Vol. 30 No.

7 July 2007

What’s New in ACP Medicine

DAVID C. DALE, MD, FACP, Editor-in-Chief DANIEL D. FEDERMAN, MD, MACP, Founding Editor
WENDY LEVINSON, MD, FACP, Associate Medical Editor, What’s New in ACP Medicine

PRACTICE OF THIS MONTH’S UPDATES

MEDICINE
Understanding the Good
News about Breast Cancer
KAREN ANTMAN, MD
Boston University School of Medicine
rends in the risk of developing
T cancer, as determined by age-
adjusted incidence per 100,000 pop-
ulation, and of dying from cancer,
measured by overall mortality and
deaths per 100,000 population, are
tracked via state cancer registries.
1 CARDIOVASCULAR MEDICINE
XII Diseases of the Aorta
KIM A. EAGLE, MD, FACP
University of Michigan Health System
WILLIAM F. ARMSTRONG, MD
University of Michigan Medical School
Blocking before Resecting
ppropriate preoperative evaluation
A and management are critical in a
patient undergoing elective aortic aneurysm
majority of patients undergo more
than one imaging study.
1. Hayter RG, Rhea JT, Small A, et al: Suspected
aortic dissection and other aortic disorders: multi-
detector row CT in 373 cases in the emergency set-
ting. Radiology 238:841, 2006 [PMID 16452396]
Will This Patient Survive
Surgery?
efinitive repair of dissections of the
D ascending aorta includes resection of
the dissected aorta and insertion of an

The risk varies considerably by the

section of the country. Statistics on
incidence and mortality normally
lag a few years because of reporting
delays. In early 2007, Jemal and
colleagues reported that in 2004,
the absolute number of deaths in
the United States from all cancers
decreased for the second consecutive
year, on the basis of mortality data
from the National Center for Health
Statistics.1 Age-standardized cancer
mortality in the United States fell
13.5% between 1991 and 2004.
Nevertheless, for Americans
younger than 85 years, cancer
remains the most common cause of
death, exceeding mortality from
heart disease.
Jemal and colleagues also
reviewed incidence data through
resection. In both urgent and emergent continued on page 3
cases, the usual medical approach is to
assume the patient may have preexist-
ing coronary disease. Unless contra-
indicated, beta blockers should be used In This Issue
to treat such patients. Ideally, beta
blockers should be started days to sev- Practice of Medicine
eral weeks before surgery; the dose Understanding the Good News about
should be titrated to achieve a target Breast Cancer 1
heart rate of 50 to 60 beats a minute.1 1 Cardiovascular Medicine
XII Diseases of the Aorta 1
1. ACC/AHA 2006 guideline update on periopera-
tive cardiovascular evaluation for noncardiac 12 Oncology
surgery: focused update on perioperative beta- XV Chronic Lymphoid Leukemias and
blocker therapy: a report of the American College
of Cardiology/American Heart Association Task Plasma Cell Disorders 3
Force on Practice Guidelines. J Am Coll Cardiol 10 Nephrology
47:2343, 2006 [PMID 16750714]
X Chronic Renal Failure and Dialysis 4
14 Respiratory Medicine
Imaging Suspected Dissection XXI Diseases of the Mediastinum
urrently, four diagnostic tools are
C used to evaluate patients with sus-
pected aortic dissection: multidetector
and Hilum
7 Infectious Disease
XXXII Human Retroviral Infections
6

2003 from state cancer registries
and found that the incidence of
breast cancer—which had been
increasing by about 1% per year
since 1980—leveled off from 2001
to 2003. The authors speculated
that this change may have stemmed
continued on page 2
computed tomography angiography Other Than HIV Infection 7
(MDCTA),1 echocardiography, mag- 2 Dermatology
netic resonance imaging, and aortogra- XVI Approach to the Diagnosis of
phy. In general, the choice of which Skin Disease 8
imaging modality to initially employ Special Alerts and Clinical Practice
will depend on local expertise and Guidelines 6
availability. In most hospitals, the FDA Approval Report
choice is either MDCTA or trans- New Treatment for Advanced Breast
Cancer 5
esophageal echocardiography, and the
2 What’s New in ACP Medicine • July 2007
PRACTICE OF MEDICINE
continued from page 1
from full utilization of mammogra-
phy, as well as the reduced use of
hormone replacement therapy
(HRT) in postmenopausal women.1
More recently, Ravdin and col-
leagues analyzed quarterly data and
reported that breast cancer inci-
dence had fallen by 6.7% in 2003
compared with 2002; this was fol-
lowed by a small incremental
decrease in 2004 that the investiga-
tors described as a leveling off. In
fact, these researchers found that the
incidence of breast cancer peaked in
mid-2001 and then declined by
8.6% through 2004.2
A decrease in mammographic
screening would also lead to a
decrease in incidence, but Ravdin
and colleagues discounted this possi-
bility. Instead, they concluded that
the abrupt change in breast cancer
incidence was most likely a result of
the 38% decrease in the use of HRT
between 2002 and 2003. However,
Jemal and colleagues, in a follow-up
analysis, again concluded that satu-
ration of mammography and a drop
in detection of smaller tumors con-
tributed to the effect, given the tim-
ing of the fall in incidence.3
The sharp decline in HRT use was
precipitated by the announcement
by the Women’s Health Initiative of
an increased risk of heart disease
and breast cancer associated with
postmenopausal estrogen and prog-
esterone use.4 When Ravdin and col-
leagues looked closely at quarterly
statistics, they found that the
drop had begun in 2002 and was
temporally related to the first report
by the Women’s Health Initiative of
the increased risk associated with
HRT.2 Jemal and colleagues con-
cluded that the drop had begun in
1999, and thus mammography was
also implicated.3
The decreased incidence of breast
cancer after 2003, apparent only for
women 50 years of age or older, pre-
dominantly involved estrogen recep-
tor–positive breast cancers.2 Al-
though other studies have suggested
that HRT increases the risk of lobu-
lar cancer compared with ductal
breast cancers, Ravdin and col-
5
leagues did not comment on histol-
ogy subsets in their analysis of the
decreased incidence.
The speed of the fall in incidence
suggests that discontinuing HRT
had a withdrawal effect on preclini-
cal occult disease, consistent with
tumor shrinkage of measurable
breast cancer upon withdrawal of
hormone therapies such as tamox-
ifen.2 Whether the decrease repre-
sents a temporary drop or a sus-
tained decline in breast cancer inci-
dence depends on the extent to
which these occult tumors require
hormone stimulation for growth.
Whether mortality from breast
cancer will demonstrate a similar
decline requires longer observation.
The drop in incidence may not be
sustained, in which case a fall in
mortality would not be expected.
Furthermore, the mortality after the
diagnosis of breast cancer is lower
in women who have taken post-
menopausal HRT than in women
who have not.6 Thus, the decreased
incidence may not translate into a
similar decrease in mortality.
References
1. Jemal A, Siegel R, Ward E, et al: Cancer statis-
tics, 2007. CA Cancer J Clin 57:43, 2007 [PMID
17237035]
2.Ravdin PM, Cronin KA, Howlader N, et al:
The decrease in breast-cancer incidence in 2003
in the United States. N Engl J Med 356:1670,
2007 [PMID 17442911]
3. Jemal A, Ward E, Thun MJ: Recent trends in
breast cancer incidence rates by age and tumor
characteristics among U.S. women. Breast Cancer
Res 9:R28, 2007 [PMID 17477859]
4. Rossouw JE, Anderson GL, Prentice RL, et al:
Risks and benefits of estrogen plus progestin in
healthy postmenopausal women: principal results
from the Women's Health Initiative randomized
controlled trial. JAMA 288:321, 2002 [PMID
12117397]
5. Chen CL, Weiss NS, Newcomb P, et al:
Hormone replacement therapy in relation to
breast cancer. JAMA 287:734, 2002 [PMID
11851540]
6. Schuetz F, Diel IJ, Pueschel M, et al: Reduced
incidence of distant metastases and lower mortal-
ity in 1072 patients with breast cancer with a
history of hormone replacement therapy. Am J
Obstet Gynecol 196:342, 2007 [PMID
17403414]
www.acpmedicine.com
Published by WebMD
EDITOR-IN-CHIEF: David C. Dale, M.D., F.A.C.P.,
Seattle
FOUNDING EDITOR: Daniel D. Federman, M.D.,
M.A.C.P., Boston
ASSOCIATE MEDICAL EDITOR, What’s New in
ACP Medicine: Wendy Levinson, M.D., F.A.C.P.,
Toronto
EDITORIAL BOARD:
Karen Antman, M.D., Boston; John P.
Atkinson, M.D., F.A.C.P., St. Louis; Mark
Feldman, M.D., F.A.C.P., Dallas; Raymond
Gibbons, M.D., Rochester, MN; R. Brian
Haynes, M.D., M.A.C.P., Hamilton, Ontario; Janet
B. Henrich, M.D., New Haven, CT; William L.
Henrich, M.D., F.A.C.P., San Antonio, TX;
Michael J. Holtzman, M.D., St. Louis; Mark G.
Lebwohl, M.D., New York; Wendy Levinson,
M.D., F.A.C.P., Toronto, Ontario; Lynn Loriaux,
M.D., PH.D., M.A.C.P., Portland, OR; Shaun
Ruddy, M.D., M.A.C.P., Richmond,VA; Jerry S.
Wolinsky, M.D., Houston
DIRECTOR OF PUBLISHING:
Cynthia M. Chevins
DIRECTOR, ELECTRONIC PUBLISHING:
Liz Pope
EDITORIAL DEPARTMENT:
Erin Michael Kelly, Managing Editor; Maureen
O’Sullivan, Associate Managing Editor; Nancy
R. Terry, John Heinegg, Development Editors;
David Terry, Copy Editor
ELECTRONIC PUBLISHING DEPARTMENT:
Janet Zinn, Electronic Projects Manager;
Betsy Klarfeld, Art and Design Editor;
Diane Joiner, Jennifer Smith, Wayne Anderson,
Associate Producers
ACP Medicine (ISSN 1548-9345) (USPS 482-310),
formerly WebMD Scientific American® Medicine, is
published monthly by WebMD Professional Publishing,
111 Eighth Avenue, Suite 700, New York, NY 10011.
Copyright © 2007 by WebMD. All rights reserved. No
part of this issue may be reproduced by any mechanical,
photographic, or electronic process or in the form of a
phonographic recording, nor may it be stored in a
retrieval system, transmitted, or otherwise copied for
public or private use without written permission of the
publisher. Periodical postage paid at New York, NY,
and at additional mailing offices. Individual subscription
rates–USA, its possessions, and Canada: $349 for the
first year ($324 for residents and students) and $269 for
renewals ($249 for residents and students). Institutional
subscription rates–USA, its possessions, and Canada:
$449 for the first year and $369 for renewals. Separate
shipping and handling apply. POSTMASTER: Send
address changes to ACP Medicine,WebMD Professional
Publishing, P.O. Box 1819, Danbury, CT 06813-9663.
FOR ASSISTANCE WITH YOUR SUBSCRIPTION
Please address all inquiries to Fulfillment Department,
WebMD Professional Publishing, P.O. Box 1819,
Danbury, CT 06813-9663, or call 800-545-0554 or
203-790-2087, fax us at 203-790-2066, or e-mail us at
acpmedicine@webmd.net. For change of address, please
provide both your new and your old addresses (include
your update mailing label if possible); be sure to notify us
at least six weeks before you expect to move to avoid
interruptions in your service.
YOUR FEEDBACK IS WELCOME
• E-mail: whatsnew@webmd.net
• Write: WebMD Professional
Publishing
111 Eighth Avenue, Suite 700
New York, NY 10011
www.acpmedicine.com
THIS MONTH’S UPDATES
continued from page 1
aortic graft. In high-volume centers,
valve replacement is required in only
25% of cases.1 For most patients, the
aortic repair includes reimplantation of
the coronary arteries. In some patients,
this repair includes resection and place-
ment of a graft to the aortic arch. Even
in the best of centers, surgical mortali-
ty ranges from 10% to 35%, depend-
ing on comorbidity.1,2 Major contribu-
tors to surgical mortality include hypo-
tension and shock, pulse deficits, and
the presence of cardiac tamponade.2
1. Trimarchi S, Nienaber CA, Rampoldi V, et al:
Contemporary results of surgery in acute type A
aortic dissection: the international registry of
acute aortic dissection experience. J Thorac
Cardiovasc Surg 129:112, 2005 [PMID
15632832]
2. Rampoldi V, Trimarchi S, Eagle KA, et al:
Simple risk models to predict surgical mortality
in acute type A aortic dissection: the internation-
al registry of acute aortic dissection score. Ann
Thorac Surg 83:55, 2007 [PMID 17184630]
Dissection Therapy Aftercare
A t many centers, either MDCTA or
MRI is performed on a regular basis
after initial treatment of aortic dissec-
tion. Imaging of the aorta is repeated 3
to 6 months after surgery to screen for
the development of aneurysm in the
false channel or at the margins of a
surgical repair. Persistence of blood
flow in the residual false lumen may
indicate that a patient is likely to expe-
rience continued expansion of the
aneurysmal aorta. After the 6-month
screening, patients undergo aortic
imaging annually, and scrupulous
attention is directed to antihyperten-
sive therapy and modification of risk
factors. Long-term survival after suc-
cessful surgical repair of type A
Assessment of Prognosis in Chronic Lymphocytic
Leukemia Using Fluorescent In Situ
Hybridization
Leukemic Cell Karyotype
17p– ± any other abnormalities
11– ± any other abnormalities except 17p–
Trisomy 12 ± any other abnormalities
except 17p– or 11q–
Normal karyotype
13q– as the only abnormality present
(ascending aorta) dissection is most
influenced by the preexisting underly-
ing comorbidities, including age, prior
cardiac surgery, and atherosclerosis.1
1. Tsai T, Evangelista A, Nienaber CA, et al:
Long-term survival in patients presenting with
type A acute aortic dissection: insights from the
international registry of acute aortic dissection
(IRAD). Circulation 114(1 suppl):I350, 2006
[PMID 16820599]
12 ONCOLOGY
XV Chronic Lymphoid Leukemias
and Plasma Cell Disorders
TAIT D. SHANAFELT, MD
MORIE A. GERTZ, MD, FACP
Mayo Clinic College of Medicine
The Future by FISH
hromosome analysis by fluorescent
C in situ hybridization (FISH) can pre-
dict survival in chronic lymphoid leuk-
emia. In a retrospective analysis of a
heterogeneous population of patients,
many of whom had advance-stage dis-
ease and had been previously treated,
Dohner and colleagues developed a
hierarchical system that assigns pa-
tients to one of five categories with
widely different median survival [see
Table, below].1
A subsequent prospective series of
159 untreated patients evaluated by
FISH shortly after diagnosis (median,
3 months) and then prospectively fol-
lowed (median, 10 years) confirmed
the ability of the Dohner system to
predict survival in newly diagnosed
patients with early-stage disease.1 In
addition to its value for prognosis,
Median Survival (Years)
2–5
7–9
9–10
>9
> 11
ACP Medicine 3
assessment of cytogenetic abnormali-
ties by FISH has also been shown to
be a predictive factor for progression-
free survival after treatment with flu-
darabine-based regimens; in such
cases, the presence of 17p– or 11q–
predicts shorter progression-free sur-
vival (< 2 years).2,3
1. Shanafelt TD, Witzig TE, Fink SR, et al:
Prospective evaluation of clonal evolution during
long-term follow-up of patients with untreated
early-stage chronic lymphocytic leukemia. J Clin
Oncol 24:4634, 2006 [PMID 17008705]
2. Byrd JC, Gribben JG, Peterson BL, et al: Select
high-risk genetic features predict earlier progres-
sion following chemoimmunotherapy with flu-
darabine and rituximab in chronic lymphocytic
leukemia: justification for risk-adapted therapy. J
Clin Oncol 24:437, 2006 [PMID 16344317]
3. Grever MR, Lucas DM, Dewald GW, et al:
Comprehensive assessment of genetic and molec-
ular features predicting outcome in patients with
chronic lymphocytic leukemia: results from the
US Intergroup Phase III Trial E2997. J Clin
Oncol 25:799, 2007[PMID 17283363]
Transplantation in CLL
ighly selected individuals with chron-
H ic lymphocytic leukemia (CLL)
who are younger than 70 years and
have good performance status are
candidates for allogeneic stem cell
transplantation. Consensus recom-
mendations suggest considering allo-
geneic transplantation (myeloablative
or nonmyeloablative) for patients
who have experienced relapse of
poor-risk CLL (i.e., CLL with an
aggressive course and significantly
reduced survival).1 Such patients are
defined by the following criteria:
• Failure to respond to first-line ther-
apy with a purine nucleoside ana-
logue (PNA)
• Relapse within 12 months after re-
ceiving a purine nucleoside ana-
logue (PNA)–based treatment or
within 24 months after receiving a
PNA-based combination regimen
• Need for therapy and presence of a
17p– abnormality on FISH testing.
Such patients should be referred to a
transplant center for evaluation. At
the present time, there is no role for
autologous transplantation in the treat-
ment of CLL, outside of clinical trials.
1. Dreger P, Corradini P, Kimby E, et al:
Indications for allogeneic stem cell transplanta-
tion in chronic lymphocytic leukemia: the EBMT
transplant consensus. Leukemia 21:12, 2007
[PMID 17109028]
4 What’s New in ACP Medicine • July 2007
Staging Multiple Myeloma
lthough the Durie-Salmon staging
A system served well for over 30 years,
it has several limitations: stage I patients
are often not candidates for treatment;
the assessment of bone lesions used in
this system is subjective; and a dispro-
portionate number of patients (80%)
are assigned to stage III. Consequently,
the International Staging System for
multiple myeloma should be used for
all patients. This system was validated
in over 10,000 patients on several con-
tinents and is independent of conven-
tional or high-dose therapy. An evalua-
tion of five different staging systems
reflected the superiority of the
International Staging System.1
The International Staging System
categorizes patients on the basis of
serum levels of β2 microglobulin and
albumin [see Table, right]. Serum β2
microglobulin is shed from the surface
of the myeloma cell and therefore
provides an indirect reflection of
tumor mass. Albumin is a negative
acute phase reactant, and its level is
depressed as the interleukin-6 (IL-6)
level rises and IL-6 exerts growth
effects on the myeloma population.
The staging system divides patients
into groups of equal size and distinct
differences in median survival.
1. Mihou D, Katodritou I, Zervas K: Evaluation of
five staging systems in 470 patients with multiple
myeloma. Haematologica 91:1149, 2006 [PMID
16885059]
Preserving Bone in Myeloma
isphosphonate therapy is now rou-
B tinely given to all patients with
myeloma bone disease. Long-term bis-
phosphonate use can be complicated
by osteonecrosis of the jaw; guidelines
developed by the Mayo Clinic suggest
that although intravenous pamidro-
nate and intravenous zoledronic acid
are equally effective in multiple myelo-
ma, pamidronate appears less likely to
result in jaw osteonecrosis.1 The Mayo
Clinic guidelines recommend cessation
of bisphosphonate use after 2 years of
therapy for patients who have
achieved either a complete response or
a plateau phase; for patients whose
disease is active, who have not
achieved a response, or who continue
to have threatening bone disease, the
frequency of bisphosphonate therapy
should be reduced to every 3 months.1
1. Lacy MQ, Dispenzieri A, Gertz MA, et al: Mayo
clinic consensus statement for the use of bisphos-
phonates in multiple myeloma. Mayo Clin Proc
81:1047, 2006 [PMID 16901028]
www.acpmedicine.com
International Staging System for
Multiple Myeloma
Stage I
Serum β2 microglobulin < 3.5 mg/dl
Serum albumin ≥ 3.5 g/dl
Stage 2
Serum β2 microglobulin 3.5–5.5 mg/dl
and/or
Serum albumin < 3.5 g/dl
Stage 3
Serum β2 microglobulin > 5.5 mg/dl
Note: Age is the only other factor that significantly affects outcome; older
patients with myeloma have poorer outcomes than other myeloma
patients. Although cytogenetic status influences outcome, chromosome 13
deletion and complex cytogenetic abnormalities do not increase the effects
of age, β2 microglobulin level, and albumin level on outcome.
10 NEPHROLOGY dialysis patients just as it does in
predialysis patients with chronic
X Chronic Renal Failure and renal failure. Its control is achieved
Dialysis by dietary phosphorus restriction,
ERIC P. COHEN, MD, FACP
use of phosphate binders, and ongo-
ing dialysis. Cross-sectional data
Medical College of Wisconsin
have shown a greater risk of mortali-
The Disappointment of Statins ty when the serum phosphorus level
is greater than 6.5 mg/dl in patients
he lipid-lowering statins that have a
T beneficial effect in lowering the risk
of coronary artery disease in the gener-
on long-term dialysis, a finding that
emphasizes the importance of inter-
ventions to limit hyperphosphatemia.
al population may not be beneficial in
Aluminum-containing phosphate
dialysis patients. A study of atorva-
binders are no longer used in stan-
statin in diabetic patients on dialysis
dard practice because of the danger
found that use of this statin was not
of aluminum intoxication. Evidence
associated with a reduction in the inci-
suggests that calcium-containing
dence of cardiovascular disease.1 In
phosphate binders may exacerbate
another study, atorvastatin showed a
existing calcific atherosclerosis. A
similar lack of benefit in lowering
coronary artery disease endpoints in
patients with stage IV chronic kidney
recent randomized study showed a
greater risk of death over a 5-year
follow-up period among new dialysis
disease who were not yet on dialysis.2
patients receiving calcium-containing
In addition to evidence of a lack of
phosphate binders as compared with
benefit, the use of statins is associated
patients receiving sevelamer, which
with an increased risk of rhabdomyo-
does not contain calcium.1
lysis.3 These findings suggest that
1. Block GA, Raggi P, Bellasi A, et al: Mortality
statins should be used with caution in effect of coronary calcification and phosphate binder
patients who have severe renal failure. choice in incident hemodialysis patients. Kidney Int
1. Wanner C, Krane V, Marz W, et al: Atorva- 71:438, 2007 [PMID 17200680]
statin in patients with type 2 diabetes mellitus
undergoing dialysis. N Engl J Med 353:238, Reining in the Parathyroids
2005 [PMID 16034009]
irtually all patients on long-term
2. Stegmayr BG, Brannstrom M, Bucht S, et al:
Low dose atorvastatin in severe chronic kidney
disease patients: a randomized controlled end-
V dialysis have secondary hyper-
parathyroidism. If left untreated,
point study. Scand J Urol Nephrol 39:489, 2005
the hyperparathyroidism may result
3. Jamal SM, Eisenberg MJ, Christopoulos S:
in bone pain, fractures, or soft tis-
Rhabdomyolysis associated with hydroxymethyl-
glutaryl coenzyme A reductase inhibitors. Am sue calcification. Management of
Heart J 147:956, 2004 [PMID 15199341] this condition includes not only the
treatment of hyperphosphatemia
A Better Way to Bind
but also the use of parenteral vita-
Phosphate? min D preparations—mainly cal-
yperphosphatemia promotes sec- citriol and paricalcitol, which are
H ondary hyperparathyroidism in given intravenously during dialysis
www.acpmedicine.com ACP Medicine 5

FDA Approval Report

The following is selected from the FDA’s list of recently
approved products. Complete, updated information on
FDA approvals and notifications is available on the FDA
Web site (http://www.fda.gov).
New Treatment for Advanced Breast Cancer
The FDA has approved lapatinib for use in combination
with capecitabine (Xeloda) for patients with advanced,
metastatic breast cancer that is HER2 positive. The combi-
nation treatment is indicated for women who have received
previous therapy with other cancer drugs, including an
anthracycline, a taxane, and trastuzumab (Herceptin).
Lapatinib is a kinase inhibitor that works through multiple
pathways to deprive tumor cells of signals needed to grow.
Unlike, for example, trastuzumab—a large monoclonal
antibody that targets the part of the HER2 protein on the
outside of the cell—lapatinib is a small molecule that enters
the cell and blocks the function of HER2 and other pro-
teins. Because of this difference in mechanism of action,
lapatinib works in some HER2-positive breast cancers that
have been treated with trastuzumab and are no longer
responding.
Lapatinib was approved on the basis of a randomized clini-
cal trial in about 400 women with advanced or metastatic
breast cancer that was HER2 positive. In the trial, half the
patients received lapatinib with capecitabine and half
received capecitabine alone. Compared with patients receiv-
ing capecitabine alone, patients receiving lapatinib with
capecitabine had a statistically significant improvement in
the time to tumor progression. In addition, the tumor
response rate was higher in the group of patients receiving
lapatinib with capecitabine (24% versus 14%). The sur-
vival data are not yet mature.
The most commonly reported side effects of lapatinib
included diarrhea; nausea; vomiting; rash; and hand-foot
syndrome, which may include numbness, tingling, redness,
swelling, and discomfort of hands and feet. Decreases in
heart function, which can lead to shortness of breath, have
also been reported in a small percentage of patients; these
decreases are generally reversible. Patients should talk to
their doctor about potential side effects, potential drug
interactions, and other medical conditions, including heart
and liver problems.
Lapatinib is available in 250 mg tablets. An undivided dose
of 1,250 mg should be taken orally once daily for 21 days
and in combination with capecitabine on days 1 through
14 of a 21-day cycle.
Generic Name: Lapatinib
Brand Name: Tykerb
Distributor: GlaxoSmithKline, Research Triangle Park,
North Carolina
FDA Approves Tykerb for Advanced Breast Cancer Patients. FDA News.
U.S. Food and Drug Administration, March 13, 2007
(http://www.fda.gov/bbs/topics/NEWS/2007/NEW01580.html)

sessions. Calcitriol and paricalcitol
act directly on the parathyroid
glands to suppress parathormone
synthesis and secretion. There is evi-
dence that medical management of
secondary hyperparathyroidism has
improved over the past 10 years,
thus reducing the need for surgical
treatment.
An additional tool in the manage-
ment of secondary hyperparathy-
roidism may be the orally active cal-
cimimetic agents, such as cinacalcet,
which act directly on the calcium
receptors of the parathyroid gland cells
to suppress parathormone secretion.1,2
However, these medications are expen-
sive, and a recent cost-utility analysis
of cinacalcet suggested that it was not
cost-effective.3 Subtotal parathyroidec-
tomy may be needed for persistent
severe hyperparathyroidism. Severe
hyperparathyroidism is considered to
be present when one or more parathy-
roid glands are enlarged to a diameter
greater than 1 cm or when there is evi-
dence of autonomous parathyroid hor- mon in ESRD patients than in the
mone secretion. general population.1
1. Block GA, Martin KJ, de Francisco ALM, et 1. Sood P, Sinson GP, Cohen EP: Subdural hema-
al: Cinacalcet for secondary hyperparathyroidism tomas in chronic dialysis patients: significant and
in patients receiving hemodialysis. N Engl J Med increasing. J Am Soc Nephrol 17:320a, 2006
350:1516, 2004 [PMID 15071126]
2. Strippoli GF, Tong A, Palmer SC, et al:
Calcimimetics for secondary hyperparathy-
roidism in chronic kidney disease patients.
Cochrane Database Syst Rev (4):CD006254,
2006 [PMID 17054287]
3. Garside R, Pitt M, Anderson R, et al: The
cost-utility of cinacalcet in addition to standard
Coming in August
care compared to standard care alone for sec-
ondary hyperparathyroidism in end-stage renal
Clinical Essentials
disease: a UK perspective. Nephrol Dial Trans- XII Complementary and Alternative
plant 22:1428, 2007 [PMID 17308322] Medicine
4 Gastroenterology
Bleeding Complications in I Esophageal Disorders
Dialysis Patients 10 Nephrology
VII Vascular Diseases of the Kidney
lthough uremic bleeding is usually
A not a problem in the well-dialyzed
patient with end-stage renal disease
12 Oncology
XIV Bladder, Renal, and Testicular
Cancer
(ESRD), the use of heparin during 14 Respiratory Medicine
each hemodialysis session can predis- XI Respiratory Failure
pose a patient to hemorrhagic compli- 16 Women’s Health
cations. For example, subdural XVIII Hirsutism and Hyperandrogenism
hematomas are ten times more com-
6 What’s New in ACP Medicine • July 2007 www.acpmedicine.com

Special Alerts Clinical Practice Guidelines

Declining rates of death and heart failure
observed in acute coronary syndromes
http://jama.ama-assn.org/cgi/content/abstract/297/17/1892
For more information, see Section 1, Chapter X Unstable
Angina and Non-ST Segment Elevation Myocardial Infarction.
Once-weekly oral alendronate protects against
bone loss in men receiving androgen deprivation thera-
py for prostate cancer
http://www.medscape.com/medline/abstract/17371886?cid=
med&src=nlbest
For more information, see Section 12, Chapter IX Prostate
Cancer.
Guidelines for the Management of Community-
Acquired Pneumonia in Adults
The Infectious Diseases Society of America and the
American Thoracic Society have developed new consensus
guidelines for the management of community-acquired
pneumonia (CAP) in adults; the guidelines were issued in
March 2007. They are designed to improve the care of
adults with CAP and are intended primarily for use by
emergency department physicians, hospitalists, and primary
care practitioners.
http://www.journals.uchicago.edu/CID/journal/issues/v44nS2/
41620/41620.web.pdf
For more information, see Section 7, Chapter XX
Pneumonia and Other Pulmonary Infections.

14 RESPIRATORY MEDICINE lated thymomas can be treated with

surgery alone, whereas those with
XXI Diseases of the Mediastinum invasive lesions are candidates for
and Hilum multimodality therapy. At the
JOHN C. KUCHARCZUK, MD
University of Pennsylvania, a combi-
nation of systems is used; patients
University of Pennsylvania School of
are classified on the basis of histol-
Medicine
ogy, using the WHO system, and
Classifying Thymomas clinical findings at the time of
hymomas were traditionally classi- surgery, using the Masaoka system.
num and sternal debridement.
Although multiple techniques have
been described for the treatment of
these infections, aggressive surgical
debridement with muscle flap clo-
sure is associated with the best
overall clinical outcomes.
1. Toumpoulis IK, Anagnostopoulos CE, DeRose
JJ, et al: The impact of deep sternal wound infec-
tion on long-term survival after coronary artery
bypass grafting. Chest 127:464, 2005 [PMID

T fied on the basis of cellular histol-

ogy. Traditional classification
1. Detterbeck FC: Clinical value of the WHO
classification system of thymoma. Ann Thorac
15705983]

Surg 81:2328, 2006 [PMID 16731193]

schemes divide thymomas into three
groups: (1) predominantly lympho-
cytic thymomas, (2) predominantly
epithelial thymomas, and (3) mixed
thymomas. Although simple, these
classification systems have little clini-
cal significance. More recently, the
World Health Organization (WHO)
adopted a more elaborate histologic
classification system. Although the
WHO system appears to be predic-
tive of outcome, it is not widely
used.1 From a clinical perspective,
the most commonly used thymoma
classification system is the Masaoka
classification; this classification takes
into consideration the clinical obser-
vation that thymomas are either
completely encapsulated or grossly
invasive of adjacent structures. Large
series of thymomas have consistently
demonstrated that approximately
70% of thymomas are completely
encapsulated, whereas 30% are inva-
sive. This distinction is clinically rele-
vant because patients with encapsu-
Anterior Mediastinal
Infections
This Month’s CME
cute infections of the anterior Chapters
A mediastinal compartment are
unusual, but they do occur. Ap-
ACP Medicine offers CME in
convenient online and print for-
proximately 1% to 3% of median mats. As many as 120 AMA PRA
sternotomies for cardiac surgery are Category 1 credits can be earned
at any time during the year. The
complicated by sternal wound infec-
following chapters are available
tion.1 Risk factors for sternal wound
for CME credit this month:
infections include diabetes, use of
bilateral internal mammary arteries, 1 Cardiovascular Medicine
and reoperation. Patients with ster- XII Diseases of the Aorta
nal wound infections present with 7 Infectious Disease
pain, drainage, and, often, a palpa- XXXII Human Retroviral Infections
ble mass at the sternal incision. Most Other Than HIV Infection
of these infections have deep exten- 10 Nephrology
sions into the anterior mediastinum X Chronic Renal Failure and Dialysis
and concomitant sternal osteomy- 12 Oncology
elitis. A CT scan of the chest should XV Chronic Lymphoid Leukemias and
be obtained to determine the extent Plasma Cell Disorders
of mediastinal soilage. Recommend- 14 Respiratory Medicine
ed treatment involves drainage of a XXI Diseases of the Mediastinum
wide area of the anterior mediasti- and Hilum
www.acpmedicine.com
Manifestation
Malignancies
Neurologic manifestations
Autoimmune disorders
Infectious diseases
ATL—adult T cell leukemia/lymphoma TSP/HAM—tropical spastic paraparesis or HTLV-1–associated myelopathy
*Opportunistic infections may include cytomegalovirus pneumonitis, Pneumocystis jiroveci pneumonia, disseminated herpes zoster, aspergillosis, cryptococcosis, disseminated
Mycobacterium avium infection, and miliary tuberculosis.
Treating Esophageal
Leiomyoma
consensus in the literature recom-
A mends that esophageal leiomy-
oma be surgically removed in symp-
tomatic patients; however, best treat-
ment of asymptomatic patients with
lesions smaller than 3 cm is not
established. Surgery has traditionally
been the treatment of choice; many
experts advocate the resection of
asymptomatic tumors on the basis of
the following considerations: (1) a
benign tumor may undergo malig-
nant transformation; (2) a patient
who is asymptomatic may develop
symptoms; (3) a definitive diagnosis
can be established on the basis of
histology; and (4) malignancy can be
excluded only by tumor resection.1
1. Lee LS, Singhal S, Brinster CJ, et al: Current
management of esophageal leiomyoma. J Am
Coll Surg 198:136, 2004 [PMID 14698321]
7 INFECTIOUS DISEASE
XXXII Human Retroviral
Infections Other Than HIV
Infection
MARK A. BEILKE, MD
CHRISTY BARRIOS, PHD
Medical College of Wisconsin
How Retroviral Infection
Presents
ike other viruses, retroviruses may
L cause latent, chronic, or persistent
Clinical Manifestations of HTLV-1 and HTLV-2 Infections
HTLV-1
Chronic ATL Large granular cell leukemia (CD8+)
Smoldering ATL CD8+ cutaneous lymphoma
T cell non-Hodgkin lymphoma T cell variant hairy cell leukemia
TSP/HAM TSP/HAM
Peripheral neuropathy
Polymyositis Hashimoto thyroiditis
Arthritis
Uveitis
Thyroiditis
Pneumonitis
Opportunistic infections in ATL patients* Bacterial pneumonia
Infective dermatitis in children Tuberculosis
Strongyloides stercoralis infections Urinary tract infections
infections. Latent infection is character-
ized by intermittent episodes of acute
or subclinical disease; between
episodes, no virus is detectable. In
chronic infection, the virus is usually
demonstrable but symptoms of disease
are absent. Persistent infection is char-
acterized by a long incubation period
with slowly increasing amounts of
virus, eventually leading to sympto-
matic disease. Clinical disease develops
in only 5% to 10% of persons infected
with human lymphotropic virus type 1
(HTLV-1) or HTLV-2.
HTLV-1 causes adult T cell
leukemia/lymphoma (ATL), T cell non-
Hodgkin lymphoma, and an unusual
neurodegenerative syndrome designat-
ed tropical spastic paraparesis or
HTLV-1–associated myelopathy
(TSP/HAM). In ATL, the latent period
between infection and the emergence
of disease lasts 20 to 30 years or more.
TSP/HAM has a median latency peri-
od of approximately 3 years, but the
latency period can be as long as 20 to
30 years. Clinical manifestations of
HTLV infection include malignancies,
neurologic disorders, autoimmune dis-
orders, and increased susceptibility to
certain other infectious diseases [see
Table, above].
Retroviruses as Coinfections
TLV-1 and HTLV-2 are frequent
H copathogens in HIV-1–infected indi-
viduals, especially in large metropoli-
tan areas where injection drug use is a
common mode of transmission. Fur-
thermore, HIV-1 and HTLV-1 coinfec-
ACP Medicine 7
HTLV-2
tions have been frequently reported in
geographic regions of high HTLV-1
seroprevalence, such as Brazil and the
Caribbean. Clinical evaluations of co-
infected patients have found a frequent
association with neurologic complica-
tions, including HTLV-associated mye-
lopathy and peripheral neuropathy.
Coinfected patients are also more like-
ly to have hematologic complications
such as thrombocytopenia, as well as
respiratory, urinary tract, and hepatitis
C virus infections.1 Although highly
active antiretroviral therapy (HAART)
has significantly decreased AIDS-asso-
ciated mortality, the potential benefit
of HAART in suppressing HTLV-1/2
viral replication in HIV-infected indi-
viduals is unclear. In fact, anecdotal
reports suggest that HAART may
actually increase HTLV-1/2 viral load.2
A 2004 cohort study documented
the clinical outcomes and survival
probabilities in patients coinfected
with HIV-1 and HTLV-1 or HTLV-
2.1 In this study, HTLV coinfection
was unexpectedly shown to result in
improved survival and delayed pro-
gression to AIDS. However, an
increased frequency of HTLV-associ-
ated complications was clearly evi-
dent, including TSP/HAM and
peripheral neuropathy.
1. Beilke MA, Theall KP, O’Brien M, et al: Clinical out-
comes and disease progression among patients coinfect-
ed with HIV and human T lymphotropic virus types 1
and 2. Clin Infect Dis 39:256, 2004 [PMID 15307036]
2. Turci M, Pilotti E, Ronzi P, et al: Coinfection with
HIV-1 and HTLV-II in intravenous drug users is asso-
ciated with delayed progression to AIDS. J Acquir Im-
mune Defic Syndr 41:100, 2006 [PMID 16340481]
8 What’s New in ACP Medicine • July 2007 www.acpmedicine.com

by using various antiretroviral com-

pounds have been disappointing. Corti-
Online Atlases of Dermatology costeroids and immunosuppressive
DermIS.net agents such as azathioprine may ame-
A cooperation between the Department of Clinical Social Medi- liorate disease progression but are
cine, University of Heidelberg, and the Department of Derma- unsuitable for long-term use because of
tology, University of Erlangen
their adverse effects. Immunotherapy
http://www.dermis.net/index_e.html
with IFN-α has produced minimal to
DermAtlas
moderate results, depending on the
http://www.dermatlas.med.jhmi.edu/derm
degree of inflammation and tissue
Interactive Dermatology Atlas destruction.1
www.dermatlas.net
1. Saito M, Nakagawa M, Kaseda S, et al: Decreased
University of North Carolina School of Medicine Dermatology human T lymphotropic virus type I (HTLV-I) provirus
Slide Atlas load and alteration in T cell phenotype after interferon-
www.med.unc.edu/derm/atlas/welcome.htm alpha therapy for HTLV-I–associated myelopathy/
tropical spastic paraparesis. J Infect Dis 189:29, 2004
Dermatologic Image Database [PMID 14702150]
Department of Dermatology, University of Iowa College of
Medicine
http://tray.dermatology.uiowa.edu/ImageBase.html
Loyola University Dermatology Medical Education Website 2 DERMATOLOGY
www.meddean.luc.edu/Lume/MedEd/medicine/dermatology/
melton/atlas.html XVI Approach to the Diagnosis of
Skin Disease
ROBERT T. BRODELL, MD
STEPHEN E. HELMS, MD
Treating Adult T Cell trial in the United States employs oral
zidovudine in combination with high Northeastern Ohio Universities
Leukemia doses of interferon alfa (IFN-α), admin- College of Medicine and Case Western
ll patients diagnosed with adult T istered daily. Arsenic trioxide may Reserve University School of Medicine
A cell leukemia (ATL) should be
referred to a tertiary care center with
induce cell cycle arrest and apoptosis
of ATL cells in vitro; it is under consid-
Visual Aids to Diagnosis
t is important to begin the assess-
expertise in the treatment of HTLV-
1–associated malignancies. Conven-
tional chemotherapy for lymphoid
eration as an adjuvant chemotherapeu-
tic agent in combination with IFN-α. I ment of a skin condition with a
broad differential diagnosis, noting
There are several reports from Japan
malignancies is ineffective against of successful allogeneic stem cell trans- the presentation as characteristic of
aggressive forms of ATL; therefore, plantation after cytoreductive chemo- one of the categories of skin disease:
treatment of ATL has become the sub- therapy. Other trials have attempted papulosquamous, blistering, nonscal-
ject of several clinical studies. immunotherapy using humanized ing erythematous, pigmentation, or
Combination chemotherapy specifi- monoclonal antibodies directed against tumor. Using physical findings,
cally designed for ATL has consider- IL-2R and other receptors expressed patient history, and diagnostic test-
ably elevated the treatment response on ATL cells. ing, the differential diagnosis is grad-
rate in ATL patients, but it has not suf- ually narrowed until a diagnosis is
ficiently extended the median survival Treating Retroviral determined. A review of illustrations
time seen with standard cytotoxic regi- of specific primary and secondary
mens (e.g., cyclophosphamide, doxoru- Autoimmune Disease skin lesions in various dermatology
bicin, vincristine, and prednisone), fforts to treat TSP/HAM and HTLV- atlases [see Table, above] may also
which is less than 2 years. One current E 1–associated autoimmune diseases aid in arriving at a diagnosis.