.pva. reflex voiding with low-pressure bladder emptying
r Regular bowel program into a condom catheter.
org/site/c.ajIRK9NJLcJ2E/b.6305831/k.986B/
r Assess AD symptoms and BP at every appointment Guidelines and Publications.htm, Accessed April 8,
r Teach SCI patients significance of AD 2013.
– Symptoms should prompt patients to empty
bladder and bowel
39
LWBK1391-SEC-B LWBK1391-Gomella ch020.xml September 19, 2014 17:58
BACTERIURIA AND PYURIA

Mary K. Powers, MD
RISK FACTORS
BASICS Age, diabetes mellitus, sexual intercourse, use of DIAGNOSIS
diaphragm or spermatocide, delayed postcoital
DESCRIPTION micturition, history of recent infection, HISTORY
r Urinary tract infection (UTI) is an inflammatory r Dysuria, frequency, urgency, malaise, rarely
immunosuppression, long-term indwelling catheters,
response of urothelium to bacterial invasion that is pregnancy, neurologic disorders, foreign bodies, low-grade fever, malodorous urine
usually associated with bacteria and pyuria. r Occasionally hematuria (gross): Especially in the
stones, obstructive uropathy, vesicoureteral reflux.
r Bacteriuria: Presence of bacteria in the urine, which female patient; uncommon in children and men
Genetics r Fever and flank pain with upper tract origin:
is normally bacteria free Certain populations may be more susceptible to
r Bacteriuria = valid indicator of bacterial infection or Pyelonephritis
bacteriuria and recurrent UTIs due to distinct r Asymptomatic or atypical symptoms: Young and old
colonization molecular defects causing impaired host responses.
– Can be either symptomatic or asymptomatic Certain receptor sites on epithelial cells may patients
– Significant bacteriuria: Quantitative count r Young patients: Abdominal discomfort, failure to
predispose some women to UTIs.
>1 × 105 colony forming units (CFL/mL) in 2 thrive, fever, vomiting, jaundice
consecutive specimens PATHOPHYSIOLOGY r Older patients: May be asymptomatic or have
r Urinary tract is normally sterile.
– Majority of individuals with significant bacteria incontinence, fevers, frequency, and urgency
r Bacteriuria usually ascends up the urinary tract from r Varied symptoms with sterile pyuria associated with
have significant pyuria
– Usually 1 organism colonizing flora of the gut, vagina, or distal urethra. differeing conditions
– >1 organism: Either contamination or r Bacteriuria can also invade the urinary tract r History of childhood fevers: May imply UTIs and
polymicrobial infection hematogenously or through direct transfer after associated congenital abnormalities
r Pyuria: Presence of WBC in the urine: instrumentation. r Problems with toilet training, urgency, incontinence
– Generally implies an inflammatory response or r Bacteria colonize the urinary tract and then multiply,
r UTI family history: Mothers, daughters, sisters
infection causing inflammation with pyuria. r History of a risk factor for bacteriuria
– Significant pyuria: >10 WBCs/HPF centrifuged r Bacterial factors:
– Close association between pyuria and bacteriuria; – Certain bacteria are more efficient at adhering to PHYSICAL EXAM
96% of patients who are symptomatic and mucosal cells than others due to fimbria. r Suprapubic tenderness: Cystitis
bacteriuric have >10 WBCs/HPF – Virulence factors: Hemolysis, adhesions, colicin, r Flank tenderness: Pyelonephritis
r Sterile pyuria: Presence of WBCs in the urine in the metabolic properties, etc. r Fever: Usually with upper tract infection
absence of bacteriuria: r Host factors: r Children may have abdominal discomfort,
– Contamination: Vaginal or prepuce secretions – Cystitis prone: Certain patients are more prone to tenderness, or distention.
– Infections: Treated UTI, mycobacterial, TB, bacteriuria (transitional cell bacterial receptor
chlamydial, gonococcal, fungal (GU or systemic), sites). DIAGNOSTIC TESTS & INTERPRETATION
viral, haemophilus, bilharzia – Menstrual cycle: Bacteriuria may be influenced by Lab
– Other infections: Appendicitis, diverticulitis, hormones. r Indications for screening:
prostatitis – Postmenopausal: Increasing incidence of – Symptomatic patients
– Noninfectious: Nephritis, stones, foreign bodies, bacteriuria – Pregnant women
transplant rejection, trauma, malignancy, – Vaginal pH: Normally acidic pH; colonization with – Prior to genitourinary procedures
chemotherapy, nephrotoxic substances, uropathogens may occur as vaginal pH rises r Urine dipstick: Best for screening:
drug-induced interstitial nephritis – Competitive organisms: Normal vaginal flora – Leukocyte esterase test:
r Cystitis: Clinical syndrome of dysuria, frequency, discourages uropathogenic colonization ◦ Detects enzyme release by WBCs
urgency occasionally with suprapubic pain – Buccal and vaginal cells: More receptive to ◦ Sensitivity 90%, specificity 95% for UTI
– Usually indicative of bacterial cystitis but can be uropathogens’ adherence in cystitis-prone patients – Conversion of nitrate to nitrite (Griess test):
associated with infections of the urethra or vagina – Local production of IgA, IgG may play defense role. 70–80% sensitivity for UTI
or noninfections process such as interstitial – Production of mucous protective layer as a local – Catalase test: Cannot differentiate infection from
cystitis, bladder carcinoma, or calculi bladder defense inflammation
– Blood group antigen (secretors) saturate or block r Microscopy:
EPIDEMIOLOGY
bacterial adherence. – Rapid in-office test: 80% accurate; usually fresh
Incidence (1) unspun
r 0.3–0.5 episodes of bacteriuria per person per year ASSOCIATED CONDITIONS
Diabetes mellitus, pregnancy, immunosuppression, – Centrifugation: Increases finding 10-fold
among asymptomatic females aged 18–40 – Difficult to see bacteria if <1 × 105 CFU/mL
r Newborns: structural urinary tract abnormalities, indwelling
catheters – Vaginal organisms may be misread as
– Males: 1.5–3.6%; females: 0.4–1.0% uropathogens: Lactobacilli and Corynebacterium
r 1–5 yr: GENERAL PREVENTION r Gram stain: Increases identification of bacteria with
– Males: 0.0–0.4%; females: 0.7–2.7% r Screening and treatment of asymptomatic
sensitivity and specificity of 96.2% and 93.0%,
r School-age: bacteriuria in at-risk populations such as pregnant respectively
– Males: 0.04–0.2%; females 0.7–2.3% patients or prior to urologic intervention can prevent
r Adult (middle-age): subsequent morbidity of UTIs.
– Males <1%; females 4–6% r Screening of asymptomatic spinal cord injury
r Older adults: patients or those with indwelling Foley catheter is
– Males 11–13%; females 6–33% not recommended.
r Almost 100% prevalence of bacteriuria in r Bacteriuria and pyuria from an incompletely treated
individuals with long-term, indwelling catheters UTI may be avoided with the appropriate use of
antibiotic class with sufficient duration; patient
Prevalence
r Pregnancy: 2–7% of all pregnant females (2) compliance should be encouraged.
r Elderly: 20% of females, 10% of males
– 24% of nursing home residents vs. 12% of
healthy domiciliary elderly (3)
40
BACTERIURIA AND PYURIA
r Urine culture: – In men and nonpregnant women, there is

– Clean-catch midstream urine: Commonly used TREATMENT moderate certainty that the harms of screening for
– Catheterized urine: May be necessary to assure asymptomatic bacteriuria outweigh the benefits.
diagnosis or in special situations (ie, children,
patients unable to void, the debilitated, the obese)
GENERAL MEASURES
r Obtain urine culture:
(1)[D]
– Adults with diabetes were included in this
B
– Segmented urine specimen, initial 10 mL, – Indwelling catheters should be used as recommendation, for the general adult
midstream, post exam: For localization of bacteria infrequently as possible population, the USPSTF did not consider evidence
or WBCs – In patients with indwelling catheter, urine for screening specific patient groups at high risk
– Quantitative counts in UTI are usually specimen for culture should be obtained at the for severe UTIs, including transplant recipients,
>1 × 105 CFU/mL with a uropathogen time catheter is changed under sterile conditions patients with sickle cell disease, and those with
◦ Range 1 × 102 to 1 × 106 from newly placed catheter recurrent UTIs.
◦ <105 per milliliter in 47% of patients
MEDICATION Patient Resources
◦ <104 per milliliter in 30% of patients r Asymptomatic bacteriuria is treated as a UTI in http://patienteducationcenter.org/articles/
◦ >102 per milliliter: Uropathogen; suspect UTI
r Conditions causing variation: Hydration, bacterial childhood, prior to urologic surgery, and in asymptomatic-bacteriuria/
pregnancy.
growth rate, urinary pH, pyelonephritis, catheterized – Persistent or recurrent bacteriuria may need
specimen: treatment for more prolonged periods followed by
REFERENCES
– Multiple organisms usually indicate contamination chronic low-dose medication.
or polymicrobial infection 1. Screening for asymptomatic bacteriuria in adults:
◦ TMP-SMX (Trimethoprim-sulfamethoxazole) US Preventive Services Task Force reaffirmation
r Uncomplicated infections: Escherichia coli, other
40/200 mg daily recommendation statement. Ann Intern Med.
Enterobacteriaceae, Staphylococcus saprophyticus, ◦ Nitrofurantoin 50–100 mg daily 2008;149:43–47.
enterococci ◦ Cephalexin 250 mg daily
r Complicated infections: E. coli, other 2. Genao L, Buhr GT. Urinary tract infections in older
– Postmenopausal: Treated only if symptomatic or adults residing in long-term care facilities. Ann
Enterobacteriaceae, Pseudomonas, S. aureus, associated with complicating factors: Longterm Care. 2012;20(4):33–38.
coagulase negative staph, enterococci – Diabetes, obstruction, immunosuppression
r Contaminants: Lactobacilli, streptococci, 3. Imade PE, et al. Asymptomatic bacteriuria among
(14–21 days of therapy)
◦ Norfloxacin 400 mg PO BID pregnant women. N Am J Med Sci. 2010;2(6):
diphtheroids, Gardnerella, Mycoplasma,
◦ Ciprofloxacin 500 mg PO BID 263–266.
coagulation-negative staph
Imaging ◦ Gentamicin 1–1.7 mg/kg IV Q8h
r Bacteriuria: ◦ Ceftriaxone 1–2 mg IV/Q 24 h
– Catheter-associated bacteriuria, if asymptomatic,
ADDITIONAL READING
– Childhood: US, VCUG, radionuclide cystogram, IV
pyelogram should not be treated (may be due to r D’Hondt F, Everaert K. Urinary tract infections in
– Adult: Only indicated if suspicious of pathology or colonization). patients with spinal cord injuries. Curr Infect Dis
r Bacteriuria in pregnancy should be treated, as Rep. 2011;13(6):544.
childhood history, obstruction, stone disease,
hematuria, febrile infections, failure to respond to untreated bacteriuria is linked with prematurity, r Siddiq DM, Darouiche RO. New strategies to prevent
therapy, recurrent UTIs IUGR, low birth weight, and neonatal death. catheter-associated urinary tract infections. Nat Rev
– Imaging in routine UTIs involving normal adult ADDITIONAL TREATMENT Urol. 2012;9(6):305.
females: Very low yield of pathology
r Pyuria: Radiation Therapy See Also (Topic, Algorithm, Media)
N/A r Bacteruria and Pyuria Image
– Associated with infection and bacteriuria: Same r Cystitis, General Considerations
indications Additional Therapies
N/A r Pyuria Algorithm
– Sterile pyuria evaluation for other causes r Urinary Tract Infection (UTI), Adult Female
– Isotopic function studies and cystogram Complementary & Alternative r Urinary Tract Infection (UTI), Adult Male
– CT: Localization of nidus or abnormality Therapies
responsible for bacteriuria/pyuria (ie, abscess) r Urinary Tract Infection (UTI), Catheter-related
Cranberry juice may decrease frequency of bacteriuria
and pyuria in selected populations. r Urinary Tract Infection (UTI), Pediatric
Localization of bacteria: Segmented urine, ureteral
catheterization, immunologic antibody studies
ONGOING CARE CODES
r Cystitis: Pyuria, positive culture, abrupt onset PROGNOSIS
r Urethritis: Pyuria, negative urine culture, gradual Variable severity ranging from asymptomatic ICD9
r 590.80 Pyelonephritis, unspecified
onset bacteriuria to severe UTI with urosepsis and secondary
organ failure r 595.9 Cystitis, unspecified
r Vaginitis: No pyuria, vaginal discharge, pruritus
r 599.0 Urinary tract infection, site not specified
r Pyelonephritis COMPLICATIONS
r Noninfectious causes 20–40% of untreated bacteriuria in pregnancy leads ICD10
– Interstitial cystitis to pyelonephritis r N12 Tubulo-interstitial nephritis, not spcf as acute or
– Nonuropathogenic cause, as in sterile pyuria FOLLOW-UP chronic
r Contamination with vaginal/skin flora r N30.90 Cystitis, unspecified without hematuria
Patient Monitoring r N39.0 Urinary tract infection, site not specified
r Repeat exam: 2 wk posttreatment, not necessary
in young women who are asymptomatic after
therapy
– Microscopic urinalysis and culture
CLINICAL/SURGICAL
r Periodic office visits to verify sterile urine PEARLS
r 2008 USPSTF guidelines:
Screening of asymptomatic spinal cord injury patients
– In pregnant women, high certainty exists that net or those with indwelling Foley catheter is not
benefit of screening for asymptomatic bacteriuria recommended.
is substantial (1)[A].
41
BALANITIS AND BALANOPOSTHITIS

H. Henry Lai, MD, FACS
r Balanitis xerotica obliterans (BXO) is a specific form DIAGNOSTIC TESTS & INTERPRETATION
BASICS of balanitis: Lab
– Chronic, progressive, fibrotic disease (a form of Swab of glans/foreskin for viral, bacterial, and fungal
DESCRIPTION lichen sclerosis isolated to the penis) culture
r Balanitis: Inflammation of the glans penis. – Elastin is replaced by collagen
r Balanoposthitis: Inflammation of the foreskin and – The skin around the meatus becomes white, Imaging
featureless, contracted, causing meatal stricture N/A
glans penis (affects uncircumcised men).
– BXO may spread to the foreskin and coronal Diagnostic Procedures/Surgery
EPIDEMIOLOGY r Potassium hydroxide and Tzanck preparation for
sulcus. In extreme cases, the entire end of the
Incidence penis is replaced by fibrotic tissue, becomes men
r Can occur at any age.
thickened and nonretractile, causing sexual and – Potassium hydroxide smear evaluates for fungus
r No incidence studies of balanoposthitis have been
voiding issues (eg, weak stream, obstruction) – Tzanck preparation for herpes virus
reported in US.
– 1.5% of uncircumcised boys ages 0–15 were ASSOCIATED CONDITIONS Pathologic Findings
r Biopsy is indicated for:
affected in a Japanese cohort. Diabetes mellitus
– Balanitis that persists and in which the cause
Prevalence GENERAL PREVENTION remains unclear warrants biopsy to rule out
r Common, the exact prevalence is unknown. r Maintain good genital hygiene
coexisting neoplasm or premalignant lesions
– Balanitis affects 11% of adult men and 3% of r Retraction of foreskin to clean the glans
– For definitive diagnosis of BXO
boys seen in urology clinics. r Keep the glans and foreskin dry
r Circumcision DIFFERENTIAL DIAGNOSIS
RISK FACTORS (1) r Fixed drug eruption (allergy)
r Presence of a foreskin (uncircumcised) r Safe sexual contact
r Contact dermatitis
r Tight foreskin (phimosis) r Manage risk factors (eg, glycemic control)
r Squamous cell carcinoma of the penis
r Poor genital hygiene r Carcinoma in situ of the penis
r Intertrigo (see below) r Zoon (plasma cell) balanitis
r Sexual contact (with or without infection)
DIAGNOSIS
r Psoriasis
r Poorly controlled diabetes mellitus HISTORY r Reiter syndrome (Reactive arthritis/reactive arthritis
r Immunocompromised host r Symptoms may include: Pain, discharge, irritation,
triad) (with circinate balanitis)
r Coexisting penile cancer voiding symptom (dysuria, weak stream) r Human papilloma virus
r Prior episodes and treatment
Genetics r Uncircumcised
N/A r Foreskin retractability TREATMENT
PATHOPHYSIOLOGY (2) r Genital hygiene habits
r The pathophysiology is usually different in young r Sexual contacts, sexually transmitted diseases GENERAL MEASURES
r Meticulous genital hygiene
boys compared to adult men: r Other systemic risk factors (eg, diabetes)
– Boys: From bacterial invasion of tissue r Keep the glans and foreskin clean and dry
– Men: Combination of poor genital hygiene, PHYSICAL EXAM r Expose the glans to air as often as possible
r Inspection (ulcers, mass, genital pus, edema) r Avoid excessive dampness in the genitals
intertrigo, irritant dermatitis, maceration injury,
and bacterial, or candidal overgrowth r Palpation (tenderness, induration, mass) r Avoid soaps while inflammation is present
– Candida is the most common infectious cause r Inguinal lymph nodes should be nonpalpable r Cleaning with soap and water routinely
r Intertrigo refers to a condition in which damp, moist r Manage risk factors (eg, glycemic control)
body areas are predisposed to inflammation:
– Involves genitals, inner thighs, underbelly MEDICATION
– Risk factors: Grossly overweight, diabetes, bed Treatment depends on the underlying cause (infectious
rest, diaper use, poor personal hygiene vs. inflammatory) and organisms
– Skin dampness predisposes to secondary
opportunistic bacterial or fungal overgrowth
42
BALANITIS AND BALANOPOSTHITIS
First Line
r Candidal infection: The most common cause of
ADDITIONAL TREATMENT ADDITIONAL READING
Radiation Therapy
infectious balanitis N/A Wikström A, Hedblad MA, Syrjänen S. Human
– Clotrimazole cream 1%
– Miconazole cream 2% Additional Therapies
papillomavirus-associated balanoposthitis–a marker
for penile intraepithelial neoplasia? Int J STD AIDS.
B
– Apply BID until symptoms resolve N/A 2013;24(12):938–943.
– Oral fluconazole if symptoms are severe Complementary & Alternative See Also (Topic, Algorithm, Media)
– Nystatin cream if allergic to imidazole Therapies r Balanitis and balanoposthitis Image
– Imidazole with hydrocortisone if inflammation N/A r Balanitis Xerotica Obliterans
r Anaerobic infection:
r Balanitis, Zoon (Plasma Cell Balanitis)
– Metronidazole 400 BID for 1 wk ONGOING CARE r Lichen Sclerosis Et Atrophicus
– Optimal dosage schedule is unknown r Penis, Lesion
– Alternatively, amoxicillin/clavulanic acid PO or PROGNOSIS
clindamycin topically r Can be recurrent or persistent
r Aerobic infection: r 10% recurrence rate
– Group A streptococci, Staphylococcus aureus, r Some patients may require circumcision to prevent CODES
Gardnerella vaginalis are all reported cases of recurrence and ensure resolution.
balanitis. ICD9
– Treatment based on sensitivity of the culture COMPLICATIONS r 605 Redundant prepuce and phimosis
r Abscess formation r 607.1 Balanoposthitis
(topical antibiotics, occasionally oral antibiotics)
r BXO: r Penile cellulitis r 607.81 Balanitis xerotica obliterans
– Topical steroids (clobetasol propionate or r Progression to Fournier gangrene
betamethasone valerate) offers limited efficacy r Scarring and subsequent phimosis ICD10
r Zoon (plasma cell) balanitis: r N47.1 Phimosis
FOLLOW-UP r N47.6 Balanoposthitis
– Topical steroids with or without antibacterial
cream
Patient Monitoring r N48.1 Balanitis
r After an acute episode and treatment is
r Circinate balanitis (Reiter syndrome):
implemented, patients should be seen again to
– Hydrocortisone cream 1% apply BID ensure resolution of symptoms and infection. CLINICAL/SURGICAL
– Treatment of associated infection
r Irritant, allergic balanitis: – Progression to cellulitis or gangrene may occur in PEARLS
diabetic patients with genital infection.
– Avoid exposure to irritants especially soaps r Follow closely with genital dysplasia among those r Maintaining good genital hygiene is a key preventive
– Emollients aqueous cream: Apply PRN and used men with condyloma with a history of strategy (keep the foreskin and glans clean and dry).
as a soap substitute while inflammation is present balanoposthitis than those with no such history. r Underlying risk factors should also be managed (eg,
– Hydrocortisone 1% apply QD or BID until glycemic control in diabetes).
symptoms resolve Patient Resources r Treatment depends on the underlying cause
N/A
Second Line (infectious vs. inflammatory) and organisms.
N/A r Circumcision is reserved for recurrent balanitis,
REFERENCES balanoposthitis, or phimosis that have failed
r Circumcision is reserved for recurrent balanitis, conservative treatments.
1. Vohra S, Badlani G. Balanitis and balanoposthitis. r Balanitis that persists and if the cause remains
balanoposthitis, or phimosis that have failed Urol Clin North Am. 1992;19(1):143–147.
conservative treatments. unclear warrants biopsy to rule out coexisting
r Occasionally dorsal slit may be performed. 2. Edwards S. Balanitis and balanoposthitis: A review. neoplasm or premalignant lesions.
Genitourin Med. 1996;72(3):155–159.
r For BXO that does not respond to steroid:
– Periodical self-dilation with tapered dilators
– Dilation by urologists
– Formal surgical reconstructive repair
43
BCG SEPSIS/BCG-OSIS
John B. Eifler, MD
GENERAL PREVENTION DIAGNOSTIC TESTS & INTERPRETATION

BASICS r The following will minimize the risk of BCG sepsis;
Lab
however, no strategy has been shown to be effective r Mild/moderate symptoms
DESCRIPTION at eliminating the risk (2,4) – Urine culture
r BCG sepsis: Potentially life-threatening event – Defer installation of BCG at least 2 wk after r Severe symptoms (Sepsis, severe cystitis symptoms
secondary to intravasation of intravesical BCG instrumentation >48 hr)
resulting in cardiovascular collapse and acute – Abort instillation if hematuria or traumatic Foley – Urine, blood cultures
respiratory distress catheter placement – Liver function tests to assess for hepatitis
– Possible etiologies include hypersensitivity – Do not treat with active UTI – CXR to assess for pneumonitis
reaction and bacterial sepsis – Avoid BCG in immunocompromised host – Acid-fast testing of urine
r “BCG-osis” is a term used to refer to disseminated – BCG cystitis (see below): Delay future instillations – Consider PCR testing for mycobacterial DNA if
disease in patients treated with BCG until complete resolution of symptoms disseminated BCG suspected
– The lungs and liver are typically involved – BCG sepsis: Avoid any future BCG instillation r Coagulation studies: PT/PTT/fibrinogen if DIC
– Patients are usually hemodynamically stable suspected
EPIDEMIOLOGY DIAGNOSIS Imaging
Incidence See “Lab”
r >95% of patients treated with BCG have no HISTORY
r BCG cystitis: Dysuria, frequency 2–4 hr after Diagnostic Procedures/Surgery
significant morbidity (1).
r 1 in 15,000 patients treated with intravesical BCG installation +/– low-grade fever, malaise, See “Lab”
will develop BCG sepsis (2). hematuria Pathologic Findings
r 10 reported deaths due to BCG sepsis (3). – Typically resolves within 48 hr r Noncaseating granulomas
r Regional infection is common though often – May be found in lung, liver, bone, prostate, kidney,
Prevalence asymptomatic (eg, 75% develop granulomatous epididymis
N/A prostatitis) and distant infection (hepatitis,
RISK FACTORS osteomyelitis, pneumonitis) may occur r Post-BCG bacterial cystitis
r Inadequate delay after transurethral instrumentation r Symptoms often occur within 2 hr of instillation but
r BCG cystitis (cytokine release without intravasation
(TURBT or bladder biopsy) may occur years after therapy
r Traumatic catheterization or gross hematuria at time r Symptoms of systemic infection: Intermittent fever of BCG)
r Gram-negative sepsis
of intravesical instillation >39◦ C (102.2◦ F) with drenching night sweats
lasting >48 hr
Genetics r BCG sepsis: Fever, rigors, progressing to vascular
N/A TREATMENT
collapse and respiratory distress
PATHOPHYSIOLOGY – Often occurs within hours of instillation GENERAL MEASURES
r BCG is live attenuated Mycobacterium bovis r Consultation with infectious disease specialist is
r Intravasation of BCG through damaged urothelium PHYSICAL EXAM recommended for septic patients (2,4)
r BCG sepsis
with subsequent systemic response r If antitubercular therapy required, intravesical BCG
r Symptoms may be related to mycobacterial infection – High fevers (>38.5◦ C/101.3◦ F) within 2 hr of
should be discontinued (2)
treatment, resembling gram-negative sepsis
and/or hypersensitivity reaction – Hypotension/shock physiology MEDICATION
ASSOCIATED CONDITIONS r BCG cystitis First Line
r Recent transurethral instrumentation – Suprapubic tenderness to palpation r Mild/moderate symptoms including low-grade fevers
r Traumatic catheterization – Hematuria <48 hr (BCG cystitis) (2,4,5)
r Concomitant UTI – Low-grade fevers – Analgesics
r Age >70 – NSAIDs
– +/– Fluoroquinolone
◦ Such as levofloxacin 500 mg/d
◦ Helpful for bacterial cystitis and has mild
antitubercular activity
44
BCG SEPSIS/BCG-OSIS
r Antitubercular medications should be initiated for

REFERENCES See Also (Topic, Algorithm, Media)
r Bladder Cancer, General
signs of sepsis or severe cystitis symptoms >48 hr
(2–5) 1. Lamm DL. Efficacy and safety of bacille r Bladder Cancer, Nonmuscle-Invasive Bladder Cancer
– Typically isoniazid 300 mg/d and rifampin
600 mg/d for 3–6 mo
calmette-guerin immunotherapy in superficial
bladder cancer. Clin Infect Dis. 2000;31(suppl 3):
(Ta, T1).
r Bladder Cancer, Urothelial, Superficial Carcinoma In
B
– For solid organ involvement, ethambutol S86. Situ (CIS) (NMIBC)
15 mg/kg/d added 2. Lamm DL, van der Meijden PM, Morales A, et al. r Urosepsis
– BCG resistant to cycloserine and pyrazinamide Incidence and treatment of complications of bacillus
– Prednisone 40 mg/d recommended for septic Calmette-Guérin intravesical therapy in superficial
shock or if hypersensitivity reaction suspected bladder cancer. J Urol. 1992;147:596–600. CODES
Second Line 3. Rawls WH, Lamm DL, Lowe BA, et al. Fatal sepsis
N/A following intravesical bacillus Calmette-Guérin
ICD9
administration for bladder cancer. J Urol. 1990;144: r 038.8 Other specified septicemias
SURGERY/OTHER PROCEDURES 1328–1330.
Not indicated; supportive care only r 995.91 Sepsis
4. Jones JS, Larchian WA. Non-muscle-invasive r 999.39 Infection following other infusion, injection,
ADDITIONAL TREATMENT bladder cancer (Ta, T1, and CIS). In: Wein AJ,
Kavoussi LR, Novick AC, Partin AW, Peters CA, eds. transfusion, or vaccination
Radiation Therapy
N/A Campbell-Walsh Urology. Vol. 3. Philadelphia, PA: ICD10
Elsevier; 2011:2343–2346. r A41.89 Other specified sepsis
Additional Therapies 5. Durek C, Rüsch-Gerdes S, Jocham D, et al. r T80.29XA Infct fol oth infusion, transfuse and
N/A
Sensitivity of BCG to modern antibiotics. Eur Urol. theraputc inject, init
Complementary & Alternative 2000;37(suppl 1):21–25.
Therapies
N/A CLINICAL/SURGICAL
ADDITIONAL READING PEARLS
ONGOING CARE r Gonzalez OY, Musher DM, Brar I, et al. Spectrum of r Patients undergoing intravesical BCG therapy who
bacille Calmette-Guérin (BCG) infection after have traumatic catheterization or gross hematuria
PROGNOSIS
intravesical BCG immunotherapy. Clin Infect Dis. should delay therapy until symptoms resolve.
Good if treatment initiated in timely manner
2003;36:140. r Patients with high fever (>38.5◦ C/101.3◦ F) or
COMPLICATIONS r Mehta AR, Mehta PR, Mehta RL. A cough
severe cystitis symptoms lasting >48 hr should be
Solid organ involvement conundrum in a patient with a previous history of hospitalized and undergo additional testing.
FOLLOW-UP BCG immunotherapy for bladder cancer. BMJ Case
Rep. 2012;2012.
Patient Monitoring
ICU admission with invasive monitoring for BCG
sepsis
Patient Resources
N/A
45
BLADDER AREFLEXIA (DETRUSOR AREFLEXIA)

H. Henry Lai, MD, FACS
r Lyme disease Diagnostic Procedures/Surgery

BASICS r Multiple sclerosis r Bladder scanner
r Myelodysplasia, spina bifida – High post-void residuals may be identified to
DESCRIPTION r Radical pelvic surgery support the diagnosis
r Bladder areflexia (detrusor areflexia) is the inability r Multi-channel urodynamics study:
r Recent spinal or brain trauma (“spinal shock”)
of the bladder to contract to empty. r Sacral spinal cord injury – No or minimal detrusor contraction (Pdet line)
r Requires urodynamics study for diagnosis. – Urodynamics criteria:
r Presentation may include urinary retention, GENERAL PREVENTION ◦ Bladder contractility index (BCI) <100
incomplete emptying, and overflow incontinence. N/A ◦ Maximal flow rate (Qmax ) <12 mL/s
◦ Detrusor pressure Pdet at Qmax <10 cm water
EPIDEMIOLOGY
– To distinguish detrusor areflexia from bladder
Incidence DIAGNOSIS outlet obstruction (benign prostatic hyperplasia).
No incidence study has been reported. The risk of – To assess detrusor compliance and storage
urinary retention may increase with aging. HISTORY
r Symptoms may include: Incomplete bladder pressure. Detrusor leak point pressure >40 cm of
Prevalence emptying, frequency, urgency, incontinence (urge or water poses risk to the upper urinary tract.
r No prevalence study has been reported in US. – To identify the etiology of incontinence.
stress), weak urine stream, straining to empty.
– 40% of men and 13% of women over the age of r History of any risk factors listed in the section – To guide rational, safe management strategy.
65 have detrusor underactivity during entitled “Associated Conditions.” Pathologic Findings
urodynamics in a Korean cohort (1,179 patients). r Medication: Recent use of anticholinergic Bladder wall thickening and fibrosis may be found in
– 48% of men and 12% of women over the age of medications or over-the-counter cold medicine. decompensated bladder from obstruction.
70 have underactivity in a study from Israel. r Recurrent bladder infections.
RISK FACTORS r Bladder outlet obstruction causing retention:
r Diabetes mellitus PHYSICAL EXAM
r Palpable suprapubic mass (distended bladder) – Benign prostatic hyperplasia
r Longstanding bladder outlet obstruction
r Stress incontinence on pelvic exam (overflow) – Urethral stricture disease
r Neurologic diseases r Functional outlet obstruction (eg, detrusor external
r High post-void residual volumes
r Recent radical pelvic surgery sphincter dyssynergia)
r Abnormal neurologic exam:
r Potential reversible causes of areflexia:
Genetics – Perianal and perineal sensation
r Genetic diseases predisposing to bladder – Anal sphincter tone – Recent spinal shock or stroke
dysfunction include: – Bulbocavernous reflex – Recent radical pelvic surgery
– Muscular dystrophy r Enlarged prostate on rectal exam – Medication use (eg, anticholinergics)
– Neurofibromatosis r Sacral abnormalities: – Fowler syndrome
PATHOPHYSIOLOGY – Sacral dimple
r May result from primary detrusor muscle failure – Tuft of hair TREATMENT
(myogenic causes) and/or neurologic causes (eg, – Sacral agenesis
from lower motor neuron lesions, injury to sacral – Spinal surgical scar GENERAL MEASURES
spinal cord, multiple sclerosis). r Intermittent catheterization is preferred over chronic
r Patients often attempt to void by valsalva.
indwelling catheters (Foley or suprapubic catheter)
r Success of emptying depends on resistance of Lab to reduce the risks of infection and stones.
r Blood: Creatinine to assess renal function.
r Sacral neuromodulation (InterStim) may be
smooth and striated sphincter mechanisms. r Urine: Urinalysis to assess urinary infection.
r Continence depends on sphincter competence. considered for nonobstructive urinary retention
Imaging (eg, good results in Fowler syndrome).
ASSOCIATED CONDITIONS Renal and bladder ultrasound (to assess renal stones,
r Cauda equina syndrome MEDICATION
bladder stones, hydronephrosis).
r Diabetes mellitus First Line
r Fowler syndrome (“nonneurogenic, neurogenic r Bethanechol was ineffective in reducing residual
bladder”) volumes in a randomized, placebo trial (1)[C].
r Intervertebral disc diseases – Bethanechol may decrease the duration of
r Longstanding bladder outlet obstruction with transient urinary retention in patients who
underwent radical hysterectomy or anorectal
detrusor decompensation (myogenic failure) surgery in randomized, controlled trials (1)[C].
r Lumbosacral spinal surgery
– Typical dosage: 10–50 mg PO BID–TID.
Second Line
N/A
46
BLADDER AREFLEXIA (DETRUSOR AREFLEXIA)
SURGERY/OTHER PROCEDURES FOLLOW-UP See Also (Topic, Algorithm, Media)

r Sacral neuromodulation (InterStim) in selected r Bladder Areflexia (Detrusor Areflexia) Image
Patient Monitoring
patients who do not have contraindications. r Patients with poor detrusor compliance need r Neurogenic Bladder, General Considerations
r Sacral Neuromodulation
– Effective in restoring voiding in patients with
Fowler syndrome (1)[C].
periodic urodynamics studies, upper tract imaging,
and creatinine lab work to minimize complications. r Spinal Cord Injury, Urologic Considerations
B
– May be selectively considered in patients with r Patients who refuse to catheterize should be r Urodynamics, Indications, and Normal Values
nonobstructive urinary retention (2)[C]. monitored closely.
r Bladder augmentation may be considered in r Patients with chronic indwelling catheter should
patients with poor detrusor compliance, and high
detrusor leak point pressure and storage pressure.
undergo cystoscopy periodically due to the increased CODES
risk of bladder neoplasm.
ADDITIONAL TREATMENT Patient Resources ICD9
Radiation Therapy N/A r 596.55 Detrusor sphincter dyssynergia
N/A r 788.29 Other specified retention of urine
r 788.38 Overflow incontinence
Additional Therapies REFERENCES
N/A
1. Kessler TM, Fowler CJ. Sacral neuromodulation for ICD10
Complementary & Alternative r R33.8 Other retention of urine
urinary retention. Nat Clin Pract Urol. 2008;5(12): r N36.44 Muscular disorders of urethra
Therapies
657–666.
N/A r N39.490 Overflow incontinence
2. van Kerrebroeck PE, van Voskuilen AC, Heesakkers
JP, et al. Results of sacral neuromodulation therapy
ONGOING CARE for urinary voiding dysfunction: Outcomes of a CLINICAL/SURGICAL
prospective, worldwide clinical study. J Urol.
PROGNOSIS 2007;178(5):2029–2034. PEARLS
r Most cases are irreversible, except the few
r Detrusor areflexia requires urodynamics for
circumstances described in “Differential Diagnosis”
r However with proper urologic management, diagnosis.
ADDITIONAL READING r Urodynamics can distinguish detrusor areflexia from
secondary complications may be minimized.
Cruz CD, Cruz F. Spinal cord injury and bladder bladder outlet obstruction.
COMPLICATIONS r Intermittent catheterization is preferred over chronic
r Bladder neoplasm from indwelling catheter dysfunction: New ideas about an old problem.
Scientific World J. 2011;11:214–234. indwelling catheters.
r Hydronephrosis and hydroureters r Sacral neuromodulation (InterStim) may be
r Recurrent urinary tract infections
selectively considered in patients with
r Renal and bladder stones nonobstructive urinary retention or Fowler syndrome.
r Renal insufficiency, failure, and dialysis r Patients with chronic indwelling catheter should
r Urethral erosion from chronic Foley catheter undergo cystoscopy and urine cytology periodically
r Urinary incontinence due to the increased risk of bladder neoplasm.
r Urosepsis and death
47
BLADDER CALCULI (VESICAL CALCULI)

Mohamed S. Ismail, MBChB, MRCS, PhD
PATHOPHYSIOLOGY
BASICS r Bladder calculi are primarily formed in the bladder, DIAGNOSIS
rarely can be a secondary renal stone that has
DESCRIPTION formed in the kidney and passed into the bladder HISTORY
r Bladder calculi (also called bladder stones) are r Patients with SCI, neurogenic bladder may be at
– Foreign bodies, retained catheter balloon
calcified material that are present in the bladder. fragments increased risk
r It can originate primarily in the bladder. r Bladder calculi may be asymptomatic and may be
– Patients on chronic intermittent catheterization
r It can be a secondary renal stone that formed in the may force pubic hair into the bladder that can incidental finding on imaging (plain x-ray, renal
kidney and passed into the bladder. become calcified over time ultrasound, CT, or flexible cystoscopy)
r Often associated with bladder outlet obstruction in r Stone analysis frequently reveals uric acid stone in r Patients commonly presents with
the US. 50% of the cases – Suprapubic or perineal pain
r Historically the removal of bladder calculus was r Other constituents are ammonium urate, calcium – Irritative urinary symptoms
performed via an incision in the perineum with the oxalate, and calcium phosphate – Intermittent urinary stream
patient in a supine position and the legs elevated r In infected urine, struvite stones are the most – Hematuria, gross, and microscopic
(the origin of the term “lithotomy position”). common – Recurrent urinary tract infection
r In patients with spinal cord injuries (SCIs), bladder PHYSICAL EXAM
EPIDEMIOLOGY r Examine the abdomen for palpable bladder or
stones are often composed of struvite or calcium
Incidence phosphate suprapubic tenderness
r The incidence of bladder calculi in the Western
r In endemic areas, low phosphate diet results in r Examine the external genitalia for any abnormalities
world has significantly dropped as a result of
increased ammonium excretion in the urine (meatal stenosis) that may contribute to outlet
improved diet, nutrition, and infection control r Low intake of animal protein contributes to high
r Bladder calculi are endemic in Thailand, Burma, obstruction
urinary oxalate and low urinary citrate levels with r Digital rectal exam to assess for BPH and prostate
Indonesia, Middle east, and north Africa
r Mostly in middle age men increased risk of stone formation cancer
r Solitary stone are present in 75% of cases
r In catheterized patients the incidence of developing DIAGNOSTIC TESTS & INTERPRETATION
bladder calculi is 25% in 5 yr ASSOCIATED CONDITIONS Lab
r The incidence in children has declined significantly r Foreign bodies in the bladder r Urine analysis: Hematuria, leukocytes, and
however in the developing countries they are r Intermittent catheterization crystalluria may be present
common in boys younger than 11 yr r Low phosphate diet r Urine culture and sensitivity in case of suspected
r Vaginal prolapse and urethral surgery are common r Low protein diet infection
causes in women r Urinary stasis (prostatic hypertrophy, stricture, r Urine cytology in the presence of calculi is
Prevalence congenital abnormalities [ureterocele], diverticulum, nonspecific
r Bladder calculi constitute 10–15% of the stone cystocele) r Serum creatinine
r Urinary tract infection r Stone analysis should be considered when removed
burden in adult and 15–30% in children
r Data on the world wide incidence are not available Imaging
GENERAL PREVENTION
r Adequate hydration r Calcified stones can be visible on plain x-ray (KUB)
RISK FACTORS
r Urinary stasis r Treatment of bladder outlet obstruction – Stones may be densely radiopaque.
– Bladder outlet obstruction r Prevention of urinary tract infection – Occasionally laminations may be visible on plain
◦ Benign prostatic hyperplasia r Prevention of urololithiasis as appropriate x-ray
r Uric acid and ammonium acid urate stones are
◦ Urethral stricture – Allopurinol for uric acid stones
◦ Bladder neck contracture – Reduce oxalate intake radiolucent but will be seen on ultrasounds or CT
– Neurogenic bladder – Increase urinary citrate scan.
r Foreign body such as urethral catheter and ureteric r Bladder calculi may not be visible on MRI
– Low sodium low diet
r CT without contrast is highly sensitive and specific
stent that act as nidus for stone formation
r Urinary tract infection to detect calculi, however it is rarely used to
r Urinary diversion and bladder substitution diagnose bladder stones
– Secondary to foreign body, infection, and systemic
acidosis
– Rarely patients may place foreign bodies in
bladder that become calcified
Genetics
N/A
48
BLADDER CALCULI (VESICAL CALCULI)
r Cystoscopy to visualize the stone and guide
r Endoscopic cystolitholapaxy using stone
REFERENCES
subsequent removal of the stone fragmenting forceps 1. Huffman JL, Ginsberg DA. Calculi in the bladder
r Electrohydraulic, ultrasonic, laser, and pneumatic
– Allows evaluation of bladder outlet obstruction or
other abnormality such as bladder diverticulum lithotrites are used for larger or harder stones
and urinary diversions. In: Coe FL, Favus MJ, Pak
CY, Parks JH, Preminger GM, eds. Kidney Stones:
B
r Large stones can be removed through small Medical and Surgical Management. Philadelphia,
Pathologic Findings
r Acute and chronic inflammation abdominal incision (open cystolitholapaxy) PA: Lippincott-Raven; 1996:1025–1034.
r Squamous metaplasia and squamous cell carcinoma r Cystolitholapaxy can be safely combined with 2. Douenias R, Rich M, Badlani G, et al. Predisposing
procedures such as TURP or TUIP for bladder outlet factors in bladder calculi. Review of 100 cases.
can result from chronic vesical calculus irritation
obstruction Urology. 1991;37(3):240–243.
DIFFERENTIAL DIAGNOSIS 3. Paez E, Reay E, Murthy LN, et al. Percutaneous
r Bladder diverticulum ADDITIONAL TREATMENT treatment of calculi in reconstructed bladder.
r Bladder malignancy with or without calcification Radiation Therapy J Endourol. 2007;21(3):334–336.
– Urothelial carcinoma N/A
– Other bladder malignancies Additional Therapies
r Chronic pelvic pain syndrome r ESWL has a limited role in treating bladder calculi ADDITIONAL READING
r Fungal bezoar or blood clot r Bladder outlet procedure may be necessary if urinary
r Interstitial cystitis Preminger GM, Tiselius HG, Assimos DG, et al;
stasis is causing vesical calculus to improve bladder EAU/AUA Nephrolithiasis Guideline Panel. 2007
r Lower urinary tract symptoms due to bladder outlet emptying
r Consideration to repair of bladder diverticulum or guideline for the management of ureteral calculi.
obstruction J Urol. 2007;178(6):2418–2434.
r Overactive bladder other anatomic abnormality if contributory
r Urinary tract infection See Also (Topic, Algorithm, Media)
Complementary & Alternative r Bladder Calculi (Vesical Calculi) Image
r Ureteral urolithiasis
Therapies r Bladder Diverticulum
– Distal ureteral stone can cause significant vesical N/A r Bladder Filling Defect
irritation
r Bladder Wall Calcification, Differential Diagnosis
ONGOING CARE r Fungal Infections, Genitourinary
TREATMENT r Urolithiasis, Adult, General Considerations
PROGNOSIS
GENERAL MEASURES r Excellent with complete stone removal and
r Surgical removal is the mainstay treatment associated bladder outlet obstruction are treated
r Determining and correcting the cause (ie, bladder r Metabolic stone evaluation may be considered if CODES
outlet obstruction) should be a priority appropriate (ie, multiple upper tract calculi,
recurrent bladder calculi, etc.) ICD9
MEDICATION r 594.0 Calculus in diverticulum of bladder
First Line COMPLICATIONS r 594.1 Other calculus in bladder
r Medical therapy is used to treat associated urinary r Recurrent urinary tract infection
r 596.0 Bladder neck obstruction
tract infection r Squamous metaplasia
r Bladder outlet obstruction is treated with alpha r Chronic irritation may result in secondary ICD10
blockers such as tamsulosin 0.4 mg QD and 5 alpha malignancy (ie, squamous cell carcinoma) r N21.0 Calculus in bladder
reductase inhibitors such as dutasteride 0.5 mg QD r N32.0 Bladder-neck obstruction
FOLLOW-UP
Second Line Patient Monitoring
r Alkalinization of urine to a PH of 6.5 in case of uric r Urine analysis CLINICAL/SURGICAL
acid stones r Flowmetry and postvoid residual
– Use potassium citrate 60 mEq/d PO r Renal ultrasound scan to screen for upper tract
PEARLS
urolithiasis If an otherwise healthy person is found to have a
bladder calculus, a complete evaluation is warranted
Patient Resources
to evaluate for causes such as urinary stasis.
PubMed Health: Bladder Stones http://www.ncbi.
nlm.nih.gov/pubmedhealth/PMH0002254/
49
BLADDER CANCER, ADENOCARCINOMA

Matthew A. Young, MD
Sandip M. Prasad, MD, MPhil
r M.D. Anderson Cancer Center Diagnostic Criteria for

BASICS Urachal Carcinoma DIAGNOSIS
– Location in bladder dome or elsewhere in the
DESCRIPTION midline of the bladder HISTORY
r Adenocarcinoma of the bladder is an uncommon r Hematuria, mucosuria (uncommon)
– Sharp demarcation between tumor and normal
and frequently aggressive nonurothelial cancer. surface epithelium – Usually painless
r It is frequently muscle-invasive or metastatic at the r Irritative voiding symptoms (frequency, urgency,
– Supportive criteria
time of diagnosis and therefore carries a poor ◦ Enteric-type histology dysuria)
prognosis. ◦ Absence of urothelial dysplasia r Foreign travel: Schistosomiasis
r A common site is the urachus. ◦ Absence of cystitis cystica or cystitis glandularis r Weight loss, flank pain, umbilical discharge (rare)
transitioning to the tumor r Chronic infection
EPIDEMIOLOGY ◦ Absence of primary adenocarcinoma of another r History of exstrophy or other bladder pathology
r 0.5–2.0% of all primary bladder malignancies,
organ r History of colon cancer or other malignancy; risk of
making it the 3rd most common epithelial tumor of r May produce stippled calcifications on plain films
the bladder metastatic lesion
r Prognosis is worse for urachal carcinoma than for
r Can arise from the urachus or nonurachal PHYSICAL EXAM
primary adenocarcinoma of the bladder r Pelvic mass by bimanual/rectal exam
epithelium, or in association with exstrophy of the r Urachal carcinoma demonstrates more extensive
bladder r Bloody or mucoid umbilical discharge or umbilical
r Most common tumor arising in the bladder of infiltration of the bladder wall, and for this reason,
radical cystectomy is preferred over partial mass
exstrophy patients, who have a 4% lifetime risk r Digital rectal exam; presence of blood in stool
r A majority of nonurachal, nonexstrophy-associated cystectomy, although the latter is still an option
r Urachal carcinomas are not always
adenocarcinomas occur in men and are frequently DIAGNOSTIC TESTS & INTERPRETATION
adenocarcinomas (most common type); others Lab
associated with long-term inflammation or infection
r Occurs more frequently in areas where Schistosoma include transitional cell carcinoma, squamous cell r Urine studies: Urinalysis, culture and sensitivity,
carcinoma, and rarely sarcoma urine cytology
is endemic r Metastatic lesions are very rare
r Urachal cancer: <1% of primary bladder cancer; 1/3 r Serum electrolytes: BUN/Creatinine, liver function
– Adenocarcinomas from the colon, stomach, tests
of bladder adenocarcinomas breast, ovary, endometrium, and prostate can r Carcinoembryonic antigen (CEA), CA125, and CA
RISK FACTORS metastasize to the bladder 19-9 may be elevated in 40–60% of patients
In tissue recombinant studies, adenocarcinoma can be – Local invasion of a colonic primary tumor is more presenting with peritoneal carcinomatosis
produced from bladder urothelium under the common than metastasis
appropriate hormonal and mesenchymal stimuli. – Bladder adenocarcinoma is histologically Imaging
r Urachal cancers may show stippled calcifications on
indistinguishable from adenocarcinoma of the
Genetics plain x-ray films
colon
Associated with gain of function in regions 20q and r Sheldon Staging System for Urachal Carcinoma r 60% of bladder tumors are detected with IVP, which
8q, or loss of function at regions 5q and 8p (1) has been largely replaced with the CT scan
– Stage I: No invasion beyond the urachal mucosa
PATHOPHYSIOLOGY – Stage II: Invasion confined to the urachus r CT scan: Imaging method of choice for staging of
r Classification: Three groups related to site of tumor – Stage III: Local extension into the bladder tumors; useful for detecting presence of
origin (2,3) ◦ bladder (IIIA) pelvic lymphadenopathy and extravesical tumor
– Primary adenocarcinoma of bladder ◦ abdominal wall (IIIB) extension
– Urachal adenocarcinoma ◦ peritoneum (IIIC) – Sensitivity: 64–94%, specificity: 62–100%
– Extravesical adenocarcinoma (metastatic) ◦ viscera other than bladder (IIID) r Other investigations: CXR (staging), bone scan
r Primary vesical adenocarcinoma: Can occur – Stage IV: Metastases to the (staging, if bone pain is present), GI endoscopy, and
anywhere in the bladder, but the dome and the ◦ regional lymph nodes (IVA) breast exam (to exclude primary tumor) if clinically
trigone of the bladder are common ◦ distant site (IVB) indicated
– Most common type of cancer in bladder exstrophy Diagnostic Procedures/Surgery
– All histologic variants of enteric carcinoma may r Bladder exstrophy r Diagnostic cystoscopy and biopsy
occur in the bladder r Schistosomiasis – Essential for definitive diagnosis
– Papillary or solid; most are mucin-producing – Bloody efflux from ureteral orifices suspicious for
– Most are poorly differentiated and invasive at the GENERAL PREVENTION upper tract pathology
time of diagnosis Elimination of factors leading to chronic bladder
– Poor response to radiotherapy and chemotherapy inflammation Pathologic Findings
r Urachal carcinoma r All histologic variants of enteric carcinoma may
– For classification as a urachal carcinoma, there occur in the bladder
r Adenocarcinoma can have glandular, mucinous, or
must be:
◦ Presence of a urachal remnant signet ring patterns
◦ Clear demarcation between the tumor and r Most produce mucin
adjacent bladder mucosa r Primary adenocarcinoma of the bladder is
◦ Predominant invasion of the muscularis propria associated with cystitis glandularis and is thought to
or deeper structures of the bladder or extension arise from glandular metaplasia of the urothelium.
to the space of Retzius, anterior abdominal wall, These tumors can be papillary or solid
or umbilicus r Signet ring tumors produce linitis plastica of the
◦ Possible production of mucoid drainage from bladder. They are aggressive and radical surgical
the umbilicus excision should be considered
50
BLADDER CANCER, ADENOCARCINOMA
DIFFERENTIAL DIAGNOSIS 4. Siefker-Radtke AO, Gee J, Shen Y, et al.

r Metastasis from colon, prostate, or other ONGOING CARE Multimodality management of urachal carcinoma:
adenocarcinoma The MD Anderson Cancer Center experience.
r Benign or malignant urothelial tumors PROGNOSIS
r Signet cell variant has a 50% mortality at 1 yr
J Urol. 2003;169:1295–1298.
5. Herr HW, Bochner BH, Sharp D, et al. Urachal
B
r Urachal adenocarcinoma: Overall 11–55% 5-yr
carcinoma: Contemporary surgical outcomes.
TREATMENT survival, but early-stage disease may have up to J Urol. 2007;178:74–78.
93% 5-yr survival 6. Siefker-Radtke A. Urachal Adenocarcinoma: A
GENERAL MEASURES r Nonurachal adenocarcinoma: 27–61% 5-yr survival
r Site of origin and tumor behavior are factors Clinician’s Guide for Treatment. Sem Oncol.
r Recurrence risk for urachal carcinoma 2012;39(5):619–624.
important in determining treatment
r Adenocarcinoma of the bladder is generally – Positive margin 7. Siefker-Radtke A. Systemic chemotherapy options
– Umbilicus sparing resections are associated with a for metastatic bladder cancer. Expert Rev
unresponsive to radiation and chemotherapy. higher risk of relapse Anticancer Ther. 2006;6:877–885.
– Radical cystectomy is treatment of choice. – Tumor involving the peritoneal surfaces or the
– Excision of the urachus and umbilicus is usually abdominal wall
required if a urachal primary is suspected
r Adjuvant chemotherapy or radiotherapy may be – Occult lymph node metastases ADDITIONAL READING
used, but surgery remains the most consistently COMPLICATIONS Zhong M, Gersbach E, Rohan SM, et al. Primary
r Ureteral obstruction from local spread of tumor
effective treatment (4,5,6) adenocarcinoma of the urinary bladder: Differential
r Metastasis to pelvic lymph nodes, liver, lung,
MEDICATION diagnosis and clinical relevance. Arch Pathol Lab Med.
mediastinum, and bone 2013;137(3):371–381.
First Line r Surgical complications: Bleeding, infection, rectal
r Generally unresponsive to radiation and cytotoxic See Also (Topic, Algorithm, Media)
injury r Bladder Cancer, Adenocarcinoma Image
chemotherapy (7)
r Some response to standard regimens such as FOLLOW-UP r Bladder Cancer, General
combination methotrexate, vinblastine, adriamycin, Patient Monitoring r Urachal Carcinoma
r Abdominal imaging (CT)
cisplatin (MVAC)
r Recently, 5-FU and cisplatin-based chemotherapy r Metastatic workup if suspected
have demonstrated a modest response rate Patient Resources CODES
r A clinical trial at M.D. Anderson using gemcitabine, r American Cancer Society:
5-FU, leucovorin, and cisplatin (Gem-FLP) reported a – www.cancer.org ICD9
clinical response rate in 30–40% of patients r National Cancer Institute r 188.1 Malignant neoplasm of dome of urinary
r Currently there is no role for neoadjuvant bladder
– www.nci.nih.gov
chemotherapy for clinically node-negative resectable r United Ostomy Association: r 188.7 Malignant neoplasm of urachus
disease – www.uoa.org r 188.9 Malignant neoplasm of bladder, part
Second Line unspecified
N/A
REFERENCES ICD10
r C67.1 Malignant neoplasm of dome of bladder
r Radical cystectomy with pelvic lymph node 1. Vauhkonen H, Böhling T, Eissa S, et al. Can bladder r C67.7 Malignant neoplasm of urachus
dissection remains the gold standard adenocarcinomas be distinguished from r C67.9 Malignant neoplasm of bladder, unspecified
r Adjuvant chemotherapy or radiotherapy has not schistosomiasis-associated bladder cancers by
improved survival significantly using array comparative genomic hybridization
r Partial cystectomy (with bladder mucosal sampling) analysis? Cancer Genet Cytogenet. 2007;177(2): CLINICAL/SURGICAL
with en bloc removal of the urachus and umbilicus is 153–157. PEARLS
an option for low-volume, low-stage urachal 2. El-Mekresh MM, el-Baz MA, Abol-Enein H, et al.
Primary adenocarcinoma of the urinary bladder: A r Umbilicus may be involved in up to 7% of patients
carcinoma
report of 185 cases. Br J Urol. 1998;82(2): with adenocarcinoma of the bladder.
ADDITIONAL TREATMENT 206–212. r Most common tumor arising in the bladder of
Radiation Therapy 3. Dahm P, Gschwend JE. Malignant non-urothelial exstrophy patients, who have a 4% lifetime risk.
Urachal adenocarcinoma is radio resistant neoplasms of the urinary bladder: A review. Eur r Adenocarcinoma of the bladder is generally
Additional Therapies Urol. 2003;44:672–681. unresponsive to radiation and chemotherapy.
N/A
Therapies
N/A
51
BLADDER CANCER, GENERAL

Matthew A. Young, MD
Sandip M. Prasad, MD, MPhil
PATHOPHYSIOLOGY Imaging
BASICS r 70% of tumors present as nonmuscle-invasive r CT abdomen/pelvis
lesions – Can detect lymphadenopathy and other
DESCRIPTION – 70% of these are Ta, 20% T1, 10% CIS intra-abdominal disease
r Bladder cancer is the most common site of r Risk of recurrence – Presence of hydronephrosis is suggestive of
malignancy in the urinary system – CIS: 50–90% muscle-invasive disease
r Includes multiple histologic types: – Ta low grade: 50–70% – CT urography has replaced IVP as standard for
– Urothelial cell carcinoma (formerly transitional cell – Ta high grade: 60% evaluating upper tracts
carcinoma) is most common – T1 high grade: 70–80% r MRI may be useful for local staging
– Other: Adenocarcinoma, squamous cell – Risk of recurrence in upper tracts 2–4% r Chest x-ray (CXR): Metastasis with muscle invasion
carcinoma, and small-cell carcinoma r Risk of progression r Bone scan is recommended only in patients with
– TNM staging: Initially based on clinical findings – CIS >50% bone pain, elevated calcium, or elevated alkaline
(bladder biopsy) (See Section VII: “Reference – Ta low grade: 5–10% phosphatase
tables: TNM Classification: Urinary Bladder – Ta high grade: 15–40%
cancer.”) Diagnostic Procedures/Surgery
– T1 high grade: 30–50% r Cystoscopy is the most accurate initial diagnostic
– T staging: Primary tumor ◦ Most important prognostic factor is grade
◦ Ta/Tis/T1: Superficial/nonmuscle invasive ◦ Concurrent upper-tract UCC in patients with procedure
bladder cancer (NMIBC) – Can be done in office with local anesthesia
bladder cancer is 2–4% r Bladder biopsy
◦ T2a/T2b: Muscle invasive bladder cancer (MIBC)
◦ T3a/T3b/4a: Locally advanced ASSOCIATED CONDITIONS – Establishes pathologic diagnosis
– Regional lymph node (N) staging: Regional lymph Other smoking related illnesses (COPD) – May be definitive treatment if tumor can be
nodes (the true pelvis); all others are considered GENERAL PREVENTION completely removed
distant metastasis r Avoid occupational exposure and smoking r Prostatic urethra biopsies are not routinely
– Distant metastasis (M) staging r Urinalysis for hematuria screening performed unless there is:
– Stage grouping: r High-fat diet has been associated with increased – Multifocal disease of the bladder
◦ Stage 0: Tis, N0, M0 – CIS of the bladder
risk of bladder cancer
◦ Stage 1: Ta-T1, N0, M0 r Vitamins A and B compounds have not shown – Visible abnormality in the prostatic urethra
◦ Stage II: T2, N0, M0 r Retrograde pyelography
◦ Stage III: T3a-T4a, N0, M0 conclusive benefit for primary prevention
r Long-term hydration may be beneficial – May be used in setting of renal impairment or
◦ Stage IV: T4b, N0, M0 or any T, N1,2,3, M0 or contrast allergy
any T, any N, M1 – Further evaluate equivocal findings on CT
EPIDEMIOLOGY DIAGNOSIS Pathologic Findings
r Carcinoma in situ (CIS) is a urothelial cancer that is
Incidence HISTORY
r American Cancer Society 2014 new case estimates: flat, high grade, and noninvasive but has metastatic
r Gross painless hematuria is the most common
74,690 (male: 56,390 female: 18,300) potential. Patients with bladder CIS have a 20% risk
presenting symptom of upper-tract disease
– Estimated 155,800 deaths in 2014 r Irritative voiding symptoms (present in 20%)
r 3:1 male–female ratio r Histologic types
r 4th most common cancer in males, 7th most – Often associated with CIS – Transitional cell carcinoma (urothelial carcinoma),
r Smoking history (quantify in pack years and if/when
common cancer in females 90%
r Median age of diagnosis is 70 yr patient quit) – Squamous cell carcinoma, 3–7%
r Occupational exposures (see “Risk Factors”) – Adenocarcinoma, <2%
Prevalence – Small cell, sarcomas (leiomyosarcoma,
3rd most prevalent cancer in men (high recurrence) PHYSICAL EXAM
r Rarely abnormal in NMIBC rhabdomyosarcoma) uncommon
RISK FACTORS r General DIFFERENTIAL DIAGNOSIS
r Tobacco smoking confers a 2–4 times risk over r Hematuria
– Weight loss, abdominal/pelvic masses,
those that have never smoked lymphadenopathy, flank tenderness – Trauma: Iatrogenic, other
– Risk reduction after quitting takes up to 20 yr r DRE with bimanual exam in men and women may – Neoplasms: Malignancies: (30% of adults with
r Occupational exposures: painless, gross hematuria and ∼10% with
reveal palpable mass in bladder
– Painters, leather, petroleum, chemical and metal painless microscopic hematuria have a
workers, dry cleaners, truck drivers, hairdressers DIAGNOSTIC TESTS & INTERPRETATION malignancy), benign tumors, endometriosis
– Aromatic amines such as aniline dyes, benzidine, Lab – Inflammatory causes: UTI (most common cause of
r Urinalysis with microscopy: RBCs
naphthylamine, 4-aminobiphenyl, and coal soot hematuria in adults), other infections
r Cyclophosphamide treatment r Urine cytology (Schistosomiasis, TB, syphilis) radiation cystitis
– Caused by toxic metabolite, acrolein – High specificity (96%), more sensitive for – Renal/glomerular diseases: Nephritis,
r Pelvic radiation high-grade tumors (50%) Goodpasture syndrome, IGA nephropathy, lupus
r Risk for squamous cell carcinoma r Other urinary markers nephritis, glomerular diseases
– Indwelling catheters, bladder calculi – FISH (evaluate aneuploidy for chromosomes (membranoproliferative, poststreptococcal, or
– Schistosomiasis (Schistosoma hematobium) 3,7,17 and 9p21) rapidly progressive glomerulonephritis)
◦ Sensitivity 77%, specificity 98% – Urolithiasis: 85% have hematuria
Genetics – NMP-22 (marker of urothelial cell death) – Congenital/Familial causes: Cystic disease, benign
r No clear hereditary causes identified
◦ Sensitivity 56%, specificity 85% familial hematuria, etc.
r Tumor suppressor p53 is the most commonly altered r Renal function tests (BUN, Creatinine) – Hematologic causes: Bleeding dyscrasias (eg,
gene in bladder cancer – May indicate renal impairment secondary to hemophilia), Sickle cell anemia/trait (renal
ureteral obstruction papillary necrosis)
r Liver function tests – Vascular causes: Hemangioma, AVM (rare),
– May be abnormal due to metastasis Nutcracker syndrome, renal artery/vein
thrombosis, arterial emboli to kidney
52
BLADDER CANCER, GENERAL
– Chemical causes: Nephrotoxins (Aminoglycosides, – Gemcitabine and cisplatin REFERENCES

cyclosporine), analgesics, oral contraceptives, ◦ Common toxicity: Myelosuppression
Chinese herbs ◦ Overall response rate 40–50%, similar to MVAC 1. Lamm DL, Blumenstein BA, Crissman JD, et al.
– Obstruction: Strictures or posterior urethral valves,
hydronephrosis (any cause) benign prostatic
with better toxicity profile
r Neoadjuvant platinum-based chemotherapy: 5-yr
Maintenance bacillus Calmette-Guerin
immunotherapy for recurrent Ta, T1 and carcinoma
B
hyperplasia: Rule out other causes of hematuria. overall survival benefit of 5% in situ transitional cell carcinoma of the bladder: A
– Other causes: Loin pain hematuria, menses randomized SWOG Study. J Urol. 2000;163:
r Bladder filling defect: Second Line 1124–1129.
r Valrubicin: Intravesical therapy of BCG-refractory CIS
– Air: Artifactual, postinstrumentation, vesicoenteric 2. Grossman HB, Natale RB, Tangen CM, et al.
in patients for whom immediate cystectomy would
fistula Neoadjuvant chemotherapy plus cystectomy
be associated with unacceptable morbidity or
– Benign tumors: Prostatic enlargement, etc. compared with cystectomy alone for locally
mortality
– Blood clot, calculus, fungus ball (bezoar) r Other intravesical agents after BCG failure: advanced bladder cancer. N Engl J Med.
– Congenital: Ureterocele 2003:349:859–866.
Mitomycin C, gemcitabine, interferon α 2b
– Extrinsic compression 3. Shipley WU, Zietman AL, Kaufman DS, et al.
– Infective, inflammatory: Inflammatory edema SURGERY/OTHER PROCEDURES Selective bladder preservation by trimodality
– Instruments (catheters), foreign body r “Blue light” (Cysview) cystoscopy FDA approved therapy for patients with muscularis
– Malignant tumor: Bladder and prostate may improve lesion detection propria-invasive bladder cancer and who are
malignancy, tumors invading urinary bladder r Narrow band imaging evolving for diagnosis cystectomy candidates—The Massachusetts
– Radiologic artifact: Fold in bladder General Hospital and Radiation Therapy Oncology
ADDITIONAL TREATMENT Group experiences. Semin Radiat Oncol. 2005;
Radiation Therapy 15:36–41.
TREATMENT r Bladder preservation approaches (trimodality
therapy) (3)
GENERAL MEASURES – 1. TURBT: Must be completely resected
r Transurethral resection of bladder tumor (TURBT) ADDITIONAL READING
– 2. Chemotherapy: Platinum-based regimens
determines diagnosis (grade/stage/type) – 3. Radiation therapy N/A
r Primary treatment is surgery – Optimal patients have solitary T2 tumors that can
– Bladder biopsy can be both diagnostic and See Also (Topic, Algorithm, Media)
be completely resected, no hydronephrosis, no r Bladder Cancer, Adenocarcinoma
therapeutic (for nonmuscle-invasive tumors) associated CIS, normal renal function r Bladder Cancer, General Image
– For T1, repeat TURBT should be performed – Usually biopsy mid-treatment: Recommend r Bladder Cancer, Intravesical Agents (Table)
2–6 wk after initial resection as upstaging occurs cystectomy if no response
in up to 30% of cases. r Bladder Cancer, Nonmuscle-Invasive Bladder Cancer
– 5-yr survival is similar to radical cystectomy
r Radical cystectomy with pelvic lymphadenectomy (Ta, T1).
Additional Therapies r Bladder Cancer, Squamous Cell Carcinoma
– Initial therapy for muscle-invasive tumors Oncovite (high-dose vitamin A, B6, C, E, and zinc)
– May be needed for recurrent high-grade T1 r Bladder Cancer, Urothelial, Muscle-Invasive (Clinical
after TUR and induction BCG had a reduction in
tumors or CIS that has failed to respond to recurrence vs. RDA vitamins (secondary prevention) and Pathologic T2/T3/T4) (MIBC) Neoadjuvant
intravesical therapy Therapy
Complementary & Alternative r Bladder Cancer, Urothelial, Muscle Invasive (Clinical
MEDICATION Therapies and Pathologic T2/T3/T4) (MIBC)
First Line N/A r Bladder Cancer, Urothelial, Superficial Carcinoma In
r Intravesical therapy for higher-risk NMIBC
r BCG (Bacillus Calmette-Guerin) (1) Situ (CIS) (NMIBC)
ONGOING CARE r Bladder Tumor Algorithm
– Only after bladder healed (usually 4 wk); 40% r Hematuria, Gross and Microscopic, Adult
reduction in recurrence, 23–27% reduction in PROGNOSIS r Reference Tables: TNM Classification: Urinary
progression r 5-yr survival by stage: I, 85–96%; II, 55–65%; III,
– Maintenance BCG increases recurrence-free time; Bladder Cancer
38–59%; IV, 15–27%
BCG: Superior to intravesical chemotherapy for CIS r Recurrence: CIS, 80%; Ta, 50%; T1, 50–70%
– Side effects: Cystitis, dysuria, hematuria, malaise, – Progression: CIS, 20% after a complete response
fatigue, low-grade fever CODES
to BCG; Ta, 5%; T1, 30–40%
– Complications: Fever >101.5◦ F (38.6◦ C) for
>12–24 hr may require broad-spectrum COMPLICATIONS ICD9
antibiotics and isoniazid r Urinary retention from gross hematuria or tumor r 188.0 Malignant neoplasm of trigone of urinary
◦ Sepsis (0.4%) – fever >102◦ F (38.8◦ C) or signs infiltrating or blocking bladder outlet bladder
of sepsis. Treat with prednisone, broad-spectrum r Ureteral obstruction r 188.8 Malignant neoplasm of other specified sites
antibiotics, and anti-tuberculosis drugs of bladder
r Mitomycin C FOLLOW-UP r 188.9 Malignant neoplasm of bladder, part
– Alternative when BCG cannot be used Patient Monitoring
r NMIBC: Cystoscopy and cytology every 3 mo for unspecified
– Reduces tumor recurrence up to 40%
– Given as a single dose within 24 hr of TURBT 2 yr, then every 6 mo for 2 yr, then annually ICD10
– Upper-tract surveillance every 1–2 yr r C67.0 Malignant neoplasm of trigone of bladder
(40 mg in 20-mL saline or sterile water) r Muscle-invasive disease
– Contraindicated with bladder perforation r C67.8 Malignant neoplasm of overlapping sites of
– Side effects: Dermatitis, irritative voiding, – Liver function tests, creatinine, electrolytes, CXR bladder
absorption may cause myelosuppression every 6–12 mo r C67.9 Malignant neoplasm of bladder, unspecified
r Platinum-based drug regimens are the most – Upper-tract imaging, baseline and every 2 yr
effective systemic chemotherapeutic agents (2) – Cytology every 6–12 mo ± male urethral wash
– Neoadjuvant or adjuvant therapy for invasive (cutaneous diversion) CLINICAL/SURGICAL
disease (Stage II/III) Patient Resources PEARLS
– Metastatic disease (Stage IV) BCAN (Bladder Cancer Advocacy Network)
◦ MVAC (mitomycin, vinblastine, adriamycin, www.bcan.org 70% of bladder cancers present as
cisplatin) nonmuscle-invasive lesions.
◦ Overall response rate 40–50%
◦ Common toxicities: Mucositis, renal toxicity,
myelosuppression, sepsis, cardiac toxicity
53
BLADDER CANCER, NON-MUSCLE-INVASIVE BLADDER CANCER (TA, T1)

(NMIBC)
John B. Eifler, MD
Genetics DIAGNOSTIC TESTS & INTERPRETATION

BASICS r 2× increased risk for 1st-degree relatives of bladder
Lab
cancer patients r U/A, including dipstick and micro evaluation for
DESCRIPTION r Genetics affect susceptibility to carcinogens (eg, RBCs
r Bladder cancer is a malignant neoplasm usually r Urine cytology: High specificity but low sensitivity.
slow acetylators NAT2, null GSTM1)
arising from originating from the lining of the r Lynch syndrome – typically increased upper-tract UC, Best at detecting HG NMIBC and CIS
bladder (urothelium) though some subtypes increase risk of bladder r Other urinary tests: Urine cytology, BTA-Stat,
– A papillary tumor confined to the mucosa is cancer NMP22, UroVysion FISH: Low sensitivity and
classified as stage Ta according to the Tumor,
PATHOPHYSIOLOGY specificity for LG disease. Not generally
Node, Metastasis (TNM) classification system.
r Inciting genetic event recommended for routine workup of microscopic
– Tumors that have invaded the lamina propria are
– Low grade (LG): Deletion of part of chr 9 (RB hematuria but may be considered for high-risk
classified as stage T1.
gene) and/or mutation in FGFR-3 patients (see “Additional Reading”)
– Ta and T1 tumors can be removed by transurethral
resection (TUR), and are called NMIBC – High grade (HG): Numerous mutations Imaging
(particularly TP53), aneuploidy of chr 7, 9, 17 r Goal: Evaluate renal parenchyma, renal collecting
(nonmuscle-invasive bladder cancer)
r Most common histology: Urothelial carcinoma r NMIBC comprises ∼70% of bladder cancer system and ureters
– Recurrence rate: ∼60% for LG, >80% for HG r CT urogram (3-phase CT abd/pelvis with IV
(previously called transitional cell carcinoma/TCC)
r ∼70% of bladder cancers are nonmuscle-invasive at ◦ Most recurrences within 1st 6 mo after TURBT, contrast): Study of choice for evaluation of
presentation but may occur after many years gross/microscopic hematuria
r Challenging management: Due to recurrence and ◦ May also recur in upper tracts or prostatic r If patient cannot receive IV contrast, consider MRI +
potential to progress to lethal disease urethra RPG (retrograde pyelogram)
r Due to need for lifelong monitoring, highest cost per – Progression influenced by stage and grade – U/S + RPG if patient cannot receive gadolinium
◦ Stage Ta, LG: 5–10%; HG: 15–40% at 5 yr
patient of any cancer ◦ Stage T1, HG 30–50% at 5 yr Diagnostic Procedures/Surgery
r Bladder CA typically detected on cystoscopy
EPIDEMIOLOGY – Eventual death rate 10–25% for HG Ta, 33% for
HG T1 (1) – Cystoscopy indicated for gross hematuria and
Incidence most cases of microscopic hematuria (see chapter
r In US, all cases estimated 74,690 in 2014 r Other risk factors for progression
“Hematuria, gross and microscopic, adult”)
– 15,580 estimated cancer deaths in 2014 – Architecture: Nodular/sessile/broad based > ◦ In office, under local anesthesia, at time of initial
r Highest incidence: Men >60, women >70 papillary
presentation. It may be combined with biopsy
r Caucasian > African American > Latino – Multifocality > solitary ◦ TURBT under general or spinal anesthesia is
r 4th most common cancer in men – Size >5 cm
definitive
– Lymphovascular invasion r Retrograde pyelography may be used for equivocal
Prevalence – Mutations in TP53, RB, and PTEN predict poor
r 2nd most prevalent cancer in middle-aged and CT urogram or when CT urogram/MRI
prognosis
elderly men contraindicated to exclude concomitant upper-tract
r Male:female ∼3:1 ASSOCIATED CONDITIONS lesions in patients with hematuria or positive
See “Risk Factors” cytology
RISK FACTORS
r Tobacco smoking history (most common risk factor) GENERAL PREVENTION Pathologic Findings
r Smoking cessation r Urothelial Dysplasia
– Overall 2.8× higher incidence in smokers r Avoidance of occupational exposure – Precursors to CIS/Urothelial cancer
– Risk increases with number of pack-years r Papilloma
◦ 6× risk for 60 pack year history r Hydration long term beneficial
– Latency often >20 yr from time of exposure – Papillary lesion with low recurrence risk (0–8%) or
– Quitting decreases risk progression risk (2%)
◦ 15 yr after quitting, relative risk 1.1 DIAGNOSIS r Papillary Urothelial Neoplasm of Low Malignant
r Occupational exposure Potential (PUNLMP)
HISTORY – Papillary growth, minimal cytologic atypia
– Organic chemicals, especially aromatic r Most common in men >50; Males > Females due
(aryl)-amines – Recurrence 35%, progression 4%
to smoking prevalence r CIS: See chapter “Bladder cancer, urothelial,
◦ Naphthalenes, benzidine, aniline dyes, r 1st occurrence: 85% present with either gross or
4-aminobiphenyl superficial, carcinoma in situ (CIS)”
microscopic hematuria. Painless gross hematuria is r Papillary cancer: Confined to either urothelium
– High-risk occupations: Petroleum/rubber/leather/ hallmark of bladder CA
paint/textile workers, hairdressers, truck drivers, r Irritative symptoms (eg, dysuria, urgency, frequency) (stage Ta) or invasion of lamina propria (stage T1)
aluminum electroplaters and may be LG or HG
occasionally due to bladder CA, especially CIS
– Arsenic contamination of drinking water – Microscopic hematuria typically present if due to DIFFERENTIAL DIAGNOSIS
– Latency may be 40 yr cancer See Section I “Bladder cancer, general” for complete
r Chemotherapy with cyclophosphamide (Cytoxan) r Smoking history: differential diagnosis of hematuria and bladder filing
r Pelvic radiation
– Record total pack-years, current packs/day, and defect
– 4× increased risk after RT for cervical cancer years since quitting if applicable
– ∼1.5× risk after RT for prostate cancer r Occupational risk factors
r Chronic cystitis → SCC
– Indwelling catheters, chronic bladder calculi, PHYSICAL EXAM
cystitis due to Schistosoma hematobium Usually unremarkable for NMIBC
54
BLADDER CANCER, NON-MUSCLE-INVASIVE BLADDER CANCER (TA, T1) (NMIBC)
ADDITIONAL TREATMENT 4. Malmström PU, Sylvester RJ, Crawford DE, et al. An

TREATMENT Radiation Therapy individual patient data meta-analysis of the
No role in superficial disease long-term outcome of randomized studies
GENERAL MEASURES
r Resection with selective use of intravesical therapy is Additional Therapies
comparing intravesical mitomycin C versus bacillus
Calmette-Guérin for non-muscle-invasive bladder
B
Adjuvant intravesical chemotherapy/immunotherapy cancer. Eur Urol. 2009;56:247–256.
the mainstay
r TURBT of all visible tumor: 1st-line treatment; both (as above)
5. de Lorgeril M, Salen P, Martin JL, et al.
diagnostic and therapeutic Complementary & Alternative Mediterranean dietary pattern in a randomized trial:
– For sessile lesions, HG disease, or CIS, random Therapies Prolonged survival and possible reduced cancer
biopsies of the bladder and prostatic urethra in Mediterranean diet (high intake of fruit, rate. Arch Intern Med. 1998;158:1181–1187.
men should be considered vegetables, legumes) thought to lower risk of
urothelial cancer (5)
MEDICATION
ADDITIONAL READING
First Line
r Intravesical therapy: Adjuvant to surgery to reduce ONGOING CARE r AUA Guideline for the Management of Non-muscle
tumor recurrence/progression Invasive Bladder Cancer: (stages Ta, T1, and Tis):
– Intravesical chemotherapy PROGNOSIS Update (2007). Available at http://www.auanet.org/
◦ Drugs: Thiotepa, doxorubicin (Adriamycin), See “Pathophysiology”
content/clinical-practice-guidelines/clinical-
mitomycin, valrubicin COMPLICATIONS guidelines.cfm?sub=bc, Accessed on April
◦ Single-dose perioperative intravesical TURBT: Bleeding, irritative symptoms, bladder 2013.
chemotherapy within 6 hr of TURBT reduces perforations (mainly extraperitoneal); usually can be r Babjuk M, Burger M, Zigeuner R, et al. EAU
tumor recurrence for LG disease managed conservatively with catheter drainage and guidelines on non-muscle-invasive urothelial
◦ Marginal (7–14%) reduction in long-term anticholinergics carcinoma of the bladder: Update 2013. Eur Urol.
recurrence rate 2013;64(4):639–653.
◦ No decrease in tumor progression FOLLOW-UP r National Comprehensive Cancer Network, Available
– Intravesical BCG Patient Monitoring
r Surveillance after TURBT: Cystoscopic and urine at http://www.nccn.org/professionals/physician gls/
◦ Live suspension of attenuated Mycobacterium PDF/bladder.pdf, Accessed on November 2013.
bovis vaccine strain instilled in bladder via Foley cytology every 3–6 mo for 2 yr, then increasing
and retained for 2 hr interval as appropriate See Also (Topic, Algorithm, Media)
◦ Give 2–4 wk after TURBT; Weekly – Schedule resets with each recurrence r BCG Sepsis/BCGosis
administration × 6 wk for induction course. r TURBT as necessary, depending on cytology results r Bladder Cancer, General
◦ Maintenance courses improve efficacy and cystoscopic appearance r Bladder Cancer, Intravesical Agents (Section II Table)
◦ Most effective intravesical agent, with initial r Upper-tract surveillance studies (CT urogram) every r Bladder Cancer, Non-Muscle-Invasive Bladder
response rates up to 84% 2–3 yr for HG bladder tumors and CIS Cancer (Ta, T1) Image
◦ Most ultimately recur (30% disease-free survival r Bladder Cancer, Urothelial, Superficial Carcinoma In
Patient Resources
at 10 yr) r Schoenberg, Mark. The Guide to Living with Bladder Situ (CIS) (NMIBC)
◦ Decreases risk of progression by ∼35%, but r Bladder Cancer, Urothelial, Invasive (Clinical and
Cancer. Baltimore: The Johns Hopkins University
benefit mostly seen in maintenance therapy Press, 2000. Pathologic T2/T3/T4)
◦ Toxicity: Generally well tolerated though urinary r BCAN (Bladder Cancer Advocacy Network) r Bladder Cancer, Urothelial, Metastatic (Clinical and
frequency, dysuria, and low-grade fever common
◦ Risk of systemic BCG infection (see Section I www.bcan.org Pathologic N+, M+)
r Bladder Tumor Algorithm
“BCG sepsis/BCGosis.”) r Bladder Tumors, Benign and Malignant, General
r BCG: Greater efficacy than intravesical
REFERENCES Considerations
chemotherapy though higher morbidity (4)
Second Line 1. Donat SM. Evaluation and follow-up strategies for
superficial bladder cancer. Urol Clin North Am.
N/A
2003;30:765–776. CODES
SURGERY/OTHER PROCEDURES 2. Sylvester RJ, Oosterlinck W, van der Meijden AP. A
r Repeat TURBT indicated for T1 and HG Ta as ICD9
single immediate postoperative instillation of
25–50% may harbor worse prognostic findings on chemotherapy decreases the risk of recurrence in 188.9 Malignant neoplasm of bladder, part
2nd TURBT patients with stage Ta T1 bladder cancer: A unspecified
r Bladder biopsies (random): Helpful if positive meta-analysis of published results of randomized ICD10
cytology with no obvious lesion clinical trials. J Urol. 2004;171:2186–2190. C67.9 Malignant neoplasm of bladder, unspecified
r Laser/electrofulguration: Useful for recurrent, small, 3. Sylvester RJ, van der Meijden AP, Lamm DL.
LG papillary tumors; may be performed under local Intravesical bacillus Calmette-Guerin reduces the
anesthesia risk of progression in patients with superficial CLINICAL/SURGICAL
r Fluorescence “Blue Light”/Cysview cystoscopy bladder cancer: A meta-analysis of the published PEARLS
– Intravesical agent binds porphyrins in neoplastic results of randomized clinical trials. J Urol.
2002;168:1964–1970. r Greatest risk factor for progression to MIBC is
tissue and fluoresces under blue light
– Improves detection of papillary tumors and CIS; high-grade disease.
Decreases recurrence but not progression r Administration of mitomycin C at the time of TURBT
– Recommended by EAU guidelines for low-grade NMIBC decreases risk of recurrence
r Narrow band imaging (NBI) is an evolving but not progression.
endoscopic technology r Though the majority of men with high-grade NMIBC
r Radical cystectomy: Indicated in HG NMIBC respond to BCG, most will ultimately recur.
refractory to BCG, particularly if 2nd induction
course fails
55
BLADDER CANCER, SQUAMOUS CELL CARCINOMA

Daniel J. Canter, MD
PATHOPHYSIOLOGY (1) DIAGNOSTIC TESTS & INTERPRETATION

BASICS r Schistosomiasis infection
Lab
r Transitional cell dedifferentiation r Urinalysis/urine culture
DESCRIPTION – Transitional cells possess unique ability to r Urinary cytology usually not reliable
r Squamous cell carcinoma (SCC) of the bladder is a
dedifferentiate into any cell type r CBC
histologic variant of bladder cancer r Chronic irritation of bladder mucosa due to a variety r Comprehensive metabolic panel, including (liver
– Most frequent histologic form of bladder cancer in of etiologies, especially SCIs
countries with endemic schistosomiasis function testing) LFTs, alkaline phosphatase, and
r Most common bladder sites are the lateral wall and
– SCC comprises 2–5% of all bladder albumin
trigone
cancers—most common histologic variant in Imaging
Western countries ASSOCIATED CONDITIONS r Cross-sectional imaging of the chest, abdomen, and
r Neurogenic bladder/SCIs pelvis based on patient’s renal function (CT scan vs.
EPIDEMIOLOGY r Need for chronic indwelling Foley/CIC MRI)
Incidence r Smoking history r Bone scan if elevated calcium, alkaline phosphatase,
r 2–5% of bladder cancers in Western countries
r Living and travel to areas endemic with or unexplained pain
r Originally reported that patients with spinal cord
schistosomiasis Diagnostic Procedures/Surgery
injuries (SCIs) had an incidence of SCC of the r Exam under anesthesia (EUA) and transurethral
bladder of 2.3%—more recent data only suggests GENERAL PREVENTION
0.39% incidence r No good screening test for bladder cancer in general resection of bladder tumor (TURBT) of primary
r Approximately 75–80% of all bladder cancers are r Smoking cessation tumor for histologic diagnosis and clinical staging
r Patients with indwelling catheters (Foley, suprapubic r Radical cystectomy with lymph node dissection and
SCCs in regions with endemic schistosomiasis
tube, etc.) should be screened with yearly urinary diversion is considered 1st-line treatment
Prevalence
Difficult to assess since so many of these patients will cystoscopy +/– biopsy Pathologic Findings
– When to start is open to debate r Mixed urothelial and squamous carcinomas are
ultimately die of bladder cancer
r Treatment of patients infected with schistosomiasis more common than pure SCCs
RISK FACTORS (praziquantel) – The term SCC of the bladder is used only if tumor
r Schistosomiasis infection
is solely composed of squamous cell component,
r Transitional cell carcinoma (TCC) can differentiate with no urothelial carcinoma component
into any histology DIAGNOSIS r Grading unreliable. Mostly considered a high-grade
r Smoking neoplasm
r Chronic bladder infection/irritation HISTORY r Histologic findings
r History of living/travel to countries with endemic
– Patients with SCIs – Squamous metaplasia
schistosomiasis
– Chronic indwelling Foley catheter/CIC r In general, in Western countries, patients who have – Keratinized islands
– Chronic infection – Squamous pearls
– Bladder stones SCC of the bladder present in the same manner as
– Intercellular bridges
– Leukoplakia urothelial carcinoma of the bladder
– Mitotic figures common
– Squamous metaplasia – Hematuria
r HPV infection – Constitutional symptoms DIFFERENTIAL DIAGNOSIS
– Flank/back pain due to ureteral obstruction r Urothelial carcinoma of the bladder
r Industrial exposures for workers involved in the
– History of chronic irritation to bladder mucosa r Squamous metaplasia
production of rubber, leather, textiles, and paint r Other histologic variant of bladder
(traditionally more associated with the development PHYSICAL EXAM
r Palpable mass on rectal/vaginal exam (adenocarcinoma, sarcomatoid, etc.)
of pure urothelial carcinoma) r Invasive cervical cancer: Often squamous cell
r Gross hematuria
Genetics
r Association with variations in inflammatory genes
r Epidermal growth factor receptor and p53
overexpression implicated as well as p16
abnormalities
r Keratin 10 and caveolin-1 identified as potential
markers of differentiation from TCC to SCC
56
BLADDER CANCER, SQUAMOUS CELL CARCINOMA
REFERENCES
1. Kim SP, Frank I, Cheville JC, et al. The impact of
GENERAL MEASURES
r Treatment is related to stage
PROGNOSIS
r Related to pathologic stage (3)
squamous and glandular differentiation on survival
after radical cystectomy for urothelial carcinoma.
B
r In general, SCC of the bladder presents with locally – Evidence suggests that patients with SCC of the J Urol. 2012;188:405–409.
advanced disease, and radical cystectomy with bladder tend to present with higher-stage 2. Rausch S, Lotan Y, Youssef RF. Squamous cell
urinary diversion is an integral part of the treatment (pT3/T4) disease at the time of radical cystectomy carcinogenesis and squamous cell carcinoma of the
r Overall survival has ranged from 4.8 to 50% urinary bladder: A contemporary review with focus
paradigm
r Although uncommon, noninvasive lesions can be r 5-yr cancer-specific survival in contemporary series on nonbilharzial squamous cell carcinoma. Urol
treated with local resection and diligent surveillance has ranged from 57 to 64% Oncol. 2014;32(1):32.e11–6.
3. Xylinas E, Rink M, Robinson BD, et al. Impact of
MEDICATION COMPLICATIONS
r Related to radical cystectomy and urinary diversion histological variants on oncological outcomes of
First Line patients with urothelial carcinoma of the bladder
r Systemic chemotherapies have been used with – Perioperative mortality approaches 2%
treated with radical cystectomy. Eur J Cancer.
limited experience in treating SCC of the bladder – 40–50% of patients will experience a
2013;49(8):1889–1897.
r Small series have reported positive responses to postoperative complication
– Gastrointestinal complication is most common,
cisplatin-based therapies, similar to pure urothelial
eg, ileus, small bowel obstruction
carcinoma ADDITIONAL READING
r At present, role for neoadjuvant/adjuvant FOLLOW-UP
chemotherapy is poorly defined Patient Monitoring N/A
r Related to tumor stage at the time of radical See Also (Topic, Algorithm, Media)
Second Line
cystectomy r Bladder Cancer, General
N/A
– In general, patients are followed with history, r Bladder Cancer, Squamous Cell Carcinoma Image
SURGERY/OTHER PROCEDURES (2) physical exam, laboratory studies (CBC and r Bladder Cancer, Urothelial, Muscle Invasive (Clinical
r After diagnosis is confirmed, radical cystectomy is
comprehensive metabolic profile, including liver and Pathologic T2/T3/T4) (MIBC)
1st-line treatment function tests) and cross-sectional imaging of
r Bladder-preserving therapies can be considered if chest, abdomen, and pelvis every 3–6 mo after
tumor is nonmuscle invasive and completely surgery for the first 2 yr then semiannually for 2 yr
resected, and patient is willing to commit to then annually
CODES
intensive surveillance protocol – Renal function needs to be followed annually as
r Limited experience with chemoradiotherapy as well ICD9
primary treatment modality 188.9 Malignant neoplasm of bladder, part
Patient Resources unspecified
ADDITIONAL TREATMENT Bladder Cancer Advocacy Network (www.bcan.org)
Radiation Therapy ICD10
C67.9 Malignant neoplasm of bladder, unspecified
Can be used in adjuvant setting for patients with
positive surgical margins at time of surgery
Additional Therapies CLINICAL/SURGICAL
N/A PEARLS
Complementary & Alternative r With the control of schistosomiasis in endemic
Therapies
regions, the rate of SCC is dropping relative to the
N/A
diagnosis of urothelial carcinoma.
r Radical cystectomy is the gold standard for
muscle-invasive SCC of the bladder.
57
BLADDER CANCER, UROTHELIAL, METASTATIC (CLINICAL AND

PATHOLOGIC N+, M+)
Jean Hoffman-Censits, MD
Wm. Kevin Kelly, DO
GENERAL PREVENTION Pathologic Findings

BASICS r Smoking cessation r Urothelial (formerly transitional cell) carcinoma is
r Limit or modify chemical exposure the most common subtype, and for which the most
DESCRIPTION r Hydration may limit toxin exposure data exists.
r Inoperable and metastatic bladder cancers are less – Many patients may have urothelial cancer with
common presentations than noninvasive-bladder squamous or other foci of dedifferentiation.
cancer. DIAGNOSIS r Less common histologic subtypes are squamous cell
r Though radical cystectomy for muscle-invasive carcinoma, adenocarcinoma, and small cell
bladder cancer is potentially curative, up to 50% of HISTORY carcinoma.
r Many tumor recurrences are noted during routine
patients will develop recurrent disease within 2 yr.
r Most deaths from bladder cancer are from radiographic surveillance, which is standard DIFFERENTIAL DIAGNOSIS
following radical cystectomy. r Pelvic and retroperitoneal adenopathy
metastatic disease. r Pain from bone metastasis, lymphatic progression in
r Lymph nodes, bones, lung, liver, and peritoneum are – Malignancy: Lymphoma (non-Hodgkin, Hodgkin,
the retroperitoneum, bowel obstruction with others); metastatic (adrenal, renal, urothelial,
the most common sites of metastasis from bladder prostate, urethral, penile, germ cell, cervical,
cancer. The brain can also be a site, especially after carcinomatosis, and symptoms of visceral
progression such as in the lungs and liver can be ovarian, uterine), GI (carcinoid, lymphomas),
systemic chemotherapy. Other unusual sites: Heart, colorectal, melanoma
kidney, spleen, pancreas, and reproductive system. symptoms of metastatic bladder cancer.
r The 5-yr survival for distant metastasis is 5.4%. This – Infectious/inflammatory:
PHYSICAL EXAM ◦ Granulomatous: TB, sarcoidosis, histoplasmosis,
is in comparison to the 5-yr survival for localized r Most with early advanced or metastatic disease
lymphogranuloma venereum, Castleman
bladder cancer of 70.2%. have no significant external exam findings. disease, etc.
– Palpable lymphadenopathy, hepatomegaly from ◦ Nongranulomatous: Viral, bacterial (if abscess in
EPIDEMIOLOGY liver involvement, as well as cachexia of
Incidence local areas), sinus histiocytosis, retroperitoneal
r 74,690 new cases of bladder cancer will be malignancy can be noted. fibrosis
r Leg edema with venous thromboembolism is
diagnosed in 2014 with 15,580 deaths – Other: Cystic retroperitoneal masses (lymphocele,
r Bladder cancer is the 4th most common cancer present (incidence 1–8%); higher incidence with urinoma, hemorrhage) aneurysms
platinum combination therapy. r Bone lesions
diagnosed in men. Bladder cancer is much more r Poor nutrition and increased abdominal girth in
common in men than women, whites, and those – Congenital (bone islands, others)
setting of ascites and soft tissue intra-abdominal – Endocrine/metabolic (hyperparathyroidism, Paget
over 55 yr of age recurrence can contribute to edema. disease)
Prevalence – Neoplasm primary (osteosarcoma) or secondary
An estimated 563,640 people are living with all stages (prostate, breast, kidney, lung, thyroid)
of bladder cancer in US. Lab
r Lab abnormalities can include anemia of chronic – Trauma fracture (stress or healing)
RISK FACTORS – Others: Autoimmune diseases, drugs (Vitamin D,
disease, iron deficiency anemia in patients with
r Cigarette smoking fluoride), infection (osteomyelitis),
longstanding hematuria, renal insufficiency in
r Chemical and occupational exposure association inflammatory/Idiopathic, vascular (hemangiomas,
patients with ureteral obstruction, transaminitis
(aromatic amine exposure, workers in rubber, textile, infarct)
(elevation of liver transaminases), and elevation in r Pulmonary nodules
leather, painting, printing, machinist, hairdressing, bilirubin in patients with liver involvement.
dry-cleaning, and trucking industries) r Hypercalcemia is rare and associated with poor – Benign: Abscesses, septic emboli, fungal
r Pelvic radiation and chemotherapy (Cytoxan) (histoplasmosis, etc.), parasites, mycobacterial,
prognosis (typically associated with squamous
inflammatory conditions (Wegner granulomatosis),
Genetics differentiation)
r No serum tumor marker for bladder cancer. pulmonary AVM, pneumoconiosis, silicosis
r A family history of bladder cancer increases risk,
– Malignant: Primary lung cancer, bladder cancer,
either from genetic or environmental factors Imaging choriocarcinoma, renal and thyroid cancer,
r Patients with hereditary nonpolyposis colorectal r Staging guidelines recommend abdomen and pelvis melanoma, Kaposi’s sarcoma
cancer (HNPCC, Lynch syndrome) are at increased imaging with CT or MRI
risk of developing urothelial cancers r Imaging of the upper tract collecting system
r Genetic alterations in FGFR3/RAS, p53, EGFR, r Chest imaging TREATMENT
PIK3CA, Her-2, and others r Bone scan if clinical suspicion of bone metastasis by
GENERAL MEASURES
PATHOPHYSIOLOGY pain or alkaline phosphatase elevation r Treatment of urothelial (transitional cell) carcinoma
r Alterations in genes which contribute to toxin r PET may be useful but not standard of care
with cisplatin-based chemotherapy has increased
breakdown within the bladder (such as GST and r Documentation of normal cardiac ejection fraction survival but cures are limited. With good
NAT), may make bladder cancer more likely required for Adriamycin performance status and renal function
r Tumor multifocality and high recurrence rate within cisplatin-based combination chemotherapy is the
the bladder, ureters, and renal pelvis with a bladder r Needle biopsy of suspected metastatic lesions initial approach (Grade 1A) (1)
cancer history support a field effect, in part from r Confirmatory needle biopsy at the time of r “Fitness” for cisplatin-based therapy is not well
toxin exposure radiographic recurrence, particularly for a patient defined: Generally assessment of renal
ASSOCIATED CONDITIONS with residual invasive or node-positive disease at function(>60 mL/min), hearing (>25 dB at 2
r The majority of bladder cancer diagnosed in US has cystectomy following preoperative chemotherapy, is contiguous frequencies), performance status
no other associations. at physician discretion (WHO/ECOG performance status 2 or less), baseline
r In Egypt and other endemic regions, chronic bladder peripheral neuropathy and cardiac function (New
York Heart Association [NYHA] Class II or better)
inflammation from schistosomiasis infection can r In the setting of impaired renal function correct
lead to squamous cell carcinoma, as can chronic
bladder irritation or inflammation, such as from reversible causes (obstruction, etc.)
chronic indwelling catheter use.
58
BLADDER CANCER, UROTHELIAL, METASTATIC (CLINICAL AND PATHOLOGIC N+, M+)
MEDICATION Complementary & Alternative 4. Bellmunt J, von der Maase H, Mead GM, et al.
First Line Therapies Randomized phase III study comparing
r Cisplatin-based chemotherapy combinations are the Supportive care includes adequate nutrition and paclitaxel/cisplatin/gemcitabine and
most active and superior to carboplatin regimens.
Survival outcome is similar in patients treated with
hydration, particularly for patients undergoing
multimodality therapy
gemcitabine/cisplatin in patients with locally
advanced or metastatic urothelial cancer without
B
standard multiday MVAC (methotrexate, vinblastine, prior systemic therapy: EORTC Intergroup Study
adriamycin, cisplatin) compared to cisplatin with 30987. J Clin Oncol. 2012;30:1107–1113.
gemcitabine (GC), with less toxicity in the GC group ONGOING CARE 5. Dodd P, McCaffrey JA, Herr H, et al. Outcome of
(1,2) PROGNOSIS postchemotherapy surgery after treatment with
r High-dose intensity chemotherapy with MVAC plus methotrexate, vinblastine, doxorubicin, and
For patients with metastatic disease, ECOG status ≥1,
GMCSF (HD-M-VAC) compared to classic M-VAC led hemoglobin ≤10, and visceral involvement are cisplatin in patients with unresectable or metastatic
to a better overall response rate (64 vs. 50%) and prognostic for overall survival (survival 14.2 mo for transitional cell carcinoma. J Clin Oncol 1999;
improved survival (21.8% in the HD-M-VAC vs. those with none of these features vs. 1.7 mo with all 3 17:2546–2552.
13.5%) at 7 yr. The toxicity profile of HD-M-VAC features) 6. Zaghloul M, Boutrus R, El-Hossieny H, et al. A
was superior with better dose intensity, and thus prospective, randomized, placebo controlled trial of
established HD-M-VAC as an alternative to standard COMPLICATIONS zolendronic acid in bony metastatic bladder cancer.
r Cisplatin: Nephrotoxicity, ototoxicity, peripheral
M-VAC (3) Int J Clin Oncol. 2010;15;382–389.
– MV chemotherapy is usually given every 14 days neuropathy, fatigue
r Adriamycin (in MVAC regimen): Cardiac toxicity
with the AC given along each 28 days
– HD-M-VAC is also referred to as “dose dense” r MVAC toxicity is a major concern: ADDITIONAL READING
MVAC (DDMVAC) regimen gives the same drugs Myelosuppression, neutropenic fever, sepsis,
at the same doses closer together, all drugs every mucositis, nausea, and vomiting are common (up to NCCN guidelines for Bladder Cancer, version 1.2013,
14 days with hematopoietic growth factor support 54% may require readmission for toxicity) http://www.nccn.org/professionals/physician gls/
and is recommended by the NCCN guidelines r Neutropenia (including life-threating febrile pdf/bladder.pdf, Accessed January 28, 2014.
r Adding paclitaxel to cisplatin and gemcitabine, neutropenia) associated with multimodality See Also (Topic, Algorithm, Media)
compared to GC led to a modest but not significant chemotherapy for bladder cancer. Granulocyte r Bladder Cancer, General
improvement in survival and is not endorsed for growth factor is standard in the high-dose intensity r Bladder Cancer, Nonurothelial
most patients (4) MVAC regimen, and is used to support patients on r Bladder Cancer, Squamous Cell Carcinoma
r Some typical regimens reported in the literature gemcitabine and platinum combinations r Bladder Cancer, Urothelial, Muscle Invasive (Clinical
include r Gemcitabine: Rash and cytopenias
and Pathologic T2/T3/T4) (MIBC)
– MVAC: Methotrexate (30 mg/m2 on days 1, 15, r Taxanes (ie, paclitaxel): Fluid retention, neuropathy, r Reference Tables: TNM Classsification: Urinary
22), vinblastine (3 mg/m2 on days 2, 15, 22), myelosuppression Bladder Cancer
doxorubicin (30 mg/m2 on day 2), and cisplatin r Ureteral obstruction (tumor or lymphadenopathy) is
(70 mg/m2 ), repeated every 28 days for 6 cycles common and can be alleviated with ureteral
– GC: Gemcitabine (1,000 mg/m2 days 1, 8, 15) stenting or percutaneous nephrostomy drainage CODES
plus cisplatin (70 mg/m2 day 2), repeated every
28 days for a maximum of 6 cycles FOLLOW-UP
Patient Monitoring ICD9
Second Line r 188.9 Malignant neoplasm of bladder, part
r There is no standard therapy for patients who have In patients with metastatic disease on chemotherapy,
imaging should be performed every 2–3 mo to assess unspecified
disease recurrence or progression following 1st-line r 196.9 Secondary and unspecified malignant
response. In patients with durable responses of
cisplatin/gemcitabine or MVAC chemotherapy, and neoplasm of lymph nodes, site unspecified
chemotherapy, imaging should be done every 3 mo for
clinical trial participation is encouraged. r 198.89 Secondary malignant neoplasm of other
r Small nonrandomized studies support the use of the 1st 2 yr of response.
Patient Resources specified sites
taxanes, gemcitabine, 5-fluorouracil, methotrexate, r Bladder Cancer Advocacy Network
pemetrexed, and others in the 2nd line with modest ICD10
benefit of single-agent therapy. – http://www.bcan.org/ r C67.9 Malignant neoplasm of bladder, unspecified
r The substitution of carboplatin for gemcitabine in r C77.9 Secondary and unsp malignant neoplasm of
the palliative setting in the GC regimen is REFERENCES lymph node, unsp
reasonable for those felt unfit for cisplatin. r C79.89 Secondary malignant neoplasm of other
SURGERY/OTHER PROCEDURES 1. von der Maase H, Hansen SW, Roberts JT, et al. specified sites
r Retrospective series support consideration of Gemcitabine and cisplatin versus methotrexate,
salvage surgery for patients who initially present vinblastine, doxorubicin, and cisplatin in advanced
with unresectable or metastatic disease with robust or metastatic bladder cancer: Results of a large, CLINICAL/SURGICAL
chemotherapy response (5). Survival rates were randomized, multinational, multicenter, phase III PEARLS
consistently better in those with pathologic complete study. J Clin Oncol. 2000;18(17):3068–3077.
r Single-agent chemotherapy provides low response
response to induction chemotherapy and in those 2. Sternberg CN, de Mulder P, Schornagel JH, et al.
Seven year update of an EORTC phase III trial of rates of usually short duration.
with node only metastasis. (See Section I “Bladder r For 1st-line chemotherapy, performance status and
cancer, urothelial, muscle invasive (clinical and high-dose intensity M-VAC chemotherapy and
pathologic T2/T3/T4)(MIBC) neoadjuvant therapy.”) G-CSF versus classic M-VAC in advanced urothelial the presence or absence of visceral metastases are
tract tumours. Eur J Cancer. 2006;42(1):50–54. independent prognostic factors for overall survival.
ADDITIONAL TREATMENT r Brisk diuresis helps limit cisplatin renal toxicity.
3. Galsky MD, Chen GJ, Oh WK, et al. Comparative
Radiation Therapy effectiveness of cisplatin-based and carboplatin-
Palliative radiotherapy is an option for patients with based chemotherapy for treatment of advanced
painful bony metastasis urothelial carcinoma. Ann Oncol. 2012;23:
Additional Therapies 406–410.
r Studies suggest benefit of zolendronic acid or
denosumab in patients with metastatic bladder
cancer to bone (6)
r Granulocyte colony-stimulating factor can help limit
myelosuppression with cisplatin and others
59
BLADDER CANCER, UROTHELIAL, MUSCLE INVASIVE (CLINICAL AND

PATHOLOGIC T2/T3/T4) (MIBC)
Zachary L. Smith, MD
S. Bruce Malkowicz, MD, FACS
ASSOCIATED CONDITIONS Pathologic Findings

BASICS Those secondary to smoking (lung disease, other r BCa will be analyzed by pathologist for grade and
malignancies) depth of invasion
DESCRIPTION r Grading (WHO/ISUP, 2004):
r Muscle-invasive bladder cancer (MIBC) refers to GENERAL PREVENTION
r Avoidance of exposure to cigarette smoke and – Papillary urothelial neoplasm of low malignant
invasion into or through the muscularis propria of potential (well-differentiated)
the bladder wall (≥T2) industrial risk factors.
r Appropriate and timely workup of both microscopic – Low-grade (moderately differentiated)
r Depth of invasion important for staging and – High-grade (poorly differentiated)
treatment decisions and/or gross hematuria (early diagnosis, not r Depth of invasion:
r Urothelial carcinoma accounts for >90% of bladder prevention)
– Into detrusor muscle (T2)
cancers (BCa) – Into perivesical fat (T3)
r Less common etiologies include: DIAGNOSIS – Into adjacent structures (prostate, uterus, vagina,
– Squamous cell carcinoma (SCC) (5%) pelvic/abdominal wall) (T4)
– Adenocarcinoma (2%) HISTORY
r History of smoking or other risk factors DIFFERENTIAL DIAGNOSIS
– Urachal carcinoma (<1%) r Gynecologic and other pelvic tumors directly
r Prior bladder tumors or hematuria
EPIDEMIOLOGY r Family history of BCa invading bladder
Incidence r Adenocarcinomas more likely to be metastatic in
r Signs and symptoms:
r 74,690 new cases of BCa in 2014 in US (1) origin
r Male > Female (4:1) – Painless hematuria (80%) r Mass seen at bladder base on imaging is sometimes
r 73 yr old: Average age at diagnosis – Irritative voiding symptoms (frequency, urgency,
actually prostate median lobe
dysuria) (35%)
– ∼90% of patients are >55 yr at diagnosis – Stigmata of locally invasive or metastatic disease
Prevalence (pelvic pain/fullness, fixed bladder or palpable TREATMENT
>500,000 in US (all stages) mass, inguinal lymphadenopathy, flank pain,
weight loss, bone pain) GENERAL MEASURES
RISK FACTORS r Preoperative evaluation, as most patients also have
r Cigarette smoking (>50% of cases) PHYSICAL EXAM
r Occupational exposure (dye, textile, rubber, and r General: Nutritional status, abdominal/pelvic significant cardiopulmonary disease
r Discuss treatment options and urinary diversion
leather factory workers) masses, lymphadenopathy
r Chronic indwelling catheters are risk factor for SCC. r Digital rectal exam (male), bimanual pelvic exam options
(female), which can be performed under anesthesia – If ileal conduit, meet with stoma therapy nurse
– Also, schistosomiasis in some parts of Middle East preop and postop for care/teaching
and Africa DIAGNOSTIC TESTS & INTERPRETATION – For continent diversion, preop teaching imperative
Genetics Lab r If bladder preservation chosen, coordinate with
r Hereditary patterns: r Blood: CBC, electrolytes, LFT (elevated alkaline radiation oncology and medical oncology
– Autosomal dominant phosphatase suggests liver or bone involvement)
– Multifactorial polygenic r Urine: MEDICATION
r Cytogenetic abnormalities: – Urinalysis with microscopy First Line
r Intravesical treatments not used for MIBC
– Loss of heterozygosity in chromosome 9 (>50% – Cytology: Specificity ∼95%; sensitivity good for r Chemotherapy used as:
all grades and stages BCa) high-grade, poor for low-grade
– Loss of chromosomes 17q, 5q, 3p (MIBC) – Other markers, less widely used: UroVysion – Neoadjuvant/adjuvant therapy with radical
– Inactivating mutation in p53, p21, or Rb (MIBC) (fluorescence in situ hybridization), BTA stat, BTA cystectomy (RC) urothelial carcinoma primarily
– TP53 and/or P16 abnormalities (high-grade BCa) TRAK, NMP22, ImmunoCyt/uCyt+ – Primary treatment of metastatic disease
– In combination with radiation therapy (RT) or
PATHOPHYSIOLOGY Imaging TURBT for bladder preservation protocols
r Growth patterns: Papillary (70%), nodular (10%), r Abdominal imaging: r Chemotherapy regimens differ based on patient
and sessile or mixed (20%) – CT urogram (triple phase: Noncontrast, factors:
r Invasive tumors (T2–T4) are present in 30% at nephrographic, excretory) is the current standard – MVAC is the historical gold standard and still
initial presentation of care commonly used
r 50–70% of noninvasive BCa will recur, despite ◦ MR urogram acceptable, where available
– Gemcitabine/cisplatin has equivalent efficacy with
conservative measures ◦ If renal insufficiency, retrograde pyelograms
much less toxicity and has become more
– Recurrent superficial BCa will progress to MIBC in combined with noncontrast CT or US commonly used
r Chest imaging: Chest x-ray (CXR) or CT
10–15%
r High-grade T1 lesions, especially if associated with r Bone scan Second Line
r Carboplatin substituted for cisplatin in renal
lymphovascular invasion and/or carcinoma in situ Diagnostic Procedures/Surgery insufficiency
(CIS), have high progression rate, requiring r Cystoscopy to evaluate bladder for lesions r Mitomycin/5-fluorouracil is a newer regimen which
aggressive management r Bladder biopsy or transurethral resection of bladder
r Metastases occurs via hematogenous and/or has emerging data to support its use
tumor (TURBT) establishes diagnosis r Taxanes also promising as both single and
lymphatic spread:
– Location (most to least common): Lymph nodes combination agent
(obturator, external iliac, common iliac), liver,
lung, bone, adrenal
– Most patients with metastatic disease die within
2 yr
60
BLADDER CANCER, UROTHELIAL, MUSCLE INVASIVE (CLINICAL AND PATHOLOGIC T2/T3/T4) (MIBC)
r RC with pelvic lymphadenectomy and urinary
ADDITIONAL READING
ONGOING CARE r American Urological Association Clinical Guidelines,
diversion considered gold standard therapy for
PROGNOSIS Bladder Cancer, 2007. Available at: www.
MIBC (2)
– Complete extirpation and pelvic
r Prognostic factors: auanet.org (accessed May 1, 2014). B
lymphadenectomy provide best chances for local – Tumor cell type (SCC and adenocarcinoma less r Herr HW, Dotan Z, Donat SM, et al. Defining optimal
control and long-term survival favorable) therapy for muscle invasive bladder cancer. J Urol.
– Ureteral frozen sections to ensure negative – Tumor grade and stage 2007;177(2):437–443.
margins before urinary tract reconstruction is – Disease-free survival correlates with stage r Huang GJ, Stein JP. Open radical cystectomy with
standard practice – Node burden (>8 positive) and node density lymphadenectomy remains the treatment of choice
– Patients with ≥T3 disease on clinical staging may (>20%) has worse prognosis for invasive bladder cancer. Curr Opin Urol.
be offered neoadjuvant chemotherapy r Survival rates after RC: 2007;17(5):369–375.
– RC gives no survival benefit in metastatic disease, – Disease-free survival (5-yr) without positive nodes: r Smith ZL, Christodouleas JP, Keefe SM, et al.
but may be palliative in patients with intractable 72% (62–84%) for pT2; 40% (19–57%) for pT3; Bladder preservation in the treatment of
hematuria or pelvic pain 24% (0–36%) for pT4 muscle-invasive bladder cancer (MIBC): A review of
– Lymphadenectomy may be prognostic and – Disease-free survival with positive nodes: 30% the literature and a practical approach to therapy.
therapeutic: (15–48%) BJU Int. 2013;112(1):13–25.
◦ Positive nodes in ∼25%
◦ Patients with limited nodal burden have higher COMPLICATIONS See Also (Topic, Algorithm, Media)
r General: r Bladder Cancer, General
survival rates
◦ Extended lymphadenectomy (to include – Commonly due to local invasion and advancement r Bladder Cancer, Nonmuscle-Invasive Bladder Cancer
of disease (Ta, T1)
presacral, paraaortic, and paracaval nodes) may ◦ Urinary obstruction, hydronephrosis
improve survival r Bladder Cancer, Urothelial, Metastatic (Clinical and
◦ Hematuria, clot retention
◦ May identify patients most suited for adjuvant Pathologic N+, M+)
– Malnutrition, infection, etc. r Bladder Cancer, Urothelial, Muscle Invasive (Clinical
therapies r Associated with RC:
r Urinary diversion (3): and PathologicS T2/T3/T4) (MIBC) Image
– 90-day hospital readmission: 32% r Bladder Cancer, Urothelial, Muscle Invasive (Clinical
– Options include continent catheterizable stoma,
– 90-day mortality: ∼6%
continent orthotopic neobladder, or ileal conduit; and Pathologic T2/T3/T4) (MIBC) Neoadjuvant
– Bowel obstruction (4–10%), ureteral anastomotic
each with advantages and disadvantages Therapy
◦ Ileal conduit used most commonly, least stricture (5–10%), PE (2%) r Bladder Mass
complications FOLLOW-UP r Bladder Tumor Algorithm
◦ Neobladders typically reserved for younger, Patient Monitoring r Bladder Tumors, Benign and Malignant, General
motivated patients who are able to perform r Follow-up remains controversial and dependent on
Considerations
self-catheterization if needed disease severity. Example: r Bladder Tumors, Benign and Malignant, General
r Partial cystectomy: – T1/T2 disease: Semiannual physical exam, serum Considerations Algorithm
– Strict patient selection criteria: Stage T2 only, chemistries, and CXR with CT scan every 2 yr (T1) r Reference Tables: TNM Classification: Urinary
solitary lesion allowing for 2-cm margins, lack of or yearly (T2)
Bladder Cancer
CIS, not involving trigone or ureteral orifices – T3/T4 disease: Exam, labs, and CXR every 3 mo
– Recurrence common within 2 yr with semiannual CT scan
– Still allows for lymphadenectomy – If disease free at 5 yr, surveillance can be lessened CODES
r Radical TURBT: per patient/practitioner comfort level
– As a sole therapy, outcomes poor for MIBC – Patients with intact urethra should be monitored
for urethral recurrence ICD9
– Usually palliative in patients who will not tolerate
◦ Consider urethral washing or cystoscopy 188.9 Malignant neoplasm of bladder, part
RC or systemic therapy (such as elderly with
unspecified
significant comorbidities) Patient Resources
r Urethrectomy: ICD10
Bladder Cancer Advocacy Network (BCAN):
– Simultaneous (during RC) or delayed urethrectomy www.bcan.org C67.9 Malignant neoplasm of bladder, unspecified
if CIS or tumor involves prostatic urethra, ducts, or
stroma
– Orthotopic reconstruction should not be made REFERENCES CLINICAL/SURGICAL
until negative frozen-section distal urethral margin
1. Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014.
PEARLS
is examined r MIBC represents an aggressive disease with lethal
CA Cancer J Clin. 2014;64(1):9–29. doi: 10.3322/
ADDITIONAL TREATMENT caac.21208. potential.
Radiation Therapy 2. Lerner SP, Sternberg CN. Management of r Surgical resection in the form of RC is the gold
r RT as a monotherapy is considered inferior to RC metastatic and invasive bladder cancer. In: Wein standard therapy.
r RT in combination with chemotherapy has a role in AJ, et al., eds., Campbell-Walsh Urology. 10th ed. r Role for multimodal treatment of MIBC with
selected patients undergoing organ preservation Philadelphia, PA: Elsevier, 2012. chemoradiotherapy and aggressive TUR is not as
(see below) 3. Dahl DM, McDougal WS. Use of intestinal well established as RC, however, has shown
Additional Therapies segments in urinary diversion. In: Wein AJ, et al., promising results.
r Combination RT and chemotherapy after TURBT is eds., Campbell-Walsh Urology. 10th ed.
the most efficacious bladder preservation technique Philadelphia, PA: Elsevier, 2012.
– Developed for patients who are either not
candidates for or refuse RC. Ideal candidates for
bladder preservation:
◦ Complete visual resection on TURBT
◦ Solitary tumor
◦ No hydronephrosis
– 5-yr overall survival 30–50%; better in T2 disease
than T3–T4
Therapies
N/A
61
BLADDER CANCER, UROTHELIAL, MUSCLE INVASIVE (CLINICAL AND

PATHOLOGIC T2/T3/T4) (MIBC) NEOADJUVANT THERAPY
Jean Hoffman-Censits, MD
William Kevin Kelly, DO

BASICS r The majority of bladder cancer diagnosed in US has r Urothelial (formerly transitional cell) carcinoma is
no other associations. most common. Many patients have urothelial cancer
DESCRIPTION r In Egypt and regions in SE Asia, chronic bladder with squamous or other differentiation.
r Detrusor muscle-invasive bladder cancer (T2, 3, 4 r Less common histologic subtypes: Squamous cell
irritation from Schistosomiasis infection can lead to
MIBC) is much less common than noninvasive squamous cell carcinoma, as can chronic bladder carcinoma (associated with chronic inflammation),
bladder cancer. irritation or inflammation, such as from chronic adenocarcinoma, and small cell carcinoma with or
r May present with de novo invasive cancer, a indwelling catheter use. without sarcomatous changes.
minority progress from superficial bladder cancer
r Radical cystectomy for muscle-invasive bladder GENERAL PREVENTION DIFFERENTIAL DIAGNOSIS
r Smoking cessation r See Section I “Bladder cancer, urothelial, muscle
cancer is potentially curative; up to 50% of patients r Limit or modify chemical exposure invasive (clinical and pathologic T2/T3/T4)(MIBC)”
will develop recurrence within 2 yr.
– This high recurrence has led to the increasing use
of neoadjuvant chemo before cystectomy. DIAGNOSIS TREATMENT
– Neoadjuvant cisplatin-based chemo has improved
survival vs. radical cystectomy alone. HISTORY GENERAL MEASURES
r Gross or microscopic hematuria is the most common r Neoadjuvant cisplatin-based chemo should be
EPIDEMIOLOGY
presenting sign considered for patients with muscle invasion
Incidence (1) r Dysuria, frequency, and urgency are common (cT2–T4) undergoing radical cystectomy
r 74,690 new cases of bladder cancer will be
r Symptoms of locally advanced disease such as pelvic r Overall survival benefit of 5% with lower recurrence
diagnosed in 2014 with 15,580 deaths
pain and constipation based on meta-analysis (2)
– Most deaths due to metastatic disease r Flank pain or renal insufficiency due to ureteral r MVAC (methotrexate, vinblastine, adriamycin,
r Bladder cancer is the 4th most common cancer
obstruction by tumor cisplatin) preferred in healthy patients <70 yr. CMV
diagnosed in men
r Bladder cancer is much more common in men than or gemcitabine (GC) are alternatives if older or with
PHYSICAL EXAM comorbidities
women, whites, and those over 55 yr old r Most with muscle-invasive bladder cancer have no
significant external exam findings MEDICATION
Prevalence r Palpable lymphadenopathy, hepatomegaly from liver
>500,000 in US (all stages) First Line
involvement, or other signs from obstructive r Cisplatin-based chemo combinations are superior to
RISK FACTORS processes in later-stage disease. carboplatin-based regimens. Carboplatin should not
r Cigarette smoking r Leg edema with DVT be substituted for cisplatin in patients being treated
r Chemical and occupational exposure association with curative intent.
– Incidence 1–8%; higher in patients treated with
(aromatic amine exposure, workers in rubber, textile, platinum combination therapy r Neoadjuvant chemo has shown benefit in overall
leather, painting, printing, machinist, hairdressing, survival and in pathologic downstaging
dry-cleaning, and trucking industries) DIAGNOSTIC TESTS & INTERPRETATION – Neoadjuvant MVAC trial (methotrexate,
Lab vinblastine, adriamycin, cisplatin) vs. cystectomy
Genetics
r A family history of bladder cancer increases risk, Lab abnormalities can include anemia of chronic alone (77 vs. 46 mo 5-yr survival) (3)
either from genetic or environmental factors
disease, iron deficiency anemia in patients with r In the advanced and metastatic setting, survival
r Patients with hereditary nonpolyposis colorectal longstanding hematuria, gross or microscopic outcome is similar in patients treated with MVAC
hematuria, and renal insufficiency in patients with compared to cisplatin with GC, with less toxicity
cancer (HNPCC) are at increased risk of developing ureteral obstruction.
urothelial cancers with GC
r Hereditary patterns: Imaging r Several studies of neoadjuvant HD-MVAC have
r Staging guidelines recommend abdomen and pelvis yielded similar rates of complete pathologic
– Autosomal dominant
– Multifactorial polygenic imaging with CT or MRI response at cystectomy compared to MVAC with
r Cytogenetic abnormalities: r Imaging of the upper tract collecting system manageable toxicity. HD-MVAC also referred to as
r Chest imaging “dose dense” MVAC (DDMVAC) gives the same
– Loss of heterozygosity in chromosome 9 (>50%
all grades and stages BCa) r Bone scan if clinical suspicion of metastasis or drugs at the same doses closer together (all drugs
– Loss of chromosomes 17q, 5q, 3p (MIBC) alkaline phosphatase elevation every 14 days with hematopoietic factor support) (4)
r PET may be useful in determining metastatic or r HD-MVAC is the neoadjuvant regimen choice at
– Inactivating mutation in p53, p21, or Rb (MIBC)
– TP53 and/or P16 abnormalities (high-grade BCa) node-positive disease but not yet standard some centers, but GC is also commonly used
r Understaging, despite adequate radiographic and r CMV neoadjuvant chemo (cisplatin, methotrexate,
PATHOPHYSIOLOGY vinblastine): Survival benefit at 10 yr (36% survival
r Alterations in genes which contribute to toxin pathologic data from transurethral resection of
bladder tumor (TURBT), is common vs. 30% without chemo) (5)
breakdown within the bladder (such as GST and r Common neoadjuvant regimens (6)
NAT), may make some more likely to develop Diagnostic Procedures/Surgery
r Cystoscopy with TURBT for staging and debulking of – MVAC: Methotrexate (30 mg/m2 days 1, 15, 22),
bladder cancer
r Tumor multifocality and the high rate of recurrence vinblastine (3 mg/m2 days 2, 15, 22), doxorubicin
invasive disease
(30 mg/m2 day 2), cisplatin (70 mg/m2 on day 2)
of urothelial cancers within the bladder, ureters, and – Detrusor muscle must be present in specimen for
every 28 days × 3 cycles
renal pelvis in patients with a bladder cancer history accurate pathologic staging
r Examination under anesthesia (EUA) is part of – CMV: Methotrexate (30 mg/m2 ) and vinblastine
can be due to the field effect in part from toxin (4 mg/m2 ) days 1 and 8 plus cisplatin (100 mg/m2
exposure bladder cancer staging; fixation suggests locally on day 2), with folinic acid (15 mg every 6 hr × 4
r T2: Muscularis propria invasion advanced disease doses) days 2, 9, repeated every 28 days × 3
r T3:Perivesical tissue invasion
cycles
r T4: Invasion of pelvic structures (eg, prostate – GC: GC (1,000 mg/m2 days 1, 8, 15) plus cisplatin
stroma, seminal vesicles, uterus, vagina, pelvic side (70 mg/m2 day 2) every 28 days × 6 cycles
wall, or abdominal wall) maximum
62
BLADDER CANCER, UROTHELIAL, MUSCLE INVASIVE (CLINICAL AND PATHOLOGIC T2/T3/T4) (MIBC) NEOADJUVANT THERAPY
r “Fitness” for cisplatin is not well defined, but 4. Sternberg CN, de Mulder P, Schornagel JH, et al.
includes: Renal function, hearing, performance ONGOING CARE Seven year update of an EORTC phase III trial of
status, baseline neuropathy, and cardiac function high-dose intensity M-VAC chemotherapy and
PROGNOSIS
Second Line
r For patients treated with perioperative
r Patients with pathologic complete response (pT0) at
G-CSF versus classic M-VAC in advanced urothelial
tract tumours. Eur J Cancer. 2006;42(1):50–54.
B
radical cystectomy have superior relapse free and 5. Griffiths G, Hall R, Sylvester R, et al. International
cisplatin-based chemo with disease recurrence,
overall survival outcomes compared to those with phase III trial assessing neoadjuvant cisplatin,
particularly for those with recurrence >12 mo
residual invasive disease methotrexate, and vinblastine chemotherapy for
following chemo, cisplatin rechallenge can be
– 10.6% complete pathologic downstaging muscle-invasive bladder cancer: Long-term results
considered. r Treatment with neoadjuvant cisplatin-based chemo
– With disease progression while on or closely of the BA06 30894 trial. J Clin Oncol. 2011;
following cisplatin-based chemo, there is no increases the rate of pT0 over patients treated with 29(16):2171–2177.
standard second line therapy. TURBT alone (38 vs. 15%) in the Phase III study of 6. Raghavan D. Neoadjuvant treatment and bladder
– Many small studies have shown modest benefit of preoperative MVAC compared to cystectomy alone preservation options for muscle-invasive urothelial
single agent or combination regimens. COMPLICATIONS (transitional cell) bladder cancer www.UpToDate.
r Cisplatin: Nephrotoxicity, ototoxicity, peripheral com, Accessed January 26, 2014.
SURGERY/OTHER PROCEDURES 7. Bi L, Huang H, Fan X, et al. Extended vs
r Radical cystectomy is the treatment of choice for neuropathy, and fatigue
r Adriamycin (in MVAC): Cardiac toxicity non-extended pelvic lymph node dissection and
patients with invasive (T2–T4) disease, patients with
r Neutropenia, including life threating febrile their influence on recurrence-free survival in
multifocal tumors, large tumors, hydronephrosis, patients undergoing radical cystectomy for bladder
node-positive disease (N1). neutropenia is associated with multimodality chemo
for bladder cancer. Granulocyte growth factor is cancer: A systematic review and meta-analysis of
– Consider consolidative cystectomy in patients with comparative studies. BJU Int. 2014;113(5b):
extensive nodes or locally advanced disease with standard in the high-dose intensity MVAC regimen,
and can be used to support patients on GC/platinum E39–E48.
durable responses to chemo.
r Bilateral pelvic lymphadenectomy: Include common combinations 8. Gakis G, Efstathiou J, Lerner SP, et al. ICUD-EAU
r GC: Rash and cytopenias International Consultation on Bladder Cancer
iliac, internal iliac, external iliac, hypogastric, 2012: Radical cystectomy and bladder preservation
presacral, and obturator nodes. r Ureteral obstruction (tumor or nodes): Alleviate with
for muscle invasive urothelial carcinoma of the
– Increased number of lymph nodes removed and ureteral stenting or percutaneous nephrostomy to
bladder. Eur Urol. 2012;63:45–57.
lymph node density (# positive LN / # total LN improve renal function
removed) in patients with positive lymph nodes r 30-day perioperative mortality following cystectomy
can improve recurrence rates (7). approximately 1%; average 30-day readmission rate
– A randomized trial of standard vs. extended pelvic 21–32%
ADDITIONAL READING
lymph node dissection is ongoing. r Perioperative morbidity following cystectomy: Ileus, NCCN Guidelines for Bladder Cancer, version 1.2013,
ADDITIONAL TREATMENT blood loss, infection, thromboembolism, wound http://www.nccn.org/professionals/physician gls/
dehiscence, ostomy complications. pdf/bladder.pdf, Accessed January 28, 2014.
Radiation Therapy
r Multimodality treatment with chemo-radiotherapy FOLLOW-UP See Also (Topic, Algorithm, Media)
can be considered for patients who are medically Patient Monitoring r Bladder Cancer, General
inoperable or selected patients who wish for bladder r Following radical cystectomy, imaging of the chest, r Bladder Cancer, Urothelial, Muscle Invasive (Clinical
preservation (8). abdomen and pelvis including upper tract evaluation and Pathologic T2/T3/T4) (MIBC) Neoadjuvant
– Tumors <5 cm, no carcinoma in situ, no and CBC and electrolyte assessment should occur Therapy Image
hydronephrosis, complete TURBT resection, every 3–6 mo. Based on recurrence risk for the first r Bladder Cancer, Urothelial, Metastatic (Clinical and
T2–T3, functional bladder at baseline. 2 yr, then as clinically indicated. Pathologic N+, M+)
r Neoadjuvant chemo followed by cystectomy and r Urine cytology and electrolytes should be monitored r Bladder Cancer, Urothelial, Muscle Invasive (Clinical
chemo-radiotherapy have not been compared head every 3–6 mo. Based on recurrence risk for the first and Pathologic T2/T3/T4) (MIBC)
to head in a prospective trial 2 yr., then as clinically indicated. r Bladder Tumor Algorithm
r Continent diversion: Monitor B12 deficiency r Reference Tables: TNM Classification: Urinary
r Multidisciplinary evaluation should be considered to Bladder cancer
Patient Resources
asses best plan of care Bladder Cancer Advocacy Network
r For patients who have received standard http://www.bcan.org/
cisplatin-based neoadjuvant chemo, there is CODES
currently no recommendation for adjuvant chemo
following cystectomy REFERENCES ICD9
r For patients with invasive or node-positive disease 188.9 Malignant neoplasm of bladder, part
1. Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014.
following cystectomy who did not receive CA Cancer J Clin. 2014 64(1):9–29. doi: 10.3322/ unspecified
neoadjuvant chemo, adjuvant platinum-based caac.21208.
therapy should be considered
ICD10
r Positive surgical margins can increase risk of local 2. Advanced Bladder Cancer Meta-analysis C67.9 Malignant neoplasm of bladder, unspecified
Collaboration. Neoadjuvant chemotherapy in
failure; consider adjuvant radiotherapy invasive bladder cancer: A systematic review and
Complementary & Alternative meta-analysis. Lancet. 2003;361(9373):1927 CLINICAL/SURGICAL
Therapies 3. Grossman HB, Natale RB, Tangen CM, et al. PEARLS
N/A Neoadjuvant chemotherapy plus cystectomy
r Outcomes after radical cystectomy indicate
compared with cystectomy alone for locally
advanced bladder cancer. N Engl J Med. 2003;349: increased survival in patients who had more, rather
859–866. than fewer, lymph nodes resected.
r Patients with pathologic complete response
following neoadjuvant chemotherapy appear to
have the best long-term survival.
63
BLADDER CANCER, UROTHELIAL, SUPERFICIAL CARCINOMA IN SITU

(CIS) (NMIBC)
Surena F. Matin, MD, FACS
BASICS r CIS usually multifocal and can occur in the upper r No imaging specific for diagnosing CIS
tracts, prostatic ducts, and urethra as well as the r Renal/bladder ultrasound (US): Detects
DESCRIPTION bladder hydronephrosis that may be caused by ureteral
r Carcinoma in situ (CIS) of the bladder is a flat, r Natural history—highly aggressive obstruction from bladder tumor; bladder US can
multifocal, “velvety” lesion of the urothelium – Progression to MIBC in 54–83% of untreated visualize larger bladder tumors
– CIS is a flat, high-grade tumor that are confined to cases (3,4) r Computed tomography (CT) urogram: Triple phase
the mucosa – Increase risk of recurrence if found with NMIBC CT abdomen/pelvis is the gold standard for
– Can be occult and diagnosed by random biopsies papillary lesions evaluation of painless gross hematuria; can detect
of normal appearing mucosa r Bacillus Calmette-Guerin (BCG) reduces risk of more advanced bladder tumors, hydronephrosis, and
– Although can occur alone, most often seen with progression by 35% compared with other upper tract filling defects that may represent upper
concomitant high-grade papillary lesions intravesical therapies (1,3) tract urothelial carcinoma
r Classified as nonmuscle-invasive bladder cancer r BCG confers disease-free rate approximately 51% at
(NMIBC) similar to stage Ta and T1, however CIS is Diagnostic Procedures/Surgery
3.75 yr (1) r Cystoscopy with bladder biopsy
considered high grade and aggressive with a r If concomitant muscle-invasive lesion, prognosis and
propensity to invade the bladder wall and – Appearance can be flat, grossly erythematous,
treatment depends on invasive lesion granular or cobblestone mucosa or visually normal
metastasize
ASSOCIATED CONDITIONS – May be performed in office at initial visit
EPIDEMIOLOGY r NMIBC (Ta,T1) – TURBT under general or spinal anesthesia may be
Incidence r Invasive bladder cancer (T2,T3,T4) required if papillary bladder tumor present
True incidence not known given the flat superficial – Retrograde pyelography also should be performed
nature of this lesion, which can be destroyed by GENERAL PREVENTION to assess the upper tracts if not already evaluated
r Smoking cessation with a CT urogram
cautery effect during transurethral resection of bladder
tumor (TURBT) r Increased fluid intake – Positive cytology with no visible tumor and
r Avoid occupational exposures negative random bladder biopsies suggests
Prevalence
r Occurs as isolated CIS in 3–5% cases disease outside of bladder
r Estimated 5–10% of patients with noninvasive ◦ Biopsy of prostatic urethra indicated
DIAGNOSIS ◦ Selective cytology from upper tracts; evaluate
urothelial carcinoma have CIS (1) for urothelial carcinoma/CIS of renal pelvis or
r 45–65% patients with invasive urothelial carcinoma HISTORY
r Age and sex ureters. CIS of upper tracts suspected in absence
have CIS (2) of solid tumor and with positive cytology, rarely
r Presence of gross hematuria
RISK FACTORS able to obtain adequate biopsy to confirm CIS
r No risk factors specific for CIS beyond that of r Irritative voiding symptoms—dysuria commonly histologically
urothelial carcinoma occurs with CIS r Fluorescent “Blue light” cystoscopy
r Tobacco smoking-cigarettes r History of bladder cancer – More sensitive than conventional white light
r Occupational exposure r Family history of bladder cancer cystoscopy for detecting CIS
r Smoking history ◦ In a prospective study additional detection rate
– Organic chemicals: Aromatic amines, benzenes,
aniline dyes r Occupational risk factors of 20% for all tumors and 23% for CIS (6)
– High-risk occupations: Petroleum, chemical, – False-positives can result in the presence of
PHYSICAL EXAM inflammation, recent TUR, or BCG instillation
rubber, textile workers, hairdressers r Usually unremarkable
r Medications r Bimanual exam should be performed at time of Pathologic Findings
– Phenacetin-containing analgesics r Arises from surface uroepithelium
cystoscopy/TURBT—If CIS is found in presence of r Severe cytologic atypia and nuclear aplasia (2)
– Cyclophosphamide advanced stage/invasive bladder cancer may
r Pelvic radiation – Large, irregular hyperchromatic nuclei
appreciate palpable mass
Genetics – Mitotic activity common
r p53 mutation most important deletion/mutation DIAGNOSTIC TESTS & INTERPRETATION r Thought to be a precursor of invasive disease
Lab r Some pathologists use the term “severe dysplasia”
found with CIS (2) r Urinalysis, including microscopic evaluation
r Chromosome 9q deletions common to describe CIS
r Urine cytology—highly specific and sensitive
r Loss of CDKN2/p16 (tumor suppressor gene) DIFFERENTIAL DIAGNOSIS
(>90%) for detecting CIS and high-grade urothelial r Nonurothelial cancers (squamous cell carcinoma,
carcinoma (5)
r UroVysion, HA-HAase, and BLCA-4 have a high adenocarcinoma)
r Inflammatory lesion from prior radiation, interstitial
sensitivity to detect CIS however should not replace
classic urine cytology (1) (Grade B) cystitis, infection
64
BLADDER CANCER, UROTHELIAL, SUPERFICIAL CARCINOMA IN SITU (CIS) (NMIBC)
6. Kausch I, Sommerauer M, Montorsi F, et al.

TREATMENT ONGOING CARE Photodynamic diagnosis in non-muscle-invasive
bladder cancer: A systematic review and cumulative
PROGNOSIS
GENERAL MEASURES
r Resection of all visible tumor followed by r Depends on stage of concomitant invasive papillary
analysis of prospective studies. Eur Urol. 2010;
57:595–606.
B
intravesical therapy urothelial lesion
r For BCG-refractory CIS: Radical cystectomy r CIS alone or with NMIBC—high rate of progression
MEDICATION
to muscle-invasive disease if untreated ADDITIONAL READING
– See “Pathophysiology”
First Line r EAU Guidelines on Non-muscle-invasive (TaT1 and
– BCG reduces risk of recurrence and progression to
r BCG—live suspension of the attenuated CIS) Bladder Cancer http://www.uroweb.org/gls/
muscle-invasive disease
Mycobacterium bovis vaccine strain r CIS of prostatic urethra unfavorable (1) pdf/07 Bladder%20Cancer LR%20II.pdf, Accessed
– Standard of care for CIS – Prostatic tissue stromal invasion worst January 28, 2014.
– Therapy initiated no earlier than 2–4 wk after r Guideline for the Management of Nonmuscle
prognosis—cystoprostatectomy advised
TURBT/biopsy to give uroepithelium time to heal r Disease-specific survival rates excellent if cystectomy Invasive Bladder Cancer: (Stages Ta, T1, and Tis):
and prevent systemic complications of BCG performed early (instead of BCG instillation), Update (2007) (Reviewed and validity confirmed
– Administered as induction therapy—6 however 40–50% could be overtreated (4) 2010). AUA Clinical Practice Guidelines.
consecutive weekly bladder instillations; then (Grade A) http//www.auanet.org/content/clinical-practice
maintenance treatment recommended for at least guidelines/clinicalguidelines.cfm?sub=bc, Accessed
1 yr (1) (Grade A) COMPLICATIONS November 2013.
– BCG has the highest complete response rate and r BCG toxicity
durable disease-free rate among all intravesical – Low, but serious risk of systemic BCG infection See Also (Topic, Algorithm, Media)
r BCG Sepsis/BCGosis
treatments (1) (Grade A) (BCGosis)—avoid treatment in presence of recent
r Bladder Cancer, General
– Initial response rates approximately 70–90%, TURBT, hematuria, foley trauma, or urinary tract
infection r Bladder Cancer, Intravesical Agents (table)
however up to 1/2 of patients will recur
– Response to BCG instillation should be assessed – Has side effect of dysuria and can be intolerable in r Bladder Cancer, Nonmuscle-invasive Bladder Cancer
at 3 mo some patients (Ta, T1)
◦ If no response can give another 6-wk course of ◦ Usually experienced within the first 6 mo of r Bladder Cancer, Urothelial, Metastatic (Clinical and
BCG vs. proceed to radical cystectomy treatment Pathologic N+, M+)
◦ Approximately 50% will respond to second r Bladder Cancer, Urothelial, Muscle Invasive (Clinical
FOLLOW-UP
course of BCG (1) (Grade B) and Pathologic T2/T3/T4) (MIBC)
Patient Monitoring r Bladder Cancer, Urothelial, Superficial Carcinoma In
Second Line At 3 mo patients should have cystoscopy and urine
r Intravesical chemotherapy Situ (CIS) (NMIBC) Image
cytology. If negative, this should be repeated every
– Mitomycin C—an alternative for patients who r Bladder Tumor Algorithm
3 mo × 2 yr, every 6 mo thereafter until year 5 and
cannot tolerate BCG then yearly (3) r Bladder Tumors, Benign, and Malignant, General
– Valrubicin—an option for poor surgical r Bladder Tumors, Benign and Malignant, General
candidates with BCG-refractory disease
Patient Resources
American Cancer Society—Bladder Cancer Considerations
– Gemcitabine r Reference Tables: TNM Classification: Urinary
http://www.cancer.org/acs/groups/cid/documents/
SURGERY/OTHER PROCEDURES webcontent/003085-pdf.pdf Bladder Cancer
r TURBT—Resection of all visible papillary bladder
tumors is essential prior to BCG therapy
r For CIS refractory to intravesical therapy—radical REFERENCES CODES
cystectomy 1. van der Meijden AP, Sylvester R, Oosterlinck W,
– Disease-specific survival rates excellent if et al. EUA guidelines on the diagnosis and ICD9
cystectomy performed early (instead of BCG treatment of urothelial carcinoma in situ. Eur Urol. 233.7 Carcinoma in situ of bladder
instillation), however 40–50% could be 2005;48:363–371. ICD10
overtreated (4) (Grade A) 2. Nese N, Gupta R, Bui MH, et al. Carcinoma in situ D09.0 Carcinoma in situ of bladder
ADDITIONAL TREATMENT of the urinary bladder: Review of clinicopathologic
Radiation Therapy characteristics with an emphasis on aspects related
to molecular diagnostic techniques and prognosis.
CLINICAL/SURGICAL
No role in treatment of CIS
J Natl Compr Canc Netw. 2009;7:48–57. PEARLS
Additional Therapies 3. Babjuk M, Oosterlinck W, Sylvester R, et al. EAU
N/A r Urine cytology is the best marker (>90%
guidelines on non-muscle invasive urothelial
sensitivity/specificity) for diagnosis of CIS.
Complementary & Alternative carcinoma of the bladder, the 2011 update. Eur r Positive cytology in absence of visible bladder
Therapies Urol. 2011;59:997–1008.
N/A lesions—differential includes CIS bladder, prostatic
4. Sylvester R, van der Meijden AP, Witjes JA, et al.
urethra, or upper tract urothelial carcinoma.
High-grade Ta urothelial carcinoma and carcinoma r BCG is the treatment of choice for CIS of the
in situ of the bladder. Urology. 2005;66(Suppl 1):
90–107. bladder; highest response rate and most durable
disease-free rates of all intravesical therapies.
5. Lotan Y, Roehrborn CG. Sensitivity and specificity r To prevent systemic complications of BCG do not
of commonly available bladder tumor markers
versus cytology: Results of a comprehensive administer after TURBT until urothelium healed
literature review and meta-analysis. Urology. (approximately 2 wk).
r For BCG refractory CIS: A second induction course
2003;61:109–118.
BCG can be administered vs. proceeding
immediately to radical cystectomy.
65
BLADDER INJURY, INTRAOPERATIVE

– Midurethral sling operations

BASICS ◦ Retropubic route DIAGNOSIS
◦ Previous caesarean delivery
DESCRIPTION ◦ Previous colposuspension HISTORY
r Bladder injury during surgery can be either r Determine any prior surgical or other interventions
◦ BMI <30 kg/m2
intraperitoneal or extraperitoneal. ◦ Rectocele that can increase the risk of intraoperative bladder
r The bladder is the urologic organ most subjected to ◦ Procedures under local anesthesia injury
iatrogenic injury. ◦ Inexperienced surgeon – Past surgical history such as bladder neck
r Described during open, endoscopic, laparoscopic, or – TURBT suspension, cesarean section, radical
robotic procedures. ◦ Tumor size prostatectomy, partial cystectomy, ureteral
r May be blunt/sharp dissection, trocar, or ◦ Elderly patients reimplantation, any lower abdominal surgery that
◦ Pretreated bladder (previous TURB, intravesical may result in the bladder adhering to the posterior
electrocautery injury.
r Needle or trocar passage during transvaginal tape or instillation, radiotherapy) fascia
◦ Tumor location at the dome or in diverticulum – Prior pelvic radiation
pubovaginal sling procedures are particularly – History of neurogenic bladder
high-risk procedures. Genetics
r Cystoscopy with overdistension and transurethral N/A PHYSICAL EXAM
r Intraoperative:
bladder tumor resections are also high risk for PATHOPHYSIOLOGY
bladder perforation injury. r Bladder injury with urinary leakage is consistent – Findings may be subtle. Need high degree of
suspicion
EPIDEMIOLOGY with complete tear through mucosa, submucosa, – Blood or gas in Foley, especially during
Incidence (1,2) and muscularis transperitoneal laparoscopic procedure
r Intraoperative bladder injuries account for: r Leakage of urine can be into the extra- or ◦ Anesthesia may be first to recognize if
– Laparoscopic injuries (0.2–8.3%) intraperitoneal space monitoring catheter collection bag
– Laparoscopic injuries intraoperative diagnosis: r Perforation of the bladder dome during Veress – Urine in wound
53.2% needle or trocar insertion – For transurethral surgery: Intraoperative
r Location: r Large bladder perforations during TURBT requiring abdominal distension/rigidity may be noted or if
– Intraperitoneal (38–40%) intervention are rare (0.16–0.57%) hypotonic irrigation is being used, patient may
– Extraperitoneal (54–56%) of injuries – Extraperitoneal TURBT perforations are more develop signs/symptoms of TUR syndrome
frequent than intraperitoneal ones r Postoperative:
Prevalence
N/A ASSOCIATED CONDITIONS – Distended abdomen
r Bladder cancer – Peritonitis and abdominal rebound pain
RISK FACTORS r Prostate benign and malignant tumors – Decreased urine production; oliguria or anuria
r General factors
r Pelvic anatomic anomalies – Abdominopelvic ascites
– Inexperienced surgeon – Urinoma
– Over aggressive TURBT or bladder biopsy r Prior pelvic surgery or radiation
– Urine leakage from wound
– Complex surgical anatomy (prior surgery or r Pelvic trauma
– Bloody urine
radiation therapy) r Tissue fibrosis or inflammation (eg, radiation, – Fever
– Poor laparoscopic visualization chronic catheter)
– Full/overdistended bladder DIAGNOSTIC TESTS & INTERPRETATION
– Thin bladder wall (transurethral injury) more GENERAL PREVENTION Lab
r Decompress bladder with a catheter placed before r With urinary ascites elevation in serum BUN and
common in older females due to thin bladder wall
r Risk factors associated with specific conditions and initial incision or trocar placement for laparoscopic creatinine as well as hyperkalemia and
cases hyponatremia can be seen
procedures based on EAU review r Initial use of Veress needle for insufflation
– Cesarean delivery – Elevated creatinine over serum level observed with
◦ Previous caesarean delivery – Small bladder perforation not as significant as urine leak due to systemic absorption
◦ Previous pelvic surgery with trocar injury r Drain fluid sent for creatinine
◦ Presence of labor – Open “Hasson” trocar technique – Urine vs. serum
r Familiarity with bladder anatomy can minimize risk:
◦ Station of presenting fetal part >+1 Imaging
◦ Fetal weight >4 kg – Pediatric bladder is primarily intraperitoneal. r Postoperative diagnosis (3):
– Hysterectomy – Adult bladder is retropubic and extraperitoneal.
– Extraperitoneal injury: Contrast contained in the
◦ Malignancy – Peritoneum is cephalad to bladder.
extraperitoneal space
◦ Endometriosis – Bladder is attached laterally and at bladder neck
– Intraperitoneal injury: Contrast extravasates
◦ Prior pelvic surgery – Bladder wall consists of 3 layers: Mucosa,
between loops of small bowel and the anterior
◦ Concomitant anti-incontinence or pelvic organ submucosa, muscularis
pararenal fascia
prolapse surgery – Ureters attached posterolateral in trigone r Cystogram can be done using standard technique or
r Perform bladder biopsy or TURBT with bladder at
– General surgery CT imaging with postcontrast evacuation (3)
◦ Malignancy mid filling
– 300 cc gravity filling
◦ Diverticulitis – Avoid over or underdistention that can increase
– 3-view cystogram or CT cystogram
◦ Inflammatory bowel disease risk of perforation of bladder
– All cystograms must include a postcontrast
evacuation study to evaluate for residual contrast
outside of the bladder
r US can identify urinoma
r CT for pelvic “urinary” ascites or urinoma
r Intraoperative diagnosis during transurethral
surgery: Intraoperative cystogram can be obtained
66
BLADDER INJURY, INTRAOPERATIVE
Diagnostic Procedures/Surgery (1,4) r Transurethral procedure: 4. Gomez, Ceballos L, Coburn M, et al. Consensus
r Intraoperative diagnosis: – Extraperitoneal perforation statement on bladder injuries. BJU Int. 2004;
– Normal saline with indigo carmine into Foley and ◦ Exploratory laparotomy with repair for large 94(1):27–32.
observe for extravasation (blue staining)
– Avoid use of methylene blue due to extensive
perforation. Carefully inspect bowel for
potential injury
5. Corriere JN, Sandler CM. Diagnosis and
management of bladder injuries. Urol Clin North
B
tissue staining risk ◦ Small leak can be initially managed with Am. 2006;33:67–71.
r Intraoperative cystoscopy can be useful in selected catheter drainage and close monitoring 6. Stav K, Dwyer PL, Rosamilia A, et al. Risk factors
situations and may be the most reliable method of – Extraperitoneal perforation for trocar injury to the bladder during mid urethral
immediately assessing bladder wall integrity – Usually managed with catheter drainage sling procedures. J Urol. 2009;182:174–179.
r Cystoscopy – Large perforations complicated by symptomatic
– Recommended after suburethral sling operations collections require drainage, with or without
via the retropubic route formal closure of the perforation
r Bladder perforation during midurethral sling or
ADDITIONAL READING
– May be considered after sling insertion via the
obturator route (controversial as bladder injuries transvaginal mesh placement EAU Guidelines on Iatrogenic Trauma - European
are rare with this technique). – Sling reinsertion and urethral catheterization Association of Urology www.uroweb.org, Accessed
r Cystoscopy after transvaginal mesh procedures is (1–2 days) should be performed (4,6). February 2, 2014.
preferable. ADDITIONAL TREATMENT See Also (Topic, Algorithm, Media)
r Some authors have recommended routine r Bladder Trauma
In the setting of any bladder perforation during TURBT
cystoscopy due to the higher risk of bladder injuries intravesical postoperative chemotherapy should not be r TUR Syndrome
during hysterectomy or after any major gynecologic administered r Ureter, Intraoperative Injury
procedure. r Ureter, Trauma
Pathologic Findings ONGOING CARE
Rupture through mucosa, submucosa, and muscularis
of detrusor usually causes urine leak PROGNOSIS CODES
r Extraperitoneal: Usually heals with Foley catheter
r Prostatourethral injury drainage and without further intervention ICD9
r Intraperitoneal: Good prognosis if identified r 867.0 Injury to bladder and urethra, without
r Small or large bowel injury
r Ureteral injury intraoperatively and repaired. Prognosis worse if mention of open wound into cavity
delayed diagnosis r 867.1 Injury to bladder and urethra, with open
r Vascular injury
COMPLICATIONS wound into cavity
r Peritonitis or abscess r 998.2 Accidental puncture or laceration during a
TREATMENT r Ileus procedure, not elsewhere classified
r Fistula
GENERAL MEASURES r Reoperation
ICD10
r Prompt recognition improves opportunity for r N99.71 Acc pnctr & lac of a GU sys org during a GU
improved outcome. FOLLOW-UP sys procedure
r Bladder injury can be found intraoperatively or r N99.72 Accidental pnctr & lac of a GU sys org
Patient Monitoring
postoperatively, and will be intraperitoneal or r Foley catheter or suprapubic tube to monitor urine during oth procedure
extraperitoneal. r S37.23×A Laceration of bladder, initial encounter
output
r For most bladder injures Foley catheter for r Usually no need for outpatient antibiotics
10–14 days with follow-up cystogram is
recommended
CLINICAL/SURGICAL
REFERENCES PEARLS
MEDICATION
First Line r Intraoperatively, visual inspection is a reliable
1. Vakili B, Chesson RR, Kyle BL, et al. The incidence
r Consider antibiotics: Gentamicin or fluoroquinolone of urinary tract injury during hysterectomy: A method of assessing bladder injury.
for 24 hr prospective analysis based on universal cystoscopy. r Extraperitoneal: Usually heals with Foley catheter
r Anticholinergic for postoperative bladder spasm: Am J Obstet Gynecol. 2005;192:1599–1604. drainage and without further intervention.
Oral or suppository 2. Ostrzenski, Ostrzenska KM. Bladder injury during r Intraperitoneal: Good prognosis if identified
Second Line laparoscopic surgery. Obstet Gynecol Surv. intraoperatively and repaired. Prognosis worse if
N/A 1998;53(3):175–180. delayed diagnosis.
3. Cass AS. Diagnostic studies in bladder rupture. r All cystograms must include a postcontrast
SURGERY/OTHER PROCEDURES (5) Urolog Clinc North Am. 1989;16:267–273. evacuation study to evaluate for residual contrast
r Laparoscopic or robotic injury:
outside of the bladder.
– 1-layer laparoscopic or robotic repair
r Intraoperative intraperitoneal injury:
– Open bladder/2-layer repair
r Intraoperative extraperitoneal injury:
– Foley or 2-layer repair
r Postoperative intraperitoneal injury:
– Exploratory laparotomy with repair
r Postoperative extraperitoneal injury:
– Initial catheter drainage with antibiotics
67
BLADDER OUTLET OBSTRUCTION (BOO)

Garjae D. Lavien, MD
Michael J. Naslund, MD
r Cystoscopy: Endoscopic evaluation of urethra and

BASICS DIAGNOSIS bladder
– Used to evaluate prostatic length, median lobe
DESCRIPTION HISTORY component of prostatic obstruction, and bladder
r Bladder outlet obstruction (BOO) refers to a r Detailed description of obstructive voiding
mucosa
pathologic obstruction to urinary flow symptoms consistent with BOO – Can reveal other etiology for the BOO, such as
r Definitions include the following: – Slow urinary stream strictures, stones, diverticula, urethral masses, and
– A reduction in urinary flow to <12 cc/s during a – Urinary hesitancy bladder tumors
sustained detrusor contraction of over 40–50 cm – Intermittent urinary stream r Urodynamics: Pressure-flow study to determine if a
H2 O – Straining to void low flow rate is due to obstruction or reduced
– BOO index >40 on the International Continence – Sense of incomplete bladder emptying bladder contractility:
Society nomogram based on urodynamic testing – Urinary retention – Videourodynamics: Fluoroscopy combined with
r History of irritative symptoms
EPIDEMIOLOGY urodynamics. Recommended in patient suspected
r Medical history of gynecologic, neurologic, and GI
to have primary bladder neck obstruction
Incidence illness – ICS nomogram is the most widely used
2.2–6.8 events of acute urinary retention per 1,000 r Past surgical history for pelvic and spinal procedures measurement of BOO; plots maximal flow against
person years (1)[A] r Medication review for anticholinergics, α-agonists, detrusor pressure at the time of flow
Prevalence psychotropic agents – EMG: Evaluates for neurogenic etiology of BOO
r Voiding diary
None Diagnostic Procedures/Surgery
r International Prostate Symptom Score See “Imaging” and “Surgery/other procedures”
RISK FACTORS
r Increasing age PHYSICAL EXAM Pathologic Findings
– Microscopic BPH starts as early as the 30s but r Abdominal exam: Depends on etiology of BOO
clinical BPH usually presents after the age of 50 – Palpate for bladder distention (>150 cc retained
r Infection DIFFERENTIAL DIAGNOSIS
urine needed to be palpable in an adult) r Inadequate bladder contractility
r Urethral trauma – Inguinal hernia can be associated with severe BPH r BOO after incontinence surgery
r Pelvic radiation and retention
r Digital rectal exam: – The most common etiology of BOO/urinary
r Prior urologic procedures
retention in women
– Examine for an enlarged prostate r Prostatic obstruction (BPH)
Genetics – Note any findings suspicious for cancer: Nodules,
N/A firmness, and asymmetry – Most common etiology of BOO in men
r Primary bladder neck obstruction
PATHOPHYSIOLOGY – Assess anal sphincter tone
r BOO can be due to both static and dynamic factors: r Pelvic exam (women) for pelvic organ prolapse and r Infection:
r Dynamic factors urethral diverticula – Prostatitis, intraurethral condyloma (men and
r Neurologic exam for gross defects woman), periurethral abscess
– Stimulation or lack of relaxation of the smooth r Neurologic:
muscle along the proximal urethra or bladder neck DIAGNOSTIC TESTS & INTERPRETATION
– Results in increased resistance along the prostatic – Detrusor sphincter dyssynergia, diabetes mellitus
Lab with atonic bladder
urethra r PSA: r Medications that affect bladder contractility
r Static factors
– If elevated, consider prostate cancer, prostatic – Anesthetics, narcotic, psychotropics
– Constricted outlet by enlarged prostatic tissue, inflammation, benign prostatic hyperplasia r Urethral caruncle, urethral diverticulum (primarily
bladder neck contracture, or urethral stricture r Urinalysis:
r Outlet obstruction leads to detrusor hypertrophy and women)
– If hematuria or urinary infection is present, further r Urethral cancer
the symptoms of BOO evaluation is necessary (see Chapter on r Penile cancer (usually advanced)
ASSOCIATED CONDITIONS “Hematuria, Gross and Microscopic, Adult”)
r BPH r Creatinine
r Urethral stricture disease – Not necessary unless patient is in urinary retention TREATMENT
r Detrusor sphincter dyssynergia
Imaging
r Renal and bladder US GENERAL MEASURES
GENERAL PREVENTION r Management of BOO depends on etiology and
None – Evaluate for hydronephrosis if there is renal
severity.
insufficiency r A urethral catheter is used for temporary
– Allows noninvasive determination of PVR
r Upper tract imaging with CT urogram to evaluate management of severe obstruction or retention.
r A suprapubic tube is used if a urethral catheter
causes of hematuria
r Uroflowmetry: cannot be placed (severe stricture or BPH) or urethral
catheter is contraindicated (acute prostatitis).
– Measures peak flow, demonstrate voiding pattern, r Long-term treatment of BOO is medical and surgical.
and voided volume
– Peak flow <10–12 cc/s (for voided volume
>150 cc) is suggestive of obstruction, although
an acontractile bladder cannot be ruled out
68
BLADDER OUTLET OBSTRUCTION (BOO)
MEDICATION ADDITIONAL READING

First Line ONGOING CARE r Dmochowski RR. Bladder outlet obstruction:
r α-Blockers: Rapidly relax the smooth muscle of the
PROGNOSIS Etiology and evaluation. Rev Urol. 2005;7:S3–S13.
bladder neck and prostate without impairing
bladder contractility: Excellent with definitive management r Groutz A, Blaivas JG, Chaikin DC. Bladder outlet B
– Alfuzosin (10 mg/d) COMPLICATIONS obstruction in women: Definition and
– Doxazosin (start 1 mg/d to max 8 mg; XL form r Urinary retention characteristics. Neurourol Urodyn. 2000;12:213.
2–8 mg daily) r Gross hematuria r Lepor H. Pathophysiology of benign prostatic
– Silodosin (8 mg/d) r Renal insufficiency/failure hyperplasia in the aging male population. Rev Urol.
– Tamsulosin (start 0.4 mg to max 0.8 mg) r Bladder stones 2005;7:S3–S12.
– Terazosin (start 1 mg/d to max 20 mg) r McConnell JD, Roehrborn CG, Bautista OM, et al.
r UTIs
r 5-α-reductase inhibitors in males: Effective in larger The long-term effect of doxazosin, finasteride, and
r Bladder diverticula and flaccid bladder
glands (>40 cc) to reduce prostate size, improve combination therapy on the clinical progression of
r Postobstructive diuresis:
symptoms, and reduce progression risk: benign prostatic hyperplasia. N Engl J Med.
– Finasteride (5 mg/d) – Occurs with severe BOO and bilateral ureteral 2003;349:2387–2398.
– Dutasteride (0.5 mg/d) obstruction due to urinary retention
– Self-limited and corrected by the fluid hydration See Also (Topic, Algorithm, Media)
Second Line r Bladder Neck Contracture
r Phosphodiesterase-5 inhibitors (PDE5i) in males – If the patient cannot keep up with the urine
r Bladder Neck Hypertrophy
output, then IV replacement with 1/2 normal
– Tadalafil only PDE5i currently approved by the saline at a rate of 1/2 of the urine output r Bladder Outlet Obstruction (BOO) Image
FDA for treatment of LUTS in the setting of BPH – Serum electrolytes must be monitored closely r Lower Urinary Tract Symptoms (LUTS)
with or without coexisting erectile dysfunction r Lower Urinary Tract Symptoms (LUTs), Male
FOLLOW-UP
(2)[A] Algorithm
Patient Monitoring r Multiple Sclerosis, Urologic Considerations
SURGERY/OTHER PROCEDURES r Periodic follow-up visits to assess symptom
r Urethral strictures r Prostate, Benign Enlargement (Benign Prostate
progression (IPSS)
– Urethral dilation r Yearly urinalysis and PSA measurement Enlargement (BPE)
– Endoscopic incision r Serial measurement of uroflow and PVR urine r Prostate, Benign Hyperplasia (BPH)
– Open excision (with primary anastomosis, grafts, r Counsel on the possibility of progression of r Prostate, Benign Obstruction (Benign Prostatic
or flaps) Obstruction, [BPO])
r Urethrolysis symptoms and complications
r Management of BPH does not eliminate the risk of
– Primary surgical approach to urethral obstruction
developing prostate cancer
following anti-incontinence surgery in women CODES
r Sphincterotomy Patient Resources
r Urology Care Foundation
– Utilized for patients with detrusor sphincter ICD9
dyssynergia – www.urologyhealth.org r 596.0 Bladder neck obstruction
r BPH r 600.01 Hypertrophy (benign) of prostate with
– Transurethral needle ablation urinary obstruction and other lower urinary tract
– Transurethral microwave therapy
REFERENCES
symptoms (LUTS)
– Transurethral incision of prostate 1. Kaplan SA, Wein AJ, Staskin DR, et al. Urinary r 788.29 Other specified retention of urine
– Transurethral resection of prostate (TURP) retention and post-void residual urine in men:
– Laser-assisted techniques such as holmium laser Separating truth from tradition. J Urol. 2008;180: ICD10
enucleation of the prostate (HoLEP), others r N32.0 Bladder-neck obstruction
47–54.
– Photovaporization of prostate r N40.1 Enlarged prostate with lower urinary tract
2. Dmochowski R, Roehrborn C, Klise S, Xu L, et al.
– Simple open prostatectomy Urodynamic effects of once daily tadalafil in men symptoms
r R33.8 Other retention of urine
ADDITIONAL TREATMENT with lower urinary tract symptoms secondary to
Radiation Therapy clinical benign prostatic hyperplasia: A randomized,
N/A placebo controlled 12-week clinical trial. J Urol. CLINICAL/SURGICAL
2013;189;S135–S140.
Additional Therapies 3. Barry MJ, Meleth S, Lee JY, et al; Complementary PEARLS
r Long-term catheter drainage for patients with
and Alternative Medicine for Urological Symptoms r If a male patient has lower urinary tract symptoms
severe comorbidities (CAMUS) Study Group. Effect of increasing doses of
r Clean intermittent catheterization check to ensure a low post-void residual which
saw palmetto extract on lower urinary tract generally confirms that treatment is not necessary.
r Prostatic stents
symptoms: A randomized trial. JAMA. 2011; r Strong consideration should be given for evaluation
r Urinary diversion 306(12):1344–1351.
for multiple sclerosis in young female patients with
Complementary & Alternative new onset urinary retention.
Therapies
r Saw Palmetto (Serenoa Repens)
– No difference in reduction of lower urinary tract
symptoms compared to placebo (3)[A]
69
BLADDER TRAUMA
Brad Figler, MD
Hunter Wessells, MD, FACS
r If ureteral injury is suspected, this should be

BASICS DIAGNOSIS assessed preoperatively (CT with delayed images) or
intraoperatively (retrograde pyelogram/direct
DESCRIPTION HISTORY inspection)
r Bladder trauma generally comprises blunt and r Type of blunt trauma to pelvis r When combined upper and lower tract urologic
penetrating types of injury. – Associated injuries injuries are suspected, upper tract contrast study
r When not distended, bladder is protected from r For gunshot, number, and trajectory
should be performed prior to cystogram (retained
injury by bony pelvis. r Stab wounds type of knife if known
bladder contrast in abdomen or retroperitoneum can
r Pelvic fracture and bladder distention increase risk r Gross hematuria obscure upper tract pathology)
of traumatic injury. r Alcohol use
r Important to distinguish between extraperitoneal r Past urologic history
r Cystogram is easy to do and highly sensitive
(EBR), intraperitoneal (IBR), and combined EBR/IBR. r Complaints – CT cystogram
r Iatrogenic bladder injury is discussed in the section – Location of lower abdominal pain ◦ At least as sensitive as conventional cystography
“Bladder Injury, Intraoperative.” – Urinary retention for diagnosing bladder rupture (1)
– Dysuria or voiding complaints ◦ Dilute contrast to limit artifact (1:6)
EPIDEMIOLOGY
◦ Postdrainage films not necessary
Incidence PHYSICAL EXAM
r Abdominal distention ◦ Excellent visualization of bladder neck
1.6% of blunt abdominal trauma ◦ Readily identify foreign bodies
r Lower abdominal/suprapubic tenderness
Prevalence r Peritonitis – Conventional cystogram
r Unknown ◦ Dilute contrast 1:2
r Seatbelt sign
◦ Scout, AP, oblique, and postdrainage films
RISK FACTORS r Site/extent of abdominal/pelvic bruising
r Motor vehicle crashes (MVCs) – For both CT and conventional cystography, fill
r Site/extent/trajectory of penetrating objects bladder to capacity (at least 350 mL in an adult,
r Falls
r Blood at meatus or determine by formula: (Age in years + 2) × 30.
r Industrial trauma (pelvic crush injury)
r Rectal and vaginal exam (assess integrity)
r Penetrating injuries to lower abdomen
r Open pelvic fractures ALERT
r Bladder outlet obstruction
CT with delayed images is inadequate for the
r Alcohol intoxication (bladder distention and
ALERT diagnosis of bladder injuries: when bladder injury is
decreased sensorium) Gross hematuria is the hallmark sign of injury to the suspected, a cystogram is mandatory (2).
r Pelvic fracture
bladder.
– ∼80% of bladder injures associated with pelvic Pathologic Findings
fracture DIAGNOSTIC TESTS & INTERPRETATION Injured tissue typically remains healthy, though there
– ∼6% of patients with pelvic fracture sustain a is potential for local ischemia (particularly if
bladder injury
Lab
r Urinalysis (UA): Blood usually present angio-embolization was performed for pelvic bleeding)
r Urethral injury (present in 15% of cases)
r Serum creatinine can be elevated with IBR due to
Genetics intraperitoneal resorption of urine DIFFERENTIAL DIAGNOSIS
N/A r Hyperkalemia, hypernatremia, uremia, acidosis can r Bladder contusion
also be seen with urinary extravasation into the r Urethral injury
PATHOPHYSIOLOGY r Renal or ureteral injury
r The bladder is generally well protected from blunt peritoneum
r CBC (assess for leukocytosis and anemia)
trauma unless significantly distended
r In an adult, the bladder lies in the true pelvis, but
Imaging TREATMENT
can rise to umbilicus when full r Indications for performing cystography:
r In a child, bladder lies in abdomen and more prone – Blunt trauma GENERAL MEASURES
to injury ◦ Pelvic ring fracture with gross or microscopic Stabilize patient if major trauma present
r EBR or combined EBR/IBR (3+ or >30 RBC/HPF) hematuria
◦ Gross hematuria in presence of otherwise MEDICATION
– Pelvic fracture leads to shearing injury from bone
fragment or compression with rupture unexplained free intraperitoneal fluid First Line
– Direct injury from penetrating trauma ◦ High clinical suspicion (pelvic fluid collection, For nonoperative management of EBR, antibiotics with
r IBR inability to void, elevated serum creatinine, gram-positive and gram-negative coverage are
– Blow to lower abdomen in the presence of a full abdominal distention, suprapubic tenderness, recommended while catheter is indwelling
bladder intoxicated or unresponsive, poorly functioning Second Line
Foley catheter, displaced obturator ring fracture, N/A
ASSOCIATED CONDITIONS or large pubic symphysis diastasis
r Bladder neck injury
– Penetrating injury
r Pelvic fracture ◦ Trajectory suggests bladder injury
r Solid abdominal organ injury ◦ Involvement of buttock, pelvis, or lower
r Urethral injury abdomen with any degree of hematuria
◦ High clinical suspicion
GENERAL PREVENTION
r Avoid high-risk activity
r Seatbelt proper positioning and use
70
BLADDER TRAUMA
SURGERY/OTHER PROCEDURES ADDITIONAL TREATMENT ADDITIONAL READING

r When associated with significant pelvic bleeding,
Radiation Therapy r Figler B, Hoffler CE, Reisman W, et al. Multi-
open pelvic fractures, and abdominal solid organ N/A
injury, supportive care is indicated while more
urgent injuries are temporized Additional Therapies
disciplinary update on pelvic fracture associated
bladder and urethral injuries. Injury. 2012;43(8):
B
r IBR Injuries to urethra, bladder neck, or ureters may 1242–1249.
necessitate endoscopic realignment, repair of bladder r Gomez RG, Ceballos L, Coburn M, et al. Consensus
– Laceration is typically large (6–8 cm), at dome
neck, or ureteral reimplant statement on bladder injuries. BJU Int. 2004;94(1):
– Nonoperative management generally
contraindicated secondary to size of defect and Complementary & Alternative 27–32.
morbidity of chemical peritonitis Therapies See Also (Topic, Algorithm, Media)
– Should be closed in 2 layers with absorbable N/A r Bladder Injury, Intraoperative
suture via midline incision r Bladder Trauma Algorithm
– Laparoscopic repair has been reported in stable ONGOING CARE r Bladder Trauma Image
patients with no other injuries (3) r Ureter, Trauma
– Drain is not necessary PROGNOSIS r Urethra, Trauma (Anterior and Posterior)
– Foley catheter 7–10 days, with cystogram to r Prompt diagnosis and appropriate management
confirm absence of extravasation allow excellent results and minimal morbidity.
r EBR r Complications usually are associated with delay in
– Nonoperative management diagnosis and management.
CODES
– Acceptable in the appropriate patient, but higher
complication risk (4) COMPLICATIONS ICD9
– 20-French or larger catheter Unrecognized injury can result in fistula, sepsis, ileus, r 867.0 Injury to bladder and urethra, without
– Cystogram after 10–14 days incontinence, and stricture. mention of open wound into cavity
– Antibiotics with gram-positive and gram-negative r 867.1 Injury to bladder and urethra, with open
FOLLOW-UP
coverage while catheter is indwelling Patient Monitoring wound into cavity
– Contraindications to nonoperative management: r Monitor for signs/symptoms of:
◦ Inadequate catheter drainage ICD10
– Pelvic bleeding r S37.20XA Unspecified injury of bladder, initial
◦ Vaginal or rectal injury – Unrecognized abdominal injury
◦ Bladder neck injury encounter
– UTI r S37.22XA Contusion of bladder, initial encounter
◦ Concomitant urethral injury – Urinary leak
◦ Internal fixation of pelvic fracture r S37.23XA Laceration of bladder, initial encounter
◦ Stable and undergoing laparotomy Patient Resources
r Operative repair www.urologyhealth.org/urology/index.
– Midline abdominal incision or Pfannenstiel cfm?article=99 CLINICAL/SURGICAL
– Avoid unnecessary pelvic dissection, as there can PEARLS
be significant bleeding from original trauma REFERENCES r Gross hematuria is hallmark of bladder injury.
– Minimal debridement to ensure healthy wound r In addition to diagnosing bladder rupture, CT
edges 1. Quagliano PVDS, Malhotra AK. Diagnosis of blunt
– Removal of foreign bodies and bony fragments bladder injury: A prospective comparative study of cystogram is useful in identifying foreign bodies and
– Assess ureteral orifices if not imaged computed tomography cystography and bladder neck injuries.
conventional retrograde cystography. J Trauma. r CT with delayed images is inadequate for the
– 2-layer watertight closure with absorbable suture
– Drain is not necessary, but may be helpful 2006;61(2):410–421. diagnosis of bladder injuries: When bladder injury is
– Foley catheter 10–14 days, with cystogram to 2. Doyle S, Master VA, McAninch JW. Appropriate use suspected, a cystogram is mandatory.
confirm absence of extravasation of CT in the diagnosis of bladder rupture. J Am Coll
– Suprapubic tube not necessary Surg. 2005;200(6):973.
3. Kim FJ, Chammas MF Jr, Gewehr EV, et al.
Laparoscopic management of intraperitoneal
bladder rupture secondary to blunt abdominal
trauma using intracorporeal single layer suturing
technique. J Trauma. 2008;65(1):234–246.
4. Kotkin L, Koch M. Morbidity associated with
nonoperative management of extraperitoneal
bladder injuries. J Trauma. 1995;38(6):895–898.
71
BLADDER TUMORS, BENIGN AND MALIGNANT, GENERAL

CONSIDERATIONS
Gurdarshan S. Sandhu, MD
PATHOPHYSIOLOGY Pathologic Findings

BASICS r Patterns of spread of bladder cancer r Benign lesions
– Lymphatic – Nephrogenic adenoma: Metaplastic response to
DESCRIPTION – Hematogenous—to liver, lung, bone, etc. chronic inflammation
r Most bladder masses represent a malignant tumor – Implantation – Von Brunn nests: Benign urothelial cells within the
r Bladder tumors can be benign, low-grade, or – Direct extension lamina propria
aggressive high-grade malignancies – Squamous metaplasia: Common in women (40%)
r There are a number of nonneoplastic and ASSOCIATED CONDITIONS
– Cystitis cystica: Central cystic degeneration of Von
None
inflammatory disorders that can manifest as a focal Brunn nests
bladder mass and mimic malignancy GENERAL PREVENTION – Eosinophilic cystitis
r Smoking cessation – Malacoplakia: Chronic reaction,
EPIDEMIOLOGY – Decreases risk after approximately 15 yr Michaelis–Gutmann bodies (bulls-eyed
Incidence r Avoid occupational exposures histiocytes) are needed for diagnosis
r Bladder cancer: 9th most common cancer r Mediterranean diet: Lowest bladder cancer risk – Papilloma: Benign growth, can recur but does not
– 73,510 cases diagnosed in US in 2012 (55,600 r Antioxidants including vitamins A, C and E, and progress or invade
males and 17,910 females) (1) – Inverted papilloma: Benign lesion with inverted
micronutrients selenium and zinc may be protective
– 14,880 total deaths in US in 2012 (10,510 males r Increased fluid intake may be protective growth pattern
and 4,370 females) – Leiomyoma: Benign smooth muscle tumor covered
– Male:female > 3:1 by urothelium
– Incidence increases with age and peaks in 8th DIAGNOSIS – Inflammatory pseudotumor (pseudosarcomatous
decade of life fibromyxoid tumor)
– Median age at diagnosis is 73 HISTORY – Endometriosis
– 3× more common in White than Black men r Painless, gross hematuria – TB
– 1.5× more common in White than Black women r Irritative voiding symptoms—frequency, urgency, – Schistosomiasis
Prevalence dysuria – Crohn disease: Fistulas from inflamed small and
Estimated 437,180 male and 148,210 female bladder r Mucosuria: Adenocarcinoma, colovesical fistula large bowel
cancer survivors in US as of 2012 (2) r Weight loss, cachexia, bone pain, flank pain – Diverticulitis: Colovesical fistulas
r Inquire about risk factors reviewed earlier r Extrinsic compression resembling masses: Prostate,
RISK FACTORS
r Malignant bladder tumors r Egyptian or Middle Eastern heritage are risk factors uterine, and ovarian organs; ureteroceles,
for SCC extramedullary hematopoiesis; urachal cysts;
– Smoking—main risk factor for bladder cancer paraganglionic tissue; hamartomas; amyloidosis;
◦ 2–6× increased risk urothelial cancer PHYSICAL EXAM and vascular malformations
◦ Risk is linearly dose and duration related, with r Rarely abnormal r Premalignant lesions
15–20 yr latency – Bimanual exam done under anesthesia before and
◦ 2nd-hand smoke does not increase risk of – Leukoplakia: Squamous metaplasia with 20% risk
after transurethral resection of bladder tumor for SCC
bladder cancer formation (TURBT) – Cystitis glandularis: Glandular metaplasia with
– Chemical exposure: – Digital rectal exam
◦ Especially aniline dyes and aromatic amines risk for adenocarcinoma
r Urothelial carcinomas (90% of tumors)
◦ High-risk industries include textiles, aluminum, DIAGNOSTIC TESTS & INTERPRETATION
dye, leather, launderers, and rubber workers Lab – Papillary urothelial neoplasia of low malignant
– Pelvic irradiation r Urinalysis (for red blood cells) and culture potential (PUNLMP)
◦ Latency is 15–30 yr r Urine cytology – Carcinoma in situ: High-grade tumor confined to
◦ Increased risk in prostate and cervical cancer – More sensitive in high-grade disease and urothelium, looks erythematous and velvety
◦ Precursor lesion for invasive disease
treated with radiation carcinoma in situ (>90%)
r Flow cytometry ◦ 40–83% progress to muscle invasive disease
– Chemotherapy
◦ Cyclophosphamide has a 4–9× increased risk – Urothelial carcinoma
– Measures DNA content of cells to quantitate ◦ 80% are nonmuscle invasive
for bladder cancer aneuploid cell populations ◦ Correlation between grade and stage
– Inflammation is a risk factor for squamous cell r Other urine markers are commercially available (eg,
r SCC (5%): Seen with chronic inflammation
carcinoma (SCC) BTA Stat, NMP 22, BladderChek), and have better
◦ Indwelling catheters r Adenocarcinoma (2%): Seen in bladder exstrophy
sensitivities but worse specificities than cytology
◦ Chronic urinary tract infection (UTI) and urachal tumors
◦ Chronic bladder stones Imaging – Important to rule out gastrointestinal primary
r Upper tract evaluation can be done with intravenous r Small cell carcinoma: Aggressive neuroendocrine
◦ Schistosoma hematobium infection
urogram, retrograde pyelography, computerized tumor (rare)
Genetics tomography (CT), or magnetic resonance imaging
r Heredity plays a minor role r Metastatic evaluation includes chest imaging and DIFFERENTIAL DIAGNOSIS
– History in a 1st-degree increases risk 2× r Bladder wall mass: See “Pathologic findings”
bone scan
◦ No clear inheritance patterns r Irritative voiding symptoms: UTI, urinary calculi,
r p53 gene on chromosome 17 Diagnostic Procedures/Surgery interstitial cystitis, bladder cancer, chronic prostatitis
r Cystoscopy with bladder tumor resection or biopsy
– Overexpression leads to higher rates of
progression and lower rates of response to – Fluorescence cystoscopy may increase detection of
chemotherapy carcinoma in situ or additional lesions
r Loss of Retinoblastoma (Rb) gene on chromosome 9
– Development of superficial tumors
r Slow metabolizers and slow acetylators more
susceptible to environmental carcinogens
72
BLADDER TUMORS, BENIGN AND MALIGNANT, GENERAL CONSIDERATIONS
ADDITIONAL TREATMENT 3. Wood DP. Urothelial tumors of the bladder. In:

TREATMENT Radiation Therapy Wein AJ, et al., eds. Campbell-Walsh Urology, 10th
r Can be used in bladder sparing protocols ed. Philadelphia, PA: Saunders, 2012:2309–2334.
GENERAL MEASURES
r Bladder cancer: Increase fluid intake; avoid or quit
– External beam radiotherapy combined with 4. Hall MC, Chang SS, Dalbagni G, et al. AUA
guideline for the management of non–muscle
B
chemotherapy to improve outcomes
smoking: Best preventive measure; avoid exposure ◦ 5-yr overall survival ∼50% invasive bladder cancer (Ta, T1, CIS): 2007 Update.
to aromatic amines or aniline dyes other J Urol. 2007;178(6):2314–2330.
occupational exposure
r Cisplatin-based therapy is 1st line for small cell 5. James ND, Hussain SA, Hall E, et al. Radiotherapy
r Form management of benign bladder lesions see with or without chemotherapy in muscle-invasive
carcinoma
individual topic in index r Neoadjuvant chemotherapy for locally advanced bladder cancer. N Engl J Med. 2012;366(16):
MEDICATION 1477–1488.
disease prior to cystectomy
r Chemotherapy for metastatic disease with either 6. http://www.livestrong.com/article/277852-vitamin-
First Line
treatments-for-bladder-cancer/#ixzz2T8kR8Mow
r Bacillus Calmette Guérin (BCG) [A] methotrexate, vinblastine, doxorubicin and cisplatin,
(accessed March 6, 2014).
– Attenuated strain of Mycobacterium bovis or gemcitabine and cisplatin
– Typical induction course consists of 6 weekly Complementary & Alternative
bladder instillations Therapies
r Phototherapy: No long-term date
ADDITIONAL READING
– Maintenance schedule improves response
– Absolute contraindications include r Laser therapy N/A
immunosuppression, prior history of BCG sepsis, r Vitamins (6)
gross hematuria, and immediately following – Regular vitamin E use for ≥10 yr may be r Bladder Cancer, General Considerations
TURBT associated with a decreased risk of bladder cancer r Bladder Cancer, SCC
Second Line mortality r Bladder Cancer, Urothelial Superficial (Ta, T1)
r Mitomycin C [A] – Megadose multivitamins A, B6, C, and E plus zinc (NMIBC)
– Alkylating antibiotic that inhibits DNA synthesis, may decrease bladder tumor recurrence in r Bladder Cancer, Urothelial, Metastatic (Clinical and
decreases recurrence patients receiving BCG immunotherapy
Pathologic N+, M+)
– Given as 40 mg in 40 mL of NS or water, given – Increased carotene intake, including r Bladder Cancer, Urothelial, Muscle Invasive (Clinical
weekly × 8 weeks then monthly × 1 yr beta-carotene, alpha-carotene and lycopene, is
associated with decreased bladder cancer risk and Pathologic T2/T3/T4) (MIBC)
– Also given perioperatively after TURBT r Bladder Cancer, Urothelial, Superficial Carcinoma In
r Interferon α-2B Situ (CIS) (NMIBC)
– Given as monotherapy or in combination with ONGOING CARE r Bladder Mass, Differential Diagnosis
low-dose BCG r Bladder Tumor Algorithm
– Dose not standardized
PROGNOSIS r Bladder Tumors, Benign and Malignant, General
r Progression and recurrence depend upon grade,
r Thiotepa: Alkylating agent
stage, size, the presence of CIS, multifocality, and Considerations Image
– Dose ranges from 30 mg in 30 mL of water/saline frequency of prior recurrences. r Bladder Wall Calcification, Differential Diagnosis
to 60 mg in 60 mL of water/saline r Bladder Wall Thickening, Differential Diagnosis
– Given weekly × 8 weeks then monthly × 1 yr COMPLICATIONS r Cystitis Cystica
– Myelosuppression when absorbed systemically r Bladder perforation from TURBT
r Disease progression and metastases r Cystitis Glandularis and Cystitis Glandularis of the
r Doxorubicin: Anthracycline antibiotic, prevents
r Hematuria Intestinal Type
recurrence, not progression r Papillary Urothelial Neoplasm of Low Malignant
r Valrubicin for BCG refractory CIS r Ureteral obstruction
r UTI or sepsis Potential (PUNLMP)
– 800 mg in 75 mL of saline, administered weekly
for 6 wk
r Gemcitabine: Activity in nonmuscle-invasive bladder FOLLOW-UP
cancer Patient Monitoring CODES
r History and physical, urinalysis, cystoscopy, and
– 2 gm in 50–100 mL NS, weekly for 6 wk
urine cytology every 3 mo for 2 yr, then every 6 mo ICD9
SURGERY/OTHER PROCEDURES for 2–3 yr, then once a year. r 188.9 Malignant neoplasm of bladder, part
r TURBT r Periodic upper tract imaging for high-risk patients unspecified
– Diagnostic: Consider repeat resection for T1 r 223.3 Benign neoplasm of bladder
disease Patient Resources r 236.7 Neoplasm of uncertain behavior of bladder
r BCAN http://www.bcan.org/facing-bladder-
– Therapeutic: For nonmuscle-invasive disease
r Partial cystectomy cancer/support-groups/
ICD10
r http://www.cancer.org/cancer/bladdercancer/ r C67.9 Malignant neoplasm of bladder, unspecified
– For selected patients with unifocal disease,
urachal tumors, and tumors in diverticula detailedguide/bladder-cancer-additional r D30.3 Benign neoplasm of bladder
r Radical cystectomy r D41.4 Neoplasm of uncertain behavior of bladder
– For muscle-invasive disease REFERENCES
– Consider for recurrent high-grade superficial
disease 1. Siegel R, Naishadham D, Jemal A. Cancer statistics, CLINICAL/SURGICAL
2012. CA Cancer J Clin. 2012;62(1):10–29. PEARLS
2. Siegel R, DeSantis C, Virgo K, et al. Cancer r Painless gross hematuria must be investigated to
treatment and survivorship statistics, 2012. CA
Cancer J Clin. 2012;62(4):220–241. rule out bladder cancer.
r Smoking is the most common risk factor for bladder
cancer.
r TURBT with biopsy is mandatory for diagnosis and
staging of all bladder tumors.
73
BOWEN DISEASE AND ERYTHROPLASIA OF QUEYRAT

Justin D. Ellett, MD, PhD
S. Walker Nickles, MD
PATHOPHYSIOLOGY DIAGNOSTIC TESTS & INTERPRETATION

BASICS r Carcinogenic insults from:
Lab
– Chronic injury and inflammation from poor Lab testing for carcinogenic HPV types
DESCRIPTION hygiene, urine, smegma
r Bowen Disease is squamous cell carcinoma in situ – Radiation Imaging
(CIS) of the follicle-bearing epithelium of the shaft – Exposure to chemical carcinogens, such as arsenic Imaging only indicated in instances of clinical suspicion
and scrotum. or smoking of invasion, and would include MRI or ultrasound
r Erythroplasia of Queyrat (EQ) is squamous cell – HPV infection Diagnostic Procedures/Surgery
carcinoma in situ (CIS) arising within the penile r Decreased immune surveillance due to HIV/AIDS or r Definitive diagnosis may only be made by biopsy
mucocutaneous (mucosal) epithelium of the glans medical immunosuppression – Early invasion should be excluded via the use of
penis or inner side of the foreskin. 80–90% of cases multiple biopsies
are seen in uncircumcised men. ASSOCIATED CONDITIONS
r Progression to invasive SCC in 5–30% of cases; Pathologic Findings
– Sometimes EQ is referred to as “Bowen disease r Pathology will show full-thickness epidermis with:
(BD) of the glans penis.” more likely with EQ
r Lichen sclerosis, balanitis xerotica obliterans (BXO) – Discordant architecture
– EQ more likely to develop into invasive squamous – Abnormal mitoses
cell carcinoma of the penis than Bowen disease. GENERAL PREVENTION – Dyskeratosis
r Circumcision – Involvement of associated pilosebaceous
EPIDEMIOLOGY
r Daily genital hygiene by retraction of foreskin and apparatus with intact epidermal junction
Incidence
r Penile cancer occurs in <1% of all malignancies in cleansing – Chronic inflammatory infiltrate into dermis
r Elimination of risk for HPV infection – Epithelial rete extension into submucosa that is
men, and EQ and BE are a fraction of these
r Most often occurs in Caucasian males r Early detection of lesions elongated and bulbous; submucosa shows
r Mostly in uncircumcised men r Treatment of phimosis capillary proliferation and ectasia with plasma-cell
r Majority in men ages 50–70, but described in adult rich infiltrate (these distinguish from localized
balanitis)
males of all ages DIAGNOSIS DIFFERENTIAL DIAGNOSIS (2)
Prevalence r Invasive SCC
N/A HISTORY
r Age: Median age >50 – Ruled out by biopsy
RISK FACTORS r Sexual promiscuity (increases risk for HPV infection) r Bowenoid papulosis
r Uncircumcised men – Benign course, but histologically similar except
r History of phimosis or difficulty retracting foreskin
– Phimosis present in 75% of cases r History of exposure to ionizing radiation or arsenic abnormal keratinocytes are spread discontinuously
– Smegma thought to be carcinogenic r History of nonhealing wounds, pruritus, bleeding, throughout epidermis
r Coinfection of HPV type 8 and carcinogenic genital – Tendency for multiple lesions that may coalesce
HPV types (16, 18, 39, 51) have been reported (1) discharge – Typically in younger patients (ages 25–30)
Relative risk factors: PHYSICAL EXAM – Usually spontaneously regresses
– Therapeutic immunosuppression for organ r Solitary or multiple nontender erythematous r Invasive SCC
transplants plaques – Ruled out by biopsy
– Immunosuppression from HIV/AIDS – EQ: Velvety, smooth, shiny on glans r Nummular eczema
– Arsenic exposure from well-water and other – BD: Scaly, verrucoid plaque on shaft – Pruritic, coin-shaped plaques of small grouped
sources r Individual lesion may be 10–15 mm in diameter papules on erythematous base
– Ionizing radiation r Bleeding from lesion r Psoriasis
– Thermal injury r Presence of ulceration increases likelihood of – Well-demarcated red or whitish, scaly lesion
– Chronic dermatoses invasive SCC – Usually associated with lesions at other sites
– Lichen sclerosis of the glans penis r Examination of inguinal nodes r Superficial basal cell carcinoma
– Smoking r Important factors to assess: – Pearly, skin-toned papule or plaque, often with
– Multiple sexual partners overlying telangiectasias
– Poor genital hygiene – Diameter of lesion
– Location – Treated with local excision; low malignant
– Penile trauma potential
– Number of lesions
Genetics – Morphology (papillary, nodular, ulcerous, or flat)
N/A – Relationship to other structures (submucosal,
corpora spongiosa and/or cavernosa, urethra)
74
BOWEN DISEASE AND ERYTHROPLASIA OF QUEYRAT
r Balanitis circinata ADDITIONAL TREATMENT 2. Buechner SA. Common skin disorders of the penis.
– Dry and scaling lesions of the glans in circumcised Radiation Therapy BJU Int. 2002;90(5):498–506.
or uncircumcised males Radiation therapy can be used for patients resistant to 3. Arlette JP. Treatment of Bowen disease and
– Associated with Reiter’s syndrome
– Can be moist and erythematous in uncircumcised
topical treatment or who are not surgical candidates. erythroplasia of queyrat. Br J Dermatol. 2003; B
149(Suppl 66):43–49.
males Additional Therapies
r Candidal balanitis Additional therapies include cryotherapy, curettage,
and photodynamic therapy, although their
– Usually found in uncircumcised diabetics
effectiveness is limited. ADDITIONAL READING
– Reddened and edematous lesions
Complementary & Alternative r NCCN Guidelines Version 1.2013, Penile Cancer;
– Usually treated with antifungal therapy
r Zoon balanitis Therapies from NCCN.org (Accessed April 10, 2014).
N/A r Pettaway CA, Lance RS, Davis JW, Tumors of the
– Usually in elderly, uncircumcised males
– Cayenne pepper-appearing red, raised lesion penis. In: Wein, et al. Campbell-Walsh Urology.
– Usually distinguished from CIS on biopsy by 10th ed. Philadelphia, PA: Saunders, 2012.
ONGOING CARE
band-like infiltrate of plasma cells See Also (Topic, Algorithm, Media)
PROGNOSIS r Bowen Disease and Erythroplasia of Queyrat
r 5–33% of cases have been reported to transform to
Image
TREATMENT SCC r Penis, Cutaneous Lesion
– 5–10% risk in BD, 10–33% in EQ r Penis, Squamous Cell Carcinoma
GENERAL MEASURES (3) – Carries significant risk of death
Treatment based on multiple biopsy samples of r Cure can be achieved up to 80% of the time
adequate depth to rule out invasion r All therapies have recurrence rates of 20–30%
MEDICATION CODES
COMPLICATIONS
First Line
r Topical therapy Progression to invasive squamous cell carcinoma ICD9
– 5-fluorouracil cream BID for 4–5 wk or FOLLOW-UP 233.5 Carcinoma in situ of penis
– 5% imiquimod cream daily for 16 wk Patient Monitoring ICD10
– Proven effective for large lesions not amenable to r BD and EQ surveillance parallels localized, invasive D07.4 Carcinoma in situ of penis
surgery or for recurrent lesions SCC of the penis with clinical exam:
– Utilized with rubber condom to increase contact – Year 1–2, every 3 mo
time – Year 3–5, every 6 mo CLINICAL/SURGICAL
Second Line – Year 5–10, every 12 mo PEARLS
N/A r Consider re-biopsy of recurrent lesions to rule out
r EQ is SCC in situ arising on the glans or inner side of
transformation to invasive SCC
SURGERY/OTHER PROCEDURES the foreskin.
r Circumcision can decrease likelihood of recurrence Patient Resources r BD is SCC in situ of the penile shaft or scrotum.
r With lesions on the foreskin, circumcision, or Medline Plus: Cancer Penis http://www.nlm.nih. r 80–90% of cases seen in uncircumcised men.
excision with 5-mm margin is adequate for local gov/medlineplus/ency/article/001276.htm r Progression to invasive SCC in 5–30%.
control
– Lesions on the glans are difficult to excise with this REFERENCES
strategy when trying to preserve penile anatomy
– Ensure adequate depth of resection to rule out 1. Wieland U, Jurk S, Weissenborn S, et al.
invasion Erythoplasia of queyrat: Coninfection with
r Mohs micrographic surgery has been utilized to cutaneous carcinogenic HPV type 8 and genital
accomplish adequate excision without disfigurement papillomaviruses in a carcinoma in situ. J Invest
r Nd:YAG, KTP, or carbon dioxide laser ablation has Dermatol. 2000;115(3):396–401.
been shown to be effective
– Nd:YAG preferred due to depth of penetration
75
BURNS, EXTERNAL GENITALIA AND PERINEUM

Brad Figler, MD

BASICS r Child and spousal abuse
Lab
r Sexual abuse r Electrolytes: Treatment of burns generally requires
DESCRIPTION r Myoglobinuria (electrical burns) large amount of fluid resuscitation
r Burns to the external genitalia and perineum can r With electrical burns, monitor creatine kinase and
damage skin, subcutaneous tissue, and surrounding GENERAL PREVENTION
r Follow occupational-specific safety precautions. urine myoglobin
organs and can be due to thermal, electrical, or
chemical contact r Handle caustic chemicals with care. Imaging
r Thermal (most common): Includes scalding and As indicated by history or physical findings
immersion injuries, direct contact with flames or hot DIAGNOSIS Diagnostic Procedures/Surgery
objects N/A
r Electrical: Passage of an electrical current from HISTORY
r Type of burn (thermal, chemical, or electrical) Pathologic Findings
1 point to another through the body r 3 zones of burns:
r Chemical: Corrosive and alkali substances found in r Causative agent or heat source (eg, flame vs. water,
– Zone of coagulation: Occurs at point of maximum
household and industrial chemicals noxious substance) damage. In this zone, there is irreversible tissue
r Location and areas involved (Rule of 9s): External loss due to coagulation of the constituent proteins.
EPIDEMIOLOGY
genitalia and perineum usually accounts for 1% of – Zone of stasis: Surrounding zone of stasis is
Incidence body surface area when using “Rule of 9s”.
r Genital/perineal burns are rarely isolated characterized by decreased tissue perfusion. The
r Possibility of other injuries (eg, fractures from motor tissue in this zone is potentially salvageable. The
r Genitals/perineum involved in 5–13% of burns
vehicle accidents, shrapnel) main aim of burn resuscitation is to increase tissue
treated at major burn centers r Pediatric considerations perfusion here and prevent any damage from
r Abuse or neglect in 10–15% of childhood burn
– Evaluate for scald and immersion injuries becoming irreversible. Additional insults – such as
injuries (higher if <2 yr of age) prolonged hypotension, infection, or edema – can
PHYSICAL EXAM convert this zone into an area of complete tissue
RISK FACTORS r Complete assessment including ABCD’s of Advanced
r Age: Very young (scald burns common in abused loss.
Trauma Life Support (ATLS). Often associated with r Zone of hyperemia: In this outermost zone, tissue
children) and very old
r Employment: Exposure to flames or caustic concomitant injuries or further burns
perfusion is increased. The tissue here will invariably
– with electrical burns determine any other
substances recover unless there is severe sepsis or prolonged
entry/exit site of current
r Gender: Women are less likely to experience genital r Rule of 9s: Based on total body surface involved. hypoperfusion.
or perineal burns (less exposed) Genitalia/perineum accounts for 1% of body area DIFFERENTIAL DIAGNOSIS
r Vital signs (patients with electrical burns will require r Diagnosis is usually apparent based on history and
Genetics
N/A cardiac monitoring for at least 24 hr) examination
r Neurologic exam: Evaluate for compartment
PATHOPHYSIOLOGY ALERT
r Classification (1) syndrome, peripheral pulses
r GU: Examine for involvement of phallus, meatus, Treat any-life-threatening conditions (ABCD’s). IVF:
– 1st-degree (superficial): Epidermis Resuscitation is critical if patient has severe burns.
– 2nd-degree (partial thickness): Dermis glans, and scrotum
◦ Superficial (involving the superficial, papillary r Classification:
dermis) – 1st-degree: Characterized by erythema, white
◦ Deep (involving reticular dermis) plaques, and mild pain
– 3rd-degree: Underlying subcutaneous tissue – 2nd-degree: Characterized by erythema, pain,
◦ Typically not painful due to nerve damage superficial blisters
– 4th-degree: Bone and muscle – 3rd/4th-degree: Characterized by eschars,
◦ Can lead to compartment syndrome blistering, and absence of pain due to loss of
◦ Often fatal nerve fibers
76
BURNS, EXTERNAL GENITALIA AND PERINEUM
ADDITIONAL READING
TREATMENT ONGOING CARE r Michielsen DP, Lafaire C. Management of genital
GENERAL MEASURES
r Treat any life-threatening conditions (ABCD)
PROGNOSIS
r Based on degree and extent of burn
burns: A review. Int J Urol. 2010;17(9):755–758.
r Peck MD, Boileau MA, Grube BJ, et al. The B
– Do not attempt to cool wound as this may cause r Most burns have matured by 6–12 mo; additional management of burns to the perineum and genitals.
more extensive injury reconstruction may be required at that time J Burn Care Rehabilitation. 1990;11(1):54–56.
r Shock may occur; IVF critical r Vanni AJ. Trauma to the external genitalia. In:
COMPLICATIONS
– >20% total body surface area (TBSA), use r Erectile dysfunction Wessells, ed. Urological Emergencies. Totowa NJ:
modified Brooke formula: r Scarring/disfigurement Humana Press, 2013.
◦ 2 mL/kg/TBSA r Urethral strictures
r Most chemical burns should be copiously irrigated. If See Also (Topic, Algorithm, Media)
r Burns, External Genitalia and Perineum Image
agent is known use guidelines: FOLLOW-UP r Penis, Trauma
– Hydrofluoric acid: Irrigate with calcium gluconate Patient Monitoring r Scrotum and Testicle, Trauma
– Hydrochloric acid or sulfuric acid: Use bicarbonate r Follow-up as indicated
irrigation
Patient Resources
– Phenol: No irrigation r American Burn Association
CODES
MEDICATION www.ameriburn.org
First Line r Phoenix Society for Burn Survivors
ICD9
r Silver sulfadiazine 1%: Apply to affected area www.phoenix-society.org r 942.05 Burn of unspecified degree of genitalia
– Does not penetrate eschar r 942.15 Erythema [first degree] of genitalia
r Mafenide acetate (Sulfamylon) 11.1% r 942.25 Blisters, epidermal loss [second degree] of
– Penetrates eschar REFERENCES
genitalia
r Pain control
1. Hettiaratchy, Dziewulski. ABC’s of burns. Br Med J.
– Narcotics 2004;328:1427–1429. ICD10
– Anti-inflammatories r T21.06XA Burn of unsp degree of male genital
r Fluid resuscitation 2. Black PC, Friedrich JB, Engrav LH, et al. Meshed
region, init encntr
unexpanded split-thickness skin grafting for r T21.07XA Burn of unsp degree of female genital
r Electrolytes as needed
reconstruction of penile skin loss. J Urol.
r Tetanus prophylaxis 2004;172(3):976–979. region, init encntr
r Antibiotic prophylaxis not necessary r T21.16XA Burn of first degree of male genital
3. Angel C, Shu T, French D, et al. Genital and perineal
– Treat specific infections as they arise. burns in children: 10 years of experience at a major region, init encntr
SURGERY/OTHER PROCEDURES (2,3) burn center. J Pediatr Surg. 2002;37(1):99–103.

r Most burns, particularly in children, should be 4. Michielsen D, Van Hee R, Neetens C, et al. Burns to CLINICAL/SURGICAL
managed with conservative treatment and require genitalia and perineum. J Urol.
1998;159(2):418–419. PEARLS
no surgical intervention.
r Foley catheter or suprapubic drainage may be used, r Genital/perineal burns are rarely isolated.
but are often not necessary r Favor conservative management initially.
r Mainstay of surgical treatment, if needed, is careful r Excellent functional and cosmetic results are
debridement. possible with split-thickness skin grafting.
r Affected areas may require skin coverage:
– Granulation indicates acceptable graft bed
– Split-thickness skin grafts have reliable graft take
and excellent cosmesis
– Skin grafts can be meshed or unmeshed
– If graft bed health is questionable, can use
temporary xenograft
r Wound contractures are not uncommon; treat with
z-plasty
r Urethral stricture may develop; should be treated in
a delayed fashion (4)
– Catheter drainage may be required in the interim
77
LWBK1391-SEC-C LWBK1391-Gomella ch039.xml September 19, 2014 18:2
CALYCEAL DIVERTICULA
Yaniv Shilo, MD
Timothy D. Averch, MD, FACS
Pathologic Findings
BASICS DIAGNOSIS r Lined by nonsecretory transitional epithelium.
r Retrograde reflux of urine from the calyx via the
DESCRIPTION HISTORY diverticular neck can cause stasis with stones in
r Calyceal diverticula are nonsecretory, transitional r Mostly incidental finding on imaging
r Flank pain calyceal diverticula in up to 50% of cases
cell epithelium-lined cystic cavities within the renal
parenchyma. r Microhematuria or macrohematuria DIFFERENTIAL DIAGNOSIS
r The cavity is usually filled retrograde from urine in r Recurrent UTI r Calcified tumor
r Complicated renal cyst
the collecting system.
r Mostly unilateral. PHYSICAL EXAM r Kidney abscess
r Usually not suggestive r Nephrolithiasis
r Most prevalent in upper calyces (70%) r Possible flank pain
r No gender nor laterality predilection
r Bilateral in 3% DIAGNOSTIC TESTS & INTERPRETATION
r Sometimes called pelvicaliceal diverticula Lab
TREATMENT
r Urinalysis
GENERAL MEASURES
EPIDEMIOLOGY – Microhematuria and pyuria r In case of uncomplicated, asymptomatic calyceal
Incidence r Urine culture diverticulum treatment can be conservative with no
<1% – Bacterial persistence further imaging follow-up.
Prevalence r Indications for therapy include pain, recurrent
Imaging
Found in up to 0.45% of routine intravenous r Abdominal x-ray (KUB): infection, increased calculus growth, hematuria or
pyelogram studies. – May demonstrate characteristic radiopaque “milk large size that compresses or progressively damages
of calcium,” which appears as a half moon or contiguous renal parenchyma
RISK FACTORS
N/A meniscus-shaped calcification MEDICATION
◦ Milk of calcium should change its location when
Genetics First Line
changing positioning from erect to lateral
N/A Antibiotic treatment can be used for recurrent UTIs;
decubitus.
otherwise no specific role
PATHOPHYSIOLOGY – Case reports of confusion as being diagnosed as
r Congenital in origin due to failure of regression of rib metastasis Second Line
ureteric bud. r Ultrasound (US): N/A
r Urine enters diverticulum passively via narrow – Provide diagnosis in up to 80% of the cases. SURGERY/OTHER PROCEDURES
communication with collecting system. – Shows cystic lesion with curvilinear, plaque-like r Shock wave lithotripsy (SWL):
r Urine trapped in diverticulum predisposes to calcification along its posterior wall.
– Exam while changing positioning is needed to – May be suitable for calyceal diverticulum with
infection and stone formation. small calculi and wide infundibulum (1)[B].
differ from complex cyst.
ASSOCIATED CONDITIONS r Intravenous pyelography (IVP): – Can resolve flank pain.
r Flank pain – Limitations are due to inadequate passage of
– Delayed imaging demonstrates the diverticulum,
r Calyceal calculi (9–50%) stone fragments through the infundibulum and
as it fills retrogradely from its connection to the
r Recurrent urinary tract infection (UTI) renal pelvis or calyx. lack of anomaly repair.
r Hematuria r CT urography (CTU): r Ureteroscopy (URS):
– Delayed imaging is critical to demonstrate – Most suitable as initial treatment for calculi
GENERAL PREVENTION <1.5 cm located in the middle or upper pole
N/A contrast medium within an apparent cystic mass
diverticulum and specifically in the anterior aspect.
Diagnostic Procedures/Surgery – Involves mechanical dilatation of the diverticular
r Retrograde pyelogram:
neck and removal of calculi if present.
– Allows greater distension of the collecting system – Ablation of diverticular cavity is not a common
than can be attained with IVP. practice.
– Delineating anatomy and assist in planning the
appropriate treatment approach.
78
CALYCEAL DIVERTICULA
r Percutaneous nephrolithotomy (PCNL): r URS:

ADDITIONAL READING
– Considered to be the definitive surgical treatment – Bleeding
specifically for diverticula containing stone burden – Thermal injury to ureteral wall or renal r Canales B, Monga M. Surgical management of the
>1.5 cm in the posterior aspect. parenchyma calyceal diverticulum. Curr Opin Urol. 2003;
– Challenging when only thin layer of parenchyma – Ureteral perforation 13(3):255–260.
surrounding the diverticula or located anteriorly. – Sepsis r Matlaga BR, Miller NL, Terry C, et al. The
– Requires direct access to diverticulum and r PCNL: pathogenesis of calyceal diverticular calculi. Urol
infundibulum widening. – Bleeding Res. 2007;35(1):35–40.
– Ablation of the calyceal diverticulum cavity is
recommended (2)[B].
– Urinary extravasation
– Pneumothorax
r Calcifications, Renal
C
r Laparoscopic nephrolithotomy (LAP): – Hemothorax r Calyceal Diverticula Image
– Collecting system perforation r Nephrocalcinosis
– May be advantageous in cases of anterior
FOLLOW-UP r Urolithiasis, Adult, General considerations
diverticula, diverticula covered with thin layer,
diverticula containing large calculi or large Patient Monitoring r Urolithiasis, Renal
r Radiographic imaging with either CTU, IVP, or
diverticula (3)[B].
kidney US should be done 6–8 wk postoperatively.
– Includes unroofing of the diverticulum and calculi
removal if present. r Patients with calculi contained in diverticulum may CODES
– Ablation of the remaining cavity and neck. need metabolic evaluation as these patients tend
to have metabolic abnormalities similar to patients ICD9
ADDITIONAL TREATMENT with nephrolithiasis (5)[B]. r 592.0 Calculus of kidney
Radiation Therapy r 593.89 Other specified disorders of kidney and
N/A Patient Resources
N/A ureter
Additional Therapies r 753.3 Other specified anomalies of kidney
N/A
REFERENCES ICD10
r N20.0 Calculus of kidney
Therapies 1. Streem SB, Yost A. Treatment of caliceal diverticular r N28.89 Other specified disorders of kidney and
N/A calculi with extracorporeal shock wave lithotripsy: ureter
Patient selection and extended followup. J Urol. r Q63.8 Other specified congenital malformations of
ONGOING CARE 1992;148:1043–1046.
kidney
2. Shalhav AL, Soble JJ, Nakada SY, et al. Long- term
PROGNOSIS outcome of caliceal diverticula following
r SWL: percutaneous endosurgical management. J Urol. CLINICAL/SURGICAL
1998;160(5):1635–1639.
– Stone-free rate is relatively low (up to 60%), PEARLS
however, symptom-free rate is higher (4)[B]. 3. Gonzalez RD, Whiting B, Canales BK. Laparoscopic
calyceal diverticulectomy: Video review of r Usually located on upper calyces.
r URS:
techniques and outcomes. J Endourol. 2011;25(10): r Associate disorders include—calyceal calculi,
– Stone-free and symptom-free rates can be high 1591–1595.
when infundibulum is identified recurrent UTI, and flank pain.
4. Rapp DE, Gerber GS. Management of caliceal r URS is suitable for anterior midpole or upper
– In significant number of diverticula the diverticula. J Endourol. 2004;18(9):805–810. diverticula with calculi <1.5 cm.
infundibulum cannot be found (4)[B]. 5. Auge BK, Maloney ME, Mathias BJ, et al. Metabolic r PCNL is the treatment of choice in general for
r PCNL: abnormalities associated with calyceal diverticular calyceal diverticula and specifically for posterior
– Excellent stone-free and symptom-free rates (over stones. BJU Int. 2006;97(5):1053–1056. diverticula with thick layer of parenchyma
80%). surrounding with calculi >1.5 cm.
– Long-term results remain good. r Growing evidence for the effectiveness of LAP
r LAP: approach in cases of anterior diverticula, diverticula
– Initial results show high stone-free rate and covered with thin layer, diverticula containing large
diverticular ablation. calculi or large diverticula.
COMPLICATIONS
r Calyceal diverticula:
– Secondary infection
– Chronic pain with stones
– Compression of surrounding tissue
r SWL:
– Flank pain
– Infection
– Subcapsular or perinephric hematoma
79
CATHETERIZABLE STOMA PROBLEMS

Zachary L. Smith, MD
S. Bruce Malkowicz, MD, FACS
PATHOPHYSIOLOGY r Status of the bladder neck in patients with native

BASICS r Stomal stenosis can be attributed to infrequent bladder intact:
catheterization, scar formation, ischemia secondary – Urethral catheterization can be attempted in
DESCRIPTION to compromised vascular supply to catheterizable patients whose native urethra is intact and who
r Catheterizable stomas (CSs) are utilized in all age channel, or a nontension-free mucocutaneous have an open bladder neck.
groups and provide a means of emptying the native anastomosis. r Review of systems should focus on abdominal
bladder or neobladder. r Difficulty catheterizing the CS channel can be symptomatology.
r Most common indications for CS vary with age attributed to angulation of a mobile and/or
groups: PHYSICAL EXAM
redundant channel. r Vital signs may reveal tachycardia, hypotension, and
– Pediatrics: Incontinence related to neurologic or r Significant weight loss or gain
congenital conditions r Improper creation of continence mechanism fever in patients with peritonitis secondary to
– Adults: Urinary diversion following extirpative perforation of the catheterizable channel or urinary
r Incomplete detubularization or augmentation of the
surgery for malignancy reservoir.
r Location of CS can vary, but is most often located in urinary reservoir can lead to incontinence secondary r Abdominal exam evaluating signs of peritonitis
to low compliance and small reservoir capacity. r Inspection of the stoma, evaluating for:
the umbilicus or right lower quadrant. r Pouchitis (lower urinary tract infection) can cause
r Catheterizable channels are commonly constructed – Stenosis
temporary failure of the continence mechanism – Mucosal ischemia
from a segment of small bowel or the appendix. because of the hypercontractility of the bowel
r Mechanism of CS continence depends on the type of – Abdominal wall deformity suggestive of
segment; can be caused by inflammation of the parastomal hernia
urinary reservoir. mucosa. r Catheterization of CS to:
r Patients with CS often have routine catheterization
ASSOCIATED CONDITIONS – Evaluate patency of stoma
schedules. r Urologic, gynecologic, and colorectal malignancies
r CS problems can be related to the stoma, – Determine capacity of urinary reservoir
r Spinal dysraphisms – Evaluate continence mechanism
catheterizable channel, or urinary reservoir. r Traumatic spinal cord injuries – Obtain urine sample
EPIDEMIOLOGY – Instill contrast for imaging.
Incidence GENERAL PREVENTION
r Maintenance of a regular catheterization regimen DIAGNOSTIC TESTS & INTERPRETATION
r Complications are reported in 10–50% of patients
r Several complications can be prevented at the Lab
with CSs: r Serum electrolytes:
– Stomal stenosis has been reported in up to 40% time of surgery when creating the catheterizable
channel: – Elevated serum creatinine may be noted in
of CS patients with urinary retention from the inability
– Most stomal-related complications are reported – Maintenance of vascular supply to catheterizable
channel to catheterize.
within the 1st yr following surgery (1)[C]. – Several metabolic abnormalities may be present in
– Incontinence is reported in 1–20% of cases and is – Minimized redundancy catheterizable channel
with fixation and stabilization of the continence patients with urinary reservoirs, depending on
associated with the mechanism of continence. bowel segment utilized:
– Parastomal hernias have been noted in 0–5% of mechanism
– Adequate construction of continence mechanism ◦ Stomach: Hypochloremic, hypokalemic alkalosis
patients. ◦ Jejunum: Hyponatremic, hypochloremic,
– Tension-free mucocutaneous anastomosis
Prevalence – Use of V-flap of skin to prevent stomal stenosis hyperkalemic acidosis
N/A ◦ Ileum: Hyperchloremic acidosis
◦ Colon: Hyperchloremic acidosis
RISK FACTORS r CBC:
r Improper stomal positioning DIAGNOSIS
r Infrequent use of CS – Leukocytosis suggestive of infection
HISTORY r Blood and urine cultures in patients presenting with
r Multiple prior abdominal procedures r Date of surgery
r Obesity r Indication for CS: abdominal pain and fever
r Surgical technique – Incontinence (urinary vs. fecal) Imaging
r Contrast study of catheterizable channel and urinary
r Wound infections – Malignancy
r Attempt to obtain operative reports reservoir to evaluate for perforation
Genetics r Type of bowel utilized r Cross-sectional imaging of the kidneys assessing for
N/A r History of CS complications the presence of hydronephrosis
r Catheterization details:
ALERT
– Typical catheterization regimen
Have a low threshold for obtaining a cross-sectional
– Type and size of catheter used
imaging study (CT/MRI) with contrast when a
– Technique utilized (direction, amount of pressure,
etc.) perforation of the CS or urinary reservoir is
– Normal catheterization volumes suspected, especially in patients with neurologic
– Time of last normal catheterization deficits.
– Character of urine at the time of last successful
catheterization (color, odor, presence of debris,
etc.)
80
CATHETERIZABLE STOMA PROBLEMS
Diagnostic Procedures/Surgery r Fistula: ADDITIONAL READING

Urodynamics in patients with incontinence may reveal – Elective revision
r Inability to catheterize secondary to false passage or r Benson MC, McKiernan JM, Olsson CA. Cutaneous
uninhibited contractions or a poorly compliant
high-pressure reservoir. redundancy of CS channel: continent urinary diversion. In: Wein AJ, Kavoussi
– Elective revision LR, Novick AC, et al., eds., Campbell-Walsh Urology.
Pathologic Findings 10th ed. Philadelphia, PA: Elsevier; 2012.
N/A – Occasionally, minor false passages can be treated
r Skinner E, et al. Complications of continent
with an indwelling catheter for a short period to
DIFFERENTIAL DIAGNOSIS allow healing of channel. cutaneous urinary diversion. In: Taneja SS, Smith RB,
r Perforation of CS channel or urinary reservoir Ehrlich RM, eds. Complications of Urologic Surgery,
r Stomal stenosis ADDITIONAL TREATMENT Prevention and Management. 4th ed. Philadelphia, C
r Incontinence Radiation Therapy PA: WB Saunders; 2010.
r False passage N/A
r Parastomal hernia Additional Therapies r Bladder Cancer, Urothelial, Muscle Invasive (Clinical
r Fistula r Stomal stenosis:
and Pathologic T2/T3/T4) (MIBC)
r Inability to catheterize due to redundancy of – Routine catheterization schedule r Bladder Cancer, Squamous Cell Carcinoma
catheterizable channel – Dilatation of stenosis r Catheterizable Stoma Problems Image
r Inability to catheterize secondary to false passage or
r Parastomal Hernia
redundancy of CS channel: r Pouchitis
TREATMENT – Change type of catheter r Urostomy Problems
– Change method of catheterization
ALERT Complementary & Alternative
Perforation of CS conduit or urinary reservoir Therapies CODES
mandates emergent exploratory laparotomy, N/A
drainage of urinary extravasation, and repair of
ICD9
urinary reservoir. ONGOING CARE r 596.82 Mechanical complication of cystostomy
r 596.83 Other complication of cystostomy
GENERAL MEASURES PROGNOSIS r V55.5 Attention to cystostomy
r Good hygiene Success following stomal revisions for stenosis ranges
r Routine catheterization of CS from 80–95% (1)[C]. ICD10
r Early intervention with difficulty r N99.512 Cystostomy malfunction
COMPLICATIONS
Recurrence of prior complication r N99.518 Other cystostomy complication
MEDICATION
r Z43.5 Encounter for attention to cystostomy
First Line FOLLOW-UP
r Incontinence related to uninhibited pouch
Patient Monitoring
contractions: r Maintenance of routine catheterization schedule CLINICAL/SURGICAL
– Anticholinergics (oxybutynin, tolterodine, etc.) r Additional follow-up with enterostomal therapist
(2)[C] PEARLS
r Pouchitis may sometimes be due to infection and Patient Resources r Cathterizable stomas are used for varying reasons
r United Ostomy Associations of America, Inc.
can be treated with appropriate antibiotics. throughout one’s life. Benign/neurogenic causes
www.ostomy.org
Second Line r Bladder Cancer Advocacy Network. www.bcan.org most common in children, malignant causes most
N/A common in adults.
r Stomal stenosis is by far the most common
r Stomal stenosis: REFERENCES complication of cathterizable stomas.
r Surgical revision is often required for most
– Elective surgical revision with V-flap of skin (3)[C]
r Incontinence: 1. Thomas JC, Dietrich MS, Trusler L, et al. Continent cathterizable stomas complications.
catheterizable channels and the timing of their r Good technique and cathterizable stomas
– Elective surgical revision of continence mechanism complications. J Urol. 2006;176:1816–1820.
– Injection of bulking agent into CS maintenance with a routine catheterization schedule
2. Farnham SB, Cookson MS. Surgical complications of can prevent most complications.
– Augmentation of urinary reservoir with intestinal
urinary diversion. World J Urol. 2004;22:157–167.
patch in cases of high pressures and poor
compliance (2)[C] 3. Hellenthal NJ, Eandi JA, DeLair SM, et al. Umbilical
r Parastomal hernia: stomal stenosis: A simple surgical revision
technique. Urology. 2007;69:771–772.
– Elective hernia repair with or without
repositioning stoma site on abdominal wall
– Surveillance in asymptomatic patients
81
CHORDEE

BASICS r Hypospadias N/A
r Epispadias
DESCRIPTION r Penile torsion DIFFERENTIAL DIAGNOSIS
r Chordee is ventral penile curvature that occurs with r Disorder of sex development
r Cryptorchidism r Epispadias
or without hypospadias: r Disorders of sexual development r Hypospadias
– Epispadias can occur with dorsal curvature
– Lateral curvature also can occur with or without GENERAL PREVENTION r Normal penile variant
hypospadias None known r Penile torsion
EPIDEMIOLOGY
Incidence DIAGNOSIS TREATMENT
The incidence of chordee is unknown
HISTORY GENERAL MEASURES
Prevalence r Visualized curvature of the penis with an erection Chordee repair is the standard approach
r 44% of fetuses through the 2nd trimester r Presence of hypospadias
suggesting chordee is a normal part of
MEDICATION
development (1)[A] PHYSICAL EXAM First Line
r Observe the individual’s erection if possible
r Chordee occurs without hypospadias in 4–10% of None usually indicated specifically for chordee
r Possible coexisting findings:
cases of congenital chordee (2)[C] Second Line
– Hypospadias or epispadias N/A
r Hypospadias occurs in 1 of 250 live births (3)[A] – Incomplete foreskin ventrally
– Chordee is identified in 1/3 of these patients – Penoscrotal webbing SURGERY/OTHER PROCEDURES
– Penile torsion r Specific surgery dependant on the associated
(3)[A]
– Hypoplasia of the ventral shaft skin conditions and the severity of the curvature
RISK FACTORS – Cryptorchidism r Performed typically after 6 mo of age
r Congenital
r General points:
r Prior penile surgery DIAGNOSTIC TESTS & INTERPRETATION
r Trauma – Following penile skin release, induce artificial
Lab
r Routine lab testing not typically indicated erection. This should be repeated to confirm
Genetics r Chromosomal testing and/or biochemical testing in correction.
r Found in syndromes associated with hypospadias – Chordee without hypospadias often can be
r Chromosomal abnormalities found in 22% of the individual with a suspected syndrome or corrected by penile degloving with excision of the
disorder of sexual differentiation fibrous tissue superficial to Buck fascia.
individuals with severe hypospadias associated with
undescended testicles Imaging – More moderate chordee requires simple plication
r 14% of hypospadias in siblings r Renal and bladder ultrasound routinely and/or excision of ellipses from the site of
r 8% incidence in offspring recommended only in individuals with: maximum curvature.
– Severe hypospadias – In the most severe cases, often associated with
PATHOPHYSIOLOGY – Hypospadias associated with other organ system hypospadias the urethra may be foreshortened
r Chordee could be considered an arrest of normal anomalies and need to be transected.
embryologic development
r Different proposed etiologies for chordee without Diagnostic Procedures/Surgery
r Intraoperative artificial erection test at the time of
hypospadias (2,4): repair
– Class I: Results when corpus spongiosum, dartos, – Infusion of injectable saline into the corpora with
and Buck fasciae are deficient over the involved a tourniquet at the base of the penis
portion of the urethra; urethra is just below the
skin, and the dense fibrous tissue beneath the
urethra is responsible for the chordee.
– Class II: Spongiosum is normal while the dartos
and Buck fasciae are dysgenetic.
– Class III: Only the dartos fascia is deficient.
– Class IV: Corporeal disproportion.
82
CHORDEE
– Chordee secondary to corporeal disproportion Patient Resources See Also (Topic, Algorithm, Media)
involves incising the tunica albuginea on the r http://men.webmd.com/guide/chordee-repair- r Chordee Image
ventral surface of the penis, transversely over the treatment r Disorders of Sexual Development (DSD)
point of maximal curvature; than covering the r http://www.mayoclinic.com/health/hypospadias/ r Epispadias
defect with either a free dermal, tunica vaginalis or DS00884 r Hypospadias
single ply small intestinal submucosal (SIS) graft.
– It is critical to identify and preserve the
neurovascular bundles during dissection and REFERENCES CODES
plication.
– Skin flaps may be required for penile skin 1. Kaplan GW, Lamm DL. Embyrogenesis of Chordee. C
coverage after correction of the chordee. J Urol. 1975;114:769–772. ICD9
2. Kramer S, Aydin G, Kelalis P. Chordee without r 607.89 Other specified disorders of penis
ADDITIONAL TREATMENT hypospadias in children. J Urol. 1982;128: r 752.61 Hypospadias
Radiation Therapy 559–561. r 752.63 Congenital chordee
N/A 3. Paulozzi LJ, Erickson JD, Jackson RJ. Hypospadias
Additional Therapies trends in two US surveillance systems. Pediatrics. ICD10
r N48.89 Other specified disorders of penis
N/A 1997;100:831–834.
r Q54.4 Congenital chordee
Complementary & Alternative 4. Devine CJ Jr., Horton CE. Chordee without
r Q54.9 Hypospadias, unspecified
hypospadias. J Urol. 1973;110:264–271.
Therapies
N/A 5. Vandersteen DR, Husmann DA. Late onset recurrent
penile chordee after successful correction at
hypospadias repair. J Urol. 1998;160:1131–1133.
CLINICAL/SURGICAL
ONGOING CARE PEARLS
PROGNOSIS r Chordee most commonly occurs with hypospadias.
r Excellent prognosis postoperatively with a low ADDITIONAL READING r Repair recommended after 6 mo of age.
complication rate Bologna RA, Noah TA, Nasrallah PF, et al. Chordee: r Consider ongoing monitoring after puberty.
r There may be progression of chordee after puberty Varied opinions and treatments as documented in a
(5)[C] survey of the American Academy of Pediatrics, Section
of Urology. Urology. 1999;53:608–612.
COMPLICATIONS
Recurrence of chordee
FOLLOW-UP
Patient Monitoring
r Postoperative checkup within several weeks after
surgery
r Consider follow-up after puberty
83
CHRONIC KIDNEY DISEASE, ADULT (RENAL FAILURE, CHRONIC)

PATHOPHYSIOLOGY r Hyperparathyroidism
BASICS r Heterogenous condition with various causes – Results from altered calcium and phosphorus
– Diabetic kidney disease metabolism
DESCRIPTION – Nondiabetic kidney disease r Anemia
r Defined as presence of kidney damage or impaired ◦ Glomerular disease r Proteinuria/albuminuria
GFR (<60 mL/min/1.73 m2 ) for >3 mo (1) ◦ Vascular diseases – Albuminuria indicates increased glomerular
– if less than 3 months considered acute kidney ◦ Tubulointerstitial disease permeability to macromolecules
injury (AKI) ◦ Cystic disease (polycystic kidney disease) – Albumin to creatinine ratio >30 mg/g indicates
– Irrespective of cause kidney damage defined as: – Transplant nephropathy increased risk of CKD progression, ESRD,
◦ Pathologic abnormalities ◦ Acute rejection cardiovascular and all cause mortality.
◦ Urinary, blood, or imaging abnormalities ◦ Chronic rejection r GFR
◦ Kidney transplantation ◦ Calcineurin toxicity
r Classification based on Kidney Disease Outcomes – Estimated GFR (mL/min/1.73 m2 ) = 1.86 ×
◦ Glomerulonephropathy (SCR)−1.154 × (age)−0.203 × (0.742 if female) ×
Quality Initiative (NKF KDOQI): (1.1212 if African American)
– Stage 1: Kidney damage with normal renal
See risk factors Imaging
function (GFR >90 mL/min/1.73 m2 ) r Broad range of findings depending on etiology and
– Stage 2: Mild renal dysfunction GENERAL PREVENTION
(GFR 60–89 mL/min/1.73 m2 ) r Screening and treatment of associated risk factors imaging modality (US, CT scan, MRI, angiography,
– Stage 3: Moderate renal dysfunction – Screening selected populations: isotope scans)
(GFR 30–59 mL/min/1.73 m2 ) ◦ Age >50 – Hydronephrosis: Potentially reversible
– Stage 4: Severe renal dysfunction ◦ History of DM (diabetes melitus), HTN – Polycystic kidneys
(GFR 15–30 mL/min/1.73 m2 ) (hypertension), or CV (cardiovascular) disease – Atrophic kidneys
– Stage 5: Kidney failure (GFR <15 or dialysis ◦ Family history – Increased echogenicity (on ultrasound)
mL/min/1.73 m2 ) ◦ Exposure to nephrotoxins – Renal artery stenosis
– Cortical scarring
EPIDEMIOLOGY
Incidence DIAGNOSIS r Renal biopsy is indicated in selected cases and
r Stage 1 or 2 CKD progress to more advanced stages
HISTORY choices can vary greatly with nephrologists
at 0.5% per year
r Stage 3 or 4 progress to end-stage renal disease at r Silent, asymptomatic until late stages – Isolated glomerular hematuria with proteinuria
– Evaluate for symptoms of associated – Nephrotic syndrome
1.5% per year (3) – Acute nephritic syndrome
conditions/risk factors
Prevalence r Symptoms of uremia in ESRD – Acute/rapidly progressive kidney disease
r 10% in noninstitutionalized adults r Urologic evaluation if gross or microscopic
– Anorexia
– Corresponds to >20 million people (4) – Decreased urine output hematuria
– 398,000 treated by dialysis in 2000, expected to – Increased thirst – Cystoscopy
increase to >2 million people by 2030 (2) – Mental status changes – Upper tract imaging
– Prevalence in US population r Angiography (CT or MR angiogram) if suspected
– Muscle cramps
◦ Stage 1: 1.8% atherosclerotic renovascular disease (asymmetric
– Nausea
◦ Stage 2: 3.2% renal size)
– Vomiting
◦ Stage 3: 7.7%
◦ Stage 4/5: 0.35% (3) PHYSICAL EXAM Pathologic Findings
r Physical exam findings uncommon until late stages r Renal biopsy findings
RISK FACTORS of disease – Reveals tubulointerstitial, glomerular, or vascular
r Diabetes disease
r Hypertension – Findings associated with increased risk
◦ BP >130/85 – May also be seen on nephrectomy/partial
r Cardiovascular disease ◦ Obesity/increased waist circumference nephrectomy specimens
r Family history – Manifestations of advanced kidney disease DIFFERENTIAL DIAGNOSIS
r Age >60 ◦ Volume overload/edema r Kidney damage with duration >3 mo is diagnostic
r Urinary tract obstruction ◦ Pruritus regardless of cause
r Urinary calculi ◦ Visual disturbances r Differentiate from acute kidney disease based on
r Nephrotoxic drugs ◦ Weight Loss duration and underlying etiology
r Obesity ◦ Confusion – Acute kidney injury
r Neoplasia DIAGNOSTIC TESTS & INTERPRETATION – Alport syndrome
r Loss of kidney mass Lab – Autosomal dominant polycystic kidney disease.
r Race r Chemistry – Chronic glomerulonephritis
– Elevated creatinine – Diabetic nephropathy
– African American, American Indian, Hispanic, – Goodpasture syndrome
Asian, or Pacific Islander – Elevated blood urea nitrogen
– Hyperkalemia – Multiple myeloma
Genetics – Acidosis – Nephrolithiasis
r Complex phenotype impacted by various genetic – Nephrosclerosis
– Hyperphosphatemia
factors in addition to environmental factors and r Urinalysis with microscopy – Rapidly progressive glomerulonephritis
comorbid disease – Renal artery stenosis
– CYP4A11 gene involved in renal vasoconstriction – Hematuria
– Systemic lupus erythematosus
and natriuresis and is associated with increased – Casts: RBC (glomerulonephritis), WBC (interstitial
– Urinary obstruction
risk in African Americans (6) nephritis)
– Wegener granulomatosis
– APOL1 associated with focal segmental – Fat bodies (nephrotic syndrome)
glomerulosclerosis and hypertension associated
ESRD (7)
84
CHRONIC KIDNEY DISEASE, ADULT (RENAL FAILURE, CHRONIC)
4. Coresh J, Astor BC, Greene T, et al. Prevalence of

TREATMENT ONGOING CARE chronic kidney disease and decreased kidney
function in the adult US population: Third National
GENERAL MEASURES PROGNOSIS Health and Nutrition Examination Survey. Am J
r Use CKD staging to guide management (ie, risk for r Variable depending on stage, patient risk factors,
Kidney Dis. 2003;41:1–12.
progression and complications of CKD). See table in and management of comorbidities 5. Chan M, Dall AT, Fletcher KE, et al. Outcomes in
Section II “Chronic Kidney Disease (CKD).” – 10–100 × increased risk of cardiovascular patients with chronic kidney disease referred late to
r Goal is reduction of morbidity and mortality from comorbidities in ESRD patients nephrologists: A meta-analysis. Am J Med.
associated comorbidities – 13–29% 1-yr mortality in patients initiating 2007;120:1063–1070.
– Patient more likely to die of cardiovascular disease hemodialysis (5) 6. Keene KL, Mychaleckyj JC, Leak TS, et al. C
than progress to dialysis (3) COMPLICATIONS Exploration of the utility of ancestry informative
– Blood glucose control (HbA1c <7) r CKD patients at increased risk of progression, markers for genetic association studies of African
– Treatment of proteinuria and hypertension cardiovascular disease, hypertension, anemia, Americans with type 2 diabetes and end stage
– Treatment of dyslipidemia to prevent disorders of mineral metabolism, and death renal disease. Hum Genet. 2008;124:147–154.
cardiovascular events r Degree of proteinuria correlates with risk of 7. Hsu CC, Kao WH, Coresh J, et al. Apolipoprotein E
– Addressing alterations in bone metabolism progression and progression of chronic kidney disease. JAMA.
(hyperphosphatemia, Vitamin D deficiency) 2005;293:2892–2899.
– Prevention of contrast-induced nephropathy FOLLOW-UP
(patient at risk if GFR <60) Patient Monitoring
– Avoidance of Gadolinium when GFR <30 to r Stage 1-2
ADDITIONAL READING
prevent nephrogenic systemic fibrosis – Monitor GFR, proteinuria, and blood pressure
◦ Clinical abnormalities rare at this stage but KDIGO. Summary of recommendation statements.
MEDICATION Kidney Int. 2013;3(suppl):5.
patients must be monitored for progression
First Line ◦ Monitor HbA1c and microalbumin in diabetics
r ACE inhibitors (ACE-I) (captopril, enalapril, ramipril, See Also (Topic, Algorithm, Media)
◦ Evaluation every 12 mo, at least every 6 mo if r Acute Kidney Injury, Adult (Renal Failure, Acute)
others) or angiotensin II receptor blockers (ARBs) proteinuria present
(losartan, olmesartan, telmisartan others) r Chronic Kidney Disease, Pediatric (Renal Failure,
r Stage 3
– Indicated with random protein to creatinine ratio Chronic)
– Monitor GFR, proteinuria, blood pressure, HbA1c, r See Table in Section II “Chronic Kidney Disease
>200 mg/G serum electrolytes, and hemoglobin
– Do not use ACE-I and Angiotensin II receptor ◦ Elevations of phosphorous, potassium, and (CKD).”
blockers (ARBs) concurrently: Risk of hypotension anemia may be seen
and worsening renal function ◦ Evaluation every 3 mo
– Monitor for hypotension, hypokalemia, or ◦ Referral to nephrology when GFR approaches CODES
worsening renal function 30 mL/min
– Common ACE-I side effects include cough, r Stage 4 ICD9
angioedema, or allergy r 585.5 Chronic kidney disease, Stage V
r Statin therapy – Monitor GFR, proteinuria, blood pressure, HbA1c,
serum electrolytes, and hemoglobin r 585.6 End stage renal disease
– Goal LDL (low density lipids) <100 and ◦ Significant electrolyte abnormalities common; r 585.9 Chronic kidney disease, unspecified
triglyceride <150 monthly follow-up with nephrology
– Side effects include myalgia, liver dysfunction, GI r Stage 5 ICD10
disturbance, and rash r N18.5 Chronic kidney disease, stage 5
– Severe electrolyte abnormalities and anemia r N18.6 End stage renal disease
Second Line present: Ongoing follow-up with renal
r Erythropoiesis-stimulating agents r N18.9 Chronic kidney disease, unspecified
replacement therapy
– Optimal hemoglobin unknown
– Increased risk of cardiovascular events and death
Patient Resources
r National Kidney Foundation
with hemoglobin >11 g/dL CLINICAL/SURGICAL
– www.kidney.org/patients
– Indicated to prevent transfusion-related risks PEARLS
(patient with Hg <10 and rate of decline
r Degree of proteinuria predicts progression.
suggesting need for blood transfusion) REFERENCES
◦ Examples include erythropoietin α and r Differentiate from acute renal failure based on
darbepoetin α 1. National Kidney Foundation: K/DOQI clinical duration.
practice guidelines for chronic kidney disease: r Treat potentially reversible causes
r Dialysis access as appropriate (vascular or Evaluation, classification, and stratification. Am J (ie, hydronephrosis).
peritoneal) Kidney Dis. 2002;39:S1–S266.
r Renal transplantation 2. Coresh J, Byrd-Holt D, Astor BC, et al. Chronic
kidney disease awareness, prevalence, and trends
ADDITIONAL TREATMENT among U.S. adults, 1999 to 2000. J Am Soc
Radiation Therapy Nephrol. 2005;16:180–188.
N/A 3. Stevens LA, Li S, Wang C, et al. Prevalence of CKD
Additional Therapies and comorbid illness in elderly patients in the
r Dietary modifications United States: Results from the Kidney Early
r Patient education Evaluation Program (KEEP). Am J Kidney Dis.
r Smoking cessation 2010;55(3 suppl 2):S23–S33.
r Weight loss
Therapies
Avoidance of herbal remedies which may have
nephrotoxic effects.
85
CHRONIC KIDNEY DISEASE, PEDIATRIC (RENAL FAILURE, CHRONIC)

Timothy E. Bunchman, MD
Megan M. Lo, MD

BASICS r In interstitial renal disease, the degree of CKD is
Lab
related to the amount of renal mass. In those r Basic metabolic panel, renal function testing
DESCRIPTION patients who were born with small kidneys or have r Regardless of the etiology of CKD, at levels of CKD 3
r National Kidney Foundation (NKF) defines chronic associated obstructive uropathy (PUV, EBS, or greater (roughly 50% kidney function), one can
kidney disease (CKD) as evidence of structural or megaureter syndrome) often will have early have:
functional kidney abnormalities (abnormal progressive loss of renal function. – Metabolic acidosis (low CO2 )
urinalysis, imaging studies, or histology) that persist r Glomerular-based renal disease is more common in
– Abnormal parathyroid activity
for at least 3 mo, with or without a decreased the school age and greater population. ◦ Low calcium, elevated phosphorus, and elevated
glomerular filtration rate (GFR), as defined by a GFR – The clinical presentation of glomerulonephritis is PTH
of <60 mL/min per 1.73 m2 (1) associated with edema, hypertension, as well as – Anemia that is usually related to a combination of
– This definition is not applicable to children younger blood and protein in the urine; most need a renal iron deficiency, as well as the lack of natural
than 2 yr, because they normally have a low GFR, biopsy. erythropoiesis.
even when corrected for body surface area r C3 C4 complement
r CKD in pediatrics ASSOCIATED CONDITIONS
r Hearing loss – Decreased in some glomerulonephritis and lupus
– 70% tubular interstitial disease (TID) r Short stature nephritis
– 30% chronic glomerular disease (CGD). r Urinalysis:
r CKD in children is often related to congenital GENERAL PREVENTION
r In CKD associated with congenital renal disease – In TID, the urine is usually benign with inability to
abnormalities. The presentation often can be silent concentrate the urine regardless of the time of day.
or associated with: Polyuria and polydipsia and there is no true prevention. – In CGD, often these patients can have blood and
failure to grow. r Often the use of prenatal ultrasounds can identify
r TID is often congenital and associated with different protein and red cell casts.
infants at risk but they are not 100% diagnostic. r Urine protein: Creatinine ratio, rarely 24-hr urine for
syndromes: Posterior urethral valves (PUVs), – Serial ultrasounds over time may identify lack of protein.
Eagle-Barrett syndrome (EBS), and renal dysplasia interstitial renal disease, primarily looking for
(most genetic syndromes are associated with renal growth. Imaging
r In TID the renal imaging is important.
dysplasia). – Further, a low level of amniotic fluid at the time of
r CGD is often associated with hypertension, birth also correlates with poor renal function. – Often these patients can have normal to small
hematuria, proteinuria, and edema. r Prevention from a glomerular-based renal disease is looking kidneys seen on ultrasound. The
r The peak age of the diagnoses of end-stage renal echogenic texture will be important. Further, some
limited as these are usually related to autoimmune
degree of obstructive uropathy may be seen.
disease is about 5 yr of age. The second age of diseases. Therefore, the general prevention in all
– Voiding cystourethrogram may be indicated
presentation of loss of kidney function is around the areas of CKD is prevention of complications of CKD.
– In those patients who have obstructive uropathy,
age of puberty.
either at a UPJ or UVJ, a diuretic renal scan or
EPIDEMIOLOGY DIAGNOSIS MAG3 scan may be important.
Incidence r In CGD, renal imaging may show nephromegaly.
10–15 cases per million per year r In glomerular-based renal disease the history is Otherwise, ultrasound will be nonspecific.
Prevalence associated with grossly bloody urine, hematuria, Diagnostic Procedures/Surgery
50–100 per million per year proteinuria, hypertension, and edema. Tissue r In glomerular-based renal diseases renal biopsy is
pathology is generally needed for diagnosis. often required.
RISK FACTORS r In the review of systems, the findings of polyuria, r Indication for biopsy in patients with CGD is: A
r Primary risk factor for dysplasia is associated
polydipsia, and exclusion of diabetes is important. normal complementemic glomerulonephritis or a
congenital diseases and/or syndromes. These children also can have associated growth
r Familial renal disease; may present at any age persistent low C3, and a low C4.
impairment. r Other indications: Glomerulonephritis associated
– Alport syndrome r Family history is important in certain renal disease,
– Benign familial hematuria with an elevated anti-dsDNA (lupus), hemoptysis
specifically in the area of the familial renal disease with associated renal glomerulonephritis
– IgA nephropathy such as IgA nephropathy, Alport, polycystic kidney
– Polycystic kidney disease (pulmonary, renal disease), and in patients with
disease, and rarely benign familial hematuria. persistent low C3 without normalization after 12 wk,
r Higher in males, African Americans – In addition, eliciting a history of reflux which excludes postinfectious glomerulonephritis
Genetics nephropathy, recurrent urinary tract infections, (historically poststreptococcal glomerulonephritis).
Diverse based upon cause. For example, mutations in and congenital renal abnormalities within the
family is important. Pathologic Findings
HNF1B are causative for cystic dysplasia of the kidney. r Histologic analysis in interstitial renal disease is not
– Further a family history of dialysis or
transplantation or unexplained hypertension essential.
earlier in life may be important. r In glomerular-based renal diseases, renal biopsy is
r In the classic Alport syndrome (a male predominant often required.
disease) there is an association with high-frequency r Depending on underlying cause, the pathologic
hearing loss, often in the 2nd or 3rd decade of life. findings are vastly different on H&E,
immunofluorescence, and electron microscopy.
PHYSICAL EXAM
r Often these children have a benign exam
– In TID, the blood pressure and poor growth are
important.
– In CGD, kids often have hypertension.
– Can have associated edema, ascites, and
cardiovascular abnormalities.
86
CHRONIC KIDNEY DISEASE, PEDIATRIC (RENAL FAILURE, CHRONIC)
r As mentioned for TID, polyuria, polydipsia can also
Radiation Therapy
be associated with diabetes, which is an easy N/A 1. National Kidney Foundation. K/DOQI clinical
diagnosis to exclude based on urinalysis and blood practice guidelines for chronic kidney disease:
work. Additional Therapies Evaluation, classification, and stratification. Am J
r Differential diagnosis of CKD is limited to underlying Dialysis (peritoneal or hemodialysis) or kidney Kidney Dis. 2002;39:S1–S266.
transplant should be considered when GFR falls into
disease 2. Wesseling-Perry K. Bone disease in pediatric
the 20’s or growth and metabolic control can no
– Congenital renal anomalies: Obstructive uropathy, chronic kidney disease. Pediatr Nephrol.
longer be maintained with medical management.
renal hypoplasia or dysplasia, reflux nephropathy, 2013;28:569–576.
polycystic kidney disease Complementary & Alternative C
– Glomerular disease: Focal segmental Therapies
glomerulosclerosis (FSGS). r Nutrition is important: At least 2 g/kg/d protein ADDITIONAL READING
– Others: Hemolytic uremic syndrome, genetic would be needed in order to maintain adequate
r Avner ED, Harmon WE, Niaudet P, et al., eds.,
diseases (cystinosis, oxalosis, Alport syndrome), protein stores and growth.
interstitial nephritis r Nutrition in CGD is associated with salt and water Pediatric Nephrology. 6th ed. Springer; 2009.
r Geary DF, Schaefer F, eds. Comprehensive Pediatric
– Rare in childhood: Diabetic nephropathy and restriction. Therefore, the nutrition construction may
hypertension be opposite in terms of the sodium and water load. Nephrology. 1st ed. Mosby; 2008.
r Acute Kidney Injury, Pediatric (Renal Failure, Acute)
TREATMENT ONGOING CARE r Megaureter, Congenital
GENERAL MEASURES PROGNOSIS r Posterior Urethral Valves
r In chronic interstitial renal disease with r Difficult to predict early in life. r Prune Belly (Eagle-Barrett or Triad) Syndrome
polyuria/polydipsia, more fluid and sodium are r Lack of renal growth with a creatinine greater than 1
needed to maintain euvolemia. at a year of age, associated hematuria, proteinuria,
r In both groups, attention to potassium and and hypertension in patients with TID portends the CODES
phosphorus load is important. need for future dialysis and transplantation.
r All NSAIDS should be avoided. Levels of potential r CGD prognosis is directly related to underlying
ICD9
nephrotoxins, if measurable such as vancomycin or cause. r 582.89 Chronic glomerulonephritis with other
gentamicin, should be followed at least twice r Certain diseases such as lupus, Wegener,
specified pathological lesion in kidney
weekly; with an initial level no later than 24–48 hr Goodpasture, membranous nephropathy, and IgA r 585.9 Chronic kidney disease, unspecified
after starting. nephropathy can be amenable to therapy. r 753.8 Other specified anomalies of bladder and
r Damage from CT contrast should be minimized with r Other renal diseases such as focal sclerosis maybe
urethra
pre- and postprocedure IV hydration. less amenable to therapy.
COMPLICATIONS ICD10
MEDICATION r N03.9 Chronic nephritic syndrome with unsp
r Growth impairment in children is a known
First Line morphologic changes
r Treatment of metabolic acidosis with either liquid complication, independent of the etiology of CKD (2) r N18.9 Chronic kidney disease, unspecified
form of Bicitra or the pill form of bicarbonate to r Hypertension is also a risk factor.
r Q64.79 Other congenital malformations of bladder
normalize the CO2 . This will preserve growth as well r Protein restriction, used in adult CKD to slow disease
as bone integrity. and urethra
progression, cannot be used with kids as this would
r Treatment of phosphorus restriction, phosphorus further hinder their growth and development.
binding (nonaluminum binders such as CaCO3 , FOLLOW-UP CLINICAL/SURGICAL
Calcium acetate, or sevelamer products), and r Newborns and infants should be seen as frequently PEARLS
institution of vitamin D to preserve and prevent as every 1–2 wk in order to ensure maintenance of
secondary hyperparathyroidism and prevent bone r Patients with interstitial disease or obstructive
euvolemia.
disease. r Primary care physicians need to be instructed that uropathy require IV hydration while NPO prior to
r Treatment with replacement doses of iron sucrose procedures.
patients with interstitial disease will get dehydrated r In contrast to adults, diabetic nephropathy and
1–3 mg/kg per dose and use of erythropoietic more quickly than the average patient; therefore,
agents (epoetin, darbepoetin) are used for anemia. attention to their care at the time of vomiting and hypertension are rare causes of CKD in children.
r Small changes in creatinine reflect large changes in
Second Line diarrhea is important for these patients will become
r Those that were mentioned above including volume depleted in a hurry. GFR for children with CKD.
antihypertensive agents if indicated. r Baseline creatinine with attention to any changes
r Often ACE inhibitors and angiotensin receptor Patient Monitoring
after potential renal insult (CT contrast,
Glomerular-based renal diseases are associated with
blockers (ARBS) are used for glomerular-based renal hypovolemia/hypertension, medications, etc.) is an
salt and water restriction as well as blood pressure
disease because of proteinuria but are important measure for monitoring and prevention of
control.
contraindicated in possible pregnancy (birth defects) progression of CKD.
and low GFR (renal failure, hyperkalemia) Patient Resources
r American Society of Pediatric Nephrology.
SURGERY/OTHER PROCEDURES www.aspneph.com/parentpatient.asp
In TID, patients may require cystoscopy with ablation r National Kidney Disease Educational Program.
of PUVs. UPJ or UVJ obstructions may need to be www.nkdep.nih.gov
relieved. Reflux may need to be corrected, if high r NKF Cares: Patient Information Center.
grade and not resolving spontaneously. www.kidney.org/patients
87
CHYLOUS ASCITES
Brett S. Carver, MD
ASSOCIATED CONDITIONS Imaging

BASICS r Testicular cancer r CT scan of the abdomen and pelvis is the imaging
r Peritonitis modality of choice to evaluate for the presence of
DESCRIPTION r Ileus or small-bowel obstruction ascites and rule out retroperitoneal recurrent
r Chylous ascites is characterized by the accumulation r Failure to thrive disease.
of chyle in the peritoneal cavity. r Abdominal ultrasonography may be used to
r Results from the obstruction or injury of the thoracic GENERAL PREVENTION document ascites and guide aspiration.
r Appropriate ligation of lymphatic vessels during
duct or cisterna chyli of the lymphatic system.
r Lymphatic leakage from the lymph vessels draining surgery to minimize lymphatic leak. Diagnostic Procedures/Surgery
r Preservation of the thoracic duct. Abdominal paracentesis is performed to aspirate the
the intestines. ascites for diagnostic testing.
r Characterized as a milky fluid due to the high r Oral diet with low lipid, high medium-chain
triglyceride component. triglyceride content. Pathologic Findings
r This section focuses primarily on chylous ascites Chylous ascites is grossly defined as a milky white
fluid. Lab testing will reveal elevated triglyceride
associated with retroperitoneal lymph node
dissection (RPLND) for testicular cancer
DIAGNOSIS content.
EPIDEMIOLOGY HISTORY DIFFERENTIAL DIAGNOSIS

r Patients often present following RPLND with r Chylous ascites can be caused by other conditions
Incidence beyond RPLND for testicular cancer:
symptoms of abdominal distention and pain,
Chylous ascites is reported to occur in ∼1% of – Postoperative
decreased appetite, nausea, and vomiting.
patients undergoing a primary RPLND for testicular r Shortness of breath may also be present associated ◦ Abdominal aneurysm repair
cancer and 3% of postchemotherapy RPLNDs. ◦ Peritoneal dialysis catheter placement
with increased abdominal pressures.
Prevalence r Secondary infection associated with peritonitis with – Infectious/inflammatory
N/A ◦ Pancreatitis
symptoms of fever, chills, abdominal pain, and
◦ Retroperitoneal radiation
RISK FACTORS lethargy.
r Predisposing factors for chylous ascites associated ◦ Pericarditis
PHYSICAL EXAM ◦ Celiac disease
with RPLND: The most common finding on physical exam is ◦ Retroperitoneal fibrosis
– Surgical resection of the vena cava. distension of the abdomen with flank bulging. The ◦ Sarcoid
– Suprahilar dissection. abdomen is dull to percussion and may demonstrate a ◦ TB
– Simultaneous hepatic resection. fluid wave upon palpation. ◦ Filariasis
– In addition, patients undergoing reoperative ◦ Mycobacterium avium-intracellulare (AIDS
RPLND are at an increased risk. DIAGNOSTIC TESTS & INTERPRETATION
related)
Genetics Lab – Neoplasm
r Serum tumor markers (AFP, HCG, LDH) should be
N/A ◦ Lymphoma
obtained to rule out recurrence. ◦ Kaposi sarcoma
PATHOPHYSIOLOGY (1) r Aspiration of the abdominal fluid reveals a milky
r Chylous ascites is caused by injury or obstruction of ◦ Other solid tumors
white fluid, which should be sent for triglyceride – Other causes
the thoracic duct or cisterna chyli. testing and culture to rule out a secondary
r Surgical injury, ligation of the thoracic duct. ◦ Cirrhosis
infection. ◦ Carcinoid
r Retroperitoneal tumor associated with obstruction – A fluid triglyceride level >110 mg/dL is diagnostic. ◦ Nephrotic syndrome
of the thoracic duct. ◦ Trauma
r Leakage of fat containing lymphatic fluid into the
◦ Right-sided heart failure
peritoneum. ◦ Dilated cardiomyopathy
◦ Idiopathic
◦ Congenital causes (defects of lacteal formation)
88
CHYLOUS ASCITES
ADDITIONAL READING
TREATMENT ONGOING CARE r Bosl GJ, Feldman DR, Bajorin DF, et al. Cancer of the
GENERAL MEASURES PROGNOSIS testis. In: DeVita VT, Hellman S, Rosenberg SA, eds.
r All patients with abdominal distention following an The prognosis is excellent for the vast majority of cases Cancer: Principles and Practice of Oncology. 9th ed.
RPLND should be evaluated for: as most will respond to conservative management. Philadelphia, Pa: Lippincott Williams & Wilkins;
– Ascites (nonchylous) COMPLICATIONS 2011:1280–1301.
– Ileus r The complications of chylous ascites related to r Evans JG, Spiess PE, Kamat AM, et al. Chylous
– Small-bowel obstruction
– Recurrent disease in the abdomen or
increased abdominal pressure:
– Renal failure
ascites after post-chemotherapy retroperitoneal
lymph node dissection: Review of the M. D.
C
retroperitoneum. – Venous thrombosis Anderson experience. J Urol. 2006;176(4 Pt 1):
r The majority of chylous effusions will heal 1463–1467.
– Pulmonary embolism
spontaneously. Abdominal paracentesis is diagnostic r Link RE, Amin N, Kavoussi LR. Chylous ascites
– Atelectasis
and often therapeutic in relieving symptoms – Pneumonia following retroperitoneal lymphadenectomy for
associated with increased abdominal pressures. r The gastrointestinal complications of chylous ascites testes cancer. Nat Clin Pract Urol. 2006;
include ileus and small-bowel obstruction. 3(4):226–232.
MEDICATION
First Line – Malnourishment and failure to thrive may also See Also (Topic, Algorithm, Media)
r Low lipid, high medium chain triglyceride oral diet. occur due to protein-losing enteropathy with r Chylous Ascites Image
– MCT oil supplement chronic diarrhea (steatorrhea), malabsorption, and r Lymphatic Ascites
◦ 1 tablespoon (15 mL) 3–4 times/d malnutrition r Testis Cancer, Adult General Considerations
◦ Mix with juices or otherwise incorporated into FOLLOW-UP
low-fat diet Patient Monitoring
◦ Do not use in patients with advanced cirrhosis: r Follow-up protocols should be followed according to CODES
Risk of narcosis and coma guidelines established by the National
r Somatostatin analogs have been demonstrated to
Comprehensive Cancer Network for testicular cancer ICD9
be effective in reducing lymphorrhagia. patients. r 125.9 Unspecified filariasis
– Octreotide 100 mcg administered subcutaneously r After initial treatment of chylous ascites, patients r 457.8 Other noninfectious disorders of lymphatic
3 times per day should be seen in follow-up to monitor for recurrent channels
Second Line ascites.
r Total parental nutrition is to be utilized in patients ICD10
Patient Resources r B74.9 Filariasis, unspecified
who fail oral diet modifications. N/A r I89.8 Oth noninfective disorders of lymphatic vessels
– Bowel rest may enhance recovery if conservative
approaches are not successful and nodes
REFERENCES
r Abdominal paracentesis, repeated as necessary. CLINICAL/SURGICAL
1. Carver BS, Sheinfeld J. Germ cell tumors of the
– Primarily for pain control and dyspnea
r Surgical exploration with direct ligation of lymphatic
testis. Ann Surg Oncol. 2005;12(11):871–880. PEARLS
2. Castillo OA, Litvak JP, Kerkebe M, et al. Case r Chylous ascites occurs in ∼1–3% of patients
vessels for persistent chylous ascites (2). report: laparoscopic management of massive
r Peritoneal venous shunts for refractory chylous chylous ascites after salvage laparoscopic undergoing a RPLND.
r Risk factors include vena cava resection, suprahilar
ascites. retroperitoneal lymph-node dissection. J Endourol.
r Direct lymphatic vessel ligation or embolization of 2006;20(6):394–396. dissections, and concomitant hepatic surgery.
r Initial management includes paracentesis for
large leaking vessels using interventional radiologic 3. Chen J, Lin RK, Hassanein T. Use of orlistat (xenical)
techniques. to treat chylous ascites. J Clin Gastroenterol. symptom of pain or pulmonary compromise and low
2005;39(9):831–833. lipid, high medium-chain triglyceride oral diet.
Radiation Therapy
N/A
N/A
Therapies
Orlistat (Xenical) has been used successfully in a
nontesticular cancer case of chylous ascites (3)
89
CHYLURIA
Matthew A. Uhlman, MD, MBA
James A. Brown, MD, FACS
PATHOPHYSIOLOGY PHYSICAL EXAM

BASICS r Parasitic r Elephantiasis of lower limbs and genitals
– Adult filariasis causes lymphangitis r Lymphadenitis/lymphangitis
DESCRIPTION – Obstruction of suprarenal lymphatics (thoracic r Male groin exam may reveal hydrocele or
r Chyluria is the presence of chyle (a combination of duct or upper retroperitoneal lymph drainage) epididymitis
lymphatic fluid and triglycerides) in urine – Results in rupture of lymphatic vessel into calyceal r Palpable abdominal or flank mass
r Presents as milky white urine that can be constant fornix, forming intrarenal lymphatic urinary fistula r Chylous output from surgical wound or surgical drain
or present primarily after meals – Lymphatic HTN, with valvular incompetence:
r Often self-limiting or resolves with conservative ◦ With obstruction between intestinal lacteals and DIAGNOSTIC TESTS & INTERPRETATION
treatment including dietary changes thoracic duct, the resulting cavernous Lab
r Extended chyluria can lead to malnutrition, vitamin malformation opens into the urinary system, r Urinalysis typically positive for albuminuria
deficiencies, and immunosuppression (due to creating a fistula r Postprandial urinary triglycerides
depletion of fat soluble vitamins) (1)[C] ◦ Common fistula sites are renal fornix, r Fat globules in urine identified by Sudan III stain
pelvicalyceal system, trigone, and prostatic r Peripheral blood eosinophilia, may indicate parasitic
EPIDEMIOLOGY urethra
◦ Primary causal agents: W. bancrofti, B. malayi, infection
Incidence r Evaluate for TB if clinically indicated (tuberculin test,
r 2–10% of patients infected with filariasis can and B. timori
develop chyluria (2)[C] ◦ Less commonly caused by external compression urine stain, and culture for acid-fast bacillus)
r Extremely low rates of clinically significant chyluria r ICT antigen card test (immunochromatographic card
or trauma
(1)[C] r Nontropical test, a commercial assay) is widely used in the
– Clinically significant in <1% of postsurgical – Disruption of peripelvic lymphatics during surgery diagnosis of W. bancrofti
r WB rapid and panLF rapid (2 commercially available
patients allows backflow into pyelocaliceal system (1)[C]
– Congenital fistulous connections between urinary assays) tests detect W. bancrofti, B. malayi, and
– Reports of subclinical chyluria based on CT in B. timori
3–41% of postpartial nephrectomy or tract and lymphatic system have been described,
radiofrequency ablation (RFA) patients (2,3)[C][B] primarily in children Imaging
ASSOCIATED CONDITIONS r Abdominal/pelvic CT (3,4)[B]:
Prevalence
r 120 million people suffer from filariasis worldwide, W. bancrofti, B. malayi, and B. timori are considered – Exclude retroperitoneal mass
primarily in Asia, Africa, Pacific Islands, and South the three causative agents of lymphatic filariasis. – Fat fluid level seen in the urinary tract
America (2)[C] Mosquitos serve as vectors for all 3 nematodes (2)[C] – Can demonstrate contrast communication
r Chyluria is a manifestation of chronic infection, most between collecting system and perinephric
GENERAL PREVENTION collection but does not show communications
often by Wuchereria Bancrofti, Brugia malayi, or r Control of mosquito vector that transmits
Brugia timori (2)[C] between perinephric collection and lymphatics
W. bancrofti, B. malayi, and B. timori (2)[C] r Lymphangiography (traditional or magnetic
r Rare in developed countries r Insect repellant and mosquito nets in endemic areas
r Nontropical chyluria most often caused by trauma, r Diethylcarbamazine (DEC) fortified salt resonance)
renal surgery, infection, mass effect (AAA, tumor, r Annual DEC + albendazole are used to treat – Demonstrates abnormal lymphatics and entrance
abscess), pregnancy, or congenital abnormality of contrast material into renal collecting system
asymptomatic filariasis via action on microfilaria r Lymphoscintigraphy
(1)[C]
– Can be useful in delineating site of fistula, though
RISK FACTORS
r Parasitic chyluria DIAGNOSIS not as precise as lymphangiography
r Retrograde pyelography
– W. bancrofti, B. malayi, and B. timori are primary HISTORY – Rarely warranted, but may show diffuse
causes of filariasis. All are transmitted by r Patient complaints of intermittent or continuous pyelolymphatic backflow
mosquito. Less common parasitic infections have milky or cloudy urine
been reported to cause chyluria (echinococcus, Diagnostic Procedures/Surgery
– If intermittent, most often occurs following meals r Blood smear: Examine for microfilariae (early stage
bilharzias, onchocerca, ascariasis) (1,2)[C] r Country of origin of patient:
r Nontropical chyluria in life cycle of nematodes) using Giemsa stain
– Asia, Africa, Pacific Islands, South America r Cystourethroscopy: Can help localize site of milky
– Retroperitoneal surgery (most often radical or r Travel to tropical regions
r History of trauma efflux of urine. Rarely, efflux seen from bladder or
partial nephrectomy, RFA, or renal tumors)
posterior urethra.
(1,3,4)[C][B] r History of renal surgery within prior 2 yr r Retrograde pyelography: Rarely warranted, but may
– Trauma r History of TB exposure/infection
show diffuse pyelolymphatic backflow
– Mass effect: Retroperitoneal tumors (primary or r Significant weight loss, anemia, lower urinary tract
metastatic) or lymphadenopathy symptoms (frequency, urgency, dysuria), hematuria,
– Infectious: TB, abscess nutritional deficiency, proteinuria, or signs of
– Aortic aneurysm immunosuppression
– Pregnancy r Heavy chyluria can cause clot colic or, rarely, urinary
– Congenital fistula or lymphangioma retention
90
CHYLURIA
Pathologic Findings ADDITIONAL TREATMENT 4. Kaur H, Matin SF, Javadi S, et al. Chyluria after
Lipid contents of chyluria are mainly chylomicrons, Radiation Therapy radiofrequency ablation of renal tumors. J Vasc
90% of which are in the form of triglycerides N/A Interv Radiol. 2011;22:924–927.
DIFFERENTIAL DIAGNOSIS 5. Zhang CJ, Chen RF, Zhu HT, et al.
r Filariasis from W. bancrofti, B. malayi, or B. timori r Sclerotherapy with various agents instilled into
Retroperitoneoscopic renal pedicle lymphatic
r Pyelolymphatic fistula disconnection for chyluria in presence of complex
collecting system (1,3)[C][B] renal vasculature. Urology. 2012;80:1273–1276.
r Phosphaturia, most common cause of cloudy urine
– Povidone iodine (5%) and dextrose (50%) in 6. Gomella LG, Shenot P, Abdel-Meguid TA.
r Pyuria renal pelvic instillation sclerotherapy; 87%
r Hyperuricosuria success reported
Extraperitoneal laparoscopic nephrolysis for the
treatment of chyluria. Br J Urol. 1998;81(2):
C
r Nephropathy—urinary sediment can cause cloudy – Silver nitrate (1–3%) instillation into the affected 320–321.
appearing urine collecting system causes sclerosis of lymphatic
r Enterovesical fistula fistulas; 48% success reported
– Case reports of successful sclerotherapy with: ADDITIONAL READING
◦ N-butyl-2-cyanoacrylate (component of medical
TREATMENT cyanoacrylate glues) Kaul A, Bhadhuria D, Bhat S, et al. Chyluria: A
◦ Radiographic contrast media mimicker of nephrotic syndrome. Ann Saudi Med.
GENERAL MEASURES 2012;32(6):593–595.
r Nontropical Complementary & Alternative
– Up to 50% of cases resolve spontaneously under Therapies See Also (Topic, Algorithm, Media)
dietary restriction (1)[C] N/A r Chyluria Image
– Bed rest and/or use of abdominal binder to r Filariasis, Urologic Considerations
increase abdominal pressure may allow r Urine, Abnormal Colored
ONGOING CARE
spontaneous closure.
– Medium-chain triglyceride (MCT) diet (avoidance PROGNOSIS
r Rarely fatal, with high success rates reported for
of long-chain triglycerides) CODES
◦ MCTs are transported via portal system, not by surgical intervention
chylomicrons through lymphatics r Recurrence rates after surgery reported as high as
ICD9
– Ureteral stent placement to reduce renal pelvis 25% r 125.0 Bancroftian filariasis
pressure r 125.9 Unspecified filariasis
COMPLICATIONS
MEDICATION r Hypoalbuminemia and anasarca from massive r 791.1 Chyluria
Nontropical protein loss (1)[C]
Dietary modifications to reduce chylomicrons in r Immunosuppression from fat soluble vitamin loss in ICD10
r B74.0 Filariasis due to Wuchereria bancrofti
diet—recommendations are often for fat-free or very chronic cases (1)[C]
r Underlying filariasis may cause epididymitis, r B74.9 Filariasis, unspecified
low-fat diet, though this should not be observed for
more than several weeks given the body’s need for r R82.0 Chyluria
hydrocele, and elephantiasis of the penis/scrotum
some fats and lower extremities
Parasitic Chyluria FOLLOW-UP CLINICAL/SURGICAL
r DEC and albendazole, or ivermectin and albendazole
r DEC fortified salt can be used to treat and prevent Patient Monitoring PEARLS
r Treatment failures are readily apparent as urine
lymphatic filariasis r Milky or cloudy urine (often after meals) is the most
returns to milky color (1,5)[C][A]
SURGERY/OTHER PROCEDURES common presentation, though phosphaturia is the
r Re-evaluate if chyluria recurs following treatment;
r Procedures of choice involve disconnection of renal most common cause of cloudy urine.
consider the contralateral kidney as the source r W. bancrofti, B. malayi, and B. timori are the
pedicle lymphatics (1,5,6)[C][A]
Patient Resources primary causes of filariasis, the most common cause
r Nephrolysis:
N/A of chyluria (parasitic chyluria).
– Stripping and ligation of all lymphatic vessels to r Following renal surgery, incidence of chyluria (up to
the kidney and upper ureter; open and 41% on CT) is likely much higher than is clinically
laparoscopic techniques described REFERENCES significant (<<1%).
– Laparoscopic transabdominal and r Up to 50% of cases of chyluria resolve
retroperitoneoscopic approaches described 1. Kim RJ, Joudi FN. Chyluria after partial
nephrectomy: Case report and review of the spontaneously with a medium chain fatty acid or
– Success rates 80–98%; recurrence rates 3–25% very low-fat diet.
r Endoscopic coagulation of fistula literature. ScientificWorldJournal. 2009;9:1–4.
r There is no “best” imaging technique, though
r Lymphangiovenous anastomosis with ligation of 2. Tandon V, Singh H, Dwivedi US, et al. Filarial
chyluria: Long-term experience of a university lymphangiography can demonstrate entrance of
renal lymphatics contrast from lymphatics into the collecting system.
r Renal autotransplantation hospital in India. Int J Urol. 2004;11:193–199.
r Nephrectomy was described prior to minimally 3. Panchal VJ, Chen R, Ghahremani GG. Non-tropical
chyluria: CT diagnosis. Abdom Imaging. 2012;
invasive techniques 37(3):494–500.
91
CIRCUMCISION, ADULT CONSIDERATIONS

Irvin H. Hirsch, MD

BASICS r Diabetes mellitus
Lab
r Balanitis r UA
DESCRIPTION r Lichen sclerosus/urethral stricture r Urine culture if indicated
r Circumcision involves the removal of the prepuce. r Penile condylomata r STD testing if indicated
This section addresses adult circumcision issues. r Squamous cell carcinoma
r Adult circumcision is indicated for elective treatment Imaging
r Erectile dysfunction
of balanitis (glans inflammation), posthitis (prepuce N/A
r Peyronie disease
inflammation), removal of preputial lesions, and at Diagnostic Procedures/Surgery
patient request for cultural and religious preference. N/A
r Emergent circumcision may be necessary for ALERT
The American Urologic Association (AUA) policy Pathologic Findings
treatment of paraphimosis after failed attempt at r Acute and chronic inflammation
manual reduction. statement now considers circumcision to be of a
r Plasma cell infiltrate (Zoon balanitis)
r Circumcision may be necessary as part of surgical health benefit, citing a 50–60% risk reduction in
HIV transmission in some African nations. r Lichen sclerosus (BXO blanaitis xerotica obliterans)
procedures requiring degloving exposure of the
penis (penile fracture repair or Peyronie disease). DIFFERENTIAL DIAGNOSIS
r Circumcision is the most common operation GENERAL PREVENTION N/A
r Local hygiene measures may prevent balanitis and
performed worldwide.
r There is some controversy concerning the need for its sequelae.
circumcision and potential effects on sexual
r Although male circumcision should not be TREATMENT
satisfaction. This is weighed against the potential substituted for other HIV risk-reduction strategies, it
has been shown to reduce the risk for HIV and some GENERAL MEASURES
health benefits. Circumcision for balanitis in adults should be
STDs in heterosexual men.
EPIDEMIOLOGY – Despite these data, male circumcision has not performed after exhausting nonsurgical medical
been demonstrated to reduce the risk for HIV or approaches.
Incidence
N/A other STDs among men who have sex with men MEDICATION
(MSM). First Line
Prevalence r Good visualization of the glans penis is crucial in all
r Male circumcision, largely in newborns, is performed r Topical antibiotics
in 77% of US males and in 30% of males worldwide. cases of circumcision to limit complications. r Topical steroids
r Circumcision rate in newborns has declined from r Topical antifungals
83% in the 1960s to 77% in 2010. DIAGNOSIS Second Line
– These incidence rates do not include N/A
out-of-hospital circumcisions HISTORY
r Increasingly adult circumcision has been advocated r Penile pain with or without erection SURGERY/OTHER PROCEDURES
r Dyspareunia r General anesthesia may be utilized
as an important adjunct to STD and HIV prevention
r Postcoital pain r Local anesthesia is recommended when tolerated
in developing countries (1).
r Lidocaine/bupivacaine combination is injected at the
RISK FACTORS PHYSICAL EXAM level of the infrapubic bone and around the base of
r Diabetes mellitus r Inability to retract prepuce (phimosis)
r Genital lesions the penis. Avoid epinephrine.
r Inability to reduce prepuce (paraphimosis) r Technique is selected based on surgeon’s preference:
Genetics r Preputial erythema or excoriation
Sleeve technique or dorsal slit circumcision.
N/A r Glans erythema
r Malodorous secretion (smegma)
PATHOPHYSIOLOGY r Associated penile lesion
r The prepuce serves as a specialized, junctional
mucocutaneous tissue marking the boundary
between mucosa and skin; it is similar to the eyelids,
anus, and lips.
r Condition that can cause problems:
– Lack of genital hygiene
– Chronic balanoposthitis may lead to phimosis
92
CIRCUMCISION, ADULT CONSIDERATIONS
ADDITIONAL TREATMENT FOLLOW-UP See Also (Topic, Algorithm, Media)

r Circumcision, Pediatric Considerations
Radiation Therapy Patient Monitoring
N/A r Routine postoperative care. r Penis, Cysts
r Follow for alterations in penile sensation and r Phimosis and Paraphimosis
N/A erectile function.
Complementary & Alternative Patient Resources
www.aafp.org/afp/1999/0315/p1514/html CODES
Therapies
r For high risk or anticoagulated patients an isolated
dorsal slit may be oversewn without circumcision. REFERENCES
ICD9
r 605 Redundant prepuce and phimosis
C
r Nonsurgical preputial compression devices are
r 607.1 Balanoposthitis
currently under investigation for HPV, HSV, and HIV 1. World Health Organization, Department of
r V50.2 Routine or ritual circumcision
risk-reduction programs in developing countries Reproductive Health and Research and Joint United
(Prepex or Shang Ring). The prepuce sloughs after Nations Programme on HIV/AIDS (UNAIDS). Male
ICD10
7 days. circumcision: Global trends and determinants of r N47.2 Paraphimosis
prevalence, safety and acceptability WHO Press, r N48.1 Balanitis
2007. r Z41.2 Encounter for routine and ritual male
ONGOING CARE 2. Fink KS, Carson CC, DeVellis RF. Adult circumcision
outcomes study: Effect on erectile function, penile circumcision
PROGNOSIS
sensitivity, sexual activity and satisfaction. J Urol.
Patient satisfaction is high
2002;167(5):2113–2116. CLINICAL/SURGICAL
COMPLICATIONS (2)
r The majority of complications relating to PEARLS
circumcision are minor and should be easily treated ADDITIONAL READING r These measures reduce risk of neural injury:
r While very infrequent, challenging complications
r Cold CJ, Taylor JR. The prepuce. BJU Int. 1999; minimize use of electrocautery and limit excision
requiring complex reconstructive surgery and should superficial to Buck fascia.
be referred to a center specializing in these 83(suppl 1):34–44. r Assure hemostasis of frenular artery.
r Millett GA, Flores SA, Marks G, et al. Circumcision
reconstructions.
r Early status and risk of HIV and sexually transmitted
– Hematoma and bleeding infections among men who have sex with men: A
– Infection meta-analysis. JAMA. 2008;300:1674–1684.
r Summerton DJ, Kitrey ND, Lumen N, et al. EAU
– Urinary retention due to tight bandaging
– Glans necrosis guidelines on iatrogenic trauma. Eur Urol.
– Removal of inadequate or excessive skin 2012;62:628–639.
– Partial penile amputation r UNAIDS, WHO. New data on male circumcision and
r Late HIV prevention: Policy and programme implications:
– Urethral injury/urethrocutaneous fistula WHO/UNAIDS technical consultation male
– Meatal stenosis circumcision and HIV prevention: Research
– Hypesthesia or hyperesthesia of penis implications for policy and programming. Geneva:
– Penile scarring and deformity Joint United Nations Programme on HIV/AIDS and
◦ Skin bridges between the glans and penile shaft World Health Organization; 2007.
– Concealed/buried penis
– Inclusion cysts
– Erectile dysfunction
93
CIRCUMCISION, PEDIATRIC CONSIDERATIONS

Mary Ellen T. Dolat, MD
r Penile cancer (see “Circumcision, Adult PHYSICAL EXAM

BASICS Considerations”) r In newborns, perform a complete male genital exam
– The relationship among hygiene, phimosis, and – In rare instances, a well-formed phallic structure in
DESCRIPTION penile cancer is uncertain a baby with nonpalpable testes may be due to
r Circumcision is the surgical removal of the foreskin – In a Danish study of penile cancer, there was a congenital adrenal hyperplasia
(prepuce) from the penis. statistical decline in the rates of penile cancer over r Look for penile developmental variations that may
r One of the oldest surgical procedures a 50-yr period despite a national circumcision rate be a contraindication of a newborn circumcision (see
r One of the most commonly performed surgical of 1.6%. These data correlated with better penile “Differential Diagnosis”)
procedures in practice today hygiene resulting from improvements in sanitary r Some instances with newborns with incomplete
r There is some controversy concerning the need for conditions. foreskin development (ie, does not have natural
circumcision and potential effects on sexual – Based on the low incidence of penile cancer in phimosis), may still be amenable to a newborn
satisfaction in adulthood. This is weighed against Israel (high prevalence of circumcision) and in clamp circumcision
the potential health benefits. Scandinavian countries (low prevalence of – Recommend obtaining a pediatric urology
circumcision), 2 ways of preventing penile cancer: consultation to determine whether the baby
EPIDEMIOLOGY ◦ Remove the foreskin
r Few data are available to help estimate accurately would be a candidate for newborn circumcision
◦ Practice good penile hygiene
the number of newborns circumcised worldwide. r Sexually transmitted disease (refer to the Chapter, DIAGNOSTIC TESTS & INTERPRETATION
– Country of origin, ethnicity, religious affiliation, “Circumcision, Adult Considerations”) Lab
and birth in a rural vs. an urban hospital clearly Not necessary unless there is suspicion for intersex
influences a child’s likelihood of being circumcised. Genetics anomaly
– In addition, lack of (or the type of) health N/A
insurance may influence a child’s likelihood of
Imaging
PATHOPHYSIOLOGY Not necessary unless there is suspicion for intersex
being circumcised. r Prepuce serves as a specialized, junctional
r Most common reasons reported by US parents for anomaly
mucocutaneous tissue marking the boundary
choosing circumcision between mucosa and skin; it is similar to the eyelids, Diagnostic Procedures/Surgery
– Health/medical benefits including hygiene anus, and lips. Not necessary unless there is suspicion for intersex
(40–60%) r Most neonates have a physiologic phimosis anomaly
– Social concerns (23–37%) r During childhood, the growth of the penile body, Pathologic Findings
– Religious requirements (11–19%) accumulation of epithelial debris, and intermittent N/A
Incidence penile erections eventually separate the prepuce DIFFERENTIAL DIAGNOSIS
r Circumcision rate in newborns has declined from from the glans, permitting retraction r The penis should be carefully examined before the
83% in the 1960s to 77% in 2010. r During the 1st 6 mo of life, there are more
procedure to identify the following conditions that
– These incidence rates do not include uropathogenic organisms around the urethral may preclude a circumcision
out-of-hospital circumcisions meatus of an uncircumcised male infant than around – Webbed penis
Prevalence those of circumcised male infants; this colonization – Microphallus
r 79% of men surveyed reported being circumcised decreases in both groups after the 1st 6 mo (3) – Chordee
r Boys with vesicoureteral reflux who are – Epispadias
(range: 42% for Mexican American; 88% for
non-Hispanic Caucasian) (1) uncircumcised have a higher risk of UTI – Hypospadias
– Prevalence rates are limited by the accuracy of the ASSOCIATED CONDITIONS – Megameatus intact prepuce (MIP) variant of
self-report r Phimosis hypospadias
r Paraphimosis ◦ The foreskin is normally developed; the
RISK FACTORS abnormal urethra is noted after the foreskin has
r Urinary tract infection
GENERAL PREVENTION been pulled back (or after the neonatal
– An increased risk for UTI in uncircumcised males Gentle periodic retraction during the newborn period circumcision has already been performed)
younger than 1 yr; risk being the greatest toward will help prevent phimosis for the inability to retract
the 1st 6 mo foreskin later in life
– Given that the risk of UTI in infant males is ∼1%, TREATMENT
the number needed to circumcise to prevent UTI is
∼100 DIAGNOSIS
– The benefits of male circumcision are, therefore, ALERT
likely to be greater in boys at higher risk for UTI, HISTORY In cases of Disorders of Sexual Development (DSD)
r Prior history of posthitis or balanitis with sex assignment concerns or significant
such as infants with underlying anatomic defects
r Need for future circumcision r Prior history of meatitis anomaly such as hypospadius the infant should not
r Report of “ballooning” of the distal foreskin during undergo neonatal circumcision.
– Future medical complications for boys (and men)
who are uncircumcised as newborns include voiding
balanitis, severe phimosis, and paraphimosis. r Prior history of circumcision GENERAL MEASURES
– For parents, there exists ∼2–5% risk that their – Incomplete removal of foreskin r The AAP states that: The health benefits of newborn
sons will need a circumcision for a medical – Iatrogenic phimosis male circumcision outweigh the risks but the
indication if they choose not to circumcise their r Some parents report “infected whitish pus,” which scientific evidence is not strong enough for the AAP
sons as newborns (2) in most instances is due to normal secretion of to recommend routine circumcision of all newborns.
smegma The AAP advises parents to learn the facts about
circumcision and weigh the risks and benefits.
r Most routine circumcision is performed between 2
and 10 days of life.
94
CIRCUMCISION, PEDIATRIC CONSIDERATIONS
r Contraindications to newborn circumcision include:

REFERENCES
– Congenital penile anomalies (see “Differential ONGOING CARE
Diagnosis”) 1. Nelson CP, Dunn R, Wan J, et al. The increasing
– Significantly premature infants PROGNOSIS incidence of newborn circumcision: Data from the
– Blood dyscrasias Some groups believe that circumcision may reduce or nationwide inpatient sample. J Urol. 2005;173:
– Babies with a family history of bleeding disorders increase the sensitivity of the tip of the penis, 978–981.
– Disorders of Sexual Development (DSD) potentially impacting sexual pleasure later in life. The 2. Lerman SE, Liao JC. Neonatal circumcision. Pediatr
r Relative contraindications to newborn circumcision: data are conflicting and mostly these subjective Clin North Am. 2001;48:1539–1557.
findings are not conclusive.
– Incomplete foreskin development
– Prominent suprapubic fat pad (retrusive penis) COMPLICATIONS
3. American Academy of Pediatrics Task Force on
Circumcision. Circumcision policy statement.
C
r Large US hospital-based studies estimate the risk of Pediatrics. 2012;130(3):585–586.
MEDICATION
First Line a significant acute circumcision complication to be
r Analgesia is safe and effective in reducing the between 0.19–0.22%.
procedural pain associated with newborn
r From neonatal circumcisions using clamp techniques ADDITIONAL READING
circumcision – Gomco clamp r Cold CJ, Taylor JR. The prepuce. BJU Int. 1999;83
– Dorsal penile nerve block ◦ Mainly related to technical factors
◦ Insufficient or inadequate skin removal requiring suppl 1:34–44.
◦ 1% lidocaine without epinephrine r Perera CL, Bridgewater FH, Thavaneswaran P, et al.
– Subcutaneous ring block additional revision procedure
◦ Since the metal bell completely covers the glans, Safety and efficacy of nontherapeutic male
◦ 1% lidocaine without epinephrine circumcision: A systematic review. Ann Fam Med.
– Topical cream may cause a higher incidence of glans injury is extremely rare
– Plastibell 2010;8:64–72.
skin irritation in low–birth-weight infants r Weiss HA, Larke N, Halperin D, et al. Complications
◦ Lidocaine–prilocaine (2.5% lidocaine and 2.5% ◦ Incomplete circumcision
◦ Retained Plastibell ring of circumcision in male neonates, infants and
prilocaine) applied for 30–40 min children: A systematic review. BMC Urol. 2010;10:2.
– Mogen clamp
◦ Potential for injury to glans, including partial See Also (Topic, Algorithm, Media)
ALERT
amputation r Circumcision, Adult Considerations
Epinephrine should not be used for pediatric r Immediate complications r Circumcision, Pediatric Considerations Images
circumcsion.
– Significant bleeding (0.08–0.18%) r Disorders of Sexual Development (DSD)
Second Line ◦ Postcircumcision bleeding may be the 1st r Hypospadias
r Nonpharmacologic techniques (eg, sucrose pacifier) manifestation on an underlying bleeding
alone are insufficient to prevent pain and are not disorder
– Significant infection (0.06%)
recommended as the sole method of analgesia
– Significant penile injury (0.04%)
CODES
– Sucrose on a pacifier has been demonstrated to be
r Late complications
more effective than water alone for decreasing
– Phimosis (iatrogenic) ICD9
crying during circumcision (2)
– Adhesions V50.2 Routine or ritual circumcision
SURGERY/OTHER PROCEDURES – Skin bridges
r Common methods for the newborn circumcision ICD10
– Excess foreskin Z41.2 Encounter for routine and ritual male
– Gomco clamp – Insufficient penile skin circumcision
– Plastibell – Penile inclusion cysts
– Mogen clamp – Meatal stenosis
r After the newborn and infant periods, circumcision CLINICAL/SURGICAL
– Penile torsion
is performed under general anesthesia – Urethrocutaneous fistula PEARLS
ADDITIONAL TREATMENT FOLLOW-UP r Make sure to carefully inspect the penis for any
Radiation Therapy Patient Monitoring congenital defects such as hypospadias or chordee
N/A r A small amount of petroleum jelly may help with before proceeding with neonatal circumcision. It is
Additional Therapies discomfort due to diaper friction the 1st few days best to delay circumcision until the primary defect
N/A postop. can be repaired as the foreskin may be used in
r Bandaging is optional after the 1st 1–2 days. reconstructive procedure.
Complementary & Alternative r Healing usually take place within 10 days. r The choice of neonatal circumcision is a matter of
Therapies r Clean site with warm water and avoid baby diaper
Traditional religious providers perform the procedures the physician’s personal preference. For
in community settings wipes. circumcisions using a Gomco clamp, or Plastibell,
select the correct size of the bell; this would ensure
Patient Resources
adequate foreskin removal.
American Academy of Pediatrics. Patient Education r Always consider the cultural and religious beliefs of
ONLINE. www.patiented.aap.org
the family when counseling about newborn
circumcision.
95
CONDYLOMA ACUMINATA (VENERAL WARTS)

Neal Patel, MD
Allen D. Seftel, MD
Pathologic Findings
BASICS DIAGNOSIS r Branching, villous, papillary connective tissue stroma
covered by epithelium.
DESCRIPTION HISTORY r Superficial hyperkeratosis and thickening of the
r Anogenital epidermal lesions caused by the r Age and sex of patient
r History of recent sexual exposure epidermis (acanthosis).
transmission of human papilloma virus (HPV) r Clear vacuolization of the prickle cells (koilocytosis),
r The most common viral sexually transmitted r Number of partners and frequency of sexual
characteristic of HPV infection, is seen.
infection in the US, they are also called genital intercourse r There is no evidence of invasion of the underlying
warts, or venereal warts r Visible warts usually seen within 2–3 mo after
stroma
r Most common sites: Penis, vulva, vagina, cervix, exposure
perineum, and perianal area. r Practice of anal intercourse DIFFERENTIAL DIAGNOSIS
r Less commonly, urethra, bladder, oropharynx, larynx, r Immunocompromised state r Bowen disease and erythroplasia of Queyrat
r Bowenoid papulosis
and trachea
PHYSICAL EXAM r Buschke-Löwenstein tumor
EPIDEMIOLOGY r Lesions are pinkish to red-grayish white r Condyloma latum (syphilis)
Incidence (1) cauliflower-like lesions found on moist surfaces, r Extramammary Paget disease
r Most common STD often coalescing. r Fibroepitheliomas
r ∼1% of sexually active adults in the US r Lesions appear pearly white and granular
r Herpes simplex virus
r Larger lesions may be verrucous or flat in
Prevalence r Malignant melanoma
r Highest prevalence: 18–28 yr olds and exceeds 50% configuration r Molluscum contagiosum
r HPV DNA can be detected in 10–15% of the US r With magnifications, a central venule can be seen
r Nevi
population within each projection.
r Male: Examine penis, meatus, scrotum, perineum, r Pearly penile papules
r HPV 6 and 11 account >90% of visible genital r Seborrheic keratosis
warts. suprapubic, and perianal region
r Female: Vagina, introitus, perineum, cervix, and r Squamous cell carcinoma/basal cell carcinoma
RISK FACTORS perianal region
r Increased risk with number of sex partners, r Examine for evidence of coexisting STD (ulcers,
frequency of sexual activity, early coitus, and discharge, adenopathy).
TREATMENT
presence of condyloma on partners
r Age <25 DIAGNOSTIC TESTS & INTERPRETATION GENERAL MEASURES (5)
r Diagnosis usually based on observation of
r Immunocompromised status Lab
r Cigarette smoking and oral contraceptives may be r HPV cannot be readily grown in culture. characteristic lesions.
r Cytologic testing with Pap smear: Exfoliated genital r Main goal of treatment is to remove visual presence
associated with an increased risk. of warts.
r Onset of sexual activity at an early age cells are stained and examined for koilocytosis and
r Current therapies have an equally low effectiveness
neoplasia
PATHOPHYSIOLOGY r Serologic assays not useful in screening for HPV in preventing wart recurrence and may not reduce
r HPV is a double-stranded, circular DNA genome disease transmission.
injection, but may provide prognostic information
consisting of ∼8,000 base pairs. Subtypes 6 and 11 r Vaccine: HPV quadrivalent recombinant (types 6, 11,
for patients with abnormal Pap smears
are associated with the majority of genital warts. r Histologic analysis from biopsy specimens 16, and 18): Gardasil (Merck) is currently available
Types 16, 18 most often associated with potential r Rapid commercial screening tests available and are for administration to females of ages 9–26 for
for malignancy. prevention of condyloma acuminata and associated
r >80 different subtypes can potentially associate fairly accurate: ViraPap, ThinPrep Pap, Hybrid
diseases. HPV bivalent Cervarix (types 16 and 18)
capture II
with condylomata. r If necessary, molecular characterization for diagnosis (GSK)
r HPV subtypes associated with malignancy include: r Gardasil can also be used in males aged 9–26 to
and serotyping (eg, Southern and/or slot blot
16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, prevent genital warts. Administration to males prior
hybridization, PCR)
and 82 (2) r Consider screening for other associated STDs: HIV, to start of sexual activity is optimal.
r Transmission is by direct sexual contact. r Topical therapy may take up to 3 mo to observe a
GC, chlamydia, syphilis
r Less common mode is autoinoculation from response.
nongenital lesions. Diagnostic Procedures/Surgery
r Magnification with colposcope or 10× handheld MEDICATION
r Basal layer of epidermis is invaded by the virus.
r Latent phase can last months to years. magnifying lens of the suspected region after First Line
r Podophyllin (Podoben 25%, Podocon, Podofin):
application of 3–5% acetic acid-soaked gauze pad
ASSOCIATED CONDITIONS for 5 min allows visualization of nonvisible lesions, – Applied to lesion (concentration 10–25%) by
r Penile cancer but has low specificity. (3,4) health care worker once weekly for up to 6 wk
r Anal cancer – However, the Centers for Disease Control (CDC) r Podofilox (Condylox):
r Cervical cancer no longer recommends acetic acid soaks to – Self-application of a 0.5% solution to warts twice
r Buschke-Lowenstein tumor improve diagnosis. The soaks are associated with daily for 3 days, followed by 4 days without
many false positives. treatment; can be repeated 4–6 times.
GENERAL PREVENTION r Subclinical lesions may appear shiny white. r 5-FU (Efudex, Fluoroplex):
r Sexual abstinence r Urethroscopy for any patients with suspected – Topical treatment with 5% cream 1–3 times per
r Condoms week for several weeks, as needed. Maybe also
urethral warts, with care to occlude proximal urethra
r Pre-exposure vaccination (Gardasil, Cervarix, to prevent flushing of virus toward bladder used as an intraurethral instillation but not
Hepatitis B) r Proctoscopy for patients at risk for anal condyloma without irritative complications.
96
CONDYLOMA ACUMINATA (VENERAL WARTS)
r Trichloroacetic acid (Tri-Chlor): FOLLOW-UP See Also (Topic, Algorithm, Media)

– An 80–90% solution of trichloroacetic acid; apply r Bowen Disease and Erythroplasia of Queyrat
Patient Monitoring
directly to lesions; repeat weekly r Educate the patient about self-exam. r Bowenoid Papulosis
r Imiquimod (Aldara): r Patients should be examined shortly after therapy, to r Buschke-Löwenstein Tumor
– Potent inducer of interferon-α, which enhances evaluate initial response rates. r Condyloma Latum (Syphilis)
cell-mediated cytolytic activity. Available as a 5% r Encourage use of condoms if sexually active. r Fibroepitheliomas
cream applied to external lesions 3 times per r Surveillance urethroscopy is recommended 3–6 mo r Herpes Simplex Virus
week up to a maximum of 16 wk after treatment of intraurethral lesions. r Malignant Melanoma
Second Line
Interferon-α IM or intralesional 3 million units 3 times
Patient Resources
r Centers for Disease Control and Prevention
r Molluscum Contagiosum
r Pearly Penile Papules
C
a week for 3 wk – http://www.cdc.gov/std/hpv/default.htm r Penis, Cancer General
SURGERY/OTHER PROCEDURES r Penis, Lesion
r Electrosurgery (electrodesiccation/loop r Seborrheic Keratosis
electrosurgical excisional procedure): To destroy REFERENCES r Urethra, Condyloma (Warts)
lesions; local anesthesia is usually sufficient
r CO laser therapy: Useful for lesions that have not 1. Workowski KA, Berman S; Centers for Disease
2 Control and Prevention (CDC). Sexually transmitted
responded to other therapies and for extensive diseases treatment guidelines, 2010. MMWR CODES
disease. Magnification necessary to maximize Recomm Rep. 2010;59(RR-12):1–110.
efficacy; may produce less scarring
r Holmium laser can be used to remove intraurethral 2. Cogliano V, Baan R, Straif K, et al. Carcinogenicity ICD9
of human papillomaviruses. Lancet Oncol. r 078.11 Condyloma acuminatum
warts via cystoscopy. 2005;6:204. r 079.4 Human papillomavirus in conditions classified
r Surgical excision: Often reserved for extensive
3. Naucler P, Ryd W, Törnberg S, et al. Human elsewhere and of unspecified site
disease; also effective for isolated warts papillomavirus and Papanicolaou tests to screen for
r Cryotherapy: Application of liquid nitrogen on ICD10
cervical cancer. N Engl J Med. 2007;357:
patients without extensive disease. This procedure r A63.0 Anogenital (venereal) warts
1589–1597.
can be repeated at 1- or 2-wk intervals. r B97.7 Papillomavirus as the cause of diseases
4. Widdice LE, Moscicki AB. Updated guidelines for
papanicolaou tests, colposcopy, and human classified elsewhere
ONGOING CARE papillomavirus testing in adolescents. J Adolesc
Health. 2008;43(4 suppl):S41–S51. CLINICAL/SURGICAL
PROGNOSIS 5. Markowitz LE, Dunne EF, Saraiya M, et al.
r Subclinical infections are probably not curative. Quadrivalent human papillomavirus vaccine: PEARLS
r Women should still undergo routine Pap smears. Recommendations of the Advisory Committee on r HPV types 6, 11, 16, and 18 most common subtypes.
r Cervical cancer is associated with HPV infection. Immunization Practices (ACIP). MMWR Recomm r Women who have received the HPV vaccine should
HPV infection is not solely responsible for the Rep. 2007;56(RR-2):1–24.
still undergo routine screening with Pap smears.
malignant transformation of genital cells, but it may r Eliminating warts may not decrease infectivity or
be a cofactor in development of malignancy. HPV 6 transmission.
and 11 are low-risk subtypes, and are seldom ADDITIONAL READING r Men along with women may benefit from
associated with malignancy. r Beutner KR, Ferenczy A. Therapeutic approaches to
r Homosexuals are at 25–50 times greater risk for vaccination.
genital warts. Am J Med. 1997;102(5A):28–37. r Vaccines are not recommended for use in women
anal cancer. r Chuang TY. Condylomata acuminata (genital warts).
r Long-term, increased risk of malignancy secondary >26 yr of age.
An epidemiologic view. J Am Acad Dermatol. r In absence of lesions, treatment is not recommended
to HPV infection (HPV types 16, 18, 31, 33, and 51 1987;16(2 Pt 1):376–384. for individuals with subclinical infections.
are at highest risk of anogenital malignancy). r Leung AK, Kellner JD, Davies HD. Genital infection
COMPLICATIONS with human papillomavirus in adolescents. Adv
Malignant transformation: Penile carcinoma, cervical Ther. 2005;22(3):187–197.
carcinoma, anal cancer, and Buschke-Löwenstein r Maymon R, Shulman A, Maymon B, et al. Penile
tumor condylomata: A gynecological epidemic disease: A
review of the current approach and management
aspects. Obstet Gynecol Surv. 1994;49(11):
790–800.
97
CONTRAST ALLERGY AND REACTIONS

Edouard J. Trabulsi, MD, FACS
r Nonidiosyncratic: r Prevention in patient with known allergy:

BASICS – Dose dependent – Review radiology department procedures at site
– Related to osmolality, chemical composition, where testing scheduled.
DESCRIPTION volume, and concentration of contrast medium – Give methylprednisolone (Medrol) 32 mg PO 12
r Allergy reactions to IV contrast used for radiologic used and 2 hr prior to scheduled test and 50 mg
imaging are common, can range from mild to – Idiosyncratic and nonidiosyncratic reactions may diphenhydramine
moderate, and occasionally life threatening. be classified as minor, moderate, or severe – Patients with allergies to other substances (food,
r Often an immune system–based response to IV – Minor: Urticaria, nausea and vomiting, sense of medicines), with history of asthma, who are
administration of contrast used for common urologic warmth, pruritus, diaphoresis allergic to iodinated contrast, who are receiving
studies such as excretory urography and CT. – Moderate: Faintness, severe vomiting, facial gadolinium (or those with allergy to gadolinium
r Contrast allergy and reactions can be divided into 3 edema, laryngeal edema, mild bronchospasm who are to receive IV contrast) DO NOT need
groups: – Severe: Hypotensive shock, pulmonary edema, steroid prep.
– Idiosyncratic anaphylactoid reactions respiratory arrest, seizures, cardiovascular collapse
– Nonidiosyncratic reactions r Delayed:
– Delayed reactions – Occurs 1 hr to 7 days from injection of RCM DIAGNOSIS
r Reactions to MRI contrast media are discussed in – Usually mild to moderate, transient, and HISTORY (4)
Section II “Nephrogenic Systemic Fibrosis/Fibrosing self-limiting r Previous ADR
Dermatopathy (NSF/NFD).” – Commonly includes rash, urticaria, pruritus, and r Cardiac or renal disease
r “Contrast Induced Nephropathy” is discussed in erythema r Metformin with chronic renal diisease
Section II. ASSOCIATED CONDITIONS r Allergies
r Asthma
EPIDEMIOLOGY PHYSICAL EXAM
r Cardiac disease
Incidence r Monitor vital signs (BP, heart rate, respirations)
r Dehydration
r Overall rate of ADR (adverse drug reaction) for ionic – Hypotension and rarely shock
r History of allergy or atopy
high-osmolar contrast media (HOCM) is 11–12% r Observe for:
r Previous adverse drug reaction
and 0.2–3% for nonionic low-osmolar contrast – Urticaria, bronchospasm, wheezing, stridor
r Renal disease
media (LOCM) (1)[B] shortness of breath, flushing, pruritus,
r It is estimated that up to 12% of patients may r Sickle cell disease
angioedema
r Renal insufficiency
experience a contrast-related reaction. DIAGNOSTIC TESTS & INTERPRETATION
Prevalence GENERAL PREVENTION Lab
r Use of alternative imaging in patients with history of r In acute setting, no labs are usually needed
N/A
previous ADR r Blood gas may be useful
RISK FACTORS r These measures may decrease likelihood of ADR r The following may be obtained immediately after
r History of asthma/bronchospasm (10 times),
but will not eliminate all risk (3)[B]. the reaction to help with the diagnosis: Elevated
previous reaction (5 times), allergy or atopy – Use of nonionic LOCM tryptase or histamine (released from activated mast
(2–3 times) (2)[B] – Antihistamines (diphenhydramine 50 mg 1 hr cells).
r Other significant risks include: Cardiac disease, prior to study). An H2 -blocker can be used in Imaging
dehydration, sickle cell disease, polycythemia, conjunction with H1 , but never without N/A
multiple myeloma, pheochromocytoma, renal H1 -blockers
disease, anxiety, and the use of ionic vs. nonionic – Preprocedure hydration Diagnostic Procedures/Surgery
contrast material r Patients with pre-existing renal impairment should N/A
r Possible risk factors: β-blockers, IL-2, aspirin,
stop metformin 24 hr prior to procedure and be well Pathologic Findings
NSAIDs hydrated to avoid RCM-related biguanide lactic N/A
r Concomitant shellfish allergy or iodine allergy, while
acidosis and contrast-induced nephropathy. DIFFERENTIAL DIAGNOSIS
a common misnomer, does not confer a higher risk – In patients with normal renal function on Complex of symptoms immediately after contrast
of cross-reaction to radiocontrast media (RCM) metformin the following comorbidities should administration supports diagnosis
Genetics prompt discontinuation of metformin before the
N/A contrast:
◦ Liver dysfunction, alcohol abuse, cardiac failure, TREATMENT
PATHOPHYSIOLOGY myocardial or peripheral muscle ischemia, sepsis
r Idiosyncratic anaphylactoid: r To limit risk for contrast-induced nephropathy, GENERAL MEASURES
– Not dose dependent r Any facility that administers IV contrast should be
special arrangements should be made with the
– Most serious and potentially fatal type of reaction radiology department for any patient with a GFR equipped to treat common reactions noted below as
– Occurs without warning, previous exposure not a <60 mL/min/1.73 m2 . well as initial steps in cardiac/respiratory arrest.
prerequisite, not preventable r The American College of Radiology classifies acute
– Not considered anaphylactic due to lack of IgE contrast reactions and treatment in adults as noted
antibody formation below. Treatment is similar in children with
– Usually begins with or immediately after injection appropriate dose modifications.
of RCM (<30 min) – Hives
◦ Mild (scattered/transient): Observe or PO
diphenhydramine or PO fexofenadine
◦ Moderate (numerous/bothersome): PO/IM/IV
diphenhydramine or PO fexofenadine
◦ Severe (widespread/progressive): Consider IM/IV
diphenhydramine; consider IM/IV epinephrine
98
CONTRAST ALLERGY AND REACTIONS
– Diffuse erythema: IV access, monitor vitals, pulse – Furosemide 20–40 mg IV over 2 min 3. Liccardi G, Lobefalo G, Di Florio E, et al. Strategies
oximeter, O2 mask – Fexofenadine: 180 mg PO for the prevention of asthmatic, anaphylactic and
◦ If hypotensive NS or LR IV bolus 1 L – Glucagon: 1 mg IM anaphylactoid reactions during the administration
◦ If no fluid response consider IM/IV epinephrine – Hydrocortisone 200 mg IV over 2 min of anesthetics and/or contrast media. J Investig
– Bronchospasm: IV access, monitor vitals, pulse – Labetalol: 20 IV over 2 min; double dose every Allergol Clin Immunol. 2008;18(1):1–11.
oximeter, O2 mask 10 min PRN 4. Schabelman E, Witting M. The relationship of
◦ Mild: β-agonist inhaler (eg, albuterol); consider – Lorazepam 2–4 mg IV slow push; 4 mg max radiocontrast, iodine, and seafood allergies: A
rapid response team or ER admit – Methylprednisolone: 40 mg IV over 2 min medical myth exposed. J Emerg Med. 2010;39(5):
◦ Moderate: Consider IM/IV epinephrine; consider – Morphine: 1–3 mg IV, repeat every 5–10 min PRN
rapid response team or ER admit – Nitroglycerine: 0.4 mg tablet SL repeat every
701–707.
5. ACR Manual on Contrast Media Version 9 2013
C
◦ Severe: IM/IV epinephrine and rapid response 5–10 min PRN (www.acr.org). Accessed October 2013.
team/911 Second Line
– Laryngeal edema: IV access, monitor vitals, pulse N/A
oximeter, O2 mask, IM/IV epinephrine; consider ADDITIONAL READING
rapid response team/911 based on response SURGERY/OTHER PROCEDURES
– Hypotension (systolic BP <90 mm Hg): IV access, N/A r Brockow K, Christiansen C, Kanny G, et al.
monitor vitals, pulse oximeter, O2 mask, elevate ADDITIONAL TREATMENT Management of hypersensitivity reactions to
legs 60◦ ; consider NS or LR IV bolus 1 L iodinated contrast media. Allergy.
◦ With bradycardia (pulse <60 BPM [vasovagal] Radiation Therapy 2005;60:150–158.
as above; give atropine; consider rapid response N/A r Schopp JG, Iyer RS, Wang CL, et al. Allergic
team/911 Additional Therapies reactions to iodinated contrast media:
◦ With tachycardia (pulse >100 BPM For life-threatening reactions: ABCs of resuscitation, Premedication considerations for patients at risk.
[anaphylactoid reaction]) IM/IV epinephrine; IV fluids, vasopressors for BP support if IV fluids not Emerg Radiol. 2013;20(4):299–306.
consider rapid response team based on response adequate
– Hypertensive crisis (DBP >120 mm Hg; SBP >200 See Also (Topic, Algorithm, Media)
Complementary & Alternative r Contrast-Induced Nephropathy (CIN)
mm Hg; IV access, monitor vitals, pulse oximeter, Therapies r Nephrogenic Systemic Fibrosis/Fibrosing
O2 mask; IV labetalol or nitroglycerine SL and N/A
furosemide; rapid response team/911 Dermatopathy (NSF/NFD)
r Reference Tables: Contrast Agents, Genitourinary
– Unresponsive and pulseless: Check for
responsiveness; rapid response team/911; initiate ONGOING CARE
CPR; apply AED device; epinephrine IV (10 mL
1:10,000) PROGNOSIS CODES
r Depends on severity of ADR
– Pulmonary edema: IV access, monitor vitals, pulse
r Risk of death of 1 in 170,000 for both ionic HOCM
oximeter, O2 mask; elevate head of bed; IV ICD9
furosemide, IV morphine; rapid response and nonionic LOCM r 708.0 Allergic urticaria
team/911 COMPLICATIONS r 995.0 Other anaphylactic reaction
– Seizures: Protect patient; turn on side to avoid r Renal failure occurs in up to 5% r 995.27 Other drug allergy
aspiration; suction airway as needed; IV access, r Generally supportive measures only with renal
monitor vitals, pulse oximeter, O2 mask; if function returning to normal in a few weeks ICD10
unremitting rapid response team/911 lorazepam r Contrast-induced nephropathy (CIN) r L50.0 Allergic urticaria
IV r T50.8X5A Adverse effect of diagnostic agents, initial
– Hypoglycemia: IV access, O2 mask; oral 2 sugar FOLLOW-UP encounter
packets or 4 oz fruit juice or D50W I amp IV with Patient Monitoring r T88.6XXA Anaphylactic reaction due to adverse
D5W or D5NS 100 mL/h adjunctively; if no IV r Appropriate supportive measures until recovery
effect of correct drug or medicament properly
glucagon 1 mg IM depending on severity of ADR administered, initial encounter
– Anxiety/panic attack: Diagnosis of exclusion; r For patients with renal insufficiency on metformin
monitor for evolving reactions if present; IV access, follow-up renal function monitoring recommended.
monitor vitals, pulse oximeter; reassure patient CLINICAL/SURGICAL
– Reaction rebound prevention: IV steroids help Patient Resources
N/A PEARLS
short-term recurrence but not acute treatment
benefit; consider IV hydrocortisone/ A shellfish or iodine allergy does not correlate with
methylprednisolone with severe allergic reaction REFERENCES contrast media allergy.
prior to transport to ED
1. Cochran ST, Bomyea K. Trends in adverse events
MEDICATION
from iodinated contrast media. Acad Radiol.
First Line 2002;9(suppl 1):S65–S68.
r Based on guidelines noted above (5):
2. Hagan JB. Anaphylactoid and adverse reactions to
– Albuterol: 2 puffs (90 mcg/puff)
radiocontrast agents. Immunol Allergy Clin North
– Atropine 0.6–1 mg slow IV with NS flush up to
Am. 2004;24:507–519.
3 mg
– Benadryl
◦ 25–50 mg PO
◦ 25–50 mg IV slowly over 2 min
– Epinephrine
◦ 0.3 mg (0.3 mL 1:1,000 solution) IM
◦ EpiPen or (equivalent) IM 0.3 mL 1:1,000
solution
◦ 1 mL 1:10,000 solution slow IV injection over
5 min repeated every 5–10 min as needed for
severe reaction
99
CUSHING DISEASE AND SYNDROME

John B. Eifler, MD
Imaging
BASICS DIAGNOSIS r Brain MRI if pituitary lesion suspected
r CT abdomen/pelvis adrenal protocol for
DESCRIPTION HISTORY ACTH-independent hypercortisolism to evaluate for
r Cushing disease is hypercortisolism due to an r Progressive weight gain
r Fatigue adrenal adenoma/carcinoma
ACTH-secreting pituitary adenoma
r Cushing syndrome is the cluster of symptoms r Proximal limb weakness Diagnostic Procedures/Surgery
r Skin abnormalities: Easy bruisability, and striae Inferior petrosal vein sampling to diagnose and
attributable to hypercortisolism
r Pituitary adenomas account for 70% of patients r Abnormal menses/decreased libido localize pituitary adenoma
with endogenously elevated cortisol (15% primary r Impotence Pathologic Findings
r Pituitary adenoma
adrenal tumor, 15% ectopic ACTH production) r New-onset hypertension/diabetes
r Iatrogenic supplementation of glucocorticoids is the r Adrenal adenoma/carcinoma
r Frequent infections
r Micronodular/macronodular adrenal hyperplasia
most common cause of hypercortisolism r Osteopenia/osteoporosis
EPIDEMIOLOGY r Visual disturbances due to pituitary impinging optic DIFFERENTIAL DIAGNOSIS
nerves r Alcoholism (pseudo-Cushing)
Incidence
r Anorexia nervosa
N/A PHYSICAL EXAM
r Obesity/weight gain (80%) r Bulimia
Prevalence r Depression
r Cushing disease: 1.2–2.4 per million r Thin skin with striae (70%)
r Cushing syndrome 4–5× more common in women r Moon facies (75%) r Hypertension
r Buffalo hump (50%) r Obesity
than men
r In diabetics, prevalence 2–5% r Hypertension (75%) r Polycystic ovarian syndrome
r Truncal obesity (50%)
RISK FACTORS
r Iatrogenic exposure to glucocorticoids r Amenorrhea (60%)
r Loss of visual fields
TREATMENT
– Includes steroid creams or nasal sprays
GENERAL MEASURES
Genetics DIAGNOSTIC TESTS & INTERPRETATION r Multidisciplinary approach: Endocrinologist,
r Associated with MEN-1, Carney complex
Lab neurosurgeon, adrenal surgeon
r GNAS1 gene mutation (McCune-Albright syndrome) r CBC, serum glucose, electrolytes, lipids r Surgical therapy is the mainstay of treatment
PATHOPHYSIOLOGY – Hyperglycemia, hypokalemia, neutrophilia,
r Elevated serum levels of cortisol, either from lymphopenia, hyperlipidemia consistent with MEDICATION
exogenous intake or endogenous production Cushing First Line
r Initial screen: Late-night salivary cortisol and 24-hr r Medical therapy only indicated when surgery not
r Hypothalamus-pituitary-adrenal physiology
urinary free cortisol. (Note: Establishes possible
– ACTH (anterior pituitary), stimulates cortisol
hypercortisolemia, not etiology) – Ketoconazole: Considered medical treatment of
production in zona fasciculate of adrenal cortex
– Elevated late-night salivary cortisol: In Cushing choice; not FDA approved for this indication.
– ACTH release governed by CRH (hypothalamus) ◦ Inhibits cytochrome p450
– Cortisol—feedback regulation of CRH/ACTH syndrome, diurnal variation of cortisol levels is lost
→ high levels of cortisol suggest Cushing ◦ 200–400 mg 2 or 3 times a day
production ◦ Side effects: Reversible hepatotoxicity,
r Cushing syndrome causes: syndrome
– 24-hr urinary free cortisol × 3 samples: Sensitivity headache, sedation, nausea, and vomiting.
– Exogenous intake (most common) ◦ Reduced androgen production may lead to
90–97%, specificity 85–96%
– Cushing disease (70% of endogenous Cushing) r Second-line tests: Late-night serum cortisol, gynecomastia, decreased libido, and impotence
– Adrenal adenoma/carcinoma (10% of in males
endogenous Cushing) low-dose DST
r Determining etiology of hypercortisolemia – Mitotane: Suppresses cortisol production by
– Ectopic ACTH producer (10%): Neuroendocrine inhibiting 11β-hydroxylase
tumor (small-cell lung cancer, thymoma, ovarian – Plasma ACTH concentration
◦ Elevated in Cushing disease/ectopic tumor ◦ Primarily used for adrenocortical carcinoma
tumors) ◦ 0.5 g start, gradually increase to 2–3 g/d
– Other: ACTH-independent macronodular adrenal ◦ Decreased in adrenal adenoma/carcinoma,
nodular adrenal hyperplasia, steroid use – Metyrapone: Inhibits 11β-hydroxylase
hyperplasia, ectopic CRH production ◦ 500–750 mg 3 or 4 times a day
– High dose DST
ASSOCIATED CONDITIONS ◦ May distinguish pituitary from ectopic
r Pituitary tumor
ACTH-secreting tumor (failure to suppress
r Steroid administration cortisol suggests ectopic tumor)
r Adrenal adenoma/carcinoma – Inferior petrosal vein sampling: Higher sensitivity
and specificity than high-dose DST
GENERAL PREVENTION
Diligent management of glucocorticoid administration
100
CUSHING DISEASE AND SYNDROME
Second Line FOLLOW-UP See Also (Topic, Algorithm, Media)

N/A r Adrenal Adenoma
Patient Monitoring
r Postoperative monitoring for adrenal insufficiency r Adrenal Cortical carcinoma
SURGERY/OTHER PROCEDURES r Pre- and postoperative management is complex and r Adrenal Mass
r Cushing disease:
should be coordinated by endocrinologist r Cushing Syndrome Algorithm
– Trans-sphenoidal resection of pituitary adenoma:
Gold standard r Post operative hydorcortisone replacement with r Nelson Syndrome
◦ Cure in 60–80% of patients prolonged wean to allow pituitary adrenal axis to
– Bilateral adrenalectomy if disease refractory to recalibrate
pituitary surgery or if life-threatening r After primary treatment (pituitary surgery), any CODES C
hypercortisolism new-onset symptoms → reevaluation
r Ectopic ACTH-secreting tumor: Surgical resection
Patient Resources ICD9
– Bilateral adrenalectomy reserved for unresectable NIH Medline Plus. http://www.nlm.nih.gov/ 255.0 Cushing’s syndrome
disease medlineplus/ency/article/000410.htm. Accessed
r Ipsilateral adrenalectomy for primary ICD10
December 2013. r E24.0 Pituitary-dependent Cushing’s disease
cortisol-secreting adrenal masses r E24.8 Other Cushing’s syndrome
ADDITIONAL TREATMENT REFERENCES r E24.9 Cushing’s syndrome, unspecified
Radiation Therapy
Pituitary irradiation effective in 15% of refractory 1. Nieman LK, Ilias I. Evaluation and treatment of
cases—not considered primary therapy Cushing’s syndrome. Am J Med. 2005;118: CLINICAL/SURGICAL
1340–1346. PEARLS
N/A 2. Nieman LK, Biller BM, Findling JW, et al. The
diagnosis of Cushing’s syndrome: An Endocrine r Initial diagnostic studies for suspected Cushing
Complementary & Alternative Society Clinical Practice Guideline. J Clin Endocrinol syndrome include late-night salivary cortisol and
Therapies Metab. 2008;93:1526–1540. 24-hr urinary free cortisol.
N/A 3. Raff H, Findling JW. A physiologic approach to r Most common cause of endogenous Cushing
diagnosis of the Cushing syndrome. Ann Intern syndrome is a pituitary adenoma.
Med. 2003;138(12):980–991. r Muscle weakness +/− skin hyperpigmentation after
ONGOING CARE
bilateral adrenalectomy may be due to pituitary
PROGNOSIS adenoma (Nelson syndrome).
r Prognosis good for adrenal adenoma or Cushing ADDITIONAL READING
disease, worse for adrenocortical carcinoma r Aggarwal S, Yadav K, Sharma AP, et al.
r Prognosis for ectopic ACTH-producing tumors
typically poor Laparoscopic bilateral transperitoneal
adrenalectomy for Cushing syndrome: Surgical
COMPLICATIONS challenges and lessons learnt. Surg Laparosc Endosc
r Bilateral adrenalectomy Percutan Tech. 2013;23(3):324–328.
– Adrenal insufficiency r Lake MG, Krook LS, Cruz SV. Pituitary adenomas: An
– Osteoporosis overview. Am Fam Physician. 2013;88(5):319–327.
– Increased infection risk
– Nelson syndrome (pituitary adenoma)
101
CYSTITIS, GENERAL CONSIDERATIONS

Kelly A. Healy, MD
Demetrius H. Bagley, MD, FACS

BASICS N/A Lab
r Urinalysis with microscopy
DESCRIPTION PATHOPHYSIOLOGY (3) r Urine culture:
r Inflammatory process of the bladder r Bacterial cystitis in females is usually an ascending
r Occurs more frequently in women. infection. – Anaerobic, aerobic
r In males, it occurs in association with urethral or ◦ Midstream standard
r In men, isolated cystitis is rare and often associated ◦ Catheterize sample if concerns about
prostatic obstruction, prostatitis, foreign bodies, or
with prostatitis that results in secondary bacterial contamination
tumors.
infection of the bladder. r Increases in tumor necrosis factor in bladder mucosa – Fungal and viral cultures only if high suspicion
r Clinical syndrome of dysuria, frequency, urgency, – A recent study compared catheterized urine with
r Increased mast cell degranulation and histamine
and suprapubic pain midstream urine cultures in acute cystitis (4)
r Can be caused by infection (bacterial, viral, fungal, release ◦ Cultures of voided midstream urine with acute
r Changes in purinergic signaling
less commonly parasitic), radiation, interstitial uncomplicated cystitis accurately showed
cystitis (IC) or due to other irritants (drugs), or a ASSOCIATED CONDITIONS evidence of bladder Escherichia coli but not of
complication of another illness See “Differential Diagnosis.” enterococci or group B streptococci
r Geriatric considerations: ◦ These bacteria which are often isolated with
GENERAL PREVENTION E. coli but appear to rarely cause cystitis by
– Bacterial cystitis increases with advancing age. r Infectious: Minimize bacterial exposure, avoid
r Pediatric considerations: themselves (urethral contaminants)
indwelling Foley catheter if possible; intermittent r CBC: Anemia in hemorrhagic cystitis, leukocytosis in
– Cystitis in children is rare. Bacterial cystitis in an catheterization if prolonged catheter needed
infant necessitates a urologic workup. r Hemorrhagic: Avoid radiation or infectious cystitis
– Eosinophilic cystitis most common in this age r Creatinine
cyclophosphamide/iphosphamide exposure r Urine cytology: If patient with symptoms of cystitis,
group.
r Pregnancy considerations: risk factors for urothelial or other bladder cancer,
– Bacterial cystitis in pregnancy requires appropriate DIAGNOSIS and negative workup for UTI or overactive bladder
r Urine culture for Mycobacterium in presence of
antibiotic coverage to prevent complications to
the mother or fetus. HISTORY sterile pyuria and suspicion for TB
r Characterization of symptoms: Frequency, urgency, r Vaginal discharge evaluation if present
– Screening and treatment of asymptomatic
bacteriuria in pregnant women is encouraged to dysuria, suprapubic pain, perineal or scrotal pain,
prevent the development of cystitis or more severe dyspareunia Imaging
r Exposure to radiation: r CT urogram or US:
UTI and fetal harm.
– Obliterative endarteritis causing ischemia – To rule out associated upper-tract pathology
EPIDEMIOLOGY – May occur several years after exposure. – May show thickened bladder wall or filling defect
Incidence r Exposure to cyclophosphamide/iphosphamide: such as blood clots or tumor
r 33% of women experience an episode of bacterial r Cystogram:
– Common cause of hemorrhagic cystitis thought to
cystitis by age 24. 50% of women will have an be due to acrolein metabolite dwelling in bladder – To rule out vesicoureteral reflux if considering
episode in their lifetime (1). r History of UTI; previous treatments intravesical formalin treatment for hemorrhagic
r Annual incidence of 0.5–0.7 infections per cystitis
r If patient immunosuppressed:
patient-year in this group Diagnostic Procedures/Surgery
r Bacterial cystitis in healthy men is rare: – Suspect viral or fungal infection r Cystoscopy for hematuria workup or if the diagnosis
r Use of personal hygiene products that can cause
– Annual incidence <0.01% in men aged 21–50 yr. is not apparent
r Hemorrhagic cystitis occurs in 10–15% of patients local irritation (douches, vaginal preparations) r Cystoscopy with hydrodistention for the diagnosis of
r Indwelling catheters
after bone marrow transplantation while on r History of hematuria IC
immunosuppression. The BK virus is present in 80% r Bladder biopsy: To rule out carcinoma in situ or for
r History of fevers, chills
of population but is reactivated only with tissue culture
r Symptoms of vaginitis or discharge present
immunosuppression (2).
– Adenovirus in the urine preceding transplantation Pathologic Findings
PHYSICAL EXAM r Evidence of acute or chronic inflammation
is greatest associated factor r Vital signs: Fever, tachycardia (from anemia or r Michaelis–Gutmann bodies in malakoplakia
r Reported rates of IC from 52/100,000 to
sepsis), pallor (anemia due to hemorrhagic cystitis)
67/100,000 r Abdomen: Suprapubic tenderness, costovertebral DIFFERENTIAL DIAGNOSIS
r Anxiety
Prevalence angle tenderness
r GYN: Bladder or vaginal tenderness, vaginal r Balanitis
N/A
discharge r Bladder cancer or other malignancy
RISK FACTORS r GU, male: Tender and/or boggy prostate, testicular r Chronic pelvic pain syndromes
r Bacterial cystitis:
tenderness, penile discharge r Cystitis cystica, cystitis glandularis
– Young women: Sexual activity, use of spermicidal
r Diabetes insipidus, excess fluid intake
condoms or diaphragm, and genetic factors such
as blood type or maternal history of recurrent r Diabetes mellitus
cystitis r Diuretics, excessive caffeine, alcohol
– Healthy, noninstitutionalized older women: r Eosinophilic cystitis
Postmenopausal changes in the perineal
epithelium and vaginal microflora, incontinence,
diabetes, and history of cystitis
102
CYSTITIS, GENERAL CONSIDERATIONS
r Epididymitis ADDITIONAL TREATMENT ADDITIONAL READING

r Extrinsic bladder compression (eg, pelvic tumor, Radiation Therapy r Del Pizzo JJ, Chew BH, Jacobs SC, et al. Treatment
radiation-induced fibrosis) May induce radiation cystitis
r Genital herpes of radiation induced hemorrhagic cystitis with
r Hemorrhagic cystitis
Additional Therapies hyperbaric oxygen: Long-term followup. J Urol.
r Intravesical installations of alum, silver nitrate for
r Infectious cystitis: Bacterial, viral, parasitic, fungal 1998;160(3 Pt 1):731–733.
hemorrhagic cystitis r Epidemiology of interstitial cystitis. Executive
r IC (painful bladder syndrome) r Hyperbaric oxygen for hemorrhagic cystitis.
r Neurogenic bladder, chronic urinary retention Committee Summary and Task Force Meeting
Complementary & Alternative Report. October 29, 2003. NIDDK. (http://archives.
r Overactive bladder
Therapies niddk.nih.gov/ic2003/TaskForce Meeting C
r Prostatitis Report.pdf)
Cranberry tablets for prevention of recurrent bacterial
r Prostatodynia cystitis; evidence that the benefit for preventing UTI is r Hu KK, Boyko EJ, Scholes D, et al. Risk factors for
r Pyelonephritis small, cranberry juice cannot currently be urinary tract infections in postmenopausal women.
r Urethral syndrome recommended for the prevention of UTIs. Arch Intern Med. 2004;164:989–993.
r Urethritis (eg, gonorrhea, chlamydia) r Sencer SF, Haake RJ, Weisdorf DJ. Hemorrhagic
r Urinary calculi cystitis after bone marrow transplantation. Risk
r Vulvovaginitis and/or pelvic inflammatory disease ONGOING CARE factors and complications. Transplantation.
PROGNOSIS 1993;56(4):875–879.
r Warren JW, Abrutyn E, Hebel JR, et al. Guidelines
Simple bacterial cystitis prognosis is excellent.
TREATMENT for antimicrobial treatment of uncomplicated acute
COMPLICATIONS bacterial cystitis and acute pyelonephritis in women.
GENERAL MEASURES r Depends on etiology of cystitis
Clin Infect Dis. 1999;29:745–758.
r Encourage adequate hydration. r Untreated simple bacterial cystitis can cause
r Proper toilet hygiene for females to limit urethral pyelonephritis. See Also (Topic, Algorithm, Media)
r Bacteruria and Pyuria
exposure to pathogens r Hemorrhagic cystitis may recur and/or be refractory
r Cystitis, Hemorrhagic (Infectious, Noninfectious,
– Cleansing perineum “from front to back” to therapy, resulting in multiple transfusions or
(controversial) requiring cystoscopy and fulguration. Radiation)
r Encourage voiding immediately before and after r Cystitis, Radiation
FOLLOW-UP r Interstitial Cystitis
sexual activity in females.
Patient Monitoring r Prostatitis, General
MEDICATION r Urinalysis r Pyuria Algorithm
First Line r History and physical exam r Urinary Tract Infection (UTI), Adult Female
r Antimicrobials for bacterial cystitis r Females with >3 episodes of cystitis per year should r Urinary Tract Infection (UTI), Adult Male
– TMP–SMZ for 3 days is a standard therapy for be considered candidates for prophylaxis: r Urinary Tract Infection (UTI), Pediatric
simple uncomplicated bacterial cystitis in females. – Prior to institution of therapy, exclude anatomic
– Other combinations may include cephalexin, abnormality (eg, stones, reflux, fistula).
250–500 mg q6h for 1–3 days; ciprofloxacin, – Single dosing at bedtime or at time of intercourse
250–500 mg q12h for 1–3 days; nitrofurantoin is recommended. CODES
(macrocrystals), 100 mg q12h for 7 days; – Common oral agents are TMP–SMZ
ofloxacin, 200 mg q12h for 1–3 days (40 mg/200 mg), nitrofurantoin (100 mg), and ICD9
r Phenazopyridine (Pyridium) for relief of dysuria: r 595.82 Irradiation cystitis
cephalexin (250 mg).
– Pregnancy category B r 595.89 Other specified types of cystitis
Patient Resources r 595.9 Cystitis, unspecified
– Contraindicated in glomerulonephritis, renal http://www.bladderandbowelfoundation.org/
insufficiency or failure, severe hepatitis, G6PD bladder/bladder-problems/bacterial-cystitis.aspN/A
deficiency ICD10
r N30.40 Irradiation cystitis without hematuria
– Side effects: Orange urine, renal failure, rash,
nausea, headache, vertigo, hemolytic anemia, REFERENCES r N30.80 Other cystitis without hematuria
methemoglobinemia r N30.90 Cystitis, unspecified without hematuria
– Dose: 1. Wang A, Nizran P, Malone MA, et al. Urinary tract
◦ Adults: 200 mg PO TID infections. Prim Care. 2013;40(3):687–706.
◦ Pediatric: 4 mg/kg PO TID 2. Rinaldo CH, Tylden GD, Sharma BN. The human CLINICAL/SURGICAL
polyomavirus BK (BKPyV): Virological background PEARLS
Second Line
and clinical implications. APMIS. 2013;121(8):
Based on culture if initial antibiotic not successful in r Acute cystitis in females is most commonly bacterial
728–745.
bacterial cystitis
3. Payne H, Adamson A, Bahl A, et al. Chemical- and and typically responds to a short course of antibiotic.
SURGERY/OTHER PROCEDURES radiation-induced haemorrhagic cystitis. Current r Cystitis in the male is much less common and
r Cystoscopy with biopsy to diagnose cystitis cystica treatments and challenges. BJU Int. 2013; usually indicates a need for further evaluation.
or glandularis 112(7):885–897.
r Cystoscopy with hydrodistention to diagnose IC; 4. Hooton TM, Roberts PL, Cox ME, et al. Voided
look for characteristic glomerulations. midstream urine culture and acute cystitis in
r Cystoscopy with clot evacuation and electro or laser premenopausal women. N Engl J Med. 2013;
fulguration for hemorrhagic cystitis 369(20):1883–1891.
r Cystectomy for refractory hemorrhagic cystitis is
rarely necessary
103
CYSTITIS, HEMORRHAGIC (INFECTIOUS, NONINFECTIOUS, RADIATION)

Ahmad Shabsigh, MD, FACS
r Pelvic radiation:
BASICS DIAGNOSIS – Usually initiated by bladder distension, minor
trauma, infection, instrumentation
DESCRIPTION HISTORY – Acute episodes wane within 12–18 mo
r Inflammation leading to damage of the bladder’s r Gross hematuria (with or without pain)
– Can occur as late as 15–20 yr after exposure
urethelium and blood vessels, causing hematuria r Frequency, urgency, dysuria r Viral infection:
and irritative voiding symptoms. r Urinary retention from clots
– Adenovirus 11 and 35, influenza A, CMV,
r Hemorrhagic cystitis (HC) is commonly caused by r Occasional mucosal sloughing Polyomavirus hominis 1, the BKV, and JC viruses
severe infection, cyclophosphamide, and radiation r Suprapubic pain – Typically seen in immunocompromised patients
therapy induced. r Fevers with chills after BMT
r Previous history of cyclophosphamide therapy, pelvic – May present dramatically, but usually resolves
EPIDEMIOLOGY
radiation, bone marrow transplant spontaneously in <2 wk
Incidence r Other infections rarely cause severe HC:
r Cyclophosphamide-induced HC: 5–7%
PHYSICAL EXAM – Bacterial: Escherichia coli, Staphylococcus
r Radiation-induced HC: 10–15% in patients with r Suprapubic pain/mass: Distended bladder, infected
saprophyticus, Proteus, Klebsiella, Mycobacterium
history of pelvic radiation. and/or clot-filled bladder tuberculosis
r 7–70% of hematopoietic stem cell transplants. r Signs and symptoms of hypovolemia, hemorrhagic
– Fungal: Candida, Aspergillus, Cryptococcus,
RISK FACTORS shock, or anemia if severe Torulopsis
r No age, sex, or race predilection. r Ocular infections: Common with adenovirus – Parasitic: Schistosoma haematobium,
r Infections. infection Echinococcus granulosus
r Exposure to certain industrial chemicals, such as r Large hypertrophied tongue: Amyloidosis r Systemic hematologic disease: Rare; often refractory
aniline or toluidine derivatives. DIAGNOSTIC TESTS & INTERPRETATION to fulguration and irrigation
r Previous treatment with oxazaphosphorine r Systemic amyloidosis associated with rheumatoid
Lab
alkylating agents (for lymphoproliferative disorders, r Urine for analysis, cytology, and cultures (including arthritis or Crohn disease
r Chemical toxins:
solid tumors, collagen diseases) such as fungal and viral cultures, if indicated)
cyclophosphamide, isophosphamide. r Coagulation factors (especially platelets, which can – Anilines, toluidines, and chlordimeform are
r History of prior pelvic radiation (prostate and be depleted) common industrial exposures (dyes, pesticides).
cervical cancers). r Serial hematocrits – Overdoses of methenamine mandelate; accidental
r Reactivation of BK virus (BKV) infection in bone r Serum creatinine urethral instillation of gentian violet douche or
nonoxynol-9 contraceptive
marrow transplant patients. r Blood tests for collagen disease markers, if indicated
– Thiotepa and acetic acid intravesically
Genetics Imaging r Medications:
N/A r CT urogram: – Penicillin, piperacillin, methicillin, carbenicillin,
PATHOPHYSIOLOGY – Often done as part of hematuria workup danazol, bleomycin, allopurinol, busulfan
r Cyclophosphamide: Acrolein enters the urethelium. – Rules out other urologic abnormalities r Prolonged high-altitude travel (Boon disease)
Activates platelet-activating factor, nitric oxide, – Usually not able to diagnose HC, but may show r Carcinomas of the urinary tract
tumor necrosis factor-α, and IL-1, eventually clots in the lumen, a thickened irregular bladder r Acute UTIs
forming peroxynitrite that causes damage. wall, and/or small capacity. r Benign prostatic hypertrophy
r Radiation-induced cystitis results from a progressive Diagnostic Procedures/Surgery r Trauma to the urinary system
obliterative endarteritis leading to mucosal r Cystoscopy ± biopsy, ± clot evacuation r Arteriovenous malformation, vascular fistulae
ischemia, ulceration, and neovascularity. r Consider electro- or laser fulguration if focal
r Penicillin toxicity is immune-mediated, whereas bleeding visualized.
danazol toxicity is likely from damaging vascular
Pathologic Findings
TREATMENT
changes. r Urothelial damage: Edema, necrosis, ulceration,
GENERAL MEASURES
ASSOCIATED CONDITIONS hemorrhage, leukocyte infiltration, and r Catheterization/bladder irrigation with normal saline
See “Differential Diagnosis.” neovascularization to clear bleeding and evacuate clots
r May reveal amyloid deposits; eosinophilic r Remove the offending toxin.
GENERAL PREVENTION
r Patients treated with cyclophosphamide once had a inflammatory response of schistosomiasis; IgG, IgM, r Treat the infectious agent.
very high incidence of HC (∼70%), with high and C3 depositions; penicillin toxicity; whitish r Hydration and diuresis
mortality rates (as high as 75%) if it became severe pseudomembranes or plaques of fungal infections; r Blood products transfusion, when necessary
inclusion bodies of viral infections
r IV hydration, frequent bladder emptying, and
DIFFERENTIAL DIAGNOSIS MEDICATION
sometimes indwelling catheters with bladder r Oxazaphosphorine agents (cyclophosphamide and First Line
irrigations are used to reduce the time toxins are in r Alum irrigation often considered 1st line:
contact with the bladder wall (1)[A] isophosphamide):
– Most common cause of severe HC – Astringent, forms precipitates over bleeding
r Mercaptoethane sulfonate Na (MESNA) and surface
– Acrolein, a liver metabolite of the agents, is the
N-acetylcysteine (Mucomyst) bind to acrolein, toxin believed to be directly implicated. – 1–4% solution at 300–1,000 mL/h
creating nontoxic compounds. – Higher dosages, IV route of administration (vs. – No need for anesthesia
r WF-10 (2)[A], sodium pentosan polysulfate oral), and increased contact time between the – Adverse effects: Spasms, precipitation and
(Elmiron), and amifostine (Ethyol) have been bladder wall and the acrolein (because of clogged catheters, rare encephalopathy from
investigated in prevention of radiation-induced dehydration and/or infrequent emptying) all aluminum toxicity
cystitis. worsen HC.
r Infectious: Minimize bacterial exposure, avoid
indwelling Foley catheter if possible; intermittent
catheterization if prolonged catheter needed
104
CYSTITIS, HEMORRHAGIC (INFECTIOUS, NONINFECTIOUS, RADIATION)
r ε-Aminocaproic acid (Amicar): ADDITIONAL TREATMENT 2. Veerasarn V, Khorprasert C, Lorvidhaya V, et al.

– Inhibits clot lysis by urinary urokinase Radiation Therapy Reduced recurrence of late hemorrhagic radiation
– Can be given orally or parenterally Contraindicated; a recognized cause of HC cystitis by WF10 therapy in cervical cancer patients:
– Contraindicated in upper-tract bleeding, as dense A multicenter, randomized, two-arm, open-label
clots can lead to ureteral obstruction Additional Therapies trial. Radiother Oncol. 2004;73:179–185.
r Hyperbaric oxygen (4):
r Silver nitrate instillation: 3. Ganguly N, Clough LA, Dubois LK, et al. Low-dose
– Promotes granulation tissue and
– 0.5–1% solution in bladder for 10–20 min, cidofovir in the treatment of symptomatic BK virus
neovascularization, causes vasoconstriction.
followed by saline flush infection in patients undergoing allogeneic
– Better for radiation-induced cystitis.
– Causes a chemical cauterization hematopoietic stem cell transplantation: A
– Painful, requires anesthesia
– Requires a hyperbaric chamber, which may not
always be readily available.
retrospective analysis of an algorithmic approach. C
– Adverse effect: Build-up can clog catheters Transpl Infect Dis. 2010;12(5):406–411.
– May require 30–60 daily treatments.
– Duration of response is often short 4. Del Pizzo JJ, Chew BH, Jacobs SC, et al. Treatment
r Prostaglandin instillation: – High rate of recurrence.
r Selective hypogastric artery embolization: of radiation induced hemorrhagic cystitis with
– Carboprost tromethamine (synthetic PGF2) hyperbaric oxygen: Long-term followup. J Urol.
– Under local anesthesia on risky patients.
0.1–0.8 mg/dL solution. Dwell for 1–4 hr, 4 times 1998;160:731–733.
– Complications: Gluteal claudication, bladder
a day for 5–7 days
necrosis, lower limb paralysis, or impotence.
– Stabilizes membranes, decreasing edema; causes
– Low success, as most bleeding is venous.
vasoconstriction and platelet aggregation ADDITIONAL READING
– Low morbidity: No anesthesia required, no Complementary & Alternative
precipitate forms, so no clogging of catheters Therapies Decker DB, Karam JA, Wilcox DT. Pediatric
– Adverse effects: Cost, requires intensive nursing Supportive care. Blood products, platelets, reverse hemorrhagic cystitis. J Pediatr Urol.
care, moderate bladder spasms anticoagulation. 2009;5(4):254–264.
r Phenol instillation:
– 30 mL 100% phenol in 30 mL of glycine for 1 min, r Chemotherapy Toxicity, Urologic Consideration
then ethanol and saline washes
ONGOING CARE r Cystitis, General Considerations
– Destroys urothelium, not muscularis; less bladder PROGNOSIS r Cystitis, Hemorrhagic (Infectious, Non-Infectious,
fibrosis than with formalin r Related to the successful treatment of etiology of Radiation) Image
– Painful, requires anesthesia HC. r Cystitis, Radiation
– Duration of response is often short r Long term increases risk of secondary urothelial r Cystitis, Viral
r Low-dose cidofovir (3)
malignancy. r Cytoxan (Cyclophosphamide) Toxicity
– 5 mg/kg in 60 mL of 0.9% NaCl intravesical over r Polyoma Virus (BK, JC), Urologic Consideration
15 min. COMPLICATIONS
r Anemia, renal failure.
Second Line r Bladder fibrosis with small, noncompliant bladder;
r Hyaluronic acid:
– Constitutes a protective barrier.
may need surgical reconstruction. CODES
r Bladder perforation.
– Intravesical treatment of 40 mg every week for r Increased risk for transitional cell carcinoma from
4–6 wk. If responds add monthly treatments ICD9
r Formalin instillation: radiation, cyclophosphamide, and similar agents; r 595.4 Cystitis in diseases classified elsewhere
may be years later r 595.82 Irradiation cystitis
– 1–4% solution of ≤50 mL for 5–30 min, with r Secondary UTIs from prolonged catheterization. r 595.89 Other specified types of cystitis
patient in reverse Trendelenburg to minimize
r Vesicoureteral reflux resulting from bladder fibrosis.
vesicoureteral reflux.
ICD10
– Check cystogram before instillation to rule out FOLLOW-UP r N30.40 Irradiation cystitis without hematuria
reflux or extravasation; may need to occlude r N30.90 Cystitis, unspecified without hematuria
Patient Monitoring
ureter with balloon to prevent potentially fatal r Repeated hematocrit, platelets, renal function, urine r N30.91 Cystitis, unspecified with hematuria
renal absorption.
culture, and sensitivities.
– Hydrolyzes proteins, coagulating mucosa and r Maintain sterile urine.
submucosa; 80% effective
– Very painful, requires anesthesia.
r Continue hydration for many days after bleeding CLINICAL/SURGICAL
– Adverse effects: Reflux could cause ureteral ceases as rebleeding is common. PEARLS
r Evaluate long-term sequelae after acute episode.
fibrosis and obstruction or papillary necrosis;
extravasation causes peritonitis and/or fistulas. r May need repeat cystoscopy Optimum treatment for chemotherapy-induced HC is
r Pentosan polysulfate 100 mg TID prevention (aggressive hydration and/or prophylactic
Patient Resources mesna therapy).
SURGERY/OTHER PROCEDURES http://emedicine.medscape.com
r Repeated cystoscopic laser ablation or cauterization
r Consider the following after all conservative
REFERENCES
modalities have failed, and patient is unstable.
– Bilateral percutaneous nephrostomy tubes with 1. Vose JM, Reed EC, Pippert GC, et al. Mesna
occlusive balloons decrease the exposure of new compared with continuous bladder irrigation as
clots to urokinase, allowing bladder to uroprotection during high-dose chemotherapy and
self-tamponade. Would consider this option prior transplantation: A randomized trial. J Clin Oncol.
to formalin instillation. 1993;11:1306–1310.
– Supravesical urinary diversion, cutaneous
ureterostomy, ureterosigmoidostomy, cystectomy
in severe retractable cases.
105
CYSTOCELE
Alana M. Murphy, MD

BASICS r Multicompartment POP
Lab
– Always suspect concomitant apical prolapse in the r No lab testing is required for the diagnosis of a
DESCRIPTION setting of stage ≥3 cystocele cystocele
r Cystocele is prolapse of the bladder into the vagina r Storage symptoms/signs: Stress UI, urinary urgency, r Urinalysis and urine culture as indicated
r Also referred to as anterior compartment prolapse urgency urinary incontinence (UI)
r Voiding symptoms/signs: Weak urinary stream, Imaging
EPIDEMIOLOGY r No imaging is required for the diagnosis or
urinary hesitancy, elevated postvoid residual (PVR)
Incidence management of a cystocele
urine, bladder outlet obstruction, urinary retention r A cystocele may inadvertently be detected on
11% lifetime risk of surgery for pelvic organ prolapse
(POP) or urinary incontinence (UI) (1) GENERAL PREVENTION imaging studies, such as a cystogram
r Reduction of modifiable risk factors r Dynamic magnetic resonance imaging (MRI) with
Prevalence r Additional studies examining the role of prophylactic
r Difficult to determine due to several factors: contrast:
– Data mostly reported in the context of surgical vaginal support at the time of pelvic surgery (eg, – Examines pelvic structures in relation to one
treatment hysterectomy) are needed another during a Valsalva maneuver
– Cystocele may be asymptomatic – Aids in differentiation between a cystocele and an
– Diagnosis requires a vaginal exam enterocele
r POP quantification (POP-Q) distribution in an DIAGNOSIS – Aids in assessment of multicompartment POP
observational study of women 18–82 yr old seeking HISTORY Diagnostic Procedures/Surgery
routine gynecologic care (2): r Symptoms/signs: Pelvic pressure, vaginal pressure, r Pelvic exam
– POP-Q stage 0: 6.4% sensation of a vaginal bulge, stress/urgency/ – Employ standardized staging system (POP-Q or
– POP-Q stage 1: 43.3% overflow UI, obstructive voiding symptoms, Baden-Walker)
– POP-Q stage 2: 47.7% recurrent urinary tract infections (UTIs) r PVR assessment
– POP-Q stage 3: 2.6% r Previous pelvic/vaginal surgical procedures r Urodynamics
r Hormonal status – Only indicated to characterize associated storage
RISK FACTORS
r Increasing age r Obstetric history and voiding symptoms/signs
r Parity r Comorbidities Pathologic Findings
r Vaginal delivery (nerve, muscle, and connective N/A
PHYSICAL EXAM
tissue damage) r Assessment of POP should be performed during a DIFFERENTIAL DIAGNOSIS
– Instrumented vaginal delivery may be associated Valsalva maneuver r Cystocele
with a higher risk of POP compared to r Leading edge of POP should be used for staging r Enterocele
spontaneous vaginal delivery r Anterior vaginal wall masses: Urethral diverticulum,
r Race (3) purposes
r Examining a patient in a standing position may help Skene gland cyst, epidermal inclusion cyst,
– Hispanic women have highest prevalence of POP
r Increased intra-abdominal pressure (obesity, chronic determine the maximum extent of POP leiomyoma, ectopic ureterocele, Bartholin duct cyst,
r Assessment of the anterior compartment should be Gartner duct cyst
cough, constipation)
r Pelvic surgery (hysterectomy, radical cystectomy) performed with support of the apical and posterior
r Congenital connective tissue disorders compartment to ensure the elimination of
potentially distracting apical and posterior POP TREATMENT
(Ehlers–Danlos syndrome) r Baden-Walker grading system:
GENERAL MEASURES
Genetics – Grade 0: No POP r Observation
r Connective tissue disorders, bladder exstrophy – Grade 1: Leading edge descends halfway to the
r POP prevalence rates differ according to race hymen r Pelvic floor exercises (Kegel exercises) (4)[B]
suggesting a genetic component (3) – Grade 2: Leading edge descends to the hymen r Vaginal pessary
– Grade 3: Leading edge descends halfway past the r Surgical repair
PATHOPHYSIOLOGY hymen
r Weakening of supporting and suspending
– Grade 4: Procidentia or vault eversion MEDICATION
structures: Cardinal ligaments, uterosacral r POP-Q staging system: First Line
ligaments, endopelvic fascia, pubocervical fascia, There are no data to support systemic or topical
– POP described using 9 reference measurements,
levator ani muscles estrogen or other medications as a therapy for the
r Defect location: including 2 measurements specific to the anterior
vaginal wall treatment of cystocele.
– Central: Attenuation of the pubocervical fascia in ◦ Aa: Distal anterior vaginal wall
the midline Second Line
◦ Ba: Proximal anterior vaginal wall N/A
– Lateral: Disruption of lateral attachments of the – Stage 0: No POP
endopelvic fascia to the arcus tendineus fascia – Stage 1: Leading edge is >1 cm above the hymen
pelvis (ATFP) – Stage 2: Leading edge is between 1 cm above and
– Combined defects 1 cm below the hymen (−1, 0, +1)
– Stage 3: Leading edge is >1 cm below the hymen
but less than total vaginal length – 2 cm
(TVL – 2 cm)
– Stage 4: Leading edge is below hymen by more
than TVL – 2 cm
106
CYSTOCELE
r Preoperative preparation:
ADDITIONAL READING
ONGOING CARE r Chow D, Rodriguez LV. Epidemiology and
– Optional hormone replacement with topical
estrogen PROGNOSIS prevalence of pelvic organ prolapse. Curr Opin Urol.
r Perioperative factors: r Recurrence rates as high as 30–70% 2013;23:293–298.
r Close to 30% of women will require reoperation for r Walters MD. Surgical correction of anterior vaginal
– Single dose of preoperative antibiotics
– DVT prophylaxis with sequential compression symptomatic POP (1) wall prolapse. In: Walters MD, Karram MM, eds.
devices COMPLICATIONS Urogynecology and Reconstructive Pelvic Surgery,
– Optional vaginal packing
– Optional temporary urethral catheterization
r Bladder injury
r Ureteral injury/obstruction
3rd ed. Philadelphia, PA: Mosby Elsevier; 2007.
C
◦ Consider in the setting of a multicompartment
r Bleeding r Baden-Walker Staging
repair with or without an anti-incontinence r Dyspareunia r Cystocele, Grading
procedure r Cystocoele Enterocele Algorithm
r Transvaginal vs. transabdominal repair: r de novo stress UI
r Recurrent cystocele r Cystocele Image
– Transvaginal repair:
◦ Central defect repair: Plication of pubocervical r Pelvic Organ Prolapse (Cystocele and Enterocoele)
FOLLOW-UP r Pelvic Organ Prolapse Quantification System (POP-Q)
fascia in the midline with horizontal mattress
Patient Monitoring r Rectocele, Urologic Considerations
sutures
◦ Lateral defect repair: Reattachment of the Evaluation for recurrent POP should largely be based r Vaginal Mesh Erosion
on symptoms or clinical signs (elevated PVR, urinary r Vaginal Pessaries, Urologic Considerations
endopelvic fascia to the ATFP
retention, recurrent UTIs)
◦ Transvaginal mesh grafts provide a superior r Vaginal Prolapse
Patient Resources
anatomic outcome but are associated with r American Urogynecologic Society.
higher complication rates (5)[A]
http://www.voicesforpfd.org/p/cm/ld/fid=6
– Transabdominal repair: r International Urogynecological Association. CODES
◦ Only repair lateral defects www.iuga.org/resource/resmgr/Brochures/eng
r Closure of the vagina (colpocleisis): ICD9
pop.pdf r 618.01 Cystocele, midline
– Excellent option for geriatric women who no
longer desire the ability to maintain sexual activity r 618.02 Cystocele, lateral
r Perform a simultaneous repair of all POP defects and REFERENCES
an anti-incontinence procedure for demonstrable ICD10
1. Olsen AL, Smith VJ, Bergstrom JO, et al. r N81.10 Cystocele, unspecified
stress UI r N81.11 Cystocele, midline
r Consider a prophylactic concomitant Epidemiology of surgically managed pelvic organ
prolapse and urinary incontinence. Obstet Gynecol. r N81.12 Cystocele, lateral
anti-incontinence procedure in patients with stage
1997;89:501–506.
≥3 cystocele and/or history of stress UI
2. Swift SE. The distribution of pelvic organ support in
ADDITIONAL TREATMENT a population of female subjects seen for routine CLINICAL/SURGICAL
Radiation Therapy gynecologic healthcare. Am J Obstet Gynecol. PEARLS
N/A 2000;183:277–285.
r Management of a cystocele should largely be based
Additional Therapies 3. Nygaard I, Barber MD, Burgio KL, et al. Prevalence
r Observation: of symptomatic pelvic floor disorders in US women. on patient preference and symptoms.
JAMA. 2008;300:1311–1316. r Always suspect concomitant apical prolapse in the
– Appropriate if a patient is not symptomatic
4. Braekken IH, Majida M, Engh ME, et al. Can pelvic setting of stage ≥3 cystocele or a recurrent
r Pelvic floor exercises (Kegel exercises) (4)[B] cystocele.
floor muscle training reverse pelvic organ prolapse
r Vaginal pessary: and reduce prolapse symptoms? An r Mesh grafts for cystocele repair provide a superior
– Good option for poor surgical candidates assessor-blinded, randomized, controlled trial. Am J anatomic outcome but they are associated with
– May be used as a temporary solution Obstet Gynecol. 2010;203:e1–e7. higher complication rates.
– Risk of vaginal discharge, vaginal ulceration, 5. Altman D, Väyrynen T, Engh ME, et al. Anterior
vesicovaginal and rectovaginal fistula formation colporrhaphy versus transvaginal mesh for
Complementary & Alternative pelvic-organ prolapse. N Engl J Med. 2011;364:
Therapies 1826–1836.
N/A
107
LWBK1391-SEC-D LWBK1391-Gomella ch054.xml September 19, 2014 18:5
DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLUS,

UROLOGIC CONSIDERATIONS
Joshua D. Roth, MD
Michael O. Koch, MD, FACS
Genetics – High-risk patients with contraindications to

BASICS r Inherited risk factors for DVT/PE (3) LMWH/LDUH who are not at high risk for bleeding
– Family history complications
DESCRIPTION – Factor V Leiden mutation ◦ Low-dose aspirin (C), fondaparinux (C), or
r Deep vein thrombosis (DVT): Aggregation of – Prothrombin G20210A mechanical ppx, preferably with IPC (C)
platelets and fibrin within a deep vein of the leg or – Protein C deficiency – Inferior vena cava (IVC) filters should not be used
pelvis that may lead to venous obstruction. – Protein S deficiency for primary VTE prevention
r Pulmonary embolism (PE): Blockage of the – Antithrombin deficiency – No need for periodic ultrasound surveillance
pulmonary artery or one of its branches by a – Sickle cell trait
thrombus that has traveled from elsewhere in the
PATHOPHYSIOLOGY DIAGNOSIS
body through the bloodstream. Can be an acute r Most PEs arise from DVTs
life-threatening illness. r DVTs arise from initiating factors of Virchow’s triad:
r Venous thromboembolism (VTE or DVT/PE) is the HISTORY
– Hypercoagulability: Regional activation of r Recent high-risk surgery, or other risk factors for VTE
disease process by which a DVT can embolize and – DVT
coagulation cascade leading to obstruction,
become a life-threatening PE. ◦ History of prolonged immobilization,
edema, pain
EPIDEMIOLOGY – Stasis: Stagnant hypoxemia causes endothelial postoperative stasis, especially in patient with
Incidence injury risk factors
r DVT – Injury: Platelet accumulation and fibrin deposition ◦ Complaint of calf pain, swelling, or discoloration
– 160/100,000/yr (1) r Need to differentiate from superficial – PE
– Increases with age: 1/100 if age ≥80 thrombophlebitis/thrombosis that does not usually ◦ High clinical suspicion with above history
r PE (1) lead to DVT/PE ◦ Acute onset of dyspnea, tachycardia,
– 70/100,000/yr, with a 1-wk survival rate of 71%; arrhythmia, hypotension
25% present with sudden death Paradoxical embolism: Systemic embolisms of venous PHYSICAL EXAM
– PE is believed to be the most common cause of r DVT: Determined by level of obstruction
origin that occur in patients with atrial or ventricular
postoperative death in the urologic population septal defects, which allow the embolus to pass into – Inspection: Unilateral edema, discoloration below
r VTE risk in urologic populations (2) level of occlusion, dilated superficial veins
the arterial circulation
– Radical cystectomy: 3.7% – Palpation: Tender cord or knot, Homans’ sign
– Percutaneous nephrostomy in patients GENERAL PREVENTION (limitation of passive dorsiflexion of foot, 55%
r DVT prophylaxis (ppx)
with/without malignancy: 3.6%/0.8% unreliable)
– Nephrectomy with/without malignancy: – Mechanical (nonpharmacologic) therapies r PE
2.0%/0.4% ◦ Early postoperative ambulation
– Inspection: Cyanotic, dyspneic, prominent jugular
– Radical prostatectomy: 1.5% ◦ Graduated compression stockings (GCSs)
veins, hemoptysis, tachypnea
– Transurethral resection of bladder ◦ Intermittent pneumatic compression (IPC)
– Palpation: Tachycardia, arrhythmia
tumors/prostate: <0.5% – Pharmacologic therapies – Auscultation: Pleural rub, rales, S3–S4 heart
– Incontinence repair: 0.3% ◦ Subcutaneous low-dose unfractionated heparin
sounds
(LDUH)
Prevalence ◦ Subcutaneous low–molecular-weight heparin DIAGNOSTIC TESTS & INTERPRETATION
Prevalence of genetic mutations causing inherited (LMWH) Lab
thrombophilia: <1–5%, which cause a 3–10× r Recommendations (4) r DVT
increase risk of VTE in heterozygous state (3) – Very low–risk surgery (VTE risk <0.5%) – D-dimers: Sensitivity approaches 95% for ELISA
RISK FACTORS ◦ No specific pharmacologic (B) or mechanical (C) method
r Patient-specific risk factors (1) ppx r PE
– Surgery – Low-risk surgery (VTE risk ∼1.5%) – ABG: Increased P(A-a)O2 gradient
– Trauma (major or lower extremity) ◦ Mechanical ppx, preferably with IPC (C) – PaO2 <80 mm Hg
– Immobility, paresis – Moderate-risk surgery (VTE risk ∼3.0%) who are Imaging
– Malignancy not at high risk for bleeding complications r DVT
– Cancer therapy (hormonal, chemotherapy, or ◦ LMHW/LDUH (B), or mechanical ppx, preferably
– Central venography (gold standard): Invasive,
radiotherapy) with IPC (C) expensive, not always available, contrast risks
– Previous VTE – Moderate-risk surgery (VTE risk ∼3.0%) who are – Doppler ultrasound (US)/sonography: 90%
– Increasing age (≥60) at high risk for bleeding complications accurate above knee, versatile, noninvasive,
– Pregnancy and the postpartum period ◦ Mechanical ppx, preferably with IPC (C)
painless
– Estrogen-containing oral contraception – High-risk surgery who are not at high risk for – Venous duplex ultrasound
– Selective estrogen receptor modulators bleeding complications ◦ Grayscale US to visualize the structure of the
– Acute medical illness ◦ LMHW/LDUH (B) and mechanical ppx, with IPC
veins and color Doppler US to visualize the flow
– Heart or respiratory failure or GCS (C) of blood through the vein; more accurate than
– Inflammatory bowel disease – High-risk patient undergoing cancer surgery who Doppler and plethysmography
– Nephrotic syndrome are not at high risk for bleeding complications
– Myeloproliferative disorders ◦ 4 wk of LMWH (B)
– Paroxysmal nocturnal hemoglobinuria – High-risk patient who are at high risk for bleeding
– Obesity complications
– Smoking ◦ Mechanical ppx, preferably with IPC until the
– Varicose veins risk of bleeding diminishes
– Central venous catheterization
– Inherited or acquired thrombophilia
108
DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLUS, UROLOGIC CONSIDERATIONS
r PE Second Line REFERENCES

– Chest x-ray (CXR) r DVT/PE
◦ Generally unremarkable, but can sometimes see – In patients with heparin-induced 1. Rice KR, Brassell SA, McLeod DG. Venous
a small, unilateral effusion thrombocytopenia (HIT), LMW heparin Thromboembolism in Urologic Surgery: Prophylaxis,
◦ Westermark sign: Asymmetric vascular markings (argatroban, lepirudin, and danaparoid) can be Diagnosis, and Treatment. Rev Urol. 2010;
with segmental or lobar ischemia used 12(2/3):e111–e124.
– Ventilation/perfusion scan (V/Q scan) 2. White RH, Zhou H, Romano PS. Incidence of
◦ A perfusion defect in ≥1 pulmonary segment or SURGERY/OTHER PROCEDURES
r DVT symptomatic venous thromboembolism after
all unmatched with ventilation defects support a different elective or urgent surgical procedures.
– Venous thrombectomy: Rarely needed
high probability of PE Thromb Haemost. 2003;90:446.
◦ Negative result is very predictive – IVC filter:
◦ Used as prophylaxis in high-risk or multitrauma 3. Beckman MG, Hooper WC, Critchley SE, et al.
– Computed tomography (CT) Venous thromboembolism: A public health concern.
◦ Most common test used to diagnose PE patients
Am J Prev Med. 2010;38(4S):S495–S501.
◦ Recommended for acute DVT with contradic-
Diagnostic Procedures/Surgery 4. Guyatt GH, Akl EA, Crowther M, et al. Executive
r Pulmonary Angiography tion to anticoagulation (4)[B] summary: Antithrombotic therapy and prevention D
r PE of thrombosis, 9th ed: American College of Chest
– Injection of contrast into the pulmonary
circulation, fluoroscopy of the lungs – Pulmonary embolectomy: Considered rarely for Physicians evidence-based clinical practice
– Gold standard for diagnosing PE; rarely done patient who remains in shock despite medical guidelines. Chest. 2012;141(suppl 2):7S–47S.
therapy
Pathologic Findings
Thrombi are a woven congealed mass of fibrin and ADDITIONAL TREATMENT
platelets Radiation Therapy
ADDITIONAL READING
DIFFERENTIAL DIAGNOSIS N/A Best Practice Statement for the Prevention of Deep
r DVT: Cellulitis, thrombophlebitis, muscle Additional Therapies Vein Thrombosis in Patients Undergoing Urologic
sprain/strain, claudication, lymphedema r Will need 3 mo of anticoagulation therapy for Surgery, AUA 2008. Accessed March 2013 at
r PE: Pneumonitis/pneumonia, pneumothorax, CHF, http://www.auanet.org/content/media/dvt.pdf
postsurgical DVT/PE (4)[B]
esophageal perforation, myocardial infarction r Protamine can reverse unfractionated heparin if See Also (Topic, Algorithm, Media)
r Reference Tables: Anticoagulation and Antiplatelet
needed. Protamine is not as effective with LMWH
but should be used if excessive bleeding is Therapy in Urologic Practice
TREATMENT r Deep Venous Thrombosis and Pulmonary Embolus,
encountered
Urologic Considerations Image
ALERT Complementary & Alternative r Deep Venous Thrombosis, Prophylaxis, AUA
DVT and PE are potentially life-threatening and Therapies Guidelines
N/A
acute decline in status can occur. This condition
must be treated/diagnosed quickly and level of
suspicion must always be high in postoperative ONGOING CARE CODES
patients.
PROGNOSIS ICD9
r 10–30% of all patients with VTE suffer mortality r 415.11 Iatrogenic pulmonary embolism and
GENERAL MEASURES
r DVT: Extremity elevation, early ambulation, pain within 30 days (3) infarction
r Following anticoagulation therapy, 1/3 of all VTE r 453.40 Acute venous embolism and thrombosis of
relief
r PE: Oxygen therapy, fluid resuscitation, maintain patients will experience a recurrence within 10 yr (3) unspecified deep vessels of lower extremity
cardiac output with pressors if needed – Highest risk of recurrence is in the 1st year (3) r 997.2 Peripheral vascular complications, not
r Overall management of anticoagulation and r 1/3–1/2 of those with LE DVTs develop
elsewhere classified
antiplatelet therapy can be found in Section VII: postthrombotic syndrome (3)
Reference Tables: Anticoagulation and Antiplatelet ICD10
COMPLICATIONS r I26.99 Other pulmonary embolism without acute cor
Therapy in Urologic Practice r DVT: Pulmonary embolus; postthrombotic syndrome:
pulmonale
MEDICATION Destruction of valves leads to chronic pain, swelling, r I82.409 Acute embolism and thrombosis of
skin necrosis, ulceration
First Line r PE: Death, pulmonary infarction, pain, arrhythmia, unspecified deep veins of unspecified lower
r DVT proximal to knee anticoagulation with (4): extremity
shortness of breath r T81.72XA Complication of vein following a
– LMWH r VTE: Requires anticoagulation with its associated
– Fondaparinux procedure, NEC, init
– Above favored over IV unfractionated heparin risk factors (increased bleeding risk), increased
(UH) drip (B) healthcare costs, prolonged hospitalization,
– Early initiation of oral warfarin, with continued rehospitalizations
r Heparin-induced thrombocytopenia with
CLINICAL/SURGICAL
parenteral anticoagulation until INR is reached for
unfractionated heparin
PEARLS
>24 hr.
r DVT Distal to knee r Prophylaxis can help prevent DVT/PE.
FOLLOW-UP
– Without severe symptoms/risk factors: Serial r PE usually develops from a venous thrombus
Patient Monitoring
noninvasive imaging for 2 wk over r Patients on heparin: Follow aPTT involving the proximal lower extremity.
anticoagulation (C). If thrombus extends, r If necessary LMWH therapy can be followed by r DVT/PE are potentially life threatening—have a high
recommend therapeutic anticoagulation (B/C). antifactor Xa assays index of suspicion.
– With severe symptoms/risk factors: r Early diagnosis and treatment are key.
Anticoagulation (as above) over imaging (C). r Patients on warfarin need close monitoring of their
r PE (4) INR for a goal between 2.0 and 3.0 (3)[B]
– Systemic anticoagulation as for DVT (B/C) Patient Resources
– PEs with hypotension: Systemic thrombolysis with r The Coalition to Prevent Deep-Vein Thrombosis
streptokinase is recommended (C). http://www.preventdvt.org
r The National Blood Clot Alliance http://www.
stoptheclot.org
109
DETRUSOR OVERACTIVITY
Lysanne Campeau, MD, CM, PhD, FRCSC
Victor W. Nitti, MD, FACS
PATHOPHYSIOLOGY Diagnostic Procedures/Surgery

BASICS r Increased connectivity and excitability between r Urodynamic testing
detrusor muscle and nerves – Filling cystometry: Measurement of the
DESCRIPTION r Inflammation pressure/volume relationship of the bladder
r Detrusor overactivity (DO) is occurrence of r Increased afferent activity during filling
involuntary detrusor contractions during filling r Neurologic lesions of the CNS above the sacral Imaging
cystometry micturition center r Can involve videourodynamics with cystogram and
– Spontaneous or provoked
voiding cystourethrogram
– Contractions produce a wave form on ASSOCIATED CONDITIONS
– Renal ultrasound can also rule out the presence of
cystometrogram of variable duration and OAB, pelvic floor disorders, urinary incontinence,
hydronephrosis caused by high bladder pressures
amplitude bladder outlet obstruction, neurologic lesions above
– Phasic or terminal the sacral micturition center, detrusor external Pathologic Findings
– Can be associated with symptoms sphincter dyssynergia DO is characterized by the presence of contractions
– Neurogenic DO: DO with evidence of a relevant that produce a wave form on cystometrogram of
GENERAL PREVENTION variable duration and amplitude
neurologic disorder r Avoiding large fluid intake or the consumption of
– Idiopathic DO: DO without a neurologic cause “bladder irritants” such as caffeine. DIFFERENTIAL DIAGNOSIS
r Timed voiding and avoiding bladder overdistension r Bladder calculi
EPIDEMIOLOGY (1,2)
r DO is a common cause of symptoms of overactive r Bladder cancer/carcinoma in situ
bladder (OAB) syndrome, however since it is defined r Bladder outlet obstruction/Prostatic hypertrophy
by urodynamics, it may not be documented if DIAGNOSIS r Congestive heart failure
urodynamics are not preformed r Detrusor external sphincter dyssynergia
r Symptoms associated with DO (urgency, frequency, r Diabetes
ALERT
and urgency incontinence) are more commonly DO, by definition can only be diagnosed by r Interstitial cystitis/Painful bladder syndrome
treated rather than DO per se urodynamics. Therefore it is more practical to talk in r Pelvic pain syndrome
r OAB is a symptom complex and is diagnosed
terms of diagnosing OAB. r Medications
without urodynamics and therefore may be r Neurogenic bladder
diagnosed in the presence or absence of DO HISTORY (3) r Pelvic organ prolapse
r Approximately one-third of patients with OAB have r Past medical and surgical history
r Polyuria/polydipsia
incontinence r Medications (diuretics, psychoactive drugs)
r Sexually transmitted infection
– OAB is defined as urinary urgency, usually r Lower urinary tract symptoms survey
accompanied by frequency and nocturia, with or r Stress incontinence
r Women with DO and OAB:
without incontinence, in the absence of urinary r Testing artifact during UDS evaluation (false positive)
– Are twice as likely to have urge urinary r Urethral diverticulum
tract infection (UTI) or other obvious pathology
incontinence.
– Urinary incontinence accounts for 2% of r UTI
– Have a higher symptom score on questionnaires
healthcare cost in the United States
– Higher episodes of daytime voiding and nocturia
Prevalence – Have lower functional bladder capacities
r OAB present in 17% of women and 16% of men TREATMENT
– Increases with age PHYSICAL EXAM
r Rule out the presence of exacerbating conditions GENERAL MEASURES
r DO present in 33% of women with OAB r Treatment aimed at inhibiting involuntary detrusor
r DO is present in 36% of patients with no OAB – Pelvic and vaginal exam
– Neurologic exam: Peripheral sensation and motor contractions and decreasing intravesical pressures
symptoms r There are a number of options used to treat
assessment
RISK FACTORS – Postvoid residual symptoms associated with DO. Only antimuscarinics,
r Neurogenic and idiopathic DO botulinum toxin, and augmentation cystoplasy have
DIAGNOSTIC TESTS & INTERPRETATION been proven to actually reduce or eliminate DO
– Most neurologic disorders are risk factors for DO
Lab r Behavioral modifications: Timed voiding, decrease
(ie, stroke, neurodegenerative disorders, multiple r Urinalysis: Determine presence of infection,
sclerosis) fluid intake, avoid caffeine
– Pelvic surgeries, metabolic syndrome, diabetes, hematuria, glycosuria – Pelvic floor exercises (Kegel): With or without
r Urine culture: Rule out infection biofeedback
pelvic floor disorders, bladder outlet obstruction
r Urine cytology: Rule out malignancy
110
DETRUSOR OVERACTIVITY
MEDICATION FOLLOW-UP r Kanai A, Zabbarova I, Oefelein M, et al. Mechanisms

r Antimuscarinics: Inhibit the effect of acetylcholine at of action of botulinum neurotoxins, β3-adrenergic
Patient Monitoring
postjunctional muscarinic receptors on detrusor r Periodic patient follow-up receptor agonists, and PDE5 inhibitors in modulating
muscle cells – Symptom assessment detrusor function in overactive bladders: ICI-RS
– Tolterodine (2–4 mg/d) – Treatment compliance 2011. Neurourol Urodyn. 2012;31(3):300–308.
– Trospium XR (60 mg/d) – Minimize medication side effects r Winters JC, Dmochowski RR, Goldman HB, et al.
– Darifenacin (7.5–15 mg/d) – Repeat urodynamic evaluation Urodynamic studies in adults: AUA/SUFU guideline.
– Solifenacin (5–10 mg/d) J Urol. 2012;188(6 suppl):2464–2472.
– Oxybutynin (IR 7.5–20 mg/d, XL 5–30 mg/d, Patient Resources
r National Association For Continence: See Also (Topic, Algorithm, Media)
patch twice weekly), r Detrusor Overactivity Image
– Fesoterodine (4–8 mg/d) www.nafc.org/bladder-health
r β3-adrenergic receptor agonist: Promotes detrusor r National Kidney and Urologic Diseases Information r Incontinence, Urinary, Adult Female
Clearing House: http://kidney.niddk.nih.gov/ r Incontinence, Urinary, Adult Male
muscle relaxation
kudiseases/pubs/urodynamic/ r Overactive Bladder (OAB)
r Intravesical botulinum toxin (OnabotulinumtoxinA)
r Urgency, Urinary (Frequency and Urgency) D
r Sacral Neuromodulation
injection: REFERENCES
– Approved for treatment of neurogenic detrusor
overactivity and OAB 1. Garnett S, Abrams P. The natural history of the
r Sacral neuromodulation: Stimulation of S3 nerve overactive bladder and detrusor overactivity. A CODES
review of the evidence regarding the long-term
root (InterStim)
r Posterior tibial nerve stimulation (PTNS): Urgent outcome of the overactive bladder. J Urol. ICD9
2003;169:843–849. r 596.51 Hypertonicity of bladder
PCTM r 788.41 Urinary frequency
r Augmentation cystoplatsy/Urinary diversion: 2. Haylen B, de Ridder D, Freeman RM, et al. An
International Urogynecological Association r 788.63 Urgency of urination
Increase functional bladder capacity and reduce (IUGA)/International Continence Society (ICS) joint
intravesical pressure report on the terminology for female pelvic floor ICD10
r Pelvic floor reconstruction: If concomitant pelvic r N32.81 Overactive bladder
dysfunction. Neurourol Urodyn. 2010;29:4–20.
floor disorder 3. Abrams P, Chapple CR, Jünemann KP, et al. Urinary r R35.0 Frequency of micturition
Additional Therapies urgency: A review of its assessment as the key r R39.15 Urgency of urination
r Infection prophylaxis symptom of the overactive bladder syndrome.
r Clean intermittent catheterization World J Urol. 2012;30:385–392.
– Decrease bladder pressure if urinary retention CLINICAL/SURGICAL
present PEARLS
ADDITIONAL READING r OAB is not synonymous with detrusor overactivity;
ONGOING CARE r Abrams P, Cardozo L, Fall M, et al. The the key symptom of OAB is urinary urgency.
standardization of terminology of lower urinary tract r DO demonstrated on cystometry needs to be
PROGNOSIS function: Report from the standardization correlated with patient’s symptoms.
r Stepwise approach to treatment with least invasive
sub-committee of the International Continence r Treatment indicated if potential complications or
pharmacologic options as first line Society. Neurourol Urodyn. 2002;21(2):167–178. patient driven.
– Patient may develop refractory OAB that may r Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis r Only antimuscarinics, botulinum toxin, and
require second- or third-line treatment and treatment of overactive bladder augmentation cystoplasy have been proven to
COMPLICATIONS (non-neurogenic) in adults: AUA/SUFU guideline. actually reduce or eliminate DO.
r Urinary incontinence: Social and hygienic issues J Urol. 2012;188(suppl 6):2455–2463.
r UTIs
r Renal deterioration
– High economic burden
111
DETRUSOR SPHINCTER DYSSYNERGIA (DSD)


BASICS DIAGNOSIS Lab
r Blood studies
DESCRIPTION HISTORY – Serum chemistry
r Detrusor sphincter dyssynergia (DSD) is found in r Neurologic disease
◦ Renal function, electrolyte levels
cases of neurogenic lower urinary tract dysfunction – Date of onset, duration of process
r Urinary voiding symptoms – Complete blood count
r DSD is contraction of the sphincter mechanism ◦ Secondary anemia due to decreased renal
occurring simultaneously with uninhibited – Frequency, urgency, urge incontinence function or chronic infection
involuntary contraction of the bladder detrusor r Method of urinary management r Urine studies
muscle (neurogenic detrusor overactivity [NDO]) – Condom catheter urinary collection – Urinalysis
– Intermittent self-catheterization ◦ Proteinuria: Renal dysfunction
EPIDEMIOLOGY – Indwelling urethral or suprapubic catheter ◦ Pyuria, nitrite, leukocyte esterase: Acute or
Incidence r Urinary tract infection (UTI)
r Unknown chronic infection
– Severity of infection ◦ Hematuria: Infection or lithiasis
– Depends on incidence of underlying neurologic ◦ Response to antibiotics
condition ◦ Need for parenteral antibiotics Imaging
r Renal ultrasound (US)
Prevalence – Frequency of occurrence of infection
r Prevalent in those with spinal cord lesions – Urolithiasis – Effective in screening for upper urinary tracts
◦ Episodes of lithiasis ◦ Calculus
– More prevalent at higher levels (cervical) than
◦ Surgical intervention ◦ Hydronephrosis
lower (sacral) injury or disease
r May affect those with multiple sclerosis (MS), spinal ◦ Masses
PHYSICAL EXAM r Excretory urography (ExU)
cord tumor, traumatic spinal cord injury (SCI), r Fever
arteriovenous malformation – Contraindicated in those with decreased renal
r Parenchymal UTI function (serum creatinine >2.0)
r Uninhibited involuntary detrusor contraction (ie,
– Men – Delayed excretion of contract with high urinary
NDO) must be present for DSD to occur ◦ Prostate, testes/epididymis, renal storage pressures
RISK FACTORS – Female – Hydroureteronephrosis
r Neurologic processes affecting central nervous ◦ Renal ◦ Marked elevation of intravesical pressure
system (CNS) r Hypertension ◦ May be due to urinary calculi
– Below level of the pons – During manipulation of GI/GU systems, autonomic r Voiding cystourethrogram
r Associated with autonomic hyperreflexia hyperreflexia may result – Bladder
r Generalized edema ◦ Wall thickening
Genetics
– Severe renal insufficiency ◦ Trabeculation
None r Palpable flank mass ◦ Diverticulum formation
PATHOPHYSIOLOGY – Secondary hydronephrosis ◦ Incomplete emptying
r DSD causes functional outflow obstruction r Flank tenderness – Ureter
– Dramatic elevation of intravesical pressure – Ureteral obstruction ◦ Vesicoureteral reflux
◦ Damages urinary tract directly with pressure and – Pyelonephritis ◦ Hydroureter
poor upper tract drainage r Abdominal mass ◦ Hydroureteronephrosis
◦ Secondarily with infection and urolithiasis – Urethra
r DSD always associated with NDO – Distended bladder, urinary retention
r Incontinence of urine ◦ Prostatic urethral dilated
– NDO may occur with synergic sphincter function ◦ Membranous urethra persistently narrow,
– Spontaneously
(without DSD) – With stress maneuvers stenotic, nonrelaxing
r Pontine mesencephalic reticular formation ◦ Distal urethra normal; rule out stricture
– During abdominal/pelvic palpation r Nuclear medicine renal scan
– Coordinates sphincter relaxation with detrusor r Testicular mass
contraction – Epididymo-orchitis/epididymitis – Objective quantification of GFR
◦ Spinal cord lesions impair transmission of – Sequential studies can detect deterioration of
– Secondary abscess formation
coordinating influences from the pons during – Hydrocele from recurrent infection renal function prior to elevation of serum
reflex detrusor contraction r Prostate mass/nodule creatinine
◦ Uninhibited detrusor contraction stimulates a
– Focal prostatitis Diagnostic Procedures/Surgery
reflex sphincter contraction, resulting in bladder r Urodynamic evaluation
– Prostate abscess
outflow obstruction – Essential to diagnose detrusor overactivity with
r 10–20% patients have internal (bladder neck)
detrusor sphincter dyssynergy
sphincter dyssynergia coexistent with external r Cystoscopy
sphincter dyssynergia – Normal penile urethral
ASSOCIATED CONDITIONS – Spastic, nonrelaxing, stenotic membranous
r SCI urethral
r MS – Dilated prostatic urethra
r Transverse myelitis – Bladder trabeculation/diverticula
– Rule out calculus or bladder tumor
GENERAL PREVENTION
N/A
Pathologic Findings
None
112
DETRUSOR SPHINCTER DYSSYNERGIA (DSD)
DIFFERENTIAL DIAGNOSIS r Augmentation cystoplasty

r Detrusor overactivity and bladder outflow
REFERENCES
– Bladder is incised in clamshell fashion to disrupt
obstruction detrusor contraction 1. Schurch B, Hauri D, Rodic B, et al. Botulinum-A
– Benign prostatic hyperplasia – Gastrointestinal segment used to enlarge bladder, toxin as treatment of detrusor sphincter
– Adenocarcinoma of the prostate increasing urinary storage with decreased dyssynergia: A prospective study in 24 spinal cord
– Urethral stricture disease pressure injury patients. J Urol. 1996;155:1023–1029.
– Urethral tumor ◦ May use large intestine, ileum, or gastric 2. Chancellor M, Gajewski J, Ackman CF, et al.
r Urinary retention/incomplete emptying and segment Long-term follow-up of the North American
neurologic disease ◦ Requires intermittent catheterization for urinary Multicenter UroLume Trial for the treatment of
– Impaired detrusor contractility drainage external detrusor-sphincter dyssynergia. J Urol.
– Detrusor areflexia ◦ Limited dexterity may mandate creation of 1999;161:1545–1550.
continent catheterizable stoma for the urinary
reservoir, especially in females
TREATMENT r Ileal conduit cutaneous vesicostomy ADDITIONAL READING
GENERAL MEASURES – Conduit of ileum connecting dome of bladder to
r Blaivas JG. The neurophysiology of micturition: A
D
r Intermittent catheterization anterior abdominal wall
r Decrease intravesical pressure ◦ Continuous low-pressure drainage through clinical study of 550 patients. J Urol. 1982;127:
incontinent ileal conduit urostomy requires 958–964.
– Decrease bladder contractility
stomal appliance for urinary collection r Consortium for Spinal Cord Medicine. Bladder
◦ Low-pressure urinary storage
◦ Useful for those who cannot perform management for adults with spinal cord injury: A
– Defeat sphincter function to establish clinical practice guideline for health care providers.
self-catheterization (ie, quadriplegia)
low-pressure urinary drainage per urethra Available at http://www.nxtbook.com/nxtbooks/
◦ Only option for males ADDITIONAL TREATMENT pva/bladdermanagement/index.php, Accessed April
◦ No effective external urinary collection device Radiation Therapy 2013.
for females N/A r Fowler C. Neurological disorders of micturition and
MEDICATION Additional Therapies their treatment. Brain. 1999;146:1213–1231.
First Line r Sacral deafferentation with sacral nerve root r Kaplan SA, Chancellor MB, Blaivas JG. Bladder and
r Anticholinergic therapy stimulation sphincter behavior in patients with spinal cord
– Effective in improving urinary storage under low – Deafferentation with dorsal rhizotomy abolishes lesions. J Urol. 1991;146:113–117.
pressure spontaneous detrusor contraction, improving
◦ Hyoscyamine 0.375 mg PO BID-TID urinary storage
r Detrusor-Sphincter Dyssynergia (DSD) Image
◦ Oxybutynin 5 mg PO TID-QID – Nerve root stimulation allows control over r Guillain–Barré Syndrome (Transverse Myelitis),
◦ Oxybutynin extended release 5–40 mg/d PO detrusor contraction
◦ Tolterodine 2–4 mg PO BID – Obstruction by sphincter may require adjunctive Urologic Considerations
r Multiple Sclerosis, Urologic Considerations
r α-Adrenergic blockade sphincteric ablation
r Spinal Cord Injury, Urologic Considerations
– Decrease internal sphincter function Complementary & Alternative r Urodynamics, Indications and Normal Values
– Largely ineffective for external sphincter Therapies
dyssynergia N/A
◦ Alfuzosin 10 mg/d PO
◦ Phenoxybenzamine 10 mg PO BID (nonselective) CODES
◦ Terazosin 2–5 mg PO daily-BID ONGOING CARE
◦ Doxazosin 2–8 mg/d PO ICD9
◦ Tamsulosin 0.4 mg PO daily PROGNOSIS r 596.0 Bladder neck obstruction
r Excellent prognosis if effectively treated
r Untreated, ∼50% of men will develop significant r 596.54 Neurogenic bladder NOS
Second Line
r Botulinum toxin injection into the external sphincter r 596.55 Detrusor sphincter dyssynergia
complication
for DSD
– Short lived COMPLICATIONS ICD10
r Vesicoureteral reflux r N31.8 Other neuromuscular dysfunction of bladder
– Requires repeated injections (1)[B] r Renal insufficiency r N31.9 Neuromuscular dysfunction of bladder,
SURGERY/OTHER PROCEDURES r Urolithiasis unspecified
r Endoscopic sphincter ablation r Urosepsis r N36.44 Muscular disorders of urethra
– Only in males as it requires condom catheter
urinary collection FOLLOW-UP
◦ Electrosurgical or laser sphincterotomy: Incise Patient Monitoring CLINICAL/SURGICAL
external sphincter from bulbous urethra to r Annual evaluation PEARLS
midprostatic urethra – Urodynamic testing
◦ Assure low intravesical pressure r DSD is always associated with NDO.
◦ Further incision through the prostate and
– Upper tract imaging (Ultrasound most comonly r Anticholinergic therapy and α-Adrenergic blockade
bladder neck may be required if internal
dyssynergia is present used; decreasing reliance on excretory urogram) are 1st-line medical therapy.
r Sphincter stent prosthesis placement ◦ Rule out upper tract changes (calculi, r If left untreated, ∼50% of men will develop
– Wire mesh stent placed endoscopically hydroneprhosis) significant complication.
r Serum chemistry
– Bridges midprostatic to bulbous urethra (2)[A]
◦ Maintains caliber of membranous urethra at – Confirm normal renal function and electrolyte
balance
42 French
◦ Suprapubic tube cystostomy may be required in Patient Resources
perioperative period N/A
113
DIABETES MELLITUS, UROLOGIC CONSIDERATIONS

Thomas M. Facelle, MD
r Bladder cancer r Voiding dysfunction

BASICS – Increased incidence and mortality seen in men and – UA, C&S
women with DM (4) – Urine specific gravity if polyuric: Dilute if <1.007
DESCRIPTION – DM medication pioglitazone associated with – Metabolic panel including serum creatinine
r Hyperglycemia with secondary metabolic increased bladder cancer risk r Infertility
abnormalities – Testosterone, FSH, LH, prolactin
r Two subtypes including insulin deficiency (DM1) and ASSOCIATED CONDITIONS
r Obesity – Semen analysis
insulin resistance (DM2) r Metabolic syndrome Imaging
EPIDEMIOLOGY r New onset diabetes after transplant (NODAT) r UTI
Incidence – Seen in up to 30% of nondiabetic renal transplant – Consider CT scan if symptoms severe to rule out
r 30% with DM1 and 10–40% with DM2 will develop patients urolithiasis and/or emphysematous pyelonephritis
kidney failure. r Papillary necrosis especially if flank pain
r 59% with DM will have urologic r Retrograde ejaculation – R/O papillary necrosis
r ED
complications/symptoms
GENERAL PREVENTION – Cavernosal Doppler ultrasound (select cases)
Prevalence r Glycemic control r Voiding dysfunction
8.3% of US population in 2010 was diabetic (1) r Weight reduction
– Renal and bladder ultrasound
RISK FACTORS Diagnostic Procedures/Surgery
r Likely genetic and environmental interplay for DM1 r Voiding dysfunction
r Genetic predisposition for DM2 DIAGNOSIS
– Post-void residual (PVR)
– Environmental: Visceral obesity for DM2 HISTORY ◦ Via straight cath or bladder scan
r General ◦ Generally acceptable if <150 mL
Genetics
r DM1: Approx one-third genetic contribution – Polyuria, polydipsia – Voiding diary: Voiding volumes and frequency
– HLA-DR3, HLA-DR4 – Weight loss, malaise – Uroflow
r Strong hereditary component for DM2 – Family history ◦ Normal 20–25 mL/s in men, 25–30 mL/s in
– 70% twin concordance after age 40 – ED, especially in younger man women
r UTI ◦ Diminished if <10 mL/s
– Several loci identified affecting pancreatic B-cell
function and propensity to visceral obesity – Recurrent UTI (may be asymptomatic) – Cystometrogram (CMG): Capacity, voiding
– Fever, nausea, vomiting, flank pain pressure, detrusor instability
PATHOPHYSIOLOGY – Dysuria, hematuria
r Urinary tract infections (UTIs) Pathologic Findings
r Voiding dysfunction r Diabetic nephropathy
– Neutrophil dysfunction due to hyperglycemia
– Urgency, frequency, weak stream, retention – Microangiopathy and glomerulopathy (5)
– Patients with DM are at increased risk and are r Bladder cancer
classified as “complicated” UTI due to risk of ◦ Thickened glomerlular capillary basement
progression to more severe manifestations such as – Hematuria, pioglitazone use membrane; diffuse mesangial sclerosis; nodular
abscess, emphysematous pyelonephritis, and PHYSICAL EXAM glomerulosclerosis
papillary necrosis r Flank – Ischemia leads to tubular atrophy and interstitial
– UTI increased incidence in women with DM but – CVA tenderness fibrosis
not men r Abdomen – Renal artery atherosclerosis
– 80% have upper tract infections – Distended bladder, bladder mass DIFFERENTIAL DIAGNOSIS
– Often atypical organisms, eg, yeast r External genitalia r UTI: Cystitis, pyelonephritis, emphysematous
– Risk of xanthogranulomatous pyelonephritis (XGP) – Phimosis, balanitis, yeast dermatitis pyelonephritis, emphysematous cystitis, XGP,
with stones – Testicular atrophy, varicocele urolithiasis, papillary necrosis, perinephric abscess,
r Erectile dysfunction (ED) sexually transmitted urethritis
– Peyronie plaques
– 3× more common in men with DM r Rectal r Voiding dysfunction: Bladder outlet obstruction,
– 15% at age 30, 55% at age 60 (2) – Tone, bulbocavernosus reflex urethral stricture, neurogenic bladder, UTI,
– 12% of men diagnosed with DM due to declining r Prostate interstitial cystitis
sexual function – Symmetry, nodules, tenderness r Polyuria: Excess fluid intake, diabetes insipidus,
– Caused by peripheral neuropathy, arterial renal failure
insufficiency, changes in cavernous smooth DIAGNOSTIC TESTS & INTERPRETATION r Infertility: Ejaculatory obstruction, retrograde
muscle, and endothelial dysfunction Lab ejaculation, varicocele, testicular causes
– Increased rates of hypogonadism r General
r Voiding dysfunction – Fasting glucose >126 mg/dL
– Sensory and motor neuropathy – Oral GTT, 2-hr value >200 mg/dL
– Impaired sensation and detrusor function – Microalbuminuria (30–300 mg/dL) predicts renal
– Chronic bladder distension or overactivity disease
– Incontinence prevalent in women (3) r UTI
r End-stage renal disease (ESRD) – Urinalysis, urine culture, and sensitivities
– DM most common cause (44%) – BUN, creatinine
– Preceded by onset of proteinuria r ED
r Polyuria – Consider testosterone level, esp if low libido
– In setting of glycosuria—osmotic diuresis ◦ if low, follicle-stimulating hormone (FSH) and
r Infertility luteinizing hormone (LH)
– ED and androgen deficiency
114
DIABETES MELLITUS, UROLOGIC CONSIDERATIONS
Complementary & Alternative 3. Goldstraw MA, Kirby MG, Bhardwa J, et al.

TREATMENT Therapies
r UTI
Diabetes and the urologist: A growing problem. Br
J Urol. 2006;99:513–517.
GENERAL MEASURES – Cranberry extract 4. Zhu Z, Zhang X, Shen Z, et al. Diabetes mellitus
r Educate patients regarding urologic manifestations r Voiding dysfunction and risk of bladder cancer: A meta-analysis of
of diabetes – Acupuncture to sacral dermatome cohort studies. PLOS One. 2013;8(2):e56662.
r Glycemic control 5. Alpers CE. The Kidney. In: Kumar V, Abbas AK,
– Dietary improvement, weight loss, exercise Fausto N, Aster J, eds. Robbins & Cotran Pathologic
ONGOING CARE Basis of Disease, 8th ed. Philadelphia, PA:
MEDICATION
PROGNOSIS Saunders, 2009.
First Line
r UTI r Good with tight glycemic control
– DM is an underlying condition that makes any UTI r Onset of proteinuria typically heralds future renal
a complicated UTI failure
ADDITIONAL READING
– Antibiotics (oral vs. intravenous)
– Fluid resuscitation
r Diabetic cystopathy typically permanent r Brown JS, Wessells H, Chancellor MB, et al. Urologic D
COMPLICATIONS complications of diabetes. Diabetes Care. 2005;28:
r ED
r UTI 177–185.
– Oral phosphodiesterase inhibitors (sildenafil, r Costabile R. Optimizing treatment for diabetes
– Upper tract infection
vardenafil, tadalafil, avandafil) mellitus induced erectile dysfunction. J Urol.
r Voiding dysfunction – Staghorn calculi; XGP
– Renal failure 2003;170:S35–S38.
– α-Blockers if outlet obstruction (terazosin, r Voiding dysfunction r Michel MC, Mehlburger L, Schumacher H, et al.
doxazosin, tamsulosin, alfuzosin, silodosin) Effect of diabetes on lower urinary tract symptoms in
◦ Add 5α-reductase inhibitor (finasteride, – UTI
– Upper tract damage/renal failure patients with benign prostatic hyperplasia. J Urol.
dutasteride) if significant benign prostatic 2000;163(6):1725–1729.
– Incontinence
enlargement (eg, >40 g)
– Bladder stones See Also (Topic, Algorithm, Media)
– Anticholinergics for detrusor overactivity r Diabetes Mellitus, Urologic Considerations Image
r Ejaculatory failure – Atonic bladder
r Diabetic nephropathy r Erectile Dysfunction (ED)/Impotence
– α-Agonist (pseudoephedrine)
r Diabetic nephropathy – ESRD r Infertility, Urologic Considerations
– Dialysis dependence r Neurogenic Bladder, General
– ACE inhibitor if proteinuria for renal protection
FOLLOW-UP r Pyelonephritis, Emphysematous
Second Line r Pyelonephritis, Xanthogranulomatous
r ED Patient Monitoring
r General r Urinary tract infection (UTI), Complicated, Adult
– Intraurethral suppository (MUSE)
– Periodic serum glucose r Urinary tract infection (UTI), Complicated, Pediatric
– Intracavernosal injection (alprostadil, Bimix,
Trimix) – Hemoglobin A1C
– Testosterone replacement if androgen deficient – Creatinine
r Voiding dysfunction – Urine protein and microalbumin CODES
r ED
– α3-Agonist (mirabegron) for overactivity
– Testosterone replacement: Check serum
testosterone, prostate-specific antigen (PSA), r 250.40 Diabetes with renal manifestations, type II or
r UTI serial hematocrit for elevation
– Retention: Catheter placement, suprapubic tube r Voiding dysfunction unspecified type, not stated as uncontrolled
r 250.41 Diabetes with renal manifestations, type I
– Urolithiasis: Ureteral stent, nephrostomy tube, – Symptomatology
ureteroscopy, extracorporeal shock wave [juvenile type], not stated as uncontrolled
– BUN/creatinine r 585.6 End stage renal disease
lithotripsy – PVR
– XGP: Nephrectomy – Repeat urodynamics as needed
r ED ICD10
Patient Resources r E10.29 Type 1 diabetes mellitus w oth diabetic
– Penile prosthesis r Centers For Disease Control and Prevention,
r Voiding dysfunction kidney complication
Diabetes Public Health Resource: r E11.29 Type 2 diabetes mellitus w oth diabetic
– Sacral nerve stimulation (InterStim)—efficacy for http://www.cdc.gov/diabetes kidney complication
overactivity and retention r American Diabetes Association: r N18.6 End stage renal disease
– Bladder outlet obstruction: Transurethral resection
http://www.diabetes.org
of prostate, photoselective vaporization of r National Diabetes Education Foundation:
prostate, etc. CLINICAL/SURGICAL
– Urinary diversion (uncommon) http://ndep.nih.gov/
r Infertility PEARLS
– Assisted reproduction REFERENCES r DM predisposes to urinary infections of greater
r Bladder cancer
severity with likely upper tract involvement.
– Transurethral resection, cystectomy 1. Masharani U. Diabetes mellitus and hypoglycemia. r Most common voiding symptom is overactivity.
In: Papadakis MA, McPhee SJ, eds. Current Medical r ED may be the presenting sign of DM.
Diagnosis and Treatment. New York, NY: McGraw r Tight glycemic control is necessary to reduce
Radiation Therapy Hill, 2013.
N/A progression of symptoms.
2. Lue T. Physiology of penile erection and
Additional Therapies pathophysiology of erectile dysfunction. In: Wein,
r Voiding dysfunction A, ed. Campbell-Walsh Urology, 10th ed.
– Bladder training, biofeedback, timed voiding Philadelphia, PA: Saunders, 2011.
– Clean intermittent catheterization (CIC) for
retention
r Erectile dysfunction
– Vacuum erection device
115
DISORDERS OF SEXUAL DEVELOPMENT (DSD)

Luigi Avolio, MD
– P450 side-chain cleavage deficiency, ASSOCIATED CONDITIONS

BASICS MIM#613743, CYP11A1 gene-chr.15q24.1. r Turner syndrome, Klinefelter syndrome, Reifenstein
Autosomal recessive syndrome
DESCRIPTION – 3β-hydroxysteroid dehydrogenase deficiency, r Inguinal hernia
r Congenital condition in which development of MIM #201810, HSD3B2 gene-chr.1p12. r Amenorrhea
chromosomal, gonadal, or anatomic sex is Autosomal recessive r Infertility
atypical (1) – P450 oxidoreductase deficiency, MIM#613571,
r Chromosomal sex is inconsistent with phenotypical POR gene-chr.7q11.23. Autosomal recessive GENERAL PREVENTION
r Prenatal treatment of fetuses at risk for CAH with
sex – 17α-hydroxylase/17,20-lyase deficiency,
r DSD is the result of a discordance among the 3 sex MIM#202110, CYP17A1 gene-chr.10q24.32. dexamethasone
Autosomal recessive r Chorionic villus sample
determination processes (chromosomal, gonadic,
and phenotypic) – 17β-hydroxysteroid dehydrogenase Type 3 r Amniocentesis
r Ambiguous genitalia and intersex disorders are no deficiency, MIM#264300, HSD17B3
longer considered correct terms gene-chr.9q22.32. Autosomal recessive
– Disorder of the Androgen Receptor (AR), DIAGNOSIS
– Classification
◦ Sex chromosome DSD MIM#300068, AR gene-chr.Xq12. X-linked HISTORY
◦ XX DSD recessive r Family anamnesis
◦ XY DSD – Anti-müllerian hormone (AMH) gene or its – DSDs, genital abnormalities, amenorrhea, sterility,
receptor, MIM#300068, AMH gene-chr.19p13.3 hirsutism
EPIDEMIOLOGY (type I), AMHR2 gene-chr.12q13.13 (type II). – Early infant deaths (missed adrenogenital
Incidence Autosomal recessive (2). syndrome)
r 1 in 5,000 live births
r Maternal exposure to androgens
– Congenital adrenal hyperplasia (CAH) represents ALERT r History of maternal virilization (androgen-producing
60–70% of neonatal DSD (1 case per 15,000 live The possible risk of an immediate life-threatening
births) tumor)
adrenal crisis must be considered in case of
Prevalence neonatal salt-wasting CAH and the general status PHYSICAL EXAM
of the child, including hydration, blood pressure, r External genitalia
N/A
and jaundice, should be documented. – Phallic structure (length, breadth, and amount of
RISK FACTORS erectile tissue)
r Family history of DSD
PATHOPHYSIOLOGY ◦ Normal penile length is ≥2.5 cm, and normal
r In utero exposure to androgens r XX DSD penile diameter is ≥0.9 cm
– Ovarian tumors – Disorders of ovarian development ◦ Normal clitoral width is from 2 to 6 mm; length
– Maternal ingestion ◦ (ovotesticular DSD): Ovary may contain some >9 mm unusual
Genetics testicular tissue (unilateral 50%—ovotestis on – Position of urethral meatus
r XX DSD one side and normal gonad in the other side; – Number of orifices in the perineum and their
– 21α-hydroxylase deficiency (21OHD), Mendelian lateral 20%—a testis on one side and an ovary characteristics
Inheritance in Man, MIM #201910 (online on the other; bilateral ovotestis 30%) that – Labioscrotal folds (separated or fused)
reference http://www.ncbi.nlm.nih.gov/omim/) secretes adequate amounts of testosterone and – Asymmetry (ovotesticular DSD can produce
– CYP21 gene-chr.6p21.33. Autosomal recessive AMH virilization on only one side)
– 3β-hydroxysteroid dehydrogenase deficiency, – Disorders of androgen excess r Gonads
MIM #201810, HSD3B2 gene-chr.1p12. ◦ 21-hydroxylase deficiency is the most common – Palpable gonads (testis, very rarely ovotestis)
Autosomal recessive cause of 46XX DSD. Impaired cortisol r Abdomen
– P450 oxidoreductase deficiency, MIM#613571, biosynthesis relieves feedback inhibition and – Mass referable to enlarged uterus
POR gene-chr.7q11.23. Autosomal recessive thus increases ACTH secretion, which leads to
hyperplasia of the adrenals and to disordered
– 11β-hydroxylase deficiency, MIM#103900,
CYP11B1 gene-chr.8q24.3. Autosomal dominant steroidogenesis: As a consequence cortisol Lab
r Karyotype
– Aromatase deficiency, MIM#613546, CYP19 precursors are shunted to androgen synthesis.
r XY DSD r Serum levels of sodium, potassium, and
gene-chr.15q21.2. Autosomal recessive
– Familial glucocorticoid resistance, MIM+138040, – Disorders of testis development 17-hydroxyprogesterone
NR3C1 gene-chr.5q31.3 r Androgens (testosterone, dihydrotesterone,
– Disorders of androgen synthesis
r XY DSD ◦ Deficiency of 7-dehydrocholesterol reductase androstenedione)
– Deficiency of 7-dehydrocholesterol reductase, (DHCR7) results in a failure of cholesterol r Cortisol, gonadotrophins, and AMH levels
MIM#270400, DHCR7 gene-chr.11q13.4. synthesis r Stimulation test with human chorionic gonadotropin
Autosomal recessive – Disorders of androgen action (suspected defect of androgen production)
– Leydig cell hypoplasia, MIM#238320, LHCGR – Persistent müllerian duct syndrome (PMDS)
gene-chr.2p16.3. Autosomal recessive
– Steroid 5α-reductase Type 2 deficiency,
MIM#264600, SRD5A2 gene-chr.2p23.1.
Autosomal recessive
– Steroidogenic acute regulatory protein,
MIM#201710, StAR gene-chr.8p11.23.
Autosomal recessive
116
DISORDERS OF SEXUAL DEVELOPMENT (DSD)
r Müllerian remnants
Imaging
r Abdominal/Pelvic ultrasound (utero presence)
ADDITIONAL READING
– Small asymptomatics are managed conservatively
r Cystogram/genitogram (visualization of vagina, – Symptomatic remnants are treated surgically r Auchus RJ, Chang AY. 46,XX DSD: the masculinised
sinus) (endoscopic incision or unroofing, laparoscopic/ female. Best Pract Res Clin Endocrinol Metab.
r MRI robotic excision) 2010;24:219–242.
r Barbaro M, Wedell A, Nordenström A. Disorders of
Diagnostic Procedures/Surgery ADDITIONAL TREATMENT
r Laparoscopy to define internal anatomy sex development. Semin Fetal Neonatal Med.
Radiation Therapy 2011;16:119–127.
r Cysto/vaginoscopy to confirm anatomy and level of N/A r Barthold JS. Disorders of sex differentiation: a
confluence of urogenital sinus Additional Therapies pediatric urologist’s perspective of new terminology
r Gonadal biopsy to analyze presence of ovarian
N/A and recommendations. J Urol. 2011;185:393–400.
and/or testicular tissue r http://www.ncbi.nlm.nih.gov/omim/ (Online
r Skin biopsy to obtain cellular lines Complementary & Alternative
Therapies Mendelian Inheritance in Man® )
Pathologic Findings Some patient groups strongly advocate to delay any
Identification of ovarian tissue, testicular tissue, surgical procedures until patients are competent to
r Androgen Insensitivity Syndrome (AIS; OR Androgen D
ovotestes, or streak gonads according to related provide informed consensus Resistance Syndrome), Complete (CAIS) and Partial
specific disorders (PAIS)
DIFFERENTIAL DIAGNOSIS r Congenital Adrenal Hyperplasia
r Hypopituitarism ONGOING CARE r Disorders of Sexual Development (DSD) Image
r Hypospadias PROGNOSIS r Disorders of Sexual Development (DSD) Algorithm
r Hydrocele and hernia Many patients can remain fertile (CAH, some r Müllerian Duct Remnants and Persistent Müllerian
r Menstruation disorders ovotesticular DSD, XY DSD 5α-RD) Duct Syndrome (PMDS)
r Microphallus r Pseudohermaphroditism, Male and Female
COMPLICATIONS
r Gonadoblastoma r Acute adrenal insufficiency in CAH not adequately
treated
TREATMENT
r Damages to clitoral innervation (clitoroplasty) CODES
r Stenosis of the vaginal introitus (vaginoplasty)
GENERAL MEASURES r Meatal stenosis, fistula (hypospadias repair) ICD9
r Gender assignment avoiding hasty decision r Rectal injury (urogenital sinus mobilization) r 255.2 Adrenogenital disorders
r Expert evaluation by an experienced r 259.50 Androgen insensitivity, unspecified
FOLLOW-UP r 752.7 Indeterminate sex and
multidisciplinary team
Patient Monitoring pseudohermaphroditism
MEDICATION r Sexual function (adequate vaginal introitus,
First Line adequate penis reconstruction) ICD10
r Newborn with salt-wasting CAH r Risk of gonadoblastoma in gonadal dysgenesis is r E25.0 Congenital adrenogenital disorders assoc w
– Fluid and electrolytes replacement 12% (occurrence of neoplasia is primarily associated enzyme deficiency
– Glucocorticoid and mineralocorticoid replacement with the Y chromosome containing karyotypes) r E34.50 Androgen insensitivity syndrome, unspecified
◦ Hydrocortisone 10 mg/m2 /d r Lifelong psychosocial support mandatory for all r Q56.4 Indeterminate sex, unspecified
◦ Fludrocortisone 0.1–0.2 mg/d patients with DSD
◦ Oral sodium chloride, 1–2 g/d added to formula
or breast milk Patient Resources CLINICAL/SURGICAL
r http://www.hopkinschildrens.org (all DSDs)
Second Line r http://www.accordalliance.org (all DSDs) PEARLS
N/A r http://www.isna.org (all DSDs) r DSD should be managed by a specialized
SURGERY/OTHER PROCEDURES r http://www.caresfoundation.org (CAH) multidisciplinary team.
r Masculinizing genitoplasty (between the ages of 6 r http://www.ahn.org.uk (CAH) r Gender assignment should be made after thorough
and 18 mo) r http://heainfo.org (hypospadias and epispadias) investigation by the team.
– Hormonal treatment with testosterone r http://www.aisdsd.org (androgen insensitivity DSD) r DSD is a heterogeneous group of conditions with
preparation to stimulate phallus different underlying molecular causes. Many disease
– Surgical excision of müllerian structures genes remain to be identified.
– Phalloplasty (hypospadias repair, chordee REFERENCES r Infants with a DSD and who present with truly
correction, scrotal transposition)
ambiguous genitalia are a rare occurrence.
– Orchidopexy 1. Hughes IA, Houk C, Ahmed SF, et al. Consensus
r Feminizing genitoplasty (during the 1st 6 mo of life) statement on management of intersex disorders.
(3) Arch Dis Child. 2006;91:554–563.
– Clitoroplasty preserving innervation to reduce the 2. Ahmed SF, Rodie M. Investigation and initial
size of the gland and shaft management of ambiguous genitalia. Best Pract
– Vaginoplasty and labioplasty to separate vagina Res Clin Endocrinol Metab. 2010;24:197–218.
and urethra from the common urogenital sinus 3. Romao RL, Salle JL, Wherrett DK. Update on the
r Gonads management of disorders of sex development.
– 46XX DSD: Normal ovaries, no treatment Pediatr Clin North Am. 2012;59:853–869.
necessary
– 46XY DSD:
◦ Female gender assigned: Orchiectomy (timing is
subject of debate)
◦ Male gender assigned: Orchidopexy
– Ovotesticular DSD:
◦ Gonadal biopsy
◦ Excision of dysgenetic gonads (streak)
117
DYSFUNCTIONAL ELIMINATION SYNDROME

ASSOCIATED CONDITIONS Diagnostic Procedures/Surgery

BASICS r Vesicoureteral reflux (VUR) r Voiding and stooling diary to assess frequency and
r UTIs volume of voids and stooling frequency and
DESCRIPTION r Encopresis consistency
r Dysfunctional voiding; various symptoms from mild r Incontinence r Uroflowmetry; evaluate pattern
daytime frequency and postvoid dribbling to daytime r VUR – Flow rates different than adults and less reliable;
and nighttime wetting, urgency, urge incontinence, r Urge syndrome curve more diagnostic
pelvic holding maneuvers, and urinary tract ◦ Bell shaped—normal
infections (UTIs) GENERAL PREVENTION ◦ Tower shaped—overactive bladder
r Sometimes referred to as bowel bladder dysfunction None have been identified ◦ Low flat curve—outlet obstruction
(BBD). ◦ Staccato pattern—sphincter overactivity
r Dysfunctional voiding often associated with bowel ◦ Interrupted flow—underactive bladder
dysfunction; constipation, encopresis, or fecal
DIAGNOSIS r Urodynamics; patients refractory to conventional
impaction (1)[C] HISTORY therapy
– Constipation and rectal dilation interferes with r Present typically after toilet training – Evaluate the filling and emptying phases of the
normal bladder function r Diurnal and/or nocturnal enuresis bladder
– No identifiable neurologic cause r Frequency and urgency – Can be done in conjunction with fluoroscopy
EPIDEMIOLOGY r Hesitancy DIFFERENTIAL DIAGNOSIS
Incidence r UTIs r Nonneurogenic neurogenic bladder
Constipation is present in up to 50% of children with r Difficulty stooling, hard or infrequent stools r Neurogenic bladder
dysfunctional voiding (2)[C] r Encopresis r Ochoa syndrome
r Overactive bladder
Prevalence PHYSICAL EXAM
20–30% school-aged children have dysfunctional r Typically normal physical exam r Giggle Incontinence
voiding (3)[C] – Evaluate for neurologic dysfunction
RISK FACTORS – Examine the external genitalia for anatomic TREATMENT
r UTIs causes of symptoms
r Sexual abuse – Evaluate for a distended bladder and palpable GENERAL MEASURES
r Attention deficit/hyperactivity disorder stool r Behavioral modification: Education on voiding
r Stressors during or after toilet training – Consider rectal exam for fecal retention patterns
DIAGNOSTIC TESTS & INTERPRETATION – Timed voiding
Genetics – Correct positions to void
r Ochoa syndrome, a genetic disorder with an Lab
Urinalysis and urine culture; rule out bacteriuria and – Relaxation techniques
autosomal recessive inheritance pattern – Proper hydration
– Associated with dysfunctional voiding glucosuria r Bowel Management
PATHOPHYSIOLOGY Imaging – Education on correlation between the bladder and
r Voiding dysfunction (variable etiologies): r Renal/bladder ultrasound; evaluate for
bowel activity
– Small bladder capacity hydronephrosis, thickened and/or distended bladder, – Daily toilet time
– Large bladder capacity secondary to urine holding post-void residual, stool in the rectum – Dietary modifications; high fiber
r MRI lumbar spine if concern for a neurogenic cause
– Discoordinated voiding with difficulty relaxing the
to evaluate for a tethered cord MEDICATION
sphincter during voiding
r Often associated with constipation r Voiding cystourethrogram to evaluate for VUR in First Line
r Treatment of constipation prior to medications for
– Rectum close to posterior wall of bladder patients with febrile UTIs.
– Also information on bladder capacity and bladder symptoms; disimpaction followed by
– Large amount stool:
◦ Obstruction by compression of the bladder and emptying, and appearance of the bladder and maintenance therapy
urethra – Initial cleanout with laxatives and enemas
bladder neck
◦ Or bladder instability leading to urgency and – Spinning top urethra; widening of the urethra in – Maintain soft daily stools with a combination of
females during voiding fiber, fluids, laxatives, and softeners
frequency
118
DYSFUNCTIONAL ELIMINATION SYNDROME
r Antimuscarinics; overactive bladders FOLLOW-UP See Also (Topic, Algorithm, Media)

– Reduce the intensity and frequency of bladder r Encopresis, Urologic Considerations
Patient Monitoring
contractions r Voiding/stooling diary r Enuresis, Pediatric
r α-Adrenergic blockers; bladder neck obstruction r Uroflowmetry r Incontinence, Urinary, Pediatric
– Relaxation of the bladder neck to improve bladder r Post-void residual monitoring r Urinary Retention, Pediatric
emptying r Urinary Tract Infection, Pediatric
r Prophylactic antibiotics; prevention of recurrent UTIs Patient Resources r Vesicoureteral Reflux, Pediatric
r http://kidshealth.org/parent/general/sick/
until dysfunctional elimination improved r Dysfunctional Elimination Syndrome Image
constipation.html
Second Line r http://kidshealth.org/parent/medical/kidney/
r Tricyclic antidepressants for urge incontinence
recurrent uti infections.html
– Mechanism not known; not FDA approved in r http://www.medicine.virginia.edu/clinical/ CODES
children departments/urology/patients/peds-urology/
SURGERY/OTHER PROCEDURES parents/DysfunctionalEliminationSyndrome-page ICD9
r Biofeedback r 599.0 Urinary tract infection, site not specified D
r Transcutaneous electrical nerve stimulation r 788.3 Urinary incontinence
REFERENCES r 788.41 Urinary frequency
Radiation Therapy 1. Koff SA, Wagner TT, Jayanthi VR. The relationship ICD10
N/A among dysfunctional elimination syndromes, r N39.0 Urinary tract infection, site not specified
primary vesicoureteral reflux and urinary tract r R32 Unspecified urinary incontinence
Additional Therapies infections in children. J Urol. 1998;160:1019.
Clean intermittent catheterization with impaired r R35.0 Frequency of micturition
2. Chase JW, Homsy Y, Siggaard C, et al Functional
bladder contractility constipation in children. J Urol. 2004;171:2641.
Complementary & Alternative 3. Lee SD, Sohn DW, Lee JZ, et al. An epidemiological CLINICAL/SURGICAL
Therapies study of enuresis in Korean children. BJU Int.
r Acupuncture 2000;85:869–873.
PEARLS
– Low utility in children given use of needles r Constipation is often associated with bladder
r Probiotics; prevention of UTIs and treatment of
dysfunction in children.
constipation ADDITIONAL READING r Treatment of constipation alone may lead to
r Cranberry supplements; potential for UTI prevention
r Ballek NK, McKenna, PH. Lower urinary tract complete resolution of urinary complaints.
r Vesicoureteral reflux may resolve after treatment of
dysfunction in childhood. Urol Clin North Am.
voiding dysfunction.
ONGOING CARE 2010;37:215–228.
r Education of the correlation between stooling
r Nijman RJ. Diagnosis and management of urinary
PROGNOSIS incontinence and functional fecal incontinence patterns and voiding complaints is a very important
Most children have resolution of symptoms in a short (encopresis) in children. Gastroenterol Clin North part of treatment; if understanding is poor there is
period of time with behavioral modifications; however, Am. 2008;37:731–748. often low compliance.
some children may have persistence requiring more
intensive management.
COMPLICATIONS
r UTIs
r Urinary incontinence
r Urinary retention
r Hydronephrosis
119
DYSORGASMIA (PAINFUL ORGASM), MALE

John Patrick Mulhall, MBBCh, FACS, FECSM
BASICS r Chronic pelvic pain syndrome (NIH category III
TREATMENT
prostatitis)
DESCRIPTION r Erectile dysfunction (1) GENERAL MEASURES
r Dysorgasmia specifically refers to pain that occurs r Prostate cancer Reassurance that the condition is most often
immediately preceding, at or immediately following self-limiting
orgasm. GENERAL PREVENTION
r The pain is usually located in the penis or testicles None known MEDICATION
but may be present in the lower abdomen, groin, First Line
r α-Blockers (daily initially; if successful attempt
perineum, or elsewhere.
r The severity of pain ranges from mild and of
DIAGNOSIS on-demand) (2).
r Up to 70% of men using α-blockers will have
nuisance value to crippling and may last seconds to HISTORY
hours after orgasm. r Medical history significant improvement in pain.
r The condition is best identified and studied in the r Focusing on assessment of orgasmic pain location, r Side effects include syncope, orthostasis, retrograde
postradical prostatectomy setting. severity and duration. ejaculation, asthenia, and nasal congestion
r Ejaculatory pain may be seen in other conditions r Prior history of radical prostatectomy, radiation – Alfuzosin 10 mg/d
therapy, or CPPS. – Doxazosin start 1 mg/d to max 8 mg
such as chronic prostatitis/chronic pelvic pain
– Silodosin 8 mg/d
syndrome (CP/CPPS), or NIH category III prostatitis, PHYSICAL EXAM – Tamsulosin start 0.4 mg to max 0.8 mg
and is discussed in Section II (“Ejaculation, painful”). r General physical exam
– Terazosin start 1 mg/d to max 20 mg
EPIDEMIOLOGY r Genital exam (although often there are no specific
Second Line
Incidence findings) r Centrally acting pain relievers
r The most frequent correlate of dysorgasmia is r Optimum dose and duration not established
radical prostatectomy and this condition occurs in r Gabapentin
Lab
about 10–15% of patients.
r In this population, the pain is usually self-limiting None are useful – 900 to 1,800 mg/d and given in divided doses
Imaging (3 times a day) using 300 or 400 mg capsules
with most sufferers experiencing complete r Pregabalin
resolution by 2 yr postoperatively None are useful
– Begin dosing at 150 mg/d, increase to 300 mg/d
Prevalence Diagnostic Procedures/Surgery within 1 wk. Maximum dose of 600 mg/d
N/A None
RISK FACTORS Pathologic Findings Case reports exist of excision of retained seminal
r Radical prostatectomy None vesicle following radical prostatectomy with relief of
r Prostate radiation DIFFERENTIAL DIAGNOSIS symptoms (3)
r Chronic pelvic pain syndrome (CPPS) r Penile pain:
Genetics – Penile compressive neuropathy
– Penile trauma Radiation Therapy
None known N/A
– Peyronie disease
PATHOPHYSIOLOGY – Sexually transmitted infection (STI) Additional Therapies
r While unproven one of the postulated mechanisms – Ureteral stone N/A
is that the pain is related to pelvic floor or bladder r Testicular pain:
neck spasm. – Epididymitis Therapies
– This is the rationale for the use of α-blockers. – Orchitis
r Dysorgasmia decreases in frequency and degree N/A
– Testicular tumor
over time after RP. – Trauma
120
DYSORGASMIA (PAINFUL ORGASM), MALE
3. Yamamoto A, et al. Case Reports: Robot-Assisted

ONGOING CARE Seminal Vesiculectomy for Dysorgasmia Following CODES
Seminal Vesicle-Sparing Radical Prostatectomy bjui.
PROGNOSIS org: 29/01/2013. DOI: 10.1002/BJUIw-2012- ICD9
r Recovery is expected following radical r 607.89 Other specified disorders of penis
072-web
prostatectomy. 4. Matsushita K, Tal R, Mulhall JP. The evolution of r 608.89 Other specified disorders of male genital
r At 24 mo, a statistically significant decrease in
orgasmic pain (dysorgasmia) following radical organs
symptoms was seen in one study (4). prostatectomy. J Sex Med. 2012;9(5):1454–1458. r 789.09 Abdominal pain, other specified site
– 72%, 26%, and 7% of patients still complained
of pain at 12, 18, and 24 mo, respectively. ICD10
ADDITIONAL READING r N48.89 Other specified disorders of penis
COMPLICATIONS
r N50.8 Other specified disorders of male genital
N/A r Anothaisintawee T, Attia J, Nickel JC, et al.
organs
FOLLOW-UP Management of chronic prostatitis/chronic pelvic r N53.12 Painful ejaculation
Patient Monitoring pain syndrome: A systematic review and network
meta-analysis. JAMA. 2011;305:78–86.
D
Routine radical prostatectomy follow-up appears most
r Salonia A, Burnett AL, Graefen M, et al. Prevention
appropriate. CLINICAL/SURGICAL
and management of postprostatectomy sexual
Patient Resources
dysfunctions part 2: Recovery and preservation of
PEARLS
N/A r Dysorgasmia is common after radical prostatectomy.
erectile function, sexual desire, and orgasmic
function. Eur Urol. 2012;62:273–286. r It is usually self-limiting.
REFERENCES See Also (Topic, Algorithm, Media) r It is often responsive to α-blocker therapy.
r Ejaculatory Disturbances (Delayed, Decreased, or
1. Mehta A, Stember DS, O’Brien K, et al. Defining the
aetiology of erectile dysfunction in men with Absent)
r Ejaculation, Painful
chronic pelvic pain syndrome. Andrology.
r Post-orgasm Illness Syndrome (POIS)
2013;1(3):483–486.
r Prostatitis, Chronic Nonbacterial, Inflammatory and
2. Barnas J, Parker M, Guhring P, et al. The utility of
tamsulosin in the management of orgasm- Noninflammatory (NIH CP/CPPS III A and B)
associated pain: A pilot analysis. Eur Urol. 2005;47:
361–365.
121
DYSPAREUNIA, FEMALE
Sandip P. Vasavada, MD, FACS
r Factors altering the pain DIAGNOSTIC TESTS & INTERPRETATION

BASICS – Positioning, specific maneuvers, location Lab
– Use of lubricants, condoms, sex toys, hygiene r Urinalysis and urine culture to screen for infection or
DESCRIPTION products cystitis
r Dyspareunia is defined as pain associated with – Specific partners or partner-related factors r Endocervical swabs for gonorrhea, chlamydia, or
sexual intercourse. – Timing of menstrual cycle bacterial vaginosis
– Most often used in associated with female sexual – Bowel or bladder habits r Cervical scrapings or brushings for malignancy and
dysfunction and is the focus of this section. r Urogenital conditions
r Present since 1st (primary) intercourse or acquired human papilloma virus
– Sexually transmitted or urinary tract infections r Vaginal pH, wet mount, or whiff test for bacterial or
(secondary) thereafter. – Complicated pregnancies
r Etiologies can be physiologic and/or psychological. fungal infection
– Endometriosis
– Uterine fibroids Imaging
EPIDEMIOLOGY r Transvaginal ultrasound for reproductive organ or
– Inflammatory bowel disease
Incidence r Urogenital interventions pelvic masses
Lacking disclosure to clinicians and treatment pursuit r Transabdominal ultrasound for abdominal masses
– Surgery or radiation
suggests underestimation – Injections or topical therapy r Pelvic magnetic resonance imaging for urethral
Prevalence r Urogenital trauma diverticula or pelvic masses
Up to a 60% prevalence in women, but varies widely – Vaginal childbirth injuries Diagnostic Procedures/Surgery
by sample and definition – Difficult or forced intercourse r Cystourethroscopy for cystitis, urethritis, urethral
r Systemic conditions diverticula
RISK FACTORS
r Menopause (physiologic or iatrogenic) – Menopause (physiologic or iatrogenic) r Double balloon urethrography for urethral diverticula
r Physical trauma (physiologic or iatrogenic) – Pain disorders or fibromyalgia r Colposcopy for human papilloma virus or
r Psychological trauma (supporting evidence is mixed) – Cancer uterocervical malignancies
r Tissue irritation (infection, inflammation, – Other chronic diseases r Colonoscopy for inflammatory bowel disease or
r Current or prior abuse
malignancy, etc.) colorectal malignancy
r Urogenital anatomy (congenital) – Sexual abuse r Diagnostic laparoscopy for endometriosis or pelvic
– Verbal or physical abuse masses
Genetics
Early menopause should be considered
PHYSICAL EXAM DIFFERENTIAL DIAGNOSIS
r Visual inspection of external genitalia r Congenital
PATHOPHYSIOLOGY – Distribution of pubic hair – Vaginal agenesis, vaginal malformation,
r Pain results from irritation or trauma to the female – Diffuse vulvo-vestibulitis imperforate hymen, rigid hymen, retroverted
reproductive tissues. – Ulcerations, pustules, discharge, or bleeding uterus
r Can be entrance, vaginal, or deep-thrust – Inflamed Bartholin or Skene glands r Gynecologic
dyspareunia per the etiology. – Prolapsed urethra, vagina, or cervix
– Structural: Hymenal remnant, introital or vaginal
– Skin or mucosal lesions suspicious for cancer
ASSOCIATED CONDITIONS r Speculum exam stenosis, prolapse, childbirth, adhesions
r Vaginal atrophy – Cellular: Vaginal atrophy, lichen sclerosis, vulvar
r Urogenital malformations – Diffuse vaginitis or cervicitis hyperplasia, cancer
r Posttraumatic stress disorder (prior physical or – Mucosal rugae, moisture, thinning, or excoriation – Infectious: Sexually transmitted, viral, bacterial
– Ulcerations, pustules, discharge, or bleeding vaginosis, fungal, pelvic inflammatory disease
psychological trauma) – Cystocele, rectocele, or enterocele
r Pelvic inflammatory disease – Allergic: Contraceptive device, condom, latex,
– Vaginal wall masses semen, hygiene product, sex toy
r Endometriosis – Mucosal lesions suspicious for cancer
r Diagnostic sampling with cervical surface scrapings, – Reproductive: Endometriosis, fibroids, ectopic
GENERAL PREVENTION pregnancy, adnexal cyst, ovarian cyst
r Maintenance of vaginal mucosal integrity brushings, and culture swabs – Iatrogenic: Implanted mesh erosion, exposed
r Good hygiene and health maintenance – Ulcerations, pustules, or discharge suture, postoperative fistula
– Masses, skin changes, mucosal changes, bleeding r Urologic
r Palpation of external genitalia, vaginal sidewalls,
– Urethral prolapse, urethral caruncle, urethral
DIAGNOSIS pelvic floor muscles, cervix, and ovaries diverticulum, urethral cancer, urethritis, cystitis
– Bartholin or Skene gland tenderness r Colorectal
HISTORY – Urethral or vaginal sidewall mass
r Description of pain – Inflammatory bowel disease, abscess,
– Surgically placed foreign bodies hemorrhoids, constipation, rectal cancer
– Specific localization: Superficial, deep, anterior, – Pelvic floor muscle tension, spasm, or tenderness r Musculoskeletal
posterior – Cervical motion, ovarian, or adnexal tenderness
– Timing and duration: When starting, throughout, – Vaginismus, pelvic floor muscle spasm, trauma,
– Vaginal cul-de-sac mass or tenderness
after finishing chronic pain disorder, fibromyalgia
r Psychological
– Consistency with intercourse: Occasional;
sometimes, always – Posttraumatic stress disorder, sexual aversion
– Character: Burning, sharp, aching, throbbing disorder, genital sexual arousal disorder
– Associations: Discharge, bleeding, urinary
symptoms, bowel symptoms
122
DYSPAREUNIA, FEMALE

TREATMENT Radiation Therapy r Frenkl TL, Potts JM. Sexually transmitted infections.
N/A
GENERAL MEASURES In: Wein A, Kavoussi LR, Novick AC, Partin AW,
r Behavioral (1,2) Additional Therapies Peters CA, eds, Campbell-Walsh Urology. 10th ed.
r Daily passive dilation with progressive vaginal
– Identify and eliminate any allergy-related hygienic Philadelphia, PA: Elsevier/Saunders; 2012. Chapter
dilators for stenosis 13. pp. 402–416.
or sexual practices r Use of pessary for problematic retroverted uterus
– Encourage using water-based lubrication or r Moore CK. Female sexual function and dysfunction.
r Pelvic floor physiotherapy or biofeedback for muscle
hypoallergenic products In: Wein A, Kavoussi LR, Novick AC, Partin AW,
– Utilize infection prophylaxis like postcoital voiding spasms Peters CA, eds, Campbell-Walsh Urology. 10th ed.
when appropriate for UTI issues r Ultrasound or electrical stimulation for persistent Philadelphia, PA: Elsevier/Saunders; 2012. Chapter
– Psychological counseling, couples therapy, or muscle spasm 30. pp. 823–833.
relaxation exercises as indicated r Tibolone (synthetic steroid) is commonly used in r Rovner ES. Bladder and female urethral diverticula.
r Careful consideration of replacing condoms or other Europe in postmenopausal women with desire and In: Wein A, Kavoussi LR, Novick AC, Partin AW,
barrier devices with another contraceptive arousal disorders Peters CA, eds, Campbell-Walsh Urology. 10th ed. D
Complementary & Alternative Philadelphia, PA: Elsevier/Saunders; 2012. Chapter
MEDICATION 78. pp. 2262–2289.
First Line Therapies
r Ospemifene is an estrogen agonist/antagonist r Education, sex therapy, psychotherapy, and cognitive See Also (Topic, Algorithm, Media)
behavioral therapy are also important in the r Dysorgasmia
indicated for the treatment of moderate to severe
dyspareunia, a symptom of vulvar and vaginal multidisciplinary management of sexual dysfunction r Dyspareunia Algorithm
atrophy, due to menopause including those with a history of sexual abuse. r Dyspareunia, Male
r Currently there are limited studies on the r Sexual Dysfunction, Female
– 1 tablet (60 mg) taken orally once daily with food
– Do not use estrogens or estrogen effectiveness of herbal remedies to aid female r Urinary Tract Infections
agonist/antagonist or fluconazole concomitantly sexual dysfunction in general. r Urogenital Prolapse
r Appropriate dose and duration of antibiotics or r Urethra, Diverticulum, Female (Urethral
antifungals for infection ONGOING CARE Diverticulum)
r Topical estrogen for atrophy considering benefits r Vaginal Atrophy, Urologic Considerations
over systemic forms PROGNOSIS
r Topical corticosteroids for vulvar hyperplasia or r Results vary with etiology and treatment of many is
testosterone for lichen sclerosis long term
r Multimodal approach to any etiology should be CODES
Second Line
N/A most beneficial
ICD9
FOLLOW-UP r 302.76 Dyspareunia, psychogenic
r Laparoscopic endometriosis excision or ablation Patient Monitoring r 625.0 Dyspareunia
r Laparoscopic lysis of adhesions if indicated r Frequent follow-up with initiation of new behavioral r 627.3 Postmenopausal atrophic vaginitis
r Laparoscopic sacral colpopexy for problematic or medical therapies is best
r Upon resolution and improved patient satisfaction ICD10
retroverted uterus r F52.6 Dyspareunia not due to a substance or known
r Urethral diverticulectomy if indicated follow-up may be spaced out
physiol cond
r Excision of implanted mesh, eroded sutures, or other r N94.1 Dyspareunia
foreign body
r Trigger point injections for muscle spasm
REFERENCES r N95.2 Postmenopausal atrophic vaginitis
1. Dhingra C, Kellogg-Spadt S, McKinney TB.

Urogynecological causes of pain and the effect of CLINICAL/SURGICAL
pain on sexual function in women. Female Pelvic
Med Reconst Surg. 2012;18(5):259–267.
PEARLS
2. Fugl-Meyer KS, Bohm-Starke N, Damsted Petersen r Do not discount behavioral interventions.
C. Standard operating procedures for female r Topical estrogen can work wonders.
genital sexual pain. J Sex Med. 2013;10(1):83–93. r Changing the hygiene routine can help.
123
DYSURIA
Mohamed S. Ismail, MBChB, MRCS, PhD
r History of recent surgery such as urethral

BASICS DIAGNOSIS instrumentation or continence surgery and history of
recent catheterization should be obtained to rule
DESCRIPTION out infection, inflammation, and urethral erosion.
r Dysuria is the symptom of discomfort, burning, or ALERT r Sexual history
pain during micturition. Unexplained dysuria may indicate carcinoma in situ
– Sexual behavior
r It is often associated with other lower urinary tract of the bladder.
– The use of contraceptives, diaphragms, condoms,
symptoms. etc.
HISTORY – Previous history of sexually transmitted diseases
EPIDEMIOLOGY r The cause of dysuria can be challenging to diagnose
r Dysuria is frequently associated with other lower and history of urethral scarring
Incidence r Drug history: Drugs associated with dysuria are
r Dysuria accounts for up to 15% of visits to family urinary tract symptoms such as urinary frequency,
ticarcillin, penicillin G, cyclophosphamide, saw
doctors hesitancy, urgency, and nocturia (1)
r In men the incidence increases with age and 5% of r Age and sex (2) palmetto, dopamine
men seeks medical help for dysuria – Dysuria is more common in women PHYSICAL EXAM
r General exam and observation should be recorded
Prevalence – The most common cause in young women is
urethritis, in middle age women gynecologic r Abdominal exam
In the United States the reported prevalence of dysuria
is 25% causes, and in elderly women urinary tract – Inspection: Look for skin rash and abdominal
infection distension which indicate full bladder
RISK FACTORS – The most common cause in young men is – Palpation: Feel for loin tenderness, palpable
See associated conditions urolithiasis and in elderly are benign prostatic bladder, suprapubic tenderness, abdominal
Genetics hyperplasia (BPH) and urinary tract infection masses, and midline pulsation
N/A – Dysuria in children may suggest sexual abuse – Percussion: To detect full bladder or any other
r Onset abdominal mass
PATHOPHYSIOLOGY – Sudden onset symptoms suggest acute bacterial – Auscultation: To rule out other causes of
r Dysuria results from the irritation of the urethra or
infection abdominal distension
bladder by inflammation or irritants – Gradual onset symptoms may suggest Chlamydia r Male genital exam
r The transient receptor potential subfamily vanilloid
trachomatis infection – Look for any penile lesions, urethral discharge,
type 1 receptor (TRPV1) exists in the urethra r Timing of pain meatal stenosis, balanitis, perineal bruising, and
r Inflammatory mediators such as leukotrienes
– At the onset of voiding indicates inflammation abnormalities in the foreskin
activate TRPV1 and result in pain and burning such as urethritis – Examine the scrotum for swelling, tenderness, and
during voiding – At the middle of voiding indicates obstruction testicular masses
ASSOCIATED CONDITIONS such as urethral stricture or BPH – Digital rectal exam to rule out prostatitis, benign
r Bladder or urethral cancer – At the end of voiding usually indicates bladder prostatic enlargement, and prostate cancer
r BPH pathology such as cystitis r Female genital exam (3)
r Connective tissue diseases r Location of pain – Look for vaginal and urethral discharge
– External discomfort associated with vaginal – Vulval lesions such as ulcers, vesicles, and rash
– Behçet disease
infection or inflammation – Identify urethral lumps that indicate urethral
– Reiter (reactive arthritis) syndrome
r Pregnancy – Internal discomfort indicates bladder or urethral caruncle, diverticulum, or stones. Look for signs of
r STD origin atrophic vaginitis
r Associated symptoms – Pelvic exam: Adnexal and cervical tenderness
r Urethral stricture disease
– Frequency, urgency, and suprapubic pain suggest which indicates pelvic inflammatory disease,
r Urinary tract infection urethral tenderness, and urethral masses
diagnosis of interstitial cystitis
r Urolithiasis – Bimanual exam to look for pelvic masses
– Frequency, nocturia, and reduced flow suggest
GENERAL PREVENTION bladder outlet obstruction or urethral stricture DIAGNOSTIC TESTS & INTERPRETATION
r Hydration to flush out the urinary tract – Fever, rigor, and flank pain suggest pyelonephritis Lab
r Women should wipe from front to back after bowel or urolithiasis r Urine dipstick is a useful and easy test to screen for
movements – Urethral discharge in young age indicates sexually urinary tract infection
r Women should empty the bladder immediately after transmitted diseases – A positive test for nitrites is suggestive of urinary
– Vaginal irritation, discharge, and dyspareunia tract infection. A negative test does not rule out
intercourse
r Keep the genital area clean and dry indicate genital tract infection such as: infection
r Avoid irritating soap and vaginal products – Vulvo-vaginitis, atrophic vaginitis, or sexually – A positive leukocyte esterase suggests the
transmitted diseases presence of white blood cells in the urine which is
r Treat infection with antibiotics
– Dyspareunia + dribbling + dysuria (“3 Ds”) associated with inflammation. It has 75%
suggests a urethral diverticulum in females sensitivity to detect infection
– The presence of joint or back pain may indicate r Urine microscopy
connective tissue diseases
– Pyuria is defined by the presence of 3–5 white
– Significant urgency occurs as a result of irritation
blood cells per high-power field
of the bladder trigone and posterior urethras due
– Hematuria is defined by the presence of 3–5 red
to inflammation, bladder stone, or tumor.
blood cells per high-power field
– Oral and genital ulcers, uveitis, vasculitis with
– Sterile pyuria is present in urolithiasis, transitional
dysuria suggest Behçet disease
cell carcinoma, and atypical microorganisms such
as tuberculosis
124
DYSURIA
r Gram staining demonstrate the urinary pathogens REFERENCES

r Urine culture and sensitivity identify the causative TREATMENT
microorganism of urinary tract infection and its 1. Bremnor J, Sadovsky R. Evaluation of dysuria in
antimicrobial sensitivities. Bacterial count of more GENERAL MEASURES adults. Am Fam Physician. 2002;65:1589–1597.
than 1,000 colony forming units is diagnostic r Encourage good hydration 2. Roberts RG, Hartlaub PP. Evaluation of dysuria in
r Vaginal and urethral smears: Important for the r Personal hygiene men. Am Fam Physician. 1999;60:865–872.
diagnosis of sexually transmitted diseases r Protective measures against STD 3. Kurowski K. The women with dysuria. Am Fam
r Vaginal PH measurement, potassium hydroxide r Treat the primary cause Physician. 1998;57:2155–2164.
microscopy, and yeast culture are indicated in
MEDICATION
patients with unexplained or recurrent dysuria
r Chlamydia: Nucleic amplification testing (NAAT) of First Line
r Mainly directed to relief symptoms and treat the
ADDITIONAL READING
vaginal swabs for women or 1st-catch urine for men r Ismail M, Mackenzie K, Hashim H. Contemporary
underlying cause
Imaging r Symptomatic relief can be achieved by using treatment options for chronic prostatitis/chronic
r Renal ultrasound scan in suspected cases of upper
phenazopyridine hydrochloride 200 mg PO TID pelvic pain syndrome. Drugs Today (Barc). D
tract pathology, urolithiasis, and bladder r Urinary tract infections are treated with oral 2013;49(7):457–462.
abnormalities r Saini S, Secord E. Dysuria in a young man. Contemp
r Plain abdominal x-ray in suspected cases of antibiotics according to the causative
microorganism. In men presumptive organisms are Pediatrics. 2014;14.
urolithiasis and emphysematous pyelonephritis and gram negative. Chronic bacterial prostatitis may (http://contemporarypediatrics.modernmedicine.
cystitis require a prolonged course com/contemporary-pediatrics/news/dysuria-young-
r Other imaging modalities can be arranged according r Urethritis in males is typically due to Chlamydia or man?page=full accessed August 8, 2014)
to the suspected diagnosis such as voiding gonorrhea See Also (Topic, Algorithm, Media)
cystourethrography, retrograde urethrogram, r Bacteruria and Pyuria
computerized tomogram with intravenous contrast, Second Line
r Associated symptoms of urgency can be treated r Cystitis, General Considerations
magnetic resonance imaging r Dysuria Algorithm
with antimuscarinic drugs such as solifenacin 5 mg
Diagnostic Procedures/Surgery PO OD r Prostatitis, Chronic Nonbacterial, Inflammatory and
Cystoscopy: Allows careful assessment of the urethra r Associated symptoms of bladder outlet obstruction Noninflammatory (NIH CP/CPPS III A and B)
and bladder. can be treated with α-blockers such as tamsulosin r Prostatitis, General
Pathologic Findings 0.4 mg PO OD r Sexually Transmitted Infections (STI) (Sexually
Based on specific diagnosis Transmitted Diseases [STDs]), General
r Urethra, Stricture, Male
DIFFERENTIAL DIAGNOSIS Surgical management is reserved for specific causes
r Disease of the urinary tract such as stones, bladder tumors, urethral diverticulum, r Urethritis, Gonococcal and Nongonococcal
– Urinary tract infection and bladder outlet obstruction r Urgency, Urinary (Frequency and Urgency)
– Urolithiasis, bladder calculus, crystalluria
– Interstitial cystitis
Radiation Therapy
– Prostatitis (acute, chronic bacterial and chronic
N/A
CODES
pelvic pain syndrome)
– Malignancy (carcinoma in situ, prostate cancer, Additional Therapies ICD9
urethral cancer) Interstitial cystitis is treated by replacing the r 592.9 Urinary calculus, unspecified
r Diseases of the genital tract glycosaminoglycan layer in the bladder using sodium r 597.80 Urethritis, unspecified
– Sexually transmitted disease: Gonorrhea, hyaluronate r 788.1 Dysuria
Chlamydia, and herpes simplex infection Complementary & Alternative
– Vulvo-vaginitis, cervicitis, pelvic inflammatory Therapies ICD10
disease r N20.9 Urinary calculus, unspecified
Acupuncture, nutritional therapy, pelvic floor exercises,
– Epididymitis and biofeedback can be useful complementary r N34.2 Other urethritis
– Urethral diverticulum treatments for dysuria r R30.0 Dysuria
r Systemic diseases
– Connective tissue diseases: Reiter (reactive
arthritis) syndrome and Behçet disease ONGOING CARE CLINICAL/SURGICAL
r Local irritants
PROGNOSIS PEARLS
– Chemicals irritants: Cyclophosphamide, laundry r Prognosis depend on the causative factor
detergents, bubble baths, intravaginal lubricants r Unexplained persistent dysuria should NEVER be
r Urinary tract infection has a good prognosis
– Mechanical irritation: Radiation cystitis ignored; must rule out occult malignancy, such as
r Infants and adolescents carcinoma in situ of the bladder.
COMPLICATIONS
– Labial adhesions Based on the primary diagnosis r Persistent hematuria after adequate treatment of
– Exploratory sexual activity, masturbation dysuria related to UTI must have formal hematuria
r Diverticulosis FOLLOW-UP workup.
Patient Monitoring
Based on the primary diagnosis
Patient Resources
http://www.aafp.org
125
LWBK1391-SEC-E LWBK1391-Gomella ch063.xml September 19, 2014 18:20
EDEMA, EXTERNAL GENITALIA (LYMPHADEMA, PENO-SCROTAL EDEMA)


BASICS r Advanced prostate cancer r Examine for anasarca
r Anasarca r Evaluate for lower extremity edema
DESCRIPTION r Ascites/hepatic failure r Pitting or nonpitting edema of the penile shaft
Pitting or nonpitting edema of 1 or both sides of the r Congestive heart failure and/or scrotal skin
penile shaft and scrotal skin due to the accumulation r Fournier gangrene r Note the presence/correct placement of an
of transudative fluid in the dartos (scrotal) or r Lymphatic obstruction (lymphangitis filariasis) indwelling Foley catheter
subcutaneous layer of the penile skin r Lymphoma r Reduce foreskin in uncircumcised males
EPIDEMIOLOGY r Pelvic or inguinal surgery (eg, pelvic or ilioinguinal r Inspect for skin integrity
Incidence lymphadenectomy) r Bruising or induration with crepitance seen in
The incidence is not well documented r Paraphimosis Fournier gangrene
r Renal insufficiency/peritoneal dialysis r Foul odor associated with Fournier gangrene
Prevalence
Prevalent condition in nursing home and hospitalized r Retroperitoneal lymphadenectomy r Examine testis and epididymis for signs of
patients r Testicular torsion epididymo-orchitis
r Examine scrotum/ spermatic cord in supine and
RISK FACTORS GENERAL PREVENTION
r Chronic liver disease r Maintenance of euvolemia standing position for presence of varicocele
r Transilluminate the scrotum for hydrocele
r Congestive heart failure r Foley catheter care r Examine external inguinal ring for herniation
r Epididymo-orchitis
r Cremasteric reflex test for testicular viability
r Genital trauma or penile fracture
r Evaluate for the presence of inflatable penile
r Hypervolemia DIAGNOSIS
r Indwelling Foley catheter prosthesis (IPP), artificial urinary sphincter (AUS), or
r Lymphoma other foreign body
ALERT
r Medications known to cause lymphedema r Edema of the penis and scrotum in an DIAGNOSTIC TESTS & INTERPRETATION
r Paraphimosis uncircumcised male may indicate paraphimosis, Lab
r Pelvic or inguinal surgery r No specific lab tests
which requires immediate foreskin reduction to
r Peritoneal dialysis avoid glans penis vascular compromise (3). r Urinalysis may suggest infection/epididymo-orchitis
r Radiation to the pelvic or inguinal region r Edema of the scrotum with areas of necrosis or r Elevated brain natriuretic peptide (BNP) associated
r Retroperitoneal surgery devitalized skin may indicate Fournier gangrene with hypervolemia
r Fractional sodium excretion may suggest fluid
r Squamous carcinoma of the penis and requires emergent urologic consultation and
surgical debridement. overload
Genetics r Albumin/pre-albumin levels assess nutritional status
r Fragile X Syndrome—mutation in FMR-1 on X
HISTORY Imaging
chromosome r Acute vs. chronic condition r Scrotal ultrasound (US) confirms thickened
– Physical manifestation of macro-orchidism/scrotal r Acute scrotal pain in a child or young adult may
edema that becomes more apparent in puberty (1) subcutaneous tissue and may suggest etiology.
indicate torsion. r CT may suggest retroperitoneal etiology.
PATHOPHYSIOLOGY r Circumcision: Severe paraphimosis can compromise
r Accumulation of transudate within the the glans penis
subcutaneous tissue of the penile shaft and scrotal r Trauma Physical exam significant for pitting edema of the
skin r Recent inguinal, pelvic or retroperitoneal surgery genital skin
– May be localized to the genital region or part of r History of lower extremity lymphedema Pathologic Findings
more extensive lower extremity edema or massive r History of STDs Edematous subcutaneous tissue of the scrotum and
body edema (anasarca) r Peritoneal dialysis: Dialysate can leak through penile shaft with possible areas of devitalized skin or
◦ In generalized edema capillary hemodynamics necrosis
are altered and fluid moves from vascular space inguinal hernias into the scrotum
r Medication history:
to interstitium according to Starling’s law (2)
– Pantoprazole, sirolimus, and mycophenolate can
Net filtration = LpS × (Hp − Op) cause lymphedema.
Lp = permeability of capillary wall – Angiotensin-converting enzyme (ACE) inhibitors:
S = surface area for fluid movement Angioedema of the genitals reported
r Indwelling Foley catheter
Hp = hydraulic pressure
Op = oncotic pressure – BPH or indwelling Foley catheter patients can
develop epididymo-orchitis.
◦ Hypoalbuminemia contributes to change in
oncotic pressure and worsens edema (2)
– Transient lymphedema can be seen after pelvic
surgery, such as radical prostatectomy or radical
cystectomy
– Often is localized to the peno-scrotal region
r Rarely, sexually transmitted diseases (STDs) such as
lymphogranuloma venereum (LGV) or donovanosis
(granuloma inguinale) may cause lymphangitis and
lymphatic genital obstruction resulting in chronic
fibrosis (elephantiasis) (3)
126
EDEMA, EXTERNAL GENITALIA (LYMPHADEMA, PENO-SCROTAL EDEMA)
r Acute idiopathic scrotal edema
Radiation Therapy
r Angioedema of the genital skin While this can be a cause of genital lymphedema, it Rabinowitz R, Hulbert WC Jr. Acute scrotal swelling.
r Cellulitis may have a role in primary palliative treatment of Urol Clin N Am. 1995:22(1):101–105.
r Chemical or allergic dermatitis prostate, penile, and retroperitoneal malignancies See Also (Topic, Algorithm, Media)
r Elephantiasis causing scrotal edema. r Edema, Lower Extremity, Urologic Considerations
r Epididymo-orchitis Additional Therapies r Fournier Gangrene
r Fournier gangrene Supportive undergarments/briefs for patient comfort r Testicular Torsion
r Hydrocele r Paraphimosis
r Idiopathic scrotal edema (usually children) r Edema, External Genitalia (Lymphedema,
Therapies
r Inguinal hernia N/A Peno-Scrotal Edema) Image
r Paraphimosis
r Retroperitoneal mass
r Squamous carcinoma of the penis
ONGOING CARE CODES
r Testicular torsion PROGNOSIS
r Varicocele Depends on etiology ICD9
COMPLICATIONS r 607.83 Edema of penis
r Skin breakdown/ulceration
TREATMENT r Urinary retention/difficulty voiding r 608.86 Edema of male genital organs E
GENERAL MEASURES r Genital and scrotal compression is NOT
r Scrotal elevation
ICD10
recommended r N47.1 Phimosis
r Genital or scrotal compression NOT recommended r N48.89 Other specified disorders of penis
r Meticulous care of skin breakdown FOLLOW-UP
r N50.8 Other specified disorders of male genital
r Correction of hypervolemia Patient Monitoring
r Physical exam for resolution organs
r Dialysis if due to severe hypervolemia r Monitor underlying condition, appropriate labs,
r Evaluate for urinary retention—Foley catheter if
nutritional status CLINICAL/SURGICAL
indicated
r Immediate postoperative edema usually resolves Patient Resources PEARLS
Sterns RH. Patient information: Edema (swelling)
spontaneously r Determine the patient’s fluid status to rule out
(Beyond the Basics). In: UpToDate, Basow DS, ed.
MEDICATION UpToDate. Wolters Kluwer, Philadelphia hypervolemia as the cause of genital edema.
First Line (www.uptodate.com, accessed August 8, 2014). r Acute scrotal pain, swelling, lack of cremasteric
r Limited utility reflex, and a high-riding ipsilateral testis could
r Diuretics may be of some utility indicate testicular torsion.
r Chemotherapy for lymphoma
REFERENCES r Evaluate for paraphimosis in uncircumcised males.
1. Lachiewicz AM, Dawson DV. Do young boys with r Crepitance, induration, necrosis, and foul odor
Second Line
N/A fragile X syndrome have macroorchidism? suggest Fournier gangrene and require emergent
Pediatrics. 1994;93:992–995. surgical debridement.
SURGERY/OTHER PROCEDURES 2. Sterns RH. Pathophysiology and etiology of edema r Complications of edema may include urinary
r Indicated to address the etiologic process: Testicular
in adults. In: UpToDate, Basow DS, ed. UpToDate. retention and skin breakdown—these should be
torsion, inguinal hernia, penile fracture, or Fournier Wolters Kluwer, Philadelphia (www.uptodate.com, evaluated for and treated accordingly.
gangrene accessed August 8, 2014).
r Manual reduction of foreskin or dorsal slit if
3. Weinberger LN, Zirwas MJ, English JC 3rd. A
necessary to address paraphimosis diagnostic algorithm for male genital oedema. J Eur
r Rarely, radical excision with gracilis flap may be Acad Dermatol Venereol. 2007;21(2):156–162.
required for severe refractory cases
127
EJACULATION, PREMATURE (PREMATURE EJACULATION)

Elizabeth K. Peacock, MD
James S. Rosoff, MD

BASICS r Erectile dysfunction
Lab
r General anxiety Usually unnecessary
DESCRIPTION r Situational anxiety
r Definition of premature ejaculation (PE) remains r Depression
Imaging
controversial: N/A
r Substance abuse
– ISSM (2008): Ejaculation within about a minute r Relationship distress Diagnostic Procedures/Surgery
and inability to delay ejaculation with all or nearly r Prostatitis N/A
all vaginal penetrations causing negative personal Pathologic Findings
consequences (1) GENERAL PREVENTION N/A
– WHO (2004): Inability to delay ejaculation with N/A
ejaculation before/soon after starting intercourse DIFFERENTIAL DIAGNOSIS
(15 s) r Erectile dysfunction
– AUA (2004): Ejaculation sooner than desired, DIAGNOSIS r Generalized anxiety disorder
before or shortly after penetration that causes r Other anxiety states
distress to 1/both partners HISTORY r Substance abuse
r Time to ejaculation is essential
– EAU (2001): Inability to control ejaculation for
sufficient time before vaginal penetration – Duration/frequency of PE
– APA (2001): Persistent or recurrent ejaculation – Rate of occurrence of PE TREATMENT
with minimal sexual stimulation – Degree of sexual stimulation causing PE
r May also be classified as primary (lifelong PE) or – Nature/frequency of sexual activity including GENERAL MEASURES
foreplay, masturbation, and intercourse r Behavioral treatment:
secondary (acquired PE) r Discuss length of time experiencing PE, perceived
r ICD-10 uses 15 s of intravaginal ejaculatory latency – Stop–squeeze method (Masters and Johnson)
lack of control, and resultant sexual dissatisfaction involves removal of penis at point of ejaculation
time (IELT) as a cutoff r Any indication of ED with squeezing of glans or frenulum
EPIDEMIOLOGY r Issues with the partner, such as dyspareunia or other – Start–stop method (Seman) involves a pause in
Incidence medical problems intercourse at point of ejaculation
Unknown r Rule out symptoms consistent with cystitis or – High initial success rates are reported, but poor
prostatitis long-term rates are present due to the
Prevalence time-consuming nature of treatment
r PE is the most common sexual dysfunction in men r Medication history: Consider PE due to withdrawal
r Psychotherapy may be beneficial
<40 from narcotics or trifluoperazine (Stelazine) r Combination of pharmacotherapy and
r Approximately 20–30% in this group r Sexual History
– Global to all sexual encounters, or with specific psychotherapy is suggested as current model for
RISK FACTORS situations and/or partners treatment
r Increased levels of arousal due to new partner or
– Religious upbringing
situation – Early sexual experiences
r Low frequency of sexual activity
– Sexual relationships, past and present
Genetics – Conflicts or concerns within current relationship
Polymorphism in the serotonin transporter promoter – Traumatic sexual experiences
region (5-HTTLPR) may play a genetic role in the PHYSICAL EXAM
etiology and/or treatment of PE, though this is r Complete physical exam with focus to rule out
controversial. biologic causes including recent pelvic surgery or
PATHOPHYSIOLOGY infectious source
r Serotonin receptor stimulation r Rectal exam to assess for prostatitis
(5-hydroxytryptamine): r Rare to have findings on exam that would define
– Serotonin 5-HT2c receptors inhibit ejaculation, etiology or change management
5-HT1a receptors facilitate ejaculation
– Hyposensitivity of 5-HT2c or hypersensitivity of
5-HT1a may cause PE
– Increase in serotonin transporter (5-HTT) may play
a genetic role in PE
r Consider psychological factors, hormone alterations,
penile sensitivity, circumcision status, chronic
prostatitis as potential causes though with limited
evidence supporting these
128
EJACULATION, PREMATURE (PREMATURE EJACULATION)

First Line ONGOING CARE
r No medications are approved for treatment of PE in Bejma JP, Hellstrom WJG. Premature ejaculation. AUA
the United States PROGNOSIS Update Series. 2007;26:366–372.
– SSRIs: Varies by treatment modality. May have up to 80%
success rate with medication and/or behavioral See Also (Topic, Algorithm, Media)
◦ Elevates level of serotonin in synapse that results r Dysorgasmia (Painful Orgasm), Male
in prolongation of ejaculatory latency time modification r Ejaculatory Disturbances (Delayed, Decreased, or
◦ 1st-line pharmacotherapeutic approach COMPLICATIONS Absent)
(off-label) r Medications carry side effects, but complications of r Ejaculation Premature Algorithm
◦ Daily treatment with PO paroxetine 20–40 mg PE are limited
(greatest evidence), sertraline 25–200 mg, r Rarely, a problem with fertility may exist due to
fluoxetine 5–20 mg inability to complete intercourse
◦ Newer agents have not been effective r May provoke anxiety or depression if PE is severe
CODES
(fluvoxamine/venlafaxine) r May interfere with development of sexual
◦ Dapoxetine approved in Europe only for ICD9
relationship 302.75 Premature ejaculation
on-demand dosing for PE
– Topical agents: FOLLOW-UP ICD10
◦ EMLA: Lidocaine–prilocaine 2.5% cream Patient Monitoring F52.4 Premature ejaculation
◦ TEMPE: Metered-dose aerosol spray with N/A
lidocaine 7.5 mg and prilocaine 2.5 mg per
spray Patient Resources
CLINICAL/SURGICAL
E
Urology Care Foundation. http://www.urologyhealth.
Second Line org/urology/index.cfm?article=122 PEARLS
r Clomipramine:
r Exact definition of PE remains controversial.
– Tricyclic antidepressant
– Daily treatment with 25–50 mg or on-demand REFERENCES r Combination of pharmacotherapy (off-label use) and
treatment with 50 mg 5 hrs prior to intercourse psychotherapy is likely the most beneficial treatment.
r Tramadol (synthetic opioid analgesic) with potential 1. McMahon CG, Althof S, Waldinger MD, et al. An
evidence-based definition of lifelong premature
treatment role in PE (little evidence) (2) ejaculation: Report of the International Society for
SURGERY/OTHER PROCEDURES Sexual Medicine Ad Hoc Committee for the
CT-guided cryoablation of unilateral dorsal penile Definition of Premature Ejaculation. BJU Int.
nerve (single study, 24 patients) (3) 2008;102(3):338–350.
2. Montague DK, Jarow J, Broderick GA, et al. AUA
guideline on the pharmacologic management of
Radiation Therapy premature ejaculation. J Urol. 2004;172(1):
N/A 290–294.
Additional Therapies 3. David Prologo J, Snyder LL, Cherullo E, et al.
European Medicines Agency’s Committee for Percutaneous CT-guided cryoablation of the dorsal
Medicinal Products for Human Use (CHMP) has penile nerve for treatment of symptomatic
recommended authorization of a cutaneous spray premature ejaculation. J Vasc Interv Radiol.
containing a mixture of 150 mg lidocaine and 50 mg 2013;24(2):214–219.
prilocaine per milliliter applied to the glans
Therapies
N/A
129
EJACULATORY DISTURBANCES (DELAYED, DECREASED, ABSENT)

Pravin K. Rao, MD
PATHOPHYSIOLOGY
BASICS r Normal ejaculation: DIAGNOSIS
– Central control in multiple brain regions
DESCRIPTION ◦ Can promote or inhibit ejaculation HISTORY
r Anorgasmia or delayed orgasm/ejaculation r Duration of symptoms
– Sympathetic (T12–L3):
– Difficulty/inability to reach orgasm ◦ Hypogastric nerve (thoracolumbar) r No defined criteria for diagnosis of delayed
r Low volume ejaculate ◦ Seminal emission by contraction of epididymis, ejaculation
– Suspect if <1.5 cc ejaculate volume vas deferens/ampulla, seminal vesicle (SV), and – Mostly normal men ejaculate after 4–10 min of
r Aspermia prostate smooth muscle penetration
– Orgasm with zero ejaculate volume ◦ Bladder neck closure preventing retrograde – Presence of significant distress to patient or
r Retrograde ejaculation ejaculation partner important to diagnosis
– Parasympathetic (S2–S4): r Presence or absence of orgasm
– Sperm seen in post-ejaculatory urine
r Ejaculatory duct obstruction (EDO) ◦ Pelvic nerve r Perceived ejaculate volume
◦ Gland secretions of prostate SV r Sources of stress/psychological disturbance
– Congenital, acquired, iatrogenic
r Failure of emissions – Somatic (S2–S4): r Past medical history
◦ Pudendal nerve r Retroperitoneal and genitourinary operations
– Can also cause low/zero volume ◦ Efferents from sacral cord r Family history of cystic fibrosis
EPIDEMIOLOGY ◦ Contraction of bulbocavernosal and
– See vas deferens, congenital absence
Incidence ischiocavernosal muscles r Medications:
r Increased in aging (age 50–80 yr) men with ◦ Relaxation of external urethral sphincter
◦ Projectile expulsion of ejaculate – Antidepressants/antipsychotics
BPH/LUTS (1)[B] – Sensory – Bladder outlet medications
– 46% decreased ejaculation ◦ Pudendal nerve – Antihypertensives (clonidine)
– 5% anejaculation ◦ Tactile stimulation of penis can activate – Methyldopa
r Men on tamsulosin 0.8 mg ejaculatory reflex PHYSICAL EXAM
r Anorgasmia/Delayed orgasm r Absence or diminished development of epididymides
– ∼90% report decreased ejaculatory volume
(2)[B] – Hypogonadism and vasa deferentia
r Selective serotonin reuptake inhibitors (SSRIs) – Medication side effect – Congenital bilateral or unilateral absence of the
– Psychological/Psychiatric (depression) vas deferens (CBAVD/CUAVD)
– 16–37% delayed or difficult orgasm r Retrograde ejaculation r Enlarged SV
r Anorgasmia is rare:
– Damage to ejaculatory nerves/reflexes – EDO
– 0.14–0.4% in general population r Hypospadias or epispadias
– Bladder neck surgery or dysfunction
Prevalence – Medications affecting bladder neck – Hypogonadism
N/A r Low volume ejaculate
RISK FACTORS – Poor development/absence of accessory sex
r Age organs Lab
r Semen analysis
r Benign prostatic hyperplasia – Retrograde ejaculation or functional problem
– Medications affecting accessory glands – Volume: Suspect if ejaculate volume <1.5 cc
r Lower urinary tract symptoms
– Decreased prostate and SV secretions seen in – Concentration: Low volume azoospermia
r Prostatitis/Ejaculatory duct stones suspicious for EDO
r Depression and related medications hypogonadism
r Ejaculation requires intact, properly developed, and – Absence of seminal fructose suggests EDO
r Hypogonadism r Post-ejaculatory urinalysis (PEU): >10–15
coordinated accessory sex organs, nerves, and
r Hypertension medications sperm/HPF demonstrates retrograde ejaculation
muscles
r Prostate/Urethral /Bladder neck surgery – Congenital, acquired, iatrogenic, infectious, Imaging
r Retroperitoneal lymph node dissection (RPLND) inflammatory causes can all prevent normal r Transrectal ultrasound (TRUS)
r Cystic fibrosis ejaculation – Usually done for low volume azoospermia
r Neurologic conditions/Diabetes – Functional causes may lead to the complaint of ◦ For patients with negative PEU
– Multiple sclerosis, spinal cord injury (SCI), spina decreased force of ejaculate – Normal SV A-P diameter <1.5 cm
bifida, diabetes – Ejaculate volume commonly decreases r MRI
r Rectal surgery by ∼0.03 mL each year with advanced age – Can help identify structural abnormalities
r Radiation therapy ASSOCIATED CONDITIONS
r Psychological/Psychiatric conditions
Genetics r See Risk Factors
N/A
GENERAL PREVENTION
r Avoidance of bladder neck procedures
– Transurethral prostate, bladder neck surgery
r Avoidance/decreased use of medications
– SSRI, α−blockers, 5α-reductase inhibitors
r Nerve sparing at time of RPLND
r Strict diabetic control
130
EJACULATORY DISTURBANCES (DELAYED, DECREASED, ABSENT)
Diagnostic Procedures/Surgery r Autonomic dysreflexia

r TRUS with SV aspiration: Presence of numerous
REFERENCES
– Risk for SCI lesions above T6
sperm suggests obstruction – Can occur with PVS or EEJ 1. Rosen R, Altwein J, Boyle P, et al. Lower urinary
– Rare: Seminal vesiculography – Consider nifedipine 10–20 mg PO 10–15 min tract symptoms and male sexual dysfunction: The
Pathologic Findings before treatment initiated multinational survey of the aging male (MSAM-7).
Scar tissue at ejaculatory duct – Monitor at-risk patients for hypertension, Eur Urol. 2003;44(6):637–649.
tachycardia, sweats 2. Hellstrom WJ, Sikka SC. Effects of acute treatment
DIFFERENTIAL DIAGNOSIS r Retrieval of sperm from bladder with tamsulosin versus alfuzosin on ejaculatory
r Anorgasmia
– See “Retrograde Ejaculation” function in normal volunteers. J Urol. 2006;
r Retarded/Delayed orgasm r Testicular or epididymal sperm retrieval 176(4 Pt 1):1529–1533.
r Erectile dysfunction – Requires IVF/ICSI 3. Sønksen J, Fode M, Löchner-Ernst D, et al.
– May present as inability to reach orgasm, or with – Donor sperm or adoption may circumvent the Vibratory ejaculation in 140 spinal cord injured
weak force of ejaculate need for IVF/ICSI men and home insemination of their partners.
r Retrograde ejaculation Spinal Cord. 2012;50(1):63–66.
r Aspermia ALERT
r EDO (ejaculatory duct obstruction) Men with spinca cord injury (SCI) above the T6 level
are at risk of autonomic dysreflexia (3). ADDITIONAL READING
r Fode M, Krogh-Jespersen S, Brackett NL, et al. Male
TREATMENT ADDITIONAL TREATMENT
GENERAL MEASURES
Radiation Therapy sexual dysfunction and infertility associated with
neurological disorders. Asian J Androl. 2012;14(1):
E
r Remove/modify correctible causes N/A
61–68.
– Medications Additional Therapies r Nelson CJ, Mulhall JP. Male orgasmic disorders:
r Pelvic floor physical therapy for associated
◦ Alfuzosin 21% vs. tamsulosin 90% of patients What do we know? Comtemp Urol. 2007; February
symptoms of pain or voiding symptoms
reported reduced ejaculatory volume (2)[B] r Cognitive-behavioral sex therapy See Also (Topic, Algorithm, Media)
– Psychological/Stress factors r Changing idiosyncratic masturbation style if present r Anorgasmia/Dysorgasmia
r Psychological assessment/counseling r Ejaculation, Painful
r Treat erectile dysfunction Complementary & Alternative r Ejaculation, Premature
r Sexual counseling on techniques for optimal arousal Therapies r Ejaculatory Disturbances (Delayed, Decreased, or
N/A
Absent) Images
MEDICATION r Ejaculatory Duct Obstruction
First Line ONGOING CARE r Retrograde Ejaculation
r Anorgasmia/Delayed ejaculation
r Vas Deferens, Congenital Absence
– No drug treatments FDA approved PROGNOSIS
– Medications that can be tried include: r Depends on the etiology, duration, and severity
◦ Pseudoephedrine r >40% SCI men doing PVS with home insemina-
◦ Yohimbine CODES
r See “Retrograde Ejaculation” tion can achieve pregnancy (3)[B]
COMPLICATIONS ICD9
Second Line r Infertility implications r 302.79 Psychosexual dysfunction with other
N/A r Relationship stress and difficulty specified psychosexual dysfunctions
SURGERY/OTHER PROCEDURES r 608.87 Retrograde ejaculation
r Most procedures reserved for infertility treatment FOLLOW-UP r 608.89 Other specified disorders of male genital
r Transurethral resection of ejaculatory ducts Patient Monitoring organs
(TUREDs) for EDO Based on response to therapy and needs of specific
r Penile vibratory stimulation (PVS) patient ICD10
r F52.32 Male orgasmic disorder
– For anorgasmic/anejaculatory men Patient Resources
N/A r N53.14 Retrograde ejaculation
– Integration with cognitive-behavioral therapy
– High success (>75%) in SCI, though usually for r N53.19 Other ejaculatory dysfunction
fertility purposes
– Procedure: Apply to ventral/frenular region for
1–3 min at a time, with 1 min rest periods, for up CLINICAL/SURGICAL
to 15–20 min PEARLS
– See images of PVS devices:
◦ Ferticare Inclusion of partner in treatment important if
◦ Viberect (dorsal and ventral stimulation) recommending change in sexual practice.
r Electroejaculation (EEJ) via rectal probe
131
ENURESIS, ADULT
Katie S. Murray, DO
Tomas L. Griebling, MD, MPH, FACS
BASICS DIAGNOSIS r Obstructive sleep apnea
r Anxiety or psychological disorders
DESCRIPTION HISTORY r Anatomic abnormalities
r Enuresis is repeated inability to control urine r Have never achieved nocturnal continence of urine
r Idiopathic detrusor instability
– Primary: Starts in childhood and never resolves r Nonspecific urinary symptoms
r Neurologic disorders
and continues into adulthood r Ask about known or potential medical history
– Secondary: New onset in adulthood r Complete surgical and trauma/incident history
r Nocturnal enuresis (NE) is involuntary urination r Obtain record of fluid intake habits TREATMENT
while asleep after the age at which bladder control r Review medications and times of administration
usually occurs r Voiding diaries to evaluate frequency, volume, and GENERAL MEASURES
r Conservative measures have varying success rates
EPIDEMIOLOGY patterns
r International prostate symptom score (IPSS) in men r Education is key when attempting to improve
2.3% of adult population affected (1)[A] enuresis without medical therapy
RISK FACTORS PHYSICAL EXAM r Timed voiding
r Family history of NE r Full urologic exam (pelvic exam in women and DRE r Complete bladder emptying
– If both parents have NE, children have 80% in men) r If associated with BPH in men management with
r Full neurologic exam
chance α-blockers for 5α-reductase inhibitors
DIAGNOSTIC TESTS & INTERPRETATION r Avoidance of caffeine and alcohol
Genetics
r Possibly hereditary Lab r Adjust timing of fluid intake
r Related to site on chromosome 13 r Urinalysis and urine culture: Rule out urinary tract – Restrict fluid intake in evening to reduce urine
infection, hematuria, proteinuria, glycosuria output at night
PATHOPHYSIOLOGY r Creatinine: Rule out renal insufficiency – Take diuretic medications early in a day
r Unknown in most situations
r Urine cytology (if other symptoms such as irritative
r Recognized hypotheses MEDICATION
voiding symptoms make carcinoma a concern) First Line
– Obstructive sleep apnea causing diminished
vasopressin secretion Imaging r If due to prostatic hypertrophy: See Section I
– Disturbance in sensation, cortical arousal, or r Post-void residual bladder scan “Bladder Outlet Obstruction (BOO).”
urinary sphincter function r Renal/ureteral imaging to evaluate for abnormalities r Antimuscarinics or β3-agonists (3)[B]
– Decreased bladder capacity initiating involuntary such as ectopic ureters – Inhibit the effect of acetylcholine at postjunc-
voiding reflex – CT urogram tional muscarinic receptors on detrusor muscle
– Nocturnal polyuria because vasopressin secretion – Renal ultrasound cells
or reduction in renal sensitivity to the antidiuretic Diagnostic Procedures/Surgery – β3-Adrenergic agonist promotes detrusor
(2)[B] r Bladder diaries/frequency–volume charts muscle relaxation
r Cystoscopy with retrograde pyelograms to evaluate – Varying results (5–40%), depends on whether
– Detrusor instability during filling phase
– Urine production increased in recumbent position bladder and ureters detrusor instability is root cause of enuresis
in patients with peripheral edema or congestive r Urodynamic testing (3)[B] – Side effects: Dry mouth, constipation, blurred
heart failure vision, confusion
– Identify anatomical urethral abnormalities r Antimuscarinics
r Normal physiology decreases nighttime, relative to
– Identify anatomical bladder abnormalities
daytime, urinary output. Excess production of urine – Evaluate bladder function for possible neurogenic – Tolterodine (2–4 mg/d)
at night, in the setting of a normal 24-hr urine bladder findings – Trospium XR (60 mg/d)
output, is termed nocturnal polyuria – May find abnormalities in up to 90% of patients – Darifenacin (7.5–15 mg/d)
– Nocturnal polyuria is nighttime excretion of (4)[B] – Solifenacin(5–10 mg/d)
>35% of a 24-hr urine volume r Consider sleep medicine consultation and/or – Oxybutynin (IR 7.5–20 mg/d, XL 5–30 mg/d,
patch twice weekly)
ASSOCIATED CONDITIONS polysomnography if clinical concern for sleep apnea – Fesoterodine (4–8 mg/d)
r Benign prostatic hypertrophy
Pathologic Findings r β3-adrenergic agonist
r Daytime urinary incontinence
N/A – Mirabegron (25–50 mg/d)
r Psychological disorders including depression
r Sleep apnea
GENERAL PREVENTION
r Timed voiding
r Complete bladder emptying
r Avoidance of caffeine and alcohol
r Adjust timing of fluid intake
132
ENURESIS, ADULT
Second Line ADDITIONAL READING

r DDAVP (Desmopressin) (5)[B] ONGOING CARE
http://www.nafc.org/bladder-bowel/bedwetting-
– Not currently FDA approved for this clinical PROGNOSIS 2/adult-bedwetting/
indication (has European regulatory approval) r Many patients may eventually become dry
– Analog of vasopressin – This is more likely in children
– Decreases urine production for about 5 hr See Also (Topic, Algorithm, Media)
– Decreases number of enuresis events but may COMPLICATIONS r Bladder Outlet Obstruction (BOO)
not eliminate it completely r Urea dermatitis r Enuresis Algorithm
◦ Oral 0.2 mg at bedtime; increase to 0.6 mg to r Skin breakdown and superficial ulcers from direct r Enuresis, Pediatrics
response contact of urine on skin r Incontinence, Adult Male
◦ Intranasal formulations are no longer indicated r Psychological effects r Nocturia
for the treatment of primary NE due to risk for – Job changes/decreased work performance r Urge Incontinence
severe hyponatremia with seizures and death – Depression r Urgency, Urinary (Frequency and Urgency)
◦ Side effects: Nasal irritation, dry mouth, sleep – Low self-esteem
disruption, water intoxication, seizures, heart – Decreased social activities
failure, electrolyte disturbances, hyponatremic
coma FOLLOW-UP CODES
◦ Use with extreme caution if at all in geriatric Patient Monitoring
r Long-term follow-up until resolution or satisfaction
patients (>65 yr) due to risk of severe ICD9
hyponatremia and other adverse events by the patient
r Psychological counseling and follow-up if necessary
r 307.6 Enuresis E
r Imipramine (5)[B] r 788.30 Urinary incontinence, unspecified
– Tricyclic antidepressant Patient Resources r 788.36 Nocturnal enuresis
– Mild anticholinergic effect and α-action to r The Simon Foundation for Continence
increase internal sphincter tone (simonfoundation.org) ICD10
r National Association for Continence (www.nafc.org) r F98.0 Enuresis not due to a substance or known
– Side effects: Sleep abnormalities, decrease
appetite, personality disturbances physiol condition
r N39.44 Nocturnal enuresis
SURGERY/OTHER PROCEDURES REFERENCES r R32 Unspecified urinary incontinence
r Consideration after all conservative and
pharmacologic measures have failed 1. Yeung CK, Sihoe JD, Sit FK, et al. Characteristics of
r If urodynamic testing shows detrusor overactivity, primary nocturnal enuresis in adults: An CLINICAL/SURGICAL
may consider additional interventions epidemiological study. BJU Int. 2004;93:341–345. PEARLS
– Botulinum toxin injections 2. Natsume O, Kaneko Y, Hirayama A, et al. Fluid
– Sacral neuromodulation control in elderly patients with nocturia. Int J Urol. r Evaluating for underlying conditions is important in
– Posterior tibial neuromodulation 2009;16:307–313. new onset enuresis.
– Augmentation cystoplasty 3. Yucel S, Kutlu O, Kukul E, et al. Impact of r Social implications are common.
– Urinary diversion urodynamics in treatment of primary nocturnal r Enuresis raised the risk for nighttime falls in elderly.
ADDITIONAL TREATMENT enuresis persisting into adulthood. Urology.
N/A 4. Yeung CK, Sihoe JD, Sit FK, et al. Urodynamic
findings in adults with primary nocturnal enuresis.
Additional Therapies J Urol. 2004;171:2595–2598.
r Psychological counseling
5. Vandersteem DR, Husmann DA. Treatment of
– Assist with coping mechanisms and finding any
primary nocturnal enuresis persisting into
potential underlying issues
adulthood. J Urol. 1999;161:90–92.
Therapies
r Enuresis (bedwetting) alarms
r Timed voiding through the day and night
r Decrease fluid hydration prior to bed
r Empty bladder to completion prior to bed
133
ENURESIS, PEDIATRIC
Ellen Shapiro, MD, FACS
Daniel A. Wollin, MD

BASICS r Neuropsychiatric disorders (children with attention
Lab
deficit hyperactivity disorder 2.7× more likely to r Macroscopic urinalysis (dipstick) to determine
DESCRIPTION have NE) glucosuria, proteinuria or UTI. If glucosuria present,
r Terminology based on 2006 (International r Upper airway obstruction and nocturnal sleep obtain serum glucose at that time
Children’s Continence Society) ICCS standards (1) apnea. Apneic episodes result in increased secretion r Microscopic urinalysis and culture if history of UTI or
– Enuresis is intermittent incontinence of urine while of atrial natriuretic factor symptoms suggestive of infection
sleeping usually referred to as nocturnal enuresis r Constipation
(NE). r Urinary tract infection Imaging
r Children with MNE do not need imaging but a
– This term is used with or without daytime
incontinence or other lower urinary tract GENERAL PREVENTION post-void residual (PVR) by bladder scan is useful
symptoms (LUTSs) MNE may not be preventable but parents should – US: May be considered in male patients, especially
r Monosymptomatic enuresis (MNE) is nocturnal maintain regular voiding and bowel patterns—may those who have failed initial therapy to ensure no
incontinence without other LUTSs help reduce risk of developing NMNE with LUTS. anatomic problem
– MNE is abnormal in children ≥5 yr of age – Some suggest most males with enuresis should
r Non-NMNE may coexist with increased/decreased have bladder US to rule out posterior urethral
voiding frequency, daytime incontinence, urgency,
DIAGNOSIS valves
r Children with history of UTI or NMNE should
hesitancy, straining, a weak stream, intermittency, HISTORY
holding maneuvers, a feeling of incomplete r Detailed history helps determine treatment undergo:
emptying, post-void dribble and genital/LUT pain – Renal US
strategies
r Primary enuresis if the child has been dry for <6 mo; r Number of nights per week enuresis occurs? – PVR
– VCUG when diagnosis suggests posterior urethral
secondary if the child has been dry for at least 6 mo r Symptoms suggestive of underlying bladder
valves or in older males; also used to evaluate for
EPIDEMIOLOGY dysfunction: bulbar stricture (unusual)
Incidence – Drops of urine in underclothing before or after – Abdominal x-ray to evaluate for vertebral
r 15% of normal children have NE at age 5 voiding abnormality; also assesses degree of stool
r Of all children with incontinence: – Frequency of leakage (intermittent or continuous) retention although history is usually sufficient
– Daytime incontinence in child over 31/2 yr of age – MRI of the spine for children suspected of having
– 70% with NE only
– Sudden urge to void a neurogenic bladder as etiology, for those
– 15% with daytime incontinence only
– Straining, posturing, holding maneuvers patients who are compliant and fail all therapeutic
– 15% with daytime incontinence and NE
– Interrupted micturition alternatives for NMNE, or who have a
– 2–3% have NE into early adulthood without
– History of urinary tract infection neurocutaneous signature or other physical
treatment
– Urinary tract malformation findings on the lower spine or physical exam
Prevalence ◦ Spinal cord or vertebral malformation
5–7 million with NE in the United States r Comorbidities that may predict treatment resistance: Diagnostic Procedures/Surgery
r Uroflowmetry: Assesses bladder outlet obstruction
RISK FACTORS – Constipation and encopresis
or hypocontractility; evaluates voiding pattern
NE is multifactorial (see “Pathophysiology”“) – Behavioral, psychological/psychiatric problems
(staccato)
such as ADHD, ADD, autism r Urodynamics: Helpful in evaluating bladder
Genetics – Motor and/or learning disabilities or delayed
r Primary NE tends to be familial: compliance and function in children with severe
development
– Both parents with history of NE—77% of children – Pattern of fluid intake (incl. caffeine) dysfunctional voiding or enuresis due to neurogenic
– If one parent with history of NE—44% of children ◦ Does patient drink during the night? bladder or posterior urethral valves
r Several chromosomes have been linked to NE, r Cystoscopy: Routine use should be avoided
including 12q, 13q, 22q PHYSICAL EXAM – May be helpful in the assessment of select
r Abdominal exam for distended bowel/bladder
– 5HTR2A gene (13q14, serotonin receptor) patients with potential anatomic causes
r Lower back inspection for stigmata of occult spinal
mutation shown to be associated with NMNE Pathologic Findings
dysraphism/tethered cord (sacral dimple, hair tuft, r Neurogenic bladder
PATHOPHYSIOLOGY hemangioma, lipoma or other neurocutaneous
r Complex, involving central nervous system, circadian r Ectopic ureter
signatures, absence of a palpable sacrum, or excess r Posterior urethral valves
rhythm (sleep and diuresis), and bladder function fat overlying the sacral region suggestive of a
abnormalities r Urethral stricture
r 3 major pathogenic mechanisms: lumbosacral abnormality)
r Genital exam for congenital anomalies such as
– Increased arousal threshold DIFFERENTIAL DIAGNOSIS
ectopic ureter or a urogenital sinus (with r Ectopic ureter in girls, extremely rare in boys
– Nocturnal polyuria incontinence due to pooling of urine in the vagina) r Giggle incontinence (enuresis risoria)
– Detrusor overactivity – Labial adhesions in girls
r Some children lack normal nocturnal increase in r Neurogenic bladder
– Urethral abnormalities or phimosis in boys r Nonneurogenic neurogenic bladder
vasopressin secretion leading to nocturnal polyuria, r Gait abnormalities, high arched foot
but not all children with polyuria are vasopressin r Posterior urethral valves (boys)
deficient r Tethered cord
r Overactive bladder leading to “small for age” r Urethral stricture
bladder volume associated with NMNE r Vaginal voiding
134
ENURESIS, PEDIATRIC
SURGERY/OTHER PROCEDURES REFERENCES

r Only in cases of congenital anomalies (ectopic
TREATMENT
ureter, posterior urethral valves, etc.) 1. Neveus T, von Gontard A, Hoebeke P, et al. The
GENERAL MEASURES (2–6) r Neurosurgical intervention for spinal anomalies, standardization of terminology of lower urinary
r Before embarking on any therapy, the interest and tethered cord tract function in children and adolescents: Report
ability of the child and family to comply should be from the Standardization Committee of the
determined ADDITIONAL TREATMENT International Children’s Continence Society. J Urol.
r Patience and compliance should be emphasized Radiation Therapy 2006;176(1):314–324.
because many months may be required to achieve N/A 2. Vande Walle J, Rittig S, Bauer S, et al. Practical
improvement or resolution Additional Therapies consensus guidelines for the management of
r Motivational therapy should be encouraged in r Children with dysfunctional voiding/elimination enuresis. Eur J Pediatr. 2012;171(6):971–983.
almost every case; it is useful in conjunction with syndromes may benefit from elimination retraining 3. O’Flynn N. Nocturnal enuresis in children and
other treatments program and selective use of anticholinergic young people: NICE clinical guideline British
r Behavioral therapy is prerequisite to medications in medications Journal of General Practice. 2011;61:360–362.
most patients with monosymptomatic NE – Use toilet at regular intervals during the day (every 4. Jones EA. Urinary incontinence in children. In:
r Enuresis alarm for MNE works with well-motivated 21/2–3 hr) Litwin MS, Saigal CS, eds. Urologic Diseases in
families and children – Waking children prior to the bedtime of the America. Washington, DC: US Government
– Treatment may take 2–3 mo parents does not promote long-term dryness Publishing Office; 2007.
r Fluid restriction useful and mandatory especially 5. Chase J, Austin P, Hoebeke P, et al. The
– Mechanism of action for behavioral therapy unclear
– Initial cure rate as high as 70%; suggest 4 mo of with dDAVP
r Treat constipation if present—patient should have
management of dysfunctional voiding in children: A E
consecutive dryness report from the Standardization Committee of the
– Relapse can be high, but 50% achieve long-term at least daily bowel movements that are easy for the International Children’s Continence Society. J Urol.
cure child to pass 2010;183(4):1296–1302.
Complementary & Alternative 6. Neveus T, Eggert P, Evans J, et al. Evaluation of
MEDICATION and treatment for monosymptomatic enuresis: A
First Line Therapies
r DDAVP (desmopressin) for NE: r Pediatric biofeedback can be effective in cases of standardization document from the International
dysfunctional voiding. Most helpful in addition to Children’s Continence Society. J Urol. 2010;
– 0.2–0.6 mg PO 1 hr before bed. No fluid intake 183(2):441–447.
2 hr before and 8 hr after bedtime improved voiding and bowel habits
– Success rate ∼20–50% – Child must have sufficient cognitive ability to
– Caution in patients with cystic fibrosis understand teaching
ADDITIONAL READING
(hyponatremic dehydration)
– Tapering schedule imperative 2007 FDA advisory on DDAVP. http://www.fda.gov/
– Give parents copy of FDA warning (Dec 2007)
ONGOING CARE Drugs/DrugSafety/PostmarketDrugSafetyInformation
regarding fluid intoxication and seizures PROGNOSIS forPatientsandProviders/ucm125561.htm
(see “Additional Reading”) r After age 5, spontaneous resolution rate of 15%/yr
Second Line for bedwetters r Dysfunctional elimination syndrome
r Imipramine for NE: Tricyclic antidepressant with r After age 15, <1% have NE r Enuresis, Adult
anticholinergic effects r Over 6.5 yr of follow-up: r Enuresis, Pediatric Algorithm
– Success rates of 25–40%, but relapse rates can be – 91% no longer incontinent during the day r Urinary Tract Infection, Pediatric
high – 84% no longer wet at night r Vesicoureteral Reflux, Pediatric
– 25–50 mg – With UTI history UTI, 82% no longer have
– Tapering schedule imperative infections
ALERT
COMPLICATIONS
r Recurrent UTI
CODES
Imipramine overdose can result in seizure, r Persistence of incontinence and LUTS—requires
hypotension, coma, and fatal arrhythmias; may ICD9
further investigation with VUDs and MRI r 307.6 Enuresis
prolong QT interval. r Persistence of enuresis into adulthood (2–3%) r 788.30 Urinary incontinence, unspecified
r Oxybutynin (anticholinergic) for NMNE: r Social consequences/withdrawal r 788.36 Nocturnal enuresis
– 2.5–5 mg BID–QID (0.2 mg/kg/dose) when PVR
negligible FOLLOW-UP
ICD10
– Available in long-acting form (5–10 mg/d) Patient Monitoring r F98.0 Enuresis not due to a substance or known
r Children with history of UTI or organic causes of
– Success primarily when the medication is used physiol condition
with a well-organized treatment program enuresis should be followed for the specific condition r N39.44 Nocturnal enuresis
r Monitor closely while on medication to treat the r R32 Unspecified urinary incontinence
including voiding 1st thing in the morning,
timed voiding during the day, and regular bowel enuresis (PVR and urinalysis)
habits. Patient Resources
– Patients should be seen in 4–6 wk for evaluation International Children’s Continence Society. CLINICAL/SURGICAL
including urinalysis and PVR. If elevated PVR, http://i-c-c-s.org/parents/ PEARLS
lower the dose and institute double voiding.
r Tolterodine (anticholinergic) for polysymptomatic The primary therapy for all children with NE should be
or daytime incontinence: initial behavioral management before relying on
medications.
– 1–2 mg BID. Also available in long-acting form
(2–4 mg/d)
– More success when the medication is used with
a well-organized treatment program
r Low-dose prophylactic antibiotics for NMNE:
– Helpful for children with recurrent UTI or
bacteriuria with LUTS and voiding dysfunction
– Nitrofurantoin recommended 1–2 mg/kg QHS
135
EPIDIDYMIS, MASS (EPIDIDYMAL TUMORS AND CYSTS)

Ramiro J. Madden-Fuentes, MD
PHYSICAL EXAM r Epididymal cystadenoma/papillary cystadenoma:

BASICS r Scrotal exam – 2/3 associated with von Hippel–Lindau syndrome
– Identify location of mass—single or multiple – 1/3 of all epididymal tumors
DESCRIPTION – Compare with contralateral scrotal contents – 2/3 associated with VHL syndrome
r Small, discernible growth anywhere along the – Evaluate if fixed, mobile, indurated, or – On US, most common appearance is 15–20-mm
epididymis encroaching on other structures solid mass with small cystic components.
r Frequently asymptomatic, discovered on routine – Identify spermatic cord/vas deferens r Epididymitis:
genital exam or incidentally by the patient – Scars from vasectomy—sperm granuloma, – Acute; very tender on exam
r Pain may be presenting symptom epidermal inclusion cyst – Chronic; may have secondary calcification
– Examine testicle for associated masses – Common cause of epididymal pain
EPIDEMIOLOGY r Inguinal exam r Fibroma of epididymis
Incidence – Evaluate for lymphadenopathy r Fibrous pseudotumor
r Not well defined
– Hernia r Funiculitis
r Epididymal cysts are usually asymptomatic and may
DIAGNOSTIC TESTS & INTERPRETATION r Granulomas: Sarcoidosis, TB, histoplasmosis
occur in up to 30% of asymptomatic males r Hernia
r Cysts more common with advancing age Lab
r Adenomatoid tumors—benign and most common r Urinalysis: to evaluate for UTI. Include urine culture r Hydrocele
if suspicious for infection. r Hydrocele of the cord
(1) r Tumor markers if any concern for testicular mass r Leiomyoma
Prevalence – α-Fetoprotein (AFP), β-human chorionic r Malignant epididymal tumor:
Not well defined gonadotropin (β-HCG), lactate dehydrogenase – Primary (very rare): Liposarcoma,
RISK FACTORS (LDH) rhabdomyosarcoma (high on differential in
r Aging r Purified protein derivative (PPD) if TB suspected children), leiomyosarcoma, adenocarcinoma,
r Von Hippel–Lindau disease associated with lymphoma
Imaging
cystadenoma r Scrotal ultrasound – Metastatic: Prostate, kidney, stomach most
r DES exposure in utero: Epididymal cysts common
– Solid vs. cystic
r Prior vasectomy r Papillary cystadenoma
– Location—testicular or paratesticular
– Vascular or avascular r Polyorchidism
Genetics r Sarcoid
Epididymal cystadenoma associated with Von – Cannot reliably differentiate between malignant
or benign r Sperm granuloma:
Hippel–Lindau syndrome (hereditary, autosomal r Chest x-ray if TB suspected
dominant) – Seen in 40% postvasectomy or 2.5% idiopathic in
r If rhabdomyosarcoma and >10 yr old—CT scan of general population
PATHOPHYSIOLOGY – Granulomatous lesion with few giant cells
r Most solid lesions benign (such as adenomatoid the abdomen and pelvic with contrast to evaluate
for retroperitoneal nodes (2)[A] – Consequence of extravasation of spermatozoa
tumors) generally postvasectomy (of vasectomized men
r Malignant lesions uncommon Diagnostic Procedures/Surgery and of general population)
r Metastatic disease is rare but reported r Rarely needed for epididymal lesions r Testicular tumor
r Inguinal approach r TB of the epididymis
ASSOCIATED CONDITIONS r Frozen section for pathology; proceed to
r Von Hippel–Lindau disease r Varicocele
r Young syndrome orchiectomy with high cord ligation if malignant r Vasitis and vasitis nodosa (usually associated with
Pathologic Findings epididymitis)
GENERAL PREVENTION r Benign r Young syndrome (obstructive azoospermia, sinusitis,
r Routine self-exam for identification of scrotal
– Adenomatoid bronchiectasis)
content masses – Epididymal cystadenoma/papillary cystadenoma
r Routine genital exam by physician
– Spermatocele
r Malignant
DIAGNOSIS – Rhabdosarcoma
– Leiomyosarcoma
HISTORY – Fibrosarcoma
r Age: Cystic lesions increase with age – Metastatic carcinoma
r Timing of identification
r Interval growth r Adenomatoid tumor of the epididymis:
r Associated pain – Most common solid tumor of the epididymis
r Dysuria, hematuria, frequency, urgency, r Ectopic tissues:
tenderness—consider epididymitis – Adrenal cortical rests
r Exposure to tuberculosis (TB) – Splenogonadal fusion
r History of sarcoidosis, histoplasmosis r Epidermoid cyst
r History of vasectomy r Epididymal calcinosis
r History of urinary tract infection (UTI) or sexually
transmitted infection
– History of anal insertive intercourse increases risk
of coliform or STD infection
r Recent GU manipulation
– Bacillus Calmette–Guérin (BCG) instillation
– Catheterization
– Transurethral procedure
136
EPIDIDYMIS, MASS (EPIDIDYMAL TUMORS AND CYSTS)
ADDITIONAL READING
Rubenstein RA, Dogra VS, Seftel AD, et al. Benign
GENERAL MEASURES PROGNOSIS intrascrotal lesions. J Urol. 2004;171(5):1765–1772.
r As most epididymal lesions are benign, observation r Adenomatoid tumors
– Benign, excellent prognosis See Also (Topic, Algorithm, Media)
for asymptomatic cystic lesions r Adenomatoid Tumors, Testicular and Paratesticular
r Epididymitis r Rhabdomyosarcoma
r Epididymal Cystadenoma/Papillary Cystadenoma
– Consider sexually transmitted infection as source – In children with low stage disease survival r Epididymis, Mass (Epididymal Tumor and Cysts)
in young men and treat accordingly (See “Sexually may be as high as 90%. Worst stage (IV), Images
Transmitted Infections [STIs] (Sexually Transmitted survival is ∼5.2% (4)[A] r Epididymis, Metastasis to
Diseases [STDs]), General)” r Epididymitis
– Older men more likely to be infected by enteric COMPLICATIONS
r Untreated epididymitis can cause severe systemic r Hydrocele
organisms Escherichia coli, other coliforms, and
Pseudomonas illness. r Paratesticular tumors
– More advanced infections can present with r Scrotum and Testicle, Mass
MEDICATION testicular swelling and pain (epididymo-orchitis). r Sexually Transmitted Infections (STIs) (Sexually
First Line r If radiation or chemotherapy needed:
Transmitted Diseases [STDs]), General
r Epididymitis (3)[A] – infertility, higher risk for secondary neoplasms r Sperm Granuloma
– <35 year old: Consider gonorrhea and including lymphoma, leukemia, soft tissue r Spermatocele
sarcomas
chlamydia
◦ Ceftriaxone IM 500 mg × 1 AND
r Von Hippel–Lindau Disease E
FOLLOW-UP
◦ Azithromycin 1 g PO × 1 Patient Monitoring
– >35 year old: Enteric organisms r Oncologic follow-up if malignant disease
◦ Levofloxacin 500 mg PO daily × 10 days r Teach patient testicular self-exam
CODES
r TB: Treat according to current CDC guidelines
(http://www.cdc.gov/tb/) r 222.3 Benign neoplasm of epididymis
National Cancer Institute. http://www.cancer.gov/
Second Line cancertopics/pdq/treatment/childrhabdomyosarcoma/ r 608.89 Other specified disorders of male genital
r Epididymitis (3)[A] Patient organs
– Doxycycline 100 mg PO BID × 10 days in lieu of ICD10
azithromycin REFERENCES r D29.30 Benign neoplasm of unspecified epididymis
SURGERY/OTHER PROCEDURES r D29.31 Benign neoplasm of right epididymis
r Excision of suspicious lesion via inguinal approach 1. Montgomery JS, Blood DA. The diagnosis and r N50.8 Other specified disorders of male genital
r Frozen section management of scrotal masses. Med Clin North
Am. 2011;95(1):235–244. organs
r If positive for malignancy, radical orchiectomy
r Further surgical therapy guided by pathology but 2. Grimsby GM, Ritchey ML. Pediatric urologic
oncology. Pediatr Clin North Am. 2012;59(4): CLINICAL/SURGICAL
may include retroperitoneal lymph node dissection if 947–959.
rhabdomyosarcoma 3. Workowski KA1, Berman S; Centers for Disease
PEARLS
ADDITIONAL TREATMENT Control and Prevention. Sexually transmitted r Most epididymal lesions are benign and should be
Radiation Therapy diseases treatment guidelines, 2010. MMWR. followed serially.
Use of radiation for local control of 2010;59(No. RR-12):1–110. r Treatment for epididymitis is guided by risk of STIs
rhabdomyosarcoma in young patient is controversial 4. Oberlin O, Rey A, Sanchez de Toledo J, et al. as a source.
Randomized comparison of intensified six-drug r Ultrasound is important to delineate a testicular vs.
Additional Therapies versus standard three-drug chemotherapy for
r Chemotherapy paratesticular origin of the mass.
high-risk nonmetastatic rhabdomyosarcoma and r Ultrasound cannot reliably differentiate malignant
– Vincristine, cyclophosphamide, dactinomycin other chemotherapy-sensitive childhood soft tissue
may have a role in rhabdomyosarcoma solid tumors from benign tumors.
sarcomas: Long-term results from the international r Rhabdomyosarcoma predominantly occurs in
depending on extent of disease and oncologist society of pediatric oncology MMT95 study. J Clin
recommendations (4)[A] Oncol. 2012;30(20):2457–2465. children.
Therapies
N/A
137
EPIDIDYMITIS
Jonathan H. Huang, MD
Wayland Hsiao, MD
r Other infectious causes: PHYSICAL EXAM

BASICS – Bacterial r Epididymal tenderness
◦ Escherichia coli, Salmonella enterica, – Positive in 90–97% of patients
DESCRIPTION Ureaplasma urealyticum, Corynebacterium – Ipsilateral and contralateral testicle may be
r Epididymitis is an inflammatory condition of the pseudotuberculosis, Mycoplasma genitalium, involved
epididymis Brucella ovis, Pseudomonas species, – Spermatic cord may be involved
– Acute epididymitis is a clinical syndrome Toxoplasma species r Erythema of the scrotum
consisting of pain, swelling, and inflammation of – Fungal (more common with HIV) r Fever
the epididymis that lasts <6 wk ◦ Cryptococcus species r Genital exam
◦ Usually infectious but occasionally inflammatory – Filarial – Lesions related to STDs
due to trauma or other cause ◦ Wucheria bancrofti
– Urethral discharge
– Chronic epididymitis is characterized by a ≥6-wk – Viral (more common with HIV) – Ulcerations from Behçet disease
history of symptoms of discomfort and/or pain in ◦ Cytomegalovirus
– Hydrocele
the scrotum, testicle, or epididymis r Noninfectious epididymitis ◦ A reactive process sometimes related to the
r Infectious epididymitis is often associated with – Trauma epididymal inflammation
orchitis – Amiodarone usage r Prostate exam
– Left untreated localized infectious epididymitis can ◦ Antiamiodarone antibodies interact with the
– Rule out prostatitis, especially in males with
lead to more extensive infection to include the elevated concentration of amiodarone in the chronic epididymitis
testicle epididymis, leading to inflammation r Prehn sign
r Thought to be the most common cause of scrotal – Behçet disease
◦ Etiology of epididymitis is unclear – Used to rule out testicular torsion
pain in men – Alleviation of pain, with elevation of the testicle, is
– Sarcoidosis
EPIDEMIOLOGY (1) ◦ Noncaseating granulomas in the epididymis more consistent with epididymitis (negative Prehn
Incidence sign)
lead to inflammation
Estimated at 1 in 100 males in the United States r Chronic epididymitis (>6-wk duration) – Only positive in 8% of children with epididymitis
Prevalence – Inadequately treated acute epididymitis DIAGNOSTIC TESTS & INTERPRETATION
r 42% of cases are in males 20–39 yr old – Postvasectomy syndrome Lab (3)
r Reported from infancy to the elderly population ◦ Reported in 1 in 100 males r Used to rule in a source of infection
r TB r Urethral exudate
RISK FACTORS
r High-risk sexual behavior (multiple sexual partners, – Suspected to be due to hematogenous spread; – Gram stain with at least 5 white blood cells (WBC)
usually a chronic granulomatous reaction per oil immersion field
sex without condoms) r BCG treatment for superficial bladder cancer can ◦ Gram-negative bacilli is suggestive of E. coli
r Poor hygiene
r Being uncircumcised lead to epididymitis infection and underlying cystitis
◦ Intracellular gram-negative diplococci suggests
r Instrumentation or manipulation of the ASSOCIATED CONDITIONS
r Orchitis a diagnosis of N. gonorrhoeae infection
genitourinary tract ◦ Findings of only WBC are suggestive of
– Catheterization, transurethral surgery r Hydrocele
C. trachomatis in 2/3 of cases
r Urinary tract obstruction (benign prostate r Immunosuppression
– Send for culture and sensitivity
hypertrophy, urethral strictures, bladder cancer, r Urine analysis
GENERAL PREVENTION
prostate cancer) r Condom usage – Assess for leukocyte esterase or at least 10 WBC
r Amiodarone usage r Proper hygiene per high power field
r Tuberculosis (TB) r Avoiding unnecessary instrumentation of the r Urine culture (midstream clean catch)
r Treatment with Bacillus Calmette–Guérin (BCG) for – Send for culture and sensitivity
genitourinary tract
superficial bladder cancer r C-reactive protein
r Systemic inflammatory diseases (Behçet disease, – Acute phase protein that is elevated in
ALERT
sarcoidosis) Emergency evaluation for testicular torsion is epididymitis
Genetics indicated when the onset of pain is sudden, pain is – Sensitivity of 96.2%; specificity of 94.2%
r When an STD is suspected, the patient should be
N/A severe, or the test results available during the initial
examination do not support a diagnosis of infection. screened for other STDs, including human
PATHOPHYSIOLOGY immunodeficiency virus (HIV)
r Acute infectious epididymitis (<6-wk duration) is
often due to retrograde spread of infection toward Imaging (4,5)
DIAGNOSIS r Color Doppler scrotal ultrasound (US)
the epididymis
– Infants and children – Hyperemia and swelling in epididymitis
HISTORY ◦ Sensitivity of 70%; specificity of 88%
◦ Associated with congenital genitourinary r Testicular pain ◦ Negative US, when positive clinical findings,
abnormalities – Gradually worsens in epididymitis
◦ Reactive process after a nongenitourinary viral should not necessarily alter management
– Rapid onset and intense in testicular torsion – Decreased blood flow in testicular torsion
infection r Sexual intercourse without condom including anal ◦ Sensitivity of 100%
– Sexually active males
◦ Associated with sexually transmitted diseases receptive unprotected sex – May identify an abscess
r Instrumentation of the genitourinary tract r Radionuclide imaging with Tc-99m pertechnetate
(STDs), often Neisseria gonorrhoeae and r Review of systems may help elucidate other causes
Chlamydia trachomatis – High sensitivity and specificity in differentiating
– Elderly males (ie, amiodarone usage, TB, Behçet disease, testicular torsion from epididymitis
◦ Associated with urinary stasis from benign sarcoidosis) – Rarely used in the United States
r Chronic Epididymitis Symptom Index (CESI) has been
prostate hypertrophy and catheterization
described for cases that last >3 mo
138
EPIDIDYMITIS
r Epididymitis due to TB
r Testicular exploration
REFERENCES
– Systemic antibiotics based on most current CDC
– Not used as 1st-line diagnostic procedure guidelines or local guidelines if available local 1. Centers for Disease Control and Prevention.
– Used when clinical suspicion for testicular torsion guidelines Epididymitis. MMWR. 2010;59(No. RR-12):67–69.
is high r Epididymitis due to intravesical BCG 2. Hori S, Sengupta A, Shukla CJ, et al. Long-term
r In infants and children with epididymitis, up to 75% – Fluoroquinolone (eg, levofloxacin 500 mg once outcome of epididymectomy for the management
have genitourinary abnormalities daily) of chronic epididymal pain. J Urol. 2009;182:
– Renal ultrasound and voiding cystourethrography 1407–1412.
Second Line
are recommended when there are clinical signs of N/A 3. Tracy CR, Steers WD, Costabile R. Diagnosis and
epididymitis and a positive urine culture management of epididymitis. Urol Clin N Am.
Pathologic Findings r Drainage if abscess present
r Inflammation 4. Wu HC, Sun SS, Kao A, et al. Comparison of
r Epididymectomy (2)
r Infection radionuclide imaging and ultrasonography in the
r Possible fibrosis – Not used as 1st-line treatment differentiation of acute testicular torsion and
– Reserved for severe acute or chronic inflammatory testicular disease. Clin Nucl Med.
DIFFERENTIAL DIAGNOSIS epididymitis/epididymalgia 2002;27:490–493.
r Abscess – Patient needs to understand that there is only at 5. Yin S, Trainor JL. Diagnosis and management of
r Chronic pelvic pain syndrome best a 50% chance of pain relief testicular torsion, torsion of the appendix testis,
r Epididymitis (acute vs. chronic) – Outcomes appear improved in the setting of and epididymitis. Clin Pediatr Emerg Med.
r Interstitial cystitis postvasectomy chronic epididymitis 2009;10:38–44. E
r Orchitis – Fertility issues need to be addressed
r Testicular denervation
r Partial spermatic cord torsion
r Prostatitis – Not widely used ADDITIONAL READING
– Reserved for patients who failed conservative
r Referred pain (inguinal hernia renal colic, aneurysm, N/A
management
hip pain, lower back pain) – Pain relief noted in 71% of cases
r Spermatocele See Also (Topic, Algorithm, Media)
ADDITIONAL TREATMENT r Acute Scrotum
r Testicular cancer
r Acute Scrotum Algorithm
r Testicular torsion Radiation Therapy
N/A r Epididymitis Image
r Varicocele
r Behçet Disease
r Scrotal elevation r Orchitis, General Considerations
TREATMENT r Limitation of activity r Scrotum and Testicle, Mass
r Ice packs r Scrotum and Testicle, Mass Algorithm
GENERAL MEASURES
r Acute epididymitis Complementary & Alternative
– Treat infections Therapies
– Decrease inflammation (NSAIDs) N/A
CODES
– Pain control (NSAIDs, prescription pain
medications) ICD9
– Scrotal support ONGOING CARE r 016.40 Tuberculosis of epididymis, unspecified
– Ice/heat based on response r 098.0 Gonococcal infection (acute) of lower
PROGNOSIS
– Avoid sexual activity for at least 1 wk following the r Pain often improves within 48–72 hr after treatment genitourinary tract
initiation of therapy and until symptoms resolved r 604.90 Orchitis and epididymitis, unspecified
r Chronic epididymitis of acute epididymitis
– Induration may remain for up to 4 wk ICD10
– Course of antibiotics is appropriate initially; if no r Chronic cases can be difficult to treat r A18.15 Tuberculosis of other male genital organs
relief observation and reassurance are
COMPLICATIONS r A54.23 Gonococcal infection of other male genital
recommended for mild symptoms
– Scrotal support r Chronic or recurrent epididymitis organs
– Avoid aggravating activities r Epididymal and/or testicular abscess r N45.1 Epididymitis
– Local heat therapy/Sitz baths r Infertility
r Testicular atrophy
MEDICATION (1)
r Fournier gangrene CLINICAL/SURGICAL
First Line PEARLS
r For infections tailor therapy to age and history
FOLLOW-UP
– Ciprofloxacin and other quinolones are no longer r In men <35-yr-old STI/STD with C. trachomatis and
Patient Monitoring
recommended for gonococcal/nongonococcal r Patients should follow up within 3–7 days after N. gonorrhoeae are the most common organisms
infections due to resistance initiation of treatment, especially if symptoms have responsible for bacterial epididymitis.
r Empiric therapy to treat N. gonorrhea and r In older men suspect coliform bacteria.
not improved
C. trachomatis should be initiated pending lab r Infants and children may need to be assessed for r Testicular torsion needs to be ruled out in cases of
results genitourinary abnormalities acute scrotal pain (clinical exam and Doppler US as
– Ceftriaxone 250 mg intramuscularly in a single r Elderly males may need to be assessed for urinary appropriate).
dose along with either tract obstructions
◦ Azithromycin 1 g PO × 1 dose OR r Screening and treatment of partners for STDs
◦ Doxycycline 100 mg orally BID for 10 days
r Epididymitis due to enteric organisms Patient Resources
– Levofloxacin 500 mg orally once daily for 10 days Urology Care Foundation. http://www.
or ofloxacin 300 mg orally twice daily for 10 days urologyhealth.org/urology/index.cfm?article=114
139
EPISPADIAS
Sarah M. Lambert, MD
Pasquale Casale, MD, FACS
Paul H. Noh, MD, FACS, FAAP
Imaging
BASICS DIAGNOSIS r Plain x-ray to assess orientation of pelvic bones;
osteotomies should be done if pubic diastasis
DESCRIPTION HISTORY is >4 cm.
r Congenital anomaly characterized by a dorsal r Usually recognized at birth r Renal/bladder US to assess presence/absence of 2
opening of the urethra, resulting in dorsal chordee r Less severe forms, especially in females, may go
kidneys and presence/absence of hydronephrosis,
and widely displaced corporeal bodies. unrecognized until the child experiences persistent due to increased risk of renal agenesis, ectopic renal
r Often associated with the so-called urinary incontinence after toilet-training or UTIs location, and VUR.
“exstrophy–epispadias complex” a wide spectrum r Urinary incontinence due to open bladder outlet and r Voiding cystourethrogram to assess bladder
of abnormalities that can include classic bladder absence of urinary sphincter. The more proximal the capacity, bladder outlet, presence/absence of VUR.
exstrophy, epispadias, and cloacal exstrophy. urethral meatus, the greater the degree of
– Each of these anomalies is considered to arise incontinence Diagnostic Procedures/Surgery
from the same basic embryologic defect. r There may be a family history of Cystourethroscopy to assess length of urethra,
exstrophy–epispadias, although rare presence/competency of sphincter, bladder
EPIDEMIOLOGY capacity/quality, location/quality of ureteral orifices.
Incidence PHYSICAL EXAM Pathologic Findings
r Males:
r 1 in 117,000 newborn males (1)[A] r N/A
– Displaced meatus, ranging from glans to penile
r 1 in 484,000 newborn females (1)[A]
shaft to peno-pubic region to subsymphyseal DIFFERENTIAL DIAGNOSIS
r Male > Female (3:1–5:1) (1)[A] location r Varying degree of epispadias
– Open urethral plate visible on dorsum of phallus r Classic bladder exstrophy
Prevalence
N/A – Divergent peno-pubic attachments due to public
diastasis, resulting in splaying of corpora
RISK FACTORS cavernosa and a short, pendular penis with dorsal TREATMENT
None identified chordee, similar to that seen in exstrophy
– Ventral hood of foreskin GENERAL MEASURES
Genetics r Usually managed along with bladder exstrophy,
None sporadic – Assess position of testes
r Females: which is commonly present.
PATHOPHYSIOLOGY r Complete continence may not be achieved for
r On the same spectrum of exstrophy – 3 degrees of female epispadias, according to
Davis (1) months to years after initial surgery.
r Failure of medial migration of mesenchyme between r In males, continence may not occur until puberty
◦ I: Urethral orifice appears patulous
the ectodermal and endodermal layers of the cloacal ◦ II: Urethra split dorsally along most of urethra with maturation of prostate.
membrane due to premature rupture of the cloacal ◦ III: Urethra open dorsally along its entire length
membrane MEDICATION
into the bladder neck, rendering patient First Line
r The mesenchyme that forms the genital tubercles at
incontinent. Most common female type Anticholinergic therapy may help with bladder
the 5th wk of gestation fails to migrate completely – Bifid clitoris
toward the midline, resulting in a defect in the development and modeling to promote increased
– Mons pubis depressed and covered in glabrous capacity with good compliance once surgery has
dorsal urethral wall skin increased outlet resistance.
ASSOCIATED CONDITIONS – Labia minora poorly developed and terminated
r Exstrophy anteriorly at clitoris Second Line
r Urinary incontinence – Vagina and internal genitalia usually normal N/A
r VUR: Incidence of 30–75% (1) r Other:
r Inguinal hernias: Incidence of 33% (1) – Should assess for any degree of bladder prolapse r Goals:
r 2.8% concomitant renal anomalies, duplicated or exstrophy – Protection of upper tracts, including correction of
– Low-set umbilicus with exstrophy VUR and maintenance of a low-pressure system
collecting system most common – Public diastasis due to outward rotation of
r Concomitant colorectal anomalies with 1.8% – Achieve urinary continence
innominate bones, usually not as wide as in – Reconstruction of external genitalia for optimal
(exstrophy/epispadias), imperforate anus most exstrophy–epispadias complex functional and cosmetic results
common – Evaluate for inguinal hernias r 1st stage:
GENERAL PREVENTION DIAGNOSTIC TESTS & INTERPRETATION – Bladder closure between 3 to 6 mo of age. Patient
N/A Lab is left with an epispadias
CBC, renal profile – Can also be done as a single stage with bladder
closure and urethral reconstruction known as the
“Complete Primary Repair of Exstrophy.” Higher
incidence of glanular loss than staged repair
– Osteotomies are needed if the pubic diastasis is
4 cm or greater on plain x-ray. It was once
thought that if the surgery was done in the 1st
48 hr of life that osteotomies are not needed.
Current management favors osteotomies to
maximize continence
– Patients need to be immobilized after surgery to
allow pelvic bone healing if osteotomies are
needed
140
EPISPADIAS
r 2nd stage: FOLLOW-UP ADDITIONAL READING

– Typically performed 6 mo to a year after 1st stage Patient Monitoring
r Males: r After epispadias repair: r Hankinson JC, Eldridge MA, Ostrander R, et al.
– Administer testosterone stimulation preoperatively – Remove urethral catheter 1–2 wk after surgery Emotional and behavioral functioning in children
if penile length not adequate. – Regular cystoscopy to assess urethra and bladder with bladder exstrophy-epispadias complex: A
– At 6 to 12 mo of age, perform modified capacity developmental perspective. J Pediatr Urol. 2013;
Cantwell–Ransley epispadias repair, involving – Regular upper tract monitoring with renal/bladder S1477–5131(13):192–197.
tubularization of intact urethral plate with reverse r Lloyd JC, Wiener JS, Gargollo PC, et al.
US to ensure healthy upper tracts.
meatal advancement and transposition of urethra r After bladder neck repair: Contemporary epidemiological trends in complex
ventral to corpora cavernosa – Initiate suprapubic tube capping trials a few congenital genitourinary anomalies. J Urol. 2013;
– Also must correct dorsal chordee by division of weeks after surgery 190(suppl 4):1590–1595.
suspensory ligaments, freeing attachments from r Stec AA, Baradaran N, Gearhart JP. Congenital renal
– Can remove SP tube once PVRS are minimal
undersurface of inferior public ramus, and – Continuation of prophylactic antibiotics until anomalies in patients with classic bladder exstrophy.
medially rotating the corpora cavernosa, and resolution of VUR confirmed and child voiding well Urology. 2012;79(1):207–209.
occasionally performing cavernostomy – Regular upper tract monitoring with US r Stec Stec, Baradaran N, Tran C, et al. Colorectal
r Females: – Urodynamics may be necessary with anomalies in patients with classic bladder exstrophy.
– At 12–18 mo of age, perform genitoplasty and cystometrogram and urethral pressure profilometry J Pediatr Surg. 2011;46(9):1790–1793.
urethroplasty in cases of persistent incontinence or infection r Suson KD, Preece J, Baradaran N, et al. The fate of
– Edges of urethra approximated for tubularization the complete female epispadias and exstrophy
Patient Resources
– Clitoris and labia minora reapproximated r PubMed Health. http://www.ncbi.nlm.nih.gov/ bladder - Is there a difference? J Urol. 2013; E
– Mons may be reconfigured 190(suppl 4):1583–1588.
r 3rd stage: pubmedhealth/PMH0002264/
– Most commonly, Young–Dees–Leadbetter bladder r Epispadias Image
neck reconstruction affords best chance at REFERENCES r Exstrophy, Bladder (Classic Exstrophy)
continence r Exstrophy, Cloacal
– Often, ureters must be reimplanted at same time 1. Gearhart JP, Mathews R. Exstrophy-epispadias
complex. In: Wein AJ, Kavoussi LR, Partin AW, r Exstrophy–Epispadias Complex
due to proximity to bladder neck or VUR. Cohen
technique usually preferred et al. eds. Campbell-Walsh Urology. 10th ed.
Philadelphia, PA: Saunders Elsevier; 2012:
ADDITIONAL TREATMENT 3497–3553. CODES
Further surgery may be necessary to correct
2. Kramer SA, Kelalis PP. Assessment of urinary
complications of initial surgery or to achieve improved
continence in epispadias: Review of 94 patients. ICD9
cosmesis or complete continence. r 752.62 Epispadias
J Urol. 1982;128:290–293.
Additional Therapies 3. Arap S, Nahas WC, Giron AM, et al. Incontinent r 753.5 Exstrophy of urinary bladder
N/A epispadias: Surgical treatment of 38 cases. J Urol. r 753.8 Other specified anomalies of bladder and
Complementary & Alternative 1988;140:577–581. urethra
Therapies 4. Ben-Chaim J, Peppas DS, Jeffs RD, et al. Complete
Psychological: If signs of self-esteem or sexual male epispadias: Genital reconstruction and ICD10
achieving continence. J Urol. 1995;153: r Q64.0 Epispadias
dysfunction arise, psychological therapy plays a crucial
role and should be implemented early on in diagnosis 1665–1667. r Q64.10 Exstrophy of urinary bladder, unspecified
of emotional issues. 5. Gearhart JP, Peppas DS, Jeffs RD. Complete
genitourinary reconstruction in female epispadias.
J Urol. 1993;149:1110–1113. CLINICAL/SURGICAL
ONGOING CARE 6. Mesrobian HJ, Kelalis PP, Kramer SA. Long-term PEARLS
PROGNOSIS followup of cosmetic appearance and genital r Female epispadias is not well recognized. It often
r Continence rates after bladder neck reconstruction function in boys with exstrophy: Review of 53
patients. J Urol. 1986;136:256–258. presents after birth because of complaints of
range from 70% to 87% (2–5).
r Satisfactory cosmesis after penile reconstruction incontinence.
7. Kajbafzadeh AM, Duffy PG, Ransley PG. The r Antenatal ultrasonography may be suggestive of
ranges from 55% to 84% (6,7). evolution of penile reconstruction in epispadias
r Erectile function is almost universally preserved. repair: A report of 180 cases. J Urol. 1995;154: exstrophy–epispadias complex: Findings of
abnormal genitalia, low set umbilical cord, inability
r The ability to participate in satisfactory intercourse 858–861.
to identify bladder on ultrasound.
and to have children is difficult to assess, as this
requires long-term follow-up. Most reports seem to
indicate the majority of patients can have intercourse
and many males have even fathered children.
COMPLICATIONS
r The most common is fistula formation, with an
incidence of 4–40% after urethroplasty in males,
although many of these will close spontaneously
(2,4,7).
r Other less common complications are stricture,
meatal stenosis, wound infection, diverticulum, and
ureteral obstruction.
r If there is tension on the closure, dehiscence is a
major complication that might result.
141
ERECTILE DYSFUNCTION, FOLLOWING PELVIC SURGERY OR RADIATION

Boback M. Berookhim, MD, MBA

BASICS Treatment effects are generally dependent upon the Lab
modality used and are discussed elsewhere. r Generally noncontributory.
DESCRIPTION r If evidence of hypogonadism, check early morning
r Erectile dysfunction (ED), defined as the inability to GENERAL PREVENTION
r Pelvic surgery/RP: serum testosterone.
achieve or maintain an erection for sexual activity, is
very common after major pelvic surgery or radiation. – Cavernous nerve sparing surgery Imaging
r Curative therapy for prostate cancer, particularly – Sparing of accessory pudendal arteries r Duplex Doppler ultrasound of the penis
intraoperatively – Can be used to evaluate for presence of
radical prostatectomy (RP) and radiation therapy r RT:
(RT), are well-defined causes of ED. vasculogenic ED
r ED after pelvic surgery is sudden in onset with – Reducing volume of tissue irradiated is postulated – Peak systolic velocity <30 cm/s indicative of
to reduce likelihood of ED arterial insufficiency
gradual improvement within 24 mo postoperatively.
r ED after pelvic RT has an insidious onset, with a – No definitive evidence supporting use of – End diastolic velocity >5 cm/s indicative of CVOD
intensity-modulated radiation therapy (IMRT), BT, Diagnostic Procedures/Surgery
“honeymoon” period of 1 yr following treatment or proton beam RT to reduce ED
and significant worsening between 3–5 yr. N/A
– Treatment plans limiting RT to the corpora
EPIDEMIOLOGY cavernosa may have a beneficial effect Pathologic Findings
r Penile rehabilitation: N/A
Incidence
Not reported – Signals from studies suggesting early DIFFERENTIAL DIAGNOSIS
rehabilitation (phosphodiesterase Type 5 Inhibitors r Hyperprolactinemia
Prevalence [PDE5i], intracavernosal injections) can impact r Medication induced: Antihypertensives,
r Rates of ED post-RP/RT vary widely due to
posttreatment erectile status after RP and RT psychotropics, antiandrogens
definitions, patient populations, and time-point – Goals: Cavernosal oxygenation, preservation of r Neurogenic ED
following treatment endothelial function, prevention of corporal
r 30–90% after RP r Profound hypogonadism
smooth muscle fibrosis r Psychogenic ED
r 6–90% after RT, including brachytherapy (BT)
– Optimal regimen for rehabilitation is not
r Vasculogenic ED
r Prospective, multicenter, cohort study reported 2-yr understood
ED rates: (1)[B]
– 65% post RP DIAGNOSIS TREATMENT
– 63% post external beam RT
– 57% post BT HISTORY GENERAL MEASURES
r Medical history: Risk factors for general ED r Perform cardiovascular risk assessment to evaluate
RISK FACTORS
r Age – Cardiovascular disease fitness for sexual activity prior to treatment.
r Pretreatment erectile function – Diabetes mellitus r Patient and partner should be informed of relevant
r Quality of nerve sparing – Smoking treatment options, risks, and benefits.
– Peripheral neuropathy
r Surgeon experience and volume MEDICATION
– Depression
r Concomitant androgen deprivation therapy (ADT) – Alcoholism First Line
with RT r Surgical history r PDE5i (2)[A]
r RT dose and duration – Type and date of surgery – Likely to be ineffective immediately after surgery
r Cardiovascular disease and risk factors – Nerve sparing status (if RP or radical cystectomy) given cavernosal nerve injury
r Radiation history – Daily dosing frequently used in rehabilitation
Genetics
r Single nucleotide polymorphisms (SNPs) have been – Dose, template, radiation modality, and date regimens
identified that are associated with ED following RT – Use of ADT – When used on-demand only, decreased
r ED history response noted 2–3 yr after RT
but require validation.
r Genetics of cavernous nerve regeneration following – Validated questionnaires, ie, International Index of – Medications:
RP are under investigation. Erectile Function (IIEF) ◦ Sildenafil 50–100 mg: Onset 15–60 min,
– Onset and severity of ED duration of action 4 hr
PATHOPHYSIOLOGY – Consistency of erectile quality ◦ Vardenafil 10–20 mg: Onset 15–60 min,
r Pelvic Surgery/RP:
– Presence of nocturnal erections duration of action 2–8 hr
– Injury to cavernosal nerves leading to neuropraxia – Prior use of therapy and response ◦ Tadalafil 10–20 mg: Onset 15–120 min,
and lethal axonal damage. duration of action 24–36 hr
– Apoptosis of smooth muscle and endothelium PHYSICAL EXAM ◦ Avanafil 100–200 mg
r General physical exam
within the penis. – Contraindications to PDE5i use:
r Penile exam focusing on presence of tunical plaques
– Potential end-organ failure with corporal smooth ◦ Absolute contraindications: Use of nitrates
muscle fibrosis leading to cavernous venocclusive and penile compliance ◦ Sildenafil: Should be postponed for 4 hr after
dysfunction over time. r Testicular volume and consistency as screening for
taking α-adrenergic antagonists
– Role of arterial injury is not well defined. hypogonadism ◦ Vardenafil: Should not be taken with type
◦ Data suggests preservation of accessory 1A or type 3 antiarrhythmics or patient with
pudendal arteries may help prevent post-op ED. long QT syndrome
r RT: – Side effects: All associated with headache,
– Endothelial cell and microvascular arterial injury dyspepsia, facial flushing
leading to arterial insufficiency and ultimately ◦ Tadalafil: Backache, myalgia
ischemia. ◦ Sildenafil: Blurred/blue vision—reacts with
– Small likely role of cavernous nerve injury PDE6 in retina
following RT.
– RT-induced corporal tissue fibrosis leading to
cavernosal vono-occlusive dysfunction (CVOD aka
venous leak).
142
ERECTILE DYSFUNCTION, FOLLOWING PELVIC SURGERY OR RADIATION
Second Line
r Intracavernosal injection therapy
Therapies
r Data does not support use of trazodone, yohimbine, r Mendenhall WM, Henderson RH, Indelicato DJ, et al.
– Highly efficacious with up to an 89% response
rate post-RP (3)[C] and herbal therapies. These medications are not Erectile dysfunction after radiotherapy for prostate
– Risks include priapism, penile pain, ecchymosis recommended for use in ED by the American cancer. Am J Clin Oncol. 2009;32:443–447.
– Used in a variety of formulations Urological Association r Mulhall JP, Bivalacqua TJ, Becher EF. SOP for the
◦ Single agent: Prostaglandin E1 r Testosterone therapy preservation of erectile function outcomes after
◦ Bimix: Papaverine and phentolamine – May be useful in aiding erectile function recovery radical prostatectomy. J Sex Med. 2013;10:
◦ Trimix: Papaverine, phentolamine, and only in patients with documented hypogonadism 195–203.
prostaglandin E1 – Controversial; must discuss risks/benefits of
r Intraurethral prostaglandin E suppository (MUSE) See Also (Topic, Algorithm, Media)
1 androgen supplementation before initiating r Erectile Dysfunction/Impotence, General
– Variable efficacy therapy, particularly in patients with a history of Considerations
– Penile pain frequently reported, especially in the prostate cancer r Penile Doppler Ultrasound, Indications and
immediate postoperative period
Parameters
SURGERY/OTHER PROCEDURES r Penile Rehabilitation
r Vacuum constriction devices ONGOING CARE r Reference Tables: International IIEF (Sex Function
– Low patient satisfaction given cumbersome PROGNOSIS Survey)
application r Improvement in erectile function can be noted after
– Cooler, cyanotic appearance of vacuum-assisted pelvic surgery, with maximal improvement noted
erection appears “unnatural” to some between 18 and 24 mo postoperatively. CODES
E
r Penile prosthesis implantation r Low likelihood of improvement in erectile quality
– Definitive therapy for patients failing or refusing after 2 yr postoperatively. ICD9
1st- and 2nd-line treatments r Nadir of erectile function 3 to 5 yr after RT.
607.84 Impotence of organic origin
– Generally, postponed until 2-yr post-RP as r Penile rehabilitation likely improves the prognosis of
regeneration of cavernous nerves during this time postsurgical/post-RT ED. Definitive data are pending. ICD10
may preclude need for surgical therapy r N52.31 Erectile dysfunction following radical
– High patient satisfaction in appropriately selected COMPLICATIONS prostatectomy
r Significant effect on patient quality of life r N52.32 Erectile dysfunction following radical
population
– Implant infection and malfunction risk must be – Noted to be strongest predictor of patient cystectomy
discussed with patient preoperatively satisfaction after prostate cancer therapy r N52.39 Other post-surgical erectile dysfunction
r Depression
Radiation Therapy FOLLOW-UP
CLINICAL/SURGICAL
N/A Patient Monitoring
r Variable dependent upon patient response to PEARLS
Additional Therapies treatment.
r Limited data on combining modalities has been r ED after pelvic surgery and RT is highly prevalent
r Close follow-up is recommended in patients on
reported and frequently underestimated in physician
– Level 3 evidence: PDE5i + either transurethral or rehabilitation protocols to evaluate for erectile marketing materials.
intracavernosal injection therapy generate better recovery. r ED after pelvic surgery is immediate in onset with
efficacy rates than either monotherapy alone Patient Resources 18- to 24-mo time to maximal recovery.
– Level 4 evidence: Enhanced efficacy with the Mulhall JP. Saving Your Sex Life: A Guide for Men with r ED after RT has an insidious onset, with nadir of
combination of vacuum-erection therapy + either Prostate Cancer. 1st ed. Chicago, IL: Hilton Publishing erectile function at 3- to 5-yr post-RT.
PDE5i or transurethral PGE1 or intracavernosal Company; 2008. r Data on penile rehabilitation is conflicting but
injection therapy increasingly shows an improvement in
REFERENCES posttreatment erectile recovery.
r The majority of postpelvic surgery/RT ED patients are
1. Alemozaffar M, Regan MM, Cooperberg MR, et al. effectively treated with PDE5i ± intracavernosal
Prediction of erectile function following treatment injection therapy.
for prostate cancer. JAMA. 2011;306(11):
1205–1214.
2. Candy B, Jones L, Williams R, et al.
Phosphodiesterase type 5 inhibitors in the
management of erectile dysfunction secondary to
treatments for prostate cancer: Findings from a
Cochrane systematic review. BJU Int. 2008;102(4):
426–431.
3. Coombs, PG, Heck M, Guhring P, et al. A review of
outcomes of an intracavernosal injection therapy
programme. BJU Int. 2012;110(11):1787–1791.
143
ERECTILE DYSFUNCTION/IMPOTENCE, GENERAL CONSIDERATIONS

Nathaniel Readal, MD
Trinity J. Bivalacqua, MD, PhD
Genetics
BASICS r Several gene polymorphisms linked with ED DIAGNOSIS
r Angiotensin-converting enzyme (ACE)
DESCRIPTION polymorphisms may be risk factors for vasculogenic HISTORY
r Medical history—comorbid conditions, medications,
Consistent or recurrent inability to attain and/or ED and endothelial nitric oxide synthase (eNOS)
maintain an erection sufficient for satisfactory sexual polymorphisms alone or in combination with other alcohol, tobacco, recreational drug use, history of
activity genetic polymorphisms implicated in ED cycling
r Surgical history
EPIDEMIOLOGY PATHOPHYSIOLOGY r Psychosexual history
Incidence r Mechanism of erection
r Crude incidence: 26 cases/1,000 man years – Status of current relationship
– Relaxation of cavernosal smooth muscle – Level of libido/interest in sex
– Incidence increases with each decade above 40 (contracted in flaccid state inhibiting inflow of – Quality of erection
◦ 12 cases/1,000 man years: 40–49 yr blood) – Duration of ED
◦ 30 cases/1,000 man years: 50–59 yr ◦ Mediated by NO release from pelvic nerves and – Onsent of ED (sudden vs. gradual)
◦ 46 cases/1,000 man years: 60–69 yr endothelial cells – Presence of nocturnal/early morning erections
◦ Increased cyclic GMP (cGMP) and cyclic AMP
Prevalence – Presence of penile curvature, plaque, pain
r Increases universally with age and medical (cAMP) trigger signaling pathways leading to – International Index of Erectile Function
comorbidities (cardiovascular disease, hypertension, decreased intracellular calcium causing smooth Questionnaire (IIEF-5)
smoking, inactivity, obesity) muscle relaxation, increased penile blood flow, ◦ 5 questions scored individually from 0–5
– Prevalence by age and tumescence (maximum of 25 points, higher score indicated
◦ Below age 40: 1–9% ◦ Smooth muscle relaxation further promoted due better function)
◦ 40–59 yr: 20–30% to inhibition of Rho-kinase ◦ Classifies ED into severe (5–7), moderate
◦ 60–69 yr: 20–40% ◦ Veno-occlusive mechanism prevents outflow of (8–11), mild to moderate (12–16), mild
◦ >70 yr: 50–75% blood from penis and maintains erection (17–21), and no ED (22–25)
◦ cGMP degraded by phosphodiesterase type 5
RISK FACTORS (PDE5) PHYSICAL EXAM
r Probability of ED increases with presence of each r Organic ED r Neurologic: Stroke, CNS disease, visual field defects,
risk factor – Vasculogenic neuropathy, perineal sensation
– Diabetes mellitus ◦ Arteriogenic—atherosclerotic lesions decrease r Endocrinologic: Atrophic testes, gynecomastia, loss
◦ Prevalence of ED 3 times higher in diabetic men arterial inflow to penis of secondary sexual characteristics
◦ ED occurs at earlier age and increases with ◦ Venogenic—failure of corporal vasoocclusion r Cardiovascular: Blood pressure, femoral/pedal
disease duration – Neurogenic—Alzheimer disease, Parkinson pulses, lower extremity ischemia
◦ Associated with 14 times increased risk of disease, injury to central nervous system, spinal r Penile: Curvature, Peyronie disease plaques
cardiovascular morbidity and mortality cord, or peripheral nerves r Rectal exam
– Cardiovascular disease (hyperlipidemia, – Anatomic
hypertension, peripheral vascular disease) – Endocrinologic (hyperprolactinemia, hyper or DIAGNOSTIC TESTS & INTERPRETATION
– Lower urinary tract symptoms/Benign prostatic hypothyroidism, adrenal disorders/Cushing Lab
hyperplasia (BPH) r Complete blood count
syndrome)
– Chronic renal failure, chronic liver disease r Psychogenic ED r Serum chemistries
– Endocrinopathies (hypogonadism, Cushing – Only accounts for 10% of ED r Fasting glucose level, hemoglobin A1C
disease) – More common in men <35 yr old r Lipid profile
– Prior abdominal/pelvic/penile surgery, radiation or ◦ May result from lack of interest in partner, r Serum total testosterone
trauma performance-related anxiety, negative mood, r Thyroid function tests (optional)
– Priapism, Peyronie disease life stressors r PSA (suspect prostate pathology)
– Neurologic disease (Parkinson disease, dementia,
ASSOCIATED CONDITIONS r Urinalysis (glucose as indicator of diabetes)
prior stroke)
r Atherosclerosis
– Depression/Psychological disorders Imaging
– Long-distance cycling r Diabetes mellitus r Duplex penile ultrasound—most reliable and least
– Smoking r Hypertension, stroke
invasive modality for assessing ED
– Medications r Depression r Provides imaging evaluation and quantification of
◦ Antihypertensives (thiazide diuretics, β-blockers, r Parkinson disease, multiple sclerosis penile blood flow
α 2 -agonists) r Priapism
◦ ACE inhibitors, angiotensin receptor blockers, r Peyronie disease
and calcium channel blockers cause less ED/may r Prostate cancer
improve erectile function
◦ Psychotropics (monoamine oxidase inhibitors, GENERAL PREVENTION
selective serotonin reuptake inhibitors, lithium) r Avoidance of tobacco use
◦ Antiandrogens r Optimal medical management of commonly
◦ Miscellaneous (digoxin, cimetidine, associated conditions
spirolactone, marijuana) r Increase exercise/weight loss
◦ Tobacco smoking r Split bicycle seat for long-distance cycling
144
ERECTILE DYSFUNCTION/IMPOTENCE, GENERAL CONSIDERATIONS
Diagnostic Procedures/Surgery – Side effects: All associated with headache, COMPLICATIONS

dyspepsia, facial flushing N/A
ALERT ◦ Tadalafil: Backache, myalgia
A trial of oral pharmacotherapy is warranted prior to ◦ Sildenafil: Blurred/blue vision—reacts with FOLLOW-UP
an invasive procedure/test PDE6 in retina Patient Monitoring
r Patients to be reevaluated periodically with
r Specialized testing indicated for:
Second Line following considerations:
– Young men <40 yr old r Intracavernous injection therapy
– Response to initial therapy
– Men with previous perineal/pelvic trauma – Mechanism: Self-injection of vasoactive agent into – Need for dose titration
◦ Combined intracavernosal injection and corpora cavernosa producing rapid erection – Patient education on proper medication use
stimulation (CIS) with duplex ultrasound (US): – Drugs: (specific PDE5i on empty stomach, use of local
Intracavernosal injection of vasodilator with ◦ Alprostadil (PGE1) injection therapy)
genital/audiovisual sexual stimulation and ◦ Bimix: Papaverine and phentolamine – Need for progression to 2nd-line therapy/surgery
measurement of erection/blood flow— ◦ Trimix: Papaverine, phentolamine, and based on therapeutic effectiveness and patient
provides objective measurement of vascular prostaglandin E1 satisfaction
parameters – Side effects: Fibrosis, priapism, painful erection,
hematoma Patient Resources
◦ Penile angiography: Reserved for young Urology Care Foundation. http://www.
patient with ED secondary to traumatic – Contraindications: Monoamine oxidase
medication usage, decreased manual dexterity urologyhealth.org/urology/index.cfm?article=60
arterial disruption/compression to evaluate for
– Efficacy: 80–90% effective in wide range of
revascularization
◦ Nocturnal penile tumescence (RigiScan®):
patients REFERENCES E
r Intraurethral therapy
Automated, portable measurement of 1. Lue TF. Physiology of penile erection and
– MUSE:Medicated urethral system for erection
presence of nocturnal erections—can confirm – Mechanism: Insertion of alprostadil containing pathophysiology of erectile dysfunction. In: Wein
integrity of neurovascular axis, diagnose pellet into distal urethral, absorbed into corpora AJ, Kavoussi LR, Novick AC, et al., eds.
psychogenic ED cavernosa production erection within 30 min Campbell-Walsh Urology. 10th ed. Philadelphia,
– Side effects: Penile/vaginal pain, dysuria PA: Saunders-Elsevier; 2012.
Pathologic Findings – Contraindications: Priapism risk 2. Carson CC, Lue TF. Phophodiesterase type 5
N/A – Efficacy: <50% effective inhibitors for erectile dysfunction. BJU Int.
r Vacuum constriction device 2005;96:257–280.
Psychogenic erectile dysfunction, depression, possible – Effective 2nd-line treatment and represents an 3. Burnett AL. Evaluation and management of erectile
early sign of cardiovascular disease alternative/adjunct to pharmacotherapy dysfunction. In: Wein AJ, Kavoussi LR, Novick AC,
– Pursued prior to surgical intervention et al., eds. Campbell-Walsh Urology. 10th ed.
– Produces negative penile pressure, engorging Philadelphia, PA: Saunders-Elsevier; 2012.
TREATMENT corpora with blood
– Constrictive ring at the base of penis maintains
GENERAL MEASURES tumescence
ADDITIONAL READING
r Treatment choice should be made among physician,
– Side effects: Penile ischemia when duration of use Montague DK, Jarow JP, Broderick GA, et al. Chapter
patient, and partner after evaluation of risk/benefits >30 min, pain, abnormal color of penis 1: The management of erectile dysfunction: An AUA
of all treatment choices update. J Urol. 2005;174(1):230–239.
r Cardiovascular risk assessment should be performed SURGERY/OTHER PROCEDURES
r IPP
before initiating therapy See Also (Topic, Algorithm, Media)
– Indications: Failed 1st- and 2nd-line r Erectile Dysfunction Algorithm
– Low risk: Asymptomatic, <3 risk factors—may
proceed with treatment pharmacotherapy or vacuum erection device r Erectile Dysfunction, Following Pelvic Surgery or
– Intermediate risk: Asymptomatic, ≥3 risk factors, – Mechanism: Definitive ED treatment with Radiation
stable angina, or mild heart failure—requires full placement of inflatable cylinders into corpora r Erectile Dysfunction/Impotence, General
cardiovascular assessment to reclassify as high vs. cavernosa Considerations Image
low risk – Complications: Infection (1–3%), erosion (<5%), r Penile Rehabilitation
– High risk: Unstable angina, recent myocardial mechanical malfunction (5–10%)
r Penile revascularization
infarction, uncontrolled hypertension, advanced
heart failure or valvular disease—defer until – Reserved for select young patients with clearly CODES
cardiac condition stabilized documented arterial occlusion
MEDICATION ADDITIONAL TREATMENT ICD9

Radiation Therapy r 302.72 Psychosexual dysfunction with inhibited
First Line
r PDE5 inhibitors (PDE5i): Inhibit breakdown of N/A sexual excitement
r 607.84 Impotence of organic origin
smooth muscle cGMP promoting smooth muscle Additional Therapies
relaxation. >50% of patients will respond Psychosexual therapy: Referral for sex therapy in ICD10
– Drugs: patients with psychogenic ED. Cognitive behavioral r F52.21 Male erectile disorder
◦ Sildenafil 50–100 mg : Onset 15–60 min, intervention identifies sexual stressors and refocus r N52.9 Male erectile dysfunction, unspecified
duration of action 4 hr maladaptive thought processes r N52.39 Other post-surgical erectile dysfunction
◦ Vardenafil 10–20 mg: Onset 15–60 min,
duration of action 2–8 hr
◦ Tadalafil 10–20 mg: Onset 15–120 min, Therapies
duration of action 24–36 hr
No FDA-approved dietary supplements or herbal CLINICAL/SURGICAL
◦ Avanafil 100–200 mg medications for ED but gingko biloba, red ginseng, PEARLS
yohimbine reportedly improve ED
– Contraindications to PDE5i use: r ED is a symptom of multiple underlying diseases
◦ Absolute contraindications: Use of nitrates
◦ Sildenafil: Should be postponed for 4 hr after that affect the following: penile nerve, artery,
ONGOING CARE endothelial or smooth muscle function.
taking α-adrenergic antagonists r Cardiac risk assessment should occur prior to
◦ Vardenafil: Should not be taken with type PROGNOSIS
1A/type 3 antiarrhythmics or with long QT Excellent if reduction of cardiovascular risk factors, initiation of therapy.
r Surgical therapy (penile prosthesis) is an essential
syndrome weight loss, exercise, smoking cessation
therapy when medical treatment has failed or is
contraindicated.
145
EXSTROPHY, BLADDER (CLASSIC EXSTROPHY)

Grahame H.H. Smith, MBBS

r Classic bladder exstrophy is a major genitourinary Any family history of exstrophy r Antenatal
anomaly characterized by the bladder laying open PHYSICAL EXAM – Consider MRI assessment and karyotyping.
on the abdominal wall with an associated lower r Bladder exposed on abdominal wall Options for termination may be discussed
midline abdominal wall hernia. The defect extends r Bladder plate size r Immediate postnatal care:
from the umbilicus to the distal end of the phallus, r Lateral ureteric orifices – 2-0 silk suture on umbilical cord as close to
resulting in coexistent epispadias in males and a r Males have an open bladder neck and prostate, the abdominal wall as possible
bifid clitoris in females. – Cover bladder with a nonadherent dressing (eg,
r Classic exstrophy is considered midway in severity short and broad phallus is open dorsally with dorsal
chordee Saran Wrap) to prevent excoriation
between cloacal exstrophy and epispadias, as part r Females have an open bladder neck and urethra, – Irrigate with normal saline and apply a new
of exstrophy–epispadias complex. dressing with each diaper change
bifid clitoris lateral to urethra and anteriorly situated
EPIDEMIOLOGY vagina MEDICATION
Incidence r Low-set umbilicus with foreshortened distance to First Line
r 1 in 10,000–50,000 pubis No medical treatment is available to close the bladder
r Male > Female (2:1) r Pubic diastasis with external rotation of pelvis wall
Prevalence DIAGNOSTIC TESTS & INTERPRETATION Second Line
N/A r Antenatal N/A
RISK FACTORS – May be diagnosed on antenatal ultrasound study SURGERY/OTHER PROCEDURES
due to absence of the bladder (1st trimester) or r Ideally the extrophy is closed on next elective list
Genetics
r Multifactorial etiology without definite genetic link reduced umbilical to pubic length (2nd trimester) with two senior staff in attendance:
(1) Lab – Requires an adequate bladder plate but the
– May be associated with p63 gene dysregulation r Full blood count, electrolytes, creatinine minimum size is not defined
– Chromosomal regions 4q31.21–22, r Blood type and cross-match in preparation for – If unable to easily approximate pubis, then may
19q13.31–41, and 22q11.21 may harbor genes surgery need pelvic osteotomy
associated with exstrophy – Pelvic osteotomy may reduce the incidence of
r Risk in sibling is 1 in 100; risk in offspring is 1 in 70 Imaging dehiscence and subsequent prolapse in females
r Renal ultrasound
r Avoid latex exposure to prevent latex allergy
PATHOPHYSIOLOGY r Pelvic x-ray to document pubic diastasis
r 3 contemporary closures (2)
r Incompletely understood, 2 predominant theories
Diagnostic Procedures/Surgery r Classic repair involves 3 stages:
r 1st theory postulates that an incomplete ingrowth of
N/A – Immediate bladder closure
mesoderm is unable to reinforce cloacal membrane, – Epispadias repair at 6 mo
which results in premature rupture and subsequent Pathologic Findings
r Exstrophic bladders may have more type III collagen – Bladder neck repair at 5 yr:
failure to develop ectoderm and mesoderm. The ◦ Requires >100-cc bladder capacity and
timing of the rupture determines cloacal (earlier) vs. and fewer myelinated nerve fibers
r If left untreated and exposed, the urothelium motivation for continence
classic exstrophy vs. epispadias (later) r Complete primary repair of bladder exstrophy
r 2nd theory describes an overgrowth of cloacal undergoes squamous metaplasia as a response to
acute and chronic inflammation (CPRE):
membrane preventing medial migration of – Epispadias repaired along with bladder as
mesenchymal tissue. Bladder smooth muscle cells in DIFFERENTIAL DIAGNOSIS neonate with penile disassembly (if male)
exstrophy patients show lower intracellular calcium r Cloacal exstrophy
r Kelly repair:
concentrations and enhanced migration r Omphalocele
– Soft tissue mobilization away from pelvic sidewall
r Gastroschisis
ASSOCIATED CONDITIONS with midline closure without the need for pelvic
r Usually healthy without any other major organ r Epispadias osteotomy
system defects r Associated surgery
r Subsequent inguinal hernia common – Prophylactic inguinal hernia repair in males is
r Rarely may be associated with duplication of advised
bladder or urethra, colorectal abnormalities (2%), – Ureteric reimplantation may be required
cleft lip and palate, subsequent testis tumors subsequently
r In contrast, cloacal exstrophy has much more
extensive anomalies
GENERAL PREVENTION
N/A
146
EXSTROPHY, BLADDER (CLASSIC EXSTROPHY)
ADDITIONAL TREATMENT r Male: Infertility, retrograde ejaculation, ADDITIONAL READING

Radiation Therapy urethrocutaneous fistula, loss of phallus (complete
r Palmer B, Frimberger D, Kropp B, et al.
N/A penile disassembly, Kelly repair), inadequate phallus,
testis tumors http://www.pediatricurologybook.com/
Additional Therapies r Female: bladder exstrophy.html
r Delayed closure in the case of a late presentation r Reiner WG. A brief primer for pediatric urologists
r All need osteotomy with option of external fixation – Vaginal stenosis, requiring vaginoplasty
– Degree of diastasis association with risk of uterine and surgeons on developmental psychopathology in
r Inadequate bladder plate:
prolapse the exstrophy-epispadias complex. Semin Pediatr
– Delay closure with osteotomies, once adequate – Enterocystoplasty may lead to false-positive Surg. 2011;20(2):130–134.
– If remains inadequate consider augmentation at pregnancy test
time of closure See Also (Topic, Algorithm, Media)
r Postoperative:
– Normal fertility possible, Cesarean delivery r Epispadias
suggested r Exstrophy, Cloacal
– Ensure maximal urinary drainage with ureteric r Increased risk of adenocarcinoma of bladder
r Exstrophy–Epispadias Complex
stents, suprapubic tube, and urethral catheter r Increased risk of colonic adenocarcinoma after
– With our without pelvic immobilization (traction, r Exstrophy, Bladder (Classic Exstrophy) Images
ureterosigmoidostomy
Buck, Bryant; Mermaid dressing; spica cast)
◦ Optimal duration of immobilization not FOLLOW-UP
established Patient Monitoring CODES
– Remove stents one at a time; suprapubic only r After discharge:
removed after ensuring appropriate bladder
emptying
– Antibiotic prophylaxis to prevent urinary tract
infections
ICD9
753.5 Exstrophy of urinary bladder
E
Complementary & Alternative – Regular ultrasound to assess for hydronephrosis,
residual volume, and bladder volume ICD10
Therapies r Q64.11 Supravesical fissure of urinary bladder
N/A – Yearly colonoscopy starting 10 yr after
r Q64.19 Other exstrophy of urinary bladder
ureterosigmoidostomy
Patient Resources
ONGOING CARE The Association of Bladder Exstrophy. Community. CLINICAL/SURGICAL
r Subsequent operative treatment options: http://bladderexstrophy.com/
PEARLS
– Bladder neck plasty (failure rate 50%)
r Achieving normal urinary continence with normal
– Bladder neck closure (failure rate 2%) with REFERENCES
augmentation and Mitrofanoff conduit voiding after repair is uncommon. It is almost always
– Ureterosigmoidostomy (plus or minus Mainz II 1. Mahfuz I, Darling T, Wilkins S, et al. New insights possible to achieve continence if the patient is
pouch) into the pathogenesis of bladder exstrophy- willing to undertake clean intermittent
– Umbilicoplasty epispadias complex. J Pediatr Urol. 2013; catheterization.
– Radial forearm flap phalloplasty (males) r Males will tend to be unhappy about the length of
9(6 Pt B):996–1005.
– Vaginoplasty, clitoroplasty (females) 2. Mahajan JK, Rao KL. Exstrophy epispadias complex their penis. However, what they lack in length they
- Issues beyond the initial repair. Indian J Urol. gain in width.
PROGNOSIS r For the inexperienced clinician it is sometimes
r Life expectancy normal 2012;28:382–387.
r Urinary continence in 50–90%; definition of 3. Lloyd JC, Spano SM, Ross SS, et al. How dry is dry? difficult to identify the gender of a newborn baby
A review of definitions of continence in the with bladder exstrophy. Boys almost always have
continence disputed; most common definition of
contemporary exstrophy/epispadias literature. bilateral palpable gonads.
continence is dry with voiding or catheterization
every 3 hr (3) J Urol. 2012;188(5):1900–1904.
r May require multiple surgeries
r Quality-of-life scores are less than the normal.
Functional results seem to be the most likely
predictive factor of health-related QOL score
COMPLICATIONS
r Failure of primary closure; 10%
r Failure to store (urinary incontinence secondary to
incompetent outlet plus or minus poor bladder
compliance)
r Failure to empty (after closure or after bladder neck
procedure)
r Upper tract damage and renal failure due to high
bladder pressures and or high outlet resistance
r Developmental psychopathology
147
EXSTROPHY, CLOACAL
Jason C. Fisher, MD
ASSOCIATED CONDITIONS r Thorough assessment for associated anomalies (see

BASICS r Upper genitourinary anomalies: “Associated Conditions”):
– Unilateral renal agenesis (33%) – Spinal and vertebral defects
DESCRIPTION – Pelvic kidney (33%) – Lower extremity malformations
r Cloacal exstrophy, or vesicointestinal failure, is a – Hydronephrosis (33%) – Patency and position of anus
congenital abnormality of the infraumbilical – Horseshoe kidney – Presence of descended testicles
abdominal wall. Its presentation is highly variable, – Fusion anomalies r Detailed exam of exstrophy:
but key features include an exomphalos with an – Ureteral anomalies – Males: Divided corpus cavernosum and glans
exstrophied cecum flanked by two hemibladders r Lower genitourinary anomalies: – Females: Divided clitoris, duplicated vagina
r Ureteral orifices present on each hemibladder. Cecal – Separation or absence of clitoral/phalic halves – Additional müllerian anomalies
plate has orifices to three structures: – Separation of scrotum or labia – Identification of ureteral orifices: Two exstrophied
– Appendix – Undescended testicles/bilateral hernias hemibladders are on either side of the exstrophied
– Blind-ending hindgut (colonic remnant) – Uterine and vaginal duplication anomalies intestinal segment. Each half usually drains the
– Ileum, often prolapsed elephant-trunk deformity r Gastrointestinal anomalies: ipsilateral ureter
r Most severe anomaly along epispadias–exstrophy – Omphalocele (88–100%) – Identification of intestinal orifices: Appendix,
complex (EEC) spectrum – Short-gut (25%; source of major morbidity) hindgut, ileum (often prolapsed)
r When neurospinal defects and omphalocele occur – Intestinal malrotation DIAGNOSTIC TESTS & INTERPRETATION
with cloacal exstrophy, it is termed OEIS complex – Intestinal duplication
(omphalocele, exstrophy, imperforate anus, spinal – Imperforate anus/anal atresia
Lab
r Karyotype
defects) r Central nervous system anomalies:
r CBC, basic metabolic panel:
EPIDEMIOLOGY – Tethered spinal cord
– Myelomeningocele – At risk for nongap metabolic acidosis due to
Incidence – Aberrant pelvic autonomic nerve anatomy absorption of urine chloride by intestinal mucosa
r One of the rarest urologic anomalies – Type and cross blood for surgery
r Widely quoted historic incidence of 1:200,000 to – Impaired continence, ambulation, erectile function
r Musculoskeletal anomalies: Imaging
1:400,000 based on statistical estimates r Plain CXR, sacral and spinal x-rays
r More accurate and contemporary international – Symphysis pubis diastasis
– Sacral dysplasias and vertebral anomalies r Ultrasounds of abdomen, kidneys, head, spine
registries now estimate 3:100,000 to 8:100,000. – Scoliosis r Consider MRI to detect occult spinal lesions if no
r Male ≥ Female (1:1–2:1)
– Hip subluxation and acetabular dysplasia obvious dysraphism and US nondiagnostic
– Lower limb anomalies r Skeletal and bony films of pelvis and lower
RISK FACTORS
r No well-defined causative factors; statistical analysis r Serious cardiovascular and pulmonary anomalies are extremities as needed
of large registries identifies the following: uncommon with cloacal exstrophy r Echocardiogram: Low incidence of associated
– Bimodal risk of maternal age: <20 year old or cardiac lesions, but advisable in the preop setting
>30 year old
– Intrauterine fetal demise of twin pregnancy DIAGNOSIS DIFFERENTIAL DIAGNOSIS
r Unique appearance makes it unlikely to confuse with
– In vitro fertilization
Cloacal exstrophy is a major congenital anomaly. other conditions
Genetics Prompt referral and coordination with a variety of r Exists along EEC spectrum
r Most cases are sporadic specialists including pediatric urology, pediatric r Consider isolated bladder exstrophy, giant isolated
r Some cases reported with genetic causation: general surgery, pediatric orthopedics, neonatology, omphalocele, large epispadias
– Unbalanced translocation of 9q and Yq pediatric gastroenterology, pediatric neurosurgery,
– Homeobox mutations at HLXB9 and HOX endocrinology, genetics, and social work is needed.
PATHOPHYSIOLOGY HISTORY (ANTENATAL)
TREATMENT
r Traditionally postulated embryologic theories:
r Major diagnostic criteria (2)[A]: GENERAL MEASURES
– Premature cloacal membrane rupture (8 wk) r Assessment of newborn with anomaly:
– Nonvisualization of the bladder (91%)
– Failed cloacal partition by lateral folds of Rathke – Immediate cardiopulmonary stabilization
– Large midline infraumbilical anterior abdominal
– Incomplete descent of a cloacal septum – Neonatology management of prematurity
wall defect or cystic anterior abdominal wall
r Current understanding of cloacal exstrophy structure (82%) – IV access: UA and UV lines not possible
r Protection and prevention maneuvers:
embryogenesis (1)[B]: – Omphalocele (77%)
– Disrupted cellular proliferation and apoptosis of – Lumbar myelomeningocele (68%) – Ligate umbilical cord with silk tie (avoid plastic
dorsal cloacal wall and infraumbilical r Prolapsed ileal segment can be pathognomic clip which will irritate bladder mucosa)
mesenchyme—this disrupts the infraumbilical – Lower half of infant in bowel-bag initially
body wall, everts the cloacal cavity, and wedges PHYSICAL EXAM – Cover exstrophic tissue with plastic wrap
r The classic collection of findings include: – Protect omphalocele: Minimal handling
the pubic bones and genital tubercles apart
– Exstrophy of the bladder – Assess for open spinal cord defects
– Complete phallic separation – Place nasogastric tube for decompression
– Wide pubic diastasis – Prophylactic antibiotics (ampicillin and gentamicin)
– Cecal plate everted between 2 hemibladders r Contact specialists (see under “diagnosis” heading
– Blind-ending hindgut; no well-formed colon above) immediately.
– Omphalocele r Detailed exam to assign gender
– Identification of phallus, labia/scrotum, testes
– Consistent with the karyotype if possible
148
EXSTROPHY, CLOACAL
MEDICATION ADDITIONAL TREATMENT 3. Stolar CH, Randolph JG, Flanigan LP. Cloacal
First Line Radiation Therapy exstrophy: Individualized management through a
r IVF support: Adjust for fluid losses across N/A staged surgical approach. J Pediatr Surg.
exstrophied mucosa 1990;25:505–507.
r At risk for hyperchloremic metabolic acidosis Additional Therapies
r Large omphaloceles not amenable to primary 4. Zderic SA, Canning DA, Carr MC, et al. The CHOP
r Generally not candidates for epidural anesthesia due experience with cloacal exstrophy and gender
closure can be treated with Silvadene-mediated
to spinal dysraphism reassignment. Adv Exp Med Biol. 2002;511:
epithelialization of sac followed by delayed closure,
135–147.
Second Line or by excision of sac and placement of a silo with
N/A gradual staged reduction of viscera
r Consider gastrostomy tube placement and/or
SURGERY/OTHER PROCEDURES tunneled central line during initial repair if patient
ADDITIONAL READING
r Open spinal anomaly: Prompt neurosurgical repair
appears at risk for short-gut syndrome r Mathews R, Jeffs RD, Reiner WG, et al. Cloacal
required before addressing exstrophy.
r Exstrophy repair at 48–72 hrs of life if stable Complementary & Alternative exstrophy: Improving the quality of life: The Johns
Therapies Hopkins Experience. J Urol. 1998;160:2452–2456.
– Combined pediatric urology and general pediatric r McHoney M, Ransley PG, Duffy P, et al. Cloacal
surgery N/A
– Usually staged approach vs. single stage exstrophy: Morbidity associated with abnormalities
r Multistage approach (3)[B]: Creates classic bladder of the gastrointestinal tract and spine. J Pediatr
ONGOING CARE Surg. 2004;39:1209–1213.
exstrophy anatomy at conclusion of initial surgery r Reiner WG. Psychosexual development in genetic
described above; preferred for most cases. General PROGNOSIS
r Survival >90% over last 20 yr males assigned females: The cloacal exstrophy
E
principles of Stage 1:
r Nutrition and growth is the most important experience. Child Adolesc Psychiatric Clin N Amer.
– Separate hemibladders from cecal plate 2004;13:657–674.
– Revert any prolapsed terminal ileum determinant of early survival and morbidity r Soffer SZ, Rosen NG, Hong AR, et al. Cloacal
– Mobilize, rescue, and preserve any hindgut – 30–50% will have failure to thrive before age 5
– Important to avoid using any bowel for GU exstrophy: A unified management plan. J Pediatr
– Tubularize the cecum to bring terminal ileum,
reconstruction procedures until child is thriving Surg. 2000;35:932–937.
cecum, and hindgut into closed continuity
– Create end colostomy from distal hindgut r After 3 yr, quality-of-life issues outweigh nutritional See Also (Topic, Algorithm, Media)
– Assess and preserve müllerian anatomy concerns r Epispadias
– Excise and close omphalocele if possible – Urinary continence: Rarely achieved; dependent r Exstrophy–Epispadias Complex
– Anastomose hemibladders in midline on a compliant reservoir and continent r Exstrophy, Bladder (Classic Exstrophy)
r Single-stage approach (4)[B]: In highly select catherizable conduit r Exstrophy, Cloacal Images
patients, can proceed with bladder and abdominal – Fecal continence: Usually managed by enema
wall closure and phallic reconstruction which may regimen, rarely are perineal pull-through
avoid osteotomies, minimize bladder scarring. maneuvers associated with any continence
– Gender assignment and reconstruction, especially CODES
Otherwise, Stage 2 is performed in late infancy,
mirroring a classic bladder exstrophy repair: for genetic males raised as females
– Mobilize bladder plate and posterior urethra – Ambulation impairments ICD9
deep into pelvis: Yields incontinent bladder. – Gynecologic issues after onset of menarche 753.5 Exstrophy of urinary bladder
– Orchiopexy with repair of inguinal hernias – Psychosexual problems ICD10
– Reconstruct gender-based external genitalia COMPLICATIONS Q64.12 Cloacal extrophy of urinary bladder
– Pubic reapproximation +/– pelvic bone r Infection and breakdown of repair
osteotomies with fixation and traction for r Abdominal compartment syndrome
4–6 wk r Short-gut syndrome CLINICAL/SURGICAL
r Stage 3 involves procedures aimed at continence r Vesicoureteral reflux and hydronephrosis PEARLS
and genital cosmesis and is addressed in older r Hirschsprung-type enterocolitis in the dysmotile r Meticulous assessment of associated anomalies can
children, often involving bladder augmentation and hindgut, even after colostomy formation prevent early clinical and surgical mishaps,
catherizable conduits
r Surgical pitfalls to avoid: FOLLOW-UP particularly with regard to spinal defects.
r A multidisciplinary team is critical to the short- and
– Injury to ureteral orifices: Place stents Requires a multidisciplinary team (see “Diagnosis”) to
coordinate regular follow-up through all stages of long-term outcomes of these children.
– Overaggressive closure of a large omphalocele r A staged surgical repair remains the preferred
defect leading to compartment syndrome surgical repair, with careful attention to nutrition and
– Excising/discarding diminutive male phalic growth in infancy, and both surgical and psychological approach for most children with cloacal exstrophy.
support for the multiple quality of life issues which r Do not underestimate the impact of early gender
remnants and assigning female gender:
Controversial and still occurs with unclear begin in childhood and persist into adulthood assignment: Avoid irreversible surgical resection of
long-term consequences Patient Resources structures that may be useful for genital
– Excising/discarding the hindgut even if short Urology Care Foundation. http://www. reconstruction.
– Primary perineal pull-through of the hindgut (can r Save as much bowel as possible, especially the short
urologyhealth.org/urology/index.cfm?article=91
be performed in highly select patients) hindgut, to maximize nutritional capability.
REFERENCES
1. Vermeij-Keers C, Hartwig NG, van der Werff JF.
et al. Embryonic development of the ventral body
wall and its congenital malformations. Semin
Pediatr Surg. 1996;5:82–89.
2. Austin PF, Homsy YL, Gearhart JP, et al. The
prenatal diagnosis of cloacal exstrophy. J Urol.
1998;160:1179–1181.
149
LWBK1391-SEC-F LWBK1391-Gomella ch075.xml September 19, 2014 18:22
FERTILITY AND CANCER THERAPY, UROLOGIC CONSIDERATIONS

James M. Hotaling, MD, MS

BASICS r Hematologic malignancies
Lab
– Whole-body radiation used before bone marrow r Evaluation of baseline FSH, LH, estradiol, total
DESCRIPTION transplant usually causes life-long infertility testosterone, sex hormone binding globulin (SHBG),
r 2006 ASCO Guidelines recommend that all patients r Prostate cancer can directly impact fertility through and albumin (to calculate bioavailable T)
in their reproductive years undergoing cancer sperm impairment and indirectly through erectile r Values for optimal spermatogenesis
therapy be offered fertility preservation options (1) dysfunction (5) – Bioavailable T >155 ng/dL
r Mainstay of fertility preservation in men is referral to – Radical prostatectomy and its effect on fertility – FSH <4.5
a reproductive specialist and sperm cryopreservation should be disclosed to the patient preoperatively – Total testosterone:estradiol ratio > 10:1
r Sperm cryopreservation is often not covered by – Brachytherapy does not give a large dose of r Semen analysis by a high-volume lab: WHO 5th
insurance but Livestrong Foundation and Fertile radiation to the testicles, and most men will edition lower limits of normal
Hope offer financial support (2) remain fertile or recover sperm production – Sperm concentration >39 million/mL
– External radiation is more likely to cause – Motility >40%
EPIDEMIOLOGY
permanent infertility, even if the testicles are – Total motile count >15 million
Incidence shielded
r 1.4 million people are diagnosed with cancer every – Morphology >4% normal by Kruger strict criterion
r Testicular cancer
year – More than half of the patients with testicular germ Imaging
r 10% of those diagnosed with cancer are <44 yr N/A
cell cancer showed impaired fertility
old (3) – Retrograde ejaculation following retroperitoneal Diagnostic Procedures/Surgery
r Testicular cancer is one of the most common cancers
lymphadenectomy If men are found to be azoospermic on semen analysis
seen by men in their reproductive years and typically consider microsurgical testicular sperm extraction
presents to urologists GENERAL PREVENTION (microTESE)
r Radiation to the testicles can cause permanent loss
Prevalence of sperm production Pathologic Findings
Advances in cancer treatment have led to increased r Unless the cancer is in the testicles, attempt to N/A
survival rates of 75–80% for those diagnosed protect them from radiation by using a shield called
<50 yr old (4) DIFFERENTIAL DIAGNOSIS
a clam shell (5) N/A
RISK FACTORS
Men with male factor infertility (azoospermia) are
significantly more likely to develop testis cancer DIAGNOSIS TREATMENT
Genetics HISTORY GENERAL MEASURES
N/A r Thorough reproductive history r Semen analysis with cryopreservation of ejaculated
– Gonadotoxin exposure? sperm by a high-volume lab
PATHOPHYSIOLOGY – Previous difficulty with conception?
r Men presenting with cancer often have reduced – Men with testis cancer or Hodgkin disease should
– Use of exogenous steroids? bank multiple times given known lower recovery
semen quality (3)
r Radiation at doses of 2.5 Gy to the testis causes – Varicocele surgery? rates (3,6)
– Diagnosis of cystic fibrosis? – Any sperm obtained from semen analysis should
prolonged azoospermia r Discussion of desire for future paternity
r Radical pelvic surgery can cause erectile and be banked
r Assessment of onset of puberty in adolescent – Patients should abstain from ejaculation for 2 days
ejaculatory dysfunction before banking sperm but not more than 3 days
r Certain common chemotherapeutic agents cause patients
– Nocturnal emissions? – At least 2–3 samples should be banked for each
prolonged azoospermia (1) – Sexually active? patient
– Cisplatin (500 mg/m2 ) – A frank discussion with the patient regarding the
– Chlorambucil (1.4 g/m2 ) PHYSICAL EXAM ongoing costs of cryopreservation and methods
r Assessment of Tanner stage in adolescent males
– Cyclophosphamide (19 g/m2 ) for patient contact in the future is vital
– Procarbazine (4 g/m2 ) r Focused testicular exam
r Attempts to obtain and bank seminiferous tubules
– Melphalan (140 mg/m2 ) – Longitudinal testicular axis
from prepubertal males for use in future-assisted
– Others shown to be gonadotoxic: – Presence of vas deferens
reproductive technologies should only be done
◦ Busulfan, carmustine, cytarabine, ifosfamide, – Presence of epididymis
under an IRB-approved research protocol (4)
lomustine, nitrosoureas r All discussions for adolescents and children should
involve both the patient and their parents
r Electroejaculation or vibratory stimulation may be
used for patients with a spinal cord injury
150
FERTILITY AND CANCER THERAPY, UROLOGIC CONSIDERATIONS
r Some men may be hypoandrogenic after completion

First Line of treatment and referral to a reproductive health
r To convert a retrograde ejaculation to an antegrade specialist is essential to ensure that they are offered WHO laboratory manual for the examination and
ejaculation medication other than testosterone for androgen processing of human semen, 5th edition,
– In the United States, ephedrine is most often used repletion http://whqlibdoc.who.int/publications/2010/
– In Europe, imipramine is also used 9789241547789 eng.pdf
Patient Resources
r α-adrenergic agents (dosing highly variable) r Oncofertility Consortium: http://oncofertility. See Also (Topic, Algorithm, Media)
– Pseudoephedrine 60 mg northwestern.edu/ r Kruger Strict Sperm Morphology
– Ephedrine 25–50 mg r Fertile Hope: www.fertilehope.org r Retrograde Ejaculation
– Imipramine 25–50 mg (may cause dizziness and r ASRM Cancer and Fertility Preservation: r Semen Analysis, Abnormal Findings, and
nausea); commonly used in Europe http://www.asrm.org/Cancer and Fertility Terminology
– Frequency ranges from QD to QID Preservation/ r Semen Analysis, Technique, and Normal Values
– Duration ranges from 2 to 14 days r Tanner Stage
– Side effects: HTN, tachycardia
Second Line REFERENCES
N/A CODES
1. Lee SJ, Schover LR, Partridge Ah, et al. American
SURGERY/OTHER PROCEDURES Society of Clinical Oncology recommendations on
In men who are azoospermic, aspiration of fertility preservation in cancer patients. J Clin ICD9
seminiferous tubules from the testis, sperm from the Oncol. 2006;24:2917–2931. r 186.9 Malignant neoplasm of other and unspecified
epididymis or microTESE with extraction of sperm and 2. Woodruff TK. The Oncofertility Consortium– testis
cryopreservation is a viable option and should be addressing fertility in young people with cancer. r 606.8 Infertility due to extratesticular causes
offered Nat Rev Clin Oncol. 2010;7:466–475. r V26.82 Encounter for fertility preservation procedure
ADDITIONAL TREATMENT 3. Hotaling JM, Lopushnyan NA, Davenport M, et al.
Radiation Therapy Raw and test-thaw semen parameters after
cryopreservation among men with newly diagnosed
ICD10
r C62.90 Malig neoplasm of unsp testis, unsp F
N/A descended or undescended
cancer. Fertil Steril. 2013;99:464–469.
Additional Therapies r N46.024 Azoospermia due to radiation
4. Trost LW, Brannigan RE. Oncofertility and the male
N/A cancer patient. Curr Treat Options Oncol. r Z31.84 Encounter for fertility preservation procedure
Complementary & Alternative 2012;13:146–160.
Therapies 5. http://www.cancer.org/treatment/
N/A treatmentsandsideeffects/treatmenttypes/radiation/
CLINICAL/SURGICAL
radiationtherapyprinciples/radiation-therapy- PEARLS
principles-side-effectsof-radiationto-specific-areas r <10% of men who bank sperm retrieve it for use in
ONGOING CARE (accessed June 14, 2014).
assisted reproductive technologies.
PROGNOSIS 6. Jeruss JS, Woodruff TK. Preservation of fertility in r Referral to a reproductive specialist and sperm
Roughly 30% of men who receive gonadotoxic patients with cancer. N Engl J Med. 2009;360:
902–911. cryopreservation prior to initiation of gonadotoxic
chemotherapy or radiotherapy will remain chemotherapy, radiation, or radical oncologic
azoospermic permanently surgery is essential.
COMPLICATIONS r Cost of sperm cryopreservation typically ranges from
N/A $200 to $500 initially usually with an annual
maintenance fee.
FOLLOW-UP
Patient Monitoring
r Men should have a repeat interrogation of their
male endocrine axis and another semen analysis by
a reproductive health specialist when they desire
paternity
151
FILLING DEFECT, UPPER URINARY TRACT (RENAL PELVIS AND URETER)

r Benign lesions
BASICS DIAGNOSIS – Air: Iatrogenic, infectious, fistula
– Blood clot
DESCRIPTION HISTORY – Fibroepithelial polyp
r Radiographic diagnosis of a radiolucent entity r Flank pain or renal colic
– Fungus ball
occupying the confines of the upper urinary tract r Hematuria
– Hemangioma
including the intrarenal collecting system or ureter, – Gross – Inflammatory lesions: Granuloma, malakoplakia,
as seen against contrast within the intraluminal – Microscopic TB
space r Pre-existing malignancy – Inverted papilloma
r The finding itself is nonspecific but may represent r History or urinary diversion – Calculus (usually radiolucent)
malignant or benign processes r Prior urinary tract manipulation (stent, stone – Benign tumors (rare): Leiomyoma, neurofibroma,
r Ureteroscopic evaluation is the gold standard to treatment, etc.) cholesteatoma
establish definitive diagnosis – Extrinsic compression of the ureter
PHYSICAL EXAM – Mucous (urinary diversion patients)
EPIDEMIOLOGY r Costovertebral angle tenderness
– Protein matrix
Incidence r Patient may by asymptomatic
– Ureteritis or pyelitis cystica
r Difficult to define given the nonspecific nature of the
DIAGNOSTIC TESTS & INTERPRETATION – Vascular impression
radiographic finding – Fibroepithelial polyp
– Upper tract urothelial carcinoma (UTUC) Lab
r Urinalysis – Papilla
◦ Estimated 5,900–7,300 new cases in USA in ◦ Prominent papilla (ectopic or end on; normal
r Urine cytology may suggest malignancy
2014 (1)[C] anatomic variant)
r Urine culture including fungal cultures
Prevalence ◦ Sloughed papilla (may cause obstruction or
r Nephrolithiasis r Serum creatinine/BUN
hematuria)
– Reported prevalence of kidney stones in USA Imaging – Foreign body
between 1976 and 1994 was 13% in men and r Filling defects are found in imaging modalities ◦ Stent fragment (retained)
7% in women (2)[C] which utilize contrast that fills the intrarenal ◦ Staple/clip (more likely with urinary diversion)
collecting system
RISK FACTORS – Intravenous injection of contrast
r For UTUC TREATMENT
◦ CT urogram
– History of smoking ◦ MR urogram
– History of urothelial carcinoma of the bladder ◦ IVP
GENERAL MEASURES
– Gene carrier or family history of Lynch syndrome r If any doubt exists about the etiology of the filling
◦ Invasive arteriograms (cardiac catheterization,
(hereditary nonpolyposis colorectal cancer) defect then diagnostic ureteroscopy is indicated
r For nephrolithiasis aortogram, etc.) r Prominent papilla may appear as filling defects in
– Intraluminal administration of contrast
– Previous stone history ◦ Retrograde pyelogram the very peripheral aspect of renal calyces in an
– Chronic dehydration ◦ Antegrade nephrostogram “end on” position
– Dietary factors ◦ Cystogram (if reflux present) MEDICATION
◦ Elevated sodium intake
◦ Purine gluttony Diagnostic Procedures/Surgery First Line
r For stones composed purely of uric acid manifesting
r For sloughed papilla Ureteroscopic evaluation is required to obtain
definitive diagnosis and provides for direct visual as filling defects, alkalization of the urine can be
– NSAID overuse
inspection with relatively low morbidity (3)[C] attempted and if pH of 6.5 or greater is achieved
– Sickle cell disease or trait
then uric acids may dissolve over time
– History of diabetes Pathologic Findings – Potassium citrate
r For fungus ball Depends on underlying etiology – Sodium bicarbonate
– Immunosuppression DIFFERENTIAL DIAGNOSIS
r Malignant lesions Second Line
Genetics N/A
N/A – UTUC
– Rare primary cancers of the upper urothelial
PATHOPHYSIOLOGY
surface
Depends on underlying etiology ◦ Squamous cell carcinoma (often associated with
ASSOCIATED CONDITIONS chronic untreated infected staghorn calculi)
r Hematuria ◦ Adenocarcinoma
– Gross ◦ Inverted papilloma (about 15% have malignant
– Microscopic components)
r Flank pain ◦ Sarcoma
◦ Leiomyosarcoma
GENERAL PREVENTION ◦ Angiosarcoma
r Depends on underlying etiology
◦ Small cell carcinoma
– UTUC – Metastatic carcinoma
◦ Smoking cessation/avoidance ◦ Melanoma
– Nephrolithiasis ◦ Renal cell carcinoma
◦ Adequate hydration
◦ Diet and lifestyle modification to prevent future
stone formation
152
FILLING DEFECT, UPPER URINARY TRACT (RENAL PELVIS AND URETER)
r UTUC
ADDITIONAL READING
ONGOING CARE r Hubosky SG, Boman BM, Charles S, et al.
– For low-grade UTUC which can be reached
ureteroscopically and completely ablated, 5-yr PROGNOSIS Ureteroscopic management of upper tract urothelial
r Depends on underlying etiology carcinoma (UTUC) in patients with Lynch syndrome
survival is equal to radical nephroureterectomy
(4)[C] – Prognosis usually excellent for benign conditions (hereditary nonpolyposis colorectal cancer
◦ After complete ablation, local recurrence can be – UTUC (prognosis depends on pathologic staging) syndrome). BJU Int. 2013;112(6):813–819. doi:
seen in up to 75% of patients if followed for at (5)[C]. TNM pathologic staging and prognosis is 10.1111/bju.12008
least 5 yr. as follows: r Matin SF, Margulis V, Kamat A, et al. Incidence of
◦ Progression of low-grade to high-grade disease ◦ pTo, pTa, and pTis have 93% and 89% downstaging and complete remission after
occurs in about 15% of cases cancer-specific survival at 5 and 10 yr neoadjuvant chemotherapy for high-risk upper tract
◦ These points should be stressed to patients ◦ pT1 has 91% and 85% cancer-specific survival urothelial cell carcinoma. Cancer. 2010;116:
when counseling on the management of UTUC at 5 and 10 yr 3127–3134.
– For high-grade UTUC or very large-volume ◦ pT2 has 75% and 70% cancer-specific survival r Stower MJ, MacIver AG, Gingell JC, et al. Inverted
low-grade UTUC, radical extirpative surgery is at 5 and 10 yr papilloma of the ureter with malignant change. BJU.
considered the gold standard for cancer control ◦ pT3 has 54% and 45% cancer-specific survival 1990;65:13.
◦ Nephroureterectomy (open or laparoscopic) at 5 and 10 yr r Xu AD, Ng CS, Kamat A, et al. Significance of upper
◦ Segmental ureterectomy ◦ pT4 has 12% and 6% cancer-specific survival at
urinary tract urothelial thickening and filling defect
r Nephrolithiasis 5 and 10 yr seen on MDCT urography in patients with a history
– Ureteroscopy with laser lithotripsy COMPLICATIONS of urothelial neoplasms. Am J Roentgenol.
– ESWL with or without retrograde pyelogram to N/A 2010;195:959–965.
assist with localization or with ultrasound
guidance FOLLOW-UP See Also (Topic, Algorithm, Media)
r Fibroepithelial Polyp, Genitourinary
– PCNL Patient Monitoring
r Sloughed papilla r UTUC r Filling Defect, Upper Urinary Tract (Renal Pelvis and
– Ureteroscopy confirms diagnosis – For those undergoing ureteroscopic conservative Ureter) Image
r Fungal Infections, Genitourinary
F
◦ Papilla can be removed primarily with treatment, regular surveillance including
cystoscopy and ureteroscopy is required given r Reference Tables: TNM: Renal Pelvis and Ureter
ureteroscopic grasper or basket
◦ Coagulation with cautery or laser will achieve high chance of local recurrence Cancer
hemostasis – Cross-sectional imaging (CT or MRI) is r Ureter and Renal Pelvic Tumors, General
◦ Avoid overuse of NSAIDs recommended to check for locally advancing Considerations
r Fibroepithelial polyp disease r Ureter and Renal Pelvis, Squamous Cell Carcinoma
– Can be removed with ureteroscopy using laser or – For those undergoing radical nephroureterectomy r Ureter and Renal Pelvis, Urothelial Carcinoma
grasper (NU), surveillance cystoscopy and cross-sectional r Urolithiasis, Ureteral
r Fungus ball imaging are also needed on a regular basis
r Nephrolithiasis
– Can be removed with ureteroscopy or
– Renal ultrasound, serum electrolyte testing
percutaneous approach
– For patients at high risk for stone recurrence,
CODES
– Antifungals
24-hr urine electrolyte evaluation
ADDITIONAL TREATMENT ICD9
Patient Resources r 189.1 Malignant neoplasm of renal pelvis
Radiation Therapy N/A r 189.2 Malignant neoplasm of ureter
N/A
r 793.5 Nonspecific (abnormal) findings on
r UTUC REFERENCES radiological and other examination of genitourinary
organs
– Neoadjuvant chemotherapy is currently under 1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics,
investigation for suspected high-stage disease 2014. CA Cancer J Clin. 2014;64(1):9–29. ICD10
with preliminary data suggesting down staging on r C65.9 Malignant neoplasm of unspecified renal
2. Stamatelou KK, Francis ME, Jones CA, et al. Time
pathologic specimens pelvis
trends in reported prevalence of kidney stones in
Complementary & Alternative the United States: 1976–1994. Kidney Int. 2003; r C66.9 Malignant neoplasm of unspecified ureter
Therapies 63:1817. r R93.4 Abnormal findings on diagnostic imaging of
N/A 3. Conlin MJ. Diagnostic ureteroscopy. In: Smith AD, urinary organs
et al. Smith’s Textbook of Endourology. 3rd ed.
Chichester: Wiley and Blackwell, 2012.
4. Grasso M, Fishman AI, Cohen J, et al. CLINICAL/SURGICAL
Ureteroscopic and extirpative treatment of upper PEARLS
urinary tract urothelial carcinoma: A 15-year r Up to 40% of patients with an upper tract urothelial
comprehensive review of 160 consecutive patients.
BJU Int. 2012;110:1618–1626. carcinoma will develop urothelial carcinoma of the
bladder.
5. Margulis V, Shariat SF, Matin SF, et al. Outcomes r Ureteroscopy can be both diagnostic and
of radical nephroureterectomy: A series from the
upper tract urothelial carcinoma collaboration. therapeutic.
Cancer. 2009;115:1224–1233.
153
FLANK PAIN, GENERAL

Taylor B. Vaughan, MD
James S. Rosoff, MD

r Urinalysis
DESCRIPTION HISTORY – Initial diagnostic step in the management of flank
r Flank pain refers to pain or discomfort in the side of r Age and sex of patient
r Pain characteristics pain. Ensure proper specimen collection: Clean
the abdomen between the last rib and the hip. catch or catheterized specimen.
r Sometimes referred to as loin pain, it is often – Location: Flank(s)/abdomen – Dipstick test is performed to evaluate for the
associated with urologic conditions, although not – Quality: Dull/sharp presence of blood and/or infection. If abnormal, it
exclusively. – Duration: How long have symptoms been present should be followed by microscopic analysis and
– Severity: Use visual analog pain scales sent for culture and sensitivities.
EPIDEMIOLOGY – Timing: Constant/intermittent, onset (sudden vs. – Presence of epithelial cells suggests a
Incidence gradual) contaminated sample.
True incidence is difficult to ascertain, as it is a – Radiation: Pain radiating from the flank down into – Hematuria suggests insult to the urologic system.
common symptom associated with many medical the testicle or labia may suggest renal colic caused – Urinary pH: >7.6 should raise suspicion for the
conditions. by passage of stone or clot down the ureter presence of urea-splitting organisms.
Prevalence – Moderating factors: Medications, rest, position – A pH <5 is often associated with the formation of
r Many medical conditions can cause flank pain, the – Aggravating factors: Movement, cough uric acid calculi.
prevalence is high. – Associated symptoms: Fever, chills, dysuria, – Nitrite and/or LE positivity: Indicates presence of
r Up to 12% of the adult US population will suffer nausea, vomiting infection or inflammation. Nitrite positivity is more
r Prior medical history
from urolithiasis at some point. specific for infection than LE positivity.
– History of nephrolithiasis (stone recurrence rates: r Urine and blood cultures: Collect prior to
RISK FACTORS 10%, 1 yr; 35%, 5 yr; 50%, 10 yr)
Risk factors are dependent upon etiology administration of antibiotic therapy.
– Diabetes mellitus, patients have higher r CBC: Elevated WBC suggests infectious or
Genetics predisposition to papillary necrosis and infections,
inflammatory process. Low Hgb/Hct may suggest
NA including xanthogranulomatous pyelonephritis
hemorrhage.
(XGP) and emphysematous pyelonephritis r Chemistry profile: Assess renal function and
PATHOPHYSIOLOGY – GYN history (pregnancy/STDs)
r Flank pain caused by urologic pathology is usually electrolytes; elevated BUN/creatinine and reduced
– History of trauma (penetrating vs. blunt)
due to sudden stretch of the renal capsule, generally r Prior surgical history creatinine clearance suggest renal
from inflammation or distal obstruction. insufficiency/failure.
r The severity of the pain is directly related to the – General surgical, urologic, and gynecologic r Liver function panel: Rule out malignant hepatic
abdominal and pelvic procedures involving a
acuity of the obstruction and not to its degree. potential risk of ureteral injury and obstruction processes.
r Flank pain from renal inflammation has a gradual r Other tests may be ordered depending on clinical
(TAH/BSO, vascular bypass, AAA repair, colectomy,
onset and is often not as severe as renal colic due to ureteral manipulation) presentation and judgment.
acute obstruction. r Social history Imaging (1)
r Flank pain from chronic obstruction is generally less r Plain radiograph. Historically, a kidney ureter bladder
– Smoking is a risk factor for development of
severe, or may be absent. urothelial carcinoma abdominal flat plate plain film (KUB) was the initial
r Family history radiograph done for the evaluation of flank pain to
Pregnancy Considerations: – Polycystic kidney disease rule out urolithiasis. However, KUB may be unable to
r Flank pain during pregnancy may be a symptom of – Renal cell carcinoma demonstrate small or radiolucent (eg, uric acid,
indinavir) calculi. May show nephrocalcinosis.
an obstructing ureteral stone or pyelonephritis, as PHYSICAL EXAM
r Vital signs Overall sensitivity for stone detection is 59%.
well as hydronephrosis of pregnancy which may be r Excretory urogram/IVP
present in 60–100% of women (more commonly on – Temperature: Fever is usually associated with
the right). – Once the standard for urologic evaluation of flank
infectious etiologies
pain, IVP is very accurate, with the diagnosis of
GENERAL PREVENTION – Blood pressure
◦ Hypotension: Suspect sepsis or hemorrhage (eg, calculous disease able to be established in 96% of
r Strategies depend on the etiology of the pain. cases.
r Preventive strategies for calculous disease may ruptured angiomyelolipoma (AML), aortic
– Aids in quantifying severity of obstruction.
aneurysm), may need immediate intervention
include dietary modification and medical ◦ Hypertension: May reflect response to pain. Rule – Contraindications to the use of IV contrast media
management to reduce recurrent stone formation. include renal insufficiency and previous reaction to
out renal parenchymal, renal cystic, or vascular
– Dietary modifications include increasing fluid contrast media.
disease
intake, and reducing intake of sodium, animal r Abdominal exam – Limitations include the complexity and length of
protein, and oxalate-rich foods. time needed to perform the series of images.
– Drugs such as citrate, allopurinol, and thiazide – Inspect for scars, skin changes, or signs of trauma r CT
diuretics may be necessary depending on the – Bruit with aneurysm
– Low-dose, noncontrast-enhanced CT has largely
underlying metabolic abnormality. – Palpate abdomen and flanks to evaluate for
replaced KUB and IVP as the standard imaging
– Calcium reduction has not been shown to affect masses, organomegaly, or tenderness
modality for the workup of acute flank pain from
the likelihood of recurrent stone formation in most – Fist percussion of flank: CVA tenderness suggests
suspected urolithiasis. It has been shown to be
patients. renal etiology
r Peripheral pulses with aneurysm very sensitive and specific (97% and 96%,
respectively) in detecting calculi.
– It can detect secondary signs of obstruction
(hydronephrosis, renal enlargement, perinephric
stranding), and can also be used to assess
nonrenal causes of flank pain (appendicitis,
pancreatitis, tubal pregnancy, etc.).
154
FLANK PAIN, GENERAL
r Renal/ureters/bladder US COMPLICATIONS
– Can diagnose hydronephrosis with a sensitivity of TREATMENT Longstanding ureteral obstruction can cause
85–94% and a specificity of 100%. permanent loss of renal function.
– Disadvantages: Sensitivity for detecting stones GENERAL MEASURES (3)
r Treatment varies based on etiology. FOLLOW-UP
only 24–57%, limited in obese patients, and
operator-dependent. – Rest and physical therapy may be recommended Patient Monitoring
r Nuclear scan: Helps to evaluate differential renal for flank pain cause by muscle spasms. Periodic renal imaging, urinalysis, or 24-hr urine may
function, degree of obstruction, and presence of – NSAIDs are excellent 1st-line agents to control be indicated for patients with stone disease. Follow-up
renal scarring. pain secondary to inflammation, but caution must may be more or less intensive based on etiology.
r MRI: Not usually indicated for initial workup unless be used in the presence of acute ureteral Patient Resources
CT is contraindicated. It may be helpful for obstruction or in patients with advanced renal MedlinePlus http://www.nlm.nih.gov/medlineplus/
evaluation of renal masses or in the evaluation of disease as they can decrease intrarenal blood flow. ency/article/003113.htm
suspected spinal cord pathology. MEDICATION
Diagnostic Procedures/Surgery First Line
r Acute pain control (NSAIDs, opioids)
REFERENCES
These are dependent upon etiology
r Antiemetics, antipyretics, antibiotics as appropriate 1. Carter MR, Green BR. Renal calculi: Emergency
Pathologic Findings
These are dependent upon etiology r IV fluids if sepsis/hypovolemia. May also help with department diagnosis and treatment. Emerg Med
passage of stones Pract. 2011;13(7):1.
DIFFERENTIAL DIAGNOSIS 2. Coursey CA, Casalino DD, Remer EM, et al. ACR
r There are many causes of flank pain. It is useful to Second Line Appropriateness Criteria acute onset flank
differentiate between urologic and nonurologic α-antagonists and calcium channel blockers may help pain–suspicion of stone disease. Ultrasound Q.
causes. Renal/ureteral etiologies are the most with expulsion of ureteral stones. 2012;28(3):227–233.
common and those that usually require urologic SURGERY/OTHER PROCEDURES 3. Marx JA, Hockberger RS, Walls RM, et al. Rosen’s
intervention. Some of the most common causes are r Prior to any diagnostics or intervention, the patient Emergency Medicine: Concepts and Clinical
listed below (2). must be stabilized. Practice. 7th ed. St Louis, MO: Mosby; 2010. F
– Urologic r Surgical management may be required in some
◦ Calculi: Mostly ureteral; however, renal pelvic
cases depending on the etiology and the patient’s
and calyceal stones (obstructing infundibulum)
can cause flank pain
medical condition. ADDITIONAL READING
r Examples of surgical management: If the collecting
◦ Acute cortical necrosis N/A
◦ Acute papillary necrosis system is infected and obstructed or renal abscess is
◦ Ptotic kidney present, percutaneous drainage and antibiotics are See Also (Topic, Algorithm, Media)
the mainstays of treatment. If dealing with a r Calcifications, Abdominal and Pelvic
◦ Polycystic kidney disease
◦ Acute/chronic pyelonephritis ruptured AML, embolization should be considered. r Hydronephrosis/Hydroureteronephrosis (Dilated
◦ Renal infarction (renal artery thrombus or Renal tumors should be treated on an elective basis. Ureter/Renal Pelvis), Adult
Emergent nephrectomy for ruptured AML or r Renal Mass
dissection)
◦ Renal cyst (especially hemorrhagic; benign cysts XGP/emphysematous pyelonephritis may be r Urolithiasis, Adult, General
necessary. r Urolithiasis, Pediatric, General Considerations
rarely cause flank pain)
◦ Renal neoplasm ADDITIONAL TREATMENT
◦ Renal trauma Radiation Therapy
◦ Renal vein thrombosis NA CODES
◦ Retroperitoneal bleed or mass
◦ Ureteropelvic junction obstruction Additional Therapies
◦ Calyceal diverticulum NA ICD9
r 592.9 Urinary calculus, unspecified
◦ Medullary sponge kidney Complementary & Alternative r 788.0 Renal colic
◦ Other ureteral obstruction (extrinsic Therapies r 789.09 Abdominal pain, other specified site
compression, blood clot, necrotic material, etc.) NA
– Nonurologic ICD10
◦ Appendicitis r N20.9 Urinary calculus, unspecified
◦ Abdominal aortic aneurysm ONGOING CARE
r N23 Unspecified renal colic
◦ Diabetes r Follow-up for flank pain will also be dictated by the r R10.9 Unspecified abdominal pain
◦ Diverticulitis
etiology and acuity of the clinical presentation.
◦ Herpes zoster
Repeat imaging or other lab studies may be required
◦ Musculoskeletal (muscle spasm, costochondritis,
depending on response to initial therapy. CLINICAL/SURGICAL
strain) r If clinical picture fails to improve or worsens, a
◦ Myocardial infarction PEARLS
◦ Ovarian torsion change in therapy should be instituted (ie, different
antibiotic, PCN, surgical intervention). r Flank pain associated with fever and chills may
◦ Pancreatitis
represent urinary tract infection (pyelonephritis).
◦ Peripheral nerve compression or trauma PROGNOSIS r Abdominal aortic aneurysm is a potentially
◦ Peripheral neuropathy In general, for nephrolithiasis, the prognosis is good
◦ Pleuritis life-threatening cause of flank pain.
but this may vary for other etiologies.
◦ Tubal pregnancy
◦ Vertebral or spinal cord/nerve root irritation
(herniated disc, sciatica, vertebral body fracture,
or collapse)
155
FOLEY CATHETER PROBLEMS (INSERTION AND REMOVAL)

James Kearns, MD
GENERAL PREVENTION DIFFERENTIAL DIAGNOSIS

BASICS r Minimization of unnecessary urethral catheterization r Difficulty placing catheter
r Removal of urethral catheter as soon as clinically – Urethral sphincter spasm
DESCRIPTION indicated – BPH
r The terms “urethral catheter” and “Foley catheter” r Proper insertion technique prevents false passages – Urethral stricture
are often used interchangeably. Urethral catheter is and potential bladder neck or urethral strictures – Bladder neck contracture
a general description of a tube that traverses the – Catheter should always be placed without undue – Urethral disruption
urethra whereas a Foley catheter refers to a urethral force, using copious lubrication – Urethral false passage
catheter with a retention balloon. ◦ Excess force may lead to false passage creation – Phimosis
r Common types of urethral catheter include: – Meatal stenosis
– Foley: rounded tip with balloon ALERT – Penile/foreskin edema
– Council: hole at distal tip to allow for passage Do not inflate foley balloon unless the catheter is – Obesity/buried penis
over wire or on the end of a stylette confirmed in the bladder. – Retracted meatus in women
– Coude’: angulated distal tip to allow for r Look for urine return and insert catheter until – Urethral stone or foreign body
navigating past large prostates or elevated r Problems with drainage
“hub” reaches urethral meatus.
bladder necks r If no urine return with “hubbed” catheter, irrigate – Clot retention
r 2-way catheters have a single drainage port and a – Bladder debris (tumor or stone)
normal saline into the bladder with a r Difficulty removing catheter
balloon port
r 3-way catheters have a drainage port, an infusion catheter-tipped syringe; 120 mL is often necessary
– Improper coupling of syringe to balloon port
before fluid can be aspirated.
port, and a balloon port r Inflation in urethra or prostate may lead to – Obstructed balloon port
– NOTE: Drainage channel is larger in a 2-way – Encrustation of balloon or catheter
catheter than 3-way catheter of the same size significant hematuria or future urethral stricture as – Catheter sutured in place
r Size measured in Charrier or French (Fr) scale well as inability to place another catheter:
– Fr = D × 3, where D = diameter in mm – Always inflate balloon with water as saline may
– Common sizes include 5–10 Fr in the pediatric crystallize and is usually not necessary to test TREATMENT
population and 16–24 Fr in the adult population balloon prior to insertion
r Common materials include latex and silicone GENERAL MEASURES
r Assess need for urethral catheterization
– Latex appropriate for short-term (<1 mo) r For difficult placement, start with an 16–18-Fr Foley
– Silicone better for longer-term or latex allergy DIAGNOSIS and note location of difficulty
r Hydrophilic coatings may facilitate easier passage of
HISTORY – If stricture suspected, attempt 1 pass with
catheter r Previous difficulty with catheterization 12–16-Fr Foley
r Problems can occur with insertion, drainage, or
r Urethral instrumentation in the past – If BPH suspected, attempt 1 pass with 18–22-Fr
removal r Episodes of urethral catheterization coude
r Choose proper catheter size for pediatric population
EPIDEMIOLOGY r Prior pelvic radiation or brachytherapy
Incidence r History of urinary symptoms – Newborns/neonates based on body weight (no
Unknown but very common in hospitalized patients retention balloon)
– Quality of urinary stream, urinary frequency, ◦ <1000 gm: 3.5 Fr
Prevalence sensation of emptying, history of urinary retention ◦ 1000–1800 gm: 5 Fr
N/A r Circumcision may lead to meatal stenosis
◦ 1800–4000 gm: 6.5 Fr
RISK FACTORS PHYSICAL EXAM ◦ >4000 gm: 8 Fr
Hospitalized patient requiring strict documentation of r Abdominal examination for palpable bladder, – Children
urine output, BPH, urethral stricture disease, bladder dullness to percussion over lower abdomen ◦ Age <5 yr, 5–8 Fr
neck contracture, previous urethral or prostate surgery, r DRE feels for evidence of prostate cancer (nodularity ◦ Age 5–10 yr, 8–10 Fr
trauma, immobility, obesity or hardness), prostatic abscess (tender prostate), ◦ Age 10–14 yr, 10 Fr
urethral disruption (high-riding or nonpalpable ◦ Age >14 yr, 10–14 Fr
Genetics
N/A prostate) MEDICATION
r Bimanual examination to evaluate for bladder or
PATHOPHYSIOLOGY First Line
pelvic masses Intraurethral lidocaine jelly may be useful in difficult
Indications for urethral catheterization include need r Palpate penis for strictures
for bladder decompression, need for accurate catheter placement
– Both location and length of stricture important
monitoring of urine output, immobility during r Blood at meatus suggests trauma/urethral disruption Second Line
postoperative setting, diversion of urine from wounds, N/A
instillation of therapeutic agents, and facilitation of DIAGNOSTIC TESTS & INTERPRETATION SURGERY/OTHER PROCEDURES
certain diagnostic studies (eg, urodynamics, VCUG, Lab r Urethral sphincter spasm
cystogram) r Electrolytes and creatinine to evaluate for renal
– Provide reassurance and ask patient to relax and
ASSOCIATED CONDITIONS function take slow, deep breaths
r BPH – Decreased renal function in an obstructed patient – Intraurethral lidocaine jelly may not decrease
r Balanitis xerotica obliterans (BXO) is risk factor for postobstructive diuresis pain (1)
r UTI Imaging – Instruct patient to attempt to void when
r Urinary retention r Generally unnecessary encountering the sphincter
r Neurogenic bladder r Retrograde urethrogram can demonstrate urethral r BPH
r Liver failure, heart failure—edema disruption, injury, or stricture – Use a coude catheter to help navigate the
r Cystourethroscopy, if needed prostate
◦ Bend of catheter always facing up toward ceiling
Diagnostic Procedures/Surgery (often matches a raised area on balloon port)
r Catheterization is both diagnostic and therapeutic
– Larger (ie, 20–22 Fr) preferable because less likely
– See treatment section to bend on itself
Pathologic Findings
If performed in OR, may consider biopsy of strictures
156
FOLEY CATHETER PROBLEMS (INSERTION AND REMOVAL)
r Urethral stricture/bladder neck contracture

ALERT REFERENCES
– If unable to pass 14 Fr or larger catheter, dilation If outflow from catheter stops while on continuous
likely necessary 1. Gordetsky J, Bendana E, O’Brien J, et al. (Almost)
bladder irrigation (CBI), immediately stop inflow.
– General principle is to place catheter over a wire r Decreased catheter output from bladder debris: painless surgery: A historical review of the
into the bladder using Seldinger technique evolution of intraurethral anesthesia in urology.
– Manually irrigate
– Flexible cystoscopy is ideal J Urology. 2010;77:12–16.
◦ Advance scope to level of stricture – Consider insertion of larger catheter
r Inability to remove catheter: 2. Lückhoff C, Mitra B, Cameron PA, et al. The
◦ Pass 0.038” wire through stricture into bladder diagnosis of acute renal trauma. Injury. 2010;
– If cystoscope unavailable, consider filiforms with – Place syringe on balloon port for 30 min 42:913–916.
followers, or blindly pass 0.038” soft-tip wire into – Cut balloon port and wait for fluid output
3. Siddiq D, Darouiche RO. New strategies to prevent
bladder and confirm location of wire in bladder – Insert stiff end of wire through balloon port to catheter-associated urinary tract infections. Nat Rev
◦ Portable pelvic x-ray attempt to unclog the port Urol. 2012;9:305–314.
◦ Insert 5-Fr open-ended catheter over wire and – If still unable to remove catheter:
aspirate; presence of urine indicates bladder ◦ Under US guidance, spinal needle may be
location of wire inserted into balloon percutaneously ADDITIONAL READING
◦ In women, transvaginal US and needle
ALERT placement may be preferable Hollingsworth M, Quiroz F, Guralnick ML. The
Never dilate urethra unless wire in bladder. ◦ If balloon palpable in bulbar or pendulous management of retained Foley catheters. Can J Urol.
r Wire rigid enough to potentially undermine 2004;11(1):2163–2166.
urethral, transcutaneous placement of a
bladder neck or enter rectum: 22-gauge needle may decompress balloon
– Dilate over wire using serial Amplatz-type renal
– If catheter sutured in place and suture r Benign Prostatic Hyperplasia
dilators to 1 size larger than desired catheter (ie, resorbable, consider waiting before removing r Foley Catheter Problems (Insertion and Removal)
22 Fr for 20-Fr catheter) catheter
r If dilators unavailable, serial silicone catheters Images
– Open cystotomy with retrograde removal is a r Foley Catheter Problems (Insertion and Removal)
may be rigid enough for dilation:
– Insert Council catheter over wire until return of
final resort Algorithm
r Postobstructive Diuresis
F
urine and inflate balloon ADDITIONAL TREATMENT r Urethral Stricture Disease
r If Council unavailable, use 14-gauge Angiocath to
Radiation Therapy
thread wire into Foley. N/A
r Urethral disruption Additional Therapies CODES
– Retrograde urethrogram generally necessary for If unable to place urethral catheter, suprapubic
diagnosis, but consider blind passage of catheter catheterization may be necessary ICD9
in trauma patient without pelvic fracture or signs r 996.64 Infection and inflammatory reaction due to
Complementary & Alternative indwelling urinary catheter
of urethral injury (ie, blood at meatus, perineal
Therapies r 996.76 Other complications due to genitourinary
hematoma, high-riding prostate) (2)
N/A
– Consider cystoscopically inserting catheter device, implant, and graft
– Low threshold for suprapubic catheter r V53.6 Fitting and adjustment of urinary devices
r Urethral false passage ONGOING CARE
– False passage generally down, so use coude with ICD10
PROGNOSIS r T83.51XA Infect/inflm reaction due to indwell
tip pointed up
– If unable to pass coude, use cystoscope to place N/A urinary catheter, init
r T83.89XA Other specified complication of
wire in bladder and place catheter over wire COMPLICATIONS
r Phimosis r False passage genitourinary prosthetic devices, implants and
– Attempt to retract foreskin r Hematuria grafts, initial encounter
r Catheter-associated UTI r Z46.82 Encounter for fitting and adjustment of
– If able to visualize meatus, attempt to place Foley
through meatus normally – Many catheters have antimicrobial coatings, non-vascular catheter
– If unable to visualize meatus, perform dorsal slit in which may not be beneficial (3)
foreskin under local anesthesia CLINICAL/SURGICAL
r Meatal stenosis FOLLOW-UP
– Inject lidocaine gel Patient Monitoring PEARLS
r Before removing difficult Foley, ensure no
– Serial dilation with Van Buren sounds r Proper initial catheter placement will prevent many
r Penile/foreskin edema foreseeable indication for recatheterization
r Consider removing catheters at midnight so a failed subsequent problems.
– Manually compress edematous skin to minimize r A calm patient and proper equipment are critical for
edema voiding trial can be managed early during the day
success.
– Place catheter once meatus visible Patient Resources r If dilation is necessary, always confirm wire in
r Retracted female meatus N/A bladder before dilating.
– Inserting a finger into the vagina may bring r Perform voiding trials at times that allow for
meatus forward
reinsertion of difficult catheter at a convenient time.
– Manually direct catheter into meatus r Suprapubic catheterization is a reliable method of
r Urethral stone or foreign body
bladder drainage, if needed.
– Cystoscopically remove stone/foreign body r Remove catheter as soon as possible to reduce risk
r Clot retention with no catheter output
of catheter-associated UTI.
– Ensure at least 20-Fr 2-way catheter in place
– Manually irrigate catheter
– If urine does not remain clear after irrigation,
consider placing 3-way catheter (22 or 24 Fr) for
continuous irrigation
157
FOURNIER GANGRENE
Brad Figler, MD
Bryan Voelzke, MD, MS

BASICS r Perianal/scrotal abscess
Lab
r Immunosuppression r CBC: Leukocytosis/leukopenia, anemia
DESCRIPTION r Obesity r Serum chemistry: Hyponatremia, hypocalcemia,
r Necrotizing soft tissue infection arising in the r Urethral stricture elevated serum creatinine, hyperglycemia, metabolic
genitalia and/or perineum r Paraplegia acidosis
r Rapidly progressive and life-threatening with a high r Myonecrosis may elevate CK levels
r Malignancy
mortality rate r Septic abortions, vulvar abscesses, and episiotomy r Coagulopathy
r Much more common in men than women
(in women) r Glucosuria and pyuria
r Wound culture (aerobes, anaerobes, fungi)
ALERT GENERAL PREVENTION
Fournier gangrene is a urologic emergency, causing r Early recognition/treatment of infection – Aspiration of subcutaneous skin at the point of
progressive tissue destruction with significant r Early and aggressive management of underlying demarcation for Gram stain and culture may be
potential for soft tissue loss, sepic shock, and death. useful
immunosuppressive conditions – Deep tissue cultures at the time of surgery should
Prompt debridement is mandatory.
be obtained
r Urine and blood culture. In spite of severe clinical
EPIDEMIOLOGY DIAGNOSIS
findings blood cultures are rarely positive
Incidence HISTORY
r 1.1 per 100,000 patients are admitted for treatment r Presentation is typically abrupt with severe pain in Imaging
r Plain radiography or ultrasound may show
of Fournier gangrene nationally (1) the perineum, abdominal wall and thighs, however
r Most common in 5th and 6th decades of life subcutaneous emphysema; less sensitive than CT
a prodrome of several days of fever and lethargy can r CT helpful in identifying nidus of infection and/or
r Male > Female (10:1)
be seen
r Limited to 60 case reports in children r Perineal or genital trauma (including bites) subcutaneous emphysema
r MRI can be used to define affected areas, but
Prevalence r Urethral instrumentation
r Perirectal/scrotal/perineal abscess or wound should not delay prompt surgical intervention
Unknown
r Urinary tract infection or STD Diagnostic Procedures/Surgery
RISK FACTORS r Immediate surgical debridement
r Alcoholism r Urethral stricture disease
r Incision should be extended until normal appearing
r Diabetes mellitus r Anal fissure, fistulae, or hemorrhoids
r Alcohol or IV drug abuse tissue is encountered
r Genital skin trauma r Infection presumed present as far peripherally as
r Impaired immunity r Malignancy
r Diabetes mellitus swelling, erythema exist, watery pus, or necrotic
r IV drug abuse fascia are found
r Recent penile, perineal, or perirectal surgery r Steroid use
r HIV Pathologic Findings
r Urethral stricture r Intact epidermis with dermal necrosis
PHYSICAL EXAM r Vascular thrombosis
PATHOPHYSIOLOGY r Altered mental status
r Primary insult is a breach in the integrity of the GI or r Acute PMN infiltrate
r Pain out of proportion with physical exam
urethral mucosal lining DIFFERENTIAL DIAGNOSIS
r Infection is frequently polymicrobial (aerobic and r Tachycardia and tachypnea
r Cellulitis
r Fever or hypothermia
anaerobic, gram-positive and gram-negative) r Balanitis
r Pathogens differs from nonnecrotizing infection: r Cellulitis
r Epididymitis/orchitis
Higher frequency of virulent organisms such as r Dusky, erythematous or frankly necrotic, skin
r Hidradenitis suppurativa
group A streptococci, community-associated r Foul odor described as strong or feculent
r Pyoderma gangrenosum
methicillin-resistant Staphylococcus aureus r Crepitus
r Strangulated inguinal hernia
(CA-MRSA), and Clostridium spp (2) r Edema of the involved skin
r Obliterative endarteritis leads to thrombosis, r Testicular torsion
r Purulent drainage
ischemia, and necrosis, which allows for further r Rectal exam essential. Assess for:
bacterial proliferation
r Process extends along Dartos and Colles fascia, – Tumor
– Perirectal abscess
potentially involving perineum, abdomen, thighs,
ischiorectal fossa, and retroperitoneum
r Rates of spread as high as 2–3 cm/h have been
reported
r Deep structure (corpus cavernosum, corpus
spongiosum, and testicles) are typically not affected
158
FOURNIER GANGRENE
r Postoperative care FOLLOW-UP

TREATMENT – If a vacuum assist closure (VAC) dressing is not Patient Monitoring
used, wet-to-dry dressing changes are performed Prolonged critical care may be required.
GENERAL MEASURES BID-TID
r Immediate and aggressive surgical therapy with – EUA after 24–48 hr to assess for and debride Patient Resources
newly necrotic tissue http://www.mayoclinic.com/health/
debridement of necrotic tissue
r Aggressive fluid resuscitation (isotonic fluid) – Follow cultures for sensitivities and adjust gangrene/DS00993
r Inotropic support is frequently necessary antibiotic therapy accordingly
r Correct coagulopathy – Nutritional support (preferably enteral) should be REFERENCES
r Quadruple antibiotics instituted early to correct the negative nitrogen
r ICU support until clinically stable balance associated with profound sepsis 1. Sorensen MD, Broghammer JA, Rivara FP, et al.
Fournier’s gangrene: Contemporary population-
ADDITIONAL TREATMENT based incidence and outcomes analysis: A HCUP
MEDICATION r VAC may result in earlier wound granulation
First Line database study. J Urol. 2008;179(4):13.
r Antibiotics should include gram-positive, compared to simple wet-to-dry dressing changes,
2. May AK, Stafford RE, Bulger EM, et al. Treatment of
but may be difficult to apply to the perineum and
gram-negative, and anaerobic coverage in full complicated skin and soft tissue infections. Surg
genitalia (Level I) (4)
therapeutic dosages r If a VAC closure is not possible, the wound should Infect (Larchmt). 2009;10(5):467–499.
r Modify antibiotics as needed, based on Gram stain, 3. Mindrup SR, Kealey GP, Fallon B. Hyperbaric
be packed with fine-mesh gauze soaked in normal
culture, and sensitivity oxygen for the treatment of Fournier’s gangrene.
saline, Dakin (25%) solution, or Clorpactin
r Appropriate empiric therapy typically consists of: r Diverting colostomy may help keep perineal or J Urol. 2005;173:1975–1977.
– Penicillin G 3–5 million international units IV q6h 4. Black PC, Friedrich JB, Engrav LH, et al. Meshed
peri-anal wounds clean
(Gram-positive coverage) r Reconstruction can be performed after the patient unexpanded split-thickness skin rafting for
– Imipenem 500–1,000 mg IV q6h (polymicrobial reconstruction of penile skin loss. J Urol.
has stabilized and the wound demonstrates 2004;172(3):976–969.
coverage) adequate granulation
– Clindamycin 600–1,200 mg/d, divided dose r When health of graft bed is uncertain, xenograft is F
(anaerobic coverage)
an inexpensive and useful method for temporary ADDITIONAL READING
– Vancomycin 1 g IV BID (MRSA)
wound coverage and is helpful in assessing
Second Line suitability of graft bed for autologous skin grafting. Vick R, Carson CC, 3rd. Fournier disease. Urol Clin
r Potential single-agent regimens include: Xenograft should be removed within 2 wk North Am, 1999;26(4):841–849.
– Imipenem/cilastatin r If <50% of scrotum is resected, can be
– Meropenem See Also (Topic, Algorithm, Media)
reconstructed primarily r Diabetes Mellitus, Urologic Considerations
– Ertapenem r Split-thickness skin grafts (meshed or unmeshed for r Urosepsis (Septic Shock)
– Piperacillin/tazobactam penis; meshed for scrotum) are useful for covering
– Ticarcillin/clavulanic acid r Fournier Gangrene Images
small or extensive wounds, with excellent long-term
– Tigecycline results (4)
r Intravenous immunoglobulin may be a useful r Thigh pouches for testicles are effective, but can
adjunct in treatment of staphylococcal or cause pain and interfere with testicular exam CODES
streptococcal infections with signs of toxic shock
syndrome (TSS) Complementary & Alternative ICD9
Therapies r 608.83 Vascular disorders of male genital organs
SURGERY/OTHER PROCEDURES r Whirlpool therapy for micro-debridement
r Immediate and aggressive wide surgical r 616.89 Other inflammatory disease of cervix, vagina
r Hyperbaric oxygen may be helpful if used early as an
debridement and irrigation with bacteriocidal and vulva
adjunct to radical debridement (3)
solution minimizes progression of necrosis. r Dakin’s solution, Sulfamylon solution, or Silvadene
r All affected tissues should be debrided; ICD10
cream can be applied during each dressing change r N49.3 Fournier gangrene
questionable involvement can be treated with r N76.89 Other specified inflammation of vagina and
incision and drainage and observation.
r Repeat exam under anesthesia and possible vulva
ONGOING CARE
debridement at 24-48 hr
r Fascia and muscle are rarely involved and do not PROGNOSIS
r Historically, Fournier gangrene carried a >50%
CLINICAL/SURGICAL
typically require wide resection.
mortality rate
PEARLS
r Testicles and tunica vaginalis are rarely involved;
r Modern mortality rates average 5–20%, which is r Signs of local infection with pain out of proportion
when possible, tunica vaginalis should be left intact
to facilitate future application of skin graft highly dependent on prompt diagnosis and tight to physical exam is highly suspicious for a diagnosis
r Consider cystoscopy if there is concern for urethral coordination of definitive care (1) of Fournier Gangrene.
r Prompt and radical debridement is mandatory.
nidus COMPLICATIONS
r Consider proximal urinary diversion (suprapubic r Coagulopathy r Infections are typically polymicrobial, so
tube, percutaneous nephrostomies) if the penis is r Death from sepsis broad-spectrum antibiotics are critical.
extensively involved r Disfiguring skin and soft tissue loss
r If perirectal disease is identified, exam with r Infertility
proctoscopy under anesthesia is necessary r Multi system organ failure
r Renal failure
r Urethral stricture
159
FUNGAL INFECTIONS, GENITOURINARY

Daniel C. Parker, MD
r Phycomycosis:
BASICS DIAGNOSIS – Stain tissue
r Blastomycosis:
DESCRIPTION HISTORY – Stain tissue and visualize secretions
r Primary fungal infection of the genitourinary (GU) r Immunocompromised state:
r Coccidioidomycosis/histoplasmosis:
tract is common with Candida, but uncommon with – Fungi are ubiquitous in the environment and can
– Culture and stain tissue
other fungi. overwhelm those with weakened immune systems
r Other fungal infections are found in the GU tract but – Those receiving chemotherapy, with AIDS, or Imaging
are seen more commonly with immunocompromised afflicted with diabetes CT abdomen with contrast and delayed imaging vs. US
r Recent antibiotic use: may elucidate bezoars, perinephric pathology, renal
patients or in setting of systemic disease.
– Risk of candiduria is 6× after use of destruction
EPIDEMIOLOGY broad-spectrum antibiotics Diagnostic Procedures/Surgery
Incidence r Indwelling GU tubes or prosthesis: r Cystoscopy/retrograde urogram
r Difficult to determine because most cases are not r Urine culture
– Risk of candiduria 12× with catheterization
reportable r GU tract abnormalities: r Tissue biopsy
– Estimated 1–2 new cases per 100,000 population
per year involving the GU tract – Risk of candiduria 6× with abnormalities (1)[A] Pathologic Findings
r Occupation: Positive histology staining for fungi in tissue
Prevalence
Difficult to estimate as cases are not reportable – Exposure to aerosolized soil; spelunkers; bird DIFFERENTIAL DIAGNOSIS
handler r Blood clots in collecting system
RISK FACTORS r Recent travel or recreation (see image): r Cystitis
r Urinary tract drainage catheter
– Blastomycosis found in Ohio, Missouri, and r GU TB
r Prior antibiotics Mississippi river basins; Great Lakes; Canada
r Diabetes/glucosuria r Nephrolithiasis
– Coccidioidomycosis found in semiarid regions of r Squamous cell carcinoma (SCC)
r Urinary tract pathology the Western US, Mexico, Central and South
r Malignancy r Urothelial carcinoma (transitional cell carcinoma)
America
r Increased age – Histoplasmosis found in Midwestern and Southern
r Neonates US in areas of high-nitrogen soil such as chicken
coops and bat caves TREATMENT
r Female sex
r Prior surgical procedures – Cryptococcus thrives with birds GENERAL MEASURES
r UTI symptoms:
r Immunosuppression r Infectious Diseases Society of America recommends
– Only 4–14% with symptomatic candiduria
Genetics treatment of candiduria in (3)[A]:
PHYSICAL EXAM – Infants with low birth weight
No heritable form of transmission r CVA tenderness
– Patients who will have GU procedures
PATHOPHYSIOLOGY r Abdominal tenderness – Neutropenic patients
r Funguria to fungemia: r Boggy or firm prostate – Symptomatic patients
– Can occur with obstruction, reflux, or r Firm testicular or epididymal masses r Treat UTI symptoms empirically for funguria only if
instrumentation r GU tubes present the patient is unable to vocalize or perceive
r Fungemia to funguria: r Manifestations of disseminated disease symptoms
– Disseminated disease seeds GU tract
◦ Multiple microabscesses develop in the renal DIAGNOSTIC TESTS & INTERPRETATION r Asymptomatic candiduria: Assess for risk factors
cortex, with subsequent penetration into the Lab (3)[A]
glomeruli and shedding into the urine from the r Candida:
MEDICATION
proximal tubules – No studies have established the importance of First Line
ASSOCIATED CONDITIONS pyuria or quantitative urine culture in diagnosing r Aspergillosis:
r Immunocompromised state: Candida UTI (2)[A] – Amphotericin B 1–1.5 mg/kg/d for 10 wk
– Diabetes – Presence of pyuria helpful in those without r Blastomycosis:
– AIDS catheter, however, up to 25% with candiduria also – Itraconazole 200 mg PO BID for 6–12 mo
r Anatomic GU abnormalities: have bacteriuria/pyuria r Candidiasis:
– Strictures – Urine cultures positive for candiduria in otherwise – Clotrimazole, miconazole, tioconazole,
– Prostatic hypertrophy asymptomatic patients should be repeated with a terconazole topical for 1 wk
– Diverticula r Candidemia (treat for 2 wk after afebrile and Cx
clean catch sample to rule out contamination
– Indwelling tubes (2)[B] negative):
– Stones – Fluconazole 400–800 mg/d IV, then PO
– >10,000 CFU/mL could mean infection; r Candiduria:
GENERAL PREVENTION 10,000–100,000 CFU/mL could mean
r Remove unnecessary catheters/tubes – Fluconazole 200 mg/d IV/PO for 1–2 wk
colonization r Coccidioidomycosis:
r Narrow antibiotic coverage – Check urine microanalysis looking for casts
r Improve nutritional status containing yeast: Very specific, not sensitive – Itraconazole 200 mg PO BID. for 1 yr
r Control hyperglycemia r Aspergillosis:
– Culture in Sabouraud medium or stain tissue with
methenamine silver or Periodic acid–Schiff stain
(PAS); can PCR
r Cryptococcosis:
– Culture; stain tissue with India ink, PAS,
methenamine silver; perform latex agglutination
160
FUNGAL INFECTIONS, GENITOURINARY
r Cryptococcosis: ADDITIONAL TREATMENT 3. Fisher JF, Sobel JD, Kauffman CA, et al. Candida
– Amphotericin B 0.5–1 mg/kg/d IV + flucytosine Radiation Therapy urinary tract infections—treatment. Clin Infect Dis
100 mg/kg/d PO for 2 wk None 2011;52:S457–466.
◦ Then fluconazole 400 mg/d PO for 8 wk OR 4. Wise GJ, Shteynshlyuger A. How to diagnose and
◦ Then Itraconazole 200 mg PO BID for 8 wk Additional Therapies
r Irrigation may be necessary in aggressive infections treat fungal infections in chronic prostatitis. Curr
– For cryptococcal suppression: Urol Rep. 2006;7:320–328.
◦ Fluconazole 200 mg/d PO OR when systemic medication is not excreted into the
◦ Amphotericin B 0.5–1 mg/kg IV every week urine
r Histoplasmosis: – Amphotericin B GU tract irrigation
◦ 50 mg in 1,000-mL water at 40 mL/hr ADDITIONAL READING
– Itraconazole 200 mg PO BID for 6–18 mo
(over 24 hr) for 5–7 days r Kauffman CA. Candiduria. Clin Infect Dis. 2005;
– For histoplasmosis suppression:
◦ Itraconazole 200 mg/d PO BID OR – In children, renal irrigation with 10–24 mg/d 41:S371–S376.
r Removing catheter may eradicate funguria in 40% r Kauffman CA, Vazquez JA, Sobel JD, et al.
◦ Amphotericin B 0.5–1 mg/kg IV every week
r Mucormycosis: of cases Prospective multicenter surveillance study of
– Amphotericin B 1–1.5 mg/kg/d IV for 6–10 wk Complementary & Alternative funguria in hospitalized patients. The National
Therapies Institute for Allergy and Infectious Diseases Mycoses
Second Line Study Group. Clin Infect Dis. 2000;30:14–18.
r Aspergillosis None
r The Medical Letter: Antifungal drugs. Treatment
– Voriconazole 6 mg/kg q12h for 2 days, then
Guidelines from The Medical Letter 2005;30:7–14.
4 mg/kg q12h (IV or oral) for 10 wk OR ONGOING CARE r Pappas PG, Rex JH, Sobel JD, et al. Guidelines for
– Itraconazole 200 mg IV BID for 4 days, then
200 mg/d IV for 12 days, then 200 mg PO BID for PROGNOSIS treatment of candidiasis. Clin Infect Dis.
r Candiduria does not predict development of 2004;38:161–189.
10 wk OR
– Itraconazole 200 mg PO TID for 9 days, then candidemia in most people See Also (Topic, Algorithm, Media)
200 mg PO BID for 10 wk – Rates 1.3–10.5% r Candidiasis, Cutaneous, External Genitalia
r Blastomycosis – No different in renal transplant population: 5%
r Aspergillosis mortality 40–90% with treatment
r Candiduria Algorithm F
– Amphotericin B 0.5–1 mg/kg/d for 6–12 wk OR r Cryptococcus, Genitourinary
– Fluconazole 400–800 mg/d PO for 6–12 mo r Phycomycosis (mucormycosis, zygomycosis) r Filling Defect, Upper Urinary Tract (Renal Pelvis and
r Candidiasis mortality 90% if untreated, 24% with nephrectomy Ureter)
– Fluconazole 150 mg in 1 dose and amphotericin B r Fungal Infections, Genitourinary Algorithm
r Candidemia (treat until 2 wk after afebrile and Cx r Fungal Infections, Genitourinary Image
COMPLICATIONS
negative): r Bezoar formation r Histoplasmosis, Genitourinary
– Caspofungin 70 mg/d IV in 1 dose, then 50 mg/d r Emphysematous pyelonephritis r Urinary Tract Infection (UTI), Adult Female
OR r Obstruction, fungemia, death r Urinary Tract Infection (UTI), Adult Male
– Amphotericin B 0.5–1 mg/kg/d r Papillary necrosis
r Candiduria: r Urinary Tract Infection (UTI), Pediatric
r Perinephric abscess
– Amphotericin B 0.3–0.5 mg/kg/d IV for 1–2 wk r Renal scarring
OR
– Flucytosine 25 mg/kg/d PO for 1–2 wk FOLLOW-UP CODES
r Coccidioidomycosis:
Patient Monitoring
– Fluconazole 400–800 mg/d PO for 1 yr OR r Surveillance cultures can be obtained to document ICD9
– Amphotericin B 0.5–0.7 mg/kg/d IV for 1 yr r 112.1 Candidiasis of vulva and vagina
clearance of infection.
r Histoplasmosis: r Prostate can be fungal reservoir for recurrent r 112.2 Candidiasis of other urogenital sites
– Fluconazole 400–800 mg/d PO for 6–18 mo OR r 116.0 Blastomycosis
infection.
– Amphotericin B 0.5–1 mg/kg/d IV for 10–12 wk
SURGERY/OTHER PROCEDURES CDC Fungal Infections Fact Sheet http://www. r B37.3 Candidiasis of vulva and vagina
r Obstructions from fungal bezoars require drainage. cdc.gov/ncezid/dfwed/PDFs/fungal-factsheet-508c.pdf r B37.4 Candidiasis of other urogenital sites
r Access to upper tracts can facilitate drainage, r B40.89 Other forms of blastomycosis
antifungal irrigation, and extraction if needed.
r Perinephric abscess can be drained percutaneously, REFERENCES
but may require operative drainage if multiple 1. Achkar JM, Fries BC. Candida infections of the CLINICAL/SURGICAL
loculations are present. genitourinary tract. Clin Microbiol Rev. 2010;23: PEARLS
r Severe aspergillus kidney infections may require 253–273.
nephrectomy. r When fungal infections are found in the GU tract in
2. Kauffman CA, Fisher JF, Sobel JD, et al. Candida
r Treatment of fungal prostatitis may require surgical urinary tract infections—diagnosis. Clin Infect Dis. patients without risk factors, a search for systemic
2011;52:452–456. disease is warranted.
intervention for prostate resection or drainage of r Disseminated fungal disease can seed the GU tract
abscess in addition to medical therapy (4)[B].
through the development of renal microabscesses.
r Fungal infections are encountered in varying
geographic locales based on type.
r Treat candiduria in infants with low birth weight,
those undergoing GU procedures, neutropenic
patients, and symptomatic patients.
r Surgical drainage of fungal infections is indicated in
cases of urinary tract obstruction.
161
LWBK1391-SEC-G LWBK1391-Gomella ch081.xml September 19, 2014 18:23
GLOMERULONEPHRITIS, ACUTE
Christopher E. Keel, DO
ASSOCIATED CONDITIONS r Evaluate proteinuria with a spot urine

BASICS r Pharyngitis protein-to-creatinine ratio:
r Hematuria – Normal <0.2.
DESCRIPTION r Hypertension – Nephrotic range proteinuria being >2.0.
r Inflammation of the glomerulus mediated through r UTI r Basic chemistry profile may reveal elevated BUN and
humoral and cell-mediated immune mechanisms r Acute renal failure creatinine consistent with ARF.
including immunoglobins, complement, and r Rapid decrease in renal function heralds the – Urea can be raised disproportionately to
circulating T cells usually in response to an infection creatinine.
(typically streptococcal). syndrome of rapidly progressive glomerulonephritis r Mild normochromic, normocytic anemia due to
r The inflammation and immunologic response results GENERAL PREVENTION hemodilution.
in immune deposits in the glomerulus. No specific prevention measures; prompt treatment of r Hyponatremia may be present due to volume
r Onset of symptoms is usually acute and includes strep infections may reduce risk overload.
oliguria, hypertension, hematuria, proteinuria, and r Acidemia and hyperkalemia may occur in those with
renal impairment. severely depressed renal function.
r Poststreptococcal acute GN is the onset of GN after DIAGNOSIS r ESR will be elevated.
a preceding group A β-hemolytic streptococcal HISTORY r Serum complement levels, in particular, C3 will be
infection, most commonly of the pharynx or skin. r Recent episode of pharyngitis or skin infection. depressed early in the disease in 90%:
– Most common glomerulonephritis affecting r Pharyngitis usually precedes renal disease by – Normalizes 2–6 wk after onset.
children. 8–14 days. – Prior penicillin therapy may attenuate the fall in
r Synonym(s): Acute nephritic syndrome; r Time between purulent skin disease and acute C3.
Postinfectious glomerulonephritis. nephritis is widely variable. – If C3 remains depressed beyond this interval, look
EPIDEMIOLOGY r Severity varies from asymptomatic microhematuria for other causes.
to anuric renal failure. r Antistreptolysin-O and antihyaluronidase titers may
Incidence
r Poststreptococcal GN, the most common form, r Gross hematuria occurs in 30–50%. be obtained and may be elevated in
occurs most frequently in children between 2 and r Volume overload occurs in up to 2/3 of patients and poststreptococcal GN (2).
r Not all strains of streptococci will cause these
10 yr of age but can occur at any age with a slight may be severe enough to cause congestive heart
predominance of males over females failure and pulmonary edema. elevations and site of infection may affect which is
– 10% cases are in adults >40 yr of age r Hypertension occurs in up to 80%. Severity may not present.
– 20/100,000/yr correlate with the degree of volume overload. Imaging
r Hypertensive encephalopathy (seizures, confusion, r No imaging is indicated to identify poststreptococcal
Prevalence
r Most patients have a complete recovery, with coma) is the presenting feature in 5%. GN.
resolution of clinical signs within a few weeks. r Often patient has contact with individuals r CXR may identify fluid overload.
r The reported incidence of chronic renal insufficiency complaining of similar symptoms. Diagnostic Procedures/Surgery
is 0–20%. r Renal biopsy not indicated in poststreptococcal GN
PHYSICAL EXAM
RISK FACTORS r Patients may have periorbital edema, peripheral unless symptoms persist or renal function
r Occurs with infection of specific types of group A edema, HTN deteriorates due to progressive disease
r Transient oliguria will be present in half of patients r Renal biopsy, thus, indicated if:
β-hemolytic streptococci, and these vary by site of
infection. It occurs more commonly after pharyngitis – Persistently low C3 beyond 8 wk
DIAGNOSTIC TESTS & INTERPRETATION – Persistent heavy proteinuria after 6 mo
than pyoderma:
– Pharyngitis is associated with types 1, 3, 4, 12, Lab – Atypical presentation—nephrotic syndrome,
r Throat swabs are rarely positive.
25, 49 with the more common sporadic variety severe acute renal failure with estimated GFR
r Urinalysis (1): <30 mL/min/1.73 m2
following infection with type 12.
– Pyoderma is associated with types 2, 49, 55, 57, – Hematuria may be microscopic or gross and is – Atypical course—failure of renal function to
60. present in all cases. improve after initial improvement during the acute
– Microscopic analysis shows dysmorphic red blood phase which usually lasts no more than 2 wk
Genetics cells and red cell casts.
N/A – >30% of red blood cells having dysmorphic
PATHOPHYSIOLOGY features is a highly sensitive test for glomerular
r Tends to occur with impetigo in the late summer and disease.
with streptococcal pharyngitis in the winter. – Red blood cell cast present after acute pharyngitis
r Note that cases of postinfective GN have also been episode is pathognomic for poststreptococcal GN.
reported from other bacteria (Pneumococcus, r Proteinuria may also be present and is usually mild
Staphylococcus, Meningococcus) and after viral (no more than 2+ on dipstick), but some may have
infections (chickenpox, hepatitis). proteinuria to the nephrotic range.
r The exact mechanism of renal injury from
poststreptococcal GN is not clear. IgG and C3
deposits are found at the capillary wall and in the
mesangium. It is unclear if the inflammatory
response is due to circulating immune complexes,
complexes in situ, or both.
– The antigen or antigens activate the alternative
complement pathway and result in renal damage.
162
GLOMERULONEPHRITIS, ACUTE
Pathologic Findings
r IgG and C3 deposits are found at the capillary wall
Renal biopsy if indicated (see evaluation)
and in the mesangium on renal biopsy. 1. Tu WH, Shortliffe LD. Evaluation of asymptomatic,
r Rapidly progressive GN is characterized ADDITIONAL TREATMENT atraumatic hematuria in children and adults. Nat
pathologically by crescents forming from the cells of
Radiation Therapy Rev Urol. 2010;7(4):189–194.
Bowman capsule. N/A 2. Lee MN, Shaih U, Butani L. Effect of
r Typically >50% of glomeruli should have crescents Additional Therapies overweight/obesity on recovery after
to be called rapidly progressive GN. This may result N/A post-infectious glomerulonephritis. Clin Nephrol.
from any of the immunologically mediated types of Complementary & Alternative 2009;71(6):632–636.
GN, but most frequently occurs with antiglomerular Therapies
basement membrane disease, antineutrophil N/A
cytoplasmic antibody GN, and Henoch–Schönlein ADDITIONAL READING
purpura nephritis. r http://kidney.niddk.nih.gov/kudiseases/pubs/
ONGOING CARE
DIFFERENTIAL DIAGNOSIS glomerular/index.htm
r Anaphylactoid purpura PROGNOSIS r Kliegman RM. Nelson Textbook of Pediatrics.
r IgA nephropathy r Most patients have a complete recovery, with 18th ed. New York, NY: Saunders, 2007.
r Alport’s disease resolution of clinical signs within a few weeks. r Lau KK, Wyatt RJ. Glomerulonephritis. Adolesc Med
r Membranoproliferative glomerulonephritis r The reported incidence of chronic renal insufficiency Clin. 2005;16(1):67–85.
r Other postinfective glomerulonephritis is 0–20%. r Wong W. Starship Children’s Health Clinical
r Infective endocarditis r Microscopic hematuria may persist for months up to Guidelines on Glomerulonephritis – Acute, 2009 –
r Rapidly progressive glomerulonephritis 2 yr, and mild proteinuria may persist for years http://www.adhb.govt.nz/starshipclinicalguidelines/
r Systemic lupus erythematosus following an episode of poststreptococcal GN. Documents/Glomerulonephritis.pdf
COMPLICATIONS See Also (Topic, Algorithm, Media)
r Rarely does poststreptococcal GN progress to r Acute Kidney Injury, Adult (Renal Failure, Acute)
TREATMENT crescentic or rapidly progressive GN resulting in r Acute Kidney Injury, Pediatric (Renal Failure, Acute)
ESRD. Most cases resolve with no sequelae. Chronic r Glomerulonephritis, Chronic
GENERAL MEASURES renal failure or marked decline in glomerular
r Supportive care and reassurance.
r Monitor weight and serum sodium daily during filtration rate is very rare
r It is rare to result in severe HTN, seizures, anuria,
acute phase. hyperkalemia, or death.
CODES G
r Bed rest does not influence rate of recovery. r Hypertensive retinopathy or encephalopathy
r Antibiotics do not change the course of illness once r Rapidly progressive glomerulonephritis ICD9
r 446.21 Goodpasture’s syndrome
established but should be given to reduce r Microhematuria may persist for years
infection-related morbidity. r 580.4 Acute glomerulonephritis with lesion of
r Nephrotic syndrome (10%)
r Restrict protein until azotemia clears. rapidly progressive glomerulonephritis
r Obesity may increase risk for residual renal injury r 580.9 Acute glomerulonephritis with unspecified
MEDICATION pathological lesion in kidney
FOLLOW-UP
First Line
r Treatment is supportive for this condition and Patient Monitoring ICD10
r Subsequent urinalysis to ensure hematuria has r M31.0 Hypersensitivity angiitis
directed at the effects of renal insufficiency and HTN.
r Sodium and water restriction is indicated in patients resolved r N00.9 Acute nephritic syndrome with unsp
r Periodic BP monitoring
who show signs of fluid overload (400 mL/m2 /d). morphologic changes
r Loop diuretics, calcium channel blockers, and Patient Resources r N01.9 Rapidly progr nephritic syndrome w unsp
vasodilators are mainstays in the treatment of r National Kidney Foundation website morphologic changes
resultant HTN. http://www.kidney.org/atoz/content/glomerul.cfm
– Furosemide 2–4 mg/kg/dose IV r MedlinePlus http://www.nlm.nih.gov/
◦ Titrate dose based on clinical response. medlineplus/ency/article/000484.htm CLINICAL/SURGICAL
Second Line PEARLS
r Patients should be treated with a 10-day course of r Dysmorphic RBC on microscopic urinalysis suggest
penicillin antibiotics to prevent the spread of the the diagnosis.
nephritogenic organisms. This will not alter the r Prior pharyngitis or skin infection suggests diagnosis
course of the disease.
r Erythromycin is substituted if penicillin allergic. of acute glomerulonephritis.
r With supportive care, recovery is usually rapid and
r Family members of patients with acute GN should
complete with an excellent prognosis.
be cultured for group A β-hemolytic streptococci
and treated if positive.
163
GLOMERULONEPHRITIS, CHRONIC
Eric Langewisch, MD
John M. Barry, MD, FACS
PATHOPHYSIOLOGY (2) DIAGNOSTIC TESTS & INTERPRETATION

BASICS r Damage to glomeruli, often mediated through
Lab
immune/inflammatory mediators, leads to decreased r Elevated plasma creatinine from loss of renal
DESCRIPTION filtering surface and nephron mass function (3)
r Chronic glomerulonephritis is the loss of renal r Remaining glomeruli are subjected to increased – Prior plasma creatinine values may help determine
function caused by damage to glomeruli filtering pressure. This results in hyperfiltering by rate of renal function deterioration
r Often mediated by inflammation and cellular remaining glomeruli. r Serologies may help identify etiology
proliferation r Increased glomerular pressure causes progressive – Antistreptolysin O, antinuclear antibody (ANA),
r Frequently associated with hematuria and sclerosis of glomeruli and interstitial fibrosis and antineutrophil cytoplasmic antibody (ANCA), C3,
proteinuria progressive loss of functioning glomeruli C4, HIV, Hep B, Hep C
r Many forms of glomerulonephritis (GN) present r Urinalysis
acutely. Progression from acute to chronic GN is – Proteinuria
See Risk Factors
variable – RBC casts
r IgA nephropathy is the most common type of GN GENERAL PREVENTION ◦ Considered diagnostic for GN or vasculitis
r Early nephrology consultation can improve outcomes
– Dysmorphic RBC
EPIDEMIOLOGY r Treat active GN, eg, immune ◦ Isomorphic RBCs appear similar to erythrocytes
Incidence suppressing/modulating agents for active lupus in the circulation (small, anucleated cells;
r 4/100,000 people in the United States (US)
nephritis biconcave discs)
r 20–50% of patients with acute GN will develop r Control blood pressure ◦ Dysmorphic RBC criterion varies; membrane
chronic GN – Target <125/75 in patients with >1 g proteinuria protrusions such as seen with peripheral
Prevalence – Target <130/80 in patients with <1 g proteinuria acanthocytes are 1 described criterion
r GN is the 3rd leading cause of end-stage renal r Treat comorbid conditions r Urine protein measurement
disease (ESRD) in the United States after diabetes – Dyslipidemia – 24-hr urine (normally <100 mg)
mellitus and hypertension (1) – Diabetes – Random urine microalbumin/ creatinine ratio
– Accounts for about 10% of dialysis patients – Infectious disease (normally <20 μ/mg)
– Malignancy – Random urine protein/creatinine ratio
RISK FACTORS r Dietary protein restriction
r The cause of many forms of chronic GN is unknown (normally <0.2)
– Must balance protein restriction with risk of r With significant chronic kidney disease
r Acute GN (focal segmental glomerulosclerosis,
malnutrition – Anemia from decreased erythropoietin production
hemolytic uremic syndrome, IgA nephropathy, r Avoid NSAIDs, aminoglycosides, and contrast media – Hyperkalemia from decreased potassium clearance
membranous GN)
r Autoimmune diseases (systemic lupus as they may further impact on the renal insufficiency – Hyperphosphatemia from decreased phosphorous
excretion
erythematosus (SLE), Goodpasture’s syndrome, – Acidemia from decreased acid buffering
systemic vasculitis) DIAGNOSIS
r Infections (β-streptococci, human immunodeficiency Imaging
r Renal ultrasound to assess kidney size and cortical
virus (HIV), Hepatitis B, Hepatitis C) HISTORY
r Other systemic diseases (diabetes mellitus, multiple r Often asymptomatic volume
myeloma, amyloidosis, Henoch–Schönlein purpura, r Past acute kidney disease – Advanced disease is associated with decreased
r Symptoms of uremia renal size, increased echogenicity, and cortical
polyarteritis nodosa, Wegener’s granulomatosis)
r Family history of hereditary GN (Alport syndrome, thinning
– Decreased energy
– Kidneys usually normal sized with diabetic
thin basement membrane disease) – Metallic taste in mouth
nephropathy
– Poor appetite
Genetics Diagnostic Procedures/Surgery
– Pruritus
Some cases of hereditary GN or nephritis (Alport r Renal biopsy can potentially diagnose different
– Slowed cognition
syndrome caused by a mutation of COL4A5 gene, glomerular diseases
usually X-linked and more severe in men; thin PHYSICAL EXAM – Biopsy may not be helpful in advanced disease
basement membrane disease) r May be unremarkable
r Weight loss Pathologic Findings
r Hypertension r Renal biopsy may determine type of glomerular
r Volume overload disease by pattern of injury and immune complex
staining
– Elevated jugular venous pressure, pulmonary rales,
– With advanced disease and small kidneys on
pedal edema
r Signs of uremia ultrasound, biopsy frequently shows advanced
sclerosis/scarring and may not be able to
– Asterixis determine etiology
– Pericardial rub
164
GLOMERULONEPHRITIS, CHRONIC
DIFFERENTIAL DIAGNOSIS ADDITIONAL TREATMENT 3. Appel GB. Glomerular disorders and nephrotic
r Aristocholic acid (for weight control) syndromes. In: Goldman L, Ausiello D, eds. Cecil
Radiation Therapy
r Chronic interstitial nephritis N/A Medicine. 23rd ed. Philadelphia, PA: Saunders
r Diabetic nephrosclerosis Elsevier; 2007; Chapter 122.
r Diuretic abuse
r Oral calcium supplements (1 g/d) and vitamin D 4. Peterson JC, Adler S, Burkart JM, et al. Blood
r Hypertensive nephrosclerosis (400–800 IU/d) for prophylaxis against osteoporosis.
pressure control, proteinuria, and the progression
r Nephrotoxin exposure r Sodium bicarbonate has been shown to slow of renal disease. The Modification of Diet in Renal
r Obstructive uropathy Disease Study. Ann Intern Med. 1995;123(10):
progressive kidney damage. 754–762.
r Prerenal disease
r Renal artery stenosis
Therapies
N/A ADDITIONAL READING
TREATMENT Kopp JB. Glomerular disease in 2012: More
ONGOING CARE mechanistic insights, but translational progress is
GENERAL MEASURES slow. Nat Rev Nephrol. 2013;9(2):67–68.
r See GENERAL PREVENTION PROGNOSIS
r Referral to nephrology r Progression of glomerular disease to ESRD is See Also (Topic, Algorithm, Media)
r Treat specific glomerular disease (eg, prednisone or variable and dependent upon cause and response to Glomerulonephritis, Acute
other immunosuppressive agents) treatment
r Control blood pressure (4) r Prognosis has negative correlation with higher
r Renal replacement therapy may be necessary long blood pressure and degree of proteinuria CODES
term COMPLICATIONS
r ESRD ICD9
MEDICATION r 582.1 Chronic glomerulonephritis with lesion of
– Uremia
First Line – Volume overload membranous glomerulonephritis
r Angiotensin-converting enzyme inhibitors (ACEIs) r 582.89 Chronic glomerulonephritis with other
– Hyperkalemia
and angiotensin receptor blockers (ARBs) slow the – Anemia specified pathological lesion in kidney
decline of the glomerular filtration rate (GFR) in – Acidosis r 582.9 Chronic glomerulonephritis with unspecified
patients with diabetic and nondiabetic proteinuric r Increased risk of cardiovascular disease pathological lesion in kidney
nephropathies
– ACEIs: Benazepril, captopril, enalapril, fosinopril,
r Increased risk of mortality
ICD10
G
lisinopril, moexipril, quinapril, ramipril, others FOLLOW-UP r N03.2 Chronic nephritic syndrome w diffuse
– ARB: Candesartan, eprosartan, irbesartan, Patient Monitoring membranous glomrlneph
losartan, telmisartan, valsartan r Lab monitoring r N03.9 Chronic nephritic syndrome with unsp
– Use may be limited by drug-induced – Estimate glomerular filtration rate (eGFR): BUN, morphologic changes
hyperkalemia, increased plasma creatinine due to plasma creatinine r N11.9 Chronic tubulo-interstitial nephritis,
decreased glomerular pressure, or anemia – Basic metabolic panel + phosphorous unspecified
Second Line – Random urine protein/creatinine ratio
r Diuretics to treat volume overload – 24-hr urine protein
r Additional antihypertensive agents to reach blood r Blood pressure CLINICAL/SURGICAL
pressure goals r Signs or symptoms of uremia PEARLS
– β-Blockers, calcium channel blockers, central Patient Resources r Many cases of acute GN can progress to chronic GN.
α2-agonists (eg, clonidine), α1-antagonists, and www.kidney.org/patients r ACEIs and ARB can slow the decline of the GFR in
direct vasodilators
patients with proteinuric nephropathies.
r Access for dialysis REFERENCES
– AV fistula or graft 1. National Kidney Foundation. K/DOQI clinical
– Hemodialysis access or peritoneal dialysis catheter practice guidelines for chronic kidney disease:
r Renal transplantation
Evaluation, classification, and stratification. Am J
– Preemptive transplantation before dialysis results Kidney Dis. 2002;39(2 suppl 1):S1–S266.
in better survival than transplantation after the 2. Remuzzi G, Bertani T. Pathophysiology of
initiation of dialysis progressive nephropathies. N Engl J Med.
1998;339(20):1448–1456.
165
GONORRHEA
Arpeet Shah, MD
Ahmer V. Farooq, DO

BASICS r Always recommend testing for other STDs
Lab (2)
r Commonly associated with concomitant infection r Gram stain of urethral or endocervical discharge
DESCRIPTION with Chlamydia trachomatis with a swab.
r A sexually transmitted disease (STD) caused by the
– Considered positive if neutrophils with
gram-negative diplococcal bacteria Neisseria GENERAL PREVENTION
r Delaying onset of sexual activity and reducing the intracellular gram-negative diplococci are
gonorrhea visualized. Sensitivity and specificity of the Gram
– Clinical manifestations range from asymptomatic number of new partners
r Consistent condom use stain varies depending on the site of infection and
disease to disseminated infection the presence of symptoms.
– In men, can cause urethritis, prostatitis, and r Culture has long been considered the gold standard
epididymitis DIAGNOSIS for diagnosis.
– In women, can cause cervicitis, salpingitis, – Advantages include high specificity and the ability
endometritis, and pelvic inflammatory disease HISTORY to test for antibiotic sensitivity.
– Anorectal and pharyngeal infections may also r Obtain detailed history of sexual activity and
– Disadvantages include strict transport and storage
occur depending on sexual practices partners requirements, specific environmental variables
– Pediatrics: Vertical transmission to newborn may r Incubation period of 3–14 days
needed for growth (Thayer–Martin agar in CO2
result in infection of conjunctiva, rectum, or r Approximately 50% of infections in men are incubator), and delays in obtaining results. Culture
respiratory tract; rule out sexual abuse in asymptomatic or minimally symptomatic; most is the test of choice for extragenital sites of
infections of young children common symptoms include dysuria and infection.
– Disseminated gonococcal infection may occur mucopurulent discharge r Nucleic acid amplification test (NAAT) use molecular
secondary to distinct strains or host factors and r Approximately 50% of women have asymptomatic techniques to amplify specific DNA and RNA
may result in a variety of clinical manifestations
infection; most common symptoms include sequences.
including skin lesions, arthritis, pericarditis,
vaginal/cervical discharge, dysuria, urinary – Optimal specimens are urine samples for males
endocarditis, and meningitis
frequency, abdominal pain, and abnormal menstrual and vaginal swabs for females.
EPIDEMIOLOGY bleeding – Advantages include higher sensitivities and
Incidence r Pregnancy does not change clinical presentation, comparable specificities of culture, minimal delay
r In the United States, gonorrhea remains the 2nd but does lower incidence of pelvic inflammatory in results, noninvasive and self-collected samples,
most commonly reported bacterial STD disease (PID) and identification of coinfections.
r The Center for Disease Control and Prevention r Anorectal infection is usually asymptomatic but can – Disadvantages include inability to screen for
(CDC) estimates 820,000 new cases per year with produce symptoms of pruritus, tenesmus, rectal antimicrobial sensitivity. CDC now recommends
over half occurring in young adults ages 15–24 bleeding, and discharge NAAT as the 1st-line diagnostic test for
r In 2011, CDC reported the rate of gonorrheal r Pharyngeal infection is usually asymptomatic but uncomplicated urogenital gonorrheal infection.
infections to be 104.2/100,000 persons can cause sore throat Imaging
r Rates in the United States have drastically declined r Approximately 50–75% of those with disseminated r Not indicated in uncomplicated cases
since the 1970s due to the public health measures gonococcal infection (DGI) have skin lesions r Computed tomography or pelvic ultrasound if pelvic
r More recently, the rate decreased 11.7% during characterized by papules and pustules with inflammatory disease (PID) or pelvic abscess
2007–2011 surrounding erythema suspected
r Retrograde urethrogram if urethral stricture
RISK FACTORS PHYSICAL EXAM
r Multiple sexual partners r In men, mucopurulent urethral discharge may be suspected
r Unsafe sexual practices seen; other signs include testicular/epididymal Pathologic Findings
r Alcohol and substance abuse tenderness Gram stain demonstrates gram-negative diplococci
r Men have a 20–30% chance and women have a r In women, pelvic exam with speculum may found inside of polymorphonuclear cells
demonstrate mucopurulent cervical discharge; other
70–80% chance after having 1 exposure DIFFERENTIAL DIAGNOSIS (3)
signs include cervical erythema, edema, and friability r Other genitourinary infections including
Genetics as well as cervical motion and adnexal tenderness
Individuals with inherited or acquired deficiency of r If suspecting anorectal infection, external inspection C. trachomatis, Trichomonas vaginalis, Mycoplasma
complement components C5–C9 are more susceptible genitalium, and Ureaplasma urealyticum, herpes
may reveal few or no signs of infection and simplex virus, bacterial vaginosis, and candidiasis
to local and systemic gonorrheal infections anoscopy may be indicated with collection of r Also consider noninfectious sources such as foreign
PATHOPHYSIOLOGY specimens for culture
r N. gonorrhea is not part of the normal flora of the r Pharyngeal cases may demonstrate exudative body, chemical irritation, allergic reaction, trauma,
carcinoma, and leukorrhea of pregnancy
genitourinary tract (1) pharyngitis and cervical adenitis r For women who present with suspected PID, must
r Bacteria are introduced to the mucosal epithelial r Conjunctival cases demonstrate severe purulent
rule out ectopic pregnancy and other
surface after direct contact with an infected discharge with crusting and lid edema intra-abdominal processes such as appendicitis
individual
r Attachment of the bacteria to the mucosal
epithelium is mediated by pili (PilC1 and PilC2) and
Opa proteins
r Penetration of the organism into submucosal tissue
usually takes 24–48 hr
r Invasion of the epithelial triggers a strong response
by neutrophils causing sloughing of epithelium,
submucosal microabscesses, and purulent drainage
166
GONORRHEA
r Chronic gonorrheal infection may lead to bulbar
REFERENCES
TREATMENT
urethral strictures requiring urologic intervention 1. Klausner J, Hook III E. Current Diagnosis and
GENERAL MEASURES r Gonorrheal abscesses may require incision and Treatment of Sexually Transmitted Diseases, 1st ed.
r Patients with suspected active infection should debridement procedures New York, NY: McGraw-Hill Medical, 2007.
abstain from sex until diagnostically excluded or 2. Leone PA. Epidemiology, pathogenesis, and clinical
adequately treated ADDITIONAL TREATMENT manifestations of neisseria gonorrhoeae infection.
r Patient counseling regarding safe sex practices and
r All sexual partners who have contacted the infected In: UpToDate, Basow DS, ed. UpToDate. Waltham,
abstinence for 7 days following treatment initiation MA; 2013.
patient within 60 days of diagnosis should also be r Patients should also be offered additional STD
evaluated 3. Mandel G, et al. Bennett’s Principles and Practice
r Treatment with penicillins and tetracycline are not testing and pregnancy testing of Infectious Diseases. 7th ed. New York, NY:
r Pregnancy considerations
effective due to the high level of penicillinase- Churchill Livingstone; 2010.
producing bacteria and plasmid-mediated high-level – 1st line still remains ceftriaxone 250 mg IM in 1 4. Swygard H, et al., Diagnosis of Gonococcal
tetracycline-resistant bacteria dose PLUS azithromycin 1 g PO in 1 dose Infections. In: UpToDate, Basow DS, ed. UpToDate,
r Over the last decade, increasing mean minimum – Doxycycline should be avoided during pregnancy Waltham, MA; 2013.
– If the patient has a penicillin allergy,
inhibitory concentrations of selective cephalosporins
desensitization procedures or 2nd-line treatments
have indicated decreasing susceptibility and have
such as azithromycin monotherapy are alternatives ADDITIONAL READING
impacted current treatment recommendations
r Fluoroquinolone resistance has impacted treatment – Microbiologic test of cure with culture is
recommended www.cdc.gov/std/Gonorrhea/STDFact-gonorrea.htm
options and is most prevalent in the states of r Ophthalmia neonatorum
California and Hawaii See Also (Topic, Algorithm, Media)
r Macrolide resistance has also been reported – Prevented by routine screening for endocervical r Epididymitis
infection during pregnancy and prophylactic use of r Gonorrhea Image
MEDICATION erythromycin ophthalmic solution r Pelvic pain, Female
First Line (4) r Sexually Transmitted Infections (STIs) STDs, General
r For uncomplicated cases of urethral and
endocervical gonorrheal infection, patients must
ONGOING CARE r Urethra, Discharge
r Urethritis
also be treated for concomitant chlamydia infection PROGNOSIS
unless diagnostically excluded >95% of uncomplicated genitourinary gonorrheal
r Ceftriaxone 250 mg IM in 1 dose PLUS azithromycin
1 g PO in 1 dose is the current gold standard
infections are cured by 1 course of treatment
CODES G
r Ceftizoxime 500 mg IM in 1 dose, cefotaxime 500 COMPLICATIONS
r In males, may lead to bulbar urethral stricture and
mg IM in 1 dose, or cefoxitin 2 g IM with probenecid ICD9
sterility r 098.0 Gonococcal infection (acute) of lower
1 g PO in 1 dose are alternatives for ceftriaxone r In females, can cause PID leading to chronic pelvic
r If an injectable cephalosporin is not an option, genitourinary tract
pain, ectopic pregnancy, and sterility r 098.11 Gonococcal cystitis (acute)
alternatives include cefixime 400 mg PO in 1 dose or r Genital abscesses may occur in either sex requiring r 098.12 Gonococcal prostatitis (acute)
cefpodoxime 400 mg PO in 1 dose. However,
patients who receive these options should return in surgical intervention
r Fitz–Hugh–Curtis Syndrome – perihepatitis ICD10
1 wk for microbiologic test of cure with culture r A54.00 Gonococcal infection of lower genitourinary
r Doxycycline 100 mg BID PO for 7 days is an characterized by acute right or bilateral upper
quadrant tenderness – may occur in either sex tract, unsp
alternative for azithromycin r Ocular infection with gonorrhea in adults may lead r A54.01 Gonococcal cystitis and urethritis,
Second Line to corneal scarring and vision loss unspecified
r The management of those with a penicillin allergy r The most common complication of DGI is septic r A54.22 Gonococcal prostatitis
depends on clinical suspicion of true allergy and the arthritis and arthritis–dermatitis syndrome; extreme
severity of the allergy. Most patients with cases may lead to destruction of articular surfaces
documented penicillin allergy are not found to have r Hematogenous spread may lead to endocarditis and CLINICAL/SURGICAL
an allergy after further testing and only 2% of those PEARLS
meningitis
with a penicillin positive skin test cross react with
cephalosporins. Thus, the physician must decide FOLLOW-UP r Maintain a high degree of suspicion for gonorrhea,
whether to give a cephalosporin vs. an alternative r All patients diagnosed with gonorrhea should be especially in patients who are in their 20s.
therapy tested to rule out repeat infection 3–4 mo after r Most common symptoms include mucopurulent
r Azithromycin 2 g PO in 1 dose monotherapy treats treatment discharge and dysuria.
gonorrhea and chlamydia; however, due to GI side r All patients who undergo PO cephalosporin therapy r Culture has been the gold standard for diagnosis,
effects and growing macrolide resistance, it is not a and all pregnant patients should undergo however, NAAT is now being widely used as a
preferred regimen unless the patient has a severe microbiologic test for cure using a Gram stain and 1st-line diagnostic modality.
penicillin allergy culture 7 days after treatment r 1st-line treatment includes ceftriaxone 250 mg IM in
r Spectinomycin 2 g IM in 1 dose is a safe and
1 dose PLUS azithromycin 1 g PO in 1 dose.
effective alternative therapy for those with severe r Antibiotic susceptibilities continue to change and
penicillin allergies, but is only available outside the vary by geographical location.
United States r Always council patients regarding safe sex practices.
r Quinolones were once a 2nd-line therapy, but due
to drug resistance in 10–100% of strains depending
on location, they are no longer recommended for
the treatment of gonorrhea
167
GROIN/INGUINAL MASS, MALE AND FEMALE

Edouard J. Trabulsi, MD, FACS

BASICS r Chronic increased intra-abdominal pressure.
Lab
r STDs associated with lymphadenopathy r Blood tests:
DESCRIPTION r Penile cancer – Full blood count and ESR
r A palpable bulge in the groin region that can be
– Renal function tests and electrolytes
benign or malignant. The groin has 2 distinct GENERAL PREVENTION – Syphilis serology, if indicated
r Avoid chronic increase in intra-abdominal pressure
anatomic areas: – HIV serology, if indicated
– Inguinal canal that may encourage hernia formation. – LGV (lymphogranuloma venereum) serologic test,
– Femoral triangle r Avoid STIs.
if suspected
r Swab and culture the base of any lesions to
EPIDEMIOLOGY
Incidence DIAGNOSIS diagnose genital herpes, syphilitic ulcer, chancroid
r Hernia: (Haemophilus ducreyi)
– Estimated that ∼5% of population will develop HISTORY
r Onset of the mass (age, activity) and any associated Imaging (2)
hernia at some point in their lifetime. r US can confirm hernia and can help to see the testes
r Cryptorchidism: symptoms
r Family history of cryptorchidism within the inguinal canal. Not sensitive for
– 3–5% in newborn and 0.7–1% by the end of r Symptoms of malignancy (fevers, weight loss) intra-abdominal testis.
1st yr. r Doppler US for vascular conditions (Valsalva
r Birth history: Premature or low birth weight (for
Prevalence maneuver should be performed during exam).
congenital hernia and cryptorchidism) r CT/MRI can help to diagnose obscure hernias. Also
N/A r History of presence or absence of testes in the
can identify related lymphadenopathy.
RISK FACTORS scrotum, contralateral testis r Arteriography may help diagnose femoral artery
r Hernia: r Alteration in the size of the mass with cough or
aneurysm.
– Low birth weights (<1,500 g) abdominal straining suggests hernia or varicocele. r Venography or Doppler US will help diagnose
– Incidence increases with aging as well as r Fever, a lesion on genitalia or lower extremity, and
saphenous varix.
complications. weakness may suggest infection and lymphadenitis.
– Full-term newborn has 3.5–5% chance r Surgical history of previous hernia repair Diagnostic Procedures/Surgery
r Cryptorchidism: r Laparoscopy: Can be diagnostic and therapeutic for
– Low birth weights (<2,500 g) PHYSICAL EXAM hernia and intra-abdominal testes.
r General: r Exploratory surgery is necessary in many cases for
– Prematurity 30%
– Factors that may lead to late testicular descent – Evidence of adenopathy elsewhere, to suggest both diagnosis and treatment.
include black or Hispanic ethnicity; a family more systemic disease such as lymphoma r Lymph node biopsy or fine needle aspiration (FNA)
r Groin:
history, low birth weight, and preterm birth for definitive diagnosis of lymphadenopathy.
delivery; and cola consumption during pregnancy – Patient should be examined in standing position r Chromosomal and hormonal analysis in situation
as well as supine, and Valsalva maneuver should with bilateral undescended testes.
Genetics be done during exam
Some connective tissue disorders are inherited and ◦ A cough impulse usually suggests an inguinal Pathologic Findings
can be associated with a groin hernia (see “Groin r Cryptorchidism:
hernia. Erythematous skin suggests infection or
Hernia, Adult and Pediatric”) – Decreased number of Leydig and Sertoli cells
strangulated hernia. Pulsatile mass may suggest
PATHOPHYSIOLOGY arterial aneurysm – Failure to develop primary spermatocyte
r The contents of the groin include skin, subcutaneous ◦ A finger in the external ring can help to – Peritubular fibrosis
r Lymphadenopathy:
tissue, the inguinal canal and contents, femoral differentiate direct and indirect hernias
triangle and contents (including vessels, nerves, and ◦ Groin tenderness: Likely infection is the etiology – Can identify neoplastic or inflammatory cause
lymph nodes), and musculoskeletal structures (1) r Genitalia:
r Lymphadenopathy: – Evaluate for masses, lesions, ulcers r The mnemonic “MINT” can be used to remember
– Infection with STD, skin infection in the lower ◦ Malignancy may result in groin adenopathy the possibilities (Malformations, Inflammatory,
extremities ◦ Ulceration may suggest a sexually transmitted Neoplasms, Trauma):
– Malignancy such as melanoma, lymphoma, other infection – Malformations:
r Hernia: r Scrotum: ◦ Hernia (inguinal or femoral), usually presents
– Persistence of patent processus vaginalis – Absent testis suggests undescended testes with a mass
– Chronic increased intra-abdominal pressure – Tender testis suggests epididymitis, testicular ◦ Hydrocele
– Connective tissue disorder altering collagen torsion, and epididymitis ◦ Hydrocele of the canal of Nuck
formation can predispose to hernia – Transillumination test, if positive, may suggest a ◦ Cryptorchidism (undescended, maldescended,
– Prematurity hydrocele/hydrocele of the spermatic cord or retractile testicles)
r Cryptorchidism: r Lower extremity exam: ◦ Testicular torsion
– Endocrine abnormality – Any source of infection or malignancy such as ◦ Femoral artery aneurysm
– Absence or abnormalities of the gubernaculum melanoma ◦ Varicocele
– Reduced intra-abdominal pressure ◦ Spermatocele
– Pronounced impairment in germ cell development
168
GROIN/INGUINAL MASS, MALE AND FEMALE
r Inflammatory Lesions: r Hernias:

REFERENCES
– Inguinal lymphadenitis (a mass found during – Congenital hernias are repaired by ligating the
exam): processus vaginalis at the internal inguinal ring 1. van den Berg JC, Rutten MJ, de Valois JC, et al.
◦ Acute secondary to venereal disease (chancroid, (60% chance of having a contralateral defect) Masses and pain in the groin: a review of imaging
gonorrhea herpes, or syphilis) or skin disease, – Strangulated, incarcerated hernias require findings. Eur Radiol. 1998;8(6):911–921.
infection in the groin area, drug reaction, and emergency intervention 2. Shadbolt CL, Heinze SBJ, Dietrich BB, et al. Imaging
viral infections – Elective surgical repair for hernia is recommended of groin masses: Inguinal anatomy and pathologic
◦ Chronic secondary to TB based on surgeon preference conditions revisited. Radiographics. 2001;
– Cellulitis S261–S271.
– Psoas abscess secondary to TB
– Thrombophlebitis of the saphenous or femoral Radiation Therapy
N/A
vein (especially postpartum) ADDITIONAL READING
– Osteomyelitis Additional Therapies
r Neoplasms: N/A r Baskin LS, Kogan BA. Handbook of Pediatric
– Lymphadenopathy (penile cancer, melanoma, Urology, 2nd ed. Philadelphia, PA: Lippincott
lymphoma, or metastatic tumor) Williams & Wilkins, 2005;20:51.
Therapies r Brunicardi FC, Andersen DK, Billiar TR, et al., eds.
– Paratesticular tumors N/A
– Skin tumor, lipoma and sarcoma of the bone Schwartz’s Principles of Surgery, 8th ed. New York,
r Trauma: NY: McGraw-Hill, 2005.
– A perforation of the femoral vein or artery ONGOING CARE See Also (Topic, Algorithm, Media)
– Contusion and fracture, or dislocation of the hip r Lymphadenopathy: Requires follow-up for chronic r Cryptorchidism
r Groin Hernia
infection, response to treatment.
r Cryptorchidism: Requires follow-up for: r Groin Inguinal Mass Image
TREATMENT r Penis Cancer, General
– Malignancy: Increased risk of malignancy in
GENERAL MEASURES undescended testis, and patient is required to r Sexually Transmitted Infections (STIs) (Sexually
Management is based on the cause of the mass and perform monthly self-exam for any abnormality Transmitted Diseases [STDs]), General
can vary from antibiotic therapy, biopsy, or further (corrective surgery does not reduce the chances of
imaging for more extensive adenopathy. malignancy).
MEDICATION – Increased risk of trauma and torsion. CODES
First Line – Requires follow-up for fertility.
r Hernia: Follow for recurrences and possible
G
r Lymphadenopathy: ICD9
– Infection requires treatment with specific occurrence on the other side in young children. r 550.90 Inguinal hernia, without mention of
antibiotics. PROGNOSIS obstruction or gangrene, unilateral or unspecified
– For STD-related adenopathy, see specific chapter. Depends on the etiology of the mass (not specified as recurrent)
– Malignancy with either requires chemotherapy or r 752.51 Undescended testis
lymph node dissection based on the etiology. COMPLICATIONS r 789.39 Abdominal or pelvic swelling, mass, or lump,
r Cryptorchidism:
– For penile cancer with lymphadenopathy, a course other specified site
of antibiotics is indicated. – Infertility
– Malignancy ICD10
Second Line – Increased risk of trauma and torsion r K40.90 Unil inguinal hernia, w/o obst or gangr, not
N/A – Hernia spcf as recur
SURGERY/OTHER PROCEDURES r Hernia: r Q53.9 Undescended testicle, unspecified
r Cryptorchidism: – Nonreducible and incarceration r R19.09 Other intra-abdominal and pelvic swelling,
– Treatment started at 6–12 mo – Obstruction mass and lump
– Hormonal treatment efficacy is <20% and is – Strangulation
dependent on testis location r Lymphadenopathy can erode into femoral vessels
– Surgery is the gold standard for management and cause exsanguination and death CLINICAL/SURGICAL
r Hydrocele: PEARLS
FOLLOW-UP
– Communicating hydrocele with patent processus
Patient Monitoring r The differential diagnosis varies greatly by the age of
vaginalis will require surgery r Cryptorchidism:
r Testicular Torsion: the patient.
– Requires follow-up for fertility r If the mass is reducible, strongly suggests a hernia.
– Manual detorsion followed by orchiopexy – Self-exam for testicular masses
r Hernia, for recurrence
Patient Resources
N/A
169
GYNECOMASTIA
Samuel Walker Nickles
James S. Rosoff, MD
r GM of aging:
BASICS DIAGNOSIS – The hypothalamic–pituitary–testis axis is variable
in age-related decline. Some men will have
DESCRIPTION HISTORY elevated gonadotropins while others will be
r Gynecomastia (GM) is benign enlargement of the r Age of patient and onset of symptoms (pubertal,
normal.
male breast due to proliferation of ductal elements. GM of aging) – Adiposity increases with age which leads to
r Pseudogynecomastia/lipomastia is an increase in r Associated fevers or chills, breast trauma, nipple
increasing peripheral conversion.
breast adipose tissue. This can be distinguished by discharge – Sex hormone–binding globulin (SHBG) levels rise
careful physical exam of subareolar tissue and r Medical conditions (cirrhosis, chronic kidney disease, with age and decreasing bioavailable
comparison to adjacent adipose tissue. HIV, hyperthyroidism) testosterone.
r Medications/drugs – Medications may also play a part in GM in older
EPIDEMIOLOGY r History of cryptorchidism men.
Incidence (1) r Sexual history: Sexual maturation, changes in libido, r Estrogen secreting tumors:
Approximately 2,000 cases of male breast cancer are – Leydig cell tumors are rare tumors of the testis;
diagnosed in the United States annually erectile dysfunction, infertility
85–90% are benign, most are nonpalpable. Some
Prevalence PHYSICAL EXAM Leydig cell tumors can directly secrete estradiol.
r 30–65% of men have palpable breast tissue and at r General appearance, weight, amount of adipose
This increases estrogen levels and inhibits LH
autopsy 40–55% of men have histologic evidence tissue (contains aromatase capable of peripheral secretion, suppressing testicular production of
of GM conversion of androgens to estrogen) testosterone.
r Age related: Asymptomatic GM is 60–90% in r Secondary sexual characteristics such as body hair
– Sertoli cell tumor: Converts androgens to
neonates, 50–60% in adolescents, and up to 70% distribution and phallus size estrogens leading to a direct increase in
r Thyroid exam circulating levels of estrogens.
in men aged 50–69 yr
r Breast exam: Special attention should be paid to – Feminizing adrenal cortical tumors are generally
RISK FACTORS distinguish true GM from pseudogynecomastia; malignant and poorly differentiated. These cancers
r Alcoholism
r Endocrinopathies unilateral vs. bilateral (if unilateral should be directly secrete estrogens as well as steroid
concerned for potential male breast cancer), firm precursors that may be aromatized to estrogens in
r Medications
and mobile vs. fixed, skin dimpling, any nipple peripheral tissues. Increased estrogen suppresses
r Obesity discharge, palpation of axillary lymph nodes LH-mediated production of testosterone as well.
r Renal failure r Genitourinary exam with special attention to the r hCG-secreting tumor such as choriocarcinoma
Genetics testicular exam stimulates Leydig cells to preferentially secrete
r Klinefelter syndrome (47, XXY) is strongly associated estradiol. Many HCG-secreting tumors also will take
with GM up steroid precursors such as DHEA and convert
r An increased risk of male breast cancer has been
Lab them to active estrogens.
r Basic studies: Creatinine, LFTs, thyroid function
r Increased peripheral aromatization to estrogens:
reported in families with a BRCA2 mutation tests, serum testosterone
r Further testing as needed: Familial aromatase excess syndrome. The enzyme
PATHOPHYSIOLOGY aromatase (P450 aroma or CYP19A1) catalyzes the
r Male breast tissue has both androgen and estrogen – Serum estrogens (estradiol, estrone) conversion of steroid precursors to estrogens.
receptors. – LH, FSH, prolactin r Estrogen receptor agonists:
r Androgens inhibit breast development and – Tumor markers: AFP, β-hCG
– Therapeutic administration of estrogens such as
estrogens stimulate it. GM develops when there is – Adrenal androgens, serum DHEA, urinary
DES (diethylstilbestrol) may be used to treat men
an imbalance of these two influences (ie, androgen 17-ketosteroids
with prostate cancer and can lead to GM.
deficiency or excess estrogen) or lack of tissue Imaging Estrogens may also be used to stimulate breast
response to them. r Testicular US if abnormal tumor markers development in male-to-female transsexuals.
r CT of the abdomen and pelvis/chest if abnormal – Unintentional exposure may occur
r Prostate cancer levels of adrenal androgens transcutaneously by sexual intercourse with a
r Testicular tumors r Mammography if cancer suspected partner that uses topical estrogen. Occupational
r Cirrhosis exposure is also possible. Estrogens can be found
Diagnostic Procedures/Surgery in hair creams, embalming creams, and in the
r Renal failure Breast biopsy for suspected breast cancer
production of medicinal estrogen products.
GENERAL PREVENTION Pathologic Findings – Marijuana smoke, digitoxin, testosterone, or other
r Proliferation of ductules embedded in a connective aromatizable androgens.
With hormonally induced GM, prophylactic breast
irradiation may reduce GM tissue stroma r Androgen deficiency or resistance:
r Over about 12 months, the breast tissue evolves into – Primary or secondary hypogonadism: Testicular
a quiescent stage, in which the amount of stroma failure from any cause may result in GM.
and fibrosis increases and the ductules become less Testosterone deficiency leads to elevated LH,
prominent. glandular acini are rare (2) which increases estradiol production by remaining
DIFFERENTIAL DIAGNOSIS Leydig cells. Increased estrogens lead to elevated
r Physiologic GM: Normal in neonatal boys secondary levels of SHBG, further decreasing free
to maternal estrogen exposure. testosterone.
– Occurs in 60–90% of neonatal boys and resolves – Klinefelter syndrome is the most common genetic
within several weeks after delivery. disorder associated with hypogonadism and
– Pubertal GM results from the earlier rise of infertility in men. GM is present in 50–70% of
estrogens in early puberty. As the normal ratio of cases. Klinefelter syndrome is the only cause of
estrogen to testosterone is restored later in GM with an established risk of breast cancer
puberty the GM resolves. (20-fold increase).
– 50–70% of boys develop GM during puberty. – Defects in genes critical for testosterone
– 20% of men still have GM at 20 yr of age. production may also lead to decreased
testosterone production.
170
GYNECOMASTIA
r Androgen resistance disorders: – Androgen receptor blocker: Flutamide,

– In both partial and complete androgen bicalutamide, nilutamide, cimetidine, marijuana, ONGOING CARE
insensitivity syndrome, cellular response to spironolactone.
androgens is inadequate (elevated gonadotropins – Increased serum prolactin: Antipsychotic agents, PROGNOSIS
r Generally favorable prognosis.
and increased serum testosterone) due to lack of metoclopramide.
negative feedback. – Possible: Refeeding GM, isoniazid, digoxin. r Patient main concerns: Ruling out breast cancer and
r Refeeding associated GM: – Unknown: HAART, human growth hormone, cosmetic correction
– Recognized after WWII when imprisoned men amiodarone, calcium channel blockers,
COMPLICATIONS
resumed normal diets and developed tender GM. amphetamines, diazepam, antidepressants
Psychological stress
Starvation is associated with hypogonadotrophic (tricyclics and SSRIs).
hypogonadism. With resumption of a healthy diet r Breast cancer: FOLLOW-UP
and regaining weight the hypothalamic–pituitary– – Rare in men; symptoms are similar to those of Patient Monitoring
testis axis returns to normal, resulting in transient female breast cancer. No regular follow-up is necessary for patients who
estrogen excess. May also explain GM associated – A hard fixed mass, ulceration, bloody nipple have physiologic GM and are untroubled by their
with several chronic diseases. discharge, or lymphadenopathy should raise symptoms and do not have symptoms suggestive of
r Renal failure: suspicion. malignancy.
– Many men with chronic kidney disease develop – Suspicious lesions should be biopsied. Patient Resources
GM upon initiation of hemodialysis. Before – Except in the setting of Klinefelter syndrome, GM N/A
initiation of dialysis men are often nauseated, does not increase the risk of breast cancer.
anorexic, and on protein-restricted diets. The
pathogenesis is thought to be similar to refeeding REFERENCES
GM.
TREATMENT
r Cirrhosis: 1. Braunstien GD. Gynecomastia. N Engl J Med.
GENERAL MEASURES 1993;328:490–495.
– Studies have shown that the prevalence of GM in Removal of the offending drug or exogenous source of
cirrhotics is no different than hospitalized 2. Bembo SA, Carlson HE. Gynecomastia: Its features,
estrogen if possible
age-matched controls. Hormonal changes in and when and how to treat it. Cleveland Clinic
chronic liver disease may increase the risk of GM. MEDICATION Journal of Medicine. 2004;(6):511–517.
– Patients with cirrhosis have decreased clearance First Line 3. Narula HS, Carleson HE. Gynecomastia. Endocinol
r SERMs have been used to block the effects of Metab Clin North Am. 2007;36:497–519.
of androstenedione, which provides more
substrate for peripheral conversion via aromatase. estrogen excess on breast tissue. Tamoxifen, 10 and
– SHBG may also be increased, decreasing free 20 mg/d, for 3–9 mo with 90% resolution. G
testosterone. Additionally, raloxifene and clomiphene citrate have ADDITIONAL READING
– Alcohol has a direct toxic effect on gonadal also been used.
Melmed S, et al. Williams Textbook of
function, and cirrhotics may have testicular Second Line
r Aromatase inhibitors such as testolactone and Endocrinology. Elsevier; Phialdephia, 2013;
atrophy and hypogonadism.
r Hyperthyroidism: 766–769, 1180–1181.
anastrazole have been used but not proven as
– 10–40% of men with thyrotoxicosis may have effective as tamoxifen. See Also (Topic, Algorithm, Media)
GM. Due to the increased peripheral conversion of r Testosterone replacement therapy in r Gynecomastia Algorithm
androgens to estrogens. There is also an increase r Gynecomastia Image
androgen-deficient men may result in partial
in SHBG in hyperthyroidism. Restoration of regression of GM, especially if breast enlargement is r Infertile Male Syndrome
euthyroid state resolves associated GM in 1–2 wk. of recent onset. r Testis, Leydig Cell Tumor
r HIV: r Testosterone, Decreased (Hypogonadism)
– Multifactorial. Use of illicit drugs (heroin or SURGERY/OTHER PROCEDURES r XXY Syndrome (Klinefelter Syndrome)
r With longstanding GM, or those that refuse medical
marijuana) may also be seen in this group. Other
chronic disease states may also be present such as treatment, cosmetic surgical excision and
Hep C, Hep B, and alcoholic liver disease. Some reconstruction may be performed
men on HAART therapy have hypogonadotropic
r Testicular cancer: Orchiectomy CODES
r Adrenal tumors: Adrenalectomy
hypogonadism.
r Diabetes Mellitus: ICD9
ADDITIONAL TREATMENT r 278.00 Obesity, unspecified
– Diabetic mastopathy presents as a discrete lump Radiation Therapy r 611.1 Hypertrophy of breast
or diffuse nodularity. The lesions are composed of r Prophylactic breast irradiation has been used prior r 758.7 Klinefelter’s syndrome
B-cell infiltration of mammary ducts and lobules to initiation of estrogens or androgen blockade for
with fibrosis and vasculitis. Can be seen in blockade for prostate cancer patients
Hashimoto thyroiditis and lupus.
ICD10
– Dose: 12 Gy in 2 fractions to 20 Gy in 5 fractions r E66.9 Obesity, unspecified
r Medications:
r N62 Hypertrophy of breast
– Androgen deprivation therapy (ADT) in prostate Additional Therapies
Radioactive iodine ablation or propylthiouracil for r Q98.4 Klinefelter syndrome, unspecified
cancer is often associated with breast pain,
tenderness, and enlargement. hyperthyroidism
– Rates of GM in men treated with ADT vary depend Complementary & Alternative CLINICAL/SURGICAL
on the type employed. Therapies
r Miscellaneous medications may be responsible for N/A PEARLS
as much as 25% of new cases of GM in adults. r Breast cancer is rare in males, representing <1%
– Destruction of Leydig cells: Chemotherapy with of all cases of breast cancer.
cytotoxic agents. r Klinefelter syndrome is the only cause of
– Decreased testosterone or DHT production:
gynecomastia with an established risk of breast
Spironolactone, ketoconazole, metronidazole,
cancer.
finasteride, dutasteride.
171
LWBK1391-SEC-H LWBK1391-Gomella ch086.xml September 19, 2014 18:25
HEMATOSPERMIA

r Urinalysis and cultures:
DESCRIPTION HISTORY – Urine culture (for acid-fast bacilli and parasites if
r Hematospermia (sometimes referred to as r Duration and amount of bleeding
r Sexual history/frequency indicated)
hemospermia) as the presence of visible blood (fresh r Serum white cell count and coagulation profile
or altered) in the ejaculate (not specified with regard – Hematospermia often associated with long
(platelets/PT/PTT)
to how many episodes or overall duration). periods of abstinence or after frequent ejaculation
r Semen can be described as bright red, r Associated voiding disorders – Complete blood count (CBC) if blood dyscrasia
r Suspected
coffee-colored, rusty, or darkened; appearance may – Hematuria
– INR for patients on coumadin
change as blood ages. – Dysuria r Tuberculin skin test should be considered,
r May occur as a single episode or persist chronically. – Urethral discharge
r Usually a self-limited and benign condition. – Lower urinary tract symptoms (LUTS) particularly in patients with exposure history or if
r Pain (pelvic, perineal) originate from or recent travel to endemic areas.
r Semen analysis can be used to confirm diagnosis of
EPIDEMIOLOGY r Systemic symptoms:
Incidence true hematospermia and, in cases of
– Fever
r Accounts for 0.02% (1/5,000) new patient visits to schistosomiasis, eggs may be noted. If performed,
– Weight loss
a urology clinic; seen in 0.5% of men presenting for r Travel history to endemic areas: semen culture should also be sent.
r Urethral swabs/urine studies for the diagnosis of
prostate cancer screening (1) – TB
r Mean presenting age of 37 yr old sexually transmitted infection if indicated
– Schistosomiasis r In patients >40 yr or with risk factors for prostate or
r Mean duration is 1–24 mo – Hydatid disease (Echinococcus)
r In men <40 yr old, cause is always almost due to an r Medications bladder malignancy:
inflammatory or infectious process. – Prostate serum antigen (PSA)
– Aspirin
r Only 2.4–3.5% of cases of hematospermia result in – Urine cytology
– Oral anticoagulants
the diagnosis of a malignancy, typically >40 yr old. – Atomoxetine (approved for the treatment of Imaging
r Trans rectal ultrasound (TRUS) of the prostate:
Prevalence attention deficit hyperactivity disorder [ADHD])
r Recurrent trauma, surgery, or infection: – To evaluate the prostate, seminal vesicles (SV’s),
Not truly known
– Transrectal ultrasound (TRUS) biopsy and possible Müllerian duct remnants
RISK FACTORS – Brachytherapy – Identifies etiology in ∼95% of cases
r Recent genitourinary trauma, surgery (prostate ◦ Prostatic calcifications (43%)
– Microwave hyperthermia
biopsy), infection – Cryoablation ◦ Ejaculatory duct calculi (39%)
r Prostatitis, bacterial – Radiation therapy ◦ SV calcifications (11%)
r Prolonged abstinence from or frequent ejaculation – High-intensity focused ultrasound (HIFU) ◦ Dilated SV (22%)
r Use of anticoagulant medication – Sexually transmitted infection ◦ Ejaculatory duct cyst (11%)
r Systemic coagulopathy/bleeding disorder – Vasectomy – Facilitates diagnostic procedures such as biopsy,
r Renal agenesis (associated with seminal vesicle [SV] r Medical conditions puncture
– HTN – Should be 1st imaging study for hematospermia
cysts) r Magnetic resonance imaging (MRI)
– Liver disease
Genetics – Bleeding disorders – Abnormal signal intensity may represent
None – Hyperuricemia in one series hemorrhage
PATHOPHYSIOLOGY r Rule out partner as a source (ie, vaginal bleeding) – Should be used if TRUS is not diagnostic or if
r Often occurs in isolation – If uncertainty exists, consider having the patient TRUS is equivocal
r Pathophysiologic causes include: ejaculate into a condom for objective verification – Cross-sectional or endorectal coil MRI may be
obtained
– Inflammation and infection PHYSICAL EXAM
– Ductal obstruction and cysts of the accessory r Assess blood pressure (BP) Diagnostic Procedures/Surgery
sexual glands r Prostate biopsy
r Abdominal exam for masses
– Neoplasms r Penis/urethra – Indicated if clinical suspicion of prostate cancer is
– Vascular abnormalities high
– Systemic factors – Meatal lesions/masses r Cystourethroscopy
– Iatrogenic factors – Discharge – Allows visualization of urethral inflammation and
– Condylomata opening of ejaculatory ducts
ASSOCIATED CONDITIONS – Meatus should be checked for bloody discharge
r Nonmalignant prostatic disease (26%) – Critical for ruling out urothelial carcinoma
after rectal exam
r Hypertension (HTN) (5%) r Scrotum, epididymides, and testes: Pathologic Findings
r Genital tuberculosis (TB) (1%) – Palpate vas deferens: N/A
r Prostate cancer (1%) ◦ Induration may indicate TB
◦ Absence may explain infertility
GENERAL PREVENTION – Assess for masses/fluctuance or tenderness
None known r Prostate
– Nodularity: Tenderness, masses
– Palpate for midline cystic structures
– SV fullness can be associated with schistosomiasis
(egg burden)
172
HEMATOSPERMIA
DIFFERENTIAL DIAGNOSIS FOLLOW-UP

r Inflammation/infection
TREATMENT Patient Monitoring
– Calculi of SVs, prostate, or urethra Follow PSA in older patients, as per prostate cancer
– Prostatitis GENERAL MEASURES screening recommendations
– Urethritis r If an underlying cause is identified (ie, bleeding
– Seminal vesiculitis disorder, GU TB, schistosomiasis), initiate
Patient Resources
– Viral: N/A
appropriate medical management.
◦ Herpes simplex r Patients should be made aware that this is very
◦ Cytomegalovirus common after prostate biopsy REFERENCES
◦ Human papilloma virus/condylomata r Spontaneous hematospermia is rarely associated
– Bacterial: with malignancy 1. Ahmad I, Krishna NS. Hemospermia. J Urol.
◦ TB r Most commonly a benign condition that resolves 2007;177:1613–1618.
◦ Chlamydia trachomatis 2. Xing C, Zhou X, Xin L, et al. Prospective trial
spontaneously and reassurance is appropriate
◦ Gonorrhea comparing transrectal ultrasonography and
◦ Syphilis MEDICATION transurethral seminal vesiculoscopy for persistent
– Parasitic: First Line hematospermia. Int J Urol. 2012;19:437–442.
◦ Schistosomiasis r In men <40 yr old without an obvious cause of 3. Badawy AA, Abdelhafez AA, Abuzeid AM.
◦ Hydatid disease (Echinococcus) hematospermia after workup (normal physical Finasteride for treatment of refractory
r Ductal obstruction and cysts of accessory glands: exam, negative urine studies): hemospermia: Prospective placebo-controlled
– Ejaculatory duct cyst – Reassurance and expectant management study. Int Urol Nephrol. 2012;44:371–375.
– SV diverticulum – Empiric antibiotic therapy with doxycycline or
– Urethral stricture fluoroquinolone
– Utricular cysts – Trial of 5α-reductase inhibitor (finasteride, ADDITIONAL READING
– Wolffian duct cysts dutasteride) for 3 mo (3)[C]
r While a similar approach can be taken in men r Kumar P, Kapoor S, Nargund V. Haematospermia—a
– Prostatic cysts
r Neoplasms: >40 yr old, diagnostic workup should be more systemic review. Ann R Coll Surg Engl. 2006;88:
– Benign exhaustive and prostate biopsy should be 339–342.
◦ BPH considered if PSA or DRE indicates. r Leocadio DE, Stein BS. Hematospermia: Etiological
◦ Leiomyoma of the SV and management considerations. Int Urol Nephrol.
Second Line
◦ Urethral adenoma 2009;41:77–83.
None r Szlauer R, Jungwirth A. Haematospermia: Diagnosis
– Malignant
◦ Bladder: Urothelial carcinoma SURGERY/OTHER PROCEDURES and treatment. Andrologia. 2008;40:120–124.
◦ Prostate: Adenocarcinoma, ductal r Prostatic calculi: Transurethral incision
r Cystoscopic resection of any lesions seen on exam See Also (Topic, Algorithm, Media)
adenocarcinoma, sarcoma, stromal tumor, Prostate Biopsy, Infections and Complications
lymphoma, malakoplakia r Cyst puncture and drainage should be considered in
◦ SV: Adenocarcinoma, sarcoma, squamous cell selected cases when indicated H
carcinoma, malakoplakia, metastases to – Can be performed via TRUS guidance,
prostate or SVs (metastatic melanoma to the transperineal or transurethral approaches
CODES
SVs or prostate, may result in melanospermia) r Transurethral cannulation of ejaculatory ducts to
◦ Urethra perform seminal vesiculoscopy with a ureteroscope ICD9
r 286.9 Other and unspecified coagulation defects
◦ Testis and perform therapeutic interventions (dilation,
◦ Epididymis: Mesothelioma r 601.9 Prostatitis, unspecified
stone extraction, biopsy) has been described (2)[C]
r Vascular abnormalities r 608.82 Hematospermia
– Arteriovenous malformations
– Prostatic varicosities Radiation Therapy ICD10
N/A r D68.9 Coagulation defect, unspecified
– Hemangioma r N41.9 Inflammatory disease of prostate, unspecified
r Systemic factors Additional Therapies r R36.1 Hematospermia
– Hematologic conditions N/A
– Hemophilia Complementary & Alternative
– Von Willebrand disease
– HTN
Therapies CLINICAL/SURGICAL
N/A PEARLS
– Chronic liver disease
– Amyloidosis of the SVs r Hematospermia is usually a benign and self-limited
r Iatrogenic causes ONGOING CARE condition, particularly in men <40 yr old.
– Prostate biopsy (most common) r Will often resolve spontaneously in all age groups.
– Genitourinary (GU) instrumentation PROGNOSIS
r Patients should be reassured, as should their r Work-up only indicated if persistent or if other
– Extracorporeal shock wave lithotripsy (ESWL) of
distal ureteral stones partners. associated symptoms (such as hematuria).
r A significant number of cases remain idiopathic r Expected symptom following prostate biopsy and
– Brachytherapy (occurs in 28% of seed cases)
– Prostate radiation even after a full workup. can last for several weeks.
r Hematospermia following prostate biopsy may take r Treatment should be directed toward underlying
– HIFU
– Postvasectomy (vasovenous fistula) several months to clear. cause if identified.
– Postorchiectomy COMPLICATIONS
N/A
173
HEMATURIA, GROSS AND MICROSCOPIC, ADULT

Surena F. Matin, MD, FACS
Genetics r Presence of clot—indicates significant degree of

BASICS Familial hematuria (Alport syndrome or hereditary hematuria and higher probability of significant
nephritis)—glomerulonephritis (GN), end-stage kidney pathology
DESCRIPTION disease, and hearing loss (2) – Amorphous clots—bladder/prostate origin
r Hematuria may be gross (GH) (visible) or – Vermiform clots—upper tract origin
microscopic (MH) PATHOPHYSIOLOGY r Lower urinary symptoms (frequency, urgency, etc.):
r Macroscopically:
r It can originate from any part of the urinary tract – BPH can cause hematuria
– Blood clots that have a vermiform (worm-like)
appearance suggest the origin of hematuria to be – Incomplete bladder emptying can predispose to
ALERT the upper tract bladder stones and infection
r Hematuria of any degree should not be ignored, – Straining to urinate or spraying of urinary stream
– Blood clots that are amorphous suggest the origin
as it may be a sign of serious renal or urologic to be the lower urinary tract—bladder or prostate can indicate a urethral stricture
disease, including malignancy. r On microscopic analysis: (2) r Activity/exercise-induced hematuria should be
r Urologic malignancy associated with microscopic excluded
– RBCs in the urine that are isomorphic and have r Trauma—significant crush injury or burn may result
hematuria in 1–3% (1). smooth, round membranes and even hemoglobin
r GH has a 5 times higher incidence of serious distribution suggests urologic disease in myoglobinuria; abdominal or pelvic trauma may
urologic disease compared to MH (2). – RBCs that are dysmorphic with irregular shapes cause urinary tract injury
r Recent upper respiratory infection—associated with
and uneven hemoglobin distribution suggests
EPIDEMIOLOGY glomerular disease GN or immunoglobulin A (IgA) nephropathy
r Medical or surgical history:
Incidence ASSOCIATED CONDITIONS
r Incidence of various disorders in patients who r Neoplasms – Renal or urologic disease or surgery
present with MH or GH: (3) r UTI – Recent urethral instrumentation (including
– No diagnosis – 60.5% catheterization)
r Urolithiasis
– UTI – 13% – Sexually transmitted diseases (STDs)
r Glomerulonephritis – History of tuberculosis (TB)
– Bladder cancer – 12% r Anatomic abnormalities of urinary tract (eg, UPJ
– Renal disease – 9.8% – History of pelvic radiation
– Stone disease – 3.6% [uretero-pelvic junction obstruction]) – History of autoimmune diseases and bleeding
r Benign prostatic enlargement disorders
– Renal cancer – 0.6%
r Current medications
– Prostate cancer – 0.4% GENERAL PREVENTION
– Upper tract cancer – 0.1% r Adequate fluid intake, especially for patients with – Anticoagulants
– Analgesic abuse
Prevalence history of calculi
– Cyclophosphamide
Prevalence of asymptomatic MH varies with age and r Smoking cessation
r History of smoking tobacco
gender, and ranges from 0.19–21% (4). r Treat/prevent underlying cause
r Menstrual history: Vaginal bleeding can be mistaken
RISK FACTORS (5) for hematuria
r Age >35 r Family history
r Male gender DIAGNOSIS
– Primary renal disease
r Current or past smoking history HISTORY – Hypertension (HTN)
r Recent trauma r Age and sex: Age >35, bladder cancer is the most – Adult polycystic kidney disease
r Urinary tract surgery or instrumentation common cause of hematuria, urologic cancer is – Alport syndrome
r Prostatic enlargement (BPH or BPE) more common in males; females may have vaginal – Urolithiasis
r Chronic indwelling Foley bleeding (4) – Urologic malignancy
r Timing of GH during urinary stream: r Occupational risk factors:
r Family history of renal disease
r Renal calculi – Initial hematuria—anterior urethral pathology – Exposures to chemicals or dyes (aromatic amines,
r Pelvic radiation – Terminal hematuria—bladder neck, prostate, or benzenes) in rubber, petroleum, and dye
urethra inflammation/pathology industries—risk of urothelial carcinoma
r Recent febrile illness
– Hematuria throughout—vesical or upper-tract
r History of irritative voiding symptoms origin
r UTI r Associated pain:
r Occupational exposure to chemicals or dyes – Painless hematuria suggests bladder cancer
– Benzenes or aromatic amines – Flank pain, GH, and abdominal mass is
r Medications pathognomonic of renal cell carcinoma
– Cyclophosphamide – Ureteral colic/flank pain can be caused by calculi
– Analgesic abuse (most common), tumor, or blood clot
– UTI/prostatitis can cause hematuria associated
with dysuria, urgency, and frequency
174
PHYSICAL EXAM r Phase-contrast microscopy or urinary sediment: r MRI

r Vital signs Differentiates glomerular (renal) and nonglomerular – Alternative imaging modality when CT scanning is
– If hypertensive evaluate for renal parenchymal bleeding based on the presence of distorted RBCs not advised (contrast allergy, renal insufficiency,
disease, chronic kidney disease (CKD) or renal (80%) in glomerular bleeding; sensitivity of 95% metallic implants)
failure, renal cystic disease or renal vascular and specificity 100% (2) – Provides excellent visualization of small renal
disease; may be hypotensive if hematuria r Urine culture: masses and arteriovenous malformations but has
persistent/severe – If urinalysis suggests infection less utility for stones
r Pallor r Urinary cytology – Gadolinium contrast is avoided in patients with
– Anemia may be associated with SLE, hemolytic – Recommended for all patients with risk factors or creatinine >2 mg/dL (eGFR <30 mL/min), due to
anemia, and CKD or renal failure irritative voiding symptoms. Not recommended as risk of progressive systemic fibrosis (nephrogenic
r Rashes part of routine evaluation for asymptomatic MH systemic fibrosis [NSF])
– Consider Henoch–Schönlein purpura, SLE, and (5)[C]. r Renal US
vasculitis – Sensitivity for detecting bladder cancer 40—76% – Detects renal cystic disease, renal masses,
r Generalized edema (1) (Better at detecting high-grade urothelial hydronephrosis
– Associated with nephrotic syndrome or renal carcinoma and CIS) – Less sensitive for detecting stone disease but
failure ◦ Negative result does not rule out malignancy useful in children and pregnancy, when radiation
r Hearing loss: Alport syndrome ◦ Atypical cells can be seen with calculi or is contraindicated
r Heart murmurs: Subacute bacterial endocarditis inflammation – Operator dependent, large body habitus can limit
r Palpable abdominal or flank masses – NMP22, BTA stat, and UroVysion are alternatives; utility
not considered standard of care but can be useful r Bladder US
– Hydronephrosis, renal cystic disease, renal tumors,
in some cases of bladder cancer – Useful to assess postvoid residuals, can detect
distended bladder r Renal function tests (creatinine and BUN)
r Flank tenderness: larger bladder tumors, bladder calculi and
r CBC – anemia may be due to GH or chronic renal diverticuli, although less sensitive than CT scan
– Pyelonephritis or urolithiasis r VCUG
r Flank lacerations, contusions or rib disease. Elevated white blood cell count (WBC) with
a left shift suggests infection – Not routinely performed in work-up of hematuria
fractures—underlying renal injury r Coagulation profile studies (PT, PTT, INR) to identify in adults
r Pelvic exam:
coagulopathy – May be done in children if hematuria is felt to be
– Urethral caruncle or vaginal prolapse, vaginal r Other lab tests as clinically indicated in conjunction with febrile UTI, concern for
bleeding urethral obstruction, or other lower urinary tract
r Digital rectal exam (DRE) – Streptozyme (antistreptolysin O titer), serum
complement, and antinuclear antibody (ANA), abnormalities
– Boggy, tender, warm prostate suggests acute r Nuclear renal scans
total serum proteins, and albumin: Globulin ratios
prostatitis – Limited utility in the initial evaluation of hematuria
for GN
– Nodularity suggest cancer r Renal arteriography and venography
– Urinary calcium: Creatinine ratio (for
– High-riding prostate suggests urethral disruption – Useful for renal artery stenosis and renal vein
hypercalciuria), peripheral smear (for sickle cell
in presence of pelvic fracture thrombosis and preoperative elucidation of
disease/trait), TB skin test, and urinary
DIAGNOSTIC TESTS & INTERPRETATION mycobacterial cultures (for TB) anatomy for surgical planning H
Lab – If in bone marrow transplant patient, consider r Retrograde urethrogram (RUG), cystogram as
r Urinalysis: Must include standard urine dipstick and cytology to look for typical changes associated clinically indicated
microscopic evaluation: with polyoma virus Diagnostic Procedures/Surgery
– MH is defined as ≥3 RBCs/high-powered field Imaging r Cystoscopy (5)[C]
(hpf) in urinary sediments from 2 of 3 properly r Plain abdominal imaging: Limited utility in initial – Should be performed in all patients >35 yr old
collected urine specimens (catheterized sample if evaluation of hematuria, may be useful in long-term with MH or GH
vaginal contamination or phimosis) (5)[C] follow-up of radiopaque stones – Patients <35 yr; cystoscopy performed if
– Color r Intravenous pyelography (excretory urography) significant risk factors for urologic malignancies
◦ Bright red: Suggests recent or ongoing bleeding present (irritative voiding symptoms, tobacco
– Traditional imaging for the detection of stones,
with urologic/anatomic origin masses, or obstruction, largely replaced by CT history, chemical exposures, etc.)
◦ Brown (tea-colored): Suggests old blood/clots or r Retrograde pyelograms +/− ureteroscopy to
urogram (CTU)
medical renal disease (GN) – Has utility for papillary necrosis and medullary evaluate the upper tract when IV contrast is
– Dipstick (4) sponge kidney contraindicated (ie, contrast allergy/elevated
◦ Specific gravity: Poorly concentrated urine—low r Computerized tomographic urogram (CTU) creatinine) or when upper tract pathology is
specific gravity (<1.007) suggests suspected but not seen on less invasive imaging
(with and without IV contrast)
hydronephrosis with renal impairment or r Renal biopsy
– The current gold standard for surveying the
intrinsic renal disease
◦ Proteinuria: Heavy (3–4+) suggests GN or renal genitourinary (GU) tract for causes of hematuria; – As directed by nephrologist when suspected
can detect stones (on noncontrast imaging), glomerulonephritis (GN)
disease
◦ Leukocyte esterase and/or nitrite positive hydronephrosis and other anatomic abnormalities, Pathologic Findings
renal masses, collecting system filling defects, Based on primary cause
(pyuria) suggests infection
◦ False-positive dipsticks for blood: Oxidizing lower urinary tract pathology (contraindicated in
serum creatinine >2 mg/dL) (5)[C]
agents (betadine, bacterial peroxidases),
– Noncontrast CT scanning is the procedure of
myoglobinuria, hemoglobinuria (microscopic
choice to evaluate kidney stones but should not
analysis is negative)
◦ False-negative dipsticks for blood: Reducing be used in the initial evaluation of hematuria.
agents (high-dose vitamin C), urine pH <5.1
– Microscopy
◦ Pyuria – suggests infection
◦ Red cell casts – pathognomonic of glomerular
bleeding
◦ Crystalluria – suggests urolithiasis
175
DIFFERENTIAL DIAGNOSIS r Exercise-induced hematuria r Gross hematuria

r Pseudohematuria r Foreign bodies: Catheters, stents, self-introduced, – If patient is urinating without difficulty and has no
– Drugs: etc. blood clots can treat conservatively—increase oral
◦ Reddish color: Pyridium, doxorubicin, phenytoin, r Inflammatory fluid intake
salicytes, senna, others – UTI/prostatitis and specific infections – For patients with clots/urinary retention: Place a
◦ Brown color: Cascara, iron supplements, (schistosomiasis, TB, etc.) large-bore 3-way Foley catheter (large-bore 2-way
nitrofurantoin, others – GN: IgA nephropathy most common (4%) or rigid catheter may be more effective to clear
– Vegetables: Beets – Radiation: Radiation cystitis and nephritis clots) and hand irrigate out all clots, followed by
– Dyes or pigments r Metabolic continuous bladder irrigation (CBI) with sterile
– Myoglobin and free hemoglobin – Urinary calculi saline or water
– Menstrual period contamination – Hypercalciuria – More severe hematuria or hemodynamic
– Dysfunctional uterine bleeding – Hyperuricosuria instability may require surgery—cystoscopy with
r Congenital/inherited: r Neoplastic: Any benign or malignant GU lesion clot evacuation/fulguration
– Cystic renal disease r Drug-induced r Microscopic hematuria
◦ Polycystic kidney disease – Work-up can be done in the office setting and
– Nephrotoxic drugs
◦ Medullary sponge kidney usually requires no immediate monitoring or
– Analgesic abuse
◦ Medullary cystic disease treatment unless associated with trauma
– Cyclophosphamide
– Benign familial hematuria or thin basement – Overanticoagulation MEDICATION
membrane nephropathy r Miscellaneous
– Alport syndrome First Line
– BPH r Not treated primarily by medications.
– Inherited renal tubular disorders that can lead to
– Renal vessel disease r Aminocaproic acid (Amicar)—for intractable gross
urolithiasis ◦ Arterial emboli or thrombosis
◦ Renal tubular acidosis type I hematuria (6)
◦ Renal vein thrombosis – Inhibitor of fibrinolysis
◦ Cystinuria
◦ Oxalosis – Endometriosis of the urinary tract—female with – Rare but serious side effects of thrombotic events
r Hematologic abnormalities cyclic hematuria and renal failure
– Benign essential hematuria r Finasteride may be effective for prostatic
– Bleeding dyscrasias
– Sickle hemoglobinopathies hemorrhage
r Anatomic causes TREATMENT Second Line
– Urethral and ureteric strictures N/A
– Phimosis GENERAL MEASURES
– Posterior urethral valves r The standard urologic evaluation should include SURGERY/OTHER PROCEDURES
r Transfuse RBCs if indicated for extreme acute blood
– Urethral caruncle urinalysis, urine culture, cytology if risk factors, CTU
– Diverticula and cystoscopy as outlined above (See also loss
r Continuous bladder irrigation (CBI) with normal
– UPJ obstruction “Hematuria Algorithm”)
– Obstructive uropathy: Hydronephrosis r Treatment depends on etiology saline for persistent hematuria with clots
r Consider and rule out pseudohematuria or medical r Consider bladder irrigation with 1% Alum if GH
– Vesicoureteric reflux
r Vascular malformations: Hemangiomas causes of hematuria based on presentation, history, persists (6)
r Traumatic r Cystoscopy, clot evacuation, fulguration if
lab data, or if evaluation for anatomic lesion is
– Abdominal and pelvic injury negative conservative treatment fails
– Degree of hematuria is a poor indicator of injury
severity
– Iatrogenic trauma after abdominal, pelvic, or
urinary tract surgery
176
r If intractable GH despite all other measures consider REFERENCES See Also (Topic, Algorithm, Media)
formalin bladder instillation (6) r Cystitis, Hemorrhagic (Infectious, Noninfectious,
– Performed under anesthesia 1. Grossfeld GD, Litwin MS, Wolf JS Jr. Evaluation of Radiation)
– Must rule out vesicoureteric reflux asymptomatic microscopic hematuria in adults: The r Glomerulonephritis, Acute
1st—contraindicated if positive American Urological Association best practice r Glomerulonephritis, Chronic
– Side effects: Renal failure, bladder policy–part II: Patient evaluation, cytology, voided r Hematuria, Athletic (Runner’s Hematuria)
contracture/decreased capacity, incontinence, markers, imaging, cystoscopy, nephrology r Hematuria Adult Algorithm
ureteral stenosis evaluation, and follow-up. Urology. 2001;57: r Hematuria, Gross and Microscopic, Pediatric
r For life-threatening hemorrhagic cystitis or 604–610.
r Hematuria, Traumatic Algorithm
recurrent/refractory hemorrhagic cystitis stabilize 2. Sutton JM. Evaluation of hematuria in adults.
r Hematuria-Dysuria Syndrome
patient then consider JAMA. 1990;263:2475–2480.
r Hematuria-Loin Pain Syndrome
– Unilateral selective arterial embolization 3. Khadra MH, Pickard RS, Charlton M, et al. A
– Urinary diversion with or without cystectomy prospective analysis of 1,930 patients with r Urine, Abnormal Color
hematuria to evaluate current diagnostic practice.
J Urol. 2000;163:524–527.
Radiation Therapy 4. Grossfeld GD, Litwin MS, Wolf JS. Evaluation of CODES
N/A asymptomatic microscopic hematuria: The
Additional Therapies American Urological Association best practice ICD9
N/A policy – part I: Definition, detection, prevalence, r 599.0 Urinary tract infection, site not specified
and etiology. Urology. 2001;57:599–603. r 599.71 Gross hematuria
Therapies 5. Davis R, Jones JS, Barocas DA, et al. Diagnosis, r 599.72 Microscopic hematuria
Hyperbaric oxygen therapy (HBO) has been shown to evaluation and follow-up of asymptomatic
be effective in hematuria caused by radiation-induced microhematuria (AMH) in adults: AUA guideline. ICD10
J Urol. 2012;188:2473–2481. r R31.0 Gross hematuria
cystitis if delivered within 6 mo of initiation of r R31.2 Other microscopic hematuria
hematuria 6. Abt D, Bywater M, Engeler DS, et al. Therapeutic
options for intractable hematuria in advanced r N39.0 Urinary tract infection, site not specified
bladder cancer. Int J Urol. 2013;20:651–660.
ONGOING CARE
CLINICAL/SURGICAL
PROGNOSIS
Based on etiology of the hematuria ADDITIONAL READING PEARLS
r Corman JM, McClure D, Pritchett R, et al. Treatment r Gross or microscopic hematuria in any patient
COMPLICATIONS
Hypotension and anemia may result on degree and of radiation induced hemorrhagic cystitis with should be evaluated, especially when significant risk
chronicity of blood loss hyperbaric oxygen. J Urol. 2003;169:2200–2202. factors are present (age >35, smoking history,
r Sieber PR, Rommel FM, Huffnagle HW, et al. The exposure to chemicals/dyes, irritative voiding
FOLLOW-UP
Patient Monitoring
treatment of gross hematuria secondary to prostatic symptoms).
r Risk of urologic malignancy is 5 times higher in
H
bleeding with finasteride. J Urol. 1998;159:
r Monitor hemodynamic status if severe gross
1232–1233. patients who present with gross hematuria.
hematuria persists or if associated with trauma r Cytology is recommended for patients with risk
– Serial hemoglobin and hematocrit factors; however, a negative result does not rule out
Patient Resources malignancy.
r Hematuria: Blood in the Urine – National Kidney r CTU is the imaging test of choice for evaluating
and Urologic Diseases Information Clearinghouse hematuria from the upper tract.
(NKUDIC). http//kidney.niddk.nih.gov/kudiseases/ r Cystoscopy should be performed on any patient
pubs/hematuria >35 yr of age presenting with unexplained MH
r Urology Care Foundation. http://www.
or GH.
urologyhealth.org/urology/index.cfm?article=113
177
HEMATURIA, GROSS AND MICROSCOPIC, PEDIATRIC

Douglas W. Storm, MD, FAAP, FACS
Christopher S. Cooper, MD, FAAP, FACS

BASICS Depends on the bleeding source Lab
r Microscopic hematuria considered clinically
DESCRIPTION GENERAL PREVENTION
r Hematuria can be macroscopic or microscopic Must understand the source of the bleeding and tailor significant if >5–10 RBC/hpf
– Macroscopic: Grossly red/pink-tinged urine prevention accordingly – Recommend that 2 of 3 urinalyses show
– Microscopic: >5–10 RBC/hpf microscopic hematuria over 2–3 wk before
– Common pediatric urology referral work-up initiated (1,2)[A]
DIAGNOSIS ◦ False-negative results occur with high urine
– Approach is different in children compared to
adults specific gravity or with high ascorbic acid
HISTORY
◦ Low risk of malignancy as cause in children r Age of child and timing of onset: concentration
◦ Medical causes more frequent than surgical ◦ False-positive results occur in presence of
– Poststreptococcal GN occurs 14–28 days after the
myoglobin, medications (eg, rifampin, pyridium,
EPIDEMIOLOGY sore throat
etc.), bile pigments, and oxidizing agents (eg,
– IgA nephropathy hematuria occurs at the time of
Incidence household bleaches)
or shortly after the respiratory illness
r Microscopic hematuria more frequently encounte- r Urinalysis
– HSP hematuria occurs 1–3 mo after the rash
red than gross hematuria (1,2)[A] r Characterize the pattern of hematuria – Proteinuria
r Microscopic hematuria – Gross pink/red urine suggests a urologic cause ◦ If 1+– or 2+ child should be evaluated for
◦ Initial or terminal hematuria suggests lower postural proteinuria
– 0.41% (41 in 1,000 pediatric visits) ◦ 2+ or greater proteinuria child should be
– 0.32% school-aged girls urinary tract source
◦ Total hematuria suggests upper tract source evaluated for glomerulonephritis and nephrotic
– 0.14% school-aged boys
r Macroscopic hematuria ◦ Idiopathic urethrorrhagia seen in prepubertal syndrome
boys with blood spotting at the end of urinary – RBC casts are highly specific for
– 0.13% (1.3 in 1,000 pediatric visits) glomerulonephritis
– 80% of cases involve males; 20% females stream
– Gross brown, tea-colored, or cola-colored – Dysmorphic RBCs predict glomerular bleeding
Prevalence suggests glomerular origin with a sensitivity of 93–95% and a specificity of
Exact prevalence is unknown – Microscopic suggests nephrologic cause 95–100%
r Any precipitating events – WBCs, bacteria, leukocyte esterase, nitrates
RISK FACTORS
r Alport syndrome – Recent viral illness, strep throat, skin rash suggest UTI
r Anaphylactoid purpura ◦ Recommend urine culture to verify UTI and
– Trauma, strenuous exercise, foreign bodies, sexual
r Benign familial hematuria abuse, or bleeding/coagulation disorders identify bacteria causing the infection
r Associated lower urinary tract symptoms (urgency, r Other blood tests:
r Dysfunctional voiding
frequency, dysuria) and/or flank and abdominal pain – Serum creatinine, BUN, electrolytes (if renal
r Glomerular bleeding
suggests UTI, stone disease, or dysfunctional voiding insufficiency noted)
r Glomerulonephritis (GN) – Complete blood count CBC)
r Hemophilia component
r Family history of renal disorders, stones, end-stage – antistreptolysin O titer/streptozyme panel
r Henoch–Schönlein purpura (HSP) (indicative of poststreptococcal GM)
renal disease, neurosensory hearing loss, HTN, or
r Genitourinary anatomic anomaly – C3/C4 levels (may be lowered in cases of SLE and
coagulopathy
r Kidney stones r Current medications GN)
r Medications – plasma IgA levels (may be increased with IgA
r Recent upper respiratory illness PHYSICAL EXAM nephritis and HSP)
r Blood pressure (BP) r Other urine tests:
r Recent strep throat
r Renal papillary necrosis – High BP is suggestive of glomerular disease, – urine calcium to creatinine ratio (varies by age, but
especially when accompanied with edema generally <0.18; if >0.18 suggests high 24-hr
r Sexual abuse r Presence of fever and costovertebral angle (CVA) excretion of calcium >4 mg/kg/d)
r Sickle cell disease or trait r Other lab tests:
tenderness suggests stone and/or pyelonephritis
r Systemic lupus erythematosus (SLE) r Presence of palpable abdominal or flank mass, bruit, – throat culture (to rule out strep throat)
r Trauma or abdominal tenderness Imaging
r UTI r Skin rashes and arthritis may suggest HSP and SLE r Renal and bladder sonography
r Vigorous exercise r Hearing loss suggests Alport disease – Evaluates for renal parenchymal disorders, stones,
r Examine the genitalia for meatal stenosis, urethral tumors, renal artery stenosis, and anatomic
Genetics
r Benign familial hematuria: Autosomal dominant prolapse, ureterocele, trauma, sexual abuse abnormalities
r Sickle cell anemia: Autosomal recessive r Edema suggestive of nephrotic syndrome r Voiding cystourethrogram (VCUG)
r Alport syndrome: X-linked – Not routinely performed in work-up of hematuria
– May be done if hematuria is felt to be in
PATHOPHYSIOLOGY conjunction with febrile UTI, concern for urethral
r Depends on source of the bleeding: obstruction, or other lower urinary tract
– Glomerular source (most common) abnormalities
– Renal tubular source r CT
– Interstitial source – Selectively used in pediatrics secondary to
– Vascular source radiation exposure
– Urinary tract – May be used to evaluate for stone disease or
anatomic abnormality or after recent trauma
178
HEMATURIA, GROSS AND MICROSCOPIC, PEDIATRIC
Diagnostic Procedures/Surgery r Urinary tract source FOLLOW-UP

r Renal biopsy – Dysfunctional voiding and elimination Patient Monitoring
– Heavy proteinuria and worsening renal function – Papillary necrosis r Current recommendation of American Academy of
are the main indications for biopsy. Only – HIV, hepatitis Pediatrics is screening urinalysis at age 5 yr
performed if the results will alter therapy. – Infestations (eg, schistosomiasis) r Annual measurements of height, weight, and BP
r Cystoscopy – Nephrolithiasis measurements after age 3 yr
– Rarely performed in children – Anatomic abnormality (eg, ureteropelvic junction
– Performed if bleeding source thought to originate obstruction, fibroepithelial polyp) Patient Resources
r http://www.uptodate.com/contents/evaluation-of-
from the lower urinary tract – Hemorrhagic cystitis (eg, viral, chemical, radiation)
– May inspect efflux of urine from each ureteral – UTI microscopic-hematuria-in-children
r http://www.uptodate.com/contents/evaluation-of-
orifice to lateralize source of bleeding – Urethritis
– May perform retrograde ureteropyelogram to look – Hypercalciuria gross-hematuria-in-children
– Tumor r www.chop.edu/healthinfo/hematuria.html
for upper tract source (eg, fibroepithelial polyp)
r Hearing test – Drug-induced cystitis (eg, chemotherapy, r http://www.childrenshospital.org/
– Alport syndrome antibiotics, Coumadin, etc.) az/Site1000/mainpageS1000P1.html
– Menstruation
Pathologic Findings – Foreign bodies (eg, urinary catheter)
Dependent on the cause of the bleeding – Exercise REFERENCES
DIFFERENTIAL DIAGNOSIS – Trauma
r Divided into categories, based on the source of the r Vascular source 1. Meyers KE. Evaluation of hematuria in children.
Urol Clin North Am. 2004;31:559–573.
bleeding – Trauma
– Glomerular sources – Sickle cell disease/trait 2. Patel HP, Bissler JJ. Hematuria in children. Pediatr
– Interstitial and tubular sources – Renal vein thrombosis Clin North Am. 2001;48:1519–1537.
– Urinary tract source – Renal artery thrombosis (20% of gross hematuria 3. AAP Committee on Practice and Ambulatory
– Vascular source in 1st months of life) Medicine. Recommendations for preventive
r Glomerular source – Arteriovenous malformation pediatric health care. Pediatrics. 2000;105:
– IgA nephropathy or Berger disease (recurrent – Nutcracker syndrome 645–646.
gross, painless hematuria, often following a mild – Vasculitis (eg, C3 arteriolar deposition)
fever, upper respiratory illness, viral illness, or – Coagulopathy
exercise) – Thrombocytopenia ADDITIONAL READING
– Benign familial hematuria (usually microscopic r Feld LG, Waz WR, Pérez LM, et al. Hematuria. An
hematuria also found in parent without hearing integrated medical and surgical approach. Pediatr
loss or renal insufficiency) TREATMENT
Clin North Am. 1997;44:1191–1210.
– Alport syndrome (usually microscopic hematuria, r Quigley R. Evaluation of hematuria and proteinuria:
GENERAL MEASURES
proteinuria, progressive renal insufficiency, r Establish diagnosis and treat any underlying medical How should a pediatrician proceed? Curr Opin
high-frequency hearing loss, family history of renal
problems causing the hematuria Pediatr. 2008;20:140–44. H
disease)
– Acute poststreptococcal glomerulonephritis r Prompt evaluation must be provided to a child with See Also (Topic, Algorithm, Media)
(PSGN) (usually acute onset edema, tea-colored any of the following in addition to the hematuria r Cystitis, Hemorrhagic (Infectious, Noninfectious,
urine, history of antecedent illness 2–4 wk prior, (1,2)[A] Radiation)
elevated BP, urinalysis with RBC casts, and – HTN r Hematuria, Gross and Microscopic, Pediatric
proteinuria) – Edema Images
– Membranoproliferative glomerulonephritis – Oliguria r Hematuria, Pediatric Macroscopic (Gross)
– SLE – Significant proteinuria (2+ or greater) Algorithm
– Rapidly progressive glomerulonephritis (pediatric – RBC casts r Hematuria, Pediatric Microscopic/Isolated
nephrology emergency, presents with signs and MEDICATION Asymptomatic
symptoms similar to PSGN, renal function though Based on underlying cause of hematuria r Hematuria, Gross and Microscopic, Adult
shows renal insufficiency, may progress to r Hematuria-Loin Pain Syndrome
end-stage renal disease in a few weeks) OTHER PROCEDURES r Urine, Abnormal Color
– Henoch–Schönlein purpura (rash on dependent Based on clinical diagnosis and etiology of the
parts of the body, renal manifestations may hematuria
include: No involvement, HTN, active ADDITIONAL TREATMENT
glomerulonephritis, nephrotic syndrome, and CODES
acute renal failure) Additional Therapies
– Goodpasture syndrome (pulmonary hemorrhage Based on clinical diagnosis and etiology of the ICD9
associated with severe and progressive hematuria r 599.0 Urinary tract infection, site not specified
glomerulonephritis) Complementary & Alternative r 599.71 Gross hematuria
r Interstitial and tubular source Therapies r 599.72 Microscopic hematuria
– Acute pyelonephritis Based on clinical diagnosis and etiology of the
– Renal tuberculosis hematuria ICD10
r N39.0 Urinary tract infection, site not specified
– Sickle cell disease or trait
r R31.0 Gross hematuria
– Acute interstitial nephritis
– Nephrocalcinosis
ONGOING CARE r R31.2 Other microscopic hematuria
– Metabolic (eg, Fabry disease) PROGNOSIS
– Nephrotoxins (eg, analgesics, NSAIDs) Based on underlying cause of the hematuria (3)
– Renal cystic disease CLINICAL/SURGICAL
– Acute tubular necrosis COMPLICATIONS PEARLS
Based on the underlying cause of the hematuria and
any interventions delivered r Prompt evaluation must be provided to a child with
any of the following in addition to the hematuria:
– HTN, edema, oliguria, significant proteinuria, RBC
casts
– Unstable BP, renal insufficiency, fevers
179
HEMORRHAGE FOLLOWING TURP OR TURBT

Frank M. Nezu, MD
Mohamed T. Ismail, MD
r Due to the sloughing of necrotic tissue in prostatic DIAGNOSTIC TESTS & INTERPRETATION
BASICS fossa or bleeding at the bladder neck Lab
r Size of tissue resected, duration of resection, or r CBC to assess for anemia
DESCRIPTION r Creatinine level for obstruction
presence of prostate cancer does not correlate with
Significant gross hematuria with or without clot r Urinalysis, urine culture
the incidence of hematuria post-TURP (1)[B]
retention that occurs following transurethral resection r Coagulopathy screen (platelets, PT/PTT) particularly
r Studies suggest that there is transient change in
of the prostate (TURP) or transurethral resection of
bladder tumor (TURBT) platelet count, prothrombin time, and fibrinogen if there is suggestion of bleeding from other sites
and serum sodium concentrations postoperatively, Imaging
EPIDEMIOLOGY which can be explained on the basis of dilution of Bladder US or pelvic CT to evaluate for large organized
r Occurs in up to 11% of patients, typically within the blood clot within bladder
the 1st 3 mo after TURP (1)[B] r Prostate cancer is known to trigger disseminated
r TURP is associated with a 2.9% transfusion rate Diagnostic Procedures/Surgery
intravascular coagulation (DIC), and this should be Bladder drainage and irrigation with large-caliber
(2)[B] kept in mind when performing resection in the face hematuria catheter
r 2.2–3.3% of patients require recatheterization, of known advanced prostate cancer
clot evacuation, or return to OR for bleeding after r In the absence of prostate cancer, up to 6% of DIFFERENTIAL DIAGNOSIS
r Bleeding from lower GU tract source: Urethra,
TURP (3)[A] patients undergoing TURP may develop mild
subclinical intravascular coagulopathy prostate, bladder
RISK FACTORS r Urinary fibrinolysis is a normal physiologic process. r Bleeding from upper GU tract source: Ureter, renal
r Excessive Valsalva/straining/constipation
Plasminogen is converted to plasmin by pelvis, kidney
r Inadequate hemostasis/coagulation of bleeding
plasminogen activators
vessels r The presence of a clot in the bladder causes the
r Infection TREATMENT
r Medications: Warfarin, heparin, low molecular release of additional plasminogen activators.
Evacuation of clot in the bladder is essential to GENERAL MEASURES
weight heaprins, aspirin, thienopyridine stopping the bleeding r Limit physical activity, encourage bed rest
(clopidogrel), etc. r Limit Valsalva and avoid constipation through stool
r Trauma ASSOCIATED CONDITIONS
r Undermining of bladder neck r BPH softeners
r Bladder cancer r Adequate hydration; IV fluid resuscitation
Genetics r Prostate cancer r Bladder drainage and clot evaluation with
Patients with deficiencies in the clotting cascade (eg, large-caliber hematuria catheter
hemophilia) or other coagulopathies are more prone r Continuous bladder irrigation (CBI) via 3-way Foley
to hemorrhage. DIAGNOSIS catheter to clear clots and prevent new clots from
GENERAL PREVENTION HISTORY forming in the bladder
r Obtain sufficient hemostasis intraoperatively r Color of urine, presence of clots r Foley traction, additional inflation of Foley balloon
r Stop anticoagulants or other blood-thinning r Patient is not able to void (clot retention) r Cessation of anticoagulants or blood-thinning
medications prior to surgery r History of TURP TURBT—timing, complications, medications
r Delay starting anticoagulant medications r Check CBC and coagulation profile
catheter removal
r Use of anticoagulation or similar medications r PRBC transfusions if necessary, vitamin K and/or FFP
postoperatively if possible, although this practice
has been questioned (4)[B] r Excessive straining or trauma; last bowel movement if coagulopathic
r Gentle postoperative catheter traction r History of clotting disorder r CBI with intravesical alum or silver nitrate
r History of prostate cancer r These are reported but rarely necessary:
r 5α-reductase inhibitors, taken pre operatively
– Hyperbaric oxygen
reduce surgical blood loss intraoperatively (5)[A] PHYSICAL EXAM – Aminocaproic acid (Amicar) antifibrinolytic
r 5α-reductase inhibitors, do not decrease rates of r General: Pallor, dehydrated, acutely ill
– Hormonal manipulation: LHRH agonists
postoperative clot retention (6)[A] r Vitals: Hypotensive or tachycardic – Urinary diversion with bilateral PCNs
r Abdomen: Bladder distended or palpable – Salvage radical prostatectomy
PATHOPHYSIOLOGY r Genitalia: Edematous; ecchymotic
r Anesthetic technique (regional or general) appears – Selective arterial prostatic embolization (SAPE)
to have no impact on TURP-related bleeding (8)[A]
r Inadequate hemostasis/coagulation of bleeding
vessels
r Narcotics may cause constipation and increased
intra-abdominal pressure
r NSAIDs are not contraindicated after TURP, they
do not increase risk of postoperative adverse
events (7)[A]
180
HEMORRHAGE FOLLOWING TURP OR TURBT
MEDICATION REFERENCES ADDITIONAL READING

First Line r Kavanagh LE, Jack GS, Lawrentschuk N, et al.
r Antibiotics if infected 1. Normand G, Guignet J, Briffaux R, et al.
r Stool softeners Macroscopic haematuria after transurethral Prevention and management of TURP-related
r 5α-reductase inhibitors such as finasteride or resection of the prostate. Prog Urol. 2006;16(4): hemorrhage. Nat Rev Urol. 2011;8:504–514.
461–463. r Mebust WK, Holtgrewe HL, Cockett AT, et al.
dutasteride (although will not have an acute effect)
2. Reich O, Gratzke C, Bachmann A, et al. Morbidity, Transurethral prostatectomy: Immediate and
Second Line mortality and early outcome of transurethral postoperative complications. A cooperative study of
N/A resection of the prostate: A prospective multicenter 13 participating institutions evaluating 3,885
SURGERY/OTHER PROCEDURES evaluation of 10,654 patients. J Urol. 2008;180(1): patients. J Urol. 1989;141:243–247.
r Transurethral clot evacuation with fulguration and 246–249. See Also (Topic, Algorithm, Media)
cauterization (laser or electrocautery) of prostate if 3. Roehrborn CG. The Agency for the Health Care r Hematuria, Gross and Microscopic, Adult
bleeding does not subside within a reasonable time Policy and Research. Clinical guidelines for the r Hemorrhage, Postop, Urologic Considerations
frame diagnosis and treatment of benign prostatic r Hemorrhagic Cystitis
– Typical Findings: Visible bleeding arterial vessel or hyperplasia. Urol Clin North Am. 1995;22(2): r Urine, Abnormal Color
discrete/nondiscrete venous bleeding 445–453.
r Post-TURBT hemorrhage, more expeditious clot 4. Ehrlich Y, Yossepowitch O, Margel D, et al. Early
evacuation and fulguration initiation of aspirin after prostate and transurethral
bladder surgeries is not associated with increased CODES
incidence of postoperative bleeding: A prospective
ONGOING CARE randomized trial. J Urol. 2007;178(2):524–528. ICD9
r 599.71 Gross hematuria
PROGNOSIS 5. Pastore AL, Mariani S, Barrese F, et al.
r 998.11 Hemorrhage complicating a procedure
r The mortality rate for hemorrhage after TURP and Transurethral resection of prostate and the role of
TURBT is unknown pharmacological treatment with dutasteride in
ICD10
r Whether hemorrhage after TURP increases the risk decreasing surgical blood loss. J Endourol. r N99.820 Postproc hemor/hemtom of a GU sys org
2013;27(1):68–70.
of future prostatic bleeding has not been described fol a GU sys procedure
in the literature 6. Hahn RG, Fagerström T, Tammela TL, et al. Blood r R31.0 Gross hematuria
r Use of stool softeners and avoidance of constipation loss and postoperative complications associated
with transurethral resection of the prostate after
for several weeks after TURP and TURBT seems
advisable
pretreatment with dutasteride. BJU Int. 2007; CLINICAL/SURGICAL
99:587–594. PEARLS
COMPLICATIONS 7. Kara C, Resorlu B, Cicekbilek I, et al. Analgesic
Severe anemia and/or hypovolemic shock can lead to efficacy and safety of nonsteroidal anti- r Proper patient selection, identify patients at risk for
syncope and/or MI Inflammatory drugs after transurethral resection of bleeding with attention to medications.
prostate. Int Braz J Urol. 2010;36(1):49–54. r Attention to detail at the end of TURP/TURBT,
FOLLOW-UP
8. Rastinehad AR, Caplin DM, Ost MC, et al. Selective complete hemostasis and evacuation of specimen.
H
Patient Monitoring r Avoid constipation postoperatively.
r Can be managed on the floor setting with staff who arterial prostatic embolization (SAPE) for refractory
hematuria of prostatic origin. Urology. 2008;71: r In patient with clot retention a large-bore catheter is
are accustomed to managing catheters and CBI
r Serial CBCs, blood transfusions as necessary 181–184. used to evacuate all clots and start continuous
r Monitor coagulation profile, FFP if needed bladder irrigation (CBI) immediately.
Patient Resources
N/A
181
HERPES SIMPLEX, GENITAL

Michael Perrotti, MD

r Herpes simplex is a common sexually transmitted r Patients may experience a prodrome before the r No cure is available
virus infection appearance of lesions r Encourage safe sex practices to reduce transmission
r Herpes simplex virus (HSV) – Tingling, pruritus, paresthesias (ie, condom use); however, lesions can sometimes
r Fever
– HSV-2 is the most common cause of genital herpes spread outside of the coverage area
– Can be caused by HSV-1 (oral sex during HSV-1 r Malaise r Common concerns regarding genital herpes include
outbreak) r Headache
the severity of initial clinical manifestations,
r An increasing proportion of anogenital herpetic r Painful genital lesions recurrent episodes, sexual relationships and
infections in some populations has been attributed r Dysuria transmission to sex partners, and ability to bear
to HSV-1 infection healthy children. The misconception that HSV causes
PHYSICAL EXAM cancer should be dispelled.
EPIDEMIOLOGY r Multiple shallow genital ulcers that may be vesicular
r Avoidance of sexual activity during recurrences
Incidence – However, these classical painful multiple vesicular r Antiviral medications can prevent or shorten
0.5–1 million new cases of genital herpes per year in or ulcerative lesions may be absent in some.
US outbreaks.
DIAGNOSTIC TESTS & INTERPRETATION r Daily suppressive therapy can reduce recurrences
Prevalence Lab and the likelihood of transmission to partners.
∼45 million people in US have genital herpes r Viral culture r Topical therapy with antiviral drugs offers minimal
r Polymerase chain reaction
RISK FACTORS clinical benefit.
r Sexual contact with an infected person r Direct fluorescence antibody r Treatment guidelines based on most current CDC
r Unprotected sexual intercourse r Type-specific serology testing recommendations (2)
r Multiple sexual partners – Both lab-based assays and point-of-care tests that r Acyclovir, valacyclovir, and famciclovir are safe for
provide results for HSV-2 antibodies from capillary use in immunocompromised patients in the doses
PATHOPHYSIOLOGY blood or serum.
r Transmission can occur by anal, vaginal, or oral sex recommended for treatment of genital herpes.
◦ The sensitivities of these glycoprotein G
r Primary infection if patient was HSV-seronegative MEDICATION
type-specific tests for HSV-2 antibody vary from
for both HSV-1 and HSV-2 80–98%, are false-negative at early stages of First Line
r Secondary infection if patient with pre-existing r Recommended regimens for 1st episode (extend
infection. The specificities are ≥96%.
HSV-1 immunity False-positive results can occur, especially in treatment if healing is incomplete after 10 days of
r Most persons infected with HSV-2 have not been patients with a low likelihood of HSV infection therapy).
diagnosed with genital herpes. Many have mild or – Acyclovir 400 mg PO TID for 7–10 days OR
Imaging 200 mg PO 5 times a day for 7–10 days
unrecognized infections and shed virus MRI in suspected CNS disease
intermittently in the genital tract. As a result, the – Famciclovir 250 mg PO TID for 7–10 days
majority of genital herpes infections are transmitted Diagnostic Procedures/Surgery – Valacyclovir 1 g PO BID for 7–10 days
r Unroofing of vesical to obtain fluid for viral culture
by persons who are unaware that they have the Second Line
infection or who are asymptomatic when r Lumbar puncture in meningitis r Suppressive therapy for recurrent genital herpes
transmission occurs (2). DIFFERENTIAL DIAGNOSIS
r Asymptomatic viral shedding is more frequent in – Acyclovir 400 mg PO BID (3)[A]
r Acute UTI
genital HSV-2 infection than genital HSV-1 infection r Neisseria gonorrhoeae – Famciclovir 250 mg PO BID
and is most frequent during the first 12 mo after – Valacyclovir 500 mg or 1,000 mg PO once daily
r Treponema pallidum ◦ Valacyclovir 500 mg once a day might be less
acquiring HSV-2. r Drug eruption effective than other valacyclovir or acyclovir
ASSOCIATED CONDITIONS r Behçet’s disease dosing regimens in patients who have very
r HIV
frequent recurrences (ie, ≥10 episodes per
r Other STDs
year).
GENERAL PREVENTION
r Monogamous seronegative partner
r Condom use
r Randomized trials have demonstrated that male
circumcision (MC) reduces heterosexual acquisition
of various STI/STD including HSV type 2, and it
reduces genital ulcer disease among female
partners (1)
182
HERPES SIMPLEX, GENITAL
r Episodic therapy for recurrent genital herpes (2) r HIV transmission 3. Bryson YJ, Dillon M, Lovett M, et al. Treatment of
– Requires initiation of therapy within 1 day of – When the sores come into contact with the first episodes of genital herpes simplex virus
lesion onset or during the prodrome that precedes mouth, vagina, or rectum during sex, they infection with oral acyclovir: A randomized
some outbreaks. increase the risk of HIV transmission if either double-blind controlled trial in normal subjects. N
– Provide patient with a supply of drug or a partner is HIV-infected. Engl J Med. 1983;308:916–921.
prescription for the medication with instructions r Some HSV-infected persons might express anxiety 4. Mattison HR, Reichman RC, Benedetti J, et al:
to initiate treatment immediately when symptoms concerning genital herpes that does not reflect the Double blind placebo controlled trial comparing
begin. actual clinical severity of their disease; the long term suppressive with short term oral acyclovir
◦ Acyclovir 400 mg TID for 5 days OR 800 mg PO psychological effect of HSV infection frequently is therapy for management of recurrent genital
BID for 5 days OR 800 mg PO TID for 2 days substantial. herpes. Am J Med. 1988;85:20–25.
◦ Famciclovir 125 mg PO BID for 5 days OR
1,000 mg PO BID for 1 day OR 500 mg once, FOLLOW-UP
followed by 250 mg BID for 2 days Patient Monitoring ADDITIONAL READING
◦ Valacyclovir 500 mg PO BID for 3 days OR 1 g r Patient’s education concerning the natural history of
PO QD for 5 days the disease, potential for recurrent episodes, Hofstetter AM, Rosenthal SL, Stanberry LR. Current
asymptomatic viral shedding, and the risks of sexual thinking on genital herpes. Curr Opin Infect Dis.
SURGERY/OTHER PROCEDURES transmission. 2014;27(1):75–83.
r Sitz baths r At 1st episode of genital herpes, advise the patient
r Foley catheter for retention of urine associated with See Also (Topic, Algorithm, Media)
that suppressive therapy is available and effective in r Aphthous Ulcer, External Genitalia
sacral nerve root involvement preventing symptomatic recurrent episodes r Genital Ulcers
ADDITIONAL TREATMENT r Encourage patients to inform their current sex
r Genital Ulcers Algorithm
Radiation Therapy partners that they have genital herpes and to inform r Herpes Simplex, Genital Image
N/A future partners before initiating a sexual
r Penis, Cutaneous Lesion
relationship.
Additional Therapies r The risk for HSV-2 sexual transmission can be r Sexually Transmitted Infections (STIs) (Sexually
r In complicated HSV infection (central nervous
decreased by the daily use of valacyclovir by the Transmitted Diseases [STDs]), General
system disease, disseminated HSV), the Centers for infected person. Episodic therapy does not reduce
Disease Control recommend intravenous acyclovir the risk for transmission and its use should be
(5–10 mg/kg) every 8 hr for 2–7 days or until clinical discouraged for this purpose among persons whose CODES
improvement partners might be at risk for HSV-2 acquisition (4).
r Suppressive or episodic therapy with oral antiviral r Symptomatic sex partners should be evaluated and ICD9
agents is effective in decreasing the clinical treated in the same manner as patients who have r 054.10 Genital herpes, unspecified
manifestations of HSV among HIV-positive persons. genital lesions. Asymptomatic sex partners of r 054.11 Herpetic vulvovaginitis
Complementary & Alternative patients who have genital herpes should be r 054.19 Other genital herpes
Therapies questioned concerning histories of genital lesions
None noted to be effective and offered type-specific serologic testing for HSV ICD10
r A60.00 Herpesviral infection of urogenital system,
H
infection.
unspecified
ONGOING CARE Patient Resources r A60.04 Herpesviral vulvovaginitis
http://www.cdc.gov/STD/Herpes/
PROGNOSIS r A60.9 Anogenital herpesviral infection, unspecified
r Symptoms may last 2–4 wk if untreated
r Symptoms less severe in nonprimary compared to REFERENCES
person without pre-existing HSV immunity
CLINICAL/SURGICAL
1. Tobian AA, Kacker S, Quinn TC. Male Circumcision:
r Treatment during primary infection lessens A globally relevant but under-utilized method for
PEARLS
morbidity (1)[A] the prevention of HIV and other sexually r It is estimated that 1 in 5 adults in US is infected
transmitted infections. Annu Rev Med. 2014;65: with HSV, but that many are asymptomatic and do
COMPLICATIONS 293–306.
r Aseptic meningitis not know that they are infected with the virus.
r Encephalitis 2. MMWR. December 17, 2010, Vol 59, no. RR-12. r Most infected individuals have recurrent episodes of
r Transverse myelitis Available at http://www.cdc.gov/std/treatment/ painful genital ulcers.
2010/STD-Treatment-2010-RR5912.pdf. Accessed r The 1st episode usually occurs a few weeks
r Hepatitis
January 3, 2014. following initial infection with the virus and may last
r Pneumonitis
r Disseminated HSV 2–3 wk.
r HSV recurrences generally decrease in frequency
over time.
183
HESITANCY AND INTERMITTENCY

Patricia Lewandoski, MD
Akhil Das, MD, FACS

r Urinalysis by dipstick testing or microscopic exam of
DESCRIPTION HISTORY the sediment should be performed to screen for
r Hesitancy is the delay in the start of micturition. r Quantification of lower urinary tract symptoms
hematuria and UTI.
r Intermittency is the involuntary stopping and – AUA/IPSS symptom index should be used.
– If UTI suspected: Urine culture.
starting of the urinary stream during voiding. – Other obstructive voiding symptoms should be r Serum PSA should be assessed in men with at least
r Hesitancy and intermittency are commonly assessed.
– Consider voiding diary if history is unclear. a 10-yr life expectancy.
characterized as obstructive (emptying) symptoms. r Assess for irritative voiding symptoms: r Renal function tests (BUN and creatinine) are NOT
These spectrum of symptoms also include: recommended in the initial evaluation of men with
– Postvoid dribbling – Cystitis/prostatitis: Can present with acute, severe
obstructive symptoms. LUTS, such as hesitancy or intermittency according
– Straining to void to the AUA guidelines for BPH.
r History of hematuria:
– Decreased force of stream
– Incomplete bladder emptying – Urethral stricture Imaging
r Upper tract evaluation (CT scan, IVP, or US) is not
– Bladder/kidney stones
EPIDEMIOLOGY – Bladder mass recommended as part of the initial work-up of
Incidence r Certain pelvic procedures can result in detrusor hesitancy and intermittency unless warranted by
r Obstructive urinary symptoms and age are highly history, exam, or lab evaluation.
underactivity.
correlated. r If urethral stricture disease is suspected, retrograde
– Other medical conditions:
r Patient symptom reporting is influenced by ◦ Certain neurologic conditions and diabetes can urethrography (RUG) may be helpful
sociodemographic and cultural factors. cause detrusor underactivity. r Transrectal US should be reserved for patients with
r Hesitancy and intermittency is primarily related to ◦ Prior pelvic irradiation can affect bladder an increased suspicion of prostate cancer
BPH and occurs mostly in men. contractility. undergoing prostate needle biopsy
r History of STD may predispose patients to urethral
Prevalence Diagnostic Procedures/Surgery
r Age-stratified prevalence of moderate-to-severe stricture disease. r Urinary flow rate should be considered:
r Medications: – May be helpful in patients with complex medical
Lower Urinary Tract Symptoms (LUTS) in men:
– 40–50 yr old: ∼20% – Certain over the counter (OTC) medications for history.
– 50–60 yr old: ∼30% colds or sinusitis may contain phenylephrine – Should be performed in patients who are to
– 60–70 yr old: ∼40% which may exacerbate LUTS. undergo invasive therapy, as this may predict
– 70–80 yr old: ∼56% – Antimuscarinics may lead to obstructive response to surgery.
symptoms. r Catheterized or scanned PVR should also be
RISK FACTORS
r Bladder outlet obstruction: PHYSICAL EXAM considered:
r Abdominal exam: Palpate for a distended bladder. – Will indicate which patients need immediate
– In men, primarily related to benign prostatic
hypertrophy (BPH), bladder neck contracture, r Focused neurologic exam should be performed. The catheterization for acute urinary retention.
bladder stones, urethral valves, urethral stricture following should be assessed: – Helps in diagnosis of voiding dysfunction or in
disease, and prostate cancer. – General mental status patients with neurologic disease.
r Cystourethroscopy should be considered in patients
– In women, primarily caused by pelvic floor – Ambulatory status
prolapse/large cystocele, bladder stones, and – Lower extremity neuromuscular function with possible urethral stricture.
r Urodynamics (pressure flow) study should be
urethral stricture disease (rarely) – Anal sphincter tone
r Detrusor underactivity: r Digital rectal exam (DRE) should be performed: considered in certain patients with complicated
– Idiopathic – Prostatic nodularity, if present, may be a sign of histories that imply neurologic disease.
– Neurogenic: Diabetes, Parkinson disease, etc. prostate cancer and should be worked up Pathologic Findings
– Non-neurogenic: Dysfunctional voiding accordingly BPH findings on pathologic exam include proliferation
r Obesity is associated with a higher incidence of LUTS – Size should be assessed, although DRE tends to of the stroma and epithelium.
underestimate size
Genetics – Bogginess or tenderness: Consistent with DIFFERENTIAL DIAGNOSIS
N/A r Bladder outlet obstruction
prostatitis
PATHOPHYSIOLOGY r In men, circumcision status, assess for urethral – BPH—common cause of hesitancy and
r Bladder outlet obstruction: Increased resistance to intermittency in men
stenosis
urinary flow due to various etiologies (BPH, stricture, r In women: – Bladder neck contracture (ie, after prostate
etc.) requires the bladder to generate higher voiding surgery)
– Pelvic exam should be performed to assess for – Urethral stricture disease
pressures which delays the initiation of micturition masses, pelvic floor prolapse, and/or cystocele. r Bladder stone
and may cause intermittency. – Urethral lesions should also be assessed.
r Inadequate detrusor contraction due to various r Foreign body
r Pediatric considerations:
r Cancer (prostate, bladder, urethral)
etiologies delays the start of voiding and may cause – Meatal stenosis should be considered in young
intermittency. r Prostatitis
boys who present with hesitancy and intermittency
r UTI
ASSOCIATED CONDITIONS r Bladder neck dyssynergia
BPH and erectile dysfunction in men
GENERAL PREVENTION
Adequate treatment of LUTS
184
HESITANCY AND INTERMITTENCY
r Detrusor-sphincter dyssynergia SURGERY/OTHER PROCEDURES FOLLOW-UP

r Pelvic organ prolapse r Urethral stricture disease and/or bladder neck
Patient Monitoring
r Detrusor underactivity (more common cause of contractures should be addressed using appropriate r After appropriate treatment has been initiated and
hesitancy and intermittency in women): endoscopic or open procedures. patients report improvement, annual follow-up
r Diabetes mellitus r Cystocele and/or pelvic floor prolapse in women should include:
r Parkinson disease should be addressed surgically if indicated. r History and physical exam, urinalysis, PSA
r Multiple sclerosis r For men with hesitancy and intermittency – Uroflowmetry and postvoid residual urine as
r Interstitial cystitis presumably due to BPH/BOO who do not respond to needed
r Radiation cystitis medical management:
Patient Resources
r Spinal cord injury/lumbosacral disk disease – Transurethral resection of the prostate (TURP)
MedlinePlus. http://www.nlm.nih.gov/medlineplus/
remains the gold standard surgical approach in
r Medications: Noradrenergic drugs are less likely ency/article/003143.htm
patients who do not respond to medical
than selective serotonin reuptake inhibitors (SSRIs) management to BPH.
to cause sexual dysfunction but more likely to cause ◦ Can be combined with various laser techniques REFERENCES
urinary hesitancy to facilitate tissue hemostasis and removal
r Transurethral laser vaporization or enucleation. 1. Rosenberg MT, Staskin DR, Kaplan SA, et al. A
r Transurethral microwave heat treatment (TUMT): practical guide to the evaluation and treatment of
TREATMENT male lower urinary tract symptoms in the primary
Minimally invasive therapy is somewhat effective in
the treatment of LUTS due to BPH. care setting. Int J Clin Pract. 2007;61:1535–1546.
GENERAL MEASURES
r When the effect of LUTS on quality of life was – Simple open prostatectomy is often reserved for 2. McConnell JD, Roehrborn CG, Bautista OM, et al.
patients with large prostates (>100 cc) who are The long-term effect of doxazosin, finasteride, and
studied, most important factors for seeking
not candidates for TURP. combination therapy on the clinical progression of
treatment were the severity and degree of bother.
r Treatments are tailored to the degree of bother and benign prostatic hyperplasia. N Engl J Med.
ADDITIONAL TREATMENT 2003;349:2387–2398.
the severity of the disease Radiation Therapy
r Review medications (anticholinergics, 3. Takeda M, Araki I, Kamiyama M, et al. Diagnosis
N/A and treatment of voiding symptoms. Urology.
sympathomimetics, and opioids) to determine if any 2003;62:11–19.
are potential cause; consider alternatives Additional Therapies
r Mild symptoms: Watchful waiting and conservative Behavioral interventions, such as timed voiding or
measures double voiding
ADDITIONAL READING
– Limit fluid intake Complementary & Alternative
– Avoid diuretics Therapies McVary KT, Roehrborn CG, Avins AL, et al. Update on
– Avoid coffee, tea, alcohol which may irritate the Saw palmetto (Serenoa repens) has been reported to AUA guideline on the management of benign prostatic
bladder improve LUTS due to BPH/BOO. Randomized clinical hyperplasia. J Urol. 2011;185(5):1793–1803.
studies have produced contradictory results.
MEDICATION (2) See Also (Topic, Algorithm, Media)
First Line r Bladder Outlet Obstruction (BOO) H
r For patients with evidence of infection, appropriate ONGOING CARE r Lower Urinary Tract Symptoms (LUTS)
antibiotic therapy should be initiated. r Prostate, Benign Hypertrophy
r For men with hesitancy and intermittency PROGNOSIS (3) r Prostatitis, General
r 25% of untreated patients with moderate-to-severe
presumably due to BPH/BOO:
– α-adrenergic antagonists (alfuzosin, doxazosin, LUTS presumably due to BPH/BOO experience
clinical progression of symptoms within 5 yr.
tamsulosin, terazosin, silodosin) reduce resistance
r Randomized clinical trials of patients receiving CODES
at the bladder outlet and provide symptom relief.
– At maximal doses, all agents are felt to be equally α-blocker therapy indicate that >1/2 will report a
>25% improvement in symptoms within 3 mo of ICD9
effective. r 788.61 Splitting of urinary stream
– Side effect profiles may include syncope, initiating treatment. r 788.64 Urinary hesitancy
orthostatic hypotension, retrograde ejaculation, r 5–10% of men with moderate-to-severe LUTS will
r 788.69 Other abnormality of urination
asthenia, and nasal congestion. fail medical therapy and will require surgical
r 5α-reductase inhibitors (5ARIs) (finasteride 5 mg/d intervention for their condition. ICD10
and dutasteride 0.5 mg/d) reduce prostate volume, COMPLICATIONS r R39.11 Hesitancy of micturition
prevent progression of BPH, and improve symptoms r Patients with disease progression who do not r R39.13 Splitting of urinary stream
in clinical trials. receive appropriate treatment may experience the r R39.19 Other difficulties with micturition
– These drugs can cause decreased libido, sexual following complications:
dysfunction, and reduce PSA by ∼50% and are of – Renal insufficiency
little use in men without evidence of clinical BPH. – UTI CLINICAL/SURGICAL
r Combination therapy: MTOPS study showed a 67%
– Stone formation PEARLS
5-yr risk reduction in BPH progression in men on – Acute urinary retention
combination therapy (doxazosin and finasteride) r Hesitancy and intermittency is often associated with
– Secondary bladder dysfunction
compared to placebo and better than either agent BPH and generally represents LUTS associated with
alone (39% and 34%, respectively). an obstruction.
r Increasing hesitancy may be seen before an episode
Second Line
r Combination therapy combining an 5ARI with an of retention.
r In men, the incidence increases with age.
α-blocker may be useful
r If ED and BPH/BOO coexist daily tadalafil (2.5–5 mg r Pressure-flow studies are helpful in determining
PO QD) can be used obstruction vs. detrusor underactivity.
185
HIV/AIDS, UROLOGIC CONSIDERATIONS

Daniel C. Parker, MD
PATHOPHYSIOLOGY
ALERT r HIV-1 binds to cells expressing CD4, leading to DIAGNOSIS
The American Urological Association (AUA) policy decline in CD4 cells and immune function.
statement now considers circumcision to be of a r Immunosuppression allows opportunistic/unusual HISTORY
health benefit, citing a 50–60% risk reduction in infections, decreases host defense against r Voiding history (1)[A]
HIV transmission in some African nations. malignancy. – Dysuria
– Frequency
r UTI – Incontinence
BASICS – Urethral discharge
– Greater if CD4 count <500/mm3
– Pelvic or testicular pain
DESCRIPTION – Associated with typical bacteria (Escherichia coli,
r HIV disease results from the acquired deficiency of – Flank pain
Enterococcus) and atypical pathogens such as
fungi, mycobacteria, and viruses r Neurologic history
cellular immunity caused by the human
immunodeficiency virus (HIV). r Epididymitis/orchitis – Numbness
– Hallmarks – Chlamydia, gonorrhea, salmonella, toxoplasmosis – Dysesthesias
◦ Reduction of the helper T-lymphocytes in the r Fournier gangrene r Social history
blood and the lymph nodes r Prostatitis – Sexual history
◦ Development of opportunistic infections – Up to 14% in patients with AIDS – IV drug use
(Pneumocystis carinii pneumonia, – Greater risk in AIDS patients for developing – Blood product transfusions
cytomegalovirus infections, tuberculosis, r Generalized lymphadenopathy, fever, weight loss,
prostatic abscess
candida infections, cryptococcosis, others) r Urolithiasis and chronic diarrhea are common symptoms.
◦ Development of malignant neoplasms r Review of systems (ROS): Constitutional symptoms,
– Risk with use of indinavir or from metabolic
(non-Hodgkin lymphoma and Kaposi sarcoma) abnormalities skin lesions, confusion, urticaria
r A spectrum of HIV infections range from r Hepatitis B virus (HBV)
PHYSICAL EXAM
asymptomatic seropositivity to AIDS r Malignancies r General: Skin lesions, adenopathy
r Urologic manifestations of HIV/AIDS
– Non-Hodgkin lymphoma r Neurologic exam: Numbness, alterations in
– Bacterial and nonbacterial infections ◦ Usually B cell sensation
– Urolithiasis ◦ May involve kidneys in 6–12% of AIDS patients r GU exam: Urethral discharge, testicular/epididymal
– Increased risk of malignancy – Kaposi sarcoma
– Renal impairment exam for masses, prostate exam for nodule or
◦ Up to 20% of untreated patients tenderness
– Voiding dysfunction – Testicular tumors r Penile lesions of Kaposi sarcoma present as
EPIDEMIOLOGY ◦ Usually seminoma
red/brown/purple nodules, macules, or patches
◦ Up to 50 times more common
Incidence
40–50,000 new cases per year in US – Renal cell carcinoma DIAGNOSTIC TESTS & INTERPRETATION
◦ Up to 8-fold increased risk vs. noninfected Lab
Prevalence individuals r HIV testing
r 0.5% of US adults <50 are infected r HIV associated nephropathy (HIVAN) – Screening HIV-1 antibody titer
– 2.6% of African American men and 1.5% of – Proteinuria >3.5 g/d, edema, and HTN ◦ If positive, need confirmation by Western blot or
African American women were HIV positive from – Associated with focal segmental immunofluorescence.
1999 to 2006 glomerulosclerosis (FSGS) on renal biopsy ◦ Need separate consent for HIV testing.
r 33.2 million people worldwide with HIV/AIDS r UA, urine C+S
– Progression to dialysis in <10 mo.
r 2.1 million deaths due to HIV/AIDS in 2007 r Voiding dysfunction – May show rectangular crystals from indinavir
RISK FACTORS – Can be retention, detrusor overactivity, and – Common bacterial pathogens in HIV-infected
r Unprotected intercourse, anal or oral sex sphincter dyssynergia patients are E. coli, Enterobacter (enterococci),
r IV drug abuse and needle sharing Pseudomonas aeruginosa, Proteus spp., Klebsiella,
GENERAL PREVENTION Acinetobacter, Staphylococcus aureus, group D
r Transfusion of blood products r Barrier protection during sex (male and female
r Concomitant STD/STI Streptococcus, Serratia, and Salmonella spp.
condoms) – If UTI suspected and C&S negative, consider
r Uncircumcised phallus – Lab studies indicate that the female condom is an atypical organisms: Fungi, parasites, viruses
r Transmission of mother to infant at birth or via effective mechanical barrier to viruses, including r CBC
breast milk HIV, and to semen. r BUN/creatinine
r Health care workers r Avoid high-risk sexual behavior
r Specific testing for STD if urethral discharge present
r Male circumcision
– Risk for HIV after percutaneous exposure to HIV
infected blood is 0.3%; after mucous membrane – Although male circumcision should not be Imaging
substituted for other HIV risk-reduction strategies, r With flank pain: Noncontrast CT
exposure 0.09%.
it has been shown to reduce the risk for HIV and – Indinavir stones may not show on CT: Consider
Genetics some STDs in heterosexual men. contrast study or retrograde pyelogram if renal
r 3 groups of HIV viruses: M, N, and O
– Despite these data, male circumcision has not impairment.
– Most infections are by class M been demonstrated to reduce the risk for HIV or r Scrotal US for palpable lesions
◦ 9 subtypes of M exist r Prostate abscess: CT scan
other STDs among men who have sex with men.
– 15–20% genetic variation between viruses r Use of precautions by health workers
r Treating STDs
186
HIV/AIDS, UROLOGIC CONSIDERATIONS
r Measure PVR urine
r Indinavir and other protease inhibitor (PI) stones
REFERENCES
r Urodynamics for voiding dysfunction or retention. – Stop indinavir 1. Breyer BN, Van den Eeden SK, Horberg MA, et al.
– Distinguishes bladder outlet obstruction from – Hydration HIV status is an independent risk factor for
acontractile bladder if in retention – Stent if necessary reporting lower urinary tract symptoms. J Urol.
◦ Bladder hypocontractility was seen in 35–45% ◦ Stones are soft and may pass after stenting. 2011;185(5):1710–1715.
r Surgical drainage of prostatic abscess 2. Lebovitch S, Mydlo JH. HIV-AIDS: Urologic
at time of urinary retention (2)[A]
r Stenting for ureteral obstruction from considerations. Urol Clin North Am. 2008;35(1):
– Common urodynamic findings: 59–68.
◦ Hypo- and hyperreflexia retroperitoneal NHL
3. von Wyl V, Yerly S, Böni J, et al. Emergence of
◦ Acontractile hypoactive bladder ADDITIONAL TREATMENT HIV-1 drug resistance in previously untreated
◦ Detrusor-sphincter dyssynergia Radiation Therapy patients initiating combination antiretroviral
Pathologic Findings Indicated in some cases of focal Kaposi sarcoma treatment: A comparison of different regimen
r Testicular tumors: Usually seminoma Additional Therapies types. Arch Intern Med. 2007;167:1782–1790.
r Lymphoma: B-cell non-Hodgkin lymphoma (NHL) r For health care worker exposure
r Penile lesions: Kaposi sarcoma from lymphatic r Post-Exposure Prophylaxis (PEP)
endothelial cells vs. squamous cell carcinoma – Occupational PEP (“oPEP”), healthcare worker ADDITIONAL READING
potentially exposed to material infected with HIV r Cohen MS, Hellmann N, Levy JA, et al. The spread,
r Other systemic disease that cause fatigue: Chronic – Non-occupational PEP (“nPEP”), someone is
treatment and prevention of HIV-1: Evolution of a
potentially exposed to HIV outside the workplace
fatigue syndrome, others global pandemic. J Clin Invest. 2008;118:
r Salmonella epididymitis pathognomonic for HIV (eg, from sexual assault, unprotected sex,
1244–1254.
needle-sharing injection drug use). r Izzedine H, Lescure FX, Bonnet F, et al. HIV
– begin within 72 hrs of exposure; 2–3 antiretorviral
medications for 28 days medication-based urolithiasis. Clin Kidney J.
TREATMENT r Pre-Exposure Prophylaxis (PrEP) 2014;7(2):121–126.
r Millett GA, Flores SA, Marks G, et al. Circumcision
GENERAL MEASURES – For people who are HIV-negative and at
r Refer to neurology, nephrology, infectious diseases substantial risk for HIV infection (relationship with status and risk of HIV and sexually transmitted
HIV infected partner, gay or bisexual man who has infections among men who have sex with men: A
when appropriate
r Patient education about risk factors, transmission had sex without a condom or been diagnosed meta-analysis. JAMA. 2008;300:1674–1684.
r www.aidsinfo.nih.gov (Accessed August 11, 2014)
with a sexually transmitted infection within the
MEDICATION r www.cdc.gov/hiv/resources/factsheets/index.htm
past six months, others
First Line – Along with other prevention methods like (Accessed August 11, 2014)
r Highly active antiretroviral therapy (HAART)
condoms, PrEP can offer good protection against See Also (Topic, Algorithm, Media)
– Combination therapy to combat the ability of HIV HIV if taken daily r HIV/AIDS, Urologic Considerations Image
to generate drug-resistant mutants (3)[A]. r Kaposi Sarcoma, Urologic Considerations
– 10 million people now on antiretroviral therapy
Therapies r Sexually Transmitted Infections (STIs) (Sexually
H
according to the WHO None Transmitted Diseases [STDs]), General
– HIV therapy should be started in patients with: r Tuberculosis, Genitourinary, General Considerations
◦ AIDS r Urolithiasis, Indinavir, and Other Protease Inhibitors
◦ New WHO guidelines recommend starting ONGOING CARE
therapy when CD4 count <500/mm3 (previous PROGNOSIS
guidelines were <350/mm3 ) Much improved prognosis leading to longer life CODES
◦ Pregnant women expectancies, primarily due to newer drug
◦ Patients with HIV nephropathy combination therapies
◦ Coinfection with HBV regardless of CD4 count. ICD9
r 042 Human immunodeficiency virus [HIV] disease
◦ New WHO guidelines also call for some people COMPLICATIONS
r Antiretroviral therapy r 599.0 Urinary tract infection, site not specified
to begin treatment as soon as they test positive r 592.9 Urinary calculus, unspecified
for HIV, regardless of CD4 count – Risk of nephrotoxicity, crystal precipitation leading
to stones, hypocalcemia
Second Line – Erectile dysfunction and decreased libido (caused ICD10
r General urologic conditions such as UTI, voiding r B20 Human immunodeficiency virus [HIV] disease
by increased estradiol) may be associated with
symptoms, calcium stones treat as per general HAART therapy r N20.9 Urinary calculus, unspecified
practice. r Drugs used for the treatment of HIV-infected r N39.0 Urinary tract infection, site not specified
– Salmonella epididymitis patients have become the most frequent cause of
◦ 2–4 wk of doxycycline 100 mg PO BID plus
drug-containing urinary calculi.
Cipro 500 mg PO BID – Among these agents, PIs are well known to induce CLINICAL/SURGICAL
◦ If difficult to eradicate may need lifelong
suppression.
kidney stones, (indinavir, atazanavir, darunavir). PEARLS
r Kaposi sarcoma FOLLOW-UP r Urologic considerations in patients with HIV/AIDS
– If focal, local radiation, cryosurgery, or retinoids. Patient Monitoring include bacterial infections, urolithiasis, malignancy,
– If disseminated use chemotherapy (doxorubicin) or r CD4 counts renal impairment, and voiding dysfunction.
immunotherapy with interferons r Serum creatinine r Urolithiasis is associated with patients taking
Patient Resources indinavir and other protease inhibitors (PI’s).
r CDC HIV/AIDS Fact Sheets. http://www.cdc.gov/ r HIV associated nephropathy (HIVAN) increases the
hiv/library/factsheets/index.html patient’s risk of dialysis.
r Salmonella epididymitis is pathognomonic for HIV.
r Highly active antiretroviral therapy (HAART)
increases estradiol and can lead to symptoms of
erectile dysfunction and decreased libido.
187
HOT FLUSHES/VASOMOTOR INSTABILITY IN MALES

Tara K. Ortiz, MD
ASSOCIATED CONDITIONS DIFFERENTIAL DIAGNOSIS

BASICS r Osteopenia, osteoporosis r Febrile states or hyperthermia
r Erectile dysfunction/loss of libido r Emotional blushing
DESCRIPTION r Metabolic syndrome (insulin resistance, unfavorable r Systemic illness:
r Hot flushes are typically described as a feeling of
lipid profile, increased fat mass) – Carcinoid syndrome
intense heat with associated flushing, sweating, r Gynecomastia – Pheochromocytoma
rapid heart rate, and anxiety r Normocytic, normochromic anemia – Medullary thyroid tumors
r Sometimes called “hot flashes”
r Fatigue – Pancreatic islet cell tumors
r Common side effect of androgen ablation therapy in – Renal cell carcinoma
men with metastatic or locally advanced prostate GENERAL PREVENTION r Other illness:
cancer r Identification of triggers
– Rosacea
r Flushing can be associated with wide ranges of – Avoid hot beverages, spicy foods, alcohol, abrupt r Neurologic disorders
other conditions and medications change in ambient temperature r Medications:
r This section primarily discusses this condition in r Keep environment cool
– Phosphodiesterase 5 inhibitors (sildenafil,
males vardenafil, tadalafil, avanafil),
EPIDEMIOLOGY DIAGNOSIS – Any vasodilatory agent (nitroglycerine, etc.)
– Nicotinic acid
Incidence
HISTORY – Calcium channel blockers most commonly
Occurs in 50–80% of men on androgen deprivation r Abrupt onset of warmth, frequently followed by nifedipine, nisoldipine, amlodipine
therapy (1)
profuse sweating requiring change of clothes – Opiates
Prevalence r More likely to occur at night – Tamoxifen
N/A r Sensation typically affects the face and trunk – Antibiotics (vancomycin, amphotericin B)
RISK FACTORS r Attacks normally last 1–5 min, but can persist for up – IV contrast media
r Age, race and ethnicity, educational level, smoking, r Dietary
to 20 min
cardiovascular risk including body mass index, and r Can occur occasionally or multiple times daily: – Ethanol ingestion
genetics – Majority of patients have daily episodes – Monosodium glutamate or other food additives
r Prostate cancer r Frequently experienced at night
r Onset is typically seen within the 1st yr after
Genetics TREATMENT
N/A androgen ablation:
– 1/3 of men will develop symptoms within the 1st GENERAL MEASURES
PATHOPHYSIOLOGY mo r For flushing related to androgen deprivation therapy
r Exact mechanism unknown; majority of theories
– Reassurance if symptoms mild
based on studies in postmenopausal women PHYSICAL EXAM – Attempt to identify and avoid lifestyle triggers
r Hot flushes in prostate cancer patients result from r During acute episode, facial flushing common
r Perspiring frequently present – Keep environment cool
decreased feedback of testosterone to the – Many men will experience resolution after several
hypothalamus. r Mild tachycardia secondary to vasodilation or anxiety
years without therapy
r Central control of thermoregulation is r Slight increase in oral and forehead temperature
preoptic/anterior area in the brain r Usually normal exam in between hot flush episodes MEDICATION
r Increases in internal and/or skin temperature sensed r May have gynecomastia, increased fat mass First Line
r For androgen deprivation therapy related hot flushes
in the anterior pituitary results in cutaneous secondary to androgen deprivation
vasodilatation (flushing) and sweating. most are hormonal agents
r Thermoregulatory zone is disrupted: DIAGNOSTIC TESTS & INTERPRETATION r Megestrol acetate (Megace) 20 mg/d:
– Reduced thermoneutral zone between an upper Lab – Synthetic derivative of progesterone
r No routine lab evaluation indicated
threshold for sweating and a lower threshold for – 1 study demonstrated complete resolution of
r No pattern of characteristic changes in testosterone,
shivering symptoms in 90% of patients, >50%
r Alterations in glucose transport across blood–brain follicle-stimulating hormone (FSH), leuteinizing improvement in 25% (2)[B]
barrier theorized to be a trigger: hormone (LH), or prolactin
– Side effects include chills, weight gain, nausea,
– Hot flushes are counterregulatory attempts to Imaging carpal tunnel–like syndrome, disease progression
increase cerebral blood flow and cerebral glucose N/A r Medroxyprogesterone acetate (Depo Provera)
levels. 400 mg/d IM:
r Decreased plasma sex hormones results in loss of Diagnostic Procedures/Surgery
N/A – 91% with symptomatic improvement (1)[B]
negative feedback, thus increasing hypothalamic
norepinephrine (NE) levels Pathologic Findings – 46% have complete response as defined as total
r NE decreases thermoneutral zone N/A elimination of hot flushes.
– Thermoregulatory center in hypothalamus is – Side effects could include weight gain, congestive
anatomically close to the GnRH-secreting neurons heart failure exacerbation, loss of bone mineral
– These neurons are stimulated by NE to secrete density, disease progression
GnRH r Transdermal estrogen patch 0.05 or 0.1 mg/d
– Increased GnRH stimulation, by being in close (1,3)[B]:
proximity to the thermoregulatory center, might – 3 studies with over 70% of men reporting
activate heat-losing mechanisms (flushing, complete resolution
sweating). – Side effects include breast swelling, nipple
tenderness
188
HOT FLUSHES/VASOMOTOR INSTABILITY IN MALES
r Diethylstilbestrol (DES): 0.30–1 mg/d: ADDITIONAL TREATMENT 3. Langenstroer P, Kramer B, Cutting B, et al.
– 70–90% of men achieve excellent results (1)[B] Radiation Therapy Parenteral medroxyprogesterone for the
N/A management of luteinizing hormone releasing
– Side effects include painful gynecomastia. hormone induced hot flashes in men with advanced
– At low doses, thromboembolic events are not a Additional Therapies prostate cancer. J Urol. 2005;174:642–645.
significant problem. Behavioral therapy: Slow, deep breathing may reduce
4. Naoe M, Ogawa Y, Shichijo T, et al. Pilot evaluation
– Generic drug, inexpensive though difficult to frequency of hot flushes
of selective serotonin uptake inhibitor
obtain in US. Complementary & Alternative antidepressants in hot flash patients under
r Cyproterone acetate (Androcur) 100 mg/d
Therapies androgen-deprivation therapy for prostate cancer.
– Not approved for use in US r Acupuncture: Prostate Cancer Prostatic Dis. 2006;9(3):275–278.
– Steroidal antiandrogen, antigonadotropin with – 10–12 wk (twice weekly × 2 wk then once 5. Moraska AR, Atherton PJ, Szydlo DW, et al.
progestin-like activity weekly × 8–10 wk) Gabapentin for the management of hot flashes in
– May interfere with ADT regimen prostate cancer survivors: A longitudinal
– 43–78% reduction in frequency of flushes,
– 1 study demonstrated resolution of symptoms in average 9-mo duration of effect (1)[B] continuation study—NCCTG Trial N00CB.
84% of patients, >50% improvement in 37% r Vitamin E: J Support Oncol. 2010;8:128–132.
(2)[B]
– 30% reduction vs. 22% of women receiving
– Side effects include fatigue, increased risk of placebo in 1 study (not studied in men)
thrombosis, anemia, potential hepatotoxicity, ADDITIONAL READING
gynecomastia – May increase the risk of prostate cancer; unclear
effect on existing cancer (1)[B] r Baum NH, Torti DC. Managing hot flashes in men
Second Line (Nonhormonal Therapy) r Soy products: being treated for prostate cancer. Geriatrics.
r Venlafaxine (Effexor) 12.5 mg/d PO:
– Contain phytoestrogens which might decrease 2007;62:18–21.
– Antidepressant of the serotonin-norepinephrine r Engstrom CA, Kasper CE. Physiology and
severity of hot flushes (1)[C]
reuptake inhibitor (SNRI) type endocrinology of hot flashes in prostate cancer. Am
– Also have shown benefit with regard to cardiac
– Median weekly hot flush scores decreased 54% and bone health J Men Health. 2007;1:8–17.
from baseline after 1 mo (2)[B] r Black cohosh: r Sharifi N, Gulley JL, Dahut WL, et al. Androgen
– Side effects include lack of sexual desire, delayed – Has been used in some postmenopausal women deprivation therapy for prostate cancer. JAMA.
orgasm, and increase in suicidal ideation. for treatment of hot flushes 2005;294:238–244.
r Paroxetine (Paxil-CR) 12.5–37.5 mg/d: – Mechanism is unknown See Also (Topic, Algorithm, Media)
– Antidepressant of the selective serotonin reuptake – In 1 trial, no difference found with men taking r Andropause (Late-Onset Hypogonadism)
inhibitor (SSRI) class placebo (1)[C] r Menopause, Urologic Considerations
– In 1 study, daily hot flushes decreased from r Testosterone, Decreased (Hypogonadism)
6.2–2.5. (4)[B] ONGOING CARE
– Side effects include sexual dysfunction,
somnolence
r Ergotamine/belladonna/phenobarbital (EBP): 1
PROGNOSIS
r Most men have symptom improvement with medical
CODES H
or complementary therapy. ICD9
tablet PO BID: r At 8 yr of treatment with ADT over 40% of men still
– Ergot alkaloid used primarily to treat migraine r 780.2 Syncope and collapse
headache had flashes. r 780.8 Generalized hyperhidrosis
r In 1 study, 72% of patients noted that hot flashes r 782.62 Flushing
– Use with caution with patients on monoamine
oxidase inhibitors (MAOIs), central nervous system interfered with sleep and 59% reported they
(CNS) depressants, anticholinergic agents interfered with the quality of life. ICD10
r R23.2 Flushing
– Generally not recommended for the treatment of COMPLICATIONS
hot flushes in men r R55 Syncope and collapse
Some men have side effects from medications taken to
r R61 Generalized hyperhidrosis
r Gabapentin (Neurontin) 900 mg/d (300 mg TID, alleviate hot flushes (bloating, weight gain,
titrated) (5)[B] hypertension)
– Anticonvulsant/treatment of neuropathic pain FOLLOW-UP CLINICAL/SURGICAL
– Modest 46% reduction in hot flush symptom Patient Monitoring
score at target dose of 900 mg r Ask patients on androgen deprivation at each PEARLS
– Side effects include nausea, vomiting, dizziness, follow-up clinical evaluation about the presence and r Symptoms are usually reversible with cessation of
and somnolence severity of hot flushes: ADT usually within 3–4 mo of stopping treatment.
r Clonidine (Catapres) 0.1–1 mg/d (PO or patch – Inquire about side effects from therapy r Most effective treatment is hormonal therapy with
formulations): – Intermittent cessation of treatment can be used if estrogen or progesterone derivatives.
– Centrally acting α-adrenergic agonist used for side effects become bothersome. r There are limited data to support alternative/
treatment of hypertension (HTN) ◦ May have positive effect on quality of life, but complementary therapies.
– 1/3 of men will report a partial response may decrease survival
although similar to placebo (1)[B]. Patient Resources
– Side effects include hypotension, dry mouth, skin N/A
irritation from patches.
REFERENCES
N/A 1. Jones JM, Kohli M, Loprinzi CL, et al. Androgen
deprivation therapy-associated vasomotor
symptoms. Asian J Androl. 2012;14(2):193–197.
2. Irani J, Salomon L, Oba R, et al. Efficacy of
venlafaxine, medroxyprogesterone acetate, and
cyproterone acetate for the treatment of vasomotor
hot flushes in men taking gonadotropin-releasing
hormone analogues for prostate cancer: A
double-blind, randomised trial. Lancet Oncol.
2010;11:147–154.
189
HYDROCELE, ADULT & PEDIATRIC

r Acquired: Can be primary (idiopathic) or secondary PHYSICAL EXAM

BASICS to disease of the testis. Secondary hydroceles may r Transilluminate scrotum:
present acutely or chronically. – If transilluminates, favors simple hydrocele, but is
DESCRIPTION r The hydrocele of the canal of Nuck is comparable in not diagnostic
r A hydrocele is a collection of serous fluid in some r Palpation of testes bilaterally:
females. The cyst is in relationship with the round
part of the processus vaginalis, usually in the tunica. ligament and located in the inguinal canal. – Especially in children, need to rule out
Can be congenital or acquired r Hydrocele fluid characteristics: undescended testicle. Adults, attempt to feel for
r Translucent swelling in the scrotum or inguinal canal testicular mass
– Amber colored; specific gravity of 1.022–1.024
or both – Components: Water, inorganic salts, 6% albumin, r Spermatoceles are always located superior to the
r Aside from congenital hydrocele, it is possible to get and fibrinogen testis and are palpated as distinct from the testis,
examining fingers above the swelling realted to a – Nonclotting, unless a drop of blood added which differentiates them from hydroceles.
hydocoele. – Chronic hydrocele: Cholesterol-rich r Positive pinch test in a secondary hydrocele (ability
r Demonstrated fluctuation in size in congenital – Occasionally, tyrosine crystals are present to pinch the tunica)
hydrocele (also called communicating hydrocele) r Examine the groin for inguinal hernia.
r Ehlers–Danlos syndrome r Lymphedema of external genitalia or lower
EPIDEMIOLOGY
Incidence r Exstrophy of the bladder extremities:
r More common in childhood r Indirect inguinal hernia – Tissue edema can be mistaken for the hydrocele.
r 1% of adult males; prevalence: 1,000 in 100,000 r Hydrocephalus (with VP shunt) r On abdominal exam, concomitant presence of a
r No racial predilection r Peritoneal dialysis mass may indicate an abdominoscrotal hydrocele
r Testicular tumors or epididymo-orchitis in secondary DIAGNOSTIC TESTS & INTERPRETATION
Prevalence
N/A hydrocele Lab
r Undescended testicle with patent procesus vaginalis r Urinalysis and urine culture if epididymo-orchitis
RISK FACTORS (PPV) suspected
r The hydrocele is produced by: r Tumor markers (bhCG, AFP) if tumor suspected
r Varicocele surgery
– Connection with the peritoneal cavity (PPV); also
known as congenital hydrocele GENERAL PREVENTION Imaging
r Transscrotal US in adults with hydrocele to detect
– Defective absorption of fluid by tunica vaginalis; None other than repair of indirect hernia defect in
eg, primary hydrocele (common in adults) infants/children underlying testicular abnormality (ie, tumor) and
– Excessive production of fluid within the sac; (eg, confirm the nature of the mass as a hydrocele.
secondary hydrocele) due to epididymitis, orchitis, r Nuclear scan or Doppler US exam in cases of torsion
testicular torsion causing a “reactive” hydrocele
DIAGNOSIS
– Trauma with bleeding (technically a hematocele) HISTORY N/A
– Lymphatic obstruction; eg, filariasis, scrotal r Symptoms of epididymitis, UTI, or acute pain:
surgery (varicocele), renal transplantation, pelvic Pathologic Findings
– Secondary hydrocele with infection, torsion, and Fibrous wall lined by mesothelial single layer cuboidal
radiation, malignancy trauma usually painful
– Migration of ventriculoperitoneal (VP) shunt r Usually not painful or flattened mesothelial cells; may contain benign
r Prematurity, low birth weight are risk factors mesothelial proliferations
r Sensation of heaviness or discomfort in the scrotum
Genetics r Change in size of the swelling (ie, size varies DIFFERENTIAL DIAGNOSIS
r Cord lipoma
N/A throughout day): r Epididymo-orchitis
PATHOPHYSIOLOGY – Suggests congenital communicating hydrocele
r Birth history: r Hydrocele of the spermatic cord
r Congenital: The PV does not close after testicular
r Inguinal/femoral hernia
descent. – Hydrocele more common in premature and
low–birth-weight infants r Lymphedema of the external genitalia
– 80–90% of newborns have patent processus
r Medical or surgical history: – Retroperitoneal process with obstruction of
vaginalis with most closing by age 2
r 4 anatomic variants: – Varicocelectomy, renal transplant, VP shunt, lymphatics (ie, malignancy, lymphatic filiariasis)
trauma to the genitalia can be causes – Nephrotic syndrome
– Vaginal (PV around the testis)
– Recent inguinal hernia repair (1) – Anasarca (protein-loosing enteropathy, cirrhosis)
– Infantile (PV around testis and cord) r Spermatocele
– Congenital communicating (PV communicates r Testicular or paratesticular tumors
with the peritoneal cavity)
r Torsion (testis or appendix testis)
– Hydrocele of the cord (PV patent with obliteration
above and below) r Traumatic injury to the testis (hematocele)
r Varicocele (large)
190
HYDROCELE, ADULT & PEDIATRIC

N/A 1. Gulino G, Antonucci M, Palermo G, et al. Urological
GENERAL MEASURES complications following inguinal hernioplasty. Arch
r Adults: Additional Therapies Ital Urol Androl. 2012;84(3):105–110.
r Aspiration of the hydrocele, with or without the
– No treatment is necessary unless the hydrocele 2. Francis JJ, Levine LA. Aspiration and sclerotherapy:
injection of sclerosing agents is not usually
causes discomfort or cosmetic concerns or there is A nonsurgical treatment option for hydroceles.
recommended
a significant underlying cause present, such as a r Nonseptated hydrocele aspiration and sclerotherapy J Urol. 2013;189(5):1725–1729.
tumor.
– Communicating hydroceles in older patients may with doxycycline has been reported to have an 84%
success rate with a single treatment (2)
have increased risk of incarceration
r Aspiration may have a role in postoperative ADDITIONAL READING
r Children:
hydroceles such as after inguinal hernia repair. r Lord PH. A bloodless operation for the radical cure of
– Most will resolve in 1st yr of life.
– For newborns and children <1 yr supportive care Complementary & Alternative idiopathic hydrocele. Br J Surg. 1964;51:914–916.
is indicated r Skoog SJ, Conlin MJ. Pediatric hernias and
Therapies
– Persistence beyond age 1 suggests the presence Scrotal support may provide relief of discomfort hydroceles: The urologist’s perspective. Urol Clin
of a patent indirect hernia sac that should be North Am. 1995;22:119–130.
repaired. r Szabo R, Kessler R. Hydrocele following internal
ONGOING CARE spermatic vein ligation: A retrospective study and
MEDICATION
review of the literature. J Urol. 1984;132:924–925.
First Line PROGNOSIS
N/A Many hydroceles do not enlarge and can be observed See Also (Topic, Algorithm, Media)
if confirmed that there is no underlying pathology r Canal of Nuck Hydrocele and Cyst (Female
Second Line Hydrocele)
(based on ultrasound confirmation).
N/A r Groin/Inguinal Mass, Male and Female
COMPLICATIONS r HIV/AIDS, Urologic Considerations Image
SURGERY/OTHER PROCEDURES r Rupture: Usually traumatic
r Children: r Hydrocele of the Spermatic Cord
r Hernia of the hydrocele sac: Tension causes
– Inguinal incision between internal and external r Scrotum and Testicle, Mass
rings. herniation through the Dartos muscle.
r Calcification of the wall: May occur with r Spermatocele
– High ligation of the processus vaginalis and
excision of the sac. longstanding cases
r Hematocele: Following trauma or aspiration, or
– In hydrocele of the cord, the sac can be completely
removed. It is imperative that the hydrocele sac be presents chronically simulating a neoplasm CODES
opened when the anatomy is confusing or the sac r Infection
is very thickened. Failure to do so may result in r Postoperative: ICD9
r 603.8 Other specified types of hydrocele
disastrous consequences if bowel, bladder, or – Testicular atrophy or infarction after repair due to
ovary is contained in the sac and not recognized. damage to vascular supply to the testicle r 603.9 Hydrocele, unspecified H
r Adults: – Infection r 778.6 Congenital hydrocele
– Scrotal approach with drainage of the hydrocele – Recurrence
and resection of the tunica vaginalis; scrotal drain ICD10
FOLLOW-UP r N43.2 Other hydrocele
for 24–48 hr
◦ Bottle procedure (thin hydrocele sac): Also Patient Monitoring r N43.3 Hydrocele, unspecified
r Periodic follow-up (baseline US) suggested if r P83.5 Congenital hydrocele
called Andrews procedure; incise anteriorly,
wrap sac back around testicle managed by observation; return for any acute
◦ Jaboulay–Winkelmann procedure (thick changes in symptoms
r Parents of a newborn with a hydrocele should be CLINICAL/SURGICAL
hydrocele sac): Hydrocele sac resected and edge
wrapped posteriorly around cord structures instructed in the natural history of the condition in PEARLS
(resected edges can also simply be oversewn) children.
r Following surgical repair, edema may take several r Tenderness, fever, or other symptoms such as
◦ Lord procedure (thin hydrocele sac): Radial
sutures used to gather sac posterior to testis weeks to resolve. nausea, vomiting, abdominal pain associated with
an acute hydrocele requires immediate evaluation to
Patient Resources
rule out other scrotal pathology.
N/A r The inability to transilluminate a hydrocele could be
due to a thick-walled or septated hydrocele, another
cause of an enlarged scrotum such as tumor or
hematocele or the presence of bowel in a large
hernia defect.
191
HYDROCOLPOS AND HYDROMETROCOLPOS, PEDIATRIC

ASSOCIATED CONDITIONS r IVP:

BASICS r Vaginal atresia – May see hydroureteronephrosis and a distended
r Cloacal anomalies bladder
DESCRIPTION r Urogenital sinus r VCUG:
r Hydrocolpos and hydrometrocolpos are congenital r Other malformations, such as imperforate anus, bifid – May see an anteriorly displaced bladder
anomalies of the female reproductive tract due to an clitoris, polycystic kidney. r MRI/MRU:
imperforate hymen or less commonly due to a r Pediatric considerations: – Maybe useful for further delineation of pelvic
transverse vaginal septum. anatomy when US is equivocal
– The diagnosis should be considered in the
– Hydrocolpos: Gross distension of the vagina with – MR urography provides dynamic images that may
pubertal female with amenorrhea.
fluid identify underlying etiologies such as ureteral
– Hydrometrocolpos: Gross distension of vagina and GENERAL PREVENTION ectopia
uterus with fluid. May also be associated with Early diagnosis may prevent urinary retention,
vaginal or cervical atresia, stenosis, urogenital hydronephrosis, and upper urinary tract complications. Diagnostic Procedures/Surgery
sinus, or cloacal anomalies N/A
r Hematocolpos: bloody fluid in vagina Pathologic Findings
r Hematometrocolpos: bloody fluid in vagina and DIAGNOSIS N/A
uterus HISTORY DIFFERENTIAL DIAGNOSIS (2)
r Can be an infrequent cause of an abdominal mass in r Sonolucent mass on prenatal ultrasound (US) r Dermoid cyst
a newborn female r Stranguria due to bladder outlet obstruction r Hematometrocolpos:
EPIDEMIOLOGY r Intestinal obstruction with larger mass – Accumulation of menstrual blood products in
r Amenorrhea in pubertal females if the problem was vaginal and uterus
Incidence
not diagnosed before menarche. In these rare cases, r Mucocolpos
0.1–3.8% of live female births
chronic cyclic lower abdominal pain may be present. r Ovarian cyst
Prevalence r Periurethral cyst:
N/A PHYSICAL EXAM
r Imperforate hymen with bulging cystic vaginal – Eccentric smooth mass displacing urethral meatus
RISK FACTORS r Prolapsed ureterocele:
r Imperforate hymen introitus. The hue is typically bluish if there is
trapped blood. – May see necrotic tissue, asymmetric urethral
r High/low transverse vaginal septum
r Palpable suprapubic mass due to distended bladder meatus
r Urogenital sinus/cloacal abnormality r Prolapsed urethra:
if associated with outlet obstruction
Genetics (1) r Lower extremity lymphedema due to decreased – Donut-shaped urethral meatus in the center of a
r McKusick–Kaufman syndrome venous return normal vaginal introitus
r Examine for stigmata of Mckusick–Kaufman r Rhabdomyosarcoma:
– Autosomal recessive multiple malformation
syndrome syndrome (see above) – Cluster of grapelike masses protruding from
– Characterized by vaginal atresia with vaginal introitus
hydrometrocolpos, polydactyly, congenital heart DIAGNOSTIC TESTS & INTERPRETATION
defects, nonimmune hydrops fetalis Lab
r Bardet–Biedl syndrome Electrolytes and creatinine if significant bilateral upper
r Langer–Giedion syndrome urinary tract dilation
r Herlyn-Werner-Wunderlich (HWW) syndrome Imaging
r Abdominal US:
PATHOPHYSIOLOGY – Large sonolucent cystic mass displacing bladder
r Hydrocolpos: Congenital obstruction of the female
anteriorly and rectum posteriorly
genital tract leading to accumulation of vaginal – May see layering of debris
secretions and distension of the vagina – Hydronephrosis or ureteral ectasia may be present
r Hydrometrocolpos: Same as hydrocolpos but the
– Prenatal sonogram can detect Hydrometrocolpos
pressure now is transmitted past the cervix into the as an antenatal diagnosis but usually cannot
uterus causing distention of both vagina and uterus. identify the etiology
– The most frequent cause of hydrometrocolpos is
the presence of imperforate hymen due to failure
of partial resorption of this membrane during the
embryonic development
– Hymen fails to rupture during the 8th wk of
gestation
192
HYDROCOLPOS AND HYDROMETROCOLPOS, PEDIATRIC
ADDITIONAL READING
Parlakgumus A, Yalcinkaya C, Kilicdag E. Prenatal
GENERAL MEASURES (3) PROGNOSIS diagnosis of McKusick-Kaufman/Bardet-Biedl
r Incision of the hymen if due to imperforate hymen. If Excellent, especially with early diagnosis and syndrome. BMJ Case Rep. 2011;2011.
an imperforate hymen is present and no mass or treatment
hydronephrosis is present, surgical correction is COMPLICATIONS r Hydrocolpos and hydrometrocolpos Image
sometimes delayed until tissues become more r Renal compromise or acute kidney injury with severe r Hydronephrosis/Hydroureteronephrosis (Dilated
estrogenized. However, the correction of the hydronephrosis Ureter/Renal Pelvis), Pediatric
imperforate hymen must take place before there is r Abdominal ascites r Hydronephrosis/Hydroureteronephrosis (Dilated
development of hydrocolpos. r Urinary retention and voiding difficulty
r Address vaginal or cervical issues as the anatomic Ureter/Renal Pelvis), Prenatal
r Reports of increasing rates of infertility based upon
pathology presents
level of obstruction
MEDICATION r Respiratory compromise in neonates due to massive CODES
First Line abdominal distension
N/A r At menarche, retrograde flow may predispose ICD9
patient to endometriosis r 623.8 Other specified noninflammatory disorders of
Second Line
N/A vagina
FOLLOW-UP r 752.42 Imperforate hymen
SURGERY/OTHER PROCEDURES Patient Monitoring r 752.46 Transverse vaginal septum
r Simple incision of the imperforated hymen. A Usually none necessary. Follow for resolution of
cruciate incision with resection of excess tissue tags hydronephrosis if present. ICD10
as necessary r N89.8 Other specified noninflammatory disorders of
Patient Resources
r Cloacal anomalies require a coordinated surgical vagina
N/A
team and planned intervention. r Q52.3 Imperforate hymen
r Vaginal septum if present needs to be incised either r Q52.11 Transverse vaginal septum
endoscopically or through open surgery REFERENCES
ADDITIONAL TREATMENT 1. Ameh EA, Mshelbwala PM, Ameh N. Congenital
vaginal obstruction in neonates and infants:
CLINICAL/SURGICAL
Radiation Therapy
N/A Recognition and management. J Pediatr Adolesc PEARLS
Gynecol. 2011;24(2):74–78.
Additional Therapies The diagnosis should be considered in the pubertal
2. Nazir Z, Rizvi RM, Qureshi RN, et al. Congenital female with amenorrhea.
N/A
vaginal obstructions: Varied presentation and
Complementary & Alternative outcome. Pediatr Surg Int. 2006;22:749–753.
Therapies 3. Puhl AG, Steiner E, Krämer WW, et al. Fetal H
N/A urogenital sinus with consecutive
hydrometrocolpos because of labial fusion: Prenatal
diagnostic difficulties and postpartal therapeutic
management. Fetal Diagn Ther. 2008;23:287–292.
193
HYDRONEPHROSIS/HYDROURETERONEPHROSIS (DILATED
URETER/RENAL PELVIS), ADULT
Kelly A. Healy, MD
r Ureter: r Site of obstruction, upper vs. lower urinary tract may

BASICS – Neoplasms: Benign papilloma, fibroepithelial relate to presentation
polyp, ureteritis cystica; malignant urothelial – Upper urinary tract—flank pain and costovertebral
DESCRIPTION carcinoma angle tenderness with acute obstruction
r Hydronephrosis includes dilation of the renal pelvis – Ureteral calculi or stricture – Lower urinary tract maybe associated with
and calyces while hydroureteronephrosis is dilation – Ureterocele or congenital megaureter obstructive voiding symptoms
of the renal pelvis, calyces, and ureter – Infection (tuberculosis, schistosomiasis)
r Both can result from obstructive and nonobstructive PHYSICAL EXAM
– Retroperitoneal lymphadenopathy (lymphoma, r General condition—pain or localized symptoms
causes other malignancy) r Hypertension can be related to obstruction
r Intrinsic and extrinsic obstructive process can affect – Inflammatory (retroperitoneal fibrosis and arterial r Abdominal, flank, or pelvic mass
the entire urinary tract aneurysms)
r Obstructive uropathy indicates impedance of urinary r Flank tenderness can occur with acute obstruction
– Gynecologic: Ovarian vein syndrome,
flow anywhere along the urinary tract, upper or endometriosis, GYN malignancy, pregnancy and with calculi or infection (pyelonephritis,
lower and damage to the renal parenchyma due to – Pelvic lipomatosis pyelonephrosis, retroperitoneal abscess)
– Retrocaval ureter r Vaginal exam
obstruction at any site
r Bladder/urethra: – Ureteral prolapse
EPIDEMIOLOGY – Malignant neoplasms: eg, urothelial carcinoma – Ureterocele through urethra
Incidence locally advanced carcinoma of the prostate r Digital rectal exam
Asymptomatic, unilateral hydronephrosis occurs in – Bladder neck contracture – Enlarged prostate, nodularity suggestive of
∼3% of population – Prostatic obstruction prostate cancer
Prevalence – Detrusor dysfunction
r 3.1% prevalence in historic autopsy series of 59,000 DIAGNOSTIC TESTS & INTERPRETATION
– Increasing intravesical storage pressure
– Urethral stricture; meatal stenosis Lab
patients r Urinalysis for hematuria, pyuria, crystalluria
– Age 20–60 more common in women, secondary – Phimosis r Urine culture
to pregnancy/gynecologic conditions Genetics r Renal function studies:
– Age >60 yr obstruction more common in men Nonobstructive hydronephrosis occurs with several
(6.2% vs. 2.9%) attributed to prostatic diseases – BUN & creatinine
congenital syndromes, usually diagnosed in infancy r CBC
r A similar 2.5% prevalence of asymptomatic (see “Hydronephrosis/Hydroureteronephrosis,
unilateral hydronephrosis in radiologic series among Pediatric”) – Anemia—associated with chronic renal
potential renal donors insufficiency
– More women than men (86% vs. 14%) PATHOPHYSIOLOGY – Elevated white blood cell count with infection
r Effective hydroureteronephrosis on renal function r Serum chemistries, special attention to potassium
– No association with potential donor age
depends on whether it is totally or partially r Serum prostatic-specific antigen (PSA)
RISK FACTORS obstructive and unilateral or bilateral r Urine cytology for urothelial carcinoma
r Urolithiasis is most common cause of upper urinary r Effects of obstruction of the kidney are time
tract obstruction, prevalence between 10–15% by dependent. Within several hours, changes are Imaging (2)
r Several modalities are available. They differ in their
age 70 yr evident but (1)
r Ureteropelvic junction (UPJ) obstruction can occur – 1–2 wk—glomerular destruction, tubular atrophy, degree of anatomic and functional information and
from anatomic-crossing vessel, high insertion, or and interstitial fibrosis occur may distinguish the presence and extent of
secondary conditions (impacted stone) – By 6–8 wk irreversible damage occurs obstruction.
r Lower urinary tract disorders can result in r Renal ultrasound: Inexpensive, widely available, no
ASSOCIATED CONDITIONS ionizing radiation, and no contrast (3)
hydroureteronephrosis, often bilateral
r Benign prostatic enlargement is the most common Numerous causal conditions can be associated. See – Excellent to define hydronephrosis
“Risk Factors” above. – Should include imaging through the bladder to
affecting 70% of men by age 70
r Hydronephrosis can develop with obstructive lesions GENERAL PREVENTION assess for distal hydroureter, ureteral jets, bladder
Hydronephrosis may be disease related and prevention wall thickening, and postvoid residual
at essentially any level.
r Kidney: then must be individualized – Renal cortex can be evaluated
r Color Doppler renal ultrasound (4):
– Benign lesions including peripelvic cysts
– Help distinguish obstructive vs. nonobstructive
– Malignant neoplasms with renal cell carcinoma DIAGNOSIS hydronephrosis
and urothelial carcinoma
HISTORY – Resistive index (RI) = (PSV – EDV)/PSV (peak
– Renal pelvic calculi
r Signs and symptoms vary dependent on the etiology systolic velocity end diastolic velocity)/peak
– UPJ obstruction
and chronicity of the condition systolic velocity
– Infection tuberculosis ◦ RI ≥0.7 suggested of obstruction (92%)
– Renal artery aneurysm r Acute obstruction can cause abdominal flank and/or
sensitivity and (88%) specificity
– Hilar lymphadenopathy back pain; may be associated with anorexia, ◦ RI is time dependent and decreases >48 hr
nausea, vomiting
r Gradual ureteral obstruction more typically presents after obstruction. Thus, less useful for chronic vs.
acute obstruction
with vague complaints or may be asymptomatic r Noncontrast CT scan:
r Insidious obstruction of solitary kidney or bilateral
– Imaging of choice for acute renal colic
can present with symptomatic obstructive uropathy – Visualizes entire urinary tract and adjacent
or evidence of renal compromise structures; best for urolithiasis and may not detect
r Complete urinary history is essential
soft tissue masses or filling defects
– Secondary signs of acute obstruction include
perinephric stranding and nephromegaly
– Normal ureter on unenhanced CT is considered to
be 3 mm in adults
194
HYDRONEPHROSIS/HYDROURETERONEPHROSIS (DILATED URETER/RENAL PELVIS), ADULT
r CT urogram
REFERENCES
– Good for incidental hydronephrosis TREATMENT
– Noncontrast phase for ureterolithiasis 1. Arena S, Magno C, Montalto AS, et al. Long-term
– Contrast phase-delayed nephrogram suggested GENERAL MEASURES follow-up of neonatally diagnosed primary
obstruction r Management is highly dependent on underlying megaureter: Rate and predictors of spontaneous
– Defined parenchymal masses, evaluate for condition and the timing (acute vs. chronic) resolution. Scand J Urol Nephrol. 2012;46:
crossing vessels with UPJ obstruction r Urgent decompression is needed with: 201–207.
– Delayed (excretory) phase may look like site of – Severe pain 2. Patatas K, Panditaratne N, Wah TM, et al.
obstruction and rule out filling defect depending – Active urinary tract infection and acute kidney Emergency department imaging protocol for
on degree of renal impairment insufficiency suspected acute renal colic: Re-evaluating our
r Excretory urogram: – Retrograde ureteral stent or percutaneous service. Br J Radiol. 2012;85:1118–1122.
– Generally replaced by CT urogram nephrostomy can provide equally effective 3. Jandaghi AB, Falahatkar S, Alizadeh A, et al.
r Magnetic resonance imaging (MRI) drainage Assessment of ureterovesical jet dynamics in
– Lack of ionizing radiation advantageous for r Hydronephrosis lower urinary tract etiology is obstructed ureter by urinary stone with color
children, pregnant patients, and those with renal typically bilateral and patients may be asymptomatic Doppler and duplex Doppler examinations.
insufficiency or contrast allergy r May warrant catheter drainage or endoscopic Urolithiasis. 2013;41:159–163.
– More time consuming, expensive, does not treatment 4. Piazzese EM, Mazzeo GI, Galipò S, et al. The renal
effectively image urolithiasis resistive index as a predictor of acute
r Pyelography: Antegrade or retrograde MEDICATION
hydronephrosis in patients with renal colic.
– Can be used with ultrasound or noncontrast CT in First Line J Ultrasound. 2012;15:239–246.
r Patients with infection and hydronephrosis require
patients with contrast allergies or renal
insufficiency; but invasive antibiotic therapy and drainage
r Functional studies to differentiate obstructive vs. – Renal failure and electrolyte abnormalities should ADDITIONAL READING
nonobstructive uropathy be corrected in conjunction with drainage
– Whitaker test: 1st described in 1980 Second Line Shapiro SR, Wahl EF, Silberstein MJ, et al.
◦ Indwelling percutaneous nephrostomy tube N/A Hydronephrosis Index: A new method to track patients
◦ Percutaneous puncture renal pelvis with hydronephrosis quantitatively. Urology.
◦ Upper urinary tract is perfused at a rate of SURGERY/OTHER PROCEDURES 2008;72:536.
r Catheter drainage of obstructed system with
5–10 mL per minute with saline or contrast See Also (Topic, Algorithm, Media)
percutaneous nephrostomy or ureteral stent is r Hydronephrosis/Hydroureteronephrosis, (Dilated
media
◦ Serial pressure recording is made in renal pelvis guided by the severity of the illness
– Hydronephrosis and fever may be ominous signs Ureter/Renal Pelvis), Adult Image
and bladder; spot films aid in evaluation r Hydronephrosis/Hydroureteronephrosis, (Dilated
◦ Pressure gradient: Obstruction >22 cm H2 O; requiring early drainage
– Other surgical procedures can be guided by the Ureter/Renal Pelvis), Pediatric
equivocal 15–22 cm H2 O; normal <15 cm H2 O r Ureter, Obstruction
findings on imaging studies
– Nuclear renography: r Urolithiasis, Ureteral
◦ Primary noninvasive study to distinguish ADDITIONAL TREATMENT H
obstructive vs. nonobstructive uropathy Radiation Therapy
◦ DTPA: Freely filtered by glomerulus. Neither N/A
secreted nor resorbed by renal tubules CODES
◦ MAG-3: Almost exclusively limited by proximal Additional Therapies
Hemodialysis may rarely be needed in the acutely ill ICD9
tubule secretion without resorption distally
◦ Preparation of patient, maintain hydration, patient r 591 Hydronephrosis
place a Foley catheter if concern for lower Complementary & Alternative r 592.0 Calculus of kidney
urinary tract dysfunction or obstruction Therapies r 600.00 Hypertrophy (benign) of prostate without
◦ Furosemide 20–40 mg given 20 min after N/A urinary obstruction and other lower urinary tract
radiotracer administration to induce diuresis symptom (LUTS)
◦ Half time (T1/2 clearance). Time it takes to
eliminate 50% of radiotracer: Obstruction
ONGOING CARE ICD10
r N13.2 Hydronephrosis with renal and ureteral
>20 min; equivocal >10–20 min; normal PROGNOSIS
<10 min; false positives: More commonly with calculous obstruction
Cause specific r N13.30 Unspecified hydronephrosis
severe dilation or poor function
r Endoluminal ultrasound (ELUS): COMPLICATIONS r N40.0 Enlarged prostate without lower urinary tract
r Progressive renal deterioration
– Evaluate periureteral anatomy, vessels of high symptoms
r With vesicoureteral reflux, scarring and hypertension
insertion and UPJ obstruction, define ureteral
stricture can occur
– Study of choice for submucosal calculi
r Postobstructive diuresis seen only with bilateral CLINICAL/SURGICAL
r Voiding cystourethrogram (VCUG): obstruction or solitary functioning kidney PEARLS
– Evaluate for reflux FOLLOW-UP r Hydronephrosis and fever especially sepsis may
– Patients with recurrent urinary tract infections, Patient Monitoring require immediate drainage.
flank pain, nonobstructive hydronephrosis r The etiology for hydronephrosis will determine the r Hydronephrosis may be nonobstructive.
Diagnostic Procedures/Surgery appropriate surveillance regimen r Generally hydronephrosis in an adult can be
Cystoscopy, retrograde ureteropyelogram r Consider renal ultrasound and renal scan at 3 mo
considered a sign of a process that must be defined
Pathologic Findings after treatment and possibly treated.
r Postoperative imaging may demonstrate the
Nephropathy related to obstruction (see above)
dilatation persists despite relief of obstruction
r Obstructive vs. nonobstructive Patient Resources
hydroureteronephrosis N/A
r See also “Risk Factors”
195
URETER/RENAL PELVIS), PEDIATRIC
Ahmad H. Bani-Hani, MD, FAAP, FACS
PATHOPHYSIOLOGY ASSOCIATED CONDITIONS

BASICS r Physiologic hydronephrosis: Unclear etiology but Hydronephrosis can by physiologic or pathologic
typically improves with serial renal ultrasound associated with many condition as noted above
DESCRIPTION monitoring
r Refers to dilatation of any part of the collecting r Pathologic hydronephrosis
system, single or combined: – Vesicoureteral reflux: Reflux can be primary or DIAGNOSIS
– Pelviectasis (renal pelvis) secondary to conditions that raises the intravesical
– Caliectasis (calyces) HISTORY
pressures (eg, bladder outlet obstruction and r Detailed prenatal history of:
– Pelvocaliectasis (both renal pelvis and calyces) neurogenic bladder)
– Ureterectasis (ureter) – Timing of 1st detection of hydronephrosis in
– Ureteropelvic junction (UPJ) obstruction (2)[A]: relation to gestational age
– Hydroureteronephrosis (entire collecting system is ◦ Defined as obstruction to the flow of urine
dilated) – Unilateral vs. bilateral
from the renal pelvis to the proximal ureter – Gender of the baby
r Society of Fetal Urology (SFU) grading of infant ◦ Considered to be the commonest cause of – Maternal diabetes mellitus, particularly type I
hydronephrosis (1)[A]: prenatal hydronephrosis (associated with fetal sacral agenesis)
◦ Obstruction can be caused by an intrinsic – Family history of renal anomalies
narrowing at the UPJ or by an extrinsic – Amniotic fluid volume
SFU grade Pattern of renal sinus splitting compression by a lower pole anteriorly crossing – Paternal allergy to penicillin
on renal ultrasound vessel r Detailed postnatal history:
◦ Examples of intrinsic obstruction can include: – Circumcision status
0 No splitting
Narrow segment with muscular discontinuity, – Birth weight
1 Urine in pelvis barely splits sinus
ureteral valves, mucosal folds, or ureteral – Jaundice
2 Urine fills intrarenal pelvis and/or urine
polyps – Urinary tract infections
fills extrarenal pelvis major calyces
dilated – Ureterovesical junction (UVJ) obstruction: – Progression with potty training
3 SFU Gr 2 and minor calyces uniformly ◦ Primary: Called primary obstructive megaureter. – Incontinence
dilated and parenchyma preserved The most common finding is a distal adynamic – Hypertension, failure to thrive
4 SFU Gr 3 and parenchyma thin ureteral segment that affects the free efflux of PHYSICAL EXAM
urine resulting in a functional obstruction r Vital signs, particularly blood pressure
◦ Secondary: Distal stone, hypertrophy of the r Weight
EPIDEMIOLOGY distal ureter and trigone in neurogenic bladder
r Prenatal hydronephrosis is detected in about 1.4% r Jaundice
or posterior urethral valves r Abdominal masses
of total prenatal ultrasound performed in US – Ureterocele:
r The true incidence is difficult to determine secondary r Is bladder palpable?
◦ Defines as cystic dilatation of the distal ureteral
to many asymptomatic, undetected cases segment r Cutaneous manifestations of spina bifida occulta
RISK FACTORS ◦ More common in females and can cause (hairy patch, sacral dimple, lipoma, asymmetric or
r Family history of hydronephrosis, maternal type I obstruction to the distal urine flow short gluteal fold)
◦ Often associated with duplication anomalies of r Genital/anorectal exam
diabetes mellitus (associated with infant sacral
agenesis) the kidneys particularly involving the upper pole
r Genetic syndromes: Downs, trisomy 13, trisomy 18, moiety
– Ectopic ureter: Lab
CHARGE, Ehlers–Danlos, Menkes, Prune belly, etc r Basic metabolic panel
r Horseshoe kidney/pelvic kidney ◦ Occurs when the distal opening of the ureter is
r Urine analysis and culture if indicated
r Duplication renal anomalies not in the normal location at the corner of the
r Neurogenic bladder secondary to tethered spinal trigone Imaging
◦ Ureter can enter the bladder neck, urethra, and, r Renal and bladder ultrasound (RUS):
cord, myelodysplasia, sacral agenesis in female, the vestibule, vagina, and rarely the – Should be 1st-line imaging study
Genetics uterus – Will give excellent idea about the laterality and
No specific genetic abnormalities except if associated ◦ Ectopic ureters opening outside the bladder or severity of hydronephrosis, associated bladder
with specific genetic syndromes as outlined above urethra tend to be obstructed and often pathology such as ureterocele, are ureters dilated
associated with nonfunctioning renal moiety too?
ALERT ◦ Commonly involves the upper pole moiety in – Bladder pathology such as abnormal bladder wall
Hydronephrosis is not a specific diagnosis but a duplicated renal anomalies thickness, key hole sign in posterior urethral valves
finding or sign. The cause of the hydronephrosis is – Posterior urethral valves: – Indirect way to assess overall renal function by
the diagnosis and indicates the appropriate ◦ The most common cause of congenital lower looking at echogenicity and thickness of renal
treatment. urinary tract obstruction in males (1/4,000 to parenchyma
1/7,500 births)
◦ Varies in severity and can result in deterioration
of fetal renal function, and progressive
oligohydramnios, which may lead to pulmonary
hypoplasia with a high risk of perinatal
morbidity and mortality
– Other causes:
◦ Anterior urethral valves
◦ Urethral atresia
◦ Nonneurogenic neurogenic bladder (Hinman
syndrome)
196
HYDRONEPHROSIS/HYDROURETERONEPHROSIS (DILATED URETER/RENAL PELVIS), PEDIATRIC
r Abdominal kidney-ureter-bladder (KUB) x-ray: SURGERY/OTHER PROCEDURES

r Vesicoureteral reflux: Antibiotic prophylaxis vs.
REFERENCES
– Displaced bowel pattern from hydronephrosis or
bladder distension surgical correction 1. Fernbach SK, Maizels M, Conway JJ. Ultrasound
– Stool load and distribution to help in management r UPJ obstruction: Pyeloplasty grading of hydronephrosis: Introduction to the
r Voiding cystourethrogram: r UVJ obstruction: Distal ureterectomy and ureteral system used by the Society for Fetal Urology.
– Assess presence of reflux reimplant Pediatr Radiol. 1993;23(6):478–480.
– During early filling, a ureterocele can be identified r Ureterocele: Several options available including 2. Koff SA. Pathophysiology of ureteropelvic junction
– Assess the entire urethra for evidence of posterior observation, intravesical puncture, obstruction. Clinical and experimental observations.
or anterior urethral valves ureteroureterostomy, and partial nephrectomy Urol Clin North Am. 1990;17:263–272.
r Diuretic renal scan (MAG-3 with Lasix): r Ectopic ureter: Several options available including 3. Liu HY, Dhillon HK, Yeung CK, et al. Clinical
– Evaluates differential renal function and drainage heminephrectomy and ureteroureterostomy outcome and management of prenatally diagnosed
curves from each kidney. r Posterior urethral valves: Endoscopic ablation primary megaureters. J Urol. 1994;152:614–617.
– Very useful for the diagnosis and evaluation of
possible UPJ/UVJ obstruction ADDITIONAL TREATMENT
r MR urogram: Radiation Therapy ADDITIONAL READING
– Can provide useful information such as renal N/A
function and anatomic details when evaluating Mesrobian HG, Mirza SP. Hydronephrosis: A view from
Additional Therapies the inside. Pediatr Clin North Am. 2012;59(4):
conditions such as ectopic ureter location r Clean intermittent catheterization in cases of
839–851.
Diagnostic Procedures/Surgery neurogenic bladder
r Usually reserved for treatment of certain conditions r Biofeedback in some patients with voiding See Also (Topic, Algorithm, Media)
r Hydronephrosis/Hydroureteronephrosis, (Dilated
such as posterior urethral valve ablation dysfunction
r Cystoscopy and retrograde pyelogram can be used Ureter/Renal Pelvis), Adult
Complementary & Alternative r Hydronephrosis/Hydroureteronephrosis, (Dilated
to define the anatomy of the collecting system and Therapies
placement of a drainage stent Ureter/Renal Pelvis), Prenatal
N/A r Hydronephrosis/Hydroureteronephrosis, (Dilated
Pathologic Findings Ureter/Renal Pelvis), Pediatric Images
Depends on the underlying pathology responsible for r Megaureter
the hydronephrosis
ONGOING CARE
r Posterior urethral valves
DIFFERENTIAL DIAGNOSIS PROGNOSIS r Ureterocele
r Prominent extrarenal pelvis Varies and depends on underlying pathology and its r Ureteropelvic junction obstruction
r Multicystic dysplastic kidney severity (3)[A]
r Polycystic renal disease
r Renal cysts
COMPLICATIONS
r Hypertension CODES
r Kidney/bladder stones
TREATMENT
r Multiple UTIs
r Reflux
ICD9
r 591 Hydronephrosis
H
GENERAL MEASURES r Renal insufficiency r 596.54 Neurogenic bladder NOS
Depends on underlying pathology responsible for the r Renal scarring r 753.3 Other specified anomalies of kidney
hydronephrosis r Urinary incontinence
ICD10
MEDICATION FOLLOW-UP r N13.30 Unspecified hydronephrosis
First Line Patient Monitoring r N31.9 Neuromuscular dysfunction of bladder,
r Antibiotic prophylaxis may be needed in severe r Patients need meticulous follow-up once unspecified
cases of hydronephrosis and/or presence of reflux hydronephrosis is diagnosed before and after r Q63.1 Lobulated, fused and horseshoe kidney
– Prophylactic daily antibiotics to keep urine sterile, treatment
preferentially given at bedtime to maximize r Referral to pediatric urology/nephrology for full
urinary retention assessment and treatment CLINICAL/SURGICAL
◦ <2 mo age: Amoxicillin 20 mg/kg/d
◦ ≥2 mo of age: Trimethoprim–sulfamethoxazole Patient Resources PEARLS
2 mg/kg/d (concentrates in urine); nitrofurantoin National Kidney Foundation. http://www.kidney.org/ r Hydronephrosis is not a diagnosis but a sign.
is an alternative, but liquid is expensive and atoz/content/hydronephrosis.cfm r Renal ultrasound, VCUG, and diuretic renal scan can
bad-tasting establish the underlying etiology of hydronephrosis.
Second Line
r Anticholinergics in cases of an overactive bladder
and/or raised intravesical pressures
r β-blockers in some cases of bladder outlet
obstruction
197
URETER/RENAL PELVIS), PRENATAL
Bruce J. Schlomer, MD
r Postnatal evaluation: Controversial. Society of Fetal

BASICS DIAGNOSIS Urology (SFU) recommendations based on severity
of PN (1)
DESCRIPTION HISTORY r Unilateral mild PN
r In utero dilation of fetal renal collecting system r Timing of prenatal detection; earlier detection
– Postnatal US at 2–4 wk
r May represent a normal developmental variant or a implies more severe condition. – Consider VCUG at 2–4 wk if hydro present on
r Presence of calyectasis and renal cortical thinning
pathologic anomaly postnatal US
r Prenatal hydronephrosis (PN) may be observed early indicate more severe condition. – Consider diuretic nuclear renal scan (MAG-3) at
r Presence of cortical cysts may indicate dysplasia.
in pregnancy but the diagnosis usually cannot be 4 wk if hydro present on postnatal US
made with certainty until 18 wk of gestation r Unilateral vs. bilateral renal involvement is a critical r Unilateral moderate-severe PN
r Severity based on anterior–posterior renal pelvis determination for diagnosis and prognosis. – Postnatal US at 2–4 wk
diameter (APD) (1) r Change in dilation in relation to bladder filling may – VCUG at 2–4 wk if hydro present on postnatal US
– Mild: 4 to <7 mm (2nd trimester); 7 to <9 mm indicate vesicoureteral reflux. – Consider diuretic nuclear renal scan (MAG-3) at
(3rd trimester) r Presence of oligohydramnios important: Suggests 4 wk of hydro present on postnatal US
– Moderate: 7 to ≤10 mm (2nd trimester); 9 to severe comprise of renal function. r Bilateral moderate-severe PN
≤15 mm (3rd trimester) – Associated with severe obstructive uropathy due – 1st postnatal US 1–3 days after birth
– Severe: >10 mm (2nd trimester); >15 mm to PUVs, congenital urethral stricture, or – VCUG 1–7 days after birth
(3rd trimester) ureterocele obstructing bladder outlet – Males: Early VCUG to rule out PUVs
– Associated with pulmonary hypoplasia and fetal – Consider diuretic nuclear renal scan (MAG-3) at
EPIDEMIOLOGY
or neonatal death 4 wk
Incidence r Special situations: Bladder/urethral abnormalities,
r 1–5% of fetuses are observed to have PN (2) PHYSICAL EXAM
N/A decreased amniotic fluid
– Mild: 57–88%
– Early evaluation similar to severe bilateral PN
– Moderate: 10–30% DIAGNOSTIC TESTS & INTERPRETATION r Postnatal US within 48–72 hr after birth may
– Severe: 2–13%
r Risk of clinically significant PN increases with Lab underestimate degree of hydronephrosis
r Maternal α-feto protein may be elevated in some r Rare cases of pulmonary compromise from mass
severity. Risk of undergoing surgery <10% with cases of fetal renal anomalies
mild and >50% with severe. effect require emergent drainage
r Assessment of pulmonary maturity in patients with
Prevalence Diagnostic Procedures/Surgery
oligohydramnios (lecithin-to-sphingomyelin ratio)
None r Amniotic fluid studies: Fetal urinary electrolyte bladder aspiration in cases of
oligohydramnios
RISK FACTORS – Volume: Composed mostly (90%) of fetal urine
r Family history of renal abnormalities or after the 16th wk of gestation Pathologic Findings
– Correlates with fetal renal function N/A
vesicoureteral reflux
r Previous fetal loss due to urinary tract causes r Fetal karyotype (may indicate gender or important
genetic information) r Urinary conditions:
Genetics r Assessment of fetal urinary electrolytes: – Autosomal recessive polycystic kidney disease
None
– Generally only done with oligohydramnios – Duplication anomalies
PATHOPHYSIOLOGY – Good prognosis: Sodium <100 mg/dL; osmolarity – Ectopic ureter
r Transient hydronephrosis (most common, <210 mOsmol/dL; chloride <90 mg/dL – Megacystis-megaureter microcolon syndrome
physiologic dilation of the ureter is seen in 41–88% (remember dilute urine is better in the fetus) – Multicystic dysplastic kidney
of cases of PN) r Postnatal serum electrolyte assessment: – PUVs
– ∼90% of mild PN will be transient – Nadir creatinine (<0.7 mg/dL in 1st yr holds good – Prune belly syndrome
r Ureteropelvic junction (UPJ) obstruction (most prognosis) – Transient hydronephrosis
common pathophysiology) – CO2 : Acidosis has a poor prognosis. – UPJ obstruction
r Ureterovesical obstruction (megaureter, obstructed r Urinalysis and urine culture as needed – UVJ obstruction
and nonobstructed) – Vesicoureteral reflux
r Bladder outlet obstruction (posterior urethral valves
Imaging r Intestinal disorders:
r Prenatal US in 3rd trimester: Based upon severity of
(PUVs), urethral atresia) PN in 2nd trimester(1) – Cloacal exstrophy
r Nonobstructive processes: Vesicoureteral reflux, – Mild: Consider 3rd trimester US – Duodenal atresia
nonrefluxing nonobstructed megaureter, and prune – Moderate: 3rd trimester US – Imperforate anus
belly syndrome – Severe: US in 3–4 wk – Intestinal duplication
r Severe PN with oligohydramnios may cause r Additional prenatal US in 3rd trimester: Based upon – Mesenteric cysts
pulmonary hypoplasia – Ovarian cysts
severity of PN in 3rd trimester (1)
– Persistent cloaca
ASSOCIATED CONDITIONS – Mild: Postnatal evaluation r Tumors:
Congenital hydronephrosis is associated with many – Moderate: Postnatal evaluation
– Severe: US in 2–3 wk – Congenital mesoblastic nephroma
syndromes. – Neuroblastoma
GENERAL PREVENTION
None
198
HYDRONEPHROSIS/HYDROURETERONEPHROSIS (DILATED URETER/RENAL PELVIS), PRENATAL
ADDITIONAL READING
Davenport MT, Merguerian PA, Koyle M. Antenatally
GENERAL MEASURES PROGNOSIS diagnosed hydronephrosis: Current postnatal
r Prenatal management: Assessment of r Most neonates have an excellent prognosis. management. Pediatr Surg Int. 2013;29(3):207–214.
hydronephrosis, oligohydramnios: Prognosis depends on etiology of the dilated system
and other associated anomalies. See Also (Topic, Algorithm, Media)
– Unilateral cases: Serial prenatal US if severe; r Hydronephrosis/Hydroureteronephrosis (Dilated
deliver at term r Severe bilateral hydronephrosis is associated with
Ureter/Renal Pelvis), Pediatric
– Bilateral cases obstruction and oligohydramnios early in gestation r Hydronephrosis/Hydroureteronephrosis (Dilated
◦ No oligohydramnios: Observation, deliver at predicts an adverse outcome.
r Fetuses with bilateral hydronephrosis, a distended Ureter/Renal Pelvis), Prenatal Image
term r Megaureter, Congenital
◦ Oligohydramnios: Termination, early delivery, bladder, and oligohydramnios are at highest risk of
prenatal treatment for pulmonary immaturity neonatal demise or pulmonary complications.
r Postnatal management: r Risk of UTI correlated with severity of PN
– Pulmonary support if respiratory compromise – Mild: ∼10% CODES
– Antibiotic prophylaxis if moderate-severe – Moderate-severe: ∼30%
unilateral or bilateral PN ICD9
– Bilateral hydronephrosis with dilated bladder:
COMPLICATIONS r 753.6 Atresia and stenosis of urethra and bladder
r Pulmonary hypoplasia with severe oligohydramnios
Place catheter to drain bladder neck
r Renal impairment r 753.20 Unspecified obstructive defect of renal pelvis
– All hydronephrosis: US, VCUG, MAG-3 renal scan
r UTIs
as indicated (see above for SFU recommendations) and ureter
r 753.29 Other obstructive defects of renal pelvis and
MEDICATION FOLLOW-UP
Patient Monitoring ureter
First Line r Based on initial evaluation, subsequent imaging
r No specific antenatal medications exist
ICD10
r Prophylactic antibiotics controversial. may be necessary (1) r Q62.0 Congenital hydronephrosis
r Most centers employ serial renal US every 3–6 mo r Q64.31 Congenital bladder neck obstruction
– Recommended by SFU with moderate-severe PN,
bladder/urethral abnormalities, dilated ureter, for the 1st yr of life r Q62.39 Other obstructive defects of renal pelvis and
oligohydramnios(1) r If febrile UTI, consider VCUG and/or MAG-3 renal
ureter
– Amoxicillin (20 mg/kg/d—1 dose per day) scan
r Surfactant to assist lung function after birth with
Patient Resources
pulmonary hypoplasia r http://urology.ucsf.edu/patient-care/children/ CLINICAL/SURGICAL
Second Line Hydronephrosis PEARLS
r http://urology.ucsf.edu/patient-care/children/urinary-
N/A r Majority of prenatal/fetal hydronephrosis (especially
tract-obstruction/ureteropelvic-junction-obstruction
SURGERY/OTHER PROCEDURES mild) is transient with no clinical significance.
r Fetal intervention (cases with oligohydramnios only):
r http://urology.ucsf.edu/patient-care/children/
r VCUG is not recommended for unilateral mild H
additional/megaureter
– Controversial(3) r http://urology.ucsf.edu/patient-care/children/urinary- hydronephrosis.
– Tapping of fetal bladder r Prophylactic antibiotics have not been shown to be
– Percutaneous shunting: Vesicoamniotic drain tract-obstruction/posterior-urethral-valves
effective. Not recommended in mild cases.
r Surgery is seldom necessary in the neonatal period r Emergent evaluation by urologist should occur with:
with the exception of severe bilateral obstruction REFERENCES – Severe bilateral prenatal hydronephrosis
due to bladder outlet obstruction or severe UPJ or – Severe unilateral prenatal hydronephrosis in
UVJ obstruction. 1. Nguyen HT, Herndon CD, Cooper C, et al. The solitary kidney
r Need for postnatal surgery based upon diagnosis Society for Fetal Urology consensus statement on – Prenatal hydronephrosis with dilated bladder
and correlated with severity of PN the evaluation and management of antenatal consistent with posterior urethral valves
– Mild: <10% hydronephrosis. J Pediatr Urol. 2010;6:212–231. – Severe prenatal hydronephrosis with pulmonary
– Severe: ∼50% 2. Lee RS, Cendron M, Kinnamon DD, et al. Antenatal compromise from mass effect (rare)
ADDITIONAL TREATMENT hydronephrosis as a predictor of postnatal
outcome: A meta-analysis. Pediatrics. 2006;118:
Radiation Therapy 586–593.
N/A
3. Morris RK, Malin GL, Khan KS, et al. Systematic
Additional Therapies review of the effectiveness of antenatal intervention
N/A for the treatment of congenital lower urinary tract
Complementary & Alternative obstruction. BJOG. 2010;117:382–390.
Therapies
N/A
199
HYPERALDOSTERONISM, PRIMARY (ALDOSTERONISM,

CONN SYNDROME)
Mark W. Ball, MD
ASSOCIATED CONDITIONS r Confirmatory studies:

BASICS r Adrenal cancer (rare) – Na-loading test with:
r Essential HTN ◦ Saline infusion: PAC at baseline and 4 hr
DESCRIPTION (positive test PAC >10 ng/dL)
r Primary hyperaldosteronism or Conn syndrome is GENERAL PREVENTION ◦ Oral Na: 24-hr urine Na and aldosterone on
characterized by HTN, hypokalemia, hypernatremia, N/A days 3 and 4 (positive if aldosterone <12 mg/d)
alkalosis, and suppressed renin, due to excess and (Na >200 mmol/d)
production of aldosterone. DIAGNOSIS ◦ Fludrocortisone suppression
r It classically refers to an aldosterone-producing r All confirmatory tests should be used with care in
adenoma (APA) of the adrenal gland that is usually HISTORY patients with compromised left ventricular cardiac
small (<3 cm), unilateral, and renin-unresponsive. r HTN, often refractory to medical therapy
function.
r APA subtype of primary hyperaldosteronism – Headaches secondary to HTN
r Symptomatic hypokalemia: Imaging
accounts for 30–60% of primary r CT with thin cuts through the adrenals is the
hyperaldosteronism. – Muscle cramps, paresthesias, tetany, nocturia,
r Secondary hyperaldosteronism is usually related to preferred noninvasive test:
polyuria
– Used to identify surgically curable disease and
HTN and/or edematous state disorders such as CHF, PHYSICAL EXAM differentiate the subtypes once primary
cirrhosis, and nephrotic syndrome. r No specific findings aldosteronism is confirmed
r Pseudohypoaldosteronism can be due to ingestion r Mild-to-moderate HTN, not usually distinguishable – aldosterone-producing adenomas (APA’s) usually
of large amounts of licorice or Liddle syndrome from essential HTN uniform, round, and hypodense with Hounsfield
EPIDEMIOLOGY r Malignant HTN rare unit ≤10
r Lack of edema – 6% probability of identifying an adrenal mass on
Incidence
CT
Incidence data is lacking. DIAGNOSTIC TESTS & INTERPRETATION – Lacks overall accuracy to distinguish between
Prevalence r Consider screening the following patients (1):
unilateral and bilateral disease:
r 5–13% of hypertensive population (recent increased – Hypertensive and hypokalemic: ◦ Bypass adrenal vein sampling only if clear
prevalence of primary aldosteronism due to ◦ HTN with K <3 highly suspicious of an adrenal mass (>1 cm) is identified in the
improved diagnostic testing) aldosterone-producing adenoma (APA). younger patient (<40) with highly suspicious
r Peak incidence during 4th and 5th decades ◦ Hypokalemia is thought to be a late biochemical findings
r 20% primary aldosteronism in resistant manifestation of aldosterone excess. r MRI is not more sensitive than CT
hypertensives (elevated BP despite 3 ◦ If patient is on restricted Na diet, severe r Adrenal scintigraphy using
antihypertensive medications) hypokalemia often absent; only test patients if Iodine-131-6-iodomethyl-19-nor-cholesterol is
r Adrenal adenoma is more common in women. adequately salt loaded. rarely available in US, cumbersome to perform, and
◦ Hypokalemia can be induced with oral Na
depends heavily on the size of the adenoma.
RISK FACTORS loading.
No known risk factors for primary hyperaldosteronism ◦ 20% of patients with hyperaldosteronism are Diagnostic Procedures/Surgery
r Adrenal vein sampling (AVS) for aldosterone is the
Genetics normokalemic; more often seen in adrenal
r Hereditary pattern for more common APAs unclear hyperplasia. gold standard in localizing the site of excess
r A rare form of autosomal dominant primary – Inappropriate kaliuresis on initiation of diuretic production:
– HTN resistant to multidrug treatment – Aldosterone and cortisol samples obtained from
hyperaldosteronism is glucocorticoid-remediable peripheral veins, IVC, right and left adrenal veins
aldosteronism (GRA). – Family history of early HTN or stroke
r Gene for aldosterone synthase (CYP11B2) recently – Adrenal incidentaloma after corticotrophin infusion
r Diagnosis may be difficult in those with normal – 44% of patients with bilateral renal masses had a
identified unilateral source of aldosterone secretion.
serum K levels and those being treated with
PATHOPHYSIOLOGY antihypertensives or diuretics – Cure also reported after adrenalectomy in patients
r The biochemical hallmark of the disease is increased with AVS-proven unilaterality despite normal
Lab adrenals on CT scan.
aldosterone after sodium (Na) loading and low r Hypernatremia, hypokalemia, metabolic alkalosis, r Postural tests, historically used to distinguish
plasma renin activity (PRA) during Na depletion
r Autonomous aldosterone secretion leads to impaired glucose tolerance adenoma from bilateral hyperplasia have become
r Plasma renin activity (PRA) low in primary
inappropriate Na and water reabsorption from the less useful with the discovery of
hyperaldosteronism; if plasma renin >1, diagnosis angiotensin-responsive APAs.
cortical collecting tubule:
unlikely
– Electrical gradient created favors secretion of r Screening: Plasma aldosterone concentration Pathologic Findings
potassium (K), resulting in hypokalemia. r Solitary, well-demarcated mass with the typical
– Extracellular fluid volume (ECF) volume causes (PAC)/plasma renin activity (PRA) in the upright
mottled yellow color of adrenal cortex
mild hypertension (HTN). position; obtain when K is corrected. Positive if: r Without diffuse thickening of the zona glomerulosa
r Renal escape limits Na retention and prevents – PAC/PRA >20 with PAC ≥15 ng/dL OR
– PAC/PRA >40 with PRA >0.2 ng/mL/h or hyperplastic nodules
significant edema: r May compress the nonneoplastic uninvolved adrenal
– Diuretics, ACE inhibitors, ARBs can falsely elevate
– Occurs after ∼1.5 kg of extracellular fluid (ECF) is gland
PRA.
absorbed, or a weight gain of ∼3 kg. r Histopathology: Foamy lipid-laden clear cells, in
– Spontaneous diuresis then occurs, lowering the sheets or nests
ECF.
– Increased Atrial natriuretic peptide (ANP),
decreased thiazide-sensitive Na-Cl cotransporter,
and pressure natriuresis are factors that may
contribute to renal escape.
200
HYPERALDOSTERONISM, PRIMARY (ALDOSTERONISM, CONN SYNDROME)
r Other causes of HTN. In Cushing disease,
Radiation Therapy r Calhoun DA. Aldosteronism and hypertension. Clin J
aldosterone and renin will both be low. In renal N/A
artery stenosis, there will be high renin and high Am Soc Nephrol. 2006;1:1039–1045.
aldosterone. Additional Therapies r Conn JW. Presidential address. I. Painting
r Other causes of HTN and hypokalemia, such as: Emerging therapies include developing drugs that background. II. Primary aldosteronism, a new
inhibit actions of aldosterone synthase enzyme, clinical syndrome. J Lab Clin Med. 1955;45:3–17.
– Overingestion of licorice
encoded on the CYP11B2 gene r Lim PO, Young WF, MacDonald TM. A review of the
– Use of chewing tobacco
– Hyperdeoxycorticosterones Complementary & Alternative medical treatment of primary aldosteronism.
r Other subtypes of primary hyperaldosteronism: Therapies J Hypertens. 2001;19(3):353–361.
– Bilateral adrenal hyperplasia: Idiopathic N/A r Mattsson C, Young WF Jr. Primary aldosteronism:
– GRA due to aldosterone-producing, Diagnostic and treatment strategies. Nat Clin Pract
renin-responsive adenoma. Familial ONGOING CARE Nephrol. 2006;2(4):198–208.
hyperaldosteronism type I, autosomal dominant r Plouin PF, Amar L, Chatellier G. Trends in the
– Familial occurrence of APA or bilateral idiopathic PROGNOSIS prevalence of primary aldosteronism,
hyperplasia or both r Patients with primary hyperaldosteronism have aldosterone-producing adenomas, and surgically
– Adrenal cancer producing aldosterone: Extremely higher rates of prior stroke (12.9% vs. 3.4%) correctable aldosterone-dependent hypertension.
rare compared to those with essential HTN. Nephrol Dial Transplant. 2004;19:774–777.
r Liddle syndrome: Autosomal dominant disorder. r Nonfatal MI (4% vs. 0.6%) r Wheeler MH, Harris DA. Diagnosis and management
Mimics hyperaldosteronism and involves problems r Atrial fibrillation (7.3% vs. 0.6%) of primary aldosteronism. World J Surg. 2003;
with excess resorption of Na and loss of K. 27:627–631.
COMPLICATIONS
r Related to HTN (left ventricular hypertrophy, See Also (Topic, Algorithm, Media)
r Adrenal Mass
TREATMENT coronary artery disease, heart failure, stroke,
r Aldosteronism (Hyperaldosteronism, Conn
intracerebral hemorrhage, etc.)
GENERAL MEASURES r Related to low K (tetany, headache, arrhythmias, Syndrome) Algorithm
r Treatment selected based on etiology of r Hypertension, Urologic Considerations
etc.)
hyperaldosteronism
r Control HTN FOLLOW-UP
Patient Monitoring
MEDICATION BP and serum electrolytes should be evaluated
CODES
First Line (2) postoperatively and following medical therapy.
r Mineralocorticoid receptor antagonist used in those ICD9
Patient Resources r 255.10 Hyperaldosteronism, unspecified
with bilateral adrenal hyperplasia and unilateral
Hyperaldosteronism - primary and secondary r 255.12 Conn’s syndrome
hyperplasia or APA who are not surgical candidates:
MedlinePlus. http://www.nlm.nih.gov/ r 255.14 Other secondary aldosteronism
– Spironolactone: Limited due to affinity for
androgen and progesterone receptors. Can cause
medlineplus/ency/article/000330.htm H
gynecomastia, sexual dysfunction, menstrual ICD10
r E26.01 Conn’s syndrome
irregularities REFERENCES r E26.1 Secondary hyperaldosteronism
– Eplerenone: No active metabolites, shorter
half-life than spironolactone, 50–75% as potent 1. Mantero F, Mattarello MJ, Albiger NM. Detecting r E26.09 Other primary hyperaldosteronism
as spironolactone but less adverse effects and treating primary aldosteronism: Primary
r Thiazide diuretics, ACE inhibitors, calcium channel aldosteronism. Exp Clin Endocrinol Diabetes.
antagonists, angiotensin blockers 2007;115:171–174. CLINICAL/SURGICAL
Second Line
2. Young WF Jr. Minireview: Primary aldosteronism– PEARLS
changing concepts in diagnosis and treatment.
Amiloride, an epithelial Na channel blocker and r Hypertension (HTN) with serum K <3 meq/L is
Endocrinology. 2003;144(6):2208–2213.
K-sparing diuretic, may also be used, especially if highly suspicious of an aldosterone-producing
spironolactone or eplerenone are intolerable. More adenoma (APA).
often used in conjunction with the above. r Treatment selection is based on etiology of
SURGERY/OTHER PROCEDURES hyperaldosteronism.
r Unilateral adrenalectomy is indicated in patients r Surgical excision provides excellent control of
with hyperaldosteronism due to an adenoma. hypertension in aldosterone-producing adenoma
r HTN is cured or improved significantly in up to 90% (APA).
of such cases. Usually takes 3–6 mo to see an effect. r Control of the adrenal vein is the most important
r Adequate control of BP (see “Medications”) for step during adrenalectomy.
several weeks and correction of metabolic
abnormalities should be done before surgery.
r Obtain PAC after surgery to confirm cure
r Monitor K closely postoperatively
201
HYPERPROLACTINEMIA, UROLOGIC CONSIDERATIONS

Mark W. Ball, MD
r Prolactinomas: Pituitary microadenomas (<10 mm) DIAGNOSTIC TESTS & INTERPRETATION

BASICS and macroadenomas (>10 mm) can be seen in Lab (2)
some patients as the cause of the elevated levels. r A single serum measurement > upper limit of
DESCRIPTION – Macroadenomas can have mass effect symptoms, normal makes the diagnosis of HPRL
r Hyperprolactinemia (HPRL) refers to serum prolactin including headache and visual disturbance by r Serum PRL >500 μg/L is diagnostic of a
levels that exceed the normal range <25 mg/L optic nerve compression macroprolactinoma
(∼500 mIU/L) in women and <20 mg/L r Rarely, chest wall injury can increase prolactin levels. r Women of reproductive age should have a
(∼400 mIU/L) in men. r Macroprolactinemia is caused by an abnormal
r It is the most common endocrine abnormality due to pregnancy test.
binding of the molecule to circulating IgG. r In men presenting with ED, a testosterone level
hypothalamic–pituitary disorders.
r It may result in hypogonadism, erectile dysfunction, ASSOCIATED CONDITIONS should be checked. If low, further evaluation of
r Amenorrhea and/or galactorrhea in women prolactin should be performed.
infertility, galactorrhea, and osteoporosis. r Hypogonadism and/or ED in men r With medication-induced HPRL, prolactin levels are
r Most common causes are pregnancy, medications,
r Hypothyroidism: Increased thyrotropin-releasing usually <50 mg/L and almost always <100 mg/L.
hypothyroidism, and prolactin-secreting pituitary r After stopping suspected medication, prolactin
tumors (prolactinomas) hormone can stimulate prolactin secretion.
r Renal failure can result in reduced clearance. levels usually return to normal within 4 days.
EPIDEMIOLOGY r Cirrhosis Imaging
Incidence r Herpes zoster (particularly involving the chest wall) r Pituitary MRI is the test of choice. Should be
r Peak incidence occurs in women of age 25–34, at
obtained in all cases where prolactin is persistently
23.9/100,000/yr. GENERAL PREVENTION elevated and no cause is apparent.
r Incidence data in men is lacking Discontinuation of medication causing symptomatic r DEXA scanning to evaluate for possible bone
HPRL (asymptomatic prolactin elevations need not be mineral density problems
Prevalence treated)
r Lifetime prevalence of prolactinoma is 30/100,000 r In women, pelvic US to assess for uterine or ovarian
in woman and 10/100,000 in men. pathology
r Pituitary microadenomas are found in 10.9% of DIAGNOSIS Diagnostic Procedures/Surgery
autopsies, with 44% prolactinomas. Formal visual field assessment should be done in
r In men with sexual dysfunction, ∼1% have HPRL. HISTORY
r Women: Often presents early in disease course. patients with macroadenomas.
r 90% of prolactinomas occur in women of
– Infertility (including pregnancy history) Pathologic Findings
reproductive age. Prolactinoma: Glands composed of cuboidal cells. May
r 40% of pituitary adenomas are prolactinomas – Amenorrhea/menstrual irregularities
– Galactorrhea be either eosinophilic or chromophobic.
RISK FACTORS r Men: Often presents late in disease course.
r Female sex DIFFERENTIAL DIAGNOSIS
– Complaints of sexual dysfunction r Hypothyroidism
r Pregnancy ◦ Decreased libido r Lab error or macroprolactinemia (abnormal prolactin
r Prolactinomas ◦ Erectile dysfunction (ED)
molecule)
r Medications (antipsychotics, antidepressants, – Gynecomastia r Medication-induced
r General
verapamil, opiates, GI motility drugs, estrogens) r Nonprolactin-secreting pituitary or hypothalamic
r MEN-1 syndrome – Headache
tumor
– Visual field defects r Polycystic ovary syndrome (PCOS)
Genetics r Psychiatric history and antipsychotic medication use
r Most prolactinomas are sporadic (1) r Pregnancy
r Alcohol abuse
r Present in about 20% of adults with MEN-1, who r Prolactinoma
r Medication use:
have an autosomal dominant mutation in the r Renal failure
– Antipsychotics: Butyrophenones (eg, haloperidol),
MEN-1 tumor suppressor gene on chromosome 11
r Can rarely occur as part of familial isolated pituitary phenothiazines (eg, chlorpromazine),
adenomas
thioxanthenes (eg, thiothixene), risperidone and TREATMENT
others: Metoclopramide, sulpiride, pimozide,
PATHOPHYSIOLOGY methyldopa, reserpine
r Prolactin is produced in the anterior pituitary – Others reported: Antiandrogens, cimetidine, ALERT
r Secretion is pulsatile and increases with stress and cyproheptadine, danazol, estrogens, INH, tricyclic Do not treat women until pregnancy is excluded.
sleep antidepressants, opiates, verapamil
r Tonically suppressed by dopamine via D2 receptors GENERAL MEASURES (3)
PHYSICAL EXAM r Women of reproductive age should have a
– Medications that inhibit dopamine secretion raise r Breast exam for gynecomastia, galactorrhea
pregnancy test 1st.
prolactin levels r Evidence of chest wall trauma or herpetic lesions r Treat underlying cause or stop offending drug if
r Elevated prolactin suppresses GnRH, with r Signs of hypogonadism
possible
subsequent reductions in LHRH, FSH, and sex r Signs of hypothyroidism r Asymptomatic HPRL secondary to medication use
steroid levels. r Visual field abnormalities
– Low testosterone can cause decreased libido, does not require treatment.
erectile dysfunction, infertility, and gynecomastia
in men.
– Low estrogen can cause oligomenorrhea,
decreased libido, anovulation, and galactorrhea in
women
– Decreased bone mineral density can occur in both
sexes secondary to low sex steroid levels.
202
HYPERPROLACTINEMIA, UROLOGIC CONSIDERATIONS
MEDICATION REFERENCES
r Cabergoline or bromocriptine (dopamine agonists): 1. Melmed S, Casanueva FF, Hoffman AR, et al.
– Usually will lower prolactin levels, regardless of PROGNOSIS Diagnosis and treatment of hyperprolactinemia: An
r 90–95% of prolactin-secreting pituitary
cause, and shrink prolactinomas Endocrine Society clinical practice guideline. J Clin
– In general, both cabergoline and bromocriptine microadenomas will not grow further, even without Endocrinol Metab. 2011;96(2):273–288.
are effective. Cabergoline is usually medical therapy. 2. Klibanski A. Clinical practice. Prolactinomas. N Engl
r Medical therapy is usually successful in normalizing
better-tolerated, more convenient, and more J Med. 2010;362(13):1219–1226.
effective than bromocriptine, whereas prolactin levels, normalizing menses, reducing or 3. Casanueva FF, Molitch ME, Schlecte JA, et al.
bromocriptine is less expensive and has been used stopping galactorrhea, inducing ovulation, and Guidelines of the Pituitary Society for the diagnosis
longer. shrinking pituitary tumors. and management of prolactinomas. Clin Endocrinol
– Use dopamine agonists with caution in patients r >90% of microadenomas do not grow significantly
(Oxf). 2006;65:265–273.
on psychotropic drugs that inhibit dopamine during pregnancy, even after medical therapy is
action. stopped.
◦ Cabergoline dosing (0.5-mg tablets): Start with r Some microadenomas disappear with time ADDITIONAL READING
0.25–0.5 mg once or twice weekly and increase (especially after menopause) or do not recur after
r Klibanski A. Clinical practice. Prolactinomas. N Engl
the dose at monthly intervals until prolactin medical therapy.
normalizes (>3 mg/wk is rarely needed). r Pituitary macroadenomas usually do not disappear J Med. 2010;362(13):1219–1226.
◦ Bromocriptine dosing (2.5-mg tablets): Start r Mancini T, Casanueva FF, Giustina A.
completely with medical therapy and require
with 0.625 or 1.25 mg with food before continuous medical therapy. Hyperprolactinemia and prolactinomas. Endocrinol
bedtime and gradually increase at weekly Metab Clin North Am. 2008;37:67–99.
intervals until prolactin level is controlled COMPLICATIONS r Melmed S, Casanueva FF, Hoffman AR, et al.
r Dopamine agonists can worsen underlying
(usually 2.5 mg BID–TID). Diagnosis and treatment of hyperprolactinemia: An
– Side effects include nausea and postural psychiatric problems in patients taking psychotropic Endocrine Society clinical practice guideline. J Clin
hypotension medications. Endocrinol Metab. 2011;96(2):273–288.
r Pregnancy considerations r Pituitary macroadenomas can secrete other r Molitch ME. Drugs and prolactin. Pituitary. 2008;
– More experience with bromocriptine. hormones or become resistant to medical therapy. 11:209–218.
– Neither bromocriptine nor cabergoline has been FOLLOW-UP r Schlecte JA. Long-term management of
associated with teratogenicity. Patient Monitoring prolactinomas. J Clin Endocrinol Metab.
– Nevertheless, either drug is usually stopped at the r Drug-induced HPRL: 2007;92:2861–2865.
1st evidence of pregnancy, except in patients with – Prolactin should normalize after switching r Zeitlin S, Rajfer J. Hyperprolactinemia and erectile
macroadenomas in whom previous mass effects medications and no further follow-up is needed. dysfunction. Rev Urol. 2000;2(1):39–42.
may recur if tumor enlarges. r Microadenomas:
– Significant enlargement of microadenomas is See Also (Topic, Algorithm, Media)
– Some microadenomas resolve spontaneously. r Erectile Dysfunction
uncommon during pregnancy. – Measure prolactin every 6–12 mo to ensure
– Lactation: Dopamine agonists will inhibit lactation. r Gynecomastia H
continued drug efficacy.
Second Line – No need for repeat pituitary MRI unless prolactin
N/A increases markedly on therapy.
– Consider stopping dopamine agonist after at least CODES
r Often performed transsphenoidally a year of successful therapy; some
r For microadenomas, generally reserved for patients microadenomas do not recur ICD9
r Macroadenomas: r 253.1 Other and unspecified anterior pituitary
intolerant of drug therapy. Tumors may recur. hyperfunction
r Only indicated for pituitary macroadenomas when – If prolactin normalizes, repeat pituitary MRI after
r 256.39 Other ovarian failure
3–6 mo to ensure tumor shrinkage and establish
medical therapy is ineffective, including persistent new baseline. r 257.2 Other testicular hypofunction
visual field abnormalities: – No consensus on frequency of further MRIs in
– Usually not curative patients whose prolactin is well-controlled ICD10
r E22.1 Hyperprolactinemia
ADDITIONAL TREATMENT medically.
r E28.39 Other primary ovarian failure
Radiation Therapy – Repeat prolactin measurements every 3–6 mo.
– Follow visual fields in patients who have visual r E29.1 Testicular hypofunction
Usually only indicated for pituitary macroadenomas
that have failed medical therapy, and where response field defects at baseline.
to surgery is inadequate or surgery is contraindicated. – Some macroadenomas resolve spontaneously.
CLINICAL/SURGICAL
Additional Therapies Patient Resources
Patient guide to hyperprolactinemia diagnosis and PEARLS
Men with ED or persistent hypogonadism may require
additional therapies. treatment. J Clin Endocrinol Metab. 2011;96: r Women present early in the disease course, while
35A–36A. men present late.
Complementary & Alternative r Dopamine agonists are the 1st-line treatment of
Therapies
Vitex agnus-castus extract can be tried in cases of mild prolactinomas.
r Surgical excision is reserved for refractory cases.
HPRL
r All women should be screened for pregnancy before
initiating treatment.
203
HYPOSPADIAS
Steve J. Hodges, MD
Anthony Atala, MD
PATHOPHYSIOLOGY
BASICS r Normal penile development: DIAGNOSIS
– Urogenital folds form on either side of the cloacal
DESCRIPTION membrane, and fuse anteriorly at the genital HISTORY
r Common congenital disorder of male external r Family history of hypospadias
tubercle
genitalia characterized by a ventrally displaced – Lateral labioscrotal folds fuse posteriorly and – Any associated congenital anomalies
urethral meatus separate the urogenital and anal membranes ◦ Exposure of mother to hormonally active agents
– Associated conditions may include: – Under influence of testosterone and DHT, phallus during pregnancy
◦ Ventral chordee r IVF may increase risk of hypospadias
elongates and the genital folds fuse in the midline
◦ Incomplete foreskin with dorsal hood and to enclose urethral proximally to distally PHYSICAL EXAM
ventral deficiency – Canalization of the glans occurs distally, fusing r Determine location of urethral opening
– May be an isolated defect or may be associated with urethra r Evaluate for chordee
with a significant underlying abnormality – Process complete by 20th wk of gestation r Evaluate foreskin
– Classification: r Glandular hypospadias likely represents failure of
r Evaluate presence of inguinal hernia, hydrocele, or
◦ Anterior (distal) 50%: Glandular, coronal, distal canalization
subcoronal, megameatus intact prepuce r Proximal hypospadias due to failure of fusion of cryptorchidism
◦ Middle (midshaft) 30% r Severely proximal hypospadias may be associated
genital folds
◦ Posterior (proximal) 20%: Penoscrotal, scrotal, r Scrotal or perineal variants result in cleft scrotum with bifid scrotum and/or penoscrotal transposition
perineal – Look for other congenital anomalies
EPIDEMIOLOGY r Growth restriction (low birth weight and length,
Incidence small head circumference) has been associated with Lab
r 1 in 250–300 live male births Karyotype and hormonal evaluation to rule out
hypospadias
r 1 in 80–100 in family history of hypospadias r Associated anomalies are more common in cases of intersex is needed in cases of severe hypospadias and
cryptorchidism
Prevalence severe hypospadias
Prevalence in US for hypospadias ranges between – Cryptorchidism (7–9%) Imaging
– Inguinal hernia/hydrocele (9–16%) r No routine imaging necessary for routine
2.01 and 56.17 per 10,000
– Syndromes: hypospadias evaluation
RISK FACTORS ◦ 49 described in which hypospadias is frequent – In setting of intersex evaluation, genitogram or
r 5× incidence in IVF births compared to controls
or occasional (Aniridia-Wilms tumor association, pelvic US may be performed
r Environmental: – VCUG in proximal hypospadias may demonstrate
Beckwith–Wiedemann, Smith–Lemli–Opitz,
– Because of increases in rates in certain areas an Trisomy syndromes [4p, 9p, 13, 18], VACTERL prominent prostatic utricle
association with chemicals with estrogenic or association, XXY, Zellweger, and many others) Diagnostic Procedures/Surgery
antiandrogenic effects has been suggested ◦ 78% of these have associated micropenis, N/A
– Examples include environmental chemicals such cryptorchidism, and/or scrotal anomaly
as bisphenol A (BPA) and hormones used during ◦ In presence of hypospadias and cryptorchidism Pathologic Findings
pregnancy such as progesterone. must rule out intersex condition (15% with N/A
– Genetics (see below) palpable undescended testicle, 50% with DIFFERENTIAL DIAGNOSIS
Genetics nonpalpable) r In cases of proximal hypospadias associated with an
r <5% of cases have genetic cause (2) r 2–12% have upper tract anomalies (horseshoe undescended testicle differential should include:
r Can be seen in isolated and syndromic genetic kidney, renal ectopia, duplicated ureters, others) r Congenital adrenal hyperplasia
abnormalities r Enlarged prostatic utricle can be associated with r Mixed gonadal dysgenesis
r Caused by mutations of genes controlling severe cases and may increase risk of UTI or r Partial androgen insensitivity
development of male gonads or penis (eg, prostatic utricle stone formation r True hermaphroditism
homeobox, FGF, and Sonic hedgehog genes) GENERAL PREVENTION
r 5α-reductase mutations
Not possible except by avoidance of environmental ALERT
r Familial propensity Do not perform circumcision in the setting of
agents or medications with estrogenic effects by
– 10% have affected 1st–3rd degree relative pregnant women (see “Risk Factors”) hypospadias. Hypospadias in the presence of
– 14% of male siblings affected cryptorchidism may signal an intersex disorder.
– 27% concordance in monozygotic twins
204
HYPOSPADIAS

N/A 1. Subramaniam R, Spinoit AF, Hoebeke P.
GENERAL MEASURES (3) Hypospadias repair: An overview of the actual
The general tenets of repair are to move the urethral
Additional Therapies techniques. Semin Plast Surg. 2011;25(3):
Patient may need revisions for chordee, meatal issues, 206–212.
meatus to an orthotopic location, straighten the penis
or recurrent chordee at later dates
(repair chordee), and either remove or modify the 2. Akre O, Boyd HA, Ahlgren M, et al. Maternal and
foreskin to give the appearance or a normal Complementary & Alternative gestational risk factors for hypospadias. Environ
circumcised or uncircumcised penis Therapies Health Perspect. 2008;116(8):1071–1076.
Psychosocial support for patient and family if needed 3. Bhat A. General considerations in hypospadias
MEDICATION
long term surgery. Indian J Urol. 2008;24(2):188–194.
First Line
r There is no specific medical therapy for hypospadias 4. Netto JM, Ferrarez CE, Schindler Leal AA, et al.
Hormone therapy in hypospadias surgery: A
– Preoperative hormonal therapy (testosterone ONGOING CARE systematic review. J Pediatr Urol. 2013;9(6 Pt B):
injections or creams, or HCG injections) may be
used to enlarge penile size to aid in repair in cases PROGNOSIS 971–979.
of small phallus (4) Most patients have normal penile function for voiding,
– However, although a preference for the use of sexual performance, and insemination
preoperative hormonal therapy is observed in the ADDITIONAL READING
COMPLICATIONS
literature, the exact protocol and benefit is not r Early: Macedo A Jr, Rondon A, Ortiz V. Hypospadias. Curr
conclusively determined – Bleeding/hematoma—treated with compression Opin Urol. 2012;22(6):447–452.
– 25–50 mg of testosterone propionate given IM or surgical exploration; infection—treated with
weekly for 3 wk preoperatively is one such antibiotics or incision and drainage;
r Bifid Scrotum
approach – UTI—treated with appropriate antibiotics; r Disorder of Sexual Development (DSD)
SURGERY/OTHER PROCEDURES – Wound dehiscence—requires reoperation 6 mo
r Indications of repair (1): r Hypospadias Image
later
r Late: r Penoscrotal Transposition
– Goals are to create a cosmetically normal
appearing penis with orthotopic meatus, and – Residual/recurrent chordee—treated with
straight phallus so the child can in the future void reoperation,
while standing, have sexual intercourse, and – Meatal stenosis—treated with meatal dilation or CODES
effectively inseminate. meatoplasty
– Timing of repair is ideal at 4–6 mo of age, – Urethral stricture—treated with dilation or ICD9
surgeries should be complete by 2 yr (the age of urethroplasty; r 752.61 Hypospadias
genital awareness) – Urethrocutaneous fistula or urethral r 752.63 Congenital chordee
– Techniques dictated by meatal location, degree of diverticulum—treated with excision and repair; r 752.69 Other penile anomalies
chordee, and skin availability – Hair in urethral repair—treated with endoscopic
laser or cauter or excision and repair;
H
– Chordee should be repaired 1st (orthoplasty) ICD10
– Distal hypospadias: MAGPI, Thiersch–Duplay, – Lichen sclerosis or balanitis xerotica r Q54.0 Hypospadias, balanic
tubularized incised plate urethroplasty, Mathieu obliterans—treated with complete excision and r Q54.1 Hypospadias, penile
(perimeatal-based flap) buccal graft r Q54.9 Hypospadias, unspecified
– Midshaft hypospadias: Tubularized incised plate FOLLOW-UP
urethroplasty, Mathieu, onlay island flap
– Proximal hypospadias: 1 stage—Thiersch–Duplay, Patient Monitoring CLINICAL/SURGICAL
r Follow-up for observation of penile development
incised plate urethroplasty, onlay island flap; 2 PEARLS
stage—1st stage repair chordee, second stage and complications noted above
6 mo after 1st (Thiersch–Duplay, incised plate – Children may present after toilet training or even r More severe cases (proximal) more likely to be
urethroplasty) as late as adolescence with newly diagnosed
associated with an intersex disorder.
◦ In cases of lack of skin may use buccal mucosal complications from repair as an infant r All members of the health care team must clearly
graft Patient Resources understand that circumcision should not be
◦ Hypospadias revision: Meatoplasty, fistula repair Urology Care Foundation http://www.urologyhealth. performed if hypospadias is present.
org/urology/index.cfm?article=130
205
LWBK1391-SEC-I LWBK1391-Gomella ch102.xml September 19, 2014 18:28
IMMUNOCOMPROMISED PATIENTS, UROLOGIC CONSIDERATIONS

Nathan Roberts, MD
r HIV/AIDS
BASICS – Unprotected high-risk sexual contact DIAGNOSIS
– Blood transfusion
DESCRIPTION – Uncircumcised Men HISTORY
r Immunocompromised patients have attenuated r HC
– Occupational exposure
immune responses caused by: r Tuberculosis – Ranging from pink urine to clot retention
– Immunosuppressive drugs (chemotherapy) – HIV infections: 14% of TB patients have HIV – Can also have bladder pain and or lower urinary
– Radiation (bone marrow irradiation) tract symptoms (LUTS)
– Hematopoietic stem cell transplant PATHOPHYSIOLOGY r HIV/AIDS (2)
r Cyclophosphamide/busulfan
– Malnutrition – Increased risk of transmission and acquisition of
– Disease processes (HIV, lymphoma, congenital – Metabolized in the liver to acrolein sexually transmitted infections
immune deficiencies, autoimmune disorders) ◦ toxic to urothelium; prolonged exposure in the ◦ Atypical and prolonged course; genital lesions
r Immunocompromised patients are at risk for bladder causes increased inflammatory do not respond to normal treatments
opportunistic infections mediators: Bladder mucosal edema, vascular ◦ Can present with symptomatic genitourinary
r Hematopoietic stem cell transplant dilation, and increased capillary fragility tract infections
◦ Long-term increased bladder cancer risk ◦ Testicular pain: Epididymitis/orchitis are
– Need preparative regimens to prevent rejection of r Polyoma virus–related hematuria (see Polyoma virus
transplanted graft: Complete myeloablative, common findings
Nonmyeloablative or +/– chemotherapy [BK, JC]), urologic considerations ◦ Can be positive for LUTS with prostatitis
r Miliary tuberculosis r HIV/AIDS ◦ Cystitis: Increased risk of bladder infections
– Virus targets CD4+ T cells ◦ Urolithiasis: Can present with typical complaints
– Hematogenous dissemination of Mycobacterium
◦ Virus targets CCR5 expressing CD4+ cells; of ureteral calculus (flank pain, nausea,
tuberculosis
– HIV coinfection is common; 38% with military TB with decreased CD4 lymphocyte count. Mucosal vomiting, dysuria, increased frequency, urgency)
tissues preferentially targeted, leads to ◦ Can present with voiding dysfunction
patients also have HIV
immunosuppression ◦ Commonly present with urinary retention
EPIDEMIOLOGY r TB genitourinary involvement ◦ Detrusor hyperreflexia, LUTS for bladder outlet
Incidence – Hematogenous spread → renal capillaries → syndrome
r HIV infections renal cortex → immune response → chronic r Miliary tuberculosis
– 2.7 million new HIV infections worldwide inflammation → granuloma with central caseous – Failure to thrive, fever of unknown origin and
r Tuberculosis necrosis → inflammation into renal tubules and night sweats, anorexia, weight loss
– 11,182 reported cases in US in 2010 medulla → renal papilla sloughing → calyceal ◦ Subacute or chronic presentation more
– 22% of cases were extrapulmonary ulceration → fibrosis from healing → calyceal common; can have dysfunction of one or more
– 2.7% were miliary TB infundibular narrowing or UPJ scarring → organ system
hydronephrosis ◦ 50% have pulmonary disease with dyspnea or
Prevalence
– Tubercles can also form in distal ureter leading to cough
HIV/AIDS: 1.2 million Americans
stricture – Genitourinary involvement
RISK FACTORS ◦ Hematuria; small percentage may be passing
r Hemorrhagic cystitis (HC) (1) ASSOCIATED CONDITIONS
r HIV/AIDS; indinavir calculus material in urine (caseous material)
– Increased degree of immunosuppression r TB ◦ Flank pain, symptoms of cystitis, LUTS (storage
◦ BK virus Hemorrhagic cystitis (HC) symptoms), scrotal pain, male infertility workup;
r Any cause requiring bone marrow transplant
– Early onset Hemorrhagic cystitis (HC) hematospermia
◦ Conditioning regimen used for Hematopoetic r Urethritis: Reiter syndrome, arthritis
stem cell transplant (HSCT) with GENERAL PREVENTION
cyclophosphamide, busulfan, or with r HIV/AIDS: Protection during sexual activity; universal
antithymocyte globulin (4) precautions for healthcare professionals
◦ Donor–recipient gender mismatch r Miliary tuberculosis: Treatment of latent TB can
– Late onset Hemorrhagic cystitis (HC)
◦ Allogenic HSCT transplant prevent miliary TB
◦ Graft versus host disease (GVHD)
– Use of corticosteroids or cyclosporine for GVHD
◦ Use of T-cell depleted grafts
◦ Need for blood transfusions
206
PHYSICAL EXAM Imaging Diagnostic Procedures/Surgery

r HC r HC r HC
– May present with palpable bladder if in clot – CT with and without contrast: Can show clot, – Cystoscopy, possible ureteroscopy
retention filling defect, calculus r HIV/AIDS
r HIV/AIDS r HIV/AIDS – Kidney biopsy: Help to diagnose HIV-associated
– Most common intrascrotal pathology in AIDS is – Urolithiasis nephropathy (HIVAN)
testicular atrophy ◦ CT non contrast may be associated with minimal – Voiding dysfunction
◦ Secondary to endocrine imbalances, febrile findings with indinavir calculus ◦ May warrant UDS, may uncover neurogenic
episodes, malnutrition, testicular infections, and – Kidney infection voiding dysfunction
toxic effects of therapeutic agents ◦ CT scan: Can see striated nephrogram in ◦ Post-void residuals, cystoscopy
– Prostatitis pyelonephritis, abscess r Tuberculosis
◦ Boggy prostate r Tuberculosis – Biopsy of the following can demonstrate
– Scrotal swelling/testicular pain – Chest radiograph (miliary disease) granulomas and be used for culture: lung, bone
◦ Epididymitis/orchitis caused by common and ◦ Faint, reticulonodular infiltrate distributed fairly marrow, lymph nodes, bones, joints, liver, brain,
uncommon organisms (Candida, CMV, uniformly throughout the lungs and other tissues
toxoplasmosis) – GU findings: Disparity in renal size. Larger may – Cystoscopy/retrograde pyelograms
– Voiding dysfunction indicate caseous lesions or shrunken and fibrotic ◦ Limited in diagnosis: Stricture, acute UO
◦ May have enlarged prostate from autonephrectomy inflammation, acute tuberculous ulcer. Golf hole
r Miliary tuberculosis ◦ Autonephrectomy: Diffuse, uniform, extensive ureter: Circular and often excessively lateral
– Pulmonary: Course breath sounds on auscultation, parenchymal, putty-like calcification, a lobar ureteral orifice
may have lymphadenopathy cast of the kidney Pathologic Findings
– Genitourinary involvement ◦ Calcifications in 30–50% of cases (seen in r Tuberculosis
◦ Possible costovertebral angle tenderness caseating lesions) – Granulomatous inflammation
◦ Epididymal/prostate tenderness ◦ Calculi may also be seen in the collecting system ◦ Contain epithelioid macrophages, Langhans
or ureter secondary to stricture formation giant cells, and lymphocytes
DIAGNOSTIC TESTS & INTERPRETATION ◦ Ureteral calcifications are rare and are
Lab ◦ Contain caseation necrosis
r HIV/AIDS characteristically intraluminal ◦ Organisms may or may not be seen with acid
◦ Bladder wall calcifications are not very common
– HIV ELISA for anti-HIV-1 and 2 fast staining
except in late cases of bladder contraction r HIV
◦ >99% sensitivity; Western blot to exclude ◦ Calcifications of the prostate and seminal
false-positive but also to confirm HIV diagnosis – HIV-associated nephropathy (HIVAN)
vesicles are seen in 10% of cases ◦ Collapsing form of focal segmental
– Plasma HIV RNA – Contrast-enhanced computed tomography
◦ Detectable by day 12; antibodies detected day ◦ Renal parenchymal masses and scarring glomerulosclerosis
21 ◦ Dilated tubules and interstitial inflammation
◦ Thick urinary tract walls
◦ Used to assess treatment response/failure ◦ Tuberculoma: Renal mass coalescing caseating DIFFERENTIAL DIAGNOSIS
HIV-associated nephropathy: Proteinuria- granulomas r HC
increased creatinine ◦ Can see hydronephrosis – Infectious source
r Tuberculosis ◦ Sensitive in seeing the calcifications ◦ Bacterial
– PPD; may be false negative ◦ Contrast can evaluate function of the kidney ◦ Viral BK vs. adenovirus, CMV, JC, and herpes
– Mycobacterial blood cultures – Ultrasound: Limited in diagnosis, Can be used for r HIV
◦ Urinalysis: Sterile pyuria, possible hematuria
◦ Urine acid fast bacilli (AFB) culture
monitoring disease progression – Voiding dysfunction
◦ Patient may have underlying neurologic
I
opportunistic infection
207
– E-aminocaproic acid Surgery

◦ Inhibits fibrinolysis preventing activation of r HIV/AIDS
TREATMENT
plasminogen to plasmin – Kidney infection abscess (Aspergillus and
GENERAL MEASURES ◦ Given orally, parenterally, or intravesically toxoplasma)
r Reduction of immunosuppression (if possible) can ◦ Patients can form hard clots that are difficult to ◦ Percutaneous or open drainage
help to reduce clinical sequelae flush from the bladder ◦ Nephrectomy
r HIV patients have higher risk of bladder infections – Intravesical instillation of prostaglandin – Prostatic abscess
than non-HIV patients ◦ PGE2: May encourage platelet aggregation and ◦ Percutaneous (transperineal vs. transrectal
– Associated with typical uropathogens induce vasoconstriction aspiration)
– Salmonella is of particular concern due to high-risk ◦ PGE2: 0.75 mg in 200 mL of normal saline and ◦ Transurethral unroofing (TUR)
fatal recurrence (may need chronic suppression) left indwelling – Testicular and epididymal infections
◦ May cause bladder spasms ◦ If intractable pain may warrant epididymectomy
MEDICATION – Intravesical instillation of formalin (40% or orchiectomy
First Line formaldehyde) r Tuberculosis
r HC ◦ Hydrolyzes proteins and coagulates tissue on – Often will proceed 3–6 wk after medications
– Increased hydration superficial level ◦ Abscess drainage
– Catheter placement with clot evacuation ◦ Painful and needs to be done with general ◦ Ureteral stenting for strictures (41% successful)
– Continuous bladder irrigation (CBI) anesthesia ◦ PCN: TB fistula can form
r HIV/AIDS ◦ Should not be done with VUR. Can fibrose the ◦ Nephrectomy: If kidney is nonfunctioning, there
– Antiretroviral therapy (ART) ureters, cause obstruction, hydronephrosis and is extensive disease involving the whole kidney,
r Miliary TB (3) also papillary necrosis coexisting renal carcinoma
– Standard pulmonary therapy ◦ Can result in small contracted bladder ◦ Partial nephrectomy
– Often directly observed therapy r HIV/AIDS ◦ Epididymectomy: Caseating abscess that has
– Isoniazid (INH), rifamycin (rifampin), – Urinary tract infection (UTI) not responded to medical therapy or firm
pyrazinamide, and ethambutol for 2 mo ◦ Can treat with prolonged 7–10-day course of swelling that has remained unchanged or
– Isoniazid and rifamycin for additional 4 mo antibiotics increased in size with medial therapy
Second Line ◦ If patients do not respond to empiric antibiotics ◦ Augmentation cystoplasty (<100 cc capacity)
r HC attention should be turned and patients vs. orthotopic bladder substitution (20 cc
– Conjugated estrogens screened for atypical and opportunistic capacity)
◦ Act by stabilization of microvasculature infections (ie, fungi, parasites, TB, and viruses)
◦ Oral vs. intravenous administration – Prostatitis/Epididymitis/Orchitis r HC
– Intravesical instillation of Alum ◦ Should be treated with antibiotics
◦ Opportunistic infections should be suspected if – Hyperbaric oxygen therapy
◦ An astringent precipitates protein over bleeding ◦ 100% oxygen in a hyperbaric chamber at 2.5
surface not resolving
atmospheres absolute for 90 min 5 days a week.
◦ 1% Alum solution in continuous bladdder – Voiding dysfunction
◦ Individualized for the patient – Cystectomy if refractory life-threatening cases
irrigation (CBI) – Selective embolization
◦ Can be used in presence of vesico ureteral reflux ◦ Males: α-blockers possibly 5α-reductase
◦ Vesical or internal iliac artery
(VUR) inhibitors
– Intravesical instillation of silver nitrate ◦ Irritative symptoms: Anticholinergics if low
◦ Chemical coagulation and eschar at bleeding PVR’s
sites
◦ 0.5–1% instilled for 10–20 min
◦ VUR may lead to renal failure due to
precipitation and obstruction of upper tracts
208
ADDITIONAL TREATMENT FOLLOW-UP

Additional Therapies Patient Monitoring CODES
r Oxazaphosphorine (cyclophosphamide)-induced HC r Hemorrhagic cystitis (HC)
– Mesna – Cyclophosphamide ICD9
◦ Binds to acrolein and inactivates it ◦ 9-fold increase in urothelial carcinoma r 279.9 Unspecified disorder of immune mechanism
– Supra hydration ◦ 10-yr latency period r 279.49 Autoimmune disease, not elsewhere
– Prophylactic Continuous bladder irrigation (CBI) classified
◦ Often occurs within 72 hr r 279.50 Graft-versus-host disease, unspecified
REFERENCES
ICD10
ONGOING CARE 1. Manikandan R, Kumar S, Dorairajan LN. r D89.9 Disorder involving the immune mechanism,
Hemorrhagic cystitis: A challenge to the urologist. unspecified
PROGNOSIS Indian J Urol. 2010;26:159–166.
r HIV/AIDS r D89.813 Graft-versus-host disease, unspecified
2. Shindel AW, Akhavan A, Sharlip ID. Urologic r M35.9 Systemic involvement of connective tissue,
– Greatly improved in the era of HAART therapy aspects of HIV infection. Med Clin North Am.
– Cancer unspecified
2011;95(1):129–151.
◦ Penile: 8-fold higher incidence
◦ Testicular cancer: 2-fold increase in seminoma 3. Cek M, Lenk S, Naber KG, et al. EAU guidelines for
r Miliary tuberculosis the management of genitourinary tuberculosis. Eur CLINICAL/SURGICAL
Urol. 2005;48(3):353–362.
– Greatly improved with the introduction of PEARLS
4. Gyurkocz B, Rezvani A, Storb RF. Allogeneic
antibiotics r Recurrent UTI in the absence of infections in other
hematopoietic cell transplantation: the state of the
– Mortality previously 100% (preantibiotics) now
art. Expert Rev Hematol. 2010;3(3):285–299. organ systems, is not a typical presentation of an
20%
immunocompromised patient.
COMPLICATIONS r Most common intrascrotal pathology in AIDS is
r Increased risk for malignancy in immunosuppressed ADDITIONAL READING testicular atrophy.
patients
r HIV/AIDS Lee SH, Hong SH, Lee JY, et al. Asymptomatic
– 3.5% of HIV-infected patients will experience hematuria associated with urinary polyomavirus
HIV-associated nephropathy infection in immunocompetent patients. J Med Virol.
◦ Caucasian patients 12:1 risk 2014;86(2):347–353.
◦ Intravenous drug use and men who have sex See Also (Topic, Algorithm, Media)
with men association r Cystitis, Hemorrhagic (Infectious, Non-Infectious,
r Tuberculosis Radiation)
– Percutanous nephrostomy (PCN) r HIV/AIDS, Urologic Considerations
◦ Tuberculosis fistula formation r HIV/AIDS, Urologic Considerations Image
– Ureteral stenting r Polyoma Virus (BK, JC), Urologic Considerations
◦ Limit high-pressure contrast injection during r Tuberculosis, Genitourinary, General Considerations
retrograde pyelogram may disseminate infection r Tuberculosis, Kidney and Ureter
209
INCONTINENCE, URINARY, ADULT FEMALE

Debra L. Fromer, MD
Drew A. Freilich, MD
r Urge incontinence: Detrusor overactivity (may be DIAGNOSTIC TESTS & INTERPRETATION

BASICS secondary to detrusor myopathy or neuropathy) Lab
r OI: Urinary retention (usually from lower motor r Urine analysis
DESCRIPTION paralytic neurogenic bladder in women) r Urine culture: Assess for infection
r Incontinence is broadly defined as the loss of urine r Total incontinence: Constant loss of urine. Ectopic
that is objectively demonstrable and is of social and Imaging
ureters in females usually open in the urethra distal r CT urogram: Determines status of upper urinary
hygienic concern to the sphincter or in the vagina, causing continuous
r Stress urinary incontinence (SUI): Involuntary loss of tract, duplicated systems for ectopic ureters, and
leakage
urine on effort of physical exertion associated pathologies (indicated only when upper
– Suspect fistula if pneumaturia or fecaluria in
r Urgency incontinence (UI): Involuntary loss of urine tract issues are suspected)
history of radiation r Voiding cystourethrogram: Preferably done in
associated with urgency r Coital incontinence: Up to 60% of women who
r Mixed incontinence (MI): Lost of urine associated combination with videourodynamic studies
report incontinence appear to leak urine during
with urgency and also with effort intercourse Diagnostic Procedures/Surgery
r Overflow incontinence (OI): High residual or chronic r 24-hr voiding diary to assess frequency, timing,
ASSOCIATED CONDITIONS volume of symptoms
urinary retention leads to urinary spillage from r Pelvic organ prolapse
bladder overdistention r Cystoscopy: If concern for fistula or malignancy
r Diabetes r Urine cytology: If hematuria and urgency (concern
r Functional incontinence: Loss of urine due to deficits
r Neurologic disease (ie, multiple sclerosis, Parkinson)
of cognition and mobility for carcinoma in situ)
r Coital incontinence: leakage urine during intercourse GENERAL PREVENTION r Urodynamic studies:
r Continuous incontinence: Continuous involuntary r Weight loss – Filling cystometry: Pressure/volume relationship
loss of urine r Optimization of medical health (ie, diabetes) during bladder filling
r Smoking cessation ◦ Assess 1st sensation, desire to void, strong
EPIDEMIOLOGY desire to void, capacity, detrusor overactivity
Incidence ◦ Assess Valsalva leak point pressure: Determines
N/A DIAGNOSIS the intra-abdominal pressure at which leakage
Prevalence is observed at the meatus or by fluoroscopy; low
r Affects 30–50% of adult women HISTORY leak point pressure (<60 mm H2 O) implies ISD
r Parity: Weakness of the pelvic floor is more likely in ◦ Assess detrusor leak point pressure: Lowest
r Stress urinary incontinence is the most common
multiparous women leading to SUI detrusor pressure at which leakage of urine
(49%), followed by mixed (29%) and urge (21%) r Amount and frequency of leakage
incontinence occurs in absence of detrusor contraction and
r Continuous slow leakage in between regular voiding increase abdominal pressure (>40 cm H2 O risk
RISK FACTORS indicates ectopic ureter, urinary fistula, etc. or renal deterioration)
r Advanced age r Pain: Suprapubic pain with dysuria implies urinary – Voiding cystometry: Pressure/volume relationship
r Cognitive impairment during micturition
infection, interstitial cystitis, etc.
r COPD r Medical history: ◦ Assess urinary flow rate, postvoid residual,
r Menopause – Cerebrovascular accidents, Parkinsons disease, detrusor sphincter synergy
r Obesity multiple sclerosis, myelodysplasia, diabetes, spinal – Videourodynamic studies: Combination of
r Pelvic organ prolapse cord injury fluorocystourethrography and urodynamic studies
r Pelvic surgery or radiation – Radiation to pelvic and vaginal areas: Causes ISD, mentioned above
r Pregnancy urgency, and low bladder compliance ◦ Most useful in patients at risk for neurogenic
r Smoking r Medications bladder to assess for detrusor sphincter
r Surgical history: Pelvic and vaginal surgeries can dyssynergia which is risk for renal deterioration
r Vaginal childbirth
weaken the pelvic floor support Pathologic Findings
Genetics N/A
Evolving data to support genetic predisposition PHYSICAL EXAM
r General neurologic exam: DIFFERENTIAL DIAGNOSIS
PATHOPHYSIOLOGY – Mental status, speech, intellectual performance r Stress incontinence: Due to urethral hypermobility or
r Stress incontinence: Occurs with increased
– Motor status: Gait, generalized or focal weakness, ISD, although in the majority it is mixed or due to
intra-abdominal pressure without detrusor rigidity, tremor both of the factors
contraction. 2 types: – Sensory status: Impairment of perineal-sacral area r Urgency incontinence: Can be due to urinary
– Anatomic: Due to urethral hypermobility from lack sensation helps localize the level of neurologic infection, interstitial cystitis, carcinoma in situ,
of pelvic support deficit bladder calculi, detrusor overactivity, or neurogenic
◦ Hammock theory: Normally, the suburethral – Reflex: A bulbocavernous reflex implies detrusor overactivity. Most often idiopathic
support contributed by the endopelvic fascia contraction of the anal sphincter in response to r Nocturnal enuresis: Idiopathic, neurogenic,
and anterior vaginal wall provides a stable squeezing the clitoris. This reflex tests the integrity cardiogenic, or obstructive causes
backboard against which the urethra is of S2–S4 spinal cord segments r Continuous leakage: Ectopic ureter, urinary fistulas,
compressed while intra-abdominal pressure r Urologic exam:
exstrophy–epispadias complex
rises. When this suburethral support layer is lax – Abdomen: Scars of previous surgeries r Postvoid dribbling: Urethral diverticulum, idiopathic
and mobile, any effective compression is not – Suprapubic tenderness: May indicate cystitis
achieved, causing leakage or iatrogenic
– Palpable bladder: Chronic urinary retention r Mobility or cognitive impairment post stroke
– Intrinsic sphincter deficiency (ISD): Impairment of r Pelvic exam: r Coital or mixed incontinence
urethral mucosal seal and inherent closure from – The patient is asked to cough or strain to
collagen, fibroelastic tissue, smooth and striated reproduce incontinence or demonstrate urethral
muscles. May be lost secondary to surgical hypermobility (Q-tip test positive if >30 degrees)
scarring, radiation, or hormonal and senile – Assess for atrophic vaginitis
changes – Examine vaginal for cystocele, enterocele,
rectocele, or uterine descensus
210
INCONTINENCE, URINARY, ADULT FEMALE
ADDITIONAL TREATMENT 4. Shamliyan T, Wyman JF, Ramakrishnan R, et al.

TREATMENT Radiation Therapy Benenefits and harms of pharmacologic treatment
N/A for urinary incontinence in women: A systematic
GENERAL MEASURES (1) review. Ann Intern Med. 2012;156(12):861–874.
r Nonsurgical management (helps ∼50–65% Additional Therapies [A]
Reduction or avoidance of spicy foods, citrus, or
patients with milder symptoms) 5. Schierlitz L, Dwyer PL, Rosamilia A, et al.
r Treat correctable causes (Atrophic vaginitis, chocolate; limiting excessive fluid intake and caffeine
Three-year follow-up of tension-free vaginal tape
can improve symptoms of urinary incontinence
constipation, UTI, fistula, etc.) compared with transobturator tape in women with
r Encourage weight loss in obese patients (especially if overactive bladder)
stress urinary incontinence and intrinsic sphincter
r Biofeedback and pelvic floor exercises (Kegel Complementary & Alternative deficiency. Obstet Gynecol. 2012;119(2 Pt 1):
exercise) (3) Therapies 321–327. [A]
r Behavioral therapy: Voiding at progressively No high-level data to support
increasing predetermined intervals
ONGOING CARE ADDITIONAL READING
MEDICATION
r Dmochowski RR, Blaivas JM, Gormley EA, et al.
First Line (2) PROGNOSIS
r Stress incontinence: Activation of α-adrenergic Update of AUA Guideline on the surgical
Excellent prognosis for many patients with awareness management of female stress urinary incontinence.
receptors in the internal urethral sphincter increases of this condition, combined with advances in diagnosis
the urethral resistance to urinary flow with J Urol. 2010;183(5):1906–1914.
and management to minimize associated morbidity of r Jha S, Strelley K, Radley S. Incontinence during
sympathomimetic drugs, estrogen, and tricyclic this condition.
agents (not used commonly due to side effects and intercourse: myths unravelled. Int Urogynecol J.
interaction concerns and potential-limited efficacy) COMPLICATIONS 2012;23(5):633–637.
r Urge incontinence: Anticholinergic, antispasmodic, r Prolonged exposure to urine causes skin breakdown r Winters JC, Dmochowski RR, Goldman HB, et al.
and tricyclic antidepressant medications have been and dermatitis, which may lead to ulceration and Urodynamic studies in adults: AUA/SUFU guideline.
used to treat overactive bladder symptoms secondary infection (4) J Urol. 2012;188(Suppl 6):2464–2472.
r Catheter-related complications can result from https://www.auanet.org/common/pdf/education/
– Mirabegron is a 1st in class β 3 -agonist for
treatment of urge incontinence. When compared long-term indwelling catheters, such as recurrent clinical-guidance/Adult-Urodynamics.pdf (Accessed
to anticholinergic medications much less dry UTIs, skin infections, and urethral erosion April 7, 2014)
mouth and constipation, but risk of hypertension FOLLOW-UP See Also (Topic, Algorithm, Media)
◦ Mirabegron (25–50 mg/d) r Coital Incontinence (Coital leakage/Intercourse
Patient Monitoring
Second Line r Initial postoperative assessment after midurethral Incontinence)
Other antichlonergic agents oxybutynin, ect. sling: Evaluate voiding function with estimation of r Ejaculation, Female
postvoid residual and need for intermittent r Incontinence, Urinary, Adult Female Image
r Stress urinary incontinence catheterization r Overactive Bladder
r Periodic long-term follow-up with validated r Pelvic Organ Prolapse
– Vaginal pessary
– Surgical management: Provides more successful outcome-based questionnaire surveys r Urethral Sling, Indications and Anatomic Positions
and sustained outcome (5) Patient Resources r Urethral Sling, Materials
◦ Periurethral injection of bulking agents: Calcium National Kidney and Urologic Diseases Information
hydroxylapatite/sodium carboxymethylcellulose Clearinghouse (NKUDIC) http://kidney.niddk.nih.
and hyaluronic acid
◦ Pubovaginal sling suspension: Used for
gov/kudiseases/pubs/uiwomen/ CODES I
coaptation and compression of the incontinent
urethra, using autologous fascia or xenograft or REFERENCES ICD9
r 625.6 Stress incontinence, female
allograft materials r 788.30 Urinary incontinence, unspecified
◦ Midurethral sling: Controversial as to if 1. Gormley EA, Lightner DJ, Burgio KL, et al.
Diagnosis and treatment of overactive bladder r 788.31 Urge incontinence
retropubic (TVT) or transobturator (TOT) better
(non-neurogenic) in adults: AUA/SUFU guideline.
for urethral hypermobility and ISD patients
Postoperative de novo urgency, urge
J Urol. 2012;188:2455–2463. [B] ICD10
r N39.3 Stress incontinence (female) (male)
incontinence, voiding difficulty, and urinary 2. Madhuvrata P, Cody JD, Ellis G, et al. Which
anticholinergic drug for overactive bladder r N39.41 Urge incontinence
retention, necessitating intermittent r R32 Unspecified urinary incontinence
self-catheterization or take-down of the symptoms in adults. Cochrane Database Syst Rev.
suspension, remain as concerns in up to 2012;1:CD005429. [A]
∼20% of patients 3. Dumoulin C, Glazener C, Jenkinson D, et al.
Determining the optimal pelvic floor muscle CLINICAL/SURGICAL
– Artificial urinary sphincter (not FDA approved for
female incontinence) training regimen for women with stress urinary PEARLS
r Refractory overactive bladder (failed 1st- and incontinence. Neurourol Urodyn. 2011;30(5):
r Recent FDA Alerts regarding vaginal mesh applies to
746–753. [B]
2nd-line therapies including anticholinergics): prolapse repair and not midurethral sling. Mesh for
– Sacral neuromodulation: Efficacy ∼50% of stress incontinence has been supported in multiple
patients who have failed other treatments randomized controlled trials.
– Percutaneous tibial nerve stimulation r Consider reduction of pelvic organ prolapse as part
– Intravesical botulinum toxin for neurogenic of evaluation for incontinence.
detrusor overactivity or refractory UI r Consider referral to neurologist in young patients
◦ Efficacy: Up to ∼75% improved/cured in those
with refractory idiopathic overactive bladder as 1st
refractory to other medical treatment
◦ Side effects: UTI (∼25%), Urinary retention presenting symptom of multiple sclerosis is isolated
urinary urgency in ∼15%.
(∼10%) (patients must be counseled about
possible need for postoperative intermittent
catheterization)
211
INCONTINENCE, URINARY, ADULT MALE


r Creatinine
DESCRIPTION HISTORY – If significant retention suspected
r Voiding symptoms
Defined by International Continence Society, urinary r Urinalysis
incontinence is the involuntary loss of urine that – Duration and characteristics of incontinence
– Stress, urge, total – Glucosuria, infection
presents a social or hygienic problem
– Precipitants and associated symptoms Imaging
EPIDEMIOLOGY – Use of pads, briefs, diapers None usually indicated
Incidence – Fluid intake Diagnostic Procedures/Surgery
No published reports on incidence – Alteration in bowel habits r Urodynamics
Prevalence – Previous treatments and effect on incontinence – Useful for confirming bladder outlet obstruction as
r 3–11% overall prevalence rate of incontinence in r Diabetes mellitus
a possible cause of detrusor overactivity
male population r Associated conditions
r NOBLE study Pathologic Findings
– Neurologic disease
r Medication use N/A
– Urge incontinence
◦ 2.6% American men of all ages – Diuretics DIFFERENTIAL DIAGNOSIS
r Alcohol and drug use including caffeine r Urge incontinence
– After age 64, prevalence rose sharply
◦ ∼10% in men ≥75 (1) r Radical pelvic surgery or radiation – Loss of urine accompanied by urgency; often
– Reaches 31% in men ≥85 (2) – Abdominoperineal resection related to triggers such as sounds of running
r Stress incontinence in men is rare – Radical prostatectomy water, cold weather, passing a restroom
r Stress incontinence
– Unless attributable to prostate surgery, neurologic
disease, or trauma PHYSICAL EXAM – Urinary leakage associated with exertion, lifting,
r Abdominal exam
r Incontinence after prostatectomy ranges from 1% coughing, sneezing
– Suprapubic mass r Mixed incontinence
after transurethral resection to 2–57% after radical ◦ Suggests retention
prostatectomy – Urinary leakage associated with both stress and
r Incontinence in male of all ages is ∼1/2 as – Suprapubic tenderness urge incontinence
◦ Suggests UTI r Low bladder compliance resulting in overflow
prevalent as it is in women – Surgical scars suggesting pelvic surgery
incontinence
RISK FACTORS – Skin lesions associated with neurologic disease r Continuous urinary incontinence is the continuous
r Age ◦ Neurofibromatosis and café au lait spots
r Neurologic disease r External genitalia loss of urine
r Post micturition dribble
r Prostate surgery r Prostate
r Pelvic trauma r Spine/back – The involuntary loss of urine immediately after he
r Skeletal deformities has finished passing urine, usually after leaving
Genetics the toilet
r Scars from previous spinal surgery r Mobility or cognitive impairment post stroke
N/A
r Sacral abnormalities may be associated with
PATHOPHYSIOLOGY neurologic bladder dysfunction
r Incontinence secondary to bladder abnormalities
– Cutaneous signs of spinal dysraphism TREATMENT
– Detrusor overactivity results in urge urinary ◦ Subcutaneous lipoma
incontinence (UUI) ◦ Vascular malformation, tuft of hair, or skin GENERAL MEASURES
◦ Associated with bladder outlet obstruction from r Bladder diaries are invaluable
dimple on lower back
benign prostatic hyperplasia (BPH) – Cutaneous signs of sacral agenesis – Help patients understand patterns of incontinence
r Incontinence secondary to outlet abnormalities ◦ Low, short gluteal cleft r Time voiding
– Sphincteric damage ◦ Flattened buttocks – Avoids significant bladder distention
◦ Secondary to pelvic surgery or radiation ◦ Coccyx not palpable r For postradical prostatectomy incontinence see
– Sphincteric dysfunction r Focal neurologic exam Section I: Incontinence, urinary, following radical
◦ Secondary to neurologic disease – Motor function prostatectomy
r Mixed incontinence is due to abnormalities of both ◦ Inspect muscle bulk for atrophy
MEDICATION
bladder and the outlet ◦ Tibialis anterior (L4–S1): Dorsiflexion of foot
◦ Gastrocnemius (L5–S2): Plantar flexion of foot First Line
ASSOCIATED CONDITIONS r Urge incontinence
r Neurologic disease ◦ Toe extensors (L5–S2): Toe extension
r Sensory function – Antimuscarinics: Inhibit the effect of acetylcholine
– Parkinson disease, multiple sclerosis at postjunctional muscarinic receptors on detrusor
r Pelvic radiation r Reflexes
muscle cells
r Pelvic trauma – Anal reflex (S2–S5) ◦ Tolterodine (2–4 mg/d)
r BPH ◦ Gently stroke mucocutaneous junction of ◦ Trospium XR (60 mg/d)
r Prostate surgery circumanal skin ◦ Darifenacin (7.5–15 mg/d)
◦ If visible contraction (wink) absent, suggests ◦ Solifenacin (5–10 mg/d)
GENERAL PREVENTION peripheral nerve or sacral (conus medullaris) ◦ Oxybutynin (IR 7.5–20 mg/d, XL 5–30 mg/d,
None abnormality patch twice weekly)
– Bulbocavernosus reflex (BCR) (S2–S4) ◦ Fesoterodine (4–8 mg/d)
◦ Elicited by squeezing glans to cause reflex – β 3 -adrenergic agonist agent: Promotes detrusor
contraction of anal sphincter muscle relaxation
◦ Absence of BCR suggests sacral nerve damage ◦ Mirabegron (25–50 mg/d)
212
INCONTINENCE, URINARY, ADULT MALE
r Stress incontinence r Absorbent products (pouches, absorbant pants, 5. Moore, KC, Lucas, MG. Management of male
– No generally accepted drug therapy small pads) were evaluated in a multi-center, urinary incontinence. Indian J Urol. 2010;26(2):
– Tricyclics sometimes used multi-crossover study (7) 236–244.
◦ Imipramine 10–25 mg PO BID-TID – The conclusion was that no one product suits 6. Moore KN, Schieman S, Ackerman T, et al.
Second Line every patient although small pads came closest Assessing comfort, safety, and patient satisfaction
r Urge incontinence – Washable absorbant pants for men with light with three commonly used penile compression
– Tricyclic antidepressants incontinence have economic advantages devices. Urology. 2004;63:150–154.
◦ Imipramine 10–25 mg PO BID-TID 7. Fader M, Macaulay M, Pettersson L, et al. A
– DDAVP for nocturnal symptoms multi-centre evaluation of absorbent products for
◦ 0.1–0.5 mg PO or intranasal QHS (off label)
ONGOING CARE men with light urinary incontinence. Neurourol
◦ Avoided in patients with cardiac disease and PROGNOSIS Urodyn. 2006;25:689–695.
older patients Continence can be improved in almost all patients
◦ Risk of significant hyponatremia
– Intradetrusor botulinum toxin injections COMPLICATIONS ADDITIONAL READING
r Candidiasis
SURGERY/OTHER PROCEDURES r Dermatitis Burden H, Warren K, Abrams P, et al. Diagnosis of
r Urge incontinence r Skin breakdown male incontinence. Curr Opin Urol. 2013;23(6):
– Sacral neuromodulation 509–514.
– Augmentation cystoplasty FOLLOW-UP
r Stress incontinence Patient Monitoring See Also (Topic, Algorithm, Media)
r Bladder Areflexia (Detrusor Areflexia)
– Urethral bulking agent Monitor post-void residual in patients on r Cunningham Clamp
– Male sling procedure anticholinergic medications
r Incontinence Clamps
◦ Promising short-term results Patient Resources r Incontinence, Urinary, Adult Male Image
◦ No long-term studies (3)[B] Urology Care Foundation. Surgical Management of r Incontinence, Urinary, Following Radical
– Artificial urinary sphincter Urinary Incontinence http://www.urologyhealth.
org/urology/index.cfm?article=33, Accessed April Prostatectomy
◦ Excellent long-term continence rates (4)[A] r Incontinence, Urinary, with Orgasm (Climcaturia)
2013.
r Lower Urinary Tract Symptoms (LUTS)
Radiation Therapy REFERENCES
N/A
1. Stewart WF, Van Rooyen JB, Cundiff GW, et al. CODES
r Pelvic floor exercise (Kegels) Prevalence and burden of overactive bladder in the
US. World J Urol. 2003;20:327–336. ICD9
– Significantly improve SUI/UUI r 788.30 Urinary incontinence, unspecified
r Biofeedback 2. Anger JT, Saigal CS, Stothers L, et al. Urologic
Diseases of America Project. The prevalence of r 788.31 Urge incontinence
r Timed voiding in UUI
urinary incontinence among community dwelling r 788.32 Stress incontinence, male
r Overflow incontinence due to poor bladder
men: Results from the National Health and
contractility with urinary retention Nutrition Exam survey. J Urol. 2006;176(5): ICD10
– Indwelling catheter r N39.3 Stress incontinence (female) (male)
2103–2108.
– Intermittent catheterization r N39.41 Urge incontinence
3. Comiter CV. The male sling for stress urinary
– Evaluate for outlet obstruction incontinence: A prospective study. J Urol.
r R32 Unspecified urinary incontinence I
Complementary & Alternative 2002;167:597–601.
Therapies 4. Elliott DS, Barrett DM. Mayo Clinic long-term
r Penile clamps, condom catheters, and pads are analysis of the functional durability of the AMS 800
CLINICAL/SURGICAL
occasionally used artificial urinary sphincter: A review of 323 cases. PEARLS
r They should be reserved for minor degrees of J Urol. 1998;159:1206–1208. r Prevalence of incontinence in males is 50% that of
incontinence or in patients who have multiple other
women.
comorbidities in whom surgery may be thought r Continence can be improved in almost all patients.
inappropriate (5)
r Penile compression clamps r An Artificial urinary sphincter has excellent
– Applied externally to the penis to exert long-term continence rates.
nonsurgical compression of the urethra, thereby
preventing leakage of urine
– 3 types of commercially available penile
incontinence clamps (C3, U-Tex Male Adjustable
Tension Band and Cunningham clamp) have been
studied in a small trial (6)
– No device completely eliminated leakage when
applied at a comfortable pressure
– Complications of penile clamps can include
edema, pain, urethral erosion, and obstruction
– Penile clamps should not be used for more than
4 hrs at a time
213
INCONTINENCE, URINARY, FOLLOWING RADICAL PROSTATECTOMY

ASSOCIATED CONDITIONS DIAGNOSTIC TESTS & INTERPRETATION (C)

BASICS r Anastomotic stricture/bladder neck contracture
Lab
r Detrusor Instability (DI)/Overactive bladder (OAB) Urinalysis to exclude urinary tract infection
DESCRIPTION r Sphincteric incompetence
r Post-prostatectomy incontinence (PPI) is a Imaging
well-recognized complication of radical GENERAL PREVENTION Sonographic post-void residual (PVR)
r Achieving a bloodless surgical field following
prostatectomy (RP) whether performed openly Diagnostic Procedures/Surgery
(perineal retropubic) or laparoscopically with or anatomic ligation of the dorsal venous complex is r Uroflowmetry
without robotic assistance. required to meticulously divide the prostatourethral r 24-hr pad test to quantify PPI
r The definition of continence following RP in the junction. r Urodynamics evaluation with or without fluoroscopy
r Maximal preservation of the rhabdosphincter is felt
literature varies widely, with the strictest definition will help define the etiology for PPI
of continence being no pads used. to minimize PPI. r Pressure flow study is useful for evaluating a
r Encourage Kegel exercises—may accelerate
EPIDEMIOLOGY possible obstructive anastomotic stricture
continence recovery.
Incidence r Preoperative pelvic floor muscle training with Pathologic Findings
r The incidence of PPI depends on the interval of time None
biofeedback has not resulted in improved
following surgery, the definition and methodology postoperative continence recovery (3) DIFFERENTIAL DIAGNOSIS
for assessing continence, and the experience of the r Anastomotic stricture
surgeon. r Detrusor Instability (DI)/Overactive bladder (OAB)
r The overwhelming majority of men have some DIAGNOSIS r Stress urinary incontinence (SUI)
degree of PPI immediately after catheter removal. r Urge incontinence
r If PPI is defined as no pads/small protective pad or HISTORY
r Assess the severity of LUTS and incontinence r Overflow incontinence
total control/occasional dribbling, experienced
preoperatively. r Mixed incontinence
surgeons consistently report continence rates
exceeding 95% at 1–2 yr after RP. – The International Prostate Symptom Score (IPSS).
r Recent evidence suggests that PPI may improve r Inquire about the use of α-blockers because these
agents may exacerbate PPI. TREATMENT
after 2 yr. r Ascertain if the PPI is exacerbated by physical
Prevalence GENERAL MEASURES
activity. r Kegel exercises should be encouraged as soon as
Approximately 6% of men will undergo a procedure r Determine the severity of PPI by: Number of pads,
for the management of PPI at a median of 20 mo after urinary catheter removal
degree of bother, and frequency of incontinence r Discontinue α-blockers
RP (1)
episodes. r Limitation of fluid intake
RISK FACTORS (2) r Assess the severity of LUTS.
r Timed voiding
r Body mass index (BMI) ≥25 r Inquire if PPI is improving, stable, or deteriorating:
r Voiding before strenuous activity
r Compromised sexual potency (IIEF-EF <10) – Deterioration of continence together with r Counsel patient that incontinence following RP is the
r Enlarged prostate volume increasing voiding symptoms suggests an
r Increasing age (>65 yr) anastomotic stricture. norm and that with time most patients will improve
r Nerve-sparing status (non vs. unilateral vs. bilateral) MEDICATION
PHYSICAL EXAM
r Presence of preoperative incontinence/lower urinary r Observe for skin excoriation secondary to PPI. First Line
tract symptoms (LUTS) r Observe degree of pad saturation. r α-Agonists generally not effective for SUI
r Previous TURP r Observe degree of incontinence when transferring r Imipramine (a tricyclic antidepressant) promotes
r Surgeon inexperience external urethral sphincter muscle tone and may
from the sitting to standing position.
r Observe caliber of urinary stream. improve mild SUI (off-label use)
Genetics – Typical off-label starting dose is 25–50 mg PO
N/A QHS
PATHOPHYSIOLOGY r Anticholinergic agents may improve PPI secondary
r PPI results primarily from injury to the to DI
rhabdosphincter resulting in SUI. – Options include: Oxybutynin, tolterodine,
r Pre-existing detrusor instability (DI) is a less likely darifenacin, solifenacin, fesoterodine, trospium
etiology of PPI.
r An anastomotic stricture may be the cause, or
exacerbate PPI.
214
INCONTINENCE, URINARY, FOLLOWING RADICAL PROSTATECTOMY
Second Line ADDITIONAL READING

Periurethral bulking agents (bovine glutaraldehyde ONGOING CARE r Ficarra V, Novara G, Rosen RC, et al. Systematic
cross-linked collagen polydimethylsiloxane elastomer)
are costly; they require multiple injections and have PROGNOSIS review and meta-analysis of studies reporting urinary
r The overwhelming majority of men will continence recovery after robot-assisted \ radical
limited durable success in this setting.
spontaneously regain urinary continence following prostatectomy. Eur Urol. 2012;62:405–417.
SURGERY/OTHER PROCEDURES RP. r Gacci M, Ierardi A, Rose AD, et al. Vardenafil can
r Surgical intervention should not be pursued until at
r The small subset of men with persistent SUI will improve continence recovery after bilateral nerve
least 1 yr post-prostatectomy because of the
improve, providing the appropriate surgical sparing prostatectomy: Results of a randomized,
temporal improvements in the condition
r Surgical intervention should not be contemplated at procedure is performed. double blind, placebo-controlled pilot study. J Sex
r The worst prognosis exists for cases with severe Med. 2010;7:234–243.
1–2 yr if there is evidence of progressive r Healy KA, Gomella LG. Retropubic, laparoscopic, or
refractory anatomic strictures (bladder neck
improvement
r Imperative to exclude anastomotic stricture and DI contractures) who must 1st be made totally robotic radical prostatectomy: is there any real
incontinent with subsequent placement of an AUS. difference? Semin Oncol. 2013;40(3):286–296.
before embarking on surgical correction of SUI r PPI secondary to DI likely to improve with
r Surgical options: See Also (Topic, Algorithm, Media)
anticholinergic agents. r Bulking Agents, Injectable
– The specific surgical procedure is dictated by
severity of PPI. COMPLICATIONS r Incontinence, Urinary, Adult Male
r Dermatitis r Stress Urinary Incontinence, Male
– More severe cases best managed with an artificial
urinary sphincter (AUS) r Diminished self-esteem:
– In many cases, surgery achieves marked – Limitation of physical activity
improvement in PPI but some degree of SUI may – Withdrawal from sexual activity CODES
persist – Complications of treatment for PPI
◦ Male slings
◦ Artificial urinary sphincter (AUS) FOLLOW-UP ICD9
r 788.39 Other urinary incontinence
Patient Monitoring
ADDITIONAL TREATMENT r Pad use r 997.5 Urinary complications, not elsewhere
Radiation Therapy r Impact of PPI on quality of life classified
Although there is no role in the treatment of PPI, data
suggest that radiation administered in the adjuvant r N39.498 Other specified urinary incontinence
http://www.webmd.com/urinary-incontinence-
setting following RP may not worsen incontinence but r N99.89 Oth postprocedural complications and
oab/mens-guide/urinary-incontinence
may limit resolution of continence particularly if the
radiation is administered before continence returns. disorders of GU sys
r Urethral dilation should be performed if evidence of REFERENCES CLINICAL/SURGICAL
bladder outlet obstruction and anastomotic stricture. 1. Kim PH Pinheiro LC, Atoria CL, et al. Trends in the PEARLS
r Transurethral incision of the stricture may be
use of incontinence procedures after radical r Post prostatectomy incontinence (PPI) is very
required if stricture reoccurs despite multiple prostatectomy: a population based analysis. J Urol.
dilation(s). 2013;189(2):602–608. common, with the vast majority (95%) resolving
r In Europe duloxetine, a serotonin-norepinephrine 6–12 mo postoperatively.
2. Abdollah F, Sun M, Suardi N, et al. A novel tool to r Kegel exercises should be instituted immediately
reuptake inhibitor is approved for stress
incontinence (US approval is only for neuropathic
assess the risk of urinary incontinence after
nerve-sparing radical prostatectomy. BJU Int. after catheter removal postoperatively.
I
pain and depression). r It is crucial to determine the exact pattern of urinary
2013;111(6):905–913.
Complementary & Alternative 3. Geraerts I, Van Poppel H, Devoogdt N, et al. leakage.
r If conservative measures fail, treatment for
Therapies Influence of Preoperative and Postoperative pelvic
Biofeedback may have a role in selected patients in floor muscle training (PFMT) compared with bothersome SUI requires surgery.
strengthening pelvic musculature. postoperative PFMT on urinary incontinence after r Type of surgery is dictated by severity of SUI.
radical prostatectomy: A randomized controlled
trial. Eur Urol. 2013;64(5):766–772.
215
INCONTINENCE, URINARY, PEDIATRIC

Steve J. Hodges, MD
Anthony Atala, MD
r Delayed voiding/defecation lead to bladder r Rule out urine in vaginal vault or labial adhesions in
BASICS overactivity, constipation girls
r Bladder overactivity/constipation compounded by r Ectopic perineal ureteral orifice can be cause of
DESCRIPTION dyssynergy of pelvic floor, with failure to relax pelvic constant wetness in girls
r Incontinence: Involuntary leaking of urine due to r Rectal exam to rule out rectal stool, evaluate normal
floor completely with emptying
any cause sensation and tone
r A “wet” child is the most common problem seen by ASSOCIATED CONDITIONS r Neurologic exam
pediatric urologists. Most wetting children will See risk factors
r Measure or observe urinary stream for force, caliber,
appear to no inciting cause, and some will improve GENERAL PREVENTION straining, duration (may obtain flow/PVR)
spontaneously r Aggressively prevent and treat constipation
r Enuresis: Involuntary leaking of urine while sleeping r Ensure an environment where children are not DIAGNOSTIC TESTS & INTERPRETATION
– “Nocturnal” enuresis implies night wetting alone, delaying micturition or defecation Lab
“diurnal” implies day and night, although these r Urinalysis
terms are outdated according to International – Rule out UTI, microhematuria, proteinuria,
Childrens Continence Society (ICCS) DIAGNOSIS glucosuria
– Primary enuresis: Child was always wet at night r If any of above discovered, require thorough
– Secondary enuresis: Child has had a dry interval ALERT evaluation and treatment
for at least 6 mo before wetting again r Urine culture if UA shows signs of infection
Incontinence in the presence of an abnormal back
EPIDEMIOLOGY exam may signal a neurologic abnormality. Imaging
Prevalence r KUB to rule out spinal anomalies and rule out occult
r Day or night wetting occurs in up to 25% of 4–6 yr HISTORY constipation
r Child’s age—more common in young r Renal US to evaluate for normal GU anatomy
old children (daytime incontinence is present in
approximately 5–10%) r Child’s sex—bedwetting is more common in boys, r VCUG only needed in the setting of febrile UTI (or
r Resolution rates of approximately 15% a year daytime wetting more common in girls any UTI in boys), hydronephrosis; allows evaluation
r At 12 yr of age 4% of children are enuretic at least r When did the symptoms begin? What is the of urethra in males
once a week, at 15 yr old it is 2% pattern? Severity? r MR urography may be needed when concerned for
r Enuresis is 3× more common in boys than girls, r Primary enuresis is highly associated with ectopic ureter
however daytime incontinence is more common in constipation r Renogram rarely needed to evaluate for urinary
females in all age groups r Secondary nocturnal enuresis implies an acquired obstruction, renal function
cause or stressor
RISK FACTORS r Dribbling upon standing or activity in girls may imply Diagnostic Procedures/Surgery
r Spinal dysraphism r Urodynamics indicated in setting of known
r Urinary tract anomalies vaginal voiding neurologic disorder
r Determine associated daytime symptoms (urgency, r Cystoscopy only needed if evaluation demonstrated
r Developmental delay
r Family history of enuresis frequency, weak or intermittent stream, or anatomic abnormality such as posterior urethral
infrequent voiding) valves
r Attention deficit disorder r History of UTI? Functional constipation?
r Urinary tract infection r History of large or firm bowel movements, or Pathologic Findings
r Constipation r Incontinence classified as structural, neurogenic,
encopresis, may signify constipation even in setting
complicated, or uncomplicated
Genetics of normal frequency of bowel movements r Structural—anatomic cause of incontinence (eg,
r Children whose parents were not bed-wetters have r Does child show holding behavior? (curtsey or
ectopic ureter in girls)
a 15% incidence of bedwetting. When one or both squatting in girls, holding genitals in boys) r Neurogenic—incontinence due to spinal dysraphism
parents were bed-wetters, the rates jump to 44% r History of neurologic disorder?
and 77%, respectively. r Family history of incontinence? UTIs? Enuresis? or other neurologic cause
r Genetic research shows that bedwetting is r Uncomplicated—nocturnal enuresis in appropriate
associated with the genes on chromosomes 13q and PHYSICAL EXAM age group in the presence of no obvious causes on
r Level of physical and emotional development diagnostic and physical exam (least
12q (possibly 5 and 22 also). r Abdominal exam—rule out masses, constipation common—almost all cases have cause if look
PATHOPHYSIOLOGY r Back exam—rule out signs of occult spinal closely)
r Daytime control attained before nighttime r Complicated—functional voiding disorders;
dysraphism (dimples, short sacrum, spinal defect,
r Constipation plays a major role in urinary continence significant incontinence without anatomic or
hairy patches)
r Normal bladder control involves 3 basic r Flattened buttocks, low gluteal cleft, or nonpalpable neurologic cause
components: Intact neurologic system, normal coccyx suggest sacral agenesis
anatomy, and a mature, motivated child r GU exam, rule out genital or perineal sensation
r Normal urinary control occurs in stages:
disorders, signs of abuse, hypospadias, or epispadias
– Infantile voiding (0–6 mo) low-pressure filling,
reflex detrusor contractions, simultaneous
relaxation of external sphincter, complete
emptying, uninhibited voids
– Transitional voiding (1–2 yr) conscious sensation
of bladder filling, continence achieved by
controlling external sphincter, increasing bladder
capacity (60 cc at birth + 30 cc/yr till 12 yr old)
– Adult voiding: Supraspinal inhibition of voiding
reflex, voluntary inhibition/initiation of voiding
216
INCONTINENCE, URINARY, PEDIATRIC
r Need KUB and renal/bladder US, urodynamics MEDICATION REFERENCES

optional First Line
r Other pediatric bladder disorders: r Treat UTI if present 1. Feldman A, Bauer S. Diagnosis and management of
– Lazy bladder syndrome (infrequent voider)—rare r Overactive bladder dysfunctional voiding. Curr Opin Pediatr. 2006;
voids, 2–3× a day, may have infections, – Anticholinergic medications 18:139–147.
associated with constipation ◦ Oxybutynin: Safety and efficacy of oxybutynin 2. Humphreys MR, Reinberg YE. Contemporary and
– Bladder overactivity—typically associated with chloride administration have been demonstrated emerging drug treatments for urinary incontinence
delayed voiding and constipation, typified by for pediatric patients 5 yr of age and older in children. Pediatr Drugs. 2005;7(3):151–162.
uninhibited bladder contraction with no ◦ Tolterodine (off label in children) 3. Hodges SJ. Overactive bladder in children. Curr
neurologic lesion ◦ Consider β 3 -agonist (mirabegron off label in Bladder Dysfunct Rep. 2012;7(1):27–32.
– Hinman-Allen syndrome—nonneurogenic children)
neurogenic bladder, may be due to constipation as r Constipation
well – PEG 3350, enemas or suppositories, Senna ADDITIONAL READING
– Daytime frequency syndrome—frequent urination laxatives, fiber supplements
in a child with no other identifiable abnormalities, Dave S, Salle JL. Surgical management of pediatric
usually do have constipation on KUB SURGERY/OTHER PROCEDURES urinary incontinence. Curr Urol Rep. 2013;14(4):
r Structural—alleviate structural cause of 342–349.
– Giggle Incontinence—rare form of incontinence
where wetting only occurs with laughing, may be incontinence
centrally mediated (brain), treated with Ritalin – Neurogenic—low compliance bladder may require r Dysfunctional Elimination Syndrome
enterocystoplasty, urethral dilation, neural r Giggle Incontinence (Enuresis Risoria)
DIFFERENTIAL DIAGNOSIS stimulation, or botulinum toxin injection
r Structural incontinence: r Hinman Syndrome
– Overactive bladder—may benefit from neural
– Ectopic ureter r Incontinence, Urinary, Adult Male
stimulation, botulinum toxin injection in bladder
– Exstrophy-epispadias complex or sphincter, rarely urethral dilation r Incontinence, Urinary, Adult Female
– Fibrotic bladder (postoperatively or postradiation) r International Children’s Continence Society (ICCS),
– Imperforate anus ADDITIONAL TREATMENT
Terminology
– Labial adhesions Radiation Therapy r Overactive Bladder (OAB)
– Posterior urethral valves N/A r Sacral Agenesis
– Urethral duplication Additional Therapies r Spinal Dysraphism
– Urogenital sinus Aggressive constipation management for severe cases r Vincent curtsey
– Vesical fistula may require chronic enemas or antegrade continence
r Neurogenic:
enema (ACE) creation
– Anterior sacral meningocele, caudal tumor
– Intradural lipoma, diastematomyelia Complementary & Alternative CODES
– Myelodysplasia Therapies
– Occult dysraphism N/A ICD9
– Sacral agenesis, spinal cord trauma, myelitis r 788.30 Urinary incontinence, unspecified
cerebral palsy ONGOING CARE r 788.36 Nocturnal enuresis
– Tight filum terminale, dermoid cyst/sinus r 788.91 Functional urinary incontinence
– Isolated nocturnal enuresis: Constipation, sleep PROGNOSIS
arousal disorder, nocturnal polyuria r Most patients do resolve over time as they grow, ICD10
r Complicated incontinence: and gain more mature toileting habits
r Severe cases may lead to pelvic floor disorders (such
r F98.0 Enuresis not due to a substance or known I
– Giggle incontinence physiol condition
– Hinman-Allen syndrome as pelvic pain syndrome, dyspareunia) in future, so r N39.44 Nocturnal enuresis
– Lazy bladder syndrome aggressive therapy indicated r R32 Unspecified urinary incontinence
– Overactive bladder FOLLOW-UP
Patient Monitoring
r Follow-up for observation of progress, adjusting
CLINICAL/SURGICAL
TREATMENT PEARLS
medications as needed
GENERAL MEASURES – Structural and neurogenic causes need routine r Aggressive constipation therapy is needed.
r Behavioral measures—timed voiding, constipation
evaluations to rule out upper tract injury and r Enemas are most effective in treating incontinence.
therapy monitor progress r Incontinence in children is never normal and is a
r Biofeedback—physical therapy to relax external
Patient Resources sign of treatable pathology.
sphincter r National Kidney and Urologic Diseases
r Diet—avoid bladder irritant, caffeine
r Perineal hygiene—voiding positioning Information Clearinghouse (NKUDIC) http://
kidney.niddk.nih.gov/kudiseases/pubs/uichildren/
217
INFERTILITY, UROLOGIC CONSIDERATIONS

Mark C. Lindgren, MD
ASSOCIATED CONDITIONS r Posttesticular:

BASICS r Pretesticular: – Obstruction of epididymis or vas deferens:
– Hypogonadotropic hypogonadism: Low follicle Congenital or acquired (eg, vasectomy)
DESCRIPTION stimulating hormone (FSH), luteinizing hormone – CBAVD: 80% have CFTR mutations—genetic
r Infertility is the inability to achieve pregnancy after (LH), and testosterone (T) with normal prolactin testing must be performed for male and female
1 yr of regular unprotected intercourse – Hypothyroidism – Ejaculatory dysfunction:
r Couples achieve pregnancy by intercourse at a rate – Medication use: See Risk Factors ◦ Anejaculation: Caused by retroperitoneal
of approximately 20–25% per month, 75% by – Elevated estradiol from morbid obesity, tumors, or surgery, neuropathic disorders, α-blockers and
6 mo, and 90% by 1 yr hepatic dysfunction psychiatric medications
– Kallmann syndrome: X-linked, absent GnRH ◦ Retrograde ejaculation: Transurethral prostate
EPIDEMIOLOGY
secretion, absent puberty, anosmia and bladder neck procedures as well as the
Incidence – Pituitary/cranial trauma, infection, or tumor same causes of anejaculation (above)
r 15% of couples have infertility
– Hyperprolactinemia: Prolactin inhibits LH action – Ejaculatory duct obstruction (EDO): Low-volume
r In approximately 30%, infertility is due to a
on Leydig cells. Brain MRI to evaluate for azoospermia; causes include previous infection,
significant male factor alone macroadenoma (>1 cm) iatrogenic trauma, and congenital
r An additional 20% of couples have both male and ◦ Macroadenoma: Refer for possible resection
female factors present ◦ Microadenoma: May respond to dopamine GENERAL PREVENTION
See “Risk Factors”
Prevalence agonist (1st line: Cabergoline, 2nd:
N/A Bromocriptine)
r Testicular: DIAGNOSIS
RISK FACTORS – Varicocele: 15% of all men, 35–40% of men with
r Anatomic: Varicocele; bilateral cryptorchidism; HISTORY
primary infertility, 70–80% of men with secondary r Mnemonic TICS:
hypospadias; testicular trauma; testicular torsion; infertility
thermal exposure (hot baths, saunas); spinal, – Bilateral cryptorchidism – Toxic: Varicocele, chemotherapy, radiation
inguinal, or retroperitoneal surgery – Testicular cancer—pretreatment sperm density exposure, thermal exposure to testes, testicular
r Medications: Cancer and cancer treatments injury, heavy alcohol use, recreational drugs
and motility are significantly decreased
(chemotherapy, radiation); recreational drugs – Gonadotoxins: Radiation, chemotherapy, (marijuana, cocaine), surgical history, medications,
(marijuana, cocaine); prescription meds (exogenous medications, environmental endocrine disrupting and other medical illnesses
testosterone [T], GnRH agonists/antagonists, chemicals (eg, phthalates used in plastics) – Infectious: Sexually transmitted disease, urinary
α-blockers, antibiotics, sulfasalazine, cimetidine, – Immunologic: Antisperm antibodies; febrile tract infections, epididymitis, recent febrile illness,
spironolactone, Ca channel blockers, colchicine, infections can decrease sperm production for 3 and postpubertal mumps
opioids, psych meds) mo; postpubertal mumps orchitis – Congenital: Bilateral cryptorchidism, testicular
r Others: Heavy alcohol use; GU infections; – Sertoli-cell only syndrome: Absent germ cells torsion, family history of difficulty conceiving or
chromosomal abnormalities; neurologic disease; – Maturation arrest: Spermatogenesis halted at a miscarriages, family history of cystic fibrosis
endocrine disorders certain stage – Sexual: Length of time attempting to conceive,
– Genetic/chromosomal factors: previous pregnancies with current or previous
Genetics partner, frequency of intercourse, lubricant use,
r Most common defects and % of men with ◦ Klinefelter: 47,XXY; small, firm testes; often
azoospermic, however, mosaicism erectile dysfunction, age at puberty, libido,
nonobstructive azoospermia (NOA) or obstructive exogenous T use, energy level
azoospermia (OA) with each: (47,XXY/46,XY) allows spermatogenesis. Up to
– Klinefelter syndrome 47,XXY (10% NOA) 69% have sperm found from TESE PHYSICAL EXAM
– Cystic fibrosis transmembrane conductance ◦ Y microdeletions: AZFa, b and c: See Genetics r General: Degree of virilization, Tanner stage
regulator protein (CFTR) found abnormal in 80% ◦ Androgenization disorders: Defects in synthesis r Penile exam: Location of urethral meatus, buried
of patients with congenital bilateral absence of of T, androgen receptor, and 5α reductase penis
the vas deferens (CBAVD) (6% OA) ◦ 47,XYY: Usually fertile due to mosaicism with r Scrotal exam:
– Azoospermia factor (AZF) a, b, and c: XYY cells arresting in meiosis and XY cells – Measure testicles by long access length or
◦ AZFa (1% NOA) predictive of testicular sperm producing mature sperm orchidometer volume (nL ≥4 cm or 20 mL)
extraction (TESE) failure ◦ 46,XX with male phenotype: No
– Testicular consistency, including careful evaluation
◦ AZFb (1–3% NOA) predicts TESE failure spermatogenesis, donor sperm/adoption for testicular masses
◦ AZFc (13% NOA) best prognosis, can be ◦ Primary ciliary dyskinesia (Kartagener
– Epididymal exam—note presence of caput,
oligospermic, if azoospermic 2/3rds have sperm syndrome): Immotile sperm; frequent respiratory corpus, and cauda as well as possible induration
on TESE infections; situs inversus or fullness suggestive of obstruction
◦ Globozoospermia (round-headed sperm): Severe
PATHOPHYSIOLOGY – Cord structures: Evaluate for varicocele in
teratospermia in which sperm lack acrosomes standing position, note presence or absence of
3 categories: giving the heads a round appearance
r Pretesticular: Endocrine abnormality vasa deferentia as well as continuity or malunion
r Testicular: Abnormal sperm production DIAGNOSTIC TESTS & INTERPRETATION
r Posttesticular: Abnormal sperm transport Lab
r Semen analysis:
– Minimum of 2 specimens due to variability
– World Health Organization (WHO) 2010 5th
edition reference values:
◦ Volume >1.5 mL normal, if low, obtain post
ejaculatory urinalysis to distinguish between
retrograde ejaculation and EDO
◦ Concentration >15 million/mL
◦ Total sperm count >39 million/mL
◦ Total Motility >40%
◦ Morphology >4%
218
INFERTILITY, UROLOGIC CONSIDERATIONS
– Azoospermia: r Anastrozole 1 mg daily: Men with abnormal semen Patient Resources

◦ Distinguish between obstructive and NOA parameters and low testosterone to estradiol ratio r UrologyCare Foundation http://www.urologyhealth.
◦ If FSH <7.6 mIU/mL and testicular long axis (<10:1) org/urology/index.cfm?article=102
>4.6 cm then 96% probability of OA r Maledoc.com
Second Line
◦ If FSH ≥7.6 and testicle ≤4.6 cm then 89% r hCG and/or recombinant FSH: If hypoandrogenism
probability of NOA (1)[B] unsuccessfully treated with clomiphene citrate
r Further specialized semen testing may aid r Alternatives for retrograde ejaculation: Imipramine REFERENCES
decision-making but not routinely obtained 25 mg, ephedrine 25 mg 1. Schoor RA, Elhanbly S, Niederberger CS, et al. The
r Endocrine workup obtained if abnormal semen role of testicular biopsy in the modern management
analysis, impaired sexual function or findings r MicroTESE: Performed for NOA, superior to other of male infertility. J Urol. 2002;167:197–200.
indicative of endocrine abnormality: sperm-retrieval techniques with 20–30% 2. Hussein A, Ozgok Y, Ross L, et al. Optimization of
– Obtain T, sex hormone binding globulin (SHBG), improvement in yield up to 67% spermatogenesis-regulating hormones in patients
albumin to calculate bioavailable T and FSH, LH r Vasectomy reversal: Time since vasectomy is the with non-obstructive azoospermia and its impact
estradiol for all patients needing workup on sperm retrieval: A multicentre study. BJU Int.
– Consider prolactin and others as indicated best predictor of success (3)[B] 2013;111(3 Pt B):E110–E114.
r Genetic testing r MicroTESE, vasovasostomy, or vasoepididymostomy 3. Belker AM, Thomas AJ Jr, Fuchs EF, et al. Results of
– CBAVD: Patient and partner should have genetic should be performed by microsurgical specialist 1469 microsurgical vasectomy reversals by the
counseling and CFTR mutation testing r OA, if patient does not desire reconstruction or it is vasovasotomy study group. J Urol. 1991;145:
– Karyotyping is indicated in patients with NOA or not possible: TESE, testicular sperm aspiration 505–511.
severe oligospermia (<5 million sperm/mL) (TESA), percutaneous or microsurgical epididymal 4. Agarwal A, Deepinder F, Cocuzza M, et al. Efficacy
– Consider Y chromosome microdeletion testing if sperm aspiration (PESA or MESA) of varicocelectomy in improving semen parameters:
azoospermic r Varicocelectomy: Recommended for men with New meta-analytical approach. Urology. 2007;
Imaging infertility, palpable varicocele, abnormal semen 70:532–538.
r Transrectal ultrasound—use in azoospermic patients parameters, elevated FSH, and female partner with
with palpable vasa and low-volume ejaculate. normal/potentially correctable infertility (4)[A]
Seminal vesical dilatation (normal <2 cm) indicative r Transurethral resection of ejaculatory ducts: For EDO ADDITIONAL READING
of EDO r Neurostimulatory ejaculation: Men with spinal cord
r Scrotal ultrasound—only used in patients with Lipshultz LI, Howards SS, Niederberger CS. Infertility in
injury may be able to retrieve sperm via ejaculate the Male. 4th ed. New York, NY: Cambridge University
difficult or inadequate scrotal exams with penile vibratory stimulation or, Press; 2009.
r Renal ultrasound—recommended if unilateral
electroejaculation or via microTESE
absent vas or CBAVD with no CFTR mutations to See Also (Topic, Algorithm, Media)
ADDITIONAL TREATMENT r Assisted Reproductive Techniques (ARTs)
evaluate for renal abnormalities
Radiation Therapy r Azoospermia, Oligospermia
Diagnostic Procedures/Surgery r Ejaculatory Disturbances
Testicular biopsy is typically unnecessary N/A
r Infertility, Urologic Considerations Image
Pathologic Findings Additional Therapies
Assisted Reproductive Technologies (ARTs), r Semen Analysis, Abnormal Findings, and
r Seminiferous tubules findings include:
Intrauterine insemination (IUI), In Vitro Fertilization Terminology
– Normal spermatogenesis—indicative of OA r Semen Analysis, Technique, and Normal Values
– Maturation arrest (∼20% of NOA)—can be (IVF) and Intracytoplasmic Sperm Injection (ICSI)
r Varicocele
“early” or “late”
– Sertoli-cell-only syndrome (∼60% of
Therapies
I
NOA)—germinal cell aplasia Coenzyme Q10 is used
– Hypospermatogenesis (∼20% of NOA) or germ CODES
cell hypoplasia
– Tubular hypoplasia—possible hypogonadotropic ONGOING CARE ICD9
r 606.1 Oligospermia
hypogonadism
PROGNOSIS r 606.8 Infertility due to extratesticular causes
– Seminiferous tubule sclerosis r Pregnancy rates are highly dependent on the age of
– Testis cancer r 606.9 Male infertility, unspecified
the female partner
DIFFERENTIAL DIAGNOSIS r MicroTESE for NOA: 67% sperm-retrieval rate
ICD10
See “Associated Conditions” r IUI: ∼15% pregnancy rate per cycle r N46.029 Azoospermia due to other extratesticular
r IVF: ∼30% pregnancy rate per cycle causes
r IVF with ICSI: ∼35–45% pregnancy/per cycle r N46.129 Oligospermia due to other extratesticular
TREATMENT
causes
COMPLICATIONS r N46.9 Male infertility, unspecified
GENERAL MEASURES r Scrotal surgery: Hematoma, bruising, pain
r The goal is to address the underlying problem to
r ART: Multiple gestations, passing genetic defects to
allow natural conception, if possible.
r Female evaluation by a reproductive specialist and offspring CLINICAL/SURGICAL
coordinated care is crucial for optimal outcomes. FOLLOW-UP PEARLS
MEDICATION Patient Monitoring
Spermatogenesis takes approximately 64 days; semen Testis biopsy is rarely indicated in the evaluation of
First Line male infertility.
analysis 3 mo after starting treatment
r Clomiphene citrate 50 mg every other day: Used
for hypoandrogenism. Stimulates GnRH resulting in
increased T and spermatogenesis. Less than 10% of
men with azoospermia and hypoandrogenism have
return of sperm to ejaculate after T normalizes
using clomiphene citrate (2)[B]. Note: Exogenous T
decreases fertility
r Pseudoephedrine 60 mg 1–2 hr prior to sex: For
retrograde ejaculation
219
INTERSTITIAL CYSTITIS (IC)/PAINFUL BLADDER SYNDROME (PBS)

Nikhil Waingankar, MD
Sonia Bahlani, MD

BASICS r Myalgia of pelvic floor: Most commonly identified
Lab
comorbid condition r Urinalysis and urine culture
DESCRIPTION r Irritable bowel syndrome r Urine cytology in high-risk groups
r Interstitial cystitis (IC) or Painful Bladder Syndrome r Fibromyalgia
(PBS) is an unpleasant sensation (pain, pressure, r Chronic fatigue syndrome Imaging
discomfort) perceived to be related to the bladder, No recommended imaging for the diagnosis of IC/PBS
r Multiple allergies
associated with lower urinary tract symptoms (LUTS) r Sjögren syndrome Diagnostic Procedures/Surgery
for more than 6 wk duration, and in the absence of r Urodynamics:
r Chronic headaches
other identifiable causes (1,2) – Normal detrusor function on cystometry; may have
r 92% of patients also complain of frequency r Depression/anxiety/panic disorder
increased sensitivity (pain) on filling and
r In females: Vulvodynia, endometriosis
(>10–12× daily); nocturia is common decreased capacity.
r 84% complain of constant/persistent urgency r In males: Chronic prostatitis/chronic pelvic pain – Late stages of “classic” IC/PBS may be associated
r Dysuria is uncommon syndrome, BPH, prostate cancer with significant decrease in capacity and bladder
r Symptoms can be associated with a wide range of compliance
GENERAL PREVENTION r Cystoscopy:
diseases (see “Differential Diagnosis”) No definitive prevention strategies, although dietary
r Two forms of IC/BPS: changes and medical therapy may mitigate symptom – Used selectively to exclude other bladder
– “Classic”: Associated with Hunner lesions on flares pathology and identify Hunner lesions
r Cystoscopy with hydrodistention under
cystoscopy (formerly known as Hunner ulcer)
– “Nonclassic”: No inflammatory lesions identified general/spinal anesthesia:
upon cystoscopy DIAGNOSIS – Findings may include: Glomerulations (small foci
r Nomenclature change from IC to IC/PBS due to the of hemorrhage), Hunner lesions, decreased
HISTORY
lack of gross inflammatory bladder wall changes r IC patients 10× more likely to have childhood anesthetic capacity, mucosal tears; low sensitivity
found in most patients and specificity
bladder problems
r Median age of onset 30–40 yr r Symptoms unrelated to any identifiable cause – Hunner lesion (ulcer) is described as circumscript,
r Female: Male ∼ 5:1 reddened area with small vessels radiating toward
(infection, STD, cancer, radiation, overactive bladder a central scar. Fibrin deposit/coagulum can be
r 5–10% of patients have Hunner lesions (OAB), diverticula, vaginitis, stones)
r Chronic pelvic pain, pressure attached to this area. With bladder distention the
EPIDEMIOLOGY (3) site ruptures with petechial blood oozing from the
r Abdominal/supra-pubic pain
Incidence and prevalence vary widely lesion and mucosal margins (5)
r Pain associated with bladder filling and/or emptying r Potassium sensitivity testing (KCl test):
Incidence r Premenstrual flares
0.6–1.6 per 100,000 people – Low sensitivity and specificity; positive result
r Urinary frequency, urgency, nocturia provokes pain
Prevalence r Urinary frequency based upon need to decrease r Residual urine/flow in males
Ranges from 1.6 to 2,600 per 100,000 people level of pelvic discomfort/pain Pathologic Findings
RISK FACTORS r Helpful evaluation/monitoring tools: r Histologic findings can vary widely and none are
No known risk factors beyond a possible genetic – Symptom evaluation with voiding diary truly pathognomonic
predisposition – O’Leary-Sant Symptom and Problem Score r Bladder biopsy
Genetics – Visual analog scale (pain score) – Indicated only to rule out other disease processes
Adult female 1st-degree relatives of IC patients have a – PUF (Pelvic Pain & Urgency/Frequency) – Hunner lesions demonstrate pan-mural
prevalence 17× greater than that of the general Questionnaire inflammation
population – Bladder Pain/Interstitial Cystitis Symptom Score
PATHOPHYSIOLOGY PHYSICAL EXAM r Bacterial cystitis
r Multifactorial etiology with a number of proposed r General: r Bladder cancer (including CIS)
mechanisms – Abdominal exam to assess for supra-pubic r Bladder effects of chemotherapy
– Epithelial permeability tenderness r Bladder outlet obstruction/urinary retention
– Antiproliferative factor – Focused neurologic exam r Bladder/lower ureteral stone
r Females:
– Mast cell activation r Genital herpes
– Neurogenic inflammation – Q-tip test to assess for vulvodynia
– Infectious – Bimanual exam with palpation of bladder, urethra,
– Autoimmunity and pelvic floor muscles to assess presence of
– Urinary abnormality: Toxic, allergic, immunologic muscle tenderness/banding
r Males:
– Digital rectal exam with palpation of prostate and
pelvic floor musculature
– External genitalia exam
220
INTERSTITIAL CYSTITIS (IC)/PAINFUL BLADDER SYNDROME (PBS)
r Overactive bladder ADDITIONAL TREATMENT 5. Hillelsohn J, Rais-Bahrami S, Friedlander JI, et al.

r Pelvic floor muscle dysfunction Radiation Therapy Fulguration for Hunner ulcers: Long term clinical
r Pudendal nerve entrapment N/A outcomes. J Urol. 2012;188(6):2238–2241.
r Radiation cystitis 6. Hanno P, Burks DA, Clemens JQ, et al. AUA
r Females: See General Measures
guideline for the diagnosis and treatment of
– Cervical/uterine/ovarian cancer interstitial cystitis/bladder pain syndrome. J Urol.
Complementary & Alternative 2011;185(6):2162–2170.
– Urethral diverticulum
– Pelvic organ prolapse Therapies
– Endometriosis See General Measures; myofascial physical therapy
– Vaginal candidiasis may help (4) ADDITIONAL READING
r Males: BPH, prostate cancer, prostatitis r Friedlander JI, Shorter B, Moldwin RM. Diet and its
ONGOING CARE role in interstitial cystitis/bladder pain syndrome and
comorbid conditions. BJU Int. 2012;109(11):
TREATMENT PROGNOSIS 1584–1591.
Spontaneous remission rate of 50% at mean of 8 mo r The Interstitial Cystitis Survival Guide: Your guide to
GENERAL MEASURES
(Adapted from AUA guidelines 2011) (6) COMPLICATIONS the latest treatment options and coping strategies.
r Patients should be aware that no single treatment N/A Moldwin RM. New Harbinger Publications, Oakland
has been found effective CA, Oct 2000.
FOLLOW-UP r Understanding the IC/PBS Diet. Beyer J, Gordon B,
r 1st line
Patient Monitoring Laumann B, Osborne J, Shorter B. ichelp.org.
– Stress reduction Follow symptoms
– Exercise See Also (Topic, Algorithm, Media)
– Warm baths
Patient Resources r Interstitial Cystitis (IC)/Painful Bladder Syndrome
Interstitial Cystitis Association http://www.ichelp.org/
– Stool softeners (PBS) Image
– Biofeedback r Lower Urinary Tract Symptoms (LUTS)
– Avoidance of spicy foods, caffeine, alcohol, REFERENCES r Pelvic Pain, Female
artificial sweetener, acidic beverages r Pelvic Pain, Male
r 2nd line 1. Hanno P, Lin AT, Nordling J, et al. Bladder pain r Prostatitis, General
– Pelvic floor physical therapy/massage syndrome. In: Abrams P, Cardozo L, Khoury S, Wein
– Multimodal pain management A, eds. Incontinence. Paris, France: Health
– Amitriptyline Publication Ltd; 2009. pp. 1459–518.
– Cimetidine 2. Van de Merwe JP, Nordling J, Bouchelouche P, et al. CODES
– Hydroxyzine Diagnostic criteria, classification, and nomenclature
– Pentosan polysulfate for painful bladder syndrome/ interstitial cystitis: An ICD9
r 595.1 Chronic interstitial cystitis
– Intravesical instillation: Author’s preferred ESSIC proposal. Eur Urol. 2008;53:60–67.
r 599.70 Hematuria, unspecified
“cocktail”: Lidocaine, gentamicin, heparin, 3. Suskind AM, Berry SH, Ewing BA, et al. The
triamcinolone prevalence and overlap of interstitial r 788.41 Urinary frequency
– Intravesical: 50% DMSO cystitis/bladder pain syndrome and chronic
– Intravesical: 4% alkalinized lidocaine prostatitis/chronic pelvic pain syndrome in men: ICD10
r 3rd line r N30.10 Interstitial cystitis (chronic) without
Results of the RAND Interstitial Cystitis
– Cystoscopy with hydrodistention (low Epidemiology male study. J Urol. 2013;189(1):
141–145.
hematuria
r N30.11 Interstitial cystitis (chronic) with hematuria I
pressure/short duration)
r R35.0 Frequency of micturition
– Fulguration of Hunner lesions 4. FitzGerald MP, Payne CK, Lukacz ES, et al.
– Submucosal injection of Hunner lesions with Randomized multicenter clinical trial of myofascial
triamcinolone physical therapy in women with interstitial
r 4th line cystitis/painful bladder syndrome and pelvic floor
CLINICAL/SURGICAL
– Neuromodulation (InterStim, etc.) tenderness. J Urol. 2012;187(6):2113–2118. PEARLS
r 5th line r IC/PBS is more common in women than in men.
– Cyclosporine A r This is primarily a clinical diagnosis based upon the
– Intradetrusor botulinum toxin A
r 6th line presence of characteristic symptoms and the
exclusion of other causes.
– Urinary diversion +/– cystectomy: May eliminate
urinary frequency but does not necessarily
eliminate the pain component
MEDICATION
First Line
See above
Second Line
See Above
See above
221
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LATEX ALLERGY, UROLOGIC CONSIDERATIONS

Genetics
BASICS r Genetic factor might be indicated. DIAGNOSIS
r Latex allergy is less frequent in adults with spinal
DESCRIPTION cord injury and multiple surgical procedures than in HISTORY
r Detailed clinical history of allergic reactions that are
r Localized or systemic reaction to latex, a natural children with similar conditions.
r Interleukin-13 (IL-13) and IL-18 promoter temporarily associated with exposure to Hevea
substance from the sap of the rubber tree, Hevea latex–containing products (eg, prior history to
brasiliensis (1)[A]. polymorphisms more likely to be found in healthcare
anaphylaxis and/or intraoperative shock, itching,
r Latex is a common ingredient in many medical and workers in comparison to nonatopic controls or
redness, or swelling following dental, rectal, or
patients with anorectal/urologic malformations.
dental products (eg, bladder catheters, blood pelvic exam; itching or swelling with condoms,
pressure cuffs, face mask, gloves, endotracheal PATHOPHYSIOLOGY diaphragms, or latex sexual aids)
tubes, IV infusion sets, etc.) r Presensitization with Hevea latex allergens is r Detailed history of associated risk factors: Healthcare
r Patients with spina bifida or congenital urogenital prerequisite to initiate an allergic response. workers, hair dressers, rubber handling, eczema/hay
abnormalities have the highest risk. r A number of proteins found in the cytoplasm of fever, multiple surgeries, food allergies, etc.
r Mild forms include pruritus and swelling. The most r 30–80% of patients with latex allergy also have
H. brasiliensis are known potent allergens that can
severe form of allergic reaction is anaphylaxis: A elicit human IgE antibody, leading to sensitization food allergy
severe, life-threatening, generalized or systemic in exposed patients and a spectrum of allergic r Allergic symptoms can include the following
hypersensitivity reaction characterized by rapidly reactions upon subsequent exposure (4)[A]. symptoms:
developing life-threatening airway and/or breathing r Symptoms of delayed (type IV) hypersensitivity – Dizziness
and/or circulation problems usually associated with – Dyspnea
usually develop within 1–2 days of exposure.
skin and mucosal changes. – Pruritus
Immediate (type I) hypersensitivity causes symptoms
– Rhinitis
within minutes of exposure.
ALERT r Immediate hypersensitivity reactions to latex (type I) – Tearing
All patients with neurogenic bladder should be – Swelling at the site of contact
are caused by cross-linking of latex protein-specific – Abdominal cramps
considered for latex precautions.
IgE antibody with mast cells and basophils. r In the most extreme cases, anaphylaxis can develop
r Cross-reactivity between various proteins is
EPIDEMIOLOGY
responsible for the clinical associations between
Incidence ALERT
r Latex sensitivity (assessed by serum latex IgE or skin latex allergy and allergic responses to a number of
Use caution when examining any child for
fruits and vegetables.
prick test) in the general population is <1% r Type IVc (T-cell–mediated type), delayed dysfunctional voiding especially if the child has
– Spina bifida population is 18–72% neurologic symptoms or suspected spina bifida.
r Latex allergy (eg, anaphylactic symptoms) is rare in hypersensitivity reaction can occur and usually
manifest as contact dermatitis 24–96 hr after
healthy population. exposure.
PHYSICAL EXAM
r Healthcare community: Up to 12.1% which fell to r Use nonlatex exam gloves
4% with the introduction of powder-free gloves GENERAL PREVENTION – Mucocutaneous manifestations:
r Exposure to multiple surgeries: 1/3–2/3 of children r Facility: ◦ Erythema
who underwent surgeries in the 1990s developed – Avoidance is the most effective and least ◦ Edema
latex sensitivity; this risk decreased dramatically expensive method. ◦ Papules, macules, urticaria
since the implementation of latex avoidance in – Establishment of a latex-safe environment should ◦ Allergic rhinitis
hospitals and products be a priority for institutions by replacing all Hevea ◦ Allergic conjunctivitis
latex–containing products with non–Hevea-based ◦ Angioedema
Prevalence synthetic products or powder-free latex products. – Cardiopulmonary manifestations:
N/A – Synthetic alternatives to rubber include butyl ◦ Tachypnea
RISK FACTORS rubber, a petroleum-based product with no ◦ Stridor, wheezing
r Occupational exposure: allergenic protein, neoprene, and copolymers of ◦ Tachycardia
– Healthcare butadiene and acrylonitrile. ◦ Hypotension
– Food handlers/restaurant workers – Non-Hevea source of natural rubber is the guayule ◦ Shock
– Hairdressers plant (Yulex). Yulex-based products pose no risk to
individuals allergic to Hevea latex and is approved
– Construction workers
by the Food and Drug Administration (FDA). Lab
– Painters
r Individuals with latex allergy: Routine resuscitation lab studies (blood gas, etc.) if
– First responders
– Should wear a medical alert bracelet indicating during acute anaphylaxis
– Security personal
– Gardeners latex allergy Imaging
r Atopic disease – Should be encouraged to have self-injectable N/A
r People with food allergies mainly to kiwi, epinephrine if they have a clinical history of Diagnostic Procedures/Surgery
strawberry, banana, avocado, chestnut systemic reaction to latex r These are performed on a routine basis and not
r Multiple surgeries at young age – Should avoid latex-containing products during an acute event
– Should report their allergies prior to any medical r Prick skin test:
r Children with anorectal or urologic malformations or surgical procedure
(5)[A]. – Extracts of Hevea latex, at least 3
– Spinal dysraphism – Commercial extracts are available
– Bladder exstrophy/cloacal anomalies – Test involves performing a puncture with a lancet
– Patients on clean intermittent catheterization device through a drop of latex extract at
sequential concentrations ranging from
0.001–1 mg/mL of protein
– Results are read after 15 min and compared with
the positive histamine and negative saline controls
– Small risk of anaphylaxis
222
LATEX ALLERGY, UROLOGIC CONSIDERATIONS
r Serology: Second Line 3. Cusik C. A latex-safe environment is in everyone’s

– An alternative test for confirming sensitization N/A best interest. Mater Manag Health Care. 2007;16:
when commercial skin test reagents are not 24–26.
available 4. Accetta D, Kelly KJ. Recognition and management
N/A
– Involves measuring serum Hevea latex–specific of the latex-allergic patient in the ambulatory
IgE antibodies ADDITIONAL TREATMENT plastic surgerical suite. Aesthet Surg J. 2011;31:
– Diagnostic sensitivity and specificity: 80% and Radiation Therapy 560–565.
>95%, respectively N/A 5. Brown RH, Hamilton RG, McAllister MA; Johns
Pathologic Findings Additional Therapies Hopkins Latex Task Force. How health care
r Biopsy of skin lesions (type IV hypersensitivity): organizations can establish and conduct a program
N/A
– Perivascular cuffing of CD4 cells identified using for latex-safe environment. Jt Comm J Qual Saf.
anti-CD4 antibody staining Complementary & Alternative 2003;29:113–123.
– Vesicular dermatitis with dermal and epidermal Therapies
r Most healthcare facilities have banned latex
mononuclear infiltrates
helium–filled balloons and are striving to become ADDITIONAL READING
DIFFERENTIAL DIAGNOSIS latex-free.
r Systemic allergic reaction to another allergen, r There is no desensitization available, but several r Bernardini R, Novembre E, Lombardi E, et al.
including medications or food products. including sublingual and other immunotherapies are Prevalence of and risk factors for latex sensitization
r Mild allergic manifestations: under study. in patients with spina bifida. J Urol. 1998;160:
– Allergic rhinitis 1775–1778.
– Asthma r Reddy S. Latex allergy. Am Fam Physician. 1998;
– Atopic dermatitis (ie, eczema) ONGOING CARE 57(1):93–100.
– Conjunctivitis
– Contact dermatitis to other allergens (ie, nickel PROGNOSIS See Also (Topic, Algorithm, Media)
r Depends on severity of symptoms and timely Myelodysplasia (Spinal Dysraphism), Urologic
products)
r Severe life-threatening manifestations: identification of responsible agents. Considerations
r High index of suspicion and immediate treatment
– Anaphylactic shock
– Cardiogenic shock are essential to good outcome.
– Septic shock
r Individuals with severe latex allergy should be CODES
– Hypovolemic shock provided with epinephrine autoinjections.
r Patients with type I hypersensitivity: Risk of fatal ICD9
r 596.54 Neurogenic bladder NOS
anaphylaxis and/or respiratory compromise
TREATMENT r 753.9 Unspecified anomaly of urinary system
COMPLICATIONS r V15.07 Allergy to latex
r Death can result from anaphylactic shock
GENERAL MEASURES
r Secondary bacterial wound infections in cases of
r Latex avoidance is by far the most-effective ICD10
severe contact dermatitis r N31.9 Neuromuscular dysfunction of bladder,
method of prevention (2,3)[A].
FOLLOW-UP unspecified
r Institutional policy changes in the use of Hevea r Q64.9 Congenital malformation of urinary system,
products are needed to reduce occupational and Patient Monitoring
r Some patients experience a biphasic or late stage unspecified
patient exposure. r Z91.040 Latex allergy status
r Always seek the use of nonlatex alternative products reaction several hours after the initial anaphylactic
(eg, silicone urethral catheters) event. Patients should be observed for at least 4 hr
r Synthetic and Yulex, non-Hevea rubber, are safe after the initial event.
r Avoidance should extend outside of the hospital to CLINICAL/SURGICAL
alternatives in Hevea-sensitized individuals. PEARLS
r Additional measures recommended for patients with items such as latex balloons, rubber bands, toys, etc.
r Inpatient admission may be necessary until r Natural rubber latex allergy is caused by
latex allergy include carrying nonlatex gloves,
wearing medical alert bracelets, and having cardiopulmonary risk is reduced. sensitization to proteins found in H. brasiliensis, the
L
r Allergy identification band, “MedicAlert” bracelet
auto-injectable epinephrine available. rubber tree.
r For acute anaphylaxis, standard shock management. r Avoid foods with latex cross-reactivity: r The highest prevalence of latex allergy (up to 68%)
– Banana, kiwi, chestnut, avocado is in patients with spina bifida or congenital
MEDICATION urogenital abnormalities.
Patient Resources
First Line r http://www.latexallergyresources.org/ r The mainstay of management of latex allergy is
r For the management of anaphylaxis
r http://www.aaaai.org/conditions-and- avoidance of latex products as there is no cure for
– Remove latex source latex allergy.
treatments/allergies/latex-allergy.aspx
– Basic life support principles (Airway, Circulation, r http://www.nlm.nih.gov/medlineplus/
Breathing)
– Injectable epinephrine in severe anaphylaxis latexallergy.html
◦ 0.3–0.5 mL of a 1:1000 solution IM (adult)
◦ 0.15–0.3 mL of a 1:000 solution IM (children)
– Epinephrine autoinjectors:
REFERENCES
◦ EpiPen, Adrenaclick (0.3 mg) in adults 1. Bernstein DI. Management of natural rubber latex
◦ EpiPen Jr., Adrenaclick (0.15 mg) in children allergy. J Allergy Clin Immunol. 2002;110:
r Supportive medications cannot be substituted for S111–S116.
epinephrine in the emergent management of 2. Blumchen K, Bayer P, Buck D, et al. Effects of latex
anaphylaxis because they do not prevent or relieve avoidance on latex sensitization, atopy and allergic
respiratory failure or shock, but can be useful after diseases in patients with spina bifida. Allergy.
initial resuscitation 2010;65:1585–1593.
– Antihistamines (diphenhydramine)
– Bronchodilators (albuterol)
– Steroids (hydrocortisone)
– H2 blockers (ranitidine)
223
LIBIDO, DIMINISHED, FEMALE

Sandip P. Vasavada, MD, FACS
PHYSICAL EXAM
BASICS DIAGNOSIS r Assessment of nongenital sexual characteristics
– Breast development
DESCRIPTION HISTORY – Axillary hair
r Diminished libido, low sexual drive, or hyposexuality r Details of low libido r Signs of endocrinologic disorder
are defined by a lack of desire for sexual activity. – Acquired or lifelong problem – Cushingoid appearance
r Hypoactive sexual desire disorder or subjective – Always or intermittently present – Hypothyroid skin and hair changes
sexual arousal disorder may be implicated. – With only specific sexual partners – Diabetic neuropathy
– After a new diagnosis or procedure r Visual inspection of the external genitalia
EPIDEMIOLOGY – Following use of a new medication
– Distribution of pubic hair
Incidence – Association with life events
r More common with advancing age and especially r Reproductive information – Ulcerations, pustules, discharge, or bleeding
– Prolapsed urethra, vagina, or cervix
following menopause – Age of menarche or onset of menses r Speculum exam
r A congenital syndrome may be causative at a young – Pregnancies and deliveries
– Mucosal rugae, moisture, thinning, or excoriation
age. – Contraception use and type
– Ulcerations, pustules, discharge, or bleeding
Prevalence – Infertility and treatment
r Other sexual information – Cystocele, rectocele, or enterocele
Estimated prevalence of 25–75% of women varies by – Vaginal wall masses
study sample and assessment – Sexually transmitted infection r Palpation of the external genitalia, vaginal sidewalls,
– Pain or discomfort with sexual activity
RISK FACTORS (1) pelvic floor muscles, cervix, and ovaries
– Problems with sexual function of the partner
r Low testosterone (physiologic or iatrogenic) r Current or prior abuse – Urethral or vaginal sidewall masses
r Advanced age – Surgically placed foreign bodies
– Sexual – Pelvic floor muscle tension, spasm, or tenderness
r Menopause (physiologic or iatrogenic) – Verbal or physical
r Pelvic floor disorder (incontinence or prolapse) r Symptoms of androgen insufficiency – Cervical motion, ovarian, or adnexal tenderness
r Physical or psychological trauma (sexual assault, – Vaginal cul-de-sac mass or tenderness
– Dysphoria, fatigue, low sense of well-being
physical abuse, or verbal abuse) – Reduced sexual receptivity and pleasure DIAGNOSTIC TESTS & INTERPRETATION
r Pregnancy (multifactorial per hormonal, emotional, – Decreased vaginal lubrication despite estrogen Lab
treatment r Estrogens: Estradiol and estrone
and physical changes)
r Signs of androgen insufficiency r Androgens: Dehydroepiandrosterone,
Genetics
Early onset menopause may be implicated – Bone loss, decreased muscle mass, less strength androstenedione, testosterone, and
– Memory changes and altered cognitive function dihydrotestosterone
PATHOPHYSIOLOGY (2,3) r Other endocrine disorders r Proteins: Sex hormone–binding globulin (SHBG)
r Testosterone drops 50% from age 30 to 60 years
– Hypothyroidism with free testosterone and total testosterone
and is linked to low libido as are other androgens. – Cushing syndrome r Adjunctive: Thyroid-stimulating hormone,
r Estrogen can increase sex hormone–binding – Diabetes glycosylated hemoglobin
globulin concentrations and lower free testosterone. r Urogenital conditions
r Progesterone may lower mood and decrease sex Imaging
– Urinary incontinence or fecal incontinence Brain magnetic resonance imaging to assess the
drive as seen with some contraceptives. – Pelvic organ prolapse
r Follicle-stimulating and luteinizing hormone hypothalamus and pituitary gland
r Medications
reduction by contraceptives lowers androgen – Oral contraceptives, estrogens, progestins, DIFFERENTIAL DIAGNOSIS
r Hormonal
creation. gonadotropin-releasing hormone agonists
r Serotonin level alterations from certain – Antidepressants, amphetamines, anticonvulsants, – Decreased free testosterone or increased sex
antidepressants can decrease sex drive. antiepileptics, psychotropics hormone–binding globulin
– Antihypertensives, antilipidemics, antiarrhythmics – Decreased androgen
ASSOCIATED CONDITIONS – Hypogonadotropic hypogonadism
r Vaginal atrophy – Steroids, narcotics
r Chronic medical conditions – Adrenal insufficiency or adrenal suppression
r Congenital syndromes
– Psychiatric conditions – Adrenal suppression or glucocorticoid excess
r Posttraumatic stress disorder (prior physical or – Hypothyroidism or hyperthyroidism
– Substance abuse
psychological trauma)
GENERAL PREVENTION
Exercise, balanced diet, healthy lifestyle
224
LIBIDO, DIMINISHED, FEMALE
r Psychological SURGERY/OTHER PROCEDURES ADDITIONAL READING

– Hypoactive sexual desire disorder, subjective Appropriate treatment of possibly causative medical
sexual arousal disorder, sexual aversion disorder (ie, endocrine tumor) conditions McDougal WS, Wein AJ, Kavoussi LR, et al. Female
– Sexual dysfunction in a partner Sexual Function and Dysfunction. In: Moore CK, ed.
r Iatrogenic ADDITIONAL TREATMENT Campbell-Walsh Urology. 10th ed. Philadelphia, PA:
– Medication side effect
Radiation Therapy Elsevier; 2012:823–833.
r Gynecologic N/A
– Dyspareunia, pelvic organ prolapse, sexually Additional Therapies r Dyspareunia
transmitted infection N/A r Female Hypoactive Sexual Desire Disorder
r Urologic Complementary & Alternative r Urinary Incontinence
– Urinary incontinence Therapies r Vaginal Atrophy
r Colorectal N/A
– Fecal incontinence
r Congenital syndrome
ONGOING CARE CODES
PROGNOSIS ICD9
TREATMENT r Results vary with etiology and treatment for many is r 799.81 Decreased libido
GENERAL MEASURES (1) long-term r 627.2 Symptomatic menopausal or female
r Behavioral r Multimodal approach to any etiology should be
climacteric states
– Identify and eliminate any libido-reducing most beneficial r 302.71 Hypoactive sexual desire disorder
behaviors, habits, or addictions COMPLICATIONS
– Psychological counseling, couples therapy, or sex Loss of libido can result in depression, infertility ICD10
therapy as indicated r F52.0 Hypoactive sexual desire disorder
– Encourage a healthy lifestyle with balanced diet, FOLLOW-UP r N95.1 Menopausal and female climacteric states
exercise, work, and sleep Patient Monitoring r R68.82 Decreased libido
r Frequent follow-up with initiation of new therapy is
MEDICATION best with regular lab work if hormones are used.
First Line r If using testosterone, monitor for signs of CLINICAL/SURGICAL
r Testosterone alone or in combination has been used
testosterone excess (acne, hirsutism, male pattern PEARLS
off-label to increase drive baldness, hyperlipidemia)
– Postmenopausal women with decreased libido r A good social history is essential.
who are not receiving estrogen therapy have Patient Resources r Sexual dysfunction in partners can cause this.
modest success using an experimental N/A r Overall physical health helps maintain libido.
testosterone patch delivering 300 μg/d
testosterone REFERENCES
r If possible elimination or replacement of
medications that may reduce libido 1. Maclaran K, Panay N. Managing low sexual desire
r Adjunctive treatment of vaginal atrophy with topical in women. Womens Health. 2011;7(5):571–581.
estrogen can be helpful 2. Brotto LA, Petkau AJ, Labrie F, et al. Predictors of
r Also consider appropriate goal-directed treatment of sexual desire disorders in women. J Sex Med.
other medical conditions 2011;8(3):742–753.
Second Line 3. Clayton AH. The pathophysiology of hypoactive
N/A sexual desire disorder in women. Int J Gynaecol
Obstet. 2010;110(1): 7–11.
225
LIBIDO, DIMINISHED, MALE

Daniel Box, MD
Anish K. Shah, MD
r Drugs: β-blockers, clonidine, diuretics, lithium, PHYSICAL EXAM

BASICS major tranquilizers, methyldopa, sedatives, r Assessment of secondary sexual characteristics.
ketoconazole, α-blockers, dihydrotestosterone – Absence of secondary sexual characteristics
DESCRIPTION inhibitors, cimetidine, antiandrogens, androgen suggests hormonal etiology.
r Diminished libido (hyposexuality) is the lack of analogs, selective serotonin reuptake inhibitors r Detailed exam of external genitalia for abnormalities
desire to engage in sexual experience. r Temporal lobe epilepsy r Assessment of testicular volume and atrophy
r Hypoactive sexual desire disorder is characterized by r Prostatitis
reduced libido and interest in sexual activity causing r Chronic and serious diseases can lead to loss of DIAGNOSTIC TESTS & INTERPRETATION
distress in women. libido through psychological or physiologic effects
Lab
r This section primarily focuses on decreased libido in r Serum testosterone
ASSOCIATED CONDITIONS r Serum prolactin
men.
r Erectile dysfunction (ED) and infertility may be r If any disturbances of the above, then serum
EPIDEMIOLOGY
associated with loss of libido and vice versa (2)[B]. follicle-stimulating hormone and LH
Incidence r Serum-free T4 and TSH
r 10–15% of men r Hypothyroidism
r Alcoholism r Serum GH and IGF-1 (primarily in children)
r 20–25% of women
r Syndromes, listed above in the Genetics section r Evlauation for increased cortisol if Cushing’s is
Prevalence suspected
N/A GENERAL PREVENTION
Imaging
N/A
RISK FACTORS MRI of the brain if prolactin is elevated
r Therapy for prostate cancer
r Congenital absence of the testicles DIFFERENTIAL DIAGNOSIS
DIAGNOSIS r Psychiatric disturbances
r Inflammatory insults to the testicles r Hormonal disturbances
r Surgical injury or removal of the testicles HISTORY
r Sexual history: r Drug induced
r Metabolic syndrome r Chronic and serious diseases
– Frequency and level of sexual desire
Genetics – Difficulty in achieving or maintaining an erection
r Loss of libido may be associated with some of the – Evidence of ejaculation disorder, overall
genetic disorders/syndromes, listed below: satisfaction with sexual life TREATMENT
– 17α-Hydroxylase deficiency – If semen volume is normal, it is unlikely that GENERAL MEASURES
– Autoimmune polyendocrine syndrome endocrine factors are responsible for loss of libido r Determine the cause and correct, if possible.
– Klinefelter syndrome – Sexual Health Inventory of Men (SHIM) score r Identify potential medications causing libido issues.
– Inactivation of the luteinizing hormone r History of psychiatric illness
r Psychiatric consultation/sexual function therapist
(LH)-receptor gene r Symptoms to suggest decreased testosterone: ED,
r Endocrinology consultation
– Mutations of steroid 5α-reductase gene increased irritability or depression, fatigue, reduced
PATHOPHYSIOLOGY muscle mass and strength, inability to concentrate, MEDICATION
r Psychological causes of diminished libido decreased bone density/osteoporosis First Line
r Previous/current medication
– Libido (sexual drive) is mediated by the cerebral r Decreased testosterone (3)[B]
cortex. r History of endocrine disorder
r Therapy for prostate cancer – Hormonal supplementation. For replacement
– Psychological disturbances of all degrees, from dosing, see chapter on “Testosterone, decreased
anxiety to major psychiatric disorders r Chronic alcoholism may result in decreased serum
(hypogonadism).”
– May be secondary to medical conditions (ie, testosterone, testicular atrophy, and decreased r Patients interested in sustaining fertility: Avoid
congenital anomaly, disfiguring injury, etc.) libido.
– Erectile dysfunction may cause loss of libido exogenous testosterone; stimulate with human
r Hormonal causes of diminished libido chorionic gonadotropin.
r If sexual dysfunction is identified as the cause:
– Hypogonadism: Androgen deficiency, particularly
testosterone, whether primary (testicular defect) Phosphodiesterase inhibitors (sildenafil, tadalafil,
or secondary to hypothalamic–pituitary etc.) are potentially useful 1st-line therapies
r Bromocriptine for prolactin-secreting tumors
dysfunction, Cushings syndrome
– Hyperprolactinemia with or without pituitary Second Line
lesion (1)[B] N/A
– Thyroid: Both hyper- and hypothyroidism can lead
to diminished sexual desire
226
LIBIDO, DIMINISHED, MALE
Only useful for pituitary adenomas causing REFERENCES CODES
hyperprolactinemia or in cases of Cushing’s disease
1. Shimon I, Benbassat C. Male prolactinomas
ADDITIONAL TREATMENT presenting with normal testosterone levels. ICD9
r 302.71 Hypoactive sexual desire disorder
Radiation Therapy Pituitary. 2014;17(3):246–250. r 752.89 Other specified anomalies of genital organs
N/A 2. Malavige LS, Jayaratne SD, Kathriarachchi ST, et al. r 799.81 Decreased libido
Additional Therapies Erectile Dysfunction among men with diabetes is
N/A strongly associated with premature ejaculation and ICD10
reduced libido. J Sex Med. 2008;5(9):2125–2134. r F52.0 Hypoactive sexual desire disorder
Complementary & Alternative 3. Aydogan U, Aydogdu A, Akbulut H, et al. Increased r Q55.0 Absence and aplasia of testis
Therapies frequency of anxiety, depression, quality of life and r R68.82 Decreased libido
L-arginine and yohimbine are touted but not proven sexual life in young hypogonadotropic hypogonadal
males and impacts of testosterone replacement
ONGOING CARE therapy. Endocr J. 2012;59(12):1099–1105. CLINICAL/SURGICAL
PEARLS
PROGNOSIS
The prognosis is good when there is a treatable ADDITIONAL READING r Decreased libido can be from a number of causes
underlying cause for loss of libido. Otherwise it can be r Carey JC. Pharmacological effects of sexual (medications, hormonal or psychiatric disorders,
permanent. etc.).
function. Obstet Gynecol Clin North Am. 2006; r A thorough history (including sexual history and
COMPLICATIONS 33(4):599–620.
Loss of libido can result in depression, infertility, and r Swerdloff R, Wang C, Goldman. Cecil Medicine. SHIM score) and physical exam (assessment of
erectile dysfunction. secondary sex characteristics and testicular volume)
23rd ed. Philadelphia, PA: WB Saunders; 2007. are critical and can often point to a diagnosis.
r Wilson B. The effect of drugs on male sexual r It is very important to distinguish decreased libido
FOLLOW-UP
Patient Monitoring function and fertility. Nurse Pract. from other disorders of sexual function (arousal,
Men treated with androgens should be followed 1991;16(9):12–17, 21–24. erectile dysfunction, premature ejaculation, orgasm,
closely with digital rectal exam and prostate-specific See Also (Topic, Algorithm, Media) and sexual pain disorders) but patients can often
antigen every 6 mo r Andropause (Late Onset Male Hypogonadism) have multiple issues simultaneously.
r Erectile Dysfunction r Surgery is usually designated for pituitary adenomas
Patient Resources
r http://www.merckmanuals.com/home/ r Female Hypoactive Sexual Desire Disorder (ie, prolactinomas), which can be found on brain
mens health issues/sexual dysfunction in men/ r Testosterone, Decreased (Hypogonadism) MRI.
decreased libido in men
r http://men.webmd.com/mens-libido-directory
227
LOWER URINARY TRACT SYMPTOMS

Matthew J. Resnick, MD
David F. Penson, MD, MPH
PATHOPHYSIOLOGY r In men:
BASICS r BOO necessitates generation of higher bladder – Inspection of the urethral meatus should be
pressures to overcome outlet resistance. performed to rule out meatal stenosis
DESCRIPTION r Bladder “remodeling” secondary to longstanding – Digital rectal exam (DRE) should be performed to
r The lower urinary tract infection (LUTS) complex evaluate for:
outlet obstruction results in overactive bladder
includes both obstructive and storage urinary syndrome, storage symptoms, and over time, ◦ Prostatic enlargement
symptoms. decreased contractility. ◦ Nodularity or firmness suggestive of prostate
– Obstructive urinary symptoms include urinary r LUTS may result from numerous conditions of the cancer
hesitancy, intermittency, post-void dribbling, and central and peripheral nervous systems. ◦ Bogginess or tenderness suggestive of
straining to void. r Result in either detrusor overactivity (storage prostatitis
– Storage urinary symptoms include urinary ◦ Anal sphincter tone, abnormalities of which
symptoms) or detrusor hypocontractility (urinary
frequency, nocturia, and urinary urgency. retention/inadequate emptying). suggest neurologic disease
r While benign prostatic hyperplasia (BPH) frequently r In women:
contributes to the development of LUTS, there are ASSOCIATED CONDITIONS – Speculum exam should be performed to evaluate
numerous other etiologies that must be considered Erectile dysfunction for mass, prolapse, and urethral abnormalities
in patients presenting with new urinary symptoms. GENERAL PREVENTION
r LUTS may result from structural or functional DIAGNOSTIC TESTS & INTERPRETATION
NA Lab
abnormalities of the genitourinary tract. r Urinalysis should be performed to evaluate for
EPIDEMIOLOGY DIAGNOSIS urinary tract infection or hematuria.
Incidence r Serum PSA should be considered as a diagnostic test
r There is a well-described relationship between age HISTORY (as opposed to a screening test).
r Essential to quantify LUTS for both diagnosis and r Serum creatinine is not recommended in the
and the development of LUTS.
r A few data specifically address the incidence of treatment planning evaluation of routine LUTS associated with BPH.
LUTS, given the basically negligible low case-fatality – Use the validated AUA Symptom Score (AUASS)
often referred to a the AUA Symptom Index Imaging
rate and the often slow onset of symptoms. r Imaging with CT or ultrasound (US) is not
[AUA-SI]) or International Prostate Symptom Score
Prevalence (I-PSS) (1–7 mild; 8–19 moderate; 20–35 severe) recommended as routine procedure.
r Disease prevalence is highly variable due to r Upper tract imaging with either CT or US may be
– Attention should be paid to nature (obstructive/
differences in disease definition. storage) and duration of LUTS considered in the context of:
r The Olmsted County Study revealed age-dependent r Consider voiding diary (frequency/volume charts) if – Acute symptom onset
increases in the prevalence of moderate-to-severe the patient is unable to elaborate the nature of his – History of upper urinary tract infection or stone
LUTS from 26% (40–49 yr) to 46% (70–79 yr) or her symptoms disease
r 21.1% of patients in the National Health and r Elicit history of prior urinary tract infection or – History of renal insufficiency
Nutrition Examination Survey (NHANES) reported at prostatitis – Recent onset of nocturnal enuresis
least one symptom of LUTS. r Elicit history of prior hematuria (gross or r Prostate imaging with transrectal or transabdominal
r Various community-based studies estimate the US may provide information for treatment planning
microscopic)
age-stratified prevalence of moderate–to-severe r Elicit history of prior urologic/pelvic surgery and is considered optional
LUTS in men as follows: Diagnostic Procedures/Surgery
– Prior lower urinary tract intervention predisposes
– 40–50 yr old: ∼20% r Assessment of post-void residual urine with US
to stricture/bladder neck contracture
– 50–60 yr old: ∼30% imaging or catheterization is optional.
– Disruption of pelvic plexus with pelvic surgery may
– 60–70 yr old: ∼40% – May aid in the noninvasive assessment of bladder
result in detrusor hypocontractility
– 70–80 yr old: ∼50–60% r Elicit history of other medical conditions function
RISK FACTORS – Neurologic disease—overactivity or bladder r Assessment of urinary flow rate is optional that may
r Bladder outlet obstruction (BOO; male) hypocontractility predict response to invasive therapy.
– Benign prostatic hyperplasia – Diabetes—bladder hypocontractility r Pressure flow urodynamic studies are not indicated
– Urethral stricture disease/bladder neck contracture – History of sexually transmitted in the evaluation of the uncomplicated patient with
– Prostate/bladder cancer infection(s)—urethral stricture disease LUTS
– Bladder calculi – History of pelvic radiation—urethral stricture – May be useful in patients with mixed symptoms or
r BOO (female) disease or bladder hypocontractility neurologic disease to develop a therapeutic
– Pelvic organ prolapse r Elicit family history of genitourinary disease strategy
– Bladder calculi (BPH/LUTS, prostate cancer, prostatitis) r Cystourethroscopy is not recommended for the
– Urethral stricture disease r Review medications as certain antihistamines, uncomplicated patient with LUTS.
r Bladder (detrusor) hypocontractility antimuscarinics, sympathomimetics, and – May be helpful to assess prostate configuration as
– Idiopathic bronchodilators may exacerbate LUTS. it relates to invasive therapies
– Neurogenic r Elicit history of sexual dysfunction – May be useful in patients with mixed symptoms or
r Obesity, diabetes, and caffeine intake all have been r Evaluate overall fitness to undergo invasive neurologic disease to develop a therapeutic
associated with increased risk of LUTS procedure(s) strategy
– May be useful in patients with a history suggestive
Genetics PHYSICAL EXAM
r Increased risk of moderate-to-severe LUTS in men of urethral stricture/bladder neck contracture
r Abdominal exam to assess suprapubic region for
with a family history of BPH. bladder distension Pathologic Findings
r The precise contribution of genetic and r Focused neurologic exam should be performed with Histopathology of BPH reveals proliferation of both
environmental factors to the development of LUTS stromal and glandular prostatic elements.
particular attention to:
remains largely unknown. – General mental status
– Ambulatory status
– Motor and sensory function of the lower
extremities and perineum
– Anal sphincter tone
228
LOWER URINARY TRACT SYMPTOMS
r BOO:
r Urethroplasty or directly visualized incision of
REFERENCES
– Urethral Stricture/bladder neck contracture urethral stricture (DVIU) should be considered for 1. AUA Guideline on the Management of Benign
– Bladder stone stricture/bladder neck contracture Prostatic Hyperplasia (BPH). 2012. http://
– Cancer (prostate, bladder, urethral) r Prolapse repair should be considered for women www.auanet.org/content/clinical-practice-
– Prostatitis with urinary symptoms and prolapse guidelines. Accessed November 23, 2013.
– Urinary tract infection r Numerous surgical options exist for men with 2. McConnell JD, Roehrborn CG, Bautista OM, et al.
– Detrusor-sphincter dyssynergia BPH/BOO. Some of these include: The long-term effect of doxazosin, finasteride, and
– Pelvic organ prolapse – Transurethral resection of the prostate (TURP) combination therapy on the clinical progression of
r Detrusor hypocontractility – Transurethral microwave therapy (TUMT) benign prostatic hyperplasia. N Engl J Med.
– Diabetes mellitus – Transurethral laser vaporization of the prostate 2003;349:2387–2398.
– Parkinson disease – Transurethral laser enucleation of the prostate 3. Barry MJ, Meleth S, Lee JY, et al. Effect of
– Multiple sclerosis – Simple open or laparoscopic prostatectomy increasing doses of saw palmetto extract on lower
– Radiation cystitis (generally reserved for men with prostate volume urinary tract symptoms: a randomized trial. JAMA.
– Spinal cord injury > 80–100 cc) 2011;306:1344–1351.
– Lumbosacral disc disease r There are a few high-quality
– Bladder stone comparative-effectiveness data upon which clinical
decisions can be based ADDITIONAL READING
TREATMENT – Patients and physicians must weigh potential r McNicholas TA, Kirby RS, Lepor H. Evaluation and
benefits and harms of treatments.
nonsurgical management of benign prostatic
GENERAL MEASURES (1,2) ADDITIONAL TREATMENT hyperplasia. In: Wein AJ, Kavoussi LR, Novick AC,
r Treatment should be offered to men with moderate
Radiation Therapy et al. Campbell-Walsh Urology. 10th ed.
to severe symptoms (AUASS or IPSS ≥8) who are Philadelphia, PA: Saunders Elsevier; 2010.
N/A
bothered enough to consider therapy. r Roehrborn CG. Benign prostatic hyperplasia:
r Men with demonstrable sequelae of BPH/BOO (renal Additional Therapies
Behavioral interventions including timed voiding, etiology, pathophysiology, epidemiology, and
failure secondary to obstruction, bladder calculi, natural history. In: Wein AJ, Kavoussi LR, Novick AC,
etc.) should be counseled on benefits of treatment. double voiding, and biofeedback may improve
et al. Campbell-Walsh Urology. 10th ed.
r Treatment is tailored to symptom type (obstructive, symptoms.
Philadelphia, PA: Saunders Elsevier; 2010.
storage, mixed). Complementary & Alternative
Therapies See Also (Topic, Algorithm, Media)
MEDICATION r Bladder Outlet Obstruction (BOO)
Saw palmetto is widely used to treat LUTS with little r LUTS Algorithm
First Line benefit in randomized trials (CAMUS trial) (3).
r α-Adrenergic blockers: relax prostatic/bladder neck r Prostate, Benign Hyperplasia/Hypertrophy (BPH)
smooth muscle tone and improve symptoms (all r Reference Tables: AUA Symptom Index/International
appear to have equal effectiveness) ONGOING CARE Prostate Symptom Score (I-PSS)
– Alfuzosin 10 mg/d
– Doxazosin start 1 mg/d to max. 8 mg PROGNOSIS
r 20% of men with untreated LUTS experience
– Silodosin 8 mg/d
– Tamsulosin start 0.4 mg to max. 0.8 mg progression within 5 yr (MTOPS trial). Options for CODES
– Terazosin start 1 mg/d to max. 20 mg men with BPH/BOO include:
– Side effects include syncope, orthostasis, – Combination therapy reduces risk of progression ICD9
by 66% (2). r 788.41 Urinary frequency
retrograde ejaculation, asthenia, and nasal
congestion r 5–10% of men with moderate-to-severe LUTS will r 788.64 Urinary hesitancy
r 5α-Reductase inhibitors: reduce prostatic volume require surgical intervention (MTOPS). r 788.99 Other symptoms involving urinary system
– Finasteride or dutasteride COMPLICATIONS ICD10
– Side effects include decreased libido and sexual
dysfunction
r Complications of BPH/LUTS include: r R35.0 Frequency of micturition L
– Recurrent UTIs r R39.9 Unsp symptoms and signs involving the
– Reduce PSA by ∼50% and correction should be – Renal insufficiency
used when evaluating risk for cancer genitourinary system
– Bladder stone formation r R39.11 Hesitancy of micturition
r Combination therapy (α-adrenergic blocker +
– Urinary retention
5α-reductase inhibitor) should be considered in men – Secondary bladder dysfunction
with moderate to severe symptoms and prostatic
enlargement. FOLLOW-UP CLINICAL/SURGICAL
r Tadalafil 2.5–5 mg/d can treat combined LUTS and Patient Monitoring PEARLS
r Monitoring with serial AUASS or IPSS to quantify
erectile dysfunction (ED). r Quantification of symptoms is paramount in the
r Antimuscarinic agents can be used alone or in symptom intensity and bother
r Urinalysis, serum PSA, urinary flow rate, and management of LUTS.
combination for overactivity/storage symptoms r Treatment should be offered to men with moderate
post-void residual as clinically indicated
Second Line to severe symptoms (AUASS ≥8).
N/A Patient Resources r Treatment should be tailored to symptoms and
Urology Care Foundation. http://www.urologyhealth. prostate volume and may include behavioral
org/urology/index.cfm?article=59&display=1 intervention, medical management, or surgical
intervention.
229
LYMPHADENOPATHY, INGUINAL
Michael E. Woods, MD
Raj S. Pruthi, MD, FACS
ASSOCIATED CONDITIONS – Herpes simplex

BASICS r Balanitis ◦ Viral culture of active lesion (50% sensitive)
r Phimosis ◦ PCR of specimen from genital ulcer
DESCRIPTION r Additional sexuallt transmitted infections (STI’s) ◦ Direct fluorescent antibody of specimen
r Clinically evident inguinal lymphadenopathy can be ◦ Serology for HSV-1/2 (90% and 95% sensitivity
secondary to infection, inflammation, or malignancy. GENERAL PREVENTION and specificity, respectively)
r Lymph nodes (LNs) are generally considered r Prepubertal circumcision is protective against penile
– LGV: Culture Chlamydia trachomatis from ulcer or
enlarged if >1 cm. cancer LN aspirate
r There is a <1% annual incidence of unexplained r Good genital hygiene ◦ Serologic identification with complement
r STD education and safe sexual practices fixation or microimmunofluorescence; PCR
peripheral (including inguinal) lymphadenopathy.
r 14% of all abnormal lymphadenopathy present in r Sun protection against melanoma – Chancroid: H. ducreyi culture (75% sensitive)
inguinal region r HPV vaccination may reduce risk (unproven) ◦ PCR >95% sensitive/specific (non-FDA
approved)
EPIDEMIOLOGY – HIV: Serology for IgG antibody to HIV-1 antigens
Incidence DIAGNOSIS (positive test confirmed via western blot assays)
r Malignancy
HISTORY Imaging
– Penile cancer (1)[A] r Constitutional symptoms: Weight loss, night sweats r CT abdomen/pelvis: Extent of disease
◦ 0.4–0.6% of male cancers in USA r Age: Penile cancer is more likely in older individuals, – Evaluates other sites of lymphadenopathy
◦ Median age at diagnosis: 68 yr lymphoma
◦ 50% of enlarged LN secondary to cancer STI more common in younger patients r CT chest/CXR: Staging in setting of malignancy
r Sexual history: Number and sex of partners, condom
– Lymphoma: ∼80,000 cases/yr in USA r Inguinal US: Evaluate solid vs. cystic lesions; identify
use
r Infectious (STD/STI) (2)[A] r Travel: International travel is common source of STI abscess
– Approximately 15 million new Sexually and other endemic diseases. Diagnostic Procedures/Surgery
Transmitted Infections (STI) cases/yr in USA r Ethnicity: Higher penile cancer in South America r Excisional biopsy of abnormal LN or primary lesion
– Chancroid (Haemophilus ducreyi)–24 cases r History of other diseases, malignancy, lower (preferred)
reported to the CDC in 2010 extremity trauma, animal exposure r Percutaneous biopsy/aspiration of abnormal LN
– Herpes simplex–775,000 cases/yr, 16% of r Bone marrow biopsy (lymphoma workup)
14–49-yr olds infected with HSV-2 PHYSICAL EXAM
r Cachexia: Suggests systemic illness DIFFERENTIAL DIAGNOSIS
– Lymphogranuloma venereum (LGV)–relatively r Nonspecific lymphadenitis
rare; rise in USA and UK associated with men – HIV, lymphoma
r Generalized lymphadenopathy (neck, axilla) r Malignancy: In a historic study of over 200 patients
who have sex with men and persons with HIV
– Syphilis–In 2011, USA, men 8.2/100,000; – Signs of systemic process (HIV, lymphoma) the order of malignancy in inguinal
women 1/100,000 r Abdominal exam lymphadenopathy was: Cutaneous malignancy of
– HIV–1.1 million people in USA infected – Palpable masses, splenomegaly lower extremity (melanoma), cervical, vulva,
– Gonorrhea: 2nd commonest STI in USA r Lower extremities bilaterally for lesions cutaneous malignancy of the trunk, rectum/anus,
r Infectious (soft tissue of the leg/foot) r Inguinal exam ovary, and penile cancer.
r Infectious
– Common causes: β-hemolytic streptococci and – Size, fixation of LNs
Staphylococcus aureus – Erythema, tenderness, warmth, – Soft-tissue infection of the lower extremity
drainage/purulence (ie, Staphylococcus)
RISK FACTORS r Genital exam – STD (HIV, gonococcus, herpes simplex, chancroid,
r Penile Cancer LGV, syphilis)
– Penis, glans, foreskin, scrotum for lesions
– Circumcision (neonatal circumcision is protective) r With more generalized lymphadenopathy consider a
– Erythema, drainage, purulence, abscess
– Poor genital hygiene; phimosis – Ulcers (can be secondary to herpes, chancroid, systemic disease
– Number of sexual partners granuloma inguinale, syphilis, neoplasias); vesicles – Infections: Epstein–Barr, toxoplasmosis,
– Human papilloma virus (HPV) infection (type 16 with herpes cytomegalovirus, mycobacteria (TB, etc.),
and 18) r Formal pelvic exam in women mononucleosis
– Incidence of LN metastases related to grade, – Lymphoma, lupus
stage, and lymphovascular invasion DIAGNOSTIC TESTS & INTERPRETATION r Medications: Cephalosporins, others
r STI: High-risk sexual practices (ie, nonuse of Lab
condom, multiple partners, men who have sex with r Suspected malignancy
men) – CBC, basic metabolic panel, liver function testing TREATMENT
PATHOPHYSIOLOGY (LFT’s)
r Inguinal lymph nodes (ILNs) serve at the primary r Infectious/STD (2) GENERAL MEASURES
r Generalized lymphadenopathy should be referred for
lymphatic drainage for the penis, scrotum, urethra, – Gonococcus
◦ Nucleic acid amplification testing (ie, polymerase global evaluation.
vulva, vagina, perineum, gluteal region, lower r A period of observation for localized
abdominal wall, lower anus, and lower extremities. chain reaction [PCR]) of vaginal samples, urine,
r ILNs lie within the femoral triangle (inguinal urethral samples—98% sensitive lymphadenopathy is reasonable if there are no other
◦ Culture–72–95% sensitive, perform if drug clinical findings.
ligament, sartorius, and adductor longus) and are r Penile cancer requires treatment of primary lesion
separated into superficial and deep groups by the resistance is suspected
– Syphilis (based on size and location), followed by inguinal
fascia lata of thigh.
r Penile squamous cell carcinoma (SCC) cancer ◦ Darkfield microscopy of primary chancre, screen lymphadenectomy if indicated.
with nontreponemal test (RPR, VDRL) confirm r Infectious etiologies need to be accurately
spreads by a relatively reliable pattern: From diagnosed so appropriate treatment can be initiated
with treponemal test (FTA-ABS)
superficial pelvic LNs to deep pelvic LNs (see below).
r Gynecologic malignancies have a high
predisposition for inguinal spread.
230
LYMPHADENOPATHY, INGUINAL
MEDICATION ◦ Routine division of saphenous vein and sartorius ADDITIONAL READING

First Line transposition; higher morbidity
r Infectious etiology r Pagliaro LC, Williams DL, Daliani D, et al.
r STD (2)[A]
– Fine-needle aspiration for culture Neoadjuvant paclitaxel, ifosfamide, and cisplatin
– Chancroid: Azithromycin 1 g PO ×1 or chemotherapy for metastatic penile cancer: A phase
ceftriaxone 250 mg IM ×1 or ciprofloxacin – Incision and drainage of abscess
r Lymphoma II study. J Clin Oncol. 2010;28:3851–3857.
500 mg PO BID ×3 days or erythromycin base r Zaren HA, Copeland EM, III. Inguinal node
500 mg PO TID ×7 days – Excisional biopsy of ILN (may consider other site if
generalized lymphadenopathy is present) metastases. Cancer. 1978;41(3):919–923.
– Herpes simplex (primary): Acyclovir 400 mg PO
TID ×7–10 days or acyclovir 200 mg PO 5×/day ADDITIONAL TREATMENT See Also (Topic, Algorithm, Media)
×7–10 days or famciclovir 250 mg PO TID r Chancroid
Radiation Therapy r Groin/Inguinal Mass, Male and Female
×7–10 days or valacyclovir 1 g PO BID ×7–10 days Penile Cancer: Palliation of bulky, unresectable
– LGV: Doxycycline 100 mg PO BID ×21 days OR r Lymphadenopathy, Inguinal Image
inguinal lymphadenopathy
erythromycin base 500 mg PO QID ×21 days r Lymphadenopathy, Pelvic and Retroperitoneal
– Syphilis (primary and secondary): Benzathine Additional Therapies r Lymphogranuloma Venereum (LGV)
r Penile cancer
penicillin G 2.4 million units IM ×1 r Penis, Cancer, General Considerations
– Syphilis (late latent): Benzathine penicillin G – Patients with fixed ILN or pelvic LNs should
r Penis, Cancer, Lymphadenopathy
2.4 million units 1×/wk ×3 wk receive cisplatin-based chemotherapy followed by
consolidative surgery when appropriate (3)[C] r Reference Tables: TNM Classification: Penis Cancer
– Gonococcus: Ceftriaxone 400 mg IM ×1 plus
◦ Paclitaxel, ifosfamide, cisplatin—50% complete r Sexually Transmitted Infections (STIs) (Sexually
azithromycin 1 g PO ×1 or doxycycline 100 mg
PO BID ×7 days OR cefixime 400 mg PO × response (CR) or partial response (PR) and Transmitted Diseases [STDs]), General
1 plus azithromycin 1 g PO ×1 or doxycycline ∼75% underwent planned surgery
100 mg PO BID ×7 days; if cephalosporin
allergy: Azithromycin 2 g PO ×1
ONGOING CARE CODES
– HIV: Antiretroviral drug regimens (see Section 1
“HIV/AIDS, Urologic Considerations” and latest PROGNOSIS ICD9
CDC guidelines) r Penile Cancer r 187.4 Malignant neoplasm of penis, part unspecified
– Node negative: 46–100% 5-yr survival (mean r 202.80 Other malignant lymphomas, unspecified
r Penile cancer (1)[A] ∼75%) site, extranodal and solid organ sites
– Node positive: 0–86% 5-yr survival based on r 785.6 Enlargement of lymph nodes
– Management of primary lesion (local excision, nodal burden (average ∼60%)
partial penectomy, total penectomy) ICD10
– Non-palpable ILNs COMPLICATIONS r C60.9 Malignant neoplasm of penis, unspecified
r ILND
– Up to 50% of all enlarged ILNs are benign in r C85.90 Non-Hodgkin lymphoma, unspecified,
patients with newly diagnosed penile cancer. – Seroma, lymphedema, wound infection, skin
unspecified site
Treated with 6 wk of antibiotics (currently necrosis r R59.0 Localized enlarged lymph nodes
controversial) prior to consideration of inguinal – 25–50% risk
lymph node dissection (ILND) or undergo a fine FOLLOW-UP
aspiration of the node in question if the primary
Patient Monitoring CLINICAL/SURGICAL
tumor is low risk.
– Occult metastases ∼25% r Penile Cancer (1)[A] PEARLS
◦ TaG1-2/T1G1—surveillance – Nx (surveillance) r Differentiate inguinal adenopathy from more
◦ T1G2—surveillance vs. ILND or dynamic ◦ Q3mo yr 1–2 then Q6mo yr 3–5
generalized LN involvement.
sentinel node biopsy (DSNB) – N0, N1 r The viability of the skin flaps developed during an
◦ ≥T2 or any G3—ILND or DSNB ◦ Q6mo yr 1–2 then Q12mo yr 3–5
inguinal dissection are based on the anastomotic
– Palpable ILNs – N2, N3
◦ Q3–6mo yr 1–2 then Q6–12mo yr 3–5 vessels within the superficial fatty layer of Camper’s
◦ Low risk—consider fine-needle aspiration to
confirm malignancy; Intermediate/high r Infectious (2)[A] fascia which course lateral to medial along the skin
lines. This is a key anatomic dissection plane as the
L
risk—ILND – Chancroid–3–7 days after initiating treatment lymphatic drainage of the penis lies beneath
r Inguinal lymphadenectomy techniques – LGV–evaluate for clinical resolution, timing Camper’s fascia allowing this superficial fatty layer
– Dynamic sentinel node biopsy (DSNB) variable to remain attached to the skin flaps.
◦ Use of blue dye + γ -emission (radio nuclide – Syphilis–clinical and serologic evaluation at r Use a modified technique in a clinically negative
tracer) 6 and 12 mo
groin to decrease morbidity. The key components:
◦ False-negative 5%; expertise required – Gonorrhea–none if symptoms resolve
Shorter incision (∼10 cm), preserve saphenous vein,
– Superficial ILND Patient Resources minimize dissection lateral to the femoral artery, and
◦ Removal of LN above fascia lata N/A avoid transposition of the sartorius muscle.
◦ If lymph positive on frozen section, then
compete ILND needed
◦ Option for prophylactic ILND REFERENCES
– Modified ILND 1. Spiess PE, Horenblas S, Pagliaro LC, et al. Current
◦ Appropriate for prophylactic ILND
concepts in penile cancer. J Natl Compr Canc Netw.
◦ Decreased morbidity
2013;11:617–624.
◦ Limited template (lateral border femoral
2. Workowski KA, Berman S; Centers for Disease
artery, caudal border fossa ovalis)
◦ Includes deep nodes medial to femoral vein Control and Prevention (CDC). Sexually transmitted
◦ Smaller incision; preserve saphenous vein diseases treatment guidelines, 2010. MMWR
◦ Avoids transposition of sartorius muscle Recomm Rep. 2010;59(RR-12):1–116.
◦ Positive on frozen, then standard ILND
– Radical/standard ILND
◦ Indicated for patient with metastatic disease
to the ILNs
◦ Larger template including tissue lateral femoral
artery and distally to apex of the femoral triangle
231
LYMPHADENOPATHY, PELVIC AND RETROPERITONEAL

Carrie L. Fitzgerald, DO, MPH

BASICS r Ureteral obstruction
Lab
r IVC compression +/– lower extremity edema r CBC, ESR, exam of peripheral smear
DESCRIPTION r DVT r Creatinine (for imaging and to check renal function)
r Enlarged nodal tissue in the pelvis and/or r Await genetics consult for others r Urinalysis for hematuria
retroperitoneum r VHL: 3p25-26 r Urine cytology
r Can be regional or generalized
r HPRC: 7q31 r Tumor markers:
r Definitions vary, but include solitary node
r HLRCC: Long arm of chromosome 1 – PSA: Prostate cancer
≥1–1.5 cm in short axis, any rounded node r BHD: 17p11.2 – AFP, β-hCG, LDH: Testicular cancer
>8 mm or multiple nodes >1 cm (1). r Hereditary paraganglioma and pheochromocytoma
r Pelvic lymph nodes (LNs) are generally considered – CA-125: Ovarian cancer
(HPP) – CEA: Colon cancer
abnormal if >1.3 cm. r Tuberous sclerosis complex: TSC, TSC1, 9q34.13;
r Often discovered incidentally or with imaging Imaging
TSC2, 16p13.3 r May diagnose cause of adenopathy (ie, renal mass)
performed for tumor staging. r Ultrasound: Can pick up larger masses;
r Usually nonacute, but potentially life threatening. PATHOPHYSIOLOGY
r Most adenopathy incidental; may be regional or false-negatives are significant
EPIDEMIOLOGY r CT/MRI: More sensitive than US (1)[A]
generalized
Incidence r Usually one of five causes: Malignant, infectious, – Nodes <7–10 mm considered reactive
r Lymphoma is the most frequent malignant tumor in
autoimmune, inflammatory (reactive), iatrogenic – CT generally considered best; use MRI if contrast
the retroperitoneum. Non-Hodgkin lymphoma contraindicated
(93.7%) occurs more commonly than Hodgkin ASSOCIATED CONDITIONS r PET: Evaluate fibrosis from metabolically active
lymphoma (6.3%). See risk factors
r Other common causes of retroperitoneal nodes, ie, postchemotherapy testicular cancer,
GENERAL PREVENTION seminoma (2); expanding role (3)
lymphadenopathy are malignancies, infections of Resolution of primary source
retroperitoneal and pelvic organs and external – Some studies show PET can define testicular
genitalia. relapse before CT.
r SPECT: Advances in lymphoscintigraphy have
Prevalence DIAGNOSIS
advanced opportunity for LN resection in select GU
No consistency in literature malignancies (1).
HISTORY
RISK FACTORS r Constitutional: Weight loss, night sweats (especially r Bipedal lymphangiography largely replaced by CT
r Tumor-associated syndromes: with lymphoma), fatigue, fever and MRI.
– Renal cancer: r Local compressive symptoms: Bowel obstruction,
◦ von Hippel–Lindau (VHL) hydronephrosis/pyelonephritis/uremia, lower limb r Nodal tissue exam unless diagnosis is clear (ie,
◦ Hereditary papillary renal carcinoma (HPRC) edema (vascular/lymphatic compromise) testicular or prostate tumor), then size or function
◦ Hereditary leiomyomatosis and renal cell cancer r Severe infection on perineum/pelvis may result in
and physiology becomes important (1).
(HLRCC) inguinal/pelvic adenopathy r CT-guided biopsy best way to obtain nodal tissue.
◦ Birt–Hogg–Dube (BHD) r History of primary GU, GI, or GYN tumor
◦ Hereditary paraganglioma and – Not always feasible (ie, proximity to major
r Paraneoplastic syndromes (ie, breast tenderness, vessels), open/laparoscopic in select cases
pheochromocytoma (HPP) anemia, etc.) r CT/MRI or SPECT imaging
◦ Tuberous sclerosis complex (TSC) r Immunocompromised states raise risk of
r Adrenal cancer: Pathologic Findings
mycobacterial infection, lymphoma, or Kaposi
– Gardner syndrome Numerous, depends on cause (see below)
sarcoma
– Beckwith–Wiedemann syndrome (associated with DIFFERENTIAL DIAGNOSIS
hemihypertrophy) PHYSICAL EXAM r Tumor
– Multiple endocrine neoplasia type 1 r Evaluate for peripheral lymphadenopathy (neck,
– Primary lymphatic: Lymphoma (non-Hodgkin,
– SBLA syndrome (Sarcoma, Breast, Lung, Adrenal supraclavicular, inguinal, axillary)
r Chest: Clear breath sounds, breast tissue, or Hodgkin, others)
carcinoma) – Secondary: Adrenal, renal, urothelial and
– Li–Fraumeni syndrome tenderness nonurothelial bladder or upper tract cancer,
r Urothelial cancer r Abdominal/pelvic exam: Meta/menorrhagia,
prostate, urethral, penile, germ cell, cervical,
– Hereditary nonpolyposis colorectal cancer palpable mass, bruits, thrills ovarian, uterine, GI (carcinoid, lymphomas),
(HNPCC) r GU/GI exam: Testicular mass, right-sided varicocele, colorectal, melanoma, Kaposi sarcoma
– Hereditary retinoblastoma penile lesions, digital rectal exam (DRE), perineal r Infectious/inflammatory
– Costello syndrome cellulitis/abscess, fecal occult blood testing, – Granulomatous: TB, sarcoidosis, histoplasmosis,
– Possibly Apert syndrome hematuria, pelvic exam in females lymphogranuloma venereum, Castleman disease
r Prostate cancer r Skin: Rash, lesions (malignant, benign), ie, (angiofollicular LN hyperplasia associated with
– Hereditary breast and ovarian syndrome (HBOS) melanoma HIV and human herpesvirus 8 [HHV-8]).
r Patients with primary tumors of GI, GU, and GYN r Lower extremity edema – Nongranulomatous: Viral, bacterial (if abscess in
tracts and associated risk factors for these local areas), sinus histiocytosis, retroperitoneal
malignancies fibrosis
r Smoking, age, family history, HPV r Other: Neoplastic, non-neoplastic, and cystic
r Immunosuppression (HIV, autoimmune) retroperitoneal masses (lymphocele, urinoma,
r Lymphadenitis seen with inflammatory/infectious hemorrhage) aneurysms
conditions of the pelvis
232
LYMPHADENOPATHY, PELVIC AND RETROPERITONEAL

ONGOING CARE r Groin/Inguinal Mass
TREATMENT r Lymphadenopathy, Inguinal
GENERAL MEASURES PROGNOSIS r Lymphadenopathy, Pelvic and Retroperitoneal
r Wide variety, based on diagnosis of primary disease Widely variable Images
r Image-guided needle biopsy, as a 1st-line r Retroperitoneal Mass and Cysts
COMPLICATIONS
investigation, is useful in the diagnosis of r Severe lymphadenopathy can result in lower
space-occupying lesions of the retroperitoneum extremity edema, varicocele
r Routine lymphadenectomy usually indicated for GU r Potential surgical complications of retroperitoneal CODES
malignancy lymphadenectomy include vascular injury,
MEDICATION lymphocele, chylous ascites, ejaculatory dysfunction, ICD9
and GI complications (pancreatitis, bowel r 202.80 Other malignant lymphomas, unspecified
First Line
injury/obstruction) site, extranodal and solid organ sites
Based on diagnosis of primary disease
r 567.9 Unspecified peritonitis
Second Line FOLLOW-UP
r 785.6 Enlargement of lymph nodes
N/A Patient Monitoring
Based on primary disease
r Open or laparoscopic nodal sampling may be Patient Resources r C85.90 Non-Hodgkin lymphoma, unspecified,
required in select cases N/A unspecified site
r Lymphadenectomy at time of organ-specific r K65.9 Peritonitis, unspecified
r R59.0 Localized enlarged lymph nodes
resection indicated in many cases of GU, GYN, and REFERENCES
GI malignancy
1. Chernyak V. Novel imaging modalities for lymph
r Underlying cause must be treated appropriately node imaging in urologic oncology. Urol Clin North CLINICAL/SURGICAL
r Benign reactive lymphadenopathy can be seen in Am. 2011;38:471–81. PEARLS
2. Becherer A. PET in testicular cancer. Methods Mol r General malignancies (testis, penile) have
the presence of malignancy and improves with
Biol. 2011;727:225–241.
appropriate treatment predictable lymphadenopathy pattern of spread.
r Lymphadenectomy for malignant lymphadenopathy 3. Bouchelouche K, Oehr P. Recent developments in r Pelvic organ malignancies may have skip lesions to
urologic oncology: Positron emission tomography
does not always affect overall survival (4). the retroperitoneum.
molecular imaging. Curr Opin Oncol. 2008;20:
Radiation Therapy r Lymphadenectomy may be curative for many
321–326.
For certain causes such as seminoma 4. Bochner BH, Coleman JA, Carver BS, et al. Role of urologic and nonurologic malignancies.
r Urinary, bowel, and vascular obstruction possible
Additional Therapies lymphadenectomy in genitourinary cancer. AUA
r In select cases, reimaging for signs of growth or Update Series. 2009;28:205–209. with advanced lymphadenopathy.
r Inflammatory and infectious conditions may lead to
assessing therapeutic response, eg, hormonal
therapy for prostate cancer, antibiotics for penile reactive lymphadenopathy.
cancer ADDITIONAL READING
r Notification of partners if HIV-positive (3)[A] Chen L, Kuriakose P, Hawley RC, et al. Hematologic
Complementary & Alternative malignancies with primary retroperitoneal
Therapies presentation: Clinicopathologic study of 32 cases.
N/A Arch Pathol Lab Med. 2005;129(5):655–660.
233
LYMPHOCELE, PELVIC
Rafael E. Yanes, MD
Fernando J. Bianco, Jr, MD
GENERAL PREVENTION DIAGNOSTIC TESTS & INTERPRETATION

BASICS r Meticulous lymphadenectomy with clips on proximal
Lab
end of lymphatic vessels. r Serum creatinine, BUN (especially to follow renal
DESCRIPTION – Monopolar electrocoagulation may not function in transplant patient)
r A lymphocoele is a localized encapsulated collection adequately seal lymph channels. r Aspirated fluid creatinine and BUN, Gram stain and
of lymphatic fluid created by disruption of lymphatic – Bipolar or harmonic devices have been shown to culture
vessels. be effective (bipolar devices created seals that r Lymphatic fluid typically contains protein, BUN,
r A collection of lymph fluid in a cavity that is not were fivefold to 10-fold stronger than the creatinine, electrolytes, and, occasionally, lipids as
lined by epithelium harmonic devices) serum
r Generally occurs following surgery such as pelvic or ◦ These vessel-sealing devices (VSDs) may reduce r In contrast, urinoma has markedly elevated
retroperitoneal lymphadenectomy or renal risk.
creatinine; lymphocele creatinine = serum creatinine
transplantation – Use of FloSeal or other hemostatic products after
lymphadenectomy may reduce the number of Imaging
EPIDEMIOLOGY symptomatic lymphoceles. r Key to diagnosis, but cannot distinguish between
Incidence (1) r Some reports that the use of anticoagulants (eg, lymphocele and urinoma
r Incidence: 0.6–18% after renal transplant r US: Imaging, lymphoceles appear as anechoic cystic
subcutaneous heparin) postop may increase
r Clinical incidence: 1–10% after pelvic structures that may contain thin septations and
lymphocele risk.
lymphadenectomy – Use of low-dose heparin in this setting when debris.
– May be up to 20–25% if all patients were imaged injected in the upper arm may reduce lymphocele – Pelvic: To identify fluid collection that is separate
postoperatively risks. from the bladder, adjacent to renal allograft
r After robot-assisted laparoscopic lymphadenectomy r Use of suction drains does not appear to impact the – Retroperitoneal: To evaluate hydronephrosis, if
(RA-PLND) is about 5%, half becoming symptomatic development of lymphoceles. suspected
– Ideal for follow-up of resolution
RISK FACTORS
r Recent pelvic surgery (ie, PLND, open or – Duplex study of the lower extremities: To evaluate
laparoscopic), renal transplant, retroperitoneal
DIAGNOSIS for DVT
r Pelvic CT: Best definition of size and location of
lymph node dissection (RPLND), RA-PLND, HISTORY
gynecologic procedures: lymphocele
– Extended PLND > conventional PLND – Seen as thin-walled hypodense lesions
– Extraperitoneal > transperitoneal procedures ALERT – Negative Hounsfield units
– Risk increases linearly with the number of nodes Lymphoceles can occur after transperitoneal – Thickened, enhanced wall suggest infection
r IVP: May show displacement of ureter and
retrieved. laparoscopic, robot-assisted surgery.
r Prior radiation or chemotherapy r Recent pelvic surgery, particularly involving compression of bladder, but is seldom necessary
r Anticoagulation or antiplatelet therapy may increase lymphadenectomy Diagnostic Procedures/Surgery
r Prior chemotherapy or pelvic radiation r Lymphangiography/lymphoscintigraphy: If other
risk
r Long-term use of steroids r Timing of onset of symptoms: studies unclear, historic value
r Presence of involved lymph nodes r Diagnostic aspiration with count and cultures
– Urine leak (urinoma), hematoma, abscess, and
PATHOPHYSIOLOGY peritonitis typically present early Pathologic Findings
r Lymphatic fluid collects in the extraperitoneal space – Lymphocele can present early in the postop Lymph fluid in a fibrous cavity not lined by
due to continued lymphatic leakage. period, but may present several weeks or epithelium-containing lymphatic fluid.
r Transperitoneal pelvic lymphadenectomy is less months after surgery DIFFERENTIAL DIAGNOSIS
r Urinary frequency (if compressing bladder) r Abscess
commonly associated with the development of a
lymphocele but can occur. r Sensation of pelvic fullness r Cystic malignancy
r Fluid is chylous in nature. r Constipation r Hematoma
r Occurs in up to 20% of kidney transplant r Flank or abdominal pain (40%) r Lymphocele
recipientscaused by leakage from lymphatic vessels r Lower-extremity pain/swelling (37%) r Urinoma due to urinary leakage
transsected during the transplant surgery r Ileus r Seroma
ASSOCIATED CONDITIONS r Fever (47%)
r Bladder cancer
r Gynecologic malignancy
PHYSICAL EXAM
r Penile cancer r Palpable abdominal mass or lower abdominal
r Prostate cancer tenderness
r Renal cancer r Lower-extremity edema
r Renal insufficiency with transplantation – Painful leg swelling suggests deep venous
r Retroperitoneal metastasis thrombosis (DVT).
– Lymphocele-related, lower-extremity swelling is
usually not painful.
r Peno-scrotal or labial edema
234
LYMPHOCELE, PELVIC
r Open marsupialization (internal drainage) into the 3. Loeb S, Partin AW, Schaeffer EM, et al.
TREATMENT peritoneum is the historic gold standard: Complications of pelvic lymphadenectomy: Do the
– A window of peritoneum is excised, allowing the risks outweigh the benefits? Rev Urol. 2010;12(1):
GENERAL MEASURES lymph to be reabsorbed by the peritoneum. 20–24.
r Treat DVT if present. r Infected lymphoceles require percutaneous or open 4. Hamilton BD, Winfield HN. Laparoscopic
r Foley catheter if the patient has significant voiding surgical drainage. marsupialization of pelvic lymphoceles. Tech Urol.
dysfunction r Omentoplasty: 1997;2(4):220–224.
r Asymptomatic small lymphoceles should be – Placing a portion of omentum in the window
monitored (<100–150 mL volume). Many will decreases recurrence maintaining patency.
resolve spontaneously. – Success: 75–100% ADDITIONAL READING
MEDICATION Taneja SS. Complications of lymphadenectomy. In:
First Line ONGOING CARE Taneja SS, ed. Complications of Urologic Surgery:
r Lymphocele management is primarily interventional Prevention and Management. 4th ed. Philadelphia,
with limited role for medications unless associated PROGNOSIS PA: Saunders/Elsevier; 2010.
r Most smaller asymptomatic lymphoceles resolve
with infection or sclerosis (see below) (2).
r Systemic antibiotics (with percutaneous drainage) if spontaneously. See Also (Topic, Algorithm, Media)
r >90% success with marsupialization r Edema, External Genitalia
lymphocele is infected. r Lymphocele, Pelvic Images
Second Line COMPLICATIONS r Urinoma (Perinephric Pseudocyst)
r DVT/PE
N/A
r Lymphostasis of the lower extremity
SURGERY/OTHER PROCEDURES r Infection
r Treatment of symptomatic or large lymphoceles is
r Ureteral obstruction CODES
immediate percutaneous drainage (3). r Bowel obstruction
– Reported success rates with aspiration and ICD9
drainage tube are approaching 80%, with a mean FOLLOW-UP 457.8 Other noninfectious disorders of lymphatic
drainage duration ranging from a few days to Patient Monitoring channels
several months. Repeat imaging: Ultrasound or CT in 2–4 mo after
– Increased risk of infection, especially in ICD10
treatment to detect recurrence. I89.8 Oth noninfective disorders of lymphatic vessels
immunocompromised (transplant) patients.
r Sclerosis therapy can be used to treat Patient Resource and nodes
extraperitoneal lymphoceles http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2498000
– Sclerotherapy (povidone–iodine, 95% ethanol, CLINICAL/SURGICAL
tetracycline 0.5–2 g in 50 mL NS, bleomycin REFERENCES PEARLS
1 U/mL, fibrin glue):
– Cavity is aspirated, then filled gently with a 1. Musch M, Klevecka V, Roggenbuck U, et al. r Use of clips on identifiable lymphatic channels can
sclerosing agent. Complications of pelvic lymphadenectomy in 1,380 minimize the occurrence of postoperative
– Sclerosis is usually contraindicated. patients undergoing radical retropubic lymphoceles.
◦ Multiseptated lymphoceles: Drainage, lack of prostatectomy between 1993 and 2006. J Urol. r A transperitoneal approach for lymphadenectomy is
access to all chambers 2008;179:923–928. not protective against the formation of a lymphocele
◦ When the ureter is in close contact with a wall 2. Glass LL, Cockett AT. Lymphoceles: Diagnosis and because loculation of lymphatic fluid can still occur.
of the lymphocele (periureteral fibrosis, ureteral management in urologic patients. Urology. r Symptomatic lymphoceles may require percutaneous
obstruction) 1998;51(5A):135–140. or laparoscopic drainage.
◦ Incomplete lymphoceles should not be treated
by sclerosis.
r Transperitoneal laparoscopic marsupialization (4)
– If unsuccessful sclerosis or not amenable to L
percutaneous drainage
– Three transperitoneal ports provide access for
excision of the peritoneal window and optional
omental wick placement to keep peritoneal
window open.
– Success: 77–100%
235
LWBK1391-SEC-M LWBK1391-Gomella ch116.xml September 19, 2014 18:31
MEDULLARY CYSTIC KIDNEY DISEASE (MCKD)

BASICS DIAGNOSIS Percutaneous renal biopsy confirms the diagnosis
HISTORY Pathologic Findings
DESCRIPTION r Gross findings
r Medullary cystic kidney disease (MCKD) is a rare r Polyuria
– Usually the 1st clinical manifestation – Initially before disease progression, the kidneys
congenital, cystic disease of the kidneys which
– Occurs due to reduced urinary concentrating are of normal size
results in progressive renal deterioration and to
ability of the kidney – Cortical atrophy with progression
eventual end-stage renal disease (ESRD)
r Symptoms develop insidiously and diagnosis is not r Polydipsia – Cysts develop at the corticomedullary junction and
r Family history of ESRD, or renal cysts range in size from 1 to 10 mm.
common until renal insufficiency is detected and – With disease advancement the kidneys become
initiates evaluation (1)[C] PHYSICAL EXAM very small and demonstrate a granular exterior
EPIDEMIOLOGY Hypertension may be noted with disease progression surface
r Microscopic findings
Incidence DIAGNOSTIC TESTS & INTERPRETATION
Less than 1: 100,000 – Interstitial nephritis
Lab – Dilated, atrophic tubules
Prevalence r Urinalysis
– Inflammatory cell infiltrates
N/A – Proteinuria and hematuria are usually absent
r CBC DIFFERENTIAL DIAGNOSIS
RISK FACTORS r Juvenile nephronophthisis
Positive family history – Anemia present in advanced cases due to lack of
erythropoietin – Clinically and anatomically similar to MCKD
Genetics r Serum electrolytes – Autosomal recessive inheritance
r Mode of inheritance is autosomal dominant (2)[C] – ESRD usually manifests as early as age 13 yr
– Elevated creatinine
– Medullary cystic kidney disease-1 (MCKD1) – Hyperkalemia or metabolic acidosis in later stages – Extrarenal manifestations are common
◦ Mutation in MCKD1 gene localized to ◦ Retinal disorders (retinitis pigmentosa)
due to renal insufficiency
chromosome 1q21 ◦ Hepatic fibrosis
– MCKD2 Imaging ◦ Bardet–Biedl syndrome (obesity, retinitis
r Renal ultrasound
◦ Mutation in MCKD2 gene localized to pigmentosa, mental retardation, polydactyly)
chromosome 16p12 – Kidneys may be atrophic depending on stage of r Polycystic kidney disease
disease – Autosomal recessive polycystic kidney disease
PATHOPHYSIOLOGY – Cysts may be visible at the corticomedullary
r Unlike other renal cystic diseases such as autosomal (infantile form)
junction in later disease but are usually not – Autosomal dominant polycystic kidney disease
dominant polycystic kidney disease (ADPKD), there detectable in early stages
is no clear correlation between genetic mutation (adult form)
– Increased parenchymal echogenicity from r Multicystic dysplastic kidney
and identifiable protein product responsible for the tubulointerstitial fibrosis r Benign multilocular cyst (cystic nephroma)
MCKD phenotype (3)[C] r CT scan
r Medullary sponge kidney
ASSOCIATED CONDITIONS – Can detect cysts at the corticomedullary junction
r Hyperuricemia and gouty arthritis are associated better than ultrasound
with MCKD2 – Need for IV contrast is suboptimal in patients with
r In contrast to juvenile nephronophthisis, MCKD does ESRD
not have many extrarenal manifestations
GENERAL PREVENTION
N/A
236
MEDULLARY CYSTIC KIDNEY DISEASE (MCKD)
ADDITIONAL READING
Hildebrandt F, Otto E. Molecular genetics of
GENERAL MEASURES PROGNOSIS nephronophthisis and medullary cystic kidney disease.
r Same as for any patient with renal insufficiency r MCKD1 patients manifest with ESRD at median age J Am Soc Nephrol. 2000;11:1753–1761.
– Control hypertension if present of 62 yr
r MCKD2 patients manifest with ESRD at median age See Also (Topic, Algorithm, Media)
– Monitor fluid balance/daily weights r Nephronophthisis (Juvenile, Infantile, and
– Monitor serum electrolytes of 32 yr
Adolescent)
MEDICATION COMPLICATIONS r Renal Cysts (Intrarenal, Peripelvic, and Parapelvic)
First Line Similar to any patient with renal insufficiency or ESRD r Renal Mass
r None for primary treatment
FOLLOW-UP
r Antihypertensive regimens sometimes necessary
Patient Monitoring
Second Line Close nephrology follow-up is essential
CODES
N/A Patient Resources
r National Kidney Foundation ICD9
SURGERY/OTHER PROCEDURES r 585.6 End stage renal disease
r Dialysis when ESRD develops – www.kidney.org/patients r 753.16 Medullary cystic kidney
r Renal transplant r 788.42 Polyuria
– Allograft is not affected by MCKD after
transplantation
REFERENCES ICD10
r N18.6 End stage renal disease
ADDITIONAL TREATMENT 1. Scolari F, Ghiggeri GM. Nephronophthisis-
r Q61.5 Medullary cystic kidney
Radiation Therapy medullary cystic kidney disease: From bedside to
bench and back again. Saudi J Kidney Dis r R35.8 Other polyuria
N/A
Transplant. 2003;14:316–327.
Additional Therapies 2. Hildebrandt F, Omram H. New Insights:
N/A Nephronophthisis-medullary cystic kidney disease. CLINICAL/SURGICAL
Complementary & Alternative Pediatr Nephrol. 2001;16:168–176. PEARLS
Therapies 3. Kim CM, Glassberg KI. Molecular mechanisms of r MCKD has an insidious disease onset.
N/A renal development. Cur Urol Rep. 2003;4: r Symptoms usually not present until patient has renal
164–170.
insufficiency documented on serum testing.
r Polyuria is commonly the 1st clinical manifestation.
237
MEDULLARY SPONGE KIDNEY (MSK)

Kelly A. Healy, MD
r Noncontrast CT (NCCT) has largely replaced contrast

BASICS DIAGNOSIS studies (IVU, EXU) in the diagnosis urinary calculus
disease
DESCRIPTION HISTORY
r Many patients are asymptomatic and are diagnosed – May demonstrate multiple calcifications and
Medullary sponge kidney (MSK) consists of possibly localize them to the renal pyramids
developmental abnormalities of the kidneys with incidentally on contrast studies
r Pain associated with renal/ureteral calculi (3)[B]
ectatic or dilated terminal collecting ducts and
associated medullary cysts r Pain without associated obstructing calculi – CT urogram (CTU) may be most useful imaging
r Hematuria, microscopic or gross study
EPIDEMIOLOGY – After the injection of contrast for CTU, a blush of
Incidence PHYSICAL EXAM the involved papillae may be seen
N/A r May be normal without associated findings r Renal ultrasonography (RUS)
r May have flank tenderness, especially among those – Nondiagnostic for MSK in adults
Prevalence
r Estimated at 1 in 5,000–20,000 in the general with episodes of pain – Does not accurately distinguish intraparenchymal
population from intraluminal calcifications
r Occurs more frequently in stone formers ranging – May be used to detect obstruction in the
Lab symptomatic patient
from 5 to 20% r Serum electrolytes usually are normal except with
r Identification and therefore recognized incidence of significant distal renal tubular acidosis (DRTA) in Diagnostic Procedures/Surgery
MSK may be decreasing since it depends on which serum bicarbonate and potassium may be low r Endoscopy, specifically ureteroscopy differentiates
radiographic contrast studies to detect the dilated r Urinary study intraluminal from intraparenchymal calcifications
collecting ducts – Urinalysis (4)[B]
RISK FACTORS ◦ Microhematuria or pyuria r 24-hr urine studies to identify metabolic
N/A – 24-hr urine collections abnormalities
– May show hypercalciuria (9–100%)
Genetics – Hypocitraturia in 19–83% Pathologic Findings
Many cases may be sporadic: r Stone composition commonly calcium oxalate in r Typical sponge appearance of the medulla results
r Increasing evidence suggests inheritability of the from the dilated intrapapillary collecting ducts and
33% (pure) to 63% (mixed)
disorder, possibly of an autosomal dominance based r Most common mineral small medullary cysts
on familial studies – Calcifications may be found in the dilated
– Calcium oxalate monohydrate
r Mutations in glial cell–derived neurotropic factor r Calcium phosphate predominate in 63–67% collecting ducts
(GDNF) account for roughly 12% of MSK cases Imaging DIFFERENTIAL DIAGNOSIS
r Dent disease
(1)[B] r Diagnosis based on blush or “paint brush”
r Other rare abnormalities of calcium phosphate
PATHOPHYSIOLOGY appearance of dilated collecting ducts after contrast
r Dilated collecting ducts and medullary pyramidal administration metabolism
r Intravenous urogram (IVU) or excretory urogram r Primary hyperparathyroidism
cysts which may actually represent ectatic ducts
r Dilated ducts may be filled with calcium apatite r RTA
(EXU)
crystal – Multiple calcifications may appear in dilated ducts
r Distal renal tubular acidosis (DRTA) (33–40%) as nephrocalcinosis. Often seen on scout film and TREATMENT
r Hypercalciuria (9–100%) appear to reside within renal parenchyma
r Hypocitraturia (19–83%) – Plain film may be useful to detect the appearance GENERAL MEASURES
of new calcifications r Majority of asymptomatic patients can be observed
ASSOCIATED CONDITIONS – Typically bilateral but can occur on one side or in a r General stone clinic measures including high fluid
r Renal calculi single renal pyramid intake should be maintained
r Urinary tract infections (UTIs) r CT r Alkalinization with potassium citrate appears to be
r Hypocitraturia and hypercalciuria (as noted above)
of value
r Reduced bone density (2)[B] r Other abnormalities such as hypercalciuria which do
not resolve should be treated specifically
GENERAL PREVENTION r Treat UTIs as necessary
r This developmental condition cannot be prevented
r Secondary complications (infections, urolithiasis) can
be prevented by appropriate measures
238
MEDULLARY SPONGE KIDNEY (MSK)
MEDICATION
r Potassium citrate is employed in patients with
FOLLOW-UP ADDITIONAL READING
Patient Monitoring r Fabris A, Anglani F, Lupo A, et al. Medullary sponge
hypocitraturia (5) r Imaging at every 6–12 mo in stone formers to
r Thiazide diuretics are used in patients with stones evaluate for change in existing stones or appearance kidney: state of the art. Nephrol Dial Transplant.
and nonresponsive hypercalciuria of new ones 2013;28:1111–1119.
r Specific antibiotics are indicated for the treatment of r In some patients, renal ultrasound (RUS) can be r McPhail EF, Gettman MT, Patterson DE, et al.
UTIs used to monitor stones and avoid radiation Nephrolithiasis in medullary sponge kidney:
– Suppressive antibiotics may be necessary in r 24-hr urine collections are used to monitor stone risk Evaluation of clinical and metabolic features.
patients with persistent or multiply recurrent UTIs factors during treatment for urinary abnormalities Urology. 2012;79:277–281.
Second Line r Serum studies are used to monitor changes related See Also (Topic, Algorithm, Media)
N/A to medication r Dent Disease
r Distal Renal Tubular Acidosis
SURGERY/OTHER PROCEDURES Patient Resources
r Shock wave lithotripsy has been utilized for r Hypercalciuria
National Kidney and Urologic Diseases
Information Clearinghouse (NKUDIC) http://kidney. r Medullary Cystic Kidney Disease (MCKD)
treatment of collecting duct stones that can be
niddk.nih.gov/kudiseases/pubs/medullaryspongekidney/ r Medullary Sponge Kidney (MSK) Image
distinguished from nephrocalcinosis as well as
symptomatic intraluminal calculi r Nephrocalcinosis
r Endoscopy with ureteroscopy or occasionally r Polycystic Kidney Disease
REFERENCES r Urolithiasis, Adult
percutaneous nephrostolithotomy can treat
collecting system stones and unroof mucosa to 1. Torregrossa R, Anglani F, Fabris A, et al.
remove obvious and accessible collecting duct Identification of GDNF gene sequence variations in
stones patients with medullary sponge kidney disease. CODES
r SWL and endoscopy have been advocated to reduce Clin J Am Soc Nephrol. 2010;5:1205–1210.
the frequency of symptomatic episodes but is 2. Fabris A, Bernich P, Abaterusso C, et al. Bone ICD9
unproven disease in medullary sponge kidney and effect of r 588.89 Other specified disorders resulting from
potassium citrate treatment. Clin J Am Soc Nephrol. impaired renal function
2009;4:1974–1979. r 592.0 Calculus of kidney
Radiation Therapy 3. Maw AM, Megibow AJ, Grasso M, et al. Diagnosis r 753.17 Medullary sponge kidney
N/A
of medullary sponge kidney by computed
Additional Therapies tomographic urography. Am J Kidney Dis. 2007; ICD10
N/A 50:146–150. r N20.0 Calculus of kidney
Complementary & Alternative 4. Miller NL, Humphreys MR, Coe FL, et al. r N25.89 Oth disorders resulting from impaired renal
Therapies Nephrocalcinosis: Re-defined in the era of tubular function
N/A endourology. Urol Res. 2010;38:421–427. r Q61.5 Medullary cystic kidney
5. Fabris A, Lupo A, Bernich P, et al. Long term
treatment with potassium citrate and renal stones
ONGOING CARE in medullary sponge kidney. Clin J Am Soc Nephrol. CLINICAL/SURGICAL
PROGNOSIS 2010;5:1663–1668. PEARLS
r Urinary calculi are the most common risk but can be
r Be suspicious of MSK in patients with multiple
followed and also may be controlled with medical
papillary calculi.
treatment r Use contrast study for diagnosis.
r Recurrent UTIs can usually be treated
r Search for metabolic defects.
r Development of renal failure is very uncommon
r Treat metabolic factors in stone formers.
COMPLICATIONS r Consider treatment of renal stones in patients with
r Stone formation and subsequent obstruction
recurrent symptomatic stones.
r Recurrent/chronic flank pain r Significant benefit in endoscopic inspection and
r UTI treatment.
239
MEGAURETER, CONGENITAL
r Refluxing, obstructed megaureter: r Voiding cystourethrogram:

BASICS – This paradox of pathology was 1st reported by – Will evaluate for the presence of VUR and urethral
Weiss and Lytton. The muscle cells in the abnormalities such as anterior or posterior
DESCRIPTION intravesical and juxtavesical sections of the distal urethral valves
r Megaureter is a ureter that is dilated out of ureter are so lacking that they become incapable r Diuretic renal scan:
proportion to the rest of the urinary tract of adequate transmission of urine. On VCUG, – 99mTc-mercaptotriglycylglycine (MAG-3 scan)
r Most consider ureters measuring ≥7 mm in delayed emptying of the refluxing contrast/sharp – Assesses renal function and presence of
diameter by ultrasound a megaureter cut-off distally is highly suggestive of the diagnosis obstruction to the flow of urine
r Four types of megaureter are described: r Nonrefluxing, nonobstructed megaureter – Furosemide washout correlates with the degree of
– Refluxing megaureter – Transient dilatation of the ureter and/or renal obstruction
– Obstructed megaureter pelvis. Renal parenchyma is preserved. Can be – In general, a washout of >20 min after
– Refluxing and obstructed megaureter primary (idiopathic) or secondary to urosepsis furosemide suggests obstruction
– Nonrefluxing-nonobstructed megaureter (bacterial toxins can paralyze the ureteral muscle Diagnostic Procedures/Surgery
r Each of the above groups further categorized as and produce atonic ureter) or polyuric kidney that r Whitaker test (perfusion-pressure test):
either primary (defect lies in the ureter itself) or lost its concentration ability, eg, following ablation – More invasive as it requires percutaneous renal
secondary (another disorder leading to megaureter of posterior urethral valves access
such as urethral obstruction) ASSOCIATED CONDITIONS – Will provide valuable information if the diuretic
r Primary megaureter represents the 2nd most r Posterior urethral valves renal scan is equivocal
common cause of hydronephrosis in the newborn, r Prune belly syndrome r Endoscopy: Invasive test as it requires anesthesia.
with ureteropelvic junction obstruction the most Can be combined with transurethral resection of
common cause urethral valves if present
EPIDEMIOLOGY DIAGNOSIS Pathologic Findings
Incidence r Varies with etiology
HISTORY
r Varies depending on etiology r Most megaureters are diagnosed currently r With electron microscopy, the muscle population
– Vesicoureteral reflux (VUR): 0.4–1.8% in children prenatally with ultrasound (asymptomatic) and the size of smooth muscle cells of megaureters
– Primary obstructive megaureter (POM): 1 per r For late diagnosis, patients may present with can be measured
10,000 population abdominal pain, UTIs, or kidney stones – In obstructed megaureters, muscle hypertrophy
– VUR is more common in females and hyperplasia are expected. These changes are
– POM is more common in males with predilection PHYSICAL EXAM absent or minimal in refluxing megaureters and
r Abdominal mass
for the left kidney ureters associated with prune belly syndrome
– Bilateral involvement in up to 40% r Abdominal pain and costovertebral angle
– Collagen fiber derangements can also be seen in
tenderness with pyelonephritis primary obstructed megaureter (Increased
Prevalence
N/A DIAGNOSTIC TESTS & INTERPRETATION collagen types I and III deposition)
RISK FACTORS Lab DIFFERENTIAL DIAGNOSIS

r Posterior urethral valves r Urine analysis and culture if UTI is suspected r Bowel segment misinterpreted as dilated ureter
r Neurogenic bladder r Serum electrolytes, BUN, and creatinine r Posterior/anterior urethral valves
r Diabetes insipidus r C-reactive protein (CRP) and erythrocyte r Prune belly syndrome
sedimentation rate (ESR) for pyelonephritis r Retrocaval/retroiliac ureter
Genetics r Ureteral stone
r No specific genetic factors can be identified in the Imaging
r Normally best to perform ultrasound imaging several r Ureterocele
majority of patients with megaureters r Ureterovesical junction obstruction
r VUR can be familial days after birth to allow relative newborn
dehydration to equilibrate r VUR
PATHOPHYSIOLOGY r Renal and bladder ultrasound:
r Refluxing megaureters
– Establishes the diagnosis of megaureter, assesses
– Caused by congenital abnormality of the renal parenchyma and may provide clues on
intravesical ureter secondary to abnormal insertion possible etiology eg, thickened bladder wall
of the ureter into the bladder or the intravesical secondary to urethral valves
portion of the ureter is not long enough to enable
closure of the ureter during bladder filling
r POM:
– Exact etiology is unclear, however, the most
common finding is a distal adynamic ureteral
segment that affects the free efflux of urine
resulting in a functional obstruction
240
MEGAURETER, CONGENITAL

N/A 1. Stehr M, Metzger R, Schuster T, et al. Management
GENERAL MEASURES of the primary obstructed megaureter (POM) and
r Serial renal and bladder ultrasounds to monitor Additional Therapies indication for operative treatment. Eur J Pediatric
N/A Surg. 2002;12(1):32–37.
progress/resolution of megaureter is important
r Workup of megaureter to assess the presence or Complementary & Alternative 2. Liu HY, Dhillon HK, Yeung CK, et al. Clinical
absence of reflux and/or obstruction will guide Therapies outcome and management of prenatally diagnosed
further treatment options r If the child is newborn or infant, temporizing the primary megaureters. J Urol. 1994;152:614–617.
r Prenatally discovered megaureter obstructing variant of megaureter can be achieved 3. Shukla AR, Cooper J, Patel RP, et al. Prenatally
– Unilateral obstructed megaureter has a good with: detected primary megaureter: A role for extended
prognosis – Ureteral stent insertion follow-up. J Urol. 2005;173(4):1353–1356.
◦ These patients can be followed expectantly in – Cutaneous ureterostomy
the prenatal period, without further intervention
or early delivery
◦ Bilaterally obstructed megaureter findings
require close monitoring for the development of Di Renzo D, Aguiar L, Cascini V, et al. Long-term
PROGNOSIS followup of primary nonrefluxing megaureter. J Urol.
oligohydramnios r Depends on the baseline renal function (2)[A] 2013;190:1021–1026.
MEDICATION r Surgical correction of obstructing megaureters See Also (Topic, Algorithm, Media)
First Line carries a high success rate r Hydronephrosis/Hydroureteronephrosis, (Dilated
r Treat active UTI with culture appropriate antibiotics
r Most nonobstructive, nonrefluxing megaureters will Ureter/Renal Pelvis), Pediatric
r Consider prophylactic antibiotics in refluxing and
resolve with time r Hydronephrosis/Hydroureteronephrosis, (Dilated
obstructed megaureter variants (eg, Amoxicillin) r Outcomes can be poor with concomitant renal Ureter/Renal Pelvis), Prenatal
Second Line anomalies such as renal hypoplasia and dysplasia r Megaureter, Congenital Image
N/A r Posterior Urethral Valves
COMPLICATIONS
SURGERY/OTHER PROCEDURES r UTIs r Prune Belly Syndrome
r Refluxing megaureters: r Ureteral obstruction, mainly technical inattention to r Vesicoureteral Reflux
– Antibiotic prophylaxis and monitor progress with details during ureteral reimplant that will cause
renal ultrasound (RUS) and VCUG either:
– Ureteral reimplant in cases of breakthrough UTIs, – Ureteral kinking at the bladder insertion site CODES
renal scarring, or noncompliance with medications – Compromised blood supply to the distal ureter
r Primary obstructed megaureter (1)[A]: associated with excisional ureteral tapering ICD9
r Nephrolithiasis 753.22 Congenital obstruction of ureterovesical
– Excision of the distal adynamic ureteral segment
and ureteral reimplant. Ureteral tapering maybe junction
FOLLOW-UP
required Patient Monitoring ICD10
r Refluxing, obstructed megaureter: Q62.2 Congenital megaureter
r Serial RUS (3)[A]
– Excision of the distal ureteral segment and ureteral
r Serial serum chemistry to monitor renal function
reimplant. Often requires ureteral tapering
r Nonrefluxing, nonobstructed megaureter: CLINICAL/SURGICAL
Patient Resources
Observation with serial ultrasound is all that is Urology Care Foundation http://www. PEARLS
needed urologyhealth.org/urology/index.cfm?article=3 r Wide spread use of prenatal ultrasound helps
identify patients with megaureters at an early stage,
commonly prenatally.
r It is important to classify megaureters based on their
refluxing and/or obstructing status with the aid of
VCUG and diuretic renal scan.
r Long-term follow-up in patients with megaureter is
important for best outcome.
M
241
MESOBLASTIC NEPHROMA, CONGENITAL (BOLANDE DISEASE)

Lauren N. Hendrix, MD
BASICS DIAGNOSIS r Biopsy
– The role of biopsy in pediatric renal tumors is
DESCRIPTION HISTORY controversial as nephrectomy is the mainstay of
r Congenital mesoblastic nephroma (CMN) is a renal r History of prenatal ultrasound finding of unilateral
treatment and preoperative biopsy upstages to
tumor arising from nephrogenic mesenchyme renal mass stage III
r Usually a solid lesion, but cystic varieties have been r History of polyhydramnios
r Neonate with abdominal mass Pathologic Findings
reported r Three histologic subtypes
r Majority are benign with a favorable prognosis r Hematuria, jaundice, hypertension, anemia,
– Classic
r First reported in 1967, referred to in older literature hypercalcemia ◦ 1/3 of cases
as Bolande’s tumor or Bolande disease PHYSICAL EXAM ◦ Similar macro- and microscopically to
r Palpable abdominal mass leiomyoma
EPIDEMIOLOGY
r Hematuria ◦ Entrapped nephrons and blood vessels seen at
Incidence
r Most common real tumor in children <6 mo of age, r Jaundice the tumor periphery
◦ Not associated with metastasis
usually diagnosed prior to 3 mo DIAGNOSTIC TESTS & INTERPRETATION
r Accounts for 3–10% of all pediatric renal – Cellular
Lab ◦ 2/3 of cases
neoplasms (1) r Complete blood count ◦ More aggressive than classic with high mitotic
r More common in males (1) r Basic metabolic panel index and atypical growth pattern
r Usually unilateral ◦ Associated with local invasion/recurrence and
– Serum creatinine
r Often detected prenatally by ultrasound metastasis
– Serum calcium
Prevalence r Urinalysis – Mixed (3)
N/A Imaging DIFFERENTIAL DIAGNOSIS
r Abdominal ultrasound r Solid renal mass
RISK FACTORS
– Preferred modality – Wilms tumor
Genetics
r ETV6-NTRK3 gene fusion – “Ring pattern” – Rhabdoid tumor
◦ Hypoechoic mass with hyperechoic rim – Metanephric adenofibroma
– Results from translocation t (12;15) (p13;q25)
signifying vessels at the tumor periphery – Renal cell carcinoma
– Found only in the cellular variant
◦ Seen only in the classic variant – Angiomyolipoma
– Also found in congenital fibrosarcoma (2,3)
– Homogeneous or heterogeneous solid mass seen – Clear cell sarcoma
PATHOPHYSIOLOGY in cellular variant – Multilocular cystic nephroma
r Tumor classification r CT r Autosomal recessive polycystic kidney disease
– Stage I: Tumor limited to kidney without – Homogeneous mass r Cross-fused ectopia
involvement of capsule or hilar vessels – May have peripheral enhancement or focal r Renal vein thrombosis
– Stage II: Tumor extends beyond capsule with enhancement at sites of hemorrhage or necrosis r Solitary kidney with compensatory hypertrophy
invasion into perinephric fat or blood vessels, but r MRI r Beckwith–Weidemann syndrome
margins of resection are negative – Signal similar to normal parenchyma with r Adrenal mass
– Stage III: Tumor not completely resectable, tumor exception of areas of hemorrhage (4) r Retroperitoneal mass (3)
spillage occurs at time of resection, or tumor was
biopsied preoperatively
– Stage IV: Hematogenous metastases or lymphatic
spread outside of abdomen
– Stage V: Bilateral tumors
r Polyhydramnios
r Hydrops fetalis
242
MESOBLASTIC NEPHROMA, CONGENITAL (BOLANDE DISEASE)
3. Ahmed HU, Arya M, Levitt G, et al. Part II:

TREATMENT ONGOING CARE Treatment of primary malignant non-Wilms’ renal
tumors in children. Lancet Oncol. 2007;8:842–848.
GENERAL MEASURES PROGNOSIS 4. Sheth MM, Cai G, Goodman TR, et al. AIRP best
r Management of associated features r Radical nephrectomy generally curative
cases in radiologic-pathologic correlation:
– Hypertension r Classic variant favorable
Congenital mesoblastic nephroma. Radiographics.
– Hypercalcemia r Metastases and local recurrence possible with 2012;32:99–103.
– Jaundice cellular type, but rare
– Anemia r Risk factors for recurrence: Cellular variant, older
r Chemotherapy reserved for patients >3 mo with patient age, tumor spillage during resection, and ADDITIONAL READING
cellular variant, tumor spillage at resection, positive surgical margins (3)
microvascular invasion, metastatic disease, and McKenna PH, Ferrer FA. Prenatal and postnatal
inoperable tumors
COMPLICATIONS urologic emergencies. In: Docimo SG, ed. The
r Prenatally
Kelalis-King-Belman Textbook of Clinical Pediatric
MEDICATION – Polyhydramnios Urology. 5th ed. London: Informa Healthcare, 2007.
First Line – Hydrops fetalis
r Vincristine, cyclophosphamide, and doxorubicin – Intrauterine fetal demise See Also (Topic, Algorithm, Media)
r After birth r Renal Mass
(VCD) r Wilms Tumor (Nephroblastoma)
r Vincristine, doxorubicin, and actinomycin D (VDA) – Hypertension
– Hemodynamic instability
Second Line
r Isophosphamide, carboplatin, etoposide (ICE) – Respiratory distress
CODES
– Has considerable nephrotoxicity (3) FOLLOW-UP
SURGERY/OTHER PROCEDURES Patient Monitoring ICD9
r Radical nephrectomy Regular abdominal ultrasound for 1 yr in classic 236.91 Neoplasm of uncertain behavior of kidney and
– Gold standard variant and longer in cellular variant ureter
– Allows for appropriate staging Patient Resources
– Decreased risk of local recurrence ICD10
www.cancer.gov/cancertopics/pdq/treatment/ r D41.00 Neoplasm of uncertain behavior of
r Partial nephrectomy wilms/Patient
unspecified kidney
– Has been reported with success in Wilms tumors r D41.01 Neoplasm of uncertain behavior of right
but not CMN
REFERENCES kidney
ADDITIONAL TREATMENT r D41.02 Neoplasm of uncertain behavior of left
Radiation Therapy 1. England RJ, Haider N, Vujanic GM, et al. kidney
No defined role Mesoblastic nephroma: A report of the United
Kingdom’s Children’s Cancer and Leukaemia Group
Additional Therapies (CGLG). Pediatr Blood Cancer. 2011;56:744–748. CLINICAL/SURGICAL
N/A 2. Mallya V, Arora R, Gupta K, et al. Congenital PEARLS
Complementary & Alternative Mesoblastic Nephroma: A rare pediatric neoplasm.
Therapies Turkish J Path. 2013;29:58–60. r Most common solid renal tumor <6 mo of age.
N/A r Radical nephrectomy is generally curative.
243
MICROPENIS (MICROPHALLUS)

BASICS r Hypogonadotropic hypogonadism:
Lab
– Most common cause of micropenis r Karyotype
DESCRIPTION – Kallmann syndrome: Anosmia, deficit in GnRH r Genetic testing if history consistent with known
r A micropenis refers to a stretched newborn penis secretion, autosomal dominant syndromes such as Prader–Willi or Kallman
that is <2.5 standard deviations below the normal – Prader Willi syndrome: Short stature, hyperphagia, r Differentiate between hypogonadotropic
mean in length (1) hypotonia, diabetes mellitus, behavior problems,
r Full-term newborn micropenis would be <1.9 cm in hypogonadism and primary testicular failure
hypogonadism – Pituitary assessment: ACTH, GH, TSH, LH, FSH.
length (1) – Laurence–Moon–Biedl syndrome Low levels suggest hypogonadotropic
r Typical normal mean stretched penile length in a – Rud’s syndrome
r Primary testicular failure: hypogonadism
newborn is 3.5 cm – High prolactin suggests hypothalamus defect vs.
r The penis is normally formed but small, ie, no – Gonadal dysgenesis low prolactin suggests pituitary defect
hypospadias (2) – Anorchia – Elevated levels of LH, FSH, and T are normal
r Scrotum usually normal but can be smaller – Klinefelter’s and polysomy X syndromes during 1st 6 mo of life. Low T during this time
r Testicles usually descended but may not function – Luteinizing hormone (LH) receptor defects suggests testicular failure. Confirm with hCG
normally – Defects in T steroidogenesis stimulation test. LH, FSH should elevate but T will
r A micropenis is generally not considered to be – Noonan syndrome remain low in testicular failure
– Robinow syndrome – hCG stimulation test: Assesses testicle for T
associated with ambiguous genitalia since the penis
– Laurence–Moon–Biedl syndrome biosynthesis: 1,000 U of hCG IV or IM for 3 days,
is normal in configuration, the scrotum is normal
– Trisomy 8, 13, 18, and 21 measure serum T and DHT levels on days 0 and 4.
and the testes are usually descended. r Defects in T action
r Micropenis is a finding with many causes If T at day 4 >100 ng/dL, response is normal. If
– PAIS no response, suggests primary testicular failure
EPIDEMIOLOGY – 5α-reductase deficiency – From 6 mo to puberty, levels of LH, FSH, and T are
Incidence r Idiopathic form: low. LH, FSH elevate with hCG stimulation test but
∼1.5/10,000 – Normal hypothalamic–pituitary–testicle axis serum T low in testicular failure
Prevalence – Hypothesized to be due to delayed onset of fetal – For patients who have undergone or started
None gonadotropin stimulation puberty, LH and FSH are normally elevated as may
be serum T. LH, FSH, and T are usually low in
RISK FACTORS GENERAL PREVENTION
micropenis. Do hCG stimulation test and look for
r Maternal exposure to antiandrogen medications Avoid maternal exposure to antiandrogens
response; assess pubertal changes to be sure it is
during pregnancy not constitutional pubertal delay
r Advanced maternal age: Nondisjunction during
DIAGNOSIS – Antimüllerian hormone is produced by functional
meiosis can lead to Down syndrome, Klinefelter sertoli cells and can be used to detect functional
syndrome, and polysomy X syndromes HISTORY testis tissue
r History of genetic syndrome (eg, Kallman) r Identifying defects in T action
Genetics r Maternal history: Medications during pregnancy,
r X-linked recessive, autosomal recessive, autosomal – LH, FSH, T normal, or elevated with PAIS
dominant have all been identified antenatal US, prior stillbirths, decreased fetal – PAIS diagnosis often given after excluding other
r Idiopathic spontaneous mutations noted activity, or hypotonia at birth diagnoses
r Specific known genetic conditions: r Family history: Genitourinary anomalies, – Penis may grow with trial of T IM in PAIS
hypospadias, cryptorchidism, infertility, major – Increased T/DHT ratio with hCG stimulation test or
– Kallmann syndrome
congenital anomalies postpubertal suggests 5α-reductase deficiency
– Prader–Willi syndrome
– AR gene mutation only found in 20% of PAIS
– Laurence–Moon–Biedl syndrome PHYSICAL EXAM
– Polysomy X (Klinefelter) r Facies suggestive of midline cranial defect, mental Imaging
– Translocation, deletion, trisomy of chromosome 8, r MRI of head: Assess hypothalamus, pituitary, brain,
retardation:
13, 18, and 21 – Microcephaly, hypertelorism, low-set ears, small craniofacial anomalies, optic chiasm, 4th ventricle,
– Partial androgen-insensitivity syndrome (PAIS) mouth, high-arched palate corpus callosum
– 5α-reductase deficiency r Weight and body habitus: Prader–Willi syndrome, r Renal imaging: Assess kidneys and bladder; VCUG
– Noonan syndrome growth hormone abnormality and MAG3 renal scan if US suggest renal or bladder
– Rud’s syndrome r Skin: Nevi, ichthyosis anomaly or ectopia
PATHOPHYSIOLOGY r Hearing: Deafness Diagnostic Procedures/Surgery
r Normal penile growth and development is both r Smell: Anosmia suggests Kallmann syndrome r Laparoscopy to assess nonpalpable undescended
androgen dependent and independent. r Retinal pigment changes on funduscopic exam testicles, look for müllerian duct structures, biopsy
r 1st trimester: Maternal hCG stimulates testicle r Penis: any dysgenetic tissue
Leydig cells to produce Testosterone (T). T is r Genitogram indicated if dysgenetic gonads,
– Always depress fat pad during exam
converted to dihydrotestosterone (DHT) by – Prepuce, meatus location, general appearance ovotestis, müllerian duct structures are found or if
5α-reductase in genital tubercle. Penis and urethra – Stretched penile length (SPL): Measure from tip of androgen insensitivity is suspected
are completely formed by end of 1st trimester by glans to pubic symphysis
influence of DHT. – Use physiologic age when comparing SPL with
r 2nd trimester: Fetal hypothalamus and pituitary standard nomograms
drive T production by fetal testis which causes penile – Penile girth usually normal and proportional to
growth. length
r Micropenis believed to be due to inadequate fetal T – Exclude other diagnoses such as hidden penis or
production or action after the 1st trimester (1). buried penis (beware of a large suprapubic fat pad
that may distort a normal penis)
r Scrotum: Size, symmetry, and appearance
r Gonads: Size, shape, and position
244
MICROPENIS (MICROPHALLUS)
Pathologic Findings FOLLOW-UP

r Newborn penis is proportional but <1.9 cm
r Kallmann syndrome: Anosmia, GnRH deficiency:
r Psychological support and psychiatric therapy as
10% KAL1 gene defect on Xp22.3, 10% KAL2 on GENERAL MEASURES needed:
8p12, 70% autosomal dominant with no identified r Generally coordinated with an endocrinologist
– Reassure concerns about penile size, function,
gene defect r Correct any metabolic disturbances gender, potency
r Prader–Willi syndrome: Short stature, hyperphagia, r Specific treatment based upon cause – Address behavioral and psychosocial problems
mental retardation, diabetes, hypotonia, behavioral r Adrenal insufficiency: Treat with hydrocortisone r Hormone biochemical monitoring:
problems; lacking expression of gene SNRPN or supplementation and IV saline to correct – Follow pituitary and gonadal hormone therapy
necdin on 15q of paternal origin hypovolemia – Assess growth, vital signs, electrolytes, serum
r Laurence–Moon–Biedl syndrome: Obesity, glucose, renin, ACTH, GH, LH, FSH, and T.
MEDICATION r Physical monitoring: Serial penile measurements
retardation, pigmented retinopathy, polydactyly
First Line
DIFFERENTIAL DIAGNOSIS r Testosterone therapy: Diagnostic and therapeutic: Patient Resources
r Concealed penis: Large suprapubic fat pad None
25–50 mg testosterone enanthate IM Q monthly ×
r Webbed penis: Prominent penoscrotal web 3 mo in infancy or prepubertal
r Postcircumcision cicatrix: r Long-term cortisol replacement, growth hormone,
REFERENCES
– Residual foreskin scarred above glans tip and thyroid hormone if pan-hypopituitarism present
r Hypospadias with and without chordee r For gonadal deficiency: Induce puberty later in life 1. Wiygul J, Palmer LS. Micropenis.
r Chordee with T IM injection or transdermal patch/gels ScientificWorldJournal. 2011;11:1462–1469.
r Disorders of sex differentiation: r For central deficiency: Administer hCG injection or 2. Tsang S. When size matters: A clinical review of
– Female DSD: Congenital adrenal hyperplasia, GnRH therapy pathological micropenis. J Pediatr Health Care.
gonads not palpable in labia/scrotum 2010;4:231–240.
Second Line
– Male DSD None 3. Bin-Abbas B, Conte FA, Grumbach MM, et al.
r Hypothalamic–pituitary axis dysfunction (50% of Congenital hypogonadotropic hypogonadism and
cases): SURGERY/OTHER PROCEDURES micropenis: Effect of testosterone treatment on
r Manage cryptorchidism with orchiopexy or adult penis size – why sex reversal is not indicated.
– Syndromes: Kallmann, Prader–Willi,
Laurence–Moon–Biedl, Rud’s orchiectomy (if dysgenetic) as needed J Pediatr. 1999;134:579–583.
r Isolated hormone deficiency: r Penile surgery for length or bulk has not been
– GnRH deficiency without Kallmann syndrome shown to be effective
– LH deficiency ADDITIONAL TREATMENT ADDITIONAL READING
– GH deficiency or growth hormone receptor defect Radiation Therapy Baskin LS, Kogan BA. Handbook of Pediatric Urology.
(Laron dwarfism) N/A
r Primary testicular failure: 2nd ed. Philadelphia, PA: Lippincott Williams &
Additional Therapies Wilkins; 2005.
– Hypergonadotropic hypogonadism (25% of cases) r Familial genetic counseling and screening
– Testicular dysgenesis (Klinefelter syndrome, See Also (Topic, Algorithm, Media)
r Prenatal care: r Androgen insensitivity syndrome (AIS; OR Androgen
47XXY)
– Laurence–Moon–Biedl syndrome – Amniocentesis or chorionic villous sampling for Resistance Syndrome), Complete (CAIS) and Partial
– Polysomy X syndromes chromosomal anomalies and sex determination (PAIS)
– Anorchia; intrauterine testicular torsion – Fetal US to look for genitourinary and central r Disorders of Sexual Development (DSD)
r 5α-reductase deficiency: Rare nervous anomalies r Micropenis (Microphallus) Image
r PAIS (Partial androgen insensitivity syndrome) Complementary & Alternative r Penis, Buried (Concealed, Trapped, or Hidden)
r CNS abnormalities: Therapies r Penis, Length, Normal
– Anencephaly, congenital pituitary aplasia, Gender reassignment: Generally not done any more r Penis, Webbed
agenesis of corpus callosum, malformation of for micropenis and is of only historical interest
fourth ventricle
r Chromosome defects: CODES
– Polysomy X syndromes
ONGOING CARE
– Translocation, deletion, and trisomy of PROGNOSIS ICD9
chromosomes 8, 13, 18, and 21 r Overall good, but long-term effects depend on 752.64 Micropenis
r Rare syndromes: Rud, Robinow, Martsolf, Fanconi
anemia, Smith–Lemli–Opitz syndromes
underlying cause
r Most have stable male gender identity ICD10
M
r Idiopathic: Normal hypothalamic pituitary axis: r Generally good response to 3-mo course of T IM Q55.62 Hypoplasia of penis
– Virilize normally at puberty with 100% increases in length seen (3)
r Final adult penis size with treatment usually CLINICAL/SURGICAL
<mean, but within 2.5 standard deviations (3) PEARLS
COMPLICATIONS r Micropenis is a condition with many causes, most of
r Relate to endocrine abnormalities if present
r Side effects of testosterone: which are either a form of hypogonadotropic
hypogonadism or primary testicular failure.
– Premature closure of epiphyseal plates; limits r Thought to be due to deficient T synthesis or action
long-bone growth
after the 1st trimester.
– Behavioral changes: More aggressiveness r Watch out for large suprapubic fat pad leading to
– Early stimulation of penile growth does not affect
ultimate penile length incorrect diagnosis.
r Psychosocial issues: r Surgery generally not indicated except for associated
– Most patients have a stable male gender identify cryptorchidism.
but some dissatisfied with penis length
245
MULTICYSTIC DYSPLASTIC KIDNEY

Daniel Wollin, MD

BASICS r Prenatal hypertrophy of the contralateral kidney r Renal maldevelopment with large cysts tend to have
(24–46%) a small amount of stroma (thin septa of fibrous
DESCRIPTION r About 1/3 will have associated congenital tissue) and primitive dysplastic elements
r Multicystic dysplastic kidney (MCDK) is a congenital – Primitive ducts (a duct encircled by a collar of
anomalies of kidneys and urinary tract (CAKUT)
renal anomaly with a kidney comprised of cysts of r Contralateral vesicoureteral reflux (∼20%); of those fibromuscular cells)
varying sizes; no identifiable renal with reflux, 40% will have grades III–V – Immature cartilage and remnants of early
parenchyma—”bunch of grapes” with a paucity of r Contralateral UPJ obstruction (3–12%) and UVJ metanephros can be present
stroma between cysts; no large central or medial cyst r Kidneys with smaller cysts tend to have more solid
r No reniform appearance of the involved kidney obstruction (6%)
r Dilated nonobstructed contralateral renal pelvis components
r Usually unilateral; bilateral incompatible with life r Hydronephrotic form
(common)
r Most common type of renal cystic disease and 2nd r Anomalies of the ipsilateral internal duct structures r Small to no vascular pedicle
most common cause of abdominal mass in neonates (15%) including seminal vesicle cyst, Gartner’s cyst, r Ureter totally or partially atretic; renal pelvis may be
and infants after hydronephrosis obstructed hemivagina absent
r Large series show no increased incidence of Wilms r Microscopic communication between cysts
EPIDEMIOLOGY
tumor or hypertension (see Patient Monitoring) r Often involute—circumscribed rims of calcifications
Incidence
r 1 in 4,300 live births (unilateral) r Ureterocele or ectopic ureter associated with single may be seen in the renal fossa on plain film of adults
r Slight male predominance system or upper pole of duplex system
r Horseshoe kidney DIFFERENTIAL DIAGNOSIS
r Slightly greater occurrence on the left r Acquired renal cysts
r Bilateral MCDK r Autosomal dominant kidney disease
GENERAL PREVENTION
– 1 in 10,000—fetal demise due to oligohydramnios N/A r Cystic congenital mesoblastic nephroma
or postnatal demise due to pulmonary hypoplasia r Cystic Wilms tumor
Prevalence r Cysts of the medulla
DIAGNOSIS r Hydronephrosis
N/A
HISTORY r Multilocular cystic nephroma
RISK FACTORS
r Possible association with in utero urinary obstruction At least 65% are detected prenatally r Neuroblastoma (calcifications)
r Possible association with teratogens (in utero viral r Renal cysts, isolated or associated with syndromes
PHYSICAL EXAM
infections, medications such as maternal r Abdominal mass palpable in 13% (tuberous sclerosis, von Hippel–Lindau, etc.)
antiepileptics) r Elevated BP (rare) r Ureteropelvic junction obstruction (UPJO)
r Maternal diabetes r Vesico ureteral reflux (VUR)
Genetics Lab
r MCDK seen in disorders of known genetic etiology r Urinalysis TREATMENT
such as renal cysts and diabetes syndrome (RCAD) r Urine microalbuminuria
which involves mutations in hepatocyte nuclear GENERAL MEASURES
factor-1β Imaging r Educate parents about the signs and symptoms of
r Genes such as PAX2, EYA1, SIX1, WNT, WT-1, GNF, r US: Multiple noncommunicating cysts of variable
UTI in infancy and childhood especially if reflux
and AT2 have an important role in ureteral bud size, scant, or no renal parenchyma status unknown
r Dilated renal pelvis in hydronephrotic form r The use of nephrectomy to manage MCDK is
formation and mutations have been identified in
r VCUG not absolutely recommended with normal
human syndromes such as: controversial
– Branchio-oto-renal (BOR) syndrome with contralateral kidney and bladder despite 20%
mutations in the EYA1 or SIX1 genes having contralateral reflux MEDICATION
– Renal-coloboma syndrome (RCS) with mutations r Renal scan (DMSA): Confirms absence of function, or First Line
in the PAX2 gene rarely minimal function especially in hydronephrotic N/A
r Linking genetic mutations with renal dysplasia form or in smaller more solid dysplastic kidneys Second Line
suggest bud theory as the pathogenesis in MCKD Diagnostic Procedures/Surgery N/A
r VCUG: To evaluate for contralateral VUR if
PATHOPHYSIOLOGY
r Ureteral bud theory: hydronephrosis or other contralateral upper tract
– If ureteral bud is atretic or connects abnormally abnormality on US
with the metanephric blastema or forms abnormal – If the contralateral kidney is normal, performing a
distal ureteral connections to the bladder, MCDK VCUG remains controversial
will result.
– Prerequisite is the normal reciprocal induction
between a normal ureteral bud and normal
metanephric mesenchyme.
246
MULTICYSTIC DYSPLASTIC KIDNEY
SURGERY/OTHER PROCEDURES r As of 2012, the American Academy of Pediatrics r Schreuder MF, Westland R, van Wijk JA. Unilateral
r Mostly nonoperative: states that contact-sport participation is generally multicystic dysplastic kidney: A meta-analysis of
– 25% totally involute OK for children who have only one functional observational studies on the incidence, associated
– 60% regress kidney. In a very large published series, none of the urinary tract malformations and the contralateral
– 15% remain stable kidney injuries were catastrophic or needed surgery kidney. Nephrol Dial Transplant. 2009;24(6):
– A very small number may increase in size r Long-term follow-up for hypertension and 1810–1818.
r Indications for nephrectomy: microalbuminuria by informed pediatrician or family r Thomas DF. Prenatally diagnosed urinary tract
– Kidneys which remain large, increase in size, or physician; referral to nephrology for renoprotective abnormalities: Long-term outcome. Semin Fetal
show an increased amount of solid tissue medications when indicated Neonatal Med. 2008;13(3):189–195.
(especially with function) Patient Resources See Also (Topic, Algorithm, Media)
– Kidneys easily removed (especially r National Kidney and Urologic Diseases r Multicystic Dysplastic Kidney Image
laparoscopically) or cysts may be sequentially r Information Clearinghouse (NKUDIC) http://kidney. r Potter Syndrome/Potter Facies
decompressed r Renal Cysts
niddk.nih.gov/kudiseases/pubs/kidneydysplasia/
– Hypertension: Uncommon (5%) in childhood and
r Renal Dysplasia, Hypodysplasia, and Hypoplasia
not likely caused by MCDK
◦ May persist after nephrectomy depending on REFERENCES
the patient age at onset of hypertension and the
presence of CAKUT (see Prognosis) 1. Westland R, Schreuder MF, Bökenkamp A, et al. CODES
ADDITIONAL TREATMENT Renal injury in children with a solitary functioning
kidney–the KIMONO study. Nephrol Dial ICD9
Radiation Therapy Transplant. 2011;26(5):1533–1541. r 593.70 Vesicoureteral reflux unspecified or without
N/A
2. Sanna-Cherchi S, Ravani P, Corbani V, et al. Renal reflux nephropathy
Additional Therapies outcome in patients with congenital anomalies of r 753.15 Renal dysplasia
N/A the kidney and urinary tract. Kidney Int. 2009;76(5): r 753.19 Other specified cystic kidney disease
Complementary & Alternative 528–533.
Therapies ICD10
r Q61.4 Renal dysplasia
N/A
ADDITIONAL READING r Q62.7 Congenital vesico-uretero-renal reflux
r Q62.39 Other obstructive defects of renal pelvis and
ONGOING CARE r Abou Jaoudé P, Dubourg L, Bacchetta J, et al.
ureter
Congenital versus acquired solitary kidney: Is the
PROGNOSIS difference relevant? Nephrol Dial Transplant.
r Usually excellent in unilateral disease
2011;26(7):2188–2194. CLINICAL/SURGICAL
r KIMONO study (1) reports renal injury (hypertension, r Hains DS, Bates CM, Ingraham S, et al.
PEARLS
albuminuria and/or the use of renoprotective Management and etiology of the unilateral
medication) present in 32% at young age (mean multicystic dysplastic kidney: A review. Pediatr r MCDK occurs as a result of renal maldevelopment
age 9.5 yr). Nephrol. 2009;24(2):233–241. due to possible mutation(s) in genes responsible for
– Increased renal injury in individuals with a solitary r Hayes WN, Watson AR; Trent & Anglia MCDK Study ureteral bud formation.
functioning kidney in later life when CAKUT Group. Unilateral multicystic dysplastic kidney: Does r Large cysts of varying sizes present with no
present. initial size matter? Pediatr Nephrol. 2012;27(8): identifiable parenchyma; ureter usually atretic.
– Study suggests long-term clinical follow-up for 1335–1340. r Most involute or become significantly smaller; rare
hypertension and microalbuminuria especially into r Mansoor O, Chandar J, Rodriguez MM, et al. enlargement.
puberty and adulthood. Long-term risk of chronic kidney disease in unilateral r Almost none require nephrectomy; consider for
– These findings are supported by an early study (2). multicystic dysplastic kidney. Pediatr Nephrol. functioning solid component or increasing size.
COMPLICATIONS 2011;26(4):597–603. r Not associated with increased risk of hypertension
r Malignant transformation extremely low with only r Psooy K. Multicystic dysplastic kidney in the during childhood or Wilms tumor in large series.
15 cases of tumors reported neonate: The role of the urologist. Can Urol Assoc J. r Long-term follow-up recommended for hypertension
r Rare hypertension; usually associated with 2010;4(2):95–97. and microalbuminuria especially at puberty and in
contralateral renal injury adulthood.
FOLLOW-UP
Patient Monitoring
r Renal US to document involution and contralateral
M
renal growth
– Every 6 mo in the 1st 3 yr and then every 1–2 yr to
assure appropriate renal growth until puberty
– Protocol personal preference of physician since
there is no consensus; some follow patients every
3–12 mo. No frequency of follow-up has been
shown to be beneficial or cost-effective
247
MULTIPLE SCLEROSIS, UROLOGIC CONSIDERATIONS

Alana M. Murphy, MD

BASICS r DSD leading to urinary retention, recurrent UTIs, and r PVR
impairment in renal function – Large (>275–300 cc) PVR on 2 separate
DESCRIPTION r Urolithiasis due to urinary stasis from incomplete occasions should initiate clean intermittent
r Multiple sclerosis (MS) is a neurologic disease catheterization
bladder emptying and recurrent UTIs
causing focal demyelination of white matter in the r UDS done by urologic specialists to assess bladder
brain and spinal cord that can impact urinary tract GENERAL PREVENTION
capacity, compliance, detrusor function, continence,
functioning. No proven methods for prevention
and detrusor–sphincter coordination:
r Plaques visible on magnetic resonance imaging – Routinely performed with fluoroscopy in MS
(MRI) are inflammatory and often lead to scar tissue DIAGNOSIS patients
deposition. They interfere with conduction of – Absolutely necessary to characterize voiding
electrical signals resulting in loss of central inhibition HISTORY dysfunction in MS patients
of reflex activity and dysfunctional conduction of r Presence of neurologic symptoms: – Assess risk for upper tract deterioration (elevated
sensory and motor signals. – Vision changes, balance problems, storage and voiding pressures)
r Neurologic impairment can vary from mild to severe. discoordination, numbness, or paresthesias – May suggest diagnosis of MS in patient with few
r Urologic manifestations include urinary frequency, r Urologic history: All patients with MS should be other neurologic symptoms
urgency incontinence, voiding symptoms, urinary screened for urologic problems – Need follow-up UDS with change in clinical
retention, and sexual dysfunction. – Recurrent UTIs symptoms
r Detrusor sphincter dyssynergia (DSD) and detrusor – Urinary frequency Pathologic Findings
overactivity (DO) are common dysfunctions noted on – Urgency incontinence Detrusor hypertrophy with trabeculation
urodynamic studies (UDS). – Voiding symptoms
– Urinary retention DIFFERENTIAL DIAGNOSIS
EPIDEMIOLOGY r Idiopathic overactive bladder
Incidence PHYSICAL EXAM r Dysfunctional voiding
r Most commonly presents between ages 20 and r Urologic exam:
r Detrusor underactivity or acontractile detrusor
50 yr old – Testicular and prostate exam in males to rule out
r Females have 1.5–3 times greater incidence than neoplasm or infection
males – Pelvic exam in females to assess pelvic support TREATMENT
and rule out urethral or vaginal pathology
Prevalence r Focused neurologic exam: GENERAL MEASURES
r 1 in 750 lifetime risk of developing MS in USA r Remissions can occur spontaneously, making
– Bulbocavernosus reflex to assess function of sacral
r Marked variations in worldwide prevalence
nerves (absent in up to 30%) management difficult
r More common in Caucasians and above 40◦ latitude – Deep tendon reflexes, proprioception, Babinski r Physical therapy and exercise to help prevent muscle
RISK FACTORS reflex, and cranial nerve exam atrophy and loss of postural tone
r Caucasian ethnicity r Avoid stressors
r Primary relative with MS r Disease-modifying medications specific to MS can
Lab
r Live about 40◦ latitude r Urinalysis: Concomitant infection or hematuria reduce relapses and control some symptoms:
r CSF for initial MS diagnosis (oligoclonal IgG bands) β interferons, glatiramer acetate, fingolimod,
Genetics natalizumab, and teriflunomide
r Increased risk if MS is present in a 1st-degree r Bladder emptying in cases of detrusor underactivity
Imaging (2,3)
relative r MRI:
r Primary relative with MS confers 20 times risk or DSD with urinary retention:
– The most useful tool for diagnosing MS; – Intermittent catheterization preferred over
r Identical twin: 300 times increased risk if other twin diagnostic in 70–95% of cases indwelling catheter
develops MS – Increased signal intensity on T2-weighted images – Consider a suprapubic catheter if intermittent
r Unknown pattern of inheritance in areas of demyelination catheterization is not possible
r Upper urinary tract imaging:
PATHOPHYSIOLOGY (1) – Patients on intermittent catheterization or with an
r Autoimmune attack on the central nervous system – Rule out presence of hydronephrosis indwelling catheter should not be treated with
– Renal ultrasound (US) is a good screening test antibiotics for asymptomatic bacterial colonization
(CNS) myelin: – Important in patients with known DSD or in
– Focal demyelination with relative axon sparing of the urinary tract
patients with indwelling catheters r Urinary frequency and urgency incontinence
– Histopathology shows perivenular lymphocytic r Lower tract imaging less commonly performed:
infiltrates, macrophages within the white matter, treatment should include behavioral modification
– Fluoroscopy during UDS can assess for bladder with avoidance of bladder irritants and management
gliosis, and scarring
r Urologic pathophysiology: pathology (stones, trabeculation), vesicoureteral of fluid intake
reflux, and DSD
– MS affects the cervical spinal cord in the
pyramidal and reticulospinal tracts, affecting
innervation of the bladder and external urethral
sphincter, causing DO and DSD
– MS can affect the sacral cord and may lead to
bladder areflexia and elevated post-void residual
(PVR) volumes
248
MULTIPLE SCLEROSIS, UROLOGIC CONSIDERATIONS
MEDICATION 3. Ukkonen M, Elovaara I, Dastidar P, et al.

First Line ONGOING CARE Urodynamic findings in primary progressive multiple
r Medical therapy is primarily aimed at urinary sclerosis are associated with increased volumes of
frequency and urgency incontinence PROGNOSIS plaques and atrophy in the central nervous system.
– Antimuscarinic medications: Most common side With proper urologic follow-up, renal function can be Acta Neurologica Scand. 2004;109(2):100–105.
effects include dry mouth and constipation preserved in most patients 4. Ginsberg D, Gousse A, Keppenne V, et al. Phase 3
◦ Fesoterodine 4–8 mg QD COMPLICATIONS efficacy and tolerability study of onabotuli-
◦ Hyoscyamine ER release 0.375 mg BID r Hydronephrosis and impairment in renal function numtoxinA for urinary incontinence from
◦ Oxybutynin 5 mg BID-TID due to elevated bladder storage or voiding pressure neurogenic detrusor overactivity. J Urol. 2012;
◦ Oxybutynin transdermal patch 3.9 mg/d r Urolithiasis due to urinary stasis, indwelling 187(6):2131–2139.
◦ Oxybutynin XL 10–15 mg/d catheters and infection
◦ Oxybutynin, topical gel 10% apply 1 sachet QD r Recurrent UTIs
to dry skin r Urethral erosion from indwelling catheters ADDITIONAL READING
◦ Solifenacin 5–10 mg/d
r Tremlett H, Zhao Y, Rieckmann P, et al. New
◦ Tolterodine LA 1–2 mg BID FOLLOW-UP
◦ Tolterodine LA 2–4 mg/d perspectives in the natural history of multiple
Patient Monitoring
◦ Trospium XR 60 mg/d r Upper urinary tract screening is especially important sclerosis. Neurology. 2010;74:2004–2015.
r Provider’s Approach to Bladder Management in
– β 3 -agonist: Most common side effects include an in men, since men with MS often develop high
increase in blood pressure and palpitations bladder storage pressure and urinary stasis without Multiple Sclerosis. http://www.va.gov/
◦ Mirabegron 25 mg/d increase to 50 mg/d after developing overt urologic symptoms such as MS/articles/Provider s Approach to Bladder
8 wk PRN incontinence. Management in Multiple Sclerosis.asp (Accessed
r Incontinence, especially in women, can become February 13, 2014)
Second Line (4)
r Botulinum toxin injection into the detrusor: problematic as the severity of MS progresses. See Also (Topic, Algorithm, Media)
– Decreases the force and frequency of neurogenic r Patients with bladder dysfunction secondary to MS r Detrusor Overactivity
DO can be stratified into low- and high-risk: r Detrusor Sphincter Dyssynergia
– Well-tolerated office-based therapy performed – High-risk patients: Incontinence, recurrent r Neurogenic Bladder, General Considerations
under local anesthesia infections, DSD, elevated storage pressures
– Neurogenic DO treated with cystoscopic injection >40 cm H2 O, indwelling catheters
of 200–300 units botulinum toxin type A ◦ Follow closely for upper tract deterioration, CODES
[onabotulinumtoxinA] into 10–25 sites within the development of squamous cell carcinoma of the
bladder muscle bladder, and other problems associated with
ICD9
– Treatment effect lasts 3–9 mo long-term indwelling catheters. r 340 Multiple sclerosis
– Risk of temporary urinary retention requiring – Low-risk patients: Those with normal continence, r 788.31 Urge incontinence
intermittent catheterization no UTIs, and complete bladder emptying. These r 788.41 Urinary frequency
patients do not require frequent upper tract
r Suprapubic catheter placement: imaging.
r All patients should undergo periodic urodynamic ICD10
– If unable to perform intermittent catheterization; r G35 Multiple sclerosis
avoids urethral erosion; reduces incidence of UTIs, testing, especially if there is a change in symptoms, r N39.41 Urge incontinence
epididymitis, and prostatitis an increase in infections, or an overall worsening of r R35.0 Frequency of micturition
– Drawbacks include risk of bladder calculi and their MS.
development of squamous cell carcinoma (usually Patient Resources
in >10 yr). r http://www.nationalmssociety.org CLINICAL/SURGICAL
r Augmentation cystoplasty: To address significantly r http://www.msfocus.org
PEARLS
impaired bladder compliance or when conservative
management of incontinence from DO has failed r Medical therapy and behavioral modification remain
r Urinary diversion: Ileal conduit, ileovesicostomy, or REFERENCES the 1st-line treatment for urinary frequency and
catheterizable stoma urgency incontinence.
1. Carr LK. Lower urinary tract dysfunction due to r Cystoscopic injection of botulinum toxin should be
ADDITIONAL TREATMENT multiple sclerosis. Can J Urol. 2006;Suppl 1:2–4. used for refractory neurogenic detrusor overactivity.
Radiation Therapy 2. Lemack GE, Hawker K, Frohman E. Incidence of r Adequate management of lower urinary tract
N/A upper tract abnormalities in patients with
neurovesical dysfunction secondary to multiple
function will lead to preservation of renal function. M
sclerosis: Analysis of risk factors at initial urologic
N/A
evaluation. Urology. 2005;65(5):854–857.
Therapies
Stress reduction therapies and acupuncture have been
associated with symptom reduction
249
MYASTHENIA GRAVIS, UROLOGIC CONSIDERATIONS

r Smooth and cardiac muscle are not affected. Diagnostic Procedures/Surgery

BASICS r The role of the thymus in MG is unclear, but it is r Edrophonium chloride test: Positive for MG if IV
suspected to be a site of autoantibody formation. administration unequivocally yields improved
DESCRIPTION r A majority of patients with MG have thymic strength
r Myasthenia gravis (MG) is a chronic autoimmune r Repetitive nerve stimulation
hyperplasia or thymoma.
disorder characterized by weakness and early r Many patients improve clinically following r Single-fiber electromyography
fatigability of the skeletal muscles due to thymectomy. r Complete urodynamic evaluation if urologic
antibody-mediated loss of nicotinic acetylcholine symptoms are present (4)
(Ach) receptors (1,2) ASSOCIATED CONDITIONS r Urodynamics:
r Involvement of the external striated urethral r Neonatal MG is a transitory disorder resulting from
passive maternal antibody transfer to the fetus. – If bladder dysfunction present, resembles lower
sphincter is rare but may be vulnerable to motor neuron pattern with variable areflexia or
dysfunction after transurethral resection of the r Congenital myasthenic syndromes result from
atonia
prostate (TURP), explaining the relatively high genetic mutations that lead to abnormal
– In one UDS series 63% failing to empty
incidence of post-TURP incontinence in this neuromuscular transmission.
r Ocular MG refers to weakness limited to the completely due to hypocontractile bladders and
group (3) 6% had complete areflexia
r Although smooth muscle is generally not affected, extraocular muscles and eyelids.
there are rare reports of detrusor areflexia (4) Pathologic Findings
r Urologic complaints are uncommon but may include GENERAL PREVENTION N/A
None
incontinence, urgency, retention, or erectile DIFFERENTIAL DIAGNOSIS
dysfunction r Acute inflammatory demyelinating
DIAGNOSIS polyradiculoneuropathy
EPIDEMIOLOGY r Botulism
Incidence HISTORY r Lambert–Eaton syndrome
Published estimates of 2–21 cases per million people r Reduced exercise tolerance that improves with rest
per year (1,2) and worsens with warm temperature (eg, after a hot
bath)
Prevalence r The natural history of MG usually follows a TREATMENT
r In patients <40 yr:
– Female > Male (7:3) characteristic pattern that initially involves weakness GENERAL MEASURES
r In the 5th decade, new cases of MG are evenly split of eyelids and extraocular muscles. r Intermittent catheterization for rare cases of
r Difficulty climbing stairs is typical of generalized refractory detrusor areflexia (4)
between the genders
r After the 5th decade: weakness in MG. r Adjust mealtimes to take advantage of daily periods
r Weakness is variable and fluctuating, but tends to of relative strength
– Male > Female (3:2) (1,2)
be worse later in the day. r Install railing in household places where it will be
RISK FACTORS needed for support in rising, such as adjacent to the
r Thymic hyperplasia is observed in 65–75% of PHYSICAL EXAM
r Muscle fatigability can be tested for many muscles bathtub and toilet
patients (1,2) r Use electric toothbrushes and can openers to
r MG has been described as a paraneoplastic by repeated action: Ptosis, diplopia, dysphagia, and
peripheral muscle weakness conserve strength
syndrome related to renal cell carcinoma (RCC) (5), r “Dropped head syndrome” r Generalized muscle weakness in the acute setting
as well as other malignancies (thymoma, lymphoma,
should prompt careful attention to the possibility of
lung cancer, Kaposi’s sarcoma) (6) DIAGNOSTIC TESTS & INTERPRETATION respiratory failure
Genetics Lab r Patients with MG have symptoms worsened with
r Congenital myasthenia syndromes, a subset of MG, r Serology tests demonstrate anti-ACh receptor
high core or ambient temperature; therefore, muscle
stem from genetic mutations resulting in abnormal antibodies in ∼90% of patients strength will likely improve when a fever is treated
neuromuscular transmission (1,2) r ∼50% of patients who test negative for anti-ACh with antipyretics
r HLA types B8 and DR3 are associated with MG receptor antibodies have antibodies against the r Urinary tract symptoms, if present, may respond
MuSK protein. favorably to therapy for MG
PATHOPHYSIOLOGY
r Autoantibodies develop against Ach nicotinic Imaging
r Chest computed tomography (CT) to rule out
postsynaptic receptors (1,2).
r The autoantibodies mechanically block the thymoma
r If level of suspicion is high, CT abdomen to rule out
neuromuscular junction binding site and eventually
destroy them. RCC (5)
r Cholinergic nerve conduction to striated skeletal
muscle is thus impaired.
r Clinical symptoms begin to develop when the
number of Ach receptors is reduced to ∼30% of the
normal level.
250
MYASTHENIA GRAVIS, UROLOGIC CONSIDERATIONS
MEDICATION 5. Torgerson EL, Khalili R, Dobkin BH, et al.

First Line ONGOING CARE Myasthenia gravis as a paraneoplastic syndrome
r Cholinesterase inhibitors (neostigmine, associated with renal cell carcinoma. J Urol.
pyridostigmine) provide temporary strength PROGNOSIS 1999;162(1):154–155.
r Most (96%) of patients have normal lifespan when
improvement in patients with MG. 6. van Sonderen A, Wirtz PW, Verschuuren JJ, et al.
r Corticosteroids can produce rapid improvements in appropriate medical care involving cholinesterase Paraneoplastic syndromes of the neuromuscular
MG but are associated with numerous inhibitors, plasmapheresis, and immunosuppressive junction: Therapeutic options in myasthenia gravis,
dose-dependent side effects agents is given. lambert-eaton myasthenic syndrome, and
r Thymectomy results in complete remission in about
neuromyotonia. Curr Treat Options Neurol.
Second Line 1/3 of patients, but the postsurgical prognosis is 2013;15(2):224–239.
r Plasmapheresis is reserved for short-term treatment
otherwise highly variable.
in response to myasthenic exacerbations or crises.
r Intravenous immunoglobulin (IgG) also provides COMPLICATIONS
r Post-TURP incontinence ADDITIONAL READING
short-term improvements in strength during
r Respiratory failure
myasthenic exacerbations or crises as an alternative Mayo ME, Chetner MP. Lower urinary tract dysfunction
for patients who are poor plasmapheresis r Cholinergic crisis from excessive use of
in multiple sclerosis. Urology. 1992;39(1):67–70.
candidates because of vascular access issues. cholinesterase inhibitors
r Immunosuppressive agents (azathioprine, r Multiple complicating effects may result from See Also (Topic, Algorithm, Media)
chronic steroid use, including poor wound healing Neurogenic Bladder, General
cyclophosphamide, cyclosporine, methotrexate,
mycophenolate mofetil, rituximab, tacrolimus) for and opportunistic infection
steroid-sparing protocols, or for refractory disease FOLLOW-UP
(6) CODES
Patient Monitoring
SURGERY/OTHER PROCEDURES Patients with MG should be followed by a neurologist ICD9
r If surgical intervention for bladder outlet obstruction with urology referral as needed. r 358.00 Myasthenia gravis without (acute)
secondary to benign prostatic hyperplasia (BPH) is exacerbation
Patient Resources
being considered, some advocate suprapubic r 788.30 Urinary incontinence, unspecified
National Institute of Neurological Disorders and
prostatectomy to reduce risk of incontinence (3) r 788.63 Urgency of urination
r Thymectomy results in complete remission in 35% of Stroke: Myasthenia Gravis Fact Sheet (http://www.
ninds.nih.gov/disorders/myasthenia gravis/detail
cases and clinical improvement in 85% of patients myasthenia gravis.htm Accessed August 8, 2014) ICD10
r If MG presents as paraneoplastic syndrome r G70.00 Myasthenia gravis without (acute)
associated with RCC, effective treatment for RCC exacerbation
may resolve MG symptoms (5) REFERENCES r N39.41 Urge incontinence
r R32 Unspecified urinary incontinence
ADDITIONAL TREATMENT 1. Phillips LH. The epidemiology of myasthenia gravis.
Radiation Therapy Ann NY Acad Sci. 2003;998:407–412.
N/A 2. Vincent A, Palace J, Hilton-Jones D. Myasthenia CLINICAL/SURGICAL
Additional Therapies gravis. Lancet 2001;357:2122–2128.
3. Wise GJ, Gerstenfeld JN, Brunner N, et al. Urinary PEARLS
β-Agonist and anticholinergic bronchodilators can
reduce bronchospasm and respiratory distress incontinence following prostatectomy in patients r Patients with MG may develop voiding dysfunction,
resulting from cholinergic medications. with myasthenia gravis. Br J Urol. 1982;54: most commonly detrusor areflexia resulting in
369–371. urinary retention.
Complementary & Alternative 4. Christmas TJ, et al. Detrusor failure in myasthenia r Urinary incontinence may develop after TURP.
Therapies gravis. Br J Urol. 1990;65:422. r Urologic symptoms may be improved by systemic
N/A
MG therapy, although specific therapy for urologic
complications, such as urinary retention or
incontinence, may need to be instituted.
251
MYELODYSPLASIA (SPINAL DYSRAPHISM), UROLOGIC CONSIDERATIONS

Blake A. Wynia, MD, MPH
r Myelodysplastic states can be subdivided: PHYSICAL EXAM

BASICS – Spina bifida occulta: The mildest form. No overt r Assess general appearance, body habitus, gait,
signs of spinal abnormality; may be associated dexterity, muscular, and neurologic development
DESCRIPTION with tethering of the spinal cord and often r Genitalia: Presence or absence of hypospadias,
r Myelodysplasia (spinal dysraphism, neural tube associated with a low-lying conus (below L2–L3); cryptorchidism, labiovulvar abnormalities
defect) is a very broad term encompassing a large usually detected by plain x-ray, demonstrating r Rectal exam: Perianal sensation, rectal tone, fecal
heterogeneous group of congenital vertebral column open vertebral bodies impaction
defects that result from defects that occur during – Posterior meningoceles, myelocystocele, and r Back exam for open (obvious exposed neural
neural tube closure. lipomyelomeningocele are closed defects tissues) or closed defects. Stigmata that may be
r Group of developmental abnormalities that can be associated with a skin-covered back mass associated with occult spinal dysraphism include:
open (meningocele, myelomeningocele, – Meningocele: The meninges or dural sac, but no – Dimples or sinuses, subcutaneous mass, skin tags,
lipomyelomeningocele) or closed (spinal bifida neural elements, extend beyond the vertebral hemangiomas, abnormal hair patches,
occulta, posterior meningoceles, canal. Mostly normal lower extremity pigmentation, or abnormal gluteal cleft.
lipomyelomeningocele, and myelocystocele). – Myelomeningocele: The nerves and spinal cord are r Neurologic exam:
r Primary functional deficits can be lower limb exposed through an opening in the spinal column,
– Gait, balance, muscular development/tone
paralysis and sensory loss, bladder and bowel meninges, and skin. Significant neurologic defects
dysfunction, and cognitive dysfunction. (paralysis, urinary incontinence) are usually DIAGNOSTIC TESTS & INTERPRETATION
r Affected children often have varying degrees of associated. Lab
neurogenic bladder dysfunction. – Lipomyelomeningocele: Fatty tissue along with Urinalysis, urine culture, basic metabolic panel with
cord structures extend with protruding sac. high-grade reflux or hydronephrosis
r Myelomeningocele account for >90% of spinal
ALERT Imaging
Patients with myelodysplasia have a high incidence dysraphism: r 15–20% of neonates have abnormality of upper
of latex allergy. From birth, parents need to be – Arnold–Chiari malformation in 85% of children tract when 1st studied
educated in latex precautions. with myelomeningocele: r Plain abdominal x-rays:
◦ Cerebellar tonsils herniated through foramen
– May show structural vertebral anomalies or
EPIDEMIOLOGY magnum
◦ The 4th ventricle is obstructed leading to evaluate for partial or complete sacral agenesis
Incidence hydrocephalus if shunting is not performed
– May visualize stones or fecal impaction
r Spinal dysraphism: r Renal US (ultrasound):
– 1 per 1,000 births in USA previously ASSOCIATED CONDITIONS – Determine baseline of urinary tract; should be
– 2.5 times more common in Caucasians than blacks r Cloacal anomalies/Cloacal exstrophy performed shortly after birth; important to repeat
– Incidence decreasing over past 20 yr due to r Hydrocephalus/Arnold–Chiari malformation after back closure prior to discharge
prenatal diagnosis and use of folic acid r Imperforate anus – Assess for hydronephrosis, hydroureter, and PVR
Prevalence r Latex allergy (postvoid residual) if patient voids spontaneously
r Open spinal dysraphism: 60,000 cases estimated in r Sacral agenesis r Voiding cystourethrogram (VCUG):
USA r VACTERL syndrome (Vertebral defects, anal atresia, – Assess for vesicoureteral reflux, bladder wall
r Spina bifida occulta: 5–10% of the general cardiac defects, tracheoesophageal fistula, renal appearance, bladder capacity, PVR
r Dimercaptosuccinic acid (DMSA) renal scan in select
population; most cases are found incidentally anomalies, and limb abnormalities)
cases including: High-grade reflux, renal scarring,
RISK FACTORS GENERAL PREVENTION and solitary functioning kidney
r Maternal folate deficiency during pregnancy r Folic acid 0.4 mg/d in all women of childbearing r Magnetic resonance imaging (MRI):
r Family history: Incidence for mother with one age; 4.0 mg/d in women with previous NTD-affected – Assess spinal cord and vertebral anomalies in
affected child is 20–50/1,000 live births; also 2nd pregnancy patients with suspected occult spinal dysraphism
and 3rd degree affected relative – Begin 2 mo before planned conception or a “closed” lesion. Spinal sonogram useful in
r Prepregnancy obesity or diabetes r Prenatal surgery for meningomyelocele at special
children <3 mo of age prior to boney ossification.
r Exposure to high temperatures in early pregnancy centers by 26 wk gestation.
– Outcomes encouraging with shunt placement in Diagnostic Procedures/Surgery
(fever or hot tub) r Urodynamic studies (UDS): Fill rate based on
r Intrauterine exposure to valproate or carbamazepine only 68% vs. 98% who underwent postnatal
repair; also results in improved mental average bladder capacity in milliliters: (24.5 × age
r Low vitamin B-12 levels
development and motor function at 30 mo of age + 62) divided by 10 is the rate of filling the bladder
r Chromosome trisomies 13 and 18, triploidy, and with warm saline
– Has not been shown to impact on urologic
single-gene mutations. – Often with video (video urodynamic studies or
outcomes
Genetics VUDS)
Genes involved in folate-homocysteine metabolism – Performed 2–3 mo after back closure or at time of
and transport (see Risk Factors) DIAGNOSIS diagnosis of occult spinal dysraphism
– Assess bladder capacity, volume, and pressure at
PATHOPHYSIOLOGY HISTORY abdominal and detrusor leak points (compliance),
r Increased maternal blood AFP (α-feto protein) at r Review medical and developmental history
r Most patients now diagnosed prenatally pressure when reflux, if present, is observed,
16 wk can indicate the presence of an NTD (neural detrusor overactivity, detrusor sphincter
tube defect). r Older patients commonly present with urinary and
dyssynergia (DSD)
r Spinal cord begins normal development on day 18 bowel incontinence: – Findings: Synergic (26%), dyssynergic with or
of gestation: r Change in bowel habits or gait, onset of leg or back without poor detrusor compliance (37%) and
– The canal closes in a cephalocaudal direction; pain, presence of seizures or other neurologic complete denervation (36%)
complete closure day 35 of gestation symptoms may suggest subsequent spinal cord Pathologic Findings
– Exact mechanism of dysraphism undefined tethering See Pathophysiology
r Other causes of neurogenic bladder (see Chapter on
Neurogenic Bladder, general)
r Tethered cord syndrome
252
MYELODYSPLASIA (SPINAL DYSRAPHISM), UROLOGIC CONSIDERATIONS

TREATMENT Therapies
r Neuromodulation of the bladder via intravesical r Biencowe H, et al. Folic acid to reduce neonatal
GENERAL MEASURES (1,2,3) electrical stimulation, sacral nerve stimulation, mortality from neural tube disorders. Int J Epidemiol.
r Urgent neurosurgical intervention is critical for open transcutaneous stimulation, and biofeedback; all of 2010;Suppl 1:110–121.
defects which may lead to hydrocephalus. unproven efficacy r De Jong T, Chrzan R, Klijn AJ, et al. Treatment of the
r Upper tract preservation is the primary goal with the r Tissue-engineered bladder augmentation neurogenic bladder in spina bifida. Pediatr Nephrol.
achievement of continence at an appropriate age. (experimental) 2008;23:889–896.
r Incomplete bladder emptying or significant upper r Artificial somatic-autonomic reflex pathway r Hopps C, Kropp K. Preservation of renal function in
tract hydronephrosis/high-grade reflux before and procedure (experimental) children with myelomeningocele managed with
after repair of the back defect basic newborn evaluation and close followup.
r Clean intermittent catheterization (CIC) for detrusor J Urol. 2003;169:305–308.
filling pressures of >30–40 cm H2 O. May often ONGOING CARE r Kochakarn W, Ratana-Olarn K, Lertsithichai P, et al.
require the addition of anticholinergic therapy (see Follow-up for long-term treatment with clean
PROGNOSIS intermittent catheterization for neurogenic bladder
Medication) r Self-performance of CIC is likely in school-aged
r Cutaneous vesicostomy or urethral dilation to lower in children. Asian J Surg. 2004;27:134–136.
children with supervision. r Tarcan T, Bauer S, Olmedo E, et al. Long-term
emptying pressures not usually performed r Regular monitoring for silent upper tract
followup of newborns with myelodysplasia and
MEDICATION deterioration including renal sonogram and VUDs normal urodynamic findings: Is followup necessary?
r Erectile and ejaculatory dysfunction
First Line J Urol. 2001;165(2):564–567.
r Anticholinergics: Decrease detrusor overactivity, r Delivery concerns especially at the end of gestation
increases bladder compliance and functional in myelodysplasia patients with bladder/bladder See Also (Topic, Algorithm, Media)
r Latex allergy, Urologic Considerations
capacity neck reconstruction
r Myelodysplasia (Spinal Dysraphism), Urologic
– Oxybutynin 0.2 mg/kg BID-TID; should be initiated
COMPLICATIONS Considerations Image
early in life when indicated to prevent upper tract r Incontinence with resulting skin ulceration due to
deterioration secondary to poor detrusor r Neurogenic Bladder, General Considerations
ammonia burns; consider delaying circumcision until r Tethered Cord Syndrome
compliance and DSD
continence program instituted since the prepuce
– Tolterodine 0.01 mg/kg BID to a maximum of
provides protection for the glans
0.4 mg/kg BID; long-acting forms when older r Renal insufficiency
– Almost always used in conjunction with CIC r Symptomatic UTIs CODES
– Side effects: Headaches, dry mouth, flushing of
r Shunt failure or infections
skin, abdominal discomfort, blurred vision ICD9
r Prophylactic antibiotics considered for reflux r Seizure disorders
r 238.75 Myelodysplastic syndrome, unspecified
r Musculoskeletal problems (scoliosis, club foot,
Second Line r 596.54 Neurogenic bladder NOS
r α-sympathomimetic, α-sympatholytic, others) r 788.30 Urinary incontinence, unspecified
β-sympatholytic, smooth muscle relaxants FOLLOW-UP
r Imipramine 0.7 mg/kg BID with maximum dosing of Patient Monitoring ICD10
r D46.Z Other myelodysplastic syndromes
1.2 mg/kg TID; consider pretreatment EKG Close follow-up with pediatric urology and neurology r N31.9 Neuromuscular dysfunction of bladder,
SURGERY/OTHER PROCEDURES from infancy and throughout childhood is required to
r When pharmacotherapy and CIC do not result in avoid upper tract deterioration and achieve urinary unspecified
r R32 Unspecified urinary incontinence
favorable bladder dynamics and/or continence in and bowel continence. Annual US and VUD when
older patients, consider: continent with stable upper tracts.
– Cystoscopy and botulinum-A toxin injection Patient Resources CLINICAL/SURGICAL
– Bladder augmentation usually with creation of Spina Bifida Association http://www.
continent catheterizable stoma since many of the spinabifidaassociation.org
PEARLS
children are wheelchair bound; wait until the child r Affected children often have varying degrees of
is 4–5 yr old for continence if upper tracts not neurogenic bladder and bowel dysfunction.
deteriorating and bladder is not hostile
REFERENCES r 1st-line treatment consists of CIC for elevated PVR
– Anti-reflux procedure for high-grade reflux 1. Bauer SB, Austin PF, Rawashdeh YF, et al. and anticholinergics when VUD testing suggests
– Bladder neck reconstructions: International Children’s Continence Society’s poor detrusor compliance and/or detrusor
Young-Dees-Leadbetter, Kropp, Pippi–Salle
modification, bladder neck closure
recommendations for initial diagnostic evaluation overactivity with or without upper tract M
and follow-up in congenital neuropathic bladder deterioration. Botulinum-A toxin injections, bladder
– Fascial sling or artificial urinary sphincters and bowel dysfunction in children. Neurourol augmentation, antireflux procedures and /or bladder
r Bowel incontinence:
Urodyn. 2012;31:610–614. neck procedures performed to protect upper tracts
– If oral laxatives, enemas/irrigation, and rectal 2. Rawashdeh YF, Austin P, Siggaard C, et al. and achieve urinary continence.
suppositories do not result in social bowel International Children’s Continence Society’s
continence consider MACE procedure selectively recommendations for therapeutic intervention in
ADDITIONAL TREATMENT congenital neuropathic bladder and bowel
Radiation Therapy dysfunction in children. Neurourol Urodyn.
N/A 2012;31:615–620.
3. de Kort LM, Bower WF, Swithinbank LV, et al. The
Additional Therapies management of adolescents with neurogenic
N/A urinary tract and bowel dysfunction. Neurourol
Urodyn. 2012;31:1170–1174.
253
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NEPHROCALCINOSIS, ADULT
Jennifer E. Heckman, MD, MPH
Stephen Y. Nakada, MD, FACS

BASICS r Nephrolithiasis
Lab
r Hypercalciuric states: r Used to identify underlying causative disorder
DESCRIPTION – Primary hyperparathyroidism (most common cause r Serum studies:
r Disorder characterized by deposition of calcium salts
in adults) – Calcium, phosphate, albumin
in the renal parenchyma – Sarcoidosis – Electrolytes
– Calcium oxalate (CaOx) – Vitamin D intoxication – BUN, Cr
– Calcium phosphate (CaPhos) – Multiple myeloma – Parathyroid hormone (PTH) levels
r May be intratubular or interstitial – Tuberculosis – Thyroid-stimulating hormone (TSH) levels
r May cause renal injury or be incidentally detected – Milk-alkali syndrome – CBC
r Associated with multiple conditions – Distal renal tubular acidosis r Urine studies:
– Renal prognosis dependent on underlying cause – Medullary sponge kidney – Urinalysis with microscopy +/– urine culture (if
– Often associated with severe metabolic defects – Inherited tubular defects (eg, Bartter syndrome) indicated)
r Can be classified by location: – Chronic hypokalemia (eg, primary aldosteronism) – 24-hr urine collection
– Renal medulla (medullary nephrocalcinosis) – Chronic immobilization
r Hyperphosphaturic states: Imaging
– Renal cortex (cortical nephrocalcinosis) r Can be detected on:
r Can also be classified as: – Tumor lysis syndrome
– Inherited tubular defects – Abdominal radiograph
– Molecular: Measurable increase in intracellular ◦ Usually only if attenuation >100 Hounsfield
r Hyperoxaluric states:
calcium concentration, but not visible units and size >2 mm
microscopically or radiographically – Primary oxaluria ◦ Medullary nephrocalcinosis: Stippled
– Microscopic: Visible microscopically – Secondary oxaluria (increased intake or enhanced
calcifications in renal pyramids
– Macroscopic: Visible radiographically absorption) ◦ Cortical nephrocalcinosis: Thin peripheral band
r Distinct entity from nephrolithiasis (calcifications in – Fat malabsorptive disorders (eg, pancreatic
with perpendicular extension; thin, peripheral
collecting system) insufficiency, inflammatory bowel disease)
r Chronic pain calcific tracts; or diffuse punctuate calcifications
r Neonatal nephrocalcinosis is discussed in Section II – Ultrasound
“Nephrocalcinosis, Neonatal” GENERAL PREVENTION ◦ Hyperechoic areas with or without acoustic
r Avoid hypercalciuric, hyperphosphaturic, and shadowing
EPIDEMIOLOGY
hyperoxaluric states – Computed tomography
Incidence r Avoid medications that enhance calcium loss (eg, ◦ Most sensitive and specific
Unclear secondary to wide range of etiologies r Pattern and distribution may be suggestive of
loop diuretics)
Prevalence etiology
r Primarily diagnosed in: r Imaging extent of calcium deposition unrelated to
– Adults DIAGNOSIS renal functional impairment or prognosis
– Low–birth-weight neonates (60% of preterm r Regardless of imaging modality, can be difficult
infants, frequently caused by loop diuretics) HISTORY
r Medullary nephrocalcinosis (97–98%), cortical r Most cases are asymptomatic (incidental finding on diagnosis, with low levels of intra-observer
nephrocalcinosis (2–3%) imaging) concordance (2)[B]
r Occasionally present with symptoms related to
RISK FACTORS underlying cause or associated condition r Radiographic diagnosis (usually incidental finding)
r Disorders that cause:
– Nausea, decreased appetite, abdominal pain, r Rarely, diagnosed on renal biopsy
– Hypercalcemia myalgias, polydipsia, lethargy (hypercalcemia)
– Hyperphosphatemia – Fatigue, edema, mental status changes, seizures Pathologic Findings
– Hypercalciuria r Primary histologic finding on renal biopsy:
(renal failure)
– Hyperphosphaturia – Renal colic, hematuria (nephrolithiasis) – Tubular, intracellular, and interstitial basophilic
– Hyperoxaluria r Review past medical history and medications calcifications
– Hypocitraturia r (+) von Kossa stain of calcifications diagnostic of
PHYSICAL EXAM CaPhos
Genetics r Nonspecific, many patients are asymptomatic
Inherited disorders may lead to risk factors for r Physical findings otherwise a manifestation of
nephrocalcinosis development (eg, autosomal
dominant hypocalcemia, familial hyperoxaluria) underlying disorder
PATHOPHYSIOLOGY
r Caused by increase in urinary excretion of calcium,
phosphate, and/or oxalate (1)
– May occur with or without hypercalcemia
– CaOx and CaPhos crystals result from urinary
supersaturation
◦ CaOx and CaPhos crystals precipitate,
aggregate, and move to interstitium
◦ May result in acute or chronic renal damage
and/or lead to calculus formation
◦ Renal ischemia or injury may augment
nucleation of CaOx or CaPhos crystals
254
NEPHROCALCINOSIS, ADULT
DIFFERENTIAL DIAGNOSIS See Also (Topic, Algorithm, Media)

r Nephrolithiasis ONGOING CARE r Calcifications, Renal
r Renal calcifications, associated with: r Hypercalcemia, Urologic Considerations
– Chronic ureteropelvic junction obstruction or PROGNOSIS r Hypercalciuria (Absorptive, Renal, and Resorptive)
r Depends on underlying etiology
ureterocele r Hyperoxaluria
r Most do not progress to end-stage renal failure
– Renal infarction r Hyperparathyroidism, Urologic Considerations
– Renal mass COMPLICATIONS r Hyperphosphatemia and Hypophosphatemia,
r Dystrophic calcifications, associated with: r Nephrolithiasis Urologic Considerations
– Renal tuberculosis r Obstructive uropathy r Hypocitraturia
– Congenital cystic kidney – May be associated with sepsis r Hypokalemia, Urologic Considerations
r Renal artery calcifications r Renal infection r Medullary Sponge Kidney
r Calcification associated with spinal injury r Renal scarring r Milk-alkali Syndrome
r Defects in renal tubular function r Nephrocalcinosis, Adult Images
r Acute renal failure r Nephrocalcinosis, Neonatal
TREATMENT r Chronic renal failure r Renal Tubular Acidosis
GENERAL MEASURES r Tumor Lysis Syndrome
r Treatment directed at underlying etiology FOLLOW-UP
r Urolithiasis, Adult, General Considerations
r No specific treatment prevents progression Patient Monitoring
r Urinalysis, 24-hr urine collection r Urolithiasis, Calcium Oxalate/Phosphate
r Early treatment of reversible causes of renal injury
r Renal function testing r Urolithiasis, Pediatric, General Considerations
important r Serum Ca
r Reduce urinary concentration and increase solubility
r Labs to monitor known metabolic abnormalities
of calcium, phosphate, and/or oxalate
– Increase fluid intake
r Imaging if symptomatic CODES
◦ Goal urine output >2 L/d Patient Resources
– If hypercalciuria: ICD9
http://www.umm.edu/ency/article/000492.htm r 275.3 Disorders of phosphorus metabolism
◦ Restrict animal protein intake (<0.7 g/kg)
◦ Restrict sodium intake (<100 mEq/d) r 275.42 Hypercalcemia
– If hypocitraturia and urine pH <7: REFERENCES r 275.49 Other disorders of calcium metabolism
◦ Potassium citrate (titrate to normal urinary
citrate) 1. Sayer JA, Carr G, Simmons NL. Nephrocalcinosis: ICD10
Molecular insights into calcium precipitation within r E83.52 Hypercalcemia
MEDICATION the kidney. Clin Sci (Lond). 2004;106:549–561. r E83.59 Other disorders of calcium metabolism
First Line 2. Cheidde L, Ajzen SA, Tamer Langen CH, et al. A r N29 Oth disorders of kidney and ureter in diseases
Must be tailored to underlying etiology (eg, for critical appraisal of the radiological evaluation of classd elswhr
hyperparathyroidism, resection of adenoma, treatment nephrocalcinosis. Nephron Clin Pract. 2007;106(3):
of renal tubular acidosis, etc.) c119–c124.
3. Miller NL, Humphreys MR, Coe FL, et al. CLINICAL/SURGICAL
Second Line
N/A Nephrocalcinosis: Re-defined in the era of PEARLS
endourology. Urol Res. 2010;38(6):421–427. r Important to distinguish nephrocalcinosis from
SURGERY/OTHER PROCEDURES 4. Kerbl K, Clayman RV. Endourologic treatment of
r Surgical intervention may be required, particularly if nephrolithiasis.
nephrocalcinosis. Urology. 2000;56(3):508. r Management directed at underlying cause of
calcification obstructs collecting system
5. Gdor Y, Faddegon S, Krambeck AE, et al.
– Endourologic management disorder.
◦ May use in diagnosis (direct visual inspection) Multi-institutional assessment of ureteroscopic r Primarily a radiographic diagnosis, does not typically
laser papillotomy for chronic flank pain associated
(3)[C] require surgical intervention.
◦ May treat with flexible ureteroscopy/ with papillary calcifications. J Urol. 2011;185(1):
192–197.
nephroscopy with laser or electrohydraulic
lithotripsy (4)[C]
◦ Ureteroscopic laser papillotomy may be safe and
effective in patients with chronic flank pain
ADDITIONAL READING
(5)[C] Monk RD, Bushinsky DA, Chapter 57. Nephrolithiasis
– Extracorporeal shockwave lithotripsy (ESWL) and nephrocalcinosis. In: Floege J, Johnson RJ,
◦ Poor fragmentation and evacuation Feehally J, eds. Comprehensive Clinical Nephrology.
ADDITIONAL TREATMENT 4th ed. Philadelphia, PA: Mosby Elsevier; 2011.
Radiation Therapy
N/A N
N/A
Therapies
N/A
255
NEPHROTIC SYNDROME
ASSOCIATED CONDITIONS r Urine analysis and microscopy

BASICS r Membranous nephropathy (24%) – Marked proteinuria causes urine to foam.
r Minimal change disease (15%) – Albuminuria detected by dipstick; all proteinuria
DESCRIPTION r Lupus (14%) detected by SSA; Protein is precipitated in urine by
r Neoprotic syndrome refers to a specific renal disease r Focal segmental glomerulosclerosis (12%) the addition of sulfosalicylic acid (SSA). Performed
with a distinct constellation of clinical and r Membranoproliferative glomerulonephritis (7%) to confirm positive protein reactions seen on a
laboratory features: r Amyloidosis (6%) urine dipstick.
– Proteinuria (>3.5 g/d) r IgA nephropathy (6%) – Positive SSA and negative dipstick: Nonalbumin
– Hypoalbuminemia (<3 g/dL) proteinuria (multiple myeloma)
– Peripheral edema GENERAL PREVENTION – Characteristic dipstick reading of 3+ to 4+ in NS
– Hyperlipidemia and thrombotic disease frequently r Avoidance of risk factors patients
seen r Treating conditions that may cause NS – Glycosuria: Suggests diabetes mellitus as possible
r Nephrotic syndrome (NS) can be caused by specific cause of NS
renal diseases or systemic diseases such as diabetes, – Hematuria common (usually microscopic)
lupus and others. DIAGNOSIS – Lipiduria: Maltese crosses seen microscopically
– Microscopic: Oval fat bodies, fatty casts, hyaline
EPIDEMIOLOGY HISTORY casts, cellular casts
Incidence r Symptoms of fluid/sodium retention: r 24-hr urine
r Uncommon Disease – Periorbital edema, especially on awakening – Protein > 3.5 g/24 h, mostly albumin
– Children: 2/100,000 new cases / year – Peripheral edema, especially at end of day r Additional testing as needed to rule out other
– Adult: 3/100,000 new cases / year – Dyspnea/orthopnea secondary to pleural effusion
r Anorexia nonrenal causes
Prevalence – Fasting blood sugar/glucose tolerance
N/A r Oliguria, foamy urine
– Hepatitis B and C antibodies
r Weight gain – Antinuclear antibody
RISK FACTORS r Foamy appearance of urine
r Primary renal disease (minimal change disease – Syphilis serology
predominant cause in children) – HIV
PHYSICAL EXAM
r Underlying systemic disease in 30% of adults with r Along with signs of fluid retention, patients may – Multiple myeloma
NS including diabetes mellitus, amyloidosis, systemic have signs of systemic disease causing NS Imaging
lupus erythematosus r Vital signs: BP, temperature, weight r Renal ultrasound: Increased echogenicity of renal
r Infection: Streptococcus, hepatitis, mononucleosis, r Skin exam: Rash (eg, butterfly rash of SLE), pallor, parenchyma
syphilis, tuberculosis, HIV r Screening for underlying malignancy with CT scan
edema, lymphadenopathy
r Medications: NSAIDs, interferons, bisphosphonates, r Ophthalmic exam: Uveitis in sarcoid, diabetic Diagnostic Procedures/Surgery
lithium, gold, captopril, penicillamine, tyrosine retinopathy Renal biopsy
kinase inhibitors r Heart/lung exam: Endocarditis, pleural effusion
r Malignancy r Abdominal exam: Masses, ascites
Pathologic Findings
r Minimal change glomerulopathy
Genetics r Neurologic exam: Diabetic neuropathy, CNS lesion, r Membranous glomerulopathy
r Rare cause mononeuritis multiplex r Focal segmental glomerulonephritis
– 2–8% of cases are familial r Mesangioproliferative glomerulonephritis
– Finnish type congenital nephritic syndrome is r Membranoproliferative glomerulonephritis
inherited as autosomal recessive Lab
r Blood chemistry: BUN, Cr, comprehensive metabolic r Diabetic glomerulosclerosis
PATHOPHYSIOLOGY panel, CBC r Fibrillary glomerulonephritis
r Severe proteinuria is due to abnormal permeability r Light chain deposition disease
– Hypoalbuminemia (<3 g/dL)
of the glomerular basement membrane (GBM) (1). r Serum lipids: Cholesterol, triglycerides often
– GBM normally restricts passage of proteins elevated DIFFERENTIAL DIAGNOSIS
r Congestive heart failure
>70 kd.
r Signs/symptoms of NS worsen as serum albumin r Cirrhosis
falls below 2.5 g/dL. r Malnutrition
r Proteinuria can be selective or nonselective. r Protein losing enteropathy
r Edema results from primary salt retention and
secondary decreased plasma oncotic pressure.
r Hyperlipidemia is secondary to increased hepatic
synthesis from low oncotic pressure and urinary loss
of regulatory proteins.
r Hypercoagulable state is likely due to loss of
antithrombin III in urine.
256
NEPHROTIC SYNDROME
COMPLICATIONS See Also (Topic, Algorithm, Media)

r Acute kidney failure r Chronic Kidney Disease, Adult (Renal Failure,
TREATMENT r Atherosclerosis, hyperlipidemia, cardiovascular Chronic)
GENERAL MEASURES disease r Chronic Kidney Disease, Pediatric (Renal Failure,
r Sodium restriction (2 g/d)[A] r Chronic kidney disease Chronic)
r Congestive heart failure r Glomerulonephritis, Acute
r Protein restriction
r Heart disease r Nephropathy, Membranous
r BP control
r Malnutrition r Nephropathy, Minimal Change
r Maintenance of fluid balance
r Pneumococcal pneumonia and other infections r Proteinuria
MEDICATION r Pulmonary edema
First Line r Arterial and venous thrombosis (particularly deep
r ACE inhibitors (captopril, enalapril, ramipril, others)
vein and renal vein thrombosis) CODES
or Angiotensin II receptor blockers (losartan, r Pulmonary emboli
olmesartan, telmisartan others) (2) ICD9
– Indicated with random protein to creatinine ratio FOLLOW-UP r 250.40 Diabetes with renal manifestations, type II or
>200 mg/G Patient Monitoring unspecified type, not stated as uncontrolled
– Should not be used concurrently due to risk of r Assess response to treatment with 24-hr urine r 250.41 Diabetes with renal manifestations, type I
hypotension and worsening renal function protein measurement [juvenile type], not stated as uncontrolled
– Monitor for hypotension, hypokalemia, or r Monitor BP and renal function r 581.9 Nephrotic syndrome with unspecified
worsening renal function r Monitor for treatment toxicity pathological lesion in kidney
– Common ACE-I side effects include cough,
angioedema, or allergy Patient Resources ICD10
r Medline Plus http://www.nlm.nih.gov/ r E10.21 Type 1 diabetes mellitus with diabetic
r Statin therapy
medlineplus/ency/article/000490.htm nephropathy
– Goal LDL <100 and triglyceride <150 r www.kidney.diddk.nih.gov
– Side effects include myalgia, liver dysfunction, GI r E11.21 Type 2 diabetes mellitus with diabetic
disturbance, and rash nephropathy
r N04.9 Nephrotic syndrome with unspecified
r Corticosteroids for primary idiopathic or minimal REFERENCES
morphologic changes
change disease (3)[A]
1. Siddall EC, Radhakrishnan L. The pathophysiology
Second Line of edema formation in the nephritic syndrome.
Cytotoxic agents (cyclophosphamide, chlorambucil, Kidney Int. 2012;62:635–642. CLINICAL/SURGICAL
cyclosporine): Minimal change disease unresponsive 2. Nakao N, Yoshimura A, Morita H, et al. PEARLS
to steroids, membranous glomerulonephritis with poor Combination treatment of angiotensin II receptor
prognosis r NS is a constellation of signs and symptoms caused
blocker and angiotensin converting enzyme
inhibitor in non-diabetic renal disease. A by different disorders that damage the kidneys.
SURGERY/OTHER PROCEDURES r The hallmark of NS is excess protein in the urine and
r Dialysis randomized controlled trial. Lancet. 2003;361:
r Renal transplantation 117–124. edema.
r The most common cause in children is minimal
3. Maas R, Hofstra JM, Wetzels JF. An overview of
ADDITIONAL TREATMENT immunosuppressive therapy in idiopathic change disease.
Radiation Therapy r The most common cause in adults is membranous
membranous nephropathy. Minerva Med.
N/A 2012;103:253–266. glomerulonephritis.
r Treatment is directed toward the underlying
Anticoagulation for thrombosis disorder, symptom reduction, and prevention of
ADDITIONAL READING complications and preservation of renal function.
r Most patients are given an ACE inhibitor or an
Therapies Cadnapaphornchai MA, Tkachenko O, Shchekochikhin angiotensin II receptor blocker to slow the loss of
N/A D, et al. The nephrotic syndrome: Pathogenesis and kidney function.
treatment of edema formation and secondary
complications. Pediatr Nephrol. 2014;29(7):
ONGOING CARE 1159–1167.
PROGNOSIS
r Prognosis depends on age, race, pathology, presence
of HTN, underlying systemic disease, degree of renal
dysfunction, and degree of proteinuria.
r Minimal change disease in children has an excellent
prognosis.
r Prognosis of the other glomerulopathies much more
N
variable.
r Prognosis of secondary NS depends on the systemic
diseases causing the NS.
257
NEUROBLASTOMA
Nilay M. Gandhi, MD

BASICS r Determined by tumor site origin, metastasis, and r Abdominal mass
presence of paraneoplastic syndromes – 65% retroperitoneal, 40% adrenal
DESCRIPTION r Likely failure of persistent primitive ganglion cells to r HTN (rare, due to catecholamine release)
r Heterogeneous malignancy arising from neural crest r Metastasis present in 70% at diagnosis
respond to normal signals
elements along the sympathetic chain with a broad r Spinal cord, sympathetic ganglia involvement: – Raccoon’s eyes
spectrum of clinical behavior – Urinary retention, constipation, extremity paresis, ◦ Upper eyelid hemorrhage (periorbital
r International Neuroblastoma Staging System
Horner syndrome metastasis)
(INSS) (1) r Presence of metastasis: – Bluish/erythematous subcutaneous nodules
– Stage 1: Localized tumor, completely excised, – Fever, lethargy, weight loss, bony pain, pallor ◦ Skin metastasis, “blueberry-muffin” spots
ipsilateral lymph nodes (LN) (–) r Bone metastasis (older children) r Acute myoclonic encephalopathy
– Stage 2a: Localized tumor, incompletely excised, r Liver metastasis (younger children) – Rapid eye movements (opsoclonus), jerky
ipsilateral LN (–) r Active biochemical products: extremities (myoclonus)
– Stage 2b: Localized tumor with/without complete – Cerebellar ataxia, dysphasia, intellectual deficit
excision, ipsilateral LN (+), enlarged contralateral – 90% produce catecholamines
◦ Paroxysmal hypertension (HTN), palpitation, – Autoimmune phenomenon
LN (–) – 70–80% with prolonged neurologic impairment
– Stage 3: Unresectable unilateral tumor crossing flushing, headache
– Homovanillic acid (HVA) in poorly differentiated (ACTH/steroid therapy)
midline or localized unilateral tumor with r Unilateral Horner’s syndrome
contralateral LN (+) tumors
– Vanillylmandelic acid (VMA) in well-differentiated – Ptosis, loss of papillary dilation, unilateral
– Stage 4: Any primary tumor with metastasis to anhydrosis
distant LN, bone, liver, skin, or bone marrow tumors
– Tumor compression on sympathetic ganglia
– Stage 4s: Localized primary tumor (stage 1, 2a, ASSOCIATED CONDITIONS r Extremity paresis, sensory deficits
2b) metastasis limited to liver, skin, and/or bone r Other disorders of neural crest derived cells
– Paravertebral tumor compressing spinal cord
marrow in infant <1 yr – Hirschsprung disease
EPIDEMIOLOGY – Neurofibromatosis type 1 DIAGNOSTIC TESTS & INTERPRETATION
– Congenital central hypoventilation syndrome Lab
Incidence r 24-hr urinary VMA and HVA
r 3rd most common childhood cancer (after leukemia GENERAL PREVENTION
r Screening with urinary catecholamines is not – Elevated in 90–95% of patients
and brain tumors) r CBC: Anemia suggests bone marrow involvement
– Most common solid extra-cranial tumor in children effective (Japan, Canada, Germany)
r PT/PTT: Elevation suggests liver involvement
– Most common cancer in infants <1 yr of age – Increased diagnosis, no impact on survival
r Comprises 6–10% of all childhood neoplasms – Majority low-grade, spontaneously resolve r Ferritin: Elevation in advanced disease
– 1 in 7,000 live births r Genetic counseling indicated if family history – 40–50% of patients (must be >3 standard
– 750 new cases/yr deviations)
◦ 50% incidence in children <2 yr of age (highest Imaging
incidence in 1st yr of life) DIAGNOSIS r Ultrasound (1st choice for children with palpable
◦ Peak age 0–4 yr (median 18–24 mo) abdominal mass)
◦ More common in Caucasian male infants HISTORY r Whole-body CT
r Early satiety, poor appetite, vomiting
Prevalence – Possible partial bowel obstruction due to – Evaluate primary tumor, regional extent, distant
r 10.5 per 1 million children <15 yr of age intra-abdominal mass metastasis
r Accounts for 15% of all pediatric cancer fatalities r Unexplained weight loss, anorexia, fever, pallor, – Intratumoral calcification and/or vascular
irritability suggests metastatic disease encasement distinguishes from Wilms tumor
RISK FACTORS r Urinary frequency/retention, constipation: r Whole-body MRI
r Risk in sibling or offspring is <6%
r Maternal factors: – Extrinsic compression of pelvic organs/nerves from – Evaluate intraspinal tumor extension, delineate
presacral mass major vessels
– Folate deficiency (increased incidence) r Poor truncal balance, jerky muscle movements, or r Bone scan (radionuclide, not skeletal)
– Gestational diabetes mellitus r Iodine123 MIBG
r Environmental factors implicated but not uncontrolled eye movement
– Acute myoclonic encephalopathy (2%) – Determine extent of disease, assess tumor
confirmed (2) recurrence
◦ Toxic byproducts/autoimmune phenomenon
– Paternal exposure to electromagnetic fields r Extremity weakness, sensory deficits
– Prenatal exposure to alcohol, pesticides, or Diagnostic Procedures/Surgery
– Paravertebral tumor compressing spinal cord r Open/laparoscopic biopsy for pathologic tissue
phenobarbital
r Pain in skull and long bones from metastasis diagnosis
– Potential relationship with assisted pregnancies
r Genetic factors: r Pallor/anemia (bone marrow involvement in 50% of r Bone marrow aspirate/biopsy
– Increased incidence in Turner’s syndrome patients) – 2 marrow aspirates (bilateral iliac crests) + 2 core
r Bleeding diathesis (from liver metastasis) biopsies recommended
Genetics r Paroxysmal HTN, sweating, headaches, palpitations – 70% positive aspirates
r Majority are sporadic
– <5% patients (catecholamines sequestered ◦ Future research into neuroblastoma-specific
– 1–2% familial (autosomal dominant 20%) immunocytology of marrow aspirates
◦ 20% bilateral adrenal or multifocal tumors within intracellular vacuoles)
r Watery diarrhea, hypokalemia due to VIP secretion
◦ Germline mutation in ALK gene
r Aneuploidy = favorable prognosis
r N-MYC amplification (20% patients), chromosome
1p deletion (25–35%), loss of 11q
heterozygosity (35–45%) = adverse prognosis
258
NEUROBLASTOMA
Pathologic Findings r High risk (stage 2 with age >1 yr with unfavorable REFERENCES
r Gross: Solid/cystic vascular, poorly encapsulated histopathology, or stage 3, 4, 4s with N-MYC
purple mass amplification regardless of age): 1. Brodeur GM, Seeger RC, Barrett A. International
r Histology: – Intensive chemotherapy with or without bone criteria for diagnosis, staging, and response to
– Small round blue cells marrow ablation and repeated surgery treatment in patients with neuroblastoma. J Clin
◦ Mitosis-Karyorrhexis index is prognostic Oncol. 1988;6(12):1874–1881.
– Homer–Wright pseudorosettes 2. Park JR, Eggert A, Caron H. Neuroblastoma:
r Histopathologic markers: Radiation Therapy Biology, prognosis, and treatment. Pediatr Clin
r Reserved for primary or secondary chemotherapy
– N-MYC North Am. 2008;55(1):97–120.
failures in low-risk patients 3. Montclair T, Brodeur GM, Ambros PF, et al. The
– DNA ploidy r Utilized for local control in bulky stage 3 or
– Shimada classification (stroma poor/rich) International Neuroblastoma Risk Group (INRG)
◦ Stroma-poor (based on age, histologic advanced stage 4 staging system: An INRG Task Force report. J Clin
maturation, mitotic rate) – Avoid if spinal cord compression due to adverse Oncol. 2009;27(2):298–303.
◦ Stroma-rich (nodular, intermixed, well effects on spine growth 4. Maris JM. Recent advances in neuroblastoma.
r Intraoperative radiation therapy not better than
differentiated) NEJM. 2010;362:2201–2211.
r Neuron-specific enolase (NSE) staining is specific for external beam irradiation 5. Wagner LM, Danks MK. New therapeutic targets
neuroblastoma Additional Therapies for the treatment of neuroblastoma. J Cell
r Periodic acid-Schiff (PAS) staining can distinguish Bone marrow transplantation Biochem. 2009;107(1):46–57.
sarcomas Complementary & Alternative
DIFFERENTIAL DIAGNOSIS Therapies (5)
r Ganglioneuroma (benign form) r 13-cis-retinoic acid improves 5-yr overall survival ADDITIONAL READING
r Ganglioneuroblastoma (intermediary between (OS) in children with advanced stage disease after r Matthay KK, George RE, Yu AL. Promising
ganglioneuroma and neuroblastoma) transplantation or intensive chemotherapy therapeutic targets in neuroblastoma. Clin Cancer
r Intra-abdominal mass in childhood: r Iodine131 MIBG targeted delivery for metastatic
Res. 2012;18(10):2740–2753.
– Wilms tumor disease r Wylie L, Philpott A. Neuroblastoma progress on
r Anti-GD2 antibodies (research pending)
– Pheochromocytoma many fronts: The neuroblastoma research
– Rhabdomyosarcoma symposium. Pediatr Blood Cancer. 2012;58(4):
– Lymphoma 649–651.
– Teratoma
ONGOING CARE
– Ewing sarcoma
PROGNOSIS r Abdominal mass, newborn/child, urologic
– Rare primary neoplasms of liver and pancreas r Dependent on risk status
considerations
– Low risk: Resection is curative, 97% 5-yr OS r Neuroblastoma Image
– Intermediate risk: neoadjuvant chemo followed by r Pheochromocytoma
TREATMENT >50% resection, 70–90% 5-yr OS r Wilms tumor (nephroblastoma)
GENERAL MEASURES – High risk: Neoadjuvant chemo 4 cycles (restage
r Multimodal treatment approach involving surgery, after 2 cycles), >50% resection, radiation,
chemotherapy, radiotherapy, and/or bone marrow or peripheral stem cell transplant, monoclonal Ab,
stem cell transplantation 20–40% 5-yr OS CODES
r Nearly all stage 4s patients spontaneously resolve r Better survival in nonadrenal primary tumors
r Shimada classification ICD9
(observation) r 194.0 Malignant neoplasm of adrenal gland
r INSS surgical stage and more recently the – Stroma-poor: <10% survival
r 197.7 Malignant neoplasm of liver, secondary
International Neuroblastoma Risk Group (INRG) COMPLICATIONS r 198.5 Secondary malignant neoplasm of bone and
pretreatment system dictates treatment (3) r Dumbbell neuroblastoma with spinal cord
bone marrow
MEDICATION compression
– Best treated with chemotherapy ICD10
First Line (4) r C74.90 Malignant neoplasm of unsp part of
r Low risk: None unless surgical failure – Neurosurgical intervention only for emergent
decompression unspecified adrenal gland
– Cyclophosphamide, Adriamycin, and r Associated with tumor presentation and with r C78.7 Secondary malig neoplasm of liver and
Cisplatin/VM-26 in low-dose cycles
r Intermediate risk: Induction with Cyclophosphamide treatment modalities intrahepatic bile duct
r C79.52 Secondary malignant neoplasm of bone
and Adriamycin with or without radiotherapy FOLLOW-UP
r High risk: Cyclophosphamide, Adriamycin, VM-26, Patient Monitoring marrow
Doxorubicin, Cisplatin, Etoposide in various r Low risk:
combinations – Imaging + lab markers 1–2 mo after therapy, CLINICAL/SURGICAL
every 6 mo for 5 yr, then annually after 5 yr
Second Line
r Intermediate risk: Cisplatin/VM-26 r Intermediate risk: PEARLS N
r High risk: Alternative use of above-listed – Imaging + lab markers 1–2 mo after therapy, r Most common malignancy in infants <1 yr.
combinations every 1–3 mo for 1st yr, then every 4–6 mo for r INSS stage determines optimum treatment modality.
2–5 yr, then annually after 5 yr r Urine HVA and VMA are diagnostic.
SURGERY/OTHER PROCEDURES r High risk: r N-MYC associated with poor prognosis.
r Low risk (stages 1, 2, or 4s with age <1 yr or >1 yr
– Imaging + lab markers 1–2 mo after therapy, r Neuroblastoma requires a minimum of 5-yr
with favorable pathology): every 1–3 mo for 5 yr, every 6 mo after 5 yr
– Surgery is curative follow-up.
– Chemotherapy indicated if recurrence, N-MYC Patient Resources
r National Cancer Institute (http://www.cancer.gov/
amplification, or unfavorable histology
r Intermediate risk (stage 3 age <1 yr or >1 yr with cancertopics/types/neuroblastoma)
r National Cancer Comprehensive Network
favorable pathology, or stage 4 <1 yr):
– Surgery + multiagent chemotherapy (http://www.nccn.com/living-with-cancer/265-
neuroblastoma.html)
259
NEUROGENIC BLADDER, GENERAL CONSIDERATIONS

Alana M. Murphy, MD
r Peripheral nerve disease: r Digital rectal exam:

BASICS – Following radical pelvic surgery: – Prostate size: BPH may coexist with NGB
◦ Abdominoperineal resection – See neurologic exam
DESCRIPTION ◦ Radical hysterectomy r Evaluate for sacral abnormalities:
Neurogenic bladder (NGB) is a general term used to – Diabetes mellitus – Sacral dimple, skin tag, discoloration or tuft of hair
describe dysfunction of the urinary bladder due to – Intervertebral disk disease may suggest occult spinal dysraphism
disease of the central nervous system (CNS) or – Spinal stenosis – Sacral agenesis
peripheral nerves involved in the control of urine – Guillain–Barré syndrome r Focused neurologic exam:
storage and micturition r Neural tube defects – Sacral root
r Cerebral palsy – Perianal sensation
EPIDEMIOLOGY
Incidence – Anal tone, sphincter control
GENERAL PREVENTION
Difficult to determine incidence due to multiple r Tight glycemic control with diabetes mellitus DIAGNOSTIC TESTS & INTERPRETATION
etiologies r Prevention aimed at preventing secondary Lab
Prevalence complications r Blood studies:
r Prevalence of voiding dysfunction by specific – Infections – Serum chemistry: Renal function, creatinine
conditions: – Incontinence – CBC: Elevated WBC, secondary anemia due to
– Cerebrovascular accident: 20–50% – Skin breakdown decreased renal function or chronic infection
– Parkinson disease: 35–70% – Urolithiasis r Urinalysis:
– Multiple sclerosis: 50–90% – Proteinuria: Renal dysfunction
– Diabetes mellitus: 5–60% DIAGNOSIS – Pyuria, nitrite, leukocyte esterase: Acute or chronic
infection
RISK FACTORS
r Neurologic disease, injury, or congenital HISTORY – Hematuria: Infection or urolithiasis
r Neurologic disease: Onset, duration
malformation Imaging
r Diabetes mellitus r Diabetes mellitus r Imaging is most important in patients with risk
r Radical pelvic surgery r Congenital disorders: factors for upper tract compromise:
– Neural tube defects – DSD (especially males who void reflexively)
Genetics – Cerebral palsy – Impaired bladder compliance
Genetic diseases that may be associated with NGB r History of radical pelvic surgery r Renal ultrasound (US): To screen for calculus,
include muscular dystrophy, hereditary spastic r Voiding symptoms hydronephrosis, or mass
paraplegia, neurofibromatosis, and familial r Storage symptoms r Excretory urography:
dysautonomia
– Urinary frequency – Delayed excretion of contrast with high urinary
PATHOPHYSIOLOGY – Incontinence storage pressures
r CNS lesions (1): r Method of urinary management: – Hydroureteronephrosis:
– Suprapontine: – Volitional or reflex voiding ◦ Marked elevation of intravesical pressure or
◦ Function: Inhibits sacral micturition center – Condom catheter urinary collection calculi
◦ Detrusor overactivity (DO) due to loss of – Intermittent self-catheterization r Nuclear medicine renal scan:
inhibition of sacral micturition center – Indwelling urethral or suprapubic catheter – Assess for obstruction
– Pontine micturition center: – Credé or Valsalva voiding – Sequential studies detect deterioration of renal
◦ Function: Coordinates sphincter relaxation r UTI: function
during bladder contraction – Severity of infection: Febrile, hospitalization, IV
◦ Lesions between pontine and sacral micturition Diagnostic Procedures/Surgery
antibiotics required r Urodynamics (UDS): Necessary to determine
centers are associated with DO and detrusor – Frequency of recurrence effective urologic management for all patients with
sphincter dyssynergia (DSD) r Urolithiasis episodes, surgical intervention, calculus neurogenic lower urinary tract dysfunction
– Sacral micturition center: r Neurogenic DO (NDO):
◦ Function: Mediates reflex and voluntary bladder composition
r Autonomic dysreflexia (AD): Associated with spinal – Loss of CNS inhibition
contraction r DSD (abnormal reflexive sphincter contraction during
◦ Detrusor underactivity or acontractility cord lesion at or above T6
r Peripheral lesions (1): Variable voiding dysfunction – Occurs with manipulation of the urinary or involuntary or voluntary detrusor contraction):
gastrointestinal tract – Functional bladder outflow obstruction with
– Detrusor underactivity
– Impaired bladder sensation PHYSICAL EXAM elevated intravesical pressure
– Impaired sphincteric function r Flank tenderness: Ureteral obstruction, – Secondary damage: Pressure, infection, urolithiasis
pyelonephritis – 10–20% of patients have internal (bladder neck)
ASSOCIATED CONDITIONS r Abdominal mass: Distended bladder, urinary sphincter dyssynergia with external sphincter
r CNS diseases:
retention dyssynergia.
– Cerebrovascular accident r Incontinence of urine: – Elevated intravesical pressure >40 cm H2 O
– Multiple sclerosis responsible for sequelae of NDO–DSD
r Testicular exam:
– Normal-pressure hydrocephalus r Detrusor underactivity or acontractility:
– Parkinson disease – Epididymo-orchitis/epididymitis; secondary
– Interruption of sacral reflex arc; no detrusor
– Spinal cord injury abscess
contraction
– Transverse myelitis – Typically low-pressure storage
– Adrenergic overgrowth: May result in decreased
bladder compliance, elevated storage pressure
260
NEUROGENIC BLADDER, GENERAL CONSIDERATIONS
Pathologic Findings SURGERY/OTHER PROCEDURES

r Endoscopic sphincter ablation or stenting:
REFERENCES
Bladder wall thickening with fibrosis and
trabeculation – Only males with DSD; requires condom catheter 1. Fowler CJ, Dalton C, Panicker JN. Review of
r Augmentation cystoplasty using an intestinal neurologic diseases for the urologist. Urol Clin
DIFFERENTIAL DIAGNOSIS North Am. 2010;37(4):517–526.
r Idiopathic overactive bladder segment to enlarge the bladder
r Dysfunctional voiding – Goal is to increase bladder volume and decrease 2. Abrams P, Agarwal M, Drake M, et al. A proposed
bladder pressure guideline for the urological management of
– Intermittent catheterization for urinary drainage patients with spinal cord injury. BJU Int. 2008;
TREATMENT – Limited dexterity mandates construction of a 101(8):989–994.
continent catheterizable stoma for the urinary 3. Ginsberg D, Gousse A, Keppenne V, et al. Phase 3
GENERAL MEASURES (2) reservoir, especially in females efficacy and tolerability study of
r UDS is essential to determine lower urinary tract r Ileovesicostomy onabotulinumtoxinA for urinary incontinence from
function/dysfunction and to plan urologic – Useful for those unable to perform neurogenic detrusor overactivity. J Urol. 2012;
management. self-catheterization (ie, quadriplegia) 187(6):2131–2139.
r Maintaining low intravesical pressure protects upper r Cystectomy with continent urinary reservoir
urinary tracts – Ileal or colon pouch; continent catheterizable
r Urinary drainage: Intermittent catheterization or stoma (appendix or tapered ileum) ADDITIONAL READING
external collection appliance r Cystectomy with ileal conduit
r Indwelling catheterization: Tapia CI, Khalaf K, Berenson K, et al. Health-related
ADDITIONAL TREATMENT quality of life and economic impact of urinary
– Associated with recurrent UTIs, urethral erosion, incontinence due to detrusor overactivity associated
urolithiasis Radiation Therapy
N/A with a neurologic condition: a systematic review.
r Intermittent self-catheterization: Most effective
Health Qual Life Outcomes. 2013;11:13–28.
treatment; requires low storage pressure Additional Therapies
r Surgical intervention is indicated when other Neuromodulation, sacral nerve stimulation and See Also (Topic, Algorithm, Media)
r Bladder Areflexia (Detrusor Areflexia)
therapies fail to protect the upper urinary tract or posterior tibial nerve stimulation are not FDA approved
for the treatment of NDO but may have some benefit. r Detrusor Overactivity
provide continence.
r Detrusor Sphincter Dyssynergia (DSD)
MEDICATION Complementary & Alternative
r Incontinence, Urinary, Adult Female
Therapies
First Line r Incontinence, Urinary, Adult Male
r Antimuscarinics aimed at decreasing urinary storage Acupuncture has been reported to improve symptoms
of neurogenic bladder. r Incontinence, Urinary, Pediatric
pressure and reducing NDO. Most common side r Neurogenic Detrusor Overactivity (NDO)
effects include dry mouth and constipation r Overactive Bladder
– Fesoterodine 4–8 mg QD ONGOING CARE r Spinal Cord Injury, Urologic Considerations
– Hyoscyamine extended release 0.375 mg BID
– Oxybutynin 5 mg BID-TID PROGNOSIS r Stroke (CVA), Urologic Considerations
– Oxybutynin transdermal patch 3.9 mg/d Proper urologic management greatly improves quality
– Oxybutynin XL 10–15 mg/d of life in patients with NGB dysfunction.
– Oxybutynin, topical gel 10% apply 1 sachet QD to
COMPLICATIONS CODES
dry skin r Recurrent UTIs
– Solifenacin 5–10 mg/d r Urinary retention ICD9
– Tolterodine LA 1–2 mg BID r Hydroureteronephrosis r 596.51 Hypertonicity of bladder
– Tolterodine LA 2–4 mg/d r 596.54 Neurogenic bladder NOS
r Neoplastic transformation: Associated with chronic
– Trospium XR 60 mg/d r 596.59 Other functional disorder of bladder
r β 3-agonist: Most common side effects include an catheter
r Urethral erosion
increase in blood pressure and palpitations ICD10
– Mirabegron 25 mg/d increase to 50 mg/d after r N31.8 Other neuromuscular dysfunction of bladder
FOLLOW-UP
8 wk PRN r N31.9 Neuromuscular dysfunction of bladder,
r α-Adrenergic blockers: Decrease internal sphincter Patient Monitoring
r Annual evaluation in high-risk patients may include unspecified
resistance, lower voiding pressure; ineffective for r N32.81 Overactive bladder
(3):
DSD. – UDS
– Alfuzosin 10 mg/d – Imaging: Typically renal US
– Doxazosin start 1 mg/d to max 8 mg – Serum creatinine
CLINICAL/SURGICAL
– Silodosin 8 mg/d PEARLS
– Tamsulosin start 0.4 mg to max 0.8 mg Patient Resources
r http://www.nationalmssociety.org Adequate management of lower urinary tract function
– Terazosin start 1 mg/d to max 20 mg
r http://www.spinalcord.org/ is essential to avoid upper urinary tract compromise
Second Line
r Botulinum toxin type A (onabotulinumtoxinA) r http://www.parkinson.org/ and preservation of renal function. N
injection into the external sphincter for DSD
– Short-lived; requires repeat injections
r Botulinum toxin injection into the detrusor for NDO
– Duration of action is 3–9 mo
– Requires repeated injections
261
NOCTURIA
r Nocturnal polyuria
BASICS – Relative increased production of urine at night DIAGNOSIS
that is often offset by lowered daytime urine
DESCRIPTION production resulting in normal 24-hr urine volume. HISTORY
r Nocturia is a symptom describing an individual who r Number of times getting up at night to urinate from
– Age-related loss of the normal diurnal secretion of
awakens at night one or more times to void. Each vasopressin, resulting in increased nocturnal urine time of going to bed until time of waking in the
void is preceded and followed by sleep. output. morning
r Can negatively impact quality of life. r Degree of bother assessment
– Peripheral edema:
– Can be associated with depression, daytime ◦ Fluid that accumulates in the lower extremities r Differentiate between awakening due to the urge to
fatigue, and increased orthopedic morbidity when upright during the day is mobilized when void vs. awakening due to other sleep disturbances
among the elderly. supine at night, due to an increase in GFR and r Fluid intake habits
r Underlying etiologies of nocturia excretion. r Timing, volume
– Nocturnal polyuria: ◦ Conditions: CHF, liver disease, nephrotic r Caffeine and alcohol consumption
◦ The rate of urine output is excessive only at night syndrome, hypoalbuminemia, venous r Previous pelvic surgery or radiation
and total 24-hr output is within normal limits. insufficiency, lymphedema, lower extremity r Daytime fatigue and depression
– Reduced bladder capacity injury/swelling. r Review of medications known to contribute to
– 24-hr polyuria – Sleep apnea:
◦ Transient periods of hypoxia lead to increased nocturia: such as diuretics, excessive calcium
– Sleep disorder
pulmonary vascular resistance and secretion of supplementation, antacids, or lithium.
EPIDEMIOLOGY r Swelling of lower extremities
atrial natriuretic peptide, a potent diuretic.
Incidence – Medications: Poorly timed/dosed diuretics that PHYSICAL EXAM
r The incidence of nocturia and total number of r Global or focal neurologic deficits
exert maximal effect during sleeping hours.
voiding episodes increases with age – Excessive fluid intake prior to bedtime, resulting in r Digital rectal: Assess anal tone, prostate exam in
– Overall: 28% a physiologic large volume excretion. men
– Age >60: 41% r Reduced bladder capacity r Pelvic exam in women: Anterior prolapse causing
r Body mass index >29: 36%
– Nonneurogenic or Neurogenic OAB (over active retention, urethral diverticulum, atrophic vaginitis
r Black and Hispanic > White bladder) causing irritative urinary symptoms
Prevalence – Inflammatory: UTI, radiation cystitis, bladder r Lung auscultation for rales, crackles
r Higher prevalence in women than men among calculi, interstitial cystitis r Dependent edema, pedal edema
young adults – Neoplastic: Bladder cancer, prostate cancer, r Suprapubic distension consistent with urinary
r Higher prevalence in men than women among extrinsic compression from pelvic masses
– Traumatic: Spinal cord injury, urethral stricture, retention
elderly population groups r Obesity and a wide neck circumference raises the
injury to pelvic nerves or bladder, foreign body
RISK FACTORS (1) within bladder possibility of sleep apnea
r Advanced age – Obstructive; BPH, urethral stricture
r Diuretic usage
r Lower urinary tract dysfunction ASSOCIATED CONDITIONS Lab
r Bladder outlet obstruction r Urinalysis: Low specific gravity (polyuria), RBCs (rule
r Cardiac disease r OAB: Idiopathic and neurogenic out stones, bladder cancer, foreign body, etc.),
r Obesity, sleep apnea r Detrusor hyperactivity with impaired contractility proteinuria (nephrotic syndrome), glucosuria
Genetics r Radiation cystitis (diabetes mellitus), pyuria (UTI)
r Diabetes mellitus r Urine culture: UTI
None
r Psychogenic polydipsia r Urine osmolality: Dilute low values suggest
PATHOPHYSIOLOGY inappropriate excretion of ADH or excess intake of
r 24-hr polyuria: r Depression
r Obesity water
– Excessive total urine production where the total r PSA if indicated
24-hr urinary volume >40 mL/kg) r See also “Pathophysiology”
r Serum electrolytes: Hypokalemia with diuretic use,
– Diabetes mellitus:
◦ Secondary to polydipsia and osmotic diuresis GENERAL PREVENTION CHF, or hyperaldosteronemia
r Avoid excessive evening fluid intake, alcohol, and
from hyperglycemia Imaging
– Diabetes insipidus: caffeine r Bladder US with PVR volume for suspected urinary
r Closely monitor and control the underlying
◦ Under-secretion (central) or impaired response retention, especially if considering antimuscarinics
(nephrogenic) to ADH conditions that cause nocturia r Renal US may demonstrate hydronephrosis in cases
– Medications: of urinary retention or poorly compliant bladders
◦ Lithium, diuretics, caffeine, nephrotoxic
medications
– Hypercalcemia: Can cause osmotic diuresis
– Hyperaldosteronism
– Psychogenic polydipsia
262
NOCTURIA
Diagnostic Procedures/Surgery SURGERY/OTHER PROCEDURES 4. Van Kerrebroeck PE, van Voskuilen AC, Heesakkers
r Voiding diaries JP, et al. Results of sacral neuromodulation therapy
Sacral neuromodulation for nocturia secondary to
– All voiding episodes and volumes should be reduced voided volumes is associated with refractory for urinary voiding dysfunction: Outcomes of a
recorded for a 24-hr period; the time the patient daytime frequency and urgency (4)[B]. prospective, worldwide clinical study. J Urol.
actually goes to sleep and awakens for the day 2007;78:2029.
should also be noted. ADDITIONAL TREATMENT 5. Johnson TM 2nd, Burgio KL, Redden DT, et al.
– Nocturnal urine volume (NUV) is the total volume Radiation Therapy Effects of behavioral and drug therapy on nocturia
of urine voided during the night (the 1st morning N/A in older incontinent women. J Am Geriatr Soc.
void is included in this sum since it represents Additional Therapies 2005;53:846.
urine excreted during sleep hours). r Behavioral training:
– Nocturnal polyuria index (NPi): NUV divided by
the total volume voided over the 24-hr period: – Pelvic floor muscle exercises, +/– biofeedback: ADDITIONAL READING
◦ NPi >33% = nocturnal polyuria More effective than both drug therapy and
– Nocturnal Bladder Capacity index (NBCi) placebo in treatment of nocturia associated with r Cornu JN, Abrams P, Chapple CR, et al. A
– NBCi = (NUV/Maximal volume per void)–1 daytime urgency and urge incontinence (5)[A] Contemporary assessment of nocturia: definition,
◦ NBCi >0 suggests that the nocturnal bladder r CPAP for obstructive sleep apnea epidemiology, pathophysiology, and
capacity cannot store the amount of urine made management—a systematic review and
Complementary & Alternative meta-analysis. Eur Urol. 2012;62;877–890.
at night.
r Urodynamics Therapies r Weiss JP, Blaivas JG, Bliwise DL, et al. The
None
– Helpful when empiric treatment for overactive evaluation and treatment of nocturia: a consensus
bladder (OAB) or bladder outlet obstruction has statement. BJU Int. 2011;108:6–21.
failed to improve nocturia ONGOING CARE See Also (Topic, Algorithm, Media)
r Polysomnographic sleep studies: Differentiate r Bladder Outlet Obstruction
PROGNOSIS
between sleep disorder and true nocturia r Diabetes Mellitus
Although it is often difficult to completely eliminate
Pathologic Findings episodes of nocturia, characterizing nocturia according r Incontinence, Adult Female
N/A to cause-specific etiologies allows for cause-specific r Incontinence, Adult Male
treatment. r Neurogenic Bladder
r Sleep disorders: r Nocturia Algorithm
COMPLICATIONS
– Most patients awaken due to the sleep r Traumatic falling accidents, including hip fractures, r Nocturnal Polyuria
disturbance, but recall this as an awakening to from rising from sleep to urinate r Overactive Bladder
void. r DDAVP can lead to hyponatremia r Urgency, Urinary (Frequency and Urgency)
– May need polysomnography r Urinary retention secondary to antimuscarinics r Urodynamics
r Urologic r Voiding Diary (see Section VII: Reference Tables)
– Bladder outlet obstruction, OAB, incomplete FOLLOW-UP
bladder emptying. Patient Monitoring
r Nonurologic: r Bladder sonography with PVR as needed,
– Renal failure, idiopathic nocturnal polyuria, particularly when treating men with antimuscarinics CODES
diabetes mellitus, central diabetes insipidus, r Repeat 24-hr voiding diaries
nephrogenic diabetes insipidus, primary r Regular monitoring of serum electrolytes with ICD9
r 596.59 Other functional disorder of bladder
polydipsia, hypercalcemia, drugs, autonomic DDAVP, starting 3 days after initiation of treatment r 788.42 Polyuria
failure, obstructive sleep apnea. Patient Resources r 788.43 Nocturia
r Medline Plus — Excessive Urination at Night
TREATMENT http://www.nlm.nih.gov/medlineplus/ency/ ICD10
article/003141.htm r N31.9 Neuromuscular dysfunction of bladder,
GENERAL MEASURES unspecified
r Nocturnal polyuria secondary to diuretics r R35.1 Nocturia
– Change to afternoon dosing to induce an early REFERENCES r R35.8 Other polyuria
evening diuresis rather than a nocturnal diuresis 1. Fitzgerald MP, Litman HJ, Link CL, et al. The
r Treatment of underlying condition associated with
association of nocturia with cardiac disease,
nocturia diabetes, body mass index, age and diuretic use:
CLINICAL/SURGICAL
MEDICATION Results from the BACH survey. J Urol. 2007;177: PEARLS
First Line 1385–1389. r The etiology of nocturia is not prostate or bladder
r Antimuscarinics are appropriate for reduced voided 2. Johnson TM 2nd, Burrows PK, Kusek JW, et al. The
related in the majority of men. Poor sleep pattern
volumes. effect of doxazosin, finasteride and combination
and fluid consumption/mobilization need to be
r Men only: α-blocker alone or combined with a therapy on nocturia in men with benign prostatic
considered. N
hyperplasia. J Urol. 2007;178:2045. r A voiding diary is extremely helpful to determine the
5-α-reductase inhibitor (only modest benefit) 3. Mattiasson A, Abrams P, Van Kerrebroeck P, et al.
(2)[A]. cause of nocturia.
Efficacy of desmopressin in the treatment of
Second Line nocturia: A double-blind placebo-controlled study
r DDAVP for nocturia associated with nocturnal in men. BJU Int. 2002;89:855.
polyuria (3)[B]:
– Dosing: 0.01 mg PO; titrate up to 0.04 mg.
– DDAVP has a high risk of hyponatremia.
– Greatest risk seen in men >65 yr old.
263
LWBK1391-SEC-O LWBK1391-Gomella ch131.xml September 19, 2014 18:34
ORCHITIS, GENERAL CONSIDERATIONS

James B. Angel, MD
PATHOPHYSIOLOGY r Obtain sexual history as appropriate

BASICS r Most commonly caused by hematogenous spread of r Evidence or history of immunocompromise
mumps virus directly attacking testicular tissue r History of BPH
DESCRIPTION resulting in parenchymal edema, congestion of r History of recent instrumentation
r Inflammatory reaction of the testes secondary to seminiferous tubules, and perivascular infiltration of (ie, catheterization, prostate biopsy, cystoscopy)
infectious or noninfectious etiology lymphocytes increases likelihood of epididymo-orchitis
– Infectious (viral, bacterial, fungal) – Rare case reports of other viruses causing orchitis r History of intravesical BCG therapy, may result in
– Noninfectious (idiopathic, trauma, autoimmune) (mononucleosis, coxsackie virus, others)
r Can be acute or chronic if present for >6 weeks r Cases of bacterial orchitis usually result from local granulomatous orchitis
r Untreated epididymitis can progress to spread from the ipsilateral epididymitis PHYSICAL EXAM
r Truly noninfectious orchitis is usually idiopathic, r Testicular exam:
epididymo-orchitis
trauma-related, or possibly autoimmune – Unilateral or bilateral involvement
EPIDEMIOLOGY r Orchitis is unilateral in 70% of cases – Enlargement, induration, tenderness common
Incidence r Contralateral testis involvement can follow in – Erythema and edema of overlying scrotal skin
r Dramatic decline in incidence following the
– An enlarged epididymis is associated with
development MMR vaccine 1–9 days
r Seminiferous tubules can experience necrosis from epididymitis, typically unilateral
(Measles-Mumps-Rubella) – May find concurrent reactive hydrocele which
r 4 out of 5 cases occur in prepubertal males increased pressure and edema transilluminates
(<10 years old) prior to widespread use of MMR ASSOCIATED CONDITIONS r Rectal exam:
vaccine r Mumps – A soft, boggy prostate, which signifies prostatitis,
r Recent increase in incidence in postpubertal males r Epididymitis can be associated with epididymitis
corresponding to mumps outbreaks following r STD in sexually active men r Other:
national shortages of MMR vaccine as well as r Urinary Tract Infections (UTI) in boys or elderly men – Fever and/or chills
controversy related to MMR vaccine itself1 r BPH particularly in men >50 – Urethral discharge
r Bacterial orchitis even more rare and usually – Abdominal masses or tenderness
r Bladder cancer and history of intravesical BCG
associated with concurrent epididymitis r Immunocompromised states – Parotitis
Prevalence – Urethritis
r ∼20% prepubertal males with mumps develop GENERAL PREVENTION
r Vaccination against mumps virus limits mumps DIAGNOSTIC TESTS & INTERPRETATION
orchitis Lab
r Recent case reports of postpubertal vaccinated orchitis r Urinalysis and urine culture
r Protection from STD
males with mumps developing orchitis in outbreaks2 r Urethral cultures if concern for urethritis
r Treatment of epididymitis prior to progression to
RISK FACTORS r Mumps: serum immunofluorescence antibody assay
r Not being vaccinated against mumps virus epididymo-orchitis
Imaging
r Sexually transmitted diseases (STD) leading to r Trans-scrotal color Doppler Ultrasound is considered
epididmo-orchitis (i.e., Neisseria, Chlamydia, DIAGNOSIS required by many clinicians:
Treponema) – Can rule out testicular torsion or malignancy
r Epididymitis or benign prostatic hypertrophy, BPH HISTORY r Additional imaging is unnecessary (i.e., CT Scan or
r Testicular pain and swelling
(ie, Escherichia, Klebsiella, Pseudomonas, MRI)
Staphylococcus, and Streptococcus) – Mild discomfort to severe pain
r Fungal infections occasionally (i.e., candidiasis, – Onset of scrotal pain and edema is acute Diagnostic Procedures/Surgery
r History of recent scrotal trauma Usually not necessary
aspergillosis, histoplasmosis, coccidioidomycosis, r Systemic symptoms
blastomycosis, actinomycosis) Pathologic Findings
r History of intravesical Bacillus Calmette Guerin – Fatigue r With viral infection, destruction of germ cells, edema
(BCG) for bladder cancer – Malaise and extensive inflammatory cell infiltrate is noted
r Immunocompromised patients (i.e., Mycobacterium, – Myalgias r Later seminiferous tubules can experience necrosis
– Fever and chills from increased pressure and edema, with
Tuberculosis, Cryptococcus, Toxoplasma,
– Nausea, emesis subsequent interstitial fibrosis.
Haemophilus, Candida)
r Case reports of mumps orchitis after immunization – Headache
r Obtain vaccination history
with MMR vaccine r Mumps orchitis follows development of parotitis by
Genetics 4–7 days
r There is no clearly defined genetic predisposition
toward or familial disorders commonly associated
with most cases of orchitis
r Autoimmune states have been implicated in truly
noninfectious orchitis
264
ORCHITIS, GENERAL CONSIDERATIONS
r Epididymitis
Radiation Therapy r Zipprich J, Murray EL, Winter K, et al. Mumps
r Granulomatous orchitis, infectious and noninfectious There is no role for radiation therapy
r Reactive hydrocele outbreak on a university campus - California, 2011.
r Scrotal pyocele
Additional Therapies MMWR 2012;61:986–989.
Interferon-α2B has been investigated in bilateral r Yapanoglu T, Kocaturk H, Aksoy Y, et al. Long-term
r Testicular malakoplakia mumps orchitis, given that the mumps virus replicates
r Testicular torsion efficacy and safety of interferon-alpha-2B in patients
with a virion-associated transcriptase
r Torsion of testicular appendage with mumps orchitis. Int Urol Nephrol 2010;42:
r Testicular tumor
Therapies
Patient specific referral for psychologic evaluation and
r Acute Scrotum
TREATMENT support for chronic refractory orchitis r Mumps Orchitis
r Orchitis, General Considerations Image
GENERAL MEASURES r Orchitis, Granulomatous
r Supportive in nature ONGOING CARE
r Scrotum and Testicle, Mass
– Bed rest PROGNOSIS
– Hot or cold packs for analgesia r Most cases of mumps orchitis are self-limited, r Testis, Pain (Orchalgia)
◦ Applied for 10–15 mins q.i.d or until pain r Testis, Tumor and Mass, Adult, General
resolving within 3-10 days
subsides r With appropriate antibacterial coverage, most cases r Testis
– Scrotal elevation and support with tight fitting of bacterial orchitis resolve without complication
underwear or athletic support Analgesics
– Nonsteroidal anti-inflammatory drugs (NSAID) COMPLICATIONS
r Unilateral testicular atrophy in up to 60% with
CODES
– Antiemetics
– Counsel patient on safe sex practices if STD mumps orchitis ICD9
suspected r Sterility is rarely a sequel of unilateral orchitis r 604.90 Orchitis and epididymitis, unspecified
r Impaired fertility reported rates of 7–13% r 604.91 Orchitis and epididymitis in diseases
MEDICATION r No definitive evidence for increased risk of testicular
First Line classified elsewhere
r There are no targeted medications indicated the tumor with history of orchitis r 604.99 Other orchitis, epididymitis, and
treatment of viral orchitis. Supportive care is FOLLOW-UP epididymo-orchitis, without mention of abscess
essential. Patient Monitoring
r Bacterial orchitis requires coverage with appropriate r Most patients can be safely monitored in an ICD10
r N45.1 Epididymitis
antibiotic for suspected pathogen(1)[C] outpatient setting r N45.2 Orchitis
– <35 years old, suspected STD as causative agent: r A patient with a STD as the cause of orchitis should
r N45.3 Epididymo-orchitis
◦ Ceftriaxone 125-250 mg IM once and either be tested for other STDs including Human immune
doxycycline 100 mg PO b.i.d. for 7 days or deficiency virus (HIV)
azithromycin 1-2 g PO once
– >35 years old, or epididymo-orchitis secondary to Patient Resources CLINICAL/SURGICAL
r http://www.mayoclinic.com/health/orchitis
UTI: PEARLS
r http://www.urologyhealth.org
◦ Additional gram-negative coverage with a r Most cases of orchitis are viral in nature and
fluoroquinolone or
self-limited, other cases are bacterial and most
trimethoprim-sulfamethoxazole (TMP-SMX)
r Tailor antibiotic prescription to local resistance REFERENCES commonly associated with epididymitis.
r Physical exam findings include tender, swollen testes
patterns of most common UTI pathogens 1. Nicholson A, Murray-Thomas T, Hughes G, et al. with associated erythema of the scrotum with or
Second Line Management of epididymo-orchitis in primary care: without fever.
N/A results from a large UK primary care database. Br J r Testicular ultrasonography is important to rule out
Gen Pract 2010;579:407–422. torsion and malignancy.
SURGERY/OTHER PROCEDURES 2. Nariculam J, Minhas S, Adeniyi A, et al. A review of
r Surgical intervention is generally not indicated in the r Medical therapy for orchitis is largely supportive;
the efficacy of surgical treatment for and antibiotic coverage should be targeted to cover STDs
treatment of acute or chronic orchitis pathological changes in patients with chronic
r Associated scrotal pyocele or symptomatic hydrocele in the young and sexually active and UTIs in the
scrotal pain. BJU Int 2007;99:1091–1093. elderly.
may require surgery 3. Larsen SM, Benson JS, Levine LA. Microdenervation r The role for surgical management of orchitis is
r Orchidectomy for chronic orchitis refractory to of the spermatic cord for chronic scrotal content limited.
supportive measures is an option, but patients pain: single institution review analyzing success
must be counseled surgery may not alleviate pain rate after prior attempts at surgical correction.
(2)[B] J Urol 2013 189:554–558.
r Consider microsurgical denervation of cord for
chronic refractory orchitis/orchalgia following
favorable response to spermatic cord block (3)[A]
– 10 mL of 0.5% bupivacaine injected to cord for
block
O
265
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OSTEITIS PUBIS, UROLOGIC CONSIDERATIONS

BASICS DIAGNOSIS r Symphysogram of joint
– Pain on injection of contrast diagnostic (4)[C]
DESCRIPTION HISTORY – Generally replaced by MRI
r Osteitis pubis is a painful sterile inflammatory r Inciting event such as a pelvic procedure or trauma r Aerobic/anaerobic culture of joint aspirate to rule
condition affecting the pubic symphysis r Insidious onset of suprapubic pain
out infection if clinically indicated
– Most commonly seen in athletes r Pain radiating to thigh adductors, lower abdomen,
r First described with suprapubic surgery and remains perineum Pathologic Findings
r Pain worse when walking or when rising from a Sclerotic changes in bony architecture and
a potential complication of pelvic procedures
degeneration of hyaline cartilage with normal
seated position (1)[C]
EPIDEMIOLOGY periosteum (5)[C]
Incidence PHYSICAL EXAM DIFFERENTIAL DIAGNOSIS
r Overall incidence in nonathlete populations r Point tenderness over pubic symphysis
r Osteomyelitis (the most critical)
unknown r Waddling gait
r Neoplasia of pelvic rami
– 0.16% in procedures using bone anchors r Low-grade fever
r Bony metastases
r Increased pain with coughing or Valsalva
Prevalence r Pubic osteolysis
r Painful hip abduction
Overall prevalence in nonathlete populations r Sports hernia (athletic pubalgia, sportsman’s hernia)
unknown DIAGNOSTIC TESTS & INTERPRETATION r Adductor strain
RISK FACTORS r Muscle tears
r Invasive pelvic procedures ALERT r Avulsion injuries
– Several urologic procedures implicated Must rule out osteomyletis, especially in r Stress fractures
◦ Radical prostatectomy postoperative patients. r Tears of acetabular labrum
◦ Prostate cryotherapy
◦ TRUS Bx of prostate Lab
r Not generally required to make diagnosis
◦ TURP
r May see moderate leukocytosis and an increased
TREATMENT
◦ Retropubic urethropexy: Specifically
Marshall–Marchetti–Krantz procedure erythrocyte sedimentation rate (2)[C] GENERAL MEASURES
◦ Sling procedures Raised levels of acute phase proteins (fibrinogen, r Rest, heat, or ice
◦ Pelvic radiation C-reactive protein), and increased erythrocyte r Physical therapy to strengthen pelvic girdle can be
r Trauma sedimentation rate are more suggestive of considered
r Rheumatic disorders osteomyelitis
MEDICATION
r Pregnancy/parturition Imaging
r Pelvic radiograph First Line
r Overuse syndrome in athletes r Nonsteroidal anti-inflammatory
– Typically normal in acute phase – Ibuprofen 200–800 mg 2–4×/d (max dose
Genetics – Articular surface erosion, sclerosis, osteophyte
No known genetic predisposition 2.4 g/d)
formation – Naproxen 250–500 mg 2×/d (max dose 1.5 g/d
PATHOPHYSIOLOGY r Scintigraphy
r Symphysis pubis is a nonsynovial amphiarthrodial for limited time)
– Increased uptake around pubic symphysis r Cyclooxygenase-2 (COX-2) inhibitor
joint at the confluence of the two pubic bones, r Symphysogram of joint
– Celecoxib 100–200 mg 1–2×/d
consisting of an intrapubic fibrocartilaginous disc – Extravasation of contrast material – Adverse CV events noted with COX-2 inhibitors,
between thin layers of hyaline cartilage – Diagnostic and therapeutic use lowest effective dose for shortest duration
r Etiology unknown but may be related to periosteal r Magnetic resonance imaging (MRI) most sensitive possible
trauma and considered gold standard
Second Line
ASSOCIATED CONDITIONS – Acute (<6 mo): Bone marrow edema, fluid in r Oral glucocorticoids such as prednisone if local
r Ankylosing spondylitis joint, periarticular edema
glucocorticoid injections fail
r Rheumatoid arthritis – Chronic (>6 mo): Subchondral
– Typical short course (ie, 60 mg for 5 days)
sclerosis/resorption, bony margin irregularities,
– Can use a taper dose
GENERAL PREVENTION osteophytes (3)[C]
N/A
266
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OSTEITIS PUBIS, UROLOGIC CONSIDERATIONS
SURGERY/OTHER PROCEDURES FOLLOW-UP See Also (Topic, Algorithm, Media)

r Glucocorticoid injection in joint may be useful for r Suprapubic Pain, General Considerations
Patient Monitoring
cases refractory to rest and NSAIDs (4)[C] Follow-up depends on patient symptomatology and r Sports Hernia (Athletic Pubalgia, Sportsman’s
– Any steroid preparation can be used based on procedures obtained Hernia)
provider preference r Osteitis Pubic Images
◦ Include an adjuvant anesthetic Patient Resources
r Various surgical techniques can be used for cases N/A
refractory to medical management CODES
– Curettage REFERENCES
– Wedge resection
1. Tibor LM, Sekiya JK. Differential diagnosis of pain ICD9
– Wide resection
around the hip joint. Arthroscopy. 2008;24(12): 733.5 Osteitis condensans
– Arthrodesis
r If bone anchors are in place, their removal may be 1407–1421. ICD10
necessary 2. Lentz SS. Osteitis pubis: A review. Obstet Gynecol M85.38 Osteitis condensans, other site
Surv. 1995;50(4):310–315.
ADDITIONAL TREATMENT 3. Kunduracioglu B, Yilmaz C, Yorobulut M, et al.
Radiation Therapy Magnetic resonance findings of osteitis pubis. CLINICAL/SURGICAL
Has been attempted in the past with mixed results, J Magn Reson Imaging. 2007;25(3):535–539. PEARLS
but not recommended due to risk of neoplasia 4. O’Connell MJ, Powell T, McCaffrey NM, et al. r Osteitis pubis pain and osteomyelitis pain worse
Additional Therapies Symphyseal cleft injection in the diagnosis and
r Cryotherapy, ultrasound therapy, laser therapy, and treatment of osteitis pubis in athletes. AJR Am J when walking or when rising from a seated position.
r Essential to rule out osteomyelitis as a more
electric stimulation have been used with variable Roentgenol. 2002;179(4):955–959.
success in athletic osteitis pubis 5. Mehin R, Meek R, O’Brien P, et al. Surgery for significant cause.
r Rarely osteitis pubis and osteomyelitis of the pubis
– No data on success of these modalities for osteitis pubis. Can J Surg. 2006;49(3):170–176.
nonathlete populations can coexist.
r Anticoagulant therapy with heparin has been r To distinguish between osteomyelitis and osteitis
suggested as a possible treatment in a postoperative ADDITIONAL READING pubis, a biopsy and culture of the affected area are
setting with some minimal success necessary.
r Pauli S, Willemsen P, Declerck K, et al. Osteomyelitis r Suspect the condition in a urologic patient where
Complementary & Alternative pubis versus osteitis pubis: A case presentation and the pubic symphysis has been involved in urologic
Therapies review of the literature. Br J Sports Med. 2002; surgical intervention such as bone anchors or sling
Physical therapy 36:71–73. procedures.
r Weber MA, Rehnitz C, Ott H, et al. Groin Pain in
ONGOING CARE Athletes. Rofo. 2013;185(12):1139–1148.
PROGNOSIS
r Typically a drawn out and variable clinical course
– Symptoms can last several months to several years
– Operative procedures may be needed in 5–10% of
cases
COMPLICATIONS
r Wedge or wide resection of pubic symphysis—risk
of posterior instability of pelvic girdle leading to
damage to sacroiliac joints
r Arthrodesis—risk of nonunion or death of bone
graft site requiring additional surgery
267
OVERACTIVE BLADDER (OAB)

Nima Baradaran, MD
Samuel Walker Nickles
Eric S. Rovner, MD, FACS

r Urinalysis, urine cultures:
DESCRIPTION HISTORY – Infection, Glycosuria: Possible diabetes,
r OAB is defined as a symptom syndrome consisting r Duration of symptoms
r Quantitative assessment of urinary frequency, Hematuria: Possible kidney/bladder pathology,
of urinary urgency, with or without incontinence Proteinuria: Kidney/chronic disease, Cytology:
usually with urinary frequency and nocturia in the nocturia, and incontinence (pad use) Atypia, urothelial carcinoma
absence of causative factors or other identified r Documentation of urgency
– The diagnosis and initial management of OAB
pathologic conditions causing such symptoms. r Quantitation of daily fluid intake does not require more than a history, physical
r Urinary urgency is the key symptom. r Aggravating factors (caffeine, stress, etc.) exam, and urine analysis. Other diagnostic studies
r Presence of dysuria, hematuria should be utilized selectively
ALERT r Response to prior therapy
Imaging
OAB is not synonymous with detrusor overactivity r GU history including childhood voiding dysfunction, r These are optional studies usually reserved for
(DO, strictly a urodynamic term) and should be prior surgery (BPH, urethral stricture, dilation, etc.) complex patients or patients who have failed initial
distinguished from bladder pain syndrome. r History should include assessment of the impact of therapy
the disorder on daily life (I-QOL (1) and ICIQ (2) for – VCUG/Cystography/video urodynamic
EPIDEMIOLOGY urinary incontinence and OAB-q (3) for men and – Renal/bladder US
Incidence women with OAB specifically)
r Medical/surgical/OB-GYN history (especially if
Overall 10.2–17.4% in adult males and 7.7–31.3% in r 1–3-day frequency–volume chart (FVC) and/or
adult females. associated with the initial symptom onset): bladder diary are helpful in documenting presence
Prevalence – Prior pelvic surgery: Prolapse, hysterectomy, and severity of OAB
∼16% of men and women over 40 suffer from OAB anti-incontinence surgery, history of radiation r Post-void residual volume (PVR) (catheterized or
and the prevalence increases to 31% and 42%, therapy, etc. ultrasound)
respectively in patients >75 yr. OAB wet is more – Pregnancy especially vaginal delivery/episiotomy – PVR >100 is found in 10–19% women with OAB,
common in females. – UTI (frequency, urgency, dysuria) 15.9% women with SUI, and 5% of asymptomatic
– Bowel function: Constipation women
RISK FACTORS – Neurologic history or events (eg, CVA/TIA, MS,
r Neurogenic: Stroke, Parkinson disease, multiple – Elevated PVR may be associated with
Parkinson disease, trauma, back surgery, etc.) urgency/frequency and nocturia
sclerosis, spinal injury, etc. – Sexual function: Dyspareunia
r Nonneurogenic: Caucasian, Insulin-dependent r Pressure flow urodynamics:
– Medical comorbidities: Congestive heart failure
diabetes mellitus, Female gender, Depression, Aging – Provides functional information about bladder and
(CHF), diabetes, obesity, venous insufficiency,
associated with estrogen deficiency, Outflow urethral function
BPH, sleep apnea, etc.
obstruction, Arthritis, Increased BMI. – Assesses bladder filling and urinary storage as
– Medications (diuretics, prescription, OTC)
well as bladder emptying, contractility, voiding
Genetics – Menopausal status and hormonal replacement:
efficacy, and outlet obstruction
For OAB a definite genetic link is not well established. Contributes to atrophic vaginitis/urethritis
r Use of tobacco, alcohol, fluid intake, caffeine, etc. – Can document presence of DO which is associated
PATHOPHYSIOLOGY with OAB but is NOT required for the diagnosis
r Not well established or understood. PHYSICAL EXAM r Cystoscopy identifies lesions, tumors, trabeculation,
r DO is found in some but not all patients with OAB. r General exam: and foreign bodies
r Urothelial afferent and efferent innervation, – Abdominal masses, bladder distention
connective tissue, smooth muscle, pharmacologic – Mental status/cognitive function ALERT
(receptors, neurotransmitters, peptides, etc.), – Neurologic exam including perineal sensation, OAB is a clinical diagnosis and does not require
hormones, and other factors may contribute to OAB anal wink, resting, and volitional sphincter tone, UDS confirmation.
in individual patients. bulbocavernous reflex
r Ultimately, OAB results from either an afferent – Knee/ankle deep tendon reflexes: Sacral nerve Pathologic Findings
mechanism (underlying urgency), or a neurogenic or compromise/injury N/A
r Pelvic exam:
myogenic source or a combination of these. DIFFERENTIAL DIAGNOSIS
– Condition of vaginal mucosa: Atrophy (thinning, r Bladder calculi
ASSOCIATED CONDITIONS pallor), narrowing of introitus, inflammation
r Pelvic floor disorders r Bladder cancer/carcinoma in situ
– Pelvic organ prolapse r Bladder outlet obstruction/prostatic hypertrophy
r IBS
– Pelvic floor tone r Congestive heart failure
r High caffeine intake – Bimanual exam for mass or tenderness
r Depression/anxiety r Detrusor-external sphincter dyssynergia
– Cough stress test: Stress incontinence
r DM – Rectal exam: Constipation and prostate r Diabetes
r Smoking evaluation for men r Interstitial cystitis/painful bladder syndrome
r ADHD r Pelvic pain syndrome
r Obesity r Medications
r Neurogenic bladder
GENERAL PREVENTION r Pelvic organ prolapse
Currently there are no known preventative measures r Polyuria/polydipsia
to reduce the potential for development of OAB. r Sexually transmitted infection
r Stress incontinence
r Urethral diverticulum
r Urinary tract infection
268
OVERACTIVE BLADDER (OAB)
ADDITIONAL TREATMENT 3. Voelzke BB. Overactive bladder; prevalence,

TREATMENT Radiation Therapy pathophysiology, and pharmacotherapy. Urol Rep.
N/A 2007;1:16–22.
GENERAL MEASURES 4. Wein AJ, Rackley RR. Overactive bladder: A better
r Lifestyle modifications and bladder/pelvic floor Additional Therapies
r Non-FDA approved: understanding of pathophysiology, diagnosis, and
training in conjunction with pharmacotherapy are management. J Urol. 2006;175:S5–S10.
– Estrogens for females (topical or oral)
1st-line therapy and are mainstays of treatment.
r Behavioral therapy: – Tricyclic antidepressants (imipramine, etc.)
r For intractable OAB, options are appliances,
– Dietary and lifestyle modification (weight loss,
catheters (urethral), and pads with careful attention
ADDITIONAL READING
reduce caffeine intake, EtOH, and nicotine r Avery K, Donovan J, Peters TJ, et al. ICIQ: A brief
to skin care
cessation)
– Bladder retraining (education, diaries, Complementary & Alternative and robust measure for evaluating the symptoms
self-monitoring) Therapies and impact of urinary incontinence. Neurourol
r Pelvic floor physiotherapy: To reestablish inhibitory r Acupuncture Urodyn. 2004;23:322.
r Cognitive therapy r Coyne K, Revicki D, Hunt T, et al. Psychometric
control over bladder storage
– Pelvic floor exercises (Kegel) validation of an overactive bladder symptom and
– Adjunctive measures include biofeedback, health-related quality of life questionnaire: The
electrical stimulation, vaginal weights/cones, ONGOING CARE OAB-q. Qual Life Res. 2002;11:563.
r Patrick DL, Martin ML, Bushnell DM, et al. Quality of
magnetic therapy, etc.
PROGNOSIS life of women with urinary incontinence: Further
MEDICATION r Varies according to severity of disorder and
development of the incontinence quality of life
First Line compliance of the patient instrument (I-QOL). Urology. 1999;53:71.
r Antimuscarinics: Inhibits the effect of acetylcholine r 50–80% of patients respond to combination of
at postjunctional muscarinic receptors on detrusor behavioral modification, pelvic floor therapy, and See Also (Topic, Algorithm, Media)
r Detrusor Overactivity
muscle cells. All used to treat OAB and all have level pharmacotherapy
r Incontinence, Urinary, Adult Female
1 evidence. COMPLICATIONS r Incontinence, Urinary, Adult Male
– Tolterodine (2–4 mg/d) r Antimuscarinic agents are contraindicated in narrow
– Trospium XR (60 mg/d) r Nocturia
angle glaucoma and patients should be aware of r Overactive Bladder (OAB) Image
– Darifenacin (7.5–15 mg/d) side effects (dry mouth, constipation, etc.)
– Solifenacin (5–10 mg/d) r Augmentation cystoplasty may lead to metabolic r Posterior Tibial Nerve Stimulation (PTNS)
– Oxybutynin (IR 7.5–20 mg/d, XL 5–30 mg/d, r Sacral Neuromodulation
abnormalities and short bowel syndrome.
patch twice weekly) r SNS implant site complications include infection and r Urgency, Urinary (Frequency and Urgency)
– Fesoterodine (4–8 mg/d)
r β -adrenergic agonist agent: Promotes detrusor pain.
3 r Botulinum toxin is associated with UTI, and urinary
muscle relaxation
– Mirabegron (25–50 mg/d) retention. CODES
Second Line FOLLOW-UP
r Urgent PC (PTNS): Tibial nerve stimulation: ICD9
Patient Monitoring r 596.51 Hypertonicity of bladder
Office-based therapy requiring repetitive weekly Depending on treatment modality close follow-up with r 788.41 Urinary frequency
therapy sessions over 3–4 mo and then periodic urologist or primary care physician is necessary r 788.63 Urgency of urination
treatments thereafter Patient Resources
r InterStim (sacral neuromodulation): Implanted r National Association for Continence ICD10
neurostimulation of sacral nerves: Modulates 1-800-BLADDER (www.nafc.org) r N32.81 Overactive bladder
activities of bladder, sphincter, and pelvic floor r Simon Foundation (www.simonfoundation.org) r R35.0 Frequency of micturition
muscles r National Institute of Diabetes and Digestive and r R39.15 Urgency of urination
r Intravesical botulinum toxin (onabotulinumtoxinA)
Kidney Diseases (http://kidney.niddk.nih.gov/
injection: kudiseases/pubs/uiwomen/)
– Addresses both motor efferent innervation and CLINICAL/SURGICAL
sensory afferent nerves that contribute to OAB. It PEARLS
is a transient effect requiring periodic retreatment REFERENCES
at intervals of 4–12 mo. r OAB is NOT synonymous with detrusor overactivity.
1. Gormley EA, Lightner DJ, Burgio KL, et al. r The key symptom of OAB is urinary urgency.
SURGERY/OTHER PROCEDURES (4) Diagnosis and treatment of overactive bladder
r Augmentation enterocystoplasty: Using a portion of r The diagnosis and initial management of OAB
(non-neurogenic) in adults: AUA/SUFU guideline.
GI tract to increase bladder capacity. Usually require only a history, physical exam, and normal
J Urol. 2012;188(suppl 6):2455–2463.
involves use of ileum or colon urinalysis.
2. Abrams P, Cardozo L, Khoury S, et al. Incontinence.
– Auto-augmentation: Incision of detrusor muscle
4th International consultation on incontinence,
creating a pseudodiverticulum (most commonly
Paris July 5–8, 2008.
performed in pediatric age group)
r Urinary diversion such as Bricker bilateral
ureteroileostomy, rarely needed
r Clinical use of endoscopic bladder transection,
bladder overdistension, or transvesical phenol O
injection is no longer recommended for
nonneurogenic OAB
269
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PAPILLARY NECROSIS, RENAL

Kelly A. Healy, MD
BASICS r The renal papilla normally exists in the state of r CT has become the imaging modality of choice
hypoxia because of the blood flow in the vasa recta r Contrast images show:
DESCRIPTION which can be affected further with conditions that – Ring shadows in the medullae
r Renal papillary necrosis is ischemic necrosis of the reduce blood flow – Contrast-filled clefts in the renal parenchyma
papillae and occasionally the medullary pyramids. – Perfusion compromise in diabetes mellitus – Renal pelvic filling defects
r The clinical course may be acute and rapidly – Diminution in blood flow because of sickling of r Excretory urography has historically been the gold
progressive or chronic blood cells (sickle cell disease) standard for diagnosis
– Acute forms are symptomatic and may present – Infection that causes inflammation of the – Findings include shrinkage and irregularity of
with hydronephrosis, pyelonephritis, and interstitium can lead to compression of the papilla defined by contrast materials as a ring
hematuria medullary vasculature shadow often in a triangular shape
– Typically chronic forms are asymptomatic and r Analgesic use causes COX inhibition and decreased – A calix without a papilla
discovered incidentally on radiographic studies prostaglandin production. This leads to decreased – Filling defect in the renal pelvis or ureter
r Acute presenting symptoms include hematuria, flank vascular perfusion, vasoconstriction and can cause – Contrast containing rice-grain–sized cavities in the
or abdominal pain, and fever and chills ischemic necrosis papilla
r Some medications can cause direct interstitial cell r Retrograde pyelogram:
EPIDEMIOLOGY
necrosis and decrease in prostaglandin production – Useful in patients with azotemia, contrast
Incidence r The necrotic, soft tissue can cause unilateral or
r Most cases occur after the 6th decade of life and sensitivity, or other situations where intravenous
bilateral ureteral obstruction contrast is contraindicated
papillary necrosis is uncommon in patients <40 yr
– Findings may reveal a club-shaped calyx or a
r Female > Male (1.1:1.0) (1)[B] ASSOCIATED CONDITIONS
r Analgesic abuse filling defect in the ureter
Prevalence r Diabetes mellitus Diagnostic Procedures/Surgery
N/A r Pyelonephritis Patient presenting with hematuria needs a full urologic
RISK FACTORS r Sickle cell disease workup even if papillary necrosis is confirmed.
r Include any condition causing ischemia that can r Urinary tract obstruction Pathologic Findings
predispose to the development of renal papillary r The cortex features depressed areas of cortical
necrosis. Many have >2 risk factors GENERAL PREVENTION atrophy (3)
r Treatment of underlying disorders including diabetes r Papilla shows various stages of necrosis,
r Diabetes mellitus
r Sickle cell trait or disease or sickle disease desquamation, and sloughing
r Avoidance of analgesic use
r Analgesic abuse: – Focal necrosis: Involves only the tip of the papilla
– Most commonly phenacetin and NSAIDs – Diffuse necrosis: The entire papilla and portions of
r Antiretroviral treatment: DIAGNOSIS the medulla are involved
r Microscopically, changes of papilla may be a patchy
– Indinavir
r Urinary tract obstruction of any cause HISTORY appearance or complete coagulative necrosis.
r Pyelonephritis r May present with hematuria or obstruction with Glomeruli are typically unchanged
r Systemic vasculitis flank pain (2)
r With infection, fever, chills, dysuria, frequency, DIFFERENTIAL DIAGNOSIS
r Lupus nephritis r Acute tubular necrosis
r Wegener granulomatosis urgency, flank pain, and renal colic can occur r Nephrolithiasis
r Rarely, bilateral ureteral obstruction with necrotic
r Renal artery stenosis r Carcinoma of the ureter or bladder
r Systemic vasculitis tissue can present as acute oliguric renal failure r NSAID abuse and/or overuse
r Global ischemia: PHYSICAL EXAM r Pyelonephritis
r Costovertebral angle tenderness r Renal trauma
– Shock, hypoxia, dehydration r Fever r TB
Genetics r Ureteral stricture disease
N/A DIAGNOSTIC TESTS & INTERPRETATION
Lab
r Urinalysis and urine culture:
– Proteinuria, pyuria, bacteriuria, and low
urine-specific gravity
– Epithelial cells and casts may be present
r CBC may demonstrate leukocytosis
r Metabolic panel can demonstrate azotemia and
elevated creatinine
270
PAPILLARY NECROSIS, RENAL
ADDITIONAL READING
Chung DC, Kim SH, Jung SI, et al. Renal papillary
GENERAL MEASURES PROGNOSIS necrosis: Review and comparison of findings at
r Hydration, oral or intravenous Depends on the basis for the ischemia, the multi-detector row CT and intravenous urography.
r Glycemic control, if diabetic compounding factors, and the amount of necrosis Radiographics. 2006;26:1827–1836.
r Definition and treatment of sickle disease COMPLICATIONS See Also (Topic, Algorithm, Media)
r Infection may develop in the desquamated necrotic r Diabetes Mellitus, Urologic Considerations
MEDICATION
papilla r Filling Defect, Upper Urinary Tract (Renal Pelvis and
First Line r Calculi can develop on the base of the sloughed
r Cessation of any associated/causative medications Ureter)
papilla r Hematuria, Gross and Microscopic, Adult
including analgesics r Obstruction can develop along the ureter from
r Treatment of underlying cause of ischemia r Nephropathy, Analgesic
r Broad-spectrum antibiotics, if associated with multiple sloughed papilla r Papillary Necrosis, Renal Image
FOLLOW-UP r Sickle Cell Disease, Urologic Considerations
pyelonephritis
Second Line Patient Monitoring
r Monitoring includes the kidney itself for further
N/A
necrosis and for changes in function CODES
SURGERY/OTHER PROCEDURES r Causes of ischemia should be closely monitored
r When a patient presents with acute urinary
obstruction, drainage is indicated with percutaneous r 584.7 Acute kidney failure with lesion of renal
nephrostomy, ureteral stent placement, or http://www.scripps.org/articles/1151-renal-papillary-
necrosis medullary [papillary] necrosis
endoscopic/ureteroscopic removal of obstructing r 590.80 Pyelonephritis, unspecified
sloughed tissue r 591 Hydronephrosis
r In the nonacute case, renal pelvic or ureteral filling
REFERENCES
defect can be electively evaluated with ureteroscopy ICD10
r Nephrectomy is rarely warranted 1. Vijayaraghavan SG, Kandasamy SV, Mylsamy A, r N12 Tubulo-interstitial nephritis, not spcf as acute or
et al. Sonographic features of necrosed renal chronic
ADDITIONAL TREATMENT papillae causing hydronephrosis. J Ultrasound Med. r N13.30 Unspecified hydronephrosis
Radiation Therapy 2003;22(9):951–956. r N17.2 Acute kidney failure with medullary necrosis
N/A 2. Gordon M, Cervellione RM, Postlethwaite R, et al.
Additional Therapies Acute renal papillary necrosis with complete
N/A bilateral ureteral obstruction in a child. Urology. CLINICAL/SURGICAL
2007;69:575e11–575e12. PEARLS
Therapies 3. Amuluru K, Erickson BA, Okotie O, et al. Bilateral
N/A ureteral obstruction from papillary necrosis Gross hematuria in a patient with sickle cell disease
secondary to household cleaner ingestion. Can J suggests papillary necrosis.
Urol. 2009;16(3):4701–4703.
271
PARATESTICULAR TUMORS
Mohamed T. Ismail, MD
Sallyanne M. Fisher, MSN, FNP-C, CUNP
RISK FACTORS DIAGNOSTIC TESTS & INTERPRETATION

BASICS r Marijuana and cocaine use in the parents is
Lab
associated with rhabdomyosarcoma. r Urinalysis (midstream) and culture if epididymitis is
DESCRIPTION r Von Hippel–Lindau syndrome is associated with suspected (1)[C].
r Intrascrotal tumors involving the testicular tunic, r Tumor markers to include β-human chorionic
epididymal cystadenomas.
epididymis, or cord structures. Can be benign r Equestrians are prone to scrotal injury with up to gonadotropin (β-hCG), α-fetoprotein (AFP), or
(∼70%) or malignant (∼30%) 77% evidence of scrotal pathology (1)[C]. lactic dehydrogenase (LDH) should be sent if the
r The paratesticular region includes the contents of
Genetics origin of the tumor is in question.
the spermatic cord, testicular tunics, epididymis, and r Partial monosomy of chromosome 11 often leads to
vestigial remnants (appendices testis and Imaging
embryonal rhabdomyosarcoma. r Gold standard: Scrotal ultrasound (US) (1)[C]
epididymis) r Alveolar rhabdomyosarcoma is characterized by
r 90% of extratesticular tumors are found within the – To evaluate location and characteristics of the
translocations t(2;13)(q35;q14) or t(1;13)(p36;q14); lesion within the scrotum
spermatic cord:
this subtype carries a poor prognosis. – Testicular vs. paratesticular
– Of these, 30% are malignant
– Solid vs. cystic (2)[C]
– The majority represent benign lipomas PATHOPHYSIOLOGY ◦ Solid lesions almost always require exploration
– Mesenchymal tumors of the spermatic cord r Electron microscopy is very helpful in differentiating
◦ Simple cystic lesions are mostly benign
include rhabdomyosarcoma, leiomyosarcoma, the type of sarcoma. r Computed tomography (CT) of the abdomen and
liposarcoma, lipoma, fibrosarcoma, and r Subtypes of sarcoma include rhabdomyosarcoma,
myxochondrosarcoma pelvis with and without contrast for staging
leiomyosarcoma, liposarcoma, fibrosarcoma, – Paratesticular tumors may spread to
r The most common paratesticular tumor in children is malignant fibrous histiocytoma, and desmoplastic retroperitoneal lymph nodes or hematogenously
rhabdomyosarcoma, which accounts for ∼24–40% round cell tumor.
r Soft tissue sarcomas tend to infiltrate local tissues depending on the histology of the primary tumor
of all paratesticular tumors r Chest radiograph
r Adenomatoid tumor accounts for 30% of epididymis widely and have a tendency for local recurrence. r Chest CT
tumors and are benign: r Rhabdomyosarcoma:
– Typically seen in 3rd and 4th decades of life – If abdominal or pelvic metastases are seen
– 97% belong to the favorable histology group of r Clinical staging of retroperitoneal lymph nodes
– Rarely arise in testicular tunicae or spermatic cord embryonal cell tumors. r Radioisotope bone scan:
(1)[C]
r Leiomyosarcoma is the most common type of ASSOCIATED CONDITIONS – Especially for elevated alkaline phosphatase or
paratesticular sarcoma in adults: Renal cell carcinoma with von Hippel–Lindau symptoms with rhabdomyosarcoma
– Incidence peaks in the 6th and 7th decades GENERAL PREVENTION Diagnostic Procedures/Surgery
– Can be bilateral Testicular self-exam should be performed monthly. Surgery is often diagnostic and therapeutic
– May accompany a hydrocele or hernia
r Cystadenoma is a benign tumor that involves the ALERT
epididymis in young adults: DIAGNOSIS Percutaneous biopsies are contraindicated due to
– Two-thirds associated with von Hippel–Lindau the documented risk of seeding in the scrotal wall
HISTORY
syndrome (2)[C] r Patient complains of mass within his scrotum, with malignancy.
– Frequently bilateral
r Malignant mesothelioma presents in older patients distinct from the testicle r Bone marrow aspirate:
– Typically painless – Routine part of staging at a time of diagnosis for
(55–75 yr) and usually presents in association with – Delays in presentation due to embarrassment
a hydrocele rhabdomyosarcoma
r Obtain complete history to include accompanying
r Malignant lymphoma: Cord structures are frequently Pathologic Findings
symptoms, duration, and constitutional changes r Electron microscopy can help differentiate between
invaded by testicular lymphoma, but primary (2)[C]
lymphomas do occur rarely the different types of sarcoma; these differences can
r Epididymal cysts occur in up to 40% of men PHYSICAL EXAM be quite subtle.
r Palpation of the testes, epididymis, and cord r Leiomyosarcoma spreads 1st by lymphatics, then
– 75% of these are true cysts and contain lymphatic
fluid (1)[C] structures bilaterally including the inguinal region: hematogenously, and last by local extension.
– Rhabdomyosarcoma reveals a firm mass that is
EPIDEMIOLOGY usually distinct from the testis. DIFFERENTIAL DIAGNOSIS
r Adenomatoid tumors
Incidence – Adenomatoid tumor appears clinically as small
r The exact incidence of paratesticular soft tissue solid lumps and is most commonly found at the – Most common benign paratesticular tumor
neoplasms is difficult to estimate r Angiomyofibroblastoma
head of the epididymis, testicular tunics, or
r Rhabdomyosarcoma spermatic cord. r Cystadenoma of the epididymis
– Occurs primarily in children and adolescents – Cystadenoma presents as asymptomatic cystic r Epididymal cyst
during the 1st 2 decades of life lumps and are bilateral in up to 1/3 of cases. r Epididymitis
r Racial differential: White > Black (3:1) – Leiomyosarcoma normally presents as a discrete r Fibrous pseudotumor of testicular tunic
r Leiomyosarcoma: Exceedingly rare, ∼110 reported nodular mass, frequently near the spermatic cord r Fibrosarcoma
cases in the literature and entirely separate from the testicle. r Leiomyosarcoma
– Liposarcoma usually presents in an older patient r Lipoma of the spermatic cord
Prevalence as a large fatty-appearing mass.
r Primary malignancies of the epididymis or r Liposarcoma
– Lymphoma presents as a hard, nontender mass,
paratesticular structures in adults extremely rare r Malignant fibrous histiocytoma
r Rhabdomyosarcoma accounts for a large proportion separate from the testis; seen in young adults.
Transillumination suggests a fluid-filled lesion r Mesothelioma, benign, testicular tunic
of the paratesticular tumors in the pediatric such as a hydrocele. r Mesothelioma, malignant, tunica vaginalis
population. r Careful exam of the groin is necessary to rule out – Associated with asbestos exposure
hernia and to evaluate for lymphadenopathy.
r Masses are occasionally accompanied by hydrocele.
272
PARATESTICULAR TUMORS
r Postoperative changes ADDITIONAL TREATMENT ADDITIONAL READING

– Sperm granuloma after vasectomy Radiation Therapy
r Spermatocele r Rhabdomyosarcoma: r Ahmed HU, Arya M, Muneer A, et al. Testicular and
r Testicular torsion – 4,000–6,000 centigray units of radiation (cGy) paratesticular tumours in the prepubertal
r Traumatic injury over 5 wk population. Lancet Oncol. 2010;11(5):476–483.
r Tunica albuginea lesions r Roman Birmingham PI, Navarro Sebastian FJ, Garcia
– Dose and port size determined by the tumor’s
– Cysts, fibrous pseudotumor primary site, patient age, and tumor burden Gonzalez J, et al. Paratesticular tumors. Description
r Varicocele of our case series through a period of 25 years. Arch
Additional Therapies Esp Urol. 2012;65(6):609–615.
r Hydrocele N/A
r Hydrocele of the spermatic cord See Also (Topic, Algorithm, Media)
Complementary & Alternative r Adenomatoid Tumors (Testis/Tunic/Epididymis)
r Inguinal hernia Therapies r Epididymis, Mass (Epididymal Tumor and Cysts)
N/A r Epididymis, Cystadenoma
TREATMENT r Fibrous Pseudotumor of Testicular Tunic
ONGOING CARE r Hydrocele of the Spermatic Cord
GENERAL MEASURES r IRS (Intergroup Rhabdomyosarcoma Study) Clinical
r US suggests initial management. PROGNOSIS
r Lesions suggestive of a benign process can be r Benign lesions—recurrence is rare Classification
r Rhabdomyosarcoma—75% 5-yr survival when r Mesothelioma, Benign, Testicular Tunic
observed with serial exams. r Mesothelioma, Malignant, Testicular Tunic
r Remove malignant or potentially malignant multimodal therapy is administered
r Leiomyosarcoma—50–80% survival with r Paratesticular Tumors Image
structures while minimizing effects on fertility,
microscopic residual disease in 27% of cases r Rhabdomyosarcoma, Pediatric
function, esthetics (2)[C].
r Benign lesions only require intervention if they – Adjuvant treatment via radiation is warranted. r Scrotum and Testicle, Mass
r Malignant mesothelioma—high recurrence and r Spermatic Cord Mass and Tumors
become massive or cause pain (1)[C].
r Any concern about malignancy and the scrotum mortality
r Larger tumor size, metastasis, higher-grade tumor,
should be explored through a high inguinal incision.
r Transscrotal manipulation or biopsy is and incomplete primary resection lead to poorer CODES
contraindicated. overall prognosis.
r Rhabdomyosarcoma always requires primary COMPLICATIONS ICD9
surgical excision via inguinal orchiectomy. r Disease associated death in ∼10% of malignant r 187.8 Malignant neoplasm of other specified sites
r Leiomyosarcoma should also be treated with radical cases of male genital organs
orchiectomy to be followed with adjuvant radiation r Treatment-associated: r 222.8 Benign neoplasm of other specified sites of
therapy to reduce local recurrence. – Retrograde ejaculation and intestinal obstruction male genital organs
– No survival benefit has been demonstrated from if RPLND is performed r 239.5 Neoplasm of unspecified nature of other
the addition of radical pelvic lymph node – Hypogonadism and/or infertility secondary to genitourinary organs
dissection (RPLND) to radical orchiectomy. chemotherapy
– Hemorrhagic cystitis secondary to chemotherapy ICD10
MEDICATION r C63.7 Malignant neoplasm of other specified male
– Growth abnormalities secondary to radiation
First Line therapy (spinal and renal) in children genital organs
r Chemotherapy for malignant rhabdomyosarcoma r D29.8 Benign neoplasm of other specified male
– Vincristine, cyclophosphamide, and dactinomycin, FOLLOW-UP genital organs
and actinomycin D-based chemotherapy in Patient Monitoring r D49.5 Neoplasm of unspecified behavior of other
patients with gross or microscopic residual disease r Serial US for equivocal lesions, especially in the
genitourinary organs
Second Line epididymis
r Benign lesions need patient-performed monthly
N/A
testicular self-exams CLINICAL/SURGICAL
SURGERY/OTHER PROCEDURES r Rhabdomyosarcoma monitoring is provider
r Testicular or paratesticular lesions suspected to be PEARLS
dependent
malignant should be removed by radical inguinal – Should be followed closely by a urologist r It is impossible to distinguish a benign from a
orchiectomy with high ligation of the spermatic malignant tumor based on physical exam.
cord. Patient Resources r Can be indistinguishable from testicular masses.
– Early clamping of the cord limits hematogenous N/A r Percutaneous biopsies contraindicated due to
spread in leiomyosarcoma.
r Rhabdomyosarcoma: documented seeding in scrotal wall with malignancy.
REFERENCES
– Consider hemiscrotectomy for any degree of
scrotal wall involvement. 1. Montgomery JS, Bloom DA. The diagnosis and
– The Intergroup rhabdomyosarcoma study group management of scrotal masses. Med Clin North
(IRS) recommended radical inguinal orchiectomy Am. 2011;95(1):235–244.
and routine RPLND in all males >10 yr and in 2. Rosevear HM, Mishail A, Sheynkin Y, et al. Unusual
boys <10 with metastasis noted on imaging. scrotal pathology: An overview. Nat Rev Urol.
r Complete surgical excision with a negative margin 2009;6:491–450.
has significant impact on local recurrence and
overall survival in soft tissue sarcomas.
273
PARKINSON DISEASE, UROLOGIC CONSIDERATIONS

Sam J. Brancato, MD
r The net effect of the basal ganglia on micturition is PHYSICAL EXAM

BASICS inhibitory, which is abolished due to cell loss in the r Cardinal features are rest tremor, rigidity, and
substantia nigra bradykinesia.
DESCRIPTION – The bladder detrusor can thus become unstable r Slow, pill-rolling tremor of the hands (4–6 cycles/s)
r Parkinson disease (PD), also called paralysis agitans and result in urgency and frequency with urge seen primarily at rest
is a neurodegenerative disorder associated with loss incontinence – Abolished by use of the affected hand
of dopaminergic neurons. r The smooth sphincter is synergic, however – Aggravated by stress and cold weather
r Three cardinal features are rest tremor, rigidity, and pseudodyssynergia, as well as delay in striated r Facial expressions can be immobile or rigid and
bradykinesia. sphincter relaxation (bradykinesia) leading to urinary speech slowed
r Postural instability, sometimes deemed a cardinal retention (2) r Slow, shuffling gait with loss of normal arm swing
feature, is nonspecific and usually absent in early – Impaired detrusor contractility may also occur (rarely prominent early in the course of PD)
disease. r PD can also be associated with bowel dysfunction r Assessment of pelvic floor reflexes, motor and
r Autonomic dysfunction is manifested by urinary (constipation) and sexual dysfunction sensory
urgency and frequency, constipation, and orthostatic r Urinary symptoms tend to become worse in the r Digital rectal exam
hypotension. Retention can also be seen. course of the disease. Early on other correctable
causes such as benign prostatic enlargement in men DIAGNOSTIC TESTS & INTERPRETATION
EPIDEMIOLOGY
can cause similar symptoms Lab
Incidence r Centrally acting anticholinergic drugs such as r No diagnostic test exists for PD as the diagnosis is
r PD incidence increases with age, from 17.4 cases
trihexyphenidyl and benztropine have been used to clinical.
per 100,000 persons per year between 50–59 yr of r Standard urologic evaluation (U/A, C&S) based on
treat PD and can cause urinary retention
age to 93.1 in 100,000 persons per year between initial symptoms
70–79 yr of age. ASSOCIATED CONDITIONS
r Life risk of developing PD is 1.5% r Autonomic dysfunction Imaging
r Voiding dysfunction occurs in 40–70% of patients r Brain MRI is reserved for patients suspected of
– Constipation
with PD. – Orthostatic hypotension having PD who fail to respond to therapeutic doses
– Urinary urgency/frequency/urge incontinence of L-dopa administered for 12 wk, to exclude rare
Prevalence r BPH secondary causes and subcortical vascular
N/A r Dementia pathology.
r Depression r Routine urologic imaging is not required.
RISK FACTORS
r Men are about 1.5 times more likely than women to r Sleep disturbance Diagnostic Procedures/Surgery
develop PD r Erectile dysfunction r PD is a clinical diagnosis, although the definition of
r The median age of onset is 60 yr and the mean
r Hyposmia PD is a postmortem finding based on the
duration of the disease from diagnosis to death is r Visual hallucination neuropathologic examination.
15 yr. r Urodynamics:
r Young-onset PD affects 5–10% of patients with the GENERAL PREVENTION – Detrusor overactivity is the most common
initial symptom arising before the age of 50 yr. N/A cystometric abnormality.
Genetics – Sporadic involuntary activity in the striated
r About 15% of patients with PD have a 1st-degree sphincter during involuntary bladder contraction is
DIAGNOSIS common, however, this does not cause
relative with the disease, typically without a clear
mode of inheritance HISTORY obstruction.
r Mutations in two genes cause autosomal dominant r Urinary symptoms usually appear after the onset of – Pseudodyssynergia may occur, as well as delay in
forms of PD neurologic symptoms striated sphincter (bradykinesia) relaxation at the
– α-Syn gene (SNCA): Located on chromosome 4q r Assess for LUTS: onset of voluntary micturition, both of which can
– Leucine-rich repeat kinase 2 (LRRK2): located on – Storage symptoms: Most common, include be misinterpreted as true dyskinesia.
chromosome 12q nocturia, urgency, frequency, and incontinence – Detrusor areflexia relatively rare in PD and when
r To date, approximately 16 risk loci have been – Voiding symptoms: Difficulty initiating stream, present may often be due to anticholinergic
weak FOS/prolonged urination, and straining medications.
identified, some of which overlap with the genes r Urodynamics is a useful tool for investigating
known to contain disease-causing mutations r Elevated PVRs are uncommon in PD patients
r Assess for concurrent urologic conditions: concomitant obstruction secondary to BPH.
PATHOPHYSIOLOGY (1)
r Selective loss of dopaminergic projections from the – BPH in men and SUI in women
r Assess for polypharmacy
substantia nigra pars compacta (a component of the
basal ganglia) to the caudate nucleus and putamen – Central acting anticholinergics listed below can be
r Dopamine deficiency in the nigrostriatal pathways used in younger patients in whom tremor is the
major symptom but may exacerbate incomplete
accounts for most of the clinical motor features of
emptying and urinary retention
the disease
– Benztropine mesylate (Cogentin), trihexyphenidyl
(Artane), biperiden (Akineton),orphenadrine
(Norflex, Flexon)
274
PARKINSON DISEASE, UROLOGIC CONSIDERATIONS
Pathologic Findings Second Line

r OnabotulinumtoxinA
REFERENCES
Intraneuronal Lewy bodies and Lewy neurites are the
pathologic hallmarks of PD. – While not specifically approved for PD, it is 1. Yeo L, Singh R, Gundeti M, et al. Urinary tract
approved for the treatment of urinary dysfunction in Parkinson’s disease: A review. Int
DIFFERENTIAL DIAGNOSIS Urol Nephrol. 2012;44(2):415–424.
r Parkinson incontinence due to detrusor overactivity
associated with a neurologic condition in adults 2. Sakakibara R, Tateno F, Kishi M, et al.
– Multiple system atrophy
who have an inadequate response to or are Pathophysiology of bladder dysfunction in
– Normal aging
intolerant of an anticholinergic medication Parkinson’s disease. Neurobio Dis. 2012;
– Vascular parkinsonism (multiple infarcts within the r The following are used but currently not FDA 46(3):565–571.
basal ganglia and subcortical white matter)
– Parkinson plus syndromes approved for urinary incontinence 3. Campeau L, Soler R, Andersson KE. Bladder
r Voiding dysfunction – Tricyclic antidepressants (TCA): Imipramine dysfunction and parkinsonism: Current
10–25 mg PO BID–TID pathophysiological understanding and
– Selective serotonin norepinephrine reuptake management strategies. Curr Urol Rep.
TREATMENT inhibitors (SSNRIs): Duloxetine 20–40 mg PO BID 2011;12(6):396–403.
r Nocturnal polyuria can be treated with desmopressin
GENERAL MEASURES
r PD is a progressive neurodegenerative disorder SURGERY/OTHER PROCEDURES ADDITIONAL READING
Bladder outlet procedure: Consider if coexisting
despite treatment. r Lees AJ, Hardy J, Revesz T. Parkinson’s disease.
r Levodopa is the mainstay of therapy for PD and the obstruction is found on urodynamic testing
ADDITIONAL TREATMENT Lancet. 2009;373(9691):2055–2066.
gold standard against which new therapies are r Wyndaele JJ, Kovindha A, Madersbacher H.
compared. r PDE5 inhibitors for treatment of erectile dysfunction:
– In the United States, levodopa is combined with – Sildenafil, tadalafil, vardenafil Neurologic urinary incontinence. Neurourol Urodyn.
the decarboxylase inhibitor carbidopa (Sinemet). r Deep brain stimulation of the subthalamic nucleus 2010;29(1):159–164.
– Levodopa has been shown to have unpredictable may decrease urinary symptoms See Also (Topic, Algorithm, Media)
effects on bladder function. r Incontinence, Adult Female
r Clinicians should offer behavioral therapies (eg, fluid Additional Therapies
r Incontinence, Adult Male
Incontinence aids may be necessary and are primarily
management, clean intermittent catherization) as chosen by the degree of absorbency required and the r Neurogenic Bladder, General
1st-line therapy. ease of use. During the night, high absorbency pads
r Evaluate medications that may result in urinary
are usually required.
symptoms (such as retention/hesitancy) with CODES
anticholinergic drugs such as trihexyphenidyl and Complementary & Alternative
benztropine used to treat some patients with PD. Therapies
Dietary fiber, laxatives, and prokinetic drugs (such as ICD9
MEDICATION serotonergic agonists) are used to treat PD-related r 332.0 Paralysis agitans
First Line bowel dysfunction. r 788.41 Urinary frequency
r For urologic symptoms of frequency, urgency, and r 788.63 Urgency of urination
urge incontinence, anticholinergics are commonly
used but should be monitored closely in elderly as ONGOING CARE ICD10
r G20 Parkinson’s disease
they may contribute to cognitive decline (3): PROGNOSIS
– Oxybutynin 5 mg PO TID r N39.41 Urge incontinence
r PD is a progressive neurodegenerative disorder.
– Tolterodine LA 4 mg PO daily r R35.0 Frequency of micturition
r Despite a variable disease course, the overall
– Others (solifenacin, fesoterodine, darifenacin,
prognosis is poor with a mean duration of the
trospium)
r β3-Adrenergic agonist agent: Promotes detrusor disease from diagnosis to death of 15 yr. CLINICAL/SURGICAL
muscle relaxation and can also be considered for COMPLICATIONS PEARLS
overactive bladder symptoms r Urinary incontinence
r Cardinal features are rest tremor, rigidity, and
– Mirabegron (25–50 mg) – Skin breakdown secondary to incontinence
r Urinary retention (often related to anticholinergics) bradykinesia.
r Urinary incontinence is a common feature of PD due
FOLLOW-UP to symptoms of overactive bladder.
Patient Monitoring
Assess for elevated PVRs, specifically if taking
anticholinergics
Patient Resources
National Parkinson Foundation: Urinary Problems in PD.
http://www.parkinson.org/NationalParkinsonFoundation/
files/6c/6c980d82-f158-481c-97a9-0649ea6ba020.
pdf
275
PELVIC ORGAN PROLAPSE (CYSTOCELE AND ENTEROCELE)

W. Stuart Reynolds, MD, MPH
Roger R. Dmochowski, MD, MMHC, FACS
r Damage or weakness to the muscular and DIAGNOSTIC TESTS & INTERPRETATION

BASICS connective tissue supporting mechanisms, including Lab
innervation, contribute to POP r Urinalysis and urine culture, as indicated
DESCRIPTION r Serum creatinine, BUN: May be abnormal in
r Pelvic organ prolapse (POP): The descent of one or ASSOCIATED CONDITIONS
r Urinary incontinence advanced POP with bladder outlet or ureteral
more of the anterior vaginal wall, posterior vaginal obstruction
wall, uterus/cervix, or apex of vagina (vaginal vault – Stress urinary incontinence (SUI)
◦ Present in 65% of POP Imaging
or cuff after hysterectomy) r Routine imaging is not indicated; imaging may
r Cystocele: Anatomic defect of the anterior vaginal – Occult SUI (“masked” or “latent” SUI)
◦ SUI only observed after reduction of POP supplement exam with complex cases
wall in which bladder prolapses into the vagina ◦ Present in 25–80% of women with POP, r Defecography
r Enterocele: Anatomic defect of the vaginal apex
especially with advanced stages – Assesses defecatory dysfunction, including degree
typically; small intestine prolapses into the vagina r Lower urinary tract symptoms
r Rectocele: Anatomic defect of the posterior vagina; of rectocele and rectal emptying
– Overactive bladder r Voiding cystourethrogram
the rectum prolapses into the vagina – Voiding dysfunction
r Defects in many or all vaginal compartments – Assesses degree bladder prolapse and bladder
◦ Advanced POP (stage III or greater) may result neck function; may detect fistula, vesicoureteral
(anterior, posterior, apex) may occur together in urethral “kinking” resulting in bladder outlet reflux, or urethral diverticulum
EPIDEMIOLOGY obstruction r Pelvic ultrasound
r Upper urinary tract obstruction
Incidence – Allows dynamic assessment of pelvic organs and
Insufficient data to conclusively establish incidence – Advanced POP may result in bilateral ureteral bladder volume
rates obstruction with hydronephrosis r Magnetic resonance imaging (MRI)
r Bowel dysfunction
Prevalence – Allows dynamic imaging of functional
r Estimates vary, based on definitions, symptoms, – Constipation relationships among the pelvic floor viscera and
– Fecal/anal incontinence supporting structures, and assesses pelvic
and/or physical exam findings r Sexual dysfunction
– 3% of US women report symptoms of vaginal pathology
– Dyspareunia – Expensive; clinical utility over exam alone not
bulging
– 40% of US women have POP on exam GENERAL PREVENTION established
r Women have an 11% lifetime risk of undergoing r Weight management Diagnostic Procedures/Surgery
surgery for POP and/or UI by age 80 r Protective role of elective cesarean section debatable r Postvoid residual (PVR) urine volume
r Urodynamic testing
RISK FACTORS
r Age – Routine use not indicated; clinical utility not
DIAGNOSIS established
r Race/ethnicity (Hispanic > White > African
HISTORY – May detect voiding dysfunction or occult
American) r Assess for prolapse symptoms
r Parity incontinence with POP reduction
r Obesity – Vaginal bulging, including visualization or – Urethral function tests (leak point pressure,
palpation of a “bulge” in the vagina urethral pressure profilometry) assess urethral
r Hysterectomy
– Pelvic pressure, heaviness, or dragging sensation function and degree of SUI, if any
r Prior POP surgery
– Vaginal mucosal irritation, bleeding, discharge, Pathologic Findings
r Menopause
and/or infection N/A
r Pelvic strain (high impact activity or work) – Splinting/digitation: Applying manual pressure to
vagina or rectum to assist with voiding or DIFFERENTIAL DIAGNOSIS
Genetics r Uterovaginal prolapse
r Increased familial risk (sisters and mothers) defecation r Cystocele
– 2.5 times more common if positive family history – Low backache, temporally associated with POP
r Assess for other pelvic floor symptoms r Enterocele
for POP r Rectocele
r Inheritable collagen disorders (eg, Ehlers–Danlos – Urinary incontinence and voiding dysfunction
– Constipation/anal incontinence r Soft tissue vaginal mass
syndrome) r Urethral diverticulum
r Genome-wide studies ongoing with several – Dyspareunia
potential candidate genes identified, most related to PHYSICAL EXAM
r Useful to employ POP staging
elastin and collagen metabolism (eg, LAMC-1) TREATMENT
PATHOPHYSIOLOGY – POP quantification system (POPQ)
r Integrated support to the bony pelvis through the ◦ Stage 0: No prolapse is demonstrated GENERAL MEASURES
◦ Stage I: Most distal portion of the prolapse is r Management is primarily surgical
endopelvic fascial structures, suspensory ligaments, r Bowel regimen for constipation
levator ani muscles, and pelvic organs help maintain >1 cm above the level of the hymen
◦ Stage II: Most distal portion of the prolapse is r Hormone replacement, topical vaginal, for atrophic
the pelvic organs in the proper anatomic position in
the pelvis. 1 cm or less proximal to or distal to the plane of vaginitis
r Classically, three levels of vaginal support are the hymen – Estrogen alone in postmenopausal with after
◦ Stage III: The most distal portion of the prolapse hysterectomy; estrogen and progesterone if uterus
described:
is >1 cm below the plane of the hymen present, even if postmenopausal
– Level I: Uterosacral and cardinal ligaments ◦ Stage IV: Complete eversion of the total length
support upper 1/3 of vagina, cervix, and uterus. MEDICATION
of the lower genital tract is demonstrated
– Level II: Pubocervical and rectovaginal fascia r Assessment of urinary incontinence First Line
attach laterally to the arcus tendineus fascia pelvis N/A
to support midportion of vagina – Provocative maneuvers (cough and Valsalva) to
– Level III: Direct attachment of vagina to urethra, demonstrate urethral leakage; repeated with Second Line
perineal body, and levator ani muscles prolapse reduced to detect occult SUI N/A
276
PELVIC ORGAN PROLAPSE (CYSTOCELE AND ENTEROCELE)
SURGERY/OTHER PROCEDURES Complementary & Alternative ADDITIONAL READING

Therapies r FDA Safety Communication. Urogynecologic surgical
ALERT r Pelvic floor muscle training
The FDA has identified safety concerns with use of – Pelvic muscle strengthening can improve stage mesh: Update on the safety and effectiveness of
synthetic mesh materials for POP repair, specifically and symptoms, best with supervision of a physical transvaginal placement for pelvic organ prolapse,
for transvaginal placement of synthetic therapist 2011: www.fda.gov.
mesh/prosthetics (See “Additional Reading”). r Haylen BT, de Ridder D, Freeman RM, et al. An
International Urogynecological Association
r Transvaginal approach ONGOING CARE (IUGA)/International Continence Society (ICS) joint
– Allows for concomitant repair of anterior, report on the terminology for female pelvic floor
posterior, and apical compartment defects and PROGNOSIS dysfunction. Neurourol Urodyn. 2010;29:4–20.
r Recurrent POP
anti-incontinence procedures
– Augmentation of native tissue repairs with – Historically 30% recurrence rate after surgery See Also (Topic, Algorithm, Media)
r Cystocele
biologic or synthetic materials/grafts COMPLICATIONS r Cystocele Grading
◦ Outcomes improved with augmented materials, r Mesh material complications occur in 10% of r Incontinence, Urinary, Adult Female
but graft materials may pose safety concerns women (1)[B] r Pelvic Organ Prolapse (Cystocele and Enterocoele)
(1)[A] r Perioperative complications of bleeding, pelvic Image
◦ Transvaginal “mesh kits”: Prepackaged medical organ injury, bladder dysfunction, infection r Pelvic Organ Prolapse Quantification System (POP-Q)
devices for transvaginal placement of mesh r Postoperative complications include vaginal and r Pelvic Organ Prolapse Terminology
material pelvic pain, vaginal shortening or narrowing, r Prolapse, Staging Systems
– Anterior colporrhaphy or paravaginal repair dyspareunia r Urethra, Caruncle
– Posterior colporrhaphy, perineorrhaphy
– Vaginal apical/vault suspension FOLLOW-UP r Urethrocele
◦ Sacrospinous ligament fixation Patient Monitoring
◦ Uterosacral ligament fixation r Evaluation for recurrent or de novo POP through
r Abdominal approach history and exam CODES
– Abdominal sacrocolpopexy (ASC) r Evaluation for urinary incontinence after POP
◦ Open, laparoscopic, or robotic approaches surgery, if anti-incontinence procedure not ICD9
◦ Vaginal apex fixation to the presacral fascia at performed r 618.00 Unspecified prolapse of vaginal walls
S3–S4 using biologic or synthetic material r Routine evaluation for complications related to r 618.6 Vaginal enterocele, congenital or acquired
r Hysterectomy synthetic mesh materials, if used in POP surgery r 618.9 Unspecified genital prolapse
– Transvaginal or transabdominal approach – Patient history for vaginal symptoms, discharge,
– Complete vs. supracervical bleeding, dyspareunia ICD10
r N81.5 Vaginal enterocele
◦ Potential increased risk of vaginal mesh – Physical exam for vaginal exposures
– Cystoscopy for lower urinary tract perforations, as r N81.9 Female genital prolapse, unspecified
exposure after ASC in setting of hysterectomy; r N81.10 Cystocele, unspecified
supracervical hysterectomy may be protective indicated
(2)[B] Patient Resources
r Colpocleisis Society of Urodynamics, Female Pelvic Medicine & CLINICAL/SURGICAL
– Closure or removal of the entire vagina Urogenital Reconstruction (SUFU). http://www.
◦ Reserved for those who are not candidates for sufuorg.com/Patient-Education/Learn-About-Pelvic- PEARLS
more extensive surgery or do not plan future Disorders.aspx r Complete assessment of all vaginal compartments
vaginal intercourse for POP staging is essential, including occult SUI.
◦ Partial colpocleisis (Le Fort colpocleisis) r Nonsurgical treatments with pelvic floor muscle
◦ Total colpocleisis REFERENCES exercises and vaginal pessary should be offered prior
r Concomitant anti-incontinence procedure
to surgical intervention.
– Retropubic colposuspension (Burch) 1. Maher CM, Feiner B, Baessler K, et al. Surgical r Surgical repair with augmentation materials
◦ Prophylactic Burch procedure with ASC can management of pelvic organ prolapse in women: improves outcomes, but may pose serious safety
decrease subsequent SUI by 50% (3)[A] The updated summary version Cochrane review. Int risks.
Urogynecol J. 2011;22:1445–1457. r Patients must be informed of ongoing FDA concerns
– Suburethral sling, including midurethral (MUS) 2. Diwadker GB, Barber MD, Feiner B, et al.
and pubovaginal, synthetic or biologic graft regarding safety of synthetic mesh materials used in
Complication and reoperation rates after apical POP surgery.
materials vaginal prolapse surgical repair: A systematic r Patient monitoring for recurrence and delayed
◦ Prophylactic, synthetic MUS at time of vaginal review. Obstet Gynecol. 2009;113:367–373. mesh-related complications is imperative.
POP surgery reduces need for additional 3. Brubaker L, Cundiff GW, Fine P, et al. Abdominal
surgery in women at 12 mo (OR 0.48, 95% CI sacrocolpopexy with Burch colposuspension to
0.30–0.77) (4)[A] reduce urinary stress incontinence. N Engl J Med.
◦ Number of slings needed to prevent 1 case of 2006;354:1557–1566.
SUI at 12 mo is 6 (4)[A] 4. Wei JT, Nygaard I, Richter HE, et al. A midurethral
ADDITIONAL TREATMENT sling to reduce incontinence after vaginal prolapse
Radiation Therapy repair. N Engl J Med. 2012;366:2358–2367.
N/A
r Vaginal pessary: Supportive and space-occupying
devices for nonsurgical management of POP
– Requires routine maintenance and care (removal,
cleaning, vaginal inspection) P
277
PELVIC PAIN, FEMALE

Kai-Wen Chuang, MD
r Urine
BASICS DIAGNOSIS – Urine pregnancy test
– Urine analysis
DESCRIPTION HISTORY – Urine culture
r Chronic pelvic pain (CPP) is defined as discomfort r History of present illness
– Nucleic acid amplification test for gonorrhea and
below the umbilicus lasting ≥6 mo – Onset/pallaition or provocation Chlamydia
r Etiology often unclear and symptom severity often quality/radiation/severity/timing (OPQRST) of pain – Cytology, if hematuria to evaluate for bladder
out of proportion to objective findings – Alleviating or aggravating factors cancer
r Bears impact on physical, mental, emotional, and – Ask if symptomatic during sexual intercourse r Others
sexual well-being – Menstrual history – Cervical culture
r Past medical and surgical history
– Vaginal wet mount
EPIDEMIOLOGY – Check history of PID, STIs, ectopic pregnancy – PAP smear
Incidence – Obtain history of trauma – Fecal occult blood test
N/A – Abdominal and pelvic surgeries contribute to
adhesions Imaging
Prevalence r Ultrasound
r Difficult to ascertain due to varied definition – Check trigger points from incisional scars
r Family and social history – Transvaginal and/or pelvic ultrasound: Modality of
– Affects ∼1 in 7 women choice in the initial evaluation of pelvic pain
– 39% prevalence rate in primary care setting – 1st-degree family with CPP
– Inquire about physical and/or sexual abuse – Renal and bladder ultrasound: Assess
– Accounts for 10% of all gynecologic referrals hydronephrosis, renal stone disease, and bladder
– Number of sex partners, method of contraception
RISK FACTORS – Substance dependence, exposure to analgesics distension
r Depression, anxiety r Plain films
r Personal history of abuse PHYSICAL EXAM – Kidney, ureter, bladder x-ray (KUB): Assess urinary
r Vital signs
r Prior sexually transmitted infections (STIs) stone burden or dermoid cyst
r Prior pelvic inflammatory disease (PID) increases risk – Fever, hypotension, and tachycardia suggest – Spinal and bony x-ray: Indicated when osseous
infectious etiology and skeletal etiologies of pelvic pain are suspected
4-fold, prior STI/STD r Abdominal exam r Hysterosalpingography: Allow anatomic evaluation
r Substance dependence
r 1st-degree family with CPP – Search for trigger points of the uterus and fallopian tubes
– Assess peritoneal signs r Pelvic venogram: Assess pelvic vascular anatomy
Genetics – Sensory evaluation of dermatomes and venous congestion
r Twin studies and familial clustering do suggest r Back and musculoskeletal exam r Axial imaging (CT, MRI)
genetic basis for increased nociception – Evaluate posture and gait – Indicated when ultrasound negative or
r No established inheritance pattern – Rule out scoliosis or lordosis inconclusive
r Pelvic exam
PATHOPHYSIOLOGY – With intravenous and/or oral contrast
r Exact mechanism unknown – Inspect vulva for skin lesions, signs of trauma, and – More sensitive evaluation of the gastrointestinal
r Complex and multifactorial, combining, biologic, irritation and genitourinary systems
– Speculum exam to assess vaginal mucopurulent
psychological, and social factors discharge and erythema Diagnostic Procedures/Surgery
r Diagnostic laparoscopy
ASSOCIATED CONDITIONS – One-hand pelvic exam to identify muscular trigger
r Endometriosis, ectopic pregnancy, ovarian cysts, points, cervical motion tenderness, urethral – Endometriosis most common (33%)
tenderness, and to delineate bladder base and – Adhesions (24%)
adhesions
r Urinary tract infections (UTIs), STIs, and PID vaginal fornix – Negative 35–66% of the time
r Irritable bowel syndrome (IBS) – Bimanual exam to assess uterine shape, direction, – Negative findings do not exclude somatic cause
tenderness and mobility; assess adnexal masses and positive findings do not necessarily represent
r Interstitial cystitis (IC)
and tenderness true etiology of CPP
r Rectal exam r Barium enema or colonoscopy
GENERAL PREVENTION
r Prompt recognition r Urodynamics
– Check rectal tone, rectovaginal septum,
r Safe sex practices r Cystoscopy, bladder biopsy, hydrodistension
cul-de-sac, and uterosacral ligaments
DIAGNOSTIC TESTS & INTERPRETATION Pathologic Findings
Based on diagnosis
Lab
r Serum DIFFERENTIAL DIAGNOSIS
– Complete blood count: Leukocytosis and left shift r Gynecologic: Accounts for 20% of CPP
suggest infection – Cervical stenosis
– Erythrocyte sedimentation rate: Nonspecific – Chronic PID (occurs after 30% of acute PID)
markers of subacute or chronic inflammation – Endometriosis/chronic endometriosis
– Cancer antigen-125: Marker for endometriosis, – Gynecologic cancers
PID, and certain cancers – Pelvic congestion syndrome
– β-Human chorionic gonadotropin: Becomes – Uterine fibroids
positive 7 days after conception, a negative test
excludes ectopic pregnancy
278
PELVIC PAIN, FEMALE
r Gastrointestinal SURGERY/OTHER PROCEDURES 3. Wiffen P, Collins S, McQuay H, et al.

– Colorectal cancers r Local injection of anesthetics Anticonvulsant drugs for acute and chronic pain.
– Diverticulitis r Sacral neuromodulation (4) Cochrane Database Syst Rev. 2005:CD001133.
– IBS r Surgical removal of endometriosis 4. Kemler MA, Barendse GA, van Kleef M, et al. Spinal
– Inflammatory bowel disease (IBD) r Hysterectomy cord stimulation in patients with chronic reflex
r Genitourinary sympathetic dystrophy. N Engl J Med. 2000;343:
– May be beneficial in women who have completed
– Bladder cancer reproduction and whose CPP is believed to be due 618–624.
– Cystitis, urinary retention to uterine disorders such as adenomyosis or
– IC/painful bladder syndrome (PBS) fibroids
– Kidney stones r Presacral neurectomy ADDITIONAL READING
– Urethral diverticulum, urethritis
ADDITIONAL TREATMENT r Engeler DS, Baranowski AP, Dinis-Oliveira P, et al.
– Urethral syndrome
r Others Radiation Therapy The 2013 EAU guidelines on chronic pelvic pain: Is
– Abdominal myofascial pain N/A management of chronic pelvic pain a habit, a
– Fibromyalgia philosophy, or a science? 10 years of development.
Additional Therapies Eur Urol. 2013;64(3):431–439.
– Pelvic floor muscular pain r Pelvic floor physical therapy
r Fall M, Baranowski AP, Elneil S, et al. EAU guidelines
– Physical and/or sexual abuse r Biofeedback and relaxation therapies
– Psychiatric disorders r Transcutaneous electrical nerve stimulation (TENS) on chronic pelvic pain. Eur Urol. 2010;57(1):35–48.
– Radiculopathy r Intravesical instillations or injections See Also (Topic, Algorithm, Media)
– Surgical adhesions r Chronic Pelvic Pain Syndrome (CPP) In Females
Complementary & Alternative Section II Table.
Therapies r Inflammatory Bowel Disease (Ulcerative Colitis and
TREATMENT r Acupuncture
Crohn Disease), Urologic Considerations
r Massage and manipulations r Interstitial Cystitis (IC)/Painful Bladder Syndrome
GENERAL MEASURES
r Goals of care for managing CPP r Prostatitis, Chronic, Nonbacterial, Inflammatory and
– Symptomatic control ONGOING CARE Noninflammatory (NIH CP/CPPS III A and B)
– Patient education
– Patient empowerment PROGNOSIS
r Multidisciplinary and individualized approach Variable and dependent on underlying etiology and CODES
– Psychosocial counseling treatment modalities
– Chronic pain management COMPLICATIONS ICD9
– Biofeedback r Risk of pharmacologic dependence, tolerance, and r 338.29 Other chronic pain
– Physical therapy abuse associated with long-term analgesia r 617.9 Endometriosis, site unspecified
– Medications and surgery when needed r Surgical complications such as bleeding and r 625.9 Unspecified symptom associated with female
r Validated questionnaires and fluid diaries can help
infections are procedure specific genital organs
monitor progress
FOLLOW-UP ICD10
MEDICATION r G89.29 Other chronic pain
Patient Monitoring
First Line r CPP is typically managed in outpatient setting r N80.9 Endometriosis, unspecified
r Target underlying condition, nerve block
r Monitor serum hepatic/renal function and r R10.2 Pelvic and perineal pain
r Nonsteroidal antiinflammatory drug (1)[B] electrocardiogram when using antidepressants
– Superior to placebo
Patient Resources CLINICAL/SURGICAL
– Can be given with acetaminophen r The International Pelvic Pain Society
r Opioids (2)[A]
– www.pelvicpain.org PEARLS
– Oral, intramuscular, or transdermal
r Tricyclic antidepressants r The pathophysiology of CPP is multifactorial, and
– More effective in neuropathic pain REFERENCES the treatment for it is multidisciplinary.
r Initial evaluation for CPP aims to identify life- or
ALERT 1. Marjoribanks J, Proctor ML, Farquhar C. organ-threatening conditions and rule out anatomic
Nonsteroidal anti-inflammatory drugs for primary or structural abnormalities.
Common contraindications to antidepressants r Subsequent management of CPP focuses on
dysmenorrhea. Cochrane Database Syst Rev.
include recent infarction, arrhythmias, and severe
2003:CD001751. symptomatic control and patient education.
hepatic/renal disease. r Treatment takes time, and cure may not be possible.
2. Eisenberg E, McNicol E, Carr DB. Opioids for
Second Line neuropathic pain. Cochrane Database Syst Rev. Therefore, it is important to set patient-centered yet
r Selective serotonin reuptake inhibitors 2006:CD006146. realistic goals of care.
r Anticonvulsants
– Gabapentin (3)[A]
◦ More effective in neuropathic pain
◦ No place in acute pain
279
PENILE PROSTHESIS PROBLEMS (INFECTION/EXTRUSION/MALFUNCTION)

Nelson Bennett Jr., MD
r Malfunction
BASICS – Mechanical failure rates are 15% at 5 yr and 30% DIAGNOSIS
at 10 yr
DESCRIPTION – Common reasons include aneurysm, tubing HISTORY
r While generally very reliable, penile prostesis can breakage, reservoir leakage, and connector failure Assess for fever, chills, pain, lethargy, fatigue, change
become infected, undergo extrusion and suffer form – Auto inflation is usually due to improperly in bowel or bladder function, dysuria, frequency,
mechanical failure. positioned reservoir urethral discharge.
r 2 types of penile prosthesis, malleable (semirigid,
noninflatable, nonhydraulic) and inflatable. r Conditions associated with erectile dysfunction r Assess penis/scrotum for erythema, edema,
Inflatables consist of 2-piece (pump and cylinders) induration, pain in palpation of penis/scrotum,
– Adrenal disorders
and 3-piece (pump, cylinders, and reservoir). presence of wound drainage, adherence of
r Implanted via suprapubic or penoscrotal approach. – AIDS-associated neuropathy
– Alzheimer’s prosthesis components to skin.
r Meticulous sterility is required. r Erosion/extrusion of device through glans, urethral
– Cardiac arterial disease
r Infections of any or all parts of the device meatus, scrotal skin, or perineum.
– CNS infections
components require removal of the entire device. – CNS tumors r Assess functionality of device by
r Extrusion/erosion of the device may occur into or – Diabetes mellitus (Type I and II) inflation/deflation—if suboptimally rigid or deflated
through the urethra, penile glans, proximal crura, – History of kidney or liver transplant pump, consider fluid leak.
bladder or bowel, or adjacent vascular structures. – History of myocardial infarction r Assess penile contour/morphology upon inflation:
r Mechanical breakdown may manifest as inability to – History of prostatectomy, cystectomy, or colectomy – Buckling of cylinder or S-shaped deformity
inflate/deflate device, abnormal erectile morphology, – Hyperprolactinemia suggests oversizing of cylinders.
or auto inflation. – Hypertension – Floppy glans (SST deformity) suggests undersized
– Hyperthyroidism cylinders or inadequate corporal dilation.
EPIDEMIOLOGY – Hypogonadism
Incidence – Hypothyroidism
N/A – Liver failure Lab
r Urinalysis
Prevalence – Multiple sclerosis
r Overall infection rate: 1–8% r Urine culture and sensitivity
– Peripheral vascular disease
r Prosthesis revision infection rate: 10–13% – Renal failure r CBC with differential
r Prosthesis revision through infected field infection r Metabolic profile
GENERAL PREVENTION r Erythrocyte sedimentation rate
rate: 18% r The preoperative assessment should include issues
r Mechanical failure rate 2-piece: 5% @ 5 yr such as the patients’ needs and expectations of the Imaging
r Mechanical failure rate 3-piece: 18% @ 15 yr device (1,2) r Usually not necessary
– Issues such as complications and the irreversibility r Ultrasound scrotum—may reveal abscess
RISK FACTORS of the procedure should be exhaustively discussed r MRI (with device inflated)—useful in assessment of
r Infection: Diabetes, spinal cord injury, previous
and documented through informed consent corporal abnormalities.
penile prosthesis, immunocompromised state, h/o r Infection
UTI, obesity Diagnostic Procedures/Surgery
r Extrusion/erosion: Previous surgery, previous pelvic – Ensure UTI or infectious skin rash is absent
Cystourethroscopy may reveal urethral erosion of
– Tight control of serum glucose and HbA1C
radiation, penile fibrosis, aggressive dilation, lack of cylinders or erosion of device component into bladder.
– Preoperative parenteral antibiotic of vancomycin
surgical experience, Peyronie disease, previous + aminoglycoside or imipenem Pathologic Findings
penile prosthesis, upsizing of cylinders – Meticulous adherence to sterile technique N/A
r Mechanical failure: Inadequate dilation of reservoir
– Limit OR traffic DIFFERENTIAL DIAGNOSIS
space – 10-min scrub of operative area r Intraoperative complications (4)
Genetics – 10-min scrub for OR staff – During corporal body dilation: Urethral
N/A – Use of alcohol-based solution for final prep perforation, cross over perforation of opposite
– Avoid having prosthesis contact skin crura during dilation
PATHOPHYSIOLOGY – Use antibiotic-coated/antibiotic dripped
r Infection – Reservoir position: Bladder perforation or
prosthesis (3) improper positioning during the implant procedure
– 1–8% this percentage increases with number of ◦ Postoperative oral antibiotics 7–10 days
revision surgeries – Component failure: Check device function before
postoperatively implantation; careful technique to avoid cylinder
– Most common bacteria – Staphylococcus r Extrusion/erosion
epidermidis injury during corporal body closure
– Avoid aggressive corporal dilation r Postoperative complications:
– Other bacteria: MRSA, Pseudomonas,
– Avoid upsizing of cylinders – Infection
Enterococcus, Prevotella, Morganella
– Avoid early/premature inflation of device – Erosion (oversized cylinder): Often associated with
– Gram-negative bacteria may be associated with r Malfunction
rapid infection pain and buckling
– Biofilm plays important role in bacterial adherence – Place corporotomy closing sutures before device – Undersized cylinder (“concorde deformity” or
and infection insertion to avoid iatrogenic puncture “floppy glans”) whereby there is excess mobility
r Extrusion/erosion – Demonstrate proper function and placement of of the glans
the device prior to conclusion of surgery – Cylinder aneurysm
– Erosion through skin is inherently infected
– Pre-existing infection may hasten erosion – Fluid leak
– Iatrogenic-facilitated erosion may result from – Auto inflation/inability to deflate or inflate
overaggressive dilation
280
PENILE PROSTHESIS PROBLEMS (INFECTION/EXTRUSION/MALFUNCTION)

TREATMENT Radiation Therapy r Best Practice Policy Statement on Urologic Surgery
N/A
GENERAL MEASURES Antimicrobial Prophylaxis (2008). http://www.
r Broad-spectrum antibiotic should be started if Additional Therapies auanet.org/education/guidelines/antimicrobial-
N/A prophylaxis.cfm (updated February 2012. Accessed
infection is suspected.
r If sepsis is present, resuscitation is indicated prior to Complementary & Alternative January 3, 2014)
explanation of prosthesis. Therapies r Bennett NE, Mulhall JP. Complication of surgery for
N/A erectile dysfunction and peyronie’s disease. In:
MEDICATION Taneja SS, ed. Complications of Urologic Surgery
First Line Prevention and Management. 4th ed. Philadelphia,
r AUA guidelines recommend the following antibiotic ONGOING CARE PA: Saunders Elsevier; 2010.
prophylaxis at the time of implantation (See
PROGNOSIS See Also (Topic, Algorithm, Media)
Additional Reading) r Prosthesis satisfaction rates approach 95% for r Erectile Dysfunction (ED)
– Aminoglycoside (or aztreonam with renal
patients and partners r Penile Prosthesis, Models and Descriptions
insufficiency) plus r Satisfaction rates for revision surgery is ∼80%
– 1st/2nd-generation cephalosporin or vancomycin r Penile Prosthesis Problems
r Infection rates have decreased with antibiotic
– Alternative regimens include: (Infection/Extrusion/Malfunction) Images
◦ Ampicillin/Sulbactam coated or antibiotic dipped prosthetics
◦ Ticarcillin/Clavulanate COMPLICATIONS
◦ Piperacillin/Tazobactam r Revision surgery may result in infection, CODES
Second Line extrusion/erosion, or malfunction
N/A r Delay replacement of device may result in corporal ICD9
fibrosis r 996.39 Other mechanical complication of
SURGERY/OTHER PROCEDURES genitourinary device, implant, and graft
r Infection FOLLOW-UP r 996.69 Infection and inflammatory reaction due to
– Removal of prosthesis may be completed on a Patient Monitoring
r In case of revision surgery, prolonged antibiotic other internal prosthetic device, implant, and graft
semiurgent basis (within 24 hr) r 996.76 Other complications due to genitourinary
– Immediate prosthesis salvage (replacement) may treatment may be required.
be possible in absence of frank purulence, erosion, r Biweekly follow-up is indicated until patient is device, implant, and graft
necrotic tissue, poorly controlled diabetes, cleared to use the device. ICD10
immunosuppression r T83.6XXA Infect/inflm react d/t prosth dev/grft in
– Mulcahy protocol for prosthesis salvage (4): Patient Resources
AUA Foundation. http://www.urologyhealth.org/ genitl trct, init
◦ 1. Antibiotic solution (1 g vancomycin and r T83.89XA Other specified complication of
80 mg gentamicin in 1 L of normal saline) urology/index.cfm?article=11
◦ 2. 1/2 strength hydrogen peroxide genitourinary prosthetic devices, implants and
◦ 3. 1/2 strength betadine grafts, initial encounter
REFERENCES r T83.420A Displacement of penile (implanted)
◦ 4. Pressure washing with 1 g vancomycin and
80 mg gentamicin in 5-L irrigation 1. Akin-Olugbade O, Parker M, Guhring P, et al. prosthesis, initial encounter
◦ 5. 1/2 strength betadine Determinants of patient satisfaction following
◦ 6. 1/2 strength hydrogen peroxide penile prosthesis surgery. J Sex Med. 2006;3(4):
◦ 7. Antibiotic solution 743–748.
CLINICAL/SURGICAL
◦ 8. Change instruments, gowns, drapes, and 2. Bettocchi C, Ditonno P, Palumbo F, et al. Penile PEARLS
gloves immediately before prosthesis insertion prosthesis: What should we do about r Meticulous sterility is required during the implant in
r Extrusion/erosion complications? Adv Urol. 2008;573560. Published the operating room.
– Proximal erosion/extrusion managed by affixing online 2008 November 4. r Infections of any or all parts of the device
RTE to the interior, proximal corpora with 3. Wilson SK, Salem EA, Costerton W. Anti-infection components require removal of the entire device.
permanent suture dip suggestions for the coloplast titan inflatable r Extrusion/erosion of the device may occur into or
– Alternatively, placing a purse-string suture in the penile prosthesis in the era of the infection
through the urethra, penile glans, proximal crura,
corpora at tubing exit site retardant coated implant. J Sex Med. 2011;8(9):
bladder or bowel, or adjacent vascular structures.
– Distal extrusion/erosion (urethral) is best managed 2647–2654. r Mechanical breakdown may manifest as inability to
by immediately removing offending cylinder and 4. Mulcahy JJ. Penile prosthesis infection: Progress in
prolonged Foley drainage. If contralateral cylinder inflate/deflate device, abnormal erectile morphology,
prevention and treatment. Curr Urol Rep. 2010;
has been placed, it may remain in place or auto inflation.
11(6):400–404.
r Malfunction
– Floppy glans: Perform corporoplasty to reposition
glans or dilate distal corpora
– Cylinder aneurysm: Replace device
– Fluid leak: Replace device
– Auto inflation: Reposition, incise fibrotic capsule,
or replace reservoir
281
PENIS, CANCER, GENERAL CONSIDERATIONS

Igor I. Kislinger, MD
Fernando J. Bianco, Jr., MD

BASICS r Phimosis r Most malignancies involve the epithelial surface of
r Balanitis the penis
DESCRIPTION r Sexually transmitted infections (STIs)/STDs r CIS (erythroplasia of Queyrat, Bowen disease of the
r Most common: Squamous cell carcinomas (SCCs)
penis, bowenoid papulosis)
– SCC in situ or CIS: Erythroplasia of Queyrat (glans GENERAL PREVENTION r Verrucous carcinoma, warty carcinoma,
r Good hygiene, avoid smegma accumulation
or prepuce), Bowen disease (shaft) Buschke–Löwenstein tumor, and giant condyloma
– Low-grade noninvasive (eg, verrucous carcinoma) r Newborn circumcision more protective than
are terms used to describe infrequently seen rare
– Progression risk 5–33% if untreated circumcision later in life tumors that may invade locally but do not
r Other penile cancer histology: Adeno- and r HPV vaccines may reduce the risk of HPV and,
metastasize. Mostly considered to be benign, but
adenosquamous carcinoma, basal cell carcinoma, consequently, penile cancer (unproven) malignant degeneration has been reported
melanoma, sarcomas, Kaposi sarcoma, r Invasive cancer:
neuroendocrine (small cell) undifferentiated ALERT – 95% are SCCs
carcinoma, sebaceous gland carcinoma, and rarely, Presentation at advanced stage is not uncommon – Tongues of invasive atypical keratinocytes with
metastases from other sites (prostate, bladder, due to denial and poor hygiene. multiple mitosis invade the lamina propria or
colon, kidney, leukemia most common) deeper. Sites with foci of aberrant and ectopic
EPIDEMIOLOGY keratinization called squamous pearls
Incidence
DIAGNOSIS – SCCs are graded using the Broders System:
r In 2014 in the United States the American Cancer ◦ Grade I: Well-differentiated, keratin pearls,
HISTORY prominent intercellular bridges
Society estimates that about 1,640 new cases of r Persistent induration, erythema, nodularity of
◦ Grade II–III: Greater nuclear atypia, increased
penile cancer will be diagnosed and 320 men will prepuce and/or glans. Usually has been treated with
die of penile cancer mitotic activity, decreased keratin pearls
several agents, lotions ◦ Grade IV: Cells deeply invasive, marked nuclear
r In the United States r Growth or sore on the penis that doesn’t heal within
pleomorphism, nuclear mitoses, necrosis,
– Hispanics (6.6 per million) 4 wk lymphatic and perineural invasion, no keratin
– Blacks (4.0 per million) r Patients often denies or ignores lesions and present
pearls
– Whites (3.9 per million) at later stages
Prevalence r Bleeding ulcer DIFFERENTIAL DIAGNOSIS
r Rare in developed countries r BXO
r Penile pain—infection
r Most common genitourinary malignancy in Uganda r Erythroplasia of Queyrat; shiny red patches on
– New onset of priapism with a mass suggests
– In Brazil 6–14/100,000 males (1) metastatic corporeal body lesion (eg, melanoma) mucosal surfaces (glans and prepuce if
uncircumcised)
RISK FACTORS PHYSICAL EXAM r Bowen disease (red, scaly patches on the keratinized
r Poor hygiene (2) r Induration, erythema, nodularity of prepuce and/or
skin of the penis typically penile shaft)
r Presence of foreskin and/or phimosis glans r Bowenoid papulosis (multiple flat, warty lesions,
r STD: HPV types 16, 18, and 33 or HIV r Bleeding ulcer
sometimes pigmented)
r Genital ultraviolet radiation, alone or combined with r Foul smell with purulence r Condyloma acuminatum, lata
8-methoxypsoralen r Phimosis r Giant condylomata
r Multiple partners, smoking r Inguinal adenopathy r Extramammary Paget disease: Adenocarcinoma of
r Premalignant conditions:
DIAGNOSTIC TESTS & INTERPRETATION apocrine gland bearing skin, often pruritic
– Leukoplakia,Lichen sclerosus r Kaposi sarcoma: Friable nodular lesions of varying
– Balanitis xerotica obliterans (BXO) Lab
CBC, urinalysis, urine culture size and varying color (purplish, red, blue, dark
– Giant condylomata brown black) often ulcerate/ bleed
Genetics Imaging r Lichen sclerosis
r Penile ultrasound
Viral genes E6 & E7 expressed on high-risk HPV, r Psoriasis
r CT pelvis—evaluate pelvic adenopathy
E-cadherin (16q22) immunoreactivity correlates with r Seborrheic keratosis
r Penile MRI—surgical planning
increased risk of nodal metastases r Ulcer from STD
PATHOPHYSIOLOGY Diagnostic Procedures/Surgery r Zoon balanitis
r Invasive SCC is thought to be preceded by superficial r Superficial lesion
CIS (Bowen disease or erythroplasia of Queyrat). – Biopsy, preferably excisional
Invasive SCC grows into the skin locally before – Circumcision TREATMENT
r Large or extensive
invading the corporal bodies and extending locally. GENERAL MEASURES
r Penile SCC spreads by a relatively reliable pattern: – Partial penectomy r 1st line is surgical excision of lesion on penis.
Form superficial pelvic lymph nodes to deep pelvic r Wound care issues are paramount after excision of
lymph nodes. the primary and after inguinal node dissections.
r SCC is found on the glans in 48%, prepuce in 21%, r Surgical care should be taken to minimize the
glans and prepuce in 9%, coronal sulcus in 6%, and complications of penile deformity and/or meatal
shaft <2%. stenosis after excising the primary and diligent
attention to avoiding infection, hematoma, and
lymphocele after inguinal node dissection is
necessary.
r Treatment based on extent of disease and specific
tumor type. Recommendations below are for
invasive SCC (3). For other tumor types, see specific
sections.
282
PENIS, CANCER, GENERAL CONSIDERATIONS
MEDICATION 3. McDougal WS, Kirchner FK Jr, Edwards RH, et al.

First Line ONGOING CARE Treatment of carcinoma of the penis: The case for
r Topical 5-fluorouracil for cases of CIS primary lymphadenectomy. J Urol. 1986;136:
r For invasive SCC of the penis, after resection of the PROGNOSIS 38–41.
r Depends on T-stage and nodal status
primary tumor, inguinal adenopathy should be 4. Mohs FE, Snow SN, Larson PO. Mohs micrographic
r AJCC staging
treated with 6 wk of broad-spectrum antibiotics surgery for penile tumors. Urol Clin N Am. 1992;
(augmentin or cephalosporin such as keflex) to – Stage I: Cancer is moderately or well-differentiated 19:291–304.
determine if the enlarged nodes resolve and only affects the subepithelial connective tissue
– Consideration to early fine-needle aspiration – Stage II: Cancer is poorly differentiated, affects
biopsy of enlarged nodes can be considered lymphatics, or invades the corpora or urethra ADDITIONAL READING
r Some authors recommend immediate fine-needle – Stage IIIa: Deep invasion into the penis and
metastasis in one lymph node. r Pettaway CA, Davis JD. Contemporary management
aspiration of enlarged inguinal nodes
– Stage IIIb: Deep invasion into the penis and of penile cancer: Part I. AUA Update Series.
Second Line metastasis into multiple inguinal lymph nodes 2012;31:15.
r There is no established chemotherapeutic regimen r Pettaway CA, Pagliaro L. Penile SCC Contemporary
– Stage IV: The cancer has invaded into structures
for metastatic disease. adjacent to the penis, metastasized to pelvic management of inguinal region: Part II. AUA Update
– Potential active agents include 5-FU, bleomycin, nodes, or distant metastasis is present Series. 2012;31:16.
methotrexate, and cisplatin. r 5-yr overall survival for men with node-negative
SURGERY/OTHER PROCEDURES disease is 80–90%. r Balanitis Xerotica Obliterans (BXO)
r Initial dorsal slit may be necessary to assess the r 5-yr survival for N+ men 30–40% r Bowen Disease and Erythroplasia of Queyrat
lesion in phimosis r Married or previously married men have better r Penis, Cancer, General Considerations Images
r Circumcision, if preputial and noninvasive prognosis r Penis, Cancer, Lymphadenopathy
r Laser ablation, if small and noninvasive r African Americans tend to present with more
r Penis, Cutaneous Lesion
r Mohs micrographic surgery, if small and noninvasive advanced disease and have a poorer prognosis r Penis, Mass (Corporal Body Mass)
or minimally invasive (4) COMPLICATIONS r Penis, Squamous Cell Carcinoma
r Wide local excision for small lesions. A 2-cm margin r Infections r Penis, Squamous Cell Carcinoma Algorithm
considered necessary r Erosion of lymphadenopathy into femoral artery r Reference Tables: TNM: Penis Cancer
r Partial or total penectomy should be considered in r After radiation or brachytherapy urethral fistula,
patients exhibiting adverse features for cure by stricture, or stenosis with or without penile necrosis,
organ preservation strategies, including tumors 4 cm
or more, grade III lesions and tumors invading
pain, and edema. Radical penectomy may be CODES
required
deeply into the glans urethra or corpora cavernosa
– Partial penectomy must achieve a 2-cm safety FOLLOW-UP ICD9
r 187.2 Malignant neoplasm of glans penis
surgical margin Patient Monitoring
r Inguinal lymphadenectomy is mandatory for r Close inspection for local recurrence usually every r 187.3 Malignant neoplasm of body of penis
3 mo for 5 yr r 187.4 Malignant neoplasm of penis, part unspecified
persistent lymphadenopathy after antibiotics and
control of the primary lesion r Consider imaging for ambiguous findings on
r Inguinal lymphadenectomy is controversial if physical exam ICD10
r C60.1 Malignant neoplasm of glans penis
inguinal nodes are palpably normal before and after Patient Resources r C60.2 Malignant neoplasm of body of penis
eradication of the primary r http://www.cancer.gov/cancertopics/types/penile. r C60.9 Malignant neoplasm of penis, unspecified
r Lymph node sampling (either sentinel node biopsy Accessed 1/3/2014.
or modified inguinal dissection) may be offered for r The American Cancer Society: Penile Cancer: What is
patients with palpable normal inguinal nodes and penile cancer? American Cancer Society. Last CLINICAL/SURGICAL
T2 or above lesion: revised: 8/31/2013.
– Usually, bilateral dissections are recommended r http://www.cancer.net/cancer-types/penile-cancer. PEARLS
– A total inguinal and pelvic lymphadenectomy is Last revised: 8/31/2013. r A painless lesion on the penis is the most common
necessary if metastases are noted on sentinel or presentation.
modified dissection r 40% of cases of penile cancer in the United States
ADDITIONAL TREATMENT REFERENCES derive from HPV infections.
Radiation Therapy r 2-cm surgical margin is critical for a successful
1. Pow-Sang MR, Ferreira U, Pow-Sang JM, et al.
r External radiation to primary lesion if patient refuses partial penectomy.
Epidemiology and natural history of penile cancer.
surgical excision r Historically 6 wk of antibiotics are required to
Urology. 2010;76(2 suppl 1):S2–S6.
r Some advocate this as primary therapy with salvage appropriate assessment of inguinal region
2. Minhas S, Manseck A, Watya S, et al. Penile
surgery with recurrences cancer–prevention and premalignant conditions. adenopathy; consideration can also be given to early
r Typical doses are 50–60 Gy over 4–6 wk Urology. 2010;76(2 suppl 1):S24–S35. fine-needle biopsy.
r Overall local control provided by interstitial
brachytherapy appears superior to that provided by
external beam radiation therapy with 5-yr local
control rates of 70%–87%
Chemotherapy-based clinical trails
Therapies
r Ketogenic diet
r Holistic approaches
P
283
PENIS, CANCER, LYMPHADENOPATHY

Jonathan H. Huang, MD
Viraj A. Master, MD, PhD, FACS
ASSOCIATED CONDITIONS DIFFERENTIAL DIAGNOSIS

BASICS r Balanitis r Reactive LNs
r Phimosis r Infections: Syphilis, herpes, chancroid,
DESCRIPTION r STDs lymphogranuloma venereum, pedal fungal disease
r Penile cancer spreads systematically to inguinal r Malignant diseases: Metastatic melanoma,
lymph nodes (LNs) before spreading to the common GENERAL PREVENTION
r Prepubertal circumcision is protective against penile lymphoma
iliac and para-aortic LNs and becoming metastatic r Systemic diseases: Mononucleosis, rubella, human
disease cancer
r Good genital hygiene immunodeficiency virus, cytomegalovirus
– Drainage is bilateral in 81% of cases r Autoimmune diseases: Sarcoidosis, lupus
r The inguinal LNs are classified as either superficial r STD education and safe sexual practices
or deep r Sun protection against melanoma
– Superficial inguinal LNs (up to 25 nodes) are r HPV vaccination may reduce risk (unproven) TREATMENT
located under dermis and above the fascia lata in
Scarpa’s triangle GENERAL MEASURES
– Deep inguinal LNs are located in the region of the DIAGNOSIS r Tis, Ta primary tumors (1)
fossa ovalis, medial to the femoral vein – Nonpalpable inguinal LNs
r Extent of LN metastasis determines survival HISTORY ◦ Surveillance
r Circumcision
r Lymphadenectomy (LAD) for penile cancer is – Palpable inguinal LNs
r Phimosis
associated with significant morbidity, but can ◦ Antibiotics for 1 mo to rule out infection vs.
r HPV infection
improve long-term survival immediate fine-needle aspiration biopsy
r LAD is the primary form of treatment for localized r Penile condylomata ◦ If persistent LNs and either FNAC or excisional
r Penile cancer biopsy are positive, ipsilateral inguinal and
lymphatic spread
r Sexual history (multiple partners, early age of initial pelvic LAD and contralateral superficial or
– Extent of LAD (radical vs. modified) remains
controversial intercourse) modified inguinal LAD
r Smoking history r T1 grade 1 and grade 2 primary tumors
EPIDEMIOLOGY r Balanitis xerotica obliterans – Nonpalpable inguinal LNs
Incidence r Treatment with sporalene and ultraviolet A ◦ Surveillance
1 in 100,000 men in the United States and Europe – Palpable inguinal LNs
phototherapy
develop penile cancer ◦ If FNAC is negative and no resolution with
Prevalence PHYSICAL EXAM antibiotics, excisional biopsy or inguinal LAD
r LN spread occurs in 10–15% of patients with Palpable inguinal LNs ◦ If FNAC is positive, ipsilateral inguinal and pelvic
nonpalpable inguinal LNs DIAGNOSTIC TESTS & INTERPRETATION LAD and contralateral superficial or modified
r LN spread occurs in 50% of patients with palpable LAD
Lab r T2–T4 primary tumors
inguinal LNs No tissue parameters, including HPV and p53 status,
– Palpable inguinal LNs are present in 60% of – Nonpalpable inguinal LNs should undergo
are predictive of LN involvement
presenting patients bilateral superficial inguinal LAD or DSNB
Imaging ◦ If frozen section is negative, surveillance
RISK FACTORS r No imaging studies are currently utilized extensively ◦ If frozen section is positive, that side should
r Inguinal LN spread is correlated with an increase in in the diagnosis of LN involvement undergo ipsilateral inguinal and pelvic LAD
clinical grade of primary tumor (0–29% in grade 1 r Ultrasound and PET-CT can be used to detect – Palpable unilateral LNs should undergo ipsilateral
vs. 33–50% in grade 3) recurrences inguinal and pelvic LAD and contralateral
r Inguinal LN spread is correlated with an increase in r Chest x-ray and CT abdomen/pelvis can be used for superficial or modified inguinal LAD
local stage of primary tumor (<10% in pT1/pTis, staging ◦ If contralateral frozen section is negative,
50–70% in pT2 disease, and 50–100% in pT3/pT4) surveillance
Diagnostic Procedures/Surgery ◦ If contralateral frozen section is positive, deep
Genetics r Ultrasound-guided fine-needle aspiration cytology
HPV contributes to the development of penile cancer inguinal or pelvic LAD
(FNAC)
through interactions with tumor protein 53 (p53) and – Palpable bilateral LNs should undergo FNAC to
– Palpable LNs: Sensitivity of 93% and specificity of
retinoblastoma (RB) tumor suppressor proteins determine the extent of LAD
91% ◦ If FNAC is negative, at least bilateral superficial
PATHOPHYSIOLOGY – Nonpalpable LNs: Sensitivity of 39% and
inguinal LAD or DSNB
r Inguinal LNs serve at the primary lymphatic drainage specificity of 100% ◦ If FNAC is positive, bilateral inguinal and pelvic
r Dynamic sentinel node biopsy (DSNB):
for the penis, scrotum, urethra, vulva, vagina, LAD and chemotherapy is warranted
perineum, gluteal region, lower abdominal wall, Lymphoscintigraphy and blue dye staining for r Fixed or LNs >4 cm
lower anus, and lower extremities identification of positive LNs
– Neoadjuvant chemotherapy potentially followed
r Inguinal LNs lie within the femoral triangle (inguinal – False-negative rate of 5%
by surgery
ligament, sartorius, and adductor longus) and are – Should only be offered in experienced centers r Pelvic LNs spread is more likely if (1) 2 or more
separated into superficial and deep groups by the Pathologic Findings inguinal node involvement, (2) extranodal
fascia lata of thigh Squamous cell carcinoma accounts for 95% of penile metastasis, (3) Cloquet node involvement
cancers r LAD should involve at least 8 LNs, as this improves
5-yr survival
284
PENIS, CANCER, LYMPHADENOPATHY
MEDICATION Additional Therapies 3. Johnson TV, Hsiao W, Delman KA, et al. Extensive
r Adjuvant chemotherapy inguinal lymphadenectomy improves overall 5-year
First Line
r Antibiotics – 3 courses of cisplatin and 5-fluorouracil for pN2–3 survival in penile cancer patients: Results from the
– Use of antibiotics has become controversial for – No adjuvant chemotherapy for pN1 surveillance, epidemiology, and end results
enlarged LNs Complementary & Alternative program. Cancer. 2010;116:2960–2966.
– Historically, a 4–6-wk course of antibiotics (such Therapies 4. Master VA, Jafri SM, Moses KA, et al. Minimally
as a cephalosporin or augmentin) was None are effective invasive inguinal lymphadenectomy via endoscopic
recommended to rule out infection in Tis and Ta groin dissection: Comprehensive assessment of
tumors with palpable LNs immediate and long-term complications. J Urol.
– Delay in LAD, a potentially curative treatment, has ONGOING CARE 2012;188:1176–1180.
brought the use of antibiotics into question 5. Kattan MW, Ficarra V, Artibani W, et al.
– FNAC can help determine if LNs are due to
PROGNOSIS
r 5-yr cancer-specific survivals: Nomogram predictive of cancer specific survival in
metastasis or infection patients undergoing partial or total amputation for
– 90–100% in pN0 disease
Second Line squamous cell carcinoma of the penis. J Urol.
– 70–80% in pN1 disease
N/A 2006;175:2103–2108; discussion 2108.
– <30% in pN2–pN3 disease
SURGERY/OTHER PROCEDURES – 15% in patients with positive pelvic LNs who had
r Radical LAD (2,3) inguinal and pelvic LAD
r Predictors of cancer-specific survival: Pathologic ADDITIONAL READING
– Superior margin: Superior margin of the external
ring to the anterior superior iliac spine (ASIS) stage of LNs, vascular and/or lymphatic involvement, Spiess PE, Horenblas S, Pagliaro LC, et al. Current
– Lateral margin: ASIS to 20 cm inferiorly primary tumor thickness concepts in penile cancer. J Natl Compr Canc Netw.
– Medial margin: Pubic tubercle to 15 cm inferiorly COMPLICATIONS 2013;11:617–624.
– Inferior margin: 20 cm inferior from the ASIS to 15 r LAD complications
cm inferior from the pubic tubercle – Wound infection r Groin/Inguinal Mass, Male and Female
r Modified LAD (after Catalona) r Lymphadenopathy, Inguinal
– Skin necrosis
– Excludes area lateral to the femoral artery and – Wound dehiscence r Penis, Cancer, General Considerations
caudal to the fossa ovalis – Thigh numbness r Penis, Cancer, lymphadenopathy Image
– Preservation of the saphenous vein – Lymphedema r Penis Cutaneous Lesion
– No transposition of the sartorius muscles – Lymphorrhea r Penis, Squamous Cell Carcinoma
– Conversion to radical LAD if there are positive LNs – Scrotal swelling
r Techniques to minimize complications of LAD r Reference Tables: TNM: Penis Cancer
– Suprapubic swelling
– Careful skin-flap management – Pulmonary embolism
– Meticulous LN dissection
– Prophylactic antibiotics: Cephalosporins for 2 mo
FOLLOW-UP CODES
– Vacuum drains Patient Monitoring
r Recurrences occur most often within 2 yr after
– Elastic and/or pneumatic stocking ICD9
– Early ambulation inguinal LAD r 187.4 Malignant neoplasm of penis, part unspecified
r Endoscopic LAD (4) r Nomograms available (5) r 196.5 Secondary and unspecified malignant
r Evaluation should include an exam and
– Complete radical LAD can be completed through 3 neoplasm of lymph nodes of inguinal region and
endoscopic ports ultrasound-guided FNAC lower limb
– Node yield is equivalent to open surgery r Maximum follow-up length of 5 yr r 785.6 Enlargement of lymph nodes
– Decreased complications r Surveillance (patient did not have LAD)
r The viability of the skin flaps developed during an – Every 3 mo for yr 1 and 2 ICD10
r C60.9 Malignant neoplasm of penis, unspecified
inguinal LN dissection are based on the anastomotic – Every 6 mo for yr 3, 4, and 5
vessels within the superficial fatty layer of Camper’s r LAD and pN0 disease r C77.4 Sec and unsp malig neoplasm of inguinal and
fascia which course lateral to medial along the skin – Every 6 mo for yr 1 and 2 lower limb nodes
lines. This is a key anatomic dissection plane as the – Every 6 mo for yr 3, 4, and 5 r R59.0 Localized enlarged lymph nodes
lymphatic drainage of the penis lies beneath r LAD and pN+ disease
Camper’s fascia allowing this superficial fatty layer – Every 3 mo for yr 1 and 2
to remain attached to the skin flaps during a groin – Every 6 mo for yr 3, 4, and 5 CLINICAL/SURGICAL
dissection
Patient Resources
PEARLS
r When performing an inguinal LN dissection for a
National Cancer Institute: Penile Cancer Treatment r Penile cancer metastasizes to regional LNs before
clinically negative groin, a modified technique (http://www.cancer.gov/cancertopics/pdq/treatment/
should be used to decrease morbidity. The key disseminating systemically.
penile/HealthProfessional) r Treatment is dependent on the clinical presence of
components of this technique include the following:
Shorter incision (∼10 cm), preservation of the LNs, tumor stage, and tumor grade.
saphenous vein, minimizing dissection lateral to the REFERENCES r Inguinal LAD is potentially curative and can improve
femoral artery, and avoiding transposition of the long-term outcomes in penile cancer with nodal
Sartorious muscle 1. Pizzocaro G, Algaba F, Horenblas S, et al. EAU metastases.
penile cancer guidelines 2009. Eur Urol. 2010;57: r Careful tissue management, antibiotics, vacuum
ADDITIONAL TREATMENT 1002–1012. drains, and compression stockings can minimize the
Radiation Therapy 2. Horenblas S. Lymphadenectomy for squamous cell morbidities associated with LAD.
r Adjuvant radiotherapy may improve locoregional
carcinoma of the penis. Part 2: The role and
control in patients with extensive metastases and/or technique of lymph node dissection. BJU Int.
extranodal disease 2001;88:473–483.
– Side effects include edema and pain
r Radiotherapy in clinical N0 patients is not
recommended P
285
PENIS, CURVATURE, AND/OR PAIN

Abhinav Sidana, MD
Anish K. Shah, MD

BASICS r Chronic intracavernous injection therapy r Radiograph of penile shaft if calcification is
r Dupuytren contracture suspected.
DESCRIPTION r ED (venoocclusive dysfunction) r Duplex Doppler US with intracavernous
r Penile pain could be a result of multiple etiologies r Ledderhose disease (Plantar fasciitis) pharmacologic injection to assess cavernous arterial
and present in both a flaccid and erect penis r Paget disease function, presence of venoocclusive dysfunction, and
– Penile pain: Flaccid penis r Tympanic sclerosis degree of erectile curvature, lateral indentation or
◦ Usually secondary to inflammation of bladder circumferential wasting.
and urethra with referred pain localized to r Private self-photography of erect penis using instant
r Hypospadias
meatus (Polaroid) or digital film imaging is useful to classify
◦ Potentially secondary to paraphimosis the extent of the curvature.
GENERAL PREVENTION
– Penile pain: Erect penis Avoidance of penile trauma during intercourse
◦ May be secondary to priapism or Peyronie Diagnostic Procedures/Surgery
r Uroflowmetry to rule out associated urethral
disease (PD)
r Acquired penile curvature in men, known as PD, is DIAGNOSIS stricture
r Bladder US for postvoid residual
an inflammatory condition of the tunica albuginea
HISTORY r Retrograde urethrogram (if history and exam
usually associated with painful erection with
curvature. If severe, it can cause dyspareunia r Obtain a thorough medical, surgical, and sexual suggest urethral injury, such as blood at meatus.
– Can be a result of complications of penile history (1)[A] May be seen with penile fracture.)
prosthesis implantation r Urethroscopy for urethral pathology
r It is critical to differentiate penile pain from urethral
– Congenital chordee may present as penile pain: History of voiding symptoms and/or recurrent Pathologic Findings
curvature in infants due to a deficiency in UTIs r PD is characterized by a fibrous noncompliant
formation of the urethra or the Buck fascia r Establish duration, degree, and location of curvature plaque within the tunica albuginea, which may
ventrally calcify, preventing uniform expansion of the corpora
and pain
– Iatrogenic chordee secondary to circumcision or r Dyspareunia cavernosa during erection.
other penile skin procedures r Painful erection (suggests PD) – Microscopy: Affected tunica albuginea
EPIDEMIOLOGY r Painful ejaculation demonstrates nonpolarized arrangement of
Incidence r Nature of deformity: Curvature, indentation or collagen fibers and disordered arrangement of
r Common at all ages, but mean age: 53 elastin fibers in PD.
instability (hinge effect)
r Mostly affects males 40–70 yr old, with 0.4–3.2% r Condition causes distress to patient or partner DIFFERENTIAL DIAGNOSIS
incidence r Coexisting ED r Balanitis, balanoposthitis, paraphimosis
r Palpable nodule r Cellulitis
Prevalence
r History of penile prosthesis r Chordee
In general 5% of men have evidence of PD
r History of penile trauma r Congenital penile curvature
RISK FACTORS r Epispadius
r Buckling erectile trauma r History of penile surgery as a child
r Fracture of the tunica albuginea during sexual r Sickle cell disease suggests predisposition to r Erectile dysfunction
r Fournier gangrene
activity priapism
r Intracavernous injection of vasoactive agents r Insect bites r Hypospadias
r Priapism r Idiopathic urethralgia
r Urethral and penile surgery PHYSICAL EXAM r Insect bite
r Circumcised/uncircumcised; retractable foreskin
r See also “Commonly Associated Conditions” r Penile ischemia (embolic, atherosclerosis)
r Measurement of stretched penile length
r Leukemic infiltration of the penile shaft
Genetics r Palpation of stretched shaft to amplify plaque and
r Penile cancer
r Associated with HLA (histocompatability B7) determine its location and size
r Plaque tenderness r Penile fracture, trauma, or contusion
cross-reactive antigens r Penile pain syndrome
r PD less frequent in patients with Asian or African r Location of meatus for evidence of hypospadias
r Evidence of hematoma that suggests acute trauma r Penile prosthesis problem: S-shaped or sigmoid
ancestry
r Solitary or multiple plaques curvature with buckling of prosthesis cylinders that
PATHOPHYSIOLOGY are too long; pain also suggests infected prosthesis
r Mechanical tunical stress forces causing r Erythema and crepitus with Fournier gangrene
components
microvascular hemorrhage and inflammation in the r Eggplant sign with penile fracture r Priapism
tunical wall or septum. The result is hypertrophic r Psychiatric causes of pain
scar formation (plaque). r Pudendal neuralgia
r Autoimmune components have been demonstrated Lab
r Usually not useful unless for workup of infections r Referred pain, GI (rectum, hemorrhoids, fistula,
in 38–75% of men with PD. r Urinalysis with or without culture in cases of
r Altered cell-mediated immunity and antielastin fissures)
referred pain from other GU cause r Referred pain, GU (cystitis, urethritis, prostatitis,
antibodies support an immunologic component. r Serum-free testosterone (morning) and prolactin
r In the setting of erectile trauma, an altered retention, urolithiasis, urethral calculus)
levels if erectile dysfunction coexists r Reiter syndrome
immunologic response to wound healing may r Corporal blood gas for priapism r STD (herpes, chancroid)
predispose a subpopulation to PD.
r Torn frenulum
r Trauma (GSW, penile fracture)
r Urethral foreign bodies
r Urethral shortening following urethroplasty
286
PENIS, CURVATURE, AND/OR PAIN
r Paraphimosis 3. Gelbard M, Mavuduru RM, Agarwal MM, et al.

TREATMENT – Dorsal slit or incision of constricting band Clinical efficacy, safety, and tolerability of
– Circumcision may be necessary collagenase clostridium histoyliticum for the
GENERAL MEASURES r Chordee and epispadias treatment of peyronie disease in 2 large
Identify the specific cause of the penile pain and/or – See specific topic for surgical correction double-blind, randomized, placebo controlled
curvature and treat accordingly r Penile Fracture phase 3 studies. J Urol. 2013;190:199–207.
MEDICATION – See specific topic for surgical correction 4. Segal RL, Burnett AL. Surgical Management for
r Priapism Peyronie’s Disease. World J Mens Health. 2013;
First Line 31:1–11.
r PD – Distal and/or proximal shunting procedures
– All oral agents yield insignificant therapeutic – See specific topic for surgical correction
r Penile reconstruction of scars, contractures, or other
benefit:
◦ Vitamin E (antioxidant), potaba (antifibrotic), deformities ADDITIONAL READING
colchicine (antifibrotic), tamoxifen (antifibrotic), – Z-plasty or other plastic operation r AUA Guideline on the Management of Priapism
L-carnitine (antioxidant), pentoxifylline ADDITIONAL TREATMENT 2003 (http://www.auanet.org/education/guidelines/
r Paraphimosis priapism.cfm)
Radiation Therapy
– Urgent manual reduction with firm pressure ± r www.urologyhealth.org
Ineffective in PD
local anesthetic (see section on paraphimosis for
details) Additional Therapies See Also (Topic, Algorithm, Media)
r Priapism N/A r Chordee
r Epispadias
– Irrigation and aspiration Complementary & Alternative
r Penile Prosthesis, Models and Descriptions (Table)
– Intracavernosal phenylephrine injection Therapies
(100–500 mcg/mL) r None have been shown to have convincing benefit r Penile Prosthesis Problems
r Referred pain to penis or urethra should be aimed at – Vitamin E (α-tocopherol) (Infection/Extrusion/Malfunction)
treating primary problem – Potaba (potassium aminobenzoate) r Penis and Corporal Body Mass
r Treat infectious causes (cellulitis, STD) with – L-carnitine r Penis, Curvature and or Pain Image
antimicrobials r Acupuncture r Peyronie Disease
r Priapism, General
Second Line
r PD intralesional therapy
ONGOING CARE
– Collagenase clostridium histolyticum (CCH)
(Xiaflex) (3)[A] PROGNOSIS CODES
r Prognosis dependent on primary etiology of penile
◦ FDA approved curvature deformity of the penis
due to the presence of a plaque in PD. curvature and/or pain. ICD9
– Surgical straightening of erection is predictably r 605 Redundant prepuce and phimosis
Restricted distribution through Risk Evaluation
and Mitigation Strategy (REMS) due to the risks successful (>85%). r 608.89 Other specified disorders of male genital
of serious adverse reactions, including penile – Shortened penile length and sensory loss may be organs
fracture and other serious penile injury noted postoperatively. r 752.63 Congenital chordee
◦ Maximum 4 treatment cycles. Each treatment COMPLICATIONS
cycle consists of 2 Xiaflex injection procedures r Residual pain and curvature ICD10
r N47.2 Paraphimosis
(in which Xiaflex is injected directly into the r Dyspareunia
r N48.89 Other specified disorders of penis
collagen-containing structure of the penis) and r Erectile dysfunction and loss of penile length due to
1 penile modeling procedure performed by the r Q54.4 Congenital chordee
PD or surgical repair
healthcare professional.
◦ Breaks down collagen, promotes remodeling FOLLOW-UP
Patient Monitoring CLINICAL/SURGICAL
– Other intralesional agents (off-label) Verapamil
(antifibrotic), collagenase (antifibrotic), Periodic monitoring of erectile function, penile length, PEARLS
interferon-α (antifibrotic) and sensory function r Focused history and physical exam allows for
– Steroid therapy Patient Resources prompt diagnosis and effective treatment.
◦ Subcutaneous, nonintralesional injections of r The Peyronie Disease Society (www.peyroniessociety. r High index of suspicion for emergent etiologies
triamcinolone (50 mg) (2)[C] org)
r Urology Care Foundation (http://www. (Fournier gangrene, penile fracture, priapism,
SURGERY/OTHER PROCEDURES paraphimosis).
r PD urologyhealth.org/urology/index.cfm?article=115) r New data suggests that CCH can significantly
– Plication of the corporal body reduce the symptoms of Peyronie disease.
– Plaque incision with graft interposition
◦ Synthetic (Dacron) REFERENCES
◦ Autologous (buccal mucosa, dermis, tunica 1. Delavierre D, Rigaud J, Sibert L, et al. Symptomatic
albuginea, tunica vaginalis) approach to chronic penile pain. Prog Urol. 2010;
◦ Prepackaged biologic (porcine small intestine 20:958–961.
submucosa) 2. Dickstein R, Uberoi J, Munarriz R. Severe, disabling,
– Penile prosthesis with manual molding, if and/or chronic penile pain associated with
necessary (4)[A] Peyronie’s disease: Management with
subcutaneous steroid injection. J Androl. 2010;31:
445–449.
287
PENIS, CUTANEOUS LESION

Kiranpreet K. Khurana, MD
Edmund S. Sabanegh, Jr., MD
Imaging
BASICS DIAGNOSIS r If locally advanced lesion or internal
lesions/tumors/malignancies suspected
DESCRIPTION HISTORY r Workup for associated abnormalities
r 3 categories: Benign, premalignant, malignant r Age
r May be male genitalia-specific (primary) or r Symptoms: Pain, pruritus, burning, discharge Diagnostic Procedures/Surgery
r Location: Scrotum, glans, shaft, preputial skin, r Cytologic smears: Potassium hydroxide or periodic
associated with other cutaneous lesions or systemic
urethral/bladder lining, other sites acid-Schiff staining for fungal infections
disease (secondary) r Tzanck smear: Herpes, varicella, Molluscum
r May occur at any age r Duration
r Rate of onset: Acute or chronic contagiosum
EPIDEMIOLOGY r Microscopic exam: Scabies, pubic lice, pinworm, and
r Exposures: New bath/laundry soap, lotions, oils,
Incidence other infections
travel (exotic plants, animals, insects, people), r Gram stain, bacterial, and fungal cultures of lesion:
Varies widely by etiology
shared towels/clothes, new medications, industrial,
Prevalence chemical Infections
r Depends on etiology r Sexual history: Sexual partner with lesions r Excisional or incisional biopsy
– Pearly penile papule found in 14–48% of r Trauma Pathologic Findings
postpubertal males r History of systemic diseases or cancers r Depth of lesion
– Genital warts found in 0.1–1% of men r Allergies r Exam of epidermis, dermis, and subcutaneous tissue
RISK FACTORS r Family history and any changes noted
Systemic disease, irritant or allergen, sexual contact, r Previous treatment – Infiltration with other cells or infectious agents
trauma, uncircumcised penis, family history, DIFFERENTIAL DIAGNOSIS
inflammation, infections, medications, local skin PHYSICAL EXAM
r Examine and describe lesion(s): r Common benign lesions (1)[A]
hygiene, obesity, age, smoking
– Elevated, nonelevated – Acrochordon: “Skin tag”
Genetics – Color of lesion – Angiokeratoma of Fordyce: Red papules on penis,
r Reiter syndrome: Associated with HLA-B27
– Morphology of lesion scrotum; ectasia of dermal blood vessels
haplotype – Configuration of lesion (linear vs. serpiginous) – Epidermoid cysts: Most common cysts of genital
r Hailey–Hailey disease: Autosomal dominant
– Degree of margination area. Filled with keratin. Postsurgical after
r Penile cancer: Associated with altered expression of – Degree of firmness circumcision or hypospadias repair
P53, P21, c-ras, myc, Ki-67 genes – Examine genitalia: Circumcised, uncircumcised, – Fordyce spots: Sebaceous glands on genitalia
PATHOPHYSIOLOGY proper placement of foreskin – Pearly penile papule: Small, white/flesh colored,
r Idiopathic, allergic, infectious, autoimmune, – Describe primary lesion(s) (1)[A]: multiple, on glans or corona
inflammatory, systemic, sexual transmission, genetic ◦ Papule: ≤0.5 cm, solid, elevated – Seborrheic keratoses: “Stuck on” appearance
r Lesions appear similar; biopsy often needed for ◦ Plaque: >0.5 cm, solid, elevated – Vitiligo: Patchy depigmentation of skin
◦ Nodule: >0.5 cm, solid, dome-shaped – Zoon balanitis: Nonelevated, erythematous,
diagnosis
◦ Vesicle: ≤0.5 cm, fluid-filled, well- glistening plaques on glans in uncircumcised
ASSOCIATED CONDITIONS circumscribed men. Biopsy to distinguish from SCC in situ
r Lesler–Trélat syndrome: Increase in size and number – Sclerosing lymphangitis: Cordlike lesion of
◦ Bulla: >0.5 cm, fluid-filled, well-circumscribed
of seborrheic keratosis lesions sometimes signaling ◦ Pustule: Vesicle with purulent fluid, coronal sulcus; after vigorous sexual activity
internal malignancy r Allergic dermatitis, eczematous lesion with
well-circumscribed
r Stevens–Johnson syndrome and toxic epidermal ◦ Wheal: Hive, edematous plaque erythema, discharge, excoriations (1)[A]
necrolysis: Prodromal upper respiratory illness – Describe secondary lesion(s) (1)[A]: – Atopic dermatitis: Also known as lichen simplex
followed by life-threatening desquamating lesions ◦ Scale: Flakes on lesion surface chronicus, pruritic, red/scaly lesion on posterior
due to medications, infections, or cancers ◦ Crust/scab: Collected cellular debris scrotum. “Atopic triad” of eczema, allergic
r Psoriasis: Lesions under preputial skin, glans, or ◦ Atrophy: Thinning of skin causing depression rhinitis, asthma
prepuce ◦ Scar: Connective tissue collection – Contact dermatitis: Irritant or allergic. Scaly with
r Reiter syndrome (reactive arthritis): Urethritis, ◦ Cyst: Lesion with wall and lumen crust. Direct cytotoxic effect of irritant or local
arthritis, conjunctivitis. Circinate balanitis ◦ Erosion: Defect with red/moist base type IV hypersensitivity reaction
r Behçet disease: Painful ulcers found in 57–93% of ◦ Fissure: Thin linear defect – Erythema multiforme: Red papules and target
patients, mostly scrotum (90%), but glans and shaft ◦ Ulcer: Deep defect lesions, blisters. Minor or major. Major:
also affected r Full dermatologic exam: Stevens–Johnson syndrome, toxic epidermal
r Inflammatory bowel disease: Arterial thrombosis of necrolysis
– Single or multiple lesions r Papulosquamous disorders, scaly lesion on
penis, penile swelling, and noncaseating – Organ-specific or generalized
granulomas on biopsy; also pyoderma gangrenosum r Lymph node exam erythematous base (2)[C]
r Hailey–Hailey disease: Vesiculobullous rash – Psoriasis: Thick plaque with silver scales. Corona
r Diabetes: Phimosis DIAGNOSTIC TESTS & INTERPRETATION and glans lesions in circumcised, underneath
r HIV: Kaposi sarcoma, seborrheic dermatitis Lab preputial skin in uncircumcised
r Urinalysis, Gram stain, culture – Reiter syndrome: Circinate balanitis, urethritis,
GENERAL PREVENTION r Complete blood count arthritis, ocular, oral, and skin lesions. History of
r Circumcision helpful in some cases r Serum chemistry profile infection with Chlamydia, Gonococcus,
r Proper hygiene r STD screening if suspected Ureaplasma, or GI bacteria
r Safe sex practices – Lichen planus: Idiopathic autoimmune reaction
r Avoid contact with allergens or irritants against basal keratinocytes; small, flat, shiny,
violaceous papules on glans
288
PENIS, CUTANEOUS LESION
– Lichen sclerosis: Pruritic pearly white papules and ◦ Psoriasis: Topical corticosteroids, clobetasol, or FOLLOW-UP
plaques on glans and inner prepuce that scar. Late systemic treatment Patient Monitoring
stage called balanitis xerotica obliterans. Biopsy to ◦ Lichen sclerosis: Biopsy to exclude SCC. Follow patients to monitor response to intervention
exclude SCC Long-term follow-up required. Circumcision and any change in lesion
– Fixed drug eruption: Hypersensitivity reaction to curative. Patient Resources
medication 1–2 wk after starting. Lesions occur in ◦ Pemphigus vulgaris: Oral corticosteroids, r http://www.cdc.gov/std/general/default.htm
same location after challenge immunosuppressive therapy r http://www.aad.org/skin-conditions/dermatology-a-
r Vesicobullous disorders, autoimmune blisters and ◦ Behçet disease: Oral corticosteroids,
to-z
erosions (1)[A] immunosuppressive therapy
◦ Genital warts: Topical 0.5% podofilox, 5%
– Pemphigus vulgaris: Extensive painful blisters and
erosions. Difficult to treat and may be fatal imiquimod, green tea polyphenol extract, 25% REFERENCES
– Bullous pemphigoid: LgG mediated, typically in podophyllin or trichloroacetic acid, cryotherapy,
patients older than 70 yr electrosurgery, laser ablation, surgical excision 1. Choi JM. Common benign dermatologic genital
◦ Balanoposthitis: Circumcision curative lesions: Diagnosis and treatment. AUA Update
– Dermatitis herpetiformis: Associated with celiac
◦ Hidradenitis suppurativa: Skin care, topical Series. 2011;30:367–371.
disease; IgA mediated
– Hailey–Hailey disease: Familial, seen in 20–30s, clindamycin or oral clindamycin and rifampin. 2. Gogstetter D and Mercurio MG. Common penile
blisters in axilla, inguinal, perianal areas Surgical excision for recurrent lesions lesions: Tips to the differential. Med Aspects of
r Noninfectious ulcers, lesions extending to dermis ◦ Fournier’s gangrene: Broad-spectrum Human Sexuality. 2001;1(2):45–51.
intravenous antibiotic coverage and emergent 3. Teichman JM, Sea J, Thompson IM, et al.
(1)[A]
surgical debridement Noninfectious penile lesions. Am Fam Physician.
– Behçet disease: Painful oral and genital ulcers, ◦ Infestation with scabies or pubic lice: 5%
uveitis and other systemic involvement 2010;81(2):167–174.
permethrin cream overnight and repeated a
– Pyoderma gangrenosum: Chronic painful ulcer
week later
associated with Crohn’s, ulcerative colitis,
collagen vascular disease MEDICATION ADDITIONAL READING
– Traumatic ulcers: Direct impact, sexual activity, First Line r Buechner SA. Common skin disorders of the penis.
body piercings, cleansing techniques r Varies with etiology (see above) (3)[B]
r Infections and infestations (1)[A] BJU Int. 2002;90:498–506.
– Low-potency topical corticosteroids for symptoms, r Köhn FM, Pflieger-Bruss S, Schill WB. Penile skin
– STDs: Herpes simplex, syphilis, chancroid, genital eg, Hydrocortisone 1%, 2.5% diseases. Andrologia. 1999;31(suppl 1):3–11.
warts, granuloma inguinale, lymphogranuloma – Specific antibiotics aimed at pathogen
venereum, molluscum contagiosum, Chlamydia, See Also (Topic, Algorithm, Media)
gonorrhea, trichomoniasis Second Line r Balanitis and Balanoposthitis
– Genital warts: HPV 6 and 11.4 variants: r Varies with etiology (3)[B] r Bowen Disease and Erythroplasia of Queyrat
Condylomata acuminate, common warts, flat- – High-potency or oral corticosteroids r Chancroid
topped papules/plaques, Buschke–Löwenstein – Immunosuppressive mediations r Condylomata Acuminata (Venereal Warts)
tumor (giant condyloma). Biopsy for flat-topped – Intravenous antibiotics r Genital Ulcers
and giant condylomas to rule out SCC r Penis, Cancer, General Considerations
– Balanoposthitis: Inflammation of glans and SURGERY/OTHER PROCEDURES
r Excision of lesion(s) and surrounding tissue r Penis, Cutaneous Lesion Image
foreskin in uncircumcised males. Can be due to r Laser ablation, electrocautery, cryotherapy r Penis, Squamous Cell Carcinoma
bacteria, yeast, irritants, trauma
r Circumcision r Phimosis and Paraphimosis
– Cellulitis: Infection of deep dermis and
subcutaneous tissues due to Staphylococcus r More extensive surgeries if neoplastic lesion r Sexually Transmitted Infections (STIs) (Sexually
aureus and Streptococcus pyogenes ADDITIONAL TREATMENT Transmitted Diseases [STDs]), General
– Folliculitis: Infection of hair-bearing follicles
– Furunculosis: “Boil” Radiation Therapy
Limited role in nonneoplastic lesions
– Hidradenitis suppurativa: Painful, firm, red CODES
nodules with draining sinuses; chronic Additional Therapies
inflammation of gland-bearing skin, N/A ICD9
superinfection possible Complementary & Alternative r 078.11 Condyloma acuminatum
– Fournier’s gangrene: Necrotizing fasciitis; Therapies r 608.89 Other specified disorders of male genital
progresses from cellulitis to blisters to N/A organs
foul-smelling necrotic lesions. Surgical emergency r 709.8 Other specified disorders of skin
– Infestation: Pubic lice (Pediculosis pubis) or
scabies (Sarcoptes Scabiei mite); very pruritic ONGOING CARE ICD10
r Neoplastic lesions, see Section I “Bowen disease and r A63.0 Anogenital (venereal) warts
PROGNOSIS r N48.89 Other specified disorders of penis
Erythroplasia of Queyrat,” “Penis, cancer, general r Most cutaneous lesions have a good prognosis but
considerations,” “Penis, squamous cell carcinoma” r R23.8 Other skin changes
should be addressed promptly
r Widespread lesions difficult to control
TREATMENT COMPLICATIONS CLINICAL/SURGICAL
r See “Differential Diagnosis” section
GENERAL MEASURES r If left untreated, lesions may progress locally or
PEARLS
r Common benign lesions (1)[A]: r Do a complete skin exam when genital cutaneous
distally and cause symptoms
– No treatment if asymptomatic lesion found.
– If inflamed or infected, treat with antibiotics r Skin lesions appear similar and excisional or
– Topical corticosteroids or emollient for incisional biopsies are often necessary for diagnosis
symptomatic relief and to rule out cancer.
– Recurrent infections or cosmetic reasons: Excise,
remove with laser or cryotherapy
r Stevens–Johnson syndrome, toxic epidermal P
necrolysis, Fournier gangrene, pemphigus vulgaris
◦ Zoon balanitis: Topical steroids for symptoms, can be life-threatening.
circumcision for cure
◦ Contact dermatitis: Remove offending agent
289
PENIS, SQUAMOUS CELL CARCINOMA

Michael A. Poch, MD

BASICS r Balanitis xerotica obliterans (BXO) r Most malignancies involve the epithelial surface of
r Bowen disease the penis
DESCRIPTION r Chronic inflammation r Subtypes of SCC
r The majority of penile carcinomas are squamous cell r Erythroplasia of Queyrat – Usual, papillary, verrucous, warty, basaloid,
carcinoma (SCC) histology r Giant condylomata sarcomatoid
r Can be SCC in situ (erythroplasia of Queyrat, Bowen r CIS (erythroplasia of Queyrat, Bowen disease of the
r Leukoplakia
disease of the penis, bowenoid papulosis), r Phimosis penis, bowenoid papulosis)
low-grade noninvasive (eg, verrucous carcinoma), or r Verrucous carcinoma, warty carcinoma,
r Premalignant lesions that predispose to the
invasive carcinoma Buschke–Löwenstein tumor, and giant condyloma
r Other rare types of penile cancer histologies include development of invasive SCC of the penis and penile
are terms used to describe infrequently seen rare
adeno- and adenosquamous carcinoma, basal cell cancer
r STIs tumors that may invade locally but do not
carcinoma, melanoma, sarcomas, Kaposi sarcoma, metastasize. Mostly considered to be benign, but
neuroendocrine (small cell) undifferentiated GENERAL PREVENTION malignant degeneration has been reported
carcinoma, sebaceous gland carcinoma, and rarely, r Good penile hygiene r Grade:
metastases from other sites (prostate, bladder, r Newborn circumcision more protective than – Broder’s classification used
colon, kidney) circumcision later in life ◦ Keratinization, nuclear pleomorphism, number
r Inguinal and pelvic lymph nodes are common sites
of mitosis
of metastases – SCC grade classification: Grade strong predictor
DIAGNOSIS for metastatic nodal involvement
EPIDEMIOLOGY
◦ Grade I: Well differentiated, no evidence of
Incidence HISTORY
r Rare in developed countries. Approximately 1,640 r Induration, erythema, nodularity of prepuce, glans, anaplasia
◦ Grade II: Moderately differentiated (<50%
new cases annually in US with approximately 320 and/or shaft
r Bleeding ulcer on glans and/or penile shaft anaplastic cells)
deaths in 2014. ◦ Grade III: Poorly differentiated (>50%
r Hispanics are more commonly affected than whites. r Inguinal adenopathy
r Circumcision is protective. r Penile pain if lesion infected anaplastic cells)
◦ Grade IV: Undifferentiated
r Accounts for up to 10% of cancers in men in South r Patients often deny or ignore symptoms resulting in r Vascular invasion is associated with prognosis
America. presentation at advanced stage
r New onset priapism with a mass suggests a DIFFERENTIAL DIAGNOSIS
Prevalence r BXO
Accounts for 0.4–0.6% of cancers in men metastatic corporal body lesion
r Constitutional symptoms may suggest metastatic r Bowen disease (red, scaly patches on the keratinized
RISK FACTORS disease skin of the penis typically penile shaft)
r Human papilloma virus (HPV) types 16, 18, 31, and r Erythroplasia of Queyrat; shiny red patches on
33 (associated with 45–80%) PHYSICAL EXAM mucosal surfaces (glans and prepuce if
r Presence of foreskin and/or phimosis r Induration, erythema, nodularity of prepuce and/or
uncircumcised)
r Poor hygiene glans r Bowenoid papulosis (multiple flat, warty lesion
r Sexually transmitted disease (STD) r Fungating mass emanating from glans or shaft
sometimes pigmented)
r HIV infection r Bleeding ulcer on glans r Condyloma acuminatum
r Chronic inflammation r Purulence suggests concomitant infection r Condyloma lata
r Lichen sclerosis r Inguinal adenopathy r Extramammary Paget disease
r Smoking – Location, number, unilateral, bilateral, mobility or r Giant condylomata
fixation r Kaposi sarcoma
Genetics r Lichen sclerosis
N/A DIAGNOSTIC TESTS & INTERPRETATION
Lab r Psoriasis
PATHOPHYSIOLOGY r Serum CBC, electrolytes (including calcium), and r Seborrheic keratosis
r HPV-associated DNA and chromosomal changes
liver function studies r Ulcer from STI
r Smegma that forms from desquamated epithelial r Urinalysis, urine culture r Balanitis of Zoon
cells is thought to be a primary instigating factor in
penile cancer; good hygiene and circumcision limit Imaging
r US or MRI of penis for local tumor (T) staging
smegma accumulation
r Penile SCC spreads by a reliable pattern: Superficial r CT/MRI of pelvis and inguinal regional to evaluate
inguinal lymph nodes to deep inguinal lymph nodes for lymphadenopathy and metastatic disease
to pelvic lymph nodes Diagnostic Procedures/Surgery
r Biopsy; punch, excisional, or incision
r Shave biopsy will not give adequate local tumor (T)
staging
290
PENIS, SQUAMOUS CELL CARCINOMA
r Metastatic disease r Mohs FE, Snow SN, Larson PO. Mohs micrographic
TREATMENT – TIP surgery for penile tumors. Urol Clin N Am. 1992;
– Clinical trial 19:291–304.
GENERAL MEASURES – Supportive/palliative care r Ornellas AA, Seixas AL, Marota A, et al. Surgical
r Treatment typically based on grade and stage of treatment of invasive squamous cell. J Urol.
primary tumor (1) Therapies 1994;151(5):1244–1249.
r Palpable lymphadenopathy r Pagliaro LC, Williams DL, Daliani D, et al.
N/A
– Fine-needle aspiration (FNA) Neoadjuvant paclitaxel, ifosfamide and ciplatin
– 6-wk course of oral antibiotics followed by repeat chemotherapy for metastatic penile cancer. A phase
physical exam ONGOING CARE II Study. J Clin Oncol. 2010;3851–3857.
r Pettaway CA, Pisters LL, Dinney CP, et al. Sentinel
MEDICATION PROGNOSIS
First Line r Depends on T-stage and nodal status lymph node dissection for penile carcinoma: The MD
r Tis/Ta lesions r Overall survival for men with node-negative disease Anderson Cancer Center experience. J Urol.
1995;154:1999–2003.
– Topical: Imiquimod 5% cream applied for 5 d/wk is 80–90%.
for 4–6 wk or 5-FU 5% cream every other day for r 20–30% of men with inguinal lymph node See Also (Topic, Algorithm, Media)
4–6 wk metastasis will have pelvic lymph node metastasis r Balanitis Xerotica Obliterans (BXO)
– Pelvic nodal metastasis have a 10% 5-yr survival r Bowen Disease and Erythroplasia of Queyrat
Second Line
N/A r When applicable, ILND associated with improved r Genital Ulcer Algorithm
disease-specific survival r Penis, Bowenoid Papulosis
SURGERY/OTHER PROCEDURES r Penis, Lesion, General
r Primary lesions COMPLICATIONS
r Infections r Penis, Leukoplakia
– Tis/Ta lesions
◦ Laser ablation: CO2 or neodymium r Erosion of lymphadenopathy into femoral vessels r Penis, Mass (Corporal Body Mass)
◦ Circumcision (preputial lesions) r Partial penectomy and total penectomy r Penis, Squamous Cell Carcinoma Algorithm
◦ Wide local excision, Mohs surgery, glansectomy, – Urethral stenosis r Penis, Squamous Cell Carcinoma Images
glans resurfacing – Loss of erective function r Reference Tables: TNM: Penis Cancer
– T1 grade 1–2 r ILND
◦ Mohs, wide local excision – Infection (43%)
◦ External beam radiation therapy – Seroma (24%) CODES
◦ Brachytherapy (with interstitial placement) – Wound breakdown (16%)
◦ Laser ablation – Lymphedema ICD9
– T1 grade 3–4 or ≥T2 – Vascular injury r 176.0 Kaposi’s sarcoma, skin
◦ Partial penectomy (with intraoperative frozen r 187.4 Malignant neoplasm of penis, part unspecified
section) FOLLOW-UP
r 233.5 Carcinoma in situ of penis
◦ Traditionally 2-cm margin is required Patient Monitoring
◦ Total penectomy with perineal urethrostomy r Close inspection for local recurrence usually every
ICD10
r Regional nodes (2) 3 mo for 5 yr (frequency depends on grade and r C46.0 Kaposi’s sarcoma of skin
– Sentinel node biopsy stage) r C60.9 Malignant neoplasm of penis, unspecified
◦ High false-negative rate (25%) r Consider imaging for ambiguous findings on
r D07.4 Carcinoma in situ of penis
– Nonpalpable nodes physical exam
◦ High-risk T2 or G3 and intermediate-risk cancer Patient Resources
with lymphovascular invasion—inguinal node National Cancer Institute. http://www.cancer.gov/ CLINICAL/SURGICAL
dissection (ILND)
– Unilateral palpable nodes <4 cm
cancertopics/types/penile PEARLS
◦ FNA or ILND if high risk r Grade and stage associated with prognosis FNA of
◦ 6 wk of oral antibiotics less recommended REFERENCES palpable nodes is preferred over 6-wk course of oral
– Palpable nodes ≥4 cm antibiotics.
◦ Standard or modified ILND 1. National Comprehensive Cancer Network. Penile r Modified ILND is associated with improved
◦ Possible preoperative EBRTchemotherapy Cancer Version 1.2013. http://www.nccn.org/
professionals/physician gls/pdf/penile morbidity.
r Pelvic lymph nodes r Bulky inguinal lymph node metastases should be
– Pelvic Lymph node dissection if >2 inguinal nodes 2. Johnson TV, Hsiao W, Delman KA, et al. Extensive
inguinal lymphadenectomy improves overall 5-year managed by multimodal therapy consisting of
positive on frozen section at the time of ILND neoadjuvant systemic chemotherapy followed by
survival in penile cancer patients: Results from the
ADDITIONAL TREATMENT surveillance, epidemiology, and end results surgical resection ( ± radiotherapy).
Radiation Therapy program. Cancer. 2010;2960–2966
r External radiation to primary lesion or inguinal
lymph nodes
r Typical doses are 50–60 Gy over 4–6 wk ADDITIONAL READING
r Interstitial brachytherapy for clinically indicated
r Burgers JK, Badalament RA, Drago JR. Penile cancer:
lesions
Clinical presentation, diagnosis, and staging. Urol
Additional Therapies Clin N Am. 1992;19:247–256.
r Neoadjuvant chemotherapy r McDougal WS, Kirchner FK Jr, Edwards RH, et al.
– TIP: Ifosfamide, paclitaxel, cisplatin Treatment of carcinoma of the penis: The case for
r Adjuvant for high-risk disease primary lymphadenectomy. J Urol. 1986;136:38–41.
– Bilateral inguinal nodal disease
– Pelvic lymph node involvement
– Extranodal extension P
– >4 cm nodes
291
PENIS, TRAUMA
Brad Figler, MD

BASICS r Injury to scrotum, testicle, urethra, or rectum may
Lab
accompany penile trauma r Urinalysis
DESCRIPTION r Pelvic fracture r Urine culture if infection suspected
Acute traumatic injury to the penis may be due to r CBC
blunt trauma (penile fracture to the erect penis), GENERAL PREVENTION
r Military services are developing devices for ballistic r For delayed presentation with abscess formation,
penetrating injury (stab wound, firearm, improvised
explosive device [IED], or amputation), degloving protection of the external genitalia culture abscess
r Protective equipment during contact sports
(MVC, power takeoff injury), burns, human and animal Imaging
bites, or constriction with reduced blood flow r Proper safety training for industrial machinery r Suspicion of urethral injury warrants evaluation with
r Proper instruction in patients prescribed penile retrograde urethrography to evaluate for the
EPIDEMIOLOGY
constriction devices for the management of erectile presence of injury and injury location.
Incidence dysfunction r Penile fracture:
r Penetrating trauma to genitals is relatively rare in
r Cautious sexual intercourse – MRI or US useful if rupture of superficial dorsal
civilian setting vein suspected
r Gunshot wounds and penetrating injuries make up
– Cavernosography historically described
40–60% of battlefield urologic injuries during times DIAGNOSIS r Scrotal ultrasound or CT scan may be useful if
of war; likely due to lack of protection to external suspicious for associated injuries
genitalia HISTORY
r In the battlefield, use of fragmentation devices r Type of injury
r Magnitude of force transmitted Cystoscopy: Used to assess for urethral injury
(mines, IED) and high-velocity missiles cause a
r Type of object in penetrating injury
significantly greater percentage of genitourinary Pathologic Findings
injuries to involve the penis and genitalia r Determine species of animal in bite injuries
N/A
r Penile fracture infrequently seen in US, with r In cases of amputation history of method of
preservation of amputated portion if available DIFFERENTIAL DIAGNOSIS
incidence of 1 in 175,000 hospital admissions r Burn
r Penile fractures are common in Iran where it is a – Method of penile preservation r Constriction injury (band or other device placed
social practice (Taghaandan) – Self-inflicted amputation may occur in psychotic
states around base of penis) can include medically
Prevalence r Timing, severity, progression of pain, swelling, approved devices
N/A r Fournier gangrene
discoloration of penis, scrotum, and genitalia
r Circumstances and timing of penile constriction r Human or animal bite
RISK FACTORS
r Occupational (military, farming, heavy machinery) r Laceration
device
r Bicycling is leading sport associated with injury to r Intercourse-related trauma to the penis may be r Penetrating injury
the external genitalia reported as a “pop” or “snap” associated with r Penile “fracture”
swelling and immediate penile detumescence r Rupture of superficial dorsal vein
Genetics
r Intercourse-related trauma with “pop,” swelling but r Penile amputation
N/A
no immediate penile detumescence is suspicious for
PATHOPHYSIOLOGY rupture of superficial dorsal vein
r Transfer of kinetic energy to the penis is most
r Associated abdominal pain, nausea, emesis TREATMENT
devastating due to penetrating mechanisms
r Blunt injuries to the flaccid phallus are much less PHYSICAL EXAM GENERAL MEASURES
r Pattern of erythema, ecchymosis r Ensure the overall stability of the patient (1)
likely to cause any damage
r Penis is very resistant to injury in flaccid state; in r Assess for injuries of adjacent organs r Recognize and appropriately manage injuries to the
erect state, bending injury can lead to rupture of r Blood at meatus concerning for urethral injury external genitalia
tunica albuginea (“penile fracture”) r Size of laceration, if present r Maintain high index of suspicion for urethral injury
– Typically results from impact with partner’s pubic r Transilluminate any palpable scrotal mass and assess with retrograde urethrogram or
symphysis or perineum – Hydrocele will transilluminate cystoscopy
r Redundant blood supply to the penis (dorsal, – Hematocele or tumor will not transilluminate r Association for the Surgery of Trauma (AAST) organ
cavernosal, and bulbourethral arteries and r Penile fracture: injury scale classification (2):
superficial skin vasculature) all protect from ischemic – Penile swelling, ecchymosis with possible palpable – I: Cutaneous laceration/contusion
loss of the penis defect in corpora cavernosa – II: Buck’s fascia (cavernosum) laceration without
r Penile strangulation – “Eggplant sign”: Hematoma deep to Buck’s fascia tissue loss
– Constricts blood flow, leading to edema, ischemia, r “Butterfly hematoma”: Hematoma deep to Colles’ – III: Cutaneous avulsion; laceration through
constricted micturition fascia glans/meatus; cavernosal/urethral defect <2 cm
– Pediatric patients: Hair or string causes r Penile strangulation: – IV: Partial penectomy; cavernosal or urethral
constriction – Penile edema, ischemic changes, gangrene defect >2 cm
– Adult patients: Penile constricting devices – Suprapubic fullness secondary to urethral – V Total penectomy
designed for sexual enhancement r For burns see section on “Burns, External Genitalia,
constriction
r Pelvic fracture can lead to avulsion of the crura of r Gunshot wounds: Search for associated injuries and Perineum”
the corpora cavernosa with subsequent dysfunction especially injured femoral vessels, urethral injury, or
r Associated injuries are common due to the proximity
rectal injury.
to other pelvic organs
r Degloving injuries: Loss of superficial penile tissue
(skin and Dartos fascia)
292
PENIS, TRAUMA
MEDICATION r Avulsions (degloving injury): 3. Waxman S, Beekley A, Morey A, et al. Penetrating

First Line – Exposed surface should be immediately covered trauma to the external genitalia and Operation Iraqi
r Appropriate fluid resuscitation based on severity of with sterile saline-soaked gauze and area Freedom. Int J Impot Res. 2009;21:145–148.
injury re-examined in 24 hr to assess extent of injury 4. Wessells H, Long L. Penile and genital injuries. Urol
r Broad-spectrum antibiotic prophylaxis for all – Penile shaft can be covered with split-thickness Clin North Am. 2006;33:117–126.
penetrating genital injuries skin graft 5. Lewis EA, Pigott MA, Randall A, et al. The
r See section on Bites to penis (animal and human) – Scrotum can be covered with meshed development and introduction of ballistic
for appropriate antibiotic coverage split-thickness skin graft protection of the external genitalia and perineum.
r Tetanus prophylaxis for all penetrating injuries r Gunshot wounds: J R Army Med Corps. 2013;159(suppl 1):i15–i17.
– If wound contaminated, then conservatively
Second Line débride and allow healing by secondary intention
N/A – If wound clean, tunical margins can be ADDITIONAL READING
SURGERY/OTHER PROCEDURES reapproximated with absorbable suture; urethral
r Surgical exploration is required in almost all cases of injuries should be identified and repaired r Avery LL, Scheinfeld MH. Imaging of penile and
r Human bites: scrotal emergencies. Radiographics. 2013;33(3):
penile injury (3–5)
– Exploration typically performed through a – Should not be closed; antibiotic therapy includes 721–740.
oral dicloxacillin or cephalexin r Garcı́a Gómez B, Romero J, Villacampa F, et al. Early
circumferential skin incision at coronal margin
– Deeper injuries require penoscrotal or perineal treatment of penile fractures: Our experience. Arch
ADDITIONAL TREATMENT Esp Urol. 2012;65(7):684–688.
incisions
r Hemostasis is achieved by closure of corporal Radiation Therapy r Morey AF, Brandes S, Dugi DD, et al. Urotrauma:
N/A AUA Guideline (https://www.auanet.org/common/
defects due to fracture, gunshot, or stab wound
r The urethra should be directly inspected for Additional Therapies pdf/education/clinical-guidance/Urotrauma.pdf
appropriate identification of any urethral injuries N/A Accessed August 21, 2014)
which need to be identified and repaired Complementary & Alternative See Also (Topic, Algorithm, Media)
r Glans injuries are repaired by debridement and Therapies r Bites to Penis (Animal and Human)
reduction in the size of the glans while maintaining N/A r Burns, External Genitalia and Perineum
its overall configuration r Penis, Strangulation
r Primary skin closure is appropriate unless significant r Penis, Trauma Algorithm
contamination of wound is noted
ONGOING CARE r Penis, Trauma Images
r Penile amputation PROGNOSIS r Scrotum and Testicle, Trauma
– Preservation of the amputated phallus r Most penile injuries can be successfully repaired r Taghaandan
– “2-bag method” (penis wrapped in saline gauze with low rate of erectile dysfunction when r Urethra, Trauma (Anterior and Posterior)
in inner bag; ice in the outer bag) immediate reconstruction is performed.
– Cold ischemia >24 hr is acceptable if it allows r Delayed repair or nonoperative approach to penile
transfer to a specialized center for microvascular injuries may lead to penile curvature and erectile
replantation dysfunction.
CODES
– Even at normal temperatures, replantation 16 hr r Even after penile amputation, with successful
after injury has been successful replantation patients can have sensation with ICD9
r 878.0 Open wound of penis, without mention of
– Technique for microvascular replantation: erectile function.
◦ Single-layer urethral repair over catheter complication
◦ Tunica albuginea reanastomosis (5-0 PDS) COMPLICATIONS r 959.13 Fracture of corpus cavernosum penis
◦ Dorsal vein and dorsal artery microvascular r Decreased sensation r 959.14 Other injury of external genitals
reanastomosis (to preserve skin perfusion and r Impotence
venous drainage; 0-0 nylon) r Penile curvature ICD10
◦ Dorsal nerve reanastomosis for sensation, r Skin loss (particularly with nonmicrovascular penile r S31.20XA Unspecified open wound of penis, initial
10-0 nylon replantation) encounter
– If amputated segment cannot be reattached: r Urethral stricture r S39.840A Fracture of corpus cavernosum penis,
◦ Close corporal bodies with 4-0 PDS r Urethral stricture or fistula initial encounter
◦ Spatulate urethral meatus to tunica r Wound infections r S39.94XA Unspecified injury of external genitals,
◦ Can gain penile length later by cutting initial encounter
suspensory ligament, defatting pubis, or FOLLOW-UP
considering reconstruction with free flap Patient Monitoring
r Penile fracture: r Patient monitoring is required for detection for CLINICAL/SURGICAL
– Circumcising incision via subcoronal approach complications. PEARLS
with evacuation of hematoma r Traumatic injury may result in erectile dysfunction r Penile injuries have high likelihood of associated
– Close cavernosal injuries with absorbable suture requiring additional therapy. injuries to the external and internal pelvic organs.
(5-0 PDS) r Urethral injury must be excluded.
Patient Resources
– Explore for urethral injuries and, if present, repair r With penile fracture there is 10–22% associated
Urology Care Foundation. http://www.urologyhealth.
(5-0 PDS)
r Penile strangulation: org/urology/index.cfm?article=12 urethral injury; surgical repair is associated with
– Incision of offending agent if possible (cut hair, lower rates of erectile dysfunction or curvature.
r Early surgical exploration and repair allows excellent
string, bands, soft rings with scissors) REFERENCES
– Solid constricting devices: Attempt removal with preservation of function and cosmesis.
1. Morey AF, Metro MJ, Carney KJ, et al. Consensus r Penile fracture characteristically causes ecchymosis,
lubrication; distal penile compression with manual
pressure may decrease tissue edema long enough on genitourinary trauma: External genitalia. BJU swelling, an associated popping or cracking sound
to remove foreign body Int. 2009;94:507–515. during intercourse followed by immediate
– Some devices may require ring cutters, operative 2. American Association for the Surgery of Trauma.
http://www.aast.org/library/traumatools/
detumescence. P
drills, industrial drills, various saws; protect phallus
with tongue depressors, malleable retractors injuryscoringscales.aspx#penis (Assessed August
– Suprapubic tube may be needed for bladder 21, 2014)
decompression
293
PEYRONIE DISEASE
Irvin H. Hirsch, MD
BASICS r ED: Occurs in 20% men with PD (1)[C]
TREATMENT
– Comorbidities: Diabetes, hypertension,
DESCRIPTION dyslipidemia, smoking, coronary disease GENERAL MEASURES
r An idiopathic, localized connective tissue disorder r PD is found in 10% men with ED r A small percent of men will undergo spontaneous
with increased collagen deposition in the tunica – Urethral stricture may coexist remission.
albuginea, resulting in a fibrous plaque that leads to r Surgery is not a common 1st-line option but
pain and penile angulation (1)[C] GENERAL PREVENTION
ultimately offers definitive resolution of curvature
r Plaque (2)[C]: Avoidance of penile trauma during intercourse
and deformity.
– Most commonly dorsal plaque on side of penis to r The lack of randomized, placebo-controlled trials
which curvature directed DIAGNOSIS makes evaluation of efficacy and comparison
r Penile angulation may cause dyspareunia and even between any medical therapies for PD difficult.
preclude sexual intercourse HISTORY r Patients most likely to respond to medical therapy:
r First described by French surgeon François Gigot de r Distress and depression resulting from Peyronie
Young patients in acute phase. (1,2)[C]
Peyronie disease r All medical therapies provide varying decrease in
r Synonym(s): Acquired penile curvature, chronic r Duration and onset of symptoms, history of erectile
pain, curvature, or plaque size; complete resolution
inflammation of the tunica albuginea (CITA), penile trauma. Severe pain or snap or popping during of curvature is uncommon.
induration, Induratio penis plastica intercourse
r Pain: With or without erection; during intercourse MEDICATION
EPIDEMIOLOGY r Penis: Induration; degree and direction of penile First Line
Incidence r Oral therapy (2):
r Affects males 40–70 yr old, with 0.4–3.2% angulation; hourglass deformity; lateral indentation;
shortening; sensory loss, partner’s perception – No therapy has proven more or less effective than
incidence (1)[C] r Erections: Quantify rigidity; sufficient for intercourse another
r 3–7% men 40–70 yr old have PD (3)[C] – Vitamin E (tocopherol):
r History of Dupuytren contractures or hand surgery
r Mean age: 53 ◦ 800–1,000 U/d PO in divided doses
for deformity ◦ Antioxidant effects; may cause bleeding
Prevalence
PHYSICAL EXAM – Potassium aminobenzoate (Potaba):
Estimated 388 in 100,000 men (1,2)[C] r Penile exam noting plaque size, tenderness and ◦ 3 g PO q6h
RISK FACTORS location ◦ May increase monoamine oxidase, decrease
r Inherent tendency to produce abnormal fibrous r Autophotography may be helpful in assessing serotonin, or increase utilization of oxygen by
tissue degree of angulation tissues; Expensive, GI side effects
r Erectile trauma or injury to the tunica albuginea of – Examine the palmar fascia for associated – Colchicine:
the penis may incite fibrotic reaction from repetitive Dupuytren contracture ◦ 0.6 mg PO q8h
microvascular injury and healing ◦ May decrease collagen synthesis and increase
r Intracorporal injection therapy and oral DIAGNOSTIC TESTS & INTERPRETATION collagenase activity
pharmacotherapy for ED not implicated as risk (2)[C] Lab – Pentoxifylline:
N/A ◦ Growth factor blocker and anti-inflammatory
Genetics ◦ 400 mg PO BID
Association with Dupuytren contracture (in 9–39%) Imaging
No imaging necessary for diagnosis/medical therapy – Other reported oral therapy: Tamoxifen,
and HLA-B7 antigens (1)[C] acetyl-L-carnitine,
Diagnostic Procedures/Surgery r Intralesional therapy (2):
PATHOPHYSIOLOGY r Preoperative assessment of stretched penile length
r Idiopathic (1,2)[C] – Collagenase clostridium histolyticum (CCH (4)[C]:
r Origin of initial inflammatory process that leads to and sensory threshold (Biothesiometry) ◦ Breaks down collagen, promotes remodeling
r Preoperative Doppler US with intracavernous
fibrosis, calcification, elastic fiber alterations, and ◦ FDA approved for curvature deformity of the
vasoactive challenge: Assess plaque size, penis due to the presence of a plaque in PD.
plaque formation in tunica albuginea unknown, but
calcification, vascular hemodynamics of penis and Restricted distribution through Risk Evaluation
likely predisposing genetic alteration with inciting
erectile curvature and Mitigation Strategy (REMS) due to the risks
trauma r Preoperative intracavernous injection of vasoactive
r Acute phase: of serious adverse reactions, including penile
agent and genital sexual stimulation with fracture and other serious penile injury
– Occurs in 1st 6–18 mo
measurement of erectile curvature ◦ A cycle consists of 2 CCH injection procedures
– Proliferation of fibroblasts, myofibroblasts, and r Photographic confirmation by the patient of degree
collagen deposition and a penile modeling procedure
– Pain with erections, slight penile curvature, and of curvature is often helpful ◦ Induce a penile erection (eg, intracavernosal
nodule formation Pathologic Findings injection of 10–20 mcg of alprostadil)
– Medical therapy most effective in acute phase Excess collagen deposition and inflammatory infiltrate ◦ With the erection, identify and mark the target
r Chronic phase: is found in the tunica albuginea area in the Peyronie plaque
◦ The penis should be in a flaccid state before
– Remodeling of connective tissue into a dense DIFFERENTIAL DIAGNOSIS
fibrotic plaque r Cancer: Primary or metastatic to corpora injecting CCH. Inject 0.58 mg CCH into the
– Stable plaque size, penile curvature possibly target plaque of a flaccid penis once on each of
r Chordee: Usually associated with hypospadias
causing ED, erections less painful 2 days, 1–3 days apart
r Kelami syndrome: Fibrosis of the corpus spongiosum
r Natural history: Minority of patients (10%) will have
that limits expansion of the ventral corpora
spontaneous regression, yet most patients will not
cavernosa
develop disease significant enough to require r Penile fracture (hematoma)
surgery
294
PEYRONIE DISEASE
◦ Perform a manual penile modeling procedure r Inflatable penile prosthesis placement: 5. Levine LA and Constabile RA. Is intralesional
1–3 days after the 2nd injection of each – Candidates: Significant erectile dysfunction, verapamil effective therapy for peyronie’s disease?
treatment cycle. For each plaque causing the severe curvature J Urol. 2012;188:704–706.
curvature deformity, up to 4 treatment cycles – Modeling: 6. Hellstrom WJ, Kendirci M, Matern R, et al.
may be administered. Each treatment cycle may ◦ When prosthesis placement alone fails to Single-blind, multicenter, placebo controlled,
be repeated at approximately 6-wk intervals. If straighten penis, manual modeling is parallel study to assess the safety and efficacy of
the curvature deformity is <15 degrees after the recommended, with good outcomes intralesional interferon α-2b for minimally invasive
1st, 2nd, or 3rd treatment cycle, or if further ◦ Forcible manual manipulation of penis treatment for Peyronie’s disease. J Urol. 2006;
treatment is not indicated, then subsequent (“modeling” over inflated prosthesis) 176:394–398.
treatment cycles should not be administered – Complications: Infection (1–3%), erosion (<5%), 7. Nelson JN, Diblasio C, Kendirci M, et al. The
◦ 10,000 U in 0.25 cm3 per injection mechanical malfunction (5–10%), urethral injury chronology of depression in men with Peyronie’s
– No other intralesional therapy has proven more or disease. J Sex Med. 2008;5:1985–1990.
less effective than another
– Verapamil (5)[C]: Radiation Therapy
◦ 12 injections (10 mg/10 mL) given once every Mixed results reported; not recommended
ADDITIONAL READING
2–4 wk Additional Therapies
◦ Calcium blockage inhibits extracellular transport Extracorporeal shockwave therapy: No good Abern MR, Larsen S, Levine LA. Combination of penile
of collagen; increases collagenase activity in placebo-controlled studies to document efficacy; traction, intralesional verapamil, and oral therapies for
vitro; must commit to full course studies report decreased pain after ESWL therapy (2) Peyronie’s disease. J Sex Med. 2012;9:288–295.
◦ Applicable for young patients in acute phase
Complementary & Alternative See Also (Topic, Algorithm, Media)
– Interferon α2a or 2b (6)[C]: r Chordee
◦ 5 × 106 U biweekly for 3–6 mo Therapies
r Penile traction therapy may have utility when r Erectile Dysfunction/Impotence (ED)
◦ Inhibits fibroblast proliferation, diminishes
combined with other therapies r Penis, Curvature and/or Pain
collagen production, increases collagenase r Carnitine supplementation: Mixed results
◦ Applicable for young patients in acute phase r Penis and Corporal Body Mass
◦ Flu-like side effects r Peyronie Disease Image
– Intralesional corticosteroids no longer ONGOING CARE
recommended due to local side effects
Second Line PROGNOSIS CODES
N/A See “Pathophysiology–Natural History”
COMPLICATIONS ICD9
SURGERY/OTHER PROCEDURES r PD can impact quality of life and cause relationship r 607.84 Impotence of organic origin
r Indications: Curvature or erectile dysfunction that
r 607.85 Peyronie’s disease
precludes intercourse (2)[C] difficulties
r Depression can be associated r 608.89 Other specified disorders of male genital
r Patient must be in chronic phase with stable
organs
painless plaques FOLLOW-UP
r Preoperative US with intracavernous vasoactive ICD10
Patient Monitoring
challenge is useful to evaluate vasculature and r Patients should be re-examined frequently to assess r N48.6 Induration penis plastica
anatomy of penis, as described above disease status and response to therapy. r N52.9 Male erectile dysfunction, unspecified
r Plication procedures: r Recent studies suggest up to 48% of men with PD r N53.12 Painful ejaculation
– Candidates: Longer penis, mild, distal curvature, have clinically relevant signs of depression and
good erectile function should be considered for mental health screening.
– Relative to corporal plaque, plication of opposite (7) CLINICAL/SURGICAL
aspect of corpora cavernosa with a 12–24-point PEARLS
plication. A relaxing incision of plaque is rarely Patient Resources
r AUA Urology Care Foundation. http://www. r Diagnosis of Peyronie disease is exclusively based on
required
– Complications/side effects: Hematoma, stitch urologyhealth.org/urology/index.cfm?article=115 history and physical exam.
r The Peyronie Disease Society. r Patients with mild curvature and no evidence of
erosion/granuloma, penile shortening
r Plaque excision with grafting: www.peyroniessociety.org erectile dysfunction should be observed.
– Candidates: Shorter penis, proximal plaque, severe r New data suggests that CCH can significantly
curvature, hourglass deformity, lateral indentation REFERENCES reduce the symptoms of Peyronie disease.
and good erectile function r The ideal candidate for CCH is having Peyronie
– Plaque incised/excised and corporotomy defects 1. Hellstrom WJ, Bivalacqua TJ. Peyronie’s disease: disease for at least 12 mo, has stable disease, and a
grafted with small intestine submucosal graft Etiology, medical, and surgical therapy. J Androl. curvature of 30 degrees or greater.
(Surgisis, Cook Biotech) 2000;21(3):347–354.
– Complications: Loss of sensitivity, infection, 2. Wespes E, Eardley I, Giuliano F, et al. Guidelines on
hematoma, shortening, de novo venoocclusive penile curvature. Eur Urol. 2012;62:543–552.
erectile dysfunction 3. Sommer F, Schwarzer U, Wassmer G, et al.
Epidemiology of Peyronie’s disease. Int J Impot Res.
2002;14:379–383.
4. Gelbard M, Goldstein I, Hellstrom WJ, et al. Clinical
efficacy, safety and tolerability of collagenase
clostridium histolyticum for the treatment of
Peyronie disease in 2 large double-blind,
randomized, placebo controlled phase 3 studies.
J Urol. 2013;190(1):199–207.
P
295
PHEOCHROMOCYTOMA

BASICS r Tumors arise from chromaffin cells of neural crest
Lab
origin in the sympathetic nervous system r Plasma or urinary-fractionated metanephrines are
DESCRIPTION r Rule of 10 (10% bilateral, 10% extra-adrenal, 10% the best screening tests:
r Pheochromocytoma is a rare catecholamine-
familial, 10% malignant) no longer accurate: – Chromaffin cells metabolize NE to NMN and EPI
producing tumor arising chromaffin cells in the – 10% of sporadic tumors bilateral, 50% of familial to MN
adrenal medulla tumors bilateral – Fractionated metanephrines refers to MN and
r Paragangliomas refer to lesions found in – Extra-adrenal up to 20% NMN
extra-adrenal sites arising from the sympathetic – Hereditary 20–30% – Both plasma metanephrines and urine
nervous system – Malignant up to 5% in adrenal metanephrines are acceptable options; current
pheochromocytoma, 33% for extra-adrenal pheo recommendations do not recommend either test
ALERT r Histologic determination of malignancy is not over the other
Hypertensive crisis and life-threatening possible; diagnosed based on metastases – Plasma metanephrines have a high sensitivity
complications can be seen with pheochromocytoma. r Tumors contain enzymes necessary to convert (96–100%) but poor specificity, particularly in
tyrosine to catecholamines older patients (77–89%) (2)
EPIDEMIOLOGY r Clinical manifestations secondary to the release of r Urine test: 24-hr urine for NE, EPI, MN, NMN, and
Incidence these catecholamines, NE, and EPI VMA:
r 3–4 cases per million population yearly in US (1) r Bladder pheochromocytomas account for <1% of – VMA highly specific (95%) but not sensitive (64%)
– Average age in sporadic cases: 40–50 yr bladder tumors and <1% of pheochromocytomas: – If urinary values are >3 times normal, then
– Average age in hereditary cases: <40 yr – Can present with micturition syncope proceed to localize the tumor
– Partial cystectomy is the treatment of choice. – If urinary values are <3 times normal and
Prevalence
r 0.005–0.1% of the general population Transurethral excision is contraindicated because suspicious, then repeat the test and proceed to
it may precipitate a hypertensive crisis pharmacologic testing
– 01–0.2% of adult hypertensive patients r Plasma metanephrine testing
r >50% of catecholamine-producing tumors
ASSOCIATED CONDITIONS – No caffeine prior
undiagnosed until death r MEN IIA
– No acetaminophen for 5 days prior
r MEN IIB
RISK FACTORS – Rest supine for 20 min prior to draw
r Familial tumors associated with MEN multiple r Von Recklinghausen syndrome – MN >96 pg/mL, NMN >130 pg/mL, or total
endocrine neoplasia (MEN) syndromes: r Von Hippel–Lindau disease metanephrines >200 abnormal (2)
– MEN IIA (Sipple syndrome): Pheochromocytoma r Pharmacologic testing:
GENERAL PREVENTION
(50%), medullary carcinoma of the thyroid (50%), r No specific preventive measures exist. – Stimulation and suppression tests are generally
and parathyroid adenoma (25%): r Screening of patients with familial not utilized
– MEN IIB (MEN III): Pheochromocytoma (50%), – Provocative tests dangerous, with several reported
medullary carcinoma of the thyroid (100%), pheochromocytomas allows earlier diagnosis and
deaths
ganglioneuromatosis, multiple mucosal neuromas treatment. r Clonidine suppression test:
of eyelids, lips, tongue – Centrally acting α 2 -agonist that suppresses
r Neurofibromatosis Type I (von Recklinghausen DIAGNOSIS sympathetic outflow
syndrome): 1% has pheochromocytoma; 5% of – Normally results in decreased BP and lower levels
patients with pheochromocytoma have HISTORY of plasma catecholamines
r Most patients symptomatic
neurofibromatosis. – Draw blood for NE/EPI before and 3 hr after
r Von Hippel–Lindau disease (retinal cerebellar – Paroxysmal HTN with severe headache, drenching, administering clonidine (0.3 mg/70 kg)
hemangioblastomatosis): 10% with perspiration, and palpitations – Plasma catecholamines remain the same or
pheochromocytoma – Additional symptoms include nervousness, tremor, elevated in patients with pheochromocytoma
pallor, panic, pain in the chest and abdomen,
Genetics nausea, fever, and flushing Imaging
r Germ-line mutations specific to each syndrome r Localization studies should be started only if clinical
r Syndromes are all autosomal dominant PHYSICAL EXAM evidence for the tumor’s existence is strong
r Hypertension: Most common sign
– Men IIA: Codon 634 of RET protein (hereditary predisposition or signs and symptoms
– Men IIB: Mutation in intracellular domain of RET – Sustained HTN: Children and MEN II with very high MN/NMN)
protein – Paroxysmal HTNL dramatic attacks, 3–4 times a r CT or MRI for initial localization:
– Von Hippel–Lindau: VHL tumor suppressor gene week – Neither CT nor MRI is recommended above the
on chromosome 3p35 – Sustained hypertension with superimposed other
– Von Recklinghausen syndrome: Neurofibromatosis paroxysms: 50% incidence – Pheochromocytoma characteristically hyperintense
r Fine tremors, pallor, perspiration
type 1 gene of T2-weighted images
– Familial nonsyndromic paraganglioma: Succinate r Palpable tumor (rare) – Scan abdomen and pelvis 1st
dehydrogenase gene (1) r Accelerated hypertensive retinopathy: Papilledema, – If no tumor found, scan chest and neck
exudate, A-V knicking – Metastases in long bones may be missed
r Raynaud phenomenon – Cannot reliably differentiate between types of
r Hyperhidrosis adrenal tumors
296
PHEOCHROMOCYTOMA
r Iodine123 -labeled MIBG scintigraphy is more specific SURGERY/OTHER PROCEDURES REFERENCES

for localization of pheo: r Preoperative adrenergic blockade is mandatory
– Provides both anatomic and functional r Volume expansion with high sodium diet 1. Mittendorf E, Evans DB, Lee JE, et al.
characterization of the tumor (>5,000 mg/daily) recommended on day 2 or 3 of Pheochromocytoma: Advances in genetics,
– Concentrated in sympathomedullary tissue α-blockade due to catecholamine-induced volume diagnosis, localization, and treatment. Hematol
through the catecholamine pump contraction Oncol Clin North Am. 2007;21(3):509–525.
– Useful to evaluate for residual or multiple tumors, r Laparoscopic surgical removal of the tumor is the 2. Lender JW, Pacak K, Walther MM, et al.
and MEN syndromes preferred treatment for tumors <10 cm (3): Biochemical diagnosis of pheochromocytoma:
Diagnostic Procedures/Surgery – Initial dissection aimed at early ligation and Which test is best? JAMA. 2002;287:1427–1434.
division of the adrenal vein before manipulation of 3. Vargas HI, Kavoussi LR, Bartlett DL, et al.
ALERT the tumor Laparoscopic adrenalectomy: A new standard of
Biopsy of adrenal mass should not be performed – Malignant pheochromocytoma is slow growing care. Urology. 1997;49:673–678.
until pheochromocytoma has been ruled out. ◦ Resection should be attempted
◦ Large masses can be debulked for palliation
Pathologic Findings
ADDITIONAL READING
r Sporadic tumors are solitary, well-circumscribed, and
Radiation Therapy r Karagiannis A, Mikhailidis DP, Athyros VG, et al.
encapsulated.
r Malignant pheo cannot be differentiated from An option for malignant pheochromocytoma Pheochromocytoma: An update on genetics and
Additional Therapies management. Endocrine-Related Cancer. 2007;
benign pheo by exam of primary tumor. Malignant
r Malignant pheochromocytoma 14:935–956.
pheo is defined by metastases. r Lenders JW, Eisenhofer G, Mannelli M, et al.
– Iodine131 -MIBG radiation is the most effective
DIFFERENTIAL DIAGNOSIS treatment after surgery Phaeochromocytoma. Lancet. 2005;366:665–675.
r Essential HTN r Pacak K, Eisenhofer G, Ahlman H, et al.
r Renovascular disease – Combination chemotherapy with
cyclophosphamide, vincristine, and dacarbazine: Pheochromocytoma: Recommendations for clinical
r Anxiety, tension states, psychoneurosis practice from the 1st International Symposium. Nat
50–60% partial response
r Hyperthyroidism – Local radiation or chronic blockade with Clin Pract. 2007;3:92–102.
r Paroxysmal tachycardia metyrosine for symptomatic disease See Also (Topic, Algorithm, Media)
r Menopause r Adrenal Mass
r Vasodilating headaches (migraine and cluster) r Adrenal Mass, Algorithm
Therapies
r Acute hypertensive encephalopathy No recommended complementary or alternative r Multiple Endocrine Neoplasia (MEN I and II)
r Nephrologic diseases therapies exist. r Pheochromocytoma Image
r Cocaine, amphetamines
ONGOING CARE CODES

TREATMENT PROGNOSIS
r 10-yr survival for nonmalignant tumors: >80% ICD9
GENERAL MEASURES
Surgical removal of the tumor is the only definitive r 5-yr survival for malignant pheo: 34–60%: 227.0 Benign neoplasm of adrenal gland
method of treatment. – Currently no cure for malignant pheo
ICD10
COMPLICATIONS r D35.00 Benign neoplasm of unspecified adrenal
MEDICATION
r Retinopathy and nephropathy from persistent HTN gland
First Line r D35.01 Benign neoplasm of right adrenal gland
r Appropriate antihypertensive drugs to manage HTN, r Catecholamine-nduced cardiomyopathy
control symptoms, and prepare for surgery – Cardiomyopathy reversible with α-blockade and r D35.02 Benign neoplasm of left adrenal gland
r α-Adrenergic blocking agents essential before β-methylparatyrosine
surgery: – All patients should have preop cardiac evaluation
– Phenoxybenzamine 0–40 mg BID or TID including echocardiogram CLINICAL/SURGICAL
r Cerebral vascular accident PEARLS
– Prazosin 1–10 mg BID
r β-Blocking agents contraindicated in the absence of r Hypertensive encephalopathy
r Hydration and adequate α-adrenergic blockade
established α-blockade: r Renal insufficiency
r Hemorrhagic necrosis preop is mandatory.
– Use only for concomitant cardiac arrhythmias or r Laparoscopic adrenalectomy treatment of choice
persistent tachycardia r Dissecting aneurysm
– Blockade of peripheral vasodilatory β-adrenergic r Ischemic enterocolitis with early control and ligation of adrenal vein.
receptors results in unopposed α-adrenergic r Neurogenic pulmonary edema
stimulation with resultant hypertension
– Can precipitate cardiomyopathy and pulmonary FOLLOW-UP
edema due to chronic catecholamine excess Patient Monitoring
r Because of uncertainties about which tumors are
Second Line
See “Additional Therapies” malignant, measure urinary or plasma
catecholamines 1–2 wk postoperatively and
annually for 5 yr.
r BP should be monitored every month for the
1st 6 mo, then every 6 mo thereafter.
r 25% of patients have persistent HTN after surgery.
Patient Resources
www.pheochromocytoma.org
P
297
PHIMOSIS AND PARAPHIMOSIS

Michael A. Poch, MD

BASICS r Penile cancer
Lab
r Balanitis (inflammation of the glans) Usually not necessary unless symptoms of urinary tract
DESCRIPTION r Posthitis (inflammation of the prepuce) infection (UTI) or sexually transmitted infection (STI)
r Phimosis (preputial stenosis) is the inability to r Balanoposthitis are present.
retract the foreskin. r Balanitis xerotica obliterans (BXO)
r Can be seen in children and adults Imaging
r Diabetes mellitus Not usually performed
– Physiologic (congenital) phimosis: Foreskin
(prepuce) is usually not retractile in a newborn. GENERAL PREVENTION Diagnostic Procedures/Surgery
The majority can be retracted by 3–5 yr of age r Good hygiene Physical exam is usually all that is necessary
– Pathologic (acquired) phimosis: The prepuce r Don’t prematurely manipulate the foreskin
Pathologic Findings
cannot be retracted when previously possible or it r Circumcision N/A
has never been retractile and is associated with
symptoms and/or complications DIFFERENTIAL DIAGNOSIS
r Paraphimosis DIAGNOSIS r Phimosis:
– The prepuce is retracted, left in position causing – Physiologic vs. pathologic
HISTORY – Trapped penis occurs when a dense cicatricial scar
vascular engorgement of the glans preventing r Was foreskin previously retractile?
reduction. traps the penis under the prepubic or scrotal skin
r Recent urethral manipulation (Foley catheter
after neonatal circumcision.
EPIDEMIOLOGY placement, cystoscopy) – BXO
Incidence r Circumcision status r Paraphimosis:
r Phimosis r Dysuria and/or other voiding symptoms – Penile edema
– 10% nonretractile at age 3–5 r Penile discharge – Postcircumcision cicatrix
– <1% nonretractile at puberty r Cracking or bleeding from the foreskin – Hair/thread tourniquet:
r Paraphimosis r Ballooning of the foreskin with voiding ◦ Hair or thread wraps around a child’s penis and
– 0.7% of uncircumcised boys r Postvoid dribbling causes penile edema or strangulation
r Penile pain r Balanitis
Prevalence
N/A
PHYSICAL EXAM
RISK FACTORS r Evaluate for penile abnormalities such as TREATMENT
r Poor hygiene
hypospadias, chordee, webbed penis
r Forced or traumatic retraction of foreskin r Local irritation and redness GENERAL MEASURES
r In the elderly male undergoing bladder
r Indwelling catheter r Appearance of foreskin:
r Chronic balanitis catheterization, failure to replace the foreskin to its
– Normal skin color normal reduced position may result in paraphimosis
r Genital piercings – Erythema and inguinal adenopathy (1,2).
Genetics – Penile discharge r Paraphimosis
N/A – Circumferential white discoloration – Manual reduction should be attempted 1st prior
– Urethral meatus cannot be visualized to medication or surgical procedure
PATHOPHYSIOLOGY – Crack in skin with attempted retraction – 1st attempt manual compression for 5 min to
r Physiologic phimosis: – Severe scarring or BXO reduce edema and reposition foreskin
– The foreskin is naturally adherent to the glans in – Smegma (normal finding) – Manual reduction technique:
infants. r Paraphimosis:
◦ Place thumbs on the glans while stabilizing the
– Glandular secretions and keratin debris (smegma) – Marked edema of inner prepuce distal to the foreskin in between the 2nd and 3rd fingers.
and intermittent erections facilitates separation of constricting band ◦ Apply pressure on the thumbs while attempting
preputial skin from glans – Ulcerations if chronic to pull the foreskin over the glans
– This is best simply observed; the newborn foreskin – Evaluate glans for ischemia/necrosis r Physiologic phimosis:
does not require manipulation or retraction. – Glans tenderness
r Pathologic phimosis: – Observation and reassurance
– Glans firm with flaccid penile shaft
– Chronic irritation, often due to poor hygiene, leads – Rule out hair or foreign body in a circumcised male
to sclerosis of the preputial opening
◦ Premature manipulation and trauma leads to
scarring of the delicate prepuce.
◦ Inadequate circumcision or postcircumcision
care allows constriction of the circumcision line
r Paraphimosis
– Retraction of the prepuce and leaving it in place
behind the glans leads to vascular engorgement
of the glans and subsequent inability to reduce
the prepuce
298
PHIMOSIS AND PARAPHIMOSIS

First Line ONGOING CARE r Choe JM. Paraphimosis: Current treatment options.
r Physiologic phimosis:
– Topical steroids (0.05% betamethasone) may PROGNOSIS Am Fam Physician. 2000;62:2623–2626.
r 95% of physiologic phimosis resolves by puberty, r Hamdy FC, Hastie KJ. Treatment for paraphimosis:
allow atraumatic retraction (3)
– Parents should be taught to never force back the with the majority retractile by the age of 5 The ‘puncture’ technique. Br J Surg. 1990;77(10):
r Circumcision is curative. 1186.
foreskin but gradually retract it over time.
r Pathologic phimosis r Hutcheson JC. Male neonatal circumcision:
COMPLICATIONS
– Topical steroid r Complications of phimosis: Indications, controversies and complications. Urol
– Aggressive retraction can cause worsening of – UTI Clin North Am. 2004;31:461–467.
preputial scarring – Postvoid dribbling See Also (Topic, Algorithm, Media)
r Paraphimosis: – Chronic inflammation with recurrent balanitis or r Circumcision, Adult Considerations
– Immediate manual reduction should be attempted balanoposthitis r Circumcision, Pediatric Considerations
– Pain medication (eg, morphine, Demerol) or local – Calculi or pearls from smegma r Penis, Cancer, General Considerations
anesthesia (lidocaine without epinephrine, – Penile carcinoma (rarely) r Phimosis and Paraphimosis Image
infiltration, or penile block) may be necessary r Complications of paraphimosis
Second Line – Glans necrosis
r Paraphimosis r Complications of circumcision:
– Hemorrhage
CODES
– Hyaluronidase injection
– If manual reduction fails, a dorsal slit or incision of – Persistent adhesions
constricting band is indicated – Skin bridges ICD9
– Recurrent paraphimosis may need definitive – Inadequate skin removal
r 607.1 Balanoposthitis
circumcision to prevent recurrence. – Insufficient skin removal
– Inclusion cyst
r Phimosis: – Cicatrix/concealed penis r N47.1 Phimosis
– Meatal stenosis r N47.2 Paraphimosis
– Preputioplasty (dorsal slit with transverse closure)
for patients wanting to maintain foreskin FOLLOW-UP r N48.1 Balanitis
– Circumcision is curative; should be generally Patient Monitoring
avoided in children unless for indications such as r Proper hygiene of uncircumcised males
recurrent UTI, vesicoureteral reflux, or superficial r Foreskin reduction after procedures CLINICAL/SURGICAL
infections
Patient Resources
PEARLS
– Circumcision is contraindicated in newborns with r In most cases physiologic phimosis will resolve.
penile deformities (hypospadias, chordee, webbed N/A
r Aggressive retraction of phimosis can cause
penis, etc.) as foreskin may be needed for possible
reconstructive surgery REFERENCES preputial scarring.
r Manual reduction of paraphimosis should be
r Paraphimosis
– Dorsal or ventral slit urgently treats narrowing and 1. Jordan GH, McCammon KA. Surgery of the penis attempted 1st prior to surgical intervention.
preserves the foreskin and urethra. In: Wein AJ, ed. Campbell-Walsh
– Immediate circumcision is occasionally necessary Urology. 10th ed. Philadelphia, PA: Elsevier; 2011.
2. Pohlman GH, Phillips JM, Wilcox DT. Simple
ADDITIONAL TREATMENT method of paraphimosis reduction revisited: Point
Radiation Therapy of technique and review of the literature. J Pediatr
N/A Urol. 2013;9:104–107.
Additional Therapies 3. Palmer LS, Palmer JS. Efficacy of topical
N/A betamethasone for treating phimosis: A
Complementary & Alternative comparison of two treatment regimens. Urology.
2008;72:68–71.
Therapies
r Paraphimosis
– Compression wraps
– Topical osmotic agents
299
PNEUMATURIA (GAS IN URINE)

DIAGNOSTIC TESTS & INTERPRETATION r Antibiotic therapy for acute diverticulitis

BASICS Lab – Ciprofloxacin 500 mg PO BID with metronidazole
r Urine analysis
500 mg PO TID [A]
DESCRIPTION r Urine culture
Passage of gas in the urine r Complete blood count – Amoxicillin clavulanate 875 mg/125 mg PO BID
– Ampicillin sulbactam 3 g IV q6h
EPIDEMIOLOGY r Comprehensive metabolic profile
– Piperacillin tazobactam 3.375 g IV q6h
Incidence Imaging – Ticarcillin clavulanate 3.1 g IV q6h
This is a rare disorder. r Computerized tomography scan identifies air or – Ceftriaxone 1 g IV q24h with metronidazole
RISK FACTORS 500 mg IV q8h
orally administered contrast in the bladder, colonic
r Diverticular disease SURGERY/OTHER PROCEDURES
and bladder wall thickening, abscess (1)[A]
r Other disease of the colon r Barium enema (definitive: 25%; suggestive: 100%) r Emphysematous UTI
r Crohn disease – Percutaneous management of purulent material
r Advanced age Diagnostic Procedures/Surgery and gas
r Colonoscopy may directly visualize the fistula, and is
r Diabetes – Percutaneous nephrostomy placement for
essential to inspect the remainder of the colon emphysematous pyelonephritis
PATHOPHYSIOLOGY r Cystoscopy may visualize the actual fistula, or – Emergent nephrectomy is associated with very
r Most commonly there is an abnormal connection identify suggestive localized inflammation and high mortality
between the enteric and urinary system secondary edema r Enterovesical fistula
to inflammation Pathologic Findings – Enterovesical fistulae typically do not close
r Much less common in gas-producing bacterial r Diverticular disease with abscess spontaneously
urinary tract infection (UTI) (Escherichia coli, r Colon malignancy – The portion of bowel responsible for the fistula is
Klebsiella pneumoniae) seen most frequently in r Crohn disease excised in a 1-stage procedure with resection and
elderly diabetic females r Bladder malignancy primary anastomosis
ASSOCIATED CONDITIONS r Radiation or surgical induced fistula – Ureteral stent placement may be performed
r Diverticulitis of sigmoid colon r UTI preoperatively to allow identification of the ureter
r Colon cancer intraoperatively
r Crohn disease DIFFERENTIAL DIAGNOSIS – Resection of the bladder is rarely necessary
r Emphysematous cystitis – A small defect in the bladder can be managed
r Diabetes
r Emphysematous pyelonephritis with suture repair, indwelling Foley catheter, and
r Iatrogenic (radical prostatectomy, radiation)
r Urethral rectal fistula closed suction drain in the pelvis
GENERAL PREVENTION r Vesical enteric fistula
r Colon health
r Prompt treatment of UTI
TREATMENT
DIAGNOSIS GENERAL MEASURES
r Antibiotic therapy
HISTORY r Percutaneous drainage of gas and purulent material
r Pneumaturia r Relief of urinary obstruction
r Dysuria
r Irritative urinary symptoms MEDICATION
r Fecaluria First Line
r Parenteral antibiotic therapy for all patients with
PHYSICAL EXAM
r Depends upon etiology gas-producing UTI [A]
r May have no significant findings if acute diverticular – Ampicillin sulbactam 1.5 g IV q6h
– Ticarcillin clavulanate 3.1 g IV q6h
abscess has resolved – Piperacillin tazobactam 3.375 g IV q6h
r In emphysematous cystitis there is frequently fever
– Meropenem 500 mg IV q8h
and abdominal tenderness – Imipenem 500 mg IV q6h
– Doripenem 500 mg IV q8h
300
PNEUMATURIA (GAS IN URINE)
REFERENCES
ONGOING CARE CODES
1. Jaret TW, Vaughan ED Jr. Accuracy of computerized
PROGNOSIS tomography in the diagnosis of colovesical fistula ICD9
r Gas-producing UTI (2)[A] secondary to diverticular disease. J Urol. 1995; r 596.1 Intestinovesical fistula
– Parenteral antibiotic therapy is successful in the 153:44–46. r 599.0 Urinary tract infection, site not specified
majority of patients with gas limited to bladder 2. Huang JJ, Tseng CC. Emphysematous r 599.84 Other specified disorders of urethra
– Patients with gas in the upper urinary tract are at pyelonephritis: Clinicoradiological classification,
increased risk of mortality and require management, prognosis and pathogenesis. Arch ICD10
percutaneous drainage with parenteral antibiotics Intern Med. 2000;160:797–805. r N32.1 Vesicointestinal fistula
– Gas in the perinephric space and pararenal 3. Bartus CM, Lipof T, Sarwar CM, et al. Colovesical r N39.0 Urinary tract infection, site not specified
tissues are at increased risk of mortality fistula: Not a contraindication to elective r R39.89 Other symptoms and signs involving the
r Diverticular abscess and enteric vesical fistula laparoscopic colectomy. Dis Colon Rectum. genitourinary system
– Patients have an excellent prognosis after 2005;48:233–236.
elective resection of the disease bowel segment
CLINICAL/SURGICAL
– In many cases this can be performed ADDITIONAL READING
laparoscopically (3)[B] PEARLS
Golabek T, Szymanska A, Szopinski T, et al. r Pneumaturia is the distinct sensation by the patient
COMPLICATIONS
r Patients with inflammatory disorders such as Crohn Enterovesical fistulae: Aetiology, imaging, and of passage of air from the urinary tract.
may have complex and recurrent fistulae management. Gastroenterol Res Pract. 2013; r Pneumaturia should be considered secondary to an
r Patients with fistulae following radiation therapy 2013:617967. enteric vesical fistula until proven otherwise.
may have impaired healing and experience See Also (Topic, Algorithm, Media) r The CT scan finding of air in the bladder is abnormal
recurrence r Cystitis, Emphysematous and of high diagnostic value in the evaluation of the
r Fistula, Enterovesical patient with suspected pneumaturia and is likely to
FOLLOW-UP r Inflammatory Bowel Disease (Ulcerative Colitis and reveal associated pathology.
Patient Monitoring r The most common cause of pneumaturia is
r Management of associated illness Crohn disease), Urologic Considerations
r Prompt treatment of disease flare r Pneumaturia (Gas in Urine) Image diverticular disease.
r Urinary Tract Infection (UTI), Adult Female
Patient Resources r Urinary Tract Infection (UTI), Adult Male
NA
301
POLYCYSTIC KIDNEY DISEASE, AUTOSOMAL DOMINANT

Megan T. Bing, MD
ASSOCIATED CONDITIONS r CT and MRI methods have greater sensitivity

BASICS r Abdominal wall hernia compared to US for detecting cysts <1 cm and in
r Cardiac valvular abnormalities evaluating individual cysts for hemorrhage or
DESCRIPTION r Colon diverticula malignancy
r Inherited disease characterized by bilateral r Hepatic cysts from 29–73% – Hemorrhagic renal cysts are fairly common
development of renal and extrarenal cysts with r Splenic and pancreatics in a small percentage – On MRI uncomplicated cysts resemble simple
variable progression to ESRD, requiring either r Intracranial aneurysms cortical cysts
dialysis or transplantation ◦ Homogeneous low signal intensity on T1 and
r Autosomal dominant polycystic kidney disease – Only screen if patient has previous rupture high signal intensity on T2
– Saccular “berry” aneurysm of cerebral arteries in r Echocardiography
(ADPKD) is the most common form of genetic kidney
3–13%
disease leading to chronic kidney disease r Pancreatic cysts – Evaluate for mitral prolapse
EPIDEMIOLOGY r Polycystic liver disease Diagnostic Procedures/Surgery
Incidence Cytogenetic analysis: May be needed when FH or
r 1–2:1,000 live births GENERAL PREVENTION imaging is equivocal
– Occurs worldwide and in all races Genetic and prenatal counseling
Pathologic Findings
– 4.4% of patients with renal replacement therapy r Gross pathology
have ADPKD DIAGNOSIS – Bilaterally enlarged kidneys with multiple colored
Prevalence and fluid-filled cysts
r 1:400 to 1:1,000 HISTORY r Histopathology
r Typical presentation is 30- to 50-yr-old patient with
– Renal volume increases 5.27% per year as cysts – Multicystic renal dysplasia in cortex and medulla
grow HTN, hematuria, flank pain – Sclerosis
r Calculi may also be present
RISK FACTORS r Family history: 3 generations with cystic renal DIFFERENTIAL DIAGNOSIS
r Having a family member with ADPKD r Patients >10 yr old
disease
– Inherited in autosomal dominant fashion – Simple cysts
– Ages range from infant to elder PHYSICAL EXAM ◦ Simple cyst not common <30 yr of age
r HTN, hypertensive retinopathy ◦ >4 simple cysts in each kidney is rare
Genetics r Heart murmur
r 1:1,000 carry mutant gene – Localized renal cystic disease
r Autosomal dominant with 100% penetrance r Enlarged kidneys on abdominal exam – Medullary sponge kidney
r Genetically heterogenous: 2 genes – Bilateral parapelvic cysts
DIAGNOSTIC TESTS & INTERPRETATION – Autosomal recessive polycystic kidney disease
– PKD1 (16p13.3) (Type 1 ADPKD) Lab (ARPKD)
◦ Accounts for 85% of cases r Serum Cr may be elevated – Tuberous sclerosis complex
◦ More severe disease r BUN may be elevated – Von Hippel–Lindau disease
◦ Encodes polycystin-1 (PC1) r Hematuria on UA – Medullary cystic disease
– PKD2 (4q21) (Type 2 ADPKD) – In up to 50% and often the initial presenting – Orofaciodigital syndrome type I
◦ Accounts for 15% – Autosomal dominant polycystic liver disease: Liver
symptom
◦ Less severe disease lesions predominate but also have renal cysts;
◦ Encodes polycystin-2 (PC2) Imaging
r Imaging is the main diagnostic tool genetic testing may be needed to differentiate
PATHOPHYSIOLOGY r Patients <10 yr of age
r Plain abdominal radiographs: Limited in early-stage
r Loss of PC1 or PC2 results in inability of tubular cells – Contiguous PKD1–TSC2 deletion syndrome
disease; later may indicate displacement of organs
to maintain polarity, increased rate of proliferation – ARPKD
with or without calcifications
and apoptosis, increased cellular secretion and r US – Meckel–Gruber syndrome
remodeling of extracellular matrix (ECM)
– With unknown genotype, the presence of 3 or
– Epithelial cell growth
more (unilateral or bilateral) renal cysts
– ECM remodeling
establishes the diagnosis in 15–39 yo, 2 or more
– Na+ -K+ ATPase found apically which leads to
cysts in each kidney is sufficient if aged 40–59 yr,
abnormal flow of fluid
and 4 or more cysts in each kidney is required for
individuals ≥60 yr
– Conversely, <2 renal cysts in at-risk individuals
aged ≥40 yr are sufficient to exclude the disease
302
POLYCYSTIC KIDNEY DISEASE, AUTOSOMAL DOMINANT
3. Harris PC, Torres VE. Polycystic kidney disease. Ann

TREATMENT ONGOING CARE Rev Med. 2009;60:321–337.
4. Torres VE, Harris PC. Autosomal dominant
GENERAL MEASURES PROGNOSIS polycystic kidney disease: The last 3 years. Kidney
r Increase fluid intake r Renal function usually normal until the 4th decade
Int. 2009;76:149–168.
r Coordinated care with nephrology of life
r Protein-restricted diet is controversial r Disease diagnosed in utero carries a poor prognosis
r Neurosurgery consult if intracranial aneurysm is r Patients on RRT carry the same or better prognosis ADDITIONAL READING
present (1) than non-ADPKD patients on RRT
r Risk factors for progression: r Grantham JJ. The etiology, pathogenesis, and
MEDICATION – Genetic factors (PKD1 vs. PKD2) treatment of autosomal dominant polycystic kidney
First Line – Hypertension disease: Recent advances. Am J Kidney Dis.
r Hypertension: 1996;28:788–803.
– Early onset of symptoms including proteinuria and
– Angiotensin-converting enzyme (ACE) inhibitors r Helal I, Reed B, Schrier RW, et al. Emergent early
hematuria
(ie, captopril, enalapril, lisinopril) or – Male gender markers of renal progression in autosomal-dominant
– Angiotensin II receptor blockers (ARBs) such as – Increased kidney size (kidney size is greater with polycystic kidney disease patients: Implications for
telmisartan, losartan, irbesartan, and candesartan PKD1 mutations) prevention and treatment. Am J Nephrol.
r Hyperlipidemia: Statin – Increased left ventricular mass index 2012;36:162–167.
– Dipstick detectable proteinuria r Steinman TI. Polycystic kidney disease: A 2011
Second Line
r Somatostatin (2) – Low birth weight update. Curr Opin Nephrol Hypertens. 2012;21:
r Inhibitors of mTOR – Decreased renal blood flow 189–194.
– Increased urinary sodium excretion See Also (Topic, Algorithm, Media)
SURGERY/OTHER PROCEDURES – Increased LDL cholesterol r Acquired Renal Cystic Disease
r Renal replacement therapy (2,4) – Increased plasma copeptin (surrogate marker for r Polycystic Kidney Disease, Autosomal Dominant
– Renal transplantation vasopressin)
– Hemodialysis/peritoneal dialysis r With more advanced renal disease, ACE inhibitors Images
r Percutaneous cyst aspiration r Polycystic Kidney Disease, Autosomal Recessive
and ARBs can cause hyperkalemia or worsen renal r Renal Cysts (Intrarenal, Peripelvic, and Parapelvic)
– <200 mL failure. Monitoring of serum chemistries is essential
r When screening family members with a family r Renal Mass
– Sclerosing agent should be used
r Cyst decortication—typically for pain with large r Retroperitoneal Mass and Cysts
history of ADPKD data suggests that individuals
dominant cysts(s) >40 yr with a family history but without renal cysts
– 95–100% success rate for relieving pain are unlikely to develop ADPKD
– Initial improvement in lowering HTN, but not
COMPLICATIONS
CODES
sustained r Cerebral hemorrhage
r Nephrectomy ICD9
r Chronic kidney disease
– Disabling symptoms due to massively enlarged r 585.9 Chronic kidney disease, unspecified
r Renal cell carcinoma risk is not elevated; but when
kidneys r 753.13 Polycystic kidney, autosomal dominant
– Worsening or development of ventral (abdominal present is often bilateral and multicentric
wall) hernias – Often present with fever ICD10
r Proteinuria r N18.9 Chronic kidney disease, unspecified
– Nephrectomy may be considered before renal
transplant r Chronic pain r Q61.2 Polycystic kidney, adult type
◦ Suspected malignancy – Nephrolithiasis in 25% of patients
◦ Recurrent infection r Pyelonephritis
◦ Extension of the polycystic kidney into the r Cyst rupture CLINICAL/SURGICAL
potential pelvic surgical transplant location r Rarely portal HTN, cholangiocarcinoma PEARLS
ADDITIONAL TREATMENT FOLLOW-UP r Lipid soluble antibiotics are needed for treatment of
Radiation Therapy Patient Monitoring renal cyst infection.
N/A r Follow BUN and Cr r Abdominal pain and flank pain is common and may
Additional Therapies r Prenatal testing for ADPKD is clinically available if be due to infection, nephrolithiasis, or cyst
r Infection: Lipid soluble antibiotic (sulfamethoxazole the mutation has been identified in an affected hemorrhage.
and trimethoprim or ciprofloxacin) family member or if linkage has been established in r Cyst decortication is useful for large painful cysts.
r Chronic pain: Avoid NSAIDs the family r Patients with a personal or family history of cranial
r A small, randomized, placebo-controlled trial found Patient Resources bleed need surveillance by neurosurgery.
that intramuscular octreotide slowed progression of r www.pkdcure.org r Acute cyst rupture usually best treated with pain
renal cystic disease r www.pkdinternational.org control and observation.
Therapies
N/A REFERENCES
1. Agarwal MM, Hemal AK. Surgical management of
renal cystic disease. Curr Urol Rep. 2011;12:3–10.
2. Caroli A, Perico N, Perna A, et al. Effect of
long-acting somatostatin analogue on kidney and
cyst growth in autosomal dominant polycystic
kidney disease (ALADIN): A randomised,
placebo-controlled, multicentre trial. Lancet.
2013;382(9903):1485–1495. P
303
POLYCYSTIC KIDNEY DISEASE, AUTOSOMAL RECESSIVE

Kymora Scotland, MD, PhD
T. Ernesto Figueroa, MD, FAAP, FACS
r Clinical course (hepatobiliary): Imaging

BASICS – Development of hepatosplenomegaly, portal HTN, r Renal ultrasound is best initial test (4):
extrahepatic bile duct dilation, gall bladder – Prenatal: Enlarged kidneys, oligohydramnios,
DESCRIPTION enlargement, occasional choledochal cyst normal liver, no bladder filling (more reliable after
r A group of inherited disorders involving cystic formation, and hepatic dysfunction 30-wk gestation)
dilatation of the renal collecting ducts and varying – Liver failure ultimately develops later in childhood – Infancy: Enlarged reniform kidneys, cortical
degrees of biliary dysgenesis and periportal fibrosis echogenicity
r Formerly known as infantile polycystic kidney disease ASSOCIATED CONDITIONS
r Ehlers–Danlos syndrome – Older children: Macrocysts (<2-cm diameter),
r An overlap in the spectrum of renal and liver decreased size, medullary echogenicity,
r Potter syndrome
involvement precludes use of the Blyth and hepatosplenomegaly
Orkenden classification (perinatal, neonatal, GENERAL PREVENTION – Loss of corticomedullary differentiation: The
infantile, and juvenile subtypes) Genetic counseling for families with proven ARPKD kidneys typically have a homogeneous appearance
r Best grouped as polycystic disease of newborn and (linkage studies with polymorphic DNA markers) r CT may be used in confusing cases: More sensitive
young infant, polycystic disease of childhood, and to inhomogeneity of cysts
congenital hepatic fibrosis Diagnostic Procedures/Surgery
DIAGNOSIS r Renal biopsy
EPIDEMIOLOGY
HISTORY r Liver biopsy
Incidence r Age of the patient:
r Most common inherited cystic renal disease in Pathologic Findings
infancy and childhood – Other cystic renal disorders rarely present in the r Renal
r Incidence: 1–2 in 10,000 live births pediatric population: – Bilateral enlarged kidneys with reniform shape
r Males = females ◦ Younger, more respiratory and renal issues;
– Pinpoint opalescent dots on capsule (cortical
r Severely affected neonates usually die hours after ◦ Older, more hepatobiliary issues
collecting duct cysts)
– ∼1/3 are diagnosed before age 1; 1/3 between – Cut surface with sponge-like quality due to linear
birth; overall survival is much improved if they live ages 1 and 20 yr; and 1/3 beyond 20 yr
beyond the neonatal period r Prenatal care distention of nephrons in radial pattern
– Normal pelvicaliceal system and renal vessels
Prevalence – Characteristic changes on prenatal US after week – In neonates, kidneys at least 10% of body weight
r Commonly discovered in perinatal period; can 30, abnormal uterine growth measurements, – Microscopic pathology: Fusiform cysts (<2 mm +
present early in childhood or adolescence maternal α-fetoprotein levels, amniocentesis diameter) lined by low columnar or cuboidal
r Survival: For patients living to 1 mo: 86% alive at results, history of stillbirth epithelium
1 yr, 67% alive at 15 yr r Birth history:
– No normal parenchyma
– Difficult delivery suggests possible flank or r Hepatobiliary
RISK FACTORS
r Definite risk factor: Heterozygous parents abdominal mass – All children with ARPKD have lesions in the
r The cause of ARPKD remains poorly understood r Family history:
periportal areas of the liver
r Genetic and/or epigenetic factors may promote – Normal parents with a normal renal US suggests – Can have hepatosplenomegaly at presentation;
recessive disease frequently normal
aberrant epithelial hyperplasia that causes cystic r Medical history:
expansion of the collecting ducts and fluid – Elongated, hyperplastic biliary ducts with ectasia
accumulation – For older patient, may suggest evolution of disease – Periportal fibrosis with normal hepatocellular
r Less is known about hepatobiliary changes; r Present illness: histology
– Polydipsia, polyuria, fatigue, unexplained fever,
however, epithelial hyperplasia may have role DIFFERENTIAL DIAGNOSIS
hematuria, pyuria, edema, difficult feeding, recent r Autosomal dominant polycystic kidney disease
Genetics GI bleed or vague GI symptoms
r Associated with mutations of the PKHD1 gene (1–3) (ADPKD)
r Autosomal recessive, heterozygotes unaffected, PHYSICAL EXAM r Bardet–Biedl syndrome
r HTN, respiratory rate, temperature r Caroli disease
gene locus at chromosome 6p21 r General appearance:
r Gene located at 6p21 produces a protein called r Chondrodysplasia syndrome
– Potter phenotype, pallor r Congenital hypernephronia nephromegaly with
fibrocystin which has been identified at the renal r Palpable kidneys: Hepatosplenomegaly
collecting ducts and the hepatic bile duct; possible tubular dysgenesis
r Extremities: Joint contractures, edema r Glutaric aciduria type II
involvement in renal cilia function
r Multiple allelism is likely responsible for variable r Ivemark syndrome
phenotypic presentation r Jeune syndrome
r Offspring of heterozygotes: 25% risk of disease, Lab
r Electrolytes, blood chemistry, urine analysis, urine r Juvenile nephronophthisis
50% carriers culture r Meckel–Gruber syndrome
r CBC (exclude anemia, hypersplenism) r Renal dysplasia
PATHOPHYSIOLOGY
r Clinical course (renal): r Coagulation profile r Trisomy 9 and 13
– Severely affected neonates commonly die of r Liver function tests (usually normal) r Zellweger syndrome
pulmonary complications hours after birth r High maternal α-fetoprotein (associated with
– Patients surviving the neonatal period have a ARPKD), high amniotic fluid release (possible
better prognosis; they can have some renal correlation)
maturation
– Progressive renal cyst enlargement, fibrosis, and
renal insufficiency
– Eventually, most develop renal failure
– Later presentation: Less severe renal component
304
POLYCYSTIC KIDNEY DISEASE, AUTOSOMAL RECESSIVE
r Older children: Palpable flank mass, abdominal 4. Levine E, Hartman DS, Mellstrup JW, et al. Current
TREATMENT mass, Potter phenotype, GI bleed, hematuria, pyuria, concepts and controversies in imaging of renal
polydipsia, polyuria, HTN, nonspecific GI complaints, cystic disease. Urol Clin North Am. 1997;24:
GENERAL MEASURES edema, growth retardation, fatigue, infection. Will 523–543. (Level III evidence)
r No specific therapy for ARPKD. Treatments are eventually develop renal failure and HTN 5. Roy S, lon MJ, Trompeter RS, et al. Autosomal
supportive r All patients with ARPKD have liver involvement. recessive polycystic kidney disease: Long-term
r Pulmonary issues 1st priority initially; survival better Those with severe ARPKD have mild congenital outcome of neonatal survivors. Pediatr Nephrol.
with advances in perinatology hepatic fibrosis and those with severe congenital 1997;11:302–306. (Level II-3 evidence)
r Goals: Delay progression to renal failure, liver hepatic fibrosis have milder ARPKD
failure, and portal HTN COMPLICATIONS
r Avoid nephrotoxic mediations r Renal: Renal failure (concentrating defect with ADDITIONAL READING
r Social support and respite care
polydipsia and polyuria), HTN, anemia, occasional Brinkert F, Lehnhardt A, Montoya C, et al. Combined
MEDICATION metabolic acidosis, hyponatremia, osteodystrophy, liver-kidney transplantation for children with
growth failure, UTI autosomal recessive polycystic kidney disease
First Line r Hepatobiliary: Hepatosplenomegaly, bleeding
r Thiazides to help urine-concentrating defect (ARPKD): Indication and outcome. Transpl Int.
r Treatment of renal osteodystrophy with vitamin D esophageal varices, portal thrombosis, 2013;26(6):640–650.
hypersplenism, choledochal cysts, bacterial
and phosphate binders See Also (Topic, Algorithm, Media)
r Recombinant human erythropoietin cholangitis r Acquired Renal Cystic Disease
r Pulmonary: Respiratory failure, pulmonary
r Growth hormone treatment r Meckel–Gruber Syndrome (Meckel Syndrome)
hypoplasia, pneumothorax, atelectasis, poor
r Multicystic Dysplastic Kidney
Second Line diaphragmatic excursion
r GI: Feeding intolerance, failure to thrive r Nephronophthisis (Juvenile, Infantile, and
N/A
Adolescent)
SURGERY/OTHER PROCEDURES FOLLOW-UP r Polycystic Kidney Disease, Autosomal Dominant
r Preemptive bilateral nephrectomy and peritoneal
Patient Monitoring r Polycystic Kidney Disease, Autosomal Recessive
dialysis catheter (significant pulmonary distress) r Progressive renal failure in most patients requiring
r Unilateral nephrectomy (improve feedings, help with Image
ongoing renal assessments r Renal Cysts (Intrarenal, Peripelvic, and Parapelvic)
breathing) r Blood pressure r Renal Dysplasia, Hypodysplasia, and Hypoplasia
r Gastrostomy tube placement (improve feedings) r Liver functions and ultrasound at least annually
r Splenorenal shunt or portocaval shunt procedures r Renal Mass
r Overall assessment of growth and nutritional status
(portal HTN) r Parental counselling is critical as there is a 1 in 4
r Renal transplantation (ESRD)
r Liver transplantation (hepatic failure)
chance of another child having the disease CODES
r Progressive liver fibrosis with portal hypertension Patient Resources
PKD Foundation http://www.pkdcure.org/learn/arpkd ICD9
may require combined liver and kidney r 751.69 Other anomalies of gallbladder, bile ducts,
transplantation and liver
REFERENCES r 753.14 Polycystic kidney, autosomal recessive
Radiation Therapy r 777.8 Other specified perinatal disorders of
1. Ward CJ, Hogan MC, Rossetti S, et al. The gene
N/A mutated in autosomal recessive polycystic kidney digestive system
Additional Therapies disease encodes a large, receptor-like protein. Nat
r Adequate hydration Genet. 2002;30:259–269. ICD10
r P78.89 Other specified perinatal digestive system
r Correct acid–base and electrolyte abnormalities 2. Adeva M, El-Youssef M, Rossetti S, et al. Clinical
disorders
r Aggressive HTN control and molecular characterization defines a r Q44.5 Other congenital malformations of bile ducts
r Peritoneal dialysis broadened spectrum of autosomal recessive r Q61.19 Other polycystic kidney, infantile type
r Enteral feedings polycystic kidney disease (ARPKD). Medicine
r Advanced pulmonary support as required (Baltimore). 2006:85:1–21. (Level II evidence)
3. Bergmann C, Senderek J, Küpper F, et al. PKHD1 CLINICAL/SURGICAL
Complementary & Alternative mutations in autosomal recessive polycystic kidney
Therapies disease (ARPKD). Hum Mutat. 2004:5:453–463. PEARLS
N/A r Renal and liver involvement is typical.
r Often fatal if present at birth.
ONGOING CARE r Treatments are supportive; no specific therapy.
PROGNOSIS
r Prenatal: Abnormal prenatal US (oligohydramnios,
enlarged reniform kidneys, absent urine in bladder,
seen after 30-wk gestation) (5)
r Neonates: If present at birth, the usual clinical
course is death. Patients have feeding intolerance,
respiratory distress
r Infants: Palpable flank masses, abdominal mass,
respiratory distress, HTN, polydipsia, polyuria,
edema, feeding intolerance, Potter phenotype,
nonspecific GI complaints, failure to thrive, growth
retardation, infection
P
305
POLYHYDRAMNIOS/OLIGOHYDRAMNIOS
r Effects of oligohydramnios GENERAL PREVENTION

BASICS – Pulmonary hypoplasia: Correlated with fetal r Oligohydramnios
outcome and main cause of fetal death – Avoid known medications (NSAIDs, etc.)
DESCRIPTION – Intrauterine growth restriction – Avoid unneeded amniocentesis
r Oligohydramnios is defined as an abnormally low – Potter facies with severe oligohydramnios – Avoid maternal dehydration
amniotic fluid (AF) volume: – Better outcome if presents in 3rd trimester vs. 2nd r Polyhydramnios
– Associated with increased fetal morbidity and trimester (3) – Control of maternal diabetes
mortality – Better outcome if cause is PROM vs. congenital – Prevention of infections transmittable from mother
r Polyhydramnios is defined as an abnormally high AF anomaly (3) to fetus
volume: r Causes of polyhydramnios – Avoid drug abuse
– Up to 20% of neonates will have a congenital – Idiopathic: ∼60%
anomaly ◦ Better outcomes
– Associated with increase in aneuploidy, congenital – Maternal causes: ∼15% DIAGNOSIS
malformations, preterm delivery, and perinatal ◦ Maternal diabetes
death ◦ Infections: Syphilis, rubella, MV, toxoplasmosis, HISTORY
r Polyhydramnios:
r These conditions are diagnosed using prenatal US parvovirus, Rh isoimmunization
◦ Drug abuse: Polyhydramnios in ∼25–30% of – Increased maternal weight
with strict criterion described below
– Maternal drug use
drug-addicted women. Leads to decreased
EPIDEMIOLOGY – Maternal infectious exposure
neurologic function of fetus and decreased r Oligohydramnios:
Incidence swallowing
r Oligohydramnios in 3–5% of pregnancies (1) – Poor weight gain
– Fetal causes:
r Polyhydramnios in 1–3% of pregnancies (1) ◦ Reduced fetal swallowing: Maternal drug use, – Medication history
r Usually discovered in 2nd trimester with 40% fetal neurologic anomalies, aneuploidy PHYSICAL EXAM
normal by term ◦ GI anomalies: T-E fistula, choanal atresia, facial r Polyhydramnios: Increased maternal fundal height
Prevalence cleft, esophageal atresia, imperforate anus r Oligohydramnios: Decreased maternal fundal height
N/A ◦ Cardiac failure with diuresis r Enlarged newborn urinary bladder due to
◦ Karyotype anomalies obstruction
RISK FACTORS r Potters facies:
r Oligohydramnios: ASSOCIATED CONDITIONS
r Oligohydramnios: – Characteristic of bilateral renal agenesis and other
– Rupture of membranes
– Some medications (eg, NSAIDs) – Rupture of membranes severe renal malformations
– Maternal HTN – Placental insufficiency – Ocular hypertelorism, low-set ears, receding chin,
– Maternal autoimmune disorders – Chronic maternal HTN flattening of the nose
r Polyhydramnios: – Postdate gestation DIAGNOSTIC TESTS & INTERPRETATION
– Maternal diabetes – Multicystic dysplastic kidney or prune-belly
syndrome Lab
– Drug abuse r Polyhydramnios:
– Severe cardiac disease
Genetics – Pulmonary hypoplasia, limb abnormalities – Maternal testing for glucose, autoantibodies,
Several genetic syndromes are associated with – Potter syndrome: TORCH screen, parvovirus, fetal karyotype
r Oligohydramnios:
oligohydramnios or polyhydramnios ◦ Characteristic appearance usually due to
bilateral renal agenesis, obstructive uropathy, – General: Fetal karyotype, pulmonary maturity,
PATHOPHYSIOLOGY maternal autoantibodies (lupus, anticardiolipin,
r After 22–23 wk, most of AF is fetal urine renal hypoplasia, autosomal recessive polycystic
r Late in gestation AF averages ∼700–800 mL kidney disease antinuclear)
◦ Less severe form referred to as Potter sequence – Renal: Fetal urinary electrolytes
r Oligo- and polyhydramnios are due to an imbalance
r Polyhydramnios – Better outcome associated with Na <100 mmol/L,
in the production and removal of amniotic fluid Cl <90 mmol/L, and osm <210 mmol/L
r Production of amniotic fluid (2) – Anencephaly
– Neural tube defects – Serial measurements may have better prognostic
– 600–1,200 mL/d fetal urine value
– GI obstruction (esophageal atresia, duodenal
– 60–100 mL/kg/d tracheal secretions
atresia) – May also measure β2-microglobulin,
r Removal of amniotic fluid (2) α-microglobulin, and retinal-binding protein
– Multiple gestation
– 200–1,500 mL/d fetal swallowing – Nonimmune hydrops fetalis Imaging
– 200–500 mL/d removed across fetal placenta into – Maternal diabetes r US measurements of AF volumes are very
fetal blood stream (intramembranous pathway) operator-dependent and very variable (4)
r Oligohydramnios causes r No perfect means to determine actual volume, but
– PROMs several surrogate markers are used:
◦ Iatrogenic: Amniocentesis
– Maximum vertical pocket: Polyhydramnios >8 cm,
◦ Spontaneous/idiopathic
oligohydramnios <1 cm
– Decreased fetal urine production – AFI: Sum of largest volumes from each of 4
◦ Prerenal: Placental insufficiency, umbilical cord
placental quadrants:
compression, fetal demise, maternal ◦ Oligohydramnios: <5 cm, polyhydramnios
hypotension or severe dehydration, chronic >25 cm
maternal HTN, autoimmune disorders, drugs r Fetal MRI increasingly used for better anatomic
(NSAIDs, ACE inhibitors)
◦ Intrarenal: Renal dysplasia, renal agenesis detail
◦ Obstructive: Posterior urethral valves (PUVs),
prune belly syndrome, urethral atresia, bilateral
ureteropelvic junction obstruction (UPJO),
bilateral ureteral obstruction, bilateral ectopic
ureters
306
POLYHYDRAMNIOS/OLIGOHYDRAMNIOS
Diagnostic Procedures/Surgery FOLLOW-UP

r Polyhydramnios
– Remove excess fluid Close monitoring by prenatal sonography
r Oligohydramnios: GENERAL MEASURES
r Polyhydramnios: Patient Resources
– Amnioinfusion: Especially for premature PROM r www.americanpregnancy.org
– US every 3–4 wk r www.acog.org/For Patients
Pathologic Findings
r Depends on cause (see pathophysiology) – Follow pregnancy to 38 wk
r Renal dysplasia common finding in oligohydramnios – Monitor for uterine hemorrhage
r Oligohydramnios:
REFERENCES
DIFFERENTIAL DIAGNOSIS – US every 3–4 wk for fetal viability and BPP
r Oligohydramnios – Consider early delivery with steroids for 1. Volante E, Gramellini D, Moretti S, et al. Alteration
– Premature rupture of membranes (PROM) pulmonary development of the amniotic fluid and neonatal outcome. Acta
◦ Iatrogenic: Amniocentesis – Newborn needs intensive care and urologic Bio Med. 2004;75:71–75.
◦ Spontaneous/idiopathic assessment 2. Sherer DM. A review of amniotic fluid dynamics
– Decreased fetal urine production and the enigma of isolated oligohydramnios. Am J
◦ Prerenal: Placental insufficiency, umbilical cord MEDICATION
First Line Perinatol. 2002;19:253–266.
compression, fetal demise, maternal r Maternal indomethacin has been used in cases of 3. Shipp TD, Bromley B, Pauker S, et al. Outcome of
hypotension or severe dehydration, chronic singleton pregnancies with severe oligohydramnios
maternal HTN, autoimmune disorders, drugs polyhydramnios
r Surfactant for the neonate with severe in the second and third trimesters. Ultrasound
(NSAIDs, ACE inhibitors) Obstet Gynecol. 2996;7:108–113.
◦ Intrarenal: Renal dysplasia, renal agenesis oligohydramnios and pulmonary hypoplasia
◦ Obstructive: PUVs, prune belly syndrome, 4. Harman CR. Amniotic fluid abnormalities. Semin
Second Line Perinatol. 2008;32:288–294.
urethral atresia, bilateral UPJO, bilateral ureteral None
obstruction, bilateral ectopic ureters
– Prolonged gestation can lead to oligohydramnios SURGERY/OTHER PROCEDURES
late in the pregnancy In utero vesicoamniotic shunt in select cases of ADDITIONAL READING
r Polyhydramnios oligohydramnios due to bladder outlet obstruction
N/A
– Idiopathic: ∼60% ADDITIONAL TREATMENT
◦ Better outcomes See Also (Topic, Algorithm, Media)
Radiation Therapy r Polyhydramnios/Oligohydramnios Image
– Maternal causes: ∼15% N/A r Posterior Urethral Valves
◦ Maternal diabetes
◦ Infections: Syphilis, rubella, MV, toxoplasmosis, Additional Therapies r Potter Syndrome/Potter Facies
parvovirus, Rh isoimmunization Amnioinfusion of isotonic sodium chloride solution in
◦ Drug abuse: Polyhydramnios in ∼25–30% of the 2nd trimester may benefit some patients with
drug-addicted women. Leads to decreased oligohydramnios CODES
neurologic function of fetus and decreased Complementary & Alternative
swallowing Therapies ICD9
◦ Placental chorioangioma or arteriovenous fistula N/A r 657.00 Polyhydramnios, unspecified as to episode of
– Fetal causes: care or not applicable
◦ Reduced fetal swallowing: Maternal drug use, r 658.00 Oligohydramnios, unspecified as to episode
anencephaly, neural tube defects, muscular ONGOING CARE
of care or not applicable
dystrophy syndromes, aneuploidy PROGNOSIS r 761.2 Oligohydramnios affecting fetus or newborn
◦ GI anomalies: T-E fistula, choanal atresia, facial r Polyhydramnios:
cleft, esophageal atresia, imperforate anus, – If idiopathic, the prognosis is usually good ICD10
gastroschisis, duodenal atresia/stenosis, r Oligohydramnios: r O40.9XX0 Polyhydramnios, unspecified trimester,
diaphragmatic hernia not applicable or unspecified
◦ Cardiac failure: Congestive heart failure, severe – With renal agenesis, mortality rate is 100%
r O41.00X0 Oligohydramnios, unspecified trimester,
– Fetal outcomes correlated to degree of pulmonary
anemia not applicable or unspecified
◦ Karyotype anomalies: Trisomy 21, etc. hypoplasia
– Mild forms of obstructive uropathy may cause r P01.2 Newborn (suspected to be) affected by
◦ Hydrops fetalis: Rh disease, severe anemia,
renal insufficiency oligohydramnios
infections in mother (eg, parvovirus, CMV),
– Better prognosis with presentation in 3rd vs. 2nd
twin–twin transfusion syndrome, maternal
trimester (3)
hyperparathyroidism, disorders of glycosylation
– Better prognosis with PROM as cause vs. CLINICAL/SURGICAL
◦ Other: Sacrococcygeal teratoma, skeletal
dysplasias, thoracic/mediastinal masses
congenital anomalies (3) PEARLS
COMPLICATIONS r If anmiotic fluid (AF) levels are normal, the fetus is
r Polyhydramnios can cause increased preterm labor
very likely to have adequate urine production even
r Oligohydramnios can cause fetal distress before or with bilateral hydronephrosis.
during labor and severe respiratory distress and r In utero intervention with vesicoamniotic shunt is
pneumothorax due to pulmonary hypoplasia controversial.
r Idiopathic polyhydramnios has good outcomes.
307
POLYOMA VIRUS (BK, JC), UROLOGIC CONSIDERATIONS

Nathan Roberts, MD
PATHOPHYSIOLOGY
BASICS r Route of transmission is unknown but seems to DIAGNOSIS
occur early in life most likely oral/respiratory
DESCRIPTION exposure (1,2) HISTORY
r JC and BK viruses are 2 of 10 different human r Hypothesized that subclinical infection leads to r Hemorrhagic cystitis
polyoma viruses viremia that seeds the kidneys – From pink colored urine to clot retention
– Small DNA viruses in the papovaridae family r Pathology is postulated to occur from reactivation of – Pt can also have bladder pain
– JC and BK viruses named after 1st patients the – Pt may have LUTS
latent infection and not reinfection r BK virus nephropathy
viruses were isolated from in 1971 r Immuno-reconstitution inflammatory syndrome
– These viruses typically manifest clinical sequelae – Typically occurs 10–13 mo after transplant
– Dominant inflammatory response to abundant
only in immunocompromised hosts – Often asymptomatic
polyoma virus antigen followed by brisk recovery
– BK virus has a tropism for genitourinary – May have hematuria
of the cellular immune response
epithelium ◦ Seen in BKV-associated hemorrhagic cystitis – May have decreased urine output
◦ Clinical manifestations: Hemorrhagic cystitis r Transplanted ureteral stenosis (3)
after allogeneic stem cell transplantation
(HC), ureteral stenosis, nephropathy, and rare r Cytopathic-inflammatory polyomavirus pathology – Typically occurs 2–4 mo after transplant
GU-associated malignancies – Often asymptomatic
– High-level virus replication and a significant
– May have decreased urine output
EPIDEMIOLOGY inflammatory response due to cytopathic lysis,
Incidence necrosis, with infiltration of granulocytes and PHYSICAL EXAM
lymphocytes. Dominant inflammatory response to r Hemorrhagic cystitis
N/A
abundant polyoma virus antigen followed by brisk – May present with palpable bladder if in clot
Prevalence retention
r BK virus has an 82–99% seroprevalence in adults of recovery of the cellular immune response
◦ Seen in BKV-associated nephropathy in kidney r BK virus nephropathy
the United States, Italy, and Australia
allografts – No significant findings on exam
– 50% @ 2 yr of age; 90% @ 10 yr of age r Oncogenic polyoma virus pathology r Ureteral stenosis of kidney transplant
r JC virus has a 39–81% seroprevalence in same
– Early viral gene expression activating host cells but – May have no significant findings
regions
without sufficient late gene expression to cause – Pelvic mass bulge from transplant hydronephrosis
– Clinically manifest only in immunocompromised
rapid host cell lysis – Due to denervation of transplanted kidney, patient
subjects ◦ Seen in rare BKV-associated urothelial and renal
r Ureteral stenosis due to BK virus infection among may not present with pain
tubular cancers
allograft recipients is approximately 3% ◦ There is conflicting evidence of BK virus DIAGNOSTIC TESTS & INTERPRETATION
r BK-induced nephropathy:1–10% of transplants Lab
involvement in these tumors
r Hemorrhagic cystitis r Hemorrhagic cystitis r Virus culture mostly used in research setting
– Reported to cause hemorrhagic cystitis in – Another theory suggests 3 phases – Takes weeks to months to grow
5.7–7.7% of bone marrow transplant recipients ◦ Conditioning regimen for stem cell transplant r Urine cytology
damages the bladder mucosa providing – Detects virus shedding
RISK FACTORS
r Immunocompromised host environment for virus replication – Characteristic finding is an enlarged nucleus with
◦ Viral replication unchecked in the absence of a single large basophilic intranuclear inclusion
– Degree of immunosupression
functional immunity (“decoy cells”)
– Transplant recipients ◦ Does not distinguish between various types of
◦ Solid organ (especially kidney), stem cell ◦ Further damage to the bladder mucosa with
immune reconstitution and return of anti-BK polyoma virus
transplants r Urine quantitative PCR
– HIV/AIDS immunity
◦ Predilection toward hemorrhagic cystitis – Correlates with BK virus associated nephropathy
ASSOCIATED CONDITIONS – Can be positive in normal controls, elderly patients
– Autoimmune disorders requiring r BK virus has a tropism for genitourinary epithelium
immunosuppression and HIV-infected patients without clinical
– Kidney transplant recipients manifestations
– Multiple sclerosis ◦ Tubulointerstitial nephritis ◦ Difficult to assess clinical significance
– Systemic lupus erythematous ◦ Ureteral stenosis r Plasma quantitative PCR
Genetics – Stem cell transplant recipients r Hemorrhagic cystitis
r Small nonenveloped icosahedral particles of ◦ Hemorrhagic cystitis
r JC virus has a tropism for neural tissue – Urinalysis positive for blood/RBCs
40–45-nm diameter, with a nonenveloped, circular r BK virus nephropathy
double-stranded DNA genome – Causes progressive multifocal
r Polyoma viruses encode 6 proteins leukoencephalopathy – Elevated creatinine
r 3 structural capsid proteins – Not as common, but JC can also be related to – Urinalysis
◦ Pyuria, hematuria, and/or cellular casts of renal
r 3 noncapsid regulatory proteins genitourinary manifestations like BK virus and vice
versa tubular cells and inflammatory cells
– Large and small T antigen (cell immortalization r Transplanted ureteral stenosis
and latency), and agnoprotein (assembly of viral GENERAL PREVENTION – Can have elevated creatinine
particles) r Route of transmission is unknown so difficult to
◦ Proteins interact with cellular target proteins prevent Imaging
r Hemorrhagic cystitis
and impair pathways involved with cell cycle r Competent immune system will prevent clinical
and DNA repair – Ultrasound or CT can show bladder thickening
sequelae
and possibly clot if present
r Transplanted ureteral stenosis
– Hydronephrosis seen on renal ultrasound, CT or
MRI
– Obstruction seen on renogram
308
POLYOMA VIRUS (BK, JC), UROLOGIC CONSIDERATIONS
Diagnostic Procedures/Surgery r Hemorrhagic cystitis

r Hemorrhagic cystitis – Cystoscopic fulguration (electro cautery or laser) ONGOING CARE
– Cystoscopy can show evidence of clots/active – Conjugated estrogens: Act by stabilization of
bleeding microvasculature PROGNOSIS
r BK virus Nephropathy r Hemorrhagic cystitis: Dramatic in presentation but
– Intravesical instillation of alum
– Renal Biopsy ◦ An astringent precipitates protein over bleeding usually resolves spontaneously within 2 wk with
◦ Most often percutaneous approach surface supportive care
◦ Histopathology results listed below ◦ 1% Alum solution in CBI r BK virus nephropathy: Graft failure in 15–50%
◦ Can also use Immunohistologic or in situ ◦ Can be used in presence of VUR
FOLLOW-UP
hybridization evidence of virally infected cells to – Intravesical instillation of silver nitrate
◦ Chemical coagulation and eschar at bleeding Patient Monitoring
make diagnosis
◦ Strongly positive using an SV40 sites BK virus nephropathy: After transplant some
◦ 0.5–1% instilled for 10–20 min recommend periodic monitoring for viremia
immunohistochemical stain
◦ VUR may lead to renal failure due to Patient Resources
Pathologic Findings
r BK Virus nephropathy precipitation and obstruction of upper tracts N/A
– E-aminocaproic acid
– Usually infects tubular epithelial cells ◦ Inhibits fibrinolysis preventing activation of
– Anisonucleosis, hyperchrmoasia, and chromatin
plasminogen to plasmin REFERENCES
clumping of infected cells ◦ Given orally, parenterally, or intravesically
– Interstitial mononuclear or polymorphonuclear cell 1. Dalianis T, Hirsch HH. Human polyomaviruses in
◦ Patients can form hard clots that are difficult to
infiltrates in the areas of tubular damage disease and cancer. Virology. 2013;437(2):63–72.
flush from the bladder
– Tubular injury with tubular cell apoptosis 2. Hirsch HH, Randhawa P. BK polyomavirus in solid
– Intravesical instillation of prostaglandin
– Intranuclear basophilic viral inclusions with a ◦ PGE2: May encourage platelet aggregation and organ transplantation. Am J Transplant. 2013;13
surrounding halo suppl 4:179–188.
induce vasoconstriction
– Not pathognomonic for BK virus ◦ PGE2: 0.75 mg in 200 mL of normal saline and 3. Thomas A, Dropulic LK, Rahman MH, et al. Ureteral
◦ CMV has cytoplasmic inclusion stents: A novel risk factor for polyomavirus
◦ HHSV has both intranuclear and cytoplasmic left indwelling
◦ May cause bladder spasms nephropathy. Transplantation. 2007;84(3):
inclusions 433–436.
– Intravesical instillation of formalin (40%
DIFFERENTIAL DIAGNOSIS formaldehyde) 4. van Aalderen MC, Heutinck KM, Huisman C, et al.
r Hemorrhagic cystitis ◦ Hydrolyzes proteins and coagulates tissue on BK virus infection in transplant recipients: Clinical
– Medication related (high-dose cyclophosphamide) superficial level manifestations, treatment options and the immune
◦ Often occurs within 72 hr ◦ Painful and needs to be done with general response. Neth J Med. 2012;70(4):172–183.
– Adenovirus related anesthesia 5. Manikandan R, Kumar S, Dorairajan LN.
– Radiation induced ◦ Should not be done with VUR. Can fibrose the Hemorrhagic cystitis: A challenge to the urologist.
– Infectious source ureters, cause obstruction, hydronephrosis and Indian J Urol. 2010;26:159–166.
– Trauma also papillary necrosis
◦ Possibly from urethral catheter placement ◦ Can result in small contracted bladder
– BPH related ADDITIONAL READING
r BK virus nephropathy SURGERY/OTHER PROCEDURES
r Hemorrhagic cystitis (5) Kazory A, Ducloux D. BK virus-associated urologic
– Cellular rejection – Cystectomy if refractory life-threatening cases complications. Pediatr Transplant. 2007;11(7):
r Transplanted ureteral stenosis
– Selective embolization 821–822.
– Surgical technique; ischemia of distal ureter ◦ Vesical or internal iliac artery
– Typically occurs in 7–10 days r BK virus Nephropathy See Also (Topic, Algorithm, Media)
r Cystitis, Hemorrhagic (Infectious, Noninfectious,
– Kidney re-transplant Radiation)
◦ Limited information for outcomes
TREATMENT ◦ Recommend patients have absence of BK
r Immunocompromised Patients, Urologic
Considerations
GENERAL MEASURES replication prior to re-transplantation r Polyoma Virus (BK, JC), Urologic Considerations
r Reduction of immunosuppression if possible (4) r Transplant ureteral stenosis
Image
– Often most effective strategy – Decompression of the transplanted kidney
◦ Percutaneous nephrostomy tube
MEDICATION ◦ Ureteral stent placement
First Line – Surgical excision of stenotic segment CODES
r Quinolone antibiotic (ciprofloxacin, etc.)
– Suggested for prophylactic role ADDITIONAL TREATMENT ICD9
r Intravenous immunoglobulin Radiation Therapy r 079.89 Other specified viral infection
– Can be used in hypogammaglobulinemic patients N/A r 593.3 Stricture or kinking of ureter
– Leflunomide: Antiviral activity Additional Therapies r 595.9 Cystitis, unspecified
r Hemorrhagic cystitis r Hemorrhagic cystitis
– Increased hydration – Hyperbaric oxygen: Promotes healing of hypoxic ICD10
– Catheter placement with clot evacuation r B33.8 Other specified viral diseases
tissues and aid in angiogenesis
– Continuous bladder irrigation (CBI) r N13.5 Crossing vessel and stricture of ureter w/o
Second Line hydronephrosis
Therapies r N30.90 Cystitis, unspecified without hematuria
r Intravesical vs. intravenous cidofovir
N/A
– Nucleotide analog of cytosine
– Active against DNA viruses
– Anecdotal evidence for use against polyoma
CLINICAL/SURGICAL
viruses PEARLS P
– Highly nephrotoxic
Polyoma virus will only have clinical sequelae in
immunocompromised patients.
309
POSTERIOR URETHRAL VALVES

Steve J. Hodges, MD
Anthony Atala, MD

BASICS r Renal dysplasia
Lab
r Bladder diverticula r Urinalysis and urine culture
DESCRIPTION r Ascites r Serum electrolytes, BUN, and Cr
r Congenital obstruction of the posterior urethra that r Urine extravasation r Cr has early prognostic value
can cause variable degrees of dysfunction of all r Vesicoureteral reflux r Elevated Cr in 1st few days of life (after the
segments of the urinary tract, including the bladder, r Azotemia
ureters, and kidneys 1st 5 days) indicates renal dysfunction and poor
r Urinary tract dysfunction can include r Hydroureteronephrosis prognosis
r VURD r Cr >1 at the end of the 1st yr of life predictive of
– Functional bladder disorders including increased
bladder wall thickness, fibrosis, and hyperactivity eventual ESRD
GENERAL PREVENTION
that may progress to myopathy and poor function No known methods of prevention Imaging
– The bladder changes may affect the upper tracts r Renal/Bladder US
by transmitting high pressure to the renal ALERT – Assesses for hydroureteronephrosis,
parenchyma, causing deterioration of renal High risk of end-stage renal disease in urethral valve corticomedullary differentiation, echogenicity,
function patients. signs of renal dysplasia, thickness of renal
– Patients may have congenital renal dysplasia parenchyma and bladder wall
r VCUG
EPIDEMIOLOGY
Incidence/Prevalence DIAGNOSIS – Diagnoses urethral valves, detects vesicoureteral
r Congenital disorder reflux and bladder trabeculation diverticula
r 1 in 4,000–7,500 live male births
HISTORY – Shows dilated posterior urethra, trabeculated
r Antenatally bladder, vesicoureteral reflux, perhaps ascites
r No racial predilection – No specific questions in the maternal or family – Hydroureteronephrosis
r Most common cause of lower urinary tract history aid in diagnosis r DMSA Renogram
obstruction in males – Prenatal US usually demonstrates bilateral – After 6 wk of life may be used to evaluate renal
r Accounts for 16.8% of children with ESRD hydroureteronephrosis and thick walled bladder in function, dysplasia
r The prevalence is 1:2,400–1:8,000 males (+/– oligohydramnios)
r Postnatally Diagnostic Procedures/Surgery
r Prenatal
RISK FACTORS – Nature or strength of urinary stream is a poor
r No racial predilection – Antenatal US: Bilateral hydroureteronephrosis
r Only affects males predictor of valves, or severity of obstruction
(+/– oligohydramnios, the earlier the diagnosis
– Failure to thrive may be seen
the worse the prognosis)
Genetics – Straining or grunting while voiding r Postnatal
r This disorder is usually sporadic. – May present with symptoms indicative of sepsis in
r Cases have been seen in twins and siblings a neonate due to UTI – US, VCUG, laboratory evaluation
– Delayed presentation considered in any male with – Cystoscopy: Confirms the diagnosis of PUV by
suggesting a poorly understood genetic component. direct visualization of the obstructing valves
a chronic history of day and night urinary
PATHOPHYSIOLOGY incontinence, UTI, and/or chronic Pathologic Findings
r Congenital mucosal membrane (fold/valve) in the
polydipsia/polyuria N/A
posterior urethra
r Hugh H. Young Classification (1919) PHYSICAL EXAM DIFFERENTIAL DIAGNOSIS
r Common neonatal presentation r Anterior urethral valves
– Type I: Folds that extend distally from the r Bilateral UPJ obstruction
verumontanum to divide into 2 membranes that – General: Palpably enlarged bladder, possible
abdominal distention due to ascites r Congenital urethral polyp
attach to the anterolateral wall, most common
variant (95%) – Pulmonary: Pulmonary distress syndrome, r Congenital urethral stricture (Cobb collar)
– Type II: Folds extending from the verumontanum pulmonary hypoplasia r Megacystis-megaureter
to the bladder neck superiorly, not clinically – Musculoskeletal: Potter’s facies, limb deformities r Megalourethra
obstructing, only of historical significance (in patients with severe oligohydramnios) r Multicystic dysplastic kidney
– Type III: Transverse membrane in the posterior – Genitalia: Bulge in the penoscrotal junction during r Neuropathic bladder
urethra, has a central aperture, located distal to urination is a sign of anterior urethral valves
r Nonneurogenic neurogenic bladder (Hinman
verumontanum, rare (5%)
syndrome)
r Plicae colliculi
– Normal anatomic finding
– Represents this folds of mucosa that extend from
the verumontanum in the prostatic urethra to the
membranous urethra
r Prune belly syndrome
r Urethral atresia
310
POSTERIOR URETHRAL VALVES
ADDITIONAL READING
TREATMENT ONGOING CARE r Heikkilä J, Holmberg C, Kyllönen L, et al. Long-term
GENERAL MEASURES PROGNOSIS risk of end stage renal disease in patients with
r Place urethral catheter immediately after birth to r Depends on the amount of congenital renal posterior urethral valves. J Urol. 2011;186(6):
drain the bladder (1) dysplasia, vesicoureteral reflux, bladder function 2392–2396.
r Measure daily weights, I/O’s (fluid balance), routine r Incontinence and later ESRD correlated r Taskinen S, Heikkilä J, Rintala R. Effects of posterior
vital signs r Cr >1 mg/dL at the end of the 1st yr of life urethral valves on long-term bladder and sexual
r Fluid and electrolytes as needed correlated with ESRD function. Nat Rev Urol. 2012;9(12):699–706.
r Long-term bladder dysfunction may progress to
MEDICATION See Also (Topic, Algorithm, Media)
overactive/fibrotic bladder or possibly eventual r Anterior Urethral Valves
First Line myogenic failure r Bladder Outlet Obstruction
r Prophylactic antibiotics r Sexual function and fertility seems to be normal in
r Hydronephrosis/Hydroureteronephrosis, (Dilated
– <2 mo age: Amoxicillin 20 mg/kg/d most patients
– ≥2 mo of age: Trimethoprim-sulfamethoxazole Ureter/Renal Pelvis), Pediatric Incontinence, Pediatric
2 mg/kg/d (concentrates in urine); nitrofurantoin is COMPLICATIONS r Hydronephrosis/Hydroureteronephrosis, (Dilated
an alternative r End-stage renal disease Ureter/Renal Pelvis), Prenatal
r Anticholinergics for bladder dysfunction r Voiding dysfunction r Posterior Urethral Valves Image
r Incontinence r Urethra, Obstruction
SURGERY/OTHER PROCEDURES r VURD Syndrome
r Transurethral ablation of urethral valves is possible FOLLOW-UP
in 80% of neonates Patient Monitoring
r Cutaneous vesicostomy in children too small for r Follow-up for observation of progress of renal
endoscopy (usually <2,000 g) function, as high risk of ESRD CODES
r Bilateral cutaneous pyelostomies of mostly historical – Usual late or difficulty toilet training; treat voiding
significance, but may be used in extreme cases dysfunction, incontinence ICD9
– Patients need serial electrolyte and Cr r 599.69 Urinary obstruction, not elsewhere classified
ADDITIONAL TREATMENT measurements, US evaluations, VCUG following r 753.8 Other specified anomalies of bladder and
Radiation Therapy ablation to monitor success of surgery, resolution urethra
N/A of reflux r 753.15 Renal dysplasia
Additional Therapies – UDS for bladder function
r Prenatal surgical intervention remains – Prophylactic antibiotics as needed ICD10
r N13.8 Other obstructive and reflux uropathy
investigational Patient Resources r Q61.4 Renal dysplasia
– Associated with risk of fetal and maternal http://www.chop.edu/healthinfo/posterior-urethral-
morbidity; long-term renal benefit proven r Q64.79 Other congenital malformations of bladder
valves-puv.html
r In children with persistent worsening renal function and urethra
and hydroureteronephrosis following valve ablation
may require upper tract diversion if possible to REFERENCE
salvage renal function
CLINICAL/SURGICAL
r Persistent vesicoureteral reflux following valve 1. Hodges SJ, Patel B, McLorie G, et al. Posterior PEARLS
urethral valves. Scientific World Journal. 2009;
ablation may require vesicoureteral reflux 9:1119–1126. r No benefit to early delivery as children with
r Low compliance fibrotic bladder or myogenic failure
pulmonary hypoplasia also have severe renal
(valve bladder) may require enterocystoplasty and/or dysplasia.
clean intermittent catheterization (CIC) r Select centers offer prenatal interventions with
Complementary & Alternative dubious efficacy.
Therapies r Poor kidney function at presentation is associated
r Behavioral measures with worse renal prognosis.
– Timed voiding, constipation therapy
r Biofeedback
– Physical therapy to relax external sphincter
r Diet
– Avoid bladder irritant, caffeine
r Perineal hygiene
– Voiding positioning
311
POSTOBSTRUCTIVE DIURESIS
John J. Pahira, MD

BASICS r Retained urea, sodium, and water; impaired sodium r Chronic obstruction:
reabsorption and concentrating ability of the renal – Pulmonary congestion, pitting edema of lower
DESCRIPTION tubule; and circulating hormones all contribute: extremities, HTN
r Postobstructive diuresis is excessive polyuria – Increased sodium, potassium, and magnesium r Acute obstruction:
resulting from the relief of bilateral ureteral losses result in increased water excretion – Abdominal mass, suprapubic tenderness, flank
obstruction or obstruction of a solitary kidney, – Accumulated urea acts as an osmotic agent, tenderness
bladder outlet obstruction bringing fluid with it as it is cleared, thereby
r More likely with chronic rather than acute increasing diuresis DIAGNOSTIC TESTS & INTERPRETATION
obstruction – Impaired concentrating ability of the renal tubule Lab
r After relief of obstruction, >3 L over 24 hr or r CBC, urine culture and sensitivity:
leads to continuing fluid losses and hypovolemia
>200 mL/hr over each of 2 consecutive hr is – Infection in the setting of obstruction requires
r ANP, which causes vasodilation, natriuresis, and
diagnostic of polyuria found with POD emergent evaluation and treatment
diuresis, has been found to be elevated in patients r SMA-7
EPIDEMIOLOGY with ureteral obstruction (1)[B] – BUN and creatinine are typically elevated and are
Incidence ASSOCIATED CONDITIONS monitored after relief of obstruction
r Peak incidence in men 70–90, due to increased r BPH – POD may cause profound hypokalemia
obstruction from BPH and prostatic cancer r Malignancies (bladder or prostate cancer) r Magnesium and calcium may need preplacement
r Peak incidence in women 40–60, due to obstruction r Urolithiasis r Urine osmolality:
from pregnancy and carcinoma of the cervix and r Any cause of chronic obstruction with – Evaluate the kidney’s ability to concentrate urine;
uterus typically impaired concentrating ability
hydronephrosis
Prevalence Imaging
N/A GENERAL PREVENTION r US is the screening test of choice to evaluate
Treat and repair the cause of obstruction to prevent
RISK FACTORS recurrence obstruction:
r Urinary tract obstruction is caused by a number of – Avoid risk of contrast agents
processes, grouped into extrinsic and intrinsic – Without hydronephrosis, diagnosis of POD should
causes: DIAGNOSIS be questioned
– Intrinsic: Nephrolithiasis, blood clot, ureteral HISTORY Diagnostic Procedures/Surgery
strictures, urethral strictures, neurogenic bladder, r Obstruction: Monitor urine output
anticholinergic agents, levodopa – Asymptomatic but often associated with flank Pathologic Findings
– Extrinsic: BPH, prostate cancer, tubo-ovarian pain radiating to groin and/or ipsilateral thigh, N/A
abscess, ovarian tumor or cyst, endometriosis, nausea, vomiting, fevers, chills
arterial aneurysms, tumors of the kidney, ureter, DIFFERENTIAL DIAGNOSIS
bladder, and urethra and their corresponding – Resulting uremia may cause mental status r Causes of polyuria:
lymphatic and metastatic spread changes, tremors, and GI bleeding (2)[A] – Medications:
r Obstructed patients most likely to have POD r Diuresis: ◦ Lithium carbonate, methoxyflurane,
– Chronic obstruction – Increase in urine output out of proportion to fluid demethylchlortetracycline, amphotericin B,
– Edema intake, usually >200 mL/hr mannitol, glycerol, diuretics, ethanol, opiate
– Congestive heart failure r Chronic obstruction: antagonist, phenytoin
– HTN – Weight gain, malaise, fatigue, shortness of breath – Diabetes insipidus, diabetes mellitus
– Weight gain r Acute obstruction – Renal disease: Diuretic phase of ATN
– Azotemia – Flank pain associated with forced diuresis – Physiologic diuresis from fluid excess
– Uremic encephalopathy (consumption of coffee, tea, or alcohol), nausea,
Genetics vomiting, hematuria, anuria
N/A
312
POSTOBSTRUCTIVE DIURESIS
ADDITIONAL READING
Nyman MA, Schwenk NM, Silverstein MD.
GENERAL MEASURES PROGNOSIS Management of urinary retention: Rapid versus
r After the obstruction is relieved, admit the patient to r The rate of recovery is largely determined by the gradual decompression and risk of complications.
the hospital to closely monitor hemodynamic status duration and severity of obstructive disease. Mayo Clin Proc. 1997;72(10):951–956.
and electrolytes, I/O’s and daily weights r Extent of recovery can be estimated by the
r Monitor urine output q2h and replace with oral See Also (Topic, Algorithm, Media)
improvement in renal function within 7–14 days r Hydronephrosis/Hydroureteronephrosis, (Dilated
fluids or if oral intake is not keeping up then with IV after the obstruction has been relieved:
Ureter/Renal Pelvis), Adult
fluids (0.5–1.0 mL of 1/2 NS/mL of urine output) in – Some patients may require short-term treatment r Polyuria
addition to PO fluids with dialysis, until their renal function recovers. r Urinary Retention, General
– If urine output decreases to <250 mL/hr replace COMPLICATIONS
fluids volume <50 mL of the urine output per r Uremic death
hour. Adjust accordingly as the diuresis resolves r Hypovolemic circulatory collapse
r If patient at risk of congestive heart failure or has r Bladder mucosal bleeding secondary to vein rupture
CODES
pulmonary edema, replace at a slower rate resulting from rapid bladder decompression
r Check serum sodium and potassium q6–12h and r Arrhythmia secondary to electrolyte abnormalities
ICD9
r 592.0 Calculus of kidney
replace as needed
r Follow BUN and creatinine values until normal: r 599.60 Urinary obstruction, unspecified
FOLLOW-UP
r Replace sodium, potassium, magnesium, and r 788.42 Polyuria
Patient Monitoring
bicarbonate as needed Serial (weekly to monthly) renal function testing
r Diuresis is usually self-limiting and typically lasts ICD10
(creatinine, BUN), renal US imaging if lab values do r N13.9 Obstructive and reflux uropathy, unspecified
<48 hr not return to normal range r N20.0 Calculus of kidney
r If diuresis lasts >48 hr, usually due to impaired Patient Resources r R35.8 Other polyuria
proximal tubular reabsorption of sodium causing a N/A
salt diuresis
– If outputs remain elevated, obtain a follow-up
REFERENCES CLINICAL/SURGICAL
renal US to rule out hydronephrosis
PEARLS
1. Li C, Wang W, Kwon TH, et al. Downregulation of
ALERT r Maintain a high degree of suspicion for the potential
AQP1, -2, and -3 after ureteral obstruction is
If there is persistent hydronephrosis, consider associated with a long term urine concentrating for postobstructive diuresis when relieving chronic
persistent obstruction of ureter(s) above the level of defect. Am J Physiol Renal Physiol. 2001;281: obstruction of the urinary tract.
the bladder or a nonfunctioning stent/percutaneous F163–F171. r Diuresis is usually self-limiting and typically lasts
tube (3)[A]. 2. Pais VM, Strandhoy JW, Assimos DG. <48 hr.
Pathophysiology of urinary tract obstruction. In:
MEDICATION Wein AJ, ed. Campbell-Walsh Urology. 9th ed.
First Line St. Louis, MO: WB Saunders; 2007.
None needed beyond replacement of fluid and 3. Gulmi FA, Felson D, Vaughan ED. Management of
electrolyte losses as noted above post-obstructive diuresis. AUA Update Series.
Second Line Lesson 23. 1998;27:177–183.
N/A
N/A
Radiation Therapy
N/A
Management of any renal insufficiency
Therapies
N/A
313
PREGNANCY, UROLITHIASIS
Kelly A. Healy, MD
r Controversial considerations may cause a higher DIAGNOSTIC TESTS & INTERPRETATION

BASICS rate of spontaneous abortions Lab
r Physiologic dilation of calyces, ureters, and renal r Urinalysis:
DESCRIPTION pelves begins in the 1st trimester and continues into – Hematuria/pyuria
r The presence of calculi in the urinary tract during r Urine culture:
the postpartum period
pregnancy can lead to severe risks and problems in r Dilation is greater on the right than the left – UTIs are more common in pregnancy associated
management r Decreased ureteral peristaltic activity because of with stone disease (10–20%)
r Urolithiasis is the most common cause of
hormonal and mechanical factors – A UTI can induce premature labor
nonobstetric abdominal pain that requires r Dilation and decreased peristalsis allowed relative r Serum creatinine:
hospitalization among pregnant patients urinary stasis – May be lower if the increased GFR (25–50%) in
r Symptoms in urolithiasis can result in premature r Increased urinary calcium excretion in pregnancy pregnancy
labor and fetal loss (↑2–3 times) r CBC
r Stones with obstruction may lead to urosepsis
– Increased levels of 1, 25-dihydroxy vitamin D Imaging
requiring appropriate treatment – GFR increases 25–50% in pregnancy r Renal ultrasound (Standard initial imaging study in
r Calcium phosphate most common followed by r Urine is more alkaline in pregnancy and thus
evaluation of pregnant patients) (1)
calcium oxylate protective against uric acid stones – Hydronephrosis
EPIDEMIOLOGY r Increase in excretion of stone inhibitors including – Renal stones/proximal ureteral stones
Incidence citrate and magnesium – Extravasation/perirenal urinoma
r Calculi in pregnant women occur at a rate of – Abscess
1/1,500 pregnant patients; a rate similar to that of r Hydroureteronephrosis is the most significant renal – Resistive index (RI) >0.70 in intrarenal arteries
nonpregnant females (0.03–0.53%) alteration during pregnancy supportive of acute obstruction
r Ureteral stones occur twice as often as kidney r Physiologic dilatation of the collecting system begins – No radiation exposure to fetus
r Transvaginal ultrasound
stones in pregnant patients in the 1st trimester and persists until 4–6 wk
r Usually present in the 2nd or 3rd trimester – Can demonstrate distal ureteral stones
following delivery. This factor may also allow the
r Incidence—right vs. left side is similar passage of relatively larger calculi – Can demonstrate ureteral jets, confirming urinary
r Hispanics and whites more likely than blacks to r Increased urinary calcium excretion during flow
– Document the diameters of distal ureter
develop stones during pregnancy pregnancy may present the major problem with r Noncontrast helical/spiral CT
r Multiparous women are more commonly affected indwelling stents and catheters
– Although utilized increasingly in nonpregnant
than are primiparous women GENERAL PREVENTION patients, delivers a relatively high radiation
Prevalence r Prophylactic measures to prevent the difficulties of exposure
N/A treating urolithiasis during pregnancy should be – Recent techniques have been decreased the
considered radiation exposure
RISK FACTORS r Metabolic evaluation should be performed for r Other imaging including standard excretory urogram
r Dehydration
r Relative immobility known stone formers at a time when they are not and computerized tomographic scan are
r Voluntary dietary modification (increased calcium) pregnant and not lactating discouraged during the 1st and 2nd trimesters
r There should be consideration of treatment of – Abdominal radiographic and one excretory
Genetics asymptomatic stones prior to pregnancy urogram has been widely used in pregnancy
r Increased stone formation is likely with a positive r As noted above, cystinurics have good management – There has been no adverse effect of contrast
family history of the disease before becoming pregnant material reported on the fetus
r Factors related to stone formation tend to group in – Radiation exposure is the major concern
families ◦ Typical urogram gives <1.5 rads of exposure
r Women with known cystinuria should obtain genetic DIAGNOSIS ◦ 5–15 rads to the maternal pelvis in the 1st
counseling and management of the stone disease trimester increases the risk of congenital
HISTORY anomalies by 1–3%
before becoming pregnant r Pregnancy history
◦ As little as 0.4–1.0 rads of fetal exposure can
PATHOPHYSIOLOGY r History of previous calculi
r Several factors occur in pregnancy may enhance increase the risk of childhood malignancy
r Flank and back pain and changes in symptoms
2.4 times
formation of stones: r Dietary modifications r MRI urography:
– Pregnancy-induced urinary stasis r Medications – Effect on fetal development poorly defined
– Hypercalcemia and hypercalciuria r Voiding symptoms—urgency and frequency with – May be able to distinguish acute obstruction from
– Decreased ureteral peristalsis
urination the dilation of pregnancy
– Physiologic hydronephrosis
◦ Starts 6–20 wk, in 90% by 3rd trimester PHYSICAL EXAM Diagnostic Procedures/Surgery
◦ Right side > left; may persist postdelivery r Abdominal tenderness r The presence of ureteral calculi with obstruction is
– Infection r Tenderness at costovertebral angle generally defined before interventional procedures
r Associated higher incidence of maternal UTI r Fever/chills – Occasionally, the diagnosis is not certain and the
(10–20%) r Nausea/vomiting presence of an obstructing calculus is defined only
r Stone passage can precipitate premature labor at the time of ureteroscopy
and/or interfere with normal labor
314
PREGNANCY, UROLITHIASIS
Pathologic Findings r Shock wave lithotripsy has generally not been 3. Bozkurt Y, Soylemez H, Atar M, et al. Effectiveness
N/A employed because of concerns of safety and the and safety of ureteroscopy in pregnant women: A
readily available alternatives comparative study. Urolithiasis. 2013;41:37–42.
r Acute pyelonephritis ADDITIONAL TREATMENT 4. Deters LA, Belanger G, Shah O, et al. Ultrasound
r Appendicitis guided ureteroscopy in pregnancy. Clin Nephrol.
Radiation Therapy 2013;79(2):118–123.
r Cholecystitis N/A
r Gastroenteritis 5. Laing KA, Lam TB, McClinton S, et al. Outcomes of
Additional Therapies ureteroscopy for stone disease in pregnancy:
r Hydronephrosis of pregnancy N/A Results from a symptomatic review of the literature.
r Neurologic/musculoskeletal pathology
Complementary & Alternative Urolo Int. 2012;89:380–386.
r Obstetric etiology of pain
r Other intra-abdominal conditions
Therapies
r Dietary changes including:
r Renal vein thrombosis – Limiting high oxalate foods and purines ADDITIONAL READING
– Increase in fluid intake
Evan AP, Lingeman JE, Matlaga BR. Surgical
– Limiting salt and sodium intake
TREATMENT – May be best preserved until metabolic evaluation
management of upper urinary tract calculi. Urology.
2007;2:1456–1458.
GENERAL MEASURES postpartum
r Often misdiagnosed initially See Also (Topic, Algorithm, Media)
r Pregnancy, Bacteruria, Pyuria, and UTI
(appendicitis/diverticulitis/placental abruption)
r Conservative measures are taken initially to manage ONGOING CARE r Pregnancy, Hematuria
r Pregnancy, Radiologic Considerations
pain and infection so that the stone may pass (2) PROGNOSIS
r Hydration and analgesia, antiemetics and antibiotics r Pregnancy, Urinary Tract Obstruction
Pregnancy outcome is not appreciably worsened
are used because of symptomatic urolithiasis with appropriate r Pregnancy, Urologic Considerations
r Approximately 60–80% of renal calculi pass management (5) r Pregnancy, Urologic Medications
spontaneously. Among pregnant patients with r Urolithiasis, Adult General
COMPLICATIONS
dilated ureter, the passage rate is not defined r Premature labor, fetal loss r Urolithiasis, Ureteral Calculi Algorithm
r Ureteral calculi associated with obstruction and r Urosepsis, renal insufficiency
upper tract infection demand immediate treatment
with drainage and antibiotics FOLLOW-UP CODES
Patient Monitoring
MEDICATION r During gestation:
First Line ICD9
r Narcotics including morphine, hydromorphone, – Conservative management with hydration r 592.1 Calculus of ureter
– Indications for intervention: r 592.9 Urinary calculus, unspecified
butorphanol, meperidine, and acetaminophen can ◦ Worsening renal function associated with
provide short-term pain relief without fetal harm r 646.80 Other specified complications of pregnancy,
persistent obstruction
r Avoid codeine during pregnancy because of its ◦ Intractable pain unspecified as to episode of care or not applicable
association with fetal defects ◦ Obstruction of a solitary kidney
r Nonsteroidal anti-inflammatory drugs are ICD10
◦ Persistent infection associated with an r N20.1 Calculus of ureter
contraindicated because of the increased risk of obstruction r N20.9 Urinary calculus, unspecified
miscarriage in the 1st trimester and other risks ◦ Renal colic, precipitation premature labor that is r O99.89 Oth diseases and conditions compl
including fetal renal anomalies, fetal pulmonary refractory to treatment
hypertension and premature closure of the ductus preg/chldbrth
– Preventive medications for stone disease have
arteriosus when used near term unacceptable side effects during pregnancy
r Medical management for the prevention of calcium ◦ Thiazides: Can cause fetal thrombocytopenia, CLINICAL/SURGICAL
stones should be delayed until after delivery hypoglycemia, and hyponatremia
◦ Xanthanine oxidase inhibitors: No adverse PEARLS
Second Line
N/A effects on fetal animals but effects on human r Most urinary stones pass.
fetus known r Intractable pain or infection with obstruction may
SURGERY/OTHER PROCEDURES ◦ Penicillamine: Teratogenic in rats; fetal defects
r Intervention may be required in 20–30% of cases (3) have been found in infants of mothers who took
necessitate drainage.
r Drainage may be necessary r Catheters, ureteral stent, or percutaneous
this during gestation
r Cystoscopy/stent placement can be done with or r Postpartum: nephrostomy (must be changed frequently at 4 to
6 wk because of the risks of encrustation).
without ultrasound guidance (4) – Metabolic screening should be undertaken r Ureteroscopic treatment with endoscopic lithotripsy
– Stents must be changed every 6 to 8 wk because postpartum and should be delayed until
of rapid encrustation in the pregnant women’s completion of lactation period appears to be the most efficacious and possibly
urine safest treatment.
r Percutaneous nephrostomy placement can be done Patient Resources
N/A
under ultrasound:
– To minimize radiation exposure
– The stone or obstruction can be addressed REFERENCES
postpartum
– The tube should be changed every 6–8 wk 1. Masselli G, Derme M, Laghi F, et al. Imaging of
– Clearly tube drainage alone must consider the stone disease in pregnancy. Abdom Imaging.
duration of pregnancy 2013;38(6):1409–1414.
r Ureteroscopy with laser lithotripsy or impact 2. Hoscan MB, Ekinci M, Tunçkıran A, et al.
lithotripsy has been very successful in treating stones Management of symptomatic calculi complicating
in the upper urinary tract in the pregnant patient pregnancy. Urology. 2012;80:1011–1014. P
315
PRIAPISM
Brad Figler, MD
r Nonischemic priapism: Straddle injury to the

BASICS perineum or direct blow to the cavernosal bodies DIAGNOSIS
anywhere along the length
DESCRIPTION HISTORY
r Prolonged, usually painful erection, occurring in the Genetics r Pain, duration of priapism, precipitating factors, and
Associated with genetic blood dyscrasias (sickle cell prior episodes
absence of sexual stimulation
anemia, sickle cell trait, thalassemia) and Fabry r Medical, drug, and social history. Include
– Named for Priapus, the Greek god of fertility who
disease intracorporal injection of PDE5 inhibitors
had an oversized, eternally erect penis
r Ischemic priapism (low-flow, veno-occlusive) is most PATHOPHYSIOLOGY r Determine current level of sexual function
r Ischemic priapism comprises the great majority of r Prior episodes; successful treatments
common: Compartment syndrome of the erectile
bodies causing ischemia, and ultimate necrosis of cases of prolonged erection r History of perineal straddle injury, malignancy
the cavernosal smooth muscle – Ischemic priapism is caused by a veno-occlusive
r Nonischemic priapism (high flow, arterial) is less phenomenon in which a variety of environmental PHYSICAL EXAM
r Palpation of penis will demonstrate nontender
common: Uncontrolled arterial inflow into the factors lead to hypoxia, acidosis, and
dysregulation of cavernosal smooth muscle tumescence (nonischemic priapism) or tender rigidity
cavernosal sinusoids without ischemia or necrosis of
relaxation leading to persistent veno-occlusion, a (ischemic priapism).
cavernosal smooth muscle r The hallmark of a priapism is that the corpora are
r Recurrent (Stuttering) priapism: Episodes are compartment syndrome, with absent further
arterial inflow involved but the glans penis and corpora
recurrent but of limited duration
r Refractory priapism: Persistent after surgical therapy – A feature of ischemic priapism is the ischemia spongiosum are flaccid and soft
reperfusion injury and oxidative stress that occurs r Abdominal, perineal, and digital rectal exam to
r Clitoral priapism (Clitorism): Described in case
after release of the ischemic insult search for traumatic or malignant etiology
reports and usually presents as severe vulvar pain; – Hematologic abnormalities generally cause a
associated with the use of antipsychotics: DIAGNOSTIC TESTS & INTERPRETATION
low-flow state with red blood cells sludging and
– Management is conservative with removal of the veno-occlusion (sickle cell disease, thrombophilia, Lab
inciting agent r CBC with differential and platelet count
r Priapism in children usually associated with thalassemia, leukemic infiltration, splenism,
erythropoietin, hemodialysis with heparin, total – Reticulocyte count (may be increased in sickle cell
leukemia or sickle cell disease parental nutrition) disease)
r Sickle cell prep for “S” hemoglobin
– Pharmacologic (α-adrenergic antagonist,
ALERT
intracavernosal injection, intraurethral alprostadil, r Hemoglobin electrophoresis
A low-flow ischemic priapism is considered an antihypertensive medications, psychotropic r Urine toxicology for prohibited drugs
emergency since early intervention improves the medications) r Psychoactive drug screen
chances for proper erectile function after. – Neurologic (spinal cord injury, brain tumor, r “Penile blood gas” (see below)
neurosyphilis)
EPIDEMIOLOGY – Neoplastic (local vs. metastatic, infiltration) Imaging
r Color Doppler US imaging of the cavernous arteries
Incidence – Idiopathic
r It is suggested that 10% of patients with sickle cell r Nonischemic priapism can distinguish ischemic priapism (minimal arterial
disease experience priapism, either recurrent short flow) from nonischemic priapism (high peak systolic
– Unregulated arterial inflow due to traumatic injury
episodes (stuttering priapism) or single prolonged arterial flow velocity)
to cavernosal artery or one of its branches with
episodes. A higher percentage of men with sickle – Color Doppler imaging may reveal cavernous
unimpeded arterial inflow to the corporal sinusoids
cell disease may report past attacks, although not all arterial fistula or perineal arterial extravasation
– Persisting fluid shear stress due to increased r Pudendal arteriography (with the potential for
of them requiring medical care inflow leads to further vasorelaxation due to
r Priapism is most common between ages 5 and 10 in endothelial NO synthase activation therapeutic super-selective embolization) if
boys and ages 20 and 50 in men nonischemic priapism is suspected
r Alprostadil intracavernosal injection for the ASSOCIATED CONDITIONS
r Alcohol abuse, psychiatric disorders Diagnostic Procedures/Surgery
treatment of erectile dysfunction associated with a r Aspiration of cavernosal blood with a “butterfly
r Attention deficit hyperactivity disorder (ADHD):
1% rate of priapism in clinical trials needle” and blood gas syringe for “penile blood
r FDA data (2007): 93 cases due to PDE5 inhibitors Methylphenidate use gas” allows differentiation between ischemic
r Blood dyscrasias
(likely higher due to unreported cases) priapism (low pH, low PO2 , high PCO2 , blood is very
r Cocaine abuse
dark) vs. nonischemic priapism (normal penile blood
Prevalence r Epidural anesthesia and analgesia gas, blood bright red). Typical values:
N/A r Hemoglobinopathies – Ischemic priapism (pO2 <30 mm Hg,
RISK FACTORS r Hypercoagulable states pCO2 >60 mm Hg, pH <7.25)
r Ischemic priapism r Intracavernous or intraurethral ED therapy – Nonischemic priapism (pO2 >90 mm Hg, pCO2
– Sickle cell, other hematologic disorders r Oral PDE5 inhibitors (sildenafil, etc.) <40 mm Hg, pH >7.4)
◦ Neonatal polycythemia, thalassemia r Pelvic/perineal trauma Pathologic Findings
– Intracavernosal injection therapy (papaverine, r Prostate or bladder cancer Initially liquefactive necrosis of the corporal tissue;
phentolamine, prostaglandin E1) r Renal failure and dialysis later corporal smooth muscle fibrosis
– Prescription drugs
◦ PDE5 inhibitors (sildenafil, others in class) GENERAL PREVENTION DIFFERENTIAL DIAGNOSIS
◦ Hydralazine, guanethidine, α-adrenergics [eg, r Ischemic vs. nonischemic priapism
Oral pseudoephedrine (60 mg) if high-risk for
tamsulosin], psychotropics (risperidone, r “Pseudo priapism” in men with penile prosthesis,
recurrence has been suggested
olanzapine, trazodone, SSRIs (fluoxetine vacuum constriction device with band, intraurethral
bupropion), heparin, coumadin, erythropoietin, foreign body causing penile rigidity
methylphenidate
– Illegal drugs: Cocaine, marijuana
– Poisonous venom, spinal cord injury
– Malignancy: Metastatic cancers (GU tumors most
common), melanoma, leukemia
– Dialysis, TPN
316
PRIAPISM
Second Line COMPLICATIONS

r Erectile dysfunction, particularly with cases of
TREATMENT Injection of epinephrine (1 mg in 1,000 mL saline) has
been used in place of phenylephrine; however, prolonged ischemic priapism
GENERAL MEASURES phenylephrine is more of a pure α-agonist with a r Cavernosal urethral fistula (after cavernosal
r Appropriate differentiation between ischemic and lower systemic side-effect profile spongiosal shunt)
nonischemic priapism is critical (1) r Cavernositis and corporal fibrosis
r Ischemic priapism of longer than 4-hr duration is a SURGERY/OTHER PROCEDURES
r Surgical intervention is considered 2nd line after r Penile deformity
urologic emergency that requires prompt penile corporal injection/aspiration attempts fail
decompression. This is usually a bedside corporal r Ischemic priapism
FOLLOW-UP
aspiration with or without irrigation Patient Monitoring
r Aspirate cavernosal blood for “penile blood gas” – If aspiration/irrigation fails, cavernosal glanular r Patient should be monitored for development of
shunting is recommended; creating a fistula erectile dysfunction
– Duplex color ultrasound has been suggested in between the corpora cavernosa and the glans.
lieu of penile blood gas to differentiate ischemic r Patient should undergo appropriate testing to
Unilateral usually sufficient; if not successful
and nonischemic priapism complete workup for any hematologic abnormalities
r All patients should undergo monitoring of blood perform bilateral procedure
or other potential underlying causes
– Distal cavernosal glanular shunt is 1st line
pressure and pulse, peripheral IV placement, ◦ Winter shunt: 16G core biopsy needle passed Patient Resources
appropriate use of pain medication and sedation from glans into 1 or both of the corporal bodies. AUA Foundation. www.auanet.org/education/
MEDICATION Biopsy needle removes tissue core guidelines/priapism.cfm
◦ Ebbehoj shunt using a pointed scalpel blade
First Line (3)
r Ischemic priapism ◦ Al-Ghorab shunt is an open excision of tunical
tip and usually next if Winter shunt fails
REFERENCES
– Use local anesthesia (lidocaine without
◦ T-shunt #11 scalpel blade inserted dorsolaterally 1. AUA Guidelines on the Management of Priapism –
epinephrine) and choose technique (local injection
site, dorsal nerve block, etc.) to the meatus on both sides, and rotated www.auanet.org/education/guidelines/priapism.cfm
– Corporal body aspiration +/− irrigation with (blade-edge) 90 degrees laterally 2. Kulmala RV, Lehtonen TA, Tammela TL, et al.
dilute adrenergic agent – Consider proximal shunting if distal shunting fails Preservation of potency after treatment after
◦ Phenylephrine 100–500 mcg/mL (1 mL/1 mg) in (cavernosal–spongiosal shunt [Quackles]) priapism. Scand J Urol Nephrol. 1996;30:313–316.
r Nonischemic priapism
9 mL of injectable normal saline 3. Salonia A, Eardley I2, Giuliano F3, et al. European
◦ A 27–29G needle is used to inject about 0.5 mL – No role for shunting in nonischemic priapism Association of Urology guidelines on priapism. Eur
directly into the corpora every 3–5 min until a – Conservative measures are appropriate in the Urol. 2014;65(2):480–489.
response. Can be repeated to a max of 1.5 mg short term as nonischemic cases of priapism do
phenylephrine has been administered or a total not lead to underlying cavernosal tissue damage
of 1 hr (if no response after 1 hr should be – Duplex Doppler Ultrasonography with color flow ADDITIONAL READING
considered initial treatment failure) to localize potential abnormal vascular
◦ Use lower volumes in children or with significant accumulation (arteriovenous fistula, see image) N/A
cardio vascular disease – Internal pudendal arteriography with selective
embolization (clot or gel foam) See Also (Topic, Algorithm, Media)
◦ Corporal compression helps facilitate the r Priapism Algorithm
process – Surgical exploration of the cavernosal body and r Sickle Cell Disease, Urologic Considerations
– This technique has best results for priapism ligation in cases refractory to embolization
<24 hr in duration: ADDITIONAL TREATMENT
◦ Aspirate with a large needle (16–18G)
connected to a 50-mL syringe and a 3-way
Radiation Therapy CODES
N/A
stopcock. Insert the needle perpendicular into
the skin into the lateral aspect of the corpora Additional Therapies ICD9
and aspirate 20–30 mL at a time (the glans is a Immediate placement of penile prosthesis if priapism 607.3 Priapism
less desirable site). Continue until the dark is of significantly prolonged duration and ED is highly
ICD10
ischemic blood turns bright red likely is advocated by some r N48.30 Priapism, unspecified
◦ If not successful, aspirate and irrigate the Complementary & Alternative r N48.33 Priapism, drug-induced
corpora with dilute solution of phenylephrine Therapies r N48.39 Other priapism
(10 mg in 500 mL saline) using 10–20 mL each N/A
time
◦ When aspirations and irrigations are completed, CLINICAL/SURGICAL
apply pressure for 5–10 min to limit hematoma ONGOING CARE
and refilling of corpora PEARLS
r Ischemic priapism in sickle cell disease: PROGNOSIS
r Based on duration/severity of ischemia. Priapism r The hallmark of a priapism: Corpora are involved but
– Opioid, analgesics, aggressive hydration, and associated with sickle cell disease may resolve in the glans is flaccid and soft.
supplemental oxygen if <4 hr duration 35% of patients treated systemically. r Penile blood gas allows appropriate diagnosis.
– Standard treatment if >4 hr, as for ischemic r Risk of permanent erectile dysfunction increases r Ischemic priapism is an emergency and intervention
priapism above should start within 4–6 hr, including decompression
substantially after 24 hr of ischemic priapism (92%
– Terbutaline or other oral agents not recommended
potency preserved with <1 day of priapism vs. 69% of the corpora cavernosa by aspiration and
per AUA guidelines intracavernous injection of sympathomimetic drugs
r Nonischemic priapism or less if more prolonged) (2).
r Monitoring of ischemic priapism may be clinical (eg, phenylephrine).
– No role for pharmacologic therapy r Nonischemic priapism can be managed in a
r Stuttering priapism (complete flaccidity of the penis) or radiologic (color
duplex Doppler ultrasonography showing persistent semielective manner once diagnosis confirmed.
– Treat as for ischemic priapism flow in cavernosal artery)
– LHRH agonists/antiandrogens may be considered
(but not for children/adolescents)
– Intracavernous self-injection who fail or reject P
systemic treatment
317
PROSTATE BIOPSY, INFECTIONS AND COMPLICATIONS

Christopher L. Starks MD
Edmund S. Sabanegh Jr., MD
PATHOPHYSIOLOGY Diagnostic Procedures/Surgery

BASICS r Normal adult prostate is approximately 20 g r A rectal probe should be gently placed with the
r The majority of prostate cancer is adenocarcinoma patient in a lateral decubitus position (5)
DESCRIPTION and located in the peripheral zone of the prostate r A periprostatic nerve block injecting approximately
r The current standard for the diagnosis of prostate r In the absence of antibiotic prophylaxis, bacteremia 5 cc of local anesthetic via a spinal needle can
cancer is transrectal ultrasound (TRUS) guided and bacteruria occur in 16% and 44% respectively decrease discomfort and pain
biopsy of the prostate of transrectal ultrasound-guided prostate biopsy r Full visualization of the prostate in transverse and
r A 12-core biopsy scheme is optimal for 1st time
sagittal views should be performed for an overview
prostate biopsy strategy using local anesthesia ASSOCIATED CONDITIONS
of the prostate and any abnormalities identified
r Active surveillance programs incorporate serial Benign prostate hypertrophy r The prostate volume should be calculated
prostate biopsy and may result in a potential for GENERAL PREVENTION r Using a spring-loaded biopsy needle, a minimum of
increased risk for biopsy-related complications r Consider urine culture before prostate biopsy if
12 cores, and additional biopsies as needed to
r Bleeding is the most common complication observed there is any concern over subclinical UTI obtain representative samples
after prostate biopsy. However, the use of aspirin or r Preprocedure enema does not appear to have any r The peripheral zone in the posterolateral aspect of
nonsteroidal anti-inflammatory drugs is not an impact on complication rates the prostate account for the majority of prostate
absolute contraindication to prostate biopsy r Rectal swab with culture and sensitivity has been cancers
EPIDEMIOLOGY suggested as a method to identify potentially r Additional biopsy of palpable nodule or hypoechoic
resistant pathogens and is not considered standard areas may be performed at the discretion of provider
Incidence
r Prostate biopsy is integral to the workup of elevated of care
r Transperineal biopsy may have a lower rate of Pathologic Findings
prostate-specific antigen (PSA) as well as abnormal r Prostate adenocarcinoma
prostate exams infection than the transrectal approach r Prostatic intraepithelial neoplasia (PIN)
r An estimated 800,000–1 million prostate biopsies r Continuing or cessation of antiplatelet or
r Atypical small acinar proliferation (ASAP)
are performed each year in the United States anticoagulant medications prior to biopsy is based r Benign prostate tissue
r In 1 recent series of repeat biopsies in men on active upon risk/benefit for each patient. Consider
discussion with the patient’s cardiologist or primary DIFFERENTIAL DIAGNOSIS
surveillance 3.5% experienced infectious r ASAP
care physician as needed
complications with most requiring hospitalization (1)
r The Rotterdam center of the ERSPC trial noted r Benign prostatic hypertrophy
r No evidence of malignancy
(0.5%) men required hospitalization for signs of DIAGNOSIS r PIN
prostatitis or urosepsis (2)
HISTORY
Prevalence r Prostate cancer most commonly presents without
Due to a variety of factors including an aging
any symptoms TREATMENT
population widespread use of PSA testing, the number r Family history of prostate cancer
of TRUS and prostate biopsies has increased r Specific review of any recent urinary tract infections,
GENERAL MEASURES
significantly over the last decade Although many clinicians have patients perform a
catheterization, or acute prostatitis self-administered enema, this is not needed. There is
RISK FACTORS r Further review of the patient’s medication list, with little evidence to support their use.
r For the diagnosis of prostate cancer:
special attention to anticoagulation or antiplatelet
– 1st-degree relatives with prostate cancer medication (ie, aspirin) MEDICATION
– Older age r Determine any symptoms of urinary tract infection First Line
– African American race r History of anorectal surgery r At our institution (Cleveland Clinic), patients receive
– Family history of breast cancer an oral single dose of fluoroquinolone as well as a
r For infectious complications the following have been PHYSICAL EXAM single dose of intramuscular aminoglycoside (80 mg
suggested as risk factors: r Digital rectal exam may reveal nodularity, gentamicin)
– Number of previous prostate biopsies was induration, or an asymmetric gland r AUA guidelines (see “Complications” below)
significantly associated with an increased risk of r Other anorectal pathology (anal stenosis, significant
infectious complications
Second Line
hemorrhoids) may be detected that might impact on
N/A
– Long-term fluoroquinolone use (3) the prostate biopsy procedure
– Healthcare workers SURGERY/OTHER PROCEDURES
DIAGNOSTIC TESTS & INTERPRETATION r For patients with anorectal malformations or
Genetics Lab
r HPC-1 gene on chromosome 1 associated with r PSA previous colorectal operations preventing TRUS, a
familial CaP transperineal biopsy can be performed.
r Screening UA with culture if indicated r The increasing incidence of antimicrobial resistance
r Many polymorphisms in genes, such as ELAC2 (locus
HPC2), RNase L (locus hereditary prostate cancer 1 Imaging with increasing concerns of the risk of sepsis is
r TRUS provides images of the prostate favoring renewed interest in transperineal biopsy as
gene [HPC1]), and MSR1 may confer an increased
risk of developing prostate cancer in many – Nodules may be hypoechoic on ultrasound a relatively sterile alternative to standard
populations (4) TRUS-guided biopsy.
318
PROSTATE BIOPSY, INFECTIONS AND COMPLICATIONS
ADDITIONAL TREATMENT FOLLOW-UP r Loeb S. Antimicrobial prophylaxis for transrectal

Radiation Therapy Patient Monitoring ultrasound biopsy. AUA Update Series. 2013;32,
N/A r Prompt medical evaluation for patient with signs lesson 1. [A]
and symptoms of infection or significant bleeding r Loeb S, Vellekoop A, Ahmed HU, et al. Systematic
Additional Therapies r Counseling regarding transient hematuria and the
r A retrospective analysis from Israel suggests that a review of complications of prostate biopsy. Eur Urol.
potential for hematospermia that may last for 2013;64(6):876–892.
single injection of 240 mg gentamicin along with a r Raman JD. Infectious complications following
quinolone for 3 days significantly reduces infectious several weeks
r Follow-up of prostate biopsy results prostate biopsy: A problem with need for solution.
complications (6)
r Another case series demonstrated that 500 mg Can J Urol. 2013;20(3):6815.
Patient Resources r Satyanarayana R, Parekh D. Prevention and
intravenous amikacin 30 min before the biopsy http://men.webmd.com/prostate-biopsy
along with several days of ciprofloxacin reduced the treatment of biopsy-related complications. Curr Urol
incidence of urosepsis/septicemia following prostate Rep. 2014;15(2):381.
biopsy (7) REFERENCES See Also (Topic, Algorithm, Media)
r Prostate Cancer, General
Complementary & Alternative 1. Ehdaie B, Vertosick E2, Spaliviero M3, et al. The
r PSA Elevation
Therapies impact of repeat biopsies on infectious
Topical rectal cleansing with povidone-iodine resulted complications in men with prostate cancer on r Urosepsis
in a 42% reduction in infectious complications in 1 active surveillance. J Urol. 2014;191(3):660–664.
prospective clinical trial but was not statistically 2. Raaijmakers R, Kirkels WJ, Roobol MJ, et al.
significant Complication rates and risk factors of 5802 CODES
transrectal ultrasound-guided sextant biopsies of
the prostate within a population-based screening ICD9
ONGOING CARE program. Urology. 2002;60:826–830. r 602.9 Unspecified disorder of prostate
PROGNOSIS 3. Akduman B, Akduman D, Tokgöz H, et al. r 998.59 Other postoperative infection
Although prostate biopsy is usually generally safe and Long-term fluoroquinolone use before the prostate r 998.9 Unspecified complication of procedure, not
well tolerated, it is an invasive procedure that is not biopsy may increase the risk of sepsis caused by elsewhere classified
without risk and required a clear understanding resistant microorganisms. Urology. 2011;78(2):
through informed consent of the patient. 250–255. ICD10
4. Alvarez-Cubero MJ, Saiz M, Martinez-Gonzalez LJ, r N42.9 Disorder of prostate, unspecified
COMPLICATIONS et al. Genetic analysis of the principal genes related r T81.4XXA Infection following a procedure, initial
r Bleeding is the most common complication and
to prostate cancer: A review. Urol Oncol. 2013; encounter
includes hematuria, hematospermia, and rectal 31(8):1419–1429. r T81.9XXA Unspecified complication of procedure,
bleeding
5. Patel AR, Jones JS. Optimal biopsy strategies for the initial encounter
– Bleeding is usually minor, self-limiting, and
diagnosis and staging of prostate cancer. Curr Opin
resolves with conservative measures. More
Urol. 2009;19:232–237. (1)[B]
significant bleeding has been reported and may
6. Lorber G, Benenson S, Rosenberg S, et al. A single
CLINICAL/SURGICAL
require transfusion or colorectal intervention PEARLS
r The 2nd most common complication is infection dose of 240 mg gentamicin during transrectal
prostate biopsy significantly reduces septic r A minimum of 12 cores is considered standard of
– The incidence of infectious complications,
complications. Urology. 2013;82(5):998–1002.
including sepsis, is increasing care in the United States.
– Compared to controls, men undergoing biopsy 7. Kehinde EO, Al-Maghrebi M, Sheikh M, et al. r Additional biopsy of nodules and hypoechoic areas
have a significant risk for serious infection as Combined ciprofloxacin and amikacin prophylaxis
may be needed.
requiring hospitalization (approximately 2.26 risk in the prevention of septicemia after transrectal r Be familiar with local resistance patterns when
increase and 2.65 risk increase, respectively) ultrasound guided biopsy of the prostate. J Urol.
2013;189(3):911–915. selecting antibiotic prophylaxis.
– Updated AUA Best Practice Policy Panel (8): r In men with prostate cancer on active surveillance
Antibiotic prophylaxis should be given for all 8. American Urological Association. Best practice
policy statement on urologic surgery antimicrobial the number of previous prostate biopsies may be
prostate biopsy procedures, duration of therapy is associated with a significant risk of infectious
<24 hr. Recommended 1/1/2014 drug of choice prophylaxis. 2008(updated January 1, 2014). [A]
complications and every previous biopsy increases
regimens and are: the risk of infectious complication.
◦ Fluoroquinolones or
◦ 1st/2nd/3rd-generation cephalosporin ADDITIONAL READING
◦ Alternative regiments: Trimethoprim r Chang DT, Challacombe B, Lawrentschuk N, et al.
Sulfamethoxazole (TMP-SMX) or
Transperineal biopsy of the prostate-is this the
Aminoglycoside (Aztreonam can be substituted
future? Nat Rev Urol. 2013;10(12):690–702.
for aminoglycosides in patients with renal r Ismail MT, Gomella LG. Transrectal prostate biopsy.
insufficiency)
◦ Familiarity with local resistance patterns Urol Clin North Am. 2013;40(4):457–472.
including fluoroquinolone-resistant bacteria is
important
319
PROSTATE CANCER, BIOCHEMICAL RECURRENCE (ELEVATED PSA)

FOLLOWING CRYOTHERAPY
Michael C. Large, MD

BASICS Lab TREATMENT
r PSA spikes initially from necrosis of the prostate
DESCRIPTION tissue GENERAL MEASURES
r Primary cryotherapy is an option for patients with r Following cryotherapy PSA rechecked every 3 mo × Confirmation of recurrence via transrectal biopsy
clinically localized prostate cancer of low-, 1 yr, then every 6 mo thereafter MEDICATION
intermediate- or high-grade (1)[B] r PSA may not decrease to undetectable
r Especially suited for comorbid patients who cannot First Line
r PSA-based definition for biochemical recurrence is r No first-line medication therapy
tolerate alternative therapy (extensive previous not standardized. Various parameters used: – Consider androgen-deprivation therapy or clinical
surgery, inflammatory bowel disease) (1)[B] – PSA >0.4 ng/mL, >0.5 ng/mL, >1.0 ng/mL, trial if metastatic disease
EPIDEMIOLOGY – 3 consecutive increases (“ASTRO” definition) – No significant data on the use of
– Nadir + 2 ng/mL (“Phoenix” definition) androgen-deprivation after local cryotherapy
Incidence
r Nearly 7,000 cryoablations for prostate cancer were Imaging failure
r Complete metastatic workup may include:
performed in US in 2005 (2)[C] Second Line
– Usage projected to increase – CXR N/A
– CT abdomen/pelvis
RISK FACTORS – Bone scan SURGERY/OTHER PROCEDURES
r For recurrence after primary cryotherapy: r Salvage prostatectomy feasible but large series are
– Endorectal MRI
– Larger glands make uniform freezing more difficult lacking
– PSA >10 ng/mL Diagnostic Procedures/Surgery r Reported techniques include:
r For complications after primary cryotherapy: r Transrectal biopsy
– Open retropubic or perineal
– Prior TURP increases risk of urethral necrosis – Commonly performed post-cryotherapy – Laparoscopic or robotically assisted
– Recommend waiting 6 mo for inflammation to r Salvage cystoprostatectomy with urinary diversion
PATHOPHYSIOLOGY resolve
r Tissue destruction from cryotherapy multifactorial – Option for extensive local recurrence with severe,
– Negative biopsy reported in 75–95% (1)[B],(2)[C] treatment-refractory lower urinary tract symptoms
– Induces apoptosis
– Intracellular ice formation and local hypoxia cause – Lower PSA nadir and lower clinical stage predict ADDITIONAL TREATMENT
necrosis negative re-biopsy
Radiation Therapy
– Maximum cell death with: Nadir temperature DIFFERENTIAL DIAGNOSIS r Conformal or Intensity-modulated radiotherapy
<−20◦ C, rapid freezing rate, slow thawing rate, r Necrosis, especially if within 3 mo of procedure – Largest series 49 patients, received conformal RT
multiple freeze/thaw cycles r Residual benign prostatic tissue (3)[C]
– Urethral warming catheter protects urothelium but r Treatment failure – Mean preradiation PSA 2.4 ng/mL
increases potential for preserving PSA-producing r Recurrent disease (local or metastatic) – Mean RT dose 62.9 Gy
tissue – At median follow-up 32 mo, biochemical-free
survival rate 61%
DIAGNOSIS Additional Therapies
r Repeat cryotherapy
HISTORY – Largest series 32 patients (4)[C]
r History of prostate cancer treated by primary
– Median follow-up 63 mo
cryotherapy ◦ 22, 23, and 29 were biochemical disease free by
– Recommend ≥3 mo elapse from primary definitions of 0.5 ng/mL, 1.0 ng/mL, and ASTRO
treatment before testing for recurrence definition
PHYSICAL EXAM Complementary & Alternative
r Digital rectal exam
Therapies
– Findings may be difficult to interpret given None widely studied
previous therapy
320
PROSTATE CANCER, BIOCHEMICAL RECURRENCE (ELEVATED PSA) FOLLOWING CRYOTHERAPY
FOLLOW-UP See Also (Topic, Algorithm, Media)

ONGOING CARE r Prostate Cancer, Biochemical Recurrence (elevated
Patient Monitoring
r No standards exist for postcryotherapy recurrence PSA) Following Radiation Therapy
PROGNOSIS follow-up r Prostate Cancer, Biochemical Recurrence (elevated
r Biochemical recurrence-free survival after primary r If biochemical disease untreated, may treat patient PSA) Following Radical Prostatectomy
cryotherapy (Phoenix definition) according to algorithms for (1) localized or (2) r Prostate Cancer, General
– 5-yr estimates based on D’Amico risk category: advanced prostate cancer outlined in prior chapters r PSA Elevation, General Considerations
(1)[B],(2)[C] r If patient has undergone salvage treatment after r Reference Tables: TNM: Prostate Cancer
◦ Low risk: 85–90% cryotherapy, no standards exist
◦ Intermediate risk: 80% – PSA often performed every 3 mo after salvage
◦ High risk: 60–70% therapy CODES
– 10-yr estimates based on D’Amico risk category: – Re-biopsy may be offered 6 mo after treatment, or
◦ Low risk: 80% if clinically indicated ICD9
◦ Intermediate risk: 75% r 185 Malignant neoplasm of prostate
Patient Resources
◦ High risk: 45% American Cancer Society http://www.cancer.org/ r 790.93 Elevated prostate specific antigen [PSA]
cancer/prostatecancer/detailedguide/prostate-cancer- r V10.46 Personal history of malignant neoplasm of
COMPLICATIONS
r No large series following postcryotherapy salvage treating-cryosurgery prostate
treatment
r Surgery: ICD10
r C61 Malignant neoplasm of prostate
– Intraoperative rectal injury REFERENCES r R97.2 Elevated prostate specific antigen [PSA]
◦ Small injury: 2-layer primary repair and omental
r Z85.46 Personal history of malignant neoplasm of
interposition 1. Babaian RJ, Donnelly B, Bahn D, et al. Best practice
◦ Large injury, gross spillage, poor tissue viability: statement on cryosurgery for the treatment of prostate
Primary repair and diverting colostomy localized prostate cancer. J Urol. 2008;180:
– Urinary incontinence, impotency 1993–2004. CLINICAL/SURGICAL
r Radiation 2. Finley DS, Pouliot F, Miller DC, et al. Primary and
– Rectourethral fistula, urethral stricture, urinary salvage cryotherapy for prostate cancer. Urol Clin PEARLS
incontinence, impotency, and bladder and rectal North Am. 2010;37:67–82. r An early rise in PSA after cryotherapy is normal, and
toxicities 3. Burton S, Brown DM, Colonias A, et al. Salvage further testing should be deferred until at least 3 mo
r Repeat cryotherapy radiotherapy for prostate cancer recurrence after following treatment.
– Rectourethral fistula, urethro-cutaneous fistula, cryosurgical ablation. Urology. 2000;56:833–838. r Various definitions of PSA failure after cryotherapy
urethral stricture, urinary incontinence, impotency, 4. Bahn DK, Lee F, Badalament R, et al. Targeted exist: >0.4 ng/mL, >0.5 ng/mL, >1.0 ng/mL, 3
and bladder and rectal toxicities cryoablation of the prostate: 7-yr outcomes in the consecutive rises, and nadir + 2 ng/mL.
primary treatment of prostate cancer. Urology. r Prostate biopsy is useful in the workup of
2002;60(2A):3–11. postcryotherapy biochemical recurrence.
r Postcryotherapy treatment of recurrent disease
should be reserved for highly experienced surgeons
ADDITIONAL READING and radiation oncologists.
AUA best practice policy statement on cryosurgery for
the treatment of localized prostate cancer:
http://www.auanet.org/content/media/cryosurgery08.pdf
(Accessed July 22, 2014)
321

FOLLOWING RADIATION THERAPY
Robert B. Den, MD
Mark Hurwitz, MD

BASICS Symptoms of urinary outlet obstruction can occur but r Prostate biopsy should be considered if more than
are uncommon during the initial period of biochemical 2 yr have elapsed since completion of radiation
DESCRIPTION recurrence. therapy and additional local therapy is being
r Rising PSA after treatment, referred to as contemplated.
biochemical recurrence, is nearly always the first GENERAL PREVENTION
r Optimized radiation therapy including dose – As the full effects of radiation are not manifested
indication of recurrent prostate cancer. The site of for 24–30 mo, biopsy before this time is not
recurrence—local, regional, distant, or a escalation with daily image guidance to ensure
indicated.
combination of sites, however, cannot be discerned proper targeting with external beam radiation and r Approximately 20% of patients who have
by PSA level alone use of proper brachytherapy techniques
r Use of androgen deprivation in combination with postradiation biopsies will have no clinical evidence
r Definitions of biochemical recurrence following of disease with additional long-term follow-up.
radiation: radiation for high risk and selected intermediate risk
Conversely, given the limitations of sampling, local
– ASTRO definition: 3 consecutive rises in PSA patients
recurrence may be present despite negative biopsy.
(backdating) r Biopsy to assess findings concerning for distant
– Phoenix definition: PSA nadir + 2 ng/mL DIAGNOSIS metastases as clinically indicated.
EPIDEMIOLOGY Pathologic Findings
HISTORY r Discerning posttreatment change from residual
Incidence r Prior radiation treatment information should be
r Most men with clinically localized disease will not disease in irradiated prostate tissue can be
obtained including type of radiation, technique, and
experience recurrence. However, given the difficult.
dose prescribed. For prostate brachytherapy
widespread use of radiation therapy for treatment of – Immunohistochemical analysis with basal
postimplant dosimetry analysis should be reviewed
prostate cancer, biochemical recurrence is not an cell-specific keratin monoclonal antibodies can aid
to determine if there were underdosed regions.
uncommon problem in routine clinical practice. r Thorough assessment of general health with in differentiating benign and malignant glands
r 5-yr rates of biochemical recurrence ∼5–40% since only benign glands display basal cell
emphasis on urinary and bowel function is immunoreactivity.
depending on risk stratification criteria important in guiding the advisability of potential
Prevalence salvage therapies. DIFFERENTIAL DIAGNOSIS
The time from biochemical recurrence to clinical r PSA bounce phenomenon
PHYSICAL EXAM – 35% incidence after brachytherapy
recurrence is typically measured in years. Therefore
General physical exam including rectal exam – Less common with external beam radiation
prevalence is relatively high as compared to
incidence. DIAGNOSTIC TESTS & INTERPRETATION r Testosterone rebound after completion of androgen
Lab deprivation with associated rise in PSA
RISK FACTORS r PSA.
r Risk of recurrence is associated with original risk
stratification including clinical stage, PSA, and – In addition to total PSA, PSA kinetics may be
helpful in identifying patients at greater risk of TREATMENT
Gleason score.
r A rise in PSA of >2 points in the year preceding development of distant vs. local recurrence. GENERAL MEASURES
diagnosis is associated with increased risk for both – Patients with short time to PSA nadir after r Efforts should be made to discern if biochemical
recurrence and prostate cancer–specific mortality treatment and short doubling times (PSADT) are recurrence is due to presence of local vs. distant
r Gleason score 4 + 3 = 7 vs. 3 + 4 = 7 and/or at greater risk of subsequent diagnosis of disease or a combination of both.
metastatic disease (PSDAT <3–6 mo) r In the presence of metastatic disease androgen
≥50% positive biopsies in intermediate-risk patients r Testosterone establishes baseline for future
r Lower doses of radiation ablation is the standard choice.
r Lack of use of androgen deprivation therapy in hormonal intervention r In cases of only localized disease there are many
r Basic metabolic panel
high-risk patients r CBC more options including observation, androgen
ablation or salvage therapies including radical
Genetics
Imaging prostatectomy or cryotherapy.
New tests linking tumor-specific genetic profiles to r Bone scan – In general candidates for local salvage therapy
adverse risk in prostate cancer including risk of r CT of abdomen and pelvis should have original clinical stage tumor T-1, T2
recurrence after prostatectomy have recently become
r Pelvic/prostatic MR. Magnetic resonance NX/N), life expectancy of >10 yr, and a PSA
clinically available. Their ultimate clinical value remains
spectroscopic imaging may improve results over MR <10 ng/mL (1)
to be fully defined. In regard to biochemical recurrence
alone – Patient who are not ideal candidates for salvage
following radiation therapy, the utility of such tests to
guide further therapy is not yet known. r New techniques for PET/CT including use of 18 F-NaF therapy should be treated by androgen
may be useful in select cases deprivation or observation
PATHOPHYSIOLOGY r Other imaging as clinically indicated
r >95% of prostate cancers are adenocarcinoma
r Rare variants such as TCC, small cell carcinoma, and
sarcomas are not associated with elevation of PSA
322
PROSTATE CANCER, BIOCHEMICAL RECURRENCE (ELEVATED PSA) FOLLOWING RADIATION THERAPY
MEDICATION Additional Therapies

r Thermal ablative therapies including cryoablation
ADDITIONAL READING
First Line
r Hormonal therapy (androgen deprivation): and high-intensity focused ultrasound remain Kanthabalan A, Arya M, Punwani S, et al. Role of focal
– LHRH agonists: Leuprolide, goserelin, triptorelin investigational. salvage ablative therapy in localised radiorecurrent
◦ Suppress LH and FSH release by the pituitary r Cryotherapy in particular has shown promise in prostate cancer. World J Urol. 2013;31(6):
– LHRH antagonists: Degarelix (only 1 FDA selected series. 1361–1368.
approved in US; – 5–10-yr freedom from biochemical recurrence See Also (Topic, Algorithm, Media)
◦ Suppress LH and FSH release by the pituitary with cryotherapy ranges between 34–59%. r Prostate Cancer, Biochemical Recurrence (Elevated
– Antiandrogens: Flutamide, bicalutamide, – Rates of ≥3 GU and GI complications average PSA) Following Cryotherapy
nilutamide, directly block the activity of androgens approximately 10% and 3% across reported r Prostate Cancer, Biochemical Recurrence (Elevated
on the androgen receptor series. PSA) Following Radical Prostatectomy
– LHRH agonists can be used alone or in r Focal ablative therapies that attempt to identify the r Prostate Cancer, Metastatic (Clinical and Pathologic
combination with oral antiandrogens site of recurrence and ablate the site are N+, M+)
– When LHRH agonist therapy is initiated, a release investigational (3). r PSA Elevation, General Considerations
of testosterone is induced (androgen flare) that Complementary & Alternative r PSA, Bounce
may exacerbate symptoms from metastatic lesions. r PSA, General Considerations
Therapies
In particular, patients with spinal metastasis may
Low-fat diets and diets high in polyphenols as found r Reference Tables: TNM: Prostate Cancer
be in jeopardy of cord compression
◦ Flare avoided by initiating antiandrogen therapy in broccoli, turmeric, pomegranate, and green tea may
be beneficial
2 wk prior to 1st LHRH agonist injection
– Orchiectomy remains an infrequently utilized CODES
option for androgen ablation ONGOING CARE
Second Line ICD9
PROGNOSIS r 185 Malignant neoplasm of prostate
Alternate androgen deprivation therapy or clinical PSA doubling time of less than approximately 6 mo r 790.93 Elevated prostate specific antigen [PSA]
trial and in particular 3 mo has been linked to increased r V15.3 Personal history of irradiation, presenting
SURGERY/OTHER PROCEDURES risk of prostate cancer–specific mortality
r Radical prostatectomy is rarely performed following hazards to health
COMPLICATIONS
prostate radiation due to high rates of morbidity (2) r Urinary outlet obstructive symptoms ICD10
– However, surgery can be considered in carefully r Proctalgia due to rectal invasion is typically seen r C61 Malignant neoplasm of prostate
selected cases for relatively young healthy patients r R97.2 Elevated prostate specific antigen [PSA]
only with advanced stages of recurrence
with established local recurrence r Z92.3 Personal history of irradiation
– 5- and 10-yr rates of freedom from biochemical FOLLOW-UP
recurrence with salvage radical prostatectomy Patient Monitoring
range up to 59% and 37% respectively with r Dependent in part on subsequent treatment CLINICAL/SURGICAL
disease-specific survival as high as 83% at 10 yr r Every 3–6 mo including general and prostate exam PEARLS
– Common toxicities include bladder neck and PSA
contracture (17–47%), rectal fistula (7–20%), r Risk stratification, morbidities associated with the
and erectile dysfunction in nearly all patients Patient Resources primary course of radiation, and PSA kinetics
American Cancer Society. http://www.cancer.org/ posttreatment are important to consider in selecting
ADDITIONAL TREATMENT cancer/prostatecancer/detailedguide/prostate-cancer- the best management option.
Radiation Therapy treating-recurrence r Participation in clinical trials should be encouraged
r Administration of additional radiation therapy in
in areas such as this where no consensus exists.
most instances should be limited to research
protocols.
– The most commonly investigated approach is REFERENCES
salvage brachytherapy following external beam 1. NCCN Practice Guidelines Version 1. 2014
radiation failures. http://www.nccn.org/. Accessed January 6, 2014
– 5-yr freedom from biochemical recurrence has
2. Punnen S, Cooperberg MR, D’Amico AV, et al.
been reported between 25–75% and
Management of biochemical recurrence after
disease-specific survival between 74–100%. Wide
primary treatment of prostate cancer: A systemic
variation in reported outcomes is likely due to
review of the literature. Eur Urol. 2013;64(6):
variation in risk criteria across studies.
905–915.
– Crude rates of grade ≥3 GU and GI complications
average 13% and 5%, respectively. Rates may be 3. Valerio M, Ahmed HU2, Emberton M2, et al. The
higher in elderly patients. role of focal therapy in the management of
localised prostate cancer: A systematic review. Eur
Urol. 2013. pii: S0302–2838(13)00557–5. doi:
10.1016/j.eururo.2013.05.048.
323

FOLLOWING RADICAL PROSTATECTOMY
ASSOCIATED CONDITIONS – ProstaScint is approved by the US Food and Drug

BASICS r Biochemical recurrence of PSA after surgery when Administration (FDA) to detect occult metastatic
the PSA after surgery was initially undetectable disease in patients with early prostate cancer
DESCRIPTION generally precedes metastatic progression and ◦ Is associated with a significant number of false
r Biochemical recurrence following radical prostate cancer specific mortality by a median of 8 positive and false-negative results
prostatectomy is a clinical state characterized by a and 13 yr, respectively (4) – Positron emission tomography/computed
detectable and increasing serum prostate specific – Importantly, not all men with biochemical tomography (PET-CT), with choline
antigen (PSA) after radical prostatectomy in the recurrence will develop metastases or die of ◦ Approved by the FDA in September 2012
absence of detectable disease based on current prostate cancer (1) ◦ Falsely positive PET scans can be observed in
imaging modalities – PSADT after recurrence is an important factor in 15–47% so confirmatory tissue sampling of
r Men with a biochemical recurrence fall into 3 assessing the risk of subsequent metastases and abnormalities detected with PET-CT is required
groups prostate cancer mortality Diagnostic Procedures/Surgery
– Those with a PSA that fails to fall to undetectable Transrectal ultrasound guided biopsy of the prostate
GENERAL PREVENTION
after surgery (persistent disease) bed may be helpful only if imaging or digital rectal
Although proper surgical technique can limit the risk
– Those with an initially undetectable PSA after exam suggest local recurrence
of PSA recurrence it cannot be guaranteed to do so
surgery that subsequently increases on 2 or more
due to varying tumor biology
tests (recurrent disease) ALERT
– Those with stable but low PSA levels (rare) “Blind biopsies” of the prostate bed in the absence
◦ Attributed generally to residual benign disease DIAGNOSIS of evidence to suggest locally recurrent disease
r Generally defined as detectable or rising PSA value
have a low yield, often do not affect decision
after surgery that is ≥0.2 ng/mL with a 2nd HISTORY making, poorly predict the efficacy of salvage
r Preoperative PSA
confirmatory level ≥0.2 ng/mL radiation and should not be a standard of care.
r Time since surgery
EPIDEMIOLOGY r Pathologic information from the radical
Incidence Pathologic Findings
prostatectomy Dictated by pathology from the radical prostatectomy.
Up to 30% of men will develop a biochemical r Postoperative continence and erectile function
recurrence after radical prostatectomy in large, Often positive surgical margins or seminal vesicle
– Timing of adjuvant/salvage therapy after surgery invasion is noted
institutional, long-term follow-up series (1)
may be affected by the patient’s functional
Prevalence recovery DIFFERENTIAL DIAGNOSIS
r PSA elevation due to residual benign epithelium
Based on the estimated probability of relapse after
surgery OR radiation therapy, more than 50,000 PHYSICAL EXAM after prostatectomy
Digital rectal exam to palpate for local recurrence in r Local recurrence of adenocarcinoma
American men have biochemical recurrence without
other detectable disease (2) the prostate bed r Systemic recurrence of adenocarcinoma
DIAGNOSTIC TESTS & INTERPRETATION r Local and systemic recurrence of adenocarcinoma
RISK FACTORS
r Biochemical recurrence is predicted by several Lab
r Serial surveillance of PSA after biochemical
factors: TREATMENT
– Advanced pathologic tumor stage (3) recurrence is necessary to monitor disease
◦ Adverse features include positive surgical progression and response to additional treatment if GENERAL MEASURES
margins, non-organ confined disease, seminal offered r Close monitoring of the serum PSA postoperatively.
vesicle invasion, and lymph node metastases – PSADT assessment (can be calculated using widely NCCN Guidelines recommend PSA every 3 mo if
– High Gleason score available online calculators) high risk or 6–12 mo up to 5 yr, then annually
– High preoperative PSA – PSA level can vary depending on the lab assay thereafter; annual DRE
r In addition to the risk factors above, risk factors for used so use of the same laboratory recommended r Follow up treatment decision primarily based on
the development of clinical metastases and prostate for serial follow-up pathology, imaging, and PSA dynamics
r Baseline testosterone to guide future therapy r Can include observation, androgen ablation, or
cancer related mortality include:
– Time to biochemical recurrence Imaging pelvic radiation
– PSA doubling time (PSADT) after recurrence r Imaging evaluation is necessary to determine if r Careful observation can be considered with slow
Genetics distant metastases are present under some PSADT, in older patients with other comorbidities
See “Prostate cancer, general considerations” circumstances (eg, short time to recurrence, short
PSADT, rapid rise in PSA) MEDICATION
PATHOPHYSIOLOGY – Computed tomography (CT) or magnetic First Line
r In a patient with biochemical recurrence, it is r Androgen deprivation therapy (ADT)
resonance imaging (MRI) of the abdomen/pelvis
important to try to distinguish local from systemic ◦ Identify local recurrence or lymphadenopathy – ADT drug classes include Gonadotropin-Releasing
– In general, low preoperative PSA, lower Gleason ◦ Multiparametric MRI has an emerging role in Hormone(GnRH) agonists (eg, goserelin, histrelin,
grade, lower tumor stage, prolonged time from this setting and appears to be more sensitive leuprolide, and triptorelin) and antagonists
surgery to biochemical recurrence and long PSADT than CT in detecting local recurrence (Degarelix)
are more suggestive of local recurrence – Bone scintigraphy to evaluate for bony metastases – Depot injections of the GnRH agonists allow
– Conversely, higher stage, higher Gleason score, ◦ Unlikely to be positive unless the PSA is dosing to extend from 28 days up to 1 yr
shorter (<2 yr) time to biochemical recurrence generally >20 ng/mL – GnRH antagonist dosing is every 28 days
and shorter (<3–6 mo) doubling time suggest – See “Prostate Cancer, metastatic” for more
distant disease information on drug classes
324
PROSTATE CANCER, BIOCHEMICAL RECURRENCE (ELEVATED PSA) FOLLOWING RADICAL PROSTATECTOMY
r No data are available on the optimal PSA value at 5. Alfarone A, Panebianco V, Schillaci O, et al.
which to initiate treatment ONGOING CARE Comparative analysis of multiparametric magnetic
– ADT is potentially detrimental to cognitive resonance and PET-CT in the management of local
function, quality of life, sexual health, PROGNOSIS recurrence after radical prostatectomy for prostate
r Prognosis is dictated by several variables including:
cardiovascular risk, and bone integrity cancer. Crit Rev Oncol Hematol. 2012;84(1):
– Timing of initiation of ADT should be based on a – Preoperative PSA 109–121.
patient’s risk of metastatic progression and risk of – Pathologic Gleason score 6. Crook JM, O’Callaghan CJ, Duncan G, et al.
death from disease as opposed to absolute PSA – Pathologic tumor stage Intermittent androgen suppression for rising PSA
levels – Time to biochemical recurrence level after radiotherapy. N Engl J Med. 2012;
– When ADT is initiated, in the absence of – PSADT: <3–6 mo associated with the 367(10):895–903.
metastases, intermittent ADT is preferred to development of metastatic disease 7. Stephenson AJ, Bolla M, Briganti A, et al.
continuous ADT given the side effects of this r For those patients that progress after biochemical
Postoperative radiation therapy for pathologically
treatment and the non-inferior overall survival of recurrence, in general, metastatic progression and advanced prostate cancer after radical
intermittent ADT (6) prostate cancer specific mortality occur at a median prostatectomy. Eur Urol. 2012;61(3):443–451.
– With the benefits that have been observed with of 8 and 13 yr after biochemical recurrence (4)
adjuvant/salvage radiation, the role of ADT as
COMPLICATIONS
monotherapy may be somewhat limited r Patient anxiety ADDITIONAL READING
Second Line r Complications are dictated by adjuvant and salvage r NCCN Practice Guidelines Version 1.2014
See “Prostate Cancer, metastatic” and “Prostate therapy offered
Cancer, rising PSA following androgen ablation” for http://www.nccn.org./ (Accessed January 6, 2014).
– Either radiation or ADT r Thompson IM, Valicenti RK, Albertsen P, et al.
more information on additional drug classes
FOLLOW-UP Adjuvant and salvage radiotherapy after
SURGERY/OTHER PROCEDURES Patient Monitoring prostatectomy: AUA/ASTRO Guideline. J Urol.
r Scrotal orchiectomy r Monitoring of serum PSA is necessary to diagnose 2013;190(2):441–449.
– Can be used instead of ADT biochemical recurrence and the response to
◦ Is more cost effective than ADT See Also (Topic, Algorithm, Media)
treatment when/if it is offered r Prostate Cancer, General
◦ Does not allow for intermittent androgen r For patients on ADT, baseline and periodic r Prostate Cancer, Locally Advanced (Pathologic T3,
deprivation
assessment of bone density is recommended T4)
– Quickly achieves castrate levels of testosterone
– If PSA begins to rise on ADT, serum testosterone r Prostate Cancer, Metastatic (Clinical and Pathologic
(<50 ng/mL) within 24 hr
should be assessed to ensure a castrate level
– Subcapsular scrotal orchiectomy can also be N+, M+)
offered in lieu of ADT Patient Resources r PSA elevation, General Considerations
◦ May help avoid the psychological consequences r NCCN. http://www.nccn.org/patients/ r PSA, General Considerations
of an empty scrotum patient guidelines/prostate/index.html r Reference Tables: TNM: Prostate Cancer
r American Cancer Society. http://www.cancer.org/
ADDITIONAL TREATMENT cancer/prostatecancer/detailedguide/prostate-
Radiation Therapy
r Patients with demonstrable disease in the prostate cancer-treating-recurrence CODES
bed or those with suspected local recurrence may be
considered for adjuvant/salvage radiation REFERENCES ICD9
r 185 Malignant neoplasm of prostate
– Favorable responses to adjuvant/salvage radiation
are associated with low PSA levels prior to 1. Roberts WB, Han M. Clinical significance and r 790.93 Elevated prostate specific antigen [PSA]
radiation(<1 ng/mL), long PSADTs, lower Gleason treatment of biochemical recurrence after definitive r V45.77 Acquired absence of organ, genital organs
scores, longer time to biochemical recurrence and therapy for localized prostate cancer. Surg Oncol.
positive surgical margins 2009;18(3):268–274. ICD10
– Adjuvant or early salvage radiation (based on a 2. Moul JW. Prostate specific antigen only progression
r R97.2 Elevated prostate specific antigen [PSA]
lower PSA trigger value) should be considered for of prostate cancer. J Urol. 2000;163(6):
patients with positive margins, extraprostatic 1632–1642. r Z90.79 Acquired absence of other genital organ(s)
extension, and seminal vesicle invasion (3) 3. Thompson IM, Valicenti RK, Albertsen P, et al.
◦ Such therapy, compared to radical Adjuvant and salvage radiotherapy after
prostatectomy only, reduces the risk of prostatectomy: ASTRO/AUA guideline. J Urol. CLINICAL/SURGICAL
biochemical recurrence, local recurrence, and 2013;190(2):441–449. PEARLS
clinical progression of cancer (3,7) 4. Pound CR, Partin AW, Eisenberger MA, et al. r Distinguishing local from systemic disease
◦ The impact on subsequent metastases, Natural history of progression after PSA elevation
prostate-cancer specific mortality, and overall following radical prostatectomy. JAMA. 1999; recurrence dictates adjuvant/salvage therapy
survival is less clear (3,7). The survival benefit 281(17):1591–1597. options.
r Adjuvant/early salvage radiation is supported by
was established in one randomized trial but was
refuted in another randomized trial, which was randomized trials for patients with adverse
not powered to look at this outcome (3,7) pathology at the time of prostatectomy and is
◦ Adjuvant/early salvage radiation is well endorsed by AUA/ASTRO Guidelines.
supported by randomized trials for patients with
adverse pathology at the time of prostatectomy
and is endorsed by AUA/ASTRO Guidelines
Clinical trials should be available and offered
Therapies
N/A P
325
PROSTATE CANCER, GENERAL

Robert B. Den, MD
Mark Hurwitz, MD
PATHOPHYSIOLOGY r Bone scan: Usually ordered in intermediate- and

BASICS r Normal adult prostate 20–25 g; secretes fluid high-risk patients; blastic bone lesions w/mets
comprising about 30% of ejaculate r CT abdomen/pelvis: Used to assess for visceral or
DESCRIPTION r Most CaP arise in peripheral zone of gland lymph node metastasis; indicated for intermediate-
Prostate cancer (CaP) usually refers to r High-grade prostatic intraepithelial neoplasia and high-risk patients
adenocarcinoma as other types are rare (HGPIN) may be a premalignant lesion: r ProstaScint: Nuclear scan using a PSMA monoclonal
EPIDEMIOLOGY – Risk of CaP on subsequent biopsy 16–44%; antibody to detect occult metastases. FDA-approved
Incidence/Prevalence repeat biopsy within a year not necessary unless post prostatectomy; limited use
r Most common solid tumor in US males other signs of cancer Diagnostic Procedures/Surgery
r 2014: 233,000 new cases; 29,480 deaths r Atypical small acinar proliferation (ASAP) considered r TRUS-guided needle biopsy extended template now
r Advent of PSA blood test led to a sharp increase of premalignant; 42–49% risk of cancer, biopsy should standard (10–12 cores)
CaP incidence from 1989 to 1992
be repeated r Effort should be made to sample all hypoechoic
r Highest worldwide incidence is in African ASSOCIATED CONDITIONS lesions and palpable nodules
Americans, with a relative incidence of ∼2 ED and urinary incontinence are associated with all r Transperineal w/ or w/o MRI image fusion increasing
compared to US whites local CaP therapies. Pathologic Findings
r Lowest worldwide incidence is in Asian men r >95% CaP adenocarcinoma, with <5%
GENERAL PREVENTION
(1.9/100,000/yr in China); however, Asians who r Randomized trials have been conducted transitional cell (next most common), small cell
immigrate to US increase risk to that of US men – Prostate Cancer Prevention Trial (PCPT) finasteride carcinoma, and sarcoma
r Mortality rate decreased sharply since 1991; now r Gleason Grade (1–5) determined by architectural
vs. placebo; REDUCE (dutasteride vs. placebo);
lower than before PSA era while there was 23–25% reduction in CaP risk, features observed at low magnification. The 2 most
r 5-yr relative survival rates ∼100% concern over slight increase in diagnosis of prominent grades are added together for Gleason
r Lifetime CaP risk is 16.15% high-grade cancers prevented these from being score (2–10):
FDA-approved agents – Main criterion of CaP: Loss of basal cell layer
RISK FACTORS
r Genetic and environmental factors are important in – SELECT: Examined antioxidants Vit E and selenium – Small, crowded acini with irregular contours,
terminated in 2008 due to lack of benefit; nuclear, and nucleolar enlargement
CaP development
r Family history: Risk is increased by number of increased risk of CaP and diabetes – Hormonal Rx artifactual grade increase
– Score <6 rare today; 6, 7, 8–10 are low-,
affected family members, degree of relation, and intermediate-, and high-grade disease,
age at diagnosis. DIAGNOSIS respectively
r Infection/inflammation: Prostatitis and STD r Staging:
r Oxidant stress: Several genetic determinant of CaP HISTORY
r Rarely presents with symptoms; most cases are – TNM staging, see Section VII
code for proteins that repair oxidant stress – 75% of newly diagnosed cases are T1c
r Western diet (high levels of meat, dairy, and detected by PSA screening and/or DRE
r Occasionally local tumor symptoms: Urinary – PSA >10, Gleason score ≥7, or T2b or higher
saturated fat); folate supplements should undergo imaging (CT/bone scan)
r Androgens: Essential for development and obstruction, irritative voiding symptoms, rarely
impotence, hematuria, hematospermia – CaP spreads from the prostate directly to adjacent
maturation of prostate gland r Metastatic symptoms: Bone pain, weight loss, tissues, usually via the perineural and
– Lack of androgen associated with decreased risk lymphovascular spaces
malaise; spinal cord compression with paralysis
of CaP, although no dose-dependent relationship – Can also directly invade the seminal vesicle
has been established PHYSICAL EXAM – Early metastasis to the pelvic lymph nodes
– Shortened CAG repeat length in the AR gene DRE may reveal induration, nodularity, or asymmetry – Distant metastasis: To bone, less common lung,
associated with increased risk in the gland (uncommon in most men) and in advanced stages, the liver and CNS
– Estrogen: Mixed effects on CaP
DIAGNOSTIC TESTS & INTERPRETATION DIFFERENTIAL DIAGNOSIS
– IGF-1 r Localized: BPH, prostatitis (granulomatous, acute,
– Vitamin D may protect against CaP Lab
r PSA, is typically elevated in serum of patients with chronic), recent instrumentation,
Genetics CaP (See Section I: PSA Elevation, General) nonadenocarcinoma prostate malignancy (sarcoma,
r HPC-1 gene on chromosome 1 associated with r PSA is the most widely used and controversial urothelial carcinoma)
familial CaP; HPC-1 mutation leads to defective screening test (sensitivity/specificity suboptimal) r Metastatic: Paget disease, other causes of
RNase L, accumulation of genetic defects, and r Recent guidelines have called PSA screening into pelvic/retroperitoneal lymphadenopathy (lymphoma,
eventually cancer TB, etc.)
r CaP susceptibility genes: P53 tumor suppressor, question
r PSA velocity of >2.0 ng/mL/yr: Poorer prognosis
ELAC2/HPC2, SR-A/MSR1, CHEK2, BRCA2, PON1,
after prostatectomy or radiation therapy TREATMENT
OGG1, and MIC1. r Free PSA: Lower % free PSA indicates higher risk of
– Multifocal and heterogeneous nature of CaP
makes clinical genetic studies difficult CaP GENERAL MEASURES
r Prostatic acid phosphatase: Limited utility r Localized disease, best treatment controversial and
r Familial CaP tends to follow a similar clinical course
r Alkaline phosphatase: Elevated in bone mets must be individualized; includes active surveillance,
to sporadic CaP
radical prostatectomy, radiation therapy, cryotherapy
Imaging r Consider age, overall health, life expectancy, patient
r Transrectal ultrasound (TRUS) primarily used to
guide biopsy; CaP classically a hypoechoic nodule and physician preferences
r Metastatic disease less controversial and relies
on TRUS, but can be iso- and hyperechoic
r Multiparametric MRI w/ or w/o endorectal coil may primarily on reduction of testosterone
r Risk groups (localized disease, per NCCN)
identify some cancers, used to assess local extent of
disease; utility of multiparametric MRI growing – Low risk: T1-2a/Gleason 2–6/PSA <10 ng/mL
– Intermediate: T2b–T2c/Gleason 7/PSA
10–20 ng/mL
– High:T3a or greater or Gleason score 8–10 or PSA
>20 ng/mL
326
PROSTATE CANCER, GENERAL
MEDICATION r Brachytherapy: Patient Resources

First Line – RT is delivered locally by permanent radioactive American Cancer Society. http://www.cancer.org/
r Metastatic disease: Androgen deprivation (low dose rate I125 or Pd103) seeds or temporary cancer/prostatecancer/index?sitearea=%26dt=10
– LHRH agonists: Leuprolide, goserelin, triptorelin; (high dose rate with Ir192) placed percutaneously
histrelin; transient flare then suppression of through the perineum:
pituitary LH and FSH – Low-dose monotherapy appropriate for low-risk REFERENCES
– LHRH antagonists: Degarelix; suppress LH and disease and gland <60 g 1. NCCN Practice Guidelines Version 1.2014
FSH release by the pituitary – Gleason ≥7, PSA ≥10, and ≥T2b use EBRT in http://www.nccn.org./ Accessed January 6, 2014
– Antiandrogens: Flutamide, bicalutamide, lieu of or in addition to brachytherapy
r Neoadjuvant/concurrent androgen deprivation for 2. Thompson IM, Goodman PJ, Tangen CM, et al. The
nilutamide, directly block the activity of androgens influence of finasteride on the development of
on the androgen receptor 6 mo–3 yr with XRT increases survival vs. XRT alone prostate cancer. N Engl J Med. 2003;349:215–224.
– LHRH agonists can be used alone or in or hormonal therapy alone (select intermediate and
3. D’Amico AV, Chen MH, Roehl KA, et al.
combination with oral antiandrogens all high-risk patients)
Preoperative PSA velocity and the risk of death
– LHRH agonist 1st dose, a release of testosterone is Additional Therapies from prostate cancer after radical prostatectomy.
induced (androgen flare) that may exacerbate r Active surveillance: Option for many patients due to N Engl J Med. 2004;351:125–135.
symptoms from metastatic lesions. In particular, the slow progression of CaP, especially in men >70 4. Tannock IF, de Wit R, Berry WR, et al. Docetaxel
patients with spinal metastasis may be in jeopardy who may be likely to die of other causes plus prednisone or mitoxantrone plus prednisone
of cord compression. Minimize flare by – Ideal patient: PSA <10 ng/mL, T1c, Gleason ≤6; for advanced prostate cancer. N Engl J Med.
antiandrogen therapy 2 wk prior to 1st LHRH <3 biopsy cores positive (<50% cancer in any 2004;351:1502–1512.
agonist injection core); PSA density <0.15 ng/mL/g 5. Pilepich MV, Winter K, John MJ, et al. Phase III
Second Line r HIFU: Investigational focal ablative therapy in use
Radiation Therapy Oncology Group (RTOG) trial
r Metastatic castrate–resistant CaP: W/rising PSA and outside of US 86–10 of androgen deprivation adjuvant to
“castrate” testosterone (<50 ng/dL) Complementary & Alternative definitive radiotherapy in locally advanced
– Secondary hormonal manipulations carcinoma of the prostate. Int J Radiat Oncol Biol
◦ Ketoconazole: Inhibits adrenal and gonadal Therapies
Consider dietary changes: Reduced meat and Phys. 2001;50:1243–1252.
androgen synthesis; castration hormone levels
saturated fat; increased vitamin D (see “Risk
in <8 hr, historically used w/ spinal compression
◦ Add/stop nonsteroidal antiandrogens Factors”); increased lycopenes (cooked tomato
products, red fruits; increased fiber and exercise ADDITIONAL READING
– Sipuleucel-T: Autologous immunotherapy;
minimally symptomatic or asymptomatic disease Thompson IM, Thrasher JB, Aus G, et al. Guideline for
– Abiraterone: Androgen biosynthesis inhibitor; ONGOING CARE the management of clinically localized prostate
approved in men with metastatic cancer: 2007 update. J Urol. 2007;177:2106–2131.
castrate–resistant prostate cancer previously PROGNOSIS
r Determining prognosis is multimodal See Also (Topic, Algorithm, Media)
treated with docetaxel and pre-docetaxel r Prostate Cancer, Castration Resistant
– Enzalutamide: 2nd gen oral antiandrogen, r Increased recurrence risk with:
r Prostate Cancer, General Images
previously treated with docetaxel and pre-docetaxel – High PSA (≥10), high Gleason score (≥7), r Prostate Cancer, Genomic Markers
– Radium 223 chloride; systemic α-emitter for advanced clinical stage (≥T3) r Prostate Cancer, Localized (T1, T2)
symptomatic bone mets, no visceral disease – Pathologic features: Positive surgical margins,
– Cabazitaxel and prednisone: Systemic microtubule r Prostate Cancer, Locally Advanced (T3, T4)
seminal vesicle invasion, capsular penetration,
inhibitor failing docetaxel lymph node involvement r Prostate Cancer, Metastatic (N+, M+)
– Docetaxel and prednisone: Systemic microtubule – New genomic markers available for prognosis (See r Prostate Cancer, Very Low Risk and Active
inhibitor Section II: “Prostate Cancer, Genomic markers.”) Surveillance
SURGERY/OTHER PROCEDURES r PSA Elevation, General
COMPLICATIONS
r For low-risk (T1 and T2a) cancer, 5-yr biochemical r Disease related: r PSA, General Considerations
disease-free rates are equivalent for prostatectomy, – Bladder outlet obstruction, bone pain, pathologic r Reference Tables: TNM: Prostate Cancer
radiation therapy, and brachytherapy. Thus, therapy fractures, spinal cord compression, ureteral
should be driven by the preferences of the obstruction usually due to metastasis
well-informed patient r Treatment related: CODES
r Radical prostatectomy:
– Local therapy (surgery, radiation): Impotence,
– Resection of prostate and seminal vesicles and incontinence, rectal injury ICD9
reanastomosis of bladder to urethra – Androgen deprivation: Hot flashes, loss of libido, r 185 Malignant neoplasm of prostate
– Nerve-sparing technique if possible impotence, fatigue, osteoporosis r 601.9 Prostatitis, unspecified
– Open (retropubic, perineal), laparoscopic, or – Chemotherapy: Neutropenia, sepsis r V16.42 Family history of malignant neoplasm of
robot-assisted laparoscopic; Laparoscopic prostate
approaches may offer quicker discharge, lower FOLLOW-UP
blood loss; equivalent functional/oncologic results Patient Monitoring ICD10
r PSA every 6–12 mo × 5 yr; yearly after: r C61 Malignant neoplasm of prostate
between techniques; robot higher cost
r Bilateral orchiectomy provides permanent androgen – Should be undetectable (<0.1 ng/mL) after r N41.9 Inflammatory disease of prostate, unspecified
ablation in men with advanced disease prostatectomy r Z80.42 Family history of malignant neoplasm of
r Cryotherapy uses multiple probes to ablate prostate – Should drop to <0.5 ng/mL after radiation for
prostate
tissue by freezing and thawing, using TRUS to best prognosis
r DRE every other year
monitor the extent of the ice ball
r CT of abdomen/pelvis and/or bone scan if patient CLINICAL/SURGICAL
ADDITIONAL TREATMENT has new bone pain, rapid PSA rise, short doubling
Radiation Therapy PEARLS
time
r External beam RT:
Prostate cancer requires informed decision making
– IMRT with IGRT: Provides high doses of radiation
to prostate, minimal dose to surrounding tissues
and a risk based approach; consider active P
surveillance if low risk and <10-yr life expectancy.
– Wide-field pelvic XRT with neoadjuvant androgen
deprivation may be considered in men at high risk
for nodal metastases
– Proton beam gaining support
– Hypofractionation approaches in clinical trials
327
PROSTATE CANCER, LOCALIZED (T1, T2)

Nicholas J. Kuntz, MD
BASICS DIAGNOSIS r Prostate biopsy (3)[C]
– Diagnosis is based on histologic exam
DESCRIPTION HISTORY – Transrectal ultrasound guided (TRUS) transrectal
r Biopsy-proven adenocarcinoma of the prostate, r LCaP is rarely symptomatic
or transperineal needle biopsy
clinically confined to the prostate gland r Unintentional weight loss or new-onset skeletal pain ◦ Laterally directed, 18G, 10–12 cores
r Clinical T1 or T2, N0, M0 suggests nonlocalized disease ◦ Increases detection rate
r LUTS – Periprostatic local anesthetic injection
EPIDEMIOLOGY – More commonly attributed to BPH – Antibiotic prophylaxis is always recommended
Incidence – Infection rate: 0.5–1% (see “Prostate biopsy,
r Prostate cancer (CaP) (American Cancer Society PHYSICAL EXAM
r Digital rectal exam (DRE) Infections and Complications”)
Data)
– Estimated 233,000 new cases and 29,480 deaths – No palpable nodule (cT1) Pathologic Findings
– Nodule confined to prostate gland (cT2) r Gleason score (See “Gleason Grading/Scoring
in 2014 in US
r Localized prostate cancer (LCaP) – Ablation of lateral sulcus or palpable seminal System”)
vesicles suggests more advanced disease than T2 r Proportion of biopsies positive for carcinoma
– 81% of newly diagnosed CaP
r Presence of extraprostatic extension
Prevalence DIAGNOSTIC TESTS & INTERPRETATION
r High-grade PIN and perineural invasion is usually
r Age dependent Lab
– CaP cumulative prevalence in US men r Prostate-specific antigen (PSA) reported
◦ Age 50–60: 44%; Age 70–80: 83% – Produced by prostatic epithelium DIFFERENTIAL DIAGNOSIS
r 20–35% worldwide – Half-life of 2–3 days; Not specific to CaP r Abnormal DRE: Granulomatous prostatitis prostatic
– A continuous parameter cyst, calcifications, cancer
RISK FACTORS ◦ The higher the value, the more likely the r Elevated PSA: UTI, BPH, acute or chronic prostatitis,
r Age
r Family history of CaP with highest risk in 1st-degree existence of CaP (1)[A] recent prostatic instrumentation
r Routine PSA screening is controversial
relative
– 2013 AUA Guidelines (2):
– Suggestion that familial breast cancer increasies
◦ Under age 40 yr: Do not screen [C] TREATMENT
prostate cancer risk
r African American race ◦ 40–54 yr, average risk: Do not screen [C]
GENERAL MEASURES
◦ <55 yr at higher risk: Individualized decision [C]
– 40% increased risk of disease r Assess life expectancy, overall health status, and
– 2.4 times risk of mortality ◦ 55–69 yr: Shared decision-making if
tumor characteristics prior to treatment decisions
considering PSA screening [B] (4)[A]
Genetics
See “Prostate cancer, general considerations” ◦ Greatest benefit of screening in men ages r Review risk and benefits of all treatments and
55–69 yr engage patient in informed decision making process.
PATHOPHYSIOLOGY ◦ Routine screening interval: 2 yr [C] r Treatment recommendations based on cancer
r Genetic predisposition
◦ >70 yr and <10–15-yr life expectancy: Do not
r Chronic inflammatory states biology, patient overall health, life expectancy, and
screen [C]
r Oxidative stress r Other PSA parameters preferences
r Gleason score and tumor stage are predictive of
ASSOCIATED CONDITIONS – PSA velocity/doubling time
cancer outcomes
r Benign prostatic hypertrophy (BPH) ◦ Limited use in diagnosis (1)[A] r Risk strata are used to develop treatment
r Lower urinary tract symptoms (LUTS) (unrelated to ◦ Velocity >2 ng/mL: Increased risk for death recommendations (4)[A]
cancer) from CaP
r Obesity – Low risk: PSA 10 and a Gleason score of 6 or less
– % free PSA <10 and clinical stage T1c or T2a
GENERAL PREVENTION ◦ Increased (56%) risk of cancer (1)[A] – Intermediate risk: PSA >10–20 or a Gleason
r See also “Prostate Cancer, prevention” score of 7 or clinical stage T2b
– PSA density
r There are unfortunately no approved agents for the ◦ ≥0.15 mg/mL/g suggests CaP – High risk: PSA >20 or a Gleason score of 8 to 10
chemoprevention of CaP. Major clinical trials include: r CaP antigen 3 (PCA3) (see “PCA3 Prostate Cancer or clinical stage T2c
r 5α-reductase inhibitors
Gene 3 urine assay”) MEDICATION
– Finasteride (PCPT trial, 2003) – Limited clinical use in diagnosis First Line
◦ 25% CaP risk reduction r Primary androgen deprivation therapy (ADT)
– May help in decision to a repeat biopsy in men
– Dutasteride (REDUCE trial, 2009) – Rarely indicated for LCaP (4)[C]
◦ 27% CaP risk reduction with a negative 1st biopsy (1)[A]
◦ Palliation of symptomatic patients
r Vitamin E and selenium (SELECT trial, 2011) Imaging ◦ Extensive or poorly differentiated tumors
r 2014 NCCN Guidelines for LCaP:
– Increases the risk of CaP by 17% ◦ Short life expectancy
– No imaging if low risk – Not recommended by 2014 NCCN Guidelines
– Bone scan: PSA >10 ng/mL or Gleason ≥8 r Neoadjuvant ADT for surgical treatment
– Pelvic CT or MRI
◦ Lymph node involvement risk >10% – Not recommended (1)[A]
r ProstaScint imaging: Not indicated for LCaP r Neoadjuvant/concurrent androgen deprivation for
r No imaging modality can accurately estimate the 6 mo–3 yr with XRT increases survival vs. XRT alone
extent of tumor and location within or surrounding or hormonal therapy alone (select intermediate and
the prostate all high-risk patients)
Second Line
N/A
328
PROSTATE CANCER, LOCALIZED (T1, T2)
r Cryosurgical ablation of the prostate (CSAP)

r Radical prostatectomy (RP)
REFERENCES
– Patients not suitable for RP or life expectancy
– Removal of prostate gland, seminal vesicles, and <10 yr, gland <40 mL 1. Heidenreich A, Bellmunt J, Bolla M, et al. EAU
ampulla of the vas; pelvic lymph node dissection – Freezing techniques to induce cell death guidelines on prostate cancer. Part 1: Screening,
for elevated risk of positive nodes ◦ Placement of 12–15 17G cryoneedles under diagnosis, and treatment of clinically localised
– Cancer “cure” in truly localized disease TRUS guidance disease. Euro Urol. 2011;59(1):61–71.
◦ Thermosensors at external sphincter and 2. Carter HB, Albertsen PC, Barry MJ, et al. Early
– Option for low, intermediate risk with ≥10-yr life
expectancy and selected high-risk patients (1)[B] bladder neck detection of prostate cancer: AUA guideline. J Urol.
◦ Insertion of urethral warmer 2013;190(2):419–426.
– Similar survival between RP and watchful waiting
◦ 2 freeze–thaw cycles: –40◦ C at midgland and 3. Damber JE, Aus G. Prostate cancer. Lancet.
in low-risk CaP, <65 yr (4)[B]
at the neurovascular bundle 2008;17:371(9625):1710–1721.
– Technique: – NCCN: Currently not recommended as routine
◦ Open (perineal or retropubic) 4. Thompson I, Thrasher JB, Aus G, et al. Guideline for
primary therapy for LCaP the management of clinically localized prostate
◦ Laparoscopic (LRP), Robotic assisted r High-intensity focused ultrasound (HIFU) and
laparoscopic prostatectomy (RALP): Lower blood cancer: 2007 update. J Urol. 2007;177(6):
vascular-targeted photodynamic (VTP) therapies 2106–2131.
loss and transfusion rates; oncologic and – Currently not considered valid treatment options
long-term outcome similar
◦ Pelvic lymphadenotomy (PLND) if predicted Complementary & Alternative
nodal mets is ≥2% Therapies ADDITIONAL READING
◦ Nerve-sparing surgery: Preoperatively potent Not applicable r Healy KA, Gomella LG. Retropubic, laparoscopic, or
patients, T1c, Gleason <7, and PSA <10 robotic radical prostatectomy: Is there any real
(1)[B] ONGOING CARE difference? Semin Oncol. 2013;40(3):286–296.
◦ Non–nerve-sparing for high risk (high erectile r NCCN Practice Guidelines Version 1.2014.
dysfunction rates) PROGNOSIS http://www.nccn.org./ Accessed January 6, 2014
r Salvage RP r Dependent on risk strata r Wilt TJ, Brawer MK, Jones KM, et al. Radical
– Highly selected patients with local recurrence – Low, intermediate, and high risk prostatectomy versus observation for localized
– Absence of metastatic disease – Indicate probability of biochemical failure after prostate cancer. N Engl J Med. 2012;367(3):
– High morbidity definitive local therapy 203–213.
r See on line prediction tools such as http://www.
ADDITIONAL TREATMENT mskcc.org/cancer-care/adult/prostate/prediction-tools See Also (Topic, Algorithm, Media)
r Prostate Cancer, Castration resistant
Radiation Therapy or Partin tables: http://urology.jhu.edu/prostate/ r Prostate Cancer, Genomic markers
r External beam RT (EBRT) partintables.php (Accessed August 23, 2014)
r Prostate Cancer, Locally Advanced (T3, T4)
– Intensity-modulated RT (IMRT) is preferred
COMPLICATIONS r Prostate Cancer, Metastatic (N+, M+)
– Image-guided RT (IGRT) if dose >78 Gy r RP
– Dose: Low risk: 75–79 Gy, 8–9-wk fractionation; r Prostate cancer, Very Low Risk and Active
– Significantly reduced if performed in a
intermediate/high risk: Up to 81 Gy Surveillance
high-volume hospital and experienced surgeon r PSA Elevation, General
– Combined with ADT
◦ Neoadjuvant, concomitant, or adjuvant ADT – Intraoperative: Rectal injury (0–5%), major
r Reference Tables: TNM: Prostate Cancer
bleeding (1–12%), death (0–2%)
◦ Increased survival in high-risk patients if given – Postoperative: Deep vein thrombosis (0–8%),
before and during EBRT (1)[B] pulmonary embolus (1–8%), lymphocele (1–3%)
◦ 4–6 mo or 2–3 yr for high risk (high Gleason or – Long term: Incontinence (0–50%), stricture CODES
high volume based on biopsy) (2–9%), impotence (30–100%)
r RT ICD9
– Irradiation to the pelvic lymph nodes; no general r 185 Malignant neoplasm of prostate
indication; ongoing trials (1)[B] – Short term: Bowel symptoms (bleeding, diarrhea,
fecal incontinence), irritative voiding symptoms r V16.42 Family history of malignant neoplasm of
r Brachytherapy
– Long term: prostate
– Delivered via interstitial seeds ◦ Genitourinary (16%): Strictures, hematuria,
◦ Temporary: High-dose rate (HDR): Ir192 cystitis, incontinence ICD10
◦ Permanent: Low-dose rate (LDR): I125 or Pd103 r C61 Malignant neoplasm of prostate
◦ Gastrointestinal (10%) Proctitis, chronic
– Monotherapy: Low-risk disease r Z80.42 Family history of malignant neoplasm of
diarrhea, small bowel obstruction
◦ Dose: I125 145 Gy and Pd103 125 Gy ◦ Increased risk of secondary cancers prostate
– Combined with EBRT: Intermediate/high risk
◦ 40–50 Gy of EBRT FOLLOW-UP
◦ ± 4–6 mo of ADT Patient Monitoring CLINICAL/SURGICAL
r No consensus for follow-up after definitive
– Higher risk of side effects: PEARLS
◦ Previous TURP treatment of LCaP
◦ Large (60–80 g) or small (<20 g) gland r Usually followed for at least 10 yr r Represents majority of newly diagnosed men with
◦ Bladder outlet obstruction r NCCN: PSA every 6–12 for 5 yr, then every year, DRE CaP; minority of men will die from their disease.
r Stereotactic body RT (SBRT), ie, CyberKnife r Nerve-sparing RP technique is standard of care.
every year (omitted if PSA undetectable)
– Highly conformal, high dose r Surgical outcomes are highly dependent on surgeon
r Palpable nodule on DRE and rising PSA can
– Hypofractionation (as little as 5 fractions) experience.
indicate local disease recurrence (1)[B] r Radiation techniques, improving disease control,
– May be equivalent to EBRT; under trial
r Proton therapy r See “Prostate cancer, biochemical recurrence
and reducing side effects.
– Not recommended for routine use currently (elevated PSA)” r Consider active surveillance if low risk and <10-yr
Additional Therapies Patient Resources life expectancy.
r Active Surveillance r National Cancer Institute. www.cancer.gov/
cancertopics/types/prostate
– See “Prostate Cancer, Very Low Risk and Active
Surveillance”
r AUA patient guide. www.auanet.org/common/ P
pdf/education/clinical-guidance/Prostate-Cancer-
PatientGuide.pdf
329
PROSTATE CANCER, LOCALLY ADVANCED (CLINICAL T3, T4)

Erin M. Burns, MD
James S. Rosoff, MD
Pathologic Findings
BASICS DIAGNOSIS TRUS biopsy can confirm T3 disease with biopsy of the
capsule or SVs
DESCRIPTION HISTORY
r Clinical stage T3 prostate cancer (CaP) refers to r Family history of CaP DIFFERENTIAL DIAGNOSIS
r Voiding symptoms: Obstructive/irritative, hematuria r PSA can be elevated in the setting of prostatic
disease that is thought to extend outside the
prostate and may be palpable or seen on imaging and/or urethral instrumentation, infection, or benign
r Pathologic stage T3 CaP refers to extracapsular PHYSICAL EXAM prostatic hypertrophy (BPH)
Digital rectal exam (DRE): Note palpable abnormalities, r Lesions of the prostate seen on imaging can be
extension (T3a), or tumor invading seminal vesicles unilateral vs. bilateral, whether prostate is fixed, any
(SVs) (T3b) based on final surgical pathology areas of infarct, prostatitis, or tumor
r Clinical stage T4 CaP refers to palpable tumor that
extension of mass into adjacent structures r No single diagnostic modality can accurately predict
is fixed and/or invading adjacent structures DIAGNOSTIC TESTS & INTERPRETATION pathologic stage of CaP; incorporating multiple
r Pathologic stage T4 CaP refers to tumor that is Lab clinical parameters helps to best determine disease
r PSA extent
invading the bladder neck, external sphincter,
rectum, or levator muscle, and/or is fixed to the – Positive predictive value (PPV): 12–32% for PSA
pelvic sidewall based on final surgical pathology levels 4–10, 60–80% for PSA levels >10, higher TREATMENT
r Transrectal ultrasound (TRUS) of the prostate, PSA increases risk for capsular penetration and SV
magnetic resonance imaging (MRI), and computed invasion GENERAL MEASURES
– Value is decreased by 5-ARIs, elevated with r Currently no consensus regarding optimal
tomography (CT) can supplement physical exam
findings to assist with diagnosing clinical stage T3 instrumentation, infection, larger prostate volume management of locally advanced CaP
and T4 disease – Lab variability: 20–25% (7)[A] r Compared to clinically localized, low-grade CaP,
r PSA density: Serum PSA/prostate volume locally advanced CaP has a higher risk of recurrence
EPIDEMIOLOGY after any single treatment modality (up to 30%),
Incidence – >0.15 is associated with CaP, >0.35 is associated
with 66% risk of extraprostatic extension and should be treated unless life expectancy is ≤5 yr
Declining incidence of locally advanced CaP: 10–15% r PSA velocity
in 1989–1990, 1–5% in 2001–2003 (1,2) MEDICATION
– Rate of rise of >0.75/yr is a specific marker for First Line
Prevalence CaP r Androgen deprivation therapy (ADT): Option for
N/A – Should be calculated over 18 mo with 3 PSA patients unable or unwilling to undergo surgery or
RISK FACTORS measurements radiation therapy (RT)
r Higher Gleason score, elevated prostate-specific r Free PSA (fPSA) – Orchiectomy, luteinizing hormone-releasing
antigen (PSA), and increased tumor volume on – Lower fPSA is found in CaP; <10% free correlates hormone (LHRH) agonist or antagonist
biopsy predict increased likelihood of locally with 56% probability of CaP – Can be administered continuously or
advanced disease ◦ PSA velocity, density, and fPSA do not correlate intermittently; optimal timing of administration
r Older males (≥75) are more likely to present with with Gleason score or CaP stage with respect to quality of life and survival benefit
high-risk prostate cancer (3) r PCA3 is debated
r African Americans and men with diabetes tend to – RNA overexpressed in CaP, higher values indicate – More effective when combined in neoadjuvant or
have more aggressive disease and higher stage at higher risk of CaP adjuvant fashion with RT
presentation (4) – Collected via post-DRE urine sample Second Line
– Sensitivity 48%, specificity 79%, not currently Antiandrogen monotherapy is less effective and not
Genetics used for routine screening
Research is ongoing to determine genetic markers that usually recommended; however, side effects are more
– May correlate with Gleason score (8) tolerable overall
differentiate organ confined from locally advanced
CaP Imaging SURGERY/OTHER PROCEDURES
r TRUS r Radical prostatectomy (RP) with pelvic lymph node
PATHOPHYSIOLOGY – Low sensitivity (23–66%), specificity (46–86%),
r Extension beyond prostatic capsule occurs when dissection (PLND)
and PPV (50–62%) for predicting extracapsular – Select patients can benefit from local control
tumor develops biologic ability to degrade physical
extension (9)[A] – Complete excision/cure is possible
barriers to cancer cell movement, such as the
prostatic capsule and/or fascial investments of the – Useful in guiding widespread sampling of prostate – Clinical overstaging of T3 disease can occur in up
prostate and SVs tissue during biopsy to 7–27% of patients, thus exclusion from surgery
– Intermediate-grade (Gleason 7) and high-grade r MRI on the basis of clinical staging may be
(Gleason 8–10) CaPs more commonly extend – May delineate T2 from T3 disease inappropriate
outside the prostate than low-grade (Gleason 6) r Neoadjuvant ADT does not confer cancer specific or
– Specificity for T3 disease is 95% when PSA >10,
CaP. abnormal DRE and >3 cores positive on TRUS overall survival (OS) benefit
biopsy (10)[A] r Adjuvant RT 55–70 Gy improves local control and
Locally invasive prostate cancer can present with r CT reduces the risk of biochemical recurrence for T3
resulting symptoms such as hematuria, obstructive – Consider for staging when PSA >20 or Gleason disease; it may also confer OS benefit (11)[A]
voiding symptoms and changes in bowel habits score ≥8 – Indications include T3 disease, positive surgical
r Bone scan margins, Gleason score of 8–10
GENERAL PREVENTION – Should be administered within 1 yr of surgery
r 5α-Reductase inhibitors (5-ARIs): Finasteride and – Indicated when PSA ≥20 to evaluate for skeletal
metastases and after operative side effects (eg, urinary
dutasteride continence) have improved/stabilized
r ProstaScint
– Discuss with patient risks/benefits of 5-ARI use
– May be useful in ruling out metastatic disease in
for CaP prevention (5)[A]
patients with locally advanced CaP
r Vitamin E, selenium, vitamin C:
– No beneficial effect; should not be used r TRUS-guided prostate biopsy
r Statins, green tea, lycopene
– Should be performed for abnormal DRE or PSA
– Insufficient evidence to advocate these elevation
supplements for CaP prevention (6)
330
ADDITIONAL TREATMENT Patient Resources 13. Chin JL, Ng CK, Touma NJ, et al. Randomized trial
r AUA Prostate Cancer Guide: http://www. comparing cryoablation and external beam
Radiation Therapy
r 75–80 Gy to prostate, SVs, and pelvic lymph nodes, auanet.org/content/media/pc08.pdf radiotherapy for T2c-T3b prostate cancer. Prostate
or 40–50 Gy and brachytherapy for cT3/T4 disease r NCCN Patient Guidelines for Prostate Cancer: Cancer Prostatic Dis. 2008;11:40–45.
– NCCN guidelines recommend 2–3 yr http://www.nccn.org/patients/patient guidelines/ 14. Stephenson AJ, Shariat SF, Zelefsky MJ, et al.
neoadjuvant/concomitant/adjuvant ADT for prostate/index.html Salvage radiotherapy for recurrent prostate cancer
higher disease free and OS in men with T3 and after radical prostatectomy. JAMA. 2004;291:
T4 disease (12)[A] 1325–1332.
r Advances in 3D conformal, intensity-modulated and
REFERENCES
image-guided RT are designed to deliver higher 1. Greene KL, Cowan JE, Cooperberg MR, et al.;
doses directly to prostate, avoiding adjacent Cancer of the Prostate Strategic Urologic Research
ADDITIONAL READING
structures and thus limiting side effects Endeavor (CaPSURE) Investigators. Who is the Thompson IM, Valicenti RK, Albertsen P, et al.
Additional Therapies average patient presenting with prostate cancer? Adjuvant and salvage radiotherapy after
r Cryoablation of the prostate Urology. 2005;66(5 suppl):76–82. prostatectomy: AUA/ASTRO Guideline. J Urol.
2. Cooperberg MR, Lubeck DP, Mehta SS, et al. Time 2013;190(2):441–449.
– Higher rates of biochemical failure than RT (87% trends in clinical risk stratification for prostate
vs. 53%) for T2c–T3 CaP (13)[A] cancer: Implications for outcomes (data from See Also (Topic, Algorithm, Media)
r High-intensity focused ultrasound (HIFU) r Prostate Cancer, General
CaPSURE). J Urol. 2003;170(6):21–27. r Prostate Cancer, Locally Advanced (Clinical T3, T4)
– Currently investigational, may prove to be an 3. Bechis SK, Carroll PR, Cooperberg MR. Impact of
option in combination with ADT for intermediate- age at diagnosis on prostate cancer treatment Images
r Prostate Cancer, Locally Advanced (Pathologic T3,
and high-risk CaP and survival. J Clin Oncol. 2011;29(2):235–241.
4. Mitin T, Chen MH, Zhang Y, et al. Diabetes T4)
Complementary & Alternative r Prostate Cancer, Positive Margin Following Radical
Therapies mellitus, race, and odds of high grade prostate
cancer in men treated with radiation therapy. Prostatectomy
Clinical trials should be considered r PSA Elevation, General Considerations
J Urol. 2011;186(6):2233–2237.
r Reference Tables: TNM: Prostate Cancer
5. Kramer BS, Hagerty KL, Justman S, et al. Use of
ONGOING CARE 5-α-reductase inhibitors for prostate cancer
PROGNOSIS chemoprevention: American Society of Clinical
r Significant risk of progression and disease-specific Oncology/American Urological Association 2008 CODES
death if locally advanced prostate cancer is left Clinical Practice Guideline. J Clin Oncol.
untreated 2009;27(9):1502–1516. ICD9
r 185 Malignant neoplasm of prostate
– OS without intervention ranges from 10 to 92% at 6. Stephenson AJ, Abouassaly R, Klein EA.
Chemoprevention of prostate cancer. Urol Clin r 198.1 Secondary malignant neoplasm of other
5 yr and 14–78% at 10 yr for high-grade/stage
CaP North Am. 2010;37(1):11–21. urinary organs
r RP for T3 CaP: OS 64–96% at 5 yr, 13–72% at 7. AUA PSA Best Practice Statement. Available at r 198.82 Secondary malignant neoplasm of genital
10 yr http://www.auanet.org/content/media/psa09.pdf. organs
– Cancer-specific survival (CSS): 85–92% at 5 yr, (Accessed May 21, 2014)
8. Artibani W. Landmarks in prostate cancer ICD10
79–82% at 10 yr r C61 Malignant neoplasm of prostate
r RT monotherapy: OS 60–70% at 5 yr and <50% at diagnosis: The biomarkers. BJU Int. 2012;110: r C79.11 Secondary malignant neoplasm of bladder
10 yr 8–13.
r C79.82 Secondary malignant neoplasm of genital
– RT with ADT: OS 72–87% at 5 yr 9. Hsu CY, Joniau S, Oyen R, et al. Detection of
clinical unilateral T3a prostate cancer-by digital organs
COMPLICATIONS rectal exam or transrectal ultrasonography. BJU
r Therapy complications are similar to those for
Int. 2006;98(5):982–985.
localized CaP CLINICAL/SURGICAL
r Untreated T3–T4 CaP may lead to hematuria, 10. Cornud F, Flam T, Chauveinc L, et al.
Extraprostatic spread of clinically localized PEARLS
obstruction at the level of the prostate requiring prostate cancer: Factors predictive of pT3 tumor r Risk assessment requires incorporating serum PSA,
indwelling catheter or transurethral resection of the and of positive endorectal MR imaging
prostate, or ureterovesical junction obstruction clinical stage, Gleason score, tumor volume, and
examination results. Radiology. 2002;224(1): patient age and comorbidities to best provide
requiring ureteral stents or percutaneous 203–210.
nephrostomy counseling and treatment recommendations.
11. Thompson IM, Tangen CM, Paradelo J, et al. r RP should include PLND for locally advanced CaP,
FOLLOW-UP Adjuvant radiotherapy for pathologic T3N0M0 and adjuvant RT should be offered for T3–T4
Patient Monitoring prostate cancer significantly reduces risk of disease, particularly if surgical pathology
r Periodic PSA measurements, initially at 3-mo metastases and improves survival: Long-term demonstrates positive margins.
intervals posttherapy and then gradually increasing followup of a randomized clinical trial. J Urol. r RT should be administered in conjunction with ADT
to annually 2009;181:956–962.
for locally advanced CaP to maximize survival
r Failure of PSA to nadir or consecutive rises in PSA 12. NCCN Prostate Cancer Guidelines. Available at benefit with support from randomized clinical trials.
should prompt further evaluation with bone scan http://www.nccn.org/professionals/physician gls/
and/or CT pdf/prostate.pdf (Accessed May 21, 2014)
– Risk of biochemical recurrence increased in:
Gleason score 8–10, PSA doubling time <10 mo
(14)
– ProstaScint scan may be helpful in identifying local
recurrence if bone scan and CT scan are negative
– Consider additional treatment options such as
ADT, adjuvant RT, and/or chemotherapy and
participation in clinical trials
P
331
PATHOPHYSIOLOGY r PSA velocity, density, and fPSA do not correlate with

r Peripheral zone tumors tend to invade the capsule Gleason score or CaP stage
BASICS more often than transition zone tumors r PCA3
r Tumor spread: – RNA overexpressed in CaP, higher values indicate
DESCRIPTION
r Pathologic T3/T4 (pT3/T4) is prostate cancer that – T3a (extracapsular invasion) occurs posteriorly and higher risk of CaP
extends beyond the confines of the prostatic gland posterolaterally by vascular invasion and increases – Collected via post-DRE urine sample
without evidence of lymph node or distant risk of recurrence after RP – Sensitivity 48%, Specificity 79%, not currently
r Tumor volume: used for routine screening
metastases after radical prostatectomy (RP) based
on pathology – Extraprostatic invasion is more common in tumors – May correlate with Gleason score
r Pathologic stage is determined by histologic analysis >0.5 cm3 and seminal vesicle invasion is more Imaging
of the prostate, SVs, and lymph nodes common in tumors >4 cm3 r Preoperative imaging for locally advanced cancer:
r Per the TNM system, this is considered locally – Tumor volume does not independently predict – Pelvic CT or MRI is indicated for locally advanced
postsurgical progression once grade, pathologic disease (PSA >20 ng/mL, Gleason score 8 or
advanced prostate cancer defined by the categories
stage, and margins are accounted for greater, or a T3/T4 tumor) to evaluate for pelvic
T3a, T3b, T4, if combined with an absence of
regional lymph node metastasis (N0) and distant ASSOCIATED CONDITIONS lymph node involvement
metastasis (M0). Where: Locally invasive prostate cancer can present with – Distal metastasis may be ruled out using
– T3a: Extracapsular extension resulting symptoms such as hematuria, obstructive Technetium 99 bone scan, axial MRI, PET, and
– T3b: Tumor invades seminal vesicle(s) voiding symptoms, and changes in bowel habits immunoscintigraphy
– T4: Tumor is fixed or invades adjacent structures – Multiparametric prostate MRI using a 3T magnet
GENERAL PREVENTION and/or an endorectal coil is being touted to
other than seminal vesicles (bladder neck, external r 5-Alpha Reductase Inhibitors (5-ARIs): Finasteride
sphincter, rectum, levator muscles, or pelvic wall) improve accuracy
r Tumor volume, grade, pelvic lymph node and dutasteride; discuss with patient risks/benefits – Repeat or 1st time staging with bone scan and/or
of 5-ARI use for CaP prevention; not FDA approved CT may be needed in selected patients who are
involvement, extracapsular and SV extension, and r Vitamin E, Selenium, Vitamin C: No beneficial effect;
surgical margin status predict biochemical significantly upstaged and/or upgraded after RP
should not be used
recurrence-free survival and cancer-specific survival r Statins, Green Tea, Lycopene: Insufficient evidence Diagnostic Procedures/Surgery
Prostate biopsy rarely indicates the presence of
EPIDEMIOLOGY to advocate these supplements for CaP prevention pathologic T3 disease; seminal vesical biopsy may
Incidence confirm T3
PSA screening has led to downward pathologic stage
migration. Since 2001, rates of extracapsular DIAGNOSIS Pathologic Findings
r Clinically localized disease is upstaged if pathologic
extension had remained stable at 25%. In 2012 and HISTORY
2013, USPSTF and AUA revised guidelines against PSA r Family history of CaP; race tissue from a prostatectomy indicate T3 or T4
screening; this may increase rates of T3–T4 disease. disease
r Voiding symptoms: Obstructive/irritative, hematuria r The risk of cancer recurrence after prostatectomy is
RISK FACTORS r Any bone/back/hip pain or hematuria?
r Poor health literacy, use of multivitamins more than based on extracapsular extension, seminal vesicle
PHYSICAL EXAM involvement, lymph node involvement, and
7 times a week, obesity, and lack of screening corresponds most strongly with a positive surgical
increase the risk of locally advanced disease at Digital rectal exam (DRE): Note palpable abnormalities,
unilateral vs. bilateral, whether prostate is fixed, any margin
presentation r A gross PSMs carry worse 5-r progression survivals
r Partin tables use DRE-based primary T stage, serum extension of mass into adjacent structures
vs. microscopic margins 65% vs. 40%
PSA, and Gleason grade to predict cancer extent DIAGNOSTIC TESTS & INTERPRETATION r PSM at the bladder neck, vas deferens, and
and long-term outcomes Lab
r D’Amico has also suggested a risk stratification into r PSA posterolateral surface of the prostate have been
shown to have a particularly poor progression-free
low, intermediate, and high risk based on DRE, PSA, – Positive predictive value (PPV): 12–32% for PSA outcomes in comparison to PSM at the apex,
and Gleason grade levels 4–10, 60–80% for PSA levels >10, higher posterior, anterior, or lateral prostate
r While these predictive models are helpful in PSA increases risk for capsular penetration and SV r With respect to the nerve-sparing technique, when
counseling patients, studies show that status post invasion patients are selected appropriately, no statistical
prostatectomy up to 3% of men were down-T-staged – Value is decreased by 5-ARIs, elevated with difference has been shown in PSM in comparison to
and 35% of men were up-T-staged (1) instrumentation, infection, larger prostate volume the nonnerve sparing technique
Genetics – Laboratory variability: 20–25%
r Abnormal p53 expression, low levels of p16 and r PSA density: Serum PSA/Prostate volume
deregulation of the RB pathway and aneuploidy of – >0.15 is associated with CaP, >0.35 is
Chr 9 have been associated with locally advanced associated with 66% risk extra-prostatic extension
r PSA velocity
prostate cancer
r In 2013, 2 commercial genetic biomarker assays – Rate of rise of >0.75/yr is a specific marker for
(Prolaris, Oncotype Dx-prostate) became available. CaP
Based on RNA expression profiles, these assays may – Should be calculated over 18 mo with 3 PSA
help to predict more advanced stage/grade measurements
r Free PSA (fPSA)
– Lower fPSA is found in CaP; <10% free correlates
with 56% probability of CaP
332
r A German trial of 395 patients demonstrated a 5. Wiegel T, Bottke D, Steiner U, et al. Phase III
TREATMENT biochemical progression-free survival benefit (72% postoperative adjuvant radiotherapy after radical
vs. 54%) to early radiation therapy in this pT3 prostatectomy compared with radical prostatectomy
GENERAL MEASURES group. The benefit of therapy was observed with or alone in pT3 prostate cancer with postoperative
r The American Society of Therapeutic Radiation without positive margins (5) undetectable prostate-specific antigen: ARO96-02/
Oncology (ASTRO) and the American Urologic r Genomic assays may allow more rationale decision AUO AP 09/95. J Clin Onc. 2009;27(28):
Association (AUA) have a joint guideline on the use making for post operative radiation following radical 2924–2930.
of adjuvant and salvage radiotherapy after prostatectomy (7) 6. Stephenson AJ, Shariat SF, Zelefsky MJ, et al.
prostatectomy Salvage radiotherapy for recurrent prostate cancer
– They note clinical benefit of adjuvant radiotherapy after radical prostatectomy. JAMA. 2004;291:
Proton beam external radiotherapy is offered at
in reducing clinical progression in high-risk 1325–1332.
selected major US centers. However, there is no Level I
patients (seminal vesicle involvement, positive 7. Den RB, Feng FY, Showalter TN, et al. Genomic
evidence that it is superior to photon-based
surgical margins, extra prostatic extension) while prostate cancer classifier predicts biochemical
radiotherapy using an intensity modulated method.
the impact on future development of metastasis failure and metastases in patients after
and survival remains less clear Complementary & Alternative postoperative radiation therapy. Int J Radiat Oncol
– It also emphasizes the value of early intervention Therapies Biol Phys. 2014;89(5):1038–1046.
with a threshold PSA ≥ 0.2 ng/mL with a 2nd No level I evidence of benefit
confirmatory after surgery to confirm relapse (2)
r Therapy is considered adjuvant if the postoperative
PSA level is undetectable (<0.2 ng/mL)
r Therapy is considered salvage if there is a PROGNOSIS NCCN Prostate Cancer Guidelines: http://www.nccn.
biochemical/PSA recurrence r With salvage EBRT and persistent or increasing PSA org/professionals/physician gls/pdf/prostate.pdf
r Lymph node metastasis is an indication for ADT, levels after surgery 45% of patients were free of (Accessed May 21, 2014)
pelvic RT, or observation disease at 4 yr after salvage EBRT See Also (Topic, Algorithm, Media)
– Patients with no adverse risk features achieved a r Prostate Cancer, General
MEDICATION 4-yr progression-free probability of 77%. A r Prostate Cancer, Locally Advanced (Clinical T3, T4)
First Line nomogram based on established risk factors to r Prostate Cancer, Locally Advanced (Pathlogic T3, T4)
r Androgen deprivation therapy (ADT) using an LHRH
more accurately identify patient-specific risks to
agonist or GNRH antagonist with or without an oral Images
assist in clinical decision-making is available (6) r PSA Elevation, General Considerations
antiandrogen is sometimes added to adjuvant or
salvage EBRT although there is not yet level I COMPLICATIONS – PSA, General Considerations
r Morbidity from pelvic RT include radiation proctitis, r Reference Tables: TNM: Prostate Cancer
evidence from RCTs in the adjuvant/salvage setting
for pathologic T3/T4 disease cystitis, incontinence, ED, lymphedema, and stricture r Prostate Cancer, Positive Margin Following RP
r Potential benefits of ADT must be balanced against disease
r Morbidity from hormone therapy include hot flushes,
the side-effect profile
breast tenderness, osteoporosis, diabetes mellitus, CODES
Second Line depression, and cardiac disease
Newer generation oral hormonal therapies
(abiraterone acetate, enzalutamide) may have future FOLLOW-UP ICD9
role in adjuvant and salvage therapy Patient Monitoring r 185 Malignant neoplasm of prostate
For pT3/T4 after RP; patients are generally followed r 198.1 Secondary malignant neoplasm of other
r In the setting of clinical T3/T4 disease, extended every 3 mo for the 1st yr, every 6 mo for the next urinary organs
2–5 yr and yearly thereafter depending on risk. r 198.82 Secondary malignant neoplasm of genital
lymph node dissection is gaining support in these
patients (obturator, external iliac, internal iliac, and Patient Resources organs
presacral nodes) r AUA Prostate Cancer Guide: http://www.auanet.org/
r Neoadjuvant ADT with leuprolide and flutamide for
ICD10
content/media/pc08.pdf r C61 Malignant neoplasm of prostate
r NCCN Patient Guidelines for Prostate Cancer:
3 mo prior to RP has shown to reduce positive r C79.11 Secondary malignant neoplasm of bladder
margins, but has no impact on lymph node http://www.nccn.org/patients/patient guidelines/ r C79.82 Secondary malignant neoplasm of genital
metastasis or 5-yr biochemical recurrence rate. It prostate/index.html
organs
may be used in selected cases for technical
downsizing
r Chemo hormonal downstaging trials are ongoing REFERENCES CLINICAL/SURGICAL
before RP for clinical T3/T4 disease 1. Cooke EW, Shrieve DC, Tward JD, et al. Clinical PEARLS
ADDITIONAL TREATMENT versus pathologic staging for prostate
r Pathologic T3/T4 prostate cancer includes
Radiation Therapy adenocarcinoma: How do they correlate? Am J Clin
r 3 randomized trials have been completed demons- Oncol. 2012;35(4):364–368. extracapsular cancer than extends beyond the
2. Thompson IM, Valicenti RK, Albertsen P, et al. gland, without distant metastasis.
trating a benefit to early adjuvant radiation therapy r High clinical stage, PSA levels, and Gleason score
r Treatment is optimally offered after continence is Adjuvant and salvage radiotherapy after
prostatectomy: AUA/ASTRO guideline. J Urol. (from biopsy cores) predict more advanced
restored, to allow healing to take place after surgery
r With a median follow-up of 12 yr, (Southwest 2013;190(2):144–149. pathologic staging.
r Level I evidence from 3 RCTs support adjuvant EBRT
Oncology Group [SWOG] 8794), confirmed a 3. Thompson IM, Tangen CM, Paradelo J, et al.
Adjuvant radiotherapy for pathological T3N0M0 for high-risk pT3/T4 prostate cancer after RP.
significant improvement in the risk of metastasis r For patients who do not receive adjuvant EBRT, close
(43% vs. 54%) and overall survival (41% vs. 52%) prostate cancer signicantly reduces risk of
among patients randomized to adjuvant radiation (3) metastases and improves survival: Long-term follow-up with early salvage EBRT is very commonly
r The largest trial included 1,000 patients with T3 follow-up of a randomized clinical trial. J Urol. practiced.
2009;181:956–962. r There is no level I evidence for adding ADT to EBRT
disease randomly assigned to 60 Gy of radiation vs.
4. Bolla M, Collette L, Blank L, et al. Long-term results as part of adjuvant or salvage EBRT, but selected
observation. At 5-yr, progression-free survival was
significantly improved (74% vs. 53%), with no with immediate androgen suppression and external high-risk patients may benefit. P
demonstration of an overall survival benefit (4) irradiation in patients with locally advanced
– A subsequent update suggested that the benefit prostate cancer (an EORTC study): A phase III
might be limited to patients with positive surgical randomized trial. Lancet. 2002;360:103–106.
margins
333
PROSTATE CANCER, METASTATIC (CLINICAL AND PATHOLOGIC N+, M+)

Divya Ajay, MD
Debasish Sundi, MD
Misop Han, MD
r CaP metastatic to the spine may result in neurologic

– LHRH antagonists (degarelix) rapidly decrease
BASICS symptoms, either from vertebral instability or testosterone levels with 44% testosterone
epidural extension of tumor. Note any leg weakness castration (<50 ng/dL) at day 1, 96% by day 3.
DESCRIPTION or urinary and fecal incontinence. No flare, so useful in situations such as spinal
r Metastatic prostate cancer (CaP) can be nodal
DIAGNOSTIC TESTS & INTERPRETATION cord compression.
disease discovered at prostatectomy or on imaging – Antiandrogens (bicalutamide, flutamide,
(N+), or can be distant spread (M+). Most Lab
r Serum PSA should be obtained on all patients prior nilutamide) block the LHRH flare reaction initially
commonly, it affects distant lymph nodes and bone. caused by LHRH agonists and should be used for
r Can be the initial presentation or develop after to the start of therapy and is a useful marker of
7–10 days. Long-term use of antiandrogens +
previous local therapy for CaP, such as radiation response to therapy.
r Prostatic acid phosphatase is elevated in up to 67% LHRH agonists past the flare period, or CAB is
therapy or RP. controversial.
of men with metastatic disease – ADT using high-dose bicalutamide (150 mg/d),
EPIDEMIOLOGY r Monitor serum testosterone to verify that androgen
Incidence called antiandrogen monotherapy, is associated
ablation has testosterone <50 ng/dL with less side effects but may also be a less
With PSA screening, the number of men with
metastatic disease at 1st presentation has declined Imaging effective form of ADT and should not be routinely
r CT of the abdomen and pelvis and bone scan should used (not FDA approved in US).
over the last 20 yr (∼4%, 2003–2009, SEER data).
be performed after initial diagnosis. Bone – Initial chemohormonal therapy has recently
Prevalence
metastases are typically osteoblastic. been reported to extend survival in men
Nearly 28,800 men die annually (US) from metastatic r Evaluate for hydronephrosis secondary to ureteral presenting with newly diagnosed metastatic
disease.
obstruction. prostate cancer (4)
RISK FACTORS ◦ ECOG3805 clinical trial demonstrated a
r African American ancestry Diagnostic Procedures/Surgery 12 month survival advantage when docetaxel
r High-fat diet Biopsy of prostate or metastatic lesions is required to was initially combined with androgen
r Family history establish a diagnosis. Identification of visceral deptivation therapy
metastasis with neuroendocrine features may alter
Genetics initial management to include initial chemotherapy. Second Line
None r Most patients initially benefit from ADT, but the
Pathologic Findings disease usually progresses after 1–4 yr
PATHOPHYSIOLOGY r Adenocarcinoma most common.
r CaP arises in prostate glandular epithelium and can r Neuroendocrine carcinoma of the prostate is – Castration-resistant CaP (CRPC): Progression on
primary hormonal with a testosterone level of
spread through the lymphatics or hematogenously. associated with high Gleason score (9–10), low or
r Batson plexus are paravertebral veins that extend up <50 ng/mL, and a rising PSA
undetectable PSA levels, and visceral and lytic bone – With measurable disease on bone or CT scan of
from the pelvis to the dural sinuses. This plexus is metastases. the abdomen and pelvis, the disease is classified
likely responsible for the high rate of spread of CaP as metastatic castration-resistant prostate cancer
to the vertebral column. DIFFERENTIAL DIAGNOSIS
r Paget disease; bone metastases from other (mCRPC)
r Testosterone and dihydrotestosterone are the r Secondary hormonal therapy is often utilized for
malignancies
primary regulators of prostate growth. r Adenopathy can be due to lymphoma or other CRPC without metastasis
r 2 sources of androgens in men; testes (95% of total
advanced malignancy. – If on antiandrogen, the antiandrogen should be
androgens); adrenal glands (remaining 5%). discontinued; this will result in a PSA decline in
ASSOCIATED CONDITIONS 5–20% of patients
Osteoporosis secondary to hormonal therapy TREATMENT – Addition of an antiandrogen will result in PSA
declines of 50% in 15–54% of patients, with
GENERAL PREVENTION GENERAL MEASURES median duration of response 4–6 mo
Early androgen blockade for high-risk patients with r Androgen blockade for metastatic disease, which is
– Ketoconazole blocks testicular and adrenal
localized cancer may delay the development of usually considered noncurative. androgen synthesis; associated with >50% PSA
detectable metastatic disease. r Androgen deprivation therapy (ADT) can be decline in over 50% of patients
administered continuously as well as intermittently – LHRH agonists are continued during therapy to
DIAGNOSIS (intermittent hormonal therapy or IHT); studies prevent escape from androgen blockade
suggest similar survivals when continuous combined r Several systemic therapies have demonstrated
HISTORY androgen blockade (CAB) is compared to
r Urinary symptoms can be indistinguishable from improved overall survival for metastatic
intermittent CAB, especially with lower disease castrate-resistant disease and are discussed in detail
those of BPH and include increased urinary burdens. in the section on Prostate cancer, rising PSA
frequency, nocturia, difficulty initiating and
MEDICATION following androgen ablation (Castratration Resistant
maintaining a steady stream of urine, dysuria, and
Prostate Cancer (CRPC, and mCRPC), Section I.
hematuria, and sexual dysfunction. First Line
r The most common symptom of metastatic disease is – Docetaxel, sipuleucel-T, cabazitaxel, abiraterone,
r ADT (1)[B]
enzalutamide, and radium 223
bone pain, often in vertebrae, pelvis, or ribs. – ADT to achieve castrate levels of testosterone, – Mitoxantrone is also an FDA-approved agent for
PHYSICAL EXAM generally considered <50 ng/mL, with some palliation of symptomatic CRPC
r DRE may reveal a nodular or enlarged prostate, but advocating <20 ng/mL (similar to orchiectomy – For asymptomatic or minimally symptomatic
the exam may be unremarkable. levels) patients, sipuleucel-T immunotherapy can be
r After RP the fossa may be empty or contain palpable – Testicular androgen secretion is regulated by the used; other agents can be used with more
recurrent cancer. hypothalamus, and the pulsatile secretion of significant symptoms
r Adenopathy may be detected in the supraclavicular luteinizing hormone releasing hormone (LHRH) – In patients with neuroendocrine features,
and inguinal lymph nodes. – LHRH agonists (leuprolide, goserelin, triptorelin) androgen blockade should be initiated along with
r Point tenderness elicited on vertebral bodies or rib interfere with this pulsatile secretion, and after an immediate chemotherapy regimen
cage may be indicative of spinal or epidural initial flare (testosterone increase) at 7–10 days, incorporating cisplatin/etoposide,
metastasis. achieve medical castration at about 30 days. carboplatin/etoposide, or a docetaxel-based
regimen
334
PROSTATE CANCER, METASTATIC (CLINICAL AND PATHOLOGIC N+, M+)
r Resection of solitary metastases is not generally
COMPLICATIONS
r ADT: Hot flashes, loss of sexual function and libido,
ADDITIONAL READING
performed with curative intent. loss of muscle mass, decreased in bone mineral r Antonarakis ES, Eisenberger MA. Expanding
r Decompression of epidural metastatic CaP can result density, weight gain, diabetes, lipid profile changes, treatment options for metastatic prostate cancer.
in stabilization of the spinal cord and neurologic and neurocognitive dysfunction. N Engl J Med. 2011;364:2055–2058.
symptoms. Best results are obtained if the procedure r In a metaanalysis of 8 randomized controlled trials, r Hussain M, Tangen CM, Berry DL, et al. Intermittent
is performed within 24 hr of the onset of symptoms. long-term ADT was not associated with an increased versus continuous androgen deprivation in prostate
r Stabilization of weight-bearing bones (femur and risk of death from cardiovascular causes, however. cancer. N Engl J Med. 2012;368(14):1314–1325.
hip) by internal fixation or replacement of the joint r Antiandrogens: Increased liver function test. r Loblaw DA, Virgo KS, Nam R, et al. Initial hormonal
prophylactically may prevent fracture. r Skeletal-related events: Defined by pathologic management of androgen-sensitive metastatic,
r In one randomized trial, immediate ADT was fracture, spinal compression/vertebral body collapse, recurrent, or progressive prostate cancer: 2006
osteonecrosis of the jaw, radiation or surgery to update of an American Society of Clinical Oncology
associated with improved overall and
bone, or change in antineoplastic therapy. Androgen practice guideline. J Clin Oncol. 2007;25(12):
disease-specific survival among men who had
blockade can cause osteopenia/osteoporosis; 1596–1605.
pathologically positive lymph nodes after RP (2)[A]. r Nguyen PL, Je Y, Schutz FA, et al. Association of
However, this study was limited by sample size and bisphosphonate/RANK ligand therapy can limit
lack of central pathologic review. In a randomized reductions in bone mineral density. androgen deprivation therapy with cardiovascular
EORTC study with clinically node-positive disease, – Zoledronic acid: Renal insufficiency, adjust based death in patients with prostate cancer: A
early ADT did not have any survival benefit. Because on creatinine. meta-analysis of randomized trials. JAMA.
of the gradual natural history of CaP (median – Osteonecrosis of the jaw can result from 2011;306(21):2359–2366.
survival after development of metastasis after RP = bisphosphonates and RANK ligand inhibitors; See Also (Topic, Algorithm, Media)
5 yr (3)[C]) and because the oncologic benefit of avoid major dental work (extractions) on therapy; r Antiandrogen Withdrawal Syndrome (Flutamide
early ADT is uncertain, many consider it reasonable perform oral exam before starting. Withdrawal Syndrome)
to delay ADT until symptoms or measurable disease FOLLOW-UP r Prostate Cancer, General
on imaging are present, to minimize systemic Patient Monitoring r Prostate Cancer, Metastatic (Clinical and Pathologic
adverse effects of ADT. r Monitoring patients is controversial. With start of N+, M+) Images
androgen blockade: Check PSA every 3 mo. Confirm r Prostate Cancer, Rising PSA Following Androgen
castrate testosterone (<50 ng/dL) periodically and Ablation (Castration-resistant Prostate Cancer,)
Radiation Therapy r PSA Elevation, General
r Radiation can be used to palliate solitary painful upon demonstration of rising PSA while on LHRH
therapy. r Reference Tables: TNM: Prostate Cancer
bony metastases. r At PSA progression, antiandrogen should be
r Strontium89 and samarium153 (β-emitters) can
withdrawn, and if the patient continues to progress,
palliate bone pain and are most useful for diffuse
metastasis.
a CT scan of the abdomen and pelvis should be CODES
r Radium-223 (α-emitter) can also be used in the obtained.
r Timing of PSA testing during chemotherapy is
setting of symptomatic bone metastasis ICD9
controversial; usually every 3 wk. r 185 Malignant neoplasm of prostate
Additional Therapies r Serum creatinine should be monitored for patients r 196.5 Secondary and unspecified malignant
r Bone health
on bisphosphonates. Zoledronic acid should not be neoplasm of lymph nodes of inguinal region and
– Patients should receive calcium (1,200 mg/d) and given with a Cr >2 mg/dL. lower limb
vitamin D (800–1,000 IU/d) supplements. r Monitoring for osteoporosis, obesity, insulin r 198.5 Secondary malignant neoplasm of bone and
– With ADT, consider zoledronate 4 mg IV yearly, resistance, lipid alteration, and the concern of
alendronate 70 mg PO weekly, denosumab (RANK bone marrow
increased risk of diabetes and cardiovascular
ligand inhibitors Prolia 60 mg q6mo SQ for men on diseases in men on ADT should be considered. ICD10
ADT or Xgeva with bone mets 120 mg SQ q4wk). r C61 Malignant neoplasm of prostate
r Metastatic CRPC: Zoledronate 4 mg adjusted to Patient Resources r C77.4 Sec and unsp malig neoplasm of inguinal and
renal function every 3–4 wk IV or denosumab American Cancer Society. http://www.cancer.org/
cancer/prostatecancer/index?sitearea=%26dt=10 lower limb nodes
(Xgeva) 120 mg SQ q4wk to prevent skeletal-related r C79.51 Secondary malignant neoplasm of bone
events.
Complementary & Alternative REFERENCES
Therapies CLINICAL/SURGICAL
1. NCCN Practice Guidelines Version 1.2014.
Weight-bearing exercise and stopping smoking
http://www.nccn.org./ Accessed January 6, 2014.
PEARLS
benefits osteoporosis.
2. Messing, EM, Manola J, Sarosdy M, et al. r ADT is the 1st-line treatment for metastatic CaP.
Immediate hormonal therapy compared with r There are several antiandrogen and
ONGOING CARE observation after radical prostatectomy and pelvic chemo-immunotherapeutic options for men with
lymphadenectomy in men with node-positive ADT-refractory metastatic CaP.
PROGNOSIS prostate cancer. N Engl J Med. 1999;341: r Bone-related issues should be considered in this
r The estimated 5-yr survival of metastatic CaP is
1781–1788. population.
28% (3)[C]. 3. Pound CR, Partin AW, Eisenberger MA, et al.
r For patients with lymph node–positive disease
Natural history of progression after PSA elevation
post-RP, adjuvant hormone ablation following RP following radical prostatectomy. JAMA. 1999;
increases overall survival by 2.6 yr vs. RP alone 281(17):1591–1597.
(13.9 vs. 11.3 yr) and reduces mortality risk by 4. NIH-funded study shows increased survival in men
∼46%. with metastatic prostate cancer who receive
r With metastatic CaP starting androgen blockade,
chemotherapy when starting hormone therapy
the median time to progression is 18–24 mo. The http://www.cancer.gov/newscenter/newsfromnci/
median survival once patients progress on androgen 2013/E3805 (Posted December 5, 2013).
blockade is 12–19 mo. P
335
PROSTATE CANCER, POSITIVE MARGIN FOLLOWING

RADICAL PROSTATECTOMY
Kiranpreet K. Khurana, MD
Eric A. Klein, MD, FACS

r Prostate cancer that extends to the margin of History of risk factors (higher PSA, clinical stage, and r Surgical approach (open, laparoscopic, robotic)
resection upon pathologic analysis of radical Gleason grade) may increase chance of PSM
does not appear to influence rate of PSM (3)[B]
prostatectomy specimen PHYSICAL EXAM – Use good surgical principles to avoid PSM
r May be reported as: Focal or extensive, solitary or
Digital rectal exam has been shown to be unnecessary – PSM vary by different pathologic sectioning
multiple if PSA is undetectable – Surgical experience decreases rate of PSM
EPIDEMIOLOGY DIAGNOSTIC TESTS & INTERPRETATION MEDICATION
Incidence Lab
r 5–27% for organ-confined prostate cancer (1) r Monitor PSA at follow-up visits First Line
r 17–65% for nonorgan-confined prostate cancer (1) N/A
r In patients with PSM, there is 25–40% chance of
Second Line
Prevalence subsequent biochemical recurrence (1)[B] N/A
N/A
Imaging SURGERY/OTHER PROCEDURES
RISK FACTORS r No additional imaging needed after radical
r Higher preoperative prostate-specific antigen (PSA) N/A
prostatectomy for PSM unless there is suspicion of
r Higher clinical stage locoregional recurrence or metastatic disease ADDITIONAL TREATMENT
r Higher Gleason score r Bone scan, pelvic MRI, and/or computer tomography Radiation Therapy
r Higher pathologic stage scan may be considered if above suspected (2)[C] r External beam, delivered as 3D-conformal or
r Surgeon experience r Indium In 111 ProstaScint is also indicated as a intensity modulated
diagnostic imaging agent in postprostatectomy – 64–65 Gy usual dose
Genetics patients with a rising PSA and a negative or r Adjuvant radiotherapy shown to decrease
None directly correlate with positive surgical margin equivocal standard metastatic evaluation in whom
(PSM) biochemical and local recurrence, and clinical
there is a high clinical suspicion of occult metastatic progression (2)[A]
PATHOPHYSIOLOGY disease. Limited utility for use in this setting r Effect on subsequent metastasis and overall survival
r 3 causes of PSM:
Diagnostic Procedures/Surgery not as clear
– Tumor extends beyond prostate to margin of None indicated r Treatment with adjuvant radiotherapy results in
resection
– Disruption of prostate capsule exposed cancerous Pathologic Findings lower use of salvage treatment
r PSM is a pathologic diagnosis r Since majority of patients with PSM do not develop
glands
– Artifact from intraoperative manipulation of – Most common site is prostatic apex clinical recurrence, immediate adjuvant radiotherapy
prostate or pathologic processing – Posterolateral margin and bladder neck also may lead to overtreatment
commonly involved r However, salvage radiotherapy may not be as
ASSOCIATED CONDITIONS – Note that capsule is missing at the apex, so PSM effective for high-risk disease
Nonorgan-confined prostate cancer: Higher likelihood at the apex may be artifactual r Controversy over use of immediate vs. salvage
of PSM compared to organ confined r Often classified as: Focal or extensive, solitary or
adjuvant therapy
GENERAL PREVENTION multiple
r Do not dissect too closely at prostatic apex or – Extensive and/or multiple PSM increase chance
posterolaterally since PSM frequently seen there of biochemical recurrence, but these
r For radical prostatectomy, choose surgical approach subclassifications of PSM do not have greater
with most familiarity to surgeon predictive usefulness than comparing positive vs.
negative surgical margin alone (1)[B]
r Nonorgan-confined disease with extraprostatic
extension or locally advanced disease
r Iatrogenic capsular incision
336
PROSTATE CANCER, POSITIVE MARGIN FOLLOWING RADICAL PROSTATECTOMY
Additional Therapies FOLLOW-UP See Also (Topic, Algorithm, Media)

r · Radiation Therapy Oncology Group trial 9601 is r Prostate Cancer, Biochemical Recurrence (Elevated
Patient Monitoring
investigating radiotherapy with or without long-term r PSA every 3–6 mo for 1st 3–5 yr, then annually PSA) Following Radical Prostatectomy
androgen deprivation in postprostatectomy men thereafter r Prostate Cancer, Locally Advanced (Pathologic T3,
with pT3N0 disease or pT2N0 disease with a – Value ≥0.2 ng/dL after surgery with confirmatory T4)
positive margin with PSA ≥0.2–4 ng/mL value of ≥0.2 ng/dL defines biochemical r Prostate Cancer, Positive Margin Following Radical
– Preliminary results show that 24 mo of recurrence Prostatectomy Image
antiandrogen therapy (bicalutamide) and r PSA Elevation, General
radiotherapy improve biochemical-free survival Patient Resources
American Cancer Society. http://www.cancer.org/ r Reference Tables: TNM: Prostate Cancer
and incidence of metastatic disease
– Full results awaited cancer/prostatecancer/detailedguide/prostate-cancer-
r Radiotherapy and androgen deprivation in treating-recurrence
CODES
combination after local surgery (RADICALS) trial is
evaluating immediate adjuvant radiotherapy vs. REFERENCES ICD9
salvage radiotherapy r 185 Malignant neoplasm of prostate
– Also addresses role of androgen deprivation 1. Stephenson AJ, Wood DP, Kattan MW, et al.
r V45.77 Acquired absence of organ, genital organs
– Results awaited Location, extent, and number of positive surgical
margins do not improve accuracy of predicting
Complementary & Alternative prostate cancer recurrence after radical
ICD10
Therapies r C61 Malignant neoplasm of prostate
prostatectomy. Journal of Urology. 2009;182: r Z90.79 Acquired absence of other genital organ(s)
See “Additional Therapies” above 1357–1363.
2. Thompson IM, Valicenti R, Albertsen PC, et al.
ONGOING CARE Adjuvant and salvage radiotherapy after CLINICAL/SURGICAL
prostatectomy: ASTRO/AUA Guideline. 2013.
PROGNOSIS Available online at https://www.auanet.org/ PEARLS
r Not all PSM result in biochemical recurrence, nor common/pdf/education/clinical- r PSM most commonly found at prostatic apex,
higher risk of metastatic disease and death, but guidance/Radiation-After-Prostatectomy.pdf. posterolaterally, and bladder neck.
those with PSM are at higher risk of both than those 3. Eastham JA, Kattan MW, Riedel E, et al. Variations r Avoid overzealous dissection at these locations
with negative margins; these risks are associated among individual surgeons in the rate of positive during radical prostatectomy in patients suspected
with other pathologic features as well surgical margins in radical prostatectomy
r Prediction tools such as http://nomograms.mskcc. of being high-risk for PSM.
specimens. J Urol. 2003;170:2292–2295. r PSM are diagnosed pathologically and may be real
org/Prostate/PostRadicalProstatectomy.aspx are 4. Den RB, Feng FY, Showalter TN, et al. Genomic or artifactual.
used at some centers for decision making prostate cancer classifier predicts biochemical r Subset of men with PSM develop biochemical
concerning postradical prostatectomy management failure and metastases in patients after
r Preliminary results with new genomic classifers may recurrence.
postoperative radiation therapy. Int J Radiat Oncol r Adjuvant radiotherapy decreases chance of
indicate which patients might benefit form adjuvant Biol Phys. 2014;89(5):1038–1046.
radiaion therap (4) biochemical and local recurrence but effect on
metastatic disease and overall survival not clear.
COMPLICATIONS
r Complications related to radiotherapy (2): ADDITIONAL READING
– Grade 1 or 2 acute toxicities: Common, up to 45% Touijer K, Kuroiwa K, Eastham JA, et al. Risk-adjusted
– Grade 3 or 4 acute toxicities: Up to 20% analysis of positive surgical margins following
– Up to 28% may develop late toxicities laparoscopic and retropubic radical prostatectomy.
◦ Urinary incontinence, stricture more common Eur Urol. 2007;52:1090–1096.
than gastrointestinal toxicities (proctitis)
337
PROSTATE CANCER, RISING PSA FOLLOWING ANDROGEN ABLATION

(CASTRATION-RESISTANT PROSTATE CANCER, CRPC AND mCRPC)
Jianqing Lin, MD
Wm. Kevin Kelly, DO

BASICS r Fatigue, muscle wasting, metabolic syndrome r Determine presence of radiographic metastasis as a
r Bone pain/fracture guide to treatment
DESCRIPTION r Hematuria, urinary retention r Bone scan, CT, or MRI of the abdomen and pelvis at
r Castration-resistant prostate cancer (CRPC) is r Edema baseline and then every 6–12 mo or based on
defined as prostate cancer with disease progression r Spinal cord compression clinical setting
despite effective androgen deprivation (serum total r Anemia r Bone density as needed
testosterone <50 ng/dL) r Renal failure, usually due to hydronephrosis
r CRPC patients are classified as having metastatic Diagnostic Procedures/Surgery
r Cognitive dysfunction r Postvoid residue (PVR) to evaluate for urinary
disease (bone or soft tissue visible on imaging)
(mCRPC) or nonmetastatic disease (CRPC rising PSA retention
GENERAL PREVENTION r Cystoscopy and other tests as needed
without any radiographic evidence of metastasis) N/A
r CRPC survival is improved significantly with more Pathologic Findings
effective treatment options N/A
r Synonym(s): The preferred term is castrate-resistant DIAGNOSIS
prostate cancer but sometimes called castrate HISTORY r Bone pain may also be due to degenerative joint
refractory prostate cancer. Older terms such as r Prostate cancer history including Gleason score, disease, osteoarthritis, Paget disease, or secondary
hormone refractory or androgen-independent disease stage at diagnosis, initial treatment for malignancy
prostate cancer are not considered accurate localized prostate cancer r Weight loss due to depression, other malignancies,
– Latest data shows that in CRPC prostate cells are r Time of 1st diagnosis of metastatic disease or failure to thrive
still sensitive to low levels of androgens r Past hormonal treatments including time when r Anemia related to iron and vitamin deficiency,
EPIDEMIOLOGY treatments were started second malignancy (ie, multiple myeloma), or prior
Incidence r PSA history therapies
r 233,000 cases of prostate cancer will be diagnosed r Extent of disease at the time of diagnosis and also
in the United States in 2014 current extent of disease on the bone and CT/MRI
r There will be 29,480 deaths due to prostate cancer scan TREATMENT
in 2014 r Recent changes in bowel and urinary habits
r The vast majority of patients who die with prostate GENERAL MEASURES
r Potency r Initial strategies for nonmetastatic CRPC are unclear
cancer will die from progressive metastatic CRPC r New neurologic symptoms as no randomized clinical trial has shown survival
r Historically the median survival with mCRPC is r Past medical history including any specific cardiac, advantage in the setting of no radiographically
<2 yr; newer agents, most introduced since 2010, renal, or gastrointestinal disease measurable metastatic disease
have improved overall survival by several months r Performance status r Continuing medical castration recommended
Prevalence r Mental status evaluation r Verify castrate levels of testosterone. If not
N/A r Current medications and allergies <50 ng/dL, consider alternative LHRH
r Caregiver agonist/antagonist administration or orchiectomy if
RISK FACTORS
r No definitive tool is available to determine the risk r Family history of prostate cancer or other cancers not castrate
r Smoking, alcohol, and drug history r Define the treatment objectives for patients:
of developing CRPC
– Molecular biomarkers and genomic profiles are Palliative vs. prolonging survival
PHYSICAL EXAM r Disease progression based on a rapidly rising PSA,
being explored for prognosis and treatment r Examine for adenopathy
r CRPC risk features for poor survival objective changes on bone scan or CT/MRI scan or
r Gynecomastia symptoms from the metastatic CRPC
– Low hemoglobin r GU and rectal exam r Sequencing of newer agents in the setting of
– Elevated lactate dehydrogenase r Extremity edema and swelling
– Elevated alkaline phosphatase disease progression remains under study
r Neurologic exam with focus on lower extremity r AUA, ASCO, NCCN, and other groups have issued
– Poor performance status
– Visceral metastasis particularly liver metastasis weakness and sensation guidelines for the management of CRPC
– Narcotic use for pain DIAGNOSTIC TESTS & INTERPRETATION MEDICATION
– Nomogram based on these clinical features can
Lab First Line
predict overall prognosis for CRPC (1) r Complete blood count r There are multiple treatment options based on
Genetics r Renal, electrolyte, and liver function panel disease acuity and prior treatment history such as
Common chromosomal translocations found in CRPC r Testosterone: Confirm <50 ng/dL before or after docetaxel-based chemotherapy;
include the TMPRSS2-ERG fusions. Epigenetic r Prostate-specific antigen (PSA) clinical trials always need to be considered.
abnormalities are common in CRPC r Often secondary or tertiary hormonal manipulation
PATHOPHYSIOLOGY is the initial therapy in asymptomatic mCRPC. These
Restored androgen receptor (AR) activity is a major include
driver of therapeutic failure and CRPC development. – Antiandrogen withdrawal (ie, stopping
This may occur through intracrine (intracellular) bicalutamide, etc.)
androgen synthesis, AR deregulation; AR mutation ◦ Paradoxical decrease in PSA after stopping
and alternative splicing; and posttranslational – 2nd-line hormonal therapy with nonsteroidal
modifications and cofactor alterations. antiandrogen: bicalutamide, flutamide, nilutamide
◦ Rarely results in a durable response
r Immunotherapy with sipuleucel-T: Autologous
immunotherapy for minimally symptomatic or
asymptomatic mCRPC; improved survival (2)
338
PROSTATE CANCER, RISING PSA FOLLOWING ANDROGEN ABLATION (CASTRATION-RESISTANT PROSTATE CANCER)
r Androgen biosynthesis inhibitors: 8. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter

– Ketoconazole/hydrocortisone (not FDA approved ONGOING CARE radium-223 and survival in metastatic prostate
for CRPC); a high-dose ketoconazole with steroid cancer. N Engl J Med. 2013;369(3):213–223.
supplementation PROGNOSIS 9. de Bono JS, Oudard S, Ozguroglu M, et al.; TROPIC
– Abiraterone acetate/prednisone Median survival of patients with CRPC range from 18 Investigators. Prednisone plus cabazitaxel or
◦ 1,000 mg (four 250 mg tabs) with 5-mg to 27 mo depending on the extent of disease mitoxantrone for metastatic castration-resistant
prednisone BID COMPLICATIONS prostate cancer progressing after docetaxel
◦ Specific CYP17 inhibitor; approved both pre- r Altered mental status treatment: A randomised open-label trial. Lancet.
and postchemotherapy r Anemia 2010;376(9747):1147–1154.
◦ Improved overall survival (3,4) r Bone marrow failure
r Pure AR antagonist:
r Cord compression with loss of motor or sensory
– Enzalutamide (160 mg PO daily)
function
ADDITIONAL READING
– Blocks AR translocation to nucleus; approved for r Cranial nerve deficits from prostate cancer in the r Basch E, Loblaw DA, Oliver TK, et al. Systemic
both pre and post docetaxel chemotherapy in
mCRPC (5,6) base of the skull Therapy in Men with Metastatic Castration-Resistant
r First-line chemotherapy: Docetaxel 75 mg/m2 IV r Depression Prostate Cancer: American Society of Clinical
r Disseminated intravascular coagulation (DIC) Oncology and Cancer Care Ontario Clinical Practice
every 3 wks w/prednisone (5 mg PO twice daily) (7)
r Radium 223 (Alpharadin) r Fatigue Guideline; JCO, Online before print September 8,
– mCRPC with symptomatic bone metastases (not r Hematuria 2014, doi: 10.1200/JCO.2013.54.8404.
r Muscle wasting/weakness r Cookson MS, Roth BJ, Dahm P, et al.
for visceral disease as only site)
– 6 injections at 4-wk intervals r Pain Castration-Resistant Prostate Cancer: AUA
– Delays time to disease progression and improves r Pathologic fractures (vertebral, hip, and long bone) Guideline. J Urol. 2013;190(2):429–438.
r Gomella LG, Petrylak DP, Shayegan B. Current
survival; low rate of adverse events (8) r Rectal bleeding
r Renal failure (acute and chronic) management of advanced and castration resistant
Second Line prostate cancer. Can J Urol. 2014;21(2 suppl 1):1–6.
r Consider abiraterone or enzalutamide with mCRPC r Urinary retention r Knudsen KE, Kelly WK. Outsmarting androgen
progression if either was not used previously
r Chemotherapy: Cabazitaxel (20–25 mg/m2 IV every FOLLOW-UP receptor: Creative approaches for targeting aberrant
Patient Monitoring androgen signaling in advanced prostate cancer.
3 wk) with 10-mg prednisone daily (9) Expert Rev Endocrinol Metab. 2011;6(3):483–493.
– Approved postdocetaxel Frequency of visits, exams, blood work, and r Smith MR, Egerdie B, Hernández Toriz N, et al.
r Mitoxantrone; chemotherapy FDA approved for radiographs will be dependent upon the patient’s
acuity and prostate cancer symptoms Denosumab in men receiving androgen-deprivation
palliation; limited utility therapy for prostate cancer. N Engl J Med.
r Consider clinical trials Patient Resources
r American Cancer Society http://www.cancer.org/ 2009;361(8):745–755.
SURGERY/OTHER PROCEDURES cancer/prostatecancer/detailedguide/prostate- See Also (Topic, Algorithm, Media)
r Urinary diversion (stents or percutaneous r Prostate Cancer, General
cancer-references
nephrostomy) in cases of hydronephrosis and renal r National Cancer Institute (NCI) http://www.cancer. r Prostate Cancer, Metastatic (N+, M+)
insufficiency r Prostate Cancer, Rising PSA Following Androgen
r Bladder outlet procedures such as TURP for gov/cancertopics/treatment/prostate
Ablation (Castration-resistant Prostate Cancer)
obstruction Algorithm
r Decompressive laminectomy for spinal cord REFERENCES
compromise
1. Halabi S, Small EJ, Kantoff PW, et al. Prognostic
ADDITIONAL TREATMENT model for predicting survival in men with
CODES
Radiation Therapy hormone-refractory metastatic prostate cancer.
r Samarium-153 or Strontium-89 ICD9
J Clin Oncol. 2003;21(7):1232–1237.
– For palliation painful bony mets; no survival r 185 Malignant neoplasm of prostate
2. Kantoff PW, Higano CS, Shore ND, et al.; IMPACT
benefit; cause bone marrow suppression r 790.93 Elevated prostate specific antigen [PSA]
Study Investigators. Sipuleucel-T immunotherapy
r Palliative radiotherapy r V45.77 Acquired absence of organ, genital organs
for castration-resistant prostate cancer. N Engl J
– Focal painful bone lesion Med. 2010;363(5):411–422.
– Epidural disease associated with neurologic ICD10
3. de Bono JS, Logothetis CJ, Molina A, et al.; r C61 Malignant neoplasm of prostate
symptoms or pain, or spinal cord compression COU-AA-301 Investigators. Abiraterone and
r Radium 223 (alpharadin) see “First Line” above r R97.2 Elevated prostate specific antigen [PSA]
increased survival in metastatic prostate cancer. r Z90.79 Acquired absence of other genital organ(s)
Additional Therapies N Engl J Med. 2011;364(21):1995–2005.
r Daily calcium (≥1,200 mg daily)/vitamin D 4. Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone
(800–1,000 IU daily) in metastatic prostate cancer without previous CLINICAL/SURGICAL
r Bisphosphonate (zoledronic acid) or denosumab for chemotherapy. N Engl J Med. 2013;368(2):
bone health for mCRPC to reduce skeletal-related 138–148. PEARLS
events (fractures, etc.) 5. Scher HI, Fizazi K, Saad F, et al.; AFFIRM r Castration resistant prostate cancer must be
r High dose of steroids (dexamethasone 2–10 mg) Investigators. Increased survival with enzalutamide classified as with (mCRPC) or without (CRPC)
useful in acute pain syndromes or neurologic in prostate cancer after chemotherapy. N Engl J radiographic metastasis.
compromise Med. 2012;367(13):1187–1197. r Bone or visceral metastasis will evolve if not initially
r Adding nonsteroidal anti-inflammatory drugs or 6. Beer TM, Armstrong AJ, Rathkopf DE, et al. present.
narcotics for pain Enzalutamide in metastatic prostate cancer before r Androgen–androgen receptor axis remains the key
r Palliative care or pain specialist referral for refractory chemotherapy. N Engl J Med. 2014;371(5): survival factor and treatment target for CRPC.
pain 424–433. r Androgen receptor targeted therapy,
7. Tannock IF, de Wit R, Berry WR, et al.; TAX 327 immunotherapy, chemotherapy, and bone-targeted
Therapies
Investigators. Docetaxel plus prednisone or
mitoxantrone plus prednisone for advanced
therapy are all effective to improve survival. P
May be helpful but randomized clinical trials needed prostate cancer. N Engl J Med. 2004;351(15):
to establish clinical benefit 1502–1512.
339
PROSTATE CANCER, UROTHELIAL

Samuel Haywood, MD
RISK FACTORS Diagnostic Procedures/Surgery

BASICS r Risk factors for prostatic involvement r Cystoscopy—sensitivity 83.3%, specificity 95.1%
– CIS of the bladder (2)[C]
DESCRIPTION – Multifocal disease in bladder – Focus on macroscopic disease and concurrent
r 1st described in 1952 by Melicow and – High-stage bladder UC bladder lesions
Hollowell—originally noted as Bowen’s disease of – Previous involvement of prostate – Unlikely to find microscopic disease or CIS
the prostatic urethra (1) – Tumors involving trigone or bladder neck r Transurethral biopsy (3)[C]
r Can occur in 1 of the 3 forms r Risk factors for stromal invasion—presence of CIS – No clear consensus on timing or methods
– Primary urothelial carcinoma (UC) of the prostate (odds ratio 3.2) and location of tumor at or below – Spectrum of sampling recommended in literature
– Direct extension of bladder UC trigone (odds ratio 3.3) (2) from few resectoscope swipes to complete TURP
– Nondirect extension of bladder UC – Pathologic analysis shows involvement most
r Multiple prior staging systems Genetics
r Genetics: frequently observed around verumontanum
r Primary UC of the prostate—TNM staging 2001 – Biopsies recommended if positive cytology and/or
– No specific genes associated with prostatic UC
– Tis pu—carcinoma in situ (CIS) affecting prostatic macroscopic lesions
urethra PATHOPHYSIOLOGY r Methods of biopsy have varying accuracy (1)[C]
r May involve any part of the prostatic urethra,
– Tis pd—CIS affecting prostatic ducts – Transurethral resection (TUR) biopsy is most
– T1—tumor invading subepithelial connective prostatic duct system, or prostate stroma accurate: 90% accuracy
r Arises from extension of bladder primary tumor, – Fine needle aspirate (FNA) biopsies: 40% accuracy
tissue
– T2—tumor invading prostatic stroma, implantation of malignant cells, or transformation – Transrectal needle biopsy: 20% accuracy
spongiosum body, periurethral muscle secondary to carcinogenic field effect r Biopsies poor at accurately detecting stromal
– T3—tumor invading cavernous body prostatic r Metastases commonly to bone, lung, liver invasion—sensitivity 53%, specificity 77%, positive
capsule or bladder neck (extraprostatic extension) predictive value (PPV) 45%
ASSOCIATED CONDITIONS r Diagnosis of primary UC of prostate requires both
– T4—tumor that invades surrounding organs
r Prostatic UC concurrent with bladder UC Almost all cases (>95%) associated with bladder UC
transrectal prostate biopsy and random biopsies of
– Prior TNM staging defined prostatic invasion of GENERAL PREVENTION bladder to exclude concurrent UC in the bladder
bladder UC as T4a disease General Prevention: Prevention strategies similar as to (4)[C].
– However, given the heterogeneity of this bladder UC
Pathologic Findings
classification, did not accurately predict survival r Urothelial cancer in situ (CIS) of the prostate:
– Most recent TNM classification (2010) clarifies DIAGNOSIS – Can involve the prostatic urethra, the prostatic
T4a as prostatic invasion from direct transmural or
ducts, and the prostatic acini.
extravesical spread HISTORY
r Risk factors similar to bladder UC—tobacco – Most prostate urothelial CIS arises along with
– Stromal invasion from subepithelial invasion of
bladder urothelial neoplasia or from pagetoid
prostatic urethra classified as organ confined exposure, chemical/workplace exposures spread from the bladder into the prostate.
disease r Hematuria is the most common complaint
r Synonyms: Transitional cell carcinoma (TCC) – Partial or complete replacement of urethra or duct
r Other symptoms include obstructive voiding by atypical urothelial cells with pleomorphic
EPIDEMIOLOGY symptoms, hematospermia, or systemic symptoms nuclei, coarse chromatin, and frequent mitoses.
Incidence (bone pain, fatigue, weight loss) Fibrosis and chronic inflammation may be seen.
r Of all patients with bladder UC undergoing r Invasive UC into prostatic stroma consists of
PHYSICAL EXAM
cystoprostatectomy, 12–48% will have prostatic r Hematuria or bloody urethral discharge irregular nests, clusters, or single atypical cells that
involvement (1). r Lymphadenopathy infiltrate prostatic tissue. There are 2 distinct
r However, underreporting of prostatic involvement r Abnormal digital rectal exam pathways that invade the prostate:
likely present in radical cystectomy specimens. – Invasive carcinoma arising from the prostatic
r Prostatic involvement of UC is a predictor of DIAGNOSTIC TESTS & INTERPRETATION urethra and duct, which is often associated with
understaging in recurrent nonmuscle invasive Lab CIS within the prostatic duct or acini.
r PSA: Elevations rare in UC – Prostatic stroma invasion, in which bladder cancer
bladder UC (2).
r Stromal invasion of the prostate is present in r Urine studies: Urinalysis, urine cytology penetrates from posterior periprostatic soft tissue
or the bladder neck.
7–17% of cystectomy specimens (1). Imaging r Immunohistochemistry (IHC) of prostatic urethral
r Primary UC of the prostate is rare r Staging workup involves abdominal and chest
carcinoma is identical to bladder UC: Positive for
malignancy—∼1–4% of all primary prostatic imaging (CT vs. MRI) to identify local, regional, and cytokeratin (CK) 7 (90%), and high–molecular-
tumors (1). distant spread
r Bone scan: UC lesions osteolytic vs. adenocarcinoma weight CK (HMWCK) 34βE12 (59%), and do not
Prevalence stain positive for PSA or PAP.
N/A (ADC) lesions osteoblastic
r High-grade prostatic intraepithelial neoplasia
(HGPIN)
r Prostatic adenocarcinoma
r Other uncommon prostatic tumors
340
PROSTATE CANCER, UROTHELIAL
3. Liedberg F, Chebil G, Månsson W. Urothelial

TREATMENT ONGOING CARE carcinoma in the prostatic urethra and prostate:
Current controversies. Expert Rev Anticancer Ther.
GENERAL MEASURES PROGNOSIS 2007;7(3):383–390.
r Risk reduction r Degree of prostatic invasion has prognostic
4. Esrig D, Freeman JA, Elmajian DA, et al.
r Assessment of the degree of invasion is implications with respect to 5-yr survival rates (1) Transitional cell carcinoma involving the prostate
imperative—management decision strongly – Involvement of the urethral mucosa: 100% with a proposed staging classification for stromal
dependent on this – Ductal/acinar involvement: 50% invasion. J Urol. 1996;156(3):1071–1076.
– Stromal invasion: 40% 5. Palou J, Baniel J, Klotz L, et al. Urothelial carcinoma
MEDICATION r In addition, the path of invasion from concurrent
of the prostate. Urology. 2007;69(1 suppl):50–61.
First Line bladder UC also has significant prognostic role on
r Bacille Calmette–Guerin (BCG)
5-yr survival rate (1)
– As with primary bladder UC, BCG efficacious for – Contiguous from bladder: 7% survival
prostatic urethra CIS
ADDITIONAL READING
– Noncontiguous from bladder: 46%
– Evidence regarding depth of penetration of BCG r Prostatic stromal invasion is associated with higher Patel AR, Cohn JA, Abd El Latif A, et al. Validation of
into prostatic stroma is unclear rates of node-positive disease as well as decreased new AJCC exclusion criteria for subepithelial prostatic
– CIS of prostatic urethra has response rates to BCG survival (3)[C] stromal invasion from pT4a bladder urothelial
of ∼70–100%. Response rate when combined r Decreased survival associated with prostatic stromal carcinoma. J Urol. 2013;189(1):53–58.
with bladder primary decreases to 47–72% (1)[C]. invasion persists regardless of concurrent bladder
– Response rate of bladder CIS of prostatic urethra See Also (Topic, Algorithm, Media)
UC stage (4) or surgical resection (3)[C] r Bladder Cancer, Urothelial, Invasive (T2/3/4)
to BCG immunotherapy is ∼70–100%.
COMPLICATIONS r Bladder Cancer, Urothelial, Superficial (CIS, Ta, T1)
– Some propose TUR prior to BCG therapy to
increase exposure—improved prevention of r Adverse reactions to BCG therapy r Prostate Cancer, General
recurrence compared to TUR alone (5)[C]. – Local reactions include hematuria, fever, dysuria r Prostate Cancer, Urothelial Images
– Absolute contraindications to BCG: Active urinary – BCG infectious complications include fevers
infection, gross hematuria, traumatic and/or sepsis, and are managed with
catheterization. hospitalization and antibiotics (eg, isoniazid, CODES
rifampin, ethambutol, and fluoroquinolones)
Second Line r Erectile dysfunction may occur after
N/A ICD9
cystoprostatectomy r 185 Malignant neoplasm of prostate
SURGERY/OTHER PROCEDURES r Bowel diversion risks include electrolyte r 198.1 Secondary malignant neoplasm of other
r Options include TUR alone, TUR with BCG (as in
abnormalities, nutritional deficiencies, bowel urinary organs
“First line” above), and radical cystoprostatectomy obstruction, and ureteral strictures r 233.6 Carcinoma in situ of other and unspecified
r Radical cystoprostatectomy is the treatment of
choice for stromal-invasive prostatic UC. It should FOLLOW-UP male genital organs
also be recommended for patients with progression Patient Monitoring
r Detection of prostatic relapse can be difficult, ICD10
or recurrence after nonsurgical therapies. (1,2,5)[C] r C61 Malignant neoplasm of prostate
r Cystoprostatectomy may also be considered as requiring frequent and/or lifelong biopsies of r C79.11 Secondary malignant neoplasm of bladder
treatment for prostatic UC involving the prostatic bladder, neck, and prostate.
r Surveillance of prostatic urethra recommended with r D09.19 Carcinoma in situ of other urinary organs
ducts.
r Pelvic lymphadenectomy should be performed as high-risk bladder UC or prior prostatic involvement.
r Monitor with urine cytology, cystoscopy, and
with primary bladder UC. CLINICAL/SURGICAL
r Options for diversion similar to bladder UC. While transurethral prostate biopsies.
r Biopsy is surveillance of choice with positive PEARLS
debated, prostatic urethral involvement of UC is
not an absolute contraindication to orthotopic cytology and no identifiable bladder lesion. (1) r Incidental prostatic involvement frequently found at
diversion (1). r Random biopsies occasionally recommended given
cystoprostatectomy.
frequent microscopic disease. r Detecting stromal invasion important for
Patient Resources determination of appropriate therapy.
Radiation Therapy r Involvement of prostatic urethra only may be treated
Radiotherapy has insufficient data to make N/A
recommendations (1)[C] with BCG therapy.
r Stromal invasion of prostate necessitates radical
Additional Therapies REFERENCES cystoprostatectomy.
r Chemotherapy r Prognosis highly dependent on degree of prostatic
r Data not sufficient to evaluate use of 1. Walsh DL, Chang SS. Dilemmas in the treatment of
urothelial cancers of the prostate. Urol Oncol. invasion.
neoadjuvant/adjuvant chemotherapy with respect to
2009;27(4):352–357.
prostatic UC (1)[C]. Data from bladder UC shows
∼5% survival advantage with neoadjuvant 2. Roupret M, Wood D, Bochner BH, et al. ICUD-EAU
chemotherapy International Consultation on Bladder Cancer
2012: Urothelial carcinoma of the prostate. Eur
Complementary & Alternative Urol. 2013;63(1):81–87.
Therapies
N/A
341
PROSTATE CANCER, VERY LOW RISK AND ACTIVE SURVEILLANCE

Michael A. Gorin, MD
Trinity J. Bivalacqua, MD, PhD
BASICS r A combination of genetic, hormonal, and r Transrectal ultrasound is used to guide
environmental factors underlies the development of template-based prostate biopsies.
DESCRIPTION PCa. r A bone scan and/or cross-sectional imaging are
r The National Comprehensive Cancer Network r >95% of all tumors are adenocarcinoma. unnecessary due to the exceedingly low risk of
(NCCN) (1) defines very−low-risk prostate cancer – Other histologic types include transitional cell, metastatic disease.
(PCa) with the following criteria: Clinical stage T1c, small cell, and sarcoma. r Magnetic resonance imaging (MRI) of the prostate is
prostate-specific antigen (PSA) <10 ng/mL, PSA ◦ NCCN risk categories and AS only pertain to currently under investigation for its utility in
density <0.15 ng/mL/g, biopsy Gleason score ≤6, adenocarcinoma. evaluating tumor extent and the presence of
≤2 positive biopsy cores, and ≤50% cancer in any r High-grade prostate intraepithelial neoplasia is felt high-grade disease.
1 core. to be a precursor to adenocarcinoma.
– This definition is based on the work of Epstein r Early-stage adenocarcinoma is androgen Diagnostic Procedures/Surgery
r PCa is definitively diagnosed with prostate biopsy.
et al. (2) which identified parameters associated dependent. As PCa becomes more advanced,
with low-volume organ-confined (ie, insignificant) – Most commonly performed in the office setting
tumors dedifferentiate and lose this dependency. using transrectal ultrasound.
PCa at the time of radical prostatectomy. r ∼70% of PCa arise from the peripheral zone of the
r Active surveillance (AS) aims to spare men with ◦ A 10–12-core biopsy should be performed to
prostate. ensure adequate sampling of the prostate.
insignificant tumors the side effects of treatment r Tumors are often multifocal. ◦ Requires only local lidocaine for analgesia.
while maintaining the ability to intervene with
◦ A hypoechoic lesion may represent an area of
curative intent upon the detection of disease ASSOCIATED CONDITIONS
progression. r Many men with PCa also have benign prostatic cancer but is not a sensitive finding.
– The goals of AS are accomplished by carefully – Transperineal biopsy is typically reserved for men
hyperplasia (BPH)/lower urinary tract symptoms.
following men with serial PSA measurements, with several negative biopsies in whom PCa is still
– BPH is not a precursor to PCa.
digital rectal exams (DREs), and prostate biopsies. suspected.
r AS is most appropriate for men with very−low-risk GENERAL PREVENTION ◦ Allows for systematic saturation biopsies using a
r The 5α-reductase inhibitors (5-ARIs) finasteride and grid-based approach.
PCa and a life expectancy of <20 yr, or for those dutasteride have been shown in 2 randomized ◦ Requires general anesthesia.
with low-risk PCa (defined by the NCCN as clinical clinical trials (PCPT and REDUCE) to decrease the – Image fusion biopsy combining ultrasound/MRI
stage T1 to T2a, biopsy Gleason score ≤6, and PSA incidence of PCa. images are being explored.
<10 ng/mL) and a life expectancy of <10 yr (1). – These medications, however, failed to receive FDA
r The exact criteria for AS enrollment vary by Pathologic Findings
approval for PCa prevention due to their r Biopsy Gleason score ≤6 and ≤2 positive cores
institution. suggested association with increased risk of
– Triggers for intervention while on AS also vary by with ≤50% cancer in each core are required for the
high-grade tumors (controversial). definition of very–low-risk PCa.
center, but typically include violation of the r The SELECT trial showed that daily selenium and/or r Evolving use of genomic assays based on the
enrollment criteria or a rapid rise in PSA. vitamin in E do not prevent PCa and should not be
◦ Dahabreh et al. (3) have reviewed the prostate biopsy to determine risk of progression on
recommended to patients. AS (Oncotype DX and Prolaris).
enrollment and progression criteria used at
number of different institutions. DIFFERENTIAL DIAGNOSIS
EPIDEMIOLOGY DIAGNOSIS r Localized PCa:
Incidence – BPH, prostatitis (granulomatous, acute, or
r ∼240,000 new cases of PCa are diagnosed HISTORY chronic), recent instrumentation,
r Uniformly asymptomatic.
annually in the United States. nonadenocarcinoma prostate malignancy
– Typically detected on prostate biopsy performed
r >90% of new cases will be clinically localized. (sarcoma, urothelial carcinoma)
for an elevated PSA and/or finding of a prostate
r Up to 40% cases would have remained clinically nodule on DRE.
insignificant had they not been detected on routine – Occasionally detected at the time of transurethral TREATMENT
screening. resection of the prostate for BPH.
Prevalence GENERAL MEASURES
PHYSICAL EXAM r Adequate patient evaluation and review of all
An estimated 2.6 million men in the United States Very−low-risk PCa has no findings on DRE (clinical
carry a diagnosis of PCa. treatment options is essential
stage T1c). r Identification of patients who may be an
RISK FACTORS DIAGNOSTIC TESTS & INTERPRETATION appropriate candidate for AS
r Age
Lab MEDICATION
r Family history/genetics
PSA <10 ng/mL and PSA density <0.15 ng/mL/g are
r African American race required for the definition of very–low-risk PCa. First Line
r No role for chemotherapy or androgen deprivation
r Possibly obesity and a Western diet
for men who are candidates for AS.
Genetics r 5-ARIs do not appear to prevent disease progression
Mutations in a number of genes have been linked to of men on AS.
PCa including BRCA1, BRCA2, HOXB13, and HPC1.
Second Line
N/A
342
PROSTATE CANCER, VERY LOW RISK AND ACTIVE SURVEILLANCE
r Radical prostatectomy may be offered to men who
Patient Monitoring r Heidenreicha A, Bellmunt J, Bolla M, et al. EAU
desire treatment. r The optimal protocol for monitoring men on AS is
– A pelvic lymph node dissection may be omitted unknown. guidelines on prostate cancer. Part 1: Screening,
given the low risk of lymph node metastases in – Most advocate for biannual PSA measurements diagnosis, and treatment of clinically localised
this population. with DRE and annual 12–14-core prostate biopsy. disease. Eur Urol. 2011;59:61–71.
– Comparing open to robotic or laparoscopic ◦ PSA kinetics do not appear to be helpful in r Thompson I, Thrasher JB, Aus G, et al. Guideline for
surgery, outcomes appear to be equivalent predicting disease progression (5). the management of clinically localized prostate
between surgical approaches (4). r Monitoring for disease progression is not indicated cancer: 2007 update. J Urol. 2007;177:2106–2131.
– Major side effects of surgery include urinary after age 75 of when life expectancy is <10 yr.
incontinence and erectile dysfunction.
r Prostate Cancer, General Considerations
Patient Resources
ADDITIONAL TREATMENT r The NCCN Guidelines for Patients: Prostate Cancer. r Prostate Cancer, Genomic Markers
Radiation Therapy (http://www.nccn.org/patients/guidelines/prostate/) r Prostate Cancer, Localized (T1, T2)
r External beam radiation therapy or brachytherapy r What You Need to Know About Prostate Cancer r PSA Elevation, General Considerations
are acceptable alternatives to AS and surgery. from the National Cancer Institute. (http://www.
– Adjuvant hormonal therapy is not indicated with cancer.gov/cancertopics/wyntk/prostate/
either approach in this group of men. prostate.pdf). CODES
– When external beam radiation therapy is
performed, treatment with either intensity-
REFERENCES ICD9
modulated or 3-dimensional conformal radiation r 185 Malignant neoplasm of prostate
therapy should be utilized to limit toxicity to r 790.93 Elevated prostate specific antigen [PSA]
surrounding organs. 1. NCCN Practice Guidelines Version 1. 2014.
http://www.nccn.org./ Accessed January 6, 2014. r V76.44 Screening for malignant neoplasms of
– Brachytherapy should be avoided in men with
symptoms of bladder outlet obstruction (high 2. Epstein JI, Walsh PC, Carmichael M, et al. prostate
International Prostate Symptom Score) due to the Pathologic and clinical findings to predict tumor
extent of nonpalpable (stage T1c) prostate cancer. ICD10
risk of worsening lower urinary tract symptoms. r C61 Malignant neoplasm of prostate
– Major side effects of radiation include urinary JAMA. 1994;271:368–374.
r R97.2 Elevated prostate specific antigen [PSA]
incontinence, irritative voiding symptoms, erectile 3. Dahabreh IJ, Chung M, Balk EM, et al. Active
r Z12.5 Encounter for screening for malignant
dysfunction, radiation induced proctitis, surveillance in men with localized prostate cancer:
hemorrhagic cystits and secondary malignancies A systematic review. Ann Intern Med. 2012; neoplasm of prostate
most commonly of the bladder and rectum. 156:582–590.
Additional Therapies 4. Magheli A, Gonzalgo ML, Su LM, et al. Impact of CLINICAL/SURGICAL
r Technologies for focal and hemi- ablation are surgical technique (open vs laparoscopic vs
robotic-assisted) on pathological and biochemical PEARLS
currently in the early phases of investigation.
– Modalities include cryotherapy, high intensity outcomes following radical prostatectomy: An r A large percentage of older men with
focused ultrasound, interstitial laser and analysis using propensity score matching. BJU Int.
screen-detected PCa will have insignificant tumors
electroporation. 2011;107:1956–1962.
and, therefore, not benefit from intervention.
5. Ross AE, Loeb S, Landis P, et al. Prostate-specific r To avoid the potential morbidity associated with
Complementary & Alternative antigen kinetics during follow-up are an unreliable
Therapies treatment, AS should be offered to men with
trigger for intervention in a prostate cancer
Low fat diet appropriate recommendation very−low-risk PCa and a life expectancy of <20 yr.
surveillance program. J Clin Oncol. 2010;28: r The optimal follow-up protocol is not well defined
2810–2816.
but typically includes biannual PSA measurements
ONGOING CARE with DRE and annual 12–14-core prostate biopsy.
r PSA kinetics are less useful than biopsy findings for
PROGNOSIS
r Up to 30% of men enrolled in AS will be reclassified accurately reclassifying men while on AS.
r It is unknown if men reclassified on AS would have
and go onto require some form of treatment.
– It remains unknown if these men would have had been better served with immediate treatment;
a superior oncologic outcome had they undergone however, long-term data from a number of centers
immediate treatment. suggest good oncologic outcomes with this
management strategy.
COMPLICATIONS
r AS spares men with insignificant tumors the side
effects of unnecessary treatment.
r The major risk of AS is missing the opportunity to
intervene when cure is still possible.
r A small percentage of men will experience an
infectious or bleeding complication related to a
prostate biopsy.
343
PROSTATE, ABSCESS
r With severe immunocompromise, such as HIV; more DIAGNOSTIC TESTS & INTERPRETATION
BASICS unusual organisms such as TB, Cryptococcus, Lab
histoplasmosis, and Candida should be considered. r Complete blood count with differential
DESCRIPTION r Melioidosis is an infection (usually abscesses in r Urinalysis, urine/blood cultures
r Prostate abscess is an infection of the prostate with
many sites including the prostate). r Gram stain/culture of prostatic fluid once drained
focal accumulation of pus within the prostate gland – Caused by the gram-negative Burkholderia r AFB or mycobacterium-specific PCR if TB suspected
r Difficult to initially clinically distinguish from acute pseudomallei. r Prostate-specific antigen should not be obtained in
bacterial prostatitis – Usually associated with diabetes.
r Usually as a result of ineffective antibiotic therapy this setting as it will usually be elevated due to the
– Very high prevalence in East Asia and Northern
inflammatory process
for acute prostatitis Australia.
– Rare in nonhospitalized patients Imaging
ASSOCIATED CONDITIONS r Transrectal ultrasound (TRUS)
EPIDEMIOLOGY r Any disease process that causes
– Will reveal hypoechoic zones with irregular
Incidence immunocompromise: internal echoes, septations, and indirect borders
Decreasing with widespread use of antibiotics – Cancer with the surrounding prostate;
– Chronic renal failure, hemodialysis – Must be performed cautiously.
Prevalence – Cirrhosis
Diagnosed in 0.2% of patients with urologic – May guide drainage and aspiration
– Diabetes – The presence of gas suggests EPA
symptoms, 0.5–2.5% of patients hospitalized for – HIV/AIDS
prostatic symptoms (1) r Color Doppler sonography
GENERAL PREVENTION – Will show an increase in vascularity around the
RISK FACTORS r Aimed at preventing and treating sexually abscess, due to hyperemia stemming from the
r Bladder outlet obstruction, history of bacterial
transmitted infections surrounding inflammation
prostatitis r Relieving/improving signs/symptoms of bladder r Computed tomography (CT)
r Chronic hemodialysis
r Compromised immune system (eg, HIV/AIDS, outlet obstruction – Can determine penetration of the abscess into the
r Diabetic glycemic control periprostatic tissues and identify gas within the
diabetes, etc.) r Appropriate treatment of patients with acute prostate
r Indwelling catheters
prostatitis – CT findings include nonenhancing fluid-density
r Lower urinary tract instrumentation collections that can be multiseptated or
r Sexually transmitted infections rim-enhancing lesions.
DIAGNOSIS r MRI
Genetics
N/A – MRI may not be feasible in patients who are
HISTORY critically ill and require acute management
r Fevers, chills
PATHOPHYSIOLOGY
r Usually an ascending infection in association with r Urinary symptoms with attention paid to voiding Diagnostic Procedures/Surgery
r TRUS with aspiration
poor bladder emptying. patterns prior to acute presentation
r Urethral infection combined with intraprostatic r Transperineal ultrasound with aspiration
– Dysuria, urinary urgency and frequency are almost
universal symptoms r Transurethral unroofing of prostate abscess
reflux of infected urine causes acute prostatitis.
r Acute prostatitis can, in patients with – Suprapubic or subpubic pain, Pathologic Findings
immunosuppression or other risk factors, progress to – Severe perineal pain r Purulent material will be expressed from prostate
abscess. – Rectal tenesmus during surgical drainage procedure:
r Hematogenous dissemination, especially with r Acute urinary retention
– Gram stain and culture of material will give
r Sexual history/social history (IV drug use, etc.) causative agent, most commonly bacterial
Staphylococcus sp. seen in immunocompromised
patients/IV drug users. r Associated medical comorbidities
r Most common etiologic agent is Escherichia coli r Clinically can be hard to distinguish from urinary
ALERT
(2)[B]. Where prostate abscess or acute prostatitis is tract infection (UTI), acute prostatitis, or any other
r With the advent of antibiotics, the incidence of lower UTI.
suspected, rectal exam may be contraindicated. r Should have clinical suspicion, which can be
Neisseria gonorrhea as causative agent has
decreased significantly. PHYSICAL EXAM confirmed with imaging.
r Most common etiologic agent seen in r Perineal pain, tenderness
r Urethral discharge
emphysematous prostate abscess (EPA) is
Klebsiella pneumoniae (3)[B]. r Digital rectal exam can reveal exquisitely tender and
warm prostate with fluctuance or simply an
enlarged prostate
r Signs of other medical comorbidities (ie, new cardiac
murmur, ascites, cough, track marks, etc.)
344
PROSTATE, ABSCESS
r Open incision and drainage through a perineal

REFERENCES
TREATMENT approach
– Utilized in patients with penetration of the 1. Granados EA, Riley G, Salvador J, et al. Prostatic
GENERAL MEASURES abscess through the capsule of the prostate or abscess: Diagnosis and treatment. J Urol.
r Initial treatment should focus on broad-spectrum through the levator ani 1992;148:80–82.
antibiotics, IV hydration, and pain control. – Allows placement of a drain 2. Ludwig M, Schroeder-Printzen I, Schiefer HG, et al.
r In the setting of acute urinary retention, a Foley – Increased morbidity compared to open Diagnosis and therapeutic management of 18
catheter placement can be attempted. percutaneous or transurethral approaches patients with prostatic abscess. Urology.
– Occasionally the transurethral catheter may block r Suprapubic cystotomy can be used as an adjunct for 1999;53(2):340–345.
drainage of an acutely inflamed prostate or cause urinary diversion in patients with urinary retention 3. Tai H. Emphysematous prostatic abscess: A case
bacteremia. report and review of literature. J Infect.
– In the setting of extreme discomfort or if the 2007;54:e51–e54.
catheter is difficult to pass, a suprapubic punch Radiation Therapy
cystostomy is preferred. N/A
MEDICATION Additional Therapies ADDITIONAL READING

r Relates to predisposing conditions
First Line r For patients with bladder outlet obstruction, therapy r Baker SD, Horger DC, Keane TE. Community-
r Broad-spectrum IV antibiotic therapy followed by
should be started to relieve obstruction, (ie, acquired methicillin-resistant Staphylococcus aureus
directed therapy after causative organism prostatic abscess. Urology. 2004;64(4):808–810.
α-blockers or 5α-reductase inhibitors)
determined by urine culture or Gram stain/culture of r Jang K, Lee DH, Lee SH, et al. Treatment of prostatic
abscess fluid: Complementary & Alternative abscess: Case collection and comparison of
– 2nd-generation cephalosporins (cefoxitin, zinacef) Therapies treatment methods. Korean J Urol. 2012:53(12):
or 3rd-generation cephalosporins (ceftriaxone, N/A 860–864.
cefotaxime, ceftazidime)
– IV fluoroquinolones See Also (Topic, Algorithm, Media)
– Clindamycin for additional anaerobic coverage is
ONGOING CARE r Prostate, Abscess Image
recommended initially r Prostatitis, Acute, Bacterial (NIH I)
PROGNOSIS r Urinary Tract Infection (UTI), Adult Male
◦ 600–900 mg IV every 8 hr (q8h) r Should recover fully once definitive therapy
– After acute phase, continue oral antibiotic undertaken r Urosepsis
regimen based on cultures for up to 4 wk r Although EPA is rare, a 25% mortality rate has been
Second Line reported
r Vancomycin for coverage of MRSA is suspected.
COMPLICATIONS
CODES
– Dose based on renal function r May progress to spontaneous fistulization into the
r Fungal infections may require 4–6 wk of systemic ICD9
urinary bladder, prostatic urethra, rectum, or r 596.0 Bladder neck obstruction
therapy in addition to drainage. perineum.
r Urosepsis, and possibly death if diagnosis not made r 601.0 Acute prostatitis
SURGERY/OTHER PROCEDURES r 601.2 Abscess of prostate
r Transurethral unroofing of prostate abscess in timely manner.
r Transperineal or transrectal needle aspiration with
FOLLOW-UP ICD10
US guidance followed by urethral catheter drainage r N32.0 Bladder-neck obstruction
Patient Monitoring
– Can be performed using local anesthesia or r Supportive once definitive therapy performed r N41.0 Acute prostatitis
sedation r Once acute events resolves, monitoring focuses on r N41.2 Abscess of prostate
– Higher risk of recurrence of abscess
optimizing medical comorbidities and improving
voiding symptoms.
r Author recommendation: CT or TRUS 4–6 wk after CLINICAL/SURGICAL
definitive therapy to confirm that no residual PEARLS
abscess remains r Prostate abscess is uncommon and thus often
r Follow-up urine culture recommended
overlooked in the differential diagnosis.
Patient Resources r Suspect prostatic abscess in patients presenting with
N/A fever and persistent lower urinary tract symptoms
that do not respond to antibiotics.
r A pelvic CT scan is generally the best test to
evaluate for the possibility of a prostate abscess.
r A delay of antimicrobial therapy in the management
of acute bacterial prostatitis can increase the risk of
prostatic abscess.
345
PROSTATE, BENIGN HYPERPLASIA/HYPERTROPHY (BPH)

r Detrusor response to increased resistance is to DIAGNOSTIC TESTS & INTERPRETATION

BASICS generate higher pressures to overcome the outlet Lab
resistance. Leads to a variety of cellular and r Urinalysis to exclude hematuria or evidence of
DESCRIPTION morphologic changes in the bladder. Causes the infection
r Benign prostatic hypertrophy (BPH) refers to common storage symptoms of frequency, urgency, r PSA:
histologic changes within the prostate gland. and nocturia. – May be a proxy for prostate size
– May not imply the presence of an enlarged r May lead to bladder decompensation, in which the ◦ PSA of 1.5 ng/dL correlates with prostate
prostate or symptoms. bladder is no longer able to generate sufficient volume >30 mL in most men (4)
– LUTS are 1 manifestation of BPH. pressures to empty. – Informed discussion of risks/benefits of PSA
– Synonym(s): Nodular hyperplasia r Primary androgen-dependent growth process screening warranted
r Definitions from the International Continence r Urine cytology: Not considered standard; only if
involves periurethral and transition zones of the
Society (ICS): prostate. there is a predominance of irritative symptoms,
– Benign prostatic hyperplasia is a term used (and hematuria, and/or risk factors for bladder cancer
reserved for) the typical histologic pattern which ASSOCIATED CONDITIONS
r OAB (overactive bladder defined as urinary such as smoking
defines the disease.
– Benign prostatic obstruction is a form of bladder frequency, urgency, nocturia, urge incontinence) Imaging
r Sexual dysfunction (erectile and/or ejaculatory r Not indicated unless there is evidence of upper tract
outlet obstruction (BOO) and may be diagnosed
when the cause of outlet obstruction is known to dysfunction) deterioration or a need to further evaluate hematuria
r TRUS may be beneficial in determining accurate size
be benign prostatic enlargement, due to histologic GENERAL PREVENTION
benign prostatic hyperplasia. r Randomized clinical trials (MTOPS) suggested that prior to surgical intervention
– Benign prostatic enlargement (BPE) is defined as the combination of an α-blocker with a Diagnostic Procedures/Surgery
prostatic enlargement due to histologic benign 5α-reductase inhibitor (5-ARI) can reduce the r Uroflowmetry is a simple noninvasive urodynamic
prostatic hyperplasia. The term “prostatic lifetime risk of acute urinary retention and may measurement in which a patient voids into a device
enlargement” should be used in the absence of prevent symptomatic disease progression in men that measures the volume/time of urine
prostatic histology. with enlarged prostate volume (>25 cc) (3). accumulation:
EPIDEMIOLOGY r Bladder decompensation may be prevented by – Combined with a measurement of PVR (post void
Incidence treatment of BOO. residual) volume (see next heading below), it is an
r 50% of men >40 yr will develop histologic evidence excellent screening tool for BOO in men with LUTS.
of BPH – Uroflowmetry measures voided volume, voiding
DIAGNOSIS time, average flow rate, and maximum flow rate
– 30–50% of these men will develop bothersome
LUTS (1) (Qmax), also called the PFR.
HISTORY
r Focus on identifying the presence of LUTS – Qmax: The single best measurement obtained by
Prevalence this study to assess voiding dysfunction. While
r Histologic prevalence of BPH increases with age: – Voiding symptoms (previously called obstructive
formal definitions vary, in general with a voided
– 10% for men in their 30s symptoms): Hesitancy, intermittency, weak
volume of >125–150 mL, a Qmax of >15 mL/s is
– 20% for men in their 40s stream, abdominal straining to void, postvoid
often considered normal, whereas a value of
– 50–60% for men in their 60s dribbling, incomplete emptying, double voiding)
<7 mL/s is suggestive of significant obstruction.
– 80–90% for men in their 70s and 80s – Storage symptoms (previously called irritative
– May need urodynamics to differentiate BOO from
r Men with significant prostate enlargement (>50 cc) symptoms): Daytime frequency, nocturia, urgency,
hypocontractile bladder (pressure flow study).
3.5 times more likely to have moderate-to-severe urge incontinence, enuresis, dysuria) ◦ Obstruction confirmed with low flow (Qmax
r Identify other contributing factors to LUTS
LUTS (2) <15 mL/s) and high voiding pressure >60 cm
– BPH is a histologic diagnosis that does not always – Medications (ie, diuretics, cold medications) water.
result in clinical LUTS – Comorbidities (ie, diabetes, multiple sclerosis, r PVR: Although generally used, PVR does not
Parkinson)
RISK FACTORS r Previous interventions/therapies convincingly correlate with the severity of LUTS, the
r Although family history and advancing age are risk r Family history presence of BOO, or treatment outcomes:
r Voiding diary to evaluate for occult polyuria or
factors for BPH, evidence for comorbidity, r IPSS is a reproducible, validated index designed to
environmental, dietary, or lifestyle-related risk polydipsia.
determine disease severity and response to therapy: r Cystoscopy not essential unless there is concern for
factors are generally weak.
r Massachusetts Male Aging Study: Cigarette – Scores of 0–7, 8–19, and 20–35 signify mild, malignancy, obstruction due to foreign body, or
moderate, and severe symptoms, respectively. stricture. May be useful to evaluate for most
smoking and increased physical activity protective – Equivalent to AUASS with the addition of a quality
against BPH, heart disease correlated with appropriate surgical or minimally invasive
of life (QOL) score treatments.
development of BPH. Possible association between
obesity and prostate volume/LUTS. PHYSICAL EXAM Pathologic Findings
r Evaluation of the abdomen, pelvis, perineum r Varying degrees of glandular and stromal nodular
Genetics r Examine external genitalia
Some men with younger age of onset and larger hyperplasia (as such, hypertrophy is a misnomer).
r DRE to estimate prostate size and detect any The glandular component is made up of small and
glands have a family history of BPH.
nodularity suggestive of prostate cancer: large acini lined by basal and secretory cells. The
PATHOPHYSIOLOGY – Anal sphincter tone and sensation should be noted stromal component is rich in smooth muscles.
r BPH/LUTS begins with abnormal microscopic r Focused neurologic exam on the anus and lower Nodular growth is a major histologic component of
hyperplasia and macroscopic growth. Causes extremity motor and sensory function. A more BPH.
outflow obstruction and obstructive voiding extensive neurologic exam is indicated for patients r Diffuse stromal infiltration of plasma cells and
symptoms (decreased force of stream, intermittent with possible neurogenic lower urinary tract lymphocytes can be seen, but no infectious agent
stream, and hesitancy). dysfunction nor clinical diagnosis of prostatitis is typically
present.
346
PROSTATE, BENIGN HYPERPLASIA/HYPERTROPHY (BPH)
DIFFERENTIAL DIAGNOSIS r Open simple prostatectomy usually for glands 2. Bushman W. Etiology, epidemiology and natural
r Obstructive symptoms: Detrusor sphincter >100 g: history of benign prostatic hyperplasia. Urol Clin
dyssynergia, foreign body, meatal stenosis, – Suprapubic prostatectomy: Enucleation of North Am. 2009;36:403–415.
neurogenic bladder, pelvic floor dysfunction, adenoma through bladder; useful with coexisting 3. McConnel JD, Roehrborn CG, Bautista OM, et al.
prostate cancer, prostatic abscess, prostatitis problems such as very large bladder calculi or to The long-term effect of doxazosin, finasteride, and
syndrome, urethral obstruction (stricture, condyloma) repair diverticulum combination therapy on the clinical progression of
r Irritative/storage symptoms: Bladder cancer, – Retropubic simple prostatectomy: Enucleation of benign prostatic hyperplasia. N Engl J Med.
detrusor hyperreflexia/OAB, interstitial cystitis, adenoma through incision in anterior prostate 2003;349:2387–2398.
polyuria/polydipsia, prostatitis syndromes commissure 4. Roehrborn CG, Boyle P, Gould AL. Waldstreicher J
r Many minimally invasive alternative surgical Serum prostate-specific antigen as a predictor of
procedures: Microwave- and water-induced prostate volume in men with benign prostatic
TREATMENT hyperthermia, transurethral needle ablation, laser hyperplasia. Urology. 1999;53(3):581–589.
vaporization (contact, noncontact, interstitial, 5. Cantrell MA, Baye J, Vouri SM. Tadalafil: A
GENERAL MEASURES diode), laser prostatectomy (holmium, KTP)
r Directed at QOL unless evidence of significant phosphodiesterase-5 inhibitor for benign prostatic
damage to urinary tract from obstruction ADDITIONAL TREATMENT hyperplasia. Pharmacotherapy. 2013;33(6):
(hydronephrosis, bladder calculi, recurrent Radiation Therapy 639–649.
infections) N/A 6. McNicholas TA, Woo HH, Chin PT, et al. Minimally
r Guidelines suggest watchful waiting for men with invasive prostatic urethral lift: surgical technique
Additional Therapies and multinational experience. Eur Urol. 2013;64(2):
mild symptoms IPSS ≤7 or for more severe r Prostatic stents; best if need TURP but poor surgical
symptoms if they are not bothersome to the patient. 292–299.
risk
Simple behavior modification (fluid restriction, r Prostatic urethral lift (UroLift TM) mechanically
decreased alcohol/caffeine) may help
r Medical therapy considered 1st-line by most, but opens the prostatic urethra with UroLift implants ADDITIONAL READING
that are placed transurethrally under cystoscopic
usually requires continuous therapy to maintain visualization, thereby separating the encroaching r AUA Practice Guidelines Committee. AUA guideline
benefit prostatic lobes (6) on management of benign prostatic hyperplasia
r α-Blocker and 5-ARIs often prescribed together
(2003). Chapter 1: Diagnosis and treatment
MEDICATION recommendations. J Urol. 2003;170:530–547.
Therapies r McVary KT, Roehrborn CG, Avins AL, et al. Update
First Line Phytotherapy (plant extracts) includes saw palmetto,
r α-Blockers (reduce muscle tone in prostate/bladder Pygeum africanum; β-sitosterols have limited support on AUA guideline on the management of benign
neck): in the literature prostatic hyperplasia. J Urol. 2011;185:1793–1803.
– Terazosin (start 1 mg/d to max 20 mg) See Also (Topic, Algorithm, Media)
– Doxazosin (start 1 mg/d to max 8 mg; XL form r Bladder Outlet Obstruction (BOO)
2–8 g/d) ONGOING CARE r Lower Urinary Tract Symptoms (LUTS)
– Tamsulosin (start 0.4 mg to max 0.8 mg) PROGNOSIS r Prostate, Benign Hyperplasia/Hypertrophy (BPH)
– Alfuzosin (10 mg/d) r Symptoms usually well managed by medications Image
– Silodosin (8 mg/d) r Progression of disease, when risk factors identified, r Prostate, Stents (UroLume and Spanner)
◦ Dizziness, orthostatic hypotension, and r Reference Tables: AUA Symptom Index/International
can be well managed
ejaculatory dysfunction are most common side
effects COMPLICATIONS Prostate Symptom Score (I-PSS)
r 5-ARIs (block intracellular DHT conversion; generally r Generally accepted sequelae of untreated,
best for larger glands, may take 6–12 mo for undertreated, or progressive BPH
improvement): r Historically, many men typically had complications of CODES
– Finasteride (5 mg/d) BPH including UTIs, hematuria, bladder calculi,
– Dutasteride (0.5 mg/d) bladder decompensation, incontinence, and upper ICD9
r α-Blocker (tamsulosin 0.4 mg) combined with 5-ARI tract deterioration. With modern awareness and r 600.00 Hypertrophy (benign) of prostate without
(dutasteride 0.5 mg) management techniques, this is less common. urinary obstruction and other lower urinary tract
r The most commonly used endpoints in medical trials symptom (LUTS)
Second Line r 600.01 Hypertrophy (benign) of prostate with
r Antimuscarinic agents may help with bladder are symptom deterioration, BPH-related surgery, and
AUR. AUR continues to be the most widely accepted urinary obstruction and other lower urinary tract
overactivity: symptoms (LUTS)
and most scientific endpoint, although the exact
– Various agents including oxybutynin (5 mg TID), r 600.10 Nodular prostate without urinary obstruction
pathophysiologic mechanism is not completely
tolterodine (2–4 mg/d), solifenacin (5–10 mg/d),
understood.
others ICD10
r Phosphodiesterase-5 inhibitor FOLLOW-UP r N40.0 Enlarged prostate without lower urinary tract
– Tadalafil (2.5–5 mg/d) Patient Monitoring symptoms
◦ FDA approved for LUTS secondary to BPH r Periodic monitoring depending on severity of r N40.1 Enlarged prostate with lower urinary tract
◦ Contraindicated in patients on nitrates, symptoms symptoms
nonselective α-blockers, and CYP 450 inhibitors – Monitor response to therapy with history, AUA SS, r N40.2 Nodular prostate without lower urinary tract
◦ Side effects include back pain, dizziness, PVR, flow rate symptoms
headache, and dyspepsia (5) – Upper tract imaging and measure of renal
SURGERY/OTHER PROCEDURES function if elevated PVR (>300 cc)
r Often considered 2nd-line after failure of medical Patient Resources CLINICAL/SURGICAL
therapy; may be 1st-line in retention or if very large Urology Care Foundation. www.urologyhealth.org PEARLS
prostate. r 5-ARIs (such as finasteride and dutasteride)
r TURP represents gold standard against which all
REFERENCES contraindicated if prostate enlargement absent
other therapies are compared.
1. Roehrborn C. Male lower urinary tract symptoms
(<25 g). P
r Goal of treatment is improving symptoms/QOL.
(LUTS) and benign prostatic hyperplasia. Med Clin
North Am. 2011;95:87–100.
347
PROSTATE, CALCULI
Christopher Amling, MD, FACS
Nicholas Cowan, MD
PATHOPHYSIOLOGY
BASICS r Urinary intraprostatic reflux implicated in stone DIAGNOSIS
formation
DESCRIPTION r Intraprostatic calculi presumed to form by the HISTORY
r Prostatic calculi are extremely common and rarely r Typically stones are asymptomatic
precipitation of prostatic secretions and calcification r Evaluate for history of lower urinary tract symptoms
symptomatic of the corpora amylacea under inflammatory
r Most stones are discovered incidentally conditions (LUTS) (2)
r Treatment typically reserved for severely – Inspissation of prostatic secretions within the – Patients should complete the international
symptomatic men prostatic ducts prostate symptom score (IPSS)
r Stones within the prostatic urethra rare and likely – Concentric layering of calcium phosphate and – Presence of large calculi associated with moderate
due to bladder or upper tract stones that become calcium carbonate on inspissated core result in LUTS
r 25–47% of men with chronic pelvic pain have
trapped in the prostatic urethra growth
r Reports of calculi in the prostatic urethra following – Stone elements may contain constituents found significant prostatic calcifications
transurethral resection of the prostate only in urine and not in prostatic secretions – Correlation seen with stone size, not number
r Stones may harbor bacteria and serve as source for r Prostatitis history
EPIDEMIOLOGY relapsing UTI r With prostatic utricle stones patients typically
Incidence r For prostatic utricle stones, prostatic utricle distends present with chronic UTI, hematuria, urethral
r 7% in pathologic specimens discharge, epididymitis, and voiding dysfunction.
during voiding and then passively drains.
r 20% in autopsies Often a history of hypospadias is present
– Impaired emptying results in urinary stasis stone
r 30% in radiologic studies, with higher percentages formation. Patients present clinically with chronic PHYSICAL EXAM
in ultrasound scan exams UTI, hematuria, urethral discharge, epididymitis, r Genitourinary exam including DRE
Prevalence and voiding dysfunction. – DRE unlikely to localize stones
r Small areas of microcalcification can be seen in 2nd r Presence of hypospadias
and 3rd decades of life r Chronic pelvic pain syndrome
r Almost all men (99%) have some degree of r Prostatitis DIAGNOSTIC TESTS & INTERPRETATION
prostatic calcification noted at autopsy r No association between prostate calculi and risk of Lab
r Urine culture
– Stone burden and size typically increase as a man prostate cancer
ages r Hypospadias (enlargement of the prostatic utricle, a – Escherichia Coli, enterococci, and Klebsiella spp.
more common
RISK FACTORS (1) Müllerian duct remnant) r Expressed prostatic secretions
r Intraprostatic calculi:
GENERAL PREVENTION – May see increased leukocytes
– Recurrent urinary tract infections (UTIs) No known preventative strategies r PSA optional
– Pelvic radiation (for prostate cancer) – PSA levels not influenced by presence or volume
– Studies are mixed on role of inflammation in stone of prostatic calculi, but infection related to chronic
development nidus may falsely elevate PSA (3)
r Prostatic urethral calculi
– Urolithiasis Imaging
r Stones often identified incidentally
– Enlarged prostatic utricle
r Transrectal ultrasound (TRUS)
– History of transurethral resection of the prostate
– Highly sensitive for large calculi
Genetics r Sometimes seen on plain film
N/A
348
PROSTATE, CALCULI
Diagnostic Procedures/Surgery ADDITIONAL TREATMENT ADDITIONAL READING

r Postvoid residual (PVR)
Radiation Therapy
r Uroflow if significant obstructive voiding symptoms r Geramoutsos I, Gyftopoulos K, Perimenis P, et al.
N/A
present Clinical correlation of prostatic lithiasis with chronic
r If intraurethral stones are suspected, cystoscopy is Additional Therapies
pelvic pain syndromes in young adults. Euro Urol.
N/A
diagnostic 2004;45:333–337.
Complementary & Alternative r Kirby RS, Lowe D, Bultitude MI, et al. Intraprostatic
Pathologic Findings Therapies
r Majority of calculi are found in the posterior and urinary reflux: An aetiological factor in abacterial
N/A prostatitis. Br J Urol. 1982;54:729–731.
posterolateral zones of the prostate
– Rare to find large stones obstructing the urethra See Also (Topic, Algorithm, Media)
ONGOING CARE r Corpora Amylacea
DIFFERENTIAL DIAGNOSIS r Prostate, Benign Hyperplasia/Hypertrophy
r Benign prostatic enlargement (BPE)
PROGNOSIS r Prostate, Nodule
r Calcified prostatic utricle cyst or utricle stone Excellent, as majority of stones are asymptomatic
r False prostatic calculi: Calculi trapped in dilated r Prostatic Utricle Anomalies
COMPLICATIONS r Prostatitis, Acute, Bacterial (NIH I)
prostatic urethra or in dilated prostatic utricle r Rarely results in urinary obstruction
r Prostate cancer r Prostatitis, Chronic, Bacterial (NIH II)
r May predispose to chronic UTI. r Prostatitis, General
r Prostatitis
r Seminal vesical calculi FOLLOW-UP r Urinary Tract Infection, Adult Male
r UTI Patient Monitoring
r No follow-up necessary for asymptomatic
incidentally identified stones CODES
TREATMENT r Consider postoperative PVR or uroflow if surgical
intervention undertaken ICD9
GENERAL MEASURES r 599.0 Urinary tract infection, site not specified
Evaluate and treat coexisting conditions such as UTI, Patient Resources
r 599.70 Hematuria, unspecified
prostatitis, and BPO N/A
r 602.0 Calculus of prostate
MEDICATION
First Line REFERENCES ICD10
Culture-directed antibiotic therapy if urine culture r N39.0 Urinary tract infection, site not specified
positive 1. Klimas R, Bennett B, Gardner WA Jr. Prostatic r N42.0 Calculus of prostate
calculi: A review. Prostate. 1985;7(1):91–96. r R31.9 Hematuria, unspecified
Second Line 2. Kim WB, Doo SW, Yang WJ, et al. Influence of
N/A prostatic calculi on lower urinary tract symptoms in
SURGERY/OTHER PROCEDURES middle-aged men. Urology. 2011;78(2):447–449. CLINICAL/SURGICAL
r Surgery rarely indicated and is typically for severely 3. Lee SE, Ku JH, Park HK, et al. Prostatic calculi do
not influence the level of serum prostate specific
PEARLS
symptomatic patients
r Transurethral resection of the prostate antigen in men without clinically detectable Prostate calculi are very common and rarely require
– Unroof stone containing cavities where nidus of prostate cancer or prostatitis. J Urol. 2003;170: treatment.
infection is thought to exist 745–748.
– Stone burned usually visible on TRUS
r Open prostatolithotomy for large stones
r Cystoscopy with lithotripsy for stones within the
prostatic urethra or prostatic utricle
349
PROSTATE, NODULE
Genetics r BPH
BASICS See “Prostate Cancer, General Considerations” – Prostate gland can be variably enlarged (size does
not correlate with extent of voiding symptoms)
DESCRIPTION PATHOPHYSIOLOGY
r Normal prostate has a soft, uniform consistency. – Rubbery consistency
r A prostatenadule is usually described as a palpable r Infectious lesions
r Prostate enlarges with age.
lesion detected on digital rectal exam (DRE) raise – Prostatitis
r Microscopically, nodular prostatic hyperplasia
concern for prostate cancer (CaP) ◦ Warm, tender prostate
r Nodules can be described as soft, rubbery, firm, consists of nodules of glands and intervening ◦ Can be fluctuant or feel “boggy”
hard, or rock hard stroma. May occasionally form benign palpable – Prostate abscess
r Nodules can be well circumscribed or irregular and nodules. ◦ Localized, fluctuant tender region in prostate
r Nodule can be subjectively graded by degree of r Calculus can present as hard, small nodule
diffuse
r A normal prostate is about the size of a chestnut firmness/hardness (grades 1–3)
r CaP has to have a volume of 0.2 mL or larger to be DIAGNOSTIC TESTS & INTERPRETATION
and has a consistency similar to that of the
contracted thenar eminence of the thumb. detected by DRE. Lab
r PSA
– This can be simulated by opposing the thumb to ASSOCIATED CONDITIONS
the little finger and palpating the contracted r Prostate adenocarcinoma – Serum levels vary with age, race, and prostate
muscle r Benign prostatic hyperplasia (BPH) volume
r Consistency of nodule can denote underlying – Improves the positive predictive value of DRE for
r History of intravesical BCG for bladder cancer
cancer
pathology.
r Rapidity of appearance and changes in size and GENERAL PREVENTION – No cut-off value below which the absence of
None prostate cancer can be guaranteed
consistency can infer malignant potential. ◦ Risk of prostate cancer is continuous as PSA
r Nodule detection by DRE is recommended as part of
increases (3)
prostate cancer detection programs. DIAGNOSIS – See “PSA Elevation, General Considerations” for
– Current recommendations from the American further specifics on PSA
Cancer Society are, if men decides to be tested for HISTORY r Urinalysis
prostate cancer, they should have the PSA blood r History of lower urinary tract symptoms
– Variable findings in men with abnormal DRE;
test with or without a rectal exam. – Irritative voiding symptoms
sterile pyuria in granulomatous prostatitis
– Obstructive voiding symptoms
EPIDEMIOLOGY – Generally normal in men with prostate cancer
– Fever
Incidence without urinary tract infection
– Previous prostate biopsy or surgery such as TURP
r Prostate nodule as an isolated finding with normal – Urine culture can be positive for gram-negative
– Previous pelvic external beam radiation or
PSA is found in <10% of cases of prostate cancer in bacteria in acute and chronic bacterial prostatitis
prostate brachytherapy
the US – Urine cytology can be positive in urothelial cancer
– History of prostatitis, abscess, or exposure to TB
r Increasingly men are being diagnosed with prostate – Systemic granulomatous disease (Wegner’s, etc.) Imaging
cancer based on an elevated serum prostate-specific – Family history of genitourinary malignancies r Transrectal ultrasound (TRUS)
antigen (PSA) and not an abnormal DRE (50% of – Classic appearance of prostate adenocarcinoma is
diagnoses in 2002) (1) ALERT a round or oval hypoechoic lesion located in the
r 94% of men diagnosed with prostate cancer in Where prostate abscess or acute prostatitis is peripheral zone
2004–2005 have localized disease (cT1 or cT2) (2) suspected, rectal exam may be contraindicated. ◦ Not very sensitive as 39% of tumors can be
isoechoic
Prevalence ◦ Also nonspecific as granulomatous lesions can
5–10% of men in screening programs have PHYSICAL EXAM
r DRE be hypoechoic
abnormal/suspicious DRE
– Carcinoma (prostatic or urothelial cell carcinoma) – BPH can have variable appearance
RISK FACTORS ◦ Firm, indurated nodules within the prostate ◦ Distinguishable from prostate cancer only by
r Prostate cancer biopsy
gland
– Nodule that changes in consistency and size over ◦ Prostate cancer most often arises in the r Abdominal computed tomography (CT) or magnetic
time posterior peripheral region of the prostate resonance imaging (MRI)
– Elevated serum PSA (>2.5–4 ng/mL) ◦ Advanced prostate cancer can make the entire – Primarily used for staging purposes in patients
– Positive family history gland firm and cause obliteration of the medial with high-risk prostate cancer
r Benign nodule r Bone scan to detect bone metastases
and lateral sulci
– No significant change over time ◦ Advanced cancer can also extend into the – Also primarily used for staging purposes in
– Nodule may be softer seminal vesicles or toward the side wall laterally patients with high-risk prostate cancer
– Prior episodes of prostatitis, biopsy, or prostate
surgery (transurethral resection)
– Prior therapy with intravesical Bacillus
Calmette–Guérin (BCG)
– Granulomatous nodules can be due to infectious
causes (eg, tuberculosis [TB]) or systemic
granulomatous diseases
350
PROSTATE, NODULE
Diagnostic Procedures/Surgery ADDITIONAL TREATMENT 3. Thompson IM, Bermejo C, Hernandez J, et al.

r TRUS-guided biopsy (4) This is dictated by the results of the TRUS biopsy and Screening for prostate cancer: Opportunities and
– Used to widely sample the prostate during biopsy presence/extent of prostate cancer challenges. Surg Oncol Clin N Am. 2005;14(4):
in men with an elevated PSA and/or abnormal DRE Radiation Therapy 747–760.
– Modern biopsy schemes have modified the While not a specific treatment of the nodule, it can be 4. Trabulsi EJ, Halpern EJ, Gomella L. Ultrasonography
standard sextant biopsy scheme to focus on used as primary therapy or as additional and biopsy of the prostate. In: Wein AJ, Kavoussi
laterally directed cores adjuvant/salvage therapy after prostatectomy in LR, Novick AC, et al., eds. Campbell-Walsh
◦ Generally 12 cores Urology. 10th ed. Philadelphia, PA: Saunders;
r Cystoscopy patients with prostate cancer
2012:2735–2747.
– Used to evaluate bladder outlet obstruction and Additional Therapies
hematuria when present May be required in cases with metastatic disease or
disease that recurs after definitive local therapy ADDITIONAL READING
Pathologic Findings
See “Prostate Cancer, General Considerations” Complementary & Alternative
Therapies American Urological Association. Prostate-specific
DIFFERENTIAL DIAGNOSIS N/A antigen (PSA): Best practice statement.
r Neoplasm, malignant http://www.auanet.org/education/guidelines/prostate-
– Lymphoma, primary and secondary cancer-detection.cfm
– Prostate adenocarcinoma ONGOING CARE
– Other prostate malignancies See Also (Topic, Algorithm, Media)
◦ Sarcoma PROGNOSIS
Depends on diagnosis after TRUS-guided biopsy r BCG Sepsis/BCG Ossis
◦ Small cell carcinoma r Prostate Biopsy, Infections and Complications
◦ Other more rare tumors and metastasis COMPLICATIONS r Prostate Cancer, General Considerations
– Urothelial carcinoma r TRUS-guided biopsy
r Benign r Prostate Cancer, Localized (T1, T2)
– Hematuria
r Prostate Cancer, Urothelial
– BPH – Hematochezia
– Hematospermia r Prostate Nodule, Image
– Calculus
– Ejaculatory duct cyst – Urinary tract infection or sepsis r Prostatitis, Granulomatous
– Granulomatous prostatitis – Urinary retention r Tuberculosis, Genitourinary, General Considerations
◦ BCG related or other cause Other complications are dictated by the treatment
– Scarring from prior radiation, surgery, or infection received for prostate cancer
(TURP, etc.)
FOLLOW-UP CODES
– Rectal wall lesions (thrombosed hemorrhoid,
carcinoma, etc.) Patient Monitoring
Negative biopsy in a patient with an abnormal DRE or ICD9
r 600.10 Nodular prostate without urinary obstruction
elevated PSA requires follow-up with serial PSA and r 600.11 Nodular prostate with urinary obstruction
TREATMENT DRE
r 790.93 Elevated prostate specific antigen [PSA]
GENERAL MEASURES Patient Resources
r Abnormal DRE is an indication for TRUS-guided r NCCN. http://www.nccn.org/patients/patient
ICD10
guidelines/prostate/ r N40.2 Nodular prostate without lower urinary tract
biopsy of the prostate
r American Cancer Society. http://www.cancer.org/ symptoms
– Workup includes assessment of PSA
– Staging investigations including bone scan, CT, cancer/prostatecancer/index?sitearea=%26dt=10 r N40.3 Nodular prostate with lower urinary tract
and/or MRI are reserved for high-risk cases as symptoms
dictated by PSA, Gleason score, and DRE r R97.2 Elevated prostate specific antigen [PSA]
REFERENCES
MEDICATION
1. Cooperberg MR, Lubeck DP, Mehta SS, et al. Time
First Line
trends in clinical risk stratification for prostate
CLINICAL/SURGICAL
Antibiotics may be required for infectious causes of
nodules such as bacterial prostatitis or TB cancer: Implications for outcomes (data from PEARLS
CaPSURE). J Urol. 2003;170:S21–S25; discussion r A firm prostate nodule generally deserves further
Second Line S26–S27.
N/A workup with a serum PSA and prostate biopsy.
2. Shao YH, Demissie K, Shih W, et al. Contemporary r Up to 40% of patients may develop granulomatous
SURGERY/OTHER PROCEDURES risk profile of prostate cancer in the United States.
prostatitis after intravesical BCG that may present as
See “Diagnostic Procedures/Surgery” above J Natl Cancer Inst. 2009;101:1280–1283.
a prostate nodule.
351
PROSTATIC INTRAEPITHELIAL NEOPLASIA (PIN)

Joseph C. Klink, MD
r mTOR pathway upregulation

BASICS r Chromosomal anomalies in >50% of HGPIN DIAGNOSIS
r Gains of chromosomes (decreasing order of
DESCRIPTION HISTORY
r Prostatic intraepithelial neoplasia (PIN) describes frequency) 8, 10, 7, 12, and Y
r Loss of heterozygosity on 8p12–21 HGPIN produces no symptoms
cytologically atypical cells confined within r Telomerase activation PHYSICAL EXAM
architecturally benign prostatic glands and acini r Epigenetic changes including hypermethylation r Digital rectal exam (DRE) is usually normal, but may
r Historically subclassified
reveal a prostate nodule or induration
– Low-grade PIN (LGPIN) and high-grade PIN PATHOPHYSIOLOGY r No other physical exam findings
(HGPIN) r HGPIN may be precursor of PCa (1)
– PIN 1, 2, or 3 – PCa can develop without HGPIN DIAGNOSTIC TESTS & INTERPRETATION
r LGPIN no longer reported because r HGPIN extent and frequency greater when PCa Lab
– Not reliably distinguished from benign prostate by present Elevated PSA may be present but not caused by the
pathologists r Usually in peripheral zone HGPIN
– LGPIN carries no increased risk of prostate cancer r Often multifocal Imaging
(PCa) on future biopsies Not reliably seen on any imaging
r HGPIN, and atypical small acinar proliferation ASSOCIATED CONDITIONS
(ASAP) are both considered by most to be ALERT r Transrectal ultrasound-guided biopsy of the prostate
premalignant and the terms should not be used
Multifocal HGPIN Predicts Increased Risk of PCa on taking at least 12 cores
interchangeably.
r Antiquated names for PIN include intraductal subsequent biopsy. – Indicated to look for PCa. HGPIN is an incidental
finding
hyperplasia, hyperplasia with malignant change, r Historically, HGPIN on prostate biopsy often
large acinar atypical hyperplasia, marked atypia, represented failure to sample a nearby PCa (2) Pathologic Findings
r Characterized by proliferation of secretory cells with
ductal-acinar dysplasia – As the number of cores routinely sampled at
r Remainder of this chapter will focus on HGPIN prostate biopsy increased, the predictive value of significant cytologic atypia within prostate glands
HGPIN for PCa decreased and acini
EPIDEMIOLOGY r With modern 12-core biopsies, a single focus of r Secretory cells are enlarged with increased
Incidence nuclear/cytoplasmic ratio and prominent nucleoli
r Parallels PCa incidence HGPIN does NOT increase the risk of PCa diagnosis r Cytoplasm of the HGPIN cells tends to stain
r Increases with age on subsequent biopsies
– Decision for repeat prostate biopsy should be positively for α-methylacyl-CoA
r In PSA screened men, incidence ranges 0–25% r Most of these features are shared by PCa
made on other clinical factors (elevated PSA, high
– Mean incidence 7.7% PSA velocity, new nodule on DRE), not influenced r In PCa, basal cells are absent. In HGPIN the basal
Prevalence by the presence of 1 focus of HGPIN cell layer is retained although is often discontinuous
r Parallels PCa prevalence r Multifocal HGPIN indicates higher risk of PCa on on H&E stain (Figure 2)
r 7% of men in their 30s repeat biopsy (3) – Basal cells can be demonstrated by
r 91% of elderly African American men – Multivariate odds ratio 3.2 for increased cancer immunohistochemical staining with antibodies to
r 67% of elderly Caucasian men detection with multifocal HGPIN high–molecular-weight cytokeratins or nuclear
r 21% of Korean men undergoing cystoprostatectomy – 16–75% (usually around 30%) PCa rate on p63
repeat biopsy for multifocal HGPIN r 4 main architectural patterns of HGPIN have been
RISK FACTORS r Repeat biopsy usually done 1 yr after initial biopsy described (tufting, micropapillary, cribriform, and
r Age flat), but these do not make a difference clinically
r PCa GENERAL PREVENTION r HGPIN usually found in the peripheral zone
r 5α-reductase inhibitors can reduce the incidence of
– HGPIN often found close to PCa, but does not
carry independent prognostic significance once PIN but are not FDA approved for this use
PCa is diagnosed – Finasteride daily for 7 yr decreased the incidence
of HGPIN from 7.1–6% in the Prostate Cancer
Genetics Prevention Trial
r Many genetic abnormalities shared by HGPIN and
– Dutasteride reduced the incidence of HGPIN from
PCa 6–3.7% in the REDUCE trial
– Leads to conclusion that HGPIN is a precursor of r The risk posed by unifocal HGPIN to a patient’s
PCa health and life in the absence of PCa is so low that
r TMPRSS2-ERG gene fusion in 16–19% of HGPIN
prevention is not indicated
lesions in patients with PCa
r Overexpression of PTOV1 in HGPIN is an
independent predictor of PCa on repeat biopsy
352
PROSTATIC INTRAEPITHELIAL NEOPLASIA (PIN)
DIFFERENTIAL DIAGNOSIS r Heidenreich A, Bellmunt J, Bolla M, et al. EAU

r Prostate Cancer (PCa) ONGOING CARE guidelines on prostate cancer. Part 1: Screening,
r ASAP diagnosis, and treatment of clinically localized
– Confers an increased risk of subsequent PCa PROGNOSIS disease. Eur Urol. 2011;59:61–71.
r Excellent prognosis in the absence of PCa r Kawachi MH, Bahnson RR, Barry M, et al. NCCN
diagnosis
r Must monitor for the development of PCa as
– Requires repeat prostate biopsy in a few months clinical practice guidelines in oncology: Prostate
to rule out PCa outlined above cancer early detection. J Natl Compr Canc Netw.
r Normal anatomic structures and embryonic rests 2010;8:240–262.
COMPLICATIONS
r Atypia induced by inflammation, infarction, or None other than the risks of biopsy See Also (Topic, Algorithm, Media)
radiation r Atypical Small Acinar Proliferation, Prostate (ASAP)
r Lobular atrophy and postatrophic hyperplasia FOLLOW-UP r Prostate Cancer, General
r Transitional cell metaplasia Patient Monitoring r Prostate Nodule
r In certain situations as noted, HGPIN may indicate
r Typical and atypical basal cell metaplasia r Prostatic Intraepithelial Neoplasia (PIN) Images
r Cribriform hyperplasia an increased risk of PCa and, therefore, may require
repeat biopsy at 1 yr r PSA Elevation, General Considerations
r Cribriform, ductal endometrioid, and urothelial r LGPIN should not be diagnosed on pathology and,
carcinoma therefore, does not require any follow-up
Patient Resources
CODES
TREATMENT r American Cancer Society http://www.cancer.org/
treatment/understandingyourdiagnosis/ ICD9
GENERAL MEASURES r 233.4 Carcinoma in situ of prostate
r If HGPIN was found on initial prostate biopsy of understandingyourpathologyreport/prostatepathology/
r 602.3 Dysplasia of prostate
high-grade-prostatic-intraepithelial-neoplasia
<10 cores, the biopsy should be repeated with an r http://prostatecancerinfolink.net/diagnosis/pin/
extended scheme ICD10
r If multifocal HGPIN is found on initial prostate r D07.5 Carcinoma in situ of prostate
r N42.3 Dysplasia of prostate
biopsy, the biopsy should be repeated within 1 yr REFERENCES
r Repeat biopsy should sample the entire prostate,
not just the HGPIN area 1. Klink JC, Miocinovic R, Magi Galluzzi C, et al.
High-grade prostatic intraepithelial neoplasia. CLINICAL/SURGICAL
MEDICATION Korean J Urol. 2012;53(5):297–303. PEARLS
First Line 2. Bostwick DG, Cheng L. Precursors of prostate
r Not necessary to treat HGPIN r If HGPIN was found on initial prostate biopsy of
cancer. Histopathology. 2012;60:4–27.
r HGPIN often used to identify patients at “high risk” <10 cores, the biopsy should be repeated with an
3. Epstein JI, Grignon DJ, Humphrey PA, et al.
of developing PCa to enroll them in clinical trials of Interobserver reproducibility in the diagnosis of extended scheme.
medications to prevent PCa r If multifocal HGPIN is found on initial prostate
prostatic intraepithelial neoplasia. Am J Surg
Pathol. 1995;19:873–886. biopsy, the biopsy should be repeated within 1 yr.
Second Line r With modern 12-core biopsies, a single focus of
N/A
HGPIN does NOT increase the risk of PCa diagnosis
SURGERY/OTHER PROCEDURES ADDITIONAL READING on subsequent biopsies.
Radical prostatectomy not indicated for HGPIN in the r Decision for repeat prostate biopsy should be made
absence of PCa r Antonelli A, Tardanico R, Giovanessi L, et al.
on other clinical factors (elevated PSA, high PSA
ADDITIONAL TREATMENT Predicting prostate cancer at rebiopsies in patients velocity, new nodule on DRE), not influenced by the
with high-grade prostatic intraepithelial neoplasia: presence of 1 focus of HGPIN.
Radiation Therapy A study on 546 patients. Prostate Cancer Prostatic
Not indicated for HGPIN in the absence of PCa Dis. 2011;14:173–176.
Additional Therapies r Bostwick DG, Qian J. High-grade prostatic
N/A intraepithelial neoplasia. Mod Pathol. 2004;17:
Therapies
r Green tea catechins for 1 yr in men with HGPIN
reduced the incidence of PCa from 30 to 3%
r Soy, vitamin E, and selenium did not slow the rate of
progression of HGPIN to PCa in a randomized
double-blind trial (SELECT Trial)
r None of these therapies routinely recommend to
men with HGPIN
353
PROSTATITIS, ACUTE, BACTERIAL (NIH I)

Nicholas J. Kuntz, MD
r NIH classification: (3)[A] DIAGNOSTIC TESTS & INTERPRETATION

BASICS – I: Acute bacterial prostatitis Lab
– II: Chronic bacterial prostatitis: Recurrent r Complete blood count
DESCRIPTION infection – Leukocytosis with left shift
r Acute bacterial prostatitis is cute, potentially r Urinalysis
– III: Chronic abacterial prostatitis/chronic pelvic
life-threatening bacterial infection of the prostate pain syndrome (CPPS): No demonstrable – Proteinuria, pyuria, and hematuria
r The symptoms are typically severe and sudden and
infection: – Positive leukocyte esterase and nitrite has a
usually cause the patient to seek emergency care ◦ IIIA: Inflammatory CPPS: White blood cells
r The NIH prostatitis classification system it is referred sensitivity of 68–88% (1)[B]
(WBCs) present in semen/expressed prostatic r Urine culture
to as NIH:I secretions or voided bladder urine (VB3)
◦ IIIB: Noninflammatory CPPS: WBCs not present r Blood cultures
EPIDEMIOLOGY – Particularly for immunosuppressed patients
in semen/expressed prostatic secretions or
Incidence voided bladder urine (VB3) r Prostate-specific antigen (PSA)
r Least common form of prostatitis
– IV: Asymptomatic inflammatory prostatitis: – Little clinical value in the acute setting
– 1–5% – Will be elevated in the majority of cases
Detected by prostate biopsy or presence of WBCs
r Incidence peaks at 20–40 yr (1)[B] in prostatic secretions during evaluation for other – Should be repeated 1–2 mo following treatment
r Not affected by race and ethnicity (1)[B] disorders Imaging
r Not routinely required
Prevalence ASSOCIATED CONDITIONS
r BPH r Indicated if fever persists despite appropriate
Estimated to be ∼10% for all types of prostatitis r Urethral stricture disease treatment to evaluate for prostatic abscess
worldwide (1)[B]
r Diabetes – CT scan
RISK FACTORS r HIV ◦ Area of low attenuation
r Bladder outlet obstruction ◦ Rim enhancing with IV contrast
r UTI
– Benign prostatic hyperplasia (BPH) – Ultrasound
– Stricture disease GENERAL PREVENTION ◦ Hypoechoic lesion
r Previous episodes of prostatitis r Safe sex practices may prevent some cases. – MRI
r Lower urinary tract procedures r Management of underlying BPH, DM, etc. ◦ High intensity on T2-weighted images
– Prostate biopsy or urethral catheterization ◦ Rim enhancing with gadolinium
r Phimosis Diagnostic Procedures/Surgery
r Immunocompromised DIAGNOSIS None: Clinical diagnosis
– Human immunodeficiency virus (HIV) HISTORY Pathologic Findings
r Immunosuppression r Systemic symptoms
Prostate biopsy is contraindicated in the presence of
– Diabetes – Fever, chills, malaise, arthralgia, myalgia acute bacterial prostatitis
r Indwelling urethral catheter r Irritative or obstructive voiding symptoms
r Urinary tract infection (UTI) – Dysuria, urgency, frequency
r UTI
r History of sexually transmitted disease r Acute urinary retention (20%)
r Pyelonephritis
Genetics – Due to bladder neck spasm r Chronic bacterial prostatitis
r Perineal/rectal pain, lower back pain
Not applicable r Granulomatous prostatitis
PATHOPHYSIOLOGY PHYSICAL EXAM r Perirectal abscess
r Intraprostatic reflux of infected urine r Prostate cancer
r Ascending urethral infection: ALERT r Prostatic abscess
Avoid vigorous prostatic exam or massage in a r Prostatodynia
– Unprotected sexual intercourse
patient with suspected acute bacterial prostatitis.
– Urologic instrumentation
This may cause bacteremia and sepsis. Likewise
– Prolonged catheterization
r Direct invasion or lymphogenous spread from the urethral instrumentation should be avoided if TREATMENT
possible (4)[C].
rectum
– Following biopsy, BPH procedures r Vital signs: GENERAL MEASURES
r Indications for admission and IV antibiotics:
r Hematogenous seeding
– Signs of sepsis including fever, tachycardia, and – High fever
– Staphylococcus aureus most common, including hypotension – Significant leukocytosis
methicillin-resistant strands (MRSA) r Abdominal exam:
r Usually a single bacterial uropathogen – Sepsis
– Palpable bladder or abdominal fullness suggesting r Analgesics/antipyretics
– Escherichia coli 87% (2)[B] acute urinary retention r Stool softeners
r Digital rectal exam (DRE): r Bladder drainage if there is evidence of urinary
– Pseudomonas, Proteus, Klebsiella
– Enterococci 5–10% – Perform cautiously retention:
r Sexually active and <35 yr – Exquisitely tender, warm, boggy, swollen prostate – A urethral catheter should be placed cautiously
– Neisseria gonorrhoeae gland – With any difficulty or if the patient is too
r Severe immunocompromise (HIV/AIDS) uncomfortable, percutaneous suprapubic tube
– Mycobacterium tuberculosis, Serratia, Salmonella, should be placed
and fungi (Candida, Histoplasma, Aspergillus,
Cryptococcus) (1)[B]
354
PROSTATITIS, ACUTE, BACTERIAL (NIH I)
r If no clinical response in 48 hr despite appropriate ADDITIONAL READING

treatment consider prostatic abscess ONGOING CARE r Barozzi L, Pavlica P. Prostatic abscess: Diagnosis
r Postprostate biopsy prostatitis suspect resistance to
fluoroquinolones PROGNOSIS and treatment. AJR Am J Roentgenol. 1998;(3):
r If initial response to therapy is favorable then 753–757.
MEDICATION patient prognosis is excellent. r Lipsky BA. Prostatitis and urinary tract infection in
First Line (4)[C] r Studies using quinolone antibiotics suggest that a men: What’s new; what’s true? Am J Med.
r Antibiotics with high lipid solubility and
negative culture after 7 days of therapy is predictive 1999;(3):327–334.
concentrated in prostatic tissue of a long-term response. r Nickel JC. Prostatitis: Myths and realities. Urology.
– Fluoroquinolones r If the patient with suspected bacterial prostatitis is 1998;51(3):362–366.
◦ Levofloxacin, 250–750 mg daily IV or by mouth not responding to initial empiric therapy, consider r Pewitt ED, Schaeffer AJ. Urinary tract infection
(PO) prostatic abscess. urology, including acute and chronic prostatitis.
◦ Ciprofloxacin, 250–750 mg PO twice daily
COMPLICATIONS Infect Dis Clin North Am. 1997;11(3):623–646.
(BID), 400 mg IV BID r Schaeffer AJ. Chronic prostatitis and the chronic
◦ Ampicillin with gentamicin (ampicillin 1–2 g IV r Prostatic abscess
every 4–6 hr, 500 mg PO every 6 hr; gentamicin r Decreased fertility pelvic pain syndrome. N Engl J Med. 2006;355:
r Epididymitis 1690–1698.
1–2 mg/kg IV every 8–12 hr or daily dosing
4–7 mg/kg every 24 hr IV) r Chronic prostatitis See Also (Topic, Algorithm, Media)
◦ Ceftriaxone 1–2 g IV or IM daily r Emphysematous prostatitis r Prostate Biopsy, Infections and Complications
– Afebrile 24–48 hr may change to oral antibiotics r Pyelonephritis r Prostate, Abscess
r Adjust antibiotic regimen based on urine and/or r Sepsis r Prostatitis, Acute, Bacterial (NIH I) Image
blood culture results r Urinary retention r Prostatitis, Chronic Nonbacterial, Inflammatory and
r Transition to oral antibiotic following resolution of Noninflammatory (NIH CP/CPPS III A and B)
acute toxicity FOLLOW-UP r Prostatitis, Chronic, Bacterial (NIH II)
r Total antibiotic duration: 2–4 wk Patient Monitoring r Prostatitis, General Considerations
r Follow-up urine cultures to verify that the infection
Second Line r Prostatitis, Granulomatous
r Oral antibiotics are a reasonable 1st option in has cleared and that chronic bacterial prostatitis is r Urinary Tract Infection (UTI), Adult Male
not present.
nontoxic patients. r If PSA was obtained during the acute episode, and
– Fluoroquinolones (see above oral dose) for
was elevated, repeat in 1–2 mo to resolution.
10 days (4)[C] CODES
– Trimethoprim–sulfamethoxazole 160/800 mg PO Patient Resources
every 12 hr Urology Care Foundation. http://www. ICD9
r If STD is suspected (sexually active male younger urologyhealth.org/urology/index.cfm?article=15 r 041.49 Other and unspecified Escherichia coli
than 35 yr) empiric treatment with ceftriaxone [E. coli]
250 mg IM and doxycycline 100 mg BID for 7 days r 098.12 Gonococcal prostatitis (acute)
may be warranted, but this is controversial (5)[C]
REFERENCES
r 601.0 Acute prostatitis
SURGERY/OTHER PROCEDURES 1. Ramakrishnan K, Salinas RC. Prostatitis: Acute and
r Suprapubic tube placement chronic. Prim Care. 2010;37(3):547–563, viii–ix. ICD10
2. Millan-Rodriguez F, Palou J, Bujons-Tur A, et al. r A54.22 Gonococcal prostatitis
– If Foley catheter cannot be passed easily in setting
of acute urinary retention Acute bacterial prostatitis: Two different r B96.20 Unsp Escherichia coli as the cause of
r If prostatic abscess develops, surgical drainage of sub-categories according to a previous diseases classd elswhr
manipulation of the lower urinary tract. World J r N41.0 Acute prostatitis
prostatic abscess is usually required (4)[B] Urol. 2006;24(1):45–50.
– Transrectal or perineal needle aspiration 3. Krieger JN, Nyberg L Jr, Nickel JC. NIH consensus
◦ Ultrasound guided CLINICAL/SURGICAL
definition and classification of prostatitis. JAMA.
◦ Local anesthetic
– Transurethral drainage
1999;282(3):236–237. PEARLS
◦ Incision or unroofing 4. National Guideline C. Prostatitis and chronic pelvic r E. coli is most common organism in acute bacterial
◦ Resection may be associated with higher rates pain syndrome. In: Guidelines On Urological
Infections Rockville MD: Agency for Healthcare prostatitis.
of sepsis r Avoid vigorous prostatic exam or massage during an
Research and Quality. [5/15/2013]. Available from
– Open drainage episode of acute bacterial prostatitis.
◦ If less invasive methods fail www.guideline.gov/content.aspx?id=
14811&search=prostatitis. r It is not advisable to measure serum PSA during an
◦ Abscess extends beyond prostate
5. Etienne M, Chavanet P, Sibert L, et al. Acute episode of acute bacterial prostatitis as it will most
ADDITIONAL TREATMENT bacterial prostatitis: Heterogeneity in diagnostic likely be falsely elevated.
criteria and management. Retrospective r Urinary retention requires bladder drainage.
Radiation Therapy
multicentric analysis of 371 patients diagnosed r May require hospital admission and IV antibiotics.
N/A
with acute prostatitis. BMC Infect Dis. 2008;8:12. r Consider prostatic abscess if no clinical response in
Limited, if any role in the acute setting 48 hr.

Therapies
N/A
355
PROSTATITIS, CHRONIC NONBACTERIAL, INFLAMMATORY AND

NONINFLAMMATORY (NIH CP/CPPS III A AND B)
Amin S. Herati, MD

BASICS r Allergies r Pelvic imaging with ultrasonography, CT, or MRI is
r Sinusitis considered optional and can be obtained if clinically
DESCRIPTION r Erectile dysfunction indicated to rule out other causes of pelvic pain
r Chronic prostatitis/chronic pelvic pain syndrome r Irritable bowel syndrome r TRUS has poor specificity in differentiating among
(CP/CPPS), NIH categories IIIA and IIIB are r Depression the subtypes of CP/CPPS
characterized by pelvic, perineal, and/or testicular r Fibromyalgia
pain ± LUTS in the absence of other well-defined Diagnostic Procedures/Surgery
r Fatigue r Stamey test (Meares–Stamey 4-glass test)
pathology. r Video-urodynamics: Should be considered in
r Neurologic disorders
– IIIA: Inflammatory CPPS: WBCs present in
prostatic secretions patients with significant lower urinary tract
GENERAL PREVENTION symptoms in addition to pain. Findings often include
– IIIB: Noninflammatory CPPS: WBCs not present in N/A
prostatic secretions decreased peak and mean urinary flow rates,
elevated maximal urethral closing pressure,
EPIDEMIOLOGY DIAGNOSIS incomplete funneling of the bladder neck, and
Incidence urethral narrowing at the level of the external
N/A HISTORY urethral sphincter (4)
r Determine duration of symptoms (of at least >3-mo r Cystoscopy is not indicated in the majority of cases:
Prevalence
Estimated prevalence of CP/CPPS is 1.8%, equating to duration) Can be performed if history indicates other etiology
r Pain in the suprapubic region, lower back, penis, r Prostate biopsy: Tissue for culture not helpful in
approximately 2,000,000 US men (1).
testes, and/or scrotum diagnosis and not recommended
RISK FACTORS r Painful ejaculation: One of the most discriminatory
r Urethral catheterization or instrumentation Pathologic Findings
symptoms associated with CP/CPPS III and a strong
r Inadequately treated urinary tract infections Not formally reported for Category III, therefore N/A
predictor of QOL and severity of pain (3)
r Pelvic trauma r Sexual dysfunction DIFFERENTIAL DIAGNOSIS
r Urethral strictures r Pelvic floor muscle spasms r Acute or chronic bacterial prostatitis
r Psychological stress or depression r Irritative and obstructive voiding symptoms r Benign prostatic hyperplasia
r Bladder calculus
Genetics – Urgency
r A large proportion of patients with CP/CPPS express – Frequency r Bladder cancer
– Hesitancy r Bladder neck contracture
the IL-10 AA genotype with low IL-10 expression
r Category IIIA patients are more likely to have a low – Poor interrupted flow r Interstitial cystitis
r History should also cover neurologic disease, r Primary voiding dysfunction
TNFα genotype
hematologic, cardiovascular, and infectious diseases r Prostate abscess
PATHOPHYSIOLOGY r NIH-CPSI is a validated questionnaire assessing pain, r Prostate cancer
r 90% of cases of CP/CPPS have an unclear etiology,
urinary function, and QOL. Can be used to measure r Prostate cyst
the remainder of cases can be attributed to bacterial
symptoms upon initial presentation and follow-up r Radiation cystitis
in origin (Category II)
r Although the exact cause is not known, it is thought PHYSICAL EXAM r Tuberculosis of the prostate
r Careful exam of the genitalia, groin, perineum, r Urethral stricture
to be multifactorial with a combination of factors
contributing to the pathophysiology (image) coccyx, external anal sphincter, and internal pelvic r Urethritis
r Current theories include: floor and side walls
r Exam is usually unremarkable except for pain:
– Nanobacterial colonization
– Atypical bacterial infection Degree of pain not helpful in differentiating
– Voiding dysfunction causing intraprostatic urinary between various categories of CP/CPPS
reflux and elevated intraprostatic pressure r Digital rectal exam should not be performed until
– Pelvic floor muscle dysfunction urine from preprostatic massage has been collected
– Endocrine
– Neuropathic
– Autoimmune Lab
r Urinalysis and urine culture
r Stratification of each patient into a 6-point clinical
r Stamey test (Meares–Stamey 4-glass
phenotyping system, termed UPOINT, based on likely
etiologic mechanisms has been proposed to improve test)—considered to be “gold standard” in
outcomes by tailoring therapies to target the diagnosis
r Limitations: EPS cannot be obtained in all patients,
involved mechanisms (2).
variable interpretation of WBC counts,
difficult-to-culture organisms not routinely identified
r 2-glass test (premassage and postmassage test)
– Difficulties encountered with interpretation of
bacterial localization studies as asymptomatic
individuals often harbor uropathogens
356
PROSTATITIS, CHRONIC NONBACTERIAL, INFLAMMATORY AND NONINFLAMMATORY (NIH CP/CPPS III A AND B)
r Pentosan polysulfate 100 mg TID 3. Shoskes DA, Landis JR, Wang Y, et al; Chronic
TREATMENT r Gabapentanoids Prostatitis Collaborative Research Network Study
– Pregabalin 150–600 mg daily Group. Impact of post-ejaculatory pain in men with
GENERAL MEASURES r Muscle relaxants category III chronic prostatitis/chronic pelvic pain
r As the pathogenesis of CP/CPPS category III is syndrome (CPPS). J Urol. 2004;172:542–547.
– Baclofen
considered multifactorial, effective treatment for – Diazepam 4. Barbalias GA, Meares EM Jr, Sant GR.
CP/CPPS III often requires multimodal therapy Prostatodynia: Clinical and urodynamic
r A meta-analysis comparing α-Blockers, antibiotics Second Line
characteristics. J Urol. 1983;130:514–517.
See above
and anti-inflammatory/immune modulating 5. Thakkinstian A, Attia J, Anothaisintawee T, et al.
therapies found a combination of α-blockers and SURGERY/OTHER PROCEDURES α-blockers, antibiotics and anti-inflammatories
antibiotics to be superior to α-blockers, antibiotics, r Not recommended. Last resort unless other have a role in the management of chronic
or anti-inflammatory/immune modulating therapies indications are discovered during the workup prostatitis/chronic pelvic pain syndrome. BJU Int.
alone in the reduction of NIH-CPSI scores (5) – Transurethral microwave thermotherapy 2012;110:1014–1022.
r Treatment should also be targeted to the etiologic
mechanisms using the UPOINT system
r Focus of therapy should be on symptom relief Radiation Therapy
N/A
ADDITIONAL READING
r Conservative measures such as diet modification,
r Nickel JC. Prostatitis and related conditions, orchitis,
myofascial physical therapy, phytotherapies, Additional Therapies
See below and epididymitis. In: Wein AJ, Kavoussi LR, Novick
acupuncture should be considered as part of the
AC, et al. eds. Campbell-Walsh Urology. 10th ed.
1st-line therapy Complementary & Alternative
r Symptoms should be followed with NIH-CPSI Philadelphia, PA: Elsevier; 2011.
Therapies r Schaeffer AJ. Chronic Prostatitis and the chronic
questionnaires and voiding diaries r Dietary and lifestyle modification
r Phytotherapy pelvic pain syndrome. N Eng J Med. 2005;355:
MEDICATION 1690–1698.
– Pollen extract
First Line See Also (Topic, Algorithm, Media)
r The choice of agents in the 1st- or 2nd-line setting is – Quercetin
r NIH-CPSI Questionnaires
– Saw palmetto
practitioner dependent with no specific agent r Acupuncture r Prostatitis, Acute Bacterial (NIH I)
approved specifically for this condition r Myofascial physical therapy r Prostatitis, Asymptomatic Inflammatory (NIH IV)
r α-Blockers: Multiple randomized, placebo-controlled
r Stress management/cognitive-behavioral therapy r Prostatitis, Chronic Bacterial (NIH II)
trials have demonstrated a duration of at least 3 mo r Prostatitis, Chronic Nonbacterial, Inflammatory and
r Frequent ejaculation
or longer may be needed before assessment can be
made of treatment failure or success. Noninflammatory (NIH CP/CPPS III A and B)
– Side effects of α-blockers include hypotension, Image
dizziness, fatigue, and retrograde ejaculation ONGOING CARE r Prostatitis, General
◦ Alfuzosin 10 mg BID for 12 wk; contraindicated r Stamey Test (3-glass test, 4-glass tests,
PROGNOSIS
with moderate hepatic insufficiency or with Remissions and flare-ups common over the long term Meares–Stamey Test)
cytochrome P450 3A4 inhibitors
◦ Doxazosin 1–4 mg daily for 12 wk; escalate COMPLICATIONS
dose until symptom relief obtained None known CODES
◦ Tamsulosin 0.4 mg daily for 12 wk FOLLOW-UP
◦ Terazosin 1–5 mg daily; escalate dose until ICD9
Patient Monitoring
symptom relief obtained r 338.4 Chronic pain syndrome
◦ Silodosin (8 mg/d) Long-term supportive care
r 601.1 Chronic prostatitis
r Antibiotic therapy: Data conflicting on the benefit Patient Resources r 789.09 Abdominal pain, other specified site
r Urology Care. Foundation. http://www.
and therapeutic benefit should be reassessed after 2
to 4 wk of initiating therapy urologyhealth.org/urology/index.cfm?article=15 ICD10
r http://www.prostatitis.org r G89.29 Other chronic pain
– Can be considered in antibiotic-naı̈ve patients
– Fluoroquinolones: Side effects include dizziness, r N41.1 Chronic prostatitis
restlessness, headache, nausea, rash r R10.2 Pelvic and perineal pain
◦ Ciprofloxacin, levofloxacin 500 mg daily for REFERENCES
4 wk (some concern over growing resistance to 1. Suskind AM, Berry SH, Ewing BA, et al. The
this class of drugs) prevalence and overlap of interstitial CLINICAL/SURGICAL
◦ Trimethoprim–sulfamethoxazole 160/80 mg BID
for 4 wk: Side effects include anorexia, nausea,
cystitis/bladder pain syndrome and chronic PEARLS
prostatitis/chronic pelvic pain syndrome in men:
vomiting, rash, urticaria Results of the RAND Interstitial Cystitis Multimodal therapy is oftentimes required because of
r 5α-Reductase inhibitor: the varied pathologies associated with this condition.
Epidemiology Male Study. J Urol. 2013;189:
– Finasteride 5 mg daily or 141–145.
– Dutasteride 0.5 mg daily 2. Shoskes DA, Nickel JC, Kattan MW. Phenotypically
r Anti-inflammatory agents
directed multimodal therapy for chronic
– Rofecoxib 25–50 mg daily: Symptom relief at prostatitis/chronic pelvic pain syndrome: A
higher doses, but not recommended because of prospective study using UPOINT. Urology.
cardiovascular risk 2010;75:1249–1253.
– Oral prednisolone
357
PROSTATITIS, CHRONIC, BACTERIAL (NIH II)

John J. Pahira, MD
r Prostatic zinc levels (zinc is thought to be DIAGNOSTIC TESTS & INTERPRETATION

BASICS antibacterial) are lower in patients with chronic Lab
bacterial prostatitis; however, it is not clear if this is r Urine analysis and culture (2):
DESCRIPTION a cause of or due to the infection. – Routine urine culture may be negative. A positive
r Chronic bacterial prostatitis (NIH II) includes r pH of prostatic fluid may increase from a normal of culture may be obtained as part of the
symptoms of prostatitis with positive urine culture ∼6.5 to >8.0 with infection. Meares–Stamey 4-glass test (see below):
and no signs of systemic infection r Common pathogens: Escherichia coli (most – Pyuria and bacteruria may be present.
r Occasionally, without local symptoms
common), Enterococcus faecalis, Klebsiella – Hematuria should prompt workup for other
r Recurrent UTI with a single organism that persists is pneumoniae, Pseudomonas aeruginosa, causes.
the classic hallmark Proteus spp. r PSA may be elevated in the setting of prostate
r Overlap of symptoms makes it difficult to distinguish r Others: Staphylococcus epidermatitis, infection and should not be obtained until the
clinically from chronic nonbacterial prostatitis (NIH S. saprophyticus, Corynebacterium, and Ureaplasma infection clears.
Type III, CP/CPPS); about 10% of these patients urealyticum, Chlamydia trachomatis, Candida, Imaging
with type III prostatitis will have positive cultures trichomonas, Mycobacterium hominis, and Imaging has low yield and is performed only to
r NIH classification and current definitions of Tuberculosis: exclude the presence of other more definable and
prostatitis (1): – Chlamydia, Ureaplasma, Mycoplasma spp. can treatable causes of the patient’s symptoms.
– Type I: Acute bacterial prostatitis cause prostatitis but do not grow in routine r Transrectal US performed in patients with pain on
– Type II: Chronic bacterial prostatitis; recurrent culture.
ejaculation may reveal enlargement of the prostate
infection
ASSOCIATED CONDITIONS or seminal vesicle. Prostatic calculi may be
– Type III: Chronic abacterial prostatitis/CPPS; no r BPH visualized.
demonstrable infection: r Detrusor/sphincter dyssynergia
◦ IIIA: Inflammatory CPPS: WBCs present in
r Sexual dysfunction ALERT
semen/expressed prostatic secretions or voided
r STDs In the setting of possible acute bacterial prostatitis
bladder urine (VB3)
◦ IIIB: Noninflammatory CPPS: WBCs not present r Subfertility/infertility or prostatic abscess, prostatic massage should not
r Urethral stricture be performed.
in semen/expressed prostatic secretions or
voided bladder urine (VB3)
GENERAL PREVENTION Diagnostic Procedures/Surgery
– Type IV: Asymptomatic inflammatory prostatitis: r Adequate treatment of acute bacterial prostatitis r Meares–Stamey 4-glass test considered gold
Detected by prostate exam or presence of WBCs r Protected intercourse standard for the diagnosis of chronic bacterial
in prostatic secretions during evaluation for other r Voiding after all sexual experiences may help prostatitis and involves isolated cultures of different
disorders
portions of the lower urinary tract:
EPIDEMIOLOGY – Make sure that the patient has a full bladder
r Prostatitis in general is the most common urologic DIAGNOSIS – Clean the glans thoroughly with antimicrobial
diagnosis in men <50 yr old, and the 3rd most solution. Retract foreskin as necessary
common diagnosis in men >50 yr old. HISTORY – Void 10 mL into sterile container (VB1).
r Affects 10–14% of men of all ages and accounts for r Fever and chills are not usual and suggest acute
Represents urethral flora sample
2 million office visits annually. bacterial prostatitis. – After voiding 100 mL, collect 10 mL midstream
r Chronic bacterial prostatitis is the most common r Dysuria, urgency, nocturia, weak stream urine in another sterile container (VB2).
r Perineal, penile, scrotal, suprapubic, or groin pain; Represents bladder flora sample
cause of recurrent UTI in the adult male population.
pain with or after ejaculation – Perform prostatic massage to collect EPS from the
RISK FACTORS r ED, decreased libido urethra; submit for culture and examine on a glass
r Inadequately treated episodes of acute bacterial
r Prior UTIs, STDs slide under 40×. Represents prostate flora
prostatitis may increase risk for developing chronic r Unprotected intercourse, new partners, sexual – Collect the next voided 10 mL in a sterile
prostatitis syndromes container. Represents a combination of prostate
r Older men with BPH/bladder outlet obstruction orientation
r Urethral catheterization or other lower genitourinary and bladder flora
r Urethral strictures r Normal:
r Urethral catheterization surgery
r NIH-CPSI, a self-administered validated symptom – Negative urethral, prostatic, and bladder cultures
r Possibly reduced sexual activity with resulting (VB1, VP2, EPS, and VB3 negative)
index, may be useful.
prostatic congestion – Normal prostatic secretions show no evidence of
PHYSICAL EXAM excess WBCs (<10 WBC cells per high-power
Genetics r Exam of the genitalia may reveal vague widespread field)
N/A r Positive:
pelvic discomfort.
PATHOPHYSIOLOGY r Perineal tenderness may be present. – If EPS or VB3 colony counts are 10× higher than
r With progressive benign prostatic enlargement, r DRE may reveal a minimally tender or boggy VB1 or VB2, bacterial prostatitis is present
obstruction causes reflux into prostatic ducts (2). prostate. – If all cultures are positive, then bacterial cystitis is
r Obstructive, turbulent, and/or high-pressure voiding r Prostatic calculi may be palpable. likely present and the test should be repeated
combined with intraprostatic ductal reflux, leads to after 5 days of antibiotics (prostatitis and cystitis
acute intraductal inflammation. can coexist, and cystitis in men is often secondary
r Progresses to chronic intraductal inflammation. to prostatitis)
r Bacteria are present in inflamed ducts in protected – EPS result is >10–20 WBC per high-power field
bacterial aggregates or bacterial biofilms. or clumping of WBC. It is not diagnostic for
r Increased incidence of prostatic calculi may serve as bacterial infection as it can also be seen with NIH
a nidus of infection. Class IIIA prostatitis
358
PROSTATITIS, CHRONIC, BACTERIAL (NIH II)
r A modified Meares–Stamey test (2-glass test) can Second Line Patient Resources
also be performed that is considered more r Anti-inflammatories (ibuprofen) for symptoms Urology Care Foundation. http://www.urologyhealth.
convenient and practical r α-Blockers (doxazosin, tamsulosin, alfuzosin, org/urology/index.cfm?article=15
– After cleansing the glans, obtain 10 mL of a silodosin) may help with LUTS
midstream urine for culture (preprostate
massage). Represents bladder flora. Should also SURGERY/OTHER PROCEDURES REFERENCES
r Not generally recommended
be dipped for white cells r TURP 1. Schaeffer AJ. Chronic prostatitis and the chronic
– Perform prostate massage and obtain 10 mL of pelvic pain syndrome. N Engl J Med. 2006;
urine (postprostate massage) for culture and – Can be considered in select cases of refractory
prostatitis with infected calculi and/or obstruction 355:1690–1698.
microscopic exam. Represents prostate and
2. Schaeffer AJ, Knauss JS, Landis JR, et al. Leukocyte
bladder flora. If white cells are present, they may ADDITIONAL TREATMENT and bacterial counts do not correlate with severity
represent bacterial prostatitis or NIH type IIIA Radiation Therapy of symptoms in men with chronic prostatitis: The
– If postmassage colony counts are 10× higher N/A National Institutes of Health Chronic Prostatitis
than premassage sample, bacterial prostatitis is
Additional Therapies Cohort Study. J Urol. 2002;168:1048–1053.
present. If both cultures have similar counts,
r Frequent ejaculation (in patients with enlarged, 3. Naber KJ. Management of chronic bacterial
cystitis is present
r Semen culture is of limited use, demonstrating low symptomatically congested glands) prostatitis: What’s New? BJU Intern. 2008;101(S3):
r Dietary modifications of common comestibles found 7–10.
sensitivity but high specificity compared to Stamey
test to irritate the lower urinary tract 4. Wagenlehner FM, Weidner W, Sörgel F, et al. The
r Uroflowmetry may demonstrate diminished flow r Moist heat with Sitz baths or heating pad for role of antibiotics in chronic bacterial prostatitis. Int
symptomatic relief J Antimicrob Agents. 2005;26:1–7.
with intermittency
r Elevated PVR may be present 5. Shoskes DA. Phytotherapy in chronic prostatitis.
Complementary & Alternative Urology. 2002;60:35–37.
Pathologic Findings Therapies
r Prostate massage (very controversial):
N/A
– May work by stimulating hibernating bacterial ADDITIONAL READING
DIFFERENTIAL DIAGNOSIS biofilms (making them more susceptible to
r Acute bacterial prostatitis/prostatic abscess
antimicrobials), draining the obstructed inflamed Krieger JN, Nyberg L Jr, Nickel JC. NIH consensus
r Bladder outlet obstruction/BPH ducts (allowing for better antimicrobial definition and classification of prostatitis. JAMA.
r Chronic nonbacterial prostatitis (NIH IIIA/B) penetration), and stimulating blood supply to the 1999;282(3):236–237.
r Cystitis area.
r Interstitial cystitis r Avoid bicycling or other activities that cause perineal See Also (Topic, Algorithm, Media)
r Prostatitis, Acute, Bacterial (NIH I)
r Prostatic cyst pressure r Prostatitis, Asymptomatic Inflammatory (NIH IV)
r Seminal vesiculitis r Zinc supplements: Unproven benefit
r Prostatitis, Chronic, Bacterial (NIH II)
r STDs r Phytotherapy: Plant extracts and herbal medications
r Prostatitis, Chronic, Nonbacterial, Inflammatory
r Tuberculous/granulomatous prostatitis (ie, saw palmetto) popular but may only be as
effective as placebo (5) (NIH CP/CPPS IIIA)
r Urethritis or urethral pathology (stricture) r Prostatitis, Chronic, Nonbacterial, Noninflammatory
(NIH CP/CPPS IIIB)
ONGOING CARE r Prostatitis, General
TREATMENT r Prostatitis, Granulomatous
PROGNOSIS r Stamey Test (3-Glass Test, 4-Glass Tests,
GENERAL MEASURES r Fluoroquinolones have improved the ability to clear
r Antibiotic course normally extends for 6–8 wk and Meares–Stamey Test)
the infection (60–90% cure reported).
sometimes longer with refractory infections. Goal is r Variable course with flare-ups possible. If
to eradicate the nidus of infection in the prostate.
culture-positive infection persists, consider longer
Follow culture results (3,4).
course of therapy (3–6 mo) with a lower daily dose. CODES
r Avoid alcohol, spicy foods, perineal pressure for
r Treating underlying obstruction or prostatic calculi if
extended times (sitting or bicycle riding), acidic ICD9
necessary may prevent further infections. r 041.49 Other and unspecified Escherichia coli [E.
beverages.
r Continue to engage in safe protected sexual activity, COMPLICATIONS coli]
as this is thought to reduce prostatic congestion. r Recurrent cystitis, epididymitis, urethritis r 131.03 Trichomonal prostatitis
r CPPS r 601.1 Chronic prostatitis
MEDICATION r Infertility (effect on semen quality debatable)
First Line r Primarily affects QOL ICD10
r Current sensitivity patterns are showing increased r A59.02 Trichomonal prostatitis
r Unknown if predisposes to prostate cancer
resistance to quinolones, TMX/SULFA, ampicillin. In r B96.20 Unsp Escherichia coli as the cause of
choosing antibiotic coverage prior to culture FOLLOW-UP diseases classd elswhr
sensitivity reports, know local resistance patterns Patient Monitoring r N41.1 Chronic prostatitis
based on your hospital antibiogram r Document clearing of positive culture
r Fluoroquinolones still preferred r Following prostate cancer screening guidelines is
– No difference in bacterial eradication between recommended. Do not obtain PSA for at least 6 wk CLINICAL/SURGICAL
levofloxacin and ciprofloxacin, although prostatic
fluid concentration of levofloxacin is higher than
after culture clears. PEARLS
ciprofloxacin. Levofloxacin has daily dosing and Inadequately treated acute bacterial prostatitis may
may have better prostatic penetration increase risk for developing chronic prostatitis
– Ciprofloxacin 500 mg PO BID for 4–6 w; syndromes including chronic bacterial prostatitis.
– Levofloxacin 500 mg/d for at least 6–8 wk
r Trimethoprim 60 mg–sulfamethoxazole 80 mg BID
for at least 6–8 wk
P
r Tetracycline derivatives (eg, doxycycline) only if
Chlamydia or Mycoplasma suspected
359
PROSTATITIS, GENERAL
Ryan S. Levey, MD
Justin D. Ellett, MD, PhD
r Phimosis
BASICS r Urethral stricture, distal DIAGNOSIS
r BPH
DESCRIPTION r Prostatic calculi HISTORY
r Prostatitis is a general term that refers to r Acute bacterial prostatitis (NIH I)
r Transurethral surgery/instrumentation
inflammation of the prostate. – Fever, chills, malaise
r Transrectal prostate biopsy
r Traditionally classified as acute bacterial prostatitis, – Perineal, suprapubic pain
r Unprotected anal sex – Irritative voiding symptoms: Urgency, frequency,
chronic bacterial prostatitis, nonbacterial prostatitis, r UTI
and prostatodynia today the definitions used are dysuria
much more precise and based on the NIH system (1). – Obstructive voiding symptoms: Hesitancy,
Genetics
r Revised 1995 NIH classification of prostatitis is intermittent stream, acute urinary retention
N/A
standard nomenclature: – Rare sepsis
– NIH Class I: Acute bacterial prostatitis; infection of
PATHOPHYSIOLOGY – 5% will develop CP
r Extension of UTI r Chronic bacterial prostatitis (NIH II)
prostate, sudden onset, often associated with UTI r Manipulation of urinary tract or prostate
◦ >10 WBC/HPF in 1st 10 mL voided urine and – Recurrent UTIs
r Bacterial: – Asymptomatic or CPPS (see below)
midstream catch
◦ Positive culture in 1st 10 mL voided urine and – Ascending infection through urethra r CP/CPPS (NIH IIIA/B)
midstream catch – Refluxing urine into prostate ducts – Pain in perineum, suprapubic region, penis,
– NIH Class II: Chronic bacterial prostatitis; insidious – Direct extension or lymphatic spread from rectum testicles, groin, low back
onset, relapsing, recurrent UTI – Hematogenous spread – Pain especially after or during ejaculation
◦ >10 WBC/HPF – Calculi serve as a nidus for infection – Irritative/obstructive voiding symptoms lasting
◦ Positive culture in expressed prostatic secretions – Aerobic gram-negative bacteria >3 mo
(EPS) and 1st 10 mL of voided urine after EPS (Enterobacteriaceae [most common cause], – ED, sexual disturbances, severe effect on quality of
– NIH Class III: Chronic prostatitis (CP)/Chronic Escherichia coli [most common organism], life
pelvic pain syndrome (CPPS): Pseudomonas, Klebsiella, Proteus, Serratia), r NIH Class IV: None; usually only elevated PSA or
– NIH Class IIIA: Inflammatory: Inflammatory cells in Neisseria gonorrhoeae, Burkholderia pseudomallei nodule that prompts biopsy
prostatic secretion, seminal fluid, postprostatic – Miscellaneous: Chlamydia trachomatis
– Gram-positive bacteria (Enterococcus, PHYSICAL EXAM
massage urine r Acute bacterial prostatitis (NIH I):
◦ >10 WBC/HPF in EPS, 1st 10 mL of voided Streptococcus faecalis, Staphylococcus aureus)
r Organisms suspected, but unproven: Staphylococcus – Suprapubic tenderness
urine after EPS, or semen – Assess for acute urinary retention
– NIH Class IIIB: Noninflammatory: Insignificant epidermidis, micrococci, nongroup D Streptococcus,
– DRE: Hot, boggy, exquisite tenderness
inflammatory cells diphtheroids, Ureaplasma urealyticum,
– Sepsis: Febrile, tachycardia
◦ <10 WBC/HPF in EPS, 1st 10 mL voided urine Trichomonas vaginalis r Chronic bacterial prostatitis/CPPS (NIH II/IIIA/IIIB)
after EPS, or semen r Nonbacterial:
– Suprapubic tenderness
– NIH Class IV: Asymptomatic inflammatory – Leading theory: Nonrelaxation of internal urinary
– DRE: May be normal or soft/boggy, variable
prostatitis, incidental biopsy finding sphincter and pelvic floor muscles leading to
◦ >10 WBC/HPF and/or bacteria in EPS, 1st amounts of pain, prostatic calculi
increased prostatic urethral pressure and
10 mL voided urine after EPS, semen, or intraprostatic urinary reflux
histologic specimens in asymptomatic patients r Uncommon: Mycobacterium tuberculosis, parasitic, ALERT
Do not perform massage or aggressive rectal exam
EPIDEMIOLOGY mycoses (blastomycosis, coccidioidomycosis,
Cryptococcus, histoplasmosis, candidiasis in the face of acute prostatitis or prostatic abscess.
Incidence paracoccidiomycosis)
r 2 million cases annually DIAGNOSTIC TESTS & INTERPRETATION
r 9–16% men have had diagnosis of prostatitis ASSOCIATED CONDITIONS Lab
r 3–12% male outpatient urology visits r Cystitis (secondary to bacterial prostatitis) r PSA may be elevated with prostatitis PSA should not
r Most common urologic diagnosis in men <50 yr, r Epididymitis
be checked in cases of acute bacterial prostatitis.
r Prostatic hypertrophy r Suspected acute bacterial prostatitis:
3rd most common >50 yr (2)
– Overall incidence of acute prostatitis or prostatitis r STD – Urinalysis, urine culture, CBC, blood culture
NOS 2.8/1,000 person-years (PY) over 70,166 PY r Urethritis/urethral stricture r Suspected CPB/CP/CPPS (NIH II/III)
of follow-up (3) r UTI – Urinalysis, urine culture
◦ 3.2/1,000 PY in patients aged 20–29 yr – Meares–Stamey 4-glass test (gold standard)
◦ 3.6/1,000 PY in patients aged 30–39 yr GENERAL PREVENTION – 2-glass test more convenient: Pre/postprostatic
r Proper treatment of acute bacterial prostatitis may
◦ 5.4/1,000 PY in patients aged 70–79 yr massage:
reduce chronic bacterial prostatitis (NIH II) ◦ Urine microscopy and culture of midstream urine
Prevalence r Safe sex practices
N/A specimen prior to prostate massage (Pre-M)
◦ Urine microscopy and culture of 10-mL urine
RISK FACTORS postprostate massage (Post-M)
r Acute epididymitis ◦ With NIH II (chronic bacterial):
r Chronic catheterization (indwelling or condom) – Pre-M: ± Urine WBC, ± culture
r Dysfunctional voiding – Post-M: + Urine WBC, + culture
r Immunocompromised states ◦ NIH IIIA inflammatory CP/CPPS:
r Intraprostatic ductal reflux – Pre-M: − Urine WBC, − culture
– Post-M: + Urine WBC, − culture
◦ NIH IIIB noninflammatory CP/CPPS
– Pre-M: − Urine WBC, − culture
– Post-M: − urine WBC, − culture
360
PROSTATITIS, GENERAL
Imaging r Chronic bacterial prostatitis: FOLLOW-UP

r CT: If suspicion of abscess/malignancy or failure – Ciprofloxacin 500 mg PO BID for 4–6 wk; Patient Monitoring
appropriate antimicrobial treatment levofloxacin has daily dosing and may have better r Most improve with antibiotics in 3–4 wk
r Transrectal US: If suspicion of abscess or fail prostatic penetration r Long-term management of CP/CPPS requires
antibiotic therapy (rule out abscess, calculi) – Fluoroquinolones more cost effective and may be multimodal therapy and supportive care
superior to TMP/SMX
Diagnostic Procedures/Surgery r CP/CPPS: Patient Resources
r PVR if sensation of incomplete emptying
– NIH IIIA: Antibiotics may reduce symptoms but Urology Care Foundation. http://www.
r Urodynamics: CPPS patients; debatable utility urologyhealth.org/urology/index.cfm?article=15
r Cystoscopy: CPPS patients with hematuria; rules out should work within 4–6 wk
– Previously treated men do not benefit from further
bladder neck pathology, lower tract malignancy antibiotics REFERENCES
Pathologic Findings r α-Adrenergic blockers:
r Sheets, clusters, nodules of lymphocytes, plasma – Chronic bacterial prostatitis (NIH II): In 1. Sharp VJ, Takacs EB, Powerll CR. Prostatitis:
cells in fibromuscular stroma combination with antibiotics, will reduce Diagnosis and treatment. Am Fam Physician.
r No relationship to the ducts and acini symptoms 2010;82(4):397–406.
r Infiltrates of inflammatory cells restricted to the – CP/CPPS (NIH III): Benefit men with recent onset 2. Roberts RO, Lieber MM, Rhodes T, et al. Prevalence
glandular epithelium and lumen found in prostate of symptoms, not heavily treated, and on of a physician-assigned diagnosis of prostatitis: The
and BPH medication for >6 mo Olmsted County Study of Urinary Symptoms and
r Inflammatory changes noted in up to 44% of r Anti-inflammatory agents: Health Status Among Men. Urology. 1998;51(4):
asymptomatic males at autopsy – NSAIDs/analgesics/antipyretics 578–584.
r Stool softeners
r Acute urinary retention Second Line
r Cystitis (bacteria, interstitial)/urethritis r Antibiotics: Erythromycin, azithromycin, ADDITIONAL READING
r Obstructive bladder calculus clarithromycin if Chlamydia trachomatis implicated Krieger JN, Nyberg L Jr, Nickel JC. NIH consensus
r Prostate cancer r Finasteride or dutasteride: Only if associated BPH in definition and classification of prostatitis. JAMA.
r Prostatic abscess patients with CP/CPPS 1999;282(3):236–237.
r Pyelonephritis SURGERY/OTHER PROCEDURES See Also (Topic, Algorithm, Media)
r Transurethral resection: If concern for prostatic r Prostate, Abscess
abscess or in the setting of intractable chronic r Prostatitis, Acute, Bacterial (NIH I)
TREATMENT bacterial disease r Prostatitis, Asymptomatic Inflammatory (NIH IV)
r Transurethral microwave therapy: Refractory CP r Prostatitis, Chronic, Bacterial (NIH II)
GENERAL MEASURES r Prostatitis, Chronic Nonbacterial, Inflammatory and
r NIH I acute prostatitis: ADDITIONAL TREATMENT
– IV antibiotics, then switch to oral agents Radiation Therapy Noninflammatory (NIH CP/CPPS III A and B)
r Prostatitis, Granulomatous
– Acute retention may be treated with in-and-out N/A
catheter or small-caliber Foley for <12 hr or r Stamey Test (3-Glass Test, 4-Glass Tests,
Additional Therapies Meares–Stamey Test)
suprapubic drainage with acute prostatitis r Numerous unproven therapies have been suggested
– Acute bacterial prostatitis that does not resolve
with little to no evidence for treatment of CP or
with conventional measures; must rule out
CPPS, including: Allopurinol, balloon dilation,
prostate abscess
TUNA, acupuncture, neuromodulation CODES
r NIH II: Long-term antibiotic therapy
r Frequent ejaculation (in patients with enlarged,
r NIH IIIA/B: Similar management; empiric antibiotics ICD9
symptomatically congested glands), prostatic r 601.0 Acute prostatitis
often used with variable success, focus on massage (not in acute prostatitis)
symptomatic and supportive therapy; α-adrenergic r Dietary modification r 601.1 Chronic prostatitis
blockers and NSAIDs may be useful adjuncts in this r Sitz baths for symptomatic relief r 601.9 Prostatitis, unspecified
population
r NIH IV is only a histologic diagnosis and no specific Complementary & Alternative ICD10
therapy necessary Therapies r N41.0 Acute prostatitis
r Phytotherapy provides modest benefit in CP/CPPS r N41.1 Chronic prostatitis
MEDICATION r Neuromodulation (CP/CPPS): Amitriptyline, r N41.9 Inflammatory disease of prostate, unspecified
First Line gabapentin, acupuncture, biofeedback, massage,
r Antibiotics: For acute bacterial prostatitis (inpatient)
neurostimulation
– Ampicillin with gentamicin (ampicillin 1–2 g IV CLINICAL/SURGICAL
every 4–6 hr, 500 mg PO every 6 hr; gentamicin
1–2 mg/kg IV every 8–12 hr or daily dosing ONGOING CARE PEARLS
4–7 mg/kg every 24 hr IV) r Prostatitis is considered the most common urologic
– Fluoroquinolones PROGNOSIS
r Prolonged course, often difficult to cure diagnosis in men <50.
◦ Levofloxacin, 250–750 mg daily IV or by mouth r If suspected CBP/CP/CPPS, perform 2-glass test to
r 50–97% cure rate, depending on category
(PO) help establish the diagnosis.
◦ Ciprofloxacin, 250–750 mg PO twice daily r 20% with recurrent or persistent infection
r Most chronic bacterial prostatitis cases improve
(BID), 400 mg IV BID COMPLICATIONS after 3–4 wk of antibiotics.
– Ceftriaxone 1–2 g IV or IM daily r Acute urinary retention
– Afebrile 24–48 hr may change to oral antibiotics r Chronic bacterial prostatitis with incomplete
r Acute bacterial prostatitis (outpatient)
treatment of acute bacterial prostatitis
– Trimethoprim–sulfamethoxazole DS PO BID for r Epididymitis, orchitis, seminal vesiculitis (rare)
2–4 wk r Gram-negative sepsis, bacteremia
– Ciprofloxacin 500 mg PO BID for 2–4 wk r Prostatic abscess P
361
PROSTATITIS, GRANULOMATOUS
Brian Cox, MD
Christopher Amling, MD, FACS

BASICS r Specific subtype: r DRE may be normal or abnormal
– Caused by identifiable infectious agent r Abnormal DRE:
DESCRIPTION (mycobacterium, fungi, syphilis, brucellosis, virus, – Indurated gland with/without nodule
r Granulomatous prostatitis is inflammation of the parasites) – Tender or nontender
prostate associated with granuloma formation ◦ It is often associated with systemic TB r TB prostatitis should be suspected if a draining
r Often confused with carcinoma of the prostate ◦ With HIV, TB may cause prostatic abscess perineal fistula is present
– Similar findings on digital rectal exam (DRE); has r Nonspecific subtype:
the findings of a “prostate nodule” – Usually an incidental finding on biopsy ALERT
– Similar elevations in prostate-specific antigen ◦ Reported 0.3–3.0% r Digital Rectal Exam (DRE) cannot differentiate
(PSA) r Iatrogenic: between prostate nodules due to granulomatous
– Similar findings on transrectal ultrasound (TRUS) – After TURP- or TRUS-guided biopsy, necrotizing prostatitis and prostate cancer.
and magnetic resonance imaging (MRI) images lesions may resemble lesions associated with r Biopsy is required to differentiate these 2
– Can be due to infectious and noninfectious rheumatoid diseases
etiologies r Eosinophilic subtype: etiologies.
EPIDEMIOLOGY – Very rare, may suggest allergic etiology DIAGNOSTIC TESTS & INTERPRETATION
Incidence – Associated with systemic condition (asthma,
Lab
N/A Wegener granulomatosis, Churg–Strauss r Urinalysis may be unremarkable
syndrome r Urine cultures
Prevalence r Autoimmune based:
r 0.8–1% of benign inflammatory prostatic specimens – Are often sterile
r Reported up to 4–10% of prostatitis cases – HLA-DR15–linked T-cell–mediated response r Elevated erythrocyte sedimentation rate (ESR), acid
against PSA
r Reported in 1.3–40% of post-Bacillus phosphatase, serum eosinophils may be present
Calmette–Guérin (post-BCG) patients ASSOCIATED CONDITIONS r PSA may rise transiently
r Prostate cancer can be coincident with r If evidence of TB/mycotic disease, appropriate
RISK FACTORS granulomatous prostatitis in 10–14% of biopsy
r Age: Mean age 62 yr (range 18–86 yr) (1) testing includes:
specimens (2) – AFB stain of urine and semen
– Typically 50–70 yr of age r May be associated with systemic conditions
r Infections: – TB cultures (may take up to 10 wk)
– Asthma, Wegener granulomatosis, Churg–Strauss – Polymerase chain reaction (PCR): Genomic
– Bacterial, viral, fungal, parasitic, Mycobacterium, syndrome, sarcoidosis, rheumatoid arthritis, amplification of Mycobacterium Tuberculosis DNA
and sexually transmitted diseases (STDs) polyarteritis nodosa, malakoplakia ◦ High sensitivity/specificity
– Human immunodeficiency virus (HIV) infection ◦ Rapid: Takes 48 hr
may increase risk for tuberculosis (TB) prostatitis GENERAL PREVENTION
– Infectious etiologies make up ∼15–20% of N/A Imaging
r TRUS
granulomatous prostatitis cases
r Iatrogenic causes: DIAGNOSIS – Limited utility except to direct biopsy
– Transurethral resection of prostate (TURP) – Appears as focal hypoechoic area
– BCG instillation for bladder cancer—up to 40% HISTORY – Difficult to discern granulomatous prostatitis and
r Often asymptomatic prostate cancer
may develop granulomatous prostatitis after BCG.
r Previous urinary tract infection (UTI) or STD: r MRI
– Iatrogenic etiologies make up ∼75% of
granulomatous prostatitis cases – Syphilis, TB, or other infectious etiology – Limited utility
r Systemic granulomatous diseases: – Often associated with UTI 2–3 m prior to onset of – Difficult to discern granulomatous prostatitis from
– Wegener granulomatosis, Churg–Strauss symptoms prostate cancer on MRI
syndrome, sarcoidosis, rheumatoid arthritis, r History of lower urinary tract symptoms (LUTS) Diagnostic Procedures/Surgery
polyarteritis nodosa, malakoplakia – Voiding symptoms including urgency, frequency, TRUS-guided prostate biopsy is needed for pathologic
– These make up a minority of granulomatous dysuria diagnosis
prostatitis cases – Obstructive voiding symptoms, including acute
r Idiopathic: No specific cause identified Pathologic Findings
urinary retention r Histologically granulomatous prostatitis appears as
– Theory: Ductal/acinar obstruction causes prostatic r Systemic granulomatous disease:
noncaseating granulomas, prominent macrophage
secretions to leak into the stroma and cause – If associated with systemic vasculitis or infiltrates with occasional multinucleated giant cells
granulomatous reaction granulomatous disease, may have constitutional (Langerhan cells) which are characteristic of
– Idiopathic etiologies make up a significant signs/symptoms granulomas
proportion of granulomatous prostatitis cases r History of prostate surgery or bladder cancer:
– Immunohistochemistry for cytokeratin (CAM 5.2)
Genetics – BCG or TURP can cause granulomatous prostatitis may stain glands positive but not the macrophage
r Fever, chills, or other constitutional signs:
N/A infiltrate
– Suggest infectious, systemic etiology – Macrophage infiltrate stains for macrophage
marker CD68
r Fibrosis replaces parenchyma
r BCG therapy related
– Caseating or noncaseating granulomas located
next to benign prostatic glands (not engulfing
them)
– Usually AFB negative
362
PROSTATITIS, GRANULOMATOUS
r Nodular DRE (neoplasm/malignant):
r Majority of symptomatic cases of granulomatous
ADDITIONAL READING
r Humphrey PA. Prostate Pathology, ASCP Press:
– Lymphoma, primary, and secondary prostatitis resolve spontaneously
– Prostatic adenocarcinoma r Reserve TURP or prostatectomy for refractory cases Chicago. 2003;87–95.
– Sarcoma, small-cell carcinoma, and other rare r Warrick J, Humphrey PA. Nonspecific granulomatous
– Reported in up to 10% of cases in some series
tumors and metastases prostatitis. J Urol. 2012;187:2209–2210.
– Urothelial carcinoma ADDITIONAL TREATMENT
Radiation Therapy See Also (Topic, Algorithm, Media)
– Granulomatous prostatitis r BCG Sepsis/BCGosis
◦ Infectious, iatrogenic, etc. (See Risk Factors) N/A
r Prostate, Nodule
r Nodular DRE (benign): Additional Therapies r Prostatitis, General
– Prostatic calculus/calcification Corticosteroids and antihistamines have been r Prostatitis, Granulomatous Image
– Ejaculatory duct cyst recommended in idiopathic cases r Prostatitis, Tuberculosis
– Scarring/fibrosis from prior surgery or infection
◦ TURP, prostate biopsy Complementary & Alternative r Tuberculosis, Genitourinary, General Considerations
Therapies
– Granulomatous prostatitis
r Rectal wall lesions (thrombosed hemorrhoid, N/A
carcinoma, etc.) CODES
ONGOING CARE
ICD9
TREATMENT PROGNOSIS r 135 Sarcoidosis
r Majority of symptomatic cases of granulomatous
r 446.4 Wegener’s granulomatosis
GENERAL MEASURES prostatitis resolve spontaneously
r Majority of granulomatous prostatitis symptoms r DRE findings may persist for months/years r 601.8 Other specified inflammatory diseases of
resolve spontaneously including those that are BCG r PSA elevation may last up to 3 mo prostate
related (3–5)
r DRE changes and PSA elevation may persist COMPLICATIONS ICD10
r Acute urinary retention r D86.9 Sarcoidosis, unspecified
r Use antibiotics as indicated for UTI
r Possible transmission of infectious etiology to sexual r M31.30 Wegener’s granulomatosis without renal
r Symptom control:
partner involvement
– Sitz baths, fluids, anti-inflammatory α-blockers, r N41.4 Granulomatous prostatitis
r Possible infertility
and other symptomatic medications
r Temporary transurethral urinary catheterization if r Possible undetected prostate cancer
acute urinary retention or severe symptoms are FOLLOW-UP CLINICAL/SURGICAL
present
r TRUS biopsy is indicated for: Patient Monitoring PEARLS
Rebiopsy may be indicated if DRE remains abnormal or r Majority of symptomatic cases of granulomatous
– Differentiating granulomatous prostatitis from PSA remains elevated after treatment to avoid missing
prostate carcinoma coincident prostate cancer (reported in 10–14% of prostatitis resolve spontaneously.
– Consider rebiopsy if PSA remains elevated or DRE r Up to 40% of patients may develop granulomatous
cases)
remains abnormal several months after treating prostatitis after intravesical BCG.
symptomatic granulomatous prostatitis Patient Resources r DRE changes and PSA elevation may persist for
Prostatitis Foundation. http://www.prostatitis.org/
MEDICATION months.
r TRUS-guided prostate biopsy is needed for
First Line
r Antibiotics as indicated for documented UTI REFERENCES pathologic diagnosis.
r Anti-TB medications for TB prostatitis: r Rebiopsy may be indicated if DRE remains abnormal
1. Stillwell T, Engen DE, Farrow GM. The clinical
– Use only if documented TB cause or PSA remains elevated after treatment to avoid
spectrum of granulomatous prostatitis: A report of
– Isoniazid, rifampin, pyrazinamide, and either missing coincident prostate cancer (reported in
200 cases. J Urol. 1987;138:320–323.
ethambutol or streptomycin for initial regimen, 10–14% of cases).
2. Oppenheimer J, Kahane H, Epstein JI.
then change based on TB isolate sensitivities Granulomatous prostatitis on needle biopsy. Arch
– Pyridoxine (Vitamin B6) 25–50 mg/d to prevent Pathol Lab Med. 1997;121:724–729.
isoniazid neuropathy
3. Uzoh CC, Uff JS, Okeke AA. Granulomatous
Second Line Prostatitis. BJU Int. 2007;99(3):510–512.
N/A 4. Eyre RC, Aaronson AG, Weinstein BJ. Palisading
granulomas of the prostate associated with prior
prostatic surgery. J Urol. 1986;136:121–122
5. Lafontaine PD, Middleman BR, Graham SD Jr, et al.
Incidence of granulomatous prostatitis and
acid-fast bacilli after intravesicular BCG therapy.
Urology. 1997;49:363–366.
363
PROTEINURIA
Anthony J. Tracey, MD, MPH
RISK FACTORS PHYSICAL EXAM

BASICS r DM r BP measurement to rule out HTN
r HTN r Edema with nephrotic syndrome, heart failure
DESCRIPTION r Obesity (BMI >35 kg/m2 ), but progression to renal r Papilledema: Uncontrolled HTN
r Persistent abnormal amounts or types of protein in r Jugular venous pressure elevation, heart sounds
disease not proven
the urine: (heart failure, HTN)
– May be 1st indication of renal disorders either Genetics
r Abdominal bruits: Renal artery stenosis
primary (eg, proliferative glomerulonephritis) or Disease specific
secondary (eg, hypertension [HTN], lupus PATHOPHYSIOLOGY DIAGNOSTIC TESTS & INTERPRETATION
nephritis, diabetes [DM]) r Glomerular proteinuria: Lab
– Marker of overall cardiovascular health – Results from increased glomerular capillary r Urine dipstick:
r Healthy adult excretes 80–150 mg of protein per permeability to albumin – Qualitative test only (1+ to 4+); detects protein
day in urine, consisting of 30% albumin, 30% – Usually >1 g/24 hr concentration >20–30 mg/dL
serum globulins, and 40% tissue proteins. – When total protein >3 g/24 hr: Nephrotic – Cannot detect microalbuminuria; if persistently
r Dipstick urinalysis detects proteinuria only when syndrome (look for hypoalbuminemia, lipiduria, positive proceed to quantitative test (spot or 24-hr
protein excretion >300 mg/d: edema, ascites) protein)
– Microalbuminuria: 30 and 300 mg/d: r Tubular proteinuria: – False positive: Alkaline urine; concentrated urine;
◦ Earliest sign of diabetic nephropathy – Inability of proximal convoluted tubule to absorb contamination with blood; recent IV contrast dye
◦ Identifies those at risk of cardiovascular disease low–molecular-weight proteins such as – False negative: Dilute urine; dipstick only detects
in both diabetic and nondiabetic populations immunoglobulin light chains, β2-microglobulin, albumin and will miss other plasma proteins (eg,
(1)[2] amino acids, and retinol-binding protein Bence Jones proteinuria in multiple myeloma)
r Important to distinguish between benign (no – Proteinuria usually 2–3 g/24 hr r Urinalysis for associated hematuria, casts
long-term renal significance) and pathologic causes r Overflow proteinuria: (glomerulonephritis)
of proteinuria. Can often differentiate based on: – No underlying renal disease r Serum creatinine to rule out renal insufficiency
– Associated clinical findings (eg, known diabetes or – Absorptive capacity of PCT is overwhelmed by r Blood glucose: DM
HTN; edema and lipiduria in nephrotic syndromes) overproduction and accumulation of r Albumin-to-creatinine ratio or total
– Persistency of proteinuria: immunoglobulins and low–molecular-weight protein-to-creatinine ratio in a random urinary
◦ Transient or intermittent proteinuria is unlikely proteins. sample:
to be associated with significant renal pathology r Tissue proteinuria: – Quantitative test that is reliable and not
◦ Example etiologies: Exercise, emotional stress, – Associated with acute inflammation of urinary dependent on concentration. Less cumbersome
fever, orthostatic proteinuria tract due to cystitis, acute prostatitis, and urinary than 24-hr collection
◦ Document proteinuria on >1 visit tract tumors – Corresponds to 24-hr albumin excretion in a linear
– Degree of proteinuria: r Transient proteinuria: manner (eg, ratio of 3 = 3 g/24 hr)
◦ 500 mg/24 hr usually heralds significant – Glomerular permeability and decreased tubular – Serial measurements monitor therapeutic response
glomerular disease reabsorption have both been proposed as possible – Preferred screening strategy for diabetic patients
◦ Proceed to quantitative measurement when mechanisms (2) – 2 out of 3 positive tests separated by 3–6 mo
dipstick is persistently positive considered persistent proteinuria
ASSOCIATED CONDITIONS r Albumin, cholesterol: Nephrotic syndrome
EPIDEMIOLOGY r See “Differential Diagnosis”
r Hypercoagulability, lipiduria, edema, and r 3% sulfosalicylic acid test:
Incidence
r In diabetic patients, progression to – Detects all types of proteinuria
hypoalbuminemia (nephrotic syndrome)
microalbuminuria 2% per year; from – Strongly consider in patients with acute renal
microalbuminuria to proteinuria 2.8% per year failure and negative or trace protein on dipstick to
r 1.7% of males and 0.9% of females DIAGNOSIS rule out myeloma
r Increases with age r Split urine collection: Daytime (7 AM to 11 PM) and
r Higher in patients with DM: HISTORY overnight (11 PM to 7 AM) to rule out orthostatic
r Presence of underlying systemic disease:
– Microalbuminuria 24.9%; proteinuria 5.3% proteinuria
– DM, HTN, autoimmune disorders, cardiac disease, r Urine protein electrophoresis: To assess for light
Prevalence multiple myeloma chain immunoglobulins/Bence Jones proteins
r African Americans afflicted with higher levels of r Transient proteinuria triggered by:
associated with multiple myeloma
proteinuria due to increased risk of associated – Exercise, emotional stress, fever, recent illness r Others as indicated: Hepatitis and/or HIV testing,
diseases r Medication-induced glomerular injury
r Orthostatic proteinuria in 2–5% of adolescents: autoantibodies (ANA, etc.) (2)
r Associated symptoms that would suggest clinically
– Uncommon in age >30 yr: significant proteinuria:
◦ Increased protein excretion in the upright – Hematuria, bone pain (myeloma)
position. Resolves in supine position (2)[2] r Age <30 and healthy (orthostatic proteinuria) (1,2)
◦ No therapy required, often resolves with time
364
PROTEINURIA
Imaging MEDICATION Patient Resources

r Renal US in cases of persistent proteinuria to rule National Kidney and Urologic Diseases Information
First Line
out anatomic abnormality r ACE inhibitors reduce proteinuria and can both Clearinghouse (NKUDIC). http://kidney.niddk.
r 3-phase CT if renal function sufficient and nih.gov/kudiseases/pubs/proteinuria/
prevent and slow deterioration of renal function in
associated hematuria
r MRI urogram patients with diabetes or nondiabetic renal disease,
independent of their antihypertensive effects (3)[A]: REFERENCES
Diagnostic Procedures/Surgery – Can reduce protein excretion by 35–45%
r Tissue analysis: – Lisinopril 2.5 mg/d PO; increase as tolerated 1. Ruiz J, Sánchez-Fructuoso A, Zárraga S.
– Renal biopsy strongly considered for: – Ramipril 2.5–5 mg/d PO, 20 mg/d max Management of proteinuria in clinical practice after
◦ Proteinuria with hematuria – Captopril 12.5–25 mg PO BID/TID, 50 mg TID kidney transplantation. Transplant Rev (Orlando).
◦ Prolonged ARF of unknown etiology max 2012;26:36–43.
◦ Nephrotic proteinuria 2. Bello A, Thompson S, Lloyd A, et al; Alberta Kidney
Second Line
◦ Transplanted kidney (3) r Angiotensin II receptor antagonists: Disease Network. Multiple versus single and other
r Cystoscopy if concurrent hematuria estimates of baseline proteinuria status as
– Use if side effects such as cough and angioedema
r Cystoscopy with retrograde pyelogram if upper tract predictors of adverse outcomes in the general
develop from ACE inhibitors
imaging indicated (hematuria, hydronephrosis) and population. Am J Kidney Dis. 2012;59:364–371.
– Candesartan, eprosartan, irbesartan, losartan,
unable to evaluate upper tracts with excretory phase valsartan 3. Turin TC, Tonelli M, Manns BJ, et al. Proteinuria
imaging – Calcium channel blockers: May be better for HTN and life expectancy. Am J Kidney Dis. 2013;61:
with less renal effect in the relatively ischemic 646–648.
Pathologic Findings
Depends on underlying etiology kidney
DIFFERENTIAL DIAGNOSIS SURGERY/OTHER PROCEDURES ADDITIONAL READING
r Glomerular proteinuria: N/A
r American Diabetes Association. Standards of
– IgA nephropathy ADDITIONAL TREATMENT
– Diabetic nephropathy medical care in diabetes–2007. Diabetes Care.
Radiation Therapy 2007;30:S4–S41.
– Medications (eg, NSAIDs, captopril, lithium) r www.kidney.org/professionals/kdoqi/guidelines.cfm.
N/A
– Minimal change
– Primary glomerulonephritides Additional Therapies See Also (Topic, Algorithm, Media)
– Autoimmune (eg, SLE, amyloidosis) N/A r Glomerulonephritis, Acute
r Tubular proteinuria: Complementary & Alternative r Glomerulonephritis, Chronic
– Obstructive uropathy Therapies r Proteinuria Algorithm
– Toxins and drugs N/A r Renal Failure, Acute
– Fanconi syndrome r Renal Failure, Chronic
r Overflow proteinuria:
ONGOING CARE r Urinalysis and Urine Studies
– Multiple myeloma
– Monoclonal gammopathy of unknown significance PROGNOSIS
– Rhabdomyolysis causing myoglobinuria r Isolated proteinuria; degree dependent:
– Any hemolytic state causing hemoglobinuria CODES
– Nonnephrotic proteinuria has low risk of
r Transient proteinuria:
progressive kidney disease (3)[2]
– Fever – Nephrotic proteinuria (>3 g/d) associated with ICD9
– Strenuous exercise glomerular disease and high risk of progression to 791.0 Proteinuria
– Emotional stress chronic kidney disease ICD10
– Pregnancy – Japanese study of screened healthy patients; r R80.0 Isolated proteinuria
– Cold exposure cumulative incidence of ESRD over 17 yr: r R80.2 Orthostatic proteinuria, unspecified
– Orthostatic proteinuria ◦ 1.4% with 1+ proteinuria r R80.9 Proteinuria, unspecified
◦ 7.1% with 2+ proteinuria
TREATMENT COMPLICATIONS
r Progression to renal failure CLINICAL/SURGICAL
GENERAL MEASURES r Proteinuria is a marker for overall cardiovascular PEARLS
r Treat specific underlying etiology.
health (3)[2]
r All patients with persistent proteinuria should be Proteinuria in excess of 500 mg/d likely represents
referred to a nephrologist. FOLLOW-UP significant glomerular disease.
r Hematology–oncology evaluation for patients with Patient Monitoring
r Transient proteinuria: Active monitoring unnecessary
Bence Jones protein for treatment of multiple
r Nephrologist for any patient with large quantity of
myeloma
r Mild dietary protein restriction may prevent proteinuria and high-risk patients with
progression of chronic kidney disease. microalbuminuria:
r Strict glycemic and BP control in diabetics – Monitor urine albumin-to-creatinine ratio
r Salt/fluid restriction for edema associated with – Monitor serum creatinine
nephrotic syndrome
365
PRUNE BELLY (EAGLE–BARRETT OR TRIAD) SYNDROME

r Testes: ASSOCIATED CONDITIONS

BASICS – Usually intra-abdominal (over iliac vessels) r Genetic:
– Epididymis poorly attached – Turner syndrome; trisomy 13, 18, and 21;
DESCRIPTION – Descent in part affected by mechanical forces Beckwith–Wiedemann syndrome
r Prune belly refers to the classic appearance of (eg, large bladder, low intra-abdominal pressures) r Gastrointestinal:
abdominal wall wrinkling and budging flanks caused r Kidneys: – Malrotation of gut (∼40%); bowel atresia,
by varying degrees of abdominal wall deficiency, – Dysplasia in 50%, to varying degrees gastroschisis, omphalocele, imperforate anus (rare)
found almost exclusively in males (image) (1) – Nonobstructive hydronephrosis is common; does r Pulmonary:
r Prune belly syndrome (PBS) triad: not correlate to degree of dysplasia – >50% with pulmonary hypoplasia
– Deficient abdominal musculature r Ureters: r Cardiac:
– Bilateral cryptorchidism – Dilated, tortuous, and redundant; distal – Atrial and ventricular septal defects, tetralogy of
– Urinary tract anomalies (eg, dilated prostatic >proximal Fallot, valvular anomalies, patent ductus arteriosus
urethra, renal dysplasia, hydroureteronephrosis) – Increased ratio of collagen to smooth muscle r Musculoskeletal:
r Incomplete variants lack abdominal wall features; – Poor peristalsis and ureteral coaptation lead to – Scoliosis; vertebral anomalies, congenital hip
females lack gonadal anomalies stasis and reflux dislocation, club feet
r Woodard classification: – ∼75% with reflux
– Type I: Usually fatal; marked oligohydramnios due r Bladder: GENERAL PREVENTION
to severe renal dysplasia or bladder outlet – Enlarged with no significant hypertrophy None known
obstruction with pulmonary hypoplasia and – May have urachal pseudodiverticulum
skeletal anomalies (Potter sequence) – Urachus patent in up to 30% DIAGNOSIS
– Type II: Full spectrum of disease with no – Increased ratio of collagen to smooth muscle
immediate threat to life; renal dysplasia; – Urodynamics commonly show normal compliance, HISTORY
hydroureteronephrosis; possible mild pulmonary delayed sensation, large capacity; 50% void with r Gestational history (eg, oligohydramnios, prenatal
hypoplasia normal pressures and flow, and have low postvoid hydronephrosis)
– Type III: Mild external features of triad or residual r Rarely positive family history
incomplete variant; no evidence of pulmonary r Prostatic urethra:
hypoplasia, mild uropathy PHYSICAL EXAM
– Dilated due to prostatic hypoplasia r 75% will have nonurologic manifestations
r Synonyms: Eagle–Barrett or Triad syndrome – 20% can have distal obstructive lesions r General: Observe for Potter facies (eg, wide set eyes,
EPIDEMIOLOGY (eg, valves, atresia, stenosis)
r Anterior urethra: flattened nasal bridge)
Incidence r Heart: Auscultate for murmurs due to atrial or
r 3.8/100,000 live births – Usually normal
ventricular septal defects, patent ductus arteriosus
r 95% males – Most common abnormalities: Megalourethra and r Lungs/chest: Auscultate for pneumothorax; evaluate
r Higher incidence in African Americans urethral atresia (latter can be fatal unless patent
urachus) for pectus excavatum/carinatum
r Lower incidence in Hispanic population r GI: Associated with gastroschisis or omphalocele;
– Megalourethra can be caused by transient
r Increased incidence in younger mothers obstruction imperforate anus; intestinal malrotation, atresia, or
– Fusiform: Defect in corpus cavernosum and stenosis
Prevalence r Urologic: Evaluate meatus, observe urinary stream,
N/A spongiosum; entire phallus dilates on voiding
– Scaphoid: Defect in corpus spongiosum; only attempt to palpate testes
RISK FACTORS ventral urethra dilates r Abdomen: Wrinkled, redundant skin over lower
Slightly increased risk in African Americans and r Fertility: abdomen with bulging flanks
younger mothers – Usually infertile (rare cases of paternity with sperm r Extremities: Observe for dimpling on lateral aspect
Genetics retrieval) due to azoospermia of knees, knock knees, clubfoot, hip dislocation,
r Most cases are sporadic, with normal karyotype. – Histologic defect in testes scoliosis
r Potential inheritance patterns in rare familial cases – Atretic vas deferens and seminal vesicles
(influenced autosomal recessive; X-linked) – Retrograde ejaculation from incompetent bladder
r Monozygotic twins reported concordant and neck
discordant for PBR suggests some nongenetic basis
PATHOPHYSIOLOGY
r Exact mechanism unknown:
– Early in utero transient urethral obstruction
– Mesodermal developmental defect
r Abdominal defects due to deficient musculature
medially and inferiorly:
May be partial hypoplasia of the abdominal wall to
complete absence of musculature
366
PRUNE BELLY (EAGLE–BARRETT OR TRIAD) SYNDROME
DIAGNOSTIC TESTS & INTERPRETATION SURGERY/OTHER PROCEDURES FOLLOW-UP

r Prenatal: Vesicoamniotic shunting for
Lab Patient Monitoring
r Serum electrolytes, urea nitrogen, and creatinine: oligohydramnios in 2nd trimester (controversial) r Serial evaluation of renal function, bladder function
r Nadir creatinine <0.7 ng/dL is predictive of r Consider circumcision to reduce incidence of UTI and emptying, and for UTIs
adequate renal function through childhood. r Urinary tract reconstruction (eg, reimplant) is r Imaging is individualized
r Urinalysis and urine culture as indicated controversial due to potential for improvement or
Patient Resources
resolution, stabilization of function, and high r http://www.urology.ucsf.edu/patient-care/
Imaging complication rates (2)
r Prenatal US: Bilateral hydroureteronephrosis, children/urinary-tract-obstruction/prune-belly-
r Early intervention may be warranted with
thin-walled distended bladder, possible syndrome
progressive/severe hydronephrosis, progressive renal r Prune belly syndrome network: www.prunebelly.org
oligohydramnios
r Chest x-ray (pneumothorax) failure, or recurrent UTIs (2)
r Postnatal renal/bladder US (degree of renal – Temporary cutaneous vesicostomy or bilateral
dysplasia and hydroureteronephrosis)
cutaneous pyelostomies (avoid proximal REFERENCES
ureterostomies)
r Radioisotope studies (technetium-99m/99Tc):
– Ureteral reimplantation with/without tapering 1. Hassett S, Smith GH, Holland AJ. Prune belly
– DMSA at 4–6 wk to assess renal parenchymal r Reduction cystoplasty reserved for large urachal syndrome. Pediatr Surg Int. 2012;28:219–228.
function diverticulum or as part of extensive reconstruction, 2. Denes FT, Arap MA, Giron AM, et al.
– MAG3 scan to assess presence/degree of since large bladder tends to recur Comprehensive surgical treatment of prune belly
obstruction r Orchidopexy: syndrome: 17 years experience with 32 patients.
Diagnostic Procedures/Surgery – Transabdominal, preferably done by 1 yr of age or Urology. 2004;64:789–793.
r VCUG: in combination with other procedures: 3. Lesavory MA, Chang EI, Suliman A, et al.
– Perform while on antibiotic prophylaxis r Abdominal wall reconstruction for cosmesis, may Long-term follow-up of total abdominal wall
– Reflux in up to 75% of cases enhance Valsalva voiding and improve bladder reconstruction for prune belly syndrome. Plast
– Large bladder and dilated prostatic urethra emptying (3) Reconstr Surg. 2012;129:104e–109e.
tapering to membranous urethra r Renal transplantation
Pathologic Findings – 1/3 will eventually need renal transplant
r Renal dysplasia on biopsy – Achieve adequate bladder emptying prior to ADDITIONAL READING
r Ureter and bladder with increased collagen and transplant
Baskin LS, Kogan BA. Handbook of Pediatric Urology,
fibrous tissue ADDITIONAL TREATMENT 2nd ed. Philadelphia, PA: Lippincott Williams &
DIFFERENTIAL DIAGNOSIS Radiation Therapy Wilkins; 2005.
r Megacystis microcolon N/A See Also (Topic, Algorithm, Media)
r Intestinal hypoperistalsis syndrome (marked female r Polyhydramnios/Oligohydramnios
predominance N/A r Prune Belly (Eagle–Barrett or Triad) Syndrome
r Posterior urethral valves (prenatal appearance can
Complementary & Alternative Image
be similar) r Undescended Testes (Cryptorchidism)
Therapies
Use of corsets for abdominal wall laxity have been
TREATMENT reported
CODES
GENERAL MEASURES
r Primary goal is to preserve renal function and ONGOING CARE ICD9
prevent UTI r 257.2 Other testicular hypofunction
r Early aggressive surgery for dilated urinary tract PROGNOSIS r 748.5 Agenesis, hypoplasia, and dysplasia of lung
r Degree of renal dysplasia most important
without evidence of progressive renal dysfunction or determinant of long-term survival r 756.71 Prune belly syndrome
UTIs should be avoided r Up to 1/3 develop renal failure and will require
– High complication rate ICD10
r Demonstrate proper bladder emptying dialysis/renal transplantation r E29.1 Testicular hypofunction
– Double voiding COMPLICATIONS r Q33.6 Congenital hypoplasia and dysplasia of lung
– Timed voiding r Renal failure r Q79.4 Prune belly syndrome
– Clean intermittent catheterization (CIC) r Respiratory failure (early)
r UTI prophylaxis r Recurrent UTIs
r Avoid instrumentation early to reduce UTI risk r Urosepsis CLINICAL/SURGICAL
MEDICATION
PEARLS
First Line r Antireflux surgery with high complication rates;
r UTI prophylaxis: avoid if possible.
– Ampicillin 25 mg/kg/d as neonates r Prenatally can be difficult to distinguish from
– Trimethoprim–sulfamethoxazole 2 mg/kg once posterior urethral valves.
daily or nitrofurantoin 1–2 mg/kg once daily r Goal is to avoid renal damage, UTIs.
beyond 2 mo of age
Second Line
None
367
PSA ELEVATION FOLLOWING NEGATIVE PROSTATE BIOPSY


BASICS r 12 biopsy cores from a standard 18G needle r Digital rectal exam (DRE)
enables only 0.04% of prostate gland to be – Induration or nodularity
DESCRIPTION evaluated for pathology (2) ◦ Concerning for malignancy
r Transrectal ultrasound-guided (TRUS) prostate r PSA elevations can be from non-PCa causes – Symmetric and enlarged gland
biopsy (PB) is the gold standard for diagnosis of r Series reporting follow-up biopsy results (Mo) ◦ BPH more likely with elevated PSA and negative
prostate cancer (CaP) – In 2012 Ca detection rates on follow-up biopsies biopsy
r While CaP screening is controversial, a subset of – Tenderness or bogginess on exam
1, 2, 3, and 4 were 22%, 10%, 5%, and 4%,
men have a negative TRUS PB with persistent or respectively; 58%, 60.9%, 86.3%, and 100% of ◦ Likely acute prostatitis
increasing elevation in PSA. This can be a challenge patients who had RP had organ-confined disease r Decreased testicular volume
for urologist and the patient on biopsies 1, 2, 3, and 4. – Consider exogenous androgen exposure
r Repeat PB performed after negative PB suggests up – A 2008 series with extended biopsies found CaP DIAGNOSTIC TESTS & INTERPRETATION
to 30% of patients have cancers not previously 18%, 7%, and 14% of patients had PCa in 2nd,
identified (1) 3rd, and 4th biopsies, respectively; significant CaP
Lab
r Free/total PSA (4)
EPIDEMIOLOGY in 85% of cases (3). r Prostate cancer antigen 3 (PCA3)
Incidence ASSOCIATED CONDITIONS – Gene that is overexpressed in PCa; measured in
800,000–1.2 million prostate biopsies are performed The following can cause elevated PSA: infection, recent 1st voided urine after attentive digital rectal exam
in the United States annually instrumentation, benign prostatic hypertrophy (BPH) – FDA approved for men >50 yr who have had 1 or
Prevalence GENERAL PREVENTION more previous negative biopsies
r 24.1% of men in a screening population undergoing r Obtain serial PSA at same lab; avoid sexual activity – Cutoff debatable 25–35
TRUS diagnosed with PCa for 24 hr before – Compared to PSA
r False-negative rate for TRUS PB as high as 35% r Preventing a false-negative PB is greatly dependent ◦ Lower sensitivity (67%); higher specificity (83%)
◦ Some studies suggest superior to F/T PSA
– Cancer detection rate as high as 14% after 3rd on technique ◦ Patient stratified into lower risk or higher risk of
repeat biopsy – 12-core template is now standard
◦ 6 parasagittal plus 6 lateral cores having a positive biopsy
RISK FACTORS
r Both technical and anatomical considerations – Sextant (6-core) biopsy can miss up to 50% of Imaging
small tumors r MRI may identify anterior tumor not reached by
contribute to a false-negative PB
r Advances in biopsy techniques have improved – No evidence of increased complication rate of biopsy needle
12-core compared to sextant biopsy – T2-weighted MRI
positive sampling rates ◦ Identify focal lesions within gland
– Digital-direct biopsy without ultrasound guidance ◦ Need to wait 6–8 wk after negative biopsy as
provides inadequate sampling DIAGNOSIS recent biopsy sites cause distortion
– TRUS guided is gold standard – Multiparametric (mp) MRI
◦ <10 cores are considered inadequate for cancer HISTORY ◦ Combination of dynamic contrast-enhanced
detection r Prior history of negative prostate biopsies
r Evaluate for nonmalignant causes of elevated PSA MRI, MR spectroscopic imaging, and
◦ “Double sextant” or 12-core with inclusion of
diffusion-weighted imaging; need access to
laterally directed cores have lower – Prostatitis experienced center
false-negative rates – Recent instrumentation of genitourinary tract – Contrast-enhanced TRUS
r Anatomical – Rarely sexual activity, bicycling can briefly elevate ◦ Neovascularity of tumor enhances with
– Large gland size (>50 cc) may limit detection of r Increase risk of PCa
microbubble contrast agent (not FDA approved)
CaP on standard core biopsy – 1st-degree relative with PCa and recent data ◦ Targeted biopsy show increase sensitivity from
– End-fire ultrasound probe allows better sampling suggestion increased risk with a relative with 38–65% vs. unenhanced imaging
anterior and apical prostate gland breast cancer – Color Doppler of limited utility w/o contrast
◦ These areas likely to harbor unrecognized ◦ Increase risk by 120–150% – Elastography ultrasound: Tumors allow less
malignancy in larger glands – Ethnicity: Black race highest risk displacement with compression than normal
r High-grade cancers (Gleason 9–10) may not have – History of exposure to exogenous androgen or tissue; color coded map allows targeted biopsy;
PSA elevation anabolic steroid use not widely available
r Percent-free PSA r MRI TRUS fusion biopsy may help identify specific
Genetics
r CaP has both familial and genetic component – With negative prior biopsy and low percent-free lesions for directed biopsy
– Relative risk increases with number of 1st-degree PSA (<12%) have higher risk of malignancy
r PSA velocity Diagnostic Procedures/Surgery
relatives affected r Mapping/saturation biopsy
◦ Higher index of suspicion if 1st-degree relatives – Rate of change of PSA over 1-yr period
– Obtaining 20 or more cores with standard biopsy
have diagnosis of prostate malignancy – Recommend biopsy if PSA velocity exceeds
technique; can be transrectal but more likely to be
0.35 ng/mL/yr
done transperineally using a brachytherapy-like
– PSA velocity independent predictor of overall PCa,
template guide
intermediate- and high-grade cancer.
– Studies vary in yield of detection with increased
cores; increased morbidity
– Usually require additional anesthesia
r Transitional zone targeted biopsy
– 15% increased detection in gland >50 cc
368
PSA ELEVATION FOLLOWING NEGATIVE PROSTATE BIOPSY
r Template transperineal PB SURGERY/OTHER PROCEDURES 3. Pinsky PF, Crawford ED, Kramer BS, et al. Repeat
– May allow better sampling of peripheral zone r The number of cores on repeat biopsy is debatable. prostate biopsy in the Prostate, Lung, Colorectal
– Controversial if better cancer detection NCCN guidelines suggest performing a 2nd and Ovarian cancer screening trial. BJU Int.
r MRI and ultrasound fusion targeted biopsy extended biopsy and consider saturation biopsies 2007;99:775–779.
– Stored MRI is fused with real-time ultrasound only in with high risk of cancer after multiple 4. Auprich M, Augustin H, Budäus L, et al. A
using a digital overlay negative biopsies comparative performance analysis of total
– Series report 41% vs. 18% compared to r Transurethral resection prostate biopsy prostate-specific antigen, percentage free
conventional ultrasound in detection of CaP in – Once advocated for diagnosis of transition zone prostate-specific antigen velocity and urinary
men with prior negative biopsies cancers prostate cancer gene 3 in the first, second, and
– Requires specialized training and equipment – Less than 5% CaP are transitional zone CaP third repeat biopsy. BJU Int. 2011;109:1627–1635.
Pathologic Findings without concomitant peripheral zone tumors 5. Jones JS. Managing patients following negative
r Quality assurance in the initial biopsy is critical. Data – Improved TRUS technique in sampling transitional prostate biopsy. Renal & Urology News.
suggests a core length of >10 mm and the presence zone; no definite value in performing transurethral 2011:10:23.
of glandular elements suggest an adequate sample resection PB
r High-grade prostatic intraepithelial neoplasia ADDITIONAL TREATMENT
(HGPIN) 0–24.6% on initial biopsy (median 4%) Radiation Therapy
ADDITIONAL READING
– Considered by some to be premalignant lesion: N/A r Elshafei A, Li YH, Hatem A, et al. The utility of PSA
23–35% risk of diagnosis cancer on subsequent velocity in prediction of prostate cancer and high
biopsy; however, EAU does not recommend repeat Additional Therapies
r The European Randomized Study of Screening for grade cancer after initially negative prostate biopsy.
biopsy with HGPIN Prostate. 2013;73(16):1796–1802.
r Atypical small acinar proliferation (ASAP) PCa (ERSPC)-based model has several calculators to
determine outcome after negative biopsy r Levy DA, Jones JS. Management of rising
– Incidence 0.7–23.4%, median 4.4% prostate-specific antigen after a negative biopsy.
(http://www.prostatecancer-riskcalculator.com/)
– Increased CaP risk on subsequent biopsy (up to r Genomic testing may help determine risk after Curr Urol Rep. 2011;12(3):197–202.
40%) r Presti JC. Management of patients with persistently
negative biopsy
DIFFERENTIAL DIAGNOSIS – Confirm MDxTM : Epigenetic assay to distinguish elevated PSA level and negative biopsy. AUA Update
r ASAP men who have a true-negative biopsy from those Series. 2012; Lesson 1, Volume 31.
r BPH with occult cancer r Scott JG, John G, Eric K, et al. Emotional
r HGPIN – Identifies methylation signature in area near PCa consequences of persistently elevated PSA with
r Prostatitis location using recent prostate biopsy material negative prostate biopsy. Am J Cancer Prevention.
Complementary & Alternative 2013;1(1);4–8.
TREATMENT Therapies See Also (Topic, Algorithm, Media)

N/A r PCA3 (Prostate Cancer Gene 3 Urine Assay)
GENERAL MEASURES r Prostate Biopsy, Infections and Complications
r Most recommendations are for repeat biopsy for r Prostate Cancer, General
ONGOING CARE r PSA Elevation, General Considerations
patients with either ASAP or multifocal HGPIN
within 3–6 mo regardless of PSA (5) PROGNOSIS r PSA, Free and Total
r For others with negative biopsy and persistently r There is no PSA threshold that can rule out PCa in r PSA, General Considerations
elevated or rising PSA, consider the use of any age range
supplementary lab tests such as PCA3, free/total – Regardless of initial PSA value, a PSA velocity
PSA Confirm MDx to guide decision greater than 0.75 ng/mL/yr warrants repeat biopsy CODES
r Repeat PB appears justified in: r Lowering PSA threshold for initial biopsy
– An initial negative biopsy and persistent suspicion – Many urologists recommend PB to men younger
than 60 yr of age once PSA >2.5 ng/mL; enables
ICD9
of PCa based on age, comorbidities, DRE findings, r 185 Malignant neoplasm of prostate
repeated PSA, PSA derivatives, (% free PSA, earlier CaP detection r 601.9 Prostatitis, unspecified
complexed PSA, PSAD, PSA velocity, or urinary COMPLICATIONS r 790.93 Elevated prostate specific antigen [PSA]
PCA3 score) and patient and physician preferences See Section I: “Prostate biopsy, Infections and
r With concerns over the interpretation of the earlier
Complications” ICD10
biopsy, consider a 2nd opinion r C61 Malignant neoplasm of prostate
FOLLOW-UP r N41.9 Inflammatory disease of prostate, unspecified
MEDICATION
Patient Monitoring r R97.2 Elevated prostate specific antigen [PSA]
First Line If low risk with negative biopsy can be followed with
r Limited utility in managing elevated PSA
routine surveillance protocol
r Antibiotics if presumed prostatitis cause of elevation
– 2–3-wk course of oral antibiotics Patient Resources CLINICAL/SURGICAL
– Sulfamethoxazole and trimethoprim (Bactrim DS) National Cancer Institute Fact Sheet: Prostate-Specific PEARLS
BID or ciprofloxacin 500 mg BID Antigen (PSA) test. www.cancer.gov/cancertopics/
factsheet/detection/PSA r Threshold for repeat biopsy should be low if atypia
◦ Repeat PSA after termination of treatment
– Studies have not shown routine antibiotics seen on initial biopsy.
r PCA3 can elucidate the need for further biopsy in
decreased need for future biopsy REFERENCES those with prior negative biopsy and persistently
r 5-α reductase inhibitors
– Finasteride 5 mg or dutasteride 0.5 mg PO QD for 1. Zaytoun O, Moussa AS, Gao T, et al. Office based elevated PSA.
r Emerging imaging modalities are promising in
6 mo transrectal saturation biopsy improves prostate
◦ Should lower PSA by 50% after 6 mo but not cancer detection compared to extended biopsy in detecting CaP not found on initial PB.
proven useful in determining repeat biopsy, but repeat biopsy population. J Urol. 2011;186:
any PSA rise after 6 mo raises CaP risk 850–854.
Second Line 2. Resnick MJ, Lee DJ, Magerfleisch L, et al. Repeat P
N/A prostate biopsy and the incremental risk of clinically
insignificant prostate cancer. J Urol. 2010;77(3):
548–552.
369
PSA ELEVATION, GENERAL CONSIDERATIONS

Adam P. Dicker, MD, PhD
Prevalence
BASICS US CaP approximately 2,106,499 men, or 1.5% all DIAGNOSIS
ages and races
DESCRIPTION HISTORY
r PSA is used for diagnosis and treatment of prostate RISK FACTORS r Difficulty with urination, such as hesitancy, straining,
r For elevated PSA
cancer (CaP). This section reviews the use of PSA in weak stream, or intermittency
the diagnosis of CaP recognizing that screening is – Advancing age r Dysuria, frequency, or urgency
an area of controversy – Benign prostatic hypertrophy (BPH) r Previous PSA levels or prostate biopsies
r CaP is only diagnosed through tissue biopsy and not – CaP r Family history of prostate carcinoma
– Infection, infarction r Medications, including herbals
by PSA alone
r Normal PSA level is controversial, and can be – Recent instrumentation (TURP, cystoscopy,
r Markedly elevated PSA >20 ng/mL with bone, back,
catheterization, prostate biopsy)
elevated due to malignant or benign causes. r CaP (See chapter “Prostate Cancer, General”) or hip pain suggests metastatic CaP
– Elevated PSA traditionally >4.0 ng/mL based on
the Baltimore Longitudinal Study of Aging Genetics PHYSICAL EXAM
r PSA associated with kallikrein genes family (long r DRE: Nodules, induration, asymmetry, bogginess,
◦ Specificity 91%, sensitivity 21% (51% for
Gleason ≥8), PPV 30% arm of chromosome 19 region q13.2–q13.4). tenderness (Note: American Cancer Society
– Elevated PSA >2.5 ng/mL has support r PSA is also called human kallikrein 3 (hKLK3) recommends PSA screening with or without DRE)
r Age/race-specific proposed, but controversial: r Adenopathy, supraclavicular
PATHOPHYSIOLOGY r Bony pain, point tenderness with metastasis
r PSA: A serine protease produced by the prostatic
r Neurologic: Lower extremity strength/sensation
Range (yr) Asian Black White epithelium and periurethral glands that liquefies
40–49 0–2.0 0–2.0 0–2.5 seminal coagulum DIAGNOSTIC TESTS & INTERPRETATION
r Seminal fluid has high PSA concentrations (mg/mL); Lab
50–59 0–3.0 0–4.0 0–3.5 r Routine UA to rule out UTI/prostatitis (1–3)
PSA is much lower (ng/mL) in serum
60–69 0–4.0 0–4.5 0–4.5 r Many forms of serum PSA: Free PSAs (nicked, intact, r Consider evaluation for prostatitis by modified
70–79 0–5.0 0–5.5 0–6.5 several forms of proPSA) and complexed PSA Stamey–Meares test or exam of EPS (See Section I:
r Based on Prostate Cancer Prevention Trial (biopsy (bound to protease inhibitors α1-antichymotrypsin Prostatitis, Chronic, Bacterial [NIH II])
[ACT], α2-macroglobulin [MG], α1-protease r Consider %FPSA (FPSA/TPSA or F/T PSA)
regardless of PSA), can have CaP with “low” PSA.
inhibitors [API]); bound PSA forms stable complex – With CaP lower FPSA; postulated that CaP
No lower cutoff or normal PSA to indicate absence
(no serum enzymatic activity) (2) produces more ACT
of cancer. PCPT data:
– 60–90% complexed to ACT; free portion is also – FPSA best with TPSA 4.0–10.0 ng/mL and
detected by assay, while that bound to MG is not prostates <50 g; not useful if TPSA >10 ng/mL
PSA CaP Rate PSA CaP Rate
detected by routine assay – FPSA stratifies CaP risk on biopsy (table) (3)
0–0.5 6.6% 3.1–4.0 26.9 – Complexed PSA: Hepatic clearance (1/2-life
0.6–1.0 10.1% 4.0–10.0 25% 2.2 days); FPSA cleared by glomerular filtration PSA ng/mL CaP Rate %FPSA CaP Prob
(1/2-life 2–3 hr)
1.1–2.0 17% >10.0 >50% r CaP PSA elevation is due to disrupted prostatic 0–2 1% 0–10 56%
2.1–3.0 23.9% architecture and compromised integrity of the basal 2–4 15% 10–15 28%
r The challenge: Lower normal PSA to recommend layer or basement membrane 4–10 25% 15–20 20%
– CaP makes less PSA/g than benign tissue >10 >50% 20–25 16%
biopsy where life-threatening cancer is present, but r Androgens influence PSA levels
not to point where “overdetection” of incidental r Sources of fluctuation in PSA: >25 8%
(autopsy/insignificant CaP) occurs
r PSA derivatives may overcome problem, but not – No PSA analytic standard; can vary by lab and use r Consider PSAD: PSA ÷ TRUS volume:
same lab to compare serial values
absolute: Used in PSA range of 4.0–10 ng/mL: PSA – Correlates PSA to TRUS prostatic size to
– 15% coefficient of variation in PSA assay
density (PSAD), PSA velocity (PSAV), newer PSA distinguish BPH from CaP:
– Physiologic variation in PSA 15–30% in the short
assays (free, molecular forms)
r PSA changes over time more useful than a single term; BPH can vary up to 30% PSA ng/mL
– 26–37% with elevated PSA return to normal 1 yr ◦ PSAD =
PSA in screening for CaP Prostate Volume (cc)
r A single PSA of >1.3 ng/mL before age 50 predicts later, and 45–55% normal within 4 yr
– Seasonal variation: PSA is higher in summer – Useful with PSA 4–10 ng/mL and a previous
increased lifetime CaP risk (1) – Infection, infarction, trauma, ejaculation within negative biopsy
r PSA >10: More risk of advanced disease. – Cutoff of 0.15 ng/mL/cm3 improves specificity by
24 hr, or prostate instrumentation or massage can
r PSA proportional to prostate volume; prostate produce elevations (not routine DRE) 50%, missed 27–48% CaP
volume/mean PSA were as follows: 14 cm3 /1; – Finasteride (5 mg BPH; 1 mg alopecia) and – Cutoff 0.1 avoids 31% of biopsies, misses 10%
25 cm3 /1.13/52 cm3 1.45 in 1 study dutasteride are 5α-reductase inhibitors; lower cancers; cutoff of 0.8 avoids 12% of biopsies,
PSA by 50% over 6 mo; “correct” PSA by misses 5% of cancers
ALERT doubling to maintain PSA utility r Consider PSAV:
PSA should not be done with acute prostatitis or – Rate of PSA increase; PSA rises more rapidly if
ASSOCIATED CONDITIONS clinically significant CaP present:
within 3–4 wk of prostate instrumentation: r BPH
false-positive risk. r Acute and chronic bacterial prostatitis – Minimum 18-mo interval with ≥3 repeat PSAs for
most accurate PSAV determination.
r Urinary retention
EPIDEMIOLOGY
PSA2 − PSA1 PSA3 − PSA2
Incidence GENERAL PREVENTION ◦ PSAV = 0.5 +
r Across all races, age >50, only 7.9% of men r None for CaP Time1 Time2
randomly screened have PSA >4.0 ng/mL r Avoid PSA measurement when false-positive ◦ PSA1 = 1st PSA (ng/mL)
r Median PSA: 4th decade, 0.7 ng/mL; 5th decade, elevation likely (See “Risk Factors” above) ◦ PSA2 = 2nd PSA (ng/mL)
0.9 ng/mL 6th decade, 1.3 ng/mL; 7th decade, r Use same lab/assay for serial measurements ◦ PSA3 = 3rd PSA (ng/mL)
1.7 ng/mL ◦ Time1 = time between PSA1 & PSA2 (yr)
◦ Time2 = time between PSA2 & PSA3 (yr)
370
PSA ELEVATION, GENERAL CONSIDERATIONS
– Baltimore Longitudinal Study: 72% CaP had PSA r Numerous assays under study to help differentiate REFERENCES
rise >0.75 ng/mL/yr vs.10% with BPH benign form malignant PA elevation (See Section II:
– PSAV > 0.35 predicts PCa death w/ PSA <4 “PSA, General Considerations.”) 1. Lilja H, Cronin AM, Dahlin A, et al. Prediction of
– PSAV >0.75 90–100% PCa sensitivity w/ PSA >4 significant prostate cancer diagnosed 20 to
MEDICATION 30 years later with a single measure of prostate-
– PSA velocity >02 in year before dx predicts PCa
mortality First Line specific antigen at or before age 50. Cancer.
r “Prostate Health Index” or phi assay r Empiric antibiotics for elevated PSA is no longer
2011;117(6):1210–1219.
– CaP low FPSA, increased % proPSA recommended by most sources 2. Shariat SF, Semjonow A, Lilja H, et al. Tumor
r With bacterial prostatitis, treat and repeat PSA 4 wk
– Calculation ([–2]proPSA/FPSA) × TPSA markers in prostate cancer I: Blood-based markers.
– phi 27–55, CaP 9.8–50%, Gl ≥7 3.9–28.9%; phi after: Fluoroquinolone (eg, ciprofloxacin 500 mg Acta Oncol. 2011;50(suppl 1):61–75.
27: 18.8% could be spared biopsy (low risk) BID.) or TMP-SMX (180/800 mg BID) 3. Catalona WJ, Beiser JA, Smith DS. Serum free
Imaging Second Line prostate specific antigen and prostate specific
r TRUS: Determine prostatic size; PSAD; most useful N/A antigen density measurements for predicting cancer
to guide systematic needle biopsy in men with prior negative biopsies. J Urol.
r Multiparametric MRI with/without endorectal coil: If patient has anorectal pathology, consider
Useful if CaP suspicion and negative biopsy. 4. Carter HB, Albertsen PC, Barry MJ, et al. Early
transperineal prostate biopsy for CaP diagnosis
Anterior tumors and other sites can be identified detection of prostate cancer: AUA Guideline. J Urol.
r CT or bone scan: No role in CaP screening ADDITIONAL TREATMENT 2013;190(2):419–426.
r CaP risk calculators are available on the Internet to
5. Greene KL, Albertsen PC, Babaian RJ, et al.
Diagnostic Procedures/Surgery predict outcome of biopsy. Prostate specific antigen best practice statement:
r TRUS-guided prostate biopsy with 18G biopsy r PCA3 urine testing after attentive DRE; FDA 2009 update. J Urol. 2013;189(1 suppl):S2–S11.
needle and local anesthesia: approved only after initial negative biopsy;
– Systematic biopsy (12 cores) with laterally directed PCA3/TMPRSS2-ERG urine test investigational
samples is now standard for CaP.
Additional Therapies ADDITIONAL READING
Pathologic Findings Any PSA rise while on finasteride/dutasteride baseline
See Section I: “Prostate Cancer, General.” Heidenreich A, Abrahamsson PA, Artibani W, et al.
raises CaP risk Early detection of prostate cancer: European
DIFFERENTIAL DIAGNOSIS Complementary & Alternative Association of Urology recommendation. Eur Urol.
r Adenocarcinoma of the prostate (CaP) Therapies 2013;64(3):347–354.
r BPH No evidence for herbals effect on PSA
r Prostatitis (usually bacterial infection) See Also (Topic, Algorithm, Media)
r Prostate Cancer Screening Guidelines
r Prostatic infarction: Idiopathic or after shock r Prostate Cancer, Biochemical Recurrence (Elevated
r Iatrogenic: Recent cystourethroscopy, Foley catheter
ONGOING CARE
PSA) Following Cryotherapy
placement, prostate biopsy PROGNOSIS r Prostate Cancer, Biochemical Recurrence (Elevated
r Prostatic massage (but not routine DRE) r With elevated PSA, positive biopsy rate is about
PSA) Following Radiation Therapy
r Trauma (cycling, extensive) 25–30%; elevated PSA and nodule 18–60% r Prostate Cancer, Biochemical Recurrence (Elevated
r Ejaculation within 24 hr of PSA test (rare) r Overall, if 2nd biopsy is performed after initial
PSA) Following Radical Prostatectomy
negative, detection rate is 10–35%. r Prostate Cancer, General
COMPLICATIONS r PSA Elevation Following Negative Prostate Biopsy
TREATMENT Failure to diagnose cancer; patient anxiety over repeat r PSA, General Considerations
GENERAL MEASURES testing; risk of biopsy and drugs
r Shared decision making before PSA based CaP
FOLLOW-UP
screening in asymptomatic patients Patient Monitoring CODES
r Due to PSA fluctuations, confirm an elevated PSA r There is no single threshold PSA which should
with a 2nd reading before biopsy. Patient should not prompt prostate biopsy. Biopsy decision based on ICD9
ejaculate for 48 hr before test. PSA, DRE, and multiple factors (F/T PSA, age, PSA r 185 Malignant neoplasm of prostate
r Review serial PSA determinations for PSAV velocity, PSA density, family history, ethnicity, prior r 600.00 Hypertrophy (benign) of prostate without
r CaP screening recommendations: biopsy history, comorbidities, patient preferences) urinary obstruction and other lower urinary tract
– See Appendix for ACS, ACP, EAU, NCCN, USPSTF (5). symptom (LUTS)
r AUA 2013 CaP Early Detection Guideline (4): r PSA <2.5 ng/mL, low PSAV: Annual DRE/PSA r 790.93 Elevated prostate specific antigen [PSA]
– No PSA screening in men under age 40 yr r PSA 2.6–10 ng/mL, low PSAV:
– Does not recommend routine screening between – Consider biopsy or obtain FPSA ICD10
ages 40 and 54 yr at average risk – F/T PSA >25%: Repeat PSA/DRE in 6 mo r N40.0 Enlarged prostate without lower urinary tract
– Shared decision-making for men 55–69 yr r Based on TRUS biopsy results:
considering PSA screening due to risks/benefits; – Negative: Repeat DRE/PSA in 6 mo; consider F/T symptoms
proceed based on a man’s values and preferences r R97.2 Elevated prostate specific antigen [PSA]
PSA as guide for another biopsy
– To reduce harms, screening intervals of 2 yr – HGPIN or ASAP:
preserves the benefits and reduces overdiagnosis ◦ Repeat biopsy (3–6 mo); consider transition
and false-positives zone sampling with any repeat biopsy.
CLINICAL/SURGICAL
– No routine PSA screening in men age 70+ yr or – Positive biopsy (CaP): Staging studies, discuss PEARLS
<10–15-yr life expectancy; but some 70+ yr in treatment options r Routine DRE will not clinically significantly elevate
excellent health may benefit from screening r Persistent PSA elevation (PSA >10 ng/mL)
r Some published prostate biopsy indications: PSA.
– Repeat biopsy; transition zone sampling; r PSA 1/2-life is 2.2 days; may remain elevated for up
– Prostate nodule, regardless of PSA multiparametric MRI of TRUS/MRI fusion biopsy
– PSA >10 ng/mL in the absence of prostatitis to 4 wk after instrumentation.
Patient Resources
– PSA >4.0 ng/mL and PSAV >0.75 ng/mL/yr
– PSA <4.0 ng/mL and PSAV >0.3–0.5 ng/mL/yr AUA Urology Care Foundation. http://www. P
– PSA >2.5 ng/mL and PSAV >0.60 ng/mL/yr urologyhealth.org/urology/index.cfm?article=68
– PSA 4–10 and F/T PSA<10%
– F/T PSA <20% and PSAV >0.75 ng/mL/yr
371
PSEUDOHERMAPHRODITISM, MALE (XY DSD) AND FEMALE (XX DSD)

Luigi Avolio, MD
ALERT ◦ β-Hydroxysteroid dehydrogenase (HSD3B2)

BASICS Newborns with salt-wasting 21-OHD CAH are at deficiency: (see XX DSD). 46 XY patients
risk for life-threatening salt-wasting crises. phenotype ranges from isolated hypospadias or
DESCRIPTION micropenis to more severe undermasculinization
r Pseudohermaphroditism is an obsolete term that r β-Hydroxysteroid dehydrogenase (HSD3B2) ◦ 17α-Hydroxylase/17,20-lyase deficiency:
referred to pathologic conditions in which deficiency: Deficiency of this enzyme results in Production of excessive corticosterone and
chromosomal sex is inconsistent with phenotypical adrenal insufficiency due to lack of conversion of δ5 deoxycorticosterone with hypertension and
sex steroids to δ-4 and consequent accumulation of hypokalemic alkalosis; aldosterone synthesis
r Disorders of sexual development (DSDs) is the
pregnenolone, dehydroepiandrosterone (DHEA) and almost totally absent. Variable degree of
preferred term which indicates a congenital androstenediol. Phenotypically girls with mild undermasculinization
condition in which development of chromosomal, virilization ◦ P450 oxidoreductase (POR) deficiency: (see XX
gonadal or anatomic sex is atypical (1) r 11b-Hydroxylase (CYP11B1) deficiency: DSD). The genitalia in 46 XY patients range
r Female pseudohermaphroditism is now defined as from isolated hypospadias or micropenis to
Characterized by accumulation of
XX DSD 11-deoxycorticosterone. This is the 2nd most more severe undermasculinization
– Karyotype 46XX common causes of virilizing CAH (5% of all cases) ◦ 17β-Hydroxysteroid dehydrogenase (17βHSD)
– Gonads: Normal ovaries r P450 oxidoreductase (POR) deficiency: Combined type 3 deficiency: The HSD17B3 isozyme
– External genitalia: Varying degree of virilization deficiencies of 21α-hydroxylase, 17α-hydroxylase catalyzes the conversion of androstenedione to
r Male pseudohermaphroditism is now defined as XY testosterone in the testis. Deleterious mutations
and aromatase enzymes.
DSD in the HSD17B3 gene cause
– Familial glucocorticoid resistance: Rare condition
– Karyotype 46XY undermasculinization in genetic males
with mutation in the glucocorticoid receptor
– Gonads: Normal testes attributable to impaired testosterone
determining high ACTH, cortisol,
– External genitalia: Incomplete virilization biosynthesis
mineralocorticoids and androgens levels. ◦ Steroid 5α-reductase type 2 deficiency: Reduced
EPIDEMIOLOGY – Aromatase (CYP19) deficiency: High serum
activity of 5α-RD type 2 with defective
Incidence androgens and low estrogen concentrations with
r 1 in 5,000 live births conversion of testosterone to DHT. Patients
progressive virilization.
r Maternal androgen excess: show ambiguous genitalia at birth, including
– 21-hydroxylase deficiency is the most common perineal hypospadias
cause of 46XX DSD; 90% of congenital adrenal – Ovarian tumors (luteoma, arrhenoblastoma) – Disorders of the androgen receptor (AR): Patients
hyperplasia (CAH); 1:15,000 live births – Ingestion of androgens, progestogens with partial or complete androgen insensitivity
r XY DSD (male pseudohermaphroditism)
Prevalence syndrome (PAIS/CAIS) have normal testosterone
N/A – Disorders of androgen synthesis level and DHT response to hCG stimulation;
◦ Cholesterol synthesis defects: Deficiency of usually normal anti-müllerian hormone (AMH)
RISK FACTORS 7-dehydrocholesterol reductase (DHCR7) results level
r Family history in a failure of cholesterol synthesis and elevated ◦ PAIS: Phenotype ranges from normal male with
r In utero exposure to androgens levels of its precursor 7-dehydrocholesterol. infertility (mild form) or isolated hypospadias to
Genetics Causative factor of Smith–Lemli–Opitz ambiguous genitalia with blind vaginal pouch
See “Disorders of Sex Development” chapter syndrome (multiple congenital malformation ◦ CAIS: Patients have female external genitalia,
and mental retardation syndrome) female breast development, blind vagina,
PATHOPHYSIOLOGY ◦ Leydig cell hypoplasia: A defect of LH receptors absent uterus and female adnexa, and
r XX DSD (Female pseudohermaphroditism) Disorders leads to Leydig cells hypoplasia or agenesia. abdominal or inguinal testes
of androgen excess Genital anomalies range from hypospadias to r Persistent müllerian duct syndrome (PMDS):
– 21-hydroxylase deficiency (21-OHD) is the most completely normal female external genitalia Phenotype produced by a mutation in the gene
common cause for CAH, a family recessive ◦ Lipoid CAH: Severe disorder of steroid hormone
disorders involving impaired synthesis of cortisol encoding AMH or by a mutation in the AMH
biosynthesis, caused by a defect in the receptor; it results from failure of müllerian duct
from cholesterol by the adrenal cortex conversion of cholesterol to pregnenolone, the
– Impaired cortisol biosynthesis relieves feedback regression in otherwise normal males. Patients
1st step in adrenal and gonadal steroidogenesis. usually present bilateral cryptorchidism and inguinal
inhibition and thus increases ACTH secretion, All affected individuals are phenotypic females
which leads to hyperplasia of the adrenals and to hernias: A uterus and fallopian tubes are found in
with a severe salt-losing syndrome, fatal if not the inguinal canal; gonads are testes (2)
disordered steroidogenesis; as a consequence promptly treated in early infancy
cortisol precursors are shunted to androgen ◦ P450 side-chain cleavage deficiency: Rare ASSOCIATED CONDITIONS
synthesis disorder with ACTH and plasma renin activity r Hypospadias
grossly elevated and adrenal steroids r Cryptorchidism
inappropriately low or absent; patients have r Inguinal hernia
female external genitalia, sometimes with
clitoromegaly GENERAL PREVENTION
See “Disorders of Sex Development” chapter
372
PSEUDOHERMAPHRODITISM, MALE (XY DSD) AND FEMALE (XX DSD)
REFERENCES
DIAGNOSIS TREATMENT
1. Hughes IA, Houk C, Ahmed SF, et al. Consensus
HISTORY GENERAL MEASURES statement on management of intersex disorders.
r Family history: r Multidisciplinary team for evaluation of the patient Arch Dis Child. 2006;91:554–563.
– Genital abnormalities r Gender assignment early 2. Ahmed SF, Rodie M. Investigation and initial
– Amenorrhea management of ambiguous genitalia. Best Pract
– Sterility MEDICATION Res Clin Endocrinol Metab. 2010;24:197–218.
– Hirsutism First Line 3. Romao RL, Salle JL, Wherrett DK. Update on the
– Early infant deaths (possible unrecognized CAH r Salt-wasting CAH
management of disorders of sex development.
with salt-wasting crisis) – Fluid and electrolytes replacement Pediatr Clin North Am. 2012;59:853–869.
r Maternal exposure to androgens – Glucocorticoid and mineralocorticoid replacement
r History of maternal virilization (androgen-producing ◦ Hydrocortisone 10 mg/m2 /d
◦ Fludrocortisone 0.1–0.2 mg/d
tumor)
– Oral sodium chloride, 1–2 g/d added to formula or
ADDITIONAL READING
PHYSICAL EXAM breast milk r Auchus RJ, Chang AY. 46,XX DSD: The masculinized
r External genitalia
Second Line female. Best Pract Res Clin Endocrinol Metab.
– Phallic structure (length, breadth, and amount of
N/A 2010;24:219–242.
erectile tissue) r Barbaro M, Wedell A, Nordenström A. Disorders of
– Position of urethral meatus SURGERY/OTHER PROCEDURES
– Number of orifices in the perineum and their r Masculinizing genitoplasty (between the ages of 6 sex development. Semin Fetal Neonatal Med.
characteristics 2011;16:119–127.
and 18 mo) (See “Disorders of Sex Development” r Barthold JS. Disorders of sex differentiation: A
– Labioscrotal folds (separated or fused) chapter)
r Gonads pediatric urologist’s perspective of new terminology
r Feminizing genitoplasty (during the 1st 6 mo of and recommendations. J Urol. 2011;185:393–400
– Palpable gonads (testis, very rarely ovotestis) r http://www.ncbi.nlm.nih.gov/omim/ (Online
r Abdomen life) (3)[A] (See “Disorders of Sex Development”
– Mass referable to enlarged uterus
chapter) Mendelian Inheritance in Man® )
r Müllerian remnants (See “Disorders of Sex
DIAGNOSTIC TESTS & INTERPRETATION See Also (Topic, Algorithm, Media)
Development” chapter) r Congenital Adrenal Hyperplasia
Lab r Disorders of Sexual Development (DSD)
r Karyotype ADDITIONAL TREATMENT
r Hypospadias
r Serum levels of sodium, potassium, and Radiation Therapy
N/A r Micropenis (Microphallus)
17-hydroxyprogesterone r Müllerian Duct Remnants and Persistent Müllerian
r Androgens (testosterone, dihydrotesterone, Additional Therapies
androstenedione) N/A Duct Syndrome (PMDS)
r Cortisol, gonadotrophins, and AMH levels
r Stimulation test with human chorionic gonadotropin
Therapies CODES
(suspected defect of androgen production) Actually some patient groups strongly advocate to
Imaging delay any surgical procedures until patients are
r Abdominal/pelvic ultrasound (utero presence) competent to provide informed consent ICD9
r Cystogram/genitogram (visualization of vagina, 752.7 Indeterminate sex and pseudohermaphroditism
sinus) ICD10
r MRI ONGOING CARE r Q56.1 Male pseudohermaphroditism, not elsewhere
PROGNOSIS classified
Diagnostic Procedures/Surgery r Generally good with appropriate care r Q56.2 Female pseudohermaphroditism, not
r Laparoscopy to define internal anatomy
r Cysto/vaginoscopy to confirm anatomy and level of r Many patients have a good quality of life elsewhere classified
r Many patients remain fertile r Q56.3 Pseudohermaphroditism, unspecified
confluence of urogenital sinus
r Gonadal biopsy to analyze presence of ovarian
COMPLICATIONS
and/or testicular tissue See “Disorders of Sex Development” chapter CLINICAL/SURGICAL
r Skin biopsy to obtain cellular lines
FOLLOW-UP PEARLS
Pathologic Findings Patient Monitoring r Infants with a DSD presenting with truly ambiguous
See “Disorders of Sex Development” chapter r Lifelong psychosocial support mandatory
genitalia are a rare occurrence.
DIFFERENTIAL DIAGNOSIS r Monitoring for increased risk for developing r DSD should be regarded as a heterogeneous group
r Cryptorchidism malignancies of conditions with substantially different prognoses
r Inguinal hernia, hydrocele r Evaluation of sexual function
and treatment prospects.
r Hypospadias r DSDs represent a broad complex field that requires
Patient Resources
r Microphallus r http://www.congenitaladrenalhyperplasia.org the interaction of multiple disciplines with a diverse
r Gonadoblastoma r http://www.livingwithcah.com knowledge base.
r Menstruation disorders r http://rch.org.au/cah book/index.cfm?doc id=1375
r http://www.ahn.org.uk
373
PYELONEPHRITIS, ACUTE, ADULT

Sanjay S. Kasturi, MD

BASICS See “Risk Factors” r In uncomplicated acute pyelonephritis, imaging
studies are unnecessary; however, the combination
DESCRIPTION GENERAL PREVENTION
r Eliminate anatomic/functional abnormalities of fever and flank pain especially with elevated WBC
r An infectious process that involves the renal pelvis count requires imaging to rule out ureteral
r Patients with recurrent infections may require
and parenchyma. obstruction, which, with fever and infection, is a
– Most often ascending infection from the lower low-dose prophylactic antibiotics surgical emergency (3)
r Proper indwelling catheter management r Failure to respond to appropriate therapy within
urinary tract.
– It is most often a result of bacterial infection, but 72 hr requires radiographic evaluation to rule out
fungi, parasites, and viruses may be involved. obstruction, abscess, or other abnormalities
r Classified as uncomplicated or complicated (ie, DIAGNOSIS r Pediatric patients are at risk of scarring and should
associated with obstruction, anatomic anomaly, or HISTORY undergo imaging
stones) making treatment more difficult. r Fevers, chills, malaise, nausea, vomiting (2) r Abdominal x-ray (KUB): Evaluate for renal or
r Flank or abdominal pain ureteral calculi
EPIDEMIOLOGY
r Dysuria, urgency or frequency, gross hematuria – Intraparenchymal gas: Emphysematous
Incidence
r Estimated at 15–17 cases per 10,000 females and r Prior episodes of UTIs pyelonephritis
3–4 cases per 10,000 males (1). r History of renal calculi or urinary tract abnormalities – Renal shadow may be enlarged and poorly
r At least 250,000 cases of pyelonephritis are r History of vaginal discharge and irritation makes a defined secondary to parenchymal edema
r IVP/ExU: 75% of patients with uncomplicated acute
diagnosed annually in the United States. urinary source less likely
r Highest among young women, then infants, then r History of diabetes, immunosuppression, or pyelonephritis will have a normal ExU
alcoholism; recent instrumentation – ExU shows an enlarged kidney (>15 cm in length
the elderly.
r Children may present with failure to thrive or 1.5 cm greater than the unaffected side with
RISK FACTORS decreased nephrogram and delayed excretion)
r Anatomic or functional abnormalities: Incomplete PHYSICAL EXAM – Cortical striations may be seen
emptying of the bladder→urine is more prone to r Vital signs for signs of sepsis – Focal enlargement of the kidney is consistent with
infection r CVA tenderness focal bacterial nephritis, or acute lobar nephronia
– Vesicoureteral reflux, neurogenic bladder, BOO r Abdominal distention with decreased bowel sounds may be confused with tumor or abscess
r Foreign body: Acts as a nidus for bacterial – Nonobstructive dilation of the renal pelvis and
may be present
colonization and infection r Pelvic exam in women may help differentiate from ureter may be present (endotoxins impair ureteral
– Calculous disease, medullary sponge kidney gynecologic disease peristalsis)
– Indwelling catheters r US: Renal enlargement with hypoechoic parenchyma
r Medical conditions: Diabetes mellitus, DIAGNOSTIC TESTS & INTERPRETATION and loss or corticomedullary differentiation
immunosuppression, alcohol abuse Lab – Noninvasive; no ionizing radiation
r Social: Poor perineal hygiene (soiling) r CBC: Leukocytosis with neutrophil predominance r CT: Noncontrast CT of the abdomen reveals an
– Variables in sexual behavior (new or multiple (90%) enlarged kidney with decreased attenuation of
r Serum chemistry: Renal failure uncommon unless parenchyma, and perinephric fat stranding
partners) and use of spermicide
– Previous episodes of pyelonephritis obstruction or sepsis present – Contrast administration shows delayed
r Blood culture: 12% of hospitalized pyelonephritis enhancement with delayed excretion
Genetics r Radionuclide scan: Cortical agents (eg, DMSA)
Related to vesicoureteral reflux patients will have bacteremia
r Pregnancy test in women reveal decreased activity in the affected kidney;
PATHOPHYSIOLOGY r Urinalysis: Pyuria >5–10 WBCs/HPF: Useful to identify areas of scarring
r Women are at increased risk because the female
– WBC casts indicate renal source of infection Diagnostic Procedures/Surgery
urethra is shorter and in close proximity to the anus, – Hematuria and bacteria may be present Determine postvoid residual if indicated.
allowing enteric organisms to more easily colonize – Leukocyte esterase often positive, but nitrite may
the urinary tract not be positive with staph or enterococci Pathologic Findings
r Most common organism are gram-negative rods: r Gross: Edematous kidney with multiple foci of
r Gram stain urine may rapidly identify organism
– Escherichia coli accounts for the majority of cases r Urine culture: Positive with >100,000 bacteria/mL inflammation
(80% in women, 70% in men) r Microscopic: Focal areas of destruction of renal
and identifies causative organism; 10,000
– Klebsiella pneumoniae is the 2nd most common architecture with lymphocytic infiltrations
bacteria/mL suggests acute pyelonephritis in
organism (5–10%) patients with catheterized urine samples DIFFERENTIAL DIAGNOSIS
r Bacteria enter urinary tract: r Newer data suggests that urinary cultures may be r Any intra-abdominal inflammatory process
– Ascending infection: Urethra and bladder negative especially if patients were started on – Appendicitis, cholecystitis, diverticulitis,
– Results from colonization of the vaginal introitus antibiotics prior to presentation pancreatitis, peptic ulcer disease
with fecal flora in females r Gynecologic conditions:
– Lymphatic and hematogenous dissemination to – Pelvic inflammatory disease, ectopic pregnancy,
the kidneys is uncommon ruptured ovarian cysts
r Bacteria adhere to the urothelium, with subsequent r Urologic conditions:
invasion and inflammatory response – Renal colic with fever
– Adhesins and fimbriae: Allow bacteria to adhere – Renal and perinephric abscesses
to urothelium r Lower lobe pneumonia
– Lipopolysaccharides: Have toxic and inflammatory r Musculoskeletal pain
effects
– Hemolysins: Allow for bacterial invasion by
damaging cells
– Aerobacter: Enables bacteria to compete for iron,
necessary for aerobic metabolism and
reproduction
374
PYELONEPHRITIS, ACUTE, ADULT
r Pregnancy considerations: 3. Piccoli GB, Consiglio V, Deagostini MC, et al. The

TREATMENT – Ampicillin, amoxicillin and, PO cephalosporins clinical and imaging presentation of acute “non
have proven to be safe; amoxicillin/clavulanic acid complicated” pyelonephritis: A new profile for an
GENERAL MEASURES (Augmentin) is recommended for resistant ancient disease. BMC Nephrol. 2011;12:68.
r Supportive care consists of hydration, antipyretics, organisms; nitrofurantoin is safe for the fetus but 4. Warren JW, Abrutyn E, Hebel JR, et al. Guidelines
and analgesics potentially toxic to the mother; fluoroquinolones for antimicrobial treatment of uncomplicated acute
r Empiric antibiotics that are active against the should be avoided in pregnancy bacterial cystitis and acute pyelonephritis in
possible causative organisms and achieve adequate SURGERY/OTHER PROCEDURES children. Clin Infect Dis. 1999;29:745–758.
levels in the renal parenchyma and urine are used r Diversion with indwelling stent or percutaneous 5. Sandberg T, Skoog G, Hermansson AB, et al.
MEDICATION drain may be necessary in patients with urinary Ciprofloxacin for 7 days versus 14 days in women
obstruction. with acute pyelonephritis: A randomised,
First Line
r Outpatient therapy: In uncomplicated acute r If a renal abscess forms: open-label and double-blind, placebo-controlled,
– 3–5 cm in size then place percutaneous drain non-inferiority trial. Lancet. 2012;380(9840):
pyelonephritis, those who are reliable, tolerate oral 484–490.
intake, and do not have signs of sepsis do not – >5 cm may require more than 1 percutaneous
drain or surgical drainage 6. Siegel J, Smith A, Moldwin R. Minimally invasive
require hospitalization (4,5)
treatment of renal abscess. J Urol. 1996;155:
– Oral fluoroquinolones (ciprofloxacin 500 mg PO
52–55.
BID, or levofloxacin 750 mg/d PO) are adequate
for empiric treatment. Levofloxacin is approved for ONGOING CARE
a 5-day regimen PROGNOSIS
– An alternative: Trimethoprim–sulfamethoxazole ADDITIONAL READING
With 1st episode of acute pyelonephritis, 1-yr risk of a
– Traditionally, continue therapy for 10–14 days. 2nd episode was 9.2% in females and 5.7% in males. Hooton TM. Clinical practice. Uncomplicated urinary
Recent data shows a 7-day course of ciprofloxacin With a 4th episode, the risk of a 5th infection was tract infection. N Engl J Med. 2012;366(11):
is not inferior to a 14-day 1 in women with 50% for females and males. 1028–1037.
uncomplicated acute pyelonephritis
– Recent data suggests increased quinolone COMPLICATIONS See Also (Topic, Algorithm, Media)
r Short term: r Pyelonephritis, Acute, Adult Image
resistance as well as susceptibility to TMP-SMZ
r Inpatient therapy: If signs of sepsis, bacteremia, or – Septic shock r Pyelonephritis, Chronic
cannot tolerate oral medications – Abscess formation (corticomedullary, perinephric) r Pyelonephritis, Emphysematous
– Also recommended for children, the elderly, – Papillary necrosis r Pyelonephritis, Xanthogranulomatous
r Long term: Renal scarring (20%) r Urinary Tract Infection (UTI), Adult Female
pregnant patients, diabetics, and the
immunocompromised and with complicated r Children with developing kidneys are at significant r Urinary Tract Infection (UTI), Adult Male
pyelonephritis risk of scarring from even 1 episode of acute r Urinary Tract Infection (UTI), Pediatric
– Parenteral antibiotic therapy uncomplicated pyelonephritis
◦ Ampicillin (2 g IV q6h) and gentamicin r Diabetics are at significant risk of developing
(1.5 mg/kg IV q8h) is traditional treatment; OR emphysematous pyelonephritis, a more fulminant
◦ Ceftriaxone (1 g/d IV) empirically; OR process with a high mortality:
CODES
◦ IV fluoroquinolones ciprofloxacin 400 mg q12h – Characterized by renal intraparenchymal gas and
or levofloxacin 750 mg q24h; aztreonam is also detectable on KUB ICD9
r Patients with calculi or urinary tract obstruction who r 041.49 Other and unspecified Escherichia coli
an acceptable alternative
– Most patients continue to have fever or flank pain have recurrent episodes of pyelonephritis may [E. coli]
r 590.10 Acute pyelonephritis without lesion of renal
for several days after appropriate therapy has develop xanthogranulomatous pyelonephritis:
been started. – Characterized by large nonfunctioning renal mass medullary necrosis
– IV therapy continued until the patient is afebrile or r 593.73 Other vesicoureteral reflux with reflux
– Stones are present in 80% of cases
cultures indicate another appropriate antibiotic. r Pregnant patients are at high risk because of the nephropathy NOS
– When able to tolerate oral intake, switch to an physiologic changes of pregnancy to the urinary
oral antibiotic as for oral therapy above. ICD10
tract: r B96.20 Unsp Escherichia coli as the cause of
– Pregnant patients: Place on suppression therapy – Sepsis
(eg, nitrofurantoin 100 mg/d PO, cephalexin diseases classd elswhr
– Adult respiratory distress syndrome r N10 Acute tubulo-interstitial nephritis
250 mg/d PO) after treatment until delivery, due – Preterm delivery with low–birth-weight infants
to a relapse rate of up to 60% in nonsuppressed r N13.729 Vesicoureter-reflux w reflux nephropathy
patients. FOLLOW-UP w/o hydrourt, unsp
– Patients with a delayed response to therapy Patient Monitoring
should be treated with a longer course of r Urine cultures 4–6 wk after completion of
antibiotics (14–21 days), even without evidence antibiotics to verify infection cleared CLINICAL/SURGICAL
of complicated disease. r 10–30% suffer a relapse and may be treated with a PEARLS
r Complicated pyelonephritis: Assess for underlying 2nd 14-day course of antibiotics
r Occasionally, a 6-wk course needed for cure r Urine cultures may be negative in patients especially
urologic abnormalities (obstruction, stones, etc.) (6)
– Parenteral antibiotic therapy in complicated cases: r Confirm hematuria clears if initially present if started on recent antibiotics.
r If fevers last for more than 72 hr after antibiotics,
◦ Piperacillin–tazobactam 3.375 g q6h,
Patient Resources obtain at CT scan to rule obstruction, soft tissue
ticarcillin–clavulanate 3.1 g q6h, cefepime 1 g
http://kidney.niddk.nih.gov/kudiseases/pubs/ infection, or abscess formation.
q12h
◦ Alternates include meropenem, and imipenem. pyelonephritis/
Dose-adjust with renal failure.
– After transitioning to species-specific antibiotics, REFERENCES
PO continued for 14–21 days
1. Czaja CA, Scholes D, Hooton TM, et al.
Population-based epidemiologic analysis of acute
pyelonephritis. Clin Infect Dis. 2007;45:273–280.
P
2. Hooton TM, Stamm WE. Diagnosis and treatment
of uncomplicated urinary tract infection. Infect Dis
Clin North Am. 1997;11:551–581.
375
PYELONEPHRITIS, ACUTE, PEDIATRIC

Ross M. Decter, MD, FRCS
Paul H. Smith III, MD

BASICS r Lobar nephronia: Pyelonephritis affecting only an r Renal and bladder ultrasonography (RBUS)
isolated focus within the kidney – Failure to improve clinically within 1st 2 days of
DESCRIPTION r Pyonephrosis: Purulent material within the collecting antibiotic treatment should prompt evaluation
r Infectious process involving the renal parenchyma with RBUS to evaluate for complications
system
and collecting system r Renal abscess ◦ Renal abscess
r Retrograde ascent of uropathogenic bacteria is most ◦ Pyonephrosis
common cause GENERAL PREVENTION – Used to identify structural abnormalities
r Prophylactic antibiotics in patients with recurrent
contributing to the development of pyelonephritis
EPIDEMIOLOGY episodes of UTI or with VUR r Voiding cystourethrogram (VCUG)
Incidence r Surgical correction of anatomic urinary tract
r 18,000–20,000 children per year hospitalized for – Identifies VUR
anomalies – Requirement for VCUG after 1st febrile UTI
diagnosis of pyelonephritis r Optimization of bladder/bowel management in
r Risk of childhood UTI 2% for boys and 8% for girls controversial
patients with neurogenic and nonneurogenic – Invasive study (requires catheterization)
r UTI more common in males during 1st yr of life bladder dysfunction r Nuclear cystogram
– Gender predilection reversed thereafter r Antibiotic prophylaxis if major GU instrumentation
– More sensitive for low-grade VUR than VCUG but
Prevalence less anatomic detail
Low, given the acuity of illness and prompt treatment r Nuclear renography (DMSA)
DIAGNOSIS – Gold standard for diagnosis of pyelonephritis
RISK FACTORS ◦ Rarely necessary in acute setting
r Circumcision reduces risk of UTI during 1st yr of life HISTORY
r Nonspecific symptoms or failure to thrive in young – Delayed study identifies renal scarring (3)
– 10× greater risk of UTI in uncircumcised boys
r Dysfunctional voiding children – Invasive study (IV injection of radionuclide)
r Anatomic urinary tract anomalies – High degree of suspicion required in young – Radiation exposure
children Diagnostic Procedures/Surgery
– Ureteropelvic junction obstruction r Fever, nausea, vomiting
– Vesicoureteral reflux (VUR) SPA for urine culture if clean catch or catheterization
r Flank or abdominal pain not feasible
– Ureterocele/ectopic ureter
r Neurogenic bladder dysfunction r Hematuria, dysuria, foul smelling urine, frequency,
Pathologic Findings
urgency r Renal scarring
Genetics r History of UTIs
P1 blood group antigen associated with recurrent – Inflammatory reaction to renal parenchymal
r Functional or anatomic urinary tract anomalies infection can cause irreversible renal scarring
pyelonephritis
PATHOPHYSIOLOGY PHYSICAL EXAM DIFFERENTIAL DIAGNOSIS
r Periurethral and fecal flora are the source of most r Fever r Renal abscess
r Sepsis r Pyonephrosis
uropathogens
r CVA tenderness r Other intra-abdominal process
– Escherichia coli is the most common organism
– Other common organisms are Klebsiella, r Exam findings nonspecific in young children
Enterococcus, Pseudomonas, Staphylococcus
saprophyticus, Enterobacter
DIAGNOSTIC TESTS & INTERPRETATION TREATMENT
r Bacterial virulence factors promote upper tract Lab
r Urinalysis GENERAL MEASURES
infection r Prompt initiation of empiric antibiotics after
– WBCs: >5 per HPF
– P fimbriae: E. coli virulence factor promotes acquisition of urine specimen suitable for culture
– Presence of any bacteria
adherence and subsequent invasion of bacteria (clean catch, catheterization, SPA)
– Positive leukocyte esterase
into the urothelium (1)
– Positive nitrites: ∼4 hr of dwell time in the r General supportive measures
r Inflammatory response initiated by interaction
bladder required for nitrites to become positive – Volume resuscitation, antipyretics, analgesics
between bacterial endotoxin and toll-like receptor r Urine culture: Specimen collected by clean catch, r Need for hospitalization based on severity of illness,
(TLR) 4 (1) however admission generally indicated for infants
catheterization or suprapubic aspiration (SPA)
– >50,000 C FU signifies positive culture (2) (<2–3 mo)
r CBC: Leukocytosis with left shift
MEDICATION
r Blood cultures
r Elevated CRP, ESR, procalcitonin First Line
r Empiric coverage
– Tailor to local antimicrobial resistance patterns
(2)[A]
– Ampicillin (25–50 mg/kg/d) + gentamicin
(2–2.5 mg/kg TID)
◦ 3rd-generation cephalosporin an alternative to
ampicillin if low risk for enterococcus UTI
376
PYELONEPHRITIS, ACUTE, PEDIATRIC
r Oral culture-directed antibiotics once clinically FOLLOW-UP See Also (Topic, Algorithm, Media)
improving and tolerating oral intake r Pyelonephritis, Acute, Pediatric Image
Patient Monitoring
– Avoid nitrofurantoin due to minimal tissue r Current American Academy of Pediatrics guidelines r Pyonephrosis
penetration recommends RUS in children with febrile UTI r Urinary Tract Infection (UTI), Complicated, Pediatric
– Parenteral antibiotics (daily ceftriaxone, IM) also – Selective VCUG in patients with abnormal RUS or r Urinary Tract Infection (UTI), Pediatric
an option for outpatient therapy recurrent episodes (2)[C] r Vesicoureteral Reflux, Pediatric
r 7–14 days total duration of therapy (2)[B] – Indications for radiographic imaging in children
with 1st episode of febrile UTI remain controversial
Second Line r Delayed DMSA scan to detect renal scarring
r Vancomycin if penicillin allergic CODES
r Aztreonam an alternate to aminoglycoside if renal Patient Resources
r National Kidney and Urologic Diseases Information ICD9
insufficiency r 041.49 Other and unspecified Escherichia coli [E.
Clearinghouse (NKUDIC)
SURGERY/OTHER PROCEDURES – http://kidney.niddk.nih.gov/kudiseases/pubs/ coli]
r Urethral catheter if critically ill or poor bladder pyelonephritis/index.aspx r 590.10 Acute pyelonephritis without lesion of renal
emptying – http://kidney.niddk.nih.gov/kudiseases/pubs/ medullary necrosis
r Surgery generally not indicated in acute treatment utichildren/ r 593.73 Other vesicoureteral reflux with reflux
r Ureteral stent or nephrostomy tube if obstruction
nephropathy NOS
r Percutaneous aspiration/drainage if progression to
renal abscess REFERENCES ICD10
r B96.20 Unsp Escherichia coli as the cause of
ADDITIONAL TREATMENT 1. Montini G, Tullus K, Hewitt I. Febrile urinary tract
diseases classd elswhr
Radiation Therapy infections in children. N Engl J Med. 2011; r N10 Acute tubulo-interstitial nephritis
N/A 365(3):239–250. r N13.729 Vesicoureter-reflux w reflux nephropathy
2. Roberts KB. Urinary tract infection: Clinical practice
Additional Therapies guidelines for the diagnosis and management of w/o hydrourt, unsp
N/A the initial UTI in febrile infants and children 2 to
Complementary & Alternative 24 months. Pediatrics. 2011;128:595–609. CLINICAL/SURGICAL
Therapies 3. Rushton HG, Majd M. Dimercaptosuccinic acid
Probiotics (experimental) renal scintigraphy for the evaluation of
PEARLS
pyelonephritis and scarring: A review of r Signs and symptoms are often nonspecific in infants
experimental and clinical studies. J Urol. and young children with pyelonephritis.
ONGOING CARE 1992;148(5 pt 2):1726–1732. r Culture of appropriately collected urine specimen
PROGNOSIS mandatory in patients with suspected UTI and in
Related to degree of renal injury from pyelonephritic infants with fever and no obvious source.
scarring ADDITIONAL READING r Acute imaging (RUS) recommended if critically ill or
r Juliano TM, Stephany HA, Clayton DB, et al. failure to respond to treatment.
COMPLICATIONS
r Pyelonephritic scarring, especially with recurrent Incidence of abnormal imaging and recurrent
episodes and delayed treatment pyelonephritis after first febrile urinary tract infection
r Pyonephrosis in children 2 to 24 months. J Urol. 2013;
r Renal abscess 190(4 suppl):1505–1510. doi: 10.1016/
r Xanthogranulomatous pyelonephritis j.juro.2013.01.049.
r Shaikh N, Ewing AL, Bhatnagar S, et al. Risk of renal
r Hypertension
scarring in children with a first urinary tract
infection: A systematic review. Pediatrics.
2010;126:1084–1091.
r Shortliffe LD. Infection and inflammation of the
pediatric genitourinary tract. In: Wein AJ,
Kavoussi LR, Novick AC, et al. Campbell-Walsh
Urology. 10th ed. Philadelphia, PA: Elsevier
Saunders; 2012.
377
PYELONEPHRITIS, CHRONIC
Debra L. Fromer, MD
Drew A. Freilich, MD

BASICS r VUR r HTN may be present
r Spinal cord injury r Nonspecific, unless associated with an episode of
DESCRIPTION r Xanthogranulomatous pyelonephritis (XGP) is a acute pyelonephritis
r Injury to the kidney with inflammation and fibrosis of r May be mild flank pain or CVA tenderness
form of chronic pyelonephritis
the renal parenchyma, pelvis, and calyces. It is most – Presents with foamy lipid laden macrophages
often caused by recurrent or chronic renal infection DIAGNOSTIC TESTS & INTERPRETATION
– Often unilateral and associated with longstanding
r Not usually diagnosed based on clinical Lab
obstructing nephrolithiasis r Urinalysis may be normal or indicate pyuria or
presentation, chronic pyelonephritis is usually a
radiologic or pathologic diagnosis GENERAL PREVENTION proteinuria. WBC casts can be seen.
r Clinical signs and symptoms are often vague but can r Upper urinary tract evaluation in patients with r Urine culture is usually only positive with an active,
be related to the infection and the severity and recurrent bacteriuria or recurrent acute symptomatic infection. Culture is often negative.
location of injury within the kidney: pyelonephritis r Microalbuminuria/proteinuria is an adverse
r Early detection, evaluation, and treatment of
– Often an incidental finding, it may present as prognostic sign.
asymptomatic bacteriuria, dysuria and frequency childhood UTIs
r Prompt detection and management of VUR Imaging
(lower urinary tract symptoms), vague complaints r CT reveals the typical findings of chronic
of flank or abdominal discomfort, and intermittent r Detection and treatment of obstructive uropathy
pyelonephritis
low-grade fevers. Geriatric Considerations – Small or atrophic kidney, unilaterally or bilaterally
– Synonym(s): Chronic interstitial nephritis r Chronic pyelonephritis can present with atypical – Compensatory hypertrophy with unilateral atrophy
EPIDEMIOLOGY symptoms and signs (ie, failure to thrive, low-grade – Blunted and dilated calyces
Incidence fevers). Diagnosis requires a high level of suspicion. – Renal cortical scarring and thinning of the cortex
r Occurs in males and females of all ages: Pregnancy Considerations r Renal US to evaluate for hydronephrosis, renal
r Antibiotic prophylaxis during pregnancy in patients anatomy, or stones. Not a good test to identify
– More common in childhood, especially with
with risk factors including: active reflux, but dilated ureters suggest obstruction
congenital anomalies such as vesicoureteral
– History of acute pyelonephritis during pregnancy or reflux
reflux (VUR) (1)[B] r VCUG for the evaluation of reflux
r Chronic pyelonephritis accounts for 15–20% of – Recurrent bacteriuria after treatment during
pregnancy r CT is more sensitive than US for nephrolithiasis; also
cases of chronic renal failure to rule out obstruction, hydronephrosis, stone
r Less common in patients having no underlying – History of recurrent UTIs on previous antibiotic
prophylaxis before being pregnant disease, urinary tract abnormality. Pyonephrosis or
functional or structural urinary tract abnormalities abscesses are usually identified if present
Pediatric Considerations
Prevalence r Assess UTI with: r Technetium-99m DMSA is the best study to evaluate
4:1,000 asymptomatic adults – Voiding cystourethrogram (VCUG) (to check for for renal scarring
RISK FACTORS VUR or anatomical abnormality) Diagnostic Procedures/Surgery
r Female sex – DMSA (to detect scar formation/progression) r Cystoscopy in selected cases
r In 50% of cases, history of a previous episode of – Renal US (to assess for hydronephrosis) r Renal biopsy
acute pyelonephritis Pathologic Findings
r VUR/reflux nephropathy r Gross kidney is often diffusely contracted, scarred at
r Congenital urinary tract anomalies DIAGNOSIS
periphery with thin cortex
r Neurogenic bladder dysfunction HISTORY r Microscopically, an interstitial infiltrate of
r Pregnancy r Frequently asymptomatic and discovered incidentally lymphocytes, plasma cells, and occasional
r Urinary tract obstruction with complicated UTI can r UTIs in childhood and during pregnancy neutrophils is present
result in renal insufficiency: r Presence of HTN, especially in children with known r Scarring is often polar with underlying calyceal
– Mechanical obstruction includes prostatic reflux nephropathy blunting. Histologic changes are patchy:
hyperplasia, calculi, retroperitoneal fibrosis, r Proteinuria, polyuria, nocturia, frequency – Periglomerular fibrosis is often seen
neoplasms, and congenital anomalies r Patients with spinal cord injury present with cloudy – Leukocytes and hyaline casts can be present in
or malodorous urine, vague abdominal discomfort, tubules, and the hyaline casts may resemble
Genetics
malaise, lethargy, leakage between catheterizations, thyroid colloid, hence the description renal
Susceptibility to acute pyelonephritis may have a
or increased spasticity or autonomic dysreflexia. thyroidization
familial component and may be associated with
decreased CXCR1 expression. r Fever of unknown origin
r Failure to thrive in infant or child
PATHOPHYSIOLOGY
r Progressive localized immune response to bacterial
infection
r Hyaline casts in tubule may cause resemblance to
thyroid colloid known as renal thyroidization
r Fibrosis around the glomeruli replaces kidney
parenchyma in patches:
– Calyceal clubbing with nonuniform localized
scarring
378
PYELONEPHRITIS, CHRONIC
DIFFERENTIAL DIAGNOSIS 3. Rivera JA, O’Hare AM, Harper GM. Update on the
r Analgesic nephropathy ONGOING CARE management of chronic kidney disease. Am Fam
r Diabetic nephropathy Physician. 2012;86(8):749–754.
r Gouty nephritis PROGNOSIS 4. Nicolle LE, Bradley S, Colgan R, et al. Infectious
r 24-hr protein excretion may be an important
r Hypertensive renal disease Diseases Society of America guidelines for the
r Psoas and subdiaphragmatic abscess prognostic indicator of progressive deterioration of diagnosis and treatment of asymptomatic
r Renal artery stenosis renal function due to focal and segmental bacteriuria in adults. Clin Infect Dis. 2005;40(5):
glomerulosclerosis superimposed on 643–654.
r Renal malakoplakia
tubulointerstitial disease 5. Dai B, Liu Y, Jia J, et al. Long-term antibiotics for
r Renal tuberculosis r Radionuclide renal scan can assess renal function
r Urolithiasis the prevention of recurrent urinary tract infection in
and scarring children: A systematic review and meta-analysis.
r Xanthogranulomatous pyelonephritis (XGP) (2)[B] COMPLICATIONS Arch Dis Child. 2010;95(7):499–508.
r Emphysematous pyelonephritis
r End-stage renal disease (rare)
TREATMENT r Focal segmental glomerulosclerosis ADDITIONAL READING
r HTN
GENERAL MEASURES N/A
r Chronic pyelonephritis is difficult to manage as it is r Perinephric abscess: Requires surgical drainage
an irreversible process r Polyuria, nocturia from loss of tubular concentrating See Also (Topic, Algorithm, Media)
r Pyelonephritis, Acute
r With mild VUR, suppressive antibiotics are used ability r Pyelonephritis, Chronic Image
until resolution or puberty in children r Pregnancy-related miscarriages in women with
r Severe reflux may require reimplantation r Pyelonephritis, Emphysematous
chronic reflux r Pyelonephritis, Xanthogranulomatous
r Correct anatomic anomalies or stones if possible r Proteinuria
r Pyonephrosis r Vesicoureteral Reflux, Pediatric
MEDICATION r XGP
First Line
r Acute episodes of pyelonephritis should be treated FOLLOW-UP CODES
(See Section I: “Pyelonephritis, Acute”) (3)[B] Patient Monitoring
r Annual serum creatinine to monitor chronic kidney ICD9
r Suppressive antibiotics VUR in children has become
disease 590.00 Chronic pyelonephritis without lesion of renal
controversial: r Blood pressure monitoring (good control of BP may medullary necrosis
– In children <3–6 mo, use low-dose amoxicillin or
limit renal damage over time)
cephalexin, cefazolin, or other 1st-generation ICD10
– 15% of patients with reflux nephropathy who r N11.1 Chronic obstructive pyelonephritis
cephalosporin can be considered
reach adulthood have HTN r N11.8 Other chronic tubulo-interstitial nephritis
– In children >6 mo, switch to nitrofurantoin,
– Some advocate screening renal scan or VCUG of r N11.9 Chronic tubulo-interstitial nephritis,
trimethoprim-sulfamethoxazole, or trimethoprim
siblings who have reflux
alone can be considered unspecified
r Hypertension is best treated by ACE inhibitors r Urine analysis to monitor for proteinuria and
(lisinopril, enalapril, ramipril) that may also protect bacteruria (4)[A]
the kidney from progressive renal failure r Selective long-term antibiotics to limit infection CLINICAL/SURGICAL
– ACE inhibitors are contraindicated in pregnancy (5)[A] PEARLS
Second Line Patient Resources For best determination of renal function the bladder
Based upon urine culture sensitivities, prior treatment National Kidney and Urologic Diseases Information
should be empty and kidneys unobstructed (ie,
attempts and patient presenting symptoms Clearinghouse (NIH). http://kidney.niddk.nih.gov/
ureteral stent if large stones).
SURGERY/OTHER PROCEDURES kudiseases/pubs/pyelonephritis/
r Correction of reflux may be necessary in children
with high-grade reflux (Grade 4–5). Low-grade REFERENCES
reflux (Grade 1–3) often resolves with time
r Nephrectomy for persistent/recurrent infection 1. Peters C, Rushton HG. Vesicoureteral reflux
unresponsive to systemic treatment, markedly associated renal damage: Congenital reflux
decreased function (ie, 10%), pain, or refractory nephropathy and acquired renal scarring. J Urol.
HTN, XGP 2010;184(1):265–273.
2. Guzzo TJ, Bivalacqua TJ, Pierorazio PM, et al.
ADDITIONAL TREATMENT Xanthogranulomatous pyelonephritis: Presentation
Radiation Therapy and management in the era of laparoscopy. BJU
N/A Int. 2009;104(9):1265–1268.
N/A
Therapies
Little data to support
379
PYELONEPHRITIS, EMPHYSEMATOUS
Jennifer E. Heckman, MD, MPH
Stephen Y. Nakada, MD, FACS
r Classification system (1)[B]:

BASICS DIAGNOSIS – Class 1: Gas confined to collecting system
– Class 2: Gas confined to renal parenchyma
DESCRIPTION HISTORY without extension to extrarenal space
r Acute necrotizing infection of the renal parenchyma r Classic triad:
– Class 3A: Perinephric extension of gas or abscess
and perirenal tissues caused by gas-forming – Fever, chills – Class 3B: Pararenal extension of gas or abscess
organisms – Nausea, vomiting (beyond Gerota’s fascia and/or extension to
– Onset may be acute or insidious – Flank pain and/or abdominal pain adjacent tissues)
– Course is potentially life threatening (mortality: r Urinary frequency/urgency, dysuria
– Class 4: Bilateral emphysematous pyelonephritis
11–42%) r Malaise or emphysematous pyelonephritis in a solitary
r 1st report in 1898 r Altered mental status kidney
r >200 reported cases r History of DM, urinary calculi, and/or – Therapeutic and prognostic implications:
immunocompromise ◦ Class 1 and 2: Percutaneous drainage
EPIDEMIOLOGY r Pneumaturia absent unless infection involves successful, low mortality
Incidence collecting system ◦ Class 3 and 4: Percutaneous drainage less
r All documented cases in adults
successful, increased mortality
– Most patients >60 yr old PHYSICAL EXAM
r Female predominance (6:1) r Pyrexia Diagnostic Procedures/Surgery
r Bilateral cases, unusual but reported (L > R) r Abdominal or flank tenderness None, diagnosis is radiographic
r Crepitus over flank (rare) Pathologic Findings
Prevalence r Lethargy, confusion, altered mental status r Gross
N/A
r Sepsis/shock (tachycardia, hypotension) – Multiple renal parenchymal abscesses with
RISK FACTORS central, gas-filled region
r Diabetes mellitus (DM) (up to 95%) DIAGNOSTIC TESTS & INTERPRETATION – Foci of micro- and macroinfarctions
– Especially with poor glycemic control Lab r Microscopic
r Urinary tract obstruction r Complete blood count (CBC) – Glomerulosclerosis, arteriosclerosis, intrarenal
– Urinary calculi – Leukocytosis vascular thrombi, or papillary necrosis
– Papillary necrosis – Thrombocytopenia
r Basic metabolic panel (BMP) DIFFERENTIAL DIAGNOSIS
– Neoplasm r Acute pyelonephritis
r Immunosuppression – Hyperglycemia r Emphysematous cystitis
– Elevated serum creatinine r Fistulous communication with gastrointestinal or
Genetics r Urinalysis +/− urine culture
N/A respiratory tracts
– Pyuria, bacteriuria, positive urine culture r Iatrogenic (instrumentation of urinary tract)
PATHOPHYSIOLOGY r Blood cultures
r Poorly understood r Necrotic renal tumor
– Bacteremia (isolated organism same as that in
r Impaired host response allows microorganism r Pyonephrosis with urinary tract obstruction
urine)
proliferation r Renal abscess
r Hypothesized that elevated tissue glucose levels Imaging r Xanthogranulomatous pyelonephritis
r Abdominal radiograph may show tissue gas in
provide substrate for microorganisms parenchyma (nonspecific, low sensitivity)
– Bacterial fermentation of sugar produces carbon r Renal ultrasound may show highly echogenic area
dioxide TREATMENT
with dirty shadowing
– Low oxygen tension allows urinary tract infection r Computed tomography (CT) is imaging modality of
to ascend ALERT
r E. coli is primary causative organism (70–90%) choice (most sensitive and specific)
– May see: Emphysematous pyelonephritis is urologic
– Klebsiella, Proteus, Streptococcus, and ◦ Absence of fluid or presence of streaky or emergency that requires prompt diagnosis and
coagulase-negative Staphylococcus less common intervention to prevent morbidity and mortality.
mottled gas +/− bubbly and loculated gas in
– Candida, Entamoeba histolytica, and Aspergillus
renal parenchyma, collecting system, and/or
fumigatus are rare causes GENERAL MEASURES
perirenal tissue
◦ Rim-like or crescent-shaped gas distribution r Rapid supportive measures:
r Alcohol abuse surrounding kidney – Fluid resuscitation
r Diabetic ketoacidosis ◦ Gas in renal vein, inferior vena cava, or – Correction of electrolyte imbalances
r Immunocompromised states, including transplant retroperitoneum – Vasopressors as needed
patients ◦ Urinary tract obstruction (seen in ∼25% of – Usually requires ICU status
r Impaired renal function cases) r Indwelling urethral catheter to maximize urinary
r Malnutrition – Contrast not necessary for diagnosis (and may be tract drainage and monitor urine output.
r Urinary tract obstruction, including urinary calculi, contraindicated in renal impairment)
papillary necrosis, or neoplasm
GENERAL PREVENTION
r Strict glycemic control in diabetes mellitus (DM)
r Adequate treatment of pre-existing pyelonephritis
r Prompt relief of urinary tract obstruction, if present
380
PYELONEPHRITIS, EMPHYSEMATOUS
MEDICATION 4. Somani BK, Nabi G, Thorpe P, et al. Is

First Line ONGOING CARE percutaneous drainage the new gold standard in
r Antimicrobial agents the management of emphysematous
– Broad-spectrum parenteral antibiotics initially PROGNOSIS pyelonephritis? Evidence from a systematic review.
r Dependent on:
(dosages assume normal renal function): J Urol. 2008;179:1844–1849.
◦ Ampicillin–sulbactam (1.5 g q6h) – Time to diagnosis and treatment 5. Chen MT, Huang CN, Chou YH, et al. Percutaneous
◦ Ticarcillin–clavulanate (3.1 g q6h) – Local extent of the infection drainage in the treatment of emphysematous
◦ Piperacillin–tazobactam (3.375 g q6h) r Mortality greatest in those presenting with (2)[B], pyelonephritis: 10-year experience. J Urol. 1997;
◦ Meropenem (500 mg q8h) (3)[B]: 157:1569–1573.
◦ Imipenem (500 mg q6h) – Acute renal failure
◦ Doripenem (500 mg q8h) – Thrombocytopenia
– Narrow to culture-directed antibiotics – Mental status changes ADDITIONAL READING
– At least 14 days of therapy – Shock r Aswathaman K, Gopalakrishnan G, Gnanaraj L,
r Hyperglycemia management r Recent meta-analysis demonstrated
– Insulin (intravenous or subcutaneous) et al. Emphysematous pyelonephritis: Outcome of
treatment-based mortality (4)[B]: conservative management. Urology. 2008;71(6):
Second Line – Medical management alone: 50% 1007–1009.
N/A – Medical management + emergency r Shokeir AA, El-Azab M, Mohsen T, et al.
nephrectomy: 25%
SURGERY/OTHER PROCEDURES Emphysematous pyelonephritis: A 15-year
r Percutaneous drainage – Medical management + percutaneous drainage:
experience with 20 cases. Urology. 1997;49:
13.5%
– Indicated if: 343–346.
◦ Affected kidney is functioning COMPLICATIONS r Ubee SS, McGlynn L, Fordham M. Emphysematous
◦ Affected kidney is obstructed r Perinephric abscess pyelonephritis. BJU Int. 2011;107(9):1474–1478.
◦ Localized area of gas identified r Renal insufficiency or failure
r Loss of renal unit See Also (Topic, Algorithm, Media)
– ≥14Fr catheter (may benefit from more than one r Diabetes Mellitus, Urologic Considerations
catheter) r Sepsis/shock r Pyelonephritis, Acute, Adult
– CT guidance preferred r Death r Pyelonephritis, Chronic
– In combination with antibiotic therapy reduces r Following procedural intervention: r Pyelonephritis, Xanthogranulomatous
mortality rate – Bowel or vascular injury r Pyelonephritis, Emphysematous Image
– Helps preserve renal function in affected kidney – Wound infection
r If clinical improvement with medical management r Urosepsis
and percutaneous drainage, may delay or avoid FOLLOW-UP r Urinary Tract Infection (UTI), Adult Female
nephrectomy Patient Monitoring r Urinary Tract Infection (UTI), Adult Male
r Nephrectomy r Follow urine and blood cultures for growth and r Urinary Tract Infection (UTI), Complex, Adult
– Requires adequate resuscitation and stabilization sensitivities for directed antibiotic therapy
preoperatively r Follow-up CT (4–7 days postpercutaneous drainage)
– Immediate vs. delayed (elective) based on clinical (5)[C] CODES
course – Look for other noncommunicating air/fluid
– Indicated if: collections (insert additional catheters as needed)
◦ Affected kidney is nonfunctioning and ICD9
– Maintain all drainage catheters until imaging r 250.40 Diabetes with renal manifestations, type II or
nonobstructed demonstration of resolution
◦ Lack of clinical improvement with medical r Nuclear renal scan to assess degree of renal unspecified type, not stated as uncontrolled
r 590.10 Acute pyelonephritis without lesion of renal
management and percutaneous drainage functional impairment and determine necessity of
– Consider if: medullary necrosis
elective nephrectomy when patient stabilized r 599.60 Urinary obstruction, unspecified
◦ Presence of risk factors, including acute renal
Patient Resources
failure, thrombocytopenia, altered mental ICD10
http://www.emedicinehealth.com/urinary tract
status, or shock
infections/article em.htm r E11.21 Type 2 diabetes mellitus with diabetic
◦ Gas limited to renal parenchyma (dry-type
nephropathy
emphysematous pyelonephritis) r N10 Acute tubulo-interstitial nephritis
– Flank approach preferred REFERENCES r N13.9 Obstructive and reflux uropathy, unspecified
ADDITIONAL TREATMENT 1. Huang JJ, Tseng CC. Emphysematous
Radiation Therapy pyelonephritis: Clinicoradiological classification,
N/A management, prognosis, and pathogenesis. Arch CLINICAL/SURGICAL
Additional Therapies Intern Med. 2000;160(6):797–805. PEARLS
N/A 2. Falagas ME, Alexiou VG, Giannopoulou KP, et al. r Must have high index of suspicion to diagnose this
Risk factors for mortality in patients with
Complementary & Alternative emphysematous pyelonephritis: A meta-analysis.
rare, potentially life-threatening condition promptly.
Therapies r Diagnosis made radiographically (CT most sensitive
J Urol. 2007;178:880–885.
N/A and specific).
3. Lin YC, Lin YC, Lin HD, et al. Risk factors of renal r Outcomes most optimal with combination of fluid
failure and severe complications in patients with
emphysematous pyelonephritis—a single-center resuscitation, systemic antibiotics, and percutaneous
15-year experience. Am J Med Sci. 2012;343(3): drainage (with nephrectomy when indicated).
186–191.
381
PYELONEPHRITIS, XANTHOGRANULOMATOUS
Kelly A. Healy, MD
PHYSICAL EXAM r Gross findings:

BASICS r Fever – Massively enlarged kidney
r Flank tenderness – Hydronephrosis
DESCRIPTION r Palpable flank mass – Obstructing stones
r Xanthogranulomatous pyelonephritis (XGP) is an r Rarely elevated BP – Pus-filled calyces and parenchymal abscesses
uncommon chronic destructive granulomatous r Weight loss – Yellow nodules surrounding the calyces
process of renal parenchyma in association with r Microscopic findings:
r Less commonly hematuria
long-term urinary tract obstruction and infection – Thin cortex with extension of inflammatory
r Associated obstruction, stones DIAGNOSTIC TESTS & INTERPRETATION response beyond kidney
r Diffuse renal destruction with nonfunctioning kidney Lab – Lipid-laden macrophages (xanthoma cells) mixed
r Local mass formation sometimes confused with r Anemia 71% with lymphocytes, plasma cells, and giant cells
malignancy r Leukocytosis 62% form sheets around the calyces and parenchymal
r Pyuria 81% abscesses, show grossly as yellow nodules
EPIDEMIOLOGY – Mass may resemble a renal cell carcinoma with
r Urine culture: Proteus and E. coli are most common
Incidence hemorrhage, necrosis and yellow appearance in
r Rare, occurring in 0.5–1.4% of patients with renal – Mixed urine cultures occur in 10% of XGP patients
r Liver enzymes abnormal in as many as 1/ of XGP gross sectioning
inflammatory disorders (1, 2) 2 – Associated rare neoplasms have been reported
r Female to male (3:1) patients with XGP
r Peak incidence in 5th–7th decade Imaging
r Reported in children as young as 6 mo r CT is the 1st-choice imaging study (4,5) DIFFERENTIAL DIAGNOSIS
r Renal tumor
r Left = right – Demonstrates stones and hydronephrosis r Pyelonephrosis
– Seen multiple renal calculi or staghorn calculi
Prevalence r Renal abscess
– Shows enlarged kidney with mass, usually diffused
N/A – Renal parenchyma replaced with multiple r Renal lymphoma
fluid-filled cavities and extension of inflammatory r TB
RISK FACTORS
r Diabetes mass to perinephric spaces
r History of stones r IV urogram shows nonvisualization in 30–80% of
r History of UTIs patients
TREATMENT
– Stone visible in 30–80% GENERAL MEASURES
Genetics – Cannot distinguish renal mass from neoplasm r Antibiotics, culture specific if possible continued
N/A r Renal ultrasound demonstrates enlargement of the
until urine cultures are negative
PATHOPHYSIOLOGY kidney r Usually managed by nephrectomy
r Stones – Hydronephrosis r Partial nephrectomy with rare segmental cases
r Obstruction – Echogenic focus of the calculus r Even less, reports of endoscopic treatment with
r Infection – Multiple anechoic areas of parenchyma
r MRI provides little additional information stone removal, drainage continued antibiotics
r Proteus mirabilis is most common organism with r In cases of nephrectomy or partial nephrectomy,
r Functional renal scans can evaluate differential renal
Escherichia coli secondary. tissue culture should be used to guide antibiotic
function and may confirm nonfunction of the therapy
ASSOCIATED CONDITIONS involved kidney
r Diabetes (3)
MEDICATION
r Renal calculi, including staghorn (35%)
ALERT First Line
r Immunosuppression r Broad-spectrum antibiotics pending urine culture,
XGP may not be distinguished clinically or
GENERAL PREVENTION radiographically from renal cell carcinoma. such as ampicillin 1 g q8h and an aminoglycoside
Adequate treatment and follow-up of known UTIs (ie, gentamicin 5 mg/kg q24h) are usually effective
Diagnostic Procedures/Surgery until culture-specific antibiotics can be initiated.
Diagnosis is made on the basis of clinical suspicion r Negative urine cultures are common, and tissue
DIAGNOSIS and radiographic imaging studies cultures taken at the time of surgery may be
Pathologic Findings necessary to identify the offending organism.
HISTORY r Diffuse involvement of the entire kidney occurs in r Some recommend continuing oral antibiotics for up
r Nonspecific signs
r Fever, chills, flank pain, fatigue, anorexia 80+% of cases to 1 wk following nephrectomy.
r Segmental involvement is much less common Second Line
r Persistent bacteriuria even after antibiotic therapy
r XGP commonly extends beyond the kidney and N/A
r ∼1/3 of XGP patients have a history of stones
r 100% found to have stones at treatment mass
– Fistulae, pyelocutaneous and ureterocutaneous
r Diabetes common
have been noted
382
PYELONEPHRITIS, XANTHOGRANULOMATOUS
r Nephrectomy is the most common treatment
Patient Monitoring
– Diffuse inflammatory process r Urinalysis and urine culture Goyal S, Gupta M, Goyal R. Xanthogranulomatous
– Nonfunctioning kidney r Serum creatinine, CBC, liver enzymes repeated to pyelonephritis: A rare entity. N Am J Med Sci.
– Concern for malignancy follow for normalization 2011;3(5):249–250.
– Inflammatory reaction, nephrectomy can be r Further radiographic studies depending upon the See Also (Topic, Algorithm, Media)
technically difficult histopathology of the kidney specimen r Pyelonephritis, Acute, Adult
r Partial nephrectomy in rare cases of segmental XGP r Pyelonephritis, Acute, Pediatric
r Mechanical and antibiotic bowel prep is performed Patient Resources
r Pyelonephritis, Xanthogranulomatous Image
since XGP may involve any adjacent organs or N/A
r Renal Mass
tissues r Urinary Tract Infection (UTI), Complicated, Adult
– Drains should be placed in renal bed REFERENCES r Urolithiasis, Renal
r Laparoscopic nephrectomy has been shown to be
safe without increasing complications but, again 1. Kim SW, Yoon BI, Ha US, et al.
difficult (6) Xanthogranulomatous pyelonephritis. Clinical
experience with 21 cases. J Infect Chemother. CODES
ADDITIONAL TREATMENT 2013;19(6):1221–1224.
Radiation Therapy 2. Korkes F, Favoretto RL, Bróglio M, et al. ICD9
N/A Xanthogranulomatous pyelonephritis. Clinical r 041.6 Proteus (mirabilis) (morganii) infection in
Additional Therapies experience with 41 cases. Urology. 2008;71: conditions classified elsewhere and of unspecified
Percutaneous drainage with antibiotics (7) 178–180. site
3. Dwivedi US, Goyal NK, Saxena V, et al. r 590.00 Chronic pyelonephritis without lesion of
Xanthogranulomatous pyelonephritis: Our renal medullary necrosis
Therapies r 599.60 Urinary obstruction, unspecified
experience with review of published reports. ANZ J
N/A
Surg. 2006;76:1007–1009.
4. Loffroy R, Guiu B, Watfa J, et al. ICD10
r B96.4 Proteus (mirabilis) (morganii) causing dis
ONGOING CARE Xanthogranulomatous pyelonephritis in adults:
Clinical and radiological findings in diffuse and classd elswhr
PROGNOSIS r N11.8 Other chronic tubulo-interstitial nephritis
r Preservation of renal function related to the function focal forms. Clin Radiol. 2007;52:884–890.
r N13.9 Obstructive and reflux uropathy, unspecified
5. Zorzos I, Moutzouris V, Korakianitis G, et al.
of the contralateral kidney
r Recurrence in the contralateral kidney is very rare Analysis of 39 cases of xanthogranulomatous
pyelonephritis with emphasis on CT findings. Scand
r Chance of recurrent stones is high
J Urol Nephrol. 2003;37:342–347. CLINICAL/SURGICAL
COMPLICATIONS 6. Shah KJ, Ganpule AP, Kurien A, et al. Laparoscopic PEARLS
r Postoperative respiratory complications vs. open nephrectomy for xanthogranulomatous r Be suspicious in patients with fever, flank pain, and
r Wound infection pyelonephritis: An outcome analysis. Indian J Urol.
weight loss.
r An injury to adjacent organs can occur during 2011;27:470–474. r Persistent UTI with adequate treatment is a warning.
nephrectomy 7. Ergun T, Akin A, Lakadamyali H. Stage III r CT scan for diagnosis and extent of disease.
r Major vascular injury related to the inflammatory xanthogranulomatous pyelonephritis treated with
r XGP is primarily a surgically managed disease
process antibiotic therapy and percutaneous drainage.
r Fistulas or abscesses postoperatively require JBR-BTR. 2011;94(4):209–211. usually by nephrectomy with antibiotics critical to
the management of this condition.
drainage and antibiotic therapy r Usually unilateral and frequently confused clinically
r Renal insufficiency related to the function of the
and radiographically with renal cell carcinoma.
contralateral kidney
r Recurrent stone formation
383
PYONEPHROSIS
Anthony J. Tracey, MD, MPH
r Infectious agents (in decreasing order of incidence) DIAGNOSTIC TESTS & INTERPRETATION
BASICS (1) Lab
– Escherichia coli r Pyuria
DESCRIPTION – Enterococcus species r Elevated white count (less specific)
r Pyonephrosis is a collection of purulent material in – Candida species and other fungal infections r Bacteriuria (less specific)
the renal collection system – Enterobacter species r Urine culture of obstructed system
r Typically resulting from an underlying obstruction – Klebsiella species r Elevated C-reactive protein
within the upper urinary tract (2) – Proteus species
– With concomitant urinary tract infection – Pseudomonas species – 1 study showed CRP levels >28 mg/L with flank
r Considered a surgical emergency with drainage of – Bacteroides species pain a reliable indication for emergent
– Staphylococcus species decompression (1)
obstructed collecting system necessary (1)
– Methicillin-resistant Staphylococcus aureus Imaging
EPIDEMIOLOGY (MRSA) r CT scan with IV contrast (2)
Incidence – Salmonella species – Diagnostic criteria for pyonephrosis
r True incidence is unknown ◦ Increased wall thickness of the renal pelvis
– Tuberculosis (causes both infection and strictures)
r Increased in patients with upper urinary tract (2) ≥2 mm
obstruction ◦ The presence of renal pelvic contents and debris
ASSOCIATED CONDITIONS ◦ Parenchymal and perirenal findings, such as
Prevalence r Nephrolithiasis (most common) (1)
See above r UPJO perirenal fat stranding (3)
r Ultrasonography (US)
RISK FACTORS r Urothelial carcinoma (UC) of the upper tracts
r Upper urinary tract obstruction r Pyelonephritis – Sensitivity of renal US for differentiating
hydronephrosis from pyonephrosis is 90%, and
r History of prior urologic instrumentation r Emphysematous pyelonephritis/pyelitis
the specificity is 97% (1)
r Immunocompromised patient r Xanthogranulomatous pyelonephritis (XGP) ◦ Debris
r Diabetes mellitus r Ureteral stricture (2) ◦ Low-level echogenic foci
r Chronic UTIs ◦ Hydronephrosis
GENERAL PREVENTION r MRI
Genetics r Relief of underlying urologic obstruction
None r Proper medical management of immunosuppression – Use increasing for inflammatory disorders of the
r Identification of any anatomic urologic abnormality GU tract
PATHOPHYSIOLOGY ◦ Diffusion MRI shows hyperintense collecting
r Etiologies of obstruction (1) (ie, horseshoe kidney) system for pyonephrosis and hypointense signal
– Stones and staghorn calculi: In as many as 75% of for simple hydronephrosis
patients ALERT ◦ May be useful for patients with impaired renal
– Mucinous adenocarcinoma of the renal pelvis Patients may rapidly decline clinically and become function (3)
– Pregnancy septic. r Renal nuclear scan
– Fungus balls – Useful in assessing renal function after
– Metastatic retroperitoneal fibrosis—eg, renal decompression and to evaluate if involved renal
tumors, testicular cancer, colon cancer DIAGNOSIS unit is salvageable
– Obstructing transitional cell carcinoma – Not helpful in the immediate diagnostic period
– Ureteropelvic junction obstruction (UPJO) HISTORY
r Fever Diagnostic Procedures/Surgery
– Obstructing ureterocele r Once pyonephrosis has been diagnosed, there are
r Flank pain
– Ureterovesical junction obstruction
– Chronic stasis of urine and hydronephrosis r Clinical evidence of UTI two possible initial interventions:
secondary to neurogenic bladder – Antegrade nephrostomy tube placement
PHYSICAL EXAM – Retrograde ureteral stent placement
– Ureteral strictures
CVA tenderness with or without palpable abdominal
– Papillary necrosis Pathologic Findings
mass (hydronephrotic kidney) r Aspiration of obstructed system will usually show:
– Tuberculosis
– Duplicated kidneys with obstructive components – WBCs
– Ectopic ureter with ureterocele – Bacteria or fungus
– Neurogenic bladder – Sloughed urothelial cells
r Nephrolithiasis/urolithiasis
r Xanthogranulomatous pyelonephritis
r Ureteropelvic junction obstruction (UPJO)
r Urothelial carcinoma (UC) of upper tracts
r Ureteral stricture
r Extrinsic obstruction with hydronephrosis
(malignancy, retroperitoneal fibrosis)
384
PYONEPHROSIS
REFERENCES
1. Peterson AC. “Pyonephrosis” Medscape Article
GENERAL MEASURES PROGNOSIS 2013; emedicine.medscape.com/article/440548
r Drainage of obstructed collecting system is the r Good in patients who receive prompt diagnosis and 2. Raynor MC, Carson CC. Urologic issues for the
mainstay of treatment therapy internist urinary infections in men. Med Clin North
– Antegrade nephrostomy tube placement r Most patients will improve 24–48 hr after drainage Am. 2011;95:43–54.
◦ Indicated in the clinically unstable patient of obstructed renal collecting system 3. Hammond NA, et al. Genitourinary imaging
◦ Best for maximal decompression r Recovery of renal function is rapid infectious and inflammatory diseases of the kidney.
– Retrograde ureteral stent placement Rad Clin North Am. 2012;50:259–270.
◦ Indicated in the stable patient able to tolerate COMPLICATIONS
r Sepsis is the most common complication of delayed
general anesthesia
◦ Relatively contraindicated in setting of a large treatment
r Other complications of delayed treatment include: ADDITIONAL READING
upper tract stone that will eventually need
percutaneous therapy or fungus ball – Rupture of pyonephrotic kidney resulting in: Schaeffer AJ, Schaeffer EM. Infections of the urinary
r Treatment of source obstruction: ◦ Generalized peritonitis tract. In: Wein AJ, et al. eds. Campbell-Walsh Urology.
◦ Renocolic fistula 10th ed. Philadelphia: Saunders; 2012.
– Once collecting system has been decompressed ◦ Renoduodenal fistula
and appropriate antibiotic/antifungal therapy has ◦ Renocutaneous fistula See Also (Topic, Algorithm, Media)
been given for 2 wk r Fungal Infections, Genitourinary
◦ Splenic rupture
– May include endoscopic, percutaneous, r Hydronephrosis/Hydroureteronephrosis, (Dilated
– Rare complications:
transurethral, laparoscopic, robotic, ◦ Pneumoperitoneum Ureter/Renal Pelvis), Adult
extracorporeal, or open approaches ◦ Renal vein thrombosis r Pyonephrosis Image
– Depends on the nature of obstruction (ie, stone, ◦ Psoas abscess r Ureter, Obstruction
stricture) (1) ◦ Perinephric abscess r Urosepsis
– Clinical feasibility of intervention ◦ Rhabdomyolysis r Urolithiasis, Staghorn
MEDICATION – Loss of renal function
First Line r Complications from nephrostomy tube:
r Broad spectrum intravenous antibiotics (ie, – Blood transfusions CODES
piperacillin and tazobactam, gentamicin, and – Hematoma
ampicillin) and antifungals if clinically indicated for – Nephrostomy tube replacement/revision ICD9
funguria r Increased risk of infection if nephrectomy is not r 590.80 Pyelonephritis, unspecified
– Antibiotics can be focused once cultures result performed when indicated. r 593.89 Other specified disorders of kidney and
Second Line FOLLOW-UP ureter
N/A Patient Monitoring r 599.0 Urinary tract infection, site not specified
SURGERY/OTHER PROCEDURES r Treatment of underlying obstruction (ie, calculus,
r Indication for nephrectomy is controversial stricture, malignancy) ICD10
r N13.6 Pyonephrosis
– May be indicated if source of infection is not found r Treatment and control of any predisposition to
r N28.89 Other specified disorders of kidney and
– Help to exclude malignant etiology of obstruction infection (ie, DM, HIV/AIDS, neurogenic bladder)
– Lack of response to percutaneous drainage and IV ureter
Patient Resources r N39.0 Urinary tract infection, site not specified
antibiotics/antifungals r http://kidney.niddk.nih.gov/kudiseases/pubs/
– Poorly functioning kidney stonesadults/
ADDITIONAL TREATMENT r http://www.medicinenet.com/kidney stone/ CLINICAL/SURGICAL
Radiation Therapy article.htm PEARLS
N/A r http://www.mayoclinic.com/health/
kidney-stones/DS00282 r Patients with pyonephrosis may be asymptomatic or
Additional Therapies present with a picture of an abscess with fever and
N/A
chills.
Complementary & Alternative r Urolithiasis, staghorn calculi, and fungus balls are
Therapies the most common clinical causes of pyonephrosis.
N/A
385
PYURIA
Christina Carpenter, MD
r Microscopic analysis—can see crystals and/or

BASICS DIAGNOSIS bacteria
r Gram stain—can identify type of bacteria
DESCRIPTION HISTORY r Culture
r Presence of WBCs in the urine r Common symptoms: Dysuria, frequency, urgency,
– Clean-catch midstream specimen = most common
r Normal #WBCs in a urine specimen malaise
r Fever (more common with upper tract infection) – Catheterized urine—required in situations in
– Men ≤2 WBC/hpf which patients are unable to collect specimen
– Women ≤5 WBC/hpf r Hematuria (gross)
(children, incontinent adults, obese population,
r When seen with bacteriuria, suggests inflammatory – Occasional patients in urinary retention)
response of urothelium (ie, infection) – More common in females – Segmented urine specimen
r When seen without bacteriuria (sterile pyuria), raises – Rare in children ◦ Sequential voided urine samples aimed to
r Atypical presentations
suspicion for tuberculosis, partially treated UTI, localize infection/inflammation source
stones, and/or malignancy – Young patients ◦ Stamey test (see Stamey test [Three-glass test,
◦ Difficulty with toilet training, urgency, Four-glass tests, Meares-Stamey Test])
EPIDEMIOLOGY incontinence r AFB culture—if patient has history of and/or
When seen in a voided urine specimen, has an ◦ Abdominal discomfort, failure to thrive, fever,
80–95% sensitivity for detecting patients with a possible exposure to TB
vomiting, jaundice r Rapid in-office microbiology testing
urinary tract infection (UTI) – Elderly – 80% accurate for detecting, quantifying, and
RISK FACTORS ◦ Incontinence, fevers, frequency, urgency
identifying specific bacteria in urine
r Urolithiasis ◦ May be asymptomatic
r History of recurrent childhood fevers—may imply – Usually performed on a fresh unspun sample
r Previous UTI r Urine cytology—if malignancy is suspected
r Sexually transmitted disease frequent UTIs and potential congenital anomalies
r Malignancy r History of UTIs among female family members Imaging
r Children: Ultrasound, VCUG, radionuclide
PATHOPHYSIOLOGY PHYSICAL EXAM cystogram, IV pyelogram
r Clean-catch midstream urine may contain r Suprapubic tenderness r Adult: Indicated only in the setting of suspected
r Costovertebral angle tenderness
contaminants (bacteria, squamous epithelial cells) pathology, obstruction, stone disease, and/or
r Significant pyuria (at least 10 WBCs/mm3 ) is r Fever hematuria
uncommonly seen in patients without true infection r Children—may have abdominal discomfort, r Sterile pyuria: Imaging to identify source/evaluate
tenderness, and/or distention cause
ALERT DIAGNOSTIC TESTS & INTERPRETATION Diagnostic Procedures/Surgery
60% of elderly women have significant pyuria r Localization of bacteria
Lab
without associated bacteriuria (1)[A]. r Dipstick – Segmented urine specimen
r Can be caused by bacteria in the urinary tract – Best screening tool – Ureteral catheterization in OR
– Leukocyte esterase (LE) – Immunologic/antibody studies
provoking an inflammatory response r Isotopic function studies
r Bacteria can colonize the genitourinary system in a ◦ Produced by granulocytes that catalyze the
hydrolysis of an indoxylcarbonic acid ester to r Cystogram
retrograde fashion r CT: Localization of nidus/abnormality responsible for
r Certain bacteria are more frequently the cause of indoxyl, which reacts with a diazonium salt to
produce a purple color on the reagent strip bacteriuria/pyuria (ie, abscess)
UTIs as they are more efficient at adhering to the
mucosal cells of the urinary tract (eg, Escherichia ◦ 75–96% sensitive for a culture-positive UTI r Cystoscopy—indicated for symptomatic patients
coli) (2)[A] with persistent pyuria and negative urine cultures
◦ Sterile pyuria (3)[A]
r Bacteriuria Produces positive LE test with negative culture
r UTI Disease process without bacteriuria r Specimen contamination
r Pyelonephritis ◦ Causes of false negatives r Cystitis
RBC >10 K/μL
r Nephrolithiasis r Epididymitis
Glucose >1 g/dL
r Pyelonephritis—acute, chronic, emphysematous,
Albumin >500 mg/dL
GENERAL PREVENTION
r Proper toileting habits Formaldehyde tuberculous, xanthogranulomatous
r Genitourinary TB
r Complete bladder emptying Medications: Cephalexin, gentamicin,
tetracycline r Interstitial cystitis

r Adequate fluid intake (stone prevention)
◦ Causes of false positives r Interstitial nephritis
Specimen contamination
Recent instrumentation of GU tract
Medications: Imipenem, meropenem,
clavulanic acid
– Presence of nitrites, blood, or protein suggests UTI
386
PYURIA
r Neoplasm See Also (Topic, Algorithm, Media)

– Urothelial carcinoma ONGOING CARE r Bacteriuria
– Renal cell carcinoma r Pyelonephritis, Chronic
r Prostatitis PROGNOSIS r Pyelonephritis, Emphysematous
r Renal abscess Dependent upon etiology r Pyelonephritis, Xanthogranulomatous
r Periurethral abscess COMPLICATIONS r Prostatitis, Chronic, Bacterial
r STI/STD r Ascending bacterial infections r Prostatitis, Chronic, Nonbacterial, Inflammatory
r Renal transplant rejection r Urosepsis r Prostatitis, General
r Urethral diverticulum r Renal failure r Pyuria Algorithm
r Urethritis r Death r Pyuria, Image
r Foreign bodies in GU tract (stents, catheters) r Tuberculosis, Genitourinary
FOLLOW-UP
r Urinary tract fistula r Urinary Tract Infection (UTI), Adult Female
r Vulvovaginitis
Patient Monitoring
r Repeat exam 2-wk post-UTI treatment r Urinary Tract Infection (UTI), Adult Male
r Kawasaki disease – Urinalysis, urine culture r Urinary Tract Infection (UTI), Pediatric
– Reassess symptoms
r Routine periodic evaluation to check for recurrence
TREATMENT
of pyuria CODES
GENERAL MEASURES Patient Resources
r Identify cause of inflammatory response ICD9
www.UrologyHealth.org
r Direct treatment at cause of pyuria 791.9 Other nonspecific findings on examination of
r UTI is most commonly the origin urine
REFERENCES
MEDICATION ICD10
First Line 1. Boscia JA, Kaye D. Asymptomatic bacteriuria in the N39.0 Urinary tract infection, site not specified
r In infection, should be empiric until targeted therapy elderly. Infect Dis Clin North Am. 1987;1:893–905.
can be initiated based on culture results (4) 2. Drekonja DM, Johnson JR. Urinary tract infections.
r See “Urinary tract infection (UTI), adult female,” Prim Care. 2008;35:345–367. CLINICAL/SURGICAL
“Urinary tract infection (UTI), adult male” and 3. Dielubanza EJ, Schaeffer AJ. Urinary tract infections PEARLS
“Urinary tract infection (UTI), pediatric” in women. Med Clin North Am. 2011;95:27–41. r Absence of pyuria should lead the clinician to
4. Schaeffer AJ, Schaeffer EM. Infections of the
Second Line question a diagnosis of UTI.
urinary tract. In: Wein AJ, Kavoussi LR, Novick AC, r Sterile pyuria does not suggest a benign process.
N/A
et al. Campbell-Walsh Urology. 10th ed. r Persistent symptomatic pyuria requires further
SURGERY/OTHER PROCEDURES Philadelphia, PA: Elsevier Saunders; 2012.
r Correct underlying abnormality workup, ie, cystoscopy, imaging.
r Treat calculus r Atypical presentations in children, the elderly, and
r Remove foreign body (eg, ureteral stent) ADDITIONAL READING the immunocompromised require the clinician to
maintain a high index of suspicion.
ADDITIONAL TREATMENT r Abrahamian FM, Moran GJ, Talan DA. Urinary tract
r Bacteriuria with pyuria is treated as a UTI in children infections in the emergency department. Infect Dis
and premenopausal women Clin North Am. 2008;22:73–87.
r Persistent or recurrent bacteriuria may require r Lin KW, Brown T. Screening for asymptomatic
prolonged antibiotic treatment followed by chronic bacteriuria in adults. Am Fam Physician. 2010;
low-dose prophylactic antibiosis 81:508.
r High-risk patients (children with congenital r Mulvey MA. Adhesion and entry of uropathogenic
abnormalities, immunocompromised adults) may Escherichia coli. Cell Microbiol. 2002;4:257–271.
need chronic suppressive antibiotic treatment
r Postmenopausal women
– May have chronic pyuria with mild bacteriuria
◦ Require treatment only if symptomatic or if
associated with complicating factors
r Diabetics, patients with obstructive uropathy, and
immunocompromised patients may have additional
requirements to address ongoing pyuria adequately
387
LWBK1391-SEC-R LWBK1391-Gomella ch192.xml September 19, 2014 18:53
RECTAL INJURY DURING RADICAL PROSTATECTOMY

OR RADICAL CYSTECTOMY
Debasish Sundi, MD
Misop Han, MD
GENERAL PREVENTION Diagnostic Procedures/Surgery

BASICS r Adequate intraoperative hemostasis to aid r After removal of the specimen (laparoscopic or
visualization robotic surgery) from the prostatic fossa, a
DESCRIPTION r Bowel preparation has not been proven to reduce suspected rectal injury can be confirmed by flooding
r Rectal injury is a rare, potential complication of the pelvis with saline irrigant and gently insufflating
the risk of intraoperative bowel injury but may limit
radical prostatectomy or radical cystoprostatectomy, contamination in the event of an injury the rectum with air injected via a Foley catheter
with a reported incidence ranging from 0.1–1.7% r Placement of a rectal tube at the start of the – A rectal enterotomy will be evident by air bubbling
– Reported for radical prostatectomy: Retropubic procedure may aid in the identification of the rectal through the irrigant
perineal, laparoscopic, and robotically assisted wall in difficult cases (ie, salvage prostatectomy Pathologic Findings
laparoscopic approaches following radiation) A through-and-through injury will involve both the
– Reported for radical cystectomy: Open and r Careful identification of the anterior and posterior rectal serosa and mucosa
robotically assisted approaches layers of Denonvilliers fascia will aid in avoiding
r Intraoperative recognition of the rectal injury is DIFFERENTIAL DIAGNOSIS
rectal injury r Intraoperative differential diagnosis is limited
paramount; this will allow primary repair in layers
and minimize the chance of subsequent r Postoperative differential includes:
rectourethral fistula DIAGNOSIS – Small bowel or large perforation (iatrogenic)
r Occasionally the problem will not be identified until – Colonic perforation secondary to pathologic
the postoperative period HISTORY distension such as in colonic pseudoobstruction,
r After removal of the specimen (open surgery),
or Ogilvie syndrome
EPIDEMIOLOGY inspection of the surgical bed using posterior – Pelvic abscess
Incidence traction to efface folds of tissue will typically reveal
r The rate of rectal injury during urologic pelvic a rectal injury by direct visualization
procedures varies by procedure and approach – Obtaining good hemostasis will aid visualization TREATMENT
r For radical prostatectomy, rectal injury rates are – Copious irrigation of the pelvis with sterile saline
may also reveal air bubbles emanating from the GENERAL MEASURES
quite low, ranging from 0.1–0.5% (open retropubic, r When a rectal injury is diagnosed postoperatively,
pure laparoscopic, or robot assisted) (1,2)[C] rectal vault (2)[C]
r Symptoms may include abdominal or pelvic pain; management depends on the patient’s clinical
– Rectal injury rates are higher for radical
picture
cystoprostatectomy (up to 1.7%) (3)[C], and nausea and vomiting may also be present r Patients who are minimally symptomatic and have a
highest for perineal prostatectomy (8–11%) (4)[C]
PHYSICAL EXAM small injury radiographically may be initially
Prevalence Postoperative manifestations may include exam managed conservatively by indwelling urethral
Extrapolating from the number of procedures findings that may include tenderness to palpation, catheter, with reassessment by cystogram after
performed annually in US, the prevalence of rectal fever, tachycardia, hypotension, ileus (2)[C] 2–3 mo (5)[C]
injury for radical prostatectomy ranges from r The GI tracts of patients who are symptomatic,
80–400 cases per yr, and for radical cystectomy, up to DIAGNOSTIC TESTS & INTERPRETATION
septic, or have a history of prior pelvic radiation
150 cases per yr Lab
r Acute injury may not manifest any lab abnormalities should be diverted with an end colostomy (5)[C]
RISK FACTORS r An unrecognized postoperative injury may – These patients’ GI tracts can be brought back in
History of pelvic radiation therapy or prior pelvic continuity if a cystogram and/or Gastrografin
demonstrate leukocytosis enema are negative in 2–3 mo. If these patients
surgery
Imaging have persistent fistulas, they should be surgically
Genetics r Postoperatively CT ± cystourethrography repaired with a transrectal advancement flap
N/A – Free air in pelvis and/or peritoneum (2)[C].
PATHOPHYSIOLOGY – Contrast communicating between rectum and
MEDICATION
N/A bladder/urethra
First Line
ASSOCIATED CONDITIONS r 7–14 days of antimicrobial therapy (4)[C]
r Prior pelvic radiation or surgical procedures may – Antibiotic regimen should cover both
increase the risk of rectal injury gram-negatives and anaerobes (such as
r Extensive transurethral resection of bladder floor for ciprofloxacin and metronidazole)
urothelial carcinoma Second Line
r Inflammatory bowel disease
N/A
r Locally advanced malignancy
388
RECTAL INJURY DURING RADICAL PROSTATECTOMY OR RADICAL CYSTECTOMY

R
r When a rectal injury is diagnosed intraoperatively, it
REFERENCES
CODES
should be repaired immediately, closing the rectal 1. Lepor H, Nieder AM, Ferrandino MN. Intraoperative
mucosa and serosa in separate layers and postoperative complications of radical ICD9
– Suture choice includes mucosal layer with 3-0 retropubic prostatectomy in a consecutive series of r 599.1 Urethral fistula
chromic and the serosa with 3-0 silk or other 1,000 cases. J Urol. 2001;166(5):1729–1733. r 863.45 Injury to rectum, without mention of open
suitable alternatives (2) 2. Evans CP. Complications of cystectomy and partial wound into cavity
– An additional flap of vascularized tissue cystectomy Chapter 32. In: Complications of r 998.2 Accidental puncture or laceration during a
(omentum or peritoneum) should be interposed Urologic Surgery. 3rd ed. Philadelphia, PA: procedure, not elsewhere classified
between the rectal repair and the bladder/urethra. Saunders; 2001.
Immediate repair minimizes the risk of subsequent 3. Lawrentschuk N, Colombo R, Hakenberg OW, et al. ICD10
rectourethral fistula. Prevention and management of complications r K91.72 Acc pnctr & lac of a dgstv sys org during oth
◦ If a rectourethral fistula does form in spite of following radical cystectomy for bladder cancer. procedure
immediate repair, management options are Eur Urol. 2010;57(6):983–1001. r N36.0 Urethral fistula
conservative treatment via Foley catheterization 4. Lassen PM, Kearse WS Jr. Rectal injuries during r S36.60XA Unspecified injury of rectum, initial
or surgical repair via diverting colostomy and, if radical perineal prostatectomy. Urology. 1995; encounter
necessary, a transrectal advancement flap (6)[C] 77(4):266–269.
ADDITIONAL TREATMENT 5. Borland RN, Walsh PC. The management of rectal
injury during radical retropubic prostatectomy.
CLINICAL/SURGICAL
Radiation Therapy
N/A J Urol. 1992;147(3):163–166. PEARLS
6. Roberts WB, Tseng K, Walsh PC, et al. Critical r Rectal injury during radical urologic pelvic surgery is
Additional Therapies appraisal of management of rectal injury during
N/A a rare but serious complication.
radical prostatectomy. Urology. 2010;76(5): r This injury can occur during open, laparoscopic and
Therapies robotically assisted laparoscopic pelvic surgery.
7. Pfalzgraf D, Isbarn H, Reiss P, et al. Outcomes after r When recognized intraoperatively, immediate
N/A recto-anastomosis fistula repair in patients who
underwent radical prostatectomy for prostate primary repair assures the best outcomes.
r When immediate repair is not possible or
ONGOING CARE cancer. BJU Int. 2014;113(4):568–573.
contraindicated, the patient may be temporized with
a diverting colostomy until the rectal injury heals
PROGNOSIS
r Among patients undergoing immediate ADDITIONAL READING and the GI tract can be brought back into continuity.
r Rectourethral fistula is a delayed complication of
intraoperative repair, there is a 12.5% incidence of r Blumberg JM, Lesser T, Tran VQ, et al. Management
subsequent rectourethral fistula (6)[C] rectal injury repair, the chance of which can be
– Rectal injuries of increasing length are associated of rectal injuries sustained during laparoscopic minimized with immediate recognition and repair of
with a higher risk of rectourethral fistulae, as are radical prostatectomy. Urology. 2009;73(1): rectal injury.
those recognized and repaired in delayed fashion 163–166.
r Kheterpal E, Bhandari A, Siddiqui S, et al.
COMPLICATIONS Management of rectal injury during robotic radical
r Need for temporary colostomy diversion
prostatectomy. Urology. 2011;77(4):976–979.
r Rectourethral fistula r Sugihara T, Yasunaga H, Horiguchi H, et al. Does
r With delayed rectoanastomotic fistula after radical mechanical bowel preparation ameliorate damage
prostatectomy: incontinence (7) from rectal injury in radical prostatectomy? Analysis
r Sepsis of 151 rectal injury cases. Int J Urol. 2014;21(6):
566–570.
FOLLOW-UP
Patient Monitoring See Also (Topic, Algorithm, Media)
r After repair, routine monitoring on a regular surgical r Fistula, Enterovesical
floor with daily labs is appropriate r Fistula, Rectourethral
– Prior to routine Foley catheter removal after
radical prostatectomy, perform cystogram to rule
out fistula at 14 days after surgery
◦ If rectourethral fistula is demonstrated, continue
Foley catheter, as resolution of fistula with
period of catheterization up to 9 wk has been
demonstrated
Patient Resources
None
389
RENAL AND PERIRENAL ABSCESS

Mary K. Powers, MD
Imaging
BASICS DIAGNOSIS r Differentiation between early renal abscess and
acute pyelonephritis is difficult due to small size
DESCRIPTION HISTORY r Abdominal CT:
r Renal abscess/carbuncle: r Significant chronic or acute illnesses including
– Diagnostic procedure of choice
– Collection of purulent material confined to the diabetes, neurogenic bladder dysfunction, chronic – Can often delineate the route of spread of
renal parenchyma renal failure, hemodialysis, and polycystic renal infection into surrounding tissues
r Perirenal abscess: disease – Abscesses are characteristically well defined both
r Renal calculi
– Results from extension of an acute cortical before and after contrast agent enhancement
abscess into the perinephric space; confined by r IV drug abuse
– Acute findings include renal enlargement and
Gerota fascia – Gram-positive source of infection 1–8 wk before focal, rounded areas of decreased attenuation
r Pararenal/perinephric abscess: the onset of urinary tract symptoms – Chronic findings include obliteration of adjacent
– Results from the rupture of a perinephric abscess ◦ Preceding infection can occur in any area of the tissue planes, thickening of Gerota (perinephric)
through Gerota fascia into the pararenal space body (eg, skin lesions, dental infections) fascia, a round or oval parenchymal mass of low
r Patients with UTI and abdominal or flank mass attenuation, and a surrounding inflammatory wall
EPIDEMIOLOGY r Persistent fever with suspected genitourinary source of slightly higher attenuation that forms a ring
Incidence after 3–5 days of antimicrobial therapy when the scan is enhanced with contrast material
Perinephric and renal abscesses are uncommon but (ring sign)
potentially lethal complications of UTI PHYSICAL EXAM – See Figure 1, Renal Abscess
r Elevated temperature
Prevalence r IV urography (if performed)
r 2/3 of gram-negative abscesses are associated with r CVA or flank tenderness
r Abdominal and/or flank mass – Abnormal in up to 80% of patients, although
renal calculi or kidneys with poor function findings often are nonspecific
r Pregnant women with untreated bacteriuria are r Distended or palpable bladder
– Generalized enlargement of involved renal unit
r Look for skin carbuncles or dermatologic evidence of with distortion of renal contour and collecting
associated with a higher incidence of pyelonephritis
and subsequent diagnosis of abscess IV drug abuse system
r Renal infection is among the most common sites for r Heart murmurs – Absence of psoas shadow on affected side
extrapulmonary disease in patients with TB – Bubbles of extraluminal gas can be seen
surrounding the kidney in large perinephric
RISK FACTORS Lab abscesses
Diabetes mellitus, polycystic kidney disease, r Serum creatinine:
r Abdominal US:
hemodialysis, neurogenic bladder, IV drug users, – Variable findings, dependent on concurrent
– Quickest and least expensive diagnostic imaging
tuberculosis, recurrent urinary tract infection and/or obstruction and underlying renal dysfunction
r CBC: study
pyelonephritis, nephrolithiasis, vesicoureteral reflux, – Common findings include an echo-free or
ureteropelvic junction obstruction or other source of – Patients typically have marked leukocytosis low-echodensity space-occupying lesion with
obstruction, any immunocompromised state r Urine analysis:
increased transmission, which is poorly
Genetics – Pyuria and bacteria often present, although marginated during the acute phase
N/A pyuria/bacteriuria may not be evident unless the – Well-defined discrete lesion during chronic stages,
abscess communicates with the collecting system which is difficult to distinguish from a renal mass
PATHOPHYSIOLOGY – Sterile pyuria often seen with TB
r Gram-negative organisms have been implicated in r Urine culture:
the majority of adults with renal abscesses
ALERT
– When abscesses contain gram-negative Evidence of air within renal parenchyma tissue is
(Escherichia coli, Proteus mirabilis, and organisms, urine culture often demonstrates the
Staphylococcus aureus) account for the majority of diagnostic for emphysematous pyelonephritis which
same organism isolated from the abscess may require urgent surgical intervention. See
infections (in descending order of occurrence) (1) – Since gram-positive organisms are most commonly
r Hematogenous renal seeding by gram-negative Section I: Emphysematous pyelonephritis.
blood borne, urine cultures in these cases typically
organisms may occur, but this is not likely to be the show no growth or a microorganism different
primary pathway for gram-negative abscess Diagnostic Procedures/Surgery
from that isolated from the abscess CT- or US-guided needle aspiration may be necessary
formation – Catheterized urine collection recommended for
r Hematogenous renal seeding: Skin infection with to differentiate an abscess from a hypervascular
female patients tumor; aspirated material can be collected for culture
gram-positive organisms, IV drug abuse, r Blood cultures:
to guide appropriate antimicrobial therapy. A
immunocompromised status – Gram-negative organisms are most commonly
r Ascending infection associated with tubular percutaneous drain may be left in place and clinical
cultured course can be evaluated.
obstruction from prior infections, vesicoureteral – Gram-positive organisms are not routinely similar
reflux, or calculi appears to be the primary pathway to those cultured from abscess Pathologic Findings
for the establishment of gram-negative abscesses Abscess fluid will demonstrate neutrophils and gram
stain will reveal bacteria
See “Risk Factors” above
GENERAL PREVENTION
Increased clinical suspicion, prompt recognition, and
treatment of infection, especially in the face of
obstruction in high-risk patients
390
RENAL AND PERIRENAL ABSCESS

R
DIFFERENTIAL DIAGNOSIS SURGERY/OTHER PROCEDURES 3. Ko MC, Liu CC, Liu CK, et al. Incidence of renal and
r Pyelonephritis (2) r Standard treatment for renal abscesses >5 cm or perinephric abscess in diabetic patients: A
r Pyonephrosis those that fail to respond to percutaneous drainage population-based national study. Epidemiol Infect.
r Xanthogranulomatous pyelonephritis and IV antibiotic therapy has been rapid incision and 2011;139(2):229–235.
r Emphysematous pyelonephritis drainage. 4. Heller MT, Haarer KA, Thomas E, et al. Acute
r Renal TB r Relief of coexisting obstruction is mandatory. conditions affecting the perinephric space: Imaging
r Bowel perforation with retroperitoneal spread of r Primary treatment remains drainage for all anatomy, pathways of disease spread, and
perinephric abscesses. differential diagnosis. Emerg Radiol. 2012;19(3):
infection
r Nephrectomy may be required for adequate 245–254.
treatment if medical therapy/incision and drainage
TREATMENT fails.
ADDITIONAL READING
GENERAL MEASURES (3,4) ADDITIONAL TREATMENT
r Hospitalization with initiation of IV antibiotics and Radiation Therapy r Meng MV, Mario LA, McAninch JW. Current
fluid resuscitation. N/A treatment and outcomes of perinephric abscesses.
r Suspected pyelonephritis treated with antibiotics for J Urol. 2002;168(4 Pt1):1337–1340.
Additional Therapies r Tanagho EA, McAninch JW. Smith’s General
48–72 hr without significant improvement requires CT- or US-guided placement of percutaneous drains
radiographic evaluation to rule out obstruction with concurrent IV antibiotic therapy is currently an Urology. 17th ed. New York, NY: McGraw Hill; 2008.
and/or abscess formation. accepted method of treatment for abscesses 3–5 cm See Also (Topic, Algorithm, Media)
r Recent evidence indicates that for very small r Pyelonephritis, Acute
in size and smaller abscesses in immunocompromised
(<3-cm abscesses), careful observation and patients who fail to respond to medical therapy. r Pyelonephritis, Chronic
IV-tailored antimicrobial agents may obviate surgical r Pyelonephritis, Emphysematous
procedures. Complementary & Alternative
Therapies r Pyelonephritis, Xanthogranulomatous
r Abscesses 3–5 cm in diameter and smaller
N/A r Pyonephrosis
abscesses in immunocompromised hosts or those r Renal and Perirenal Abscess Image
that do not respond to antimicrobial therapy should
r Retroperitoneal Abscess
be drained percutaneously. ONGOING CARE
r Surgical drainage, however, currently remains the
procedure of choice for most renal abscesses >5 cm PROGNOSIS
r Perinephric abscess is historically associated with
in diameter or if perirenal extension of abscess CODES
occurs. mortality rates approaching 39–50%.
r Obstruction, if present, must be relieved. r Recent series with prompt implementation of IV
ICD9
antibiotics and subsequent percutaneous or surgical r 590.2 Renal and perinephric abscess
MEDICATION drainage report mortality rates of 5–12%. r 590.80 Pyelonephritis, unspecified
First Line r 592.0 Calculus of kidney
r Antibiotic therapy: May prevent surgical intervention COMPLICATIONS
r Delay in diagnosis is associated with higher
unless abscess involves perinephric space. ICD10
r Initiate empiric treatment with fluid resuscitation mortality rate. r N12 Tubulo-interstitial nephritis, not spcf as acute or
r Delay in diagnosis and treatment is associated with
and broad-spectrum IV antibiotics. chronic
loss of renal function and, in rare circumstances, r N15.1 Renal and perinephric abscess
– 3rd-generation cephalosporins
◦ Cefotaxime—1–2 mg IV/Q8–12h genitourinary fistulas to the pleura, colon, skin, etc.
r N20.0 Calculus of kidney
◦ Ceftriaxone—1–2 mg IV/Q24h FOLLOW-UP
◦ Ceftazidime—1 g IV/Q8–12h Patient Monitoring
– Aminoglycosides r Address the underlying medical conditions to CLINICAL/SURGICAL
◦ Gentamicin—1–1.7 mg/kg IV/Q8h
◦ Amikacin—7.5 mg/kg IV/Q12h
prevent recurrent infections.
r Repeat radiographic studies to confirm complete
PEARLS
◦ Tobramycin—1–1.7 mg/kg IV/Q8h resolution. r Abscesses <3 cm can be managed with medical
– Antipseudomonal penicillins r Extended antibiotic therapy is often required. treatment initially.
◦ Piperacillin/Tazobactam—3.375 g IV/Q6h r Continued fevers require surgical drainage of
◦ Ticarcillin/Clavulanate—3.1 g IV/Q4–6h Patient Resources
r Medline Patient Information: abscess.
r IV antibiotics until afebrile for 24–48 hr, switch to r Include gram-positive antibiotic coverage if suspect
PO for at least 2 wk based on culture. – http://www.nlm.nih.gov/medlineplus/ency/
hematogenous spread (IV drug use).
r Adjust dose for renal function. article/001274.htm
r Urology Care Foundation Patient Guide:
Second Line – http://www.urologyhealth.org/urology/
r For a suspected hematogenous source, expand
index.cfm?article=18
coverage to include penicillin-resistant
Staphylococcus.
– Vancomycin—1 g IV/Q12h REFERENCES
1. Gardiner RA, Gwynne RA, Roberts SA. Perinephric
Abscess. BJU Int. 2011;107(Suppl 3):20–23.
2. Shields J, Maxwell AP. Acute pyelonephritis can
have serious complications. Practitioner. 2010;
254(1728):19, 21, 23–24, 2.
391
RENAL ANGIOMYOLIPOMA
Casey Allison Seideman, MD
Ganesh V. Raj, MD, PhD, FACS
DIFFERENTIAL DIAGNOSIS (2)

BASICS DIAGNOSIS r Renal masses:
– Oncocytoma
DESCRIPTION HISTORY – Renal and retroperitoneal liposarcoma
r Angiomyolipoma (AML): Benign renal tumor r Most asymptomatic, discovered incidentally
– Renal cell carcinoma
composed of vascular tissue (angio), muscle (myo), r Occasionally diagnosed by flank pain, hypotension,
– Renal cysts
and adipose (lipoma) tissue elements and spontaneous hemorrhage – Renal lipoma
r Tumors <4 cm are less likely to be symptomatic r History of LAM, TSC – Sarcoma (including fibrosarcoma,
r Tumors >4 cm have increased risk of spontaneous r GI complaints due to mass effect leiomyosarcoma, and liposarcoma)
bleeding r Hematuria, hypertension, anemia – Teratoma
r Can be sporadic, but is associated with tuberous – Upper-tract urothelial carcinoma
PHYSICAL EXAM – Wilms tumor
sclerosis (TS) and lymphangioleiomyomatosis (LAM) r Hypertension, or hypotension (in the setting of
r Can be a cause of Wunderlich syndrome: – Xanthogranulomatous pyelonephritis
hemorrhage) r Renal/retroperitoneal hemorrhage:
– Spontaneous, nontraumatic renal hemorrhage r TSC: Mental retardation, adenoma sebaceum,
– Bleeding usually confined to renal capsule – Arteriovenous malformation
ungula/subungual fibromas, lung disease – Coagulopathy
EPIDEMIOLOGY r Flank pain/mass
– Hemorrhage of other renal mass such as renal cell
Incidence – Up to 50% of patients who are symptomatic may carcinoma
r 20–30% of cases are seen in patients with tuberous have a palpable mass – Iatrogenic
sclerosis (TS) DIAGNOSTIC TESTS & INTERPRETATION – Ruptured aneurysm
r Mean age: – Traumatic injury
Lab
– Sporadic AML: 5th or 6th decade r Anemia – Vasculitis
– Tuberous sclerosis complex (TSC) patients: Age 30 r Gross/micro hematuria
r Female > male (4:1) overall; 2:1 in TS patients
r Renal insufficiency TREATMENT
r Right side more common
r Genetic testing if TS is suspected
Prevalence GENERAL MEASURES (3)
Imaging r Benign renal masses, rarely transform to malignant
Prevalence 0.13%, 2–3% of all renal tumors r CT: AML is commonly diagnosed on CT scans that
entities
RISK FACTORS reveal solid masses with areas of fat density r Observation unless large, or symptomatic
r TSC (50% develop AML) (Hounsfield units below −20); most reliable
r LAM (40% develop AML) imaging modality; IV contrast not necessary MEDICATION
r Patients with TC tend to develop larger, bilateral, r Fat density is not identified on CT in some cases First Line
with reduced fat content (1)[C] r Medical management is not currently standard
multicentric, tumors which grow more rapidly, and
tend to have more spontaneous bleeds r Rare reported cases of RCC containing fat densities r Everolimus (4)
(finding of calcification in mass is suspicious for – Approved in adults with renal AML and TSC not
Genetics
r TSC, AD with variable expression RCC) (2)[C] requiring immediate surgery
r 2/3 result from sporadic mutations – US: Well-circumscribed, hyperechoic mass with – May benefit other TSC-associated disease
r 2 genes: TSC1 (9q34), TSC2 (16p13) shadowing (other RCTs may also be echogenic) manifestations, such as skin manifestations,
– IVP: Similar appearance to other RCTs pulmonary LAM, cardiac rhabdomyomas, and
PATHOPHYSIOLOGY – Angiogram: Increased vascularity (also seen in epilepsy
In rare cases, can cause: Renal failure (large volume of many malignant renal lesions); 50% of AMLs are – An inhibitor of mammalian target of rapamycin
tumor, or solitary kidney) found to have aneurysmal dilation (mTOR), a serine-threonine kinase, downstream of
– MRI: Adipose tissue has high signal intensity on the PI3K/AKT pathway
ASSOCIATED CONDITIONS T1-weighted images and lower on T2-weighted – 10 mg once daily with or without food
r TS (1)
images Second Line
– 50–80% of patients with TS develop AML
– TS: Autosomal dominant condition, comprised of Pathologic Findings N/A
r Pathology findings:
mental retardation, epilepsy, angiofibromas of the
face (adenoma sebaceum), hamartomas in the – Thick-walled vessels, smooth muscle, and adipose
kidney, brain (subependymal giant-cell tissue with spindle and epithelioid cells
astrocytomas [SEGAs]), eye (retinal phakomas), – The amount of each component varies
heart, lung, and bone r Epithelioid AMLs
r LAM—rare lung disease, associated with TS – Variant of AML characterized by epithelioid cells
– Characterized by smooth muscle growth in the that are cytokeratin negative and HMB-45
lungs, resulting in obstruction of small airways. positive. More aggressive clinical course
Also occurs with TS
392
RENAL ANGIOMYOLIPOMA
R
SURGERY/OTHER PROCEDURES FOLLOW-UP r Rakowski SK, Winterkorn EB, Paul E, et al. Renal
r Indications: Diagnostic uncertainty, hemorrhage manifestations of tuberous sclerosis complex:
Patient Monitoring
causing significant symptoms, pain, hematuria, risk r Controversial in patients with newly diagnosed Incidence, prognosis, and predictive factors. Kidney
of rupture AML; screen for TS Int. 2006;70(10):1777–1782.
r Asymptomatic AML <4 cm: r Conservative management: Serial imaging (usually r Roy C, Tuchmann C, Lindner V, et al. Renal cell
– Observation with serial imaging at 12-mo intervals with CT or US) every 6–12 mo carcinoma with a fatty component mimicking
r Asymptomatic AML >4 cm: r Growth rate typically 5% per yr for solitary AML angiomyolipoma on CT. Br J Radiol. 1998;71:
– Treatment should be considered; observation with r TSC patients and those with multicentric AMLs have 977–979.
serial imaging r Steiner MS, Goldman SM, Fishman EK, et al. The
growth rate of 20% per yr
– The risk of spontaneous hemorrhage appears natural history of renal angiomyolipoma. J Urol.
greatest in masses >4 cm Patient Resources 1993;150:1782–1786.
r TS alliance www.tsalliance.com
– Women of childbearing age may consider
r LAM Foundation www.theLAMfoundation.com See Also (Topic, Algorithm, Media)
proactive treatment r Renal Angiomyolipoma Image
r Symptomatic AML/lesion >4 cm:
r Renal Cell Carcinoma, General
– Selective arterial embolization or nephron-sparing
surgery
REFERENCES r Renal Mass
r Acute hemorrhage: r Retroperitoneal Hematoma
1. Kennelly MJ, Grossman HB, Cho KJ. Outcome r Tuberous sclerosis
– Initially treated with embolization (stabilizes analysis of 42 cases of renal angiomyolipoma.
patient and often eliminates need for more J Urol. 1994;152:1988–1991.
intervention) 2. Margulis V, Matin SF, Wood CG. Chapter 51:
– If explored emergently, total nephrectomy usually Benign Renal Tumors. In: Campbell-Walsh Urology.
CODES
necessary Philadelphia, PA: Elsevier; 2010:1492–1505.
3. Nelson CP, Sanda MG. Contemporary diagnosis
ICD9
ADDITIONAL TREATMENT r 223.0 Benign neoplasm of kidney, except pelvis
Radiation Therapy and management of renal angiomyolipoma. J Urol. r 593.81 Vascular disorders of kidney
N/A 2002;168:1315–1325.
r 759.5 Tuberous sclerosis
4. Dabora SL, Franz DN, Aswal S, et al. Multicenter
Additional Therapies phase 2 trial of sirolimus for tuberous sclerosis:
r Limited reports of treatment using cryoablation and ICD10
Kidney angiomyolipomas and other tumors regress r D17.71 Benign lipomatous neoplasm of kidney
radiofrequency ablation and VEGF-D levels decrease. PLoS One. 2011;6(9):
r In patients with LAM or TS, mTOR inhibitors such as r N28.89 Other specified disorders of kidney and
e23379.
sirolimus/temsirolimus have been shown to decrease ureter
mass size by 30% r Q85.1 Tuberous sclerosis

Therapies r Folpe AL, Mentzel T, Lehr HA, et al. Perivascular CLINICAL/SURGICAL
N/A
epitheliod cell neoplasms of soft tissue and PEARLS
gynecological origin: A clinicopathologic study of 26 r Benign renal tumor characterized by presence of
ONGOING CARE cases and review of the literature. Am J Surg Pathol.
2005;29(12):1558–1575. vascular, muscle, and adipose components.
PROGNOSIS r Moavero R, Coniglio A, Garaci F, et al. Is mTOR r Larger lesions have increased risk of spontaneous
r Local recurrence rare after removal. hemorrhage.
r Extrarenal lesions are multicentric and not inhibition a systemic treatment for tuberous r Diagnosis is usually made by imaging.
sclerosis? Ital J Pediatr. 2013;39:57.
metastatic. r Observation for small masses, consider embolization
r Extended follow-up is necessary after selective for larger masses.
embolization due to complications and recurrence r Everolimus (mTOR inhibitor) can shrink large
risk. multifocal lesions in patients with tuberous sclerosis
r Extremely rare case reports of malignant (TS) and lymphangioleiomyomatosis (LAM).
transformation.
COMPLICATIONS
r Flank/abdominal pain
r Hematuria
r Hemorrhage (may cause anemia or shock)
r Mass effect on surrounding organs
393
RENAL ARTERY STENOSIS/RENOVASCULAR HYPERTENSION

Brian M. Benway, MD
r FMD is a nonatherosclerotic, noninflammatory DIAGNOSTIC TESTS & INTERPRETATION

BASICS process of the renal vessels Lab
– Intimal fibroplasia occurs in children and young r Plasma renin activity (PRA)
DESCRIPTION adults – By itself, not diagnostic of RAS or RVH
r Renal artery stenosis (RAS) refers to anatomic ◦ Accounts for 10% of FMD r Captopril test
vascular lesion that causes decreased blood flow to ◦ Can be associated with dissection and – Useful for excluding RVH
the kidney hematoma – Diuretics and ACE inhibitors stopped 1 wk prior
r May not be associated with hypertension (HTN) ◦ Involves proximal or midportion of artery, – PRA measured before and 1 hr after 25-mg dose
r May be atherosclerotic in nature (athersclerotic appears smooth on angiography of captopril
renal artery stenosis or ARAS) ◦ Invariably progressive if untreated – Positive test if postdose PRA >12 ng/mL/h,
r Rarely caused by fibromuscular dysplasia (FMD) – Medial fibroplasia absolute increase of PRA >10 ng/mL/h, 4-fold
r Renovascular HTN (RVH) refers to HTN that is ◦ 70–80% of FMD increase in PRA over baseline
◦ More common in women aged 25–50 – Not appropriate in children or in patients with
caused by renal hypoperfusion and is reversed by
◦ Usually bilateral azotemia
correction of the lesion or nephrectomy
◦ “String of beads” appearance on angiography
EPIDEMIOLOGY ◦ Rarely associated with functional loss and may Imaging
r Arteriography is gold standard
Incidence be managed medically
r RAS often found incidentally – Perimedial fibroplasia – Highly sensitive and specific (99%)
– 33% of patients with aorto-occlusive disease ◦ Women aged 15–30 – Provides detailed anatomy, and allows for
– 20% of patients with coronary artery disease ◦ Dense collar of collagen constricting the artery discrimination between FMD subtypes
(CAD) ◦ Length is variable – Allows for simultaneous endovascular treatment
– 43% of patients with diabetes ◦ Frequently associated with development of – Invasive
– 7% of asymptomatic normotensive adults collaterals – Recommended as initial diagnostic intervention in
>65 yr (1) ◦ Invariably progressive if not treated patients with high suspicion for RVH
r Captopril renography
Prevalence – Fibromuscular hyperplasia
◦ Extremely rare (2–3% of all renal artery lesions) – Keep well hydrated on a liberal salt diet
RVH <1% of hypertensive patients – Off ACE inhibitors for 3–5 days prior to exam
◦ Most commonly affects children and young
RISK FACTORS adults – 99m Technetium-MAG3 renal scan generally used
r Atherosclerosis ◦ Progressive if untreated before and 1 hr after captopril dose
r Diabetes – Diagnostic criteria for RVH: Delay in maximal
r CAD ASSOCIATED CONDITIONS activity >11 min, asymmetrical peak activity,
r High-grade retinopathy
r Advanced age cortical retention of radionuclide, significant
r Atherosclerosis
decrease in glomerular filtration rate
Genetics r Diabetes – Recommended as initial diagnostic intervention in
N/A r CAD patients with low-to-moderate suspicion for RVH
r Peripheral vascular disease r Duplex ultrasonography
PATHOPHYSIOLOGY
r Atherosclerosis – Positive diagnostic criteria: Peak systolic velocity
GENERAL PREVENTION of renal artery >80 cm/s, ratio of diameter of
– Accounts for 70% of all RAS Reduction of risk factors for cardiovascular disease
– Nearly half of patients will have progressive renal artery to aorta >3.5
and diabetes – Inexpensive, noninvasive, but quality of study is
obstruction within 2 yr of diagnosis
– Usually located at the ostium or proximal renal operator dependent
DIAGNOSIS r Magnetic resonance angiography (MRA)
artery
– 10% caused by FMD, which causes primarily distal – May be more sensitive than ultrasound or
lesions HISTORY renography, but inferior to conventional
r Onset of HTN after age 50
r RVH arteriography
r No family history of HTN
– Results from significant vascular stenosis which – Poorly visualizes distal arteries
r Difficult-to-control HTN, on multiple – Contraindicated in patients with metal or
produces renal hypoperfusion
– Hypoperfusion results in increased renin levels, antihypertensives claustrophobia
r Increase in serum creatinine with use of ACE – Contrast must be used with caution in patients
which in turn increases angiotensin II levels
– Angiotensin elevates blood pressure through inhibitors or angiotensin receptor blockers (ARBs) with renal insufficiency (2)
r Computed tomography angiography (CTA)
several mechanisms PHYSICAL EXAM
◦ Generalized vasoconstriction r Blood pressure measurement – Uses potentially nephrotoxic contrast agents
◦ Increased aldosterone production, promoting r Abdominal exam with auscultation for bruit – More widely available and cost-effective
sodium absorption and excretion of potassium r Retinal exam compared to MRA
and hydrogen
◦ Causes efferent arteriolar vasoconstriction to
maintain glomerular filtration
394
RENAL ARTERY STENOSIS/RENOVASCULAR HYPERTENSION

R
Diagnostic Procedures/Surgery r One recent clinical trial suggests that the addition of 3. Novick AC. Options for therapy of ischemic
r Renal angiography renal artery stenting to comprehensive, nephropathy: Role of angioplasty and surgery.
r Renal vein renin sampling multifactorial medical therapy did not confer a Semin Nephrol. 1996;16:53–60.
– Useful in determining which kidney is primary significant benefit (4) 4. Cooper CJ, Murphy TP, Cutlip DE, et al. Stenting
contributor to RVH in patients with bilateral r Aortorenal bypass (hypogastric or saphenous vein) and medical therapy for atherosclerotic renal-artery
lesions r Nephrectomy (especially in patients with a poorly stenosis. N Engl J Med. 2014;370(1):13–22.
Pathologic Findings functioning ipsilateral renal unit) 5. Krum H, Schlaich M, Whitbourn R, et al.
r Renal biopsy indicated in patients with creatinine Catheter-based renal sympathetic denervation for
>4 mg/dL resistant hypertension: A multicentre safety and
Radiation Therapy proof-of-principle cohort study. Lancet. 2009;
– Tubular atrophy, interstitial fibrosis, arteriosclerosis N/A
indicate functional recovery may be possible 373:1275–1281.
– Widespread glomerular hyalinization indicates Additional Therapies
r Treatment of concomitant disease
irreversible injury
– Antiplatelet agents ADDITIONAL READING
DIFFERENTIAL DIAGNOSIS – Statins
r Aortic aneurysm r O’Neill WC, Bardelli M, Yevzlin AS. Imaging for
– Smoking cessation
r Essential HTN renovascular disease. Semin Nephrol. 2011;31:
– Weight loss
r Functional adrenal adenoma 272–282.
r Intrinsic renal disease Complementary & Alternative r Piecha G, Wiecek A, Januszewicz A. Epidemiology
r Renal artery aneurysm Therapies and optimal management in patients with renal
Sympathetic renal denervation using radiofrequency artery stenosis. J Nephrol. 2012;25:872–878.
ablation is investigational at the present time, but r Safian RD, Textor SC. Renal-artery stenosis. N Engl J
shows promise (5)
TREATMENT Med. 2001;344:431–442.
GENERAL MEASURES See Also (Topic, Algorithm, Media)

r Recognition of underlying cause is critical in guiding ONGOING CARE r HTN, Urologic Considerations
r Renal Artery Aneurysm
management PROGNOSIS
r Smoking cessation r Renal Artery FMD
Untreated disease, except for medial fibroplasia, is
r Weight loss r Renin, Plasma and Renal Vein
often progressive and can result in renal functional
r Reduction of risk factors for cardiovascular disease loss r Renal Artery Stenosis Images
and diabetes COMPLICATIONS
r Functional loss, worsening HTN, pulmonary edema,
MEDICATION CODES
First Line congestive heart failure in untreated patients
r ACE inhibitors/ARBs: Improves HTN in 96% of r Endovascular interventions: Access site hematoma,
renal artery dissection, thrombosis, contrast-induced ICD9
patients with RVH. May not prevent progression of r 250.40 Diabetes with renal manifestations, type II or
atherosclerotic lesions. nephropathy
– Captopril: 25–50 mg PO BID-TID r Surgical interventions: Hemorrhage, wound unspecified type, not stated as uncontrolled
r 405.91 Unspecified renovascular hypertension
– Enalapril: 10–40 mg PO QD infection, hematoma, anesthesia complications
r 440.1 Atherosclerosis of renal artery
– Losartan: 25–100 mg PO divided QD-BID FOLLOW-UP
– Telmisartan: 20–80 mg PO QD ICD10
r Aspirin 81 mg PO QD Patient Monitoring
High-risk patients and those on medical therapy should r E11.21 Type 2 diabetes mellitus with diabetic
r Statins
be observed with serial metabolic and renal function nephropathy
Second Line studies in addition to Doppler ultrasonography r I15.0 Renovascular hypertension
r Thiazide diuretics r I70.1 Atherosclerosis of renal artery
r Loop diuretics
Patient Resources
http://www.nlm.nih.gov/medlineplus/ency/
r Calcium channel blockers article/000204.htm
r β-blockers CLINICAL/SURGICAL
PEARLS
r Surgical intervention recommended for patients with r RVH HTN is caused by significant stenosis of the
high-grade stenosis, bilateral disease, solitary 1. Hansen KJ, Edwards MS, Craven TE, et al. renal artery and is reversed by correction of stenosis
kidney, declining renal function, pulmonary edema, Prevalence of renovascular disease in the elderly: A or nephrectomy.
congestive heart failure (3) population-based study. J Vasc Surg. 2002;36: r Renal angiography remains gold standard for
r Angioplasty with or without endovascular stenting 443–451. diagnosis.
– Percutaneous access through common femoral 2. Grobner T. Gadolinium–a specific trigger for the r With the exception of medial fibroplasia, untreated
artery development of nephrogenic fibrosing dermopathy RVH disease often leads to progressive renal
– Selective angiography performed and nephrogenic systemic fibrosis? Nephrol Dial functional loss.
– ≥70% stenosis treated with angioplasty and Transplant. 2006;21:1104–1108.
deployment of balloon-mounted stent
– Angioplasty without stenting is associated with
increased risk of restenosis
395
RENAL CAPSULAR NEOPLASMS

Mathew C. Raynor, MD
Raj S. Pruthi, MD, FACS
r Hemangiopericytoma
BASICS DIAGNOSIS – Solid, encapsulated mass
– Microscopically, varied cell shapes and sizes with
DESCRIPTION HISTORY morphologic variability
r Predominantly mesenchymal neoplasms arising from r Usually asymptomatic or discovered incidentally
– Immunostaining positive for vimentin, BCL2,
the renal capsule encompassing a wide variety of r May present with hematuria or flank pain
CD99 and negative for S100, cytokeratins, and
cell progenitors r Weight loss, anorexia, malaise, or bone pain may HMB-45 (2)[C]
– Tumors can be composed of fibrous, smooth signify metastatic disease r Lymphangioma
muscle, vascular, adipose, nerve, or other tissue – Well-encapsulated, multilocular cystic mass
PHYSICAL EXAM
differentiation r Usually normal – Microscopically, communicating cysts seen with
◦ Encompasses benign and malignant neoplasms flattened endothelial cells
– Rarely, flank mass may be palpable
EPIDEMIOLOGY – Immunostaining positive for D2-40
DIAGNOSTIC TESTS & INTERPRETATION ◦ Labels lymphatic endothelium (1,3)[C]
Incidence r Solitary fibrous tumor
r Very rare tumors Lab
r Urinalysis – Well-encapsulated firm mass without necrosis,
r Represent up to ∼1.5% of all surgically treated
– Microscopic hematuria may be identified, but cysts, or hemorrhage
benign renal masses (1) usually normal
r Incidentally found at autopsy in up to ∼5% of – Microscopically, usually shows areas of spindle
r CBC cells intermixed with hypocellular areas of fibrous
cases (1) – Anemia may be present with advanced disease or tissue
r Similar gender preference
bleeding mass – Immunostaining strongly positive for CD34
Prevalence r Serum chemistries usually normal ◦ May also stain positive for CD99 and BCL2 and
Unknown, due to rarity of tumor can be misclassified as hemangiopericytoma
Imaging
r CT or MRI with and without contrast (1,2)[C]
RISK FACTORS r Leiomyosarcoma
r None known – May show enhancing mass arising from the
kidney – Usually large circumscribed mass with areas of
– Increased cross-sectional imaging use may identify
◦ Indistinguishable from renal cell carcinoma in necrosis
incidental mass
most cases – Microscopically, spindle cells with haphazard
Genetics ◦ Presence of fat may signify angiomyolipoma, growth pattern, nuclear pleomorphism, mitoses,
r No recognized genetic predisposition
lipoma, or liposarcoma and necrosis
r Some common genetic alterations seen in soft tissue – Immunostaining positive for SMA, desmin, and
r Chest x-ray
sarcomas calponin (1)[C]
– Evaluate for metastatic disease r Fibrosarcoma
– No current clinical application for genetic
alterations Diagnostic Procedures/Surgery – Large encapsulated mass
r Core needle biopsy
PATHOPHYSIOLOGY – Microscopically, elongated spindle cells
r Benign – May be used in cases of suspected renal ◦ “Herringbone” pattern
malignancy or if active surveillance considered – Immunostaining positive for vimentin
– Leiomyoma, hemangiopericytoma, hemangioma, r Angiography ◦ Differentiates fibrosarcoma from sarcomatoid
lymphangioma, myxoma, schwannoma, solitary
– May be utilized for bleeding lesions RCC and leiomyosarcoma (1)[C]
fibrous tumor, paraganglioma, lipoma, fibroma, r Malignant fibrous histiocytoma
– Benign lesions usually hypovascular
myolipoma ◦ Except hemangiopericytoma, which is highly
r Malignant – Solid, well-encapsulated mass
vascular – Microscopically, proliferation of fibrohistiocytes
– Leiomyosarcoma, malignant fibrous histiocytoma,
fibromyxoid sarcoma, hemangiosarcoma, Pathologic Findings – Immunostaining positive for α1-antitrypsin and
r Leiomyoma vimentin
liposarcoma, fibrosarcoma
– Firm, well-circumscribed, exophytic mass
ASSOCIATED CONDITIONS – Microscopically, composed of spindle cells
Some renal hemangiomas may be associated with arranged in fascicles typical of smooth muscle
Sturge–Weber or Klippel–Trénaunay syndromes (1) – Immunostaining positive for desmin, smooth
GENERAL PREVENTION muscle actin, and usually HMB-45 (1)[C]
No preventive strategies identified
396
RENAL CAPSULAR NEOPLASMS

R
DIFFERENTIAL DIAGNOSIS ADDITIONAL TREATMENT 3. Kalof AN, Cooper K. D2-40 immunohisto-
r Angiomyolipoma chemistry—so far! Adv Anat Pathol. 2009;16(1):
Radiation Therapy
r Renal cysts r May be beneficial in cases of renal capsular 62–64.
r Cystic nephroma sarcoma 4. Wang X, Xu R, Yan L, et al. Adult renal sarcoma:
r Hemorrhagic/proteinaceous cysts – Usually given in adjuvant setting Clinical features and survival in a series of patients
r Juxtaglomerular cell tumor Additional Therapies treated at a high-volume institution. Urology.
r Metastasis to kidney 2011;77(4):836–841.
Angioembolization for bleeding masses
r Oncocytoma
r Renal cell carcinoma
r Renal pseudotumor/scar
Therapies ADDITIONAL READING
None known
r Splenule (ectopic or traumatic) r MacLennan GT, Cheng L. Neoplasms of the kidney.
r Urothelial carcinoma In: Bostwick DG, Cheng L, eds. Urologic Surgical
r Wilms tumor ONGOING CARE Pathology. 2nd ed. Philadelphia, PA: Mosby Elsevier;
r Xanthogranulomatous pyelonephritis PROGNOSIS 2008:104–106.
r Surgical excision usually curative r Soft Tissue Sarcoma. NCCN Clinical Practice
r Renal capsular sarcoma has poor prognosis Guidelines in Oncology (www.nccn.org).
TREATMENT – Locally advanced disease is common See Also (Topic, Algorithm, Media)
– Recurrence and metastases common r Hemorrhage, Retroperitoneal and Perinephric
GENERAL MEASURES – Overall prognosis is poor, despite adjuvant r Renal Capsular Neoplasms Image
r Surgical excision is both diagnostic and therapeutic
r Multimodal therapy generally recommended for chemoradiation r Renal Mass
◦ 5-yr overall survival ∼15% r Renal Masses, Benign WHO Classification
malignancies such as sarcoma ◦ Median survival 28 mo (4)[C] r Renal Sarcoma, Adult and Pediatric
MEDICATION COMPLICATIONS
First Line r Injury to adjacent organs
r Chemotherapy may be beneficial for certain r Thromboembolic event CODES
advanced renal capsular malignancies (sarcoma) r Delayed bleed
and metastatic lesions (4)[C]. – AV fistula ICD9
– Usually given in the adjuvant setting. – Pseudoaneurysm r 189.0 Malignant neoplasm of kidney, except pelvis
r Targeted therapies may be beneficial in certain r Development of metastatic disease r 223.0 Benign neoplasm of kidney, except pelvis
cases. r 239.5 Neoplasm of unspecified nature of other
– Sunitinib, sorafenib, bevacizumab active in FOLLOW-UP
angiosarcoma, solitary fibrous tumor, and genitourinary organs
Patient Monitoring
hemangiopericytoma. r Periodic surveillance imaging
ICD10
r Serum chemistry panel and liver function tests r C64.9 Malignant neoplasm of unsp kidney, except
r Surgical excision remains gold standard Patient Resources renal pelvis
– Radical nephrectomy None due to rarity of disease r D30.00 Benign neoplasm of unspecified kidney
◦ Open or minimally invasive r D49.5 Neoplasm of unspecified behavior of other
– Partial nephrectomy genitourinary organs
◦ Open or minimally invasive REFERENCES
◦ Renal capsule margin should be excised with
1. Katabathina VS, Vikram R, Nagar AM, et al. CLINICAL/SURGICAL
mass Mesenchymal neoplasms of the kidney in adults:
◦ Should be procedure of choice for patients with PEARLS
Imaging spectrum with radiologic-pathologic
chronic kidney disease, when feasible correlation. Radiographics. 2010;30(6):
r Active surveillance r Renal capsular neoplasms difficult to distinguish
1525–1540.
– Similar surveillance protocol for patients with from RCC by imaging alone.
2. Brescia A, Pinto F, Gardi M, et al. Renal r Surgical excision (partial or radical nephrectomy) can
small renal masses hemangiopericytoma: Case report and review of
be diagnostic and curative in most cases.
the literature. Urology. 2008;71(4):755.e9–e12. r Renal capsular sarcomas carry generally poor
prognosis, despite adjuvant therapy.
397
RENAL CELL CARCINOMA WITH TUMOR THROMBUS

Chandy Ellimoottil, MD
Marcus L. Quek, MD, FACS

BASICS r Pulmonary embolus Biopsy can be performed if urothelial cell carcinoma is
r Bilateral lower-extremity edema suspected or patient is poor surgical candidate
DESCRIPTION r Lower-extremity DVT
r Patients with renal cell carcinoma (RCC) are at risk Pathologic Findings
r Varicocele r All subtypes of RCC have been associated with IVTT
for developing intravenous tumor thrombus (IVTT) r Caput medusa r Clear cell is the most common histologic subtype
with tumor extending into the renal vein (RV) and
associated with IVTT
inferior vena cava (IVC). GENERAL PREVENTION
r RCC is the most common malignancy to extend into Modification of above risk factors for RCC DIFFERENTIAL DIAGNOSIS
IVC. Other tumors associated (rarely) with IVTT include
r Tumor growth follows the path of least resistance urothelial cell carcinoma, adrenocortical carcinoma,
DIAGNOSIS and angiomyolipoma
into the venous system extending into the RV and
IVC (and into the right atrium) or it can invade into HISTORY
the vein wall. r Presentation of patients with RCC with IVTT is
r Multiple staging systems exist for RCC with venous similar to RCC without tumor thrombus, but those
TREATMENT
extension. 3 common staging systems include: with tumor thrombus are more likely to be GENERAL MEASURES
– TNM symptomatic r For those with no evidence of distant metastatic
◦ pT3a—RV extension r Up to 95% of patients with intracaval extension
disease, surgical resection is the gold standard for
◦ pT3b—IVC below diaphragm present with symptoms it is an incidental finding RCC with IVTT
◦ pT3c—IVC above diaphragm in 23% r For patients who present with metastatic disease,
– Anatomic (Hinman system) r Symptoms include:
◦ Level I—RV/infrahepatic IVC biopsy may be indicated for consideration of
– Hematuria (35%) systemic therapy
◦ Level II—Intrahepatic IVC – Flank/abdominal pain (17%) r For select patients with metastatic disease,
◦ Level III—Supradiaphragmatic IVC/right atrium – Constitutional symptoms including fatigue, weight
r Anatomic (Neves/Novick system) cytoreductive nephrectomy with tumor
loss, or paraneoplastic syndrome (9%) thrombectomy may be considered, although the
– Level 0—RV – Flank/abdominal mass (2%) outcomes in this setting are usually poor
– Level I—IVC <2 cm above RV
– Level II—IVC >2 cm above RV and below hepatic PHYSICAL EXAM MEDICATION
r Physical exam findings can include:
veins First Line
– Level III—IVC above hepatic veins and below – Bilateral lower-extremity edema r Anticoagulation (preoperatively) should be
diaphragm – Varicocele (right side)
considered for patients with IVTT to prevent bland
– Level IV—IVC above diaphragm – Dilated superficial abdominal wall veins
thrombus development and propagation below the
– Caput medusa
EPIDEMIOLOGY tumor
DIAGNOSTIC TESTS & INTERPRETATION r Preoperative tyrosine kinase inhibitors (TKIs)
Incidence
There are approximately 63,920 cases of RCC Lab – Controversial
r Basic lab work is necessary for preoperative workup – May be utilized in the metastatic setting or when
diagnosed each year; about 10% have IVTT.
including tumor felt not to be surgically resectable
Prevalence (1) – Liver function tests – Most common TKIs used preoperatively are
r RCC with IVTT is seen in 4–15% of cases.
– Complete blood count sorafenib and sunitinib; may decrease tumor size
– In 50% of these cases, IVTT only extends to the RV. – Basic metabolic panel before surgical resection; may reduce level of IVTT,
– IVTT extends into the right atrium in 1% of cases. – Urinalysis potentially altering surgical approach
r Among patients that have IVTT, 29–55% will have
Imaging Second Line
concomitant metastatic disease. r Chest imaging (preferably CT) and bone scan should N/A
RISK FACTORS be ordered as part of staging workup
Risk factors for RCC with IVTT are the same for RCC r Assessment of IVTT cephalad extension should be r Surgery is the gold standard for the treatment of
and include smoking, obesity, hypertension, family performed 7–14 days before surgery because it can RCC with IVTT (2,3,4)
history. affect the surgical approach and the need for bypass r Accurate assessment of the cephalad extent of the
Genetics procedures
r Ultrasonography and standard CT can be used to tumor thrombus is critical in determining the surgical
No known genetic factors exist that predict IVTT. approach and need for adjunctive procedures
detect the presence of IVTT, but may not be r While there are some reports of robotic and
PATHOPHYSIOLOGY sufficient for surgical planning
r RCC with IVTT can occur with all histologic subtypes laparoscopic approaches to RCC with IVTT, the
r MRI (T1-weighted images) is the gold standard
including clear cell, papillary, and chromophobe mainstay is open surgery
r RCC can occur sporadically or in a hereditary form imaging technique used to assess the cephalad r Midline, subcostal (chevron), or thoracoabdominal
extent of the IVTT, the degree of occlusion, and its
(although there is no known genetic predisposition incisions can be used
relationship to liver, diaphragm, and atrium r Median sternotomy or thoracoabdominal
to IVTT) r Multidetector CT (MDCT) can also be used in
r IVTT can cause occlusion of the IVC, which can approaches can be used for IVTT above the
patients who are not candidates for MRI
cause lower-extremity edema, varicocele in males r Studies comparing MRI to MDCT for staging IVTT diaphragm
r IVTT can also cause a pulmonary embolism
have shown comparable results
r Acute caval obstruction may rarely lead to r Transesophageal echocardiography can be used
disseminated intravascular coagulation, though intraoperatively for real-time monitoring of thrombus
more commonly IVTT may cause chronic venous r Size of tumor thrombus on imaging studies may
obstruction leading to the development of collateral
predict vein wall invasion and need for vein
venous drainage
reconstruction
398
RENAL CELL CARCINOMA WITH TUMOR THROMBUS

R
r For all levels, IVC should be resected if tumor is ADDITIONAL TREATMENT Patient Resources
invading into the wall and reconstruction can be r American Cancer Society http://www.cancer.org/
Radiation Therapy
performed with graft (if lumen diameter No role, except for palliation acs/groups/cid/documents/webcontent/003107-
compromised >50%) pdf.pdf
r Resection of retroperitoneal lymph nodes and/or Additional Therapies r Kidney Cancer Foundation http://www.
r IVC filter can be used to prevent pulmonary
metastasectomy can be performed as needed kidneycancer.org/
r Surgical steps include: embolus, however its use is controversial
– IVTT may become incorporated into IVC filter
– Expose renal hilum, ligate renal artery causing a surgical challenge
– Expose the RV and IVC REFERENCES
– When IVC is chronically occluded, simple ligation
– Isolate venous inflow into IVC of IVC below hepatic veins may be performed 1. González J. Update on surgical management of
– Cavotomy, tumor extraction r Preoperative renal artery embolization renal cell carcinoma with venous extension. Curr
– Caval repair/reconstruction/ligation
r Level I Thrombus Specifics – Allows for early venous clamping when renal Urol Rep. 2012;13(1):8–15.
artery control may be difficult; may cause pain and 2. Karnes RJ, Blute ML. Surgery insight: Management
– Milk the thrombus into the RV and take a side bite complications (angioinfarction syndrome) of renal cell carcinoma with associated inferior
of the IVC using a vascular clamp making sure not – Can be used as a palliative procedure vena cava thrombus. Nat Clin Pract Urol. 2008;
to occlude IVC flow
Complementary & Alternative 5(6):329–339.
– Incise the IVC and remove the thrombus and
kidney under direct vision Therapies 3. Lawindy SM, Kurian T, Kim T, et al. Important
– Oversew the caval defect None surgical considerations in the management of renal
r Level II Thrombus Specifics cell carcinoma (RCC) with inferior vena cava (IVC)
tumour thrombus. BJU Int. 2012;110(7):926–939.
– Mobilize the liver and divide minor hepatic veins ONGOING CARE 4. Pouliot F, Shuch B, Larochelle JC, et al.
to expose the intrahepatic IVC
– Place Rummel tourniquets or vascular clamps PROGNOSIS Contemporary management of renal tumors with
sequentially on the infrarenal vena cava, r Prognostic factors include TNM stage, nuclear venous tumor thrombus. J Urol. 2010;184(3):
contralateral RV, and suprarenal vena cava above grade, presence of necrosis, histologic type (worse 833–841.
the thrombus for unclassified RCC and collecting duct
– Incise IVC, remove the thrombus and kidney carcinomas), sarcomatoid features, invasion into
– Flush-exposed IVC with heparinized saline adjacent structures (renal sinus, perinephric fat, ADDITIONAL READING
– Suture cavotomy; release vascular clamps hepatic veins, collecting system, RV ostium), ECOG None
r Level III–IV Thrombus Specifics performance status, presence of lymph nodes, and
– A wide variety of surgical approaches have been distant metastasis See Also (Topic, Algorithm, Media)
r Prognostic significance of tumor thrombus level r Deep Venous Thrombosis and Pulmonary Embolus,
described
– Clamping of the IVC at the this level can remains controversial Urologic Considerations
r Median survival for nonmetastatic disease: 38–116 r RCC, General
compromise hemodynamic stability
– Cardiopulmonary bypass: Used for IVTT above the mo; 5-yr disease specific survival 40–60% when all r Renal Cell Carcinoma, Locally Advanced (T3–T4)
diaphragm, maintains continuous arterial/venous gross disease is resected r Renal Cell Carcinoma with Tumor Thrombus
blood flow during IVC occlusion r Median survival for metastatic disease: 11–20 mo Image
– Deep hypothermic circulatory arrest (DHCA) cools and 5-yr disease specific survival is 4–30%. Patients r Renal Vein Thrombosis, Adult and Pediatric
the body and create a bloodless field that present with metastatic disease: 5-yr survival
– Venovenous bypass can be used for level II–IV 0–10%.
tumors. Venovenous bypass allows for continuous
COMPLICATIONS CODES
venous return to the heart while IVC is clamped. r Overall complication rate is 12.5%, however, the
– Pringle maneuver (clamping of the hepatic
complication rates vary greatly with level of tumor ICD9
pedicle) can be used to avoid hepatic congestion r 189.0 Malignant neoplasm of kidney, except pelvis
and/or IVC bleeding that may occur when IVC is thrombus.
r Perioperative death varies from 0.8–10%. There has r 453.2 Other venous embolism and thrombosis of
clamped above the hepatic veins (limit warm
hepatic ischemia to 20 min) been a reported rate of mortality up to 40% for level inferior vena cava
IV IVTT. r 453.3 Other venous embolism and thrombosis of
– Cephalad IVC control can be obtained by exposing
the intrapericardial IVC via pericardiotomy r Most common complications are hemorrhage, renal vein
– Langenbuch maneuver (medial mobilization of pulmonary embolism, wound infection, acute renal
ICD10
liver) to expose retrohepatic IVC failure, ileus, and need for additional surgery. r C64.9 Malignant neoplasm of unsp kidney, except
– Transesophageal echocardiography should be r The incidence of intraoperative tumor thrombus
renal pelvis
used for real-time intraoperative monitoring to embolization is 1.5% and is associated with 75% r I82.3 Embolism and thrombosis of renal vein
identify tumor emboli mortality rate. r I82.220 Acute embolism and thrombosis of inferior
– A multidisciplinary approach, including the r Cardiopulmonary bypass is a risk factor for stroke
involvement of cardiac, vascular, hepatic surgeons vena cava
(6% of cases) during nephrectomy for RCC with
as well as a specialized anesthesia team, is highly IVTT.
encouraged for these complex tumors
FOLLOW-UP CLINICAL/SURGICAL
Patient Monitoring PEARLS
r Surveillance based on TNM staging
r Surveillance labs include metabolic panel, liver Preoperative assessment of cephalad extent of
thrombus is critical for surgical planning.
function tests
r Surveillance imaging includes abdominal and
thoracic imaging
399
RENAL CELL CARCINOMA, GENERAL

Matthew A. Meissner, MD

BASICS r Clear cell and papillary RCC develop from the
Lab
proximal convoluted tubules. r Initial evaluation includes CBC, electrolytes,
DESCRIPTION r Chromophobe and collecting-duct RCC develop creatinine, LFTs, and UA
r Renal cell carcinomas (RCC’s) are malignant tumors r Elevated ESR is present in 56% of patients
from the distal convoluted tubule and collecting
of the kidney arising from different parts of the duct, respectively. r Stauffer syndrome found in 14.4% of patients
nephron r VEGF and TNF-α are growth factors altered in
r Majority of renal neoplasms are RCC (80%) – Characterized by abnormal LFTs from a
development and progression of RCC. paraneoplastic syndrome and not from liver
r RCC is typically resistant to conventional r Local invasion is common; 20% of cases have metastases
chemotherapy and radiation, making it primarily a invasion of the capsule or collecting system, and – Also find elevated alkaline phosphatase, PTT, low
surgical disease 10% have a tumor thrombus. albumin, elevated bilirubin, or transaminases
r Bilateral tumors occur 2–4% of the time with r Hypercalcemia seen in 13% overall, and in 4.9%
EPIDEMIOLOGY
Incidence sporadic RCC, either at diagnosis or metachronously. resulting from paraneoplastic syndromes
r Anemia may be due to blood loss
r 65,150 estimated new cases of RCC in 2014 in ASSOCIATED CONDITIONS
r For ESRD patients there is a 5–20-fold increase in Imaging
USA (39,140 in men and 24,780 in women); r Thin-slice renal CT scan with and without IV contrast
12 new cases per 100,000/yr (1)[B] risk of developing RCC, most commonly papillary
r Male > Female, 3:2 subtype. is the best test for diagnosing renal masses
r Acquired renal cystic disease in conjunction with r Any enhancing lesion on CT or MRI is RCC until
r Increase in incidence since the 1970s of 3–4%/yr
ESRD has a 1–2% risk of developing RCC. proven otherwise
due to increased use of abdominal CT r VHL-related RCC is associated with retinal angioma, – Enhancement generally defined as ≥20 HU
r Estimated 13,860 deaths will occur in 2014 from pancreatic cysts, cerebellar and spinal increase between contrast and noncontrast phases
RCC in USA (1)[B] hemangioblastomas, and neuroendocrine tumors. r R.E.N.A.L. Nephrometry score may provide a
r Primarily occurs in 6th–7th decade of life r BHD-related RCC is associated with facial standardized system for radiologic comparison of
r 2–3% are familial; majority are sporadic fibrofolliculomas in addition to lung cysts and renal masses (See RENAL Nephrometry in Section II)
spontaneous pneumothoraces. r Any renal mass with a negative CT attenuation
Prevalence (<−20 HU) consistent with fat density is an AML
r 3rd most common GU malignancy in men (prostate, GENERAL PREVENTION
r Smoking cessation reduces the relative risk of r Metastatic evaluation may include CT or MRI of the
bladder); most common urinary tract malignancy in
developing RCC by 20–50% abdomen, chest x-ray for pulmonary lesions, and a
women
r RCC represents 2.3–6.6% of all pediatric renal r Weight reduction: It is estimated that 40% of the bone scan in patients with elevated alkaline
phosphatase or bone pain
tumors cases of RCC in USA may be linked to obesity
RISK FACTORS r Biopsy of a renal mass is typically not included in the
r Tobacco exposure: 1.4–2.5 times increased risk, this DIAGNOSIS workup due to high false-negative rate, risk of
increases with duration, decreases after cessation bleeding, and remote possibility of seeding the
(2)[C] HISTORY biopsy tract
r Obesity r Most cases of localized RCC are asymptomatic and
– Difficult to distinguish between oncocytoma and
r Hypertension (HTN) has a 1.4–2-fold increase of >50% of cases are detected incidentally during
RCC on biopsy
RCC abdominal imaging for other reasons.
r Classic Triad: Flank pain, palpable flank mass, and – 83–90% of solid renal masses thought to be RCC
r Family history in a 1st- or 2nd-degree relative are confirmed on final pathology
associated with a relative risk of 2.9 of developing hematuria. This is rarely seen except in advanced – Sensitivity and specificity of FNA biopsy is 80%
RCC disease. and 95%, which is no better than imaging alone
r Other potential environmental factors include r Paraneoplastic symptoms found in 20% of patients. r Biopsy helps differentiate primary renal neoplasms
viruses, lead compounds, and aromatic These include hypercalcemia (due to paraneoplastic from metastasis or renal lymphoma
hydrocarbons phenomena or osteolytic bone involvement), HTN, r Biopsy is now considered more frequently in
polycythemia.
Genetics r Constitutional symptoms such as fever, weight loss, patients being considered candidates for
r Clear-cell RCC is associated with chromosomal 3p observation vs. surgical extirpation
and anemia are thought to be due to paraneoplastic – Biopsy is being used for surveillance in small RCC
deletion and/or mutations of VHL gene syndromes. with >90% accuracy with adequate specimens
r Alterations of chromosome 3p25–26 lead to
PHYSICAL EXAM Pathologic Findings
clear-cell RCC in VHL syndrome (3)[A] r Physical exam findings are usually absent, except in r RCCs are adenocarcinomas, arising from renal
r Nonhereditary papillary RCC is linked to changes in cases of advanced disease. tubular epithelial cells
chromosomes 7 and 17 r Deep palpation for upper quadrant masses and r Clear cell RCC (formerly known as “conventional
r Hereditary pRCC typically involves type 1 pRCC and auscultation for a renal artery bruit should be RCC”) 70–80% of RCC
is due to missense mutations of the c-met included in the abdominal exam. r Papillary RCC accounts for 10–15%
proto-oncogene r Assess for a varicocele with a careful testicular exam
r Chromophobe RCC is a result of allelic loss of – Type 1: Associated with Hereditary papillary renal
as venous outflow obstruction can occur due to a cell carcinoma (HPRCC)
chromosome 17 renal vein tumor thrombus. An epididymal mass may – Type 2: Aggressive, associated with Hereditary
r Birt–Hogg–Dubé syndrome (BHD) includes be seen in VHL-related disease. leiomyomatosis and renal cell cancer (HLRCC)
cutaneous manifestations, spontaneous r Chromophobe 3–5% of solid renal masses,
pneumothoraces, and chromophobe RCC, renal associated with a good prognosis
oncocytomas, or hybrid tumors consisting of both r Collecting duct (Bellini) RCC is rare (<1%), but
due to mutations in BHD gene on chromosome 17 associated with a very poor prognosis. Occurs in
r Translocation Xp11.2 Translocation carcinoma;
younger patients (3rd–5th decades of life).
predominantly younger patients
400
RENAL CELL CARCINOMA, GENERAL

R
r Renal medullary RCC found in African Americans ADDITIONAL TREATMENT REFERENCES
with sickle cell trait, and is often metastatic at the Radiation Therapy
time of diagnosis Radiation is limited to palliation of systemic 1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics,
r Furhman nuclear grading: Graded 1–4 according to metastases; no role in the management of clinically 2014. CA Cancer J Clin. 2014;64(1):9–29.
localized RCC 2. Parker AS, Cerhan JR, Janney CA, et al. Smoking
nuclear aberrations in RCC. Independent prognostic
cessation and renal cell carcinoma. Ann Epidemiol.
indicator with higher grades portending worse Additional Therapies
r Resection of solitary metastatic lesions (ie, lung) 2003;13:245–251.
outcomes (4)[B]
r Sarcomatoid differentiation: Reported as presence 3. Linehan WM, Walther MM, Zbar B. The genetic
may be useful in selected cases
r No role for adjuvant systemic therapy in localized basis of cancer of the kidney. J Urol. 2003;170:
and extent found in the primary histologic subtype; 2163–2172.
not a distinct category. Associated with a worse RCC
4. Pantuck AJ, Zisman A, Belldegrun A. Biology of
prognosis Complementary & Alternative renal cell carcinoma: Changing concepts in
DIFFERENTIAL DIAGNOSIS Therapies classification and staging. Semin Urol Oncol.
r Adrenal mass Renal masses <2 cm can be observed in many 2001;19:72–79.
r Angiomyolipoma (fat poor) patients including those who are poor surgical 5. Campbell SC, Lane BR. Malignant renal
r Collecting duct tumor (Bellini) candidates (∼30% benign). tumors.Chapter 49. In: Wein AJ, ed.
r Cystic nephromas (multilocular cystic nephroma) Campbell-Walsh Urology. 10th ed. Philadelphia,
r Cysts (hemorrhagic, infected) ONGOING CARE PA: Saunders/Elsevier; 2011:1413–1474.
r Focal pyelonephritis 6. Eggener S, Reiher FK, Campbell SC. Surveillance for
r Hemangioma PROGNOSIS renal cell carcinoma after surgical management.
r The single most important prognostic factor for RCC Am Urol. 2001;20:202–207.
r Inflammatory masses (xanthogranulomatous
is pathologic stage (5):
pyelonephritis, abscess, infected calyceal
– pT1a: 90–100% 5-yr survival
diverticulum) ADDITIONAL READING
r Leiomyoma – pT1b: 80–90% 5-yr survival
r Metanephric adenoma – pT2: 70–80% 5-yr survival r Kattan MW, Reuter V, Motzer RJ, et al. A
– pT3: 45–69% 5-yr survival in the absence of
r Metastasis from other primary tumor postoperative prognostic nomogram for renal cell
nodal or systemic metastases
r Oncocytoma – pT4: 0–20% 5-yr survival in the absence of nodal carcinoma. J Urol. 2001;166:63–67.
r Pseudotumors (hypertrophied column of Bertin, or r Kutikov A, Uzzo RG. The R.E.N.A.L. Nephrometry
or systemic metastases
fetal lobulations: Can mimic a central tumor, r Direct invasion ipsilateral adrenal: 0–30% 5-yr Score: A comprehensive standardized system for
particularly in congenitally solitary kidneys) survival; node-positive RCC: 0–20% 5-yr survival; quantitating renal tumor size, location, and depth.
r Renal cell carcinoma metastatic RCC: 0–10% 5-yr survival J Urol. 2009;182:844–853.
r Renal lymphoma r Paraneoplastic syndromes, poor performance status, See Also (Topic, Algorithm, Media)
r Renal medullary carcinoma (sickle cell trait) weight loss >10% worse outcome r Birt–Hogg–Dubé Syndrome
r Renal sarcomas r Other important prognostic factors include Fuhrman r Renal Cell Carcinoma, General Image
r Reninoma (JG apparatus tumors) nuclear grade, histologic subtype, sarcomatoid r Renal Cell Carcinoma, Localized (T1–T2)
r Urothelial carcinoma features. Nomograms exist to predict risk of r Renal Cell Carcinoma, Locally Advanced (T3–T4)
r Wilms tumor (nephroblastoma) recurrence based on the above features. r Renal Cell Carcinoma, Metastatic (N+, M+)
COMPLICATIONS r Renal Cell Carcinoma, Pediatric
r Surgical complications include bleeding, infection, r Renal Mass
TREATMENT urine leak, damage to surrounding structures r Reference Tables: TNM: Kidney Cancer
including bowel, liver, spleen r Von Hippel–Lindau Disease/Syndrome
GENERAL MEASURES r Large or locally invasive tumors may compromise GI
r Surgical extirpation (radical or partial nephrectomy)
or pulmonary function
is the primary treatment for solid renal masses r Bone metastases may result in pain and pathologic
r Radical nephrectomy: Removal of the entire kidney, CODES
fractures
perinephric fascia, lymph nodes, and ipsilateral r Paraneoplastic syndromes causing cachexia,
adrenal gland in upper pole tumors ICD9
bleeding, HTN r 189.0 Malignant neoplasm of kidney, except pelvis
MEDICATION r 599.70 Hematuria, unspecified
FOLLOW-UP
First Line r 789.09 Abdominal pain, other specified site
Systemic immunotherapy and targeted molecular Patient Monitoring
r See follow-up recommendations in “Renal Cell
therapies have no role in clinically localized RCC ICD10
Carcinoma, Localized (T1–T2)” r C64.9 Malignant neoplasm of unsp kidney, except
Second Line r Incidence of local recurrence and the development
N/A renal pelvis
of systemic metastases are directly associated with r R10.9 Unspecified abdominal pain
SURGERY/OTHER PROCEDURES tumor stage (6)[B]: r R31.9 Hematuria, unspecified
r Partial nephrectomy is now the standard of care for
– T1: 0% local; 4% metastatic
clinical T1 renal masses (≤7 cm) in patients with a – T2: 2% local; 5.3% metastatic
normal contralateral kidney who are surgical r Surveillance is tailored to tumor stage CLINICAL/SURGICAL
candidates. Oncologic outcomes equal to radical
nephrectomy in selected patients. Renal function is Patient Resources PEARLS
r Kidney Cancer Association www.kidneycancer.org
preserved. r Most common solid renal mass is clear cell RCC.
r Radical nephrectomy is the standard of care for r National Cancer Institute, Kidney Cancer
r Most renal masses are detected incidentally.
large tumors, and for patients with metastases www.cancer.gov/cancertopics/types/kidney r VHL syndrome is associated with chromosome 3p
undergoing cytoreductive nephrectomy.
r Radiofrequency ablation/cryoablation minimally deletion and RCC, as well as other tumors.
r Surgical removal is the mainstay of treatment for
invasive; considered in selected small masses.
RCC.
r Partial nephrectomy is increasingly utilized for larger,
clinically localized tumors.
401
RENAL CELL CARCINOMA, LOCALIZED (T1–T2)

Reza Mehrazin, MD
Robert G. Uzzo, MD
r Histology, grade, and stage are independent factors Imaging

BASICS that correlate with survival r Pre- and postcontrast-based CT or MRI is essential
– Lower risk: Low-grade (type I) papillary, (>20 Hounsfield units enhancement on CT of
DESCRIPTION chromophobe, and oncocytic carcinomas >20% increase in postcontrast region of interest
r Renal cell carcinoma (RCC) refers to an – Intermediate risk: Clear cell tumors (ROI) on MR)
adenocarcinoma and is the most common type of – High risk: Collecting duct carcinomas, sarcomatoid r US can usually distinguish cystic from solid masses.
renal neoplasm. Stage T1 and T2 differ by size and clear cell carcinomas, renal medullary carcinomas Hyperdense cyst which may look solid and exhibit
are localized to the parenchyma with no extension associated with sickle cell pseudoenhancement. CT or MRI (not US) is used to
outside the capsule. r Lesions <4 cm: Up to 20–30% can be benign. assign Bosniak grade.
r Stage T1 is further classified as T1a (tumor <4 cm) Progression to metastasis appears to be a late event r Extent of disease evaluation includes CXR or CT
or T1b tumor (4–7 cm). Stage T2 is confined to the although up to 3–5% of small renal masses can chest. Bone scan and CNS imaging performed if
kidney and further classified as T2a (tumor present with synchronous metastases. symptoms/signs mandate.
7–10 cm) and T2b (>10 cm). r In highly selected series, median radiographic r FDG-PET not useful in evaluation of T1/T2 RCC due
EPIDEMIOLOGY growth rate during a period of active surveillance for to low sensitivity and specificity
a small renal mass is 0.08–0.58 cm/yr with mean
Incidence Pathologic Findings
r 63,920 new cases; 13,570 deaths in USA in 2014 growth rate of ∼0.28 cm/yr (1) r Staging (see “TNM Staging” section)
– Most lethal of all GU neoplasms (21% of those ASSOCIATED CONDITIONS r Needle biopsy:
diagnosed will ultimately die of disease) r Extrarenal manifestations associated with RCC – Appropriate if wide range of options are under
r Male > Female (∼1.7:1) typically part of hereditary syndromes (such as Von consideration (focal therapy vs. observation)
– 7th most frequent tumor in men (lifetime risk 1:61 Hippel-Lindau syndrome [VHL], Hereditary – Needle-tract seeding very uncommon
in men and 1:103 in women) leiomyomatosis and renal cell cancer [HLRCC], – Good at distinguishing cancer and histologic type.
r Peak incidence: 6th and 7th decades of life Birt–Hogg–Dubé [BHD]) Unreliable for tumor grade.
r 10–20% higher incidence in African Americans r Renal medullary carcinomas associated with sickle
r 96% of cases are sporadic, whereas 4% are cell trait are highly aggressive (mean survival: r Adrenal mass
associated with familial syndromes 12–15 mo) and present during 3rd decade of life r Angiomyolipoma (fat poor)
RISK FACTORS GENERAL PREVENTION r Collecting duct tumor (Bellini)
r Only accepted environmental risk factor is tobacco N/A r Cystic nephromas (multilocular cystic nephroma)
exposure: Increases relative risk by 1.4–2.5. All r Cysts (hemorrhagic, infected)
forms of tobacco implicated; Risk increases with DIAGNOSIS r Focal pyelonephritis
cumulative exposure r Hemangioma
r Family history, obesity, hypertension, end stage renal HISTORY r Inflammatory masses (xanthogranulomatous
disease (ESRD), autosomal dominant polycystic r Most stage T1/T2 lesions are asymptomatic,
pyelonephritis, abscess, infected calyceal
kideny disease (ADPCKD) and horseshoe kidney incidentally discovered on cross-sectional imaging
diverticulum)
have all been implicated but not proven to be for unrelated reasons r Leiomyoma
genetic or acquired risk factors r Symptoms of more advanced disease include
r Metanephric adenoma
Genetics hematuria, flank pain, fever, weight loss (>10% of r Metastasis from other primary tumor
r 3p25 (VHL gene) (tumor suppressor) implicated in total body weight), bone pain
r Oncocytoma
>70% of all acquired (somatic mutations) cases of PHYSICAL EXAM r Pseudotumors (hypertrophied column of Bertin, or
clear cell RCC. In cases of germ line Von Hippel- r In stage T1/T2 disease, typically few physical
fetal lobulations: Can mimic a central tumor,
Lindau syndrome (VHL) mutation, additional findings. Larger tumors may be palpable or particularly in congenitally solitary kidneys)
manifestations include retinal angiomas, CNS symptomatically compressing on adjacent organs. r RCC
hemangioblastomas, epididymal cystadenomas, r Palpable abdominal mass, lymphadenopathy,
r Renal lymphoma
endolymphatic sac tumors, pancreatic cysts, islet cell nonreducing or rapid onset of varicocele may r Renal medullary carcinoma (sickle cell trait)
tumors, and pheochromocytomas. suggest advanced disease (renal vein or IVC
r 7q31 (cMet gene) (oncogene) implicated in papillary r Renal sarcomas
involvement)
type I RCC. With germ line mutations there are no r Absence of symptoms or findings on physical exam r Reninoma (JG apparatus tumors)
known extrarenal manifestations. r Urothelial carcinoma
does not rule out advanced disease
r 17p11 (Birt–Hogg–Dubé/folliculin gene) (tumor r Wilms tumor (nephroblastoma)
suppressor) implicated in cases of chromophobe/ DIAGNOSTIC TESTS & INTERPRETATION
oncocytoma. With germ line mutations can see: Lab
r CBC: Anemia may suggest worse prognosis, TREATMENT
Cutaneous fibrofolliculomas, nevus, PTH adenomas,
colonic polyps/tumors and pneumothorax. polycythemia may suggest paraneoplastic state
r 1q42 (HLRCC gene) (Tumor suppressor) HLRCC r Serum creatinine: eGFR clearance better estimate of GENERAL MEASURES
r To avoid future renal insufficiency and metabolic
syndrome (type II papillary RCC) manifestations renal function. Calculate CKD stage.
include painful cutaneous leiomyomas, and uterine r Liver function tests: If abnormal consider Stauffer disturbances, assess global renal function (eGFR)
fibroids syndrome (reversible hepatitis), metastasis, or biliary and consider nephron-sparing approaches,
duct obstruction especially in those patients with low-to-intermediate
PATHOPHYSIOLOGY r Calcium: Elevated in paraneoplastic syndromes due complex renal masses and reasonable life
r RCC arises from the proximal convoluted tubule. expectancy
to PTH-like substances r For T1/T2 lesions, depending on pathology, surgery
Chromophobe, oncocytoma, and papillary tumors, r Alkaline phosphatase: Elevation suggests bone or
believed to arise from the distal tubule. by radical or partial nephrectomy is highly likely to
r Tumors may grow locally and/or systemically liver involvement
result in a long-term cure
concurrently. Local symptoms occur late and renal r For T1 tumors radical and partial nephrectomy
insufficiency is rare even with large tumors. appear cancer equivalent. For T2 tumors partial is
emerging as oncologically equivalent option (2).
402
RENAL CELL CARCINOMA, LOCALIZED (T1–T2)

R
MEDICATION REFERENCES
r Localized RCC is a surgical disease. Limited role for 1. Smaldone MC, Kutikov A, Egleston BL, et al. Small
tyrosine kinase inhibitors and antiangiogenic PROGNOSIS renal masses progressing to metastases under
r Related to stage, grade, histology. Nomograms active surveillance: A systematic review and pooled
therapy in localized RCC.
r Control of blood pressure, diabetes, lipids and available to calculate risk at analysis. Cancer. 2012;118:997–1006.
minimization of atherosclerotic risk factors www.cancernomograms.com. 2. Long CJ, Canter DJ, Kutikov A, et al. Partial
r Local recurrence after resection is ∼2–3% after nephrectomy for renal masses ≥7 cm: Technical,
(smoking) are all important to subsequent renal
function mandating physician involvement and radical nephrectomy and 4–6% after partial oncological and functional outcomes. BJU Int.
patient counseling depending on pathology 2012;109(10):1450–1456.
r Use of ACE inhibitors or angiotensin receptor r 5-yr risks of recurrence for local or regional RCC fully 3. Uzzo RG, Novick AC. Nephron sparing surgery for
blockers may slow hyperfiltration injury excised are approximately: renal tumors: Indications, techniques and
– 5–9% low-risk disease outcomes. J Urol. 2001;166:6–18.
Second Line – 20–25% intermediate-risk disease 4. Simhan J, Smaldone MC, Tsai KJ, et al. Objective
N/A – 60–80% high-risk disease measures of renal mass anatomic complexity
SURGERY/OTHER PROCEDURES r Prognosis for partial nephrectomy with a positive predict rates of major complications following
r Approach is dictated by many factors (3) including margin is less clear. Related to pathology and partial nephrectomy. Eur Urol. 2011;60(4):
patient risks (comorbidities, underlying renal biology. Every attempt should be made 724–730.
function, prior surgeries, trade-offs), tumor risk intraoperatively to avoid a positive surgical margin; 5. Mehrazin R, Palazzi KL, Kopp RP, et al. Impact of
(size/location of the tumor, complexity of the mass with focal positive margin, close observation is often tumor morphology on renal functional decline after
[ie, nephrometry score—www.nephrometry.com], indicated. partial nephrectomy. BJU Int. 2013;111(8):
number of lesions), hospital and physician factors COMPLICATIONS E374–E382.
r Excision: Partial or radical nephrectomy via open, r Acute surgical/medical risks depend on treatments,
laparoscopic, or robotic techniques techniques, comorbidities, and complexity of the
r Nephron-sparing surgery:
mass. Overall perioperative death rate <0.5%. Risk ADDITIONAL READING
– Partial nephrectomy is the standard of care for of major Clavien grade 3–5 complications: 6.4%, r AUA Guideline for Management of the Clinical
masses T1 in young otherwise healthy individuals 11.1%, 21.9% for low-, intermediate-, and
for absolute, relative, and elective indications. Stage 1 Renal Mass, 2009: http://www.auanet.
high-complexity lesions (4). org/content/media/renalmass09.pdf
Removal of mass with a small rim of normal r Risks after partial nephrectomy: Urinary leak/ r NCCN Guidelines: www.NCCN.org
parenchyma. fistulas, AVF, bleeding, transient or permanent
– Other indications for partial nephrectomy: decline in renal function (5) See Also (Topic, Algorithm, Media)
Absolute indications (patients with bilateral renal r Increased risk of Nephrogenic systemic fibrosis r Birt–Hogg–Dubé Syndrome
masses, a tumor in a solitary kidney) and relative (NSF), with gadolinium (eGFR <30 mL/min r Renal Cell Carcinoma, General
indications (existing or comorbidities with per 1.73 m2 ) and/or risk of contrast-induced r Renal Cell Carcinoma, Localized (T1–T2) Image
potential for future renal insufficiency) nephropathy following use of iodinated contrast for r Renal Cell Carcinoma, Locally Advanced (T3–T4)
– Enucleation (removal of mass by dissection radiographic surveillance r Renal Cell Carcinoma, Metastatic (N+, M+)
between normal parenchyma and pseudocapsule r Renal Cell Carcinoma, Pediatric
of the tumor) is acceptable for small and/or FOLLOW-UP
r Renal Mass
multiple renal masses as long as negative margins Patient Monitoring
are achieved r Periodic history, physical (including BP monitoring), r Reference Tables: TNM: Kidney Cancer
r Bilateral (synchronous) RCC: ∼1–6%. Stage and selected lab studies (calcium, hemoglobin, liver, r Von Hippel–Lindau Disease/Syndrome
surgeries (Nephron sparing surgery (NSS) on easier renal profiles, urine analysis) at least yearly
side 1st as it provides more options for the difficult r Radiographic stage/grade/histology-specific
side). Can alter if there is a large discrepancy surveillance mandatory based on clinical stage and CODES
between complexity, size, and risks of the two sides. mode of treatment. Surveillance may be adjusted for
r Ablation: Cryoablation or radio frequency ablation other risk factors (grade/histology). ICD9
(RFA) by minimally invasive surgery (MIS) or r Following ablation, initial radiographic follow-up
189.0 Malignant neoplasm of kidney, except pelvis
percutaneous (preferred) technique: requires lack of enhancement on pre-/
– Best with advanced age, significant comorbidities, postcontrast-based CT or MRI at 3–6 mo after ICD10
r C64.1 Malignant neoplasm of right kidney, except
and potentially amenable recurrence after prior procedure. Biopsy confirmation of successful
NSS ablation is recommended. Occasionally after renal pelvis
r C64.2 Malignant neoplasm of left kidney, except
– Best: <3.5 cm, peripheral, solid, exophytic, cryotherapy, an area of rim enhancement can be
remote from vessels/collecting system seen that should resolve within 1st 3 mo. renal pelvis
– Survival data are short term and there are no r NCCN (National Comprehensive Cacner Network) r C64.9 Malignant neoplasm of unsp kidney, except
definitive data to date proving that ablation guidelines (level of evidence 2B—lower level but renal pelvis
impacts tumor biologic potential consensus recommended)
r Active surveillance: Elderly or with significant – Every 6 mo for 2 yr, then annually for 5 yr: History,
medical risks. Serial radiographic surveillance with physical, metabolic panel
CLINICAL/SURGICAL
assessment of the growth kinetics of the untreated – At 2 yr (based on recurrence risk) chest and PEARLS
mass and continued reassessment. abdominal ± pelvic imaging then risk based r Always review the images and carefully assess the
ADDITIONAL TREATMENT Patient Resources presence of the contralateral kidney and the adrenal
r Kidney Cancer Association www.kidneycancer.org
Radiation Therapy glands.
r No role in localized RCC outside of clinical trials of r National Cancer Institute, Kidney Cancer r Do not overtreat or undertreat renal mass.
focal radiotherapy (CyberKnife) or HIFU www.cancer.gov/cancertopics/types/kidney
r Used for painful bony metastases and CNS
metastasis in advanced RCC
N/A
Therapies
N/A
403
RENAL CELL CARCINOMA, LOCALLY ADVANCED (T3–T4)

Ahmad Shabsigh, MD, FACS

BASICS r 20% of cases will have frank invasion of the capsule r Palpable abdominal mass
or collecting system. r Flank or abdominal tenderness
DESCRIPTION r 10% will demonstrate venous involvement with r Bilateral lower-extremity edema
r T3 renal cell carcinoma (RCC) extends into major r Isolated right-sided varicocele, or one that does not
tumor thrombus.
veins or perinephric tissues but not into the r Adjacent organs are usually compressed by growing decompress
ipsilateral adrenal gland and not beyond Gerota tumor, whereas direct invasion of liver, spleen, r Caput medusa (dilated abdominal veins)
fascia. colon, pancreas, diaphragm, and duodenum are rare
– T3a tumor grossly extends into the renal vein or its but associated with very poor prognosis. DIAGNOSTIC TESTS & INTERPRETATION
segmental (muscle containing) branches, or tumor Lab
invades perirenal and/or renal sinus fat but not ASSOCIATED CONDITIONS r LFTs, creatinine, electrolytes, CBC, and urine analysis
r Acquired renal cystic disease in conjunction with
beyond Gerota fascia. are standard initial evaluation, serum calcium
– T3b tumor grossly extends into the vena cava ESRD has a 1–2% risk of developing RCC, an overall r Elevated ESR is present in 55.6%
below the diaphragm. 5–20-fold increase in risk of RCC for ESRD patients r Abnormal liver function tests (LFT’s) are found in
– T3c tumor grossly extends into the vena cava r VHL-related RCC:
14.4%, which is called Stauffer syndrome if
above the diaphragm or invades the wall of the – Retinal angioma
elevation is due to paraneoplastic syndrome and not
vena cava. – Cerebellar and spinal hemangioblastoma
r T4 RCC invades beyond Gerota fascia (including due to liver metastases
– Pancreatic cysts
– Stauffer syndrome:
contiguous extension into the ipsilateral adrenal – Neuroendocrine tumors ◦ Elevated alkaline phosphatase
gland). r Facial fibrofolliculomas in the malar region, lung
◦ Increased PTT
cysts, and spontaneous pneumothoraces are ◦ Low albumin, and sometimes elevated bilirubin
EPIDEMIOLOGY associated with BHD-related RCC
Incidence r Familial leiomyomatosis and RCC: or transaminases
r 63,920 new cases in USA in 2014 (39,140 in men r Elevated serum calcium is seen in up to 13% overall
– Type 2 papillary RCC and in 4.9% as a result of paraneoplastic syndromes
and 24,780 in women) – Cutaneous leiomyomas
r 13,860 deaths in USA in 2014 r Polycythemia can be detected in 3.5%
– Uterine leiomyomas r Elevated C-reactive protein
r 20% of patients present with locally advanced or r Birt–Hogg–Dubé syndrome:
node-positive RCC – Chromophobe RCC Imaging
r RCC with IVC involvement is seen in 4–10% of r CT scan with IV contrast if renal function is
– Oncocytoma
patients – Occasional clear cell RCC acceptable.
– Cutaneous fibrofolliculomas r MRI is generally considered best for IVC tumor
Prevalence
8.3–12 new cases per 100,000 per year – Lung cysts thrombus evaluation, although multiplanar CT with
– Spontaneous pneumothorax contrast is similar in accuracy.
RISK FACTORS r Possibly an increased risk of RCC in individuals with r Transabdominal US with color Duplex imaging can
r Cigarette smoking results in a 1.4–2.5 increased
TS be used but may not be as accurate in evaluation of
risk of RCC; risk increases with higher pack/yr the extent of thrombus (85% accuracy).
consumption, may not be as much of a factor for GENERAL PREVENTION r Transesophageal echocardiography (TEE) can be
r Smoking cessation
women as men.
r Obesity: 40% of RCC may be attributed to r Physical activity helpful pre-op and intraoperatively (1).
r Venacavography is only for those who cannot have
overweight or obesity. r Weight loss
r A positive family history of RCC in a 1st- or r Questionable association with certain foods and an MRI or have an indeterminate MRI.
r Nonfunction of affected kidney may indicate
2nd-degree relative carries a relative risk of 2.9 of alcohol consumption
extensive venous thrombus formation.
developing RCC. r Chest CT: Evaluate for pulmonary metastasis.
r HTN has a 1.4–2-fold increase in risk of RCC.
DIAGNOSIS r CT or MRI of the brain if symptomatic.
r Low socioeconomic status, urban background, and
parity have been associated with an increased risk HISTORY Diagnostic Procedures/Surgery
of RCC. r The classic triad of symptoms: Flank pain, palpable Biopsy or FNA has a role in differentiating RCC from a
flank mass, and hematuria are rarely seen since the renal metastasis of another primary and from renal
Genetics
r Nonhereditary clear cell RCC is associated with advent of CT scanning. lymphoma; rarely used for routine diagnosis except in
r Associated symptoms are due to local tumor cases of percutaneous ablation
deletion of chromosome 3p and/or mutations of the
VHL gene. growth, hemorrhage, paraneoplastic syndromes Pathologic Findings
r VHL manifests clear cell RCC due to alterations of (hypercalcemia, hypertension, polycythemia, r Tumors with histologic necrosis are almost twice as
the VHL gene on chromosome 3p25–26. Stauffer’s syndrome), or metastatic disease and likely to have lymph node metastases as those
r Nonhereditary papillary RCC has been linked with generally indicate advanced disease. without necrosis.
r Locally invasive RCC causes pain from invasion of r All RCC are adenocarcinomas, arising from renal
changes in both chromosome 7 and 17.
r Hereditary papillary renal cell carcinoma (HPRCC) posterior abdominal wall, nerve roots, or tubular epithelial cells.
paraspinous muscles. r Clear cell RCC is 70–80%.
arises from mutation of the MET protooncogene on
r History of pulmonary embolism should increase r Higher Fuhrman nuclear grading is linked to worse
chromosome 7p34.
r Chromophobe RCC: Loss of chromosome 17. index of suspicion for venous thrombus in patient outcome and more aggressive disease.
r Birt–Hogg–Dubé syndrome develops from changes with kidney mass. r Papillary RCC makes up 10–15% and has
r Caput medusa 2 subtypes:
in the BHD1 gene on chromosome 17p11.2.
r FH (fumarate hydratase) mutations on chromosome r Early satiety or emesis – Type 1 associated with HPRCC: Basophilic cells
r Varicocele, lower-extremity edema with low-grade nuclei
1q42 in hereditary leiomyomatosis: Predispose to
papillary Type 2 RCC. r Lower-extremities edema – Type 2 very aggressive and associated with
r Mutations in the TSC1/2 genes predispose to HLRCC: Eosinophilic cells with high-grade nuclei
– Immunohistochemistry (IHC): Low molecular
tuberous sclerosis.
weight cytokeratins (LMWCKs), CK7 (type 1 >
type 2), alpha-methylacyl-CoA racemase (AMACR)
positive in over 75%
404
RENAL CELL CARCINOMA, LOCALLY ADVANCED (T3–T4)

R
r Chromophobe RCC is 3–5% of solid renal masses Additional Therapies 3. Blute ML, Leibovich BC, Cheville JC, et al. A
and may be less aggressive. Targeted agents to growth factors are being evaluated protocol for performing extended lymph node
r Collecting duct RCC is rare (<1%) but very lethal. in both an adjuvant and neoadjuvant setting for dissection using primary tumor pathological
r Medullary carcinoma associated with sickle cell trait patients at high risk for recurrence (4). features for patients treated with radical
in young African Americans, is often advanced and Complementary & Alternative nephrectomy for clear cell renal cell carcinoma.
metastatic at the time of diagnosis; death occurs J Urol. 2004;172:465–469.
Therapies
within a few months of diagnosis. None proven 4. Cost NG, Delacroix SE Jr, Sleeper JP, et al. The
r Sarcomatoid variants of all subtypes have been impact of targeted molecular therapies on the level
described and are associated with a worse of renal cell carcinoma vena caval tumor thrombus.
prognosis. ONGOING CARE Eur Urol. 2011;59:912–918.
DIFFERENTIAL DIAGNOSIS PROGNOSIS
r Adrenal mass r T3a: 60–80% 5-yr survival
r Angiomyolipoma (fat poor) r T3b/c: 40–60% 5-yr survival
ADDITIONAL READING
r Collecting duct tumor (Bellini) r T4: 0–20% 5-yr survival r Hass NB, Uzzo RG. Targeted therapies for kidney
r Cystic nephromas (multilocular cystic nephroma) r Ipsilateral adrenal involvement has 0–40% 5-yr cancer in urologic practice. Urol Oncol. 2007;
r Cysts (hemorrhagic, infected) survival 25(5):420–432.
r Focal pyelonephritis r Node-positive RCC has 0–20% 5-yr survival r Thillai K, Allan S, Powles T, et al. Neoadjuvant and
r Hemangioma r For T4 tumors, the median time to recurrence is only adjuvant treatment of renal cell carcinoma. Expert
r Inflammatory masses (xanthogranulomatous Rev Anticancer Ther. 2012;12(6):765–776.
9.5 mo
pyelonephritis, abscess) See Also (Topic, Algorithm, Media)
r Leiomyoma COMPLICATIONS r Brit–Hogg–Dubé Syndrome
r Surgical complications are bleeding, infection, injury
r Metanephric adenoma r Renal Cell Carcinoma, Localized (T1–T2)
to surrounding organs (liver, spleen, bowel, r Renal Cell Carcinoma, Locally Advanced (T3–T4)
r Metastasis from other primary tumor pancreas). Urine leak in partial nephrectomy.
r Oncocytoma r Pulmonary embolism from tumor thrombus Image
r Renal lymphoma r Advanced tumors can bleed spontaneously either r Renal Cell Carcinoma, General
r Urothelial carcinoma r Renal Cell Carcinoma, Metastatic (N+, M+)
locally causing flank pain or into the urine resulting
r Wilms tumor (nephroblastoma) r Renal Cell Carcinoma, Pediatric
in hematuria and/or clot-induced urinary
obstruction. r Renal Mass
r Venous congestion resulting in bilateral r Reference Tables: TNM: Kidney Cancer
TREATMENT lower-extremity edema, varicoceles, or portal HTN r Von Hippel–Lindau Disease/Syndrome
from tumor thrombi into the renal, caval, or hepatic
GENERAL MEASURES vasculature.
r Preoperative renal artery embolization may cause
the tumor thrombus to regress and reduce the FOLLOW-UP CODES
morbidity of surgery as a result. Patient Monitoring
r Avoid IVC filter placement. r T3: Every 6 mo for 2 yr then annually for 5 yr: H+P, ICD9
r 189.0 Malignant neoplasm of kidney, except pelvis
comprehensive metabolic panel, LDH. Chest and
MEDICATION abdomen imaging at 2–6 mo then as indicated. r 198.89 Secondary malignant neoplasm of other
The role of neoadjuvant targeted therapies (eg, r T4: Every 3 mo history and physical exam, CXR, specified sites
sunitinib, sorafenib, others) for downsizing the primary
labs; every 6 mo abdominal CT for 3 yr
tumor and the IVC thrombus is controversial: 5–10% ICD10
reduction in primary site. Patient Resources r C64.1 Malignant neoplasm of right kidney, except
r Kidney Cancer Association www.kidneycancer.org renal pelvis
SURGERY/OTHER PROCEDURES r National Cancer Institute, Kidney Cancer r C64.9 Malignant neoplasm of unsp kidney, except
r Radical nephrectomy is standard of care.
r Nephron-sparing surgery is possible in selected www.cancer.gov/cancertopics/types/kidney renal pelvis
r C79.89 Secondary malignant neoplasm of other
patients with locally advanced RCC, with equivalent
specified sites
oncologic efficacy to radical nephrectomy (2). REFERENCES
r 45–70% of T3b patients can be cured with
aggressive surgery. 1. Glazer AA, Novick AC. Preoperative CLINICAL/SURGICAL
r No clear survival benefit of extended lymph node transesophageal echocardiography for assessment
dissection, except in HLRCC patients (3). of resonance imaging. Urology. 1997;49:32–34. PEARLS
r In patients with single lymph node metastasis or 2. Margulis V, Tamboli P, Jacobsohn KM, et al. r Detailed evaluation of extent of the disease is
micrometastasis, a regional lymphadenectomy may Oncological efficacy and safety of nephron-sparing critical.
be beneficial. surgery for selected patients with locally advanced r Consult vascular and/or cardiothoracic surgeon if
r Open or minimally invasive surgery is acceptable. renal cell carcinoma. BJU Int. 2007;100(6):
needed.
1235–1239.
Radiation Therapy
r Role is limited; no survival benefit to preoperative
treatment
r May slow growth if residual tumor left after surgery;
rarely used
r May palliate symptomatic local recurrences in
nonsurgical candidates
405
RENAL CELL CARCINOMA, METASTATIC (N+, M+)

Jianqing Lin, MD
Wm. Kevin Kelly, DO
BASICS DIAGNOSIS r Renal masses:
– Angiomyolipoma (fat-poor)
DESCRIPTION HISTORY – Collecting-duct tumors
r Advanced stage of renal cell carcinoma (RCC) r Usually no symptoms in early stage but incidental
– Cystic nephromas
– N1: Metastasis in regional lymph node(s) diagnosis of kidney mass. Metastasis may or may – Cysts (hemorrhagic, infected)
– M1: Distant metastasis not cause symptoms. – Focal pyelonephritis
– Nodal involvement is now simplified to N0 vs. N1 r Gross hematuria
– Hemangioma
r Other changes for staging from the AJCC Cancer r Flank or abdominal pain – Inflammatory masses (xanthogranulomatous
Staging Manual (7th edition): r Symptoms related to involved organ(s) pyelonephritis, abscess)
– Ipsilateral adrenal involvement is reclassified as T4 r Constitutional symptoms: – Leiomyoma
if contiguous invasion and M1 if not contiguous – Fatigue, weight loss, fever, or lower-extremity – Metanephric adenoma
– Renal vein involvement is reclassified as T3a edema – Metastasis from other primary tumor
– Oncocytoma
EPIDEMIOLOGY PHYSICAL EXAM
r With attention to abdominal mass, adenopathy, – Pseudotumors (column of Bertin, others)
Incidence – RCC
r Renal cancer increased by 2% per year for the past lower-extremity edema – Renal lymphoma
65 yr. Increased by 3.1% per year from 2005–2009 r Varicocele (classically on left)
– Renal medullary carcinoma
primarily due to an increase in early-stage disease. – Sarcomas
Renal cancer accounts for 2–3% of all malignancies. DIAGNOSTIC TESTS & INTERPRETATION
Lab – Reninoma (Juxtaglomerular tumors)
Median age of diagnosis is 65 yr, median age of r CBC: Anemia of chronic disease in up to 30% – Urothelial carcinoma
death is 70 yr. – Wilms tumor (nephroblastoma)
r Urinalysis: Hematuria
– 1/3 of patients with RCC present M+/N+ r Lymphadenopathy:
r 40–50% will develop metastatic disease after initial r Complete metabolic panel
r Paraneoplastic syndromes (found in 20% of – Inflammatory related to RCC
diagnosis. Male > Female (ratio is 3:2). – RCC
r Death rates for kidney cancer decreased by 0.5% patients): – Infectious/inflammatory:
per year from 2005–2009 – Hypercalcemia ◦ Granulomatous: TB, sarcoidosis, histoplasmosis,
– Hypertension lymphogranuloma venereum, Castleman
Prevalence – Erythrocytosis
N/A disease, etc.
– Elevated erythrocyte sedimentation rate (ESR) ◦ Nongranulomatous: Viral, bacterial (if abscess in
RISK FACTORS – Nonmetastatic hepatic dysfunction (Stauffer local areas), sinus histiocytosis
r Smoking syndrome) – Primary lymphatic malignancy: Lymphoma
r Obesity r Urine cytology: R/O urothelial carcinoma
(non-Hodgkin and Hodgkin, others)
r Hypertension and chronic renal failure – Other metastatic malignancies:
Imaging
Chemicals or radiation exposure slightly increases r MRI or CT of abdomen and pelvis (∼85% of ◦ Gastrointestinal (GI) (carcinoid, colorectal,
risk. enhancing renal masses are RCC) lymphoma), urothelial, prostate, melanoma,
r Rare hereditary conditions – Most enlarged lymph nodes by imaging are penile, germ cell, cervical, ovarian, uterine
– Von Hippel–Lindau (VHL) disease inflammatory rather than neoplastic r Pulmonary nodules:
– Hereditary papillary RCC r CNS imaging: In patients with symptoms or – Benign hamartoma/AVM, nonspecific granuloma,
Genetics radiographic evidence of advanced disease infectious granuloma (aspergillosis,
r Majority of cases are sporadic r Positron emission tomography (PET) has poor coccidioidomycosis, cryptococcosis,
r VHL tumor suppressor gene (on 3p25–26) sensitivity and not commonly used histoplasmosis, tuberculosis, atypical
associated with clear cell RCC mycobacterial infections), septic emboli, abscesses
Diagnostic Procedures/Surgery – Malignancy: Lung primary, metastasis
r Chromosome 7q31 is associated with papillary RCC, r Needle biopsy to the metastatic site or
(choriocarcinoma, RCC, melanoma, thyroid
type 1 associated with mutations in c-MET metastasectomy usually required to establish
r Fumarate hydratase (FH) associated with papillary carcinoma, Kaposi’s sarcoma), non-Hodgkin
diagnosis lymphoma
RCC type 2 r Needle biopsy is generally safe and warranted if any
r Birt–Hogg–Dubé (BHD) syndrome associated with uncertainty for M1 disease
chromophobic RCC Pathologic Findings TREATMENT
r Xp11.2 translocation: Patients under 45 yr r Histologic subtypes:
r BRCA1-associated protein-1 (BAP1) loss associated GENERAL MEASURES
– Clear cell: 70–80% r Stage IV disease may also benefit from cytoreductive
with high tumor grade – Papillary: 10–15% surgery
PATHOPHYSIOLOGY – Chromophobe: 3–5% r Minimal regional adenopathy does not preclude
r RCCs derived from renal tubular epithelium – Collecting duct/medullary cancer <1%
surgery
r Mode of spread is via direct extension, propagation – Translocation Xp11.2: Clear and/or eosinophilic, r Potential candidate for nephrectomy and/or surgical
into renal vein, or hematogenous voluminous cytoplasm
r Sarcomatoid variants all histologic subtypes: metastasectomy:
r Rare reports of spontaneous regressions, usually – Resectable primary RCC and a solitary resectable
pulmonary, following nephrectomy – Represent poorly differentiated regions
metastasis
– Portends a much more aggressive biology with
ASSOCIATED CONDITIONS – A solitary recurrence after prolonged disease-free
recurrence/resistance to therapy
r VHL syndrome interval from nephrectomy
r Chronic renal failure r Tends to be resistant to both traditional
r Lymphoma chemotherapy and radiation therapy
GENERAL PREVENTION
Smoking cessation helps prevent primary tumor
406
RENAL CELL CARCINOMA, METASTATIC (N+, M+)

R
r Antiangiogenesis via targeting vascular endothelial r Strongly consider metastasectomy for amendable 3. Hudes G, Carducci M, Tomczak P, et al.
growth factor (VEGF) pathway is the mainstay of and isolated solitary metastasis (synchronous or Temsirolimus, interferon alfa, or both for advanced
treatment; improve survival for M1 metachronous) renal-cell carcinoma. N Engl J Med. 2007;356:
r Multityrosine kinase inhibitors (TKI) or mTOR – Lymphadenectomy should be performed in 2271–2281.
inhibitors or monoclonal antibody radiographically suspicious cases; however, 4. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in
r Data for nonclear cell RCC therapy limited ultimate role and benefit is yet to be defined. advanced clear cell renal-cell carcinoma. N Engl J
r Sarcomatoid RCC: Gemcitabine- or capecitabine- or Med. 2007;356:125–134.
floxuridine- or 5-FU- or doxorubicin-based Radiation Therapy 5. Motzer RJ, Escudier B, Tomczak P, et al. Axitinib
chemotherapy (category 3 and limited data) versus sorafenib as 2nd-line treatment for
Palliative role for osseous or CNS metastasis or pain
r Other immunotherapy is under development advanced renal cell carcinoma: Overall survival
control
analysis and updated results from a randomised
MEDICATION Additional Therapies phase 3 trial. Lancet Oncol. 2013;14(6):552–562.
First Line r Many other agents under study and reported:
6. Flanigan RC. Debulking nephrectomy in metastatic
r High-dose (bolus) interleukin-2 (IL-2) (Aldesleukin, – Nonmyeloablative allogeneic hematopoietic cell renal cell carcinoma. Clin Cancer Res. 2004;10:
Proleukin) (1) transplantation 6335S–6341S.
– IL-2: Only agent shown to produce durable and – Interferon-γ , vaccines, other interleukins alone 7. Lara PN Jr, Tangen CM, Conlon SJ, et al. Predictors
complete responses (CR) in 6–8% of patients; and in combination of survival of advanced renal cell carcinoma:
Partial response 10–15% r Multiple studies under way addressing sequencing
Long-term results from SWOG Trial S8949. J Urol.
– 1st line. Selected patients: Mostly clear cell, and combination of targeted therapies along with 2009;181(2):512–516.
<65 yr old, good cardiac, pulmonary, liver and immunotherapy
renal function, no brain mets
– Typical regimen 600,000–720,000 IU/kg IV Q8h ADDITIONAL READING
Therapies
for 5 days. One course as 2 cycles on days 1–5 and
N/A r Motzer RJ, Bander NH, Nanus DM. Renal-cell
15–19 of 28-day cycle. If no progression, repeat
approximately every 3 mo to a max of 3 courses. carcinoma. N Engl J Med. 1996;335:865–875.
– Systemic inflammatory response syndrome (SIRS), ONGOING CARE r NCCN Guidelines. Available at http://www.nccn.
“capillary leak syndrome” side effects org/clinical.asp (Acessed August 20, 2014)
– “Treat as tolerated” significantly reduces PROGNOSIS
r 5-yr survival: Improving (7) See Also (Topic, Algorithm, Media)
treatment-related mortality r Renal Cell Carcinoma, General
r Sunitinib: Targets VEGF receptor tyrosine kinase and – Stage III: 15–35%
– Stage IV: 0–10% r Renal Cell Carcinoma, Localized (T1–T2)
other pathways (2)
– Enhanced survival with the following r Renal Cell Carcinoma, Locally Advanced (T3–T4)
– 1st line
– 50 mg/d PO for 4 wk of 6-wk cycle (4 wk on, 2 wk characteristics: Long interval between r Renal Cell Carcinoma, Metastatic (N+, M+)
off) nephrectomy and the appearance of distant Image
r Pazopanib: Targets VEGF receptors and other metastases, a single metastatic site, and the r Renal Cell Carcinoma, Pediatric
absence of retroperitoneal adenopathy r Reference Tables: TNM: Kidney Cancer
pathways
– 1st line or postcytokine: 800 mg PO daily COMPLICATIONS
r Bevacizumab: VEGF antibody r Related to treatment
– 1st line with interferon-α 10 mg/kg IV Q2wk – High-dose IL-2: Vascular leak syndrome CODES
r Interferon-α: Stimulates immune function – TKIs: Fatigue, HTN, hand and foot syndrome, GI
– 1st line, only combination with bevacizumab toxicity, hypothyroidism ICD9
– SubQ a start of 9 MU on 3 nonconsecutive days – mTOR inhibitors: Fatigue, rash, hyperglycemia, r 189.0 Malignant neoplasm of kidney, except pelvis
per week, with dose reduction to 6 MU and to dyslipidemia r 196.2 Secondary and unspecified malignant
3 MU if toxicity r Others related to disease progression
neoplasm of intra-abdominal lymph nodes
r Temsirolimus: mTOR inhibitor (3)
FOLLOW-UP
– 1st line for poor-risk patients or nonclear cell ICD10
Patient Monitoring r C64.1 Malignant neoplasm of right kidney, except
histology: 25 mg IV weekly r Depends on stage of disease and treatment
r Sorafenib: Targets VEGF receptor and other renal pelvis
– Usually chest and abdominal imaging every r C64.9 Malignant neoplasm of unsp kidney, except
pathways: 1st or 2nd line: 400 mg PO BID (4) 3–6 mo if not being treated
renal pelvis
Second Line – Imaging every 3–4 cycles if underactive systemic r C77.2 Secondary and unsp malignant neoplasm of
r Agents as noted above after failure of 1st targeted treatment
therapy – Serum chemistries and liver function tests as intra-abd nodes
r Axitinib: Potent, selective, 2nd-generation inhibitor routine
of VEGFR 1, 2, and 3 (5): Patient Resources CLINICAL/SURGICAL
– 2nd line: 5 mg PO BID,10 mg PO BID max r Kidney Cancer Association www.kidneycancer.org
r Everolimus: mTOR inhibitor PEARLS
r National Cancer Institute, Kidney Cancer
– 2nd line: 10 mg PO daily r Cytoreductive surgery should be considered for M1
www.cancer.gov/cancertopics/types/kidney
disease.
SURGERY/OTHER PROCEDURES r Only high-dose IL-2 provide durable complete
r Cytoreductive nephrectomy in patients with
metastatic disease is generally considered standard REFERENCES response (CR).
r No targeted agents show significant complete
of care (6): 1. McDermott DF, Rini BI. Immunotherapy for
– SWOG 8949: Improved overall survival for response (CR).
metastatic renal cell carcinoma. BJU Int. r Patients achieving response with targeted agents
debulking nephrectomy in interferon-treated 2007;99:1282–1288.
patients with advanced RCC. However, no similar such as TKI have a response duration of ∼8–10 mo
2. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib (medium <12 mo) with continuous therapy
data is available in TKI era.
versus interferon alfa in metastatic renal-cell treatment.
carcinoma. N Engl J Med. 2007;356:115–124. r Combination therapies are being explored.
407
RENAL CELL CARCINOMA, PEDIATRIC

BASICS DIAGNOSIS r Benign renal mass in children:
– Choledochal cyst, intestinal duplication cyst
DESCRIPTION HISTORY – Congenital mesoblastic nephroma
r Gross hematuria (∼40%), flank pain, abdominal
Renal cell carcinoma (RCC) is a very rare tumor in – Hydronephrosis
childhood arising from the renal tubular epithelium distension (2) – Mesenteric cyst
r Nausea, vomiting, malaise common
EPIDEMIOLOGY – Multicystic dysplastic kidney
r Pain in up to 50% – Polycystic kidney
Incidence r 30% found incidentally (2) – Renal abscess
r 2–6% of all pediatric renal tumors
r Only ∼4 cases of pediatric RCC per year – Splenomegaly
PHYSICAL EXAM r Malignant renal masses in children:
r Estimated at <0.3% of all pediatric tumors r Palpable abdominal mass (∼40%) (2)
r Triad of hematuria, flank pain, and palpable mass – Hepatoblastoma
r Just over 350 cases reported in the literature
– Lymphoma
r Mean age of presentation between 8 and 10 yr vs. found in <6% of children (3)
– Lymphosarcoma
<3 yr for Wilms tumor DIAGNOSTIC TESTS & INTERPRETATION – Neuroblastoma
r Equal male:female – RCC
Lab
r Urinalysis: Hematuria found in >40% of patients (3) – Rhabdomyosarcoma
Prevalence
N/A r CBC: Polycythemia is rare – Wilms tumor
r Liver and renal function tests: Baseline prior to
RISK FACTORS
r Von Hippel–Lindau syndrome treatment TREATMENT
r Tuberous sclerosis Imaging
r Abdominal x-ray may show tumor calcifications GENERAL MEASURES
Genetics (∼25%) vs. Wilms tumor (∼5%) (3) Management is primarily surgical excision by either
r Translocation type of RCC, which forms a distinct radical nephrectomy or partial nephrectomy
r US demonstrates solid or cystic renal mass.
category has recently emerged as the predominant r CT or MRI with and without contrast reveal MEDICATION
type of RCC in children and adolescents, whereas it
is rarely diagnosed in adults. enhancing renal mass. First Line
r Pediatric RCCs typically present as large, r The use of chemotherapy, immunotherapy, or
r Chromosomal translocations in Xp11.3 region
heterogeneous masses, commonly hemorrhage and tyrosine kinase inhibitors is not adequately
involving TFE3 gene (1).
r Less frequently, 6p21 translocation. contain internal calcifications. described in pediatric population.
r IVP can demonstrate renal mass by displacement of r The use of tyrosine kinase inhibitors should be
r If seen with Von Hippel–Lindau, more likely to be
the collecting system. considered in the pediatric patient with
bilateral. r Chest x-ray or chest CT scan for workup of unresectable, metastatic, or advanced-stage RCC.
PATHOPHYSIOLOGY metastatic disease. r Small series of patients treated with neoadjuvant
r Thought to arise from renal tubular epithelium r Radionuclide bone scan is indicated based on chemotherapy according to Wilms tumor protocol.
r Most frequently papillary subtype with Xp11 concern for mets. Second Line
translocation N/A
– Role of translocation at Xp11.2 region involving
Biopsy is not indicated SURGERY/OTHER PROCEDURES
TFE3 gene unknown (1)
r Lung and bone are the most common distant Pathologic Findings r Radical nephrectomy (4)
r Predominately papillary histologic features in – Removal of entire kidney and portion of the ureter
metastases.
children vs. clear cell features in adults – Common approaches in children include flank and
ASSOCIATED CONDITIONS r Pathologic staging based on modified Robson abdominal incisions
r Tuberous sclerosis, chronic renal failure, r Partial nephrectomy (5)
staging system
neuroblastoma, and teratoma with chemotherapy r Up to 25% pediatric RCC cannot be clearly classified r Laparoscopic and robotic-assisted radical or partial
r Rarely associated with adult familial RCC
due to atypical features nephrectomy for RCC in children are described in
GENERAL PREVENTION r Pathologic parameters typically associated with poor select cases (6,7)
N/A outcome in adults (metastasis/high tumor stage,
high Fuhrman nuclear grade, angiolymphatic
invasion, tumor necrosis), do not appear to have
similar implications in pediatric patients
408
RENAL CELL CARCINOMA, PEDIATRIC

R
ADDITIONAL TREATMENT REFERENCES ADDITIONAL READING
Radiation Therapy r Dome JS, Fernandez CV, Mullen EA, et al. Children’s
Has been used for both initial treatment and 1. Ramphal R, Pappo A, Zielenska M, et al. Pediatric
recurrence but not well studied in pediatric renal cell carcinoma: Clinical, pathologic, and Oncology Group’s 2013 blueprint for research:
populations molecular abnormalities associated with the Renal tumors. Pediatr Blood Cancer. 2013;
members of the MiT transcription factor family. Am 60(6):994–1000.
Additional Therapies J Clin Pathol. 2006;126:349–364. r Spreafico F, Collini P, Terenziani M, et al. Renal cell
r Adjuvant chemotherapy for metastatic disease has
2. Estrada CR, Suthar AM, Eaton SH, et al. Renal cell carcinoma in children and adolescents. Expert Rev
been tried in the pediatric population but not well
carcinoma: Children’s Hospital Boston experience. Anticancer Ther. 2010;10(12):1967–1978.
characterized.
r Tyrosine inhibitors have been used in children with Urology. 2005;66:1296–1300.
metastatic disease but data are limited (9).
3. Undolfi P, Terenziani M, Casale F, et al. Renal cell r Neuroblastoma
carcinoma in children: A clinicopathologic study. r Reference Tables: TNM: Kidney Cancer
Complementary & Alternative J Clin Oncol. 2003;21:530–535. r Reference Tables: TNM: Kidney Cancer
Therapies 4. Caran A, Akyuz C, Sari N, et al. Renal cell r RCC, General
N/A carcinoma in children: Experience of a single r RCC, Localized (T1, T2)
center. Nephron Clin Pract. 2007;105:c58–c61.
r RCC, Locally Advanced (T3–T4)
ONGOING CARE 5. Cook A, Lorenzo AJ, Salle JL, et al. Pediatric renal
r RCC, Metastatic (N+, M+)
cell carcinoma: Single institution 25 year case
PROGNOSIS series and initial experience with partial r Renal Mass
r Overall survival similar to adult RCC and depends on nephrectomy. J Urol. 2006;175:1456–1460. r Robson Staging System
(Robson) stage: 6. Perlman EJ. Pediatric renal cell carcinoma. Surg r Translocation Renal Cell Carcinoma; Translocation
– Rest prognosis stage with stage I (>90%) and II Pathol Clin. 2010;3(3):641–651. Xp11.2
(>80%) 7. Cost NG, Geller JI, DeFoor WR Jr, et al. A r Von Hippel–Lindau Disease/Syndrome
– Stage III ∼75%, stage IV ∼15% (2) robotic-assisted laparoscopic approach for pediatric r Wilms Tumor
COMPLICATIONS renal cell carcinoma allows for both
r Surgical complications (bleeding, infection, nephron-sparing surgery and extended lymph node
diathesis, bowel injury) dissection. J Pediatr Surg. 2012;47(10): CODES
r Metastasis to lung and bone, multiple other sites 1946–1950.
8. Cozzi DA, Ceccanti S, Frediani S, et al. Chronic ICD9
FOLLOW-UP kidney disease in children with unilateral renal r 189.0 Malignant neoplasm of kidney, except pelvis
Patient Monitoring tumor. J Urol. 2012;187(5):1800–1805. r 197.0 Secondary malignant neoplasm of lung
r Adult protocols followed as there are no pediatric
9. Chowdhury T, Prichard-Jones K, Sebire NJ, et al. r 198.5 Secondary malignant neoplasm of bone and
protocols Persistent complete response after single-agent
r No long-term follow-up guidelines: bone marrow
sunitinib treatment in a case of TFE translocation
– Physical exam, chest x-ray, chemistry panel, CBC, positive relapsed metastatic pediatric renal cell ICD10
and urinalysis every 6 mo for 5 yr carcinoma. J Pediatr Hematol Oncol. 2013;35(1): r C64.9 Malignant neoplasm of unsp kidney, except
– CT on yearly basis for 5 yr e1–e3. renal pelvis
r Risk of chronic kidney disease likely attributed to r C78.00 Secondary malignant neoplasm of
reduced renal reserve capacity should be recognized unspecified lung
and treated with nephrologic evaluation (8) r C79.51 Secondary malignant neoplasm of bone
Patient Resources
National Cancer Institute http://www.cancer.gov/
cancertopics/pdq/treatment/wilms/patient CLINICAL/SURGICAL
PEARLS
The most common subtypes of RCC in children are the
translocation-associated tumors, papillary RCC, renal
medullary carcinoma, and oncocytic RCC.
409
RENAL COLIC

BASICS r Any process causing obstruction of the upper urinary r General appearance is that of a restless patient
tract unable to be still
DESCRIPTION – Ureteral stone r Usually unilateral flank pain with radiation to
r Renal colic is a constellation of symptoms that – Ureteral stricture ipsilateral lower quadrant
usually accompanies upper urinary tract obstruction – Upper tract urothelial neoplasm
(1)[C] – Extrinsic ureteral obstruction DIAGNOSTIC TESTS & INTERPRETATION
– Pain – Iatrogenic ureteral injury Lab
◦ Involves the flank and/or groin, with radiation to ◦ Ureteral ligation during hysterectomy or r Serum creatinine/BUN and electrolytes
the ipsilateral scrotum or labia majora colectomy r Complete blood count
◦ Pain character is colicky with patients r Upper urinary tract infection r Urinalysis
demonstrating a restless nature, unable to stay – Pyelonephritis – Look for signs of blood or infection
still – Renal abscess r Urine culture
◦ Pain is abrupt in onset and not associated with r Recent urologic surgery
physical activity or positions Imaging
– Obstructing blood clots from upper tract r CT scan of abdomen and pelvis without any
– Nausea/vomiting – Ureteral stent in poor position
◦ Simultaneously presents with flank pain but not contrast
– Presence of poorly draining percutaneous – Most sensitive way to detect urinary tract calculi
in all cases nephrostomy tube
– Irritative or obstructive voiding complaints which (99% sensitivity to detect ureteral stones)
– Residual ureteral stone fragments after lithotripsy – Relatively expensive and subjects patients to
are not present at baseline r Miscellaneous
◦ Urinary frequency, feeling of incomplete radiation exposure
– Renal artery embolus/infarction ◦ Low-dose radiation stone protocol still gives
emptying, hesitancy – Renal vein thrombosis
– Hematuria 95% sensitivity for ureteral stone detection with
◦ Gross or microscopic GENERAL PREVENTION 60% less radiation exposure
r Empiric advice for nephrolithiasis prevention r CT urogram
◦ Presence of hematuria strongly suggests
underlying urologic etiology over – Adequate hydration – CT scan of abdomen/pelvis with IV contrast which
gastrointestinal origin ◦ Enough fluid consumption to generate 2.5 L of is useful to expand diagnostic capability when no
urine output per day ureteral stones are found
EPIDEMIOLOGY – Low-sodium diet ◦ Can diagnose causes of colic not caused by
Incidence ◦ Daily sodium intake should be <2,500 mg stones such as UPJ obstructions or intraluminal
Renal colic accounts for about 1% of all emergency ◦ Diets high in sodium result in hypercalciuria filling defects such as neoplasms, fungus balls,
department visits (2,3)[C] representing over ◦ About 82% of renal stones produced have or blood clots
1 million cases per year calcium as a constituent r Renal/bladder ultrasound
Prevalence – Normal calcium diet – No radiation exposure/safe in pregnancy and in
r Renal colic caused by nephrolithiasis has an ◦ Daily calcium intake should range between 800 pediatric patients
estimated prevalence of 6.3% in men and 4.1% in and 1,200 mg – Ask for Doppler assessment of ureteral jets
women over a study period of 1988–1994 (4)[C] ◦ Vitamins, supplements, and antacids should be ◦ Presence of ureteral jets rules out complete
– Prevalence seems to be increasing compared to considered ureteral obstruction (although partial
past estimates obstruction may exist)
◦ Absence of ureteral jet may indicate obstruction
RISK FACTORS DIAGNOSIS or dehydration
r History of nephrolithiasis
HISTORY – Relies on indirect evidence to diagnosis
r Recent urologic surgery
r Sudden onset of colicky flank pain obstruction
r History of ureteral stricture ◦ Hydronephrosis
– May be associated with simultaneous nausea or
– Pelvic radiation history ◦ Presence or absence of ureteral jets
vomiting
Genetics – May have associated gross or microhematuria – Not very sensitive for detecting small ureteral
N/A – May have radiation to ipsilateral groin or stones
r KUB x-ray
PATHOPHYSIOLOGY scrotum/labia majora
r Presence of obstruction anywhere along the course – Pain is colicky and intermittent – May detect calcification along the expected course
r The location and characteristics of renal colic pain of the ureter
of the ureter results in stretching of involuntary – Not very sensitive or specific
smooth muscle lining the ureter and renal pelvis relating to urolithiasis (5):
– Stones obstructing UPJ: Mild to severe deep flank – Benefits are low-radiation dose and is inexpensive
r This stretching of the ureteral smooth muscle is
exacerbated by baseline ureteral peristalsis pain without radiation to the groin; irritative Diagnostic Procedures/Surgery
voiding symptoms (eg, frequency, dysuria); r Relief of obstruction may be necessary
r Stretching of hollow viscera, such as the ureter/renal
suprapubic pain, urinary frequency/urgency, – Ureteral stent placement
pelvis, is a well-known stimulus for pain as – Percutaneous nephrostomy
dysuria, stranguria, bowel symptoms
transmitted by the autonomic nervous system (1)[C] r Culture-specific antibiotics
r The kidneys, proximal ureters, and stomach are all – Stones within ureter: Abrupt, severe, colicky pain
in the flank and ipsilateral lower abdomen; – If infection is present
served by the celiac ganglion thus explaining why radiation to testicles or vulvar area; intense r Definitive surgical procedure as dictated by
nausea and vomiting frequently accompany renal nausea with or without vomiting underlying condition
colic – Upper ureteral stones: Radiate to flank or lumbar
areas Pathologic Findings
– Midureteral calculi: Radiate anteriorly and caudally N/A
– Distal ureteral stones: Radiate into groin or
testicle (men) or labia majora (women)
– An objective clinical prediction rule for
uncomplicated ureteral stones that uses 5 patient
factors—sex, timing, origin (ie, race), nausea, and
erythrocytes (STONE)—to create a score between
0 and 13 (the STONE score). With a high STONE
score, patients are likely to have a kidney stone.
410
RENAL COLIC
R
DIFFERENTIAL DIAGNOSIS r UPJ obstruction 3. Chauhan V, Eskin B, Allegra JR, et al. Effect of
r Ureteral calculus – Pyeloplasty (open, laparoscopic, robotic) season, age and gender on renal colic incidence.
r Ureteral stricture – Endopyelotomy (retrograde, antegrade) Am J Emerg Med. 2004;22:560–563.
r UPJ obstruction r Upper tract neoplasm 4. Stamatelou KK, Francis ME, Jones CA, et al. Time
r Upper tract urothelial neoplasm – Ureteroscopic ablation trends in reported prevalence of kidney stones in
– Upper tract urothelial carcinoma – Nephroureterectomy (open or laparoscopic) the United States: 1976–1994. Kidney Int.
– Fibroepithelial polyps 2003;63:1817–1823.
r Iatrogenic ureteral obstruction 5. Wolf JS. Medscape practice essentials:
Radiation Therapy Nephrolithiasis. Available online at
– Ureteral ligation after hysterectomy or colon N/A
resection http://emedicine.medscape.com/article/437096-
– Obstructing residual stone fragments after Additional Therapies overview. Accessed January 5, 2014.
r Obtain adequate drainage if necessary, especially if
lithotripsy
– Obstructing blood clots following upper tract the patient appears septic
urologic procedure – Ureteral stenting is usually a good 1st choice ADDITIONAL READING
r Upper urinary tract infection ◦ Chronically obstructed patients often have
r Malo C, Audette-Côté JS, Emond M, et al.
– Pyelonephritis significant ureteral tortuosity making retrograde
access challenging Tamsulosin for treatment of unilateral distal
– Pyonephrosis ureterolithiasis: A systematic review and
– Renal abscess – Percutaneous drainage
◦ Can be performed with conscious sedation meta-analysis. CJEM. 2013;15(0):1–14.
– Obstructing fungus ball r Moore CL, Bomann S, Daniels B, et al. Derivation
r Renal vascular etiology ◦ Optimal in cases of significant extrinsic ureteral
compression and validation of a clinical prediction rule for
– Renal artery embolus/renal infarction uncomplicated ureteral stone–the STONE score:
– Renal vein thrombosis Complementary & Alternative
retrospective and prospective observational cohort
Therapies
studies. BMJ. 2014;348:g2191.
N/A
TREATMENT See Also (Topic, Algorithm, Media)
r Flank Pain, General
GENERAL MEASURES
r Rule out sepsis
ONGOING CARE r Pyonephrosis
r Treat infection PROGNOSIS r Pyelonephritis, Acute, Adult
r Control pain Depends on underlying etiology but usually good once r Renal Colic Image
r Alleviate obstruction, if present obstruction is relieved and infection treated, if present r Urolithiasis, Renal
r Urolithiasis, Ureteral
COMPLICATIONS
MEDICATION r Persistent obstruction if left untreated
First Line – Renal cortical loss
r Analgesia based on degree of discomfort
◦ Could lead to nonfunctioning kidney CODES
– Narcotic analgesics for more severe pain – Serious infection
◦ Given PO or IV
FOLLOW-UP ICD9
◦ Morphine sulfate, oxycodone/APAP, r 599.69 Urinary obstruction, not elsewhere classified
hydrocodone/APAP, meperidine, nalbuphine Patient Monitoring r 787.01 Nausea with vomiting
– Ketorolac Renal/bladder ultrasound after treatment to ensure no r 788.0 Renal colic
– IV acetaminophen evidence of silent hydronephrosis or recurrent
◦ Less dizziness and hypotension than morphine obstruction ICD10
in one study Patient Resources r N13.8 Other obstructive and reflux uropathy
r Antiemetics (metoclopramide, ondansetron) r N23 Unspecified renal colic
Urology Care Foundation http://www.urologyhealth.
Second Line org/urology/index.cfm?article=148 r R11.2 Nausea with vomiting, unspecified
r α-blockers: Tamsulosin, alfuzosin, silodosin
– Given to relieve ureteral smooth muscle spasm
patients with ureteral stones
REFERENCES CLINICAL/SURGICAL
– Off-label use in cases of urolithiasis 1. Silen W. The colics. In: Cope’s Early Diagnosis of PEARLS
◦ Alfuzosin (10 mg/d) the Acute Abdomen. 22nd ed. New York, NY:
◦ Silodosin (8 mg/d) r Vast majority of patients with renal colic will have
Oxford University Press; 2010.
◦ Tamsulosin (start 0.4 mg to max 0.8 mg); most calculi.
2. Brown J. Diagnostic and treatment patterns for r Young patients with hydronephrosis and no
reported data renal colic in US emergency departments. Int Uro
Nephrol. 2006;38:87–92. evidence of calculus likely have congenital UPJ
SURGERY/OTHER PROCEDURES obstruction or other upper tract narrowing.
r Initial stent placement for significant obstruction
r Support patient with medicines to alleviate the
r Lithotripsy for nephrolithiasis
acute pain of renal colic.
– Ureteroscopy with laser lithotripsy r Treat infection if present.
– ESWL (extracorporeal shock wave lithotripsy)
– PCNL (Percutaneous nephrolithotomy)
r Ureteral stricture treatment
– Balloon dilation, laser incision
– Open or laparoscopic reconstruction
411
RENAL CYSTS (INTRARENAL, PERIPELVIC, AND PARAPELVIC)

Jeffrey J. Tomaszewski, MD
Robert G. Uzzo, MD
Other genetic cystic diseases: Juvenile nephronoph- (Hounsfield units (HU) ranging from −10 to
BASICS thisis, medullary cystic kidney disease, glomerulo- +20); no enhancement with IV contrast
cystic kidney disease, Von Hippel–Lindau syndrome ◦ CT diagnosis of a simple cyst is almost 100% if
DESCRIPTION (VHL), tuberous sclerosis, Birt–Hogg–Dubé study performed properly (bi- or triphasic)
r Renal cycts are fluid-filled renal structures not syndrome ◦ Enhancement is defined as an increase in HU by
continuous with the nephron or collecting system at least 15–20
r Simple cyst PATHOPHYSIOLOGY ◦ If cyst does not meet criteria for being simple,
r Simple cysts
– Arise from the renal parenchyma further workup of the lesion is necessary
– Development of discrete fibrous saccules of clear
– Size varies, often <2 cm but may be significantly – Parapelvic cyst
fluid lined with cuboidal epithelium ◦ Appears on US as a medially located cystic mass
larger
– Estimated growth rate: 2.18 mm/yr
– Typically asymptomatic incidentally detected on with surrounding echogenic walls (located
– Some will involute and disappear over time
CT or US within the fatty renal sinus)
although most will not ◦ On US or even CT can be confused with
– Can be single, multiple, and/or bilateral
– It is controversial if renal cysts are causative
– If large, may impinge on the renal pelvis causing hydronephrosis. An excretory phase CT is most
agents of HTN
obstruction r Parapelvic cysts helpful in distinguishing a parapelvic cyst from a
– Diagnostic US findings include a mass that is free simple parcehncymal renal cyst.
of internal echos (anechoic), through transmission – Found on <2% of kidneys at autopsy r MRI:
with posterior acoustic enhancement – Can be confused with hydronephrosis
– Bosniak criteria can be applied to MRI (exception:
r Complex cyst ASSOCIATED CONDITIONS Calcifications may not be well seen)
– Features not consistent with simple cyst; raise the r ADPKD (Autosomal dominant polycystic kidney – Low signal T1, high signal T2 is consistent with
possibility of malignancy disease) benign simple cyst
◦ Increased fluid density, internal thick-walled r ARPKD (Autosomal recessive polycystic kidney – Hyperdense cysts can be high signal on T1 and
septations, thickened wall, nodular projections disease) low on T2 but appearance depends on
into the lumen, calcifications, and contrast r Birt–Hogg–Dubé syndrome hemoglobin breakdown
enhancement r ESRD (end stage renal disease) – MRI may have a role in a subset of patients (VHL,
r Pyogenic cysts are infected cysts r Tuberous sclerosis multiple renal masses) if concern exists regarding
r Parapelvic cyst (aka peripelvic, parapelvic lymphatic, excessive radiation due to multiple long-term
– 50% have multiple renal angiomyolipomas
parapelvic lymphangiectasia, and renal sinus cysts); imaging studies
– 20–25% of have renal cysts
arise from the renal sinus r VHL disease – May be superior in characterization of internal cyst
contents (blood, mucin)
– Individuals develop cysts in multiple organs r Bi- or triphasic CT represents the gold standard for
ALERT
(kidney, pancreas, liver, epididymis)
Parapelvic cysts may be confused with distinguishing renal cysts:
– Increased risk of clear cell renal cell carcinoma
hydronephrosis given their central location. – Discriminate between cysts and collecting system
(RCC) in cyst wall
r Acquired cyst on excretory phase
GENERAL PREVENTION – Particularly important in assessing hydronephrotic
– Associated with chronic hemodialysis
Family members of patients with ADPKD and VHL systems
– Occasionally regress spontaneously ◦ US may be misleading/difficult to interpret
r Bosniak classification used to classify cysts based on should be screened
r Bosniak classification system of cystic renal masses
CT complexity and likelihood of malignancy
DIAGNOSIS originally based on CT (image) (1):
EPIDEMIOLOGY – Category I: Benign simple cysts; thin wall without
Incidence HISTORY septa, calcifications, or solid components, water
r 0.22% from birth to 18 yr r Patients may present with an abdominal mass, pain, density, and no contrast enhancement; No further
r 20% by age 40 hematuria, or HTN but most are radiographically imaging needed
r 33% by age 60 incidental ◦ Nearly all are benign
r In autopsy series, 50% of patients >50 have ≥1 r Family member with polycystic kidney disease or – Category II: Benign cysts with a few thin septae;
other inherited cystic disease the wall or septa may contain fine calcification,
simple renal cysts
r Acquired cystic renal disease is more common sharp margins, nonenhancing
PHYSICAL EXAM – Category IIF: Well marginated and may have thin
among men r Abdominal/flank mass (rare)
r Bilateral simple cysts infrequent <50 yr r Often a benign exam septae or minimal smooth thickening of the septa
or wall, which may contain calcification that may
Prevalence DIAGNOSTIC TESTS & INTERPRETATION also be thick and nodular; no contrast
N/A Lab enhancement; includes totally intrarenal
r Urinalysis most often normal unless concurrent nonenhancing complex lesions >3 cm
RISK FACTORS ◦ These require follow-up (designated by the F
r Age, a known risk factor for simple renal cysts medical renal disease present
r Increasing age (7-fold increase from 4th–8th decade r Renal function tests—calculate eGFR and stage designation)
◦ 5–20% of Bosniak II/IIF cysts contain
or an increased incidence from 5–36%) chronic kidney disease (CKD)
malignancy in wall
r Polycystic kidney disease (autosomal dominant and Imaging – Category III: Indeterminate cysts with thickened
recessive types) r Ultrasound irregular or smooth walls or septae; enhancement
r Hemodialysis – Simple cyst present
– In ESRD, cysts in 8–13% prior to hemodialysis (HD) ◦ No internal echoes, distinct walls with defined ◦ 40–60% of these are malignant (cystic RCC and
– 10–20% have acquired cystic renal disease after margins, spherical shape with no internal echoes multiloculated cystic RCC)
3 yr of dialysis, 40–60% after 5 yr, and >90% ◦ Other class III lesions are benign (infected cysts
after 10 yr ALERT and multiloculated cystic nephroma)
Complex renal cysts including hyperdense cysts may – Category IV: Characteristics of category III cysts
Genetics
r ARPKD: PKHD1 gene, chromosome 6, protein mimic solid renal masses. Doppler US is helpful. plus they contain contrast-enhancing soft tissue
r CT components that are adjacent to and independent
product fibrocystin
r ADPKD: PKD1 & PKD2 genes, chromosome 16, – Simple cysts of the wall or septum
◦ Have sharp walls with smooth margins, ◦ Risk of malignancy is 85–100%
protein products polycystin-1,-2 spherical shape, homogenous throughout
412
RENAL CYSTS (INTRARENAL, PERIPELVIC, AND PARAPELVIC)

R
r Cyst aspiration is rarely curative as fluid
Second Line REFERENCES
N/A
reaccumulates. Infected cysts may require aspiration 1. Bosniak MA. The Bosniak renal cyst classification:
SURGERY/OTHER PROCEDURES 25 years later. Radiology. 2012;262(3):781–785.
and catheter placement. r Radical or partial nephrectomy for complex or
– Infected cysts often represent calyceal diverticula 2. Minor LD, Picken MM, Campbell SC, et al. Benign
r Cyst biopsy is difficult and frequently results in suspicious cysts
r Cyst decortication with marsupialization should be renal tumors. AUA Update Series. 2003;22:
indeterminate pathology 170–175. Lesson: 22.
r Cytologic evaluation of fluid for malignancy or reserved for very select cases
3. Skolarikos A, Laguna MP, de la Rosette JJ.
– Laparoscopic, open, and percutaneous approaches
culture based on the indication and characteristics Conservative and radiological management of
of the cyst ADDITIONAL TREATMENT simple renal cysts: A comprehensive review. BJU
Additional Therapies Int. 2012;110(2):170–178.
Pathologic Findings r Cyst aspiration and sclerotherapy (3)
r Simple renal cyst
– Single layer of cuboidal epithelium – Rarely employed for large simple symptomatic
r Not continuous with the collecting system renal cysts ADDITIONAL READING
– Pain often does not resolve with surgical r Feiner HD, Katz LA, Gallo GR. Acquired renal cystic
DIFFERENTIAL DIAGNOSIS (2) management of renal cysts
r ADPKD (Autosomal dominant polycystic kidney – Not for parapelvic/peripelvic cysts disease of kidney in chronic hemodialysis patients.
disease) – Many consider this approach as primary therapy Urology. 1981;17:260–264.
r ARPKD (Autosomal recessive polycystic kidney r Terada N, Ichioka K, Matsuta Y, et al. The natural
for large symptomatic cysts before surgical
disease) management; others support laparoscopic history of simple renal cysts. J Urol. 2002;167:
r Calyceal diverticulum (evaluate for connection to the management initially 21–23.
collecting system) – Simple aspiration rarely leads to resolution; See Also (Topic, Algorithm, Media)
r Cystic degeneration (necrosis) of RCC reaccumulation common r Acquired Renal Cystic Disease
r Cystic malignancy (cystic RCC; sometimes called – Negative cyst fluid cytology required r Birt–Hogg–Dubé Syndrome
papillary cystadenocarcinoma) – Sclerosing agents increase success but associated r Cystadenocarcinoma, Genitourinary
r Hydronephrosis (parapelvic cysts) with pain and infection r Medullary Sponge Kidney
r Juvenile nephronophthisis – Multiple sessions are usually required, and use of r Multicystic Dysplastic Kidney
r Medullary sponge kidney indwelling percutaneous catheter may increase r Polycystic Kidney Disease, Autosomal Dominant
success rates
r Multicystic dysplastic kidney r Polycystic Kidney Disease, Autosomal Recessive
– Sclerosing agents: Ethanol, bismuth phosphate,
r Renal abscess n-butyl cyanoacrylate, povidone-iodine, and r Renal Cell Carcinoma, General
r Urinoma tetracycline; No agent superior r Renal Mass
r Pararenal (retroperitoneal or adjacent r Tuberous Sclerosis
mesenteric/liver/splenic/adrenal cyst) r VHL Disease
r Xanthogranulomatous pyelonephritis ONGOING CARE r Renal Cysts (Intrarenal, Peripelvic, and Parapelvic)
PROGNOSIS Images
r Up to 15% of ADPKD will require hemodialysis
TREATMENT r Benign simple cysts demonstrate little risk of
GENERAL MEASURES progressing to malignancy CODES
r The major issue with renal cysts is differentiating a r Bosniak classification and risk of malignancy
simple cyst from more serious diseases: Malignancy – Bosniak I: No risk ICD9
(RCC), polycystic kidney disease, complex cysts, and – Bosniak II/IIF: 5–20% risk depending on imaging r 593.2 Cyst of kidney, acquired
solid masses (such as a renal carcinoma or abscess) characteristics r 753.12 Polycystic kidney, unspecified type
r Risk of RCC with Bosniak III and IV lesions – Bosniak III: 50% risk r 753.16 Medullary cystic kidney
r Bosniak I (benign cyst) – Bosniak IV: 75–90% risk
– No action necessary COMPLICATIONS ICD10
r N28.1 Cyst of kidney, acquired
r Bosniak II (septae and/or wall calcifications) r Rupture and hemorrhage with simple renal cyst;
r Q61.3 Polycystic kidney, unspecified
– Some clinicians consider 1 follow-up study (US) to usually associated with flank pain and hematuria r Q61.5 Medullary cystic kidney
confirm stability or if unable to differentiate from r Infected renal cyst
IIF cyst r ADPKD
r Bosniak IIF (increased, thicker walls and
calcifications compared to type I) ALERT
CLINICAL/SURGICAL
– Require follow-up studies for 2–3 yr r Associated with cerebral berry aneurysms. PEARLS
r Bosniak III (irregular thick walls with calcification) r Bosniak cyst type malignancy risk:
– In up to 40% of patients.
– Excision vs. alternative diagnostic evaluation – 9% mortality (subarachnoid hemorrhage). – II/IIF (5–20%), III (50%), IV (up to 90%).
(needle biopsy, MRI). May be observed in elderly
and infirmed.
r Bosniak IV (enhancement with contrast, malignancy FOLLOW-UP
likely); surgical management
Patient Monitoring
r Follow-up imaging of Bosniak type IIF cysts
MEDICATION r Multicystic dysplastic kidney/VHL
First Line – Periodic sonography to monitor for neoplastic
Specific to those cystic diseases noted that cause HTN changes
or renal insufficiency r Acquired renal cystic disease
– Periodic imaging (US) on dialysis
Patient Resources
http://kidney.niddk.nih.gov/kudiseases/pubs/cysts/
413
RENAL DYSPLASIA, HYPODYSPLASIA, AND HYPOPLASIA

RISK FACTORS – Abnormal ureteral orifice:

BASICS r Vesicoureteral reflux (VUR) ◦ Pan-bud anomaly; abnormal budding leads to
r Posterior urethral valves an ectopic ureteral orifice with thin renal
DESCRIPTION r Ureteral abnormalities: Primary megaureter, parenchyma and ectatic calyces
r Renal dysplasia, hypoplasia, and hypodysplasia are ◦ Lateral ectopia: Often associated with reflux;
Ureteropelvic junction obstruction (UPJO),
forms of renal dysgenesis; namely, maldevelopment ureterocele rounded calyces are a result of premature
of kidney size, shape, or structure r Prune-belly syndrome termination of calyceal development
r Renal dysplasia: Chiefly a histologic diagnosis based ◦ Medial or caudal ectopia and ureteroceles:
on the presence of primitive renal components (ie, Genetics Dilated ureter is the norm with thin renal cortex
r A majority of dysplastic and hypoplastic kidney
ducts) and embryonic mesenchymal cells (ie, – Urethral obstruction:
cartilage): disorders are sporadic and nonheritable ◦ Position of ureteral orifices correlates with
r Genetic pathways can affect ureteric bud formation,
– Classification of renal dysplasia: degree of renal dysgenesis in posterior urethral
◦ Total dysplasia: Involves both cortex and branching morphogenesis within the metanephric valves (PUV): Orthotopic has normal histology;
medulla; spectrum ranging from aplastic (small blastema, and normal nephrogenesis lateral orifice has hypoplasia; extremely lateral
and solid) to multicystic (enlarged) kidneys (eg, r Familial renal adysplasia: Heterogenous autosomal has hypodysplasia
Multicystic dysplastic kidney [MCDK]) dominant inheritance of renal agenesis, renal ◦ Prune-belly syndrome: Large laterally displaced
◦ Subtotal dysplasia: Segmental distribution in dysplasia, MCDK, etc., within 1 family ureteral orifices with dysplastic kidneys
cortex and medulla explained by abnormal budding theory
◦ Hereditary: Zellweger and Meckel syndromes
PATHOPHYSIOLOGY
r Normal metanephric differentiation requires ASSOCIATED CONDITIONS
r Renal hypoplasia: Small kidneys that have a normal r Branchio-oto-renal syndrome
induction via the ureteric bud (1)
nephron density with less than normal number of r The branching of the collecting system, as well as r Ectopic ureteral orifice
calyces and nephrons and are not dysplastic (1): nephron formation, are determined by the ureteric r Fraser syndrome
– Classification: bud r Jeune syndrome
◦ With urethral obstruction r Epithelial–mesenchymal interactions and peptide
◦ Prune-belly syndrome r Kallmann syndrome
◦ True oligonephronia growth factors play a central role in nephrogenesis r Meckel–Gruber syndrome
r Dysplasia: Histologically manifests as distortion of r Oral–facial–digital syndromes
◦ With normal ureteral orifice
◦ With abnormal ureteral orifice renal architecture, immature or primitive glomeruli, r Posterior urethral valves
◦ Oligomeganephronia cartilage, and tubules encircled by fibromuscular r Potter syndrome
◦ Segmental (Ask-Upmark kidney) cells (primitive ducts): r Primary obstructing megaureter
r Renal hypodysplasia: Small kidneys that have normal – Aplastic dysplasia: Region of nonfunctioning
r Prune-belly syndrome
parenchyma
nephron density with less than normal number of ◦ Inhibition of nephron development r Pulmonary hypoplasia
calyces and nephrons and are dysplastic: ◦ Increased TGF-β r Renal coloboma syndrome
– Classification: ◦ S-shaped bodies and cysts r Simpson–Golabi–Behmel syndrome
◦ Normal ureteral orifice: With and without
◦ Dedifferentiation of renal cells r Townes–Brocks syndrome
obstruction r Hypoplasia: Normal nephron density despite smaller
◦ Ectopic ureteral orifice with or without r Uretero pelvic junction obstruction (UPJO)
ureterocele: Lateral, medial, or caudal size, bilateral or unilateral; can be associated with r Vesico ureteral reflux (VUR)
◦ With urethral obstruction reflux: r Zellweger syndrome
◦ Prune-belly syndrome – Oligomeganephronia:
r Renal development is dependent on the interaction ◦ Reduction in nephron number and hypertrophy GENERAL PREVENTION
of each nephron N/A
between the ureteric bud and the metanephric ◦ Usually bilateral, but contralateral renal
mesenchyme
agenesis has been reported
EPIDEMIOLOGY ◦ No clear distinction between cortex and DIAGNOSIS
Incidence medulla, reduced number of renal segments, HISTORY
N/A small renal artery, elongated nephrons r Systemic:
– Ask-Upmark kidney: – Failure to thrive, abnormal growth, headache,
Prevalence ◦ Likely secondary to reflux nephropathy
r Renal dysplasia: fever, chills, shortness of breath, nausea, emesis,
◦ Deep groove(s) on lateral convexity with anorexia, skin pallor, vision change, mental status
– Unilateral or bilateral in 2–4 per 1,000 births
underlying tubules resembling thyroid tissue change
– Male > Female (1.3:1) ◦ Underdeveloped medulla
– Male > Female (1.9:1) r Renal disease:
r Renal hypoplasia ◦ Arteriosclerosis and juxtaglomerular hyperplasia
r Hypodysplasia: Most often seen in conjunction – Polyuria, polydipsia, abdominal pain or mass,
– Oligomeganephronia: flank pain, hematuria
◦ Male > Female (3:1) with an ectopic ureteral orifice or obstruction; extent r Bladder disease:
◦ Increased with low birth weight, often present of dysplasia correlates with degree of ureteral – Lower urinary tract symptoms (LUTS), dysuria,
ectopia: nocturia, incontinence
by age 2
– Normal ureteral orifice:
– Ask-Upmark kidney: ◦ With obstruction: Primary obstructive PHYSICAL EXAM
◦ Male < Female (1:2) r Abnormal weight or height
◦ Commonly present ≤10 yr of age megaureter and UPJO
◦ Without obstruction: Dwarf kidney; according to r Vital signs: Hypertensive
bud theory is the result of deficient metanephric r Mental status: Encephalopathic
blastema r HEENT: Retinopathy, papillary edema, dehydration
r Lungs: Crackles
r Abdomen: Distention, palpable mass, guarding,
CVA tenderness, ascites
r Extremities: Pallor, peripheral edema
414
RENAL DYSPLASIA, HYPODYSPLASIA, AND HYPOPLASIA

R
DIAGNOSTIC TESTS & INTERPRETATION r Renal vein thrombosis REFERENCES
Lab r Simple cysts
r Urinalysis: Proteinuria, hematuria, low specific r Sporadic glomerulocystic kidney disease 1. Glassberg KI. Renal dysgenesis and cystic disease
gravity, bacteria r Tuberous sclerosis of the kidney. In: Wein AJ, Kavoussi LR, Novick AC,
r Urine culture r UPJO et al, eds. Campbell-Walsh Urology. 9th ed.
r Electrolytes, BUN, Cr, K+ r Von Hippel–Lindau disease Philadelphia, PA: WB Saunders; 2007:3305–3358.
– Elevated Cr, hyperkalemia, uremia r VUR 2. Grantham JJ, Winklhofer F. Cystic diseases of the
kidney. In: Brenner BM, ed. The Kidney. 7th ed.
Imaging r Wilms tumor
Philadelphia, PA: Saunders; 2004:1743–1775.
r Renal bladder ultrasound
3. La Scola C, Hewitt I, Pasini A, et al. Postnatal
– Kidney number and size, pelvicaliectasis, ureteral management of congenital bilateral renal
dilation, presence of cysts or mass, hyperechoic or TREATMENT
hypodysplasia. J Matern Fetal Neonatal Med.
hypoechoic parenchyma GENERAL MEASURES 2010;23:97–100.
– Bladder volume, ureterocele Consultation with nephrology and multimodality
r CT abdomen and pelvis
management
– Anomalous GU anatomy, presence of dilation,
MEDICATION
ADDITIONAL READING
calculus disease
r Static fluid and excretory MR urography First Line r Hubert KC, Palmer JS. Current diagnosis and
– GU anatomy, renal function, obstruction Antibiotics for UTI or as prophylaxis for VUR management of fetal genitourinary abnormalities.
r Renal scan Second Line Urol Clin N Am. 2007;34:89–101.
r Weber S, Moriniere V, Knüppel T, et al. Prevalence of
– Split function or obstruction N/A
r Voiding cystourethrogram mutations in renal developmental genes in children
r Retrograde pyelography: SURGERY/OTHER PROCEDURES with renal hypodysplasia: Results of the ESCAPE
r Indications for nephrectomy: Pain, chronic infection,
– Defines anatomy study. J Am Soc Nephrol. 2006;10:2864–2870.
HTN, or increasing size (3)
Diagnostic Procedures/Surgery r Renal transplantation for end-stage renal disease See Also (Topic, Algorithm, Media)
r Cystoscopy may help define anatomic abnormalities r Ask-Upmark Kidney
r Ureteral reimplantation: Reflux, primary megaureter
r Renal biopsy r Chronic Kidney Disease, Pediatric (Renal Failure,
r Pyeloplasty for UPJO
r Valve ablation for posterior urethral valves Chronic)
Pathologic Findings r Prune Belly (Eagle Barrett or Triad) Syndrome
r Gross findings (2)
ADDITIONAL TREATMENT r Renal Agenesis (Bilateral and Unilateral)
– Smaller renal size, mass, and contour r Renal Dysplasia, Hypodysplasia and Hypoplasia
Peritoneal or hemodialysis for ESRD
– Renal lobulations and cysts
– Pale and firm kidneys Complementary & Alternative Image
Therapies r Renal Malrotation
– Duplicated kidney or ureter
– Dilated collecting system N/A r VUR, Pediatric
– Ectopic ureteral orifice
– Ureterocele ONGOING CARE
– Thickened bladder wall CODES
r Histologic findings PROGNOSIS
– Dysplasia Varies with degree of renal insufficiency and degree of ICD9
◦ Always with decreased nephron number comorbid conditions r 753.0 Renal agenesis and dysgenesis
◦ Embryonic mesenchyme r 753.15 Renal dysplasia
◦ Primitive renal components COMPLICATIONS r 756.71 Prune belly syndrome
◦ Distortion of renal architecture Renal failure, anemia, UTI, failure to thrive
◦ Primitive glomeruli FOLLOW-UP ICD10
◦ Nephron precursors: Comma and S-bodies r Q60.2 Renal agenesis, unspecified
Patient Monitoring
◦ Primitive ducts: Cartilage and tubules encircled r BP and growth chart annually r Q60.5 Renal hypoplasia, unspecified
by collars of fibromuscular cells r Electrolytes, Cr, BUN annually r Q61.4 Renal dysplasia
– Hypoplasia r Urinalysis and urine culture as indicated
◦ May have a normal nephron density r Bilateral disease: Renal US annually
◦ Oligomeganephronia: Reduction in nephron
r MCDK: Renal US every 2 yr to observe for involution CLINICAL/SURGICAL
number with corresponding hypertrophy of the PEARLS
nephrons, nephron diverticula Patient Resources
◦ Ask-Upmark kidney: Arteriosclerosis, National Kidney and Urologic Diseases Information Prognosis varies; however, most patients have renal
juxtaglomerular hyperplasia, tubules resembling Clearinghouse (NKUDIC) http://kidney.niddk.nih. insufficiency and its sequelae.
thyroid tissue gov/kudiseases/pubs/kidneydysplasia/
– Hypodysplasia
◦ Both dysplastic and hypoplastic
r Polycystic kidney disease, autosomal dominant
(ADPKD)
r Polycystic kidney disease, autosomal recessive
(ARPKD)
r Juvenile nephronophthisis
r Medullary sponge kidney
r Reflux nephropathy
415
RENAL ECTOPIA
Vani S. Menon, MD
Derek Matoka, MD
PATHOPHYSIOLOGY
BASICS r Failure of ascent DIAGNOSIS
– Anomalous vasculature impeding ascent; possibly
DESCRIPTION and abnormally situated umbilical artery HISTORY
r Renal ectopia describes a kidney that is located r UTIs (30%), vague abdominal pain or renal colic
– Thought to occur at the 4th–8th wk of gestation
outside of the normal orthotopic position within the r Incidentally during pre- or postnatal screening
– Normal kidney ascent to the level of L2 at the end
renal fossa of the 8th wk of gestation r Abdominal mass, hypertension, hematuria,
r Positions for ectopia: r Abnormality of the ureteric bud or metanephric incontinence, renal insufficiency
– Pelvic kidney: Below aortic bifurcation; this is the blastema PHYSICAL EXAM
most common ectopic position r Fusion abnormalities occur early in embryogenesis r Usually normal
– Lumbar: Near sacral promontory – Horseshoe kidney is the most common fusion r May find abdominal mass or flank tenderness
– Abdominal: Above iliac crest anomaly r Genitourinary abnormalities
– Cephalad: Seen in conjuncture with omphalocele – Two renal moieties joined at lower pole in 90% of
when intra-abdominal organs herniate into the cases DIAGNOSTIC TESTS & INTERPRETATION
defect and cranial ascent of kidney is limited by r Anatomic considerations: Lab
the diaphragm – Orthotopically located adrenal gland r Urine analysis and culture
– Thoracic: Above the diaphragm with vasculature – Ureter inserts into bladder in orthotopic position r BUN/Cr
arising from a cranial source – Renal pelvis of ectopic kidney is usually anterior to
r Crossed fused renal ectopia Imaging
the parenchyma secondary to malrotation r If kidney absent on ultrasound (US), radionucleotide
– Fusion occurs in up to 90% of cases – Failure of development of fascial layers in the
– Left to right crossing and more common in males imaging should be performed to evaluate for an
flanks on the side not occupied by renal tissue
– Solitary and bilateral crossed varieties less r Malrotation of the ectopic kidney almost always ectopic kidney
common – Average differential function of ectopic kidney is
occurs 35% (1)[C]
– Type of anomaly is descriptive of the fusion
ASSOCIATED CONDITIONS r Diuretic renography if moderate-to-severe
anomaly
◦ (inferior, lump, S-shaped [aka sigmoid], r Vesicoureteral reflux: Estimated incidence between pelvicalyceal dilation or progressive dilation found to
L-shaped, disc, or pancake) 20 and 30% evaluate for obstructive process
– Fused unit usually caudal to the orthotopic renal – Contralateral kidney demonstrates reflux in r Voiding cystourethrogram for febrile UTI and/or
moiety approximately 50% of cases pelvicalyceal dilation
r Horseshoe kidney is a noncross-fused ectopia – Bilateral renal ectopia carries highest risk for r If kidney is nonfunctional, computed tomography
reflux—>70% (1)[C] scan or abdominal US for localization
EPIDEMIOLOGY r Hydronephrosis: Seen in over 50% r Recent use of magnetic resonance urogram for
Incidence – Half of these cases are due to either ureteropelvic small, poorly functioning kidneys can be utilized
r 1 in 500 to 1 in 1,290 in postmortem studies
junction obstruction (UPJO) or ureterovesical
– Incidence is higher in autopsy series than in junction obstruction (UVJO) Diagnostic Procedures/Surgery
clinical studies, suggesting many clinically – 25% of the hydronephrotic cases are secondary to N/A
insignificant and not recognized reflux and the remaining 25% due to malrotation Pathologic Findings
– Left side favored over right (2)[C] N/A
r Pelvic kidney 1 in 2,200 and 1 in 3,000 r Genital anomalies: Estimated incidence between
r Crossed renal ectopia: Extremely rare DIFFERENTIAL DIAGNOSIS
15 and 45% r Horseshoe kidney
Prevalence – 10–20% of males will have cryptorchidism, r Malrotated kidney
N/A hypospadias, or duplicated urethras r Ptosis of orthotopically located kidney
– 20–66% of females will have uterine or vaginal r Supernumerary kidney:
RISK FACTORS anomalies
Potential relationship with maternal r Cloacal anomalies: 14% of these patients will have – Usually caudad to orthotopic kidney
illnesses/teratogenic exposure an ectopic kidney
Genetics r Nephrolithiasis
N/A r Recurrent urinary tract infections (UTIs)
GENERAL PREVENTION
N/A
416
RENAL ECTOPIA
R
3. Gupta M, Lee MW. Treatment of stones associated
TREATMENT ONGOING CARE with complex or anomalous renal anatomy. Urol
Clinic N Am. 2007;34(3):431–441.
GENERAL MEASURES PROGNOSIS 4. van den Bosch CM, van Wijk JA, Beckers GM, et al.
r Outcomes for treatment of nephrolithiasis and UPJO
Specific treatment for renal ectopia itself is not Urological and nephrological findings of renal
indicated. However, special considerations for are comparable to management of these entities in ectopia. J Urol. 2010;183:1574–1578.
associated conditions may be necessary. the orthotopic-positioned kidney
r Current literature suggests no adverse effects on
MEDICATION
First Line blood pressure or kidney function (4)[B] ADDITIONAL READING
Antibiotic prophylaxis for reflux based on clinical need r No evidence for increased risk of malignancy
Cinman NM, Okeke Z, Smith AD. Pelvic kidney:
Second Line COMPLICATIONS Associated diseases and treatment. J Endourol.
N/A r Vesicoureteral reflux 2007;21(8):836–842.
r Nephrolithiasis
SURGERY/OTHER PROCEDURES See Also (Topic, Algorithm, Media)
r Nephrolithiasis – Most likely due to urinary stasis r Horseshoe Kidney
r UPJO/UVJO r Malrotated Kidney/Renal Malrotation
– Shock-wave lithotripsy, ureteroscopy,
percutaneous nephrolithotomy, laparoscopic r UTIs r Renal Dysplasia, Hypodysplasia and Hypoplasia
nephrolithotomy (3)[C] r Bowel laxity in the region of the empty renal fossa r Renal Ectopia Image
r UPJO r Traumatic injury to renal unit due to poor protection r Renal Fusion Anomalies
– <15% are due to an aberrant crossing vessel in ectopic location r UPJO
– Goal of management is to achieve dependent r UTI, Complicated, Pediatric
FOLLOW-UP
pelvic drainage r Urolithiasis, Pediatric, General Considerations
– Dismembered pyeloplasty: Open and minimally Patient Monitoring
r Nephrolithiasis
invasive
– Ureterocalicostomy – Imaging by renal US and/or CT scans
– Endopylotomy could be a consideration for failed
r Vesicoureteral reflux CODES
pyeloplasty but is rarely indicated as the initial – VCUG and/or DMSA
surgical intervention r Hydronephrosis ICD9
r Vesicoureteral reflux – Renal US and/or nuclear scans 753.3 Other specified anomalies of kidney
– Open vs. endoscopic repair for clinically significant r Yearly blood pressure measurements
ICD10
reflux r Yearly BUN/Cr measurements r Q63.2 Ectopic kidney
Patient Resources r Q63.1 Lobulated, fused and horseshoe kidney
r Urology Care Foundation: Ectopic Kidneys
Radiation Therapy
N/A http://www.urologyhealth.org/urology/
index.cfm?article=22 CLINICAL/SURGICAL
Additional Therapies PEARLS
N/A
REFERENCES r Renal ectopia carries an increased risk of urologic
Therapies abnormalities such as reflux, hydronephrosis, and
1. Guarino N, Tadini B, Camardi P, et al. The incidence genital abnormalities.
N/A r Over half the cases of reflux occur in the orthotopic
of associated urological abnormalities in children
with renal ectopia. J Urol. 2004;172:1757–1759. kidney.
2. Shapiro E, Bauer S, Chow J. Anomalies of the upper r >80% of ectopic kidneys will have differential
urinary tract. In: Campbell-Walsh Urology. 10th ed. function of approximately 35%.
Philadelphia, PA: Elsevier Saunders; 2012. r An anterior renal pelvis and anomalous vasculature
must be a consideration prior to surgical
intervention.
r Surgical interventions for nephrolithiasis have
similar success rates as for orthotopic kidneys.
417
RENAL FUSION ANOMALIES

Ross M. Decter, MD, FRCS
Paul H. Smith III, MD
r Proper renal development is coordinated through

BASICS interactions between the metanephric blastema and DIAGNOSIS
ureteric bud
DESCRIPTION r The developing kidney ascends and rotates medially HISTORY
r Reanl fusion is a congenital condition in which the r Most are asymptomatic and are incidentally
to reach its usual anatomic position by the 9th wk of
renal units are joined gestation discovered
r Horseshoe kidney and crossed-fused ectopia are the r Several theories have been offered to explain r May be diagnosed on prenatal ultrasound (US)
most common variants r Symptoms are usually the result of infection, stones,
crossed ectopia
– Horseshoe kidney: – One theory proposes that an aberrantly oriented or obstruction of the abnormally positioned
◦ Most common renal fusion anomaly ureteric bud induces renal development in the collecting system (UPJO)
◦ Poles of the kidney are fused by the isthmus contralateral mesonephric blastema – Nonspecific abdominal pain, nausea, vomiting,
◦ Fusion occurs at the lower poles in 95% – An alternate theory suggests that the developing hematuria
r Crossed-fused ectopia: kidney is channeled/displaced to the contralateral PHYSICAL EXAM
– 2nd most common renal fusion anomaly side during its ascent by the presence of an r Palpable abdominal mass (hydronephrosis)
◦ Kidney is on opposite side of where ureter aberrant umbilical or common iliac artery or other r CVA tenderness (stone or pyelonephritis)
inserts (ureter crosses midline) pelvic structures
◦ The ectopic renal unit is fused to its companion r The developing left and right metanephric blastemas DIAGNOSTIC TESTS & INTERPRETATION
in 90% of cases are in close proximity to each other within the pelvis Lab
– Crossing from left to right is the most common and, if abutting, may merge to form a horseshoe r Urinalysis (hematuria)
morphology kidney or other fusion anomaly (2) r Serum creatinine (elevated with obstruction)
r Metabolic evaluation for urolithiasis
EPIDEMIOLOGY ASSOCIATED CONDITIONS
Incidence r Other congenital anomalies are present in up to a – Metabolic etiologies for stone disease common in
r Male > Female one-third of patients with horseshoe kidney patients with horseshoe kidney
r Horseshoe kidney occurs in 1 in every 400–500 live ◦ Serum chemistries
– Skeletal, cardiovascular, neural tube, and
◦ 24-hr urinalysis
births anorectal anomalies are the most common
r Crossed-fused ectopia occurs in 1 in every r Other GU anomalies associated with horseshoe Imaging
kidney r Renal US: Hydronephrosis
1,000–2,000 live births (1)
– Cryptorchidism or hypospadias in 4% of males r VCUG:
Prevalence
r Horseshoe Kidney: ∼1:400–500 – Vesicoureteral reflux (VUR) in >50% of patients – High incidence of VUR
◦ Voiding cystourethrogram (VCUG) is routine r Diuretic renography (MAG3):
r Crossed-fused ectopia: ∼1:3,000
part of evaluation – If clinical or radiographic concern for obstruction
RISK FACTORS r 2–8 times increased risk of Wilms tumor r Contrast-enhanced CT or gadolinium-enhanced MRI
r Crossed-fused ectopia is frequently seen with r 2–4 times increased risk of TCC with delayed images can accurately characterize the
vertebral anomalies such as myelomeningocele and r Imperforate anus in 4% with crossed ectopia renal, collecting system, and vascular anatomy for
sacral agenesis (1) r Horseshoe kidney associated with imperforate anus surgical planning
r Horseshoe kidney is present in 60% of female
and Meckel’s diverticulum Diagnostic Procedures/Surgery
patients with Turner syndrome and 20% of patients r Increased risk of urolithiasis due to both anatomic Karyotype in females with horseshoe kidney if
with trisomy 18 and metabolic factors dysmorphic features suggestive of Turner syndrome
Genetics Pathologic Findings
GENERAL PREVENTION
Specific genetic causes unknown, but renal fusion r Preventative measures aim to minimize risk factors r Wilms tumor in children and TCC in adults are more
anomalies commonly seen in association with a variety common in horseshoe kidneys:
for future renal deterioration:
of chromosomal and congenital abnormalities (Turner – Unclear if carcinoma related to embryologic
– Prophylactic antibiotics or surgical correction if
syndrome, trisomy 18) mechanisms, urinary sepsis, or infection
VUR present
PATHOPHYSIOLOGY – Decompression of obstructed moieties DIFFERENTIAL DIAGNOSIS
r Metanephric blastema is the embryologic precursor (pyeloplasty) r Renal mass
to the adult kidney r Supernumerary kidney:
r Development of the kidney begins in the
– An accessory organ with its own blood supply and
4th–5th wk with ingrowth of the ureteric bud, an collecting system
outpouching of the mesonephric duct, into the – It may not be reniform, but possesses a distinct
surrounding metanephric blastema capsule surrounding a parenchymal mass
r Malrotated kidneys: Can look like a horseshoe
kidney on radiographic imaging
418
RENAL FUSION ANOMALIES

R
– ESWL: REFERENCES
TREATMENT ◦ It may be difficult to target stones for ESWL
1. Glodny B, Petersen J, Hofmann KJ, et al. Kidney
due to the abnormal location of the kidney.
GENERAL MEASURES fusion anomalies revisited: Clinical and radiological
ESWL is most appropriate for stones <1.5 cm
No treatment if asymptomatic. Specific management analysis of 209 cases of crossed fused ectopia and
associated with unobstructed collecting
dictated by complicating features. horseshoe kidney. BJU Int. 2009;103:224–235.
systems. Repeat treatments may be required in
order to achieve a stone-free status (4)[B]. 2. Glassberg KI. Normal and abnormal development
MEDICATION
of the kidney: A clinician’s interpretation of current
First Line – Ureteroscopy: knowledge. J Urol. 2002;167:2339–2351.
r Antibiotics: ◦ Safe and effective approach for calculi
3. Yohannes P, Smith AD. The endourological
– VUR treated the same as in those without fusion associated with horseshoe or ectopic renal management of complications associated with
anomalies moieties; however, the smaller ureteroscopic horseshoe kidney. J Urol. 2002;168:5–8.
– Antibiotic prophylaxis may be used until resolution instruments generally limit this approach to
4. Gupta NP, Mishra S, Seth A, et al. Percutaneous
for low-grade reflux smaller stone burdens
nephrolithotomy in abnormal kidneys: Single-center
Second Line ADDITIONAL TREATMENT experience. Urology. 2009;73(4):710–714.
N/A Radiation Therapy
SURGERY/OTHER PROCEDURES N/A
r General operative considerations:
ADDITIONAL READING
– Horseshoe and ectopic kidneys often have N/A r Boyan N, Kubat H, Uzum A. Crossed renal ectopia
abnormal and complex renal vasculature with fusion: Report of two patients. Clin Anat.
◦ Renal vessels may arise from the aorta, common Complementary & Alternative
Therapies 2007;20:699–702.
iliac artery, or both, and typically enter the r Decter RM. Renal duplication and fusion
kidney anteriorly N/A
◦ Angiography (including CT and MR angiogram) abnormalities. Pediat Clin N Am.
1997;44(5):1323–1341.
may be useful to delineate renal vascular ONGOING CARE
anatomy for operative planning See Also (Topic, Algorithm, Media)
– The renal pelvis and ureteropelvic junction of the PROGNOSIS r Horseshoe Kidney
horseshoe kidney often have an abnormal Related to complicating features. Outcomes r Malrotated Kidney/Renal Malrotation
configuration, which can result in urinary stasis or comparable to those for anatomically normally r Renal Ectopia
obstruction. This anatomic abnormality contributes positioned kidneys. r Renal Fusion Anomalies Image
to the majority of the symptoms associated with COMPLICATIONS r Vesicoureteral Reflux, Pediatric
horseshoe kidney, including stone formation, r Possible increased risk of malignancy
infection, hydronephrosis, and frank UPJO. r UTI
– In the horseshoe kidney, the lower poles are r Urolithiasis
joined by an isthmus, which is typically situated
CODES
r UPJO
just caudal to the inferior mesenteric artery. The
r VUR ICD9
isthmus may be divided if necessary during
nephrectomy. 753.3 Other specified anomalies of kidney
FOLLOW-UP
r UPJO, best managed with dismembered pyeloplasty:
Patient Monitoring ICD10
r Due to slight increase in incidence of Wilms tumor in r Q63.1 Lobulated, fused and horseshoe kidney
– Endoscopic management of UPJO is feasible
(3)[B] children, some advocate imaging every 6 mo once r Q63.2 Ectopic kidney
r Stone procedures: the diagnosis is made
r The abnormalities and conditions for crossed-fused
– PCNL: CLINICAL/SURGICAL
◦ Provides the highest stone-free rates for larger ectopia are similar to horseshoe kidneys, and
treatment often follows similar lines PEARLS
renal stones and is typically the primary
procedure for renal calculi in the horseshoe Patient Resources r Renal fusion anomalies often associated with other
kidney. Access to the collecting is usually best National Kidney and Urologic Diseases Information congenital anomalies.
achieved through a posterior upper pole calyx. Clearinghouse (NKUDIC) http://kidney.niddk. r Ureteropelvic junction obstruction (UPJO) in up to
(4)[B] nih.gov/kudiseases/pubs/ectopicKidney/index.aspx 1/3 of patients with horseshoe kidney.
r Renal vasculature usually aberrant.
r Increased risk of urolithiasis due to medical and
anatomic abnormalities.
419
RENAL INFARCTION
Matthew A. Meissner, MD

BASICS r The main mechanism is embolization of the renal r Diffuse abdominal pain without peritonitis
vasculature: r CVA tenderness
DESCRIPTION – Clot emboli are the most common (a-fib) r Fever
r Renal infarction is a rare condition that occurs – Atherosclerotic emboli r Acute hypertension
secondary to any process that interrupts or halts – Vegetative emboli (endocarditis) r Flank ecchymosis in trauma patients
blood flow to the kidney causing necrosis and – Fat emboli r Heart murmur
cessation of function r Renal arterial occlusion is more common on the left
r Most commonly caused by thromboembolic r Peripheral vascular disease
side, due to the more acute angle of the left renal r Decreased urine output
phenomenon in conditions such as atrial fibrillation artery with the aorta (1)
r Acute infarction due to trauma may show a r Abdominal bruit from an aneurysm
(a-fib), bacterial endocarditis, or cardiac mural
thrombi hematoma in the vessel wall (intimal flap); infarction DIAGNOSTIC TESTS & INTERPRETATION
EPIDEMIOLOGY due to clot emboli will reveal a clot, blocking the Lab
Autopsy data reveal an estimated prevalence of renal artery or its branches (2)[C] r Leukocytosis: 70% of patients
r Renal vasoconstriction from sepsis, α-adrenergics, r Elevated or normal creatinine
0.48–1.4%
cocaine, others r Microscopic hematuria: 80% of patients
RISK FACTORS
r Acute tubular necrosis ASSOCIATED CONDITIONS r Proteinuria: 90% of patients
r Antiphospholipid antibody syndrome r Aneurysms of the aorta or renal artery r Elevated LDH: 100% of patients. If LDH is elevated
r Atherosclerosis r Angina with normal transaminases, this is highly suggestive
r A-fib r Atrial fibrillation of renal infarction in the presence of appropriate
r Chagas disease r Claudication symptoms.
r Collagen vascular disease (Ehlers–Danlos) r Elevated ALT: 83% of patients
r Cocaine abuse
r Congestive heart failure r Elevated AST: 66% of patients
r Collagen vascular disease
r Congestive heart failure r Mesenteric ischemia Imaging
r Diabetes mellitus r Patent foramen ovale r The best study is abdominal CT with and without IV
r Dilated cardiomyopathy r Prosthetic heart valve contrast
r Endocarditis r Sub acute bacterial endocarditis (SBE) r Classic CT findings of renal infarction:
r Hypercoagulable states (factor V Leiden) r Polyarteritis nodosa with vasculitis – Lack of IV contrast uptake in affected kidney
r Hypertension r Sickle cell disease (papillary necrosis) – Areas of low attenuation secondary to local edema
r Iatrogenic (surgical manipulation of renal – Sharply demarcated, wedge-shaped area of
GENERAL PREVENTION devascularized infarct
vasculature) r Reduce risk factors for coronary artery disease
– Cortically based, hypodense areas triangular in
r Intimal dissection (CAD), hypertension, and diabetes shape, widest part at the cortex (base of infarct)
r Long bone fractures (fat emboli) r Appropriate anticoagulation for a-fib, deep vein – Cortical rim sign: Perfusion to infarcted aspect of
r Myocardial infarction thrombosis, and valvular heart disease cortex is maintained by collateral branches,
r Patent foramen ovale (paradoxical embolism) r Treatment of hypercholesterolemia with statins showing a thin rim of enhanced cortex (3)[C]
r Pyelonephritis r Measures to reduce the risk of trauma (seat belts) r IVP reveals poorly or nonvisualized kidney on the
r Renal artery aneurysm and stenosis affected side
r Renal artery or vein thrombosis r Renal ultrasound with Doppler flow
r Sickle cell disease causing papillary necrosis
DIAGNOSIS
r Trauma: Blunt or iatrogenic HISTORY ALERT
r Valvular heart disease r A high suspicion is mandated in patients with A noncontrast CT, often obtained due to suspicion
underlying heart disease, hypercholesterolemia, or for renal colic, will fail to show a renal infarct.
Genetics recent trauma who present with abdominal or flank
r Patients with inherited hypercoagulable disorders
pain Diagnostic Procedures/Surgery
such as factor V Leiden mutation, protein C or S r Suspect a ventricular thrombus in patients with a r Renal angiography will diagnose any renal vascular
deficiency, lupus, antiphospholipid antibody occlusion and allow for intervention
recent myocardial infarction
syndrome, neurofibromatosis, Ehler–Danlos, and r Acute flank pain: ∼75% r ECG to diagnose arrhythmias
other collagen vascular disorders are at increased r Nausea/vomiting: ∼50% r Echocardiography for diagnosis of mural thrombi
risk
r Familial history of coronary artery disease, diabetes, r Gross hematuria may be seen and valvular vegetations
or metabolic syndrome portends an increased risk
for these diseases, and consequently, renal infarction ALERT
The symptoms associated with acute renal infarction
closely mimic those of an acute episode of
urolithiasis or pyelonephritis resulting in delayed
diagnosis. This detrimentally impacts long-term
renal function and potential for recovery.
420
RENAL INFARCTION
R
Pathologic Findings SURGERY/OTHER PROCEDURES REFERENCES
r Acutely, histology demonstrates apoptosis of r Surgical intervention is not considered a primary
glomerular and renal tubular epithelial cells treatment for thromboembolic renal infarction. 1. Fergany A, Novick AC. Renovascular hypertension
r Chronic changes include necrosis and nuclear loss in Exceptions include: and ischemic nephropathy Chapter 39. In: Wein AJ,
glomeruli and tubules – Young patients diagnosed within 6 hr of the ed. Campbell-Walsh Urology. 10th ed.
infarct. Philadelphia, PA: Elselvier/Saunders; 2012:
DIFFERENTIAL DIAGNOSIS – Bilateral infarcts or infarcts in a solitary kidney. 1047–1083.
r Acute abdominal processes (acute mesenteric
r For traumatic injuries leading to renal infarction 2. Rajeev TP, Köhler TS, Ryndin I, et al. Case report:
ischemia, appendicitis, bowel obstruction)
r Cystic renal disease (avulsion of the renal pedicle), open surgical repair Renal infarct mimicking renal mass: Further
r Pyelonephritis may be attempted during exploration for other rationale for minimally invasive management.
injuries. J Endourol. 2007;21:1065–1068.
r Renal artery stenosis
ADDITIONAL TREATMENT 3. Lang EK, Sullivan J, Frentz G. Renal trauma:
r Renal calculi
Radiologic studies. Comparison of urographic,
r Renal tumor Radiation Therapy computerized tomography, angiography, and
r Renal vein thrombosis N/A
radionuclide studies. Radiology. 1985;154(1):1–6.
Percutaneous angioplasty of the renal artery or
TREATMENT thrombectomy ADDITIONAL READING
GENERAL MEASURES Complementary & Alternative Saeed K. Renal Infarction. Int J Nephrol Renovasc Dis.
r The optimal therapy for renal infarction is not clear Therapies 2012;5:119–123.
r Initial therapy includes supportive measures with IV N/A
fluids and pain control See Also (Topic, Algorithm, Media)
r Since thromboembolic disease is the most common r Flank Pain
ONGOING CARE r Renal Colic
cause of renal infarction, primary anticoagulation is
r Renal Infarction Image
considered 1st line PROGNOSIS
r Other acute treatment options include thrombolysis, r The duration of renal ischemia is the critical factor in r Renal Trauma, Adult
endovascular stenting, and thrombectomy determining prognosis r Renal Trauma, Pediatric
r Prognosis also depends on the cause of the infarct r Renal Artery Stenosis/Renovascular Hypertension
MEDICATION r Sickle Cell Disease, Urologic Considerations
and the amount of parenchyma affected
First Line r Patients often die of illness related to the comorbid
r Antihypertensives to control hypertension
r Anticoagulation therapy: medical conditions causing the infarct
– Heparin: Start with a bolus of 80 U/kg followed by COMPLICATIONS CODES
r Chronic renal insufficiency
a continuous infusion titrated to a therapeutic PTT
– Begin warfarin therapy concurrently, goal INR of r Renal atrophy ICD9
r Hypertension r 440.1 Atherosclerosis of renal artery
2–3
r 584.5 Acute kidney failure with lesion of tubular
– Continue in patients with known causes of
thromboembolic disease
FOLLOW-UP necrosis
Patient Monitoring r 593.81 Vascular disorders of kidney
Second Line r Regular blood pressure monitoring to assess for
r Thrombolytic therapy may be used, especially in
new-onset hypertension following infarct ICD10
unstable patients r Follow-up imaging to monitor the progression or r I70.1 Atherosclerosis of renal artery
– Direct intra-arterial infusion to limit systemic side remission of an infarct r N17.0 Acute kidney failure with tubular necrosis
effects r Medical therapy for underlying condition that led to r N28.0 Ischemia and infarction of kidney
– Many contraindications: Cerebral malignancy or
the infarct
AVM, history of cerebral hemorrhage, GI bleed, r Monitoring of serum creatinine
active hemorrhage, or aortic dissection CLINICAL/SURGICAL
– Relative contraindications: Pregnancy, major Patient Resources
surgery within the last 3 wk, uncontrolled N/A PEARLS
hypertension r Renal infarction is most commonly due to
thromboembolic disease from underlying medical
conditions.
r Prompt diagnosis is paramount for preserving renal
parenchyma and function.
r Signs and symptoms may mimic more common GU
or intra-abdominal pathology.
r Renal infarction should be in the initial differential
diagnosis of nephrolithiasis and pyelonephritis.
r Anticoagulation therapy is the primary form of
treatment for renal infarction.
421
RENAL INFARCTION
r Renal cysts: Autosomal dominant polycystic kidney PHYSICAL EXAM

disease (ADPKD)—PKD1 (85%)/PKD2 r Eye exam (TSC hamartomas; VHL angiomas)
BASICS (polycystins-cilia, Ca2+ channel); autosomal r Skin (With TSC adenoma sebaceum & ash leaf
recessive polycystic kidney disease (ARPKD) PKD1 spot & shagreen patches & finger nail fibromas);
DESCRIPTION
r Masses in kidney can be benign or malignant, cystic (chromosomal locus 6p12.2) expressed via Potter’s With BHD fibrofolliculomas
sequence; VHL (75%); TSC (50%) TSC2 gene lies r Lung exam (BHD associated with pneumothorax)
(simple or complex) or solid, unilateral or bilateral,
next to PKD1; medullary cystic kidney disease r Neurologic exam (may be abnormal in TSC, VHL)
single or multifocal, primary or metastatic
r Most common renal mass on imaging: Benign cysts MCKD1 (chromosome 1q21), MCKD2 (chromosome r Leg lymphedema (might suggest retroperitoneal LN
16p12)
(60–70%) r WT: WT1 (11p13)/WT2 (11p15), tumor suppressor mets)
r Most renal cell carcinoma (RCC) are now detected r Supraclavicular lymph nodes (possibly distant mets)
gene; associated with WAGR, Denys–Drash, r Genital exam (RCC nonreducing varicocele with
incidentally (up to 70%) Beckwith–Wiedemann (BWS), mixed gonadal
r Most common malignant renal mass is RCC (90%), renal vein thombosis due to RCC; TSC/VHL
dysgenesis (MGD), Trisomy 18, Perlman syndrome
urothelial (∼5%), mets to kidney (∼4%) epididymal cysts/masses)
r Asymptomatic patients (CT screening for colon PATHOPHYSIOLOGY r Flank mass (part of RCC triad) <10%; more
r Renal cysts: Structural abnormalities in the nephron
cancer) may have incidental renal masses 15% of common in Wilms tumor
time (90% determined to be benign, 10% causing fluid to accumulate r Signs of comorbid conditions that will increase
r WT1 encodes a zinc-finger transcription factor that
indeterminate requiring follow-up) peri-op surgical risk (CVA, CAD, HTN, DM, COPD)
r Most common renal masses in children: is expressed in the kidney and gonads and is r Paraneoplastic signs:
Hydronephrosis (a “pseudomass”), multicystic necessary for ureteric bud outgrowth and – Hypertension (RCC and Pheo too)
dysplastic kidney (MCDK), and Wilms tumor (WT) nephrogenesis. Considered tumor suppressor gene – Cachexia, weight loss (check albumin)
r Angiomyolipoma (AML) most common benign renal but only 20% of Wilms have identifiable WT1 – Neuromyopathy (also part of TSC & VHL)
mutation. Undifferentiated blastema, epithelial, or – Signs of anemia
tumor in addition to oncocytoma
stroma leads to cancer.
EPIDEMIOLOGY r VHL: HIF-1–mediated VEGF angiogenesis DIAGNOSTIC TESTS & INTERPRETATION
Incidence upregulated because normal VHL protein-mediated Lab
r Rates of “kidney cancer” are highest in Europe, r Urine analysis: Hematuria keeps RCC, UTUC, AML
degradation of HIF-1 decreased due to mutation
North America, and Australia, whereas low in India, r AML: Vascular component does not have normal in the differential diagnosis; nitrite and leukocyte
Japan, Africa, and China wall, and prone to bleeding when mass size >3 cm esterase positive suggests infection (renal abscess,
r 2% worldwide kidney cancer incidence increase per (prophylactic intervention at 3.5–4 cm) etc.)
r RCC: Clear cell 80% (proximal tubule), papillary r Voided urine cytology: May detect TCC of urinary
year stabilized in 2008
r Kidney cancer in USA incidence 63,920 with 13,860 15% (proximal tubule), chromophobe 5% tract (not useful if “atypical”)
r CBC (anemia or polycythemia in RCC), renal
deaths in 2014; most lethal GU malignancy (collecting duct), collecting duct carcinoma <1%,
r Antenatal hydronephrosis 0.15% of all pregnancies medullary renal carcinoma <1% (sickle cell) function tests (BUN and creatinine)
r Untreated small renal masses (SRM), <4 cm, are r Increased LFTs (Stauffer syndrome: Reversible
(50% of GU abnormalities)
r AML 40–80% in tuberous sclerosis (TSC) patients; unlikely to metastasize (∼1%) at 3 yr but size and hepatic dysfunction not due to liver mets)
growth rates are variable and not predictive r Serum calcium: May be elevated in RCC secondary
0.13–0.03% of general population; ∼80% are
sporadic & ∼20% are in TSC patients r RCC size at diagnosis can predict synchronous to paraneoplastic syndrome
r WT: 6% of all pediatric tumors, 95% of all urologic mets Imaging
tumors, ∼500 diagnosed annually – <3 cm, 0.2% r CT scan w/ and w/o contrast gold standard for renal
– 3–5 cm, 2% masses (>10 Hounsfield unit (HU) increase =
Prevalence
r On autopsy 50% of people over 50 yr old have at – 5–7 cm, 7% enhancement = 90% neoplasm) (25–35 mSv
– >7 cm ∼20% effective radiation)
least one renal cyst
r Kidney cancer: 340,000 in USA r CT scan with above plus delayed excretory phase for
r Kidney failure (APKD, papillary RCC) upper-tract neoplasms
RISK FACTORS r Congenital diseases (Wilms, ARPKD, TSC, BWS, r Bosniak cyst CT classification (1 and 2 benign, no
r Kidney cancer: Male 2:1; median age 64 yr old;
BHD, Li–Fraumeni, Cowden syndrome) follow-up; 2F indeterminate, CT 6 mo [5%
genetic factors; 1/4 of kidney cancer occurs under r Von Hippel–Lindau (clear cell RCC) malignant]; 3 [50% malignant: Surgery or close
age of 55; smoking increases risk by 40%; smoking r Cerebral bleeds (ADPKD) obs]; 4 ∼100% malignant [surgery])
cessation >10 yr almost reverses risk completely; r GFR for contrast-induced nephropathy (CIN)
r Sickle cell disease (medullary RCC)
diet effects inconsistent, occupational also – CIN leading to dialysis high if GFR <30
conflicting but PCE (perchloroethylene also called r Hereditary leiomyomatosis (RCC)
– CIN risk increases if GFR <60
tetrachloroethylene), solvents, wool and glass fibers, GENERAL PREVENTION – CIN risk 0.6% if GFR >40 and 8% if <40 in one
brick dust, and lead have up to 2-fold increase for r Early screening if genetic predisposition high study (GFR 45 may be threshold)
RCC, end-stage renal disease (ESRD) debated r Eliminate modifiable risk factors – 15% of patients can have normal Cr but GFR <50
r Renal cysts: Genetic factors, age, risk factors for
r In VHL remove only tumors >3 cm so GFR better indicator of CIN risk
medical renal disease, hemodialysis r If GFR between 30 and 60 gadolinium is safe so
Genetics consider MRI for these renal masses
r RCC 2–3% familial: Von Hippel–Lindau (clear cell DIAGNOSIS – Gadolinium not safe if GFR <30 (nephrogenic
RCC)—chromosome 3p25–26 (VHL gene); systemic fibrosis—NSF)
Hereditary papillary RCC (papillary type 1)— HISTORY r MRI optimal for assessing IVC thrombus and
r Most RCC patients asymptomatic (why was imaging
chromosome 7q31 (C-met); familial leiomyomatosis anomalous renal hilar vessels (no radiation)
(papillary type 2)—chromosome 1q42 (fumarate done that detected incidental mass?) r Patients on dialysis can get CT contrast without
r Cough or bone pain (mets)
hydratase); Birt–Hogg–Dubé (chromophobe RCC, need for immediate dialysis
r Flank pain, hematuria (2 of RCC triad of flank
oncocytoma)—chromosome 17p11.2 (Folliculin); r Consider CT chest no contrast in patients at risk for
TSC same risk for RCC as general population based pain/hematuria/mass) <10% of patients with RCC
mets (CXR misses 10%)
on meta-analysis.
r AML: TSC—TSC1/TSC2 (50:50), chromosome 16 &
9 respectively, tumor suppressor genes
422
RENAL INFARCTION
R
r Nuclear medicine for split functional differentiation COMPLICATIONS
rarely needed if Cr <1.5 and kidney size and shape TREATMENT Surgical complications include hematoma,
similar to contralateral side pneumothorax, infection, adjacent organ injury (liver,
r Brain/bone imaging for mets if symptomatic GENERAL MEASURES spleen, pancreas, duodenum, and bowel), urinary
r Renal lesions suspicious for RCC are treated leak, myocardial infarction, thromboembolism,
surgically (laparoscopically or open) usually with positive surgical margins
Biopsy necessary for metastatic disease prior to
radical nephrectomy or partial nephrectomy (PNx).
initiation of systemic therapy and if concern for mets FOLLOW-UP
PNx use dependent on surgeon experience and
to the kidney. Indeterminate biopsy occurs 10–20%. Patient Monitoring
location of tumor to hilum; most <3–4 cm (1). r AML: Renal US every 6–12 mo
Biopsy not routinely needed due to high positive r PNx decreases long-term risk of CVD mortality and
predictive value of enhanced imaging but has role in r Poor surgical candidate with SRM imaging every
ablation. ESRD vs. nephrectomy
r Most recommend surgery for Bosniak III (50% 6 mo alternating with renal US and CT scan with
DIFFERENTIAL DIAGNOSIS yearly CXR or chest CT
malignant) and IV cysts (∼100%) r Stage 1–3 RCC, 20–30% relapse, lung most
r Adults: A solid primary renal mass in adult is most r TCC of the renal pelvis: By endoscopic ablation for
likely to be a RCC, although UCC or metastatic common (50–60%), median relapse 1–2 yr,
small superficial lesions (low-grade Ta), or radical
disease is an important consideration evaluate every 6 mo for 2 yr, then annually.
nephroureterectomy
– AML: Fat in a renal mass strongly suggests AML; r Asymptomatic AML >3.5 cm or small symptomatic Stage 4 RCC f/u dependent on primary treatment
fat-poor AML may resemble RCC and provider dependent.
lesions are treated by embolization, partial
– Carcinoid tumors Patient Resources
nephrectomy, or nephrectomy
– Collecting duct tumor (Bellini) r Painful simple renal cysts and infected cysts: Kidney Cancer Association www.kidneycancer.org/
– Cystic nephromas
– Cysts (simple, hemorrhagic, infected) Percutaneous aspiration and sclerotherapy
r Although cytoreductive nephrectomy is debated in
– Focal pyelonephritis REFERENCE
– Hemangioma post-IL-2 era, FDA approval of TKI & mTOR
– Inflammatory masses (xanthogranulomatous inhibitors based on studies where almost half 1. Buethe DD, Spiess PE. Current management
pyelonephritis, abscess) patients had received a nephrectomy considerations for the incidentally detected small
– Leiomyoma: Usually in renal capsule renal mass. Cancer Control. 2013;20(3):211–221.
MEDICATION
– Metanephric adenoma First Line
– Metastasis: Lung, gastric, breast cancers most r Usually used for advanced mRCC
common; melanoma and others r Sunitinib or bevacizumab + IFN-α: 1st line in
ADDITIONAL READING
– Oncocytoma: Benign; cannot be reliably
low/intermediate risk r 2012 EUA Guidelines: http://www.uroweb.org/
differentiated from RCC on imaging studies r Temsirolimus: 1st line in high risk gls/pdf/10 Renal Cell Carcinoma LRV2.pdf
– Pseudotumors (column of Bertin, others) r Pazopanib: 1st line and after cytokine failure r NCCN Guidelines: http://www.nccn.org/
– Renal capsule neoplasm
r Interleukin-2 has more side effects than INF-α. professionals/physician gls/pdf/kidney.pdf
– RCC
– Renal cortical adenoma: Controversial entity; High-dose IL-2 gives durable complete responders in See Also (Topic, Algorithm, Media)
cannot be distinguished from RCC on imaging: a limited number of patients. IL-2 can be r RCC, General Considerations
<2 cm, metastasis exceedingly rare monotherapy in selected good prognosis. r Renal Capsule Neoplasm
– Renal lymphoma Second Line r Renal Mass, Algorithm
– Renal medullary carcinoma r Sorafenib: 2nd line after cytokine failure r Renal Mass Image
– Renal sarcomas: 1–2% of all renal masses r Everolimus: 2nd line after TKI r Renal Mass, Intraoperative Consultation
(leiomyosarcomas, fibrosarcomas, malignant r Renal Masses, Benign WHO, Classification
fibrous histiocytomas, anaplastic sarcoma) ADDITIONAL TREATMENT
r Renal Pseudotumors
– Reninoma (JG apparatus tumors) Radiation Therapy
r Radiation used in pediatric tumors: Wilms stage r Renal Sarcoma, Adult and Pediatric
– Urothelial carcinoma upper tract (UTUC)
r Benign renal mass in children: 3–4, all clear cell and rhabdoid stages r Reference Tables: TNM: Kidney Cancer
– Choledochal cyst, intestinal duplication cyst r Metastatic RCC for pain/CNS mets in adults
– Congenital mesoblastic nephroma Additional Therapies
– Crossed-fused ectopia r RCC: Embolization prior to nephrectomy not CODES
– Cystic nephroma (multiloculated cystic nephroma) beneficial but can be palliative for pain and bleeding
– Hydronephrosis if nonsurgical candidate ICD9
– Mesenteric cyst r Ablation (cryotherapy or radio frequency) of smaller r 189.0 Malignant neoplasm of kidney, except pelvis
– MCDK—involuted nonfunctional kidney r 593.9 Unspecified disorder of kidney and ureter
renal masses (<3 cm) may be considered in selected
– Polycystic kidney disease
cases (elderly, poor surgical risk) (1)
– Renal abscess ICD10
– Splenomegaly Complementary & Alternative r C64.9 Malignant neoplasm of unsp kidney, except
r Malignant renal masses in children: Therapies renal pelvis
– Lymphoma, lymphosarcoma N/A r N28.89 Other specified disorders of kidney and
– Neuroblastoma (actually adrenal origin) ureter
– Ossifying renal tumor of infancy ONGOING CARE
– RCC (rare in children)
– Sarcomas (clear cell, rhabdomyosarcoma) PROGNOSIS
CLINICAL/SURGICAL
– WT (nephroblastoma): Renal mass in a child is WT r MSKCC (Motzer) criteria to predict survival of PEARLS
until proven otherwise patients with advanced RCC; for RCC, Kattan and r Much less than 10% of patients with RCC present
UCLA nomograms popular (based on 2002 TNM)
r RCC 5-yr cancer-specific survival (2010) is with the “classic triad” of hematuria, flank pain,
and a renal mass.
88–100% stage T1–T2, T3 45–75%, T4 <5–30%; r A solid renal mass in childhood is WT until proven
+LN 0–30%, or +mets 0–10%
r Wilms: 4-yr survival stage 1–4 favorable histology otherwise.
(FH): 90–98%, stage 5 FH ∼56–87%; stage 1–5
unfavorable histology ∼66%; clear cell RCC any
stage ∼75%; rhabdoid sarcoma any stage ∼25%
423
RENAL MASS, INTRAOPERATIVE CONSULTATION

Mark R. Anderson, MD, MSc
Anthony T. Corcoran, MD
Robert G. Uzzo, MD
– VHL (VHL gene; 3p25) r Enhancement characteristics on imaging.

BASICS ◦ Retinal and CNS hemangioblastomas, Objectify risk:
pheochromocytoma, pancreatic cyst and r Overall survival vs. competing risks of death.
DESCRIPTION endocrine tumor, endolymphatic sac tumor, – Competing risks nomogram operationalized
r Most renal masses are incidentally found epididymal and broad ligament cystadenomas online at www.cancernomograms.com (2)[B].
preoperatively on routine axial imaging (eg, CT or r Remaining renal function.
MRI of the abdomen) GENERAL PREVENTION
r Although rare today, some renal masses are 1st N/A – Can estimate percent functional volume
preservation if partial nephrectomy planned as
identified intraoperatively volume loss correlates well with ultimate renal
– Typically associated with trauma or urgent cases DIAGNOSIS function after partial nephrectomy (3)[B].
where preoperative imaging was either not done
or inadequate for renal visualization HISTORY
r Obtain history from operative team and review Diagnostic Procedures/Surgery
r Diagnostic procedures
EPIDEMIOLOGY available medical and radiographic records
Incidence – Consider intraoperative renal mass biopsy and
– Prior or current cancers
r Renal cell carcinoma (RCC) – Inheritable tumor syndromes
frozen section analysis
◦ Obtain core biopsy with biopsy gun
– 63,920 estimated new cases in 2014 (NCI data) – History of renal or abdominal trauma
– Primarily occurs in 6th or 7th decade ◦ ∼20% of intraoperative frozen sections of
– Male > Female (3:2) PHYSICAL EXAM renal lesions nondiagnostic (4)[B]
r Intraoperative evaluation—location of mass
– 4% of RCC are familial; majority are sporadic ◦ Management options include active
– 10–20% higher incidence in African Americans – Check adrenal
– Intrarenal surveillance, ablation, or extirpation (Note:
Prevalence – Extrarenal within Gerota fascia Renal biopsy and frozen section analysis yield
N/A – Perirenal poor tumor grade information)
RISK FACTORS – Renal pelvis Pathologic Findings
r RCC r Approximately 14% of incidentally found renal
– Family history, smoking, obesity, hypertension, Lab masses are benign depending on size (5)[B]
end stage renal disease (ESRD) Serum creatinine and eGFR – 68% clear cell RCC
r For intraoperative renal mass consult, risk factors – Positive association between tumor size and:
include: Imaging ◦ Rates of clear cell RCC
r Review all preoperative ultrasound (US),
– Pre-existing nonrenal primary cancer ◦ Fuhrman grade for clear cell RCC
◦ Possible metastatic lesion on kidney contrast-enhanced CT, and/or MR if available ◦ Tumor stage
– Inheritable tumor syndrome – If serial images available, determine growth rate
◦ Associated renal tumor component to help define risk (1)[B] DIFFERENTIAL DIAGNOSIS
r Renal masses (see Section I “Renal Mass” for more
– Renal insufficiency preventing use of contrast ◦ Average yearly linear growth rate of 0.3 cm for
during imaging all masses vs. 0.8 cm found in patients with information)
– Centrally located or small tumors initially missed progression – Abscess (acute or chronic)—consider history and
on imaging ◦ Masses with no growth under surveillance available labs
unlikely to metastasize – Angiomyolipoma (AML)—check for fat on imaging
PATHOPHYSIOLOGY – Adrenal lesion—check for presence of
r Intraoperative US with color Doppler (use
N/A contralateral gland prior to removal—if unable
laparoscopic or finger probe in open surgery) beware of postoperative insufficiency
ASSOCIATED CONDITIONS – Features suggesting malignant pathology
r Polycystic kidney disease – Benign lesion—oncocytoma, etc.
◦ Purely cystic lesions without septation can be – Calyceal diverticulum (chronic and infected can
– Autosomal dominant (autosomal dominant observed
polycystic kidney disease) or recessive (autosomal cause mass-like appearance with heavy
◦ Remove lesions with solid elements perinephric reaction)
recessive polycystic kidney disease) – Color Doppler also useful to:
r Inheritable tumor syndromes with renal and – Hemorrhagic cyst—may appear solid and
◦ Assess flow to ipsilateral and contralateral pseudoenhance
extrarenal manifestations kidney – Lymphoma—may cause renomegaly
– Birt–Hogg–Dubé (BHD gene; 17p11) ◦ Differentiate an isoechoic lesion with renal
◦ Cutaneous lesions, lung cysts, spontaneous – Metastatic lesion from other primary tumor
parenchyma since vessels are displaced around – Pseudotumor (column of Bertin)
pneumothorax, colonic polyps, or cancer solid renal masses – Renal lobulations
– Hereditary leiomyomatosis and renal cell cancer ◦ Identifies deep vessels near the wall of the – RCC, Wilms tumor
syndrome (HLRCC gene; 1q42) (aka: Reed’s lesion that may be encountered during excision – Renal cysts
syndrome)
◦ Uterine leiomyoma and leiomyosarcoma, – Sarcoma (renal or retroperitoneal—including
ALERT leiomyosarcoma and liposarcoma)
cutaneous leiomyoma and leiomyosarcoma Obtain all available informatIon on renal function. – Subcapsular hematoma—may be chronic
– Hereditary hyperparathyroidism-jaw tumor r Calculate overall renal function (GFR— especially with old trauma or extracorporeal shock
syndrome (CDC23 gene; 1q24–32) Cockcroft–Gault equation; calculators available
◦ Parathyroid tumor, fibroosseous mandibular and wave lithotripsy
online) and classify CKD status. – Upper-tract urothelial carcinoma
maxillary tumor, uterine tumor r Status of contralateral renal unit presence, flow, – Vascular—hemangioma, renal artery aneurysm,
– Papillary thyroid carcinoma with associated
and function. malformation
papillary renal neoplasia (1q21) r Perirenal
◦ Papillary thyroid cancer, nodular thyroid disease
– Tuberous sclerosis complex (TSC1, 9q34) – Adrenal lesion or adrenocortical carcinoma
◦ Facial angiofibroma, subungual fibroma, – Mesothelial cyst
hypopigmentation and café au lait spots, cardiac – Teratoma
rhabdomyoma, seizure, mental retardation, CNS
tubers, lymphangioleiomyomatosis
424
RENAL MASS, INTRAOPERATIVE CONSULTATION

R
r Remember to place perirenal closed suction drain for 3. Simmons MN, Hillyer SP, Lee BH, et al. Functional
TREATMENT most nephron-sparing procedures recovery after partial nephrectomy: Effects of
volume loss and ischemic injury. J Urol. 2012;
GENERAL MEASURES 187:1667–1673.
r What to do if called to the operating room emergen- Radiation Therapy 4. Krishnan B, Lechago J, Ayala G, et al.
tly to evaluate a renal mass (See Section III: Renal N/A Intraoperative consultation for renal lesions.
Mass, Intraoperative Consultation Algorithm) Additional Therapies Implications and diagnostic pitfalls in 324 cases.
r If patient unstable and involved kidney uninjured, r Investigate adjuvant therapies or eligibility for Am J Clin Pathol. 2003;120:528–535.
defer to later date adjuvant clinical trials based on pathology 5. Corcoran A, Russo P, Lowrance WT, et al. A review
r If films unavailable, safely defer if possible r Follow functional (nephrologic) results of contemporary data on renal masses—benign or
r If unable to defer treatment—assess presence, r If adrenalectomy was performed—beware of malignant? Urology. 2013;81(4):707–713.
function, and anatomy of both kidneys and consider postoperative adrenal insufficiency
biopsy Complementary & Alternative
r Look at available films to see if pre-/postcontrast
Therapies ADDITIONAL READING
phases available N/A NCCN guidelines: http://www.nccn.org/
– If preoperative imaging suggests a solid,
enhancing mass amenable to partial nephrectomy See Also (Topic, Algorithm, Media)
◦ Consider intraoperative biopsy and frozen ONGOING CARE r Birt–Hogg–Dubé Syndrome
section analysis r Renal Cell Carcinoma, General
◦ Reasonable to perform partial nephrectomy PROGNOSIS r Renal Cell Carcinoma, Localized (T1–T2)
r Influenced by stage, grade, histology
after family discussion (if present) r Margin status appears not to portend an adverse r Renal Cell Carcinoma, Locally advanced (T3–T4)
– Do not get fooled by hyperdense cyst or r Renal Cell Carcinoma, Metastatic (N+ , M+ )
pseudotumor—see clinical pearls prognosis or increased local recurrence
r Local recurrence after resection is ∼2–3% after r Renal Cell Carcinoma, Pediatric
r If no films, and cannot postpone intervention,
partial or radical nephrectomy r Renal Mass
consider biopsy r Renal Mass, Intraoperative Consultation Algorithm
r 5-yr risks of recurrence for local or regional RCC fully
– If solid elements with flow on Doppler US, normal
excised are approximately: r Renal Masses, Benign, WHO Classification
contralateral kidney and amenable to partial
nephrectomy, then intervene – >95% for pT1, ∼85% for pT2, range from r Von Hippel–Lindau Disease/Syndrome
– If radical required for technical reasons, perform 40–60% for pT3b
biopsy with frozen section pathologic analysis and COMPLICATIONS
possibly deferring intervention until permanent r For partial and radical nephrectomy: Acute renal CODES
section results obtained failure, need for dialysis
◦ Unless absolute indication for radical r Long-term risk of chronic renal insufficiency after ICD9
nephrectomy (≥cT3, adjacent organ radical nephrectomy associated with increased r 189.0 Malignant neoplasm of kidney, except pelvis
involvement, vascular compromise) cardio- and cerebrovascular morbidity r 593.9 Unspecified disorder of kidney and ureter
r Avoid the following: r For partial nephrectomy: Urinary fistulas, and r 753.10 Cystic kidney disease, unspecified
– Rely on US as only test for radical nephrectomy bleeding
(get biopsy) r Major complications, including urine leak, increase ICD10
– Rely solely on intraoperative single shot IVP to r C64.9 Malignant neoplasm of unsp kidney, except
with increasing tumor complexity
evaluate contralateral kidney renal pelvis
– Low complexity—6% r N28.89 Other specified disorders of kidney and
– Perform a radical nephrectomy because technically
– Moderate complexity—11%
easier ureter
– High complexity—22%
– Assume presence, flow, or function of r Q61.9 Cystic kidney disease, unspecified
contralateral kidney FOLLOW-UP
MEDICATION Patient Monitoring
r NCCN guidelines (level of evidence 2B—lower level CLINICAL/SURGICAL
First Line
N/A
but consensus recommended) PEARLS
– Every 6 mo for 2 yr, then annually for 5 yr
Second Line ◦ History and physical exam r Traumatic hemorrhage into a cyst can mimic a
N/A ◦ Comprehensive metabolic panel hypoechoic, solid renal mass. Color Doppler can
SURGERY/OTHER PROCEDURES – At 2 yr as indicated based on recurrence risk establish blood flow ruling out hemorrhagic cysts.
r Extirpative procedures ◦ Chest and abdominal ± pelvic imaging r Failing to check preoperative films if available as
◦ Risk-based follow-up clinical practice guidelines AML can often be distinguished by macroscopic fat
– Partial nephrectomy
◦ Tumor enucleation may yield equivalent operationalized at www.cancernomograms.com on CT/MR.
r Avoid getting fooled by renal pseudotumor or
oncologic outcomes. Best used when mass Patient Resources
locally confined on preoperative imaging, easily N/A adrenal lesion.
delineated intraoperatively, and do not appear r Avoid expanding the goals of planned operation
to grossly invade beyond the pseudocapsule. without consent or clearly thought out plan.
◦ Frozen section analysis on margin if in question REFERENCES
– Radical nephrectomy 1. Smaldone MC, Kutikov A, Egleston BL, et al. Small
– Resection of mass adjacent to kidney ± partial or renal masses progressing to metastases under
radical nephrectomy, if only way to get specimen active surveillance: A systematic review and pooled
out safely analysis. Cancer. 2012;118:997–1006.
r Surgical approach
2. Kutikov A, Egleston BL, Wong YN, et al. Evaluating
– Attempt to use existing approach overall survival and competing risks of death in
(laparoscopic/robotic) or incision patients with localized renal cell carcinoma using a
◦ Convert from laparoscopic to open if needed for
comprehensive nomogram. J Clin Oncol. 2010;28:
imperative indications only, otherwise may defer 311–317.
if oncologic risk low
◦ If nephron sparing requires conversion for
technical reasons, consider performing at later
date with patient consent
425
RENAL ONCOCYTOMA
Gillian Stearns, MD
Oleg Shapiro, MD, FACS
Pathological-Findings (3,4)
BASICS DIAGNOSIS r The term “oncocytoma” is a general descriptor of an
epithelial tumor that consists of oncocytes.
DESCRIPTION HISTORY Oncocytes are large eosinophilic cells with small,
r Renal oncocytoma is the most common benign solid r Most patients asymptomatic
round, benign-appearing nuclei without nucleoli.
renal tumor in adults r Incidentally detected
– Oncocytomas can arise in a number of different
r Usually asymptomatic at time of presentation r Gross hematuria/flank pain/flank mass rare organs
r Frequently detected incidentally at time of CT scan r Family history of renal tumors, fibrofolliculomas, r Renal oncocytoma: Gross findings
lung cysts/pneumothorax—rule out BHD – Well-circumscribed mass, mahogany brown, often
EPIDEMIOLOGY
PHYSICAL EXAM with pseudocapsule
Incidence r No specific findings for sporadic oncocytoma – Average size 6–7 cm
r 3–7% of all renal masses
r Palpable flank mass rare – 33% with central stellate scar
r Epidemiology similar to renal cell carcinoma (RCC)
r Dermatologic exam if suspected BHD – 20% demonstrate extension into perinephric fat
r Male > female (2:1) – Calcifications and necrosis rarely seen
r Median age of diagnosis 62 yr DIAGNOSTIC TESTS & INTERPRETATION r Renal oncocytoma: Microscopic findings
r 6% occur bilaterally – Round to polygonal eosinophilic cells
Lab
r 17% multifocal r No lab test can identify renal tumor as oncocytoma – Abundance of mitochondria seen on electron
r Lab panel as with any newly diagnosed renal mass microscopy
Prevalence
– CBC, chemistry panel, LFTs – Mitotic figures rare
N/A
– Regular nuclei
RISK FACTORS Imaging – Cells arranged in distinct nests
r Familial renal oncocytoma syndrome r Cannot be used to reliably distinguish oncocytoma
– May be difficult to distinguish from chromophobe
– Described rarely to date from RCC RCC
r Birt–Hogg–Dubé (BHD) r CT with and without IV contrast ◦ Colloidal iron stain positive in chromophobe
– Diagnostic test of choice for solid renal mass RCC but not oncocytoma
Genetics – Central scar within mass often seen in ◦ Chromophobe RCC is vimentin, cytokeratin 7
r Most frequent abnormalities (1,2):
oncocytoma, but this can be confused with positive
– Loss of chromosome 1p necrosis, commonly seen with RCC ◦ CD82 and epithelial-related antigen (MOC31)
– Loss of chromosome Y (males) r MRI may be helpful in the distinction between
r Less frequent translocations
– Solid enhancing renal mass ± central scar chromophobe RCC and renal oncocytoma
– Breakpoint region on 11q13 – Test of choice with IV contrast allergy, renal ◦ Gene expression differences are being explored
– Region encoding mDNA insufficiency ◦ The World Health Organization (2004) renal
– Loss of heterozygosity at chromosomes 1,14,21 r Renal US tumor classification indicates renal oncocytomas
◦ May reflect progression of oncocytoma to
– Not typically helpful for identification of mass as are benign neoplasms. In the past some renal
chromophobe RCC oncocytoma oncocytomas were classified as malignant.
PATHOPHYSIOLOGY r Renal angiogram ◦ This may have resulted from confusion with
r Arise from intercalated cells in collecting duct of – Spoke wheel pattern of feeding vessels clear cell renal carcinomas with eosinophilic
kidney (like chromophobe RCC) ◦ Not definitive for diagnosis component or due to eosinophilic chromophobe
r Occasionally oncocytoma and RCC may be found in – Usually not helpful in evaluation of renal mass RCC (low metastatic potential)
the same kidney r Metastatic evaluation for solid renal mass
– Chest x-ray vs. chest CT ALERT
ASSOCIATED CONDITIONS r Additional studies may be indicated clinically Although oncocytoma has “Classic Findings” on
r Most usually sporadic
r BHD imaging, no radiographic studies exist to
Diagnostic Procedures/Surgery differentiate benign oncocytoma from malignant
– Autosomal dominant r Percutaneous biopsy
RCC.
– Mutation in gene for folliculin – May be useful to exclude metastasis to kidney
– Renal tumors based on patient history
◦ Chromophobe/oncocytoma – May guide management of poor surgical DIFFERENTIAL DIAGNOSIS
r Adrenal mass
– Spontaneous pneumothorax, lung cysts candidates
r Pitfalls of biopsy r Angiomyolipoma
– Fibrofolliculomas, especially on face
r Carcinoid tumor
– Difficult to distinguish oncocytoma from
GENERAL PREVENTION r Collecting duct tumor
chromophobe RCC
No preventative strategies have been described. r Cystic nephroma
– Coexistence of RCC and oncocytoma in up to
Relatives of those with genetic syndromes may be r Cysts
10% cases
screened.
r Focal pyelonephritis
r Hemangioma
426
RENAL ONCOCYTOMA
R
r Inflammatory masses (xanthogranulomatous 5. Breen DJ, Bryant TJ, Abbas A, et al. Percutaneous
pyelonephritis (XGP), abscess) ONGOING CARE cryoablation of renal tumours: Outcomes from 171
r Leiomyoma tumours in 147 patients. BJU Int. 2013;112(6):
r Metanephric adenoma PROGNOSIS 758–765.
r Oncocytoma is uniformly considered a benign tumor
r Metastasis 6. Romis L, Cindolo L, Patard JJ, et al. Frequency,
r Pseudotumor (column of Bertin) and surgical removal is curative clinical presentation, and evolution of renal
r Multiple series report no metastases or death from
r RCC oncocytomas: Multicentric experience from a
r Renal cortical adenoma oncocytoma on long-term follow-up european database. Eur Urol. 2004;45:53–57.
r Older, rare reports of metastases may represent
r Renal lymphoma 7. Van der Kwast T, Perez-Ordoñez B. Renal
unrecognized, low-grade RCC (6,7) oncocytoma, yet another tumour that does not fit
r Renal medullary carcinoma r Risk of metachronous oncocytoma 4–6% in the dualistic benign/malignant paradigm. J Clin
r Renal sarcoma
Pathol. 2007;60(6):585–586.
r Reninoma COMPLICATIONS
r Perioperative for partial/radical nephrectomy
r Urothelial carcinoma
r Wilms tumor – Bleeding, infection, urine leak
r Long term after nephrectomy depends on renal ADDITIONAL READING
reserve r Chen YT, Tu JJ, Kao J, et al. Messenger RNA
TREATMENT – Chronic renal insufficiency/dialysis expression ratios among 4 genes predict subtypes of
FOLLOW-UP renal cell carcinoma and distinguish oncocytoma
GENERAL MEASURES from carcinoma. Clin Cancer Res. 2005;11:
Mainstay of treatment is surgical Patient Monitoring
r Patient monitoring 6558–6566.
r Dechet CB, Bostwick DG, Blute ML, et al. Renal
MEDICATION – Long-term surveillance of renal units
First Line recommended annually to semiannually oncocytoma: Multifocality, bilateralism,
No medical treatment exists – Metachronous ipsilateral and bilateral metachronous tumor development and coexistent
oncocytomas have been reported renal cell carcinoma. J Urol. 1999;162:40–42.
Second Line r Renal US preferred modality r Linehan WM, Walther MM, Zbar B. The genetic
N/A basis of cancer of the kidney. J Urol. 2003;
– Minimizes radiation exposure
SURGERY/OTHER PROCEDURES – No need for IV contrast 170:2163–2172.
r Establishes diagnosis of oncocytoma r Urinalysis
r Partial nephrectomy whenever feasible based on See Also (Topic, Algorithm, Media)
– Hematuria/proteinuria r BHD
size and location r Serum creatinine r Reference Tables: TNM: Kidney Cancer
r Radical nephrectomy rarely indicated unless very r Renal Cell Carcinoma, Chromophobe
large, uncertain diagnosis or partial not possible Patient Resources
r Kidney Cancer Association r Renal Cell Carcinoma, General Considerations
ADDITIONAL TREATMENT www.kidneycancer.org/ r Renal Mass, Algorithm
Radiation Therapy r Renal Mass, Intraoperative Consultation
No role r Renal Masses, Benign WHO, Classification
REFERENCES r Renal Oncocytoma Image
N/A r Renal Pseudotumors
1. Al-Saleem T, Cairns P, Dulaimi EA, et al. The
Complementary & Alternative genetics of renal oncocytosis: A possible model for
Therapies neoplastic progression. Cancer Genet Cytogenet.
r Renal cryotherapy and radiofrequency ablation (5) 2004;152:23–28. CODES
– Being studied as treatment option 2. Boris RS, Benhammou J, Merino M, et al. The
– Unable to differentiate between oncocytoma and impact of germline BHD mutation on histological ICD9
RCC due to lack of tissue for histology concordance and clinical treatment of patients with 223.0 Benign neoplasm of kidney, except pelvis
– Primarily for smaller lesions (<3 cm) bilateral renal masses and known unilateral ICD10
– May be done laparoscopically or percutaneously oncocytoma. J Urol. 2011;185(6):2050–2055. r D30.00 Benign neoplasm of unspecified kidney
– No long-term follow-up exists 3. Gudbjartsson T, Hardarson S, Petursdottir V, et al. r D30.01 Benign neoplasm of right kidney
– Usually considered for poor surgical candidates Renal oncocytoma: A clinicopathological analysis of r D30.02 Benign neoplasm of left kidney
r Active surveillance 45 consecutive cases. BJU Int. 2005;96:
– Good for select patients with solid renal masses, 1275–1279.
but no size can reliably differentiate between 4. Kuroda N, Tanaka A, Ohe C, et al. Review of renal CLINICAL/SURGICAL
benign and malignant processes oncocytosis (multiple oncocytic lesions) with focus
◦ 3 cm usually used as cutoff in BHD on clinical and pathobiological aspects. Histol
PEARLS
Histopathol. 2012;27(11):1407–1412. r Oncocytoma is a benign solid renal lesion.
r No imaging study reliably differentiates oncocytoma
from RCC. The CT finding of a central scar, previously
felt to be specific for oncocytoma, has been found
with RCCs, and this finding is not specific.
427
RENAL SARCOMA, ADULT AND PEDIATRIC

Adam O. Kadlec, MD
r RCC with sarcomatoid features is an increasingly r Leiomyosarcoma (most common)

BASICS recognized variant of RCC (<5% of all cases) that – Cell origin is smooth muscle of capsule or the
contains regions of mesenchymal-appearing perinephric structures
DESCRIPTION malignant cells adjacent to or within another typical – Displaces rather than invade parenchyma
r Sarcomas of the kidney are rare solid tumors that RCC histology r Fibrosarcoma, malignant fibrous histiocytomas,
arise from the embryonic mesoderm r Later metastasis to the lung and liver can occur anaplastic sarcoma of the kidney are other
– Sarcomas of the renal parenchyma itself are very r Wilms tumor is categorized into favorable or histologic types
rare. More commonly, “renal sarcomas” represent
a soft tissue sarcoma that either invades or abuts unfavorable histology; this has important DIFFERENTIAL DIAGNOSIS
implications regarding treatment (1)[A] r Adults: A solid primary renal mass in adult is most
the kidney.
– In large case series of adult patients, ASSOCIATED CONDITIONS likely to be a RCC, although urothelial carcinoma or
leiomyosarcoma and liposarcoma are the most metastatic diseases are other considerations
Wilms tumor is associated with aniridia,
common histologic subtypes – AML: Fat in a renal mass strongly suggests AML;
hemihypertrophy, Beckwith–Wiedemann syndrome,
r Renal sarcomas are more likely to be seen in Denys–Drash, and GU abnormalities (hypospadias and
fat-poor AML may resemble RCC
childhood than adulthood – Carcinoid tumors
cryptorchidism)
r Childhood sarcomas – Collecting duct tumor (Bellini)
GENERAL PREVENTION – Cystic nephromas
– Represented almost exclusively (approximately N/A – Cysts (simple, hemorrhagic, infected)
95%) by Wilms tumor (historically called – Focal pyelonephritis
nephroblastoma) (1)[A] – Hemangioma
– Other sarcomas of childhood include clear cell
DIAGNOSIS – Inflammatory masses (xanthogranulomatous
sarcoma, rhabdomyosarcoma, congenital HISTORY pyelonephritis, abscess)
mesoblastic nephroma, and fibrosarcoma r Age and sex of patient – Leiomyoma: Usually in renal capsule
r Family history – Metanephric adenoma
EPIDEMIOLOGY – Metastasis: Lung, gastric, breast cancers most
r History of mental retardation or GU anomalies
Incidence common; melanoma and others
r Adults: 1–2% of genitourinary cancer with peak r Noticeable abdominal mass (esp. Wilms)
r Shortness of breath, lethargy, abd pain, weight loss, – Oncocytoma: Benign; cannot be reliably
incidence in 5th decade differentiated from RCC on imaging studies
r Children: 6–7% of childhood cancers represented and other systemic symptoms may be present – Pseudotumors (column of Bertin, others)
mainly by Wilms tumor PHYSICAL EXAM – Renal capsule neoplasm
r Wilms tumor occurs equally in boys and girls, with a r Abdominal exam for mass – Renal cell carcinoma (RCC)
median age of onset of 3.5 yr – In children, a palpable mass will be seen with – Renal cortical adenoma: Controversial; cannot be
Prevalence Wilms tumor in >80% of cases distinguished from RCC on imaging: <2 cm
N/A r Assess for associated lymphadenopathy – Renal lymphoma
r GU exam to assess for GU anomalies such as – Renal medullary carcinoma
RISK FACTORS – Renal sarcomas
r Specific etiologies are not known hypospadias or undescended testis, which may alert
◦ Angiosarcoma
r HIV is associated with Kaposi sarcoma of the kidney to syndromes such as Denys–Drash
◦ Chondrosarcoma
r Wilms tumor does have a small component of family DIAGNOSTIC TESTS & INTERPRETATION ◦ Clear cell sarcoma
history Lab ◦ Ewing sarcoma/primitive neuroectodermal
r Comprehensive metabolic panel to include liver tumor
Genetics ◦ Fibrosarcoma
r Adult renal sarcomas unknown; suggestion of function tests
r CBC ◦ Kaposi sarcoma
familial tendency with angiosarcoma ◦ Leiomyosarcoma (including the myxoid types)
r UA (microhematuria, pyuria)
– Possible role of DNA mismatch repair pathway ◦ Liposarcoma
r 1–2% of Wilms tumor patients have an inherited r No reliable tumor markers for sarcoma
◦ Malignant fibrous histiocytoma
genetic predisposition Imaging ◦ Malignant hemangiopericytoma
– Most common loss or inactivation of a tumor r CXR or CT to evaluate for metastatic disease in the ◦ Malignant mesenchymoma
suppressor gene called WT1 on chromosome 11 chest or abdomen ◦ Malignant schwannoma
– WT1 located at 11p13 and is associated with r CT/MRI to assess local extent of tumor may aid ◦ Osteogenic sarcoma
renal and gonadal development surgical planning ◦ Rhabdomyosarcoma
– WT2 located at 11p15 and is associated with r On MRA, sarcomas tend to be avascular ◦ Sarcomatoid renal cell carcinoma
Beckwith–Wiedemann syndrome r Renal US may be helpful in evaluation of cystic renal ◦ Synovial sarcoma
– 90% of Wilms tumors arise from somatic ◦ Wilms tumor
mutations with overall genetic paradigm mass
– Reninoma (JG apparatus tumors)
remaining unknown Diagnostic Procedures/Surgery – Urothelial carcinoma upper tract (UTUC)
Biopsy of limited utility r Benign renal mass in children:
PATHOPHYSIOLOGY
r Most common adult renal sarcomas are Pathologic Findings – Choledochal cyst, intestinal duplication cyst
r Morphologically, renal sarcomas are similar to their
leiomyosarcomas, representing as many as – Congenital mesoblastic nephroma
extrarenal counterparts – Crossed-fused ectopia
50–60% of such tumors. A wide variety of other r In adults they can arise from both the parenchyma
types, such as liposarcoma and fibrosarcoma, are – Cystic nephroma (multiloculated cystic nephroma)
and the renal capsule – Hydronephrosis
also found (2)[B]. r Wilms tumor
r Sarcomas exhibit aggressive local growth with high – Mesenteric cyst
– Generally soft and friable with hemorrhage and – Multicystic dysplastic kidney (MCDK): involuted
rate of local recurrence, even in the event of necrosis nonfunctional kidney
negative surgical margins, due to a tendency for – Classic: Coexistence of blastemal, epithelial, and – Polycystic kidney disease
“skip lesions.” stromal cells – Renal abscess
– Unfavorable histology is associated with nuclear – Splenomegaly
enlargement, hyperchromasia, and abnormal
mitotic figures
428
RENAL SARCOMA, ADULT AND PEDIATRIC

R
r Malignant renal masses in children: ADDITIONAL TREATMENT ADDITIONAL READING
– Lymphoma, lymphosarcoma Radiation Therapy
– Neuroblastoma (actually adrenal origin) r Sometimes employed in management of Wilms r Buckley K. Pediatric genitourinary tumors. Curr Opin
– Ossifying renal tumor of infancy tumor postoperatively. Radiation of the tumor bed is Oncol. 2012;24(3):291–296.
– RCC (rare in children) r Russo P, Brady MS, Conlon K, et al. Adult urological
indicated if the tumor extended beyond the renal
– Sarcomas (clear cell, rhabdomyosarcoma) capsule to involve adjacent organs or lymph nodes sarcoma. J Urol. 1992;147(4):1032–1036.
– Wilms tumor (nephroblastoma): A renal mass in or with intraoperative tumor spillage.
childhood is Wilms until proven otherwise r Radiation therapy after surgery in adult sarcomas See Also (Topic, Algorithm, Media)
r Ossifying Renal Tumor of Infancy
may reduce local recurrence. r Renal Capsular Neoplasms
ALERT r Renal Cell Carcinoma, General Considerations
Primary renal sarcoma is extremely rare. Primary Additional Therapies
N/A r Renal Cell Carcinoma, Sarcomatoid
retroperitoneal soft tissue sarcoma (such as
Complementary & Alternative r Renal Leiomyosarcoma
leiomyosarcoma or liposarcoma) with secondary
Therapies r Renal Mass
renal invasion is the more common clinical
presentation. N/A r Renal Sarcoma, Adult and Pediatric Image
r Wilms Tumor
ONGOING CARE
TREATMENT CODES
PROGNOSIS
GENERAL MEASURES r Adult sarcomas, especially high grade, have a
r In adults, the lesions are usually approached as for generally poor prognosis, with 5-yr survival rates of ICD9
approximately 50% r 171.5 Malignant neoplasm of connective and other
RCC, with surgical excision being 1st-line therapy,
– Poor prognostic variables include high-grade soft tissue of abdomen
as the histology of lesion is rarely known r 236.91 Neoplasm of uncertain behavior of kidney
histology, metastases at presentation, large tumor
preoperatively (3)[B]
size, and incomplete resection/margin positivity and ureter
r Masses tend to be quite large, presumably due to r Local recurrence alone is associated with a better
rapid growth pattern survival rate than local recurrence with concomitant ICD10
r The primary treatment of renal sarcomas is surgical r C49.4 Malignant neoplasm of connective and soft
metastasis
excision. Local recurrences should be resected when r Pediatric patients with Wilms tumors can expect a tissue of abdomen
feasible. r D41.00 Neoplasm of uncertain behavior of
>90% cure rate, but prognosis for clear cell sarcoma
r The role of adjuvant and neoadjuvant therapy in the unspecified kidney
and especially rhabdoid tumors is much worse
adult population is poorly understood r D41.01 Neoplasm of uncertain behavior of right
COMPLICATIONS kidney
MEDICATION Children should be monitored for long-term effects of
First Line radiation and/or chemotherapy (such as cardiac
r Dactinomycin and vincristine are used for more dysfunction, HTN, secondary malignancies, CLINICAL/SURGICAL
favorable stages of Wilms, with the addition of endocrinologic abnormalities, and ovarian or testicular
doxorubicin and abdominal radiation for more failure)
PEARLS
advanced stages r Primary renal sarcomas are very rare. Soft tissue
r Doxorubicin for clear cell sarcoma in children FOLLOW-UP
r Careful patient monitoring is essential due to the sarcomas that involve the kidney are the more
r Doxorubicin, dacarbazine, and ifosfamide have been common presentation.
high recurrence rate
used with adult sarcomas; however, response rates r Renal sarcomas are more likely to be seen in
– Adults: Close follow-up for 2–5 yr
at best are poor ◦ CXR every 3–6 months childhood than adulthood. Wilms tumor is the most
Second Line ◦ Abd MRI or CT screening every 3–6 min common pediatric renal sarcoma and has a distinct
N/A ◦ No specific tumor markers to follow treatment algorithm.
– Children: Same as adults. Try to limit studies such r The primary treatment of renal sarcomas is surgical
SURGERY/OTHER PROCEDURES as CT due to long-term ionizing radiation risks. excision. Wide excision is the preferred approach
r Mainstay of treatment for all sarcomas involving due to sarcomas’ tendencies toward skip lesions.
Patient Resources
the kidney is radical nephrectomy with excision of Kidney Cancer Association www.kidneycancer.org/ Local recurrences should be resected when feasible.
entire tumor mass, which may require resection of r It is important to differentiate renal or soft tissue
adjacent organs. In some cases, partial sarcomas from RCC with sarcomatoid features,
nephrectomy may be possible (2)[B]. REFERENCES which is an aggressive variant of RCC, not a primary
r Wide excision is the preferred approach due to sarcoma.
1. Davidoff AM. Wilms tumor. Adv Pediatr.
sarcomas’ tendencies toward skip lesions 2012;59(1):247–267.
r Sarcomas tend to surround the renal vasculature as
2. Wang X, Xu R, Yan L, et al. Adult renal sarcoma:
well as surrounding vascular structures Clinical features and survival in a series of patients
r No defined role for lymphadenectomy
treated at a high-volume institution. Urology.
r Preoperative chemotherapy is given in advanced 2011;77(4):836–841.
cases of Wilms to downstage prior to surgery, 3. Dotan ZA, Tal R, Golijanin D, et al. Adult
usually with external radiation therapy. In bilateral genitourinary sarcoma: The 25-year Memorial
disease, nephron sparing is indicated. Sloan-Kettering experience. J Urol. 2006;176(5):
2033–2038.
429
RENAL TRAUMA, ADULT

Lee C. Zhao, MD, MS
Allen F. Morey, MD, FACS
PATHOPHYSIOLOGY r CT
BASICS r Kidneys are well protected in the retroperitoneum – Contrast enhanced is best
– Deceleration can lead to intimal tearing of renal – Delayed films to evaluate urine leak and collecting
DESCRIPTION artery and thrombosis system
r Renal injuries can occur by either blunt or – Medial urine extravasation
penetrating trauma ASSOCIATED CONDITIONS r IV urography (IVP)
r Rib fractures
– Renal contusions, renal laceration, and renal r Injury to other organ systems – While mostly replaced by CT scan, single shot
vascular injury are the general categories intraoperative IVP when pre-op imaging is not
r Renal injury classification: Based on American GENERAL PREVENTION available before abdominal exploration in the OR
Association for the Surgery of Trauma (AAST) renal r General trauma preventative measures with a film under patient on OR table
injury grading system (1) – Restraints in motor vehicles ◦ Single plain film 10 min after 2 mL/kg of IV
– Grade I: Subcapsular hematoma contrast (max 150 mL)
– Grade II: Laceration <1 cm deep into cortex, small
hematoma with Gerota’s fascia DIAGNOSIS Diagnostic Procedures/Surgery
Angiography may be performed if embolization is
– Grade III: Laceration >1 cm into medulla, no HISTORY being considered
collecting system injury r Ample trauma history:
– Grade IV: Laceration into collecting system, – Allergies DIFFERENTIAL DIAGNOSIS
vascular segmental vein or artery injury, renal r Spontaneous hemorrhage in patients with renal
– Medications
pelvis laceration and/or complete ureteral pelvic – Past medical history mass: Traumatic or atraumatic
disruption – Last meal – Renal angiomyolipoma
– Grade V: Main renal artery or vein injury or – Event – Renal cell carcinoma
thrombosis r Contrast allergy, previous renal surgeries, stones, – Wunderlich syndrome: Atraumatic renal
– Substratification of grade IV injuries (2)[B] hemorrhage
◦ Grade IVb: Higher risk of intervention trauma, cancer r Injury to other organs
(angioembolization or exploration) if 2 or more PHYSICAL EXAM
Active vascular extravasation r Tachycardia and hypotension suggest major bleeding
Perinephric hematoma >3.5 cm r Primary survey TREATMENT
Medial/complex laceration
– Flank contusion
– Abdominal tenderness GENERAL MEASURES
EPIDEMIOLOGY r Supportive care
Incidence r Assessment of associated injuries
r 1–3% of all traumatic injuries ALERT
Degree of hematuria does not correlate with degree r Decision for nonoperative or operative management
r Most commonly injured GU organ of renal injuries (for operative management see
of injury.
Prevalence “Surgery/Other Procedures” below)
r Nonoperative management: Blunt trauma
Estimated 245,000 cases of traumatic renal injuries DIAGNOSTIC TESTS & INTERPRETATION
per year, world wide – Hemodynamically stable patients with well-staged
Lab
r Urinalysis renal injury may be managed nonoperatively
RISK FACTORS
r Blunt trauma – Hematuria >90% of renal injuries – 97% blunt renal injuries can be managed
– Rapid deceleration – Hematuria absent in 36% renal vasculature nonoperatively (1)[B]
◦ Motor vehicle injuries – Monitor with serial Hct and imaging
◦ Falls – Hematuria with hypotension predictor for major – Consider angiography and embolization as
◦ Direct strike to abdomen or flank (sports injury renal injury alternative to renal exploration
related, bicycle accident, pedestrian in motor r Basic labs: Hgb, Hct, Cr, electrolytes
◦ Large perinephric hematoma and extravasation
vehicle accident [MVA]) Imaging of contrast predictive for need of angiographic
r Penetrating trauma r Indications for imaging embolization (3)[B]
– Upper abdominal – Blunt trauma
◦ Stab, gunshot, or industrial injury – Isolated renal injuries
◦ Hypotension (SBP < 90) and hematuria ◦ Most managed nonoperatively except for grade
r Iatrogenic injury ◦ Gross hematuria
V pedicle avulsion
– Laparoscopic, endourologic, renal biopsy, ◦ Clinical indicators of renal injury from ◦ Consider placement of ureteral stent for
percutaneous procedures mechanism or associated injury persistent urine extravasation
– Penetrating trauma
◦ Any degree of hematuria
r US
– Focused abdominal sonography for trauma (FAST)
used in some centers for detection of
hemoperitoneum
430
RENAL TRAUMA, ADULT

R
r Nonoperative management: Penetrating trauma
ADDITIONAL READING
– 55% of stab wounds and 24% of GSW can be ONGOING CARE r Alsikafi NF, Rosenstein DI. Staging, evaluation, and
managed nonoperatively
– If laparotomy is required for other reasons PROGNOSIS nonoperative management of renal injuries. Urol
explore the retroperitoneum for pulsatile, Most blunt trauma does not require surgical Clin N Am. 2006;33:13–19.
expanding hematoma intervention and prognosis is excellent r American Association for the Surgery of Trauma
MEDICATION COMPLICATIONS (AAST) Injury Scoring Scale. http://www.aast.org/
r Urinoma/urinary extravasation Library/TraumaTools/InjuryScoringScales.aspx.
First Line Accessed January 26, 2014.
r Basic fluid and transfusion management – May require internal stent or external drainage
r Broad-spectrum antibiotics for penetrating injury r Urinary fistula See Also (Topic, Algorithm, Media)
r Delayed bleeding r Bladder Trauma
and blunt trauma with urinary extravasation or large
retroperitoneal hematoma r Perinephric abscess r Renal Trauma, Adult Algorithm
r Sepsis r Renal Trauma, Adult Images
Second Line r Calculus formation r Renal Trauma, Pediatric
N/A
r Hydronephrosis r Retroperitoneal Hematoma
SURGERY/OTHER PROCEDURES r Hypertension r Ureter, Trauma
r Indications for operative management
– Due to renal vessel injury r Wunderlich Syndrome
– Absolute: Persistent bleeding, expanding and
– Compression of kidney
pulsatile retroperitoneal hematoma
– Posttraumatic AV fistula
– Relative: Urine extravasation, urinoma, nonviable r Pseudoaneurysm
parenchyma, delayed diagnosis, segmental arterial CODES
injury FOLLOW-UP
– Isolated urine extravasation can be managed Patient Monitoring ICD9
r Bed rest for continued hematuria r 866.00 Injury to kidney without mention of open
nonoperatively with expectation of >90%
resolution (4)[B] r Repeat CT scan wound into cavity, unspecified injury
r Serial Hct r 866.01 Injury to kidney without mention of open
◦ Stent placement if no resolution after 3–7 days
wound into cavity, hematoma without rupture of
– Nonviable tissue >20%, then complications are Patient Resources capsule
greater r Urology Care Foundation: Kidney (renal) Trauma r 866.02 Injury to kidney without mention of open
r Renal exploration: Transperitoneal approach http://www.urologyhealth.org/urology/index. wound into cavity, laceration
– Early isolation of vessels cfm?article=61
– Retroperitoneal exploration for expanding and ICD10
pulsatile hematoma r S37.009A Unspecified injury of unspecified kidney,
r Renal reconstruction REFERENCES initial encounter
– Debridement of nonviable tissue, closure of r S37.019A Minor contusion of unspecified kidney,
1. Buckley JC, McAninch JW. Revision of current
collecting system, coverage of parenchymal defect initial encounter
American Association for the Surgery of Trauma r S37.039A Laceration of unsp kidney, unspecified
– For polar injury, consider partial nephrectomy with
Renal Injury grading system. J Trauma. 2011;
removal of devitalized tissue degree, init encntr
70:35–37.
ADDITIONAL TREATMENT 2. Dugi DD, Morey AF, Gupta A, et al. American
Radiation Therapy Association for the Surgery of Trauma grade 4 renal CLINICAL/SURGICAL
N/A injury substratification into grades 4a (low risk) and
4b (high risk). J Urol. 2010;183:592–597. PEARLS
Bed rest for nonoperative management 3. Nuss GR, Morey AF, Jenkins AC, et al. Radiographic r CT with IV contrast is single best study.
predictors of need for angiographic embolization r Most blunt renal trauma is managed nonoperatively.
Complementary & Alternative after traumatic renal injury. J Trauma. 2009; r Angioembolization should be considered for stable
Therapies 67:578–582.
N/A patients with isolated renal laceration and renal
4. Alsikafi NF, McAninch JW, Elliott SP, et al. vascular laceration.
Nonoperative management outcomes of isolated r Renal vascular avulsions should be explored.
urinary extravasation following renal lacerations r Grade IV renal injuries may be substratified by
due to external trauma. J Urol. 2006;176:
2494–2497. additional findings of active vascular extravasation,
perinephric hematoma, medial/complex laceration.
431
RENAL TRAUMA, PEDIATRIC

r CT:
BASICS DIAGNOSIS – Currently the most commonly used imaging
modality in these patients
DESCRIPTION HISTORY – Triphasic abdominal and pelvic CT (ideally):
r Traumatic injury overall is the leading cause of r Mechanism of injury: Degree of actual traumatic
Clinically stable patients; most sensitive method
childhood death in the United States. injury may not correlate with the mechanism for diagnosing and classifying GU trauma,
r Pediatric renal trauma is subdivided into blunt and – Blunt: Falls, automobile collision, sporting injuries, precontrast phase, nephrogram phase after
penetrating mechanisms of injury. etc. injection of contrast, and delayed images at
r The pediatric kidney is believed to be more – Penetrating: Gunshot wound, stabbing, etc. 15 min. The downside of this is radiation exposure.
r Vital signs in the field:
susceptible to trauma vs. the adult kidney. – Single-phase CT: Clinically labile patients; allows
r Over the past 2 decades, the management of – Hypotension: Children will often have a normal BP for determination of renal perfusion and major
pediatric renal trauma has shifted from operative despite a significant blood loss. renal fractures. This can be followed by a KUB to
r Hematuria: Unlike adults, an unreliable indicator of assess renal integrity.
intervention to conservative management.
underlying renal injury in children: – Delayed CT: Obtained postoperatively after patient
EPIDEMIOLOGY – Up to 70% of children with grade II or higher is stabilized or after patient is resuscitated in the
Incidence renal injury may have neither gross nor ICU for full trauma evaluation; used to assess
r 10–20% of all abdominal blunt trauma involves a microscopic hematuria. grade 3–5 renal injuries 2–3 days posttrauma to
renal injury. r Medical history: Any acute or chronic medical assess for baseline hematoma or urinoma
r 90% of GU injuries are from blunt trauma. conditions and any previous GU abnormality r Focused assessment with sonography for trauma
r Nearly 90% of patients with GU injuries have r Surgical history: Previous urologic procedure for (FAST):
coexisting injuries to the thorax, spine, pelvis, or reflux, stone, hypospadias, etc. – Often combined with serial physical exams as a
intra-abdominal organs. r Iodine or latex allergy screening modality after blunt trauma
r Loss of consciousness – Sensitivity ranges from 70–85% and specificity
Prevalence
N/A ranges from 93–100%; operator dependent
PHYSICAL EXAM – Option in areas with limited radiologic resources
r Vital signs and ABCD of resuscitation to stabilize r Arteriography:
RISK FACTORS
r Pre-existing GU abnormalities (ie, ureteropelvic patient – Used for diagnosis of arteriovenous fistula in the
junction obstruction horseshoe kidney vs. pelvic r BP is often normal in severely hypovolemic children
setting of delayed hemorrhage following renal
kidney): r Exposure: Observe for obvious signs of abdominal/ trauma
– 3–5-fold more common in pediatric patients flank/thoracic trauma, abdominal/flank tenderness, r Retrograde pyelography:
undergoing CT for trauma flank ecchymosis, gross hematuria, pelvic instability – Rule out presence of partial/total ureteral
– Classically presents with a history of hematuria r DRE: Observe for perineal ecchymosis disruption
disproportionate to the severity of trauma r If blood at the urethral meatus, do not insert – Management of symptomatic urinoma with
r Decrease in physical renal protective mechanisms:
catheter placement of ureteral stent
– More pliable thoracic cage and weaker abdominal r Single-shot IVP:
muscles ALERT – Increasingly limited role
– Less renal fat Degree of hematuria does not correlate with degree – Done after patient is hemodynamically stable
– Position of the kidney within the abdomen of injury. following trauma-exploratory laparotomy; allows
Genetics for visualization of functioning contralateral
Disorders that lead to an increase in GU anomalies DIAGNOSTIC TESTS & INTERPRETATION kidney when considering unilateral nephrectomy
have a greater risk for traumatic injury r DMSA scan:
Lab
r CBC, basic metabolic profile, coagulation profile – Allows for quantification of renal function for
PATHOPHYSIOLOGY r Urinalysis
r Tissue or organ injury from external source of energy grade 3–5 injuries; obtain at least 1 wk after
r Grading system: – Unreliable in determining the extent of GU trauma traumatic injury, also indicated
r Follow-up imaging:
– Grade I: Subcapsular hematoma, microscopic or – Up to 70% of children with grade II renal trauma
will have neither gross nor microscopic hematuria. – Triphasic CT is indicated for patients with
gross hematuria, normal radiographic studies
persistent fever, worsening flank pain, or gross
– Grade II: Nonexpanding perirenal hematoma or
ALERT hematuria >72 hr after injury
cortical laceration <1 cm deep
– Grade III: Laceration >1 cm in parenchyma The patient’s hemodynamic status determines when Diagnostic Procedures/Surgery
without collecting system rupture or urine and what type of imaging modality is indicated. N/A
extravasation Pathologic Findings
– Grade IV: Parenchymal laceration through renal Imaging N/A
cortex, medulla, collecting system; contained main r Indications for radiographic imaging: All penetrating
renal artery or vein hemorrhage abdominal trauma or blunt trauma victims with 1 of DIFFERENTIAL DIAGNOSIS
– Grade V (shattered kidney): Renal pedicle the following criteria (1): Injury to other major abdominal viscera in the setting
avulsion, multiple parenchymal lacerations, major – Significant deceleration or high-velocity injury: of acute trauma
injury to the renal vessels, urinary extravasation MVA, fall from >15 ft
– Trauma resulting in fracture of the thoracic cage,
ASSOCIATED CONDITIONS spine, pelvis, or femur, or bruising of the
Injury to other organ systems
torso/perineum
GENERAL PREVENTION – Acute peritonitis
Measures that decrease traumatic injury in general, – Gross hematuria
such as seat belts, air bags – Microscopic hematuria (>50 RBC/HPF) associated
with shock (SBP <90 mm Hg)
– Delayed hemorrhage following renal trauma
432
RENAL TRAUMA, PEDIATRIC

R
– Renal vascular injuries: The kidney is an end REFERENCES
TREATMENT organ; segmental renal vessel repair should not be
attempted, main renal artery reconstruction 1. Buckley JC, McAninch JW. The diagnosis,
GENERAL MEASURES should only be considered if patients are management, and outcomes of pediatric renal
r The major challenge facing the urologist in hemodynamically stable and have either a solitary injuries. Urol Clin N Am. 2006;33:33–40.
evaluating pediatric renal trauma is in determining kidney or bilateral renal injuries. 2. Husmann D. Pediatric genitourinary trauma. In:
when to surgically intervene. – Endoscopic stent placement and/or percutaneous Wein AJ, Kavoussi LR, Novick AC, et al, eds.
r The decision to intervene operatively is based on 3 placement of perirenal drain or nephrostomy tube Campbell-Walsh Urology. 9th ed. Philadelphia, PA:
clinical indicators: Hemodynamic stability, accurate in cases of expanding urinoma Saunders Elsevier; 2007:3929–3945.
radiographic staging, presence of associated organ ADDITIONAL TREATMENT 3. Jacobs MA, Hotaling JM, Mueller BA, et al.
injuries (2). Conservative management vs early surgery for high
r In general: Radiation Therapy
grade pediatric renal trauma–do nephrectomy rates
N/A
– Irrespective of the mechanism of injury and differ? J Urol. 2012;187(5):1817–1822.
provided there are no absolute indications for Additional Therapies
r Nonoperative management (3)
abdominal exploration then all renal trauma can
be observed. – Initially only for if hemodynamically stable ADDITIONAL READING
– Renal exploration and renorrhaphy for grade III or – Admission to ICU for monitoring is warranted:
◦ Bed rest, monitor urine output, serial abdominal r Kawashima A, Sandler CM, Corl FM, et al. Imaging
higher renal injuries should be carried out if
laparotomy is necessary for coexisting exams, serial hemoglobin/HCT, resuscitate and of renal trauma: A comprehensive review.
intra-abdominal injuries. transfuse as necessary Radiographics. 2001;21:557–574.
– Renal exploration may be excluded in patients r Ideal candidate will have grade I–II injury
with concurrent intra-abdominal injuries if the r Patients with isolated grade III, IV, and V renal r Bladder Trauma
urinary tract is separated from the enteric tract by injuries are candidates for nonoperative treatment: r Renal Trauma, Adult
omentum or other tissue, and adequate drains are – Conservative management of isolated grade III–IV r Renal Trauma, Adult Algorithm
left in place. renal injuries will prevent 95% of patients from r Renal Trauma, Adult Images
r Renal injury classification: Based on American requiring operative intervention r Retroperitoneal Hematoma
Association for the Surgery of Trauma (AAST) renal – Angiographic, endoscopic, or percutaneous r Ureter, Trauma
injury grading system (see “Renal Trauma, Adult”) intervention will be required in up to 55% of
r Wunderlich Syndrome
patients
MEDICATION
First Line Complementary & Alternative
r Basic fluid and transfusion management Therapies
r Broad-spectrum antibiotics for penetrating injury N/A
CODES
and blunt trauma with urinary extravasation or large ICD9
retroperitoneal hematoma ONGOING CARE r 866.00 Injury to kidney without mention of open
Second Line wound into cavity, unspecified injury
PROGNOSIS r 866.01 Injury to kidney without mention of open
N/A r Based on the overall renal function following the
SURGERY/OTHER PROCEDURES traumatic injury wound into cavity, hematoma without rupture of
r Absolute indications for renal exploration: r Renal vascular HTN capsule
r 866.02 Injury to kidney without mention of open
– Hemodynamic instability from a renal source – Usually develops within 36 mo after injury
– Expanding or pulsatile retroperitoneal hematoma – DMSA scan is indicated to determine differential wound into cavity, laceration
– Inability to stop persistent or delayed hemorrhage renal function ICD10
via selective vascular embolization – CT angiogram may be necessary to rule out r S37.009A Unspecified injury of unspecified kidney,
r Relative indications for renal exploration: arteriovenous fistula as the source of HTN initial encounter
– Patients with vascular instability resulting in an r End-stage renal disease r S37.019A Minor contusion of unspecified kidney,
inability to obtain adequate preoperative – Bilateral renal injury initial encounter
radiographic studies – May require peritoneal or hemodialysis r S37.039A Laceration of unsp kidney, unspecified
– Retroperitoneal hematoma found at the time of
FOLLOW-UP degree, init encntr
surgical exploration
– Known grade III or higher renal injury during Patient Monitoring
r Repeat CT of the kidney 2–3 days after trauma for
concomitant abdominal exploration: Either
grade III or higher renal injuries.
CLINICAL/SURGICAL
perform renal exploration with renorrhaphy or
separation of GI from GU tract and drain – Have low threshold for repeat CT if patient has PEARLS
placement decreasing hemoglobin/HCT despite blood
Hemodynamically stable patients can be managed
r Renal salvage via renorrhaphy or partial transfusion or if child is hemodynamically unstable.
r Ambulation should resume when gross hematuria conservatively.
nephrectomy requires complete exposure of the
injured kidney, debridement of nonviable tissue, resolves.
repair of the collecting system, and ligation of all – Strenuous physical activity should be avoided
bleeding vessels. for 6 wk.
– Renal pelvic or ureteral injuries should be closed
watertight; if not, then ureteral stents or
nephrostomy tube may be necessary.
– Nephrectomy should be considered in the setting
of irreparable grade IV–V injures and in cases
where nephrectomy would help control bleeding
in the coagulopathic or hypothermic patient.
433
RENAL TUBULAR ACIDOSIS

Steve Dong, MD
BASICS r Acquired RTA type I: DIAGNOSIS
– Autoimmune disease: Systemic lupus
DESCRIPTION erythematosus (SLE), Sjögren syndrome, primary HISTORY
r Renal tubular acidosis (RTA) is a metabolic condition r Failure to thrive, rickets, and osteomalacia in children
biliary cirrhosis, chronic active hepatitis
characterized by abnormal urinary acidification due r Anorexia, nausea, vomiting
– Chronic pyelonephritis
to a defect in renal tubules, resulting in – Diseases causing nephrocalcinosis r Weakness and polyuria due to potassium loss
hyperchloremic nonanion gap metabolic acidosis, – Drugs (amphotericin B, lithium, analgesics) r Constipation
increased pH of the urine – Ehlers–Danlos syndrome r Polydipsia
r 4 major types of RTA are now considered to be – Fabry disease r History of hematuria, urinary tract infections (UTIs),
only 3: – Glycogenosis type III passage of stones in urine
– Type I (distal): Defective distal tubular H+ – Hepatic cirrhosis r History of recurrent, familial, or childhood renal
secretion – Hypercalciuria stone disease
– Type II (proximal): Defective proximal tubular – Hypergammaglobulinemic syndrome r Ask about systemic diseases causing RTA
bicarbonate reabsorption – Leprosy
– Type III (mixed): No longer considered as a distinct – Malnutrition PHYSICAL EXAM
entity – Medullary cystic disease r Urologic exam of genitalia, suprapubic area for
– Type IV: Aldosterone deficiency/resistance – Obstructive uropathy swelling and tenderness
– Sickle cell disease, hereditary elliptocytosis r Exam for osteomalacia, hypokalemic muscle
EPIDEMIOLOGY
– Toxins (toluene, glue) weakness, and growth retardation
Incidence – Vitamin D intoxication r Exam for other systemic diseases
r RTA I: More common in adults (2/3 adults, 1/3
– Wilson disease
children) and women; endemic in certain regions of r Acquired RTA type II: DIAGNOSTIC TESTS & INTERPRETATION
Thailand – Fanconi syndrome due to toxin-related or Lab
r RTA II: Usually more predominant in males r Renal function test usually normal
immunologic nephrotoxic damage
associated with Fanconi syndrome; urinary loss of – Tubular toxicity causing acute tubular necrosis: r Electrolytes and blood gas reveal hyperchloremic,
glucose, amino acids, uric acid, phosphate, and ◦ Sepsis nonanion gap metabolic acidosis:
bicarbonates ◦ Rhabdomyolysis – Hypokalemia or normokalemia in type I and II
r Most RTAs are sporadic occurring at any age. ◦ Hypotension – Hyperkalemia in type IV
Familial RTA are rare and usually occurs in childhood. ◦ Nephrotoxins: Intravenous (IV) contrast, r Urine pH (fasting, under oil, pH meter):
RISK FACTORS aminoglycoside antibiotics – pH > 5.5: Complete type I RTA
r Genetic disorders – Interstitial renal disease: – pH > 5.5, but systemic acidosis mild or absent:
r Secondary to systemic disease. See “Commonly ◦ Multiple myeloma Ammonium chloride loading test and measure
◦ Heavy metal poisoning (cadmium, lead, urinary bicarbonates; failure of urine pH to go
Associated Conditions.”
mercury) below 5.5 is diagnostic of RTA (1)[C]
Genetics ◦ Medications (methicillin, cisplatin, adefovir, r RTA II is diagnosed by bicarbonate loading test:
r Familial RTA I (1):
tenofovir, COX-2 inhibitors, cimetidine, After IV bicarbonate infusion, fractional excretion of
– Autosomal dominant (AD) form is associated with acetazolamide, sulfanilamide, ifosfamide, bicarbonate >15% is diagnostic (1)[C]
mutation in anion exchanger 1 gene tetracycline, Topamax) r Urine calcium: High in type I, normal in type II
– Autosomal recessive (AR) form is due to a ◦ Infections: Leptospirosis, corynebacterium, r Phosphaturia, glycosuria, and aminoaciduria in
mutation in the B1 or H+ -ATPase (V-ATPase) gene diptheria, polyomavirus, cytomegalovirus Fanconi’s syndrome
and associated with sensorineural deafness ◦ Autoimmune disease: SLE, Sjögren’s syndrome,
r Familial RTA II: sarcoidosis Imaging
r Plain x-ray and computed tomography (CT)
– AD form is rare – Amyloidosis
– AR form associated with ocular abnormalities and r Acquired RTA type IV: urogram:
mental retardation – Addison disease – Likely to demonstrate nephrocalcinosis and
– AR form associated with osteopetrosis and – Diabetic nephropathy nephrolithiasis
cerebral calcification – Hypertension Pathologic Findings
– AR form associated with Fanconi syndrome – Lupus nephropathy r Nephrocalcinosis
r Familial RTA IV: Associated with – Obstructive nephropathy r Nephrolithiasis
pseudohypoaldosteronism type 1 – Tubulointerstitial nephropathies r Osteomalacia
r Gordon syndrome
PATHOPHYSIOLOGY
r Type I (distal) tubular acidosis: Secondary to r Sickle cell nephropathy
impaired ability to secrete hydrogen ions into the GENERAL PREVENTION
distal tubule or collecting duct. Urine pH > 5.5. N/A
r Type II (proximal) tubular acidosis: Impaired
bicarbonate absorption in the proximal tubule. Urine
pH may be <5.5.
r Type IV: Presence of aldosterone resistance or
deficiency leading to hyperkalemia (not seen in type
I and II) along with acidosis. Urine pH may be <5.5.
434
RENAL TUBULAR ACIDOSIS

R
DIFFERENTIAL DIAGNOSIS SURGERY/OTHER PROCEDURES REFERENCES
r Other causes of metabolic acidosis (2)[C] r Management of stone by shock wave lithotripsy,
– Lactic and ketoacidosis, chronic renal failure, ureteroscopy, percutaneous nephrolithotomy, and 1. Laing CM, Unwin RJ. Renal tubular acidosis.
chronic diarrhea, etc. rarely, open surgery J Nephrol. 2006;19(suppl 9):S46–S52.
r Azotemia r Management of obstructive uropathy 2. Casaletto JJ. Differential diagnosis of metabolic
r Bilateral stones acidosis. Emerg Med Clin North Am. 2005;23:
r Calcium phosphate stones ADDITIONAL TREATMENT 771–787, ix.
r Chronic pyelonephritis Radiation Therapy 3. Rodriguez SJ. Renal tubular acidosis: The clinical
N/A entity. J Am Soc Nephrol. 2002;13:2160–2170.
r Hypocitraturia < 0.5 mmol/24 h
r Hypokalemia Additional Therapies 4. Domrongkitchaiporn S, Khositseth S, Stitchantrakul
r Medullary nephrocalcinosis Monitor osteoporosis W, et al. Dosage of potassium citrate in the
r Medullary sponge kidney Complementary & Alternative correction of urinary abnormalities in pediatric
distal renal tubular acidosis patients. Am J Kidney
r Recurrent stones: >2/yr Therapies
Dis. 2002;39:383–391.
N/A
TREATMENT ONGOING CARE ADDITIONAL READING

GENERAL MEASURES PROGNOSIS Haque SK, Ariceta G, Batlle D. Proximal renal tubular
r Identifiable causes, such as obstructive uropathy or r Primary RTA I: Although a permanent disease, acidosis: A not so rare disorder of multiple etiologies.
drug-induced RTA, should be corrected or eliminated prognosis is excellent if diagnosis and treatment Nephrol Dial Transplant. 2012;27(12):4273–4287.
r If there is no identifiable etiology, then direct
initiated early.
treatment to correction of acidosis r Prognosis of other RTAs depends on associated See Also (Topic, Algorithm, Media)
r Calcifications, Renal
MEDICATION disease r Fanconi Syndrome
First Line COMPLICATIONS r Nephrocalcinosis
r Alkali therapy decreases stone formation and r Hypercalciuria r Osteoporosis and Osteopenia, Urologic
growth, prevents nephrocalcinosis, normalizes r Hyperkalemia or hypokalemia Considerations
growth retardation in children, and corrects r Nephrocalcinosis r Urolithiasis, Renal
hypokalemia in most cases: r Nephrolithiasis
– Oral alkali therapy: In both type I and type II RTA r Osteomalacia/osteoporosis
with the goal of treatment to restore urinary
citrate to high-normal levels, and not simply FOLLOW-UP
CODES
correct the metabolic acidosis (3)[C] Patient Monitoring
◦ Sodium bicarbonate (7.7 mEq HCO3 /tab) r Spot urine testing for NAG ICD9
◦ Bicitra (1 mEq Na, 1 mEq citrate/mL) r 255.42 Mineralocorticoid deficiency
(N-acetyl-β-D-glucosaminidase) has eliminated the r 276.7 Hyperpotassemia
◦ Polycitra (1 mEq Na, 1 mEq K, 2 mEq citrate/mL) need for 24-hr urine collection. Levels increased
– Type I RTA generally requires lifelong treatment: r 588.89 Other specified disorders resulting from
secondary to renal tubular cell damage and
◦ 1–4 mEq/kg/d of oral bicarbonate or citrate in hypercalciuria. impaired renal function
2–3 divided doses in adults (4)[C] r Urinary calcium excretion should be kept
◦ May require potassium supplementation for ICD10
<0.05 mmol/kg/d in infants and children r E27.40 Unspecified adrenocortical insufficiency
hypokalemia r Potassium levels should be monitored during alkali
r Type II (proximal) RTA: r E87.5 Hyperkalemia
therapy and replaced appropriately r N25.89 Oth disorders resulting from impaired renal
– 5–20 mEq/kg/d in 4–6 doses/d due to the severe r Monitor underlying disease as indicated
bicarbonate wasting. tubular function
– Adults with bicarbonate levels >10 mEq/mL and Patient Resources
no evidence of bone disease may not require National Kidney and Urologic Diseases Information
treatment. Clearinghouse (NKUDIC) http://kidney.niddk.nih.gov/
CLINICAL/SURGICAL
– Supplemental potassium, calcium, vitamin D, and kudiseases/pubs/tubularacidosis/ PEARLS
phosphate may become necessary. r Type I RTA is the only type associated with increased
r Type IV RTA treatment is directed toward correction
stone formation, nephrocalcinosis.
of hyperkalemia rather than acidosis: r Potassium levels should be monitored during alkali
– Dietary potassium restriction
therapy for RTA and replaced appropriately.
– Thiazide or loop diuretics r A young person with multiple stones with systemic
– Mineralocorticoid replacement in cases of adrenal
disease or hyporeninemia (fludrocortisone acidosis and high urine pH, a diagnosis of type I RTA
0.1 mg/d) should be considered.
Second Line
N/A
435
RENAL VEIN THROMBOSIS, ADULT AND PEDIATRIC

Adonteng A. Kwakye, MD
r Adult:
BASICS – Abdominal tumors, especially renal cell carcinoma DIAGNOSIS
– Endothelial damage
DESCRIPTION – Intrinsic hypercoagulability (eg, Factor V Leiden HISTORY
r Renal vein thrombosis (RVT) is an acute or chronic r Newborn/infant:
deficiency)
thrombosis in the renal vein leading to a reduction – Nephrotic syndrome: – Risk factors: Mother’s history, birth, and early
in venous drainage of the kidney. – Membranous nephropathy: Lesion most frequently postnatal course
r In infants, RVT typically presents as a severe illness, associated with nephrotic syndrome–related RVT; – Gross hematuria
r Adult:
occasionally with colicky pain: also reported in many other nephropathies.
– 60% have enlarged kidneys on physical exam; – Use of oral contraceptives, steroids – Sudden onset of hematuria and flank pain should
gross hematuria and microangiopathic hemolytic – Renal transplantation, particularly in those taking raise the question of RVT, as should a history of
anemia and thrombocytopenia can also be present OKT-3 and cyclosporine for immunosupression nephrotic syndrome in the presence of hematuria
r In the adult, RVT presentation depends on onset of – Shock, sepsis, dehydration PHYSICAL EXAM
RVT: – Trauma r Newborn/infant:
– Acute RVT: Triad of sudden flank pain – Use of IV contrast agents – Unilateral, or often bilateral, flank masses
– Costovertebral angle tenderness and gross – Vasculitis – Evidence of dehydration
hematuria only present in minority of cases. – Compression from aortic aneurysm, – Evidence of cyanotic heart disease
– Chronic RVT: Generally asymptomatic; lymphadenopathy, retroperitoneal fibrosis (2) – If the thrombosis is bilateral, oliguria may be
◦ Can have proteinuria and microscopic or gross Genetics present; urine output may be normal with a
hematuria. Unknown unilateral thrombus (4)
r Adult:
EPIDEMIOLOGY PATHOPHYSIOLOGY
Incidence r Newborn/infant: – Evidence of blunt trauma, abdominal mass
r Newborns and infants: – Diminished intrarenal blood flow due to
– Edema or anasarca suggestive of nephrotic
– Commonly associated with hypoxia, dehydration, syndrome
hypovolemia (sepsis, dehydration, diarrhea)
shock, and/or sepsis – Creates prothrombotic state DIAGNOSTIC TESTS & INTERPRETATION
– Usually acute and unilateral (more common on – Clot can then propagate in antegrade and/or Lab
the left side); although 30% bilateral retrograde manner, resulting in RVT r Newborn/infant:
– Male-to-female ratio 2:1 in the neonate, with no – May become bilateral, produce vena caval – Thrombocytopenia, leukocytosis, hemolytic anemia
sex predilection beyond age 1 occlusion and/or renal artery thrombosis – Consumptive coagulopathy (prolonged clotting
– Accounts for approximately 10% of venous – 65% in neonates, 30% beyond 1 yr age time, elevated fibrinogen and fibrin split products)
thrombosis in newborns – Associated with adrenal hemorrhage in 15% of – Proteinuria
– Most common form of thrombosis not associated cases – Elevated BUN and creatinine
with a vascular catheter (1) r Adults: Most often unilateral; acute and chronic r Adult:
r Adults: forms described: – Proteinuria and microscopic hematuria
– Associated with nephrotic syndrome (reported – Acute RVT: Severe dehydration, sudden – Hemolytic anemia, consumptive coagulopathy,
incidence of RVT in patients with nephrotic hypercoagulability, renal vein obstruction from and thrombocytopenia may be present
syndrome ranges from 5–62%), renal cell tumor or transplant rejection – Elevated BUN and creatinine
carcinoma, or renal transplantation – Chronic RVT: – Hypoalbuminemia
– More often chronic and unilateral ◦ Nephrotic syndrome leads to alterations in – Marked elevation in LDH with normal
Prevalence coagulation pathway that creates prothrombotic transaminases
N/A conditions (3)
◦ RVT is a result of nephrotic syndrome and not Imaging
r Newborn/infant:
RISK FACTORS the cause
r Newborn/infant: ◦ Slow onset allows the development of collateral – The extent of thrombus may be assessed by
– Acute hypoxia venous kidney drainage duplex ultrasonography, and only rarely will CT,
– Birth trauma MRI, or renal venography be required for
– Cyanotic congenital heart disease with ASSOCIATED CONDITIONS confirmation of the diagnosis or determination of
r DVT in patients with nephrotic syndrome the extent of thrombus
polycythemia
r Pulmonary embolus – Ultrasonography: Enlarged and echogenic kidneys
– Cytomegalovirus infection
– Dehydration from diarrhea/vomiting (90%) with attenuation or loss of corticomedullary
GENERAL PREVENTION
– Maternal diabetes, polyhydramnios r Adults: Long-term anticoagulation is appropriate if differentiation
– Hyperosmolar state form angiocardiography ◦ Doppler studies may detect increased resistance
RVT has recurred when patients discontinued
– Preterm (<36 wk) infants at greater risk or absence of flow in renal venous branches;
anticoagulation
– Sickle cell disease r Treatment of underlying cause increased resistance in the renal artery may be
present
◦ Doppler ultrasonography is the primary modality
for the detection of RVT; however, its utility is
operator specific (3)
– IVP: Delayed opacification and renomegaly
– A renal scan may be obtained to assess the
function of the involved kidney.
– MRI is more expensive and requires sedation in
pediatric patients (6)
436
RENAL VEIN THROMBOSIS, ADULT AND PEDIATRIC

R
r Adult: SURGERY/OTHER PROCEDURES REFERENCES
– Inferior vena cavography with selective r Infants: No role for surgical thrombectomy
catheterization of the renal vein is the gold r Thrombectomy in adults: 1. Schmidt B, Andrew M. Neonatal thrombosis:
standard for the diagnosis. – Rarely used, because neither renal preservation Report of a prospective Canadian and international
– CT findings are similar in noninvasive evaluation nor improvement in survival demonstrated registry. Pediatrics. 1995;96:939–943.
of acute RVT. – Surgical thrombectomy (either open or 2. Ferri F. Ferri’s clinical advisor 2013. R - Renal vein
◦ Sensitivity of CT angiography approaches 100%; percutaneous) in patients with acute bilateral RVT thrombosis. 1st ed. Philadelphia, PA: Elsevier;
considered current imaging modality of choice with poor prognosis 2013.
◦ Low attenuation within the renal vein; proximal – Postoperative posttransplant RVT 3. Singhal R, Brimble KS. Thromboembolic
venous enlargement r Nephrectomy in highly selected patients for complications in the nephrotic syndrome:
◦ Capsular venous collaterals, thickened Gerota’s lifesaving measures Pathophysiology and clinical management. Throm
fascia and pericapsular stranding r Radical nephrectomy and thrombectomy in renal cell Res. 2006;118:397–407.
– Doppler ultrasonography is helpful, especially in a carcinoma 4. Lum GM. Kidney & urinary tract. In: Hay WW Jr.,
transplanted kidney. Levin MJ, Deterding RR, et al., eds. Current
– MRI: Excellent imaging; avoids iodinated contrast, ADDITIONAL TREATMENT Diagnosis & Treatment: Pediatrics. 21st ed.
r Infants with renal failure—dialysis if needed
but concerns with gadolinium in patients with Chapter 24. New York, NY: McGraw-Hill; 2012.
renal insufficiency r IVC filters are indicated in high-risk adult patients
5. Llach F. Hypercoagulability, renal vein thrombosis,
– IVP for pulmonary embolism. and other thrombotic complications of nephrotic
◦ Faint or absent excretion of contrast syndrome. Kidney Int. 1985;28(3):429–439.
Radiation Therapy
◦ Enlarged kidney due to congestion 6. Textor SC, Leung N. Chapter 286. Vascular injury to
N/A
◦ Collateral circulation may cause collecting the kidney. In: Longo DL, Fauci AS, Kasper DL,
system opacification and/or notching of ureter Additional Therapies
N/A et al., eds. Harrison’s Principles of Internal
◦ Renal pelvis is often distorted Medicine. 18th ed. New York, NY: McGraw-Hill;
Diagnostic Procedures/Surgery Complementary & Alternative 2012.
Renal biopsy in the setting of nephrotic syndrome and Therapies
RVT confirms etiology and may guide therapy N/A
Pathologic Findings ADDITIONAL READING
r Membranous nephropathy is the most common ONGOING CARE r Asghar M, Ahmed K, Shah SS, et al. Renal vein
finding in the setting of nephrotic syndrome and thrombosis. Eur J Vasc Endovasc Surg. 2007;
RVT. PROGNOSIS
r Neonates: Mortality rate of 3% 34(2):217–223.
r In infants the condition is pathologically more r Lau KK, Stoffman JM, Williams S, et al. Neonatal
r The kidney may recover completely, atrophy, or
correctly described as “renal venous thrombosis” as renal vein thrombosis: Review of the
the interlobular and arcuate renal veins are primarily recover partially, resulting in renovascular
hypertension or chronic tubular dysfunction. English-language literature between 1992 and
affected rather than the main renal vein in adults. 2006. Pediatrics. 2007;120(5):e1278–e1284.
r Nephrectomy may be required if renovascular
DIFFERENTIAL DIAGNOSIS hypertension or chronic infection develops. See Also (Topic, Algorithm, Media)
r Other causes of flank pain (eg, urolithiasis, r ACE inhibitors and/or angiotensin II receptor r Nephrotic Syndrome
pyelonephritis, renal infarction) blockers may decrease proteinuria from nephrotic r Renal Cell Carcinoma with Tumor Thrombus
r Renal cell carcinoma with direct compression or r Renal Vein Thrombosis, Adult and Pediatric Image
syndrome as decreased urinary protein loss
tumor thrombus decreases hypercoagulability. r Renal Vein, Leiomyosarcoma
r Renal vein leiomyosarcoma (filling defect)
COMPLICATIONS (5)
r Consumptive coagulopathy
TREATMENT r Pulmonary embolism CODES
r Renal failure
GENERAL MEASURES r Loss of graft in transplant patient ICD9
r Evaluate and treat all underlying causes r 453.3 Other venous embolism and thrombosis of
r Aggressive rehydration and treatment of sepsis, FOLLOW-UP renal vein
diarrhea, and electrolyte abnormalities Patient Monitoring r 581.9 Nephrotic syndrome with unspecified
r Newborn/infant:
MEDICATION pathological lesion in kidney
– Renal function may be followed using nuclear r 788.0 Renal colic
First Line scanning. Atrophy is often detected long term.
r Newborn/infant:
About 5% of affected neonates progress to ICD10
– Use of thrombolytic agents is reported, but dialysis or transplantation. r I82.3 Embolism and thrombosis of renal vein
controversial – Monitor blood pressure, as renovascular r N04.9 Nephrotic syndrome with unspecified
– Systemic heparinization: hypertension may occur after RVT in ∼20%, even
◦ Prevents thrombus propagation into vena cava morphologic changes
with normal renal function. r N23 Unspecified renal colic
(risk of propagation low with fluid and r Adult:
electrolyte repletion). – Treat cause of nephrotic syndrome
◦ Used in neonates with bilateral RVT
◦ Equivocal results regarding long-term
– Long-term anticoagulation as preventive measure CLINICAL/SURGICAL
preservation of renal function
in nephrotic syndrome not supported PEARLS
r Adult: – Because RVT may be asymptomatic, all patients
with nephrotic syndrome should be monitored for r Renal vein thrombosis (RVT) is associated with
– Unilateral RVT: Heparin anticoagulation and symptoms of RVT nephrotic syndrome in adults.
long-term anticoagulation with warfarin: r Membranous nephropathy is most common
– Optimum duration of anti-coagulation unknown Patient Resources
MedlinePlus: Renal vein thrombosishttp://www.nlm. pathology in RVT with nephrotic syndrome.
– Most experts feel that warfarin should be r Newborns and infants more likely than adults to
continued for as long as nephrotic syndrome nih.gov/medlineplus/ency/article/000513.htm
have bilateral RVT.
persists (3).
Second Line
N/A
437
RETROGRADE EJACULATION
Pravin K. Rao, MD
PATHOPHYSIOLOGY
BASICS r Normal ejaculation requires: DIAGNOSIS
– Seminal emission
DESCRIPTION – Bladder neck closure HISTORY
r Expulsion of semen from posterior urethra into r Absence or presence of orgasm
– Antegrade expulsion from urethra
bladder with low- or zero-volume antegrade r Neurologic control: r Presence of erectile dysfunction
ejaculate. r Cloudy urine after sex/orgasm
– Central control in multiple brain regions
r Suspected in men with symptoms or semen analysis ◦ Can promote or inhibit ejaculation r Symptoms of hypogonadism
findings suggesting low or absent ejaculate volume. – Sympathetic (T12–L3): r Medical history (see risk factors)
r Primary implications are for infertility. ◦ Hypogastric nerve (thoracolumbar) r Surgical history (see risk factors)
– Also: Sexual function/satisfaction. ◦ Seminal “emission” into posterior urethra by r Medications (see risk factors)
r No other known medical health effects. contraction of epididymis, vas deferens/ampulla, r Accuracy of semen analysis findings:
r Men with failure of emissions are often labeled as seminal vesicle (SV), and prostate smooth – Low measured volume may be due to spillage
having “retrograde ejaculation.” muscle – Some patients report subjective low volume only
– Failed deposition of ejaculate contents into ◦ Bladder neck closure preventing retrograde
at time of sample collection
posterior urethra before expulsion. ejaculation ◦ Anxiety due to lab/atmosphere
– Parasympathetic (S2–S4): ◦ Anxiety related to medical condition
EPIDEMIOLOGY ◦ Pelvic nerve
Incidence ◦ Gland secretions of prostate SV PHYSICAL EXAM
r Usually normal physical exam findings
r 74–78% incidence after transurethral prostate – Somatic (S2–S4):
◦ Pudendal nerve r Absent vasa suggests congenital absence of the vas
surgery (1)[B]
r 4–26% incidence with α-blocker tamsulosin ◦ Efferents from sacral cord deferens
◦ Contraction of bulbocavernosal and r Small testes may suggest hypogonadism
(2,3)[A] r Seminal vesical (SV) dilation may suggest
r As low as 14% incidence after bilateral ischiocavernosal muscles
◦ Relaxation of external urethral sphincter ejaculatory duct obstruction (EDO)
nerve-sparing retroperitoneal lymph node ◦ Projectile expulsion of ejaculate r Muscle weakness or focal neurologic deficit may
dissection (RPLND) (4)[B] – Sensory suggest primary neurologic cause
Prevalence ◦ Pudendal nerve
N/A ◦ Tactile stimulation of penis can activate DIAGNOSTIC TESTS & INTERPRETATION
ejaculatory reflex Lab
RISK FACTORS r Retrograde ejaculation occurs from impaired bladder r If ejaculate volume <1.5 cc, consider
r Bladder neck/prostate procedures
neck closure due to various causes postejaculatory urinalysis (PEU)
– Transurethral resection of the prostate r PEU
– Transurethral incision of the prostate (TUIP) – Poor coaptation of bladder neck
◦ Medication side effect – >10–15 sperm/HPF is diagnostic for retrograde
– Bladder neck incision (BNI)
r Surgical/traumatic/congenital neuropathy ◦ Prostate surgery ejaculation
◦ Idiopathic – Small number of sperm may be normal
– Retroperitoneal surgery
◦ eg, RPLND – Neural disruption – Technique:
◦ Spinal cord injury (SCI) ◦ Abstain from ejaculation 2–3 days
– Pelvic surgery ◦ Diabetes mellitus (DM) ◦ Empty bladder
◦ eg, abdominoperineal resection
◦ Retroperitoneal lymphnode dissection (RPLND) ◦ Collect/attempt antegrade ejaculate
– Spinal cord injury (SCI)/surgery ◦ Pelvic surgery ◦ Collect urine by void or catheter
– Spina bifida/myelomeningocele r Endocrine evaluation if clinical suspicion for
r Medical neuropathy ASSOCIATED CONDITIONS
– Diabetes mellitus (DM) r See risks factors hypogonadism
– Multiple sclerosis (MS) r Benign prostatic hyperplasia (BPH) Imaging
r Iatrogenic from medications r Bladder neck dysfunction Only performed for concurrent medical conditions
– α-blockers r Diabetes mellitus (DM) Diagnostic Procedures/Surgery
◦ Reduce bladder neck muscle tone r Multiple sclerosis (MS) N/A
◦ Reduce seminal emissions r Rectal cancer
◦ Tamsulosin, terazosin, doxazosin Pathologic Findings
r Testicular cancer N/A
– Antipsychotic and psychotropic medications
◦ Risperidone GENERAL PREVENTION
– Antidepressants r Avoidance of iatrogenic causes
◦ Selective serotonin reuptake inhibitors r Nerve sparing during RPLND
Genetics
N/A
438
RETROGRADE EJACULATION
R
DIFFERENTIAL DIAGNOSIS SURGERY/OTHER PROCEDURES 3. Lepor H. Long-term evaluation of tamsulosin in
r Anejaculation r Sperm retrieval benign prostatic hyperplasia: Placebo-controlled,
r Anorgasmia (inability to reach orgasm) – For use with assisted reproductive techniques double-blind extension of phase III trial. Tamsulosin
r Aspermia due to failure of emission ◦ IUI (intrauterine insemination) Investigator Group. Urology. 1998;51:901–906.
r Congenital bilateral/unilateral absence of the vas ◦ IVF In vitro fertilization 4. Steiner H, Zangerl F, Stöhr B, et al. Results of
◦ ICSI Intracytoplasmic sperm injection bilateral nerve sparing laparoscopic retroperitoneal
deferens
r EDO r Sperm retrieval technique lymph node dissection for testicular cancer. J Urol.
r Erectile dysfunction – Prior to collection, alkalinize urine to pH 7 2008;180(4):1348–1352.
◦ Sodium bicarbonate 650 mg QID or 5. van der Linden PJ, Nan PM, te Velde ER, et al.
– Failure to reach orgasm
– Poor expulsion of ejaculate through flaccid penile 1–3 tablespoons of baking soda, 12–48 hr Retrograde ejaculation: Successful treatment with
urethra before collection artificial insemination. Obstet Gynecol. 1992;
r Hypogonadism – Catheterize or void for collection 79:126–128.
r Sperm retrieval from the testis and epididymis, an
r Semen spillage in lab
r Poor semen collection technique option for unsuccessful retrograde collection
– Adoption and use of donor sperm can prevent the ADDITIONAL READING
need for IVF/ICSI
Ohl DA, Quallich SA, Sønksen J, et al. Anejaculation
TREATMENT ADDITIONAL TREATMENT and retrograde ejaculation. Urol Clin North Am.
GENERAL MEASURES N/A
r Treatment typically reserved for fertility purposes See Also (Topic, Algorithm, Media)
r Treat reversible causes Additional Therapies r Anorgasmia/Dysorgasmia
r Modify causative medications N/A r Ejaculatory Disturbances
– Change or discontinue causative medications Complementary & Alternative r Infertility, Urologic Considerations
– Some clinicians favor alfuzosin for BPH (possibly Therapies r Semen Analysis, Abnormal Findings and Terminology
less RE than other α-blockers) N/A r Semen Analysis, Technical and Normal Value
MEDICATION
r α-adrenergic agents CODES
– Dosing structure highly variable: PROGNOSIS
r Success rates with assisted reproductive techniques
◦ Pseudoephedrine 60 mg ICD9
◦ Ephedrine 25–50 mg largely dependent on female factors r 355.9 Mononeuritis of unspecified site
r 44% pregnancy rates with intrauterine insemination r 608.87 Retrograde ejaculation
◦ Imipramine 25–50 mg (may cause dizziness and
nausea) (5)[C] r 606.9 Male infertility, unspecified
◦ Frequency ranges from QD to QID COMPLICATIONS
◦ Duration ranges from 2–14 days r Main issue is infertility ICD10
◦ Side effects: HTN, tachycardia r G62.9 Polyneuropathy, unspecified
r Emotional distress
r Author recommendation: Pseudoephedrine 60 mg r N46.8 Other male infertility
QID × 2–7 days prior to ejaculation (titrate to FOLLOW-UP r N53.14 Retrograde ejaculation
effectiveness) Patient Monitoring
r Medical therapy less likely to be effective after Follow up semen analysis to determine effectiveness
bladder neck injury or surgery of medical therapy CLINICAL/SURGICAL
Second Line Patient Resources PEARLS
N/A MedlinePlus: Retrograde Ejaculation http://www.nlm.
In men with spinal cord injury (SCI) or history of
nih.gov/medlineplus/ency/article/001282.htm
retroperitoneal surgery, men may have failure of
seminal emission, so sperm retrieval from the bladder
REFERENCES may not be feasible.
1. Briganti A, Naspro R, Gallina A, et al. Impact on

sexual function of holmium laser enucleation versus
transurethral resection of the prostate: Results of a
prospective, 2-center, randomized trial. J Urol.
2006;175(5):1817–1821.
2. Wilt TJ, Mac Donald R, Rutks I. Tamsulosin for
benign prostatic hyperplasia. Cochrane Database
Syst Rev. 2003;(1):CD002081.
439
RETROPERITONEAL ABSCESS
Jessica H. Hannick, MD
Ahmer V. Farooq, DO
r Most common source is from renal diseases

BASICS accounting for 47% of retroperitoneal abscesses. DIAGNOSIS
r Infection seeds a contained space in
DESCRIPTION retroperitoneum: HISTORY
r A retroperitoneal abscess is an infectious process r Abdominal or flank pain (60–75%)
– Depending on the source, anaerobic and aerobic r Sweats, fever, and chills (30–90%)
that involves the retroperitoneum. organisms may be present.
r The retroperitoneum spans anteroposteriorly from r Malaise (10–22%)
– Usual source is normal flora from a nearby organ
the peritoneum to posterior parietal wall of the site (eg, GI, GU, female reproductive tract). r Nausea/vomiting
abdominal cavity and craniocaudally from the – Multimicrobial infections are common. r Altered bowel habits
diaphragm to the pelvic floor. – Malignancy frequently violates fascial barriers, r Dysuria
r Most common source of infection is from renal whereas abscesses tend to be contained by the r Weight loss (12%)
diseases. fascia. r Duration of symptoms is typically longer than 1 wk
– Hypoxia and lack of appropriate blood supply limit r Recent instrumentation/surgery/trauma
EPIDEMIOLOGY
effective immune response. r Recent treatment for UTI
Incidence – If untreated, bacteremia, followed by shock
Reported highest incidence in 3rd–6th decades. r History of urolithiasis, inflammatory bowel disease,
ensues.
Prevalence r TB and Staphylococcus (skin source) were previously pancreatitis, diverticulitis, appendicitis,
N/A major pathogens, but are less common today. osteomyelitis, malignancy, TB
r Proteus and Escherichia coli are the most commonly r Medical comorbidities: Diabetes, renal insufficiency,
RISK FACTORS immunosuppression (ie, HIV)
r Appendicitis cultured bacteria in retroperitoneal abscesses.
r Diabetes r Common pathogens (aerobic and anaerobic) (2,3): PHYSICAL EXAM
– Enterobacteriaceae: r General vital signs:
r Diverticulitis
r Existing osteomyelitis or epidural infection ◦ E. coli – Fever
◦ Klebsiella pneumonia – Tachycardia
r GU tract obstruction
◦ Proteus sp. – Tachypnea
r Immunosuppression ◦ Pseudomonas aeruginosa r Unlike peritoneal cavity, retroperitoneum is relatively
r Inflammatory bowel disease (Crohn’s disease) – Anaerobes: concealed on exam.
r Malignancy ◦ Peptostreptococcus sp. r Assess for:
r Osteomyelitis ◦ Bacteroides fragilis – Tenderness: Usually localized, dull, and mild
r Pyelonephritis ◦ Prevotella sp. – Costovertebral angle tenderness
r Recent instrumentation or surgery of the GU or GI ◦ Clostridium sp. – Palpable flank/abdominal mass
tract – Enterococcus sp. – Lower abdominal, groin, and/or upper thigh
r Systemic infection (ie, hematogenous spread from – Streptococcus sp. referred pain due to irritation of retroperitoneal
– S. aureus nerves
remote infection) r Site-specific pathogens:
r Trauma – Psoas sign: Increased pain when flexing patient’s
r Tuberculosis – Pancreatic abscess: thigh against examiner’s hand; suggests
◦ S. aureus involvement of psoas muscle
PATHOPHYSIOLOGY ◦ K. pneumoniae
r Retroperitoneal abscess is an infectious process that ◦ P. aeruginosa DIAGNOSTIC TESTS & INTERPRETATION
can be found in 1 of 4 retroperitoneal compartments – Pelvic retroperitoneal: Lab
◦ Neisseria gonorrhoeae r Lab findings often nonspecific (ie, elevated ESR)
(1):
◦ Streptococcus B r Obtain CBC (leukocytosis)
– Anterior retroperitoneum:
◦ Esophagus, duodenum, pancreas, bile duct, – Anterior retroperitoneal: r BMP: Serum glucose often elevated
portal and splenic veins, appendix, ◦ Clostridium sp. r Urinalysis
ascending/descending colon, rectosigmoid ◦ Fusobacterium nucleatum – Approximately 30% will have microscopic
– Posterior retroperitoneum (aka ASSOCIATED CONDITIONS hematuria.
perinephric/perirenal): r Diabetes, liver disease, renal insufficiency, – Pyuria is also very common.
◦ Kidneys, ureters, gonadal vessels, aorta, inferior r Urine/blood/abscess cultures
immunosuppression, retroperitoneal hematoma
vena cava, lymphatics r GU specific: Urinary tract infection (UTI), urolithiasis,
◦ See “Renal and Perirenal Abscess” Imaging
instrumentation/surgery, malignancy r Cross-sectional CT or MRI is most helpful:
– Retrofascial (aka iliopsoas): r GI specific: Malignancy, surgery, pancreatic
◦ 12th rib, spine, paraspinous muscles – CT (100% sensitivity, 77% specificity):
pathology ◦ Low-density mass in retroperitoneum with
– Pelvic retroperitoneal:
◦ Prevesical, retrovesical, presacral, perirectal surrounding inflammation
GENERAL PREVENTION ◦ Gas may be present in approximately 33% of
spaces Perioperative antibiotic prophylaxis
r Primary infection if spread is hematogenous cases
◦ Evaluates surrounding organs (ie, possible
(75–90% Staphylococcus aureus) sources)
r Secondary infection if spread is from infected
adjacent organs (78% enteric bacteria).
440
RETROPERITONEAL ABSCESS
R
r MRI: SURGERY/OTHER PROCEDURES
r Early percutaneous drainage (5)
REFERENCES
– Thick purulent collections have high-intensity
signal on T1-weighted images – Essential in lesions >3 cm 1. Solomkin JS. Peritonitis, pancreatitis and
– Edema in surrounding fat seen as high signal on – May consider antibiotics only in abscesses <3 cm intra-abdominal abscesses. In: Cohen J, Powderly
T2-weighted images r Surgical drainage must be considered if: WG, eds. Cohen & Powderly: Infectious Diseases.
– High soft tissue contrast resolution sensitive for – Safe percutaneous drainage not possible 2nd ed. Philadelphia, PA: Mosby; 2004:517–527.
detecting psoas muscle pathology and – Percutaneous drainage has failed 2. Anaya DA, Dellinger EP. Surgical infections and
intervertebral disc involvement – Multiple abscesses choice of antibiotics. In: Townsend CM Jr,
– May not show calcifications or gas collections – Multiloculated abscesses Beauchamp RD, Evers M, et al., eds. Sabiston
r US: Can reveal gas/fluid collections – Purulent material too thick to be drained Textbook of Surgery. 18th ed. Philadelphia, PA:
r KUB: May show psoas shadow, loss of renal outline, – If patient is persistently febrile after 48–72 hr of Saunders Elsevier; 2008.
displacement of organs, gas, or urolithiasis appropriate antibiotics 3. Brook I, Frazier EH. Aerobic and anaerobic
r Gallium67 citrate and indium111 chloride scanning – If primary cause must be addressed surgically (ie, microbiology of retroperitoneal abscesses. Clin
can be helpful: xanthogranulomatous pyelonephritis (XGP), Infect Dis. 1998;26:938–941.
– False positives: Pyelonephritis, acute tubular malignancy, urolithiasis) 4. Crepps JT, Welch JP, Orlando R 3rd. Management
necrosis, vasculitis, and neoplasms r Surgical approach should be retroperitoneal unless and outcome of retroperitoneal abscesses. Ann
r Chest x-ray may show elevation of hemidiaphragm, pancreatic pathology is present: Surg. 1987;205:276–281.
pleural effusions, secondary pneumonia – Obtain cultures 5. Tunuguntla A, Raza R, Hudgins L. Diagnostic and
– Irrigate abscess cavity aggressively therapeutic difficulties in retroperitoneal abscess.
Diagnostic Procedures/Surgery – Use drains liberally
r CT, MRI, or US-guided aspiration and drainage of South Med J. 2004;97:1107–1109.
abscess cavity ADDITIONAL TREATMENT
r Specimens must be sent for both aerobic and Radiation Therapy
anaerobic cultures No role ADDITIONAL READING
r Consider sending for AFB culture r Brook I. Microbiology and management of
Pathologic Findings N/A abdominal infections. Dig Dis Sci. 2008;53:
Coagulation necrosis 2585–2591.
Complementary & Alternative r Heller MT, Haarer KA, Thomas E, et al. Acute
DIFFERENTIAL DIAGNOSIS Therapies
r Malignancy N/A conditions affecting the perinephric space: Imaging
r Necrotizing fasciitis anatomy, pathways of disease spread, and
differential diagnosis. Emerg Radiol. 2012;19:
r Osteomyelitis ONGOING CARE 245–254.
r Pancreatitis r Negus S, Sidhu PS. MRI of retroperitoneal
r Perforated viscus (ie, duodenal ulcer) PROGNOSIS collections: A comparison with CT. Br J Radiol.
r Mortality is considerable (5–50%) despite modern
r Perinephric aneurysm/pseudoaneurysm 2000;73:907–912.
r Perinephric/perirenal abscess management that combines antibiotics, drainage,
and intensive care support. See Also (Topic, Algorithm, Media)
r Psoas abscess r High success with antibiotics and percutaneous r Psoas Abscess, Urologic Considerations
r Pyelonephritis r Renal and Perirenal Abscess
drainage (>80%):
r Ruptured aortic aneurysm r Only 1–4% recurrence with percutaneous drainage r Retroperitoneal Abscess Image
r TB r If abscess is not drained and only antibiotics are r Retroperitoneal Hematoma
r Trauma/retroperitoneal hematoma r Retroperitoneal Mass and Cysts
used, mortality approaches 100%
r Urinoma
COMPLICATIONS
r Abscess crossing the midline to opposite side or
TREATMENT tracking into the ipsilateral thigh CODES
r DVT
GENERAL MEASURES r GI bleed ICD9
r Supportive care r 567.31 Psoas muscle abscess
r Organ failure
r DVT prophylaxis r 567.38 Other retroperitoneal abscess
r Pneumonia
r Secondary infections: Osteomyelitis, involvement of r 998.59 Other postoperative infection
MEDICATION
First Line psoas muscle, fistulization to the skin ICD10
r Broad-spectrum antibiotics to empirically cover most r K68.11 Postprocedural retroperitoneal abscess
FOLLOW-UP
likely pathogens (ampicillin, gentamicin, and r K68.12 Psoas muscle abscess
metronidazole) (4) Patient Monitoring
r Reimaging necessary r K68.19 Other retroperitoneal abscess
– Refine antibiotic coverage based on culture results
– Tailor duration of treatment to clinical progress – CT or MRI (MRI avoids radiation)
– Timing depends on clinical progress
Second Line r Drains: CLINICAL/SURGICAL
N/A – Must be monitored carefully and irrigated PEARLS
appropriately r Nonspecific signs and symptoms frequently lead to a
r Can be removed when:
delay in diagnosis and treatment.
– Patient is clinically improved r Early percutaneous drainage is essential in lesions
– Drainage stops (<10 mL/d) or becomes serous
– Abscess cavity involution is documented on >3 cm.
imaging
Patient Resources
N/A
441
RETROPERITONEAL FIBROSIS (RPF, ORMOND DISEASE)

Steve Dong, MD
r Secondary RPF: 30% of patients with RPF have an PHYSICAL EXAM

BASICS identifiable cause of their RPF: r Patient can appear pale, ill, and has malaise if
– Medications: significant azotemia is present
DESCRIPTION ◦ Prolonged therapy with ergot alkaloids such as r Low-grade fevers and hypertension
r Retroperitoneal fibrosis (RPF) also refered to as methylsergide (Sansert, once widely used for r Abdominal exam: Mass, abdominal bruit,
Ormond disease, is characterized by sclerotic tissue migraine headaches) costovertebral angle tenderness
from inflammatory processes causing encasement of ◦ Others include LSD, methyldopa, phenacetin, r Testicular masses
the retroperitoneal structures including the ureters, β-blockers, amphetamines, hydralazine, and r Lower-extremity edema, varicosities
aorta, and inferior vena cava. The main analgesics
manifestation is obstructive uropathy. – Malignancy: DIAGNOSTIC TESTS & INTERPRETATION
r Exhibits a perivascular distribution, typically ◦ Lymphoma (most common), multiple myeloma, Lab
including the periaortic, pericaval, and peri-iliac carcinoid, pancreatic tumors, prostate cancer, r No tests are diagnostic
retroperitoneum. testicular cancer, and sarcoma r Metabolic profile: Electrolyte abnormalities will
r Generally classified as either primary (idiopathic) or – Radiotherapy for malignancies such as seminoma, depend upon the degree of ureteral obstruction
secondary RPF. colon, or pancreatic cancer r Erythrocyte sedimentation rate (ESR) and C-reactive
r Hallmark is medial deviation of the ureters on – Infections: Tuberculosis, actinomycosis, protein (CRP) are usually elevated
imaging with or without hydronephrosis. histoplasmosis r Ferritin and other acute phase reactants are often
– Others: Trauma (hemorrhage, urinary
EPIDEMIOLOGY high
extravasation), surgical injury, Crohn disease, r Polyclonal hypergammaglobulinemia
Incidence inflammatory bowel disease, asbestos exposure, r ANA is positive in 60% of patients along with other
r In Finland, incidence is 0.1:100,000/yr fat necrosis, collagen vascular disease,
r Unknown, but estimated at perianeurysmal inflammation autoantibodies including antismooth muscle
1:200,000–1:500,000/yr antibodies and rheumatoid factor
Prevalence r Atherosclerotic disease (abdominal aortic aneurysm) Imaging
r Excretory Urography (2):
1–38 per 100,000 r Autoimmune diseases: Ankylosing spondylitis and
– Medial deviation of the ureters with tapering of
RISK FACTORS Wegener granulomatosis
r Membranous glomerulonephritis the middle 1/3 of the ureter beginning at the 3rd
r Asbestos exposure
or 4th lumbar vertebra
r Associated with autoimmune disorders r Multifocal fibrosclerosis: RPF may present as part of
– Varying degrees of hydronephrosis; may see a
r Abdominal aortic aneurysm a systemic sclerosis nonfunctioning kidney
r Male > Female (2–3:1) – Presentation may include sclerosing mediastinitis, – Encasement of ureters may prevent dilation of
r RPF most common in the 5th–6th decades, but can sclerosing cholangitis, orbital pseudotumor, and middle and distal ureteral segments
Riedel thyroiditis r Ultrasound (US)
occur at any age
r Use of implicated medications (see below) GENERAL PREVENTION – More useful for following the response to therapy
r Malignancy Avoid medication implicated in RPF (see above) r Computed tomography (CT)
– Imaging modality of choice
Genetics – Typically shows a symmetric, geometrically shaped
r Evidence suggests an immunogenetic role with DIAGNOSIS mass encasing the retroperitoneal structures
certain HLA haplotypes: – Demonstrates the medial deviation of the ureters
– HLA-DRB1*03 and HLA-B*08 HISTORY and extrinsic compression with hydronephrosis
r Constitutional symptoms (fatigue, weight loss,
PATHOPHYSIOLOGY – Mass is often isodense to muscle with contrast
r Idiopathic RPF recently identified as a anorexia, low-grade fever)
r Pain (back, flank, abdominal) and duration enhancement
immunoglobulin G4-related disease (IgG4-RD) and r Magnetic resonance imaging (MRI)
r Signs of vascular obstruction:
is a multisystem, fibroinflammatory condition (1) – Hypodensity on T1 images but high intensity on
r Most commonly, the retroperitoneal thickening is – Testicular pain, varicocele, hydrocele, leg edema, T2-weighted images
deep vein thrombosis, claudication r Positron emission tomography (PET):
located between L5 and S1, close to the aortic r GI symptoms such as weight loss, nausea, anorexia,
bifurcation – Investigational; may visualize other disease sites
r Mechanical obstruction of the ureters is usual constipation, or vomiting – May reveal neoplastic or infectious processes to
r Urinary symptoms, including frequency, and dysuria,
presentation; may also cause venous or arterial which the RPF may be secondary
occlusion also oliguria if severe
r Medication history especially ergot alkaloids Diagnostic Procedures/Surgery
r Primary RPF: r Retrograde pyelography may be indicated in
r History of malignancies, other autoimmune or
– 70% of cases are idiopathic, and the exact patients with severe azotemia prohibiting the use of
pathogenesis is unclear collagen vascular diseases, fibrotic processes, contrast-enhanced imaging. Usually shows medial
r Mitchinson and Parums classify idiopathic RPF in a inflammatory bowel diseases, asbestos exposure, deviation of ureters.
range of diseases collectively termed chronic radiation exposure r CT-guided biopsy may be necessary to rule out a
r Surgical history:
periaortitis malignant process.
– Immune-mediated reaction to antigens (ceroid – Abdominal, vascular, or endoscopic procedures
and low-density lipoprotein) within atherosclerotic
plaques
– Often have autoantibodies, and thus overlap with
many autoimmune disorders
– IgG4-bearing plasma cells may also be involved in
the pathogenesis of RPF
442
RETROPERITONEAL FIBROSIS (RPF, ORMOND DISEASE)

R
Pathologic Findings r Ureterolysis:
r Gross findings secondary RPF:
REFERENCES
– May be performed via an open approach
– Smooth, flat, firm, grayish/tan-colored mass (transabdominal) or laparoscopically 1. Khosroshahi A, Carruthers MN, Stone JH, et al.
– Extends from the origin of the renal vessels to the (hand-assisted or standard) (3) Rethinking ormond’s disease: “Idiopathic”
distal extent of the common iliac vessels – Ureters are often wrapped in omentum or retroperitoneal fibrosis in the era of IgG4-related
– May also involve the thoracic aorta and other intraperitonealized to prevent further fibrous disease. Medicine (Baltimore). 2013;92(2):82–91.
atypical areas entrapment 2. Caiafa RO, Vinuesa AS, Izquierdo RS, et al.
r Microscopic findings r Other procedures: May require ileal interposition Retroperitoneal fibrosis: Role of imaging in
– Early findings: Collagen bundles with capillary graft, autotransplantation, nephrectomy, or urinary diagnosis and follow-up. Radiographics.
proliferation and inflammatory cells diversion in complicated or severe cases 2013;33(2):535–552.
– Later acellular and avascular mass with sheets of 3. Brown JA, Garlitz CJ, Hubosky SG, et al.
hypocellular collagen Hand-assisted laparoscopic ureterolysis to treat
– Vasculitis of small retroperitoneal vessels with Radiation Therapy ureteral obstruction secondary to idiopathic
plasma cells staining for IgG4 (rarest IgG subclass) N/A
retroperitoneal fibrosis: Assessment of a novel
DIFFERENTIAL DIAGNOSIS Additional Therapies technique and initial series. Urology. 2006;68(1):
r Observation:
r Medial deviation of the ureters 46–49.
– There may be a role in patients on methylsergide
– Malignancies, aneurysms, bladder diverticulum,
after discontinuation of the medication if normal
and prior surgery
– 20% of normal individuals have medial deviation
renal function. ADDITIONAL READING
– These patients should be monitored for resolution
of the ureters, especially on the right r Scheel PJ Jr, Feeley N. Retroperitoneal fibrosis.
r Retroperitoneal mass: See also Section I of hydronephrosis. If the hydronephrosis does not
resolve, then the standard combination of medical Rheum Dis Clin North Am. 2013;39(2):365–381.
“Retroperitoneal masses, fluid, and cysts” and surgical therapy should be administered. r Vaglio A, Palmisano A, Corradi D, et al.
– Malignant processes; inflammatory r Tamoxifen has been used Retroperitoneal fibrosis: Evolving concepts. Rheum
myofibroblastic tumors r Low-protein, sodium-restricted diet for patients with Dis Clin N Am. 2007;33:803–817.
– Desmoid-type fibromatosis; associated with r Vaglio A, Salvarani C, Buzio C. Retroperitoneal
Gardner syndrome; presents as soft tissue mass renal insufficiency
fibrosis. Lancet. 2006;367:241–251.
with mass effect Complementary & Alternative
Therapies See Also (Topic, Algorithm, Media)
N/A r Hydronephrosis/Hydroureteronephrosis (Dilated
TREATMENT Ureter/Renal Pelvis), Adult
r Discontinue any offending medications r Retroperitoneal fibrosis (RPF, Ormond Disease)
ONGOING CARE Image
r Relieve urinary obstruction:
r Retroperitoneal Hematoma
– Monitor for postobstructive diuresis after the PROGNOSIS
Prognosis is excellent with combined medical and r Retroperitoneal Masses, Fluids and Cysts
urinary system is decompressed
r Biopsy to rule out malignancy surgical therapy
r Unclear if trial of steroids or immediate ureterolysis COMPLICATIONS
is optimal therapy r Recurrence of RPF: Typically in 1st yr; usually limited CODES
to those treated with medical therapy
MEDICATION r Ureteral injury, requiring further surgical ICD9
First Line r 590.80 Pyelonephritis, unspecified
r After ureteral obstruction has been relieved, 1st-line management
r Vascular injury r 593.4 Other ureteric obstruction
therapy is generally glucocorticoids (prednisone). No r Postoperative adhesions due to intraperitoneal r 599.60 Urinary obstruction, unspecified
consensus as to duration of therapy:
– Prednisone 60 mg every other day for 2 mo, then procedure ICD10
tapered over 5 mo to 5 mg/d FOLLOW-UP r N13.5 Crossing vessel and stricture of ureter w/o
– Alternate regimen: 60 mg/d for 6 wk, and tapered Patient Monitoring hydronephrosis.
over the next 2–3 mo to 10 mg/d for a total of 1 yr r Patients can be monitored at regular intervals with r N13.6 Pyonephrosis.
Second Line symptom check, ESR/CRP levels, creatinine, and r N13.9 Obstructive and reflux uropathy, unspecified.
r In patients with glucocorticoid-resistant RPF or who degree of hydronephrosis on US
have recurrent disease, immunosuppressive agents r CT/MRI is usually performed 2–4 mo after the
may also be helpful: beginning of the steroid treatment (1) CLINICAL/SURGICAL
– Prednisone in combination with r Patients treated with definitive surgical intervention PEARLS
cyclophosphamide or azathioprine for 6–12 mo require less frequent follow-up r Although no tests are diagnostic of RPF, most will
– Mycophenolate mofetil has also been used in
combination with glucocorticoids Patient Resources present with medial deviation of the ureters on
r Medline Plus: Retroperitoneal Fibrosis
imaging.
SURGERY/OTHER PROCEDURES http://www.nlm.nih.gov/medlineplus/ency/ r CT is the image modality of choice.
r Relief of ureteral obstruction: article/000463.htm r Stents are often placed for relief of obstruction.
– Ureteral stents may be helpful during subsequent r Patients who fail steroid treatment without evidence
ureterolysis
– Usually not difficult; often elect to stent both sides of malignancy should undergo ureterolysis.
even if not bilaterally obstructed to prevent
obstruction or provide guide for surgery
r Percutaneous nephrostomy undertaken only in
acutely ill patients; rarely necessary
443
RETROPERITONEAL MASSES, FLUID, AND CYSTS

Mark R. Anderson, MD, MSc

BASICS r The retroperitoneum extends from the diaphragm
Lab
superiorly to the pelvis inferiorly and is situated r CBC: Leukocytosis (infection or lymphoma),
DESCRIPTION between the posterior parietal peritoneum anteriorly leukopenia, anemia
r Retroperitoneal masses and cysts can originate from and the transversalis fascia posteriorly (1). r Serum chemistry: Elevated serum creatinine,
retroperitoneal organs or nonorgan tissue. The latter r The anterior pararenal space is bordered anteriorly
azotemia (obstructive uropathy), transaminitis
are relatively rare. by the posterior parietal peritoneum, posteriorly by (biliary obstruction), and elevated alkaline
r 70–80% of primary retroperitoneal neoplasms are the anterior renal fascia (Gerota fascia), and laterally phosphatase (bone involvement).
malignant in nature, and these account for by the lateroconal fascia. r AFP, LDH, and β-HCG: Testicular tumor markers
0.1–0.2% of all malignancies in the body. r The anterior pararenal space is subdivided into the r ESR: Elevated in retroperitoneal fibrosis
r Most cystic lesions within the retroperitoneum are pancreaticoduodenal space (contains the pancreas r Urinalysis: Hematuria, pyuria
benign; unless the lesion is mostly solid then suspect and duodenum) and the pericolonic space (contains r Urine cytology: Evidence of a malignant urothelial
malignancy. ascending and descending colon).
r Metastatic disease is the most common etiology of a r The posterior pararenal space is situated between source
r Blood and urine culture
solid retroperitoneal mass. the posterior renal fascia (Zuckerkandl fascia) and r Adrenal mass: Pheochromocytoma screen
r Liposarcomas are among the most common of the transversalis fascia.
primary retroperitoneal tumors and are r The perirenal space is located between the anterior – Plasma metanephrines
◦ 96–100% sensitivity, 85–89% specificity
distinguished by their often large dimensions and renal fascia and the posterior renal fascia.
range of subtypes. r The great vessel space is the fat-containing region – 24-hr urine-fractionated metanephrines
◦ 91–98% sensitivity and specificity
– Peak incidence: Ages 40–60. that surrounds the aorta and the inferior vena cava
– 10–15% of sarcomas, and approximately 20% of (IVC) and lies anterior to the vertebral bodies and Imaging
these lesions arise in the retroperitoneum. r Adrenal: CT washout for adenoma, MRI “light bulb”
psoas muscles.
– Often recur usually within the 1st 6 mo after r Below the kidneys, the anterior and posterior sign/T2 bright for carcinoma and
surgery. pararenal spaces merge to form the infrarenal pheochromocytoma, MIBG scan for
retroperitoneal space, which communicates pheochromocytoma (2)
EPIDEMIOLOGY r CT urogram for RCC and urothelial carcinoma
Incidence inferiorly with the prevesical space and
extraperitoneal compartments of the pelvis. r CT can show enhancement, fat density, water
Retroperitoneal sarcoma: Accounts for <1% of all r Due to the loose connective tissue in the density to help characterize underlying components
adult malignancy, or 9,500 new diagnoses per year, r MRI better at defining local invasion
∼2.7 cases per million per year of retroperitoneal retroperitoneum, tumors can have widespread
growth and extension before clinical presentation. r Ultrasound can differentiate between solid and
sarcoma
fluid-filled masses but not good at determining
Prevalence ASSOCIATED CONDITIONS
malignant potential or regional mets.
N/A N/A r CT with contrast has relative contraindication if GFR
RISK FACTORS GENERAL PREVENTION <60, MRI has relative contraindication if GFR <30.
r Primary, solid/cystic retroperitoneal mass: Previous N/A r MAG-3 diuretic renal scan can determine relative
radiotherapy (dose dependant), chemical exposure differential function between each kidney and urine
(vinyl chloride, arsenic), HIV/AIDS DIAGNOSIS obstruction.
r Primary, cystic retroperitoneal mass: Parasitic r Testicular sonogram for mass
infection, embryonic remnants, prior HISTORY r Bone scan, mammogram if needed
lymphadenectomy r Headaches, palpitations, etc. for hypertension r Cystogram if pelvic lipomatosis
Genetics secondary to pheochromocytoma
r Tuberous sclerosis (TS1, TS2 mutation, tumor r Unexplained weight loss Diagnostic Procedures/Surgery
r Image-guided biopsy: CT- or US-guided fine-needle
suppressor loss) r Constitutional symptoms
r Night sweats aspiration is usually feasible, but core-needle biopsy
r Werner syndrome (chromosome 8 alteration,
improves diagnostic capability
premature aging) r History of chemotherapy, radiation therapy r Open surgical biopsy: Best option if the mass is
r Li–Fraumeni syndrome (p53 mutation, tumor r Back or bone pain
small and inconveniently located for needle biopsy
suppressor loss) r Medications: Methysergide, methyldopa, LSD r Be prepared to complete the resection if sarcoma
r Neurofibromatosis (NF1, NF2 mutation) r GI complaints: Nausea, vomiting, pain, constipation, identified
r Liposarcomas are being reclassified based on a increasing abdominal girth r Aspiration of cyst: Fluid for cytology, culture,
molecular basis. Well-differentiated and creatinine
PHYSICAL EXAM
dedifferentiated lesions are a continuum of lesions r Vitals for hypertension r Angiogram: To delineate relationship of tumor to
based on the genetic abnormality of giant and ring r Cachexia vascular anatomy or to determine extent of
chromosomes usually involving chromosome 12. r Lymphadenopathy aneurysm
r Gene amplification, particularly of MDM2, drives
r Neurologic deficits from paraneoplastic syndrome
their pathology.
r Myxoid and round-cell lesions are another r Lower-extremity lymphedema
r Breast exam
continuum that have fusion transcripts caused by
translocations in chromosomes 16 and 12. r Testicular exam
r Alveolar rhabdomyosarcoma t(2;13) (q35;q14) r Abdominal mass
PAX3-FKHR, and t(1;13) (p36;q14) PAX7-FKHR r Signs of virilization
r Sporadic gastrointestinal stromal tumor activating
kinase mutations KIT or PDGFRA
444
RETROPERITONEAL MASSES, FLUID, AND CYSTS

R
Pathologic Findings COMPLICATIONS
r Metastasis pathology is consistent with primary r Bowel injury
TREATMENT r Adjacent organ injury (liver, spleen, pancreas)
tumor pathology.
r Determination of benign vs. malignant tissue is not GENERAL MEASURES r Lymphocele
always possible, leaving final determination to the r Need tissue diagnosis via primary excision or needle r Deep vein thrombosis
surgical pathology. biopsy r Wound infection
r Well-differentiated liposarcomas mostly resemble r Core biopsy better than fine needle if possible r Transfusion-dependent anemia
lipomas and are typically low grade. MEDICATION
r Pleomorphic liposarcomas comprise 10–15% FOLLOW-UP
First Line Patient Monitoring
defined as high-grade malignant variants with very r Metastatic lesions and lymphoproliferative cancers
bizarre nuclei and huge lipoblasts and carry poor Schedule imaging that is intensive during 1st 2 yr
are best treated with systemic, tumor-specific (q3–6mo) followed by biannual, migrating to annual
prognosis.
r Liposarcoma is most common (35%), followed by chemotherapy (in most cases). by year 5 is generally recommended for most
r Sarcomas respond variably to chemotherapy,
leiomyosarcoma (30%), malignant fibrous retroperitoneal masses.
depending on the histology, and generally do not
histiocytoma (20%), rhabdomyosarcoma, and Patient Resources
influence survival.
peripheral nerve neoplasm. r Pheochromocytoma needs α-blocking blood N/A
r Lymphoma: Diffuse, monomorphous proliferation of
pressure control, followed by β-blockade. Some
lymphocytes.
r Fibrosis: Cellular and acellular variants coexist; advocate single agent calcium channel blockade. REFERENCES
r May need stress steroids if functional adrenal tumor
fibroblast and collagen proliferation. 1. Osman S, Lehnert BE, Elojeimy S, et al. A
suppresses contralateral function.
DIFFERENTIAL DIAGNOSIS r Infected retroperitoneal cysts are treated with comprehensive review of the retroperitoneal
r Solid masses—Benign (malignant variant in broad-spectrum (gram positive and negative) anatomy, neoplasms, and pattern of disease
parenthesis) antibiotics until culture sensitivities are known: spread. Curr Probl Diagn Radiol. 2013;42(5):
– Lipoma (liposarcoma) – Ampicillin 1 g IV q6h (gram positive) 191–208.
– Leiomyoma (leiomyosarcoma) – Gentamicin 5–7 mg/kg/d (gram negative) 2. Rajiah P, Sinha R, Cuevas C, et al. Imaging of
– Fibroma (chondro-, synovial cell-, fibrosarcoma) uncommon retroperitoneal mass. Radiographics.
Second Line 2011;31:949–976.
– Rhabdomyoma (rhabdomyosarcoma)
N/A
– Hemangioma (angiosarcoma)
– Perivascular epithelioid cell tumor (PECT): SURGERY/OTHER PROCEDURES
Angiomyolipoma, lymphangioleiomyomatosis, r Metastatic site resection may be beneficial for ADDITIONAL READING
clear cell “sugar” tumor, clear cell prognosis and/or symptoms for RCC and testicular
myomelanocytic tumor, pigmented melanotic tumors N/A
tumor (sarcoma variants) r Liposarcoma needs primary excision See Also (Topic, Algorithm, Media)
– Gastrointestinal stromal tumor, aka GIST r Extensive lymph node resection commonly needed r Retroperitoneal Abscess
– Myxoma (myxosarcoma) in liposarcoma and testicular cancer (modified r Retroperitoneal Fibrosis (RPF, Ormond Disease)
– Chordoma templates used in some instances) r Retroperitoneal Hematoma
– Schwannoma, neurofibroma r Benign cysts can be aspirated and sclerosed r Retroperitoneal Liposarcoma
– Ganglioneuroma, ganglioneuroblastoma r Retroperitoneal Lymphoma
(neuroblastoma) ADDITIONAL TREATMENT
r Retroperitoneal Masses, Fluids, and Cysts Image
– Paraganglioma, pheochromocytoma Radiation Therapy
r Retroperitoneal sarcoma is typically radiation r Retroperitoneal Rheumatoid Nodules
(pheochromocytoma)
– Mature teratoma (seminoma, nonseminoma germ resistant. r Retroperitoneal Sarcoma
cell tumors; choriocarcinoma, malignant teratoma, r Intraoperative radiotherapy for sarcoma has been r Retroperitoneum, Fat Necrosis
yolk sac, embryonal, mixed) shown to improve local control rates, but does not
– Sex cord: Granulose, thecoma, Sertoli–Leydig improve survival.
(rarely malignant)
Additional Therapies CODES
– Malignant lymphoma, extramedullary
N/A
plasmacytoma, fibrous histiocytoma ICD9
r Cystic malignant masses Complementary & Alternative r 158.0 Malignant neoplasm of retroperitoneum
– Mucinous cystadenoma or cystadenocarcinoma Therapies r 568.89 Other specified disorders of peritoneum
– Mesothelioma N/A r 789.39 Abdominal or pelvic swelling, mass, or lump,
– Cystic teratoma
other specified site
– Paraganglioma, neurilemmoma, sarcoma ONGOING CARE
r Cystic nonmalignant mass
ICD10
– Hematoma PROGNOSIS r C48.0 Malignant neoplasm of retroperitoneum
– Urinoma r 5- and 10-yr survival following surgical resection of r K68.9 Other disorders of retroperitoneum
– Lymphocele retroperitoneal sarcoma is 45% and 29%. r R19.09 Other intra-abdominal and pelvic swelling,
– Pancreatic cyst and pseudocyst r Poorly differentiated liposarcoma metastasize.
mass and lump
– Lymphangioma r Completely resected, nonmetastatic, and low-grade
– Postoperative seroma sarcomas are associated with improved survival.
r Leiomyosarcoma is an independent predictor of poor CLINICAL/SURGICAL
outcome. PEARLS
r Adrenal carcinoma typically presents late stage and
has poor prognosis even with complete resection. Most solid retroperitoneal masses are malignant.
r Pheochromocytoma has good prognosis.
r RCC has good prognosis though is most lethal GU
cancer and present with mets ∼25% of time.
445
RHABDOMYOLYSIS
Sanjay S. Kasturi, MD
PATHOPHYSIOLOGY
BASICS r Muscle cell destruction DIAGNOSIS
– Pressure or crush
DESCRIPTION – Cellular hypoxia HISTORY
r Rhabdomyolysis is muscle necrosis resulting in the r Reperfusion injury results in large quantities of r Trauma
egress of cellular muscle particles (namely r Sepsis
potassium, phosphate, myoglobin, CK, and urate
myoglobin, potassium, creatine kinase [CK], and r New medication
leak into the circulation
lactic acid dehydrogenase [LDH]) into the blood – Electrolyte alterations further impact cellular r Toxin exposure, drug use or infection
stream. integrity r Excessive muscle use
r In particular myoglobin is harmful to the kidney and r Normal plasma myoglobin is very low r Electrolyte or endocrine disorder
often causes acute kidney injury. (0–0.003 mg/dL) r Prolonged operating room time—most common
– Up to 15% of patients who have rhabdomyolysis – With >100 g of skeletal muscle damaged, serum reason in urology (2,3,4)
can have renal failure. haptoglobin binding capacity becomes saturated – Most commonly reported in the laparoscopic
r There are many causes for rhabdomyolysis; this – At this point circulating myoglobin becomes nephrectomy data when patients are in flank or
section primarily focuses on operative causes. “free” and is filtered by the glomeruli modified flank position for >6 hr but also seen in
EPIDEMIOLOGY – Myoglobin precipitates in the kidney and cause exaggerated lithotomy and steep Trendelenburg
renal tubular obstruction, potentially leading to – Male sex predominates
Incidence acute kidney injury
r 2,600 cases per year (likely underreported) – Elevated BMI, reported mean BMI of 33.2 in
r Myoglobin levels return to normal values in 1–6 hr review of the laparoscopic nephrectomy data
r Overall incidence of 0–4.9% in the laparoscopic
after injury due to hepatic metabolism and renal
nephrectomy data excretion
PHYSICAL EXAM
r Generalized fatigue, nausea, fevers
RISK FACTORS r Up to 12 L of fluid may be sequestered in the
r Trauma and immobilization (1) r Mental status changes
necrotic muscle tissues r Skin discoloration
– Lying unconscious on hard surface under the – This relative hypovolemia is an additional cause of
r Muscular pain and swelling (symptoms may be out
influence of alcohol or drugs renal failure in rhabdomyolysis
– Crush injury – Free iron, which catalyses free radical production of proportion with exam)
– Prolonged compression as seen in excessive further enhances ischemic renal tubule damage r Muscle weakness
operating times (esp. males) r Compartment syndrome r Symptoms may be absent in 50% of patients
◦ Laparoscopic, robotic, and open – Caused by insufficient blood supply to muscles due r Reddish-brown urine
◦ Dorsal lithotomy positioning to increased pressure within a body compartment r Classic triad of muscle pain, weakness, and dark
r Elevated BMI (esp. muscle mass) (arm, leg, any enclosed space within the body) urine
r Sepsis and shock – 6 “Ps” associated with compartment syndrome:
r Toxins (spider and snake venom [mostly in South Pain out of proportion based on exam, DIAGNOSTIC TESTS & INTERPRETATION
America, Asia, Africa]) paresthesia, pallor, paralysis, pulselessness, and Lab
r Myoglobinuria:
r Medications (cocaine, Ecstasy [MDMA] LSD, pressure
– For most prolonged operative cases the – Myoglobin only appears in the urine when serum
amphetamines, statins [especially in combination
paraspinous muscles and the extremities are at level >1.5 mg/dL
with fibrate-derived lipid-lowering agents such as ◦ Red-brown urine when urine levels >100 mg/dL
niacin], cyclosporin, itraconazole, colchicine, risk for compartment syndrome
– Positive for blood on urine dipstick but no RBCs
steroids) ASSOCIATED CONDITIONS
r Infections (HIV, influenza) r Acidosis suggests myoglobinuria (5)
– Short half-life only 2–3 hr, so it may return to
r Excessive muscle use (status epilepticus, prolonged r Cardiac arrest (hyperkalemia)
normal if muscle damage is limited
exercise) r Compartment syndrome r Elevated CK levels (5× upper limit of normal which
r Electrolyte and endocrine abnormalities r Disseminated intravascular coagulation (DIC) is about >1,000 U/L)
(hyponatremia, hyperthyroidism, ketoacidosis) – Activation of the coagulation cascade by the – CK half-life of 26 hr and remains elevated longer
r Electrical shock injury, lightning strike substances released from damaged muscle cells than myoglobin, peaks at 1–3 days and declines
r 3rd-degree burns r Hepatic dysfunction at 3–5 days after all muscle injury has stopped
r High body temperature, heat stroke, malignant r Myoglobinuric acute renal failure r Basic metabolic panel
hyperthermia – Monitor for acute renal failure and hyperkalemia
r Myopathy (eg, Duchenne muscular dystrophy) GENERAL PREVENTION r Calcium level:
r Avoid immobilization or prolonged operating times
Genetics r Appropriate patient padding in the operating room – Can be hypocalcemic early, then hypercalcemic
r Suspect a genetic disorder with recurrent r Some reports of using pulse oximetry monitoring of later
r Uric acid:
rhabdomyolysis after minimal to moderate exertion lower extremity to monitor for compartment
or after viral infections starting in childhood – Conversion of purines from lysed muscle cells
syndrome r CBC/clotting studies (for DIC)
– Glycogen and lipid disorders (McArdle disease, r Monitor for malignant hyperthermia
carnitine deficiency, others) r LFTs, ABG
– Duchenne muscular dystrophy r Microscopic urine: Pigmented casts, dysmorphic red
cells
Imaging
r Often unnecessary
r MRI with gadolinium best modality for muscle
injury
– Sensitivity of 100% vs. 42% for US and 62% for
CT scan
446
RHABDOMYOLYSIS
R
Diagnostic Procedures/Surgery SURGERY/OTHER PROCEDURES 4. Reisiger KE, Landman J, Kibel A, et al. Laparoscopic
r Muscle biopsy is unnecessary r Fasciotomy for compartment syndrome. renal surgery and the risk of rhabdomyolysis:
r Forearm ischemic test to differentiate genetic causes – For the extremity such as the leg Diagnosis and treatment. Urology. 2005;66(suppl
of rhabdomyolysis (6) recommendations for fasciotomy vary. In general 5):29–35.
– Relies on forearm compression with exercise and an intracompartmental pressure of >30 mmHg or 5. Bagley WH, Yang H, Shah KH. Rhabdomyolysis.
determination of ammonia and lactate levels a >30 mm Hg difference between diastolic blood Intern Emerg Med. 2007;2(3):210–218.
pressure and the compartment pressure. 6. Sauret JM, Marinides G, Wang GK.
Pathologic Findings r Dialysis for hyperkalemia, acidosis, and/or fluid
r Though muscle biopsy is not needed, one would see Rhabdomyolysis. Am Fam Physician. 2002;65(5):
noninflammatory loss of the nucleus and muscular overload. 907–913.
stria. – In general, only 4% of patients require dialysis, but 7. Huerta-Alardı́n AL, Varon J, Marik PE.
r Renal biopsy: Myoglobin precipitates and forms up to 55% in the laparoscopic nephrectomy data Bench-to-bedside review: Rhabdomyolysis–an
obstructive casts. ADDITIONAL TREATMENT overview for clinicians. Crit Care. 2005;9(2):
Radiation Therapy 158–169.
r Acidotic states N/A
r Compartment syndrome Additional Therapies ADDITIONAL READING
r DIC Monitor osteoporosis
r Nephritic syndromes Complementary & Alternative Wen T, Deibert CM, Siringo FS, et al.
r Rhabdomyolysis can be the result of another process Positioning-related complications of minimally invasive
Therapies
radical prostatectomies. J Endourol.
(ie, sepsis) and result in other complications (ie, N/A
2014;28(6):660–667.
compartment syndrome, DIC)
ONGOING CARE r Acute Kidney Injury, Adult
TREATMENT PROGNOSIS
r Acute Tubular Necrosis (ATN)
r Overall survival rate of 78.6% at 14 yr r Compartment Syndrome, Urologic Considerations
GENERAL MEASURES r Myoglobin Nephrotoxicity
r Prevention of acute renal failure (ARF) r Initial mortality rate as high as 8%
r Recognition of compartment syndrome r ARF develops in 33% of patients r Myoglobinuria
r Elderly patients and those with comorbidities should – In review of the laparoscopic nephrectomy data, r Urine, Abnormal Color
be treated in an intensive care unit patients who developed ARF had a higher peak
CK than those who did not (46,780 U/L vs.
MEDICATION 25,650 U/L) CODES
First Line (6,7)
r Aggressive hydration initially with normal saline COMPLICATIONS
r Long-term weakness, pain, and numbness; may ICD9
– Urine output should be maintained at (goal of r 728.88 Rhabdomyolysis
2 mg/kg/h of urine output) until myoglobinuria have permanent disability
r Morbidity associated with dialysis and fasciotomy r 929.9 Crushing injury of unspecified site
has ceased r 958.5 Traumatic anuria
– High rates of IV fluid administration should be FOLLOW-UP
used at least until the CK level decreases to or Patient Monitoring ICD10
below 1,000 U/L r Check for return of renal function r M62.82 Rhabdomyolysis
r Consider mannitol for osmotic diuresis to purge r Physical therapy as needed r T79.5XXA Traumatic anuria, initial encounter
nephrotoxic agents r T79.6XXA Traumatic ischemia of muscle, initial
r Diuretics should not be used as they may worsen the Patient Resources
r Medline Plus: Rhabdomyolysis http://www.nlm. encounter
condition
r Alkalinize urine to prevent ARF: nih.gov/medlineplus/ency/article/000473.htm
– Bicarbonate: 1 ampule in 1 L of normal saline CLINICAL/SURGICAL
◦ Goal: Urine pH >6.5 and serum pH 7.4–7.45 REFERENCES PEARLS
r There are retrospective data to suggest aggressive
r The classic triad of muscle pain, weakness, and dark
hydration is sufficient for treatment and that 1. Khan FY. Rhabdomyolysis: A review of the
mannitol and bicarbonate are not needed literature. Neth J Med. 2009;67(9):272–283. urine suggests rhabdomyolysis.
r Avoid correction of early hypocalcemia as r Limit operative times especially in obese and
2. Glassman DT, Merriam WG, Trabulsi EJ, et al.
hypercalcemia can develop later Rhabdomyolysis after laparoscopic nephrectomy. muscular patients. Consider high BMI as a risk factor
JSLS. 2007;11(4):432–437. for intraoperative rhabdomyolysis.
Second Line r Some advocate not using a kidney rest/bar during
May need to correct acidosis, DIC, and hyperkalemia, 3. Wolf JS Jr, Marcovich R, Gill IS, et al. Survey of
neuromuscular injuries to the patient and surgeon laparoscopic surgery to help prevent rhabdomyolysis.
if present r Appropriately pad all pressure points in the
during urologic laparoscopic surgery. Urology.
2000;55(6):831–836. operating room.
r Early recognition and aggressive hydration (better
outcomes within the 1st 6 hr of presentation).
447
RHABDOMYOSARCOMA, PEDIATRIC (SARCOMA BOTRYOIDES)

Nicholas G. Cost, MD
Paul H. Noh, MD, FACS, FAAP
Pathologic Findings
BASICS DIAGNOSIS r Embryonal:
– Most common subtype
DESCRIPTION HISTORY – Accounts for majority of GU RMS
r Rhabdomyosarcoma (RMS) (sarcoma botryoides) is a r Family history of malignancy or genetic syndromes
– Embryonal variants associated with excellent
malignancy arising from embryonal mesenchyme (Li–Fraumeni, neurofibromatosis) prognosis:
that tends to occur mostly in children (Sometimes r Bladder/prostate: ◦ Sarcoma botryoides
also called Embryonal Rhabdomyosarcoma) – Urinary frequency ◦ Spindle cell/leiomyomatous
r Most common soft tissue sarcoma in children – Stranguria r Alveolar:
r Sarcoma botryoides describes a polypoid variant of – Urinary retention – Less common in GU RMS
RMS originating in a hollow viscus (vagina, bladder) – Hematuria – More common in trunk/extremity RMS
r Of all types of pediatric RMS15–20% involve GU r Paratesticular:
– Higher rates of local recurrence, LN spread, and
system: – Scrotal swelling or pain distant metastasis
– Paratesticular – Back pain r Pleomorphic:
r Vaginal/uterine:
– Bladder – Undifferentiated/anaplastic variant
– Prostate – Vaginal discharge/bleeding – Poor prognosis
– Uterus PHYSICAL EXAM DIFFERENTIAL DIAGNOSIS
– Vagina r Bladder/prostate r Bladder/prostate
EPIDEMIOLOGY – Abdominal mass – TCC of bladder
Incidence – Bladder distention – Inflammatory pseudotumor of bladder
r 0.5–0.7 cases per million children <15 yr – Firm prostate or mass on rectal exam – Nephrogenic adenoma of bladder
r Bimodal age distribution: r Paratesticular – Fibroepithelial polyps of prostatic urethra
– Scrotal mass r Testis
– 1st peak: 2–4 yr r Vagina/uterine
– 2nd peak: 15–19 yr – Primary testicular tumor
r 3rd most common solid tumor in children (behind – Vaginal mass (may be prolapsing) – Benign adnexal mass
– Abdominal mass r Vagina/uterine
neuroblastoma and Wilms tumor)
DIAGNOSTIC TESTS & INTERPRETATION – Prolapse of ureterocele, urethra, vagina
Prevalence
N/A Lab
r Basic metabolic panel: BUN/Cr may be elevated with
RISK FACTORS TREATMENT
ureteral obstruction
See genetics r Complete blood count: May see anemia due to GENERAL MEASURES
Genetics vaginal bleeding or hematuria r Pre- and post-op staging and risk classification are
r Li–Fraumeni syndrome: r β-HCG or AFP: Evaluate for testicular tumors critical in evaluation and treatment planning
– Mutation of p53 tumor suppressor gene – Preoperative staging: Intergroup
– Higher incidence of RMS Imaging
r CT/MRI of abdomen/pelvis: Evaluate local extent of Rhabdomyosarcoma Study Group (IRSG) staging/
r Neurofibromatosis: classification system based on TNM and primary
tumor, pelvic or retroperitoneal LN involvement,
– Higher incidence of RMS location
r Cytogenetic abnormalities: distant metastasis
r Chest x-ray/CT: Evaluate for pulmonary metastases – Postoperative grouping: IRSG grouping based on
– Alveolar histology subtype: r PET scan: Evaluate the metabolic activity of the primary resection
◦ 1;13 translocation (favorable prognosis) – Risk classification: Combines stage, group, and
◦ 2;13 translocation (unfavorable prognosis) primary for future comparison after therapy, as well histology—helps determine therapy and prognosis
– Embryonal histology subtype: as assess for metastasis r Preoperative staging: TNM system
r Bone scan: Evaluate for osseous metastasis
◦ Loss of heterozygosity on chromosome 11 – T1: Confined to organ of origin
r Scrotal US: Characterize paratesticular mass ◦ (a) ≤5 cm in diameter
PATHOPHYSIOLOGY ◦ (b) >5 cm in diameter
r The Latin word “botryoides” refers to the polypoid Diagnostic Procedures/Surgery
r Bone marrow aspirate/biopsy: Evaluate for – T2: Extension or fixed to surrounding tissue
or “grape-like lesion” appearance of the tumor ◦ (a) ≤5 cm in diameter
beneath the mucosa metastases for all primary sites of RMS
r Bladder/prostate ◦ (b) >5cm in diameter
– Some sources refer to this as “embryonal RMS”
r Rapid growth with local invasion – Cystoscopy: Transurethral resection/biopsy for – N0: Regional LNs clinically negative
r Can spread by lymphatic and hematogenous routes pathologic diagnosis – N1: Regional LNs clinically positive
– Image-guided needle biopsy: Pathologic diagnosis – Nx: Unknown
r Thought to arise from immature cells that are
r Paratesticular – M0: No distant metastasis
destined to form striated skeletal muscle: – M1: Metastasis present
– However, may arise in locations where skeletal – Radical inguinal orchiectomy: Diagnostic and r Preoperative staging: IRSG
muscle is not typically found, such as the bladder therapeutic
r Vagina/uterine – Stage 1: Vaginal and paratesticular, any T, any N,
r Defect in regulatory mechanism that controls
M0
proliferation and differentiation of skeletal muscle – Cystoscopy/vaginoscopy: Evaluate extent of tumor,
– Stage 2: Bladder/prostate, T1/T2a, N0/Nx, M0
r Prognosis and pattern of spread depends on biopsy for pathologic diagnosis
– Stage 3 Bladder/prostate, T1/T2a and N1, OR
histologic subtype and clinical staging T1b/T2b, any N, M0
r Lymph nodes (LNs) and lungs are the most common – Stage 4: Any T, M1
sites of distant metastasis
See Genetics
GENERAL PREVENTION
None
448
RHABDOMYOSARCOMA, PEDIATRIC (SARCOMA BOTRYOIDES)

R
r Postoperative grouping r Paratesticular: REFERENCES
– Group I: Localized disease, completely excised, no – Radical inguinal orchiectomy: All cases should be
microscopic residual approached inguinally with radical resection 1. Wu HY, Snyder HM 3rd. Pediatric urologic
◦ (a) Confined to site of origin, completely – RPLND (2): oncology: Bladder, prostate, testis. Urol Clin North
resected ◦ All >10 yr regardless of imaging Am. 2004;31:619–627.
◦ (b) Infiltrating beyond site of origin, completely ◦ <10 yr if evidence of LN involvement on 2. Wiener ES, Anderson JR, Ojimba JI, et al.
resected imaging, prior to chemotherapy Controversies in the management of paratesticular
– Group II: Total gross resection r Vagina/uterine: rhabdomyosarcoma: Is staging retroperitoneal
◦ (a) Gross resection with microscopic local – Vaginectomy: If evidence of residual disease on lymph node dissection necessary for adolescents
residual postchemotherapy biopsy with resected paratesticular rhabdomyosarcoma?
◦ (b) Regional disease with involved LNs, Semin Pediatr Surg. 2001;10:146–152.
completely resected, no microscopic residual ADDITIONAL TREATMENT 3. Wu HY, Snyder HM 3rd, Womer RB. Genitourinary
◦ (c) Microscopic local or nodal residual Radiation Therapy rhabdomyosarcoma: Which treatment, how much,
r Bladder/prostate:
– Group III: Incomplete resection with gross residual and when? J Pediatr Urol. 2009;5:501–506.
disease or biopsy only for diagnosis – Postdiagnostic biopsy, in addition to 4. Leuschner I, Harms D, Mattke A, et al.
– Group IV: Distant metastasis chemotherapy: Most cases (Group III) Rhabdomyosarcoma of the urinary bladder and
r Risk grouping – Following initial attempted resection initial vagina: A clinicopathologic study with emphasis on
– Low risk resection with residual margins, in addition to recurrent disease. A report from the Kiel Pediatric
◦ Embryonal histology, Stage 1, all groups chemotherapy: Group II Tumor Registry and the German CWS Study. Am J
◦ Embryonal histology, Stage 2/3, Group I/II r Paratesticular:
Surg Pathol. 2001;25:856–864.
– Intermediate risk – Positive LNs on RPLND 5. Arndt CA, Donaldson SS, Anderson JR, et al. What
◦ Embryonal histology, Stage 2/3, Group III r Vagina/uterus:
constitutes optimal therapy for patients with
◦ Alveolar histology, Stage 1/2/3, Group I/II/III – After chemotherapy or surgical resection unless an rhabdomyosarcoma of the female genital tract?
– High risk initial upfront resection (Group I) Cancer. 2001;91:2454–2468.
◦ Any histology, Stage 4, Group IV Additional Therapies
r All sites of GU RMS require a multidisciplinary
N/A
approach to curative therapy including appropriate
ADDITIONAL READING
surgical excision, chemotherapy, and radiation (1)
r For bladder/prostate and vaginal/uterine RMS, Therapies N/A
N/A
chemotherapy is 1st-line therapy after biopsy and See Also (Topic, Algorithm, Media)
before radiation or extirpative surgery in all cases r Bladder Mass, Differential Diagnosis
except rare instances amenable to immediate partial ONGOING CARE r Bladder Tumors, Benign and Malignant, General
cystectomy with negative margins Considerations
r For paratesticular RMS, retroperitoneal staging is PROGNOSIS r IRS (Intergroup Rhabdomyosarcoma Study) Clinical
r Bladder/prostate:
critical. Any boys <10 yr with radiologic evidence of Classification
enlarged retroperitoneal LNs, and all patients – 3-yr disease-free survival (3) r Rhabdomyosarcoma, Pediatric (Sarcoma Botryoides)
◦ Embryonal: 83% (Botryoid variant: 92%) (4)
>10 yr should have an ipsilateral retroperitoneal LN Images
◦ Alveolar: 40%
dissection (RPLND). This should be done to complete r Testis, Tumor, and Mass, Pediatric, General
r Paratesticular:
staging and must be done before chemotherapy or r Vaginal Mass, Newborn
radiation (1). – 3-yr disease-free survival: 81% (3)
– Overall survival: 96%
MEDICATION r Vagina/uterine:
First Line
r Bladder/prostate
– 5-yr disease-free survival: 69% (3) CODES
– Overall survival: 82% (94%in those <10 yr, 76%
– Low risk: Vincristine, actinomycin-D (VA) in those >10 yr) (5) ICD9
– Low-risk N1, intermediate risk, high-risk: VA + r 171.6 Malignant neoplasm of connective and other
Cyclophosphamide (VAC) COMPLICATIONS
r Paratesticular r Bladder/prostate soft tissue of pelvis
r 171.9 Malignant neoplasm of connective and other
– VA: Stage 1, <10 yr, no evidence of LN – Bladder dysfunction
– Hematuria/dysuria soft tissue, site unspecified
involvement on imaging (1) r 184.9 Malignant neoplasm of female genital organ,
– VAC: Positive LNs on RPLND – Secondary malignancy
r Vagina/uterine (1) – Incontinence site unspecified
r Paratesticular
– VAC: Chemotherapy followed by repeat biopsy to ICD10
assess residual disease – Complications of RPLND r C49.5 Malignant neoplasm of connective and soft
◦ Bowel obstruction
Second Line tissue of pelvis
◦ Ejaculatory dysfunction r C49.9 Malignant neoplasm of connective and soft
r 2nd-line chemotherapy with addition of carboplatin, r Vaginal/uterine
etoposide, irinotecan, or topotecan tissue, unsp
– Infertility r C57.9 Malignant neoplasm of female genital organ,
r Phase I studies
– Sexual dysfunction
r Chemotherapy-related toxicity unspecified
r Bladder/prostate: – Neurotoxicity
– Partial cystectomy: Primary treatment in rare cases – Secondary malignancy CLIN

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LWBK1391-FM LWBK1391-Gomella September 26, 2014 11:32

Acquisitions Editor: Keith Donnellan

Library of Congress Cataloging-in-Publication Data

To Tricia, Leonard, Patrick, Andrew, and

“En tierra de los ciegos el tuerto es rey.”

Strength of recommendation Definition

B Recommendation based on inconsistent or limited-quality patient-oriented evidence.

EDITOR-IN-CHIEF Judd W. Moul, MD, FACS

Alana M. Murphy, MD Michael L. Blute, Sr., MD, FACS

Thomas Jarrett, MD Richard J. Macchia, MD, FACS

W. Marston Linehan, MD James S. Rosoff, MD

John H. Lynch, MD, FACS Howard M. Sandler, MD, MS, FASTRO

Ihor S. Sawczuk, MD, FACS Laurence S. Baskin, MD, FACS, FAAP

Dolores Shupp-Byrne, PhD Ruth C. Birbe, MD

Dan Theodorescu, MD, PhD, FACS Gennady Bratslavsky, MD

J. Brantley Thrasher, MD, FACS James A. Brown, MD, FACS

Scott E. Eggener, MD Costas D. Lallas, MD, FACS

Eric A. Klein, MD, FACS Allen F. Morey, MD, FACS

John Patrick Mulhall, MBBCh, FACS, FECSM Philippe E. Spiess, MD

Stephen Nakada, MD, FACS Edouard J. Trabulsi, MD, FACS

Abrahamsson Per-Anders, MD, PhD Magdy El-Akkad, MD

Atsushi Mizokami, MD, PhD Arnulf Stenzl, MD

Francesco Montorsi, MD Teuvo L.J. Tammela, MD, PhD

Jacob Ramon, MD Dr. Huberto Villavicencio

Divya Ajay, MD Angela M. Arlen, MD Nima Baradaran, MD

Megan T. Bing, MD Erin M. Burns, MD Kai-Wen Chuang, MD

Bic N. Cung, MD Mary Ellen T. Dolat, MD Ahmer V. Farooq, DO

Jonathan H. Huang, MD Mark L. Jordan, MD, FACS Tariq A. Khemees, MD

Chandan R. Kundavaram, MD Michael C. Large, MD Xiaolong Shawn Liu, MD

Daniel D. Sackett, MD Arpeet Shah, MD Zachary L. Smith, MD

Preface v Hematuria, Adult 846

Proteinuria 881 Anticoagulation and Antiplatelet Therapy in

Athletic Hematuria 652 Bites to Penis, Animal, and Human 656

Bladder, Pheochromocytoma 659 Bulbocavernosus Reflex 664

Cystocele 106 Dysfunctional Voiding 682

Epididymis, Obstruction 686 Fine-Needle Aspiration (FNA) of Prostate 689

Genomic Testing, Prostate Cancer 694 Growing Teratoma Syndrome 699

Intermittent Hormonal Therapy (IHT)/Intermittent Lactate Dehydrogenase (LDH), Urologic

Lymphangioma, Renal 720 Megacystis, Congenital 724

Mulcahy Protocol 729 Nephropathy, Obstructive 733

Osteoporosis and Osteopenia, Urologic Pelvic Fracture, Urologic Considerations 742

Prostatitis, Chronic, Bacterial (NIH II) 358 Pyelitis Cystica 766

Renal Carcinoid Tumor 770 Renal Tubular Acidosis 434

Sacral Neuromodulation 778 Seminal Vesicle, Cysts and Masses 460

Ureteritis Cystica 801 Urethritis, Acute 805

ABDOMINAL MASS, ADULT, UROLOGIC CONSIDERATIONS

r Renal abscesses: Usually follow insufficient DIAGNOSTIC TESTS & INTERPRETATION

ABDOMINAL MASS, ADULT, UROLOGIC CONSIDERATIONS

ABDOMINAL MASS, NEWBORN/CHILD, UROLOGIC CONSIDERATIONS

ABDOMINAL MASS, NEWBORN/CHILD, UROLOGIC CONSIDERATIONS

ACUTE KIDNEY INJURY, ADULT (RENAL FAILURE, ACUTE)

ASSOCIATED CONDITIONS r Neck vein distention, lung rales

ACUTE KIDNEY INJURY, ADULT (RENAL FAILURE, ACUTE)

ACUTE KIDNEY INJURY, PEDIATRIC (RENAL FAILURE, ACUTE)

ACUTE KIDNEY INJURY, PEDIATRIC (RENAL FAILURE, ACUTE)

r Appendix torsion is a result of vascular compromise PHYSICAL EXAM

ACUTE TUBULAR NECROSIS

ASSOCIATED CONDITIONS r Urine tests

ACUTE TUBULAR NECROSIS

ADENOMATOID TUMORS, TESTICULAR AND PARATESTICULAR

ADENOMATOID TUMORS, TESTICULAR AND PARATESTICULAR

DIAGNOSTIC TESTS & INTERPRETATION r SCS is an indication for adrenalectomy.