TG13 Actualización Guías de Manejo Tokio!!!

J Hepatobiliary Pancreat Sci (2013) 20:17
DOI 10.1007/s00534-012-0566-y
GUIDELINE
TG13: Updated Tokyo Guidelines for acute cholangitis

and acute cholecystitis
TG13: Updated Tokyo Guidelines for the management of acute

cholangitis and cholecystitis
Tadahiro Takada Steven M. Strasberg Joseph S. Solomkin Henry A. Pitt Harumi Gomi Masahiro Yoshida
Toshihiko Mayumi Fumihiko Miura Dirk J. Gouma O. James Garden Markus W. Buchler
Seiki Kiriyama Masamichi Yokoe Yasutoshi Kimura Toshio Tsuyuguchi Takao Itoi Toshifumi Gabata
Ryota Higuchi Kohji Okamoto Jiro Hata Atsuhiko Murata Shinya Kusachi John A. Windsor
Avinash N. Supe SungGyu Lee Xiao-Ping Chen Yuichi Yamashita Koichi Hirata Kazuo Inui
Yoshinobu Sumiyama
Published online: 11 January 2013

Japanese Society of Hepato-Biliary-Pancreatic Surgery and Springer 2012
Abstract In 2007, the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07) were
first published in the Journal of Hepato-Biliary-Pancreatic
Surgery. The fundamental policy of TG07 was to achieve
the objectives of TG07 through the development of consensus among specialists in this field throughout the world.
Considering such a situation, validation and feedback from
the clinicians viewpoints were indispensable. What had
been pointed out from clinical practice was the low diagnostic sensitivity of TG07 for acute cholangitis and the
presence of divergence between severity assessment and

clinical judgment for acute cholangitis. In June 2010, we
set up the Tokyo Guidelines Revision Committee for the
revision of TG07 (TGRC) and started the validation of
TG07. We also set up new diagnostic criteria and severity
assessment criteria by retrospectively analyzing cases of
acute cholangitis and cholecystitis, including cases of noninflammatory biliary disease, collected from multiple
institutions. TGRC held meetings a total of 35 times as
well as international email exchanges with co-authors
abroad. On June 9 and September 6, 2011, and on April 11,
T. Takada (&) F. Miura

Department of Surgery, Teikyo University School of Medicine,
2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan
e-mail: takada@med.teikyo-u.ac.jp
D. J. Gouma
Department of Surgery, Academic Medical Center, Amsterdam,
The Netherlands
S. M. Strasberg
Section of Hepatobiliary and Pancreatic Surgery, Washington
University in Saint Louis School of Medicine, Saint Louis,
MO, USA
J. S. Solomkin
Department of Surgery, University of Cincinnati College of
Medicine, Cincinnati, OH, USA
H. A. Pitt
Department of Surgery, Indiana University School of Medicine,
Indianapolis, IN, USA
H. Gomi
Center for Clinical Infectious Diseases, Jichi Medical University,
Tochigi, Japan
M. Yoshida
Clinical Research Center Kaken Hospital, International
University of Health and Welfare, Ichikawa, Japan
T. Mayumi
Department of Emergency and Critical Care Medicine,
Ichinomiya Municipal Hospital, Ichinomiya, Japan
O. J. Garden
Clinical Surgery, The University of Edinburgh, Edinburgh, UK
M. W. Buchler
Department of Surgery, University of Heidelberg,
Heidelberg, Germany
S. Kiriyama
Department of Gastroenterology, Ogaki Municipal Hospital,
Ogaki, Japan
M. Yokoe
General Internal Medicine, Nagoya Daini Red Cross Hospital,
Nagoya, Japan
Y. Kimura
Department of Surgical Oncology and Gastroenterological
Surgery, Sapporo Medical University School of Medicine,
Sapporo, Japan
T. Tsuyuguchi
Department of Medicine and Clinical Oncology, Graduate
School of Medicine Chiba University, Chiba, Japan
123
2012, we held three International Meetings for the Clinical

Assessment and Revision of Tokyo Guidelines. Through
these meetings, the final draft of the updated Tokyo Guidelines (TG13) was prepared on the basis of the evidence from
retrospective multi-center analyses. To be specific, discussion took place involving the revised new diagnostic criteria,
and the new severity assessment criteria, new flowcharts of
the management of acute cholangitis and cholecystitis, recommended medical care for which new evidence had been
added, new recommendations for gallbladder drainage and
antimicrobial therapy, and the role of surgical intervention.
Management bundles for acute cholangitis and cholecystitis
were introduced for effective dissemination with the level of
evidence and the grade of recommendations. GRADE systems were utilized to provide the level of evidence and the
grade of recommendations. TG13 improved the diagnostic
sensitivity for acute cholangitis and cholecystitis, and presented criteria with extremely low false positive rates
adapted for clinical practice. Furthermore, severity assessment criteria adapted for clinical use, flowcharts, and many
new diagnostic and therapeutic modalities were presented.
The bundles for the management of acute cholangitis and
cholecystitis are presented in a separate section in TG13.
Free full-text articles and a mobile application of TG13
are available via http://www.jshbps.jp/en/guideline/tg13.html.
Keywords Acute cholangitis Acute cholecystitis

Charcots triad Biliary infection GRADE
T. Itoi
Department of Gastroenterology and Hepatology, Tokyo
Medical University, Tokyo, Japan
A. N. Supe
Department of Surgical Gastroenterology, Seth G S Medical
College and K E M Hospital, Mumbai, India
T. Gabata
Department of Radiology, Kanazawa University Graduate
School of Medical Science, Kanazawa, Japan
S. Lee
HepatoBiliary Surgery and Liver Transplantation, Asan Medical
Center, Ulsan University, Seoul, Korea
R. Higuchi
Department of Surgery, Institute of Gastroenterology, Tokyo
Womens Medical University, Tokyo, Japan
X.-P. Chen
Department of Surgery, Hepatic Surgery Centre,
Tongji Hospital, Tongi Medical College,
Huazhong Universty of Science & Technology,
Wuhan, China
K. Okamoto
Department of Surgery, Kitakyushu Municipal Yahata Hospital,
Kitakyushu, Japan
J. Hata
Department of Endoscopy and Ultrasound, Kawasaki Medical
School, Okayama, Japan
A. Murata
Department of Preventive Medicine and Community Health,
School of Medicine, University of Occupational and
Environmental Health, Kitakyushu, Japan
S. Kusachi
Department of Surgery, Toho University Medical Center Ohashi
Hospital, Tokyo, Japan
J. A. Windsor
Department of Surgery, The University of Auckland, Auckland,
New Zealand
123
Background before Tokyo Guidelines 2007

Acute cholangitis and cholecystitis require appropriate
treatment in the acute phase. Severe acute cholangitis may
result in early death if no appropriate medical care is
provided in the acute phase. Before the publication of the
Tokyo Guidelines for the management of acute cholangitis
and cholecystitis (TG07) in January 2007 [1], there were no
practical guidelines throughout the world primarily targeting acute cholangitis and cholecystitis.
TG07 had substantial influence on medical care for
biliary infections throughout the world in that they clearly
defined the diagnostic criteria and severity assessment
criteria for acute cholangitis and cholecystitis, the definition of which had until then been ambiguous. TG07 has
provided international standards for diagnostic and severity
assessment criteria. This has enabled the comparison and
integration of multiple studies (i.e., meta-analysis or systematic reviews).
TG07 was initially developed through the following
processes. An international consensus meeting was held in
Tokyo on April 1 and 2, 2006. A total of 29 experts from
Y. Yamashita
Department of Gastroenterological Surgery, Fukuoka University
School of Medicine, Fukuoka, Japan
K. Hirata
Department of Internal Medicine, Second Teaching Hospital,
Fujita Health University School of Medicine, Nagoya, Aichi,
Japan
K. Inui
Department of Surgery I, Sapporo Medical University Hospital,
Sapporo, Hokkaido, Japan
Y. Sumiyama
Toho University School of Medicine, Tokyo, Japan
22 countries and Japanese experts in this field attended the

meeting. To obtain consensus, a voting system was used.
As the final product of this international consensus meeting, TG07 [2] was published in 2007.
The process of preparation was by no means easy. TG07
was the worlds first clinical practice guidelines on the
management of acute cholangitis and cholecystitis. There
were many obstacles to overcome. The preparation of
TG07 started according to the principle of evidence-based
medicine. However, due to the absence of diagnostic criteria and severity assessment criteria, studies available at
that time were very few in number, and even if there was
extracted evidence, the criteria lacked unity and the contents were often ambiguous. Furthermore, items to be
discussed included diagnostic methods and clinical decision-making such as the selection of antimicrobial agents
and their biliary penetration, the route and timing of biliary
drainage, the timing of surgical intervention, and healthcare-associated (e.g., postoperative) cholangitis and cholecystitis. It took an enormously long time to cover the
overall guidelines.
3
Table 1 Summary of citations of TG07 (from January 2007 to
December 2011)
Number of papers in TG07 cited at least once
14
Total number of times of citation
209
Number of articles citing papers in TG07
122
Number of journals publishing articles citing papers in TG07
77
Fig. 1 Annual number of citations of TG07

5.2
3.9
Citation analysis 20072011 of TG07

TG07 has been cited widely since its publication. The
number of papers citing TG07 [1, 35] has been increasing
every year [6] and has reached approximately 209 treatises.
Those treatises have been cited in textbooks of surgery,
internal medicine, and guidelines of abdominal infections
[79]. The significance of this is that TG07 has had substantial influence on medical education and has become
disseminated throughout the world as a global standard.
The results of the survey that examined the number of
citations of TG07 until December 2011 show that the total
number of citations of TG07 was 209 in 2009 (Table 1).
The number of citations occurring each year since 2007 is
presented in Fig. 1.
The number of journals that cited TG07 was 77.
Figure 2 provides a breakdown of the fields of the journals
that cited TG07.
There were 112 treatises that had been cited from TG07.
Figure 3 provides a breakdown of the residential areas of
the authors. Table 2 shows the types of articles which cited
TG07. Of the 76 original treatises, 20 (26.3 %) were cited
in method sections (Fig. 4). The citation of original treatises in method sections has been on a rapid increase since
2011 (Fig. 5). Of the treatises cited in the method sections,
studies had been conducted in 17 titles concerning diagnostic criteria and/or severity assessment criteria (Fig. 4).
In summary, TG07 has been cited in journals in various
fields throughout the world, although only 5 years citations were totaled.
6.5
33.8
11.7
14.3
Fig. 2 Categories of the journals publishing articles citing papers in

TG07 (n = 77)
1.6
1.6
11.5
32.8
23.8
28.7
Fig. 3 Geographical origin of authors citing papers in TG07

(n = 122)
Need for revision of TG07

1. The development of evidence-based guidelines, clinical
practice and assessment
The publication of TG07 enabled the presentation of the
first international diagnostic criteria and severity assessment
123
Develop Clinical Guidelines
Table 2 Types of articles citing TG07

Types of articles
No. of articles
Original article
76 (62.3 %)
Review
20 (16.4 %)
Case report
11 (9.0 %)
Guideline
7 (5.7 %)
Others
8 (6.6 %)
Total
122
Evidence and consensus based
Publication and
distribution
assessment
Use Guidelines
Fig. 6 Evidencepractice cycle
In 17 articles, patients were diagnosed according to the diagnostic

criteria and severity assessment of TG.
Fig. 4 Section where cited in original articles (n = 76)
and therapeutic methods. Therefore clinical practice

guidelines require regular update and revision [12]. In view
of these circumstances, an evidence-based revision process
is also required for TG07. After its publication, an
appraisal from clinicians has been taking place concerning
dissemination/use and the results are being made good use
of for future revision (Fig. 6).
2. Validity of TG07
Given the critical appraisal of TG07, there are problems
in applying it in clinical settings. First, the sensitivity of
acute cholangitis is low. Second, there are impractical
aspects in the severity assessment criteria for moderate
acute cholangitis such as deciding the timing of biliary
drainage. There were discordances between clinical
judgement by clinicians and the level of severity utilizing
TG07 severity assessment criteria.
Process of the development of Tokyo Guidelines 2013

(TG13)
Fig. 5 Annual number of original articles citing papers in TG07
criteria [1, 36] and, at the same time, the presentation of

those criteria improved the quality of medical care
throughout the world, and the usefulness of TG07 has
become a target of appraisal from clinical viewpoints [10,
11]. TG07 should have been prepared primarily on the
basis of evidence. However, due to the paucity of evidence,
it was completed through combining best available evidence and the worldwide knowledge cultivated at the
international consensus meeting. Therefore, a test by clinicians for its usefulness is indispensable. TG07 has now
reached the stage when it can be further improved on the
basis of evidence and consensus as well as feedback from
clinical practice.
In general, following the publication of clinical practice
guidelines, new findings are reported concerning diagnosis
123
1. The First International Meeting for the development of

TG13
On June 9, 2011, the first International Meeting for
Clinical Assessment and Revision of the Tokyo Guidelines
was held. In this meeting, it was made clear that: (1) TG07
should be updated due to the presence of divergence
between TG07 and real clinical settings; (2) the validity of
the diagnostic criteria for acute cholangitis was to be
investigated on the basis of retrospective analysis of
patients with acute cholangitis collected from multiple
institutions; (3) there was divergence between severity
assessment and clinical judgement for acute cholangitis.
2. The Second International Meeting for the development of TG13
On September 6, 2011, the Second International Meeting for Clinical Assessment and Revision of the Tokyo
Guidelines was held. At the meeting, the overall action
plans for the new guidelines were determined with the draft
revision of the TG07 and the newly introduced Grades of
Recommendation, Assessment, Development and Evaluation
(GRADE) systems to provide the levels of evidence and

grade of recommendations. In this meeting, antimicrobial
therapy was mainly discussed. Using the two international
meetings mentioned above as a basis, the revision work of
TG07 started in 2011.
3. The validation study for acute cholangitis was presented in Kiriyama et al.s paper [13].
4. The clinical study for Charcots triad was also
described in Kiriyama et al.s paper [13].
5. The validation study for acute cholecystitis was presented in Yokoe et al.s paper [14].
6. Third International Meeting for the development of
TG13
On April 11, 2012, the Third International Meeting for
the Clinical Assessment and Revision of Tokyo Guidelines was held. In this meeting, the final draft of the
updated Tokyo Guidelines was prepared on the basis of
the evidence from the validation studies of TG07. To
begin with, a discussion took place involving the updated
new diagnostic criteria for which sensitivity and specificity had been improved, the new severity assessment
criteria adapted for practical medical care, new flowcharts
prepared for reducing divergence between evidence and
clinical care, recommended medical care to which new
evidence had been added, the new idea of gallbladder
drainage and biliary drainage methods in clinical use,
antimicrobial therapy, and the role of surgical
intervention.
The concept and methodology of management bundles
was introduced and discussed as tools for the effective
dissemination and implementation of clinical practice
guidelines by utilizing the GRADE systems for evidence
assessment, and the concept of the grade of recommendation. As the results of the Third International Meeting for
the Clinical Assessment and Revision of Tokyo Guidelines,
the final draft was prepared through an international email
conference with overseas co-authors. Thus TG13 was
formulated.
the quality of the study was re-assessed based on the limitations and the body of evidence was re-classified as
moderate evidence. Observational studies (a non-randomized study, a cohort study, or a casecontrol study) are
classified as having low-level evidence in general. The
body of evidence may be upgraded to high level if it has
significant influences in clinical practice. Case series or
case reports are classified as having very low evidence, in
general. It is extremely rare that the body of evidence is
re-classified to a higher level. However, reports of cases of
deaths due to complications or cases of significant side
effects may be considered as a higher level.
The strength of recommendations was classified as
high (strong) (recommendation 1) and low (weak)
(recommendation 2). Four factors that determine the
strength of recommendations are: (1) the quality of evidence; (2) sense of value and patients preference (less
burden on staff members and patients); (3) net profits and
cost/source (cost saving); and (4) benefits and harm burden
(benefits and risks). The general decision was made by
taking into account these four factors. Strong and weak
recommendations were then determined by the Tokyo
Guidelines Revision Committee. A strong recommendation
suggests that desirable effects clearly exceed undesirable
effects and is applied to recommendations on which more
than 70 % of the members of the Tokyo Guidelines
Revision Committee have agreed. The use of We recommend has been adopted for the style of the
expression. A weak recommendation shows that desirable
effects probably exceed undesirable effects and the use of
We suggest has been adopted.
The recommendation 1 level A (strong recommendation; evidence level high), 1B, 1C, 1D, 2A, 2B, 2C, and 2D
(weak recommendation; evidence level very low) are
shown at the end of recommendations. However, cases
with strong recommendation (recommendation 1) may
include those cases for which to perform is strongly
recommended and those for which not to perform is
strongly recommended.
The GRADE systems

The assessment of the evidence and the grading of recommendations in TG13 are based on the GRADE systems
reported in 2004 and 2008 by the working team for the
GRADE [1517]. The assessment of the quality of evidence and the strength of recommendation are shown in
Figs. 7 and 8), respectively.
In the assessment of the quality of evidence, the level of
evidence is classified as high (level A), moderate
(level B), low (level C), or very low (level D). A
randomized trial is, in general, classified as having highlevel evidence. However, due to limitations in each study,
Introduction of bundles for the management of acute

We presented and discussed the concept and the method of
management bundles in TG13. Concrete objectives and
anticipated effects of the bundles are as follows: (1) to
achieve improved prognosis by using bundles of treatment
methods with evidence presented in the guidelines (TG13);
(2) to achieve higher compliance and remove barriers
among institutions by presenting a list of guidelines in the
form of bundles; (3) to carry out a survey involving compliance with the items of the medical care recommended by
123
Fig. 7 GRADE system (quality

of evidence) [1517]
Initial quality of
evidence
Study design
Lower if
Higher if
High
Study limitations:
1 Serious
2 Very serious
Inconsistency:
1 Serious
2 Very serious
Observational
Indirectness:
study
1 Serious
(cohort study, case 2 Very serious
control study
Impression:
1 Serious
Any other
2 Very serious
evidence
Publication bias
(case series, case
study)
1 likely
2 Very likely
RCT, systematic
review, metaanalysis
Moderate
Low
Very low
Magnitude of effect:
2 Very strong
1 Strong
Dose-response
gradient
1
All plausible
confounders would
have reduced the
effect
1
Definition: Overall quality of evidence across studies for the outcome

level A
High
1. How to judge a Grade of recommendation

Totally judgment with evidence, harm and benefit
Level of evidence
A, B, C, D
Patients preference Yes, No
Harm and benefit
Yes, No
Cost effectiveness
Yes, No
2. How to show a Grade of recommendation 2 steps
Recommendation 1 : Strong recommendation (Do it, Dont do it):
Over 70 of clinical practitioners will agree
= We recommend
Recommendation 2 Weak recommendation (probably do it,
probably dont do it)
Less than 70 will agree = We suggest
Fig. 8 GRADE system (grade of recommendation) [1517]
the guidelines and to provide guidelines for conducting a

survey concerning changes in medical care before and after
publication of TG13.
Summary
This paper presents the background of TG07, its clinical
impact since publication, the clinical appraisal emerging
from clinical research, the process of revision of TG07, and
the development of TG13. The guidelines need continuous
evaluation and revision. TG13 has been developed to
improve the quality of medical care for patients with acute
cholangitis and cholecystitis. The guidelines should be
widely utilized and prospective clinical studies are needed
for further improvement in the near future.
Conflict of interest
123
None.
level B
Moderate
level C
Low
level D
Very low
References
1. Takada T, Kawarada Y, Nimura Y, Yoshida M, Mayumi T,
Sekimoto M, et al. Background: Tokyo Guidelines for the management of acute cholangitis and cholecystitis. J Hepatobiliary
Pancreat Surg. 2007;14:110.
2. Tokyo Guidelines for the management of acute cholangitis and
cholecystitis. Proceedings of a consensus meeting, April 2006,
Tokyo, Japan. J Hepato-Biliary Pancreat Surg. 2007;14:1121.
3. Miura F, Takada T, Kawarada Y, Nimura Y, Wada K, Hirota M,
et al. Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo guidelines. J Hepatobiliary
4. Wada K, Takada T, Kawarada Y, Nimura Y, Miura F, Yoshida
M, et al. Diagnostic criteria and severity assessment of acute
cholangitis: Tokyo guidelines. J Hepatobiliary Pancreat Surg.
2007;14:528.
5. Hirota M, Takada T, Kawarada Y, Nimura Y, Miura F, Hirata K,
et al. Diagnostic criteria and severity assessment of acute cholecystitis: Tokyo guidelines. J Hepatobiliary Pancreat Surg.
2007;14:7882.
6. Strasberg SM. Acute calculous cholecystitis. N Engl J Med.
2008;358:280411.
7. Cameron JL, Cameron AM. Current surgical therapy. 10th ed.
Elsevier Mosby: Philadelphia. 2011; p. 345348.
8. Dooley JS, Lok A, Burroughs A, Heathcote J. Sherlocks diseases
of the liver and biliary system, 12th ed. Blackwell: Hoboken;
2011.
9. Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein
EJ, Baron EJ, et al. Diagnosis and management of complicated
intra-abdominal infection in adults and children: guidelines by
the Surgical Infection Society and the Infectious Diseases Society
of America. Clinical Infect Dis. 2010;50(2):13364.
10. Murata A, Matsuda S, Kuwabara K, Fujino Y, Kubo T, et al.
Evaluation of compliance with the Tokyo Guidelines for the
management of acute cholangitis based on the Japanese administrative database associated with the Diagnosis Procedure
Combination system. J Hepatobiliary Pancreat Sci. 2010;18:539.
11. Yokoe M, Takada T, Mayumi T, Yoshida M, Hasegawa H,
Norimizo S, et al. Accuracy of the Tokyo Guidelines for the
diagnosis of acute cholangitis and cholecystitis taking into

consideration the clinical practice pattern in Japan. J Hepatobiliary Pancreat Sci. 2011;18:2507.
12. Shekelle PG, Ortiz E, Rhodes S, Morton SC, Eccles MP,
Grimshaw JM, Woolf SH. Validity of the Agency for Healthcare
Research and Quality clinical practice guidelines: how quickly do
guidelines become outdated? JAMA. 2001;286:14617.
13. Kiriyama S, Takada T, Strasberg SM, Solomkin JS, Mayumi T,
Pitt HA, et al. New diagnostic criteria and severity assessment of
acute cholangitis in revised Tokyo guidelines. J Hepatobiliary
Pancreat Sci. 2012;19:54856.
14. Yokoe M, Takada T, Strasberg SM, Solomkin JS, Mayumi T,
Gomi H, et al. New diagnostic criteria and severity assessment of
acute cholesystitis in revised Tokyo guidelines. J Hepatobiliary
Pancreat Sci. 2012;19:57885.
7
15. Atkins D, Eccles M, Flottorp S, Guyatt GH, Henry D, Hill S,
et al. Systems for grading the quality of evidence and the strength
of recommendations I: critical appraisal of existing approaches.
The GRADE Working Group. BMC Health Serv Res. 2004;
4(1):38.
16. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y,
Alonso-Coello P, et al. Rating quality of evidence and strength of
recommendations. GRADE: an emerging consensus on rating
quality of evidence and strength of recommendations. BMJ.
2008;336:9246.
17. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y,
Schunemann HJ, et al. Rating quality of evidence and strength of
recommendations. What is quality of evidence and why is it
important to clinicians? BMJ. 2008;336:9958.
123

DOI 10.1007/s00534-012-0564-0
GUIDELINE

TG13 current terminology, etiology, and epidemiology of acute

Yasutoshi Kimura Tadahiro Takada Steven M. Strasberg Henry A. Pitt Dirk J. Gouma O. James Garden
Markus W. Buchler John A. Windsor Toshihiko Mayumi Masahiro Yoshida Fumihiko Miura
Ryota Higuchi Toshifumi Gabata Jiro Hata Harumi Gomi Christos Dervenis Wan-Yee Lau
Giulio Belli Myung-Hwan Kim Serafin C. Hilvano Yuichi Yamashita

Abstract While referring to the evidence adopted in the

Tokyo Guidelines 2007 (TG07) as well as subsequently
obtained evidence, further discussion took place on terminology, etiology, and epidemiological data. In particular,
new findings have accumulated on the occurrence of
symptoms in patients with gallstones, frequency of severe
cholecystitis and cholangitis, onset of cholecystitis
and cholangitis after endoscopic retrograde cholangiopancreatography and medications, mortality rate, and recurrence rate. The primary etiology of acute cholangitis/
Electronic supplementary material The online version of this

article (doi:10.1007/s00534-012-0564-0) contains supplementary
material, which is available to authorized users.
Y. Kimura (&)
S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan
e-mail: kimuray@sapmed.ac.jp
T. Takada F. Miura
Tokyo, Japan
S. M. Strasberg
University in Saint Louis School of Medicine,
Saint Louis, MO, USA
H. A. Pitt
D. J. Gouma
The Netherlands
O. J. Garden
123
cholecystitis is the presence of stones. Next to stones, the

most significant etiology of acute cholangitis is benign/
malignant stenosis of the biliary tract. On the other hand,
there is another type of acute cholecystitis, acute acalculous cholecystitis, in which stones are not involved as
causative factors. Risk factors for acute acalculous cholecystitis include surgery, trauma, burn, and parenteral
nutrition. After 2000, the mortality rate of acute cholangitis
has been about 10 %, while that of acute cholecystitis has
generally been less than 1 %. After the publication of
TG07, diagnostic criteria and severity assessment criteria
were standardized, and the distribution of cases according
to severity and comparison of clinical data among target
populations have become more subjective. The concept of
M. W. Buchler
Department of Surgery, University of Heidelberg, Heidelberg,
Germany
J. A. Windsor
New Zealand
T. Mayumi
M. Yoshida
R. Higuchi
Department of Surgery, Institute of Gastroenterology,
Tokyo Womens Medical University, Tokyo, Japan
T. Gabata
healthcare-associated infections is important in the current

treatment of infection. The treatment of acute cholangitis
and cholecystitis substantially differs from that of community-acquired infections. Cholangitis and cholecystitis
as healthcare-associated infections are clearly described in
the updated Tokyo Guidelines (TG13).
are available via http://www.jshbps.jp/en/guideline/tg13.
html.
mortality rate, and recurrence rate are introduced along

with epidemiological data.
Keywords Terminology Etiology Epidemiology

Acute cholangitis Acute cholecystitis
Acute cholangitis is a morbid condition with acute

inflammation and infection in the bile duct [1, 2].
Terminology
Acute cholangitis
Definition
Pathophysiology
Introduction
Acute biliary infection comprises manifold disease concepts and is mostly separated into [1] acute cholangitis, a
systemic infectious disease that is occasionally life-threatening and requires immediate treatment, and [2] acute
cholecystitis, frequently presenting a mild clinical course.
The definition, pathophysiology, and epidemiology of
acute cholangitis are presented in the Tokyo Guidelines for
the management of acute cholangitis and chlecystitis 2007
(TG07) [1], while the updated Tokyo Guidelines (TG13)
present more subjective data acquired throughout the
revision of TG07. As for the data of current clinical trials in
particular, the data concerning frequency of severe cases,
J. Hata
H. Gomi
Tochigi, Japan
C. Dervenis
First Department of Surgery, Agia Olga Hospital, Athens,
Greece
W.-Y. Lau
Faculty of Medicine, The Chinese University of Hong Kong,
Hong Kong, Hong Kong
G. Belli
General and HPB Surgery, Loreto Nuovo Hospital, Naples, Italy
M.-H. Kim
Department of Internal Medicine, Asan Medical Center,
University of Ulsan, Seoul, Korea
S. C. Hilvano
Department of Surgery, College of Medicine-Philippine General
Hospital, University of the Philippines, Manila, Philippines
Y. Yamashita
The onset of acute cholangitis involves two factors: (1)

increased bacteria in the bile duct, and (2) elevated intraductal pressure in the bile duct allowing translocation of
bacteria or endotoxin into the vascular and lymphatic
system (cholangio-venous/lymphatic reflux). Because of its
anatomical characteristics, the biliary system is likely to be
affected by the elevated intraductal pressure. In acute
cholangitis, bile ductules tend to become more permeable
to the translocation of bacteria and toxins with the elevated
intraductal biliary pressure. This process results in serious
and fatal infections such as hepatic abscess and sepsis [1].
Historical aspect of terminology
Signs of hepatic fever Hepatic fever was a term used for
the first time by Charcot in his report published in 1887 [3].
Intermittent fever accompanied by chills, right upper
quadrant abdominal pain, and jaundice have been established as Charcots triad.
Acute obstructive cholangitis Acute obstructive cholangitis was defined by Reynolds and Dargan [4] in 1959 as a
syndrome consisting of lethargy or mental confusion and
shock, as well as fever, jaundice, and abdominal pain
caused by biliary obstruction. They indicated that emergency surgical biliary decompression was the only effective procedure for treating the disease. These five
symptoms were thus called Reynolds pentad.
Longmires classification Longmire classified patients
with three characteristics of intermittent fever accompanied
by chills and shivering, right upper quadrant abdominal
pain, and jaundice as acute suppurative cholangitis, and
those with lethargy or mental confusion and shock along
with the triad as acute obstructive suppurative cholangitis
(AOSC). He also reported that the latter corresponded to
the morbidity of acute obstructive cholangitis as defined by
Reynolds [5].
123
10
However, terms such as acute obstructive cholangitis

and acute obstructive suppurative cholangitis (AOSC) are
not appropriate as current clinical terminology because
their definition is conceptual and ambiguous.
Pathological classification
(1)
Acute cholangitis/cholecystitis as healthcare-associated

infections
(2)
In the US IDSA/SIS guidelines on abdominal infection,
acute cholangitis/cholecystitis refers to biliary tract infection that has developed in any of the following patients:
patients with a history of less than 12 months hospital stay,
patients undergoing dialysis, patients staying at nursing
home/rehabilitation facility, and patients in an immunecompromised state [6].
That concept has been extrapolated, and acute cholangitis/cholecystitis as a healthcare-associated infection
in Japan refers to infection that has developed in patients
(long-term recumbency, admission to nursing home,
gastrostomy, tracheostomy, repeated aspiration pneumonia, bed sore, uretheral catheter placement, history of
recent postoperative infection, or undergoing antimicrobial therapy due to other diseases) at risk of having
resistant bacteria (bacteria with a high minimum inhibitory concentration, MIC). Those infections should
be treated independently from community-required
infections.
Edematous cholecystitis: 1st stage (24 days) The

gallbladder has interstitial fluid with dilated capillaries and lymphatics. The gallbladder wall is edematous. Gallbladder tissue is intact histologically with
edema in the subserosal layer [1].
Necrotizing cholecystitis: 2nd stage (35 days) The
gallbladder has edematous changes with areas of
hemorrhage and necrosis. When the gallbladder wall
is subject to elevated internal pressure, the blood flow
is obstructed with histological evidence of vascular
thrombosis and occlusion. There are areas of scattered
necrosis but they are superficial and do not involve
the full thickness of the gallbladder wall [1] (Fig. 1).
Acute cholecystitis
Definition
Acute inflammatory disease of the gallbladder, often
attributable to gallstones, but many factors, such as ischemia, motility disorders, direct chemical injury, infections
by microorganism, protozoon and parasites, collagen disease, and allergic reaction are also involved [1].
Pathophysiology
In the majority of patients, gallstones are the cause of
acute cholecystitis. The process is one of physical
obstruction of the gallbladder at the neck or in the cystic
duct by a gallstone. This obstruction results in increased
pressure in the gallbladder. There are two factors which
determine the progression to acute cholecystitisthe
degree of obstruction and the duration of the obstruction.
If the obstruction is partial and of short duration, the
patient experiences biliary colic. If the obstruction is
complete and of long duration, the patient develops acute
cholecystitis. If the patient does not receive early treatment, the disease becomes more serious and complications can occur [1].
123
Fig. 1 Necrotizing cholecystitis. a Contrast-enhanced CT images

show discontinuity of the gallbladder wall, suggesting possible
presence of necrosis in a portion of the wall. b Resected specimen
showing extensive falling-off of the gallbladder membrane, erosion,
ulcer, and exposed fascia. Histologically, necrosis of the gallbladder
wall and suppurative inflammation accompanying abscess (data not
shown) were observed with fibrillation and regenerating hyperplastic
epithelium as background
(3)
(4)
Suppurative cholecystitis: 3rd stage (710 days) The

gallbladder wall has white blood cells that present
areas of necrosis and suppuration. In this stage, the
active repairing process of inflammation is evident.
The enlarged gallbladder begins to contract and the
wall is thickened due to fibrous proliferation. Intramural abscesses are observed and do not involve the
entire thickness of the wall. Pericholecystic abscesses
are also present [1] (Fig. 2).
Chronic cholecystitis: Chronic cholecystitis occurs
after the repeated occurrence of mild cholecystitis
attacks, and is characterized by mucosal atrophy and
fibrosis of the gallbladder wall. It can also be caused
by the chronic irritation of large gallstones and may
often induce acute cholecystitis [1]. Acute on chronic
cholecystitis refers to acute infection that has
occurred in chronic cholecystitis [7, 8] (Fig. 3).
Histologically, neutrophil invasion is observed in
the gallbladder wall with chronic cholecystitis accompanying lymphocyte/plasma cell infiltration and
fibrosis.
11
position, pendulum-like movement in the anteflexion

position, hyperperistalsis of the organs near the gallbladder, defecation, and blow to the abdomen.
Advanced forms of and the type of complications of acute
cholecystitis [1]
(1)
(2)
(3)
(4)
Special forms of acute cholecystitis
(1)
(2)
(3)
(4)
Acalculous cholecystitis: Acute cholecystitis without

cholecystolithiasis
Xanthogranulomatous cholecystitis: Cholecystitis
characterized by xanthogranulomatous thickening of
the gallbladder wall [9] and elevated intra-gallbladder
pressure due to stones with a rupture of the RokitanskyAchoff sinuses. This causes leakage and entry
of bile into the gallbladder wall. It is ingested by
histocytes to form granulomas consisting of foamy
histocytes. Patients usually have symptoms of acute
cholecystitis in the initial stage.
Emphysematous cholecystitis: In emphysematous
cholecystitis, air appears in the gallbladder wall due
to infection by gas-forming anerobes including Clostridium perfringens. It is often seen in diabetic
patients, and is likely to progress to sepsis and
gangrenous cholecystitis [1].
Torsion of the gallbladder: Cause of acute cholecystitis [10]. Torsion of the gallbladder is known to
occur by inherited, acquired, and other physical causes.
The inherited factor is the floating gallbladder, which is
very mobile because the gallbladder and cystic ducts are
connected with the liver by a fused ligament. The
acquired factors include splanchnoptosis, senile humpback, scoliosis, and weight loss. Physical factors causing
torsion of the gallbladder include sudden change of
intraperitoneal pressure, sudden change of body
Perforation of gallbladder: Perforation of the gallbladder is caused by acute cholecystitis, injury, or

tumors, and occurs most frequently as a result of
ischemia and necrosis of the gallbladder wall.
Biliary peritonitis: Biliary peritonitis occurs with the
entry into the peritoneal cavity of bile leakage due to
various causes including cholecystitis-induced gallbladder perforation, trauma, and a detached catheter
during biliary drainage and incomplete suture after
biliary operation.
Pericholecystic abscess: A morbid condition in which
perforation of the gallbladder wall is covered by the
surrounding tissues along with the formation of
abscesses around the gallbladder
Biliary fistula: A biliary fistula can occur between the
gallbladder and the duodenum following an episode
of acute cholecystitis. This is usually caused by a
large gallbladder stone eroding through the wall of
the gallbladder into the duodenum. If the stone is
large in size, the patient can develop gallstone ileus
with the stone causing mechanical small bowel
obstruction at the ileocecal valve.
Frequency of symptom appearance

Incidence
Q1. What is the incidence proportion of the appearance
of symptoms in patients with asymptomatic gallstones
or those with mild gallstones?
Asymptomatic, mild symptom- patients
Acute cholangitis
Acute cholecystitis
Annual proportion;
~40 %/5 - 10years

0.3 ~ 1.6 %
3.8 ~ 12%
1~3%/year
Incidence in patients with gallstones

Acute cholecystitis is the most frequent complication
occurring in patients with cholelithiasis. According to the
Comprehensive Survey of Living Conditions of the People
on Health and Welfare (conducted by the Medical Statistics
Bureau of the Ministry of Health and Welfare), the number
of cases with acute cholecystitis has increased from 3.9
123
12
c
d
Fig. 2 Suppurative cholecystitis. a Contrast-enhanced CT visualizing

the gallbladder wall under extrinsic compression (up arrow) suggests
possible presence of abscess in a portion of the gallbladder wall.
GB
Fig. 3 US images of acute-on-chronic cholecystitis patients. a The

gallbladder wall is shown to have thickened prior to the onset of acute
inflammation. b The gallbladder itself continued to swell after the
onset of acute inflammation and the wall has further thickened along
123
bc Many minute stones were observed within the gallbladder. d The

resected specimen shows the gallbladder membrane accompanying
extensive abscess formation within the wall (arrowhead)
GB
with striated intraluminal lucency (up arrow). Only by comparing the

images before (a) and after (b) the onset of acute inflammation can a
decision of the wall thickening and the swelling of gallbladder be
correctly made
13
Table 1 Natural history of asymptomatic, mildly symptomatic, and symptomatic cholelithiasis patients
References
Characteristic
No. of
cases
Average
follow-up
period (years)
No. of acute
cholecystitis
cases (%)
Only those
with remarkable
jaundice cases
(%)
Cholangitis
Cholecystitis
Gallbladder
cancer
Comfort
et al.
Asymptomatic
112
15
Lund
Asymptomatic
95
13
1(?)
Gracie
et al.
Asymptomatic
123
11
McSherry
et al.
Asymptomatic
135
Friedman
et al.
Asymptomatic
123
Thistle
et al.
Asymptomatic ?
symptomatic
305
C3
Wenckert
et al.
Mildly
symptomatic
781
11
81 (10.4)
\59a
\59a
Ralston
et al.
Mildly
symptomatic
116
22
Friedman
et al.
Mildly
symptomatic
344
20 (5.8)
10
Newman
et al.
Symptomatic
332
10
38(11.4)
McSherry
et al.
Symptomatic
556
47 (8.5)
19
Review by Friedman [12]

a
In this report, 59 cases were diagnosed as jaundice and/or acute pancreatitis based on the serum bilirubin and amylase values
million in 1979 to over 10 million in 1993 (Public Welfare

Index in Japan, 1993). No large epidemiological study has
been conducted to date, but it can be estimated that
approximately 10 % of the general population have gallstones [11].
Natural history of patients with asymptomatic gallstones
According to a review by Friedman, 12 % of patients
with asymptomatic gallstones and 13 % of patients with
mild symptoms annually presented severe symptoms or
complications (acute cholecystitis, acute cholangitis,
severe jaundice, or pancreatitis (Table 1)). The risk of
such complications was high during the first few years
after gallstones had been detected and it decreased subsequently. The probability of undergoing operation due to
subsequent severe symptoms was 68 %/year in patients
initially presenting moderate symptoms and the symptoms
decreased year by year [12]. Observational studies
involving patients with mild cholecystolithiasis have
found that, during 57 years observation, 15 % of the
subjects presenting mild or nonspecific symptoms developed complications associated with gallstones, 12 %
developed acute cholecystitis (n = 153), 21.9 % of the
subjects were without symptoms during 8.7 years
observation (median), and 42 % of those with mild

symptoms developed abdominal pain of higher than mild
severity (n = 856), respectively. The above data show
that 2040 % of patients with asymptomatic cholelithiasis
have a risk for developing some type of symptoms/signs
(13 % annually) [1218].
Incidence of severe cases of acute cholecystitis
and cholangitis
Q2. What is the incidence proportion of severe cases of
acute cholangitis?
The proportion of severe cases is 12.3%based on the severity

assessment criteria of TG07
Severe cases (grade III) in TG07 refer to those having

poor prognostic factors including shock, consciousness
disturbance, organ failure, and disseminated intravascular
coagulation. The definition was ambiguous before the
publication of TG07, which, after review of the frequency
123
14
of acute cholangitis, reported that the incidence of severe

cases was 725.5 % for shock, 722.2 % for consciousness disturbance, and 3.57.7 % for Reynolds pentad
[19].
The proportion of cases diagnosed as severe (grade III)
according to the TG07 severity assessment criteria was
12.3 % or 23 of the 187 cases of acute cholangitis due to
bile duct stones [20].
Etiology
Acute cholangitis
Q5. What are the etiology and mechanism of acute
cholangitis?
Acute cholangitis occurs as results of a biliary tract obstruction
Q3. What is the proportion of severe cases of acute

cholecystitis?
The proportion of severe cases (accompanying organ dysfunction)
is 6.0% according to TG07 severity assessment criteria.
Severe in TG07 refers to acute cholecystitis accompanying organ dysfunction (grade III), and the proportion
of the above cases was 6.0 % (14 of 235 cases) [21].
Acute cholangitis and cholecystitis as complications
following ERCP
Q4. What is the proportion of acute cholangitis and
cholecystitis following ERCP?
Acute cholangitis; 0.5~2.4 %

Acute cholecystitis; 0.2~1.0 %
(cholestasis) and bacterial growth in bile (bile infection).
The onset of acute cholangitis requires two factors, [1]

biliary obstruction and [2] bacterial growth in bile (bile
infection). Causes of frequent biliary obstruction are choledocholithiasis, benign biliary stenosis, stricture of the
biliary anastomosis, and stenosis by malignant diseases
[38, 39]. Choledocholithiasis used to be the most frequent
cause, but recently the incidence of acute cholangitis
caused by malignant disease, sclerosing cholangitis, and
non-surgical instrumentation of the biliary tract has been
increasing. It is reported that malignant disease accounts
for about 1030 % of cases with acute cholangitis [38, 39].
Tables 2 and 3 show the results of studies on the causes of
acute cholangitis.
Table 2 Etiology of acute cholangitis

Cholelithiasis
The incidence of complications following endoscopic retrograde cholangiopancreatography (ERCP) is

0.812.1 % and the mortality rate is 0.00231.5 % [22
37]. The most frequently encountered complication is acute
pancreatitis, although mild to moderate cases account for
the greater part (Supplementary Table 1).
The proportion of acute cholangitis and cholecystitis
after ERCP is 0.52.4 % for cholangitis and 0.21.0 % for
cholecystitis [2226, 2933].
There are differences in the proportion of complications
between diagnostic ERCP and therapeutic ERCP, and those
of cholangitis and overall complications associated with
therapeutic ERCP are more likely to become elevated
[31, 33, 42].
Due to the diffusion of procedures and improved
techniques of operators, complications following ERCP
have increased in recent years, although no change has
been observed in the frequency of the occurrence of
acute cholecystitis, so its occurrence is unpredictable
[31].
123
Benign biliarystricture
Congenital factors
Post-operative factors (damaged bile duct, strictured
choledojejunostomy, etc.)
Inflammatory factors (oriental cholangitis, etc.)
Malignant occlusion
Bile duct tumor
Gallbladder tumor
Ampullary tumor
Pancreatic tumor
Duodenal tumor
Pancreatitis
Entry of parasites into the bile ducts
External pressure
Fibrosis of the papilla
Duodenal diverticulum
Blood clot
Sump syndrome after biliary enteric anastomosis
Iatrogenic factors
Reviewed by Kimura et al. [1]
15
Acute cholecystitis
4Fs and 5Fs
Q6. What are the etiology and mechanism of acute

cholecystitis?
Acute cholecystitis and four (or five) Fs

The 4Fs (forties, female, fat, fair) and 5Fs (4Fs
plus fecund or fertile) have been shown to be associated
with lithogenesis in the gallbladder [50]. However, it has
not been established whether or not all these factors are
associated with the development of acute cholangitis/
cholecystitis.
Age and female gender
There is no evidence to suggest the association of age/
sex with the onset of acute cholangitis/cholecystitis.
According to the Framingham study which examined
risk factors of cholelithiasis in subjects 3059 years of age
followed for 10 years, the risk for the development of
cholelithiasis was largest in those subjects in the age range
5562 years, and the incidence of onset in females was
more than twice as large as in males in any age range, and
increased with age [58].
Obesity
Patients with cholelithiasis are more likely to be obese
than those without [58], and cholelithiasis is a major
comorbidity of obesity. The proportion of cholelithiasis
and cholecystitis in the obese aged 3760 years (female
BMI [ 34 [(weight kg)/(height m)2], and male BMI [ 38)
was significantly higher than that in the non-obese
(cholelithiasis: 5.8 vs. 1.5 %, odds ratio [OR] = 4.9;
cholecystitis: 0.8 vs. 3.4 %, OR = 5.2) [59].
Role of pregnancy, fecundity, and fertility
No evidence exists to suggest an association between
pregnancy/fecundity and the onset of acute cholangitis/
cholecystitis.
The risk for cholecystectomy due to gallbladder diseases
in middle-aged females (5064 years of age) increased
with the frequency of delivery and decreased in proportion
to the duration of lactation [60]. Cholelithiasis accounted
Etiology Cystic duct obstruction (Galltones are involved

in 90 95% of the causes.)
Mechanism Bile stasis, activation of inflammatory
mediators and mucosal injuries
Gallstones account for 9095 % of the causes of acute

cholecystitis [4649]. Following cystic duct obstruction
and cholestasis within the gallbladder due to the torsion of
stones, gallbladder mucosa disorder occurs, thereby
inducing the activation of infectious mediator [50]. On the
other hand, acute acalculous cholecystitis accounts for
3.714 % of acute cholecystitis [5155]. Risk factors
include surgery, trauma, long-term intensive care unit
stay, infection, thermal burn, and parenteral nutrition [56,
57].
Risk factors
Q7. What are the factors for which association with
the development of acute cholangitis/cholecystitis is
suggested?
Obesity; Acute cholecystitis

Medication;
Hormone replacement therapy: Increased risk for the
development of cholecystitis
or cholecystectomy
Statin: Decreased risk for carrying out cholecystectomy
Table 3 Percentage causes of acute cholangitis

References
Years
Setting
Causes
Gallbladder
stones (%)
Benign
stenosis
(%)
Malignant
stenosis
(%)
Sclerosing
cholangitis
(%)
Others/
unknown
(%)
Gigot [39]
19631983
University Paris
412
48
28
11
1.5
Saharia and Cameron [40]
19521974
Johns Hopkins Hospital, USA
76
70
13
17
Pitt and Couse [41]
19761978
40
70
18
10
Pitt and Couse [41]
19831985
48
32
14
30
24
Thompson [42]
19861989
96
28
12
57
Basoli [43]
19601985
University of Rome
80
69
16
13
Daida [44]
1979
Questionnaire throughout Japan
472
56
36
Salek [45]
20002005
Long Island Jewish Medical

Center, USA
108
68
24
123
16
Table 4 Etiological
mechanism of gallbladder
diseases
Etiological mechanism
Drug/treatment
Direct chemical toxicity
Hepatic artery infusion
Promoted stone formation by bile

Inhibition of ACAT activity
Progesterone, fibrate
Increased hepatic lipoprotein receptors
Estrogen
Induction of acute cholecystitis in patients with

cholelithiasis
Thiazides (unconfirmed)
Promoted precipitation of calcium salt in bile
Ceftriaxone
Altered mobility of the gallbladder
Octreotide
Narcoid
Anticholinergic drugs
Promoted hemolysis
Dapson
Immunological mechanism
Antimicrobial drugs (erythromycin,

ampicillin)
Review by Michielsen et al.

[62]
for more than 90 % of the causes of cholelithiasis in

pregnancy and cholelithiasis was the most frequently
encountered surgical disease next to appendicitis [61].
Gallstones were detected by routine ultrasound imaging in
3.5 % of pregnant women, although it is not known whether or not pregnancy is associated with an increased risk of
cholangitis [61].
Drugs as etiological agents
According to a review by Michielsen et al., drugs promoting the generation of gallbladder stones were indirectly
associated with a risk of acute cholecystitis [62]. A
developmental mechanism of drug-associated gallbladder
diseases in that review is presented in Table 4.
Statins, which are drugs for hyperlipidemia, may
decrease the risk for cholecystectomy due to gallbladder
stones [6366]. There are also reports suggesting that
thiazide was involved in the increased risk for cholecystectomy due to acute cholecystitis/gallbladder diseases
[6769], although there is a report that failed to detect an
association [70]. Transcatheter hepatic arterial chemotherapy has been indicated to potentially induce chemical
cholecystitis due to direct toxicity [62, 71]. The relative
risk for the onset of cholecystitis or cholecystectomy due
to hormone replacement therapy was two-fold larger [72,
73].
AIDS as a risk factor
Typical gallbladder diseases in AIDS patients are AIDS
cholangiopathy and acute acalculous cholecystitis [74].
The former showed higher frequency similar to sclerosing
cholangititis while the latter showed relatively low
123
Immunotherapy
frequency. Abdominal operations in AIDS patients have

found that the most frequently encountered causative disease was acute cholecystitis [75].
AIDS cholangiopathy is frequently observed in middleaged patients (mean age 37 years; 2159) with a mean
15 2.2 month history of AIDS, and 90 % of chief
complaints occur in the right upper quadrant abdomen.
Biochemical examination demonstrates a marked elevation
in the level of alkaline phosphatase [74]. Abdominal
ultrasound, computed tomography (CT) [74], magnetic
resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) [76], CT [74], and MRI/MRCP
[76] shows imaging (occasionally, beading) of stenosis/
dilatation in the intra-/extrahepatic bile duct.
Acute acalculous cholecystitis in AIDS patients was
characterized by young age, availability of oral intake, pain
in the right upper quadrant abdomen, marked elevation in
the level of alkaline phosphatase and a slight increase in
the serum bilirubin level, and accompanying cytomegalovirus infection or cryptosporidium infection [74].
Other etiologies of acute cholangitis
There are two other etiologies of acute cholangitis: Mirizzi
syndrome and Lemmel syndrome. Mirizzi syndrome is a
morbid condition with stenosis of the common bile duct
caused by mechanical pressure and/or inflammatory changes caused by the stones present in the gallbladder neck
and cystic ducts [77]. Two types have been described: type
I, which is a morbid condition with the bile duct compressed from the left by the stones present in the gallbladder neck and cystic ducts and pericholecystic
inflammatory changes (Fig. 4ac, Supplementary Fig. 1ac);
and type II, which is a morbid condition with biliobilary
17
Fig. 4 Mirizzi syndrome. a MRCP showed the obstructed common

hepatic duct but failed to visualize the gallbladder. b Cholangiography
with an ENBD tube showed the stenosed common hepatic duct but
failed to visualize the gallbladder. c Coronal images by contrast-
Fig. 5 Lemmel syndrome.

a Upper gastrointestinal
endoscopy showing a
diverticulum just above the
papilla of Vater (right arrow).
b ERCP demonstrating findings
of extrinsic compression in the
lower biliary tract (right arrow)
fistulation caused by pressure necrosis of the bile duct due

to cholecystolithiasis [77]. Lemmel syndrome (Fig. 5a, b;
Supplementary Fig. 2a, b) is a series of morbid conditions
in which the duodenal parapapillary diverticulum
enhanced CT clearly showing that stones impacted in the gallbladder

duct have expanded the common hepatic duct, thereby inducing
stenosis
compresses or displaces the opening of the bile duct or

pancreatic duct and obstructs the passage of bile in the bile
duct or hepatic duct, thereby causing cholestasis, jaundice,
gallstone, cholangitis, and pancreatitis [78].
123
18
19811990s, and 2.710 % after 2000 [42, 45, 7997].

Such differences in mortality rate are assumed to have
arisen from differences in severity and diagnostic criteria
for the accumulated cases.
Prognosis
Mortality
Q8. What is the mortality rate of acute cholangitis/
cholecystitis?
Acute cholangitis 2.7-10 %

Acute cholecystitis ~1 %
Acute cholangitis (Table 5)

It has been reported that the mortality rate of acute cholangitis was higher than 50 % before 1980, 1030 % in
Acute cholecystitis (Table 6)

The mortality rate in patients with acute cholecystitis has
been reported to be 010 % [17, 21, 98115]. According to
reports after 2000, the mortality rate was less than 1 % [17,
105115], and no marked difference according to eras and
communities is present.
The mortality rate according to severity in TG07 was
classified as mild (grade I) (1/161, 0.6 %), moderate
(grade II) (0/60, 0 %), or severe (grade III) (3/14,
21.4 %). Overall, acute cholecystitis accounts for 1.7 %
[21].
Table 5 Mortality rate of acute cholangitis

References
Period/year
Country
No. of cases
Mortality (%)
Andrew [79]
19571967
US
17c
64.71
Shimada [80]
19751981
Japan
42b
57.1
Csendes [81]
19801988
Chile
512
11.91
Himal [82]
19801989
Canada
61
18.03
Chijiiwa [83]
19801993
Japan
27
11.11
Liu [84]
19821987
Taiwan
47a
27.66
Lai [85]
19841988
Hong Kong
86b
19.77
Thompson [42]
19841988
USA
127
3.94
Arima [86]
19841992
Japan
163
2.45
Kunisaki [87]
19841994
Japan
82
10.98
Tai [88]
Thompson [89]
19861987
19861989
Taiwan
USA
225
96
6.67
5.21
Sharma [90]
20002004
India
75 (7Fr-NBD)
2.7
75 (7Fr stent)
2.7
Lee [91]
20012002
Taiwan
112 (bacteremia)
13.4
Rahman [92]
2005
UK
122
10
Pang [93]
20032004
Hong Kong
171
6.4
Agarwal [94]
20012005
India
175
2.9
Tsujino [95]
19942005
Japan
343 (38d)
5.3d
Rosing [96]
19952005
USA
117
Salek [45]
20002005
USA
108
24.1
Yeom [97]
20052007
Korea
181
0.5 (2d)
a
b
Only patients with shock

Only severe cases
Only patients with AOSC(Acute Obstructive Supprative Cholangitis)
Only patients with Acute supprative cholangitis
123
19
Table 6 Mortality rate of acute cholecystitis

Author
Period/year
Country
Subjects
No. of cases
Mortality (%)
4.49
Meyer [98]
19581964
USA
245
Ranasohoff [99]
19601981
USA
298
3.36
Gagic [100]
19661971
USA
93
9.68
Girald [101]
19701986
Canada
1691
0.65
Addison [102]
19711990
UK
236
4.66
Bedirli [103]
19911994
Turkey
368
2.72
Gharaibeh [104]
19941999
Jordan
204
Russo MW [105]
2004
USA
Papi [106]
2004
Meta
Giger [107]
Johansson [108]
2005
20022004
System. rev.
Sweden
262,411
0.6
Cholecystectomy
1009
0.9
LC
246
Cholecystectomy
35
0.260.6
0
LC
35
Al Salamah [109]
19972002
Saudi Arabia
LC
311
Gurusamy [110]
2006
Meta
Early operation
223
Delayed operation
228
1408
202
152,202
Borzellino [111]
2008
Meta
Lee [112]
20052006
USA
Csikesz [113]
20002005
USA
Lee [21]
20072008
Taiwan
Gurusamy [114]
2010
Meta
Cholecystectomy
LC
Sekimoto [115]
859,747
0.4
235
1.7
Early operation
223
Delayed operation
228
20042005
Japan
Total (operated cases)
738 (512)
0.9 (0.2)
20062007
Japan
3,858 (1,897)
1.9 (0.4)
20082009
Japan
8,026 (5,158)
2.9 (0.5)
Meta meta-analysis, System. rev. systematic review, LC laparoscopic cholecystectomy
Recurrence
Recurrence rate of acute cholecystitis
Q9. What is the recurrence rate for cases having
undergone
conservative
treatment
for
acute
cholecystitis?
The recurrence rate for cases needed emergent hospitalization
after having undergone conservative treatment or waiting for
cholecystectomy was 19~36% (level B) and 22~47%
for cases that do not undergo surgery after percutaneous
gallbladder drainage.
Fundamentally, no recurrence has occurred for cases

undergoing cholecystectomy for acute cholecystitis.
(1) Recurrence of acute cholecystitis for which remission was achieved with conservative treatment
According to randomized controlled trials comparing

outcomes of cholecystectomy and follow-up after remission of acute cholecystitis, 36 % of the cases in the followup group subsequently required emergency hospitalization
due to pain and gallstone-associated complications (acute
cholecystitis, bile duct stones, acute pancreatitis) [116,
117] and 2430 % required cholecystectomy [116118].
On the other hand, the recurrence rate of acute cholecystitis cases waiting for cholecystectomy was 2.522 %
[104, 116, 117, 119], and 19 % required emergency hospitalization [116, 117]. It has been reported that, of these
recurrence cases, the recurrence of acute cholecystitis
accounted for 2.5 % [104], 22 % [119], and gallbladder
perforation 6 %, respectively [119].
(2) Recurrence of acute cholecystitis for which no
cholecystectomy was carried out for some reason
Recurrence occurred in 2247 % of acute cholecystitis
cases undergoing follow-up without cholecystectomy subsequent to percutaneous gallbladder drainage [120122].
123
20
Recurrence rate after treatment for gallbladder stones

Q10. What is the recurrence rate after endoscopic
treatment for cholelithiasis?
Biliary events (cholelithiasis biliary colic cholangitis) 7~47%
Acute cholecystitis with gallstone in-situ 5.6 -22%
Recurrence of complications in the biliary system

Following endoscopic sphincterectomy (EST), recurrence occurred in 747 % of cases with complications in
the biliary tract system (cholelithiasis, biliary tract colic,
cholangitis) within the 2.515-year follow-up period [123
129].
Recurrence of acute cholecystitis
It has been reported that the proportion of symptom
appearance of acute cholecystitis (including cases in which
symptoms have appeared) was 5.622 % [123, 125, 126,
128130] when calculous gallbladder was left untreated
after EST [123126, 128133] and 07 % for cases with
acalculous gallbladder or after cholecystectomy [123126,
130, 133] (Supplementary Table 2).
A risk factor for recurrence after endoscopic treatment
for bile duct stones by means of endoscopic papillary
balloon dilation (EPBD) is the occurrence of calculous
gallbladder [134, 135]. Compared with treatment by means
of EST, the incidence of acute cholecystitis a long time
after treatment with EPBD is lower [136], although the
recurrence rates of bile duct stones are the same (5.5 and
8.8 %) for both treatment methods [137].
Acknowledgments We would like to express our deep gratitude to
the Japanese Society of Hepato-Biliary-Pancreatic Surgery, the Japanese Society of Abdominal Emergency Medicine, the Japanese
Society of Surgical Infection, the Japan Biliary Association, and the
Japan Radiological Society for their substantial support and guidance
in the preparation of this article.
None.
References
1. Kimura Y, Takada T, Kawarada Y, Nimura Y, Hirata K,
Sekimoto M, et al. Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines.
J Hepatobiliary Pancreat Surg. 2007;14(1):1526 (clinical
practice guidelines CPGs).
2. Ahrendt S, Pitt H. The biliary tract. In: Sabiston textbook of
surgery. 17th edn. Philadelphia: W. B. Saunders; 2004. p. 1625.
3. Charcot M. De la fievre hepatique symptomatiquecomparaison avec la fievre uroseptique. Lecons sur les maladies du foie
des voies biliares et des reins). Paris: Bourneville et Sevestre;
1877. p. 176185.
123
4. Reynolds BM, Dargan EL. Acute obstructive cholangitisa

distinct syndrome. Ann Surg. 1959;150:299303.
5. Longmire WP. Suppurative cholangitis. In: Hardy JD, editor.
Critical surgical illness. New York: Saunders; 1971. p. 397424.
EJ, Baron EJ, et al. Diagnosis and management of complicated
intra-abdominal infection in adults and children: guidelines by
the Surgical Infection Society and the Infectious Disease Society
of America. Clin Infect Dis. 2010;50:13364 (clinical practice
guidelines CPGs).
7. Fitzgibbons RJ Jr, Tseng A, Wang H, Ryberg A, Nguyen N, Sims
KL. Acute cholecystitis. Does the clinical diagnosis correlate with
the pathological diagnosis? Surg Endosc. 1996;10:11804.
8. Yacoub WN, Petrosyan M, Sehgal I, Ma Y, Chandrasoma P,
Mason RJ. Prediction of patients with acute cholecystitis
requiring emergent cholecystectomy: a simple score. Gastroenterol Res Pract. 2010. doi:901739
9. Goodman ZD, Ishak KG. Xanthogranulomatos cholecystitis.
Am J Surg Pathol. 1981;5:6539.
10. Gross RE. Congenital anomalies of the gallbladder. Arch Surg.
1936;32:13162.
11. Tazuma S. Gallstone disease: epidemiology, pathogenesis, and
classification of biliary stones (common bile duct and intrahepatic). Best Pract Res Clin Gastroenterol. 2006;20:107583.
12. Friedman GD. Natural history of asymptomatic and symptomatic gallstones. Am J Surg. 1993;165:399404.
13. Persson GE. Expectant management of patients with gallbladder
stones diagnosed at planned investigation. A prospective 5- to
7-year follow-up study of 153 patients. Scand J Gastroenterol.
1996;31:1919.
14. Festi D, Reggiani ML, Attili AF, Loria P, Pazzi P, Scaioli E,
Capodicasa S, Romano F, Roda E, Colecchia A. Natural history
of gallstone disease: expectant management or active treatment?
Results from a population-based cohort study. J Gastroenterol
Hepatol. 2010;25:71924.
15. Ransohoff DF, Gracie WA, Wolfenson LB, et al. Prophylactic
cholecystectomy or expectant management for silent gallstones.
A decision analysis to assess survival. Ann Intern Med.
1983;99:199204.
16. Stinton LM, Myers RP, Shaffer EA. Epidemiology of gallstones.
Gastroenterol Clin North Am. 2010;39:1579.
17. Portincasa P, Moschetta A, Palasciano G. Cholesterol gallstone
disease. Lancet. 2006;15(368):2309.
18. Portincasa P, Moschetta A, Petruzzelli M, Palasciano G, Di
Ciaula A, Pezzolla A. Gallstone disease: symptoms and diagnosis of gallbladder stones. Best Pract Res Clin Gastroenterol.
2006;20:101729.
cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg.
2007;14:528 (clinical practice guidelines CPGs).
20. Kiriyama S, Kumada T, Tanikawa M, Hisanaga Y, Toyota H,
Kanamori A, et al. Verification of the current JPN guidelines for
the management of acute cholangitis and cholecystitis: diagnostic criteria and severity assesment. J Abdom Emerg Med.
2011;31:47582 (in Japanese).
21. Lee SW, Yang SS, Chang CS, Yeh HJ. Impact of the Tokyo
guidelines on the management of patients with acute calculous
cholecystitis. J Gastroenterol Hepatol. 2009;24:185761.
22. Andriulli A, Loperfido S, Napolitano G, Niro G, Valvano MR,
Spirito F, et al. Incidence rates of post-ERCP complications: a
systematic survey of prospective studies. Am J Gastroenterol.
2007;102:1781817.
23. Vitte RL, Morfoisse JJ. Evaluation of endoscopic retrograde
cholangiopancreatography procedures performed in general
hospitals in France. Gastroenterol Clin Biol. 2007;31:7409.

24. Williams EJ, Taylor S, Fairclough P, Hamlyn A, Logan RF,
Martin D, et al. Are we meeting the standards set for endoscopy?
Results of a large-scale prospective survey of endoscopic retrograde cholangio-pancreatograph practice. Gut. 2007;56:8219.
25. Chong VH, Yim HB, Lim CC. Endoscopic retrograde cholangiopancreatography in the elderly: outcomes, safety and complications. Singapore Med J. 2005;46:6216.
26. Ong TZ, Khor JL, Selamat DS, Yeoh KG, Ho KY. Complications of endoscopic retrograde cholangiography in the postMRCP era: a tertiary center experience. World J Gastroenterol.
2005;11:520912.
27. Thompson AM, Wright DJ, Murray W, Ritchie GL, Burton HD,
Stonebridge PA. Analysis of 153 deaths after upper gastrointestinal
endoscopy: room for improvement? Surg Endosc. 2004;18:225.
28. Kaneko E. Complications of digestive endoscopy. Nihon Shokakibyo Gakkai Zasshi. 2004;101:5717 (in Japanese).
29. Vandervoort J, Soetikno RM, Tham TC, Wong RC, Ferrari AP
Jr, Montes H, et al. Risk factors for complications after performance of ERCP. Gastrointest Endosc. 2002;56:6526.
30. Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME,
Dorsher PJ, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med. 1996;335:90918.
31. Lenriot JP, Le Neel JC, Hay JM, Jaeck D, Millat B, Fagniez PL.
Retrograde cholangiopancreatography and endoscopic sphincterotomy for biliary lithiasis. Prospective evaluation in surgical
circle. Gastroenterol Clin Biol. 1993;17:24450.
32. Benchimol D, Bernard JL, Mouroux J, Dumas R, Elkaim D,
Chazal M, et al. Infectious complications of endoscopic retrograholangio-pancreatography managed in a surgical unit. Int
Surg. 1992;77:2703.
33. Cotton PB, Lehman G, Vennes JA, Geenen JE, Russell RCG,
Meyers WC, et al. Endoscopic sphincterotomy complications
and their management: an attempt at consensus. Gastrointest
Endosc. 1991;37:2558.
34. Reiertsen O, Skjoto J, Jacobsen CD, Rosseland AR. Complications of fiberoptic gastrointestinal endoscopy; five years experience in a central hospital. Endoscopy. 1987;19:16.
35. Roszler MH, Campbell WL. Post-ERCP pancreatitis: association with urographic visualization during ERCP. Radiology.
1985;157:5958.
36. Escourrou J, Cordova JA, Lazorthes F, Frexinos J, Ribet A.
Early and late complications after endoscopic sphincterotomy
for biliary lithiasis with and without the gall bladder in situ.
Gut. 1984;25:598602.
37. Bilbao MK, Dotter CT, Lee TG, Katon RM. Complications of
endoscopic retrograde cholangiopancreatography (ERCP). A
study of 10,000 cases. Gastroenterology. 1976;70:31420.
38. Lipsett PA, Pitt HA. Acute cholangitis. Surg Clin North Am.
1990;70:1297312.
39. Gigot JF, Leese T, Dereme T, Coutinho J, Castaing D, Bismuth
H. Acute cholangitis: multivariate analysis of risk factors. Ann
Surg. 1989;209:4358.
40. Saharia PC, Cameron JL. Clinical management of acute cholangitis. Surg Gynecol Obstet. 1976;142:36972.
41. Pitt HA, Couse NF. Biliary sepsis and toxic cholangitis. In: Moody
FG, Carey LC, editors. Surgical treatment of digestive diseases.
2nd ed. Chicago: Year Book Medical Publishers; 1990. p. 332.
42. Thompson JE Jr, Pitt HA, Doty JE, Coleman J, Irving C. Broad
spectrum penicillin as an adequate therapy for acute cholangitis.
Surg Gynecol Obstet. 1990;171:27582.
43. Basoli A, Schietroma M, De Santis A, Colella A, Fiocca F,
Speranza V. Acute cholangitis: diagnostic and therapeutic
problems. Ital J Surg Sci. 1986;16:2617.
44. Daida A, Miki M, Yoshioka M, Moriyama Y. Collective study
results on the bacteriological examination during biliary surgery.
Jpn J Gastroenterol Surg. 1980;13:4459 (in Japanese).
21
45. Salek J, Livote E, Sideridis K, Bank S. Analysis of risk factors
predictive of early mortality and urgent ERCP in acute cholangitis. J Clin Gastroenterol. 2009;43:1715.
46. Gouma DJ, Obertop H. Acute calculous cholecystitis. What is
new in diagnosis and therapy? HPB Surg. 1992;6:6978.
47. Mack E. Role of surgery in the management of gallstones.
Semin Liver Dis. 1990;10:22231.
48. Hermann RE. Surgery for acute and chronic cholecystitis. Surg
Clin North Am. 1990;70:126375.
49. Sharp KW. Acute cholecystitis. Surg Clin North Am. 1988;68:
26979.
50. Jpn. Societ. Gastroenterol. Practice guidelines of the gallstone
disease. Tokyo: Dai Nippon Printing Co., Ltd., 2009. p. 301 (in
Japanese, clinical practice guidelines CPGs).
51. Williamson RC. Acalculous disease of the gall bladder. Gut.
1988;29:86072.
52. Barie PS, Fischer E. Acute acalculous cholecystitis. J Am Coll
Surg. 1995;180:23244.
53. Ryu JK, Ryu KH, Kim KH. Clinical features of acute acalculous
cholecystitis. J Clin Gastroenterol. 2003;36:1669.
54. Wang AJ, Wang TE, Lin CC, Lin SC, Shih SC. Clinical predictors of severe gallbladder complications in acute acalculous
cholecystitis. World J Gastroenterol. 2003;9:28213.
55. Matsusaki S, Maguchi H, Takahashi K, Katanuma A, Osanai M,
Urata T, et al. Clinical features of acute acalculous cholecystitis
nosocomial manner and community-acquired manner. Nihon
Shokakibyo Gakkai Zasshi. 2008;105:174957 (in Japanese).
56. Laurila J, Syrjala H, Laurila PA, Saarnio J, Ala-Kokko TI. Acute
acalculous cholecystitis in critically ill patients. Acta Anaesthesiol Scand. 2004;48:98691.
57. Theodorou P, Maurer CA, Spanholtz TA, Phan TQ, Amini P, Perbix
W, et al. Acalculous cholecystitis in severely burned patients:
incidence and predisposing factors. Burns. 2009;35:40511.
58. Friedman GD, Kannel WB, Dawber TR. The epidemiology of
gallbladder disease: observations in the Framingham Study.
J Chronic Dis. 1966;19:27392.
59. Torgerson JS, Lindroos AK, Naslund I, Peltonen M. Gallstones,
gallbladder disease, and pancreatitis: cross-sectional and 2-year
data from the Swedish Obese Subjects (SOS) and SOS reference
studies. Am J Gastroenterol. 2003;98:103241.
60. Liu B, Beral V, Balk Will A. Million Women Study Collaborators. Childbearing, breastfeeding, other reproductive factors
and the subsequent risk of hospitalization for gallbladder disease. Int J Epidemiol. 2009;38:3128.
61. Sharp HT. The acute abdomen during pregnancy. Clin Obstet
Gynecol. 2002;45:40513.
62. Michielsen PP, Fierens H, Van Maercke YM. Drug-induced
gallbladder disease. Incidence, aetiology and management. Drug
Saf. 1992;7:3245.
63. Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Statin
use and the risk of cholecystectomy in women. Gastroenterology.
2009;136:1593600.
64. Bodmer M, Brauchli YB, Krahenbuhl S, Jick SS, Meier CR.
Statin use and risk of gallstone disease followed by cholecystectomy. JAMA. 2009;302:20017.
65. Merzon E, Weiss NS, Lustman AJ, Elhayani A, Dresner J,
Vinker S. Statin administration and risk of cholecystectomy: a
population-based case-control study. Expert Opin Drug Saf.
2010;9:53943.
66. Erichsen R, Frslef T, Lash TL, Pedersen L, Srensen HT.
Long-term statin use and the risk of gallstone disease: A population-based case-control study. Am J Epidemiol. 2011;173:
16270.
67. Rosenberg L, Shapiro S, Slone D, Kaufman DW, Miettinen OS,
Stolley PD. Thiazides and acute cholecystitis. N Engl J Med.
1980;303:5468.
123
22
68. Gonzalez-Perez A, Garcia Rodriguez LA. Gallbladder disease in
the general population: association with cardiovascular morbidity
and therapy. Pharmacoepidemiol Drug Saf. 2007;16:52431.
69. Leitzmann MF, Tsai CJ, Stampfer MJ, Willett WC, Giovannucci
E. Thiazide diuretics and the risk of gallbladder disease requiring
surgery in women. Arch Intern Med. 2005;165:56773.
70. Porter JB, Jick H, Dinan BJ. Acute cholecystitis and thiazides.
N Engl J Med. 1981;304:9545.
71. Wagnetz U, Jaskolka J, Yang P, Jhaveri KS. Acute ischemic
cholecystitis after transarterial chemoembolization of hepatocellular carcinoma: incidence and clinical outcome. J Comput
Assist Tomogr. 2010;34:34853.
72. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD.
Postmenopausal hormone replacement therapy: scientific
review. JAMA. 2002;288:87281.
73. Cirillo DJ, Wallace RB, Rodabough RJ, Greenland P, LaCroix
AZ, Limacher MC, et al. Effect of estrogen therapy on gallbladder disease. JAMA. 2005;293:3309.
74. Cello JP. AIDS-related biliary tract disease. Gastrointest Endosc
Clin North Am. 1998;8:963.
75. LaRaja RD, Rothenberg RE, Odom JW, Mueller SC. The incidence of intra-abdominal surgery in acquired immunodeficiency
syndrome: a statistical review of 904 patients. Surgery. 1989;105:
1759.
76. Bilgin M, Balci NC, Erdogan A, Momtahen AJ, Alkaade S, Rau
WS. Hepatobiliary and pancreatic MRI and MRCP findings in
patients with HIV infection. AJR Am J Roentgenol. 2008;191:
22832.
77. McSherry CK, Ferstenberg H, Virshup M. The Mirizzi syndrome: suggested classification and surgical therapy. Surg
Gastroenterol. 1982;1:21925.
78. Lemmel G. Die kliniscle Bedeutung der Duodenal Divertikel.
Arch Venduungskrht. 1934;46:5970.
79. Andrew DJ, Johnson SE. Acute suppurative cholangitis, a
medical and surgical emergency. A review of ten years. Am J
80. Shimada H, Nakagawara G, Kobayashi M, Tsuchiya S, Kudo T,
Morita S. Pathogenesis and clinical features of acute cholangitis
accompanied by shock. Jpn J Surg. 1984;14:26977 (in
Japanese).
81. Csendes A, Diaz JC, Burdiles P, Maluenda F, Morales E. Risk
factors and classification of acute suppurative cholangitis. Br J
Surg. 1992;79:6558.
82. Himal HS, Lindsay T. Ascending cholangitis: surgery versus
endoscopic or percutaneous drainage. Surgery. 1990;108:62933.
83. Chijiiwa K, Kozaki N, Naito T, Kameoka N. Treatment of
choice for choledocholithiasis in patients with acute obstructive
suppurative cholangitis and liver cirrhosis. Am J Surg.
1995;170:35660.
84. Liu TJ. Acute biliary septic shock. HPB Surg. 1990;2:17783.
85. Lai EC, Tam PC, Paterson IA, Ng MM, Fan ST, Choi TK, et al.
Emergency surgery for severe acute cholangitis. The high risk
patients. Ann Surg. 1990;211:559.
86. Arima N, Uchiya T, Hishikawa R, Saito M, Matsuo T, Kurisu S,
et al. Clinical characteristics of impacted bile duct stone in eldery. Jpn J Geriat. 1993;30:9648 (in Japanese).
87. Kunisaki C, Kobayashi S, Kido Y, Imai S, Harada H, Moriwaki
Y, et al. Clinical evaluation of acute cholangitis with speciaal
reference to detection of prognostic factor for acute obstructive
supprative cholangitis. J Abdom Emerg Med. 1997;17:2616 (in
Japanese).
88. Tai DI, Shen FH, Liaw YF. Abnormal pre-drainage serum creatinine as a prognostic indicator in acute cholangitis. Hepatogastroenterology. 1992;39:4750.
89. Thompson J, Bennion RS, Pitt HA. An analysis of infectious
failures in acute cholangitis. HPB Surg. 1994;8:13945.
123

90. Sharma BC, Kumar R, Agarwal N, Sarin SK. Endoscopic biliary
drainage by nasobiliary drain or by stent placement in patients
with acute cholangitis. Endoscopy. 2005;37:43943.
91. Lee CC, Chang IJ, Lai YC, Chen SY, Chen SC. Epidemiology
and prognostic determinants of patients with bacteremic cholecystitis or cholangitis. Am J Gastroenterol. 2007;102:5639.
92. Rahman SH, Larvin M, McMahon MJ, Thompson D. Clinical
presentation and delayed treatment of cholangitis in older
people. Dig Dis Sci. 2005;50:220710.
93. Pang YY, Chun YA. Predictors for emergency biliary decompression in acute cholangitis. Eur J Gastroenterol Hepatol.
2006;18:72731.
94. Agarwal N, Sharma BC, Sarin SK. Endoscopic management of
acute cholangitis in elderly patients. World J Gastroenterol.
2006;12:65515.
95. Tsujino T, Sugita R, Yoshida H, Yagioka H, Kogure H, Sasaki
T, et al. Risk factors for acute suppurative cholangitis caused by
bile duct stones. Eur J Gastroenterol Hepatol. 2007;19:5858.
96. Rosing DK, De Virgilio C, Nguyen AT, El Masry M, Kaji AH,
Stabile BE. Cholangitis: analysis of admission prognostic indicators and outcomes. Am Surg. 2007;73:94954.
97. Yeom DH, Oh HJ, Son YW, Kim TH. What are the risk factors
for acute suppurative cholangitis caused by common bile duct
stones? Gut Liver. 2010;4:3637.
98. Meyer KA, Capos NJ, Mittelpunkt AI. Personal experiences
with 1261 cases of acute and chronic cholecystitis and cholelithiasis. Surgery. 1967;61:6618.
99. Ransohoff DF, Miller GL, Forsythe SB, Hermann RE. Outcome
of acute cholecystitis in patients with diabetes mellitus. Ann
Intern Med. 1987;106:82932.
100. Gagic N, Frey CF, Galness R. Acute cholecystitis. Surg Gynecol
Obstet. 1975;140:86874.
101. Girard RM, Morin M. Open cholecystectomy: its morbidity and
mortality as a reference standard. Can J Surg. 1993;36:7580.
102. Addison NV, Finan PJ. Urgent and early cholecystectomy for
acute gallbladder disease. Br J Surg. 1988;75:1413.
103. Bedirli A, Sakrak O, Sozuer EM, Kerek M, Guler I. Factors
effecting the complications in the natural history of acute cholecystitis. Hepatogastroenterology. 2001;48:12758.
104. Gharaibeh KI, Qasaimeh GR, Al-Heiss H, Ammari F, Bani-Hani
K, Al-Jaberi TM, Al-Natour S. Effects of timing of surgery, type
of inflammation, and sex on outcome of laparoscopic cholecystectomy for acute cholecystitis. J Laparoendosc Adv Surg
Tech. 2002;12:1938.
105. Russo MW, Wei JT, Thiny MT, Gangarosa LM, Brown A,
Ringel Y, Shaheen NJ, Sandler RS. Digestive and liver diseases
statistics, 2004. Gastroenterology. 2004;126:144853.
106. Papi C, Catarci M, DAmbrosio L, Gili L, Koch M, Grassi GB,
Capurso L. Timing of cholecystectomy for acute calculous
cholecystitis: a meta-analysis. Am J Gastroenterol. 2004;99:
14755.
107. Giger U, Michel JM, Vonlanthen R, Becker K, Kocher T,
Krahenbuhl L. Laparoscopic cholecystectomy in acute cholecystitis: indication, technique, risk and outcome. Langenbecks
Arch Surg. 2005;390:37380.
108. Johansson M, Thune A, Nelvin L, Stiernstam M, Westman B,
Lundell L. Randomized clinical trial of open versus laparoscopic
cholecystectomy in the treatment of acute cholecystitis. Br J
Surg. 2005;92:449.
109. Al Salamah SM. Outcome of laparoscopic cholecystectomy in
acute cholecystitis. J Coll Phys Surg Pak. 2005;15:4003.
110. Gurusamy KS, Samraj K. Early versus delayed laparoscopic
cholecystectomy for acute cholecystitis. Cochrane Database
Syst Rev. 2006;4:CD005440.
111. Borzellino G, Sauerland S, Minicozzi AM, Verlato G, Di Pietrantonj C, de Manzoni G, et al. Laparoscopic cholecystectomy
112.
113.
114.
115.
116.
117.
118.
119.
120.
121.
122.
123.
124.
125.
for severe acute cholecystitis. A meta-analysis of results. Surg

Endosc. 2008;22:815.
Lee AY, Carter JJ, Hochberg MS, Stone AM, Cohen SL, Pachter
HL. The timing of surgery for cholecystitis: a review of 202
consecutive patients at a large municipal hospital. Am J Surg.
2008;195:46770.
Csikesz N, Ricciardi R, Tseng JF, Shah SA. Current status of
surgical management of acute cholecystitis in the United States.
World J Surg. 2008;32:22306.
Gurusamy K, Samraj K, Gluud C, Wilson E, Davidson BR.
Meta-analysis of randomized controlled trials on the safety and
effectiveness of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Br J Surg. 2010;97:14150.
Sekimoto M, Okuma K, Imanaka Y, Yoshida M, Hirata K,
Mayumi T, et al. The practical guideline for acute cholecystitis
and acute cholangitis were published in 2005. In this study, we
utilized administrative data to examine trends in patients characteristics, process of care, patient outcome, and medical
resource utilization for patients with acute cholecustitis.
J Abdom Emerg Med. 2010;30:4139 (in Japanese).
Vetrhus M, Soreide O, Eide GE, Nesvik I, Sondenaa K. Quality
of life and pain in patients with acute cholecystitis. Results of a
randomized clinical trial. Scand J Surg. 2005;94:349.
Vetrhus M, Soreide O, Nesvik I, Sondenaa K. Acute cholecystitis: delayed surgery or observation. A randomized clinical trial.
Scand J Gastroenterol. 2003;38:98590.
Sondenaa K, Nesvik I, Solhaug JH, Soreide O. Randomization
to surgery or observation in patients with symptomatic gallbladder stone disease. The problem of evidence-based medicine
in clinical practice. Scand J Gastroenterol. 1997;32:6116.
Lahtinen J, Alhava EM, Aukee S. Acute cholecystitis treated by
early and delayed surgery. A controlled clinical trial. Scand J
Andren-Sandberg A, Haugsvedt T, Larssen TB, Sondenaa K.
Complication and late outcome following percutaneous drainage
of the gallbladder in acute calculous cholecystitis. Dig Surg.
2001;18:3938.
Granlund A, Karlson BM, Elvin A, Rasmussen I. Ultrasoundguided percutaneous cholecystectomy in high-risk surgical
patients. Langenbecks Arch Surg. 2001;386:2127.
McLoughlin RF, Patterson EJ, Mathieson JR, Cooperberg PL,
MacFarlane JK. Radiologically guided percutaneous cholecystectomy for acute cholecystitis: long-term outcome in 50
patients. Can Assoc Radiol J. 1994;45:4559.
Ando T, Tsuyuguchi T, Saito M, Ishihara T, Yamaguchi T,
Saisho H. Risk factors for recurrent bile duct stones after
endoscopic papillotomy. Gut. 2003;52:11621.
Sugiyama M, Atomi Y. Risk factors predictive of late complications after endoscopic sphincterotomy for bile duct stones:
long-term (more than 10 years) follow-up study. Am J Gastroenterol. 2002;97:27637.
Costamagna G, Tringali A, Shah SK, Mutignani M, Zuccala G,
Perri V. Long-term follow-up of patients after endoscopic
23
126.
127.
128.
129.
130.
131.
132.
133.
134.
135.
136.
137.
sphincterotomy for choledocholithiasis, and risk factors for

recurrence. Endoscopy. 2002;34:2739.
Tanaka M, Takahata S, Konmi H, Matsunaga H, Yokohata K,
Takeda T, et al. Long-term consequence of endoscopic sphincterotomy for bile duct stones. Gastrointest Endosc. 1998;48:
4659.
Prat F, Malak NA, Pelletier G, Buffet C, Fritsch J, Choury AD,
et al. Biliary symptoms and complications more than 8 years
after endoscopic sphincterotomy for choledocholithiasis. Gastroenterology. 1996;110:8949.
Schreurs WH, Vles WJ, Stuifbergen WH, Oostvogel HJ.
Endoscopic management of common bile duct stones leaving
the gallbladder in situ. A cohort study with long-term followup. Dig Surg. 2004;21:604.
Boerma D, Rauws EA, Keulemans YC, Janssen IM, Bolwerk
CJ, Timmer R, Boerma EJ, Obertop H, Huibregtse K, Gouma
DJ. Wait-and-see policy or laparoscopic cholecystectomy after
endoscopic sphincterotomy for bile-duct stones: a randomised
trial. Lancet. 2002;360:7615.
Lau JY, Leow CK, Fung TM, Suen BY, Yu LM, Lai PB, et al.
Cholecystectomy or gallbladder in situ after endoscopic
sphincterotomy and bile duct stone removal in Chinese patients.
Gastroenterology. 2006;130:96103.
Lee KM, Paik CN, Chung WC, Kim JD, Lee CR, Yang JM. Risk
factors for cholecystectomy in patients with gallbladder stones
after endoscopic clearance of common bile duct stones. Surg
Endosc. 2009;23:17139.
Lee JK, Ryu JK, Park JK, Yoon WJ, Lee SH, Lee KH, et al. Risk
factors of acute cholecystitis after endoscopic common bile duct
stone removal. World J Gastroenterol. 2006;12:95660.
Kwon SK, Lee BS, Kim NJ, Lee HY, Chae HB, Youn SJ, et al.
Is cholecystectomy necessary after ERCP for bile duct stones in
patients with gallbladder in situ? Korean J Intern Med.
2001;16:2549.
Tsujino T, Kawabe T, Komatsu Y, Yoshida H, Isayama H,
Sasaki T, et al. Endoscopic papillary balloon dilation for bile
duct stone: immediate and long-term outcomes in 1000 patients.
Clin Gastroenterol Hepatol. 2007;5:1307.
Tsujino T, Kawabe T, Isayama H, Yashima Y, Yagioka H,
Kogure H, et al. Management of late biliary complications in
patients with gallbladder stones in situ after endoscopic papillary balloon dilation. Eur J Gastroenterol Hepatol. 2009;21:
37680.
Bergman JJ, Rauws EA, Fockens P, van Berkel AM, Bossuyt
PM, Tijssen JG, et al. Randomised trial of endoscopic balloon
dilation versus endoscopic sphincterotomy for removal of bileduct stones. Lancet. 1997;349:11249.
Liu Y, Su P, Lin S, Xiao K, Chen P, An S, et al. Endoscopic
papillary balloon dilatation vs endoscopic sphincterotomy in the
treatment for choledocholithiasis: a meta-analysis. J Gastroenterol Hepatol. 2012;27:464471.
123

DOI 10.1007/s00534-012-0561-3
GUIDELINE

TG13 guidelines for diagnosis and severity grading of acute

cholangitis (with videos)
Seiki Kiriyama Tadahiro Takada Steven M. Strasberg Joseph S. Solomkin Toshihiko Mayumi
Henry A. Pitt Dirk J. Gouma O. James Garden Markus W. Buchler Masamichi Yokoe Yasutoshi Kimura
Toshio Tsuyuguchi Takao Itoi Masahiro Yoshida Fumihiko Miura Yuichi Yamashita Kohji Okamoto
Toshifumi Gabata Jiro Hata Ryota Higuchi John A. Windsor Philippus C. Bornman Sheung-Tat Fan
Harijt Singh Eduardo de Santibanes Harumi Gomi Shinya Kusachi Atsuhiko Murata Xiao-Ping Chen
Palepu Jagannath SungGyu Lee Robert Padbury Miin-Fu Chen Christos Dervenis Angus C. W. Chan
Avinash N. Supe Kui-Hin Liau Myung-Hwan Kim Sun-Whe Kim
Abstract Since the publication of the Tokyo Guidelines

for the management of acute cholangitis and cholecystitis
(TG07), diagnostic criteria and severity assessment criteria
for acute cholangitis have been presented and extensively
used as the primary standard all over the world. However,
it has been found that there are crucial limitations in these
criteria. The diagnostic criteria of TG07 do not have
enough sensitivity and specificity, and its severity assessment criteria are unsuitable for clinical use. A working
S. Kiriyama (&)
4-86 Minaminokawa-cho, Ogaki, Gifu 503-8502, Japan
e-mail: skiriya@ip.mirai.ne.jp
T. Takada F. Miura
Tokyo, Japan
S. M. Strasberg
Section of Hepatobiliary and Pancreatic Surgery,
Washington University in Saint Louis School of Medicine,
J. S. Solomkin
Department of Surgery, University of Cincinnati College of
Medicine, Cincinnati, OH, USA
T. Mayumi
H. A. Pitt
123
team for the revision of TG07 was organized in June, 2010,

and these criteria have been updated through clinical
implementation and its assessment by means of multicenter analysis. The diagnostic criteria of acute cholangitis
have been revised as criteria to establish the diagnosis
where cholestasis and inflammation demonstrated by clinical signs or blood test in addition to biliary manifestations
demonstrated by imaging are present. The diagnostic criteria of the updated Tokyo Guidelines (TG13) have high
sensitivity (87.6 %) and high specificity (77.7 %). TG13
has better diagnostic capacity than TG07. Severity
assessment is classified as follows: Grade III: associated
with organ failure; Grade II: early biliary drainage should
D. J. Gouma
The Netherlands
O. J. Garden
M. W. Buchler
Germany
M. Yokoe
Nagoya, Japan
Y. Kimura
Sapporo, Japan
T. Tsuyuguchi
be conducted; Grade1: others. As for the severity assessment criteria of TG07, separating Grade II and Grade I at
the time of diagnosis was impossible, so they were
unsuitable for clinical practice. Therefore, the severity
assessment criteria of TG13 have been revised so as not to
lose the timing of biliary drainage or treatment for etiology.
Based on evidence, five predictive factors for poor prognosis in acute cholangitishyperbilirubinemia, high fever,
leukocytosis, elderly patient and hypoalbuminemiahave
been extracted. Grade II can be diagnosed if two of these
five factors are present.
Free full-text articles and a mobile application of TG13 are
available via http://www.jshbps.jp/en/guideline/tg13.html.
25
Patients with acute cholangitis are at risk of developing

severe and potentially lethal infections such as sepsis
unless appropriate medical care is provided promptly. As a
therapeutic procedure for severe cases or to prevent
increased severity, decompression of the biliary tract (i.e.,
biliary tract drainage) is necessary. Recent advances in and
diffusion of endoscopic biliary tract drainage along with
the administration of antimicrobial agents have contributed
to the decrease in the number of deaths due to acute cho-
langitis. However, it remains a life-threatening disease if

the timing of biliary tract drainage has been missed.
Therefore, immediate and precise judgment of severity is
of the utmost importance.
Since Charcot reported a patient with severe acute
cholangitis as a case of hepatic fever in 1877, Charcots
triad has been widely used as one of the most important
diagnostic criteria [15]. However, Charcots triad has
extremely low sensitivity despite its high specificity. In
2006, we conducted a systematic review of references and
sponsored the International Consensus Meeting of Tokyo
Guidelines, which resulted in the introduction of new
diagnostic criteria and severity assessment criteria in the
and cholecystitis (TG07) [6].
Diagnostic criteria and severity assessment criteria
should be reconsidered and updated according to their
implementation in clinical settings and their assessment. In
TG07, there are impractical aspects and discrepancies
between the diagnostic criteria and severity assessment
criteria of acute cholangitis and the actual clinical settings
[7]. Therefore, in order to make the updated Tokyo
Guidelines (TG13), the working team carried out a retrospective observational study in multiple tertiary care centers in Japan. This study found limitations in the diagnostic
criteria and severity assessment criteria of TG07. The
problems which were made clear by the implementation
and assessment of TG07 were then corrected, and new
updated diagnostic criteria and severity assessment criteria
were presented [8]. TG13 provides more accurate and
T. Itoi
J. A. Windsor
New Zealand
M. Yoshida
P. C. Bornman
Division of General Surgery, Health Sciences, University of
Cape Town, Cape Town, South Africa
Y. Yamashita
S.-T. Fan
Department of Surgery, The University of Hong Kong, Queen
Mary Hospital, Hong Kong, Hong Kong
K. Okamoto
Kitakyushu, Japan
H. Singh
Department of Hepato-Pancreato-Biliary Surgery, Hospital
Selayang, Kuala Lampur, Malaysia
T. Gabata
E. de Santibanes
Department of Surgery, Hospital Italianio, University of Buenos
Aires, Buenos Aires, Argentina
J. Hata
H. Gomi
Tochigi, Japan
R. Higuchi
Department of Surgery, Institute of Gastroenterology Tokyo
S. Kusachi
Keywords Acute cholangitis Diagnostic criteria

Severity assessment Diagnostic imaging guidelines
Introduction
123
26
reliable diagnostic criteria and severity assessment criteria

for acute cholangitis to enable us to perform biliary
drainage or other procedures without delay as compared
with TG07.
Diagnostic criteria for acute cholangitis

Background
Charcots triad
Q1. What is the role of Charcots triad in the diagnostic
criteria for acute cholangitis?
Charcots triad shows very high specificity. The presence
of any one sign of Charcots triad strongly suggests the
presence of acute cholangitis. However, due to the low sensitivity,
it is not applicable in using as diagnosis criteria for acute
cholangitis (level B).
A diagnosis of acute cholangitis has traditionally been

made according to the presence of Charcots triad, that is, a
clinical sign. Charcots triad has high specificity [9] but
low sensitivity. According to several reports, cases presenting all the symptoms of Charcots triad accounted for
26.472 % [2, 3, 814].
The previous definition of acute cholangitis was not
clear and varied in different references. Therefore, in the
analysis of cases of biliary tract diseases collected from
A. Murata
Department of Preventive Medicine and Community Health,
School of Medicine, University of Occupational and
Environmental Health, Kitakyushu, Japan
X.-P. Chen
Hepatic Surgery Centre, Department of Surgery, Tongji
Hospital, Tongi Medical College, Huazhong University of
Science and Technology, Wuhan, China
P. Jagannath
Department of Surgical Oncology, Lilavati Hospital and
Research Centre, Mumbai, India
S. Lee
HepatoBiliary Surgery and Liver Transplantation, Asan Medical
Center, Ulsan University, Seoul, Korea
R. Padbury
Division of Surgical and Specialty Services, Flinders Medical
Centre, Adelaide, Australia
M.-F. Chen
Chang Gung Memorial Hospital, Chang Gung University,
Taoyuan, Taiwan
123
multiple facilities, we defined the gold standard for acute

cholangitis, that one of the three following conditions was
present: (1) Purulent bile was observed. (2) Clinical
remission followed bile duct drainage. (3) Remission was achieved by antibacterial therapy alone, in
patients in whom the only site of infection was the biliary
tree. So it showed low sensitivity (26.4 %) when Charcots
triad was adopted as a diagnostic criterion for acute cholangitis. On the other hand, the specificity was very
favorable (95.9 %), but it was positive (11.9 %) for acute
cholecystitis. The presence of Charcots triad supports the
diagnosis of acute cholangitis. However, judging from the
low sensitivity, Charcots triad as a diagnostic criterion for
acute cholangitis is doubtful [8].
TG07 diagnostic criteria for acute cholangitis
Q2. How are the diagnostic criteria for acute cholangitis
in TG07 appraised?
Although the sensitivity has been improved compared a with
Charcots triad, TG07 have limitations and their validity is
insufficient for using them to make a diagnosis of life-threatening
acute cholangitis without a rapid clinical suspicion and appropriate
treatment (level B).
As has already been mentioned, there were limitations in

Charcots triad due to its low diagnostic sensitivity; however, there was no alternative diagnostic criterion. Under
these circumstances, the International Consensus Meeting
was held in Tokyo in 2006 so that an international
C. Dervenis
Greece
A. C. W. Chan
Surgery Centre, Department of Surgery, Hong Kong Sanatorium
and Hospital, Hong Kong, Hong Kong
A. N. Supe
Department of Surgical Gastroenterology, Seth G. S. Medical
College and K. E. M. Hospital, Mumbai, India
K.-H. Liau
Hepatobiliary and Pancreatic Surgery, Nexus Surgical
Associates, Mount Elizabeth Hospital, Singapore, Singapore
M.-H. Kim
Department of Internal Medicine, Asan Medical Center
S.-W. Kim
Department of Surgery, Seoul National University College of
Medicine, Seoul, Korea
agreement could be reached on diagnostic criteria and

severity assessment criteria. At that meeting, diagnostic
criteria were presented combining blood tests and diagnostic imaging together with Charcots triad [15]. Diagnostic criteria were then established in TG07.
However, there has been a report showing that, even in
TG07, the sensitivity is low (63.9 %) for making a definite diagnosis of acute cholangitis [7]. We carried out a
multi-center analysis and found that the sensitivity was
82.6 % and the specificity was 79.8 % [8]. The diagnostic
criteria for acute cholangitis in TG07 were found to be
insufficient for making a diagnosis of life-threatening
acute cholangitis without a rapid diagnosis and appropriate treatment.
Revision of TG07 diagnostic criteria for acute cholangitis
Due to the inappropriate combination of such items as
clinical context and manifestations, laboratory data and
imaging findings, TG07 failed to associate them with three
types of morbid conditions of acute cholangitis. We then
performed an analysis of each of the items of the diagnostic
criteria in TG07, which can be classified as the following
three morbidities: (1) fever and/or evidence of inflammatory response such as inflammation, (2) jaundice and
abnormal liver function test results such as cholestasis, and
(3) a history of biliary diseases, abnormal pain and biliary
dilatation, or evidence of etiology such as biliary manifestations. It was considered that those cases meeting these
3 categories can be diagnosed as acute cholangitis. However, a history of biliary diseases and abdominal pain is not
specific to biliary manifestations, thus making the differentiation from acute cholecystitis or acute hepatitis
impossible. Consequently, abdominal pain and a history of
biliary diseases were excluded. To make up for the reduced
sensitivity due to the exclusion of abdominal pain, suspected diagnosis in which inflammatory findings are
dispensable was added. By establishing suspected diagnosis, early biliary drainage or source control of infection
among patients with acute cholangitis can be provided
without waiting for the definitive diagnosis [8].
27
clinical signs or blood test in addition to biliary manifestations based on imaging are present.
Q3. How are TG13 diagnostic criteria for acute cholangitis appraised?
TG13 diagnostic criteria for acute cholangitis is more accurate
and reliable diagnostic capacity than TG07 (recommendation
1, level B).
A multi-center analysis assessing TG13 found that the

sensitivity was 91.8 % and the specificity was 77.7 %.
TG13 showed similar specificity to TG07 but showed
markedly increased sensitivity and further improvement in
diagnostic ability (Table 2). The specificity of Charcots
triad was the highest. The presence of Charcots triad
strongly suggested the presence of acute vasculitis [8].
Systemic inflammation
Acute cholangitis is accompanied by the findings of systemic inflammation due to fever or an increased inflammatory response such as an increased white blood cell
count and high levels of C-reactive protein (CRP). While
an increase in the white blood cell count is observed in
82 %, a decrease may be observed in severe vasculitis [5].
Cholestasis
Many reports show that jaundice is observed in 6070 % of
cases of acute cholangitis (Table 2). A blood test shows an
increase in the levels of ALP, cGTP, LAP and transaminases (AST, ALT). The threshold in liver function tests is
particularly important in differentiating from acute cholecystitis when making a diagnosis of acute cholangitis
according to the present diagnostic criteria. The thresholds
of the tests needed to be established. However, the normal
range of liver function tests differs from facility to facility.
A fixed threshold is, therefore, not practical. From the
results of multi-center analysis, it is appropriate and practical that the threshold is set at 1.5 times the normal upper
limit for the liver function test [8].
TG13 diagnostic criteria for acute cholangitis

Imaging findings
The revised diagnostic criteria for acute cholangitis are
shown in Table 1. The morbidity of acute cholangitis is
associated with the occurrence of cholangiovenous and
cholangiolymphatic reflux along with elevated pressure in
the biliary ducts and bile infections due to bile duct
obstruction induced by stones and tumors. TG13 Diagnostic Criteria of Acute Cholangitis are criteria to establish
the diagnosis when cholestasis and inflammation based on
There were no direct imaging findings which showed evidence of bile infection. Recently, it has been reported that
acute cholangitis can directly be depicted by computed
tomography (CT) of the abdomen with contrast (Figs. 1, 2).
However, in clinical practice, imaging modalities usually support the diagnosis of acute cholangitis by showing
indirect findings, which are biliary dilatation or evidence of
123
28
Table 1 TG13 diagnostic criteria for acute cholangitis

A. Systemic inflammation
A-1. Fever and/or shaking chills
A-2. Laboratory data: evidence of inflammatory response
B. Cholestasis
B-1. Jaundice
B-2. Laboratory data: abnormal liver function tests
C. Imaging
C-1. Biliary dilatation
C-2. Evidence of the etiology on imaging (stricture, stone, stent etc.)
Suspected diagnosis: One item in A ? one item in either B or C
Definite diagnosis: One item in A, one item in B and one item in C
Note:
A-2: Abnormal white blood cell counts, increase of serum C-reactive protein levels, and other changes indicating inflammation
B-2: Increased serum ALP, cGTP (GGT), AST and ALT levels.
Other factors which are helpful in diagnosis of acute cholangitis include abdominal pain [right upper quadrant (RUQ) or upper abdominal] and
a history of biliary disease such as gallstones, previous biliary procedures, and placement of a biliary stent.
In acute hepatitis, marked systematic inflammatory response is observed infrequently. Virological and serological tests are required when
differential diagnosis is difficult.
Thresholds
BT [38 C
A-1
Fever
A-2
Evidence of inflammatory response
WBC (91000/lL)
CRP (mg/dl)
B-1
Jaundice
B-2
Abnormal liver function tests
\4, or [10
C1
T-Bil C2 (mg/dL)
ALP (IU)
cGTP (IU)
[1.5 9 STD
[1.5 9 STD
AST (IU)
[1.5 9 STD
ALT (IU)
[1.5 9 STD
Cited from the Ref. [8]

STD upper limit of normal value, ALP alkaline phosphatase, cGTP (GGT) c-glutamyltransferase, AST aspartate aminotransferase, ALT alanine
aminotransferase
Table 2 Retrospective comparison of various diagnostic criteria of

acute cholangitis in a multi-center study in Japan
Charcots
triad (%)
TG07
(%)
The first draft criteria

(with abdominal pain
and history of biliary
disease) (%)
TG13
(%)
Sensitivity
26.4
82.6
95.1
91.8
Specificity
95.9
79.8
66.3
77.7
11.9
15.5
38.8
5.9
[Positive rate]
Acute
cholecystitis
Cited from Ref. [8]
its etiology. A diagnosis of acute cholangitis requires that

the presence of stones, tumors or stents inducing bile duct
dilatation or cholangitis is confirmed with ultrasonography
(US) of the abdomen (Supplementary Figures 1, 2, Supplementary Movie), CT of the abdomen with contrast
123
(Figs. 1, 2; Supplementary Figure 3) and magnetic resonance cholangiopancreatography (MRCP) (Supplementary

Figure 6).
Q4. Is it possible to diagnose acute cholangitis by
computed tomography (CT) of the abdomen?
We suggested that dynamic CT of the abdomen with
contrast enables making the diagnosis of acute cholangitis
(recommendation 2, level D).
Radiological examinations such as ultrasonography, CT

and magnetic resonance imaging (MRI) are carried out for
evaluation of the site and cause of biliary obstruction and
degree of biliary dilatation. However, CT of the abdomen
with contrast has limitations in the diagnosis and evaluation of acute cholangitis [16]. Because helical CT is clinically available, the whole of the upper abdominal organs
29
Fig. 1 CT demonstrating acute cholangitis with gallstone and

common bile duct stone (74-year-old female). Precontrast CT
(a) shows gallstone (arrow) and common bile duct stone (arrowhead).
The arterial phase of contrast-enhanced dynamic CT (b) shows
diffuse inhomogeneous enhancement of the liver. In the equilibrium

phase of dynamic CT (c), the inhomogeneous enhancement
disappears
Fig. 2 CT demonstrating acute cholangitis with gallstone and

papillary tumor of the duodenum (77-year-old female). a, b Precontrast CT, c, d arterial phase of dynamic CT, e, f equilibrium phase.
Precontrast CT shows gallstones (b arrow). Arterial phase of dynamic
CT shows enhanced papillary tumor of the duodenum (d arrowhead).

The liver parenchyma shows inhomogeneous enhancement surrounding the bile ducts, indicating acute cholangitis. In the equilibrium
phase, inhomogeneous enhancement disappears
123
30
can be assessed by contrast-enhanced dynamic CT. Preand postcontrast CT can depict biliary stones, pneumobilia, bile duct dilatation, bile duct wall thickening, and
bile duct stenosis or occlusion. However, such CT findings do not necessarily suggest the presence of acute
cholangitis.
Hepatic parenchymal changes seen at imaging in acute
cholangitis are likely to be related to the extension of the
inflammatory process into the periportal tissues [1720]. In
acute cholangitis, the inflammatory process of the peripheral bile duct spreading as far as the periportal areas
(Glissons sheath) causes a decreased portal blood flow and
an increased arterial blood flow. On the arterial phase of
dynamic CT, inhomogeneous hepatic parenchymal
enhancement (nodular, patchy, wedge-shaped or geographic) is frequently seen in patients with acute cholangitis [16, 17] (Figs. 1, 2). This inhomogeneous hepatic
enhancement of contrast-enhanced dynamic CT appears in
the arterial phase only, and disappears in the portal and
equilibrium phases. Follow-up dynamic CT performed
after treatment for acute cholangitis showed decreased or
no inhomogeneous enhancement, according to the
improvement of biliary inflammation (Supplementary
Figure 4).
In conclusion, contrast-enhanced dynamic CT is recommended for making a prompt diagnosis of clinically
suspected acute cholangitis.
Q5. Can CT make a diagnosis of the etiology and
complications of acute cholangitis?
CT is suggested as the most effective imaging method for the
diagnosis of etiology and complication of acute cholangitis
CT scan is a useful imaging modality for exploring the

etiology of acute cholangitis such as biliary stones (cholelithiasis, choledocholithiasis, hepatolithiasis) and pancreaticobiliary malignancies (extrahepatic bile duct
carcinoma, gallbladder carcinoma, pancreatic head carcinoma). Because non-calcified biliary stones cannot be
detected by CT, ultrasonography and/or MRI (MRCP) is
also recommended (Supplementary Figure 5).
Hepatic abscesses sometimes occur in patients with
acute cholangitis. It is important to differentiate abscesses
from malignant hepatic tumors such as liver metastasis or
intrahepatic cholangiocarcinoma. Characteristic imaging
findings of hepatic abscesses have also been reported in
dynamic CT as well as acute cholangitis [2124] (Supplementary Figure 6). Hepatic abscess shows a double
target sign with a transient segmental enhancement in the
arterial phase of dynamic CT. The segmental enhancement
123
disappears in the equilibrium phase. This transient segmental enhancement in dynamic CT reflects a decrease in
segmental portal blood flow and an increase in compensatory hepatic arterial blood flow due to periportal
inflammation within the Glisons sheath adjacent to the
hepatic abscess [24, 25].
Q6. What are the indication and significance of MRI
(MRCP) for acute cholangitis?
MRI (MRCP) is suggested for the etiologic diagnosis of acute

cholangitis (recommendation 2, level D).
Magnetic resonance cholangiopancreatography (MRCP)

has a high sensitivity for detecting biliary calculi and
malignant biliary obstruction [2527] (Supplementary
Figure 7). Inhomogeneous enhancement in dynamic MRI
as well as dynamic CT is also able to depict acute cholangitis [28].
Other factors which are helpful in diagnosis of acute
cholangitis
A past history of gallbladder diseases is found in many
reports of acute cholangitis [2, 3, 1014], and it is referred
to as the past history of surgery for the diseases of
the biliary system, supposedly cholecystectomy for
gallbladder stones in particular [3, 1013].
The importance of the past history of biliary diseases
in a diagnosis of acute cholangitis was recognized at the
International Consensus Meeting in 2006. The presence of
bile stones and the placement of stents in the biliary tract
were also considered to be contributing factors in making a
diagnosis of acute cholangitis.
Abdominal pain is reported to be observed in 80 % or
more cases (Table 3). However, it is not a symptom specific to cholangitis. It was excluded from the diagnostic
criteria for acute cholangitis for the reason that its presence
reduced the specificity and complicated the differentiation
from acute cholecystitis [8].
Severity assessment criteria for acute cholangitis

Background
Patients with acute cholangitis may present with any
severity ranging from self-limiting to severe and/or
potentially life-threatening diseases. Most cases respond to
initial medical treatment consisting of general supportive
therapy and intravenous antimicrobial therapy.
31
Table 3 Incidence of clinical manifestations of acute cholangitis

Disease
Welch [2]
Boey [3]
ASC
Charcots
triad (%)
Fever
(%)
Jaundice
(%)
Abdominal
pain (%)
Reynolds
pentad (%)
Shock
(%)
Disturbed
consciousness
(%)
History of
biliary diseases
50
80
60
20
100
AOSC
15
50
88
67
33
27
46.7
AC
SC
99
14
69.7
93.9
78.8
87.9
16.2
57
16.2
28
75
12
22
38.7
65.4
92.2
7.2
About 60
100
66
59
NonSC
72
5.1
7
4
Csendes
[9]
ASC
512
Thompson
[10]
AC
66
Gigot [11]
AC
412
72
3.5
7.8
61
OConnor
[12]
AC
65
60
7.7
32
14
21.5
SC
NonSC
19
46
53
63
5
9
47
26
11
15
Lai [13]
Severe
AC
86
56
66
93
90
Haupert
[14]
ASC
13
15.4
100
61.5
100
64
7.7
23.1
66
27.9
7.7
53.8
AC acute cholangitis, SC suppurative cholangitis, AOSC acute obstructive suppurative cholangitis
It has been reported in the United States that approximately 70 % of patients with acute cholangitis are able to
achieve improvement with medical therapy alone [29].
Some cases do not respond to medical treatment and the
clinical manifestations and laboratory data do not improve.
Such cases may progress to sepsis with or without organ
dysfunction and require appropriate management that
includes intensive care, organ-supportive care, and urgent
biliary drainage, in addition to medical treatment. There is
also a report showing approximately a 10 % mortality rate
due to acute cholangitis despite the occurrence of responses
to antimicrobial therapy and biliary drainage [30, 31].
TG07 severity assessment criteria for acute cholangitis
TG07 established the worlds first severity assessment
criteria for acute cholangitis at the International Consensus
Meeting in Tokyo in 2006 [6] and classified those conditions with organ dysfunction as severe (Grade III), those
showing no responses to the initial treatment as moderate
(Grade II), and those responding to the initial treatment as
mild (Grade I).
However, the use of TG07 severity assessment criteria in
actual situations has shown that it is impossible to distinguish moderate cases (Grade II) and mild cases (Grade I) as
soon as the initial diagnosis has been made. In TG07,
Grades II and I were only assessed after observation of the
treatment courses. In this treatment strategy, urgent biliary
drainage can be indicated for cases assessed as severe, but
provision of early biliary drainage is impossible. Acute

cholangitis can progress rapidly to sepsis and disseminated
intravascular coagulation (DIC) and the observation
strategy in TG07 may induce increased severity during the
initial treatment. In Japan, many cases (46.8 %, 258 of 551
cases) of Grades II or I underwent urgent biliary drainage in
the same manner as Grade III. In these cases, differentiation
between Grade II and Grade I was impossible, because the
definition of Grade II in TG07 was ambiguous [8].
Revision of TG07 severity assessment criteria for acute
cholangitis
Given these inconveniences of TG07 in clinical practice,
revision was made to improve severity assessment strategies upon diagnosis to allow provision of immediate source
control of infection among patients with acute cholangitis.
To begin with, we examined the items reported as predictive factors of poor prognosis among patients with acute
cholangitis and those who required urgent biliary drainage.
Furthermore, factors endoscopic gastroenterologists value
in determining the timing of biliary drainage were integrated, except for the factors that define Grade III cases
(severe cases). Factors which were inappropriate for use as
items of severity assessment were excluded. Consequently,
five
factorshypoalbuminemia,
elderly
patients,
high fever, leukocytosis and hyperbilirubinemiawere
extracted [8, 32]. Cases with two of these five factors
present were classified as Grade II (moderate) [8].
123
32
Table 4 TG13 severity assessment criteria for acute cholangitis

Grade III (Severe) acute cholangitis
Grade III acute cholangitis is defined as acute cholangitis that is associated with the onset of dysfunction in at least one of any of the
following organs/systems:
1. Cardiovascular dysfunction
Hypotension requiring dopamine C5 lg/kg per min, or any dose of norepinephrine
2. Neurological dysfunction
Disturbance of consciousness
3. Respiratory dysfunction
PaO2/FiO2 ratio \300
4. Renal dysfunction
Oliguria, serum creatinine [2.0 mg/dl
5. Hepatic dysfunction
PT-INR [1.5
6. Hematological dysfunction
Platelet count \100,000/mm3
Grade II (moderate) acute cholangitis

Grade II acute cholangitis is associated with any two of the following conditions:
1. Abnormal WBC count ([12,000/mm3, \4,000/mm3)
2. High fever (C39 C)
3. Age (C75 years old)
4. Hyperbilirubinemia (total bilirubin C5 mg/dL)
5. Hypoalbuminemia (\STD 9 0.7)
Grade I (mild) acute cholangitis
Grade I acute cholangitis does not meet the criteria of Grade III (severe) or Grade II (moderate) acute cholangitis at initial diagnosis.
Notes
Early diagnosis, early biliary drainage and/or treatment for etiology, and antimicrobial administration are fundamental treatments for acute
cholangitis classified not only as Grade III (severe) and Grade II (moderate) but also Grade I (mild).
Therefore, it is recommended that patients with acute cholangitis who do not respond to the initial medical treatment (general supportive care
and antimicrobial therapy) undergo early biliary drainage or treatment for etiology (see flowchart).
Cited from Ref. [8]
STD lower limit of normal value
TG13 severity assessment criteria for acute cholangitis

The revised assessment criteria for acute cholangitis are
shown in Table 4.
The severity of acute cholangitis is classified as follows;
Grade III (severe): presence of organ dysfunction.
Grade II (moderate): risk of increased severity without
early biliary drainage.
Grade I (mild).
The severity assessment criteria are very important for
determining the treatment strategy for acute cholangitis,
especially for Grade II cases which may progress to Grade
III without immediate intervention. Treatment of acute
cholangitis requires treatment for causes for cases with
any severity, along with the administration of antimicrobial
agents and biliary drainage.
Q7. What morbid conditions are referred to as Grade
III (severe) in assessing severity for acute cholangitis?
Organ dysfunction is the most common predictor of poor

outcome. On the other hand, based on the pathophysiology,
severe acute cholangitis can also be defined as that which
accompanies organ dysfunction caused by sepsis. Thus, the
presence of organ dysfunction is an important factor in the
definition of Grade III (severe) acute cholangitis [6].
Q8. What morbid conditions are referred to as moderate in assessing severity for acute cholangitis?
Grade II (moderate) is referred to as a condition suggesting
cholangitis requiring emergent or early biliary drainage without
presence of organ dysfunction, but with risks of progression to
Grade III.
Q9. How are TG13 Severity Assessment Criteria for

acute cholangitis appraised?
TG13 Severity Assessment Criteria for Acute Cholangitis
Severe is referred to as a condition that gives rise to organ

dysfunction due to acute cholangitis requiring intensive care
such as respiratory and circulatory support.
123
is more suitable and practical for clinical use than TG07,

because of enabling us to identify Grade II which requires
early biliary drainage at the time of initial diagnosis
(recommendation 1, level B).
According to TG13 severity assessment criteria, the

number of cases for which biliary drainage was carried out
within 48 h included 50 Grade III cases (69.4 %), 129
Grade II cases(59.7 %), and 181 Grade I cases (54.0 %).
However, many of the Grade I cases that had undergone
biliary drainage within 48 h were accounted for as the
treatment of etiology such as bile stones. Grade I cases that
had undergone biliary drainage as an urgent treatment were
very few in number [8].
Q10. Are the acute cholangitis cases that meet Charcots triad considered as severe cases?
The presence or absence of Charcots triad does not reflect
severity. So, cases that meet Charcots triad are not necessarily
assessed as severe (level B).
In the multi-center analysis, of the 110 cases of acute

cholangitis that showed Charcots triad, only 13 cases
(11.8 %) were classified as Grade III. Compared with the
cases that did not show Charcots triad, there were no
differences in terms of severity. Furthermore, many
(approximately 80 %) of the Grade III cases in TG13 failed
to satisfy Charcots triad [8]. The presence or absence of
conformity with Charcots triad was not associated with
severity. Cases that meet Charcots criteria are not necessarily classified as severe cases.
None.
References
1. Dow RW, Lindenauer SM. Acute obstructive suppurative cholangitis. Ann Surg. 1969;169:2726.
2. Welch JP, Donaldson GA. The urgency of diagnosis and surgical
treatment of acute suppurative cholangitis. Am J Surg. 1976;131:
52732.
3. Boey JH, Way LW. Acute cholangitis. Ann Surg. 1980;191:
26470.
4. Saharia PC, Cameron JL. Clinical management of acute cholangitis. Surg Gynecol Obstet. 1976;142:36972.
5. Ostemiller W Jr, Thompson RJ Jr, Carter R, Hinshaw DB. Acute
cholangitis. World J Surg. 1984;8:9639.
2007;14(1):528 (Clinical practical guidelines: CPGs).
Norimizu S, et al. Accuracy of the Tokyo Guidelines for the
diagnosis of acute cholangitis and cholecystitis taking into consideration the clinical practice pattern in Japan. J Hepatobiliary
Pancreat Sci. 2011;18:2507.
acute cholangitis in revised Tokyo Guidelines. J Hepatobiliary
Pancreat Sci. 2012;19:54856.
33
Surg. 1992;79:6558.
10. Thompson J, Bennion RS, Pitt HA. An analysis of infectious
failures in acute cholangitis. HPB Surg. 1994;8:13944.
11. Gigot JF, Leese T, Dereme T, Coutinho J, Castaing D, Bismuth
H. Acute cholangitis. Multivariate analysis of risk factors. Ann
Surg. 1989;209(4):4358.
12. OConnor MJ, Schwartz ML, McQuarrie DG, Sumer HW. Acute
bacterial cholangitis: an analysis of clinical manifestation. Arch
Surg. 1982;117:43741.
13. Lai EC, Tam PC, Paterson IA, Ng MM, Fan ST, Choi TK, et al.
Emergency surgery for severe acute cholangitis. The high-risk
patients. Ann Surg. 1990;211:559.
14. Haupert AP, Carey LC, Evans WE, Ellison EH. Acute suppurative cholangitis. Experience with 15 consecutive cases. Arch
Surg. 1967;94:46068.
15. Takada T, Kawarada Y, Nimura Y, Yoshida M, Mayumi T, Sekimoto M, et al. Background: Tokyo Guidelines for the management of acute cholangitis and cholecystitis. J Hepatobiliary
Pancreat Surg. 2007;14:110 (CPGs).
16. Arai K, Kawai K, Kohda W, Tatsu H, Matsui O, Nakahama T.
Dynamic CT of acute cholangitis. AJR. 2003;181:1158.
17. Pradella S, Centi N, La Villa G, Mazza E, Colagrande S. Transient hepatic attenuation difference (THAD) in biliary duct disease. Abdom Imaging. 2009;34:62633.
18. Lee NK, Kim S, Lee JW, Kim CW, Kim GH, Kang DH, et al.
Discrimination of suppurative cholangitis from nonsuppurative
cholangitis with computed tomography (CT). Eur J Radiol.
2009;69:52835.
19. Bader TR, Braga L, Beavers KL, Semelka RC. MR imaging
findings of infectious cholangitis. Magn Reson Imaging. 2001;19:
7818.
20. Catalano OA, Sahani DV, Forcione DG, Czermak B, Liu CH,
Soricelli A, et al. Biliary infections: spectrum of imaging findings
and management. Radiographics. 2009;29:205980.
21. Rubinson HA, Isikoff MB, Hill MC. Morphologic aspects of
hepatic abscesses: a retrospective analysis. AJR. 1980;135:
73540.
22. Halvorsen RA, Korobkin M, Foster WL, Silverman PM,
Thompson WM. The variable CT appearance of hepatic abscesses. AJR. 1984;141:9416.
23. Mathieu D, Vasile N, Fagniez PL, Segui S, Grably D, Larde D.
Dynamic CT features of hepatic abscesses. Radiology.
1985;154:74952.
24. Gabata T, Kadoya M, Matsui O, Kobayashi T, Kawamori Y,
Sanada J, et al. Dynamic CT of hepatic abscesses: significance of
transient segmental enhancement. AJR. 2001;176:6759.
25. Laokpessi A, Bouillet P, Sautereau D, Cessot F, Desport JC, Le
Sidaner A, et al. Value of magnetic resonance cholangiography in
the preoperative diagnosis of common bile duct stones. Am J
26. Lomanto D, Pavone P, Laghi A, Panebianco V, Mazzocchi P,
Fiocca F, et al. Magnetic resonance cholangiopancreatography in
the diagnosis of biliopancreatic diseases. Am J Surg.
1997;174:338.
27. Fulcher AS, Turner MA, Capps GW, Zfass AM, Baker KM. HalfFourier RARE MR cholangiopancreatography: experience in 300
subjects. Radiology. 1998;207:2132.
28. Balci NC, Semelka RC, Noone TC, Siegelman ES, de Beeck BO,
Brown JJ, et al. Pyogenic hepatic abscesses: MRI findings on T1and T2-weighted and serial gadolinium-enhanced gradient-echo
images. J Magn Reson Imaging. 1999;9:28590.
29. Attasaranya S, Fogel EL, Lehman GA. Choledocholithiasis,
ascending cholangitis, and gallstone pancreatitis. Med Clin North
Am. 2008;92(4):92560.
123
34
30. Lai EC, Mok FP, Tan ES, Lo CM, Fan ST, You KT, et al.
Endoscopic biliary drainage for severe acute cholangitis. N Engl J
Med. 1992;326(24):15826.
31. Leung JW, Chung SC, Sung JJ, Banez VP, Li AK. Urgent
endoscopic drainage for acute suppurative cholangitis. Lancet.
1989;1(8650):13079.
123

32. Tsuyuguchi T, Sugiyama H, Sakai Y, Nishikawa T, Yokosuka O,
Mayumi T, et al. Prognostic factors of acute cholangitis in cases
managed using the Tokyo Guidelines. J Hepatobiliary Pancreat
Sci. 2012;19:55765.

DOI 10.1007/s00534-012-0568-9
GUIDELINE

TG13 diagnostic criteria and severity grading of acute

cholecystitis (with videos)
Masamichi Yokoe Tadahiro Takada Steven M. Strasberg Joseph S. Solomkin Toshihiko Mayumi
Harumi Gomi Henry A. Pitt O. James Garden Seiki Kiriyama Jiro Hata Toshifumi Gabata
Masahiro Yoshida Fumihiko Miura Kohji Okamoto Toshio Tsuyuguchi Takao Itoi Yuichi Yamashita
Christos Dervenis Angus C. W. Chan Wan-Yee Lau Avinash N. Supe Giulio Belli Serafin C. Hilvano
Kui-Hin Liau Myung-Hwan Kim Sun-Whe Kim Chen-Guo Ker

Abstract Since its publication in 2007, the Tokyo

Guidelines for the management of acute cholangitis and
cholecystitis (TG07) have been widely adopted. The validation of TG07 conducted in terms of clinical practice has
shown that the diagnostic criteria for acute cholecystitis are
highly reliable but that the definition of definite diagnosis is
ambiguous. Discussion by the Tokyo Guidelines Revision
Committee concluded that acute cholecystitis should be
suspected when Murphys sign, local inflammatory findings in the gallbladder such as right upper quadrant

M. Yokoe (&)
2-9 Myoken-cho, Showa-ku, Nagoya, Aichi 466-8650, Japan
e-mail: yokoe@nagoya2.jrc.or.jp
T. Takada F. Miura
Tokyo, Japan
S. M. Strasberg
J. S. Solomkin
Department of Surgery, University of Cincinnati College
of Medicine, Cincinnati, OH, USA
T. Mayumi
abdominal pain and tenderness, and fever and systemic

inflammatory reaction findings detected by blood tests are
present but that definite diagnosis of acute cholecystitis can
be made only on the basis of the imaging of ultrasonography, computed tomography or scintigraphy (HIDA scan).
These proposed diagnostic criteria provided better specificity and accuracy rates than the TG07 diagnostic criteria.
As for the severity assessment criteria in TG07, there is
evidence that TG07 resulted in clarification of the concept
of severe acute cholecystitis. Furthermore, there is evidence that severity assessment in TG07 has led to a
reduction in the mean duration of hospital stay. As for the
factors used to establish a moderate grade of acute cholecystitis, such as leukocytosis, ALP, old age, diabetes, being
H. A. Pitt
O. J. Garden
S. Kiriyama
Ogaki, Japan
J. Hata
T. Gabata
M. Yoshida
H. Gomi
Tochigi, Japan
123
36
male, and delay in admission, no new strong evidence has

been detected indicating that a change in the criteria used
in TG07 is needed. Therefore, it was judged that the
severity assessment criteria of TG07 could be applied in
the updated Tokyo Guidelines (TG13) with minor changes.
TG13 presents new standards for the diagnosis, severity
grading and management of acute cholecystitis.
Keywords Acute cholecystitis Diagnostic criteria
Severity grading Diagnostic imaging Guidelines
Introduction
Acute cholecystitis is a disease frequently encountered in
daily practice presenting with right hypochondrial pain as
the main symptom [14]. However, there were no diagnostic criteria and severity assessment criteria for this
commonplace disease before the publication in 2007 of the
and cholecystitis (TG07) in the Journal of Hepato-BiliaryPancreatic Surgery (vol. 14.1:1121, 2007). There is a
treatise in TG07 released with the expectation that it will
present international guidelines for improvement in the
diagnosis and treatment of acute cholecystitis [5].
The diagnostic criteria in TG07 were set at high sensitivity to provide medical care suitable for a larger number
of cases and the sensitivity has been reported as 84.9 % on
K. Okamoto
Kitakyushu, Japan
T. Tsuyuguchi
T. Itoi
Y. Yamashita
C. Dervenis
Greece
A. C. W. Chan
Department of Surgery, Surgery Centre, Hong Kong Sanatorium
W.-Y. Lau
Hong Kong, Hong Kong
123
the basis of the test results for TG07 diagnostic criteria [6].
TG07 guidelines have already been recognized as the
diagnostic criteria to be recommended in todays medical
care for acute cholecystitis [1]; however, guidelines should
achieve further evolution. In view of the current situation
where diagnostic imaging such as ultrasonography (US),
CT and scintigraphy (HIDA scan) are frequently used for
the definite diagnosis of acute cholecystitis, integration of
such diagnostic modalities in guidelines is the main theme
in the present revision.
Acute cholecystitis sometimes requires emergency
treatment for morbidities such as gangrenous cholecystitis,
emphysematous cholecystitis and gallbladder torsion. An
indication that it may require high-level skills is given by
its other name, difficult gallbladder [7, 8]. In making a
diagnosis of acalculous cholecystitis, challenges may be
encountered. There may be cases with a poor prognosis
[9, 10]. The severity assessment criteria in TG07 defined
severe acute cholecystitis as acute cholecystitis accompanying organ dysfunction directly related to vital prognosis.
Actually, the overall mortality rate of acute cholecystitis is
approximately 0.6 % [11, 12], and that of severe cases was
reported in TG07 as 6.0 % [13]. Acute cholecystitis is
essentially not a disease with a high mortality rate. However, it was thought that guidelines should make it clear
that appropriate management with appropriate use of
severity assessment criteria does lead to improved vital
prognosis.
A. N. Supe
G. Belli
S. C. Hilvano
K.-H. Liau
M.-H. Kim
S.-W. Kim
Department of Surgery, Seoul National University College of
Medicine, Seoul, Korea
C.-G. Ker
Yuans General Hospital, Kaohsiung, Taiwan
Six years have passed since the publication of TG07 and

the Tokyo Guidelines Revision Committee has been
charged with examining the results of the validation that has
been conducted so far, involving problems such as inconvenience of their use in actual clinical settings [6, 1315].
Considering the progress of diagnostic technology and
detection of new evidence, diagnostic criteria and severity
grading revised as the updated Tokyo Guidelines (TG13) are
presented in accordance with actual clinical settings [16].
Diagnostic criteria for acute cholecystitis; TG13
Background
37
At an international consensus meeting held in Tokyo in

2007, the worlds first diagnostic criteria were presented in
the Tokyo Guidelines for the management of acute cholangitis and cholecystitis; these are international clinical
practice guidelines. According to a review referring to
these diagnostic criteria, a definite diagnosis of acute
cholecystitis can be made when a local sign or symptom
and a systemic sign are present, and test imaging provides
confirmation [1]. There is a report of cases for which
favorable sensitivity (84.9 %) and specificity (50.0 %)
have been achieved when using TG07 diagnostic criteria in
clinical practice [6]. Multicenter analysis by the Tokyo
Guidelines Revision Committee showed that the sensitivity
was 92.1 % and the specificity was 93.3 % in TG07 [16].
Murphys sign
Revision of TG07 diagnostic criteria for acute cholecystitis
Q1. How large is the diagnostic capacity of Murphys
sign for acute cholecystitis?
Murphys sign shows high specificity, however the sensitivity
has been reported low. It is not applicable in making a
diagnosis of acute cholecystitis due to the low sensitivity
(level D).
Murphys sign refers to where the patient stops breathing

due to pain when an examiner touches the inflammatory
gallbladder of the patient. In 1903, Murphy [17] described
the condition as a sign of cholelithiasis. Murphys sign has
also been widely known as a diagnostic factor of acute
cholecystitis. Substantial numbers of clinicians throughout
the world providing treatment for acute cholecystitis refer to
Murphys sign. It has been reported in previous studies to
have a sensitivity of 5065 % and a high specificity of 79 %
[18] or 96 % [2] for the diagnosis of acute cholecystitis
although the sensitivity was once reported to be as low as
20.5 %, while the specificity was 87.5 % [6]. It has a weak
point in that an accurate diagnosis of cholecystitis can be
made when Murphys sign is present, while its absence does
not necessarily mean the absence of cholecystitis.
TG07 diagnostic criteria for acute cholecystitis
Q2. How are the diagnostic criteria for acute cholecystitis in TG07 appraised?
Although the sensitivity had been improved compared with
Murphy s sign, TG07 diagnostic criteria have limitations
and their validity is insufficient for using them to make
a definite diagnosis (level D).
The most important problem in TG07 was that the criteria

for definite diagnosis were ambiguous and difficult to use.
In TG07, there were two categories determining the definite diagnosis of acute cholecystitis. Definite diagnosis
1: To obtain a definite diagnosis one item in A and one
item in B had to be positive. Definite diagnosis 2:
Imaging findings (criterion C) confirmed the diagnosis
when acute cholecystitis was suspected clinically.
The Tokyo Guidelines Revision Committee concluded
that the term definite diagnosis could not be supported in
current practice without positive diagnostic imaging studies. We have now changed the expressions: suspected
diagnosis is achieved when one item from section A and
one item from section B are present. Definite diagnosis
is achieved when imaging findings characteristic of acute
cholecystitis (item C) are also present (one item in
A ? one item in B ? C) [16].
TG13 diagnostic criteria for acute cholecystitis
The revised diagnostic criteria for acute cholecystitis are
shown in Table 1.
A diagnosis of acute cholecystitis is made as follows
according to diagnostic criteria. When acute cholecystitis is
suspected from clinical signs and results of blood tests, a
definite diagnosis is made after it has been confirmed by
diagnostic imaging.
Q3. How are the diagnostic criteria for acute cholecystitis in TG13 appraised?
TG13 diagnostic criteria of acute cholecystitis have a high
sensitivity and a high specificity (recommendation 1, level B).
123
38
The main symptom of uncomplicated cholelithiasis

is biliary colic caused by the obstruction of the gallbladder neck by stones [1]. The proportion of patients
with right hypochondrial pain and epigastric pain
combined is 7293 %. This is followed in frequency
by nausea and vomiting. Note that the proportion of
patients with fever is not high; that of fever exceeding
38 (C) is low (about 30 %). Muscular defense is
observed in about half of cases; palpable tumors are
rare in the right hypochondrial region. Rebound tenderness and stiffness are also rare (Tables 2, 3) [24,
1923].
Table 1 TG13 diagnostic criteria for acute cholecystitis

A. Local signs of inflammation etc.
(1) Murphys sign, (2) RUQ mass/pain/tenderness
B. Systemic signs of inflammation etc.
(1) Fever, (2) elevated CRP, (3) elevated WBC count
C. Imaging findings
Imaging findings characteristic of acute cholecystitis
Suspected diagnosis: One item in A ? one item in B
Definite diagnosis: One item in A ? one item in B ? C
Acute hepatitis, other acute abdominal diseases, and chronic cholecystitis should be excluded
RUQ right upper abdominal quadrant, CRP C-reactive protein, WBC
white blood cell
An assessment by multicenter analysis of TG13 diagnostic criteria shows that sensitivity (91.2 %) and specificity (96.9 %) are favorable and that diagnostic capacity is
almost the same as that in TG07 [16]. It is pointed out that
the diagnostic criteria for acute cholecystitis in TG07 have
limitations in that patients with few systemic symptoms
tends to be underdiagnosed [1]. There is also a report
showing that neither fever nor an elevated white cell count
were observed in 16 % of cases with gangrenous cholecystitis or in 28 % of cases with non-gangrenous cholecystitis [8]. It is important that the diagnosis is confirmed
repeatedly for cases with suspected cholecystitis.
Laboratory data
What is the most important blood test for making
a diagnosis of acute cholecystitis?
There are no specific blood tests for making a diagnosis of acute cholecystitis. So, the diagnosis can be
made if the following findings are present: general
inflammatory findings (abnormal white blood cell
count, elevated CRP level), an increase in blood cell
count of more than 10000 mm3/dl, an increase in CRP
level of more than 3 mg/dl, and a mild increase of
serum enzymes in the hepato-biliary-pancreatic system
and bilirubin.
The bilirubin level may rise to 4 mg/dl (68 lmol/dl) in
the absence of complications [1]. When ultrasonography
shows findings that suggest acute cholecystitis and a CRP
level exceeding 3 mg/dl, a diagnosis of acute cholecystitis
can be made with 97 % sensitivity, 76 % specificity, and
95 % positive predictive value [24].
Clinical context and manifestations

Q4. What is the most important physical manifestation
for making a diagnosis of acute cholecystitis?
The most typical clinical sign of acute cholecystitis is abdominal
pain.
Table 2 Incidence of clinical symptoms of acute cholecystitis

n
Eskelinen [2]
124
Brewer [19]
26
RUQ
pain
(%)
Epigastralgia
(%)
Nausea
(%)
Emesis
(%)
Fever
(%)
Rebound
(%)
Guarding
(%)
Rigidity
(%)
Mass
(%)
Murphys
sign (%)
56
25
31
60
62 (C37.1 C)
48
30
66
16
62
77
30 (C38 C)
35
58
3.9
About 30
About 45
About 10
Schofield [20]
Staniland [21]
64
100
Halasz [3]
191
93
Johnson [4]
37
70
Singer [22]
40
Adedeji [23]
62
38
About 80
83
About 70
31 ([37.5 C)
34
11
73
62
24
62
10 ([38.0 C)
65
23
RUQ right upper abdominal quadrant
123
14
About 25
48
39
Imaging findings
Ultrasonography (US)
Q5. Which type of diagnostic imaging method should be
used, first of all, for making a diagnosis of acute
cholecystitis?
Ultrasonography should be performed at the initial consultation
for all cases for which acute cholecystitis is suspected
(recommendation 1, level A).
Ultrasonography is the test that should be performed

first of all for every case of suspected acute cholecystitis.
Even emergency physicians who are not specialists in
ultrasonography are able to make a satisfactory diagnosis
[25, 26].
In view of its convenience and lack of invasiveness,
ultrasonography should be considered the first option
among morphological tests for this morbidity.
Q6. How large is the diagnostic capacity of ultrasonography for acute cholecystitis?
Ultrasonography shows 50~88 % sensitivity and 80~88 %
specificity.
A report by Chatziioannou et al. [27] discussing 107 cases

of acute cholecystitis in terms of the diagnostic capacity of
ultrasonography has found that sensitivity is 50 %, specificity 88 %, PPV 64 %, NPV 80 %, and accuracy 77 %.
On the basis of a meta-analysis of five treatises

involving a total of 532 cases, Shea et al. show that the
diagnostic capability of ultrasonography for acute cholecystitisis: sensitivity 88 % (95 % CI 0.741.00) and specificity 80 % (95 % CI 0.620.98) [28]. The diagnostic
capacity of ultrasonography for acute cholecystitis is generally thought to be good.
Q7. What are the ultrasonographic imaging findings
characteristic of acute cholecystitis?
They are mainly enlarged gallbladder, thickening of the
gallbladder wall, gallbladder stones, and debris echo.
A diagnosis of acute calculous cholecystitis can be made

radiologically when the following findings are present at
the same time: thickening of the gallbladder wall (5 mm or
greater), pericholecystic fluid, or direct tenderness when
the probe is pushed against the gallbladder (ultrasonographic Murphys sign) [1]. Other ultrasonographic findings may include gallbladder enlargement, gallbladder
stones, debris echo and gas imaging (Fig. 1).
However, due to differences among reports in the frequency of the occurrence of individual findings, sensitivity,
and specificity, diagnosis should be made after a comprehensive judgment has been made of individual findings
[29, 30] (Supplement Table 1).
There are many diagnostic modalities enabling depiction
of stones. However, there is a report showing that bile
stones could be depicted by ultrasonography in only 13 %
of cases (1 of 7 cases). Therefore, the use of other
Table 3 Diagnostic capability of clinical symptoms for acute cholecystitis

No. of studies
No. of patients
Summary LR (95 % CI)

Positive
Negative
Sensitivity (95 % CI)
Specificity (95 % CI)
Anorexia
1135
1.11.7
0.50.9
0.65 (0.570.73)
0.50 (0.490.51)
Emesis
1338
1.5 (1.12.1)
0.6 (0.30.9)
0.71 (0.650.76)
0.53 (0.520.55)
Fever
Guarding
8
2
1292
1170
1.5 (1.02.3)
1.12.8
0.9 (0.81.0)
0.51.0
0.35 (0.310.38)
0.45 (0.370.54)
0.80 (0.780.82)
0.70 (0.690.71)
Murphys sign
565
2.8 (0.88.6)
0.5 (0.21.0)
0.65 (0.580.71)
0.87 (0.850.89)
Nausea
669
1.01.2
0.61.0
0.77 (0.690.83)
0.36 (0.340.38)
Rebound
1381
1.0 (0.61.7)
1.0 (0.81.4)
0.30 (0.230.37)
0.68 (0.670.69)
Rectal tenderness
1170
0.30.7
1.01.3
0.08 (0.040.14)
0.82 (0.810.83)
Rigidity
1140
0.502.32
1.01.2
0.11 (0.060.18)
0.87 (0.860.87)
RUQ mass
408
0.8 (0.51.2)
1.0 (0.91.1)
0.21 (0.180.23)
0.80 (0.750.85)
RUQ pain
949
1.5 (0.92.5)
0.7 (0.31.6)
0.81 (0.780.85)
0.67 (0.650.69)
RUQ tenderness
1001
1.6 (1.02.5)
0.4 (0.21.1)
0.77 (0.730.81)
0.54 (0.520.56)
Cited from Ref. [18]

RUQ right upper abdominal quadrant, LR likelihood ratio, CI confidence interval
123
40
techniques, such as MR cholangiography (MRCP), should

be considered depending on conditions [31].
According to a report by Cohan et al. [32] who examined 51 cases that had developed thickening of the gallbladder wall, including 13 cases of acute cholecystitis, a
so-called sonolucent layer (hypoechoic layer), referred to
as a low-echo zone, within the gallbladder wall showed
8 % sensitivity (95 % CI 022.1) and 71.0 % specificity
(95 % CI 56.685.5). Therefore, it cannot be considered a
good diagnostic measure for acute cholecystitis. The

presence of a low-echoic area with an irregular multiple
structure showing 62 % sensitivity (95 % CI 35.188.0)
and 100 % specificity (95 % CI 100100) has a higher
diagnostic value [32] (Supplement Fig. 1; Supplement
Movie 1).
Q8. What findings are to be noted when ultrasonography is conducted for cases for which acute cholecystitis
is suspected?
Ultrasonographic Murphys sign shows high specificity and it
hypoechoic layer
Wall thickening
liver
debris
Stone impaction
Fig. 1 US images of acute cholecystitis. Gallbladder swelling, wall

thickening with hypoechoic layer, massive debris, and stone impaction are demonstrated
Fig. 2 US images of perforated
duodenal ulcer case with
positive Murphys sign (nonultrasonographic), increased
white blood cell count and
elevated C-reactive protein.
Wall thickening of the anterior
wall of the duodenal bulb as
well as a large wall defect
accompanied with extramural
air is clearly demonstrated by
US
123
is useful for making a diagnosis .
Ultrasonographic Murphys sign refers to the pain that

occurs when the gallbladder is pressed while it is being
depicted with an ultrasonographic probe. It is superior to
the ordinary Murphys sign in that it is possible to press the
gallbladder accurately. On the basis of the examination of
219 cases of right upper quadrant abdominal pain, Ralls
et al. have reported that ultrasonographic Murphys sign is
somewhat inferior to the ordinary Murphys sign in sensitivity (63.0 %, 95 % CI 49.177.0 %), although it is
superior in specificity (93.6 %, 95 % CI 90.097.3 %)
[33]. According to Bree et al. who examined 200 cases (of
which 73 cases were acute cholecystitis) with complaints
of right upper quadrant abdominal pain, the sensitivity of
ultrasonographic Murphys sign is good (86.3 %; 95 % CI
78.494.2 %) although the specificity is inferior (35.0 %;
95 % CI 26.443.0 %), so the presence of bile stones
should be taken into account when a diagnosis is made
[34]. Ultrasonographic Murphys sign can also be used to
distinguish acute cholecystitis from cases of Murphys sign
41
positive due to other diseases and for diagnosis of the

causative disease, such as duodenal ulcer (Fig. 2).
Q9. Is color or power Doppler imaging useful for
making a diagnosis of acute cholecystitis?
The findings of power Doppler imaging are useful for making
a diagnosis of acute cholecystitis (recommendation 2, level C).
Soyer et al. examined 129 cases complaining of acute

pain in the upper right quadrant abdomen and reported that
the diagnostic capacity for acute cholecystitis on the basis
of Doppler sonographic findings were: sensitivity 95 %,
specificity 100 %, accuracy 99 %, PPV 100 %, and NPV
99 %, exceeding that of the B-mode Doppler sonography
(sensitivity 86 %, specificity 99 %, accuracy 92 %, PPV
92 %, and NPV 87 %) [35] (Supplement Table 2).
On the other hand, Tessler et al. [36] who examined a small
number of cases have found that intramural Doppler signals
are also observed in normal cases and that signal depiction
becomes more remarkable after food intake. Furthermore,
Jeffrey et al. carried out detailed discussion of 54 cases
undergoing surgery for cholecystitis and 115 normal controls
including the area of depiction and have found that the presence or absence of signal depiction alone is not a finding
specific to cholecystitis. They looked at the presence of a
blood flow signal extending over more than half of the anterior
wall (26 % occurrence rate compared with 2 % for normal
cases), and discovered that the signal depicted on the bottom is
a more specific finding (the frequency of occurrence being
0 % for normal cases and 19 % for cholecystitis cases) [37].
On the basis of the above observations, it may be possible
to make a diagnosis of cholecystitis by means of color or
power Doppler sonography. However, the detective capacity
of Doppler signals is influenced by the performance and
settings of the instruments used and, and the physique of
subjects. Careful judgment should be made when using
Doppler sonographic findings as the only reference findings
including B-mode findings (Supplement Fig. 2).
CT
Q10. What are the characteristic contrast enhanced CT
findings of acute cholecystitis?
CT findings of acute cholecystitis are gallbladder distention,
pericholecystic fat stranding, gallbladder wall thickening,
subserosal edema, mucosal enhancement, transient focal
enhancement of the liver adjacent to the
pericholecystic fluid collection,
gas collection within gallbladder.
gallbladder,
pericholecystic abscess,
CT findings of acute cholecystitis were reported as: GB

distention (41 %), gallbladder wall thickening (59 %),
pericholecystic fat density (52 %), pericholecystic fluid
collection (31 %), subserosal edema (31 %), and highattenuation gallbladder bile (24 %) (Fig. 3; Supplement
Fig. 3) [38].
Anatomically, a part of the cholecystic vein directly
drains into the liver parenchyma surrounding the gallbladder fossa. In patients with acute cholecystitis, venous
blood flow from the gallbladder wall into the liver
increases. So, the arterial phase of dynamic CT shows
transient focal enhancement of the liver adjacent to the
inflamed gallbladder (Fig. 3; Supplement Fig. 3) [3942].
This enhancement disappears during the portal and equilibrium phase.
In mild acute cholecystitis, gallbladder distention
without wall thickening or edema are the only signs on
CT. Because gallbladder size is variable depending on the
individual, gallbladder distention is difficult to evaluate
on diagnostic imaging (such as ultrasonography or noncontrast CT) of acute cholecystitis. Dynamic CT, especially during the arterial phase, is very useful in mild
cholecystitis because of the high sensitivity of transient
focal enhancement of the liver adjacent to the gallbladder
[41].
Tc-HIDA scans
Hepatobiliary scintigraphy involves intravenous injection
of technetium-labeled analogues of iminodiacetic acid,
which are excreted into the bile. The failure of the gallbladder to fill within 60 min after administration of the
tracer indicates that the cystic duct is obstructed and has a
sensitivity of 8090 % for acute cholecystitis. The false
positive rate of 1020 % is largely explained by cystic duct
obstruction induced by chronic inflammation, although in
some cases normal gallbladders do not fill due to insufficient resistance at the sphincter of Oddi. When the cystic
duct is patent (i.e., no cholecystitis), the gallbladder is
normally visualized within 30 min. The rim sign is a
blush of increased pericholecystic radioactivity, which is
present in about 30 % of patients with acute cholecystitis
and in about 60 % with acute gangrenous cholecystitis [1].
In patients with suspected acute cholecystitis, hepatobiliary
scintigraphy has significantly higher specificity [27] and
higher accuracy [43] than ultrasonography. Nevertheless,
ultrasonography is usually preferred as the first test because
of its immediate availability, easy access, a lack of interference by elevated serum bilirubin levels (since cholestasis interferes with biliary excretion of the agents used for
scintigraphy), the absence of ionizing radiation, and the
123
42
Fig. 3 Acute cholecystolithiasis (62-year-old male). Non-contrast

CT (a) shows gallbladder distention, wall thickening, and gallstone
(arrow). The arterial phase of contrast-enhanced dynamic CT (b, c,
f) shows gallbladder wall edema (asterisk) and focal hepatic

enhancement adjacent to the gallbladder (arrowheads). Hepatic
enhancement disappears on the equilibrium phase of CT (d, e)
ability to provide information regarding the presence of

stones [1].
grading of acute cholecystitis was classified into the following 3 categories: mild (Grade I), moderate (Grade
II) and severe (Grade III). Severe (Grade III) acute
cholecystitis was defined as acute cholecystitis associated
with organ dysfunction.
Moderate (Grade II) acute cholecystitis was defined as
acute cholecystitis in which the degree of acute inflammation is likely to be associated with increased operative
difficulty in performing cholecystectomy [4449].
Mild (Grade I) acute cholecystitis was defined as
occurring in a patient who has no findings of organ dysfunction and mild disease in the gallbladder, enabling
cholecystectomy as a safe and low risk procedure. These
patients do not have a severity index that meets the criteria
for moderate (Grade II) and severe (Grade III) acute
cholecystitis in TG07.
There are reports that discussed and appraised the TG07
severity assessment criteria. According to those papers, the
distribution varies as follows: 39.368.5 % of the cases
were classified as Grade I, 25.559.5 % as Grade II, and
1.26 % as Grade III [14, 15]. In addition, there is a report
Severity assessment criteria for acute cholecystitis;

TG13
Background
Patients with acute cholecystitis may present a spectrum
of disease stages ranging from a mild, self-limited illness
to a fulminant and potentially life-threatening disease. In
fact, the overall mortality rate of acute cholecystitis is
approximately 0.6 % [11, 12]. There were no severity
assessment criteria for this common disease until 2007
[16].
TG07 severity assessment criteria for acute cholecystitis
The severity assessment criteria were first presented
throughout the world in TG07 [5], where the severity
123
43
TG13 severity assessment criteria for acute cholecystitis
suggesting that the assessment criteria have contributed to

a decrease in the period of hospital stay [13]. This demonstrates that TG07 severity assessment criteria have
received good appraisal; there has so far been no treatise or
report that has pointed out matters to be improved and
weak points of TG07.
The revised severity grading for acute cholecystitis is

shown in Table 4.
TG07 severity assessment criteria have been adopted in
TG13 with minor changes [16].
Revision of severity grading for acute cholecystitis; TG07
Q11. What morbid conditions are referred to as severe

in assessing severity for acute cholecystitis?
There are reports on poor prognostic factors of acute

cholecystitis and those enabling the estimation of emergency surgery. Factors reported after 2000 include leukocytosis [13, 15, 5055], ALP [50, 56, 57], old age [53,
54, 58], diabetes [51, 52], male sex [51, 53], and
admission delay [55]. There are also reports of imaging
findings such as ultrasonographic findings of gallbladder
wall thickening [53] and common bile duct distention
[57]. To date there has been a small number of new
reports of AST, ALT, LDH, BUN, and creatinine. The
severity assessment criteria were reconsidered by the
Tokyo Guidelines Revision Committee with new information, evidence, and evaluations of TG07. Consequently, the TG07 severity assessment criteria did not
have significant problems that required major revision of
the definitions or structures [16]. However, minor changes were made to the description of Grade III severity:
dopamine and norepinephrine were both considered as
evidence of cardiovascular dysfunction consistent with
the SOFA scoring system [59].
Severe is referred to as a condition that has developed

organ dysfunction as circulatory failure
consciousness
disturbance
respiratory failure
renal failure
hepatic
failure or blood coagulation disorder . Intensive care with

respiratory and circulatory management should be performed.
Acute cholecystitis has a better outcome/prognosis than

acute cholangitis but requires prompt treatment when
gangrenous cholecystitis, emphysematous cholecystitis, or
torsion of the gallbladder are present. The progression of
acute cholecystitis from the mild/moderate to the severe
form means the development of multiple organ dysfunction
syndrome (MODS). Organ dysfunction scores, such as
Marshalls multiple organ dysfunction (MOD) score and
the sequential organ failure assessment (SOFA) score [60],
are sometimes used to evaluate organ dysfunction in critically ill patients. The six factors involved in organ dysfunction have therefore been adopted in TG07 as factors
that enable severity assessment.
Table 4 TG13 severity grading for acute cholecystitis

Grade III (severe) acute cholecystitis
Associated with dysfunction of any one of the following organs/systems:
1. Cardiovascular dysfunction
Hypotension requiring treatment with dopamine C5 lg/kg per min, or any dose of norepinephrine
2. Neurological dysfunction
Decreased level of consciousness
3. Respiratory dysfunction
PaO2/FiO2 ratio \300
4. Renal dysfunction
Oliguria, creatinine [2.0 mg/dl
5. Hepatic dysfunction
PT-INR [1.5
6. Hematological dysfunction
Platelet count \100,000/mm3
Grade II (moderate) acute cholecystitis
Associated with any one of the following conditions:
1. Elevated white blood cell count ([18,000/mm3)
2. Palpable tender mass in the right upper abdominal quadrant
3. Duration of complaints [72 h
4. Marked local inflammation (gangrenous cholecystitis, pericholecystic abscess, hepatic abscess, biliary peritonitis, emphysematous
cholecystitis)
Grade I (mild) acute cholecystitis
Does not meet the criteria of Grade III or Grade II acute cholecystitis. Grade I can also be defined as acute cholecystitis in a healthy
patient with no organ dysfunction and mild inflammatory changes in the gallbladder, making cholecystectomy a safe and low-risk operative
procedure
123
44
Fig. 4 Emphysematous cholecystitis. The presence of intramural/intraluminal gas indicates emphysematous cholecystitis. The echo from small
gas bubbles shows multiple reverberation
Q12. What morbid conditions are referred to as moderate in assessing severity for acute cholecystitis?
When acute cholecystitis is accompanied by acute

cholangitis, the criteria for the severity assessment of acute
cholangitis should also be taken into account [62, 63].
Moderate is referred to as a condition of acute cholecystitis

without organ dysfunction but with its risk, accompanying
serious local complication , and for which cholecystectomy
and biliary drainage are to be carried out immediately.
Q14. What are the findings to be noted when the

assessment of gangrenous cholecystitis and emphysematous cholecystitis is carried out by means of
ultrasonography?
Q13. In making a diagnosis of acute cholecystitis, what

are the factors that enable the assessment of moderate
cases?
Irregular thickening of the gallbladder wall and imaging

of the ruptured gallbladder wall should be noted.
The presence of leucocytosis palpable right upper quadrant

abdominal pain persistence of symptoms for more than 72
hours after onset or severe inflammation findings.
TG07 included findings such as an elevated level of

WBC and imaging findings in assessment items specifically applied in moderate (Grade II) acute cholecystitis.
Included in these items is evidence such as leukocytosis
([18,000 mm3) detected at the time of hospitalization,
prognostic factors that contribute to the change of surgical techniques from laparoscopic surgery to open surgery, and the time of symptom persistence (of more than
72 h) from the onset of symptoms [44, 61]. The criteria
for Grade II (moderate) acute cholecystitis can be
defined as acute cholecystitis associated with local
inflammatory conditions that make cholecystectomy
difficult.
As for the factor old age, the following statement had
been adopted to call attention in TG07; however the
statement is useful for the revised edition, too. Elderly
per se is not a criterion for severity itself but indicates a
propensity to progress to the severe form, and thus is not
included in the criteria for severity assessment [5].
123
Through the discussion of 19 cases of gangrenous cholecystitis, Jeffrey et al. [7] found that the membraneous
structure of the lumen within the gallbladder is observed in
31.6 % (6 cases), irregular thickening of the gallbladder
wall in 47.4 % (9 cases), both of these findings in 21.1 %
(4 cases), and either of these findings in 57.9 % (11 cases).
Regarding perforation, Forsberg et al. [64] also reported on
the basis of the discussion involving 24 cases of perforation
and 21 cases of acute cholecystitis without perforation that
no specific findings were observed, although a slightly
thickened wall was observed (320 mm, mean 7 mm, for
cases with perforation; 213 mm, mean 5.3 mm, for cases
without perforation). On the other hand, according to Sood
et al. [65] depiction of the ruptured wall as a direct finding
of gallbladder perforation was able to be made with
ultrasonography in 70 % (16 of 23 cases) and with CT in
78 % (14 of 18 cases). Depending on the performance of
the instrument used, it can be assumed that the diagnosis
can be made for considerable numbers of cases (Fig. 4;
Supplement Movie 2).
the Japanese Society for Abdominal Emergency Medicine, the Japan
Biliary Association, Japan Society for Surgical Infection, and the
Japanese Society of Hepato-Biliary-Pancreatic Surgery, which

provided us with great support and guidance in the preparation of the
Guidelines.
None.
References
1. Steven M, Strasberg MD. Acute calculous cholecystitis. N Engl J
Med. 2008;358:280411.
2. Eskelinen M, Ikonen J, Lipponen P. Diagnostic approaches in
acute cholecystitis; a prospective study of 1333 patients with
acute abdominal pain. Theor Surg. 1993;8:1520.
3. Halasz NA. Counterfeit cholecystitis, a common diagnostic
dilemma. Am J Surg. 1975;130:18993.
4. Johnson H Jr, Cooper B. The value of HIDA scans in the initial
evaluation of patients for cholecystitis. J Natl Med Assoc.
1995;87:2732.
et al. Diagnostic criteria and severity assessment of acute cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg.
2007;14(1):7882 (Epub 2007 Jan 30) (clinical practice guidelines: CPGs).
Norimizu S, et al. Accuracy of the Tokyo Guidelines for the
diagnosis of acute cholangitis and cholecystitis taking into consideration the clinical practice pattern in Japan. J Hepatobiliary
Pancreat Sci. 2011;18:2507.
7. Jeffrey RB, Laing FC, Wong W, Callen PW. Gangrenous cholecystitis: diagnosis by ultrasound. Radiology. 1983;148:21921.
8. Gruber PJ, Silverman RA, Gottesfeld S, Flaster E. Presence of
fever and leukocytosis in acute cholecystitis. Ann Emerg Med.
1996;28:2737.
10. Barie PS, Eachempati SR. Acute acalculous cholecystitis. Curr
Gastroenterol Rep. 2003;5:3029.
11. Portincasa P, Moschetta A, Palasciano G. Cholesterol gallstone
disease. Lancet. 2006;15(368):2309.
12. Shaffer EA. Epidemiology and risk factors for gallstone disease:
has the paradigm changed in the 21st century? Curr Gastroenterol
Rep. 2005;7:13240.
13. Lee SW, Yang SS, Chang CS, Yeh HJ. Impact of the Tokyo
guidelines on the management of patients with acute calculous
cholecystitis. J Gastroenterol Hepatol. 2009;24(12):18571861.
14. Asai K, Watanabe M, Kusachi S, Tanaka H, Matsukiyo H, Osawa
A, et al. Bacteriological analysis of bile in acute cholecystitis
according to the Tokyo guidelines. J Hepatobiliary Pancreat Sci.
2012;19(4):476486.
15. Lee SW, Chang CS, Lee TY, Tung CF, Peng YC. The role of the
Tokyo guidelines in the diagnosis of acute calculous cholecystitis. J Hepatobiliary Pancreat Sci. 2010;17(6):879884.
acute cholecystitis in revised Tokyo guidelines. J Hepatobiliary
Pancreat Sci. 2012;19:57885.
17. Murphy JB. The diagnosis of gall-stones. Am Med News.
1903;82:82533.
18. Trowbridge RL, Rutkowski NK, Shojania KG. Does this patient
have acute cholecystitis? JAMA. 2003;289:806.
19. Brewer BJ, Golden GT, Hitch DC, Rudolf LE, Wangensteen SL.
Abdominal pain. An analysis of 1,000 consecutive cases in a
University Hospital emergency room. Am J Surg. 1976;131:
21923.
45
20. Schofied PF, Hulton NR, Baildam AD. Is it acute cholecystitis?
Ann R Coll Surg Engl. 1986;68:146.
21. Staniland JR, Ditchburn J, De Dombal FT. Clinical presentation
of acute abdomen: study of 600 patients. Br Med J. 1972;3:
3938.
22. Singer AJ, McCracken G, Henry MC, Thode HC Jr, Cabahug CJ.
Correlation among clinical, laboratory, and hepatobiliary scanning findings in patients with suspected acute cholecystitis. Ann
Emerg Med. 1996;28:26772.
23. Adedeji OA, McAdam WA. Murphys sign, acute cholecystitis
and elderly people. J R Coll Surg Edinb. 1996;41:889.
24. Juvonen T, Kiviniemi H, Niemela O, Kairaluoma MI. Diagnostic
accuracy of ultrasonography and C reactive protein concentration
in acute cholecystitis: a prospective clinical study. Eur J Surg.
1992;158:3659.
25. Rosen CL, Brown DF, Chang Y, Moore C, Averill NJ, Arkoff LJ,
et al. Ultrasonography by emergency physicians in patients with
suspected cholecystitis. Am J Emerg Med. 2001;19:326.
26. Kendall JL, Shimp RJ. Performance and interpretation of focused
right upper quadrant ultrasound by emergency. J Emerg Med.
2001;21:713.
27. Chatziioannou SN, Moore WH, Ford PV, Dhekne RD. Hepatobiliary scintigraphy is superior to abdominal ultrasonography in
suspected acute cholecystitis. Surgery. 2000;127:60913.
28. Shea JA, Berlin JA, Escarce JJ, Clarke JR, Kinosian BP, Cabana
MD, et al. Revised estimates of diagnostic test sensitivity and
specificity in suspected biliary tract disease. Arch Intern Med.
1994;154:257381.
29. Ralls PW, Coletti PM, Lapin SA, Chandrasoma P, Boswell WD,
Ngo C, et al. Real-time sonography in suspected acute cholecystitis. Radiology. 1985;155:76771.
30. Martinez A, Bona X, Velasco M, Martin J. Diagnostic accuracy
of ultrasound in acute cholecystitis. Gastrointest Radiol.
1986;11:3348.
31. Park MS, Yu JS, Kim YH, Kim MJ, Kim JH, Lee S, et al. Acute
cholecystitis: comparison of MR cholangiography and US.
Radiology. 1998;209:7815.
32. Cohan RH, Mahony BS, Bowie JD, Cooper C, Baker ME, Illescas
FF. Striated intramural gallbladder lucencies on US studies:
predictors of acute cholecystitis. Radiology. 1987;164:315.
33. Ralls PW, Halls J, Lapin SA, Quinn MF, Morris UL, Boswell W.
Prospective evaluation of the sonographic Murphy sign in suspected acute cholecystitis. J Clin Ultrasound. 1982;10:1135.
34. Bree RL. Further observations on the usefulness of the sonographic Murphy sign in the evaluation of suspected acute cholecystitis. J Clin Ultrasound. 1995;23:16972.
35. Soyer P, Brouland JP, Boudiaf M, Kardache M, Pelage JP, Panis
Y, et al. Color velocity imaging and power Doppler sonography
of the gallbladder wall: a new look at sonographic diagnosis of
acute cholecystitis. AJR. 1998;171:1838.
36. Tessler FN, Tublin ME. Blood flow in healthy gallbladder walls
on color and power Doppler sonography: effect of wall thickness
and gallbladder volume. AJR. 1999;173:12479.
37. Jeffrey RB Jr, Nino-Murcia M, Ralls PW, Jain KA, Davidson HC.
Color Doppler sonography of the cystic artery: comparison of
normal controls and patients with acute cholecystitis. J Ultrasound Med. 1995;14:336.
38. Fidler J, Paulson EK, Layfield L. CT evaluation of acute cholecystitis: findings and usefulness in diagnosis. AJR. 1996;166:
10858.
39. Yamashita K, Jin MJ, Hirose Y, Morikawa M, Sumioka H, Itoh
K, et al. CT finding of transient focal increased attenuation of the
liver adjacent to the gallbladder in acute cholecystitis. AJR.
1995;164:3436.
40. Ito K, Awaya H, Mitchell DG, Honjo K, Fujita T, Uchisako H,
et al. Gallbladder disease: appearance of associated transient
123
46
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.

increases attenuation in the liver at biphasic, contrast enhanced
dynamic CT. Radiology. 1997;204:7238.
Kim YK, Kwak HS, Kim CS, Han YM, Jeong TO, Kim IH, et al.
CT findings of mild forms or early manifestations of acute cholecystitis. Clin Imaging. 2009;33(4):27480.
Singh AK, Sagar P. Gangrenous cholecystitis: prediction with CT
imaging. Abdom Imaging. 2005;30(2):21821.
Freitas JE, Mirkes SH, Fink-Bennett DM, Bree RL. Suspected
acute cholecystitis: comparison of hepatobiliary scintigraphy
versus ultrasonography. Clin Nucl Med. 1982;7:3647.
Brodsky A, Matter I, Sabo E, Cohen A, Abrahamson J, Eldar
S. Laparoscopic cholecystectomy for acute cholecystitis: can
the need for conversion and the probability of complications
be predicted? A prospective study. Surg Endosc. 2000;14:
75560.
Teixeira JP, Sraiva AC, Cabral AC, Barros H, Reis JR, Teixeira
A. Conversion factors in laparoscopic cholecystectomy for acute
cholecystitis. Hepatogastroenterology. 2000;47:62630.
Halachmi S, DiCastro N, Matter I, Cohen A, Sabo E, Mogilner
JG, et al. Laparoscopic cholecystectomy for acute cholecystitis:
how do fever and leucocytosis relate to conversion and complications? Eur J Surg. 2000;166:13640.
Rattner DW, Ferguson C, Warshaw AL. Factors associated with
successful laparoscopic cholecystectomy for acute cholecystitis.
Ann Surg. 1993;217:2336.
Araujo-Teixeria JP, Rocha-Reis J, Costa-Cabral A, Barros H,
Saraiva AC, Araujo-Teixeira AM. Laparoscopic versus open
cholecystectomy for cholecystitis (200 cases). Comparison of
results and predictive factors for conversion. Chirurgie.
1999;124:52935 (in French with English abstract).
Merriam LT, Kanaan SA, Dawes JG, Angelos P, Prystowsky JB,
Rege RV, et al. Gangrenous cholecystitis: analysis of risk factors
and experience with laparoscopic cholecystectomy. Surgery.
1999;126:6805.
Nguyen L, Fagan SP, Lee TC, Aoki N, Itani KM, Berger DH,
et al. Use of a predictive equation for diagnosis of acute gangrenous cholecystitis. Am J Surg. 2004;188(5):4636.
Fagan SP, Awad SS, Rahwan K, Hira K, Aoki N, Itani KM, et al.
Prognostic factors for the development of gangrenous cholecystitis. Am J Surg. 2003;186(5):4815.
Aydin C, Altaca G, Berber I, Tekin K, Kara M, Titiz I. Prognostic
parameters for the prediction of acute gangrenous cholecystitis.
J Hepatobiliary Pancreat Surg. 2006;13(2):1559.
Yacoub WN, Petrosyan M, Sehgal I, Ma Y, Chandrasoma P,
Mason RJ. Prediction of patients with acute cholecystitis
requiring emergent cholecystectomy: a simple score. Gastroenterol Res Pract. 2010;2010:901739 (Epub 2010 Jun 8).
123
cholecystitis. World J Gastroenterol. 2003;9(12):28213.
55. Contini S, Corradi D, Busi N, Alessandri L, Pezzarossa A,
Scarpignato C. Can gangrenous cholecystitis be prevented? A
plea against a wait and see attitude. J Clin Gastroenterol.
2004;38(8):7106.
56. McChesney JA, Northup PG, Bickston SJ. Acute acalculous
cholecystitis associated with systemic sepsis and visceral arterial
hypoperfusion: a case series and review of pathophysiology. Dig
Dis Sci. 2003;48(10):19607.
57. Young AL, Cockbain AJ, White AW, Hood A, Menon KV,
Toogood GJ. Index admission laparoscopic cholecystectomy for
patients with acute biliary symptoms: results from a specialist
centre. HPB (Oxford). 2010;12(4):2706.
58. Girgin S, Gedik E, Tacyildiz IH, Akgun Y, Bac B, Uysal E.
Factors affecting morbidity and mortality in gangrenous cholecystitis. Acta Chir Belg. 2006;106(5):545549.
59. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM,
Jaeschke R, International Surviving Sepsis Campaign Guidelines
Committee, et al. Surviving sepsis campaign: international
guidelines for management of severe sepsis and septic shock:
2008. Crit Care Med. 2008;36(1):296327.
60. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A,
Bruining H, et al. The SOFA (Sepsis-related Organ Failure
Assessment) score to describe organ dysfunction/failure. On
behalf of the Working Group on Sepsis-Related Problems of the
European Society of Intensive Care Medicine. Intensive Care
Med. 1996;22(7):70710.
61. Hadad SM, Vaidya JS, Baker L, Koh HC, Heron TP, Hussain K,
et al. Delay from symptom onset increases the conversion rate in
laparoscopic cholecystectomy for acute cholecystitis. World J
Surg. 2007;31:1298301.
Pancreat Sci. 2012;19:54856.
Sci. 2012;19:55765.
64. Forsberg L, Andersson R, Hederstrom E, Tranberg KG. Ultrasonography and gallbladder perforation in acute cholecystitis.
Acta Radiol. 1988;29:2035.
65. Sood BP, Kalra N, Gupta S, Sidhu R, Gulati M, Khandelwal N,
Suri S. Role of sonography in the diagnosis of gallbladder perforation. J Clin Ultrasound. 2002;30:2704.

DOI 10.1007/s00534-012-0563-1
GUIDELINE

TG13 flowchart for the management of acute cholangitis

and cholecystitis
Fumihiko Miura Tadahiro Takada Steven M. Strasberg Joseph S. Solomkin Henry A. Pitt Dirk J. Gouma
O. James Garden Markus W. Buchler Masahiro Yoshida Toshihiko Mayumi Kohji Okamoto
Harumi Gomi Shinya Kusachi Seiki Kiriyama Masamichi Yokoe Yasutoshi Kimura Ryota Higuchi
Yuichi Yamashita John A. Windsor Toshio Tsuyuguchi Toshifumi Gabata Takao Itoi Jiro Hata
Kui-Hin Liau

Abstract We propose a management strategy for acute

cholangitis and cholecystitis according to the severity
assessment. For Grade I (mild) acute cholangitis, initial
medical treatment including the use of antimicrobial agents
may be sufficient for most cases. For non-responders to
initial medical treatment, biliary drainage should be considered. For Grade II (moderate) acute cholangitis, early
biliary drainage should be performed along with the
administration of antibiotics. For Grade III (severe) acute
cholangitis, appropriate organ support is required. After
hemodynamic stabilization has been achieved, urgent
endoscopic or percutaneous transhepatic biliary drainage

should be performed. In patients with Grade II (moderate)
and Grade III (severe) acute cholangitis, treatment for the
underlying etiology including endoscopic, percutaneous, or
surgical treatment should be performed after the patients
general condition has been improved. In patients with
Grade I (mild) acute cholangitis, treatment for etiology
such as endoscopic sphincterotomy for choledocholithiasis
might be performed simultaneously, if possible, with biliary drainage. Early laparoscopic cholecystectomy is the
first-line treatment in patients with Grade I (mild) acute
F. Miura (&) T. Takada

2-11-1, Kaga, Itabashi-ku, Tokyo 173-8605, Japan
e-mail: f-miura@med.teikyo-u.ac.jp
M. Yoshida
S. M. Strasberg
J. S. Solomkin
H. A. Pitt
D. J. Gouma
Department of Surgery, Academic Medical Center,
Amsterdam, The Netherlands
O. J. Garden
M. W. Buchler
Heidelberg, Germany
T. Mayumi
K. Okamoto
Kitakyushu, Japan
H. Gomi
Shimotsuke, Tochigi, Japan
S. Kusachi
S. Kiriyama
Ogaki, Japan
M. Yokoe
Nagoya, Japan
123
48
cholecystitis while in patients with Grade II (moderate)

acute cholecystitis, delayed/elective laparoscopic cholecystectomy after initial medical treatment with antimicrobial agent is the first-line treatment. In non-responders to
initial medical treatment, gallbladder drainage should be
considered. In patients with Grade III (severe) acute cholecystitis, appropriate organ support in addition to initial
medical treatment is necessary. Urgent or early gallbladder
drainage is recommended. Elective cholecystectomy can
be performed after the improvement of the acute inflammatory process.
Biliary drainage Laparoscopic cholecystectomy
Guidelines
Introduction
This article describes strategies for the management of
acute cholangitis and cholecystitis including initial medical
treatment flowcharts. We established a flowchart for the
diagnosis and treatment of acute cholangitis and cholecystitis as reported in the Tokyo Guidelines 2007 [1].
Flowcharts for the management of acute cholangitis and
cholecystitis have been revised in the updated Tokyo
Guidelines (TG13).
We consider that the primary purpose of the flowcharts
is to allow clinicians to grasp, at a glance, the outline of the
management strategy of the disease. Flowcharts have been
colored for easy access and rapid understanding, and most
of the treatment methods are included in the flowcharts to
achieve their primary purpose.
Y. Kimura
Sapporo, Japan

Acute
Cholangitis
Suspicion of
Acute Biliary
Infection
Diagnostic
Criteria
of TG13
Acute
Cholecystitis
Other
Diseases
Fig. 1 General guidance for the management of acute biliary

inflammation/infection
General guidance for the management of acute

cholangitis
The general guidance for the management of acute biliary
inflammation/infection including acute cholangitis is presented in Fig. 1.
Clinical presentations
Clinical findings associated with acute cholangitis include
abdominal pain, jaundice, fever (Charcots triad), and
rigor. The triad was reported in 1887 by Charcot [2] as the
indicators of hepatic fever and has been historically used as
the generally accepted clinical findings of acute cholangitis. All three symptoms are observed in about 5070 % of
the patients with acute cholangitis [36]. Reynolds pentadCharcots triad plus shock and decreased level of
consciousnesswere presented in 1959 when Reynolds
and Dargan [7] defined acute obstructive cholangitis.
Reynolds pentad is often referred to as the findings representing serious conditions, but shock and a decreased
level of consciousness are only observed in less than 30 %
of patients with acute cholangitis [36]. A history of biliary
T. Gabata
R. Higuchi
T. Itoi
Department of Gastroenterology and Hepatology,
Tokyo Medical University,
Tokyo, Japan
Y. Yamashita
J. Hata
Department of Endoscopy and Ultrasound,
Kawasaki Medical School, Okayama, Japan
J. A. Windsor
Department of Surgery, The University of Auckland,
Auckland, New Zealand
K.-H. Liau
Hepatobiliary and Pancreatic Surgery,
Nexus Surgical Associates, Mount Elizabeth Hospital,
Singapore, Singapore
T. Tsuyuguchi
123
diseases such as gallstones, previous biliary procedures, or

the placement of a biliary stent is very helpful when a
diagnosis of acute cholangitis is suspected [1].
Blood test
The diagnosis of acute cholangitis requires the measurement of white blood cell count, C-reactive protein, and
liver function test including alkaline phosphatase, GGT,
AST, ALT, and bilirubin [8]. The assessment of the
severity of the illness requires knowledge of the platelet
count, blood urea nitrogen, creatinine, prothrombin timeinternational normalized ratio (PT-INR), albumin, and
arterial blood gas analysis. Blood cultures are also helpful
for selection of antimicrobial drugs [810]. Hyperamylasemia is a useful parameter for identifying complications
such as choledocholithiasis causing biliary pancreatitis
[11].
49
Early treatment, while fasting as a rule, includes sufficient infusion, the administration of antimicrobial and
analgesic agents, along with the monitoring of respiratory
hemodynamic conditions in preparation for emergency
drainage [1].
When acute cholangitis has become more severe, that is,
if any one of the following signs is observed such as shock
(reduced blood pressure), consciousness disturbance, acute
lung injury, acute renal injury, hepatic injury, and disseminated intravascular coagulation (DIC) (decreased
platelet count), emergency biliary drainage is carried out
together with appropriate organ support (sufficient infusion
and anti-microbial administration), and respiratory and
circulatory management (artificial respiration, intubation,
and use of vasopressors) [1].
Q2. Should the severe sepsis bundle be referred to for
the early treatment of acute cholangitis accompanying
severe sepsis?
Diagnostic imaging
Abdominal ultrasound (US) and abdominal computerized
tomography (CT) with intravenous contrast are very useful
test procedures for evaluating patients with acute biliary
tract disease. Abdominal US should be performed in all
patients with suspected acute biliary inflammation/infection [1]. Ultrasonic examination has satisfactory diagnostic
capabilities when performed not only by specialists but
also by emergency physicians [12, 13]. The role of diagnostic imaging in acute cholangitis is to determine the
presence of biliary obstruction, the level of obstruction, and
the cause of the obstruction such as gallstones and/or biliary strictures [1]. The assessment should include US and
CT. These studies complement each other and CT may
yield better imaging of bile duct dilatation and
pneumobilia.
Differential diagnosis
Diseases which should be differentiated from acute cholangitis are acute cholecystitis, liver abscess, gastric and
duodenal ulcer, acute pancreatitis, acute hepatitis, and
septicemia from other origins.
Q1. What is the initial medical treatment of acute
cholangitis?
On condition that biliary drainage is conducted during hospital
stay as a rule, sufficient infusion, electrolyte correction, and
antimicrobial and analgesic administration take place while
fasting (recommendation 1, level C).
The severe sepsis bundle should be referred to for the early

treatment of acute cholangitis accompanying severe sepsis
Acute cholangitis is frequently accompanied by sepsis.

As for the early treatment of severe sepsis, there is a
detailed description in Surviving Sepsis Campaign
Guidelines (SSCG) published in 2004 and updated in
2008. To improve treatment results, a severe sepsis bundle (Table 1, http://www.ihi.org/knowledge/Pages/Changes/
ImplementEffectiveGlucoseControl.aspx) has been presented in SSCG as the core part of the treatment for septic
shock. However, there are reports of validation by several
multi-institutional collaborative studies that have found a
significant decrease in mortality rate in patients with a
higher rate of compliance [14] or after the implementation of
the severe sepsis bundle [1517]. These studies include
severe sepsis cases induced by a disease other than acute
cholangitis [1417]. However, the severe sepsis bundle
should be referred to for the early treatment of acute cholangitis accompanying severe sepsis.
Flowchart for the management of acute cholangitis

A flowchart for the management of acute cholangitis is
shown in Fig. 2. Treatment of acute cholangitis should be
performed according to the severity grade of the patient.
Biliary drainage and antimicrobial therapy are the two most
important elements of treatment. When a diagnosis of acute
cholangitis is determined based on the diagnostic criteria of
123
50
Table 1 Severe sepsis bundle, quoted from http://www.survi

vingsepsis.org/Bundles/Pages/default.aspx
Sepsis resuscitation bundle
Tasks that should start immediately but must be performed
within 6 h in patients with severe sepsis or septic shock:
1. Measure serum lactate.
2. Obtain blood cultures prior to antibiotic administration.
3. Administer broad-spectrum antibiotics within 3 h after admission
to the emergency department (ED) and within 1 h after
admission to the department other than ED.
4. In the event of hypotension and/or serum lactate [4 mmol/L:
a. Deliver the initial minimum of 20 mL/kg of crystalloid
or the equivalent.
b. Apply vasopressors for hypotension showing no response
to initial fluid resuscitation in order to maintain the
mean arterial pressure (MAP) [65 mmHg.
5. In the event of persistent hypotension despite fluid resuscitation
(septic shock) and/or lactate [4 mmol/L:
a. Achieve central venous pressure (CVP) of [8 mmHg.
b. Achieve central venous oxygen saturation (ScvO2) [70 %
or mixed venous oxygen saturation (SvO2) [65 %.
Grade I (mild) acute cholangitis
Sepsis management bundle

Tasks that should be initiated immediately but must be carried
out within 24 h in patients with severe sepsis or septic shock:
1. Administer low-dose steroids for septic shock in accordance
with the standardized ICU policy. If not administered, document
why the patient did not qualify for low-dose steroids based
upon the standardized protocol.
2. Administer recombinant human activated protein C (rhAPC)
in accordance with the standardized ICU policy. If not
administered, document why the patient did not qualify for rhAPC.
3. Maintain glucose control \180 mg/dL.
4. Maintain the median inspiratory plateau pressure
(IPP) \30 cmH2O in patients on mechanical ventilation.
Fig. 2 Flowchart for the

management of acute
cholangitis: TG13
acute cholangitis of TG13 [9], initial medical treatment

including nil per os (NPO), intravenous fluid, antimicrobial
therapy, and analgesia together with close monitoring of
blood pressure, pulse, and urinary output should be initiated. Simultaneously, severity assessment of acute cholangitis should be conducted based on the severity
assessment criteria for acute cholangitis of TG 13 [9] in
which acute cholangitis is classified into Grade I (mild),
Grade II (moderate), or Grade III (severe). Frequent reassessment is mandatory and patients may need to be reclassified into Grade I, II, or III based on the response to
initial medical treatment. Appropriate treatment should be
performed in accordance with the severity grade. Patients
with acute cholangitis sometimes suffer simultaneously
from acute cholecystitis. A treatment strategy for patients
with both acute cholangitis and cholecystitis should be
determined in consideration of the severity of those diseases and the surgical risk in patients.
Diagnosis and
Severity
Assessment by
TG13
Guidelines
Grade I
(Mild)
Grade II
(Moderate)
Initial medical treatment including antimicrobial therapy may

be sufficient. Biliary drainage is not required for most cases.
However, for non-responders to initial medical treatment,
biliary drainage should be considered. Endoscopic, percutaneous, or operative intervention for the etiology of acute
cholangitis such as choledocholithiasis and pancreato-biliary
malignancy may be performed after pre-intervention work-up.
Treatment for etiology such as endoscopic sphincterotomy for
choledocholithiasis might be performed simultaneously, if
possible, with biliary drainage. Some patients who have
Treatment According to Grade, According to Response,

and According to Need for Additional Therapy
Antibiotics
and General
Supportive Care
Early Biliary Drainage

Antibiotics
General Supportive Care
Finish course
of antibiotics
Treatment
Biliary
Drainage
for etiology
if still needed
(Endoscopic treatment,
percutaneous treatment,
Grade III
(Severe)
Urgent Biliary Drainage

Organ Support
Antibiotics
or surgery)
Performance of a blood culture should be taken into consideration before initiation of administration of
antibiotics. A bile culture should be performed during biliary drainage.
Principle of treatment for acute cholangitis consists of antimicrobial administration and biliary drainage
including treatment for etiology. For patient with choledocholithiasis, treatment for etiology might be
performed simultaneously, if possible, with biliary drainage.
123
developed postoperative cholangitis may require antimicrobial

therapy only and generally do not require intervention.
Grade II (moderate) acute cholangitis
Early endoscopic or percutaneous drainage, or even emergency operative drainage with a T-tube, should be performed in patients with Grade II acute cholangitis. A
definitive procedure should be performed to remove a cause
of acute cholangitis after the patients general condition has
improved and following pre-intervention work-up.
Grade III (severe) acute cholangitis
Patients with acute cholangitis accompanied by organ
failure are classified as Grade III (severe) acute cholangitis.
These patients require appropriate organ support such as
ventilatory/circulatory management (non-invasive/invasive
positive pressure ventilation and use of vasopressor, etc.).
Urgent biliary drainage should be anticipated. When
patients are stabilized with initial medical treatment and
organ support, urgent (as soon as possible) endoscopic or
percutaneous transhepatic biliary drainage or, according to
the circumstances, an emergency operation with decompression of the bile duct with a T-tube should be performed. Definitive treatment for the cause of acute
cholangitis including endoscopic, percutaneous, or operative intervention should be considered once the acute illness has resolved.
General guidance for the management of acute

cholecystitis
The general guidance for the management of acute biliary
inflammation/infection including acute cholecystitis is
presented in Fig. 1.
Clinical presentations
Clinical symptoms of acute cholecystitis include abdominal
pain (right upper abdominal pain), nausea, vomiting, and
pyrexia [1820]. The most typical symptom is right epigastric pain. Tenderness in the right upper abdomen, a palpable
gallbladder, and Murphys sign are the characteristic findings
of acute cholecystitis. A positive Murphys sign shows
7996 % specificity [18, 20] for acute cholecystitis.
Blood test
There is no specific blood test for acute cholecystitis;
however, the measurement of white blood cell count and
C-reactive protein is very useful in confirming an
51
inflammatory response [21]. The platelet count, bilirubin,

blood urea nitrogen, creatinine, prothrombin time-international normalized ratio (PT-INR), and arterial blood gas
analysis are useful in assessing the severity status of the
patient [21].
Diagnostic imaging
Abdominal ultrasound (US) and abdominal computerized
tomography (CT) with intravenous contrast are very
helpful procedures for evaluating patients with acute biliary tract disease. Abdominal US should be performed in
every patient with suspected acute biliary inflammation/
infection [1]. Ultrasonic examination has satisfactory
diagnostic capability when it is performed not only by
specialists but also by emergency physicians [12, 13].
Characteristic findings of acute cholecystitis include the
enlarged gallbladder, thickened gallbladder wall, gallbladder stones and/or debris in the gallbladder, sonographic Murphys sign, pericholecystic fluid, and
pericholecystic abscess [21]. Sonographic Murphys sign
is a reliable finding of acute cholecystitis showing about
90 % sensitivity and specificity [22, 23], which is higher
than those of Murphys sign.
Differential diagnosis
Diseases which should be differentiated from acute cholecystitis are gastric and duodenal ulcer, hepatitis, pancreatitis, gallbladder cancer, hepatic abscess, Fitz-Hugh
Curtis syndrome, right lower lobar pneumonia, angina
pectoris, myocardial infarction, and urinary infection.
Q3. What is the initial medical treatment of acute
cholecystitis?
While considering indications for surgery and emergency
drainage, sufficient infusion and electrolyte correction
take place, and antimicrobial and analgesic agents are
administered while fasting continuing the monitoring of
respiratory and hemodyanamics (recommendation 1, level C).
Early treatment, with fasting as a rule, includes sufficient infusion, the administration of antimicrobial and
analgesic agents, along with the monitoring of respiratory
hemodynamics in preparation for emergency surgery and
drainage [1].
When any one of the following morbidities is observed:
further aggravation of acute cholecystitis, shock (reduced
blood pressure), consciousness disturbance, acute respiratory injury, acute renal injury, hepatic injury, and DIC
(reduced platelet count), then appropriate organ support
123
52
(sufficient infusion and antimicrobial administration), and

respiratory and circulatory management (artificial respiration, intubation, and use of vasopressors) are carried out
together with emergency drainage or cholecystectomy [1].
There are many reports showing that remission can be
achieved by conservative treatment only [2426]. On the
other hand, there is a report demonstrating that mild cases
may not require antimicrobial agents; however, prophylactic administration should take place due to possible
complications such as bacterial infection. Furthermore,
there is a report that was unable to detect a difference in the
positive rate of sonographic Murphys sign depending on
the presence or absence of the use of analgesic agents [27].
The administration of analgesic agents should therefore be
initiated in the early stage.
CQ4. Is the administration of NSAID for the attack of
impacted stones gallstone attack effective for preventing acute cholecystitis?
NSAID administration is effective for impacted gallstone
attack for preventing acute cholecystitis (recommendation
1, level A).
urgent/early cholecystectomy [31, 32]. When a diagnosis of

acute cholecystitis is determined based on the diagnostic
criteria of acute cholecystitis in TG13 [33], initial medical
treatment including NPO, intravenous fluids, antibiotics,
and analgesia, together with close monitoring of blood
pressure, pulse, and urinary output should be initiated.
Simultaneously, severity assessment of acute cholecystitis
should be conducted based on the severity assessment criteria for the acute cholecystitis of TG13 [33], in which acute
cholecystitis is classified into Grade I (mild), Grade II
(moderate), or Grade III (severe). Assessment of the operative risk for comorbidities and the patients general status
should also be evaluated in addition to the severity grade.
After resolution of acute inflammation with medical
treatment and gallbladder drainage, it is desirable that
cholecystectomy is performed to prevent recurrence. In
surgically high-risk patients with cholecystolithiasis,
medical support after percutaneous cholecystolithotomy
should be considered [3436]. In patients with acalculous
cholecystitis, cholecystectomy is not always required since
recurrence of acute acalculous cholecystitis after gallbladder drainage is rare [31, 37].
Grade I (mild) acute cholecystitis
Administration of non-steroidal anti-inflammatory drugs

(NSAIDs) for gallstone attack is effective in preventing
acute cholecystitis, and they are also widely known as
analgesic agents. A NSAID such as diclofenac is thus used
for early treatment. According to a report of a double blind
randomized controlled trial (RCT) that compared the use of
NSAIDs (diclofenac 75 mg intramuscular injection) with
placebo [28] or hyoscine 20 mg intramuscular injection
[29] for cases of impacted gallstone attack, NSAIDs prevented progression of the disease to acute cholecystitis and
also reduced pain. Although NSAIDs have been effective
for the improvement of gallbladder function in cases with
chronic cholecystitis, there is no report showing that the
administration of NSAIDs has contributed to improving the
course of cholecystitis after its acute onset [30].
Flowchart for the management of acute cholecystitis

A flowchart for the management of acute cholecystitis is
shown in Fig. 3. The first-line treatment of acute cholecystitis is early or urgent cholecystectomy, with laparoscopic cholecystectomy as a preferred method. In high-risk
patients, gallbladder drainage such as percutaneous transhepatic gallbladder drainage (PTGBD), percutaneous
transhepatic gallbladder aspiration (PTGBA), and endoscopic nasobiliary gallbladder drainage (ENGBD) is an
alternative therapy in patients who cannot safely undergo
123
Early laparoscopic cholecystectomy is the first-line treatment. In patients with surgical risk, observation (follow-up
without cholecystectomy) after improvement with initial
medical treatment could be indicated.
Grade II (moderate) acute cholecystitis
Grade II (moderate) acute cholecystitis is often accompanied by severe local inflammation. Therefore, surgeons
should take the difficulty of cholecystectomy into
consideration in selecting a treatment method. Elective
cholecystectomy after the improvement of the acute
inflammatory process is the first-line treatment. If a patient
does not respond to initial medical treatment, urgent or
early gallbladder drainage is required. Early laparoscopic
cholecystectomy could be indicated if advanced laparoscopic techniques are available. Grade II (moderate) acute
cholecystitis with serious local complications is an indication for urgent cholecystectomy and drainage.
Grade III (severe) acute cholecystitis
Grade III (severe) acute cholecystitis is accompanied by
organ dysfunction. Appropriate organ support such as
ventilatory/circulatory management (noninvasive/invasive
positive pressure ventilation and use of vasopressors, etc.)
in addition to initial medical treatment is necessary. Urgent
or early gallbladder drainage should be performed. Elective

Fig. 3 Flowchart for the
management of acute
cholecystitis: TG13
53
Diagnosis and
Severity
Assessment by
TG13
Guidelines
Grade I
(Mild)
Grade II
(Moderate)
Treatment According to Grade and According to Response
Observation
Antibiotics
and General
Supportive Care
Antibiotics
and General
Supportive Care
Early LC
Advanced laparoscopic
technique
available
Emergency
Surgery
Successful therapy
Failure
therapy
Grade III
(Severe)
Antibiotics
and General
Organ Support
Delayed/
Elective
LC
Urgent/early
GB drainage
LC: laparoscopic cholecystectomy, GB: gallbladder

Performance of a blood culture should be taken into consideration before initiation of administration of
antibiotics.
A bile culture should be performed during GB drainage.
cholecystectomy may be performed after the improvement

of acute illness has been achieved by gallbladder drainage.
Biliary Association, Japan Society for Surgical Infection, and the
Japanese Society of Hepato-Biliary-Pancreatic Surgery, which provided us with great support and guidance in the preparation of the
Guidelines.
None.
References
1. Miura F, Takada T, Kawarada Y, Nimura Y, Wada K, Hirota M,
et al. Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines. J Hepatobiliary
Pancreat Surg. 2007;14:2734. (clinical practice guidelines:
CPGs).
2. Charcot M. De la fievre hepatique symptomatiquecomparaison
avec la fievre uroseptique. Paris: Bourneville et Sevestre; 1877.
3. Boey JH, Way LW. Acute cholangitis. Ann Surg. 1980;191:
26470.
Surg. 1992;79:6558.
treatment of acute suppurative cholangitis. Am J Surg.
1976;131:52732.
Surg. 1982;117:43741.
7. Reynolds BM, Dargan EL. Acute obstructive cholangitis; a distinct clinical syndrome. Ann Surg. 1959;150:299303.

2007;14:528. (clinical practice guidelines: CPGs).
Pancreat Sci. 2012;19:54856.
Sci. 2012;19:55765.
11. Abboud PA, Malet PF, Berlin JA, Staroscik R, Cabana MD,
Clarke JR, et al. Predictors of common bile duct stones prior to
cholecystectomy: a meta-analysis. Gastrointest Endosc. 1996;44:
4505.
12. Rosen CL, Brown DF, Chang Y, Moore C, Averill NJ, Arkoff LJ,
et al. Ultrasonography by emergency physicians in patients with
suspected cholecystitis. Am J Emerg Med. 2001;19:326.
13. Kendall JL, Shimp RJ. Performance and interpretation of focused
right upper quadrant ultrasound by emergency physicians.
J Emerg Med. 2001;21:713.
14. Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT,
Marshall JC, Bion J, et al. The Surviving Sepsis Campaign:
results of an international guideline-based performance
improvement program targeting severe sepsis. Crit Care Med.
2010;38:36774.
15. Ferrer R, Artigas A, Levy MM, Blanco J, Gonzalez-Diaz G,
Garnacho-Montero J, et al. Improvement in process of care and
outcome after a multicenter severe sepsis educational program in
Spain. JAMA. 2008;299:2294303.
16. El Solh AA, Akinnusi ME, Alsawalha LN, Pineda LA. Outcome
of septic shock in older adults after implementation of the sepsis
bundle. J Am Geriatr Soc. 2008;56:2728.
17. Nguyen HB, Corbett SW, Steele R, Banta J, Clark RT, Hayes SR,
et al. Implementation of a bundle of quality indicators for the
early management of severe sepsis and septic shock is associated
with decreased mortality. Crit Care Med. 2007;35:110512.
123
54
18. Eskelinen M, Ikonen J, Lipponen P. Diagnostic approaches in
acute cholecystitis; a prospective study of 1333 patients with
acute abdominal pain. Theor Surg. 1993;8:1520.
19. Staniland JR, Ditchburn J, De Dombal FT. Clinical presentation
of acute abdomen: study of 600 patients. Br Med J. 1972;3:
3938.
20. Trowbridge RL, Rutkowski NK, Shojania KG. Does this patient
have acute cholecystitis? JAMA. 2003;289:806.
2007;14:7882. (clinical practice guidelines: CPGs).
22. Ralls PW, Halls J, Lapin SA, Quinn MF, Morris UL, Boswell W.
Prospective evaluation of the sonographic Murphy sign in suspected acute cholecystitis. J Clin Ultrasound. 1982;10:1135.
23. Soyer P, Brouland JP, Boudiaf M, Kardache M, Pelage JP, Panis
Y, et al. Color velocity imaging and power Doppler sonography
of the gallbladder wall: a new look at sonographic diagnosis of
acute cholecystitis. AJR Am J Roentgenol. 1998;171:1838.
24. Indar AA, Beckingham IJ. Acute cholecystitis. BMJ. 2002;325:
63943.
25. Law C, Tandan V. Gallstone disease: surgical treatment. In:
Based Evidence, editor. Gastroenterology and hepatology. London: BMJ Books; 1999. p. 26070.
26. Cameron IC, Chadwick C, Phillips J, Johnson AG. Acute cholecystitisroom for improvement? Ann R Coll Surg Engl.
2002;84:103.
27. Noble VE, Liteplo AS, Nelson BP, Thomas SH. The impact of
analgesia on the diagnostic accuracy of the sonographic Murphys sign. Eur J Emerg Med. 2010;17:803.
28. Akriviadis EA, Hatzigavriel M, Kapnias D, Kirimlidis J, Markantas A, Garyfallos A. Treatment of biliary colic with diclofenac: a randomized, double-blind, placebo-controlled study.
123

29. Kumar A, Deed JS, Bhasin B, Thomas S. Comparison of the
effect of diclofenac with hyoscine-N-butylbromide in the symptomatic treatment of acute biliary colic. Aust NZ J Surg.
2004;74:5736.
30. Goldman G, Kahn PJ, Alon R, Wiznitzer T. Biliary colic treatment and acute cholecystitis prevention by prostaglandin inhibitor. Dig Dis Sci. 1989;34:80911.
31. Sugiyama M, Tokuhara M, Atomi Y. Is percutaneous cholecystostomy the optimal treatment for acute cholecystitis in the very
elderly? World J Surg. 1998;22:45963.
32. Chopra S, Dodd GD 3rd, Mumbower AL, Chintapalli KN,
Schwesinger WH, Sirinek KR, et al. Treatment of acute cholecystitis in non-critically ill patients at high surgical risk: comparison of clinical outcomes after gallbladder aspiration and after
percutaneous cholecystostomy. AJR Am J Roentgenol.
2001;176:102531.
Pancreat Sci. 2012;19:57885.
34. Inui K, Nakazawa S, Naito Y, Kimoto E, Yamao K. Nonsurgical
treatment of cholecystolithiasis with percutaneous transhepatic
cholecystoscopy. Am J Gastroenterol. 1988;83:11247.
35. Boland GW, Lee MJ, Mueller PR, Dawson SL, Gaa J, Lu DS, et al.
Gallstones in critically ill patients with acute calculous cholecystitis treated by percutaneous cholecystostomy: nonsurgical
therapeutic options. AJR Am J Roentgenol. 1994;162:11013.
36. Majeed AW, Reed MW, Ross B, Peacock J, Johnson AG. Gallstone removal with a modified cholecystoscope: an alternative to
cholecystectomy in the high-risk patient. J Am Coll Surg.
1997;184:27380.
37. Shirai Y, Tsukada K, Kawaguchi H, Ohtani T, Muto T, Hatakeyama K. Percutaneous transhepatic cholecystostomy for acute
acalculous cholecystitis. Br J Surg. 1993;80:14402.

DOI 10.1007/s00534-012-0562-2
GUIDELINE

TG13 management bundles for acute cholangitis and cholecystitis

Kohji Okamoto Tadahiro Takada Steven M. Strasberg Joseph S. Solomkin Henry A. Pitt
O. James Garden Markus W. Buchler Masahiro Yoshida Fumihiko Miura Yasutoshi Kimura
Ryota Higuchi Yuichi Yamashita Toshihiko Mayumi Harumi Gomi Shinya Kusachi Seiki Kiriyama
Masamichi Yokoe Wan-Yee Lau Myung-Hwan Kim

Abstract Bundles that define mandatory items or procedures to be performed in clinical practice have been
increasingly used in guidelines in recent years. Observance
of bundles enables improvement of the prognosis of target
diseases as well as guideline preparation. There were no
bundles adopted in the Tokyo Guidelines 2007, but the
updated Tokyo Guidelines 2013 (TG13) have adopted this
useful tool. Items or procedures strongly recommended in
clinical practice have been prepared in the practical
guidelines and presented as management bundles. TG13
defined the mandatory items for the management of acute
cholangitis and acute cholecystitis. Critical parts of the
bundles in TG13 include diagnostic process, severity
assessment, transfer of patients if necessary, therapeutic

approach, and time course. Their observance should
improve the prognosis of acute cholangitis and cholecystitis. When utilizing TG13 management bundles, further
clinical research needs to be conducted to evaluate the
effectiveness and outcomes of the bundles. It is also
expected that the present report will lead to evidence
construction and contribute to further updating of the
Tokyo Guidelines.
K. Okamoto (&)
4-18-1 Nishihon-machi, Yahatahigashi-ku, Kitakyushu,
Fukuoka 805-8534, Japan
e-mail: kohji.okamot@gmail.com
M. W. Buchler
Heidelberg, Germany
T. Takada F. Miura
Tokyo, Japan
S. M. Strasberg
J. S. Solomkin
H. A. Pitt
O. J. Garden
Keywords
Cholangitis bundle Cholecystitis bundle
M. Yoshida
Y. Kimura
Sapporo, Japan
R. Higuchi
Y. Yamashita
T. Mayumi
123
56
Introduction
A bundle is a group of therapies for a disease that, when
implemented together, may result in better outcomes than
if implemented individually. In recent years, bundles that
define mandatory items or procedures to be performed in
clinical practice have been increasingly used in guidelines
[1]. Compliance with bundles results in the preparation of
guidelines as well as an improved prognosis of targeted
diseases arising from the use of the guidelines [2, 3]. Levy
et al. [4] reported that data from 15,022 subjects at 165
sites were analyzed to determine compliance with bundle
targets and association with hospital mortality, and compliance with the entire resuscitation bundle increased linearly from 10.9 % in the first site quarter to 31.3 % by the
end of 2 years. Furthermore the odds ratio for mortality
improved the longer a site was in the Surviving Sepsis
Campaign, resulting in an adjusted absolute drop of 0.8 %
per quarter and 5.4 % over 2 years.
Murata et al. [5, 6] examined a total of 60,842 patients
with acute cholangitis using the Japanese national administrative database. This report demonstrated the improved
prognosis of in-hospital mortality with odds ratio of 0.856
among patients who were managed with high compliance
with the items of recommendation Grades A and B in Tokyo
Guidelines 2007 (TG07) as compared with the patients who
were low-compliance. This shows the importance of preparing bundles by setting the recommended items to be
observed in the guidelines. Although TG07 did not prepare
bundles at that time, the updated Tokyo Guidelines 2013
(TG13) have adopted the management bundles for acute
cholangitis and cholecystitis. The care bundles are designed
H. Gomi
Tochigi, Japan
S. Kusachi
S. Kiriyama
Ogaki, Japan
M. Yokoe
General Internal Medicine Nagoya Daini Red Cross Hospital,
Nagoya, Japan
W.-Y. Lau
Shatin, Hong Kong
M.-H. Kim
123
to be easily achievable and sustainable both to implement

and to audit.
Furthermore, we made a checklist. We hope to use the
acute cholangitis and cholecystitis bundle checklist to help
track your organizations compliance with implementing
each element of these bundles.
Efficacy of the bundle

In the process of developing TG13, mandatory items or
procedures to be included in the management bundles have
been discussed and defined among the Tokyo Guidelines
Revision Committee members. The bundles have been
developed and finalized by obtaining consensus. Based on
the recommendations in TG13, items which are expected to
yield favorable treatment results are included in the bundles. To underscore the time course or timing of the performance of each item, management bundles for acute
cholangitis and cholecystitis have been developed. A
checklist has also been prepared to confirm compliance
with the bundles.
The bundles such as sepsis bundle [79], ventilator
bundle [10, 11] or central line bundle [12], when implemented together, may result in better outcomes than if
implemented individually. Good prognosis is also reported
in cases in which a bundle has been achieved, but this
may show that those cases which have achieved a bundle
are in such good condition as to enable achievement of a
bundle.
However, the improvement in prognosis in patients
achieved through education concerning bundles demonstrates that implementation of bundles and education concerning them have been useful [9, 13].
Controversial points and harmful effects of bundles

There are many problems to be solved for the spread and
implementation of bundles. In the guidelines, even if useful
items have been implemented, the prognosis in patients is
not improved without common knowledge of management
bundles among medical care workers [13]. Furthermore, it
is not possible to put bundles into practice without sufficient manpower and equipment [14], which should be
improved, if possible. If improvement is impossible, an
alternative treatment should be provided or patients should
be transferred to a medical facility where the contents of
bundles can be put into practice [15].
There is also a concern that bundles are used not for the
purpose of improving the prognosis in patients and
increasing efficiency, but for limiting the contents of
medical care to keep health care costs down. Furthermore,
failure to carry out the contents of bundles should not lead

to lawsuits [15].
57

Revision Committee members. The diagnostic criteria and
the severity assessment of acute cholangitis in TG13 was
made based on the article of Kiriyama et al. [16].
Acute cholangitis management bundle (Table 1)

Items in the cholangitis management bundle are described
in Table 1. The content of every bundle is developed from
the recommendation of TG13. The mandatory items or
Acute cholecystitis management bundle (Table 2)

Items in the cholecystitis management bundle are described
in Table 2. The content of every bundle is classified into
Table 1 Management bundle of acute cholangitis

1.
When acute cholangitis is suspected, diagnostic assessment is made using TG13 diagnostic criteria every 612 h
2.
Abdominal X-ray (KUB) and abdominal US are carried out, followed by CT scan, MRI, MRCP and HIDA scan
3.
Severity is repeatedly assessed using severity assessment criteria; at diagnosis, within 24 h after diagnosis, and during the time zone of
2448 h
4.
As soon as a diagnosis has been made, the initial treatment is provided. The treatment is as follows: sufficient fluids replacement,
electrolyte compensation, and intravenous administration of analgesics and full dose of antimicrobial agents are provided
5.
For patients with Grade I (mild), when no response to the initial treatment is observed within 24 h, biliary tract drainage is carried out
immediately
6.
For patients with Grade II (moderate), biliary tract drainage is immediately performed along with the initial treatment. If early drainage
cannot be performed due to the lack of facilities or skilled personnel, transfer of the patient is considered
7.
For patients with Grade III (severe), urgent biliary tract drainage is performed along with the initial treatment and general supportive care.
If urgent drainage cannot be performed due to the lack of facilities or skilled personnel, transfer of the patient is considered
8.
For patient with Grade III (severe), organ supports (noninvasive/invasive positive pressure ventilation, use of vasopressors and
antimicrobial agents, etc.) are immediately performed
9.
Blood culture and/or bile culture is performed for Grade II (moderate) and III (severe) patients
10.
Treatment for etiology of acute cholangitis with endoscopic, percutaneous, or operative intervention is considered once acute illness has
resolved. Cholecystectomy should be performed for cholecystolithiasis after acute cholangitis has resolved
KUB kidneyureterbladder, US ultrasonography, CT computed tomography, MRI magnetic resonance imaging, MRCP magnetic resonance
cholangiopancreatography, HIDA hepatobiliary iminodiacetic acid
Table 2 Management bundle of acute cholecystitis
1.
When acute cholecystitis is suspected, diagnostic assessment is made using TG13 diagnostic criteria every 612 h
2.
Abdominal US is carried out, followed by HIDA scan and CT scan if needed to make the diagnosis
3.
Severity is repeatedly assessed using severity assessment criteria; at diagnosis, within 24 h after diagnosis, and during the time zone of
2448 h
4.
Take that cholecystectomy is performed into consideration, as soon as a diagnosis has been made, the initial treatment takes place involving the
replacement of sufficient fluid after fasting, electrolyte compensation, intravenous injection of analgesics and full dose antimicrobial agents
5.
For patients with Grade I (mild), cholecystectomy at an early stage within 72 h of onset of symptoms is recommended
6.
If conservative treatment patients with Grade I (mild) is selected and no response to the initial treatment is observed within 24 h, reconsider
early cholecystectomy if still within 72 h of onset of symptoms or biliary tract drainage
7.
For patients with Grade II (moderate), perform immediate biliary drainage or drainage if no early improvement (or cholecystectomy in
experienced centers) along with the initial treatment
8.
For patients with Grade II (moderate) and III (severe) at high surgical risk, biliary drainage is immediately carried out
9.
Blood culture and/or bile culture is performed for Grade II (moderate) and III (severe) patients
10.
Among patients with Grade II (moderate), for those with serious local complications including biliary peritonitis, pericholecystic abscess,
liver abscess or for those with gallbladder torsion, emphysematous cholecystitis, gangrenous cholecystitis, and purulent cholecystitis,
emergency surgery is conducted (open or laparoscopic depending on experience) along with the general supportive care of the patient. If
surgery cannot be performed due to the lack of facilities or skilled personnel, transfer of the patient is considered
11.
For patients with Grade III (severe) with jaundice and those in poor general conditions, emergency gallbladder drainage is considered with
initial therapy with antibiotics and general support measures. For patients who are found to have gallbladder stones during biliary
drainage, cholecystectomy is performed at after 3 month interval after the patients general conditions are improved
US ultrasonography, CT computed tomography, HIDA hepatobiliary iminodiacetic acid
123
58
Table 3 Acute cholangitis bundle checklist

h
Repeat diagnosis every 612 h
Diagnostic imaging X-ray (KUB), US, CT scan, MRI, MRCP,

HIDA scan
Severity assessment at diagnosis and within 24 h after a

diagnosis
Repeat severity assessment every 24 h
Immediately start antibiotics administration and general

supportive care
Grade I (mild): carry out biliary drainage when no symptom

improvement is observed within 24 h
Grade II (moderate): carry out biliary drainage immediately
Grade III (severe): conduct emergency biliary drainage and

perform organ support
Consider transfer when procedures are unavailable as above
h
h
Grade II (moderate) and III (severe): blood culture and bile

culture
Consider surgical procedures to remove causes after biliary

drainage and improvement of organ failure
the recommendation of TG13. The mandatory items or

Revision Committee members. The diagnostic criteria and
the severity assessment of acute cholecystitis in TG13 was
made based on the article of Yokoe et al. [17].
Check list for the use of management bundles for acute

cholangitis and cholecystitis (Tables 3, 4)
A check list is shown for the effective use of bundles. The
use of this list for medical care ensures standards, and is
thought to improve effectiveness of the bundles. These
check lists, including procedures, laboratories, monitoring
and interventions required, should be placed by the
bedside.
Conclusions
Table 4 Acute cholecystitis bundle checklist
h
Repeat a diagnosis every 612 h
Diagnostic imaging US, HIDA scan and CT scan
Severity assessment at diagnosis and within 24 h after

diagnosis
Repeat severity assessment every 24 h
Immediately initiate antibiotics administration and general

supportive care
Grade I (mild): Cholecystectomy at an early stage within 72 h of

onset of symptoms
Conservative treatment for Grade I (mild): Worsening condition

or no improvement is in condition observed within 24 h.
Reconsider early cholecystectomy if still within 72 h or biliary
drainage (cholecystostomy)
Grade II (moderate): Immediate biliary drainage or drainage if no

early improvement (or cholecystectomy in experienced centers)
along with the initial treatment*
After drainage treatment for Grade II (moderate): Elective

cholecystectomy after symptom improvement at after 3 month
interval
Poor local control** for Grade II (moderate): Emergency abdominal

drainage and/or cholecystectomy in experienced centers
Grade II (moderate) and III (severe) at high surgical risk:

Immediately biliary drainage
Grade II (moderate) and III (severe): Blood culture and/or bile

culture
Grade III (severe): Initiate therapy with antibiotics and general

support measures. Conduct emergency biliary drainage as soon
as stable
After drainage treatment for Grade III (severe): Elective

cholecystectomy after symptom improvement at after 3 month
interval
Consider transfer when procedures are unavailable as above
* see bundle No.4

**see bundle No.10
123
Bundles consist of important items for the effective use of

TG13. Compliance with the bundles is expected to improve
the prognosis of acute cholangitis and acute cholecystitis.
Reports from various facilities have demonstrated that
improved prognosis is expected through the use of the
Tokyo Guidelines for acute cholangitis and cholecystitis.
Furthermore, good use of those reports will contribute to
evidence construction and future revision of TG13.
the following organizations for their great support and guidance in the
preparation of TG13: Japanese Society for Abdominal Emergency
Medicine, Japan Biliary Association, Japan Society for Surgical
Infection, and the Japanese Society of Hepato-Biliary-Pancreatic
Surgery.
None.
References
1. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM,
Jaeschke R, et al. Surviving sepsis campaign: international
guidelines for management of severe sepsis and septic shock. Crit
Care Med. 2008;36:296327.
2. Daniels R, Nutbeam T, McNamara G, Galvin C. The sepsis six
and the severe sepsis resuscitation bundle: a prospective observational cohort study. Emerg Med J. 2011;28:50712.
3. Benneyan JC, Taseli A. Exact and approximate probability distributions of evidence-based bundle composite compliance measures. Health Care Manag Sci. 2010;13:193209.
4. Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, et al. The Surviving Sepsis Campaign: results of an
international guideline-based performance improvement program
targeting severe sepsis. Intensive Care Med. 2010;36:22231.
5. Murata A, Matsuda S, Kuwabara K, Fujino Y, Kubo T, Fujimori
K, et al. Evaluation of compliance with the Tokyo Guidelines for
6.
7.
8.
9.
10.
the management of acute cholangitis based on the Japanese

administrative database associated with the Diagnosis Procedure
Combination system. J Hepatobiliary Pancreat Sci. 2011;18:539.
Murata A, Matsuda S, Kuwabara K, Fujino Y, Kubo T, Fujimori
K, et al. An observational study using a national administrative
database to determine the impact of hospital volume on compliance with clinical practice guidelines. Med Care. 2011;49:
31320.
Gao F, Melody T, Daniels DF, Giles S, Fox S. The impact of
compliance with 6-hour and 24-hour sepsis bundles on hospital
mortality in patients with severe sepsis: a prospective observational study. Crit Care. 2005;9:R76470.
Nguyen HB, Corbett SW, Steele R, Banta J, Clark RT, Hayes SR,
et al. Implementation of a bundle of quality indicators for the
early management of severe sepsis and septic shock is associated
with decreased mortality. Crit Care Med. 2007;35:1012105.
Ferrer R, Artigas A, Levy MM, Blanco J, Gonzalez-Daz G,
Garnacho-Montero J, et al. Improvement in process of care and
outcome after a multicenter severe sepsis educational program in
Spain. JAMA. 2008;299:2294303.
Galpern D, Guerrero A, Tu A, Fahoum B, Wise L. Effectiveness
of a central line bundle campaign on line-associated infections in
the intensive care unit. Surgery. 2008;144:4925.
59
11. Berriel-Cass D, Adkins FW, Jones P, Fakih MG. Eliminating
nosocomial infections at Ascension Health. Jt Comm J Qual
Patient Saf. 2006;32:61220.
12. Crocker C, Kinnear W. Weaning from ventilation: does a care
bundle approach work? Intensive Crit Care Nurs. 2008;24:1806.
13. De Miguel-Yanes JM, Andueza-Lillo JA, Gonzalez-Ramallo VJ,
Pastor L, Munoz J. Failure to implement evidence-based clinical
guidelines for sepsis at the ED. Am J Emerg Med. 2006;24:
5539.
14. McNeill G, Dixon M, Jenkins P. Can acute medicine units in the
UK comply with the Surviving Sepsis Campaigns six-hour care
bundle? Clin Med. 2008;8:1635.
15. Mayumi T, Takada T, Hirata K, Yoshida M, Sekimoto M, Hirota
M, et al. Pancreatitis bundles. J Hepatobiliary Pancreat Sci.
2010;17:879.
Pancreat Sci. 2012;19:54856.
Pancreat Sci. 2012;19:57885.
123

DOI 10.1007/s00534-012-0572-0
GUIDELINE

TG13 antimicrobial therapy for acute cholangitis and cholecystitis

Harumi Gomi Joseph S. Solomkin Tadahiro Takada Steven M. Strasberg Henry A. Pitt Masahiro Yoshida
Shinya Kusachi Toshihiko Mayumi Fumihiko Miura Seiki Kiriyama Masamichi Yokoe Yasutoshi Kimura
Ryota Higuchi John A. Windsor Christos Dervenis Kui-Hin Liau Myung-Hwan Kim

Abstract Therapy with appropriate antimicrobial agents

is an important component in the management of patients
with acute cholangitis and/or acute cholecystitis. In the
updated Tokyo Guidelines (TG13), we recommend antimicrobial agents that are suitable from a global perspective
for management of these infections. These recommendations focus primarily on empirical therapy (presumptive
therapy), provided before the infecting isolates are identified. Such therapy depends upon knowledge of both local
microbial epidemiology and patient-specific factors that
affect selection of appropriate agents. These patient-specific factors include prior contact with the health care
system, and we separate community-acquired versus
healthcare-associated infections because of the higher risk
H. Gomi (&)
3311-1, Yakushiji, Shimotsuke, Tochigi 329-0431, Japan
e-mail: hgomi-oky@umin.ac.jp
S. Kiriyama
Ogaki, Japan
J. S. Solomkin
Department of Surgery, University of Cincinnati
College of Medicine, Cincinnati, OH, USA
T. Takada F. Miura
Tokyo, Japan
S. M. Strasberg
H. A. Pitt
M. Yoshida
S. Kusachi
Department of Surgery, Toho University Medical Center
Ohashi Hospital, Tokyo, Japan
T. Mayumi
123
M. Yokoe
Nagoya, Japan
Y. Kimura
Sapporo, Japan
R. Higuchi
J. A. Windsor
C. Dervenis
First Department of Surgery, Agia Olga Hospital,
Athens, Greece
K.-H. Liau
M.-H. Kim
of resistance in the latter. Selection of agents for community-acquired infections is also recommended on the basis
of severity (grades IIII).
Antimicrobial therapy Treatment guidelines Biliary tract
infection
Introduction
Acute cholangitis and cholecystitis are common conditions
that may result in progressively severe infection, particularly in debilitated hosts. Epidemiology and risk factors for
acute cholangitis and cholecystitis are provided in a separated section of TG13: Current terminology, etiology, and
epidemiology of acute cholangitis and cholecystitis. The
primary goal of antimicrobial therapy in acute cholangitis
and cholecystitis is to limit both the systemic septic
response and local inflammation, to prevent surgical site
infections in the superficial wound, fascia, or organ space,
and to prevent intrahepatic abscess formation [1].
In acute cholangitis, drainage of the obstructed biliary
tree (termed source control) was recognized as the mainstay
of therapy long before the introduction of antimicrobial
agents [1]. An additional role of antimicrobial therapy,
allowing delay in operation until patients are more physiologically stable, was initially defined by Boey and Way [2].
They retrospectively reviewed 99 consecutive patients with
acute cholangitis, and reported that 53 % of their patients
who responded well to antimicrobial therapy were therefore
given elective instead of emergency operation [1, 2].
The role of antimicrobial therapy in the broad range of
diseases subsumed under the term acute cholecystitis
also varies with severity and pathology. In early and nonsevere cases, it is not obvious that bacteria play a significant role in the pathology encountered. In these patients,
antimicrobial therapy is at best prophylactic, preventing
progression to infection. In other cases, with clinical findings of a systemic inflammatory response, antimicrobial
therapy is therapeutic, and treatment may be required until
the gallbladder is removed.
Rationale for changes in these guidelines
Five years have passed since the Tokyo Guidelines were
published in 2007, and it is now referred to as TG07 [3, 4].
During the last five years, there have been several developments in the management of biliary tract infections. For
antimicrobial therapy, other guideline sources for biliary tract
infections have been revised. These include the Surviving
61
Sepsis Campaign 2008 [5] and treatment guidelines for

complicated intra-abdominal infections developed by the
Surgical Infection Society of North America (SIS-NA) and
the Infectious Diseases Society of America (IDSA) 2010 [6].
Additionally, new agents and dosing regimens have been
approved, including higher dose regimens for piperacillin/
tazobactam, meropenem, levofloxacin and doripenem. The
issues of pharmacokinetics and pharmacodynamics of antimicrobial agents have been clarified [3, 4]. Since the release
of TG07 [3, 4], the emergence of antimicrobial resistance
among clinical isolates of Enterobacteriaceae from patients
with community-acquired intra-abdominal infections has
been more widely reported [714]; in particular, antimicrobial resistance in Gram-negative bacilli driven by the
appearance of extended-spectrum b-lactamases (ESBL) and
carbapenemases (i.e., metallo-b-lactamase and non-metallob-lactamase) [1519]. Finally, in the updated Tokyo
Guidelines (TG13), both the diagnostic and severity criteria
for acute cholangitis and cholecystitis have been revised and
recommendations for antimicrobial therapy are reconsidered
against this new structure.
There are new topics dealt with in these guidelines. We
now make specific recommendations for antimicrobial
therapy of healthcare-associated biliary infections. This
was prompted by recognition of the increasing number of
elderly patients with multiple medical problems exposed to
the health care system and thereby being at risk of
acquiring resistant organisms [14]. In addition, there are
several agents that are no longer recommended by the SISNA/IDSA 2010 guidelines [6]. We also clarify concerns
regarding the importance (or lack thereof) of biliary penetration. We also now address prophylaxis for elective
endoscopic retrograde cholangiopancreatography (ERCP).
Background
The bacteria commonly found in biliary tract infections are
well known, and are presented in Tables 1 and 2 [3, 4, 2031].
Antimicrobial therapy largely depends on local antimicrobial susceptibility data. In the international guidelines for
acute cholangitis and cholecystitis (TG13), a framework for
selecting antimicrobial agents will be provided, with classbased definitions of appropriate therapy. Listed agents in
the guideline are appropriate for use, and recommendations
for modification based upon the local microbiological
findings, referred to as antibiogram, are made.
Decision process
A systematic literature review was performed using PubMed from January 1, 2005 to May 15, 2012. All references
were searched with the keywords Acute cholangitis
AND Antibiotics OR Antimicrobial therapy, and Acute
123
62
Table 1 Common microorganisms isolated from bile cultures among

patients with acute biliary infections
Isolated microorganisms
from bile cultures
Proportions of isolated
organisms (%)
Gram-negative organisms
Escherichia coli
3144
Klebsiella spp.
Pseudomonas spp.
920
0.519
Enterobacter spp.
59
Acinetobacter spp.
Citrobacter spp.
Gram-positive organisms
Enterococcus spp.
334
Streptococcus spp.
210
Staphylococcus spp.
0a
Anaerobes
420
Others
Clinical questions
The data are from references [3, 2027, 30]

a
A recent study by Salvador et al. [27] reported none from bile
cultures, while a study by Sung et al. [14] reported 3.6 % from blood
cultures among community-acquired (2 %) and healthcare-associated
(4 %) bacteremic acute biliary infections
Table 2 Common isolates from patients with bacteremic biliary tract
infections
Isolated microorganisms
from blood cultures
Proportions of isolates (%)

Communityacquired
infectionsa
Healthcareassociated
infectionsb
Escherichia coli
3562
23
Klebsiella spp.
1228
16
Pseudomonas spp.
414
17
Gram-negative organisms
Enterobacter spp.
27
Acinetobacter spp.
Citrobacter spp.
26
Gram-positive organisms
Enterococcus spp.
1023
Streptococcus spp.
Staphylococcus spp.
69
2
5
4
Anaerobes
Others
17
11
The data are from references [14, 2830]
The data are from reference [14]
20
cholecystitis AND Antibiotics OR Antimicrobial therapy among human studies. Sixty-five and 122 articles
were found, respectively. These references were further
narrowed using keywords Clinical trials and Randomized trials. Literature cited in the TG07 was also
reviewed and integrated for revision. If there were few data
123
and few new developments on clinical questions addressed

since 2005, a consensus process was used by the members
of the Tokyo Guidelines Revision Committee after consultations with internationally recognized experts.
The structure of recommendations for selecting antimicrobial agents has been revised. Antimicrobial agents
appropriate for initial therapy (empirical therapy or presumptive therapy) for various grades of severity of biliary
tract infections have been developed. Table 3 lists antimicrobial agents appropriate for use for the treatment of
patients with both community-acquired and healthcareassociated cholangitis and cholecystitis.
Clinically relevant questions are provided with brief

answers and explanations below.
Q1. What specimen should be sent for culture to identify the causative organisms in acute cholangitis and
cholecystitis?
Bile cultures should be obtained at the beginning of any
procedure performed. Gallbladder bile should be sent for
culture in all cases of acute cholecystitis excepting those
with grade I severity (recommendation 1, level C).
We suggest cultures of bile and tissue when perforation,
emphysematous changes, or necrosis of gallbladder are
noted during cholecystectomy (recommendation 2,
level D).
Blood cultures are not routinely recommended for
grade I community-acquired acute cholecystitis
Identifying the causative organism(s) is an essential step

in the management of acute biliary infections. Positive
rates of bile cultures range from 59 to 93 % for acute
cholangitis [3, 4, 2027], and positive rates of either bile or
gallbladder cultures range from 29 to 54 % for acute
cholecystitis [3, 4, 2027]. In a recent study which utilized
the TG07 diagnostic classification, positive rates of bile
cultures among patients with cholangitis were 67 % (66 of
98 patients) and 33 % (32 of 98) without [27]. Table 1
shows common microbial isolates from bile cultures
among patients with acute biliary infections [3, 4, 2027].
Common duct bile should be sent for culture in all cases of
suspected cholangitis.
On the other hand, previous studies indicated that positive rates of blood cultures among patients with acute cholangitis ranged from 21 to 71 % [3]. For acute cholecystitis,
the prevalence of positive blood cultures is less than acute
cholangitis, and in the last two decades it has been reported
Moxifloxacin
Moxifloxacin
Aztreonam metronidazoled
Aztreonam metronidazolec
Imipenem/cilastatin,
meropenem, doripenem,
ertapenem
Cefepime, or ceftazidime, or
cefozopran metronidazoled
Piperacillin/tazobactam
Healthcare-associated
Imipenem/cilastatin,
meropenem, doripenem,
ertapenem
Cefepime, or ceftazidime, or
cefozopran metronidazoled
Cholangitis and cholecystitis
Grade IIIe
Ampicillin/sulbactam has little activity left against Escherichia coli. It is removed from the North American guidelines [6]
Local antimicrobial susceptibility patterns (antibiogram) should be considered for use
Moxifloxacin
Ciprofloxacin, or levofloxacin, or
pazufloxacin metronidazolec
Ertapenem
Cefoperazone/sulbactam
Ceftriaxone, or cefotaxime, or
cefepime, or cefozopran, or
ceftazidime metronidazoled
Cholangitis and cholecystitis
Grade II
Healthcare-associated biliary
infectionse
Vancomycin is recommended to cover Enterococcus spp. for grade III community-acquired acute cholangitis and cholecystitis, and healthcare-associated acute biliary infections. Linezolid or
daptomycin is recommended if vancomycin-resistant Enterococcus (VRE) is known to be colonizing the patient, if previous treatment included vancomycin, and/or if the organism is common in
the community
Anti-anaerobic therapy, including use of metronidazole, tinidazole, or clindamycin, is warranted if a biliary-enteric anastomosis is present. The carbapenems, piperacillin/tazobactam,
ampicillin/sulbactam, cefmetazole, cefoxitin, flomoxef, and cefoperazone/sulbactam have sufficient anti-anerobic activity for this situation
Fluoroquinolone use is recommended if the susceptibility of cultured isolates is known or for patients with b-lactam allergies. Many extended-spectrum b-lactamase (ESBL)-producing Gramnegative isolates are fluoroquinolone-resistant
pazufloxacin metronidazoled
pazufloxacin metronidazoled
Fluoroquinolonebased therapyc
Cefmetazole,a Cefoxitin,a
Flomoxef,a Cefoperazone/
sulbactam
Monobactambased therapy
Cefmetazole,a Cefoxitin,a
Flomoxef,a Cefoperazone/
sulbactam
Cefazolina, or cefotiama, or
cefuroximea, or ceftriaxone, or
cefotaxime metronidazoled
Cephalosporinbased therapy
Ertapenem
Cefazolina, or cefotiama, or
cefuroximea, or ceftriaxone, or
cefotaxime metronidazoled
Ampicillin/sulbactamb is not
recommended without an
aminoglycoside
Penicillin-based
therapy
Ertapenem
Ampicillin/sulbactamb is not
recommended without an
aminoglycoside
Cholangitis
Antimicrobial
agents
Carbapenembased therapy
Cholecystitis
Grade I
Severity
Community-acquired biliary infections
Table 3 Antimicrobial recommendations for acute biliary infections

63
123
64
to range from 7.7 to 15.8 % [28, 31]. Table 2 shows the most
recently reported microbial isolates from patients with
bacteremic biliary tract infections [14, 2830].
There is a lack of clinical trials examining the benefit of
blood cultures in patients with acute biliary tract infections.
Most of the bacteremic isolates reported (Table 2) are
organisms that do not form vegetations on normal cardiac
valves nor miliary abscesses. Their intravascular presence
does not lead to an extension of therapy or selection of
multidrug regimens. We therefore recommend such cultures be taken only in high-severity infections when such
results might mandate changes in therapy [5]. Blood cultures are not routinely recommended for grade I community-acquired acute cholecystitis (level D).
The SIS-NA/IDSA 2010 guidelines recommended
against routine blood cultures for community-acquired
intra-abdominal infections, since the results do not change
the management and outcomes [6]. This is in part driven by
a study of the clinical impact of blood cultures taken in the
emergency department [32]. In this retrospective study,
1,062 blood cultures were obtained during the study period,
of which 92 (9 %) were positive. Of the positive blood
cultures, 52 (5 %) were true positive, and only 18 (1.6 %)
resulted in altered management.
Q2. What considerations should be taken when selecting antimicrobial agents for the treatment of acute
cholangitis and cholecystitis?
When selecting antimicrobial agents, targeted organisms,
pharmacokinetics and pharmacodynamics, local antibiogram,
a history of antimicrobial usage, renal and hepatic function,
and a history of allergies and other adverse events
should be considered (recommendation 1, level D).
We suggest anaerobic therapy if a biliary-enteric
anastomosis is present (recommendation 2, level C).
There are multiple factors to consider in selecting

empiric antimicrobial agents. These include targeted
organisms, local epidemiology and susceptibility data
(antibiogram), alignment of in-vitro activity (or spectrum)
of the agents with these local data, characteristics of the
agents such as pharmacokinetics and pharmacodynamics,
and toxicities, renal and hepatic function, and any history of
allergies and other adverse events with antimicrobial agents
[3, 4, 2027]. A history of antimicrobial usage is important
because recent (\6 months) antimicrobial therapy greatly
increases the risk of resistance among isolated organisms.
Before dosing antimicrobial agents, renal function should
be estimated with the commonly used equation: Serum creatinine = (140 age) [optimum body weight (kg)]/
72 9 serum creatinine (mg/dl) [3, 4, 33]. Individual dosage
123
adjustments for altered renal and hepatic function are available in several recent publications [34, 35]. Consultation with
a clinical pharmacist is recommended if there are concerns.
Regarding the timing of therapy, it should be initiated as
soon as the diagnosis of biliary infection is suspected. For
patients in septic shock, antimicrobials should be administered within 1 h of recognition [5]. For other patients, as
long as 4 h may be spent obtaining definitive diagnostic
studies prior to beginning antimicrobial therapy. Antimicrobial therapy should definitely be started before any
procedure, either percutaneous, endoscopic, or operative, is
performed. In addition, anaerobic therapy is appropriate if
a biliary-enteric anastomosis is present (level C) [6].
Selected newer agents
Moxifloxacin has been investigated for intra-abdominal
infections in several randomized studies [3639]. It was
demonstrated that moxifloxacin is safe, well-tolerated, and
non-inferior to the comparators, such as ceftriaxone plus
metronidazole [37], or piperacillin/tazobactam followed by
amoxicillin/clavulanic acid [39]. This study was conducted
prior to the appearance of ESBL-mediated resistance [40].
There are few data specifically regarding the treatment of
acute cholangitis or cholecystitis, and resistance rates of
E. coli and other common Enterobacteriacae to fluoroquinolones have risen [714].
Tigecycline was under clinical trials for approval during
preparation of the manuscript, and is now approved for clinical use in Japan. Tigecycline has in-vitro activity against a
wide range of clinically significant Gram-positive and Gramnegative bacteria [41]. These include multidrug-resistant
Gram-positive cocci such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp.
For Gram-negative bacilli, ESBL-producing Enterobacteriaceae are susceptible, as are most anaerobes. Tigecycline has
no activity against Pseudomonas aeruginosa. Tigecycline has
been investigated for skin and soft tissue infections and
complicated intra-abdominal infections [41]. Tigecycline
causes nausea and vomiting in approximately 1020 % of
patients, and is dose-related. This limits the dose that can be
routinely administered and suggests only a secondary role for
this agent, in the event of unusual pathogens or allergy to
other classes of antimicrobial agents. Recent meta-analyses
have demonstrated an increased mortality rate and treatment
failure rate in randomized trials with this agent [42].
Antimicrobial agents appropriate for use
in the management of community-acquired acute
Table 3 summarizes antimicrobial recommendations. It
should be kept in mind that in the treatment of cholangitis,
source control (i.e., drainage) is an essential part of management. The indications and timing for drainage are
provided in the severity and flowchart of the management
sections regarding acute cholangitis. Since 2005, there
have been no randomized clinical trials of antimicrobial
therapy for community-acquired acute cholangitis and/or
acute cholecystitis. There have been multiple reports on
clinical isolates with multiple drug resistance from intraabdominal infections worldwide, and biliary infections in
particular [714, 40].
Recommendations for antimicrobial therapy are based
primarily upon extrapolations of microbiological efficacy
and behavior of these agents against the more susceptible
isolates treated in the clinical trials cited [3639, 4349].
Some concerns about this approach to defining efficacy
against resistant isolates has been raised [50].
The use of severity of illness as a guide to antimicrobial
agent selection has been questioned in the face of the
increasing numbers of ESBL-producing E. coli and Klebsiella in the community. These organisms are not reliably
susceptible to cephalosporins, penicillin derivatives, or
fluoroquinolones. Previous guidelines have recommended
that if more than 1020 % of community isolates of E. coli
are so resistant, then empiric coverage should be provided
for these organisms until susceptibility data demonstrates
sensitivity to narrower spectrum agents. Carbapenems,
piperacillin/tazobactam, tigecycline, or amikacin may also
be used to treat these isolates [6].
For grade III community-acquired acute cholangitis and
cholecystitis, agents with anti-pseudomonal activities are
recommended as initial therapy (empirical therapy) until
causative organisms are identified. Pseudomonas aeruginosa is present in approximately 20 % of recent series [14,
27], and is a known virulent pathogen. Failure to empirically cover this organism in critically ill patients may result
in excess mortality.
Enterococcus spp. is another important pathogen for
consideration in patients with grade III communityacquired acute cholangitis and cholecystitis. Vancomycin
is recommended to cover Enterococcus spp. for patients
with grade III community-acquired acute cholangitis and/
or cholecystitis, until the results of cultures are available.
Ampicillin can be used if isolated strains of Enterococcus
spp. are susceptible to ampicillin. Ampicillin covers most
of the strains of Enterococcus faecalis from communityacquired infections in general. For Enterococcus faecium,
vancomycin is the drug of choice for empirical therapy.
However, in many hospitals, vancomycin-resistant
Enterococcus spp., both E. faecium and E. faecalis, have
emerged as important causes of infection. Treatment for
these organisms requires either linezolid or daptomycin.
Surgeons and other physicians making treatment decisions
for patients with healthcare-associated infections should be
65
aware of the frequency of these isolates in their hospital

and unit. Then, regarding infrequently isolated anaerobes
such as the Bacteroides fragilis group, we suggest to cover
these organisms empirically when a biliary-enteric anastomosis is present (level C) [6].
For grade I and II community-acquired cholangitis and
cholecystitis, Table 3 shows the agents appropriate for use.
Of note, the intravenous formulation of metronidazole has
not been approved in Japan. As a result, clindamycin is one
of the alternatives where intravenous metronidazole is not
available. Clindamycin resistance among Bacteroides spp.
is significant and the use of clindamycin is no longer recommended in other intra-abdominal infections [6]. Cefoxitin, cefmetazole, flomoxef, and cefoperazone/sulbactam
are the agents in cephalosporins that have activities against
Bacteroides spp. Cefoxitin is no longer recommended by
the SIS-NA/IDSA 2010 guidelines due to the high prevalence of resistance among Bacteroides spp. [6]. Local
availability of agents as well as local susceptibility results
are emphasized when choosing empirical therapy.
Table 4 summarizes antimicrobial agents with high
prevalence of resistance among Enterobacteriaceae [714].
Ampicillin/sulbactam is one of the most frequently used
agents for intra-abdominal infections. Nonetheless, the
activity of ampicillin/sulbactam against E. coli, with or
without ESBLs, has fallen to levels that prevent a recommendation for its use.
In the TG13, ampicillin/sulbactam alone is not recommended as empirical therapy if the local susceptibility is
\80 %. It is reasonable to use ampicillin/sulbactam as
definitive therapy when the susceptibility of this agent is
proven. Ampicillin/sulbactam may be used if an aminoglycoside is combined until susceptibility testing results are
available.
Table 4 Antimicrobial agents with high prevalence of resistance
among Enterobacteriaceae
Antimicrobial class
Antimicrobial agents
Penicillin
Ampicillin/sulbactam
Cephalosporins
Cefazolin
Cefuroxime
Cefotiam
Cefoxitin
Cefmetazole
Flomoxef
Ceftriaxonea or cefotaximea
Fluoroquinolones
Ciprofloxacin
Levofloxacin
Moxifloxacin
References [411]
a
This resistance indicates the global spread of extended-spectrum blactamase (ESBL)-producing Enterobacteriaceae
123
66
Fluoroquinolone use is only recommended if the susceptibility of cultured isolates is known since antimicrobial
resistance has been increasing significantly [714]. This
agent can also be used as an alternative agent for patients
with b-lactam allergies.
Antimicrobial agents appropriate for use
in the management of healthcare-associated acute
There is no evidence to support any agent as optimal
treatment of healthcare-associated acute cholangitis and
cholecystitis. The principles of empirical therapy of healthcare-associated infections include using agents with antipseudomonal activity until definitive causative organisms are
found. This paradigm is now expanded to include empirical
coverage for ESBL-producing Gram-negative organisms
based on local microbiological findings (local antibiogram).
Table 3 shows empirical agents (presumptive therapy) for
healthcare-associated acute cholangitis and cholecystitis.
Vancomycin is recommended when patients are colonized
with resistant Gram-positive bacteria such as methicillinresistant Staphylococcus aureus and/or Enterococcus spp. or
when these multidrug-resistant Gram-positives are of concern. Staphylococcus aureus is not as common an isolate for
acute biliary infections as Enterococcus spp. Vancomycinresistant Enterococcus (VRE) should be covered empirically
with linezolid or daptomycin if this organism is known to be
colonizing the patient, if previous treatment included vancomycin, and/or if the organism is common in the community.
Regarding anaerobes such as the Bacteroides fragilis
group, we suggest to cover these organisms empirically in
the presence of a biliary-enteric anastomosis (level C) [6].
Is it necessary for agents used in acute biliary infections
to be concentrated in bile?
Historically, biliary penetration of agents has been considered in the selection of antimicrobial agents. However, there
is considerable laboratory and clinical evidence that as
obstruction occurs, secretion of antimicrobial agents into bile
stops [1]. Well-designed randomized clinical trials comparing agents with or without good biliary penetration are needed to determine the clinical relevance and significance of
biliary penetration in treating acute biliary infections.
How should highly resistant causative organisms be
managed in treating acute cholangitis and cholecystitis?
The major microbiological phenomenon of the last decade has
been the emergence of novel b-lactamase-mediated resistance
mechanisms in Enterobacteriaceae. These have been seen in
intra-abdominal infections worldwide [719, 27]. These
123
organisms have moved into many communities, and are now

seen increasingly in community-acquired infections such as
cholangitis and cholecystitis. The frequency of ESBLproducing E. coli and Klebsiella spp. has reached the point in
some countries where decisions regarding empirical therapy
must be guided by their prevalence. ESBL-producing E. coli
is highly susceptible to carbapenems and to tigecycline. In
some communities, highly resistant Klebsiella spp. and
E. coli with carbapenemases are now seen [5154]. The
widely accepted rule for empirical therapy is that resistant
organisms occurring in more than 1020 % of patients
should be treated. Colistin is the salvage agent for the above
multidrug-resistant Gram-negative bacilli epidemic strains
[40, 54]. This agent is toxic, dosing is uncertain, and its
use should involve consultation with infectious disease
specialists [40].
In the SIS-NA/IDSA 2010 guidelines [6], antimicrobial
agents as empirical therapy for healthcare-associated
intra-abdominal infections were given. In the guidelines,
carbapenems, piperacillin/tazobactam, and ceftazidime or
cefepime, each combined with metronidazole, have been
recommended when the prevalence of resistant Pseudomonas
aeruginosa, ESBL-producing Enterobacteriaceae, Acinetobacter or other multidrug-resistant Gram-negative bacilli is
less than 20 %. For ESBL-producing Enterobacteriaceae,
carbapenems, piperacillin/tazobactam, and aminoglycosides
are recommended. For Pseudomonas aeruginosa, if the
prevalence of resistance to ceftazidime is more than 20 %,
carbapenems, piperacillin/tazobactam, and aminoglycosides
are recommended. Even with this guide, selecting appropriate
agents for antimicrobial stewardship is often difficult.
Q3. What are the special concerns for communityacquired acute cholecystitis in management with
antimicrobial agents?
When cholecystectomy is performed, antimicrobial therapy
can be stopped within 24 hours since the source of infection
is controlled (recommendation 2, level C).
Grade II or Grade III acute cholecystitis should be treated
with antimicrobial therapy even after cholecystectomy is
performed (recommendation 1, level D).
In patients with pericholecystic abscesses or perforation of
the gallbladder, treatment with an antimicrobial regimen as
listed in Table 3 is recommended. Therapy should be continued
until the patient is afebrile, with a normalized white count,
and without abdominal findings (recommendation 1, level D).
In most cases, cholecystectomy removes the infection,

and little if any infected tissue remains. Under these circumstances, there is no benefit to extending antimicrobial
therapy beyond 24 h.
67
Recent randomized clinical trials for antimicrobial

therapy of acute cholecystitis are limited [43, 4648]. In
these randomized studies, comparisons were made such as
ampicillin plus tobramycin versus piperacillin or cefoperazone, pefloxacin versus ampicillin and gentamicin, and
cefepime versus mezlocillin plus gentamicin [4, 43, 46,
48]. There were no significant differences between the
agents compared. In the TG13, the agents considered as
appropriate therapy, and detailed in Table 3, have all been
utilized in randomized controlled trials of intra-abdominal
infections. These studies included patients with pathologically advanced cholecystitis (abscess or perforation).
Table 3 is provided for both community-acquired and
healthcare-associated acute cholecystitis.
significantly affected the overall management strategies for

at least the last two decades.
In the SIS-NA/IDSA 2010 guidelines, the recommended
duration of antimicrobial therapy for complicated intraabdominal infections is 47 days once the source of infection is controlled [6]. Since there are very few data available
for the duration of either community-acquired or healthcare-associated acute cholangitis and cholecystitis, Table 5
was developed to guide the duration of antimicrobial therapy as expert opinion. When bacteremia with Gram-positive bacteria such as Enterococcus spp. and Streptococcus
spp. is present, it is prudent to offer antimicrobial therapy
for two weeks since these organisms are well known to
cause infective endocarditis.
Antimicrobial therapy after susceptibility testing results

are available
Conversion to oral antimicrobial agents
Once susceptibility testing results of causative microorganisms are available, specific therapy (or definitive therapy) should be offered. This process is called de-escalation
[5]. Agents in Table 4 can be used safely once the susceptibility is proven.
Duration of treatment of patients with clinical
and laboratory success
The optimal duration of antimicrobial therapy for community-acquired and healthcare-associated acute cholangitis
and cholecystitis has not been determined in well-designed
randomized controlled studies. Whether the source of
infection (i.e., biliary obstruction) is well controlled or not is
critical in determining the duration of therapy. In addition,
recent technological advances for biliary drainage have
Patients with acute cholangitis and cholecystitis who can

tolerate oral feeding may be treated with oral therapy [55].
Depending on the susceptibility patterns of the organisms
identified, oral antimicrobial agents such as fluoroquinolones (ciprofloxacin, levofloxacin, or moxifloxacin),
amoxicillin/clavulanic acid, or cephalosporins may also be
used. Table 6 lists commonly used oral antimicrobial agents
with good bioavailabilities.
What is the optimal prophylaxic agent before elective
endoscopic retrograde cholangiopancreatography
(ERCP)?
A Cochrane meta-analysis examining the benefits of antibiotic prophylaxis for elective ERCP has been performed,
and found benefit to the practice [56]. The international
guidelines on prophylaxis with endoscopy indicated that
Table 5 Recommended duration of antimicrobial therapy

Community-acquired biliary infections
Healthcare-associated biliary infections
Severity
Grade I
Diagnosis
Cholecystitis
Cholangitis
Duration of
therapy
Antimicrobial therapy can be

discontinued within 24 h after
cholecystectomy is performed
Once source of infection is controlled,

duration of 47 days is recommended
If perforation, emphysematous changes,

and necrosis of gallbladder are noted
during cholecystectomy, duration of
47 days is recommended
If residual stones or obstruction of the bile tract are present, treatment should be
continued until these anatomical problems are resolved
Specific
conditions
for
extended
therapy
Grade II
Grade III
Cholangitis
and
cholecystitis
Cholangitis
and
cholecystitis
If bacteremia with Gram-positive cocci

such as Enterococcus spp.,
Streptococcus spp. is present, minimum
duration of 2 weeks is recommended
Healthcare-associated cholangitis and

cholecystitis
If bacteremia with Gram-positive cocci
such as Enterococcus spp.,
Streptococcus spp. is present, minimum
duration of 2 weeks is recommended
123
68
Table 6 Representative oral antimicrobial agents for communityacquired and healthcare-associated acute cholangitis and cholecystitis
with susceptible isolates
Table 7 Antimicrobial prophylaxic agents for elective endoscopic

retrograde pancreatocholangiography (ERCP)
Antimicrobial class
Cephalosporins
Cefazolin
Antimicrobial class
Penicillins
Amoxicillin/clavulanic acid
Cefoxitin
Cephalosporins
Cephalexin metronidazolea
Cefmetazole
Fluoroquinolones
Ciprofloxacin or
levofloxacin metronidazolea
Moxifloxacin
Flomoxef
Piperacillina
Penicillins
Piperacillin/tazobactama
Anti-anaerobic therapy, including use of metronidazole, tinidazole,

or clindamycin, is warranted if a biliary-enteric anastomosis is present
prophylaxis with ERCP is recommended [57]. As consensus statements, the guidelines [57] recommended the
standard prophylaxis regimen to prevent infective endocarditis. The regimen includes amoxicillin or clindamycin
orally, or ampicillin or cefazolin as intravenous agents, and
vancomycin for patients with b-lactam allergies to prevent
infective endocarditis. However, the regimens for preventing cholangitis and bacteremia due to obstructive biliary tract were not included.
Recent meta-analyses [56, 58] had conflicting conclusions regarding the effectiveness of prophylactic therapy
before elective ERCP. Bai et al. concluded that prophylaxic
agents cannot prevent cholangitis [58], while a Cochrane
review indicated that prophylaxic antimicrobial therapy
before elective ERCP reduces the incidence of bacteremia
[relative risk (RR) 0.50], cholangitis (RR 0.54), and pancreatitis (RR 0.54) [56]. However, overall mortality was
not reduced with prophylaxis before elective ERCP [RR
1.33, confidence interval (CI) 0.325.44]. In this review,
the numbers needed to treat (NNT) to prevent bacteremia
(NNT = 11) and cholangitis (NNT = 38) were also demonstrated. The Cochrane review concluded that further
studies are needed, including randomized placebocontrolled studies, to investigate the effectiveness of
prophylaxis for elective ERCP with low risk of bias,
randomized comparison of the timing of administration of
prophylaxis (before vs. during or after ERCP), and randomized head-to-head comparison of antimicrobial agents
as prophylactic therapy with elective ERCP [56].
Antimicrobial agents investigated with elective ERCP
include minocycline orally [59], piperacillin [60, 61],
clindamycin plus gentamicin [62], cefuroxime [63], cefotaxime [64, 65], and ceftazidime [66].
In the TG13, antimicrobial prophylactic agents appropriate for use in preventing cholangitis or bacteremia due to
biliary tract obstruction are provided on a consensus basis.
Table 7 lists those agents. Cefazolin or other narrowerspectrum cephalosporins can be used as prophylactic
agents. Cefazolin is one of the agents for preventing
infective endocarditis with endoscopy and a convenient
agent to be used to prevent both endocarditis and
123
Anti-pseudomonal agents
cholangitis. Piperacillin is one of the anti-pseudomonal

agents that have been studied as a prophylactic agent for
elective ERCP [60, 61]. Given the emergence of resistance
among Gram-negative organisms worldwide, including
ESBL-producing strains [714, 27], we recommend antipseudomonal agents such as piperacillin or piperacillin/
sulbactam listed in Table 7.
Use of antibiotic irrigation
There has been continuing interest in irrigation of surgical
fields with antimicrobial agents, and the subject has
recently been reviewed [67]. The authors concluded that
topical antimicrobial agents are clearly effective in reducing wound infections and may be as effective as the use of
systemic antimicrobial agents. The combined use of systemic and topical antimicrobial agents may have additive
effects, but this is lessened if the same agent is used for
both topical and systemic administration.
Conclusions
Antimicrobial agents should be used prudently while promoting antimicrobial stewardship in each institution, local
area, and country. The recent global spread of antimicrobial
resistance gives us warning in current practice. TG13 provides a practical guide for physicians and surgeons who are
involved in the management of community-acquired and
healthcare-associated acute biliary infections. There are still
many areas of uncertainty in this subject. Continuous monitoring of local antimicrobial resistance and further studies
on acute cholangitis and cholecystitis should be warranted.
None.
References
1. van den Hazel SJ, Speelman P, Tytgat GNJ, Dankert J, van
Leeuwen DJ. Role of antibiotics in the treatment and prevention of
acute and recurrent cholangitis. Clin Infect Dis. 1994;19:27986.

2. Beoy JH, Way LW. Acute cholangitis. Ann Surg. 1980;191:
26470.
3. Tanaka A, Takada T, Kawarada Y, Nimura Y, Yoshida M, Miura
F, et al. Antimicrobial therapy for acute cholangitis: Tokyo
Guidelines. J Hepatobiliary Pancreat Surg. 2007;14:5967
(Clinical practice guidelines: CPGs).
4. Yoshida M, Takada T, Kawarada Y, Tanaka A, Nimura Y, Gomi H,
et al. Antimicrobial therapy for acute cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14:8390 (CPGs).
5. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: International
guidelines for management of severe sepsis and septic shock:
2008. Crit Care Med. 2008;36:296327 (CPGs).
EJC, Baron EJ, et al. Diagnosis and management of complicated
intra-abdominal infection in adults and children: Guidelines by
the Surgical Infection Society and the Infectious Diseases Society
of America. Clin Infect Dis. 2010;50:13364 (CPGs).
7. Paterson DL, Rossi F, Baquero F, Hsueh P-R, Woods GL, Satishchandran V, et al. In vitro susceptibilities of aerobic and facultative Gram-negative bacilli isolated from patients with intraabdominal infections worldwide: the 2003 Study for Monitoring
Antimicrobial Resistance Trends (SMART). J Antimicrob Chemother. 2005;55:96573.
8. Rossi F, Baquero F, Hsueh P-R, Paterson DL, Bochicchio GV,
Snyder TA, et al. In vitro susceptibilities of aerobic and facultatively anaerobic Gram-negative bacilli isolated from patients
with intra-abdominal infections worldwide: 2004 results from
SMART (Study for Monitoring Antimicrobial Resistance
Trends). J Antimicrob Chemother. 2006;58:20510.
9. Yang Q, Wang H, Chen M, Ni Y, Yu Y, Hu B, et al. Surveillance
of antimicrobial susceptibility of aerobic and facultative Gramnegative bacilli isolated from patients with intra-abdominal
infections in China: the 20022009 Study for Monitoring Antimicrobial Resistance Trends (SMART). Int J Antimicrob Agents.
2010;36:50712.
10. Hsueh P-R, Badal RE, Hawser SP, Hoban DJ, Bouchillon SK, Ni
Y, et al. Epidemiology and antimicrobial susceptibility profiles of
aerobic and facultative Gram-negative bacilli isolated from
patients with intra-abdominal infections in the Asia-Pacific
region: 2008 results from SMART (Study for Monitoring Antimicrobial Resistance Trends). Int J Antimicrob Agents. 2010;36:
40814.
11. Chen Y-H, Hsueh P-R, Badal RE, Hawser SP, Hoban DJ,
Bouchillon SK, et al. Antimicrobial susceptibility profiles of
aerobic and facultative Gram-negative bacilli isolated from
patients with intra-abdominal infections in the Asia-Pacific region
according to currently established susceptibility interpretive criteria. J Infect. 2011;62:28091.
12. Ishii Y, Tateda K, Yamaguchi K. Evaluation of antimicrobial
susceptibility for b-lactams using the Etest method against clinical isolates from 100 medical centers in Japan (2006). Diagn
Microbiol Infect Dis. 2008;60:17783.
13. Ishii Y, Ueda C, Kouyama Y, Tateda K, Yamaguchi K. Evaluation of antimicrobial susceptibility for b-lactams against clinical
isolates from 51 medical centers in Japan (2008). Diagn Microbiol Infect Dis. 2011;69:4438.
14. Sung YK, Lee JK, Lee KH, Lee KT, Kang C-I. The clinical
epidemiology and outcomes of bacteremic biliary tract infections
caused by antimicrobial-resistant pathogens. Am J Gastroenterol.
2012;107:47383.
15. Paterson DL. Resistance in gram-negative bacteria: Enterobacteriaceae. Am J Infect Control. 2006;34 (5, Supplement):S20S8.
16. Choi SH, Lee J, Park S, Kim MN, Choo E, Kwak Y, et al.
Prevalence, microbiology, and clinical characteristics of
extended-spectrum; beta-lactamase-producing Enterobacter spp.,
69
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
Serratia marcescens, Citrobacter freundii and Morganella morganii in Korea. Eur J Clin Microb Infect Dis. 2007;26:55761.
Kang CI, Cheong H, Chung D, Peck K, Song JH, Oh MD, et al.
Clinical features and outcome of community-onset bloodstream
infections caused by extended-spectrum b-lactamase-producing
Escherichia coli. Eur J Clin Microb Infect Dis. 2008;27:858.
Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F,
Balakrishnan R, et al. Emergence of a new antibiotic resistance
mechanism in India, Pakistan, and the UK: a molecular, biological,
and epidemiological study. Lancet Infect Dis. 2010;10:597602.
Peirano G, van der Bij AK, Gregson DB, Pitout JDD. Molecular
epidemiology over an 11-year period (2000 to 2010) of extendedspectrum b-lactamase-producing Escherichia coli causing bacteremia in a centralized Canadian region. J Clin Microbiol. 2012;
50:2949.
Kune G, Schutz E. Bacteria in the biliary tract. A study of their
frequency and type. Med J Aust. 1974;1:2558.
Csendes A, Fernandez M, Uribe P. Bacteriology of the gallbladder bile in normal subjects. Am J Surg. 1975;129:62931.
Csendes A, Becerra M, Burdiles P, Demian I, Bancalari K, Csendes
P. Bacteriological studies of bile from the gallbladder in patients
with carcinoma of the gallbladder, cholelithiasis, common bile duct
stones and no gallstones disease. Eur J Surg. 1994;160:3637.
Csendes A, Burdiles P, Maluenda F, Diaz J, Csendes P, Mitru N.
Simultaneous bacteriologic assessment of bile from gallbladder
and common bile duct in control subjects and patients with gallstones and common duct stones. Arch Surg. 1996;131:38994.
Csendes A, Mitru N, Maluenda F, Diaz J, Burdiles P, Csendes P,
Pinones E. Counts of bacteria and pyocites of choledochal bile in
controls and in patients with gallstones or common bile duct
stones with or without acute cholangitis. Hepatogastroenterology.
1996;43:8006.
Maluenda F, Csendes A, Burdiles P, Diaz J. Bacteriological study
of choledochal bile in patients with common bile duct stones,
with or without acute suppurative cholangitis. Hepatogastroenterology. 1989;36:1325.
Chang W, Lee K, Wang S, Chuang S, Kuo K, Chen J, Sheen P.
Bacteriology and antimicrobial susceptibility in biliary tract disease: an audit of 10-years experience. Kaohsiung J Med Sci. 2002;
18:2218.
Salvador V, Lozada M, Consunji R. Microbiology and antibiotic
susceptibility of organisms in bile cultures from patients with and
without cholangitis at an Asian Academic Medical Center. Surg
Infect. 2011;12:10511.
Kuo CH CC, Chen JJ, Tai DI, Chiou SS, Lee CM. Septic acute
cholecystitis. Scand J Gastroenterol. 1995;30:2725
Melzer M, Toner R, Lacey S, Bettany E, Rait G. Biliary tract
infection and bacteremia: presentation, structural abnormalities,
causative organisms and clinical outcomes. Postgrad Med J.
2007;83:7736.
Lee CC, Chang IJ, Lai Y-C, Chen S-Y, Chen S-C. Epidemiology and prognostic determinants of patients with bacteremic
cholecystitis or cholangitis. Am J Gastroenterol. 2007;102:5639.
Baitello AL, Colleoni Neto R, Herani Filho B, Cordeiro JA,
Machado AMO, Godoy MF, et al. Prevalencia e fatores associados a` bacteremia nos portadores de colecistite aguda litiasica.
Revista da Associacao Medica Brasileira. 2004;50:3739.
Kelly AM. Clinical impact of blood cultures taken in the emergency department. J Accid Emerg Med. 1998;15:2546.
Brunton LL, Chabner BA, Knollman BC, editors. Goodman and
Gilmans the pharmacological basis of therapeutics, 12th edition.
New York: The McGraw-Hill Companies; 2011.
Amsden G. Chapter 49, Tables of antimicrobial agent pharmacology. In: Mandell G, Bennett J, Dolin R, editors. Principles and
practice of infectious diseases, 7th edition, Volume 1. Philadelphia: Churchill Livingston, Elsevier; 2010. p. 70561.
123
70
35. McKenzie C. Antibiotic dosing in critical illness. J Antimicrob
Chemother. 2011;66 (suppl 2):ii2531.
36. Goldstein EJ, Solomkin JS, Citron DM, Alder JD. Clinical efficacy and correlation of clinical outcomes with in vitro susceptibility for anaerobic bacteria in patients with complicated intraabdominal infections treated with moxifloxacin. Clin Infect Dis.
2011;53:107480.
37. Solomkin J, Zhao YP, Ma EL, Chen MJ, DRAGON Study Team.
Moxifloxacin is non-inferior to combination therapy with ceftriaxone plus metronidazole in patients with community-origin
complicated intra-abdominal infections. Int J Antimicrob Agents.
2009;34:43945.
38. Weiss G, Reimnitz P, Hampel B, Muehlhofer E, AIDA Study
Group. Moxifloxacin for the treatment of patients with complicated intra-abdominal infections (the AIDA Study). J Chemother.
2009;21:17080.
39. Malangoni MA, Song J, Herrington J, Choudhri S, Pertel P.
Randomized controlled trial of moxifloxacin compared with
piperacillin-tazobactam and amoxicillin-clavulanate for the
treatment of complicated intra-abdominal infections. Ann Surg.
2006;244:20411.
40. Schultsz C, Geerlings S. Plasmid-mediated resistance in Enterobacteriaceae: changing landscape and implications for therapy.
Drugs. 2012;72:116.
41. Doan TL, Fung HB, Mehta D, Riska PF. Tigecycline: a glycylcycline antimicrobial agent. Clin Ther. 2006;28:1079106.
42. Prasad P, Sun J, Danner RL, Natanson C. Excess deaths associated with tigecycline after approval based on non-inferiority trials. Clin Infect Dis. 2012;54:16991709.
43. Muller E, Pitt HA, Thompson JE Jr, Doty J, Mann L, Manchester
B. Antibiotics in infections of the biliary tract. Surg Gynecol
Obstet. 1987;165:28592.
44. Gerecht W, Henry N, Hoffman W, Muller S, LaRusso N, Rosenblatt J, Wilson W. Prospective randomized comparison of
mezlocillin therapy alone with combined ampicillin and gentamicin therapy for patients with cholangitis. Arch Intern Med.
1989;149:127984.
45. Thompson JE Jr, Pitt HA, Doty J, Coleman J, Irving C. Broad
spectrum penicillin as an adequate therapy for acute cholangitis.
Surg Gynecol Obstet. 1990;171:27582.
46. Chacon J, Criscuolo P, Kobata C, Ferraro J, Saad S, Reis C. Prospective randomized comparison of pefloxacin and ampicillin plus
gentamicin in the treatment of bacteriologically proven biliary tract
infections. J Antimicrob Chemother. 1990;26,Suppl B:16772.
47. Thompson JE Jr, Bennion R, Roettger R, Lally K, Hopkins J,
Wilson SE. Cefepime for infections of the biliary tract. Surg
Gynecol Obstet. 1993;177 Suppl:304. discussion 3540.
48. Yellin AE, Berne TV, Appleman MD, Heseltine PN, Gill MA,
Okamoto MP, Baker FJ, Holcomb C. A randomized study of cefepime versus the combination of gentamicin and mezlocillin as an
adjunct to surgical treatment in patients with acute cholecystitis.
Surg Gynecol Obstet. 1993;177 Suppl:2329; discussion 3540.
49. Sung J, Lyon D, Suen R, Chung S, Co A, Cheng A, Leung J, et al.
Intravenous ciprofloxacin as treatment for patients with acute
suppurative cholangitis: a randomized, controlled clinical trial.
J Antimicrob Chemother. 1995;35:85564.
50. Powers JH. Editorial commentary: Asking the right questions:
morbidity, mortality and measuring whats important in unbiased
evaluations of antimicrobials. Clin Infect Dis. 2012;54:17101713.
51. Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F,
Balakrishnan R, et al. Emergence of a new antibiotic resistance
mechanism in India, Pakistan, and the UK: a molecular, biological,
and epidemiological study. Lancet Infect Dis. 2010;10:597602.
123

52. Won SY, Munoz-Price LS, Lolans K, Hota B, Weinstein RA.
Centers for Disease Control and Prevention Epicenter Program.
Emergence and rapid regional spread of Klebsiella pneumoniae
carbapenemase-producing Enterobacteriaceae. Clin Infect Dis.
2011;53:53240.
53. Di Carlo P, Pantuso G, Cusimano A, DArpa F, Giammanco A,
Gulotta G, Latteri AM, Madonia S, Salamone G, Mammina C.
Two cases of monomicrobial intraabdominal abscesses due to
KPC3 Klebsiella pneumoniae ST258 clone. BMC Gastroenterol.
2011;30(11):103.
54. Bogdanovich T, Adams-Haduch JM, Tian GB, Nguyen MH,
Kwak EJ, Muto CA, et al. Colistin-resistant, Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae
belonging to the international epidemic clone ST258. Clin Infect
Dis. 2011;53:3736.
55. Solomkin JS, Dellinger EP, Bohnen JM, Rostein OD. The role of
oral antimicrobias for the management of intra-abdominal
infections. New Horiz. 1998;Suppl 2:S4652.
56. Brand M, Bizs D, OFarrell PJR. Antibiotic prophylaxis for
patients undergoing elective endoscopic retrograde cholangiopancreatography (review). Cochrane Database Syst Rev. 2010
Oct 6;(10):CD007345.
57. Hirota WK, Petersen K, Baron TH, Goldstein JL, Jacobson BC,
Leighton JA, et al. Guidelines for antibiotic prophylaxis for GI
endoscopy. Gastrointest Endosc. 2003;58:47582 (CPGs).
58. Bai Y, Gao F, Gao J, Zou DW, Li ZS. Prophylactic antibiotics
cannot prevent endoscopic retrograde cholangiopancreatographyinduced cholangitis: meta-analysis. Pancreas. 2009;38:12630.
59. Branders JW, Scheffer B, Lorenz-Meyer H, Korst HA, Littmann
KP. ERCP: complications and prophylaxis. A controlled study.
Endoscopy. 1981;13:2730.
60. Byl B, Deviere J, Struelens MJ, Roucloux I, De Coninck A, Thys
JP, et al. Antibiotic prophylaxis of infectious complications after
therapeutic endoscopic retrograde cholangiopancreatography: a
randomized, double-blind, placebo-controlled study. Clin Infect
Dis. 1995;20:123640.
61. Van den Hazel SJ, Speelman P, Dankert J, Huibregtse K, Tytgat
GNJ, Van Leeuen DJ. Piperacillin to prevent cholangitis after
endoscopic retrograde cholangiopancreatography. A randomized,
controlled trial. Ann Intern Med. 1996;125:4427.
62. Llach J, Bordas JM, Almela M, Pellise M, Mata A, Soria M, et al.
Prospective assessment of the role of antibiotic prophylaxis in
ERCP. Hepatogastroenterology. 2006;53:5402.
63. Lorenz R, Lehn N, Born P, Hermann M, Neuhaus H. Antibiotic
prophylaxis with cefuroxime in therapeutic endoscopy of the bile
ducts. Dtsch Med Wochenschr. 1996;121:22330.
64. Sauter G, Grabein B, Mannes GA, Reckdeschel G, Sauerbruch T.
Antibiotic prophylaxis of infectious complications with endoscopic retrograde cholangiopancreatography. A randomized
controlled study. Endoscopy. 1990;22:1647.
65. Niederau C, Pohlmann U, Lubke H, Thomas L. Antibiotic prophylaxis during therapeutic or complicated diagnostic ERCP:
results of a randomized controlled clinical study. Gastrointest
Endosc. 1994;40:5337.
66. Raty S, Sand J, Pulkkinen M, Matikainen M, Norback I. PostERCP pancreatitis: reduction by routine antibiotics. J Gastrointest
Surg. 2001;5:33945.
67. Alexander JW, Solomkin JS, Edwards MJ. Updated recommendations for control of surgical site infections. Ann Surg. 2011;
253:108293 (CPGs).

DOI 10.1007/s00534-012-0569-8
GUIDELINE

TG13 indications and techniques for biliary drainage

in acute cholangitis (with videos)
Takao Itoi Toshio Tsuyuguchi Tadahiro Takada Steven M. Strasberg Henry A. Pitt
Myung-Hwan Kim Giulio Belli Toshihiko Mayumi Masahiro Yoshida Fumihiko Miura
Markus W. Buchler Dirk J. Gouma O. James Garden Palepu Jagannath Harumi Gomi
Yasuyuki Kimura Ryota Higuchi

Abstract The Tokyo Guidelines of 2007 (TG07) described the techniques and recommendations of biliary
decompression in patients with acute cholangitis. TG07
recommended that endoscopic transpapillary biliary
drainage should be selected as a first-choice therapy for
acute cholangitis because it is associated with a low mortality rate and shorter duration of hospitalization. However,
TG07 did not include the whole technique of standard
endoscopic transpapillary biliary drainage, for example,
biliary cannulation techniques including contrast medium-

T. Itoi (&)
Tokyo Medical University, 6-7-1 Nishishinjuku,
Shinjuku-ku, Tokyo 160-0023, Japan
e-mail: itoi@tokyo-med.ac.jp
T. Tsuyuguchi F. Miura
School of Medicine, Chiba University, Chiba, Japan
T. Takada
Tokyo, Japan
S. M. Strasberg
University School of Medicine, St. Louis, USA
assisted cannulation, wire-guided cannulation, and treatment of duodenal major papilla using endoscopic papillary
balloon dilation (EPBD). Furthermore, recently singleor double-balloon enteroscopy-assisted biliary drainage
(BE-BD) and endoscopic ultrasonography-guided biliary
drainage (EUS-BD) have been reported as special techniques for biliary drainage. Nevertheless, the updated
Tokyo Guidelines (TG13) recommends that endoscopic
drainage should be first-choice treatment for biliary
decompression in patients with non-surgically altered
anatomy and suggests that the choice of cannulation technique or drainage method (endoscopic naso-biliary drainage and stenting) depends on the endoscopists preference
but EST should be selected rather than EPBD from the
G. Belli
T. Mayumi
M. Yoshida
M. W. Buchler
Germany
D. J. Gouma
The Netherlands
H. A. Pitt
O. J. Garden
M.-H. Kim
P. Jagannath
123
72
aspect of procedure-related complications. In terms of BEBD and EUS-BD, although there are many reports on the
their usefulness, they should be performed by skilled endoscopists in high-volume institutes, who are good at enteroscopy or echoendosonography, respectively, because
procedures and devices are not yet established.
html.
Keywords Cholangitis Percutaneous biliary drainage
Endoscopic biliary drainage Endoscopic cholangiopancreatography Guidelines
Introduction
Acute cholangitis varies in severity, ranging from a mild form
which can be treated by conservative therapy to a severe form
which leads to a life-threatening state, e.g. shock state and
altered sensorium. In particular, the severe form often results in
mortality in the elderly [13]. Biliary drainage, which is the
most essential therapy for acute cholangitis, is divided into
three types, surgical, percutaneous transhepatic, and endoscopic drainage. Of these therapies, it is well known that surgical intervention leads to the highest mortality rate [1].
Recently, mortality due to acute cholangitis has decreased due
to development of percutaneous transhepatic cholangial
drainage (PTCD) [4] and endoscopic biliary drainage [5, 6].
Nevertheless, acute cholangitis can still be fatal unless it is
treated in a timely way. The Tokyo Guidelines of 2007 (TG07)
described the fundamental biliary drainage techniques for acute
cholangitis [7]. Subsequently, new biliary drainage techniques
for the therapy of acute cholangitis have been reported. Herein,
we describe the indications and techniques of biliary drainage
for acute cholangitis in the updated Tokyo Guidelines (TG13).
Indications and techniques of biliary drainage

In TG13, biliary drainage is recommended for acute cholangitis regardless of degree of severity other than some
H. Gomi
Tochigi, Japan
Y. Kimura
Sapporo, Japan
R. Higuchi
123
cases of mild acute cholangitis in which antibiotics and

general supportive care are effective.
Q1. What is the most preferable biliary drainage?
endoscopic vs percutaneous vs surgical drainage for
acute cholangitis?
We recommend endoscopic biliary drainage for acute
cholangitis (recommendation 1, level B).
We suggest that percutaneous
transhepatic biliary
drainage
may be
considered as
alternative
methods when endoscopic biliary drainage is difficult
(recommendation 2, level C).
Endoscopic drainage should be considered the first-choice

drainage procedure because several studies have described it
as less invasive than other drainage techniques [711].
Percutaneous transhepatic cholangial drainage
(supplement video 1)
Indications
Nowadays, percutaneous transhepatic cholangial drainage
(PTCD), also known as percutaneous transhepatic biliary
drainage (PTBD), has become the second choice of therapy
for acute cholangitis following endoscopic drainage
because of possible complications, including intraperitoneal hemorrhage and biliary peritonitis, and the need for a
long hospital stay. However, PTCD can still be conducted
in any of the following circumstances: (1) in patients with
an inaccessible papilla due to upper GI tract obstruction, as
in duodenal obstruction or surgically altered anatomy like
Whipple resection or Roux-en-Y anastomosis, in which the
passage of endoscope or endoscopic drainage is thought to
be difficult or impossible; (2) when skilled pancreaticobiliary endoscopists are not available in the institution.
Furthermore, even in patients with non-surgically altered
anatomy, PTCD can be salvage therapy when conventional
endoscopic drainage has failed. In general, coagulopathy is
a relative contraindication. However, if there is no other
life-saving method, PTCD would be indicated.
Techniques
Before the prevalence of transabdominal ultrasonography,
needle puncture of the bile duct was conducted under
fluoroscopy [4]. Currently, needle puncture is safely performed under ultrasonography to avoid the intervening
blood vessel [12]. Therefore, in the current PTCD procedure, operators should continuously observe the bile duct
using ultrasonography regardless of the presence of
dilation. The PTCD procedure is performed as follows, and

as previously described [4]. Briefly, at first, ultrasonography-guided transhepatic puncture of the intrahepatic bile
duct is conducted using an 18- to 22-G needle. After
confirming backflow of bile, a guidewire is advanced into
the bile duct. Finally, a 7- to 10-Fr catheter is placed in the
bile duct under fluoroscopic control over the guidewire.
Puncture using a small-gauge (22-G) needle is safer in
patients without biliary dilation than with biliary dilation.
According to the Quality Improvement Guidelines produced by American radiologists, the success rates of
drainage are 86 % in patients with biliary dilation and
63 % in those without biliary dilation [12].
Surgical drainage
Indications
In benign diseases like bile duct stones, surgical drainage is
extremely rare because of the prevalence of endoscopic
drainage or PTCD for the therapy of acute cholangitis.
However, in patients with acute cholangitis due to unresectable neoplasms like cancer of the pancreatic head,
hepaticojejunostomy can be performed as bypass surgery
only in limited patients without severe acute cholangitis. In
particular, when periampullary neoplastic lesions like
cancer of the pancreatic head or ampullary cancer, show
both acute cholangitis and duodenal obstruction, double
bypass surgery, hepaticojejunostomy and gastrojejunostomy, may be a rare choice.
Techniques
Open drainage for decompression of the bile duct is performed as a surgical intervention. When surgical drainage
in critically ill patients with bile duct stones is performed,
prolonged operations should be avoided and simple procedures, such as T-tube placement without choledocholithotomy, are recommended [13].
Endoscopic biliary drainage

Indications
Endoscopic transpapillary biliary drainage has become the
gold standard technique for acute cholangitis, regardless of
whether the pathology is benign or malignant, because it is a
minimally invasive drainage method [4]. On the other hand,
endoscopic drainage using a standard duodenoscope in patients with duodenal obstruction and surgically altered anatomy,
like Roux-en-Y anastomosis, seems to be contraindicated.
73
The timing of endoscopic biliary drainage is very

important for the clinical outcome. Khashab et al. [14]
described that delayed (more than 72 h after administration)
and unsuccessful ERCP are associated with worse outcomes
in patients with acute cholangitis. Actually, in TG07, two
thirds of outstanding pancreatobiliary surgeons and endoscopists supported the use of emergent or early drainage in
patients with moderate or severe cholangitis [15].
Techniques
Biliary cannulation
Biliary cannulation should be conducted in advance of
biliary drainage. Basically, there are two biliary cannulation techniques, namely contrast medium-guided cannulation (standard cannulation) and wire-guided cannulation.
Q2. What technique should be used for biliary
cannulation? Standard cannulation or wire-guided
cannulation?
We suggest that either standard cannulation or wire-guided
cannulation can be considered for bile duct access
Two meta-analyses of a randomized controlled trial (RCT)

on the comparison between standard cannulation and wireguided cannulation showed that wire-guided cannulation
was able to increase the successful biliary cannulation rate
and prevent post-ERCP pancreatitis [16, 17]. Recently,
however, two RCTs have shown that there is no statistically significant difference between standard cannulation
and wire-guided cannulation on the success rate of biliary
cannulation or the prevention rate of post-ERCP pancreatitis [18, 19]. Therefore, the choice of techniques for biliary
cannulation is still controversial.
When biliary cannulation using standard cannulation or
wire-guided cannulation techniques fails, precutting, which
means an incision of the papilla enabling the bile duct
orifice to be opened for biliary cannulation, may be performed if an alternative method, like PTCD or surgical
intervention, is not performed. In the main, two types of
precutting methods are used. Needle knife precutting using
needle-type sphincterotome is well known as a basic precutting method (Fig. 1a). Alternatively, several endoscopists prefer pancreatic sphincter precutting using a pulltype sphincterotome for biliary access (Fig. 1b). The use of
precutting methods depends on the institution and endoscopist. It is known that precutting is likely to cause serious
complications, such as acute pancreatitis and perforation,
and therefore it should be performed only by skilled
endoscopists [20, 21].
123
74
cholangitis, they may be contraindicated in patients in

whom the endoscope cannot reach the papilla due to GI
tract obstruction or surgically altered anatomy, or in whom
endoscopic procedures are inadequate because of critical
illness. In particular, ENBD should be avoided in patients
with poor compliance, who may remove the tube, and those
with abnormalities of the nasal cavity causing difficulty in
naso-biliary tube insertion.
In the case of biliary drainage for therapy of acute
cholangitis, skillful endoscopic technique is mandatory
because long and unsuccessful procedures may lead to
serious complications in critical ill patients. Therefore,
endoscopists who perform endoscopic biliary drainage in
these patients, should already have a high success rate of
biliary cannulation including the precutting technique.
Q3. What procedure should be used for endoscopic
biliary drainage? ENBD or EBS?
We suggest that either ENBD or EBS may be considered
for biliary drainage (recommendation 2, level B).
Fig. 1 Precutting technique. a Needle knife precutting using needletype sphincterotome. Bile duct orifice is opened by precutting.
b Schema of pancreatic sphincter precutting. Cutting wire is bowed
toward the bile duct direction
Three comparative studies have shown that there is no

statistically significant difference in technical success,
clinical success, complications and mortality between
ENBD and EBS, although a visual analogue scale was
higher in the ENBD group than in the EBS group
(Table 1) [2224]. In consequence of these results, TG13
suggests that either drainage procedure can be selected
according to the preference of the endoscopist. However,
if ENBD is selected for the treatment of acute cholangitis, we should bear in mind that if the patient has
discomfort from the transnasal tube placement, they are
likely to remove the tube themselves, especially elderly
patients.
One RCT has revealed that biliary drainage is not
mandatory after endoscopic clearance of the common bile
duct in patients with choledocholithiasis-induced cholangitis (level B) [25].
Techniques
ENBD (supplement video 2)
Endoscopic naso-biliary drainage and endoscopic

biliary stenting
Indications
Endoscopic transpapillary biliary drainage is divided into
two types: endoscopic naso-biliary drainage (ENBD) as an
external drainage and endoscopic biliary stenting (EBS) as
an internal drainage. Although, basically, both endoscopic
biliary drainage types can be conducted in all acute
123
ENBD procedures are described in detail in TG07 [4].

Briefly, after selective biliary cannulation, a 5-Fr to 7-Fr
tube is placed in the bile duct as an external drainage over
the guidewire (Fig. 2a).
EBS (supplement video 3)
EBS procedures is also described in the previous guideline
[4]. In brief, after selective biliary cannulation, a 7- to
75
Table 1 Comparison of results between ENBD and stent placement in acute cholangitis cases
References
Method
Lee [22]
ENBD
40
RCT
Technical success (%)
Clinical success (%)
100
85100
3.9 (2.7)
Yes
Sharma [23]
EBS
34
ENBD
74
Adverse events (%)
Mortality rate (%)
2.5
12
2.7
p = 0.02
98
8292a
99
100
1.8 (2.6)
Yes
Park [24]
VAS
N/A
EBS
73
98
ENBD
41
100
100
86100b
EBS
39
100
80100b
No
2.7
32
39
N/A
ENBD endoscopic naso-biliary drainage, EBS endoscopic biliary stenting, RCT randomized controlled trial, VAS visual analog scale [mean
(SD)], N/A not applicable
a
Including pain, fever, and jaundice
Including pain, fever, altered sensorium, hypotension, and renal failure
10-Fr plastic stent is placed in the bile duct as an internal

drainage over the guidewire. There are two different stent
shapes, a straight type with a single flap with a sidehole
(Amsterdam type) (Fig. 2b) or radial flaps without a sidehole (Tannenbaum type) on both sides, and a double pigtail type to prevent inward and outward stent migration.
There is no comparative study between straight type and
pig-tail type stents. Therefore, either stent can be selected
according to the preference of the endoscopist.
Treatment of the major papilla
Endoscopic sphincterotomy (EST)
hemorrhage is one of the risk factors of acute cholangitis

[20]. In particular, the use of EST in patients with severe
(grade III) disease complicated by coagulopathy should be
avoided. Nevertheless, EST has some advantages as follows: (1) it provides not only drainage but also clearance of
bile duct stones at a single session in patients with choledocholithiasis (not complicated by severe cholangitis).
(2) Precutting can allow bile duct access, providing biliary
drainage in patients in whom selective biliary cannulation
is impossible using the standard cannulation technique. In
particular, stone removal in one session can shorten the
hospital stay. Therefore, TG13 suggests that addition of
EST should be determined according to the patients condition and the operators skill.
Indications
Techniques
EST technique is usually used for stone removal and, at
times, prevention of the occlusion of the pancreatic duct
orifice by placement of a large-bore biliary stent (more than
10-Fr or a self-expandable metal stent).
Q4. Is EST necessary in endoscopic biliary drainage?
We suggest that addition of EST should be determined
according to the patients condition and the operators
skill (recommendation 2, level C).
We suggest that EST followed by stone removal without
biliary drainage can be recommended as an alternative
procedure in patients with choledocholithiasis - induced
acute cholangitis (recommendation 2, level C).
As TG07 described, an additional EST is not necessary in

acute cholangitis as follows: (1) additional EST causes
complications such as hemorrhage [26, 27]; (2) post-EST
The detail of EST procedures is described in TG07 [4].

Briefly, after selective biliary cannulation with or without a
guidewire, a pull-type sphincterotomy incision is performed below the transverse fold (Fig. 3). When the
transverse fold is not present, the superior margin of the
papilla bulge is used as a landmark to determine the length
of the sphincterotomy (supplement video 4). An electrosurgical generator with a controlled cutting system
(Endocut mode, ICC200, VIO300, ERBE Elektromedizin
GmbH, Tubingen, Germany) is used for EST; the pushtype is used for EST in patients with Billroth II gastrectomy or Roux-en-Y anastomosis. Only a limited incision is
necessary in EST for drainage purposes using a large-bore
stent, unlike that for stone removal [10]. Endoscopists
should remember that EST may cause acute pancreatitis or
cholangitis, which may become life-threatening when
severe [20].
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76
Fig. 3 Endoscopic sphincterotomy. A pull-type sphincterotomy

incision was performed below the transverse fold
drainage to treat acute cholangitis due to bile duct stones.

EPBD, like EST, has the advantage of reducing the number
of therapeutic sessions and shortening the hospital stay in
patients with acute cholangitis caused by bile duct stones.
One systematic review revealed that EPBD is statistically
less successful for stone removal, requires higher rates of
mechanical lithotripsy, and carries a higher risk of pancreatitis, although it also has statistically significant lower
rates of bleeding [29]. Thus, TG13 suggests that EPBD
appears to be useful for treatment in patients who have
coagulopathy and acute cholangitis caused by a small
stone.
On the other hand, theoretically, since the aim of EPBD
is to preserve the function of the sphincter of Oddi, EPBD
alone without biliary drainage is contraindicated for the
therapy of acute cholangitis. In addition, EPBD should be
avoided in patients with biliary pancreatitis.
Techniques
Fig. 2 Endoscopic biliary drainage. a Endoscopic naso-biliary

drainage. b Endoscopic biliary stenting. A 7-Fr plastic stent is placed
after performing EST and pus comes from the bile duct
Endoscopic papillary balloon dilation (EPBD)
After selective biliary cannulation, a small balloon up to

8-mm in diameter, depending on the diameters of the bile
duct and the stone, is advanced into the bile duct across the
papilla. Then, the sphincter of Oddi is gradually dilated by
inflation of the balloon until the waist of the balloon disappears. Then, clearance of the bile duct stone is conducted
using a basket catheter and balloon catheter.
Indications
Special techniques of endoscopic biliary drainage
The EPBD procedure is usually used instead of EST for
removal of bile duct stones [28]. Until now, there has been
no comparative study on the use of EPBD during biliary
123
Recently, several new techniques of endoscopic biliary

drainage have been developed.
77
Balloon enteroscope-assisted bile duct drainage

Indications
ERCP in patients with surgically altered anatomy can be
challenging. In general, Roux-en-Y anastomosis has been
thought to preclude endoscopic access for ERCP because of
the extensive lengths of the efferent and afferent limbs that
must be traversed to reach the major papilla or hepaticojejunostomy site. Recently, single balloon enteroscopy (SBE)
and double balloon enteroscopy (DBE) have enabled successful ERCP to be performed in patients with such surgically altered anatomy. Several investigators have reported
various success rates (40 to 95 %) with adverse events rates
below 5 % (Tables 2, 3) [3042]. However, since this
technique may be unsuccessful and time-consuming, its
indication should be cautiously decided. Although ideal
operators are those who are skilled in both balloon enteroscopy and ERCP, in some institutions, GI endoscopists
advance an endoscope to the papilla or anastomotic site and
then pancreaticobiliary endoscopists perform ERCP.
Therefore, if the operators are not good at this technique,
therapy using balloon enteroscopy should be avoided.
Tokyo, Japan and long-type DBE: EN-450T5, short-type

DBE: EC-450B15/EI-530B, Fujifilm Co., Ltd., Saitama,
Japan), a sliding tube with a balloon and a balloon controller. The DBE has a balloon at the tip of the endoscope
in addition to the balloon of the overtube. Endoscopes are
advanced to the papilla or anastomotic site using the
pushing and pulling techniques (Fig. 4a, b). An injection
catheter and a tapered catheter are used for initial cannulation. First, 0.0250.035-inch guidewires are inserted into
the bile duct. Finally, 58.5-Fr naso-biliary drainage
catheters and self-expandable metallic stents are placed
into the bile duct for biliary decompression. In cases
requiring an endoscopic sphincterotomy, a sphincterotome
and needle knife are advanced into the bile duct over or
alongside the guidewire. In cases of EPBD, a conventional
dilation catheter is used for the papilla or
Techniques (supplement video 5)

The SBE and DBE balloon system consists of a video
enteroscope (XSIF-Q260Y; Olympus Medical Systems,
Table 2 Outcome of single-balloon enteroscopy-assisted ERCP
References
Technical success
(1st attempt) (%)
Adverse
events (%)
Itoi [30]
11
72
None
Saleem [31]
56
91
None
Wang [32]
12
90
17
Total
79
89
2.50
Table 3 Outcome of double-balloon enteroscopy-assisted ERCP

(n [ 5)
References
Mehdizadeh [34]
Technical success
(1st attempt) (%)
Adverse
events (%)
40
None
Emmett [35]
14
80
None
Aabakken [36]
13
85
None
67
None
Masser [37]
Kuga [38]
83
None
Pohl [39]
15
87
None
Shimatani [40]
68
96
Tsujino [41]
12
94
17
67
None
151
86
3.3
Itoi [42]
Total
Fig. 4 Balloon enteroscope-assisted ERCP. a ERCP in esophagojejunostomy with Roux-en-Y patient. b ERCP in hepaticojejunostomy
with Roux-en-Y patient
123
78
hepaticojejunostomy site. When selective cannulation is

not possible, a needle knife is used for pre-cutting. A
basket catheter, retrieval balloon catheter, and/or mechanical lithotriptor are used for removal of stones.
Endoscopic ultrasonography-guided bile duct drainage
Indications
Recently, endoscopic ultrasonography (EUS)-guided biliary drainage has been reported as a salvage therapy when
standard endoscopic drainage has failed [4354]. Since the
technique and devices of this procedure are not yet established and there is no dedicated device for this procedure, it
should be conducted only in selected patients in whom
standard biliary drainage by means of ERCP or PTCD has
failed or is contraindicated for various reasons like considerable ascites. There are two methods of approach in
EUS-guided biliary drainage: (1) EUS-guided intrahepatic

Table 4 Outcome of endosonography-guided bile duct drainage
Drainage
No. of
cases
Technical
success (%)
Clinical
success (%)
Complications
(%)
EUS-guided
IHBD
drainage
HES 4
100
100
25
16
EUS-guided
EHBD
drainage
HGS 50
96
98
HJS 4
75
100
CDS 61
95
100
16
CGS 6
100
100
17
IHBD intrahepatic bile duct, EHBD extrahepatic bile duct, HES hepaticoesophagostomy, HGS hepaticogastrostomy, HJS hepaticojejunostomy, CDS choledochoduodenostomy, CGS choledochogastrostomy
bile duct drainage (Fig. 5a) by a transesophageal, transgastric or transjejunal approach; (2) EUS-guided extrahepatic bile duct drainage (Fig. 5b) by a transduodenal or
transgastric approach. The choice of drainage route
depends on the presence of a gastric outlet obstruction and
the stricture site of the bile duct. Several published data on
EUS-guided intrahepatic bile duct drainage and extrahepatic bile duct drainage show that the success rate is high
(95 %), with 93100 % (intention-to-treat) response rates
(Table 4) [4354]. Most of the reported cases of adverse
events were pneumoperitonitis but there was no serious
adverse event. However, since the procedure is not yet
established, it should be conducted by endoscopists skilled
in both echoendosonography and ERCP.
Techniques [55] (supplement video 6 and video 7)
Fig. 5 EUS-guided biliary approaches. a EUS-guided intrahepatic

bile duct approach. b EUS-guided extrahepatic bile duct approach
123
Theoretically, the intrahepatic bile duct and liver, including

the extrahepatic bile duct does not adhere to the GI tract.
Therefore, there is a possibility of bile leakage during the
procedure; particularly, if the procedure fails, serious bile
peritonitis can occur. A needle knife (Zimmon papillotomy
knife, or Cystotome, Wilson-Cook, Winston-Salem, NC)
catheter using electrocautery (EndoCut ICC200, VIO300D,
ERBE Elektromedizin GmbH, Tubingen, Germany), or a
19-gauge needle (EchoTip, Wilson-Cook), is advanced into
the bile duct under EUS visualization after confirming the
absence of intervening blood vessels to avoid bleeding.
After the stylet is removed, bile is aspirated and then
contrast medium is injected into the gallbladder for cholecystography, then a 450 cm long, 0.025- or 0.035-inch
guidewire is advanced into the outer sheath. If necessary, a
biliary catheter for dilation (Soehendra Biliary Dilator,
Wilson-Cook), papillary balloon dilation catheter (Maxpass, Olympus Medical Systems), and electrical cautery
needle, are used for dilation of the hepaticoenterostomy
site and choledochoenterostomy site. Finally, a 7-Fr plastic
stent or a self-expandable metal stent are advanced into the
bile duct.

Acknowledgments We are indebted to Professor J. Patrick Barron,
Chairman of the Department of International Medical Communications at Tokyo Medical University, for his editorial review of the
English manuscript.
None.
References
1. Reynolds BM, Dargan EL. Acute obstructive cholangitis. A
distinct syndrome. Ann Surg. 1959;150:299303.
Surg. 1982;117:43741.
treatment of acute suppurative cholangitis. Am J Surg. 1976;131:
52732.
4. Takada T, Hanyu F, Kobayashi S, Uchida Y. Percutaneous
transhepatic cholangial drainage: direct approach under fluoroscopic control. J Surg Oncol. 1976;8:8397.
5. Nagai N, Toki F, Oi I, Suzuki H, Kozu T. Continuous endoscopic
pancreatocholedochal catheterization. Gastrointest Endosc. 1976;
23:7881.
6. Sohendra N, Reynders-Frederix V. Palliative bile duct drainage.
A new endoscopic method of introducing a transpapillary drain.
Endoscopy. 1980;12:811.
7. Tsuyuguchi T, Takada T, Kawarada Y, Nimura Y, Wada K,
Nagino M, et al. Techniques of biliary drainage for acute
2007;14(1):3545. (clinical practice guidelines:CPGs).
8. Lai EC, Mok FP, Tan ES, Lo CM, Fan ST, You KT, et al.
Endoscopic biliary drainage for severe acute cholangitis. N Engl J
Med. 1992;24:15826.
9. Leung JW, Chung SC, Sung JJ, Banez VP, Li AK. Urgent
endoscopic drainage for acute suppurative cholangitis. Lancet.
1989;10:13079.
10. Boender J, Nix GA, de Ridder MA, Dees J, Schutte HE, van
Buuren HF, et al. Endoscopic sphincterotomy and biliary drainage in patients with cholangitis due to common bile duct stones.
Am J Gastroenterol. 1995;90:2338.
11. Lau JY, Chung SC, Leung JW, Ling TK, Yung MY, Li AK.
Endoscopic drainage aborts endotoxaemia in acute cholangitis.
Br J Surg. 1996;83:1814.
12. Saad WE, Wallace MJ, Wojak JC, Kundu S, Cardella JF. Quality
improvement guidelines for percutaneous transhepatic cholangiography, biliary drainage, and percutaneous cholecystostomy.
J Vasc Interv Radiol. 2010;21:78995.
13. Saltzstein EC, Peacock JB, Mercer LC. Early operation for acute
biliary tract stone disease. Surgery. 1983;94:7048.
14. Khashab MA, Tariq A, Tariq U, Kim K, Ponor L, Lennon AM,
et al. Delayed and unsuccessful endoscopic retrograde cholangiopancreatography are associated with worse outcomes in patients
with acute cholangitis. Clin Gastroenterol Hepatol 2012;10:
115761
15. Nagino M, Takada T, Kawarada Y, Nimura Y, Yamashita Y,
Tsuyuguchi T, et al. Methods and timing of biliary drainage for
acute cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat
Surg. 2007;14(1):6877. (CPGs)
16. Cheung J, Tsoi KK, Quan WL, Lau JY, Sung JJ. Guidewire
versus conventional contrast cannulation of the common bile duct
for the prevention of post-ERCP pancreatitis: a systematic review
and meta-analysis. Gastrointest Endosc. 2009;70:12119.
79
17. Cennamo V, Fuccio L, Zagari RM, Eusebi LH, Ceroni L, Laterza
L, et al. Can a wire-guided cannulation technique increase bile
duct cannulation rate and prevent post-ERCP pancreatitis?: a
meta-analysis of randomized controlled trials. Am J Gastroenterol. 2009;104:234350.
18. Manbu T, Ukita T, Shigoka H, Omuta S, Maetani I. Wire-guided
selective cannulation of the bile duct with a sphincterotome: a
prospective randomized comparative study with standard method.
Scand J Gastroenterol. 2011;46:10915.
19. Kawakami H, Maguchi H, Mukai T, Hayashi T, Sasaki T, Isayama H, et al. A multicenter, prospective, randomized study of
selective bile duct cannulation performed by multiple endoscopists: the BIDMEN study. Gastrointest Endosc 2012;75:36272.
20. Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME,
Dorsher PJ, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med. 1996;335:90918.
21. Testoni PA, Mariani A, Giussani A, Vailati C, Masci E, Macarri
G, et al. Risk factors for post-ERCP pancreatitis in high- and lowvolume centers and among expert and non-expert operators: a
prospective multicenter study. Am J Gastroenterol. 2010;105:
175361.
22. Lee DW, Chan AC, Lam YH, Ng EK, Lau JY, Law BK, et al.
Biliary decompression by nasobiliary catheter or biliary stent in
acute suppurative cholangitis: a prospective randomized trial.
Gastrointest Endosc. 2002;56:3615.
23. Sharma BC, Kumar R, Agarwal N, Sarin SK. Endoscopic biliary
drainage by nasobiliary drain or by stent placement in patients
with acute cholangitis. Endoscopy. 2005;37:43943.
24. Park SY, Park CH, Cho SB, Yoon KW, Lee WS, Kim HS, et al.
The safety and effectiveness of endoscopic biliary decompression
by plastic stent placement in acute suppurative cholangitis compared with nasobiliary drainage. Gastrointest Endosc. 2008;68:
107680.
25. Lee JK, Lee SH, Kang BK, Kim JH, Koh MS, Yang CH, et al. Is
it necessary to insert a nasobiliary drainage tube routinely after
endoscopic clearance of the common bile duct in patients with
choledocholithiasis-induced cholangitis? A prospective, randomized trial. Gastrointest Endosc. 2010;71:10510.
26. Sugiyama M, Atomi Y. The benefits of endoscopic nasobiliary
drainage without sphincterotomy for acute cholangitis. Am J
27. Hui CK, Lai KC, Yuen MF, Ng M, Chan CK, Hu W, et al. Does
the addition of endoscopic sphincterotomy to stent insertion
improve drainage of the bile duct in acute suppurative cholangitis? Gastrointest Endosc. 2003;58:5004.
28. Komatsu Y, Kawabe T, Toda N, Ohashi M, Isayama M, Tateishi
K, et al. Endoscopic papillary balloon dilation for the management of common bile duct stones: experience of 226 cases.
Endoscopy. 1998;30:127.
29. Weinberg BM, Shindy W, Lo S. Endoscopic balloon sphincter
dilation (sphincteroplasty) versus sphincterotomy for common
bile duct stones. Cochrane Database Syst Rev. 2006;(4):
CD004890.
30. Itoi T, Ishii K, Sofuni A, Itokawa F, Tsuchiya T, Kurihara T, et al.
Single balloon enteroscopy-assisted ERCP in 206 patients with
Billroth II gastrectomy or Roux-en-Y anastomosis (with video).
Am J Gastroenterol. 2010;105:939.
31. Saleem A, Baron TH, Gostout C, Topazian MD, Levy MJ,
Petersen BT, et al. Endoscopic retrograde cholangiopancreatography using a single-balloon enteroscope in patients with altered
Roux-en-Y anatomy. Endoscopy. 2010;42:65660.
32. Wang AY, Sauer BG, Behm BW, Ramanath M, Cox DG, Ellen
KL, et al. Single-balloon enteroscopy effectively enables diagnostic and therapeutic retrograde cholangiography in patients
with surgically altered anatomy. Gastrointest Endosc. 2010;71:
6419.
123
80
33. Haruta H, Yamamoto H, Mizuta K, Kita Y, Uno T, Egami S, et al.
A case of successful enteroscopic balloon dilation for late anastomotic stricture of choledochoduodenostomy after living donor
liver transplantation. Liver Transpl. 2005;11:160810.
34. Mehdizadeh S, Ross A, Gerson L, Leighton J, Chen A, Schembre
D, et al. What is the learning curve associated with double-balloon enteroscopy? Technical details and early experience in 6
U.S. teriary care centers. Gastrointest Endosc. 2006;64:74050.
35. Emmett DS, Mallat DB. Double-balloon ERCP in patients who
have undergone Roux-en-Y surgery: a case series. Gastrointest
Endosc. 2007;66:103841.
36. Aabakken L, Bretthauer M, Line PD. Double-balloon enteroscopy for endoscopic retrograde cholangiography in patients with
a Roux-en-Y anastomosis. Endoscopy. 2007;39:106871.
37. Masser C, Lenze F, Bokemeyer M, Ullerich H, Domagk D,
Bruewer M, et al. Double balloon enteroscopy: a useful tool for
diagnostic and therapeutic procedures in the pancreaticobiliary
system. Am J Gastroenterol. 2008;103:894900.
38. Kuga R, Furuya CK Jr, Hondo FY, Ide E, Ishioka S, Sakai P.
ERCP using double-balloon enteroscopy in patients with Rouxen-Y anatomy. Dig Dis. 2008;26:3305.
39. Pohl J, May A, Aschmoeneit I, Ell C. Double-balloon endoscopy
for retrograde cholangiography in patients with choledochojejunostomy and Roux-en-Y reconstruction [Germany with English
abstract]. Z Gastroenterol. 2009;47:2159.
40. Shimatani M, Matsushita M, Takaoka M, Koyabu M, Ikeura T,
Kato K, et al. Effective shortdouble-balloon enteroscope for
diagnostic and therapeutic ERCP in patients with altered gastrointestinal anatomy: a large case series. Endoscopy. 2009;41:
84954.
41. Tsujino T, Yamada A, Isayama H, et al. Experiences of biliary
interventions using short double-balloon enteroscopy in patients
with Roux-en-Y anastomosis or hepaticojejunostomy. Dig Endosc. 2010;22:211216.
42. Itoi T, Ishii K, Sofuni A, Itokawa F, Tsuchiya T, Kurihara T, et al.
Long and short type double-balloon enteroscopy-assisted therapeutic ERCP for intact papilla in patients with a Roux-en-Y
anastomosis. Surg Endosc. 2011 25:71321.
43. Burmester E, Niehaus J, Leineweber T, Huetteroth T. EUS-cholangio-drainage of the bile duct: report of 4 cases. Gastrointest
Endosc. 2003;57:24651.
44. Giovannini M, Dotti M, Bories E, Moutardier V, Pesenti C,
Danisi C, et al. Hepaticogastrostomy by echo-endoscopy as a
123
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
palliative treatment in a patient with metastatic biliary obstruction. Endoscopy. 2003;35:10768.

Kahaleh M, Hernandez AJ, Tokar J, Adams RB, Shami VM,
Yeaton P. Interventional EUS-guided cholangiography: evaluation of a technique in evolution. Gastrointest Endosc. 2006;64:
529.
Artifon EL, Chaves DM, Ishioka S, Souza TF, Matuguma SE,
Sakai P. Echoguided hepatico-gastrostomy: a case report. Clinics
(Sao Paulo). 2007;62:799802.
Bories E, Pesenti C, Caillol F, Lopes C, Giovannini M. Transgastric endoscopic ultrasonography-guided biliary drainage:
results of a pilot study. Endoscopy. 2007;39:28791.
Park do H, Koo JE, Oh J, Lee YH, Moon SH, Lee SS, et al. EUSguided biliary drainage with one-step placement of a fully covered metal stent for malignant biliary obstruction: a prospective
feasibility study. Am J Gastroenterol. 2009;104:216874
Horaguchi J, Fujita N, Noda Y, Kobayashi G, Ito K, Obana T,
et al. Endosonography-guided biliary drainage in cases with
difficult transpapillary endoscopic biliary drainage. Dig Endosc.
2009;21:23944.
Giovannini M, Moutardier V, Pesenti C, Bories E, Lelong B,
Delpero JR. Endoscopic ultrasound-guided bilioduodenal anastomosis: a new technique for biliary drainage. Endoscopy.
2001;33:898900.
Yamao K, Bhatia V, Mizuno N, Sawaki A, Ishikawa H, Tajika M,
et al. EUS-guided choledochoduodenostomy for palliative biliary
drainage in patients with malignant biliary obstruction: results of
long-term follow-up. Endoscopy. 2008;40:3402.
Itoi T, Itokawa F, Sofuni A, Kurihara T, Tsuchiya T, Ishii K, et al.
Endoscopic ultrasound-guided choledochoduodenostomy in
patients with failed endoscopic retrograde cholangiopancreatography. World J Gastroenterol. 2008;14:607882.
Binmoeller KF, Nguyen-Tang T. Endoscopic ultrasound-guided
anterograde cholangiopancreatography. J Hepatobiliary Pancreat
Sci. 2011;18:31931.
Hara K, Yamao K, Niwa Y, Sawaki A, Mizuno N, Hijioka S,
et al. Prospective clinical study of EUS-guided choledochoduodenostomy for malignant lower biliary tract obstruction. Am J
Itoi T, Isayama H, Sofuni A, Itokawa F, Kurihara T, Tsuchiya T,
et al. Stent selection and tips of placement technique of EUSguided biliary drainage: trans-duodenal and trans-gastric stenting.
J Hepatobiliary Pancreat Sci. 2011;18:66472.

DOI 10.1007/s00534-012-0570-2
GUIDELINE

TG13 indications and techniques for gallbladder drainage

in acute cholecystitis (with videos)
Toshio Tsuyuguchi Takao Itoi Tadahiro Takada Steven M. Strasberg Henry A. Pitt Myung-Hwan Kim
Avinash N. Supe Toshihiko Mayumi Masahiro Yoshida Fumihiko Miura Harumi Gomi
Yasutoshi Kimura Ryota Higuchi Kohji Okamoto Yuichi Yamashita Toshifumi Gabata
Jiro Hata Shinya Kusachi

Abstract Percutaneous transhepatic gallbladder drainage

(PTGBD) is considered a safe alternative to early cholecystectomy, especially in surgically high-risk patients with
acute cholecystitis. Although randomized prospective
controlled trials are lacking, data from most retrospective
studies demonstrate that PTGBD is the most common
gallbladder drainage method. There are several alternatives
to PTGBD. Percutaneous transhepatic gallbladder aspiration is a simple alternative drainage method with fewer

T. Tsuyuguchi (&)
Department of Medicine and Clinical Oncology,
Graduate School of Medicine Chiba University,
1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan
e-mail: tsuyuguchi@faculty.chiba-u.jp
T. Itoi
Tokyo Medical University, Tokyo, Japan
T. Takada F. Miura
Tokyo, Japan
S. M. Strasberg
University in Saint Louis School of Medicine, Saint Louis, MO,
USA
H. A. Pitt
M.-H. Kim
complications; however, its clinical usefulness has been

shown only by case-series studies. Endoscopic naso-gallbladder drainage and gallbladder stenting via a transpapillary endoscopic approach are also alternative methods in
acute cholecystitis, but both of them have technical difficulties resulting in lower success rates than that of PTGBD.
Recently, endoscopic ultrasonography-guided transmural
gallbladder drainage has been reported as a special technique for gallbladder drainage. However, it is not yet an
established technique. Therefore, it should be performed in
high-volume institutes by skilled endoscopists. Further
prospective evaluations of the feasibility, safety, and efficacy of these various approaches are needed. This article
A. N. Supe
T. Mayumi
M. Yoshida
H. Gomi
Shimotsuke, Tochigi, Japan
Y. Kimura
Sapporo, Japan
R. Higuchi
123
82
describes indications and techniques of drainage for acute

cholecystitis.
are available via http://www.jshbps.jp/en/guideline/tg13.html.
Keywords Acute cholecystitis Gallbladder drainage
Endoscopic ultrasound Percutaneous transhepatic
gallbladder drainage (PTGBD) Endoscopic
naso-gallbladder drainage (ENGBD)
Introduction
The Tokyo Guidelines (TG07) defined diagnostic criteria
and severity assessment of acute cholecystitis in January
2007[1]. In the TG07, percutaneous transhepatic gallbladder drainage (PTGBD) should be used in patients with
grade II (moderate) cholecystitis only when they do not
respond to conservative treatment and for patients with
grade III (severe) disease [2]. One controlled study (level
C) [3] compared PTGBD with medical treatment alone and
did not find lower mortality using PTGBD, but this study
has several serious limitations as follows; (1) selection bias
[the PTGBD group had many intensive care unit (ICU)
patients] , (2) drainage methods were changed after a fatal
complication, (3) randomization was achieved using a
playing card and was not blinded. Thus, PTGBD, which
has been endorsed by many studies of case-series but not
by proper controlled trials (level C) [414], is the most
common gallbladder drainage method for elderly and
critically ill patients. There are several alternatives to
PTGBD. Percutaneous transhepatic gallbladder aspiration
(PTGBA) is an alternative in which the gallbladder contents are puncture-aspirated without placing a drainage
catheter (level C) [6, 15]. Endoscopic naso-biliary gall-
K. Okamoto
Kitakyushu, Japan
Y. Yamashita
T. Gabata
J. Hata
S. Kusachi
123
bladder drainage (ENGBD) and endoscopic gallbladder

stenting (EGBS) are also alternatives via the transpapillary
route [16]. With the recent improvement in endoscopic
ultrasound (EUS), EUS-guided gallbladder drainage is
performed via the antrum of the stomach and the bulbus of
the duodenum [16]. However, these alternatives are not
fully examined; PTGBD is still recognized as a standard
drainage method.
In this article, we describe the indication and details of
gallbladder drainage for acute cholecystitis, and show the
grades of recommendation for the procedures established
by the Guidelines.
Q1. What are the standard gallbladder drainage
methods for surgically unfit patients with acute
cholecystitis?
PTGBD is an essential technique for non-surgical gallbladder

drainage. Thus, we recommend PTGBD for surgically unfit
patients with acute cholecystitis (recommendation 1, level B).
We recommend PTGBD as a standard drainage method

according to the GRADE system [17]. Factors that affect
the strength of a recommendation are summarized in
Table 1.
Indications and significance of PTGBD

Although early cholecystectomy, a one-shot definitive
treatment for acute cholecystitis, remains the reference
standard, perioperative mortality rates in elderly or critically ill patients are reported to be high (up to 19 %) [18].
Therefore, PTGBD is considered a safe alternative, especially in surgically high-risk populations. There is no doubt
that PTGBD with administration of antibiotics can convert
a septic cholecystitis into a non-specific condition. From a
technical point of view, it is a rather uncomplicated procedure with a low complication rate reported to range from
0 to 13 % [412]. A systematic review [18] reports that
30-day or in-hospital mortality after PTGBD is high
(15.4 %), but that procedure-related mortality is low
(0.36 %). Of note, mortality is predominantly related to the
severity of the underlying disease rather than the ongoing
gallbladder sepsis. By contrast, mortality rates after cholecystectomy in elderly patients with acute cholecystitis
have been lower than those of previous years (prior to 1995
vs. after 1995, 12.0 vs. 4.0 %) [18]. Recent advances in
anesthesiology and perioperative care may have improved
the outcomes of cholecystectomy for critically ill patients.
There are no controlled studies evaluating the outcomes of
83
Table 1 A critical comparison of drainage methods for acute cholecystitis according to GRADE system [17]
Drainage methoda
Factors that affect the strength of a recommendation

Quality
of evidence
The balance between

desirable and undesirable effects
Technical
difficulty
Patient values
and preferences
Cost
PTGBD
B (moderate)
Very good
No
Yes
Low cost
PTGBA
C (low)
Good (insufficient drainage effect)
No
No
Very low cost
ENGBD/EGBS
Surgical cholecystostomy
C (low)
C (low)
Good (low success rate)

Good (surgical risk)
Yes (difficult)
No
Yes/no
Yes
Low cost
High cost
See details in each section
PTGBD versus early cholecystectomy. A few papers report

comparative studies in a well-defined patient group.
Melloul et al. [19] analyzed a matched case-controlled
study of critically ill patients with acute cholecystitis. A
series of 42 consecutive patients at a single ICU center
during a 7-year period were retrospectively analyzed.
Surgery was associated with an increased complication
rate of 47 % compared with PTGBD (8.7 %), but mortality rates were not different. One Spanish retrospective
study [20] compared mortality rates in 62 consecutive
patients critically ill with acute cholecystitis divided
between a PTGBD group and a cholecystectomy group,
and they found a significantly higher mortality rate in the
PTGBD group (17.2 vs. 0 %). This study, however, has
several limitations: the study design is not prospective,
inclusion criteria in the PTGBD group may have selection
bias because the highest-risk patients could have been
treated mainly by PTGBD. These biases and shortcomings
in the study design make any comparison between the
outcomes of PTGBD and early cholecystectomy hazardous. Therefore, it is not possible to make definitive recommendations regarding treatment using PTGBD or
cholecystectomy in elderly or critically ill patients with
acute cholecystitis. Large multicenter randomized trials of
PTGBD versus early cholecystectomy are undoubtedly
needed to resolve these controversies.
Optimal timing of gallbladder drainage

For patients with moderate (grade II) disease, gallbladder
drainage should be used only when a patient does not
respond to conservative treatment. For patients with severe
(grade III) disease, gallbladder drainage is recommended
with intensive care. One prospective study [21] shows that
predictors for failure of conservative treatment are: age
above 70 years old, diabetes, tachycardia and a distended
gallbladder at admission. Likewise, WBC [15000 cell/ll,
an elevated temperature and age above 70 years old were
found to be predictors for the failure of conservative
treatment at 24-h and 48-h follow-up.
Procedures for gallbladder drainage

Percutaneous transhepatic gallbladder drainage
(Video 1)
PTGBD is a standard technique for nonoperative gallbladder drainage. After ultrasound-guided transhepatic
gallbladder puncture has been performed with an 18-G
needle, a 6- to 10-Fr pigtail catheter is placed in the gallbladder, using a guidewire under fluoroscopy (Seldinger
technique; Fig. 1). There was no technical difficulty and
the technique could be available around the world
(Table 1). However, it has several disadvantages as follows: (1) the drainage tube cannot be extracted until a
fistula forms around the tube, (2) there is a risk of
dislocation of the tube, (3) patient discomfort may cause
self-decannulation of the PTGBD tube.
Percutaneous transhepatic gallbladder aspiration
PTGBA is a method to aspirate bile via the gallbladder
with a small-gauge needle under ultrasonographic guidance
(Fig. 2). This method is an easy low-cost bedside-applicable procedure, without the patient discomfort seen in
PTGBD (Table 1). Theoretically, the drainage effect of
single PTGBA is lower than that of PTGBD as described in
a randomized controlled trial (RCT) [12]. However,
repetitive PTGBA [6, 15] can improve its effectiveness
(from 71.1 to 95.6 %) and this methodology has not been
compared with PTGBD. Although PTGBA with a smallgauge (21-G) needle has a lower risk of leakage after
removal, aspiration of highly viscous bile is difficult with
such needles and should be conducted while washing with
saline containing antibiotics.
Endoscopic transpapillary gallbladder drainage

Endoscopic naso-biliary gallbladder drainage (Video 2)
ENGBD can be used for patients with severe comorbid
conditions, especially those with end-stage liver disease, in
123
84
Fig. 1 Percutaneous
transhepatic gallbladder
drainage (PTGBD) procedure.
A guidewire is inserted into the
gallbladder after a needle is
inserted into the gallbladder
(left). Then a drainage tube is
passed over the guide-wire into
the gallbladder (right)
Fig. 2 Percutaneous
transhepatic gallbladder
aspiration (PTGBA) procedure.
Under ultrasound guidance, the
gallbladder is punctured
transhepatically by a needle
(left). Then bile is aspirated by
using a syringe (right)
Fig. 3 Endoscopic nasobiliary

gallbladder drainage (ENGBD)
procedure. Left Schema of
ENGBD. Right X-ray shows
nasobiliary catheter placed in
the gallbladder
123
85
Fig. 4 Endoscopic gallbladder

stenting (EGBS) procedure. Left
Schema of EGBS. Right X-ray
shows double-pig tail stent
placed in the gallbladder
whom the percutaneous approach is difficult to perform.

However, because it requires a difficult endoscopic technique (technical success rate varies from 64 to 100 %), and
relevant case-series studies have been conducted only at a
limited number of institutions [2228], ENGBD has not yet
been established as a standard method. Therefore, it should
be performed in high-volume institutes by skilled
endoscopists.
ENGBD involves placement of a naso-gallbladder
drainage tube and generally does not require biliary
sphincterotomy. After successful bile duct cannulation, a
0.035-in. guidewire is advanced into the cystic duct and
subsequently into the gallbladder. At times, a hydrophilic
guidewire is useful for seeking the cystic duct. Finally, a
58.5 Fr pigtail naso-gallbladder drainage tube catheter is
placed into the gallbladder (Fig. 3).
Endoscopic transpapillary gallbladder stenting
Since endoscopic transpapillary gallbladder stenting
(EGBS) requires a difficult endoscopic technique, and
relevant case-series studies have been conducted only at a
limited number of institutions [2936], EGBS also has
not been established as a standard method. Therefore, it
should be performed in high-volume institutes by skilled
endoscopists. The procedure is identical to ENGBD, but a
610-Fr diameter double pigtail stent is placed (Fig. 4).
When 10-Fr stents or a gallbladder stent and a biliary stent
are placed (for example in Mirizzis syndrome), an endoscopic biliary sphincterotomy is performed to prevent postERCP pancreatitis.
Q2. What are the special techniques as gallbladder
drainage?
There is endoscopic ultrasonography - guided gallbladder

drainage (EUS-guided gallbladder drainage).
EUS-guided gallbladder drainage is performed via the

antrum of the stomach and bulbus of the duodenum (Fig. 5)
[16, 42]. It includes EUS-guided naso-gallbladder drainage
[37, 38] and EUS-guided gallbladder stenting [39, 44]
(Table 2). Recently one controlled study [42] showed that
EUS-GBD is comparable to PTGBD in terms of the technical feasibility and efficacy. However, EUS-guided gallbladder drainage has not been established as a standard
method. Therefore, they should be performed in highvolume institutes by skilled endoscopists [3746].
Technique of EUS-guided gallbladder drainage [16, 44]
(Video 3)
Theoretically, the gallbladder does not have adhesions to
the GI tract. Therefore, there is a possibility of bile leakage
123
86
Fig. 5 EUS-guided gallbladder

approach via bulbus of the
duodenum. Left Schema of
EUS-guided gallbladder
drainage. Right X-ray shows
double-pig tail stent placed in
the gallbladder
Table 2 Outcome of endosonography-guided gallbladder drainage

References
No. of
cases
NGD/
Stenting
Approach
route
Technical
success
(%)
Clinical
success
(%)
Complication (no. of cases)
Baron [39]
PS
TD
100
100
None
Kwan [37]
NGD
TD
100
100
Bile leakage (1)a
Lee [38]
Takasawa [40]
9
1
NGD
PS
TD
TG
100
100
100
100
Pneumoperitoneum (1)
None
Kamata [46]
SEMS
TD
100
100
None
Song [41]
PS
1TG/7TD
100
100
Bile leakage (1)a, pneumoperitoneum (1),

stent migration (1)
Itoi [42]
PS
1TG/1TD
100
100
Bile leakage (1)a
Jang [43]
15
SEMS
10TG/5TD
100
100
None
Itoi [44]
SEMS
1TG/4TD
100
100
None
Jang [45]
30
NGD
NA
97
100
Pneumoperitoneum (2)
SEMS self-expandable metal stent, PS plastic stent, NGD naso-gallbladder drain, TD transduodenal approach, TG transgastric approach, NA not
available
a
Minor bile leakage without serious bile peritonitis
during the procedures; in particular, if the procedure fails,

serious bile peritonitis can occur. The choice of endoscope
position is important to accomplish the procedure safely.
The gallbladder is visualized from the duodenal bulb or the
antrum of the stomach using a curved linear array
echoendoscope in a long scope position (pushing scope
position) (Fig. 5). At this time, the direction of the EUS
probe is toward the right side of the body. A needle knife
(Zimmon papillotomy knife, or Cystotome, Wilson-Cook,
Winston-Salem, NC, USA) catheter using electrocautery,
or a 19-gauge needle (EchoTip, Wilson-Cook), is advanced
into the gallbladder under EUS visualization after confirming the absence of intervening blood vessels to avoid
bleeding. After the stylet has been removed, first bile is
aspirated and then contrast medium is injected into the
gallbladder for cholecystography, then a 0.025- or 0.035-in.
123
guidewire is advanced into the outer sheath. If necessary, a

biliary catheter for dilation (Soehendra Biliary Dilator,
Wilson-Cook), or papillary balloon dilation catheter
(Maxpass, Olympus Medical Systems) are used for dilation
of the gastrocholecystic and duodenocholecystic fistula.
Finally, a 5-10 Fr naso-gallbladder tube is advanced via the
cholecystogastrostomy and cholecystoduodenostomy site
into the gallbladder. The basic procedure of EUS-guided
gallbladder stenting is the same as EUS-guided nasogallbladder drainage. A 7-10Fr double pigtail plastic or
self-expanding metallic stent is placed in the final step.
There have been 9 retrospective and 1 prospective
analyses on 3 EUS-guided naso-gallbladder drainages and
7 EUS-guided gallbladder stentings (4 plastic stent, 3 selfexpanding metal stent) (Table 2). The success rates and
response rates of both procedures were approximately
100 %, but the incidence of accidents was fairly high

(1133 %), indicating the necessity for further investigations emphasizing safety evaluation. There are several
possible procedure-related early adverse events, e.g., bile
leakage, stent migration into the gallbladder or intraabdominal space, deviation of stent from the gallbladder,
puncture-induced hemorrhage, and perforation of peritoneum. Late adverse events include relapse of acute cholecystitis due to stent occlusion, and inadvertent tube
removal.
None.
References
2007;14:7882.
2. Tsuyuguchi T, Takada T, Kawarada Y, Nimura Y, Wada K,
Nagino M, et al. Techniques of biliary drainage for acute cholecystitis: Tokyo guidelines. J Hepatobiliary Pancreat Surg.
2007;14:4651 (clinical practice guidelines, CPGs).
3. Hatzidakis AA, Prassopoulos P, Petinarakis I, Sanidas E, Chrysos
E, Chalkiadakis G, et al. Acute cholecystitis in high-risk patients:
percutaneous cholecystostomy vs conservative treatment. Eur
Radiol. 2002;12:177884 (CPGs).
4. Kiviniemi H, Makela JT, Autio R, Tikkakoski T, Leinonen S,
Siniluoto T, et al. Percutaneous cholecystostomy in acute cholecystitis in high-risk patients: an analysis of 69 patients. Int Surg.
1998;83:299302.
5. Sugiyama M, Tokuhara M, Atomi Y. Is percutaneous cholecystostomy the optimal treatment for acute cholecystitis in the very
elderly? World J Surg. 1998;22:45963.
6. Chopra S, Dodd GD 3rd, Mumbower AL, Chintapalli KN,
Schwesinger WH, Sirinek KR, et al. Treatment of acute cholecystitis in non-critically ill patients at high surgical risk: comparison of clinical outcomes after gallbladder aspiration and after
percutaneous cholecystostomy. AJR Am J Roentgenol.
2001;176:102531.
7. Akhan O, Akinci D, Ozmen MN. Percutaneous cholecystostomy.
Eur J Radiol. 2002;43:22936.
8. Donald JJ, Cheslyn-Curtis S, Gillams AR, Russell RC, Lees WR.
Percutaneous cholecystolithotomy: is gall stone recurrence
inevitable? Gut. 1994;35:6925.
9. Hultman CS, Herbst CA, McCall JM, Mauro MA. The efficacy of
percutaneous cholecystostomy in critically ill patients. Am Surg.
1996;62:2639.
10. Melin MM, Sarr MG, Bender CE, van Heerden JA. Percutaneous
cholecystostomy: a valuable technique in high-risk patients with
presumed acute cholecystitis. Br J Surg. 1995;82:12747.
11. Davis CA, Landercasper J, Gundersen LH, Lambert PJ. Effective
use of percutaneous cholecystostomy in high-risk surgical
patients: techniques, tube management, and results. Arch Surg.
1999;134:72731.
12. Ito K, Fujita N, Noda Y, Kobayashi G, Kimura K, Sugawara T,
et al. Percutaneous cholecystostomy versus gallbladder aspiration
for acute cholecystitis: a prospective randomized controlled trial.
AJR Am J Roentgenol. 2004;183:1936.
13. Babb RR. Acute acalculous cholecystitis. J Clin Gastroenterol.
1992;15:23841.
87
14. Lillemoe KD. Surgical treatment of biliary tract infections. Am
Surg. 2000;66:13844.
15. Tsutsui K, Uchida N, Hirabayashi S, Kamada H, Ono M, Ogawa
M, et al. Usefulness of single and repetitive percutaneous transhepatic gallbladder aspiration for the treatment of acute cholecystitis. J Gastroenterol. 2007;42:5838.
16. Itoi T, Coelho-Prabhu N, Baron TH. Endoscopic gallbladder
drainage for management of acute cholecystitis. Gastrointest
Endosc. 2010;71:103845.
17. Schunemann HJ, Oxman AD, Brozek J, Glasziou P, Jaeschke R,
Vist GE, et al. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ.
2008;17(336):110610.
18. Winbladh A, Gullstrand P, Svanvik J, Sandstrom P. Systematic
review of cholecystostomy as a treatment option in acute cholecystitis. HPB (Oxford). 2009;11:18393.
19. Melloul E, Denys A, Demartines N, Calmes JM, Schafer M.
Percutaneous drainage versus emergency cholecystectomy for the
treatment of acute cholecystitis in critically ill patients: does it
matter? World J Surg. 2011;35:82633.
20. Rodriguez Sanjuan JC, Arruabarrena A, Sanchez Moreno L,
Gonzalez Sanchez F, Herrera LA, Gomez Fleitas M. Acute
cholecystitis in high surgical risk patients: percutaneous cholecystostomy or emergency cholecystectomy? Am J Surg.
2012;204(1):549.
21. Barak O, Elazary R, Appelbaum L, Rivkind A, Almogy G. Conservative treatment for acute cholecystitis: clinical and radiographic predictors of failure. Isr Med Assoc J. 2009;11:73943.
22. Baron TH, Schroeder PL, Schwartzberg MS, Carabasi MH.
Resolution of Mirizzis syndrome using endoscopic therapy.
23. Feretis C, Apostolidis N, Mallas E, Manouras A, Papadimitriou J.
Endoscopic drainage of acute obstructive cholecystitis in patients
with increased operative risk. Endoscopy. 1993;25:3925.
24. Itoi T, Sofuni A, Itokawa F, Tsuchiya T, Kurihara T, Ishii K, et al.
Endoscopic transpapillary gallbladder drainage in patients with
acute cholecystitis in whom percutaneous transhepatic approach
is contraindicated or anatomically impossible (with video). Gastrointest Endosc. 2008;68:45560.
25. Kjaer DW, Kruse A, Funch-Jensen P. Endoscopic gallbladder drainage of patients with acute cholecystitis. Endoscopy. 2007;39:3048.
26. Nakatsu T, Okada H, Saito K, Uchida N, Minami A, Ezaki T,
et al. Endoscopic transpapillary gallbladder drainage (ETGBD)
for the treatment of acute cholecystitis. J Hepatobiliary Pancreat
Surg. 1997;4:315.
27. Ogawa O, Yoshikumi H, Maruoka N, Hashimoto Y, Kishimoto
Y, Tsunamasa W, et al. Predicting the success of endoscopic
transpapillary gallbladder drainage for patients with acute cholecystitis during pretreatment evaluation. Can J Gastroenterol.
2008;22:6815.
28. Toyota N, Takada T, Amano H, Yoshida M, Miura F, Wada K.
Endoscopic naso-gallbladder drainage in the treatment of acute
cholecystitis: alleviates inflammation and fixes operators aim
during early laparoscopic cholecystectomy. J Hepatobiliary
29. Conway JD, Russo MW, Shrestha R. Endoscopic stent insertion
into the gallbladder for symptomatic gallbladder disease in
patients with end-stage liver disease. Gastrointest Endosc.
2005;61:326.
30. Gaglio PJ, Buniak B, Leevy CB. Primary endoscopic retrograde
cholecystoendoprosthesis: a nonsurgical modality for symptomatic cholelithiasis in cirrhotic patients. Gastrointest Endosc.
1996;44:33942.
31. Kalloo AN, Thuluvath PJ, Pasricha PJ. Treatment of high-risk
patients with symptomatic cholelithiasis by endoscopic gallbladder stenting. Gastrointest Endosc. 1994;40:60810.
123
88
32. Pannala R, Petersen BT, Gostout CJ, Topazian MD, Levy MJ,
Baron TH. Endoscopic transpapillary gallbladder drainage:
10-year single center experience. Minerva Gastroenterol Dietol.
2008;54:10713.
33. Schlenker C, Trotter JF, Shah RJ, Everson G, Chen YK, Antillon
D, et al. Endoscopic gallbladder stent placement for treatment of
symptomatic cholelithiasis in patients with end-stage liver disease. Am J Gastroenterol. 2006;101:27883.
34. Shrestha R, Bilir BM, Everson GT, Steinberg SE. Endoscopic
stenting of gallbladder for symptomatic cholelithiasis in patients
with end-stage liver disease awaiting orthotopic liver transplantation. Am J Gastroenterol. 1996;91:5958.
35. Tamada K, Seki H, Sato K, Kano T, Sugiyama S, Ichiyama M,
et al. Efficacy of endoscopic retrograde cholecystoendoprosthesis
(ERCCE) for cholecystitis. Endoscopy. 1991;23:23.
36. Johlin FC Jr, Neil GA. Drainage of the gallbladder in patients
with acute acalculous cholecystitis by transpapillary endoscopic
cholecystotomy. Gastrointest Endosc. 1993;39:64551.
37. Kwan V, Eisendrath P, Antaki F, Le Moine O, Deviere J. EUSguided cholecystoenterostomy: a new technique (with videos).
38. Lee SS, Park DH, Hwang CY, Ahn CS, Lee TY, Seo DW, et al.
EUS-guided transmural cholecystostomy as rescue management
for acute cholecystitis in elderly or high-risk patients: a prospective feasibility study. Gastrointest Endosc. 2007;66:
100812.
39. Baron TH, Topazian MD. Endoscopic transduodenal drainage of
the gallbladder: implications for endoluminal treatment of gallbladder disease. Gastrointest Endosc. 2007;65:7357.
123

40. Takasawa O, Fujita N, Noda Y, Kobayashi G, Ito K, Horaguchi J,
et al. Endosonography-guided gallbladder drainage for acute
cholecystitis following covered metal stent deployment. Dig
Endosc. 2009;21:437.
41. Song TJ, Park do H, Eum JB, Moon SH, Lee SS, Seo DW, et al.
EUS-guided cholecystoenterostomy with single-step placement
of a 7F double-pigtail plastic stent in patients who are unsuitable
for cholecystectomy: a pilot study (with video). Gastrointest
Endosc. 2010;71:63440.
42. Itoi T, Itokawa F, Kurihara T. Endoscopic ultrasonography-guided gallbladder drainage: actual technical presentations and
review of the literature (with videos). J Hepatobiliary Pancreat
Sci. 2011;18:2826.
43. Jang JW, Lee SS, Park do H, Seo DW, Lee SK, Kim MH, et al.
Feasibility and safety of EUS-guided transgastric/transduodenal
gallbladder drainage with single-step placement of a modified
covered self-expandable metal stent in patients unsuitable for
cholecystectomy. Gastrointest Endosc. 2011;74:17681.
44. Itoi T, Binmoeller, Shah J, Sofuni A, Itokawa F, Kurihara T, et al.
Clinical evaluation of a novel lumen-apposing metal stent for
endosonography-guided pancreatic pseudocyst and gallbladder
drainage (with videos). Gastrointest Endosc. 2012;75:8706.
45. Jang JW, Lee SS, Song TJ, Hyun YS, Park do H, Seo DW, et al.
Endoscopic ultrasound-guided transmural and percutaneous
transhepatic gallbladder drainage are comparable for acute cholecystitis. Gastroenterology. 2012;142(4):80511.
46. Kamata K, Kitano M, Komaki T, Sakamoto H, Kudo M. Transgastric endoscopic ultrasound (EUS)-guided gallbladder drainage
for acute cholecystitis. Endoscopy. 2009;41(Suppl 2):E3156.

DOI 10.1007/s00534-012-0567-x
GUIDELINE

TG13 surgical management of acute cholecystitis

Yuichi Yamashita Tadahiro Takada Steven M. Strasberg Henry A. Pitt Dirk J. Gouma
O. James Garden Markus W. Buchler Harumi Gomi Christos Dervenis John A. Windsor
Sun-Whe Kim Eduardo de Santibanes Robert Padbury Xiao-Ping Chen Angus C. W. Chan
Sheung-Tat Fan Palepu Jagannath Toshihiko Mayumi Masahiro Yoshida Fumihiko Miura
Toshio Tsuyuguchi Takao Itoi Avinash N. Supe

Abstract
Background Laparoscopic cholecystectomy is now
accepted as a surgical procedure for acute cholecystitis
when it is performed by an expert surgeon. There are
several lines of strong evidence, such as randomized controlled trials (RCTs) and meta-analyses, supporting the
introduction of laparoscopic cholecystectomy for patients
with acute cholecystitis. The updated Tokyo Guidelines
2013 (TG13) describe the surgical treatment for acute
cholecystitis according to the grade of severity, the timing,
and the procedure used for cholecystitis in a question-andanswer format using the evidence concerning surgical
management of acute cholecystitis.
Methods and materials Forty-eight publications were
selected for a careful examination of their full texts, and the
types of surgical management of acute cholecystitis were
investigated using this evidence. The items concerning the
surgical management of acute cholecystitis were the optimal surgical treatment for acute cholecystitis according to
Y. Yamashita (&)
Hospital, Fukuoka University School of Medicine,
7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
e-mail: yuichiya@fukuoka-u.ac.jp
H. Gomi
Tochigi, Japan
T. Takada F. Miura
Tokyo, Japan
S. M. Strasberg
H. A. Pitt
D. J. Gouma
O. J. Garden
M. W. Buchler
Heidelberg, Germany
C. Dervenis
First Department of Surgery, Agia Olga Hospital,
Athens, Greece
J. A. Windsor
S.-W. Kim
Department of Surgery, Seoul National University College
of Medicine, Seoul, Korea
E. de Santibanes
Department of Surgery, Hospital Italianio,
University of Buenos Aires, Buenos Aires, Argentina
R. Padbury
Division of Surgical and Specialty Services,
Flinders Medical Centre, Adelaide, Australia
X.-P. Chen
Department of Surgery, Hepatic Surgery Centre,
Tongji Hospital, Tongi Medical College, Huazhong Universty
of Science and Technology, Wuhan, China
123
90
the grade of severity, optimal timing for the cholecystectomy, surgical procedure used for cholecystectomy, optimal timing of the conversion of cholecystectomy from
laparoscopic to open surgery, and the complications of
laparoscopic cholecystectomy.
Results There were eight RCTs and four meta-analyses
concerning the optimal timing of the cholecystectomy.
Consequently, it was found that cholecystectomy is preferable early after admission. There were three RCTs and
two meta-analyses concerning the surgical procedure,
which concluded that laparoscopic cholecystectomy is
preferable to open procedures. Literature concerning the
surgical treatment according to the grade of severity could
not be quoted, because there have been no publications on
this topic. Therefore, the treatment was determined based
on the general opinions of professionals.
Conclusion Surgical management of acute cholecystitis
in the updated TG13 is fundamentally the same as in the
Tokyo Guidelines 2007 (TG07), and the concept of a critical
view of safety and the existence of extreme vasculobiliary
injury are added in the text to call the surgeons attention
to the need to reduce the incidence of bile duct injury.
html.
Keywords Acute cholecystitis Laparoscopic
cholecystectomy Cholecystostomy Bile duct injury
Gallbladder drainage
Introduction
Cholecystectomy has been widely used as a surgical
procedure for acute cholecystitis. There have been several
A. C. W. Chan
Department of Surgery, Surgery Centre, Hong Kong Sanatorium
S.-T. Fan
Department of Surgery, The University of Hong Kong,
Queen Mary Hospital, Hong Kong, Hong Kong
P. Jagannath
T. Mayumi
M. Yoshida
123
studies on the timing of cholecystectomy beginning in the

era of open surgery and also in the current era of laparoscopic surgery. These studies have shown that early
surgery conducted within 7296 h after the onset of
symptoms is associated with advantages such as reduced
hospital stay, sick leave, and health care expenditures, and
no disadvantages with regard to mortality and morbidity.
Since the initial introduction of laparoscopic cholecystectomy, it has been considered to be contraindicated for
acute cholecystitis. However, due to the establishment of
the critical view of safety introduced by Strasberg et al.
[1] for the dissection of Calots triangle, the development
of new techniques, and the improvements made to the
instruments used for endoscopic surgery, laparoscopic
cholecystectomy is now accepted as a safe surgical
technique when it is performed by expert surgeons.
Recent randomized clinical trials and meta-analyses have
indicated that laparoscopic cholecystectomy is preferable
to open cholecystectomy.
In 2007, the Tokyo Guidelines for the management of
acute cholangitis and cholecystitis [2] were published in
the Journal of Hepato-Biliary-Pancreatic Surgery, in
which a severity classification was presented for the first
time. Previously, there was no severity classification for
acute cholecystitis. There were therefore no reports of the
effects of surgical treatment or gallbladder drainage
according to the severity of acute cholecystitis. Consequently, the treatment methods were determined based on
the general opinions of professionals. Four years have
passed since the publication of the Tokyo Guidelines 2007
[2], but there are still no reliable reports of the optimal
treatment for each severity grade of acute cholecystitis.
The therapeutic strategy for acute cholecystitis is presented
here in the question-and-answer format prepared in the
revision of TG07 [2] while referring to recent reports.
T. Tsuyuguchi
School of Medicine, Chiba University, Chiba, Japan
T. Itoi
Tokyo Medical University, Tokyo, Japan
A. N. Supe
Q1. What is the optimal surgical treatment for acute

cholecystitis according to the grade of severity?
We recommend the optimal treatment according to the grade
of severity as follows;
Grade I
(Mild)
acute
cholecystitis:
Early
laparoscopic cholecystectomy is the preferred procedure.
Grade II (Moderate) acute cholecystitis: Early cholecystectomy
is recommended in experienced centers. However, if
91
inflammation of the gallbladder. Delayed cholecystectomy

is required 2 to 3 months later, after the improvement of the
patients general condition when cholecystectomy is
indicated.
Q2. Which surgical procedure is preferred, laparoscopic cholecystectomy or open cholecystectomy?
We recommend that laparoscopic cholecystectomy is preferable
to open cholecystectomy (recommendation 1, level A).
patients have severe local inflammation, early gallbladder

drainage (percutaneous or surgical) is indicated. Because early
cholecystectomy may be difficult,
medical treatment and
delayed cholecystectomy are necessary.

Grade III
(Severe)
acute
cholecystitis:
Urgent
management of organ dysfunction and management of severe
local inflammation by gallbladder drainage should be carried
out. Delayed elective cholecystectomy should be performed
when cholecystectomy is indicated.
The optimal treatment for acute cholecystitis is essentially early cholecystectomy, and the use of an established
optimal surgical treatment for each grade of severity of
acute cholecystitis is necessary. Early laparoscopic cholecystectomy is indicated for patients with Grade I (Mild)
acute cholecystitis, because laparoscopic cholecystectomy
can be performed in most of these patients. Early laparoscopic or open cholecystectomy (within 72 h after the
onset of acute cholecystitis) is required in patients with
Grade II (Moderate) acute cholecystitis in experienced
centers, but for some patients with Grade II (Moderate)
acute cholecystitis, it is difficult to remove the gallbladder
surgically because of severe inflammation limited to the
gallbladder. This severe local inflammation of the gallbladder is defined by factors such as [72 h from the onset,
a white blood cell count [18,000, and a palpable tender
mass in the right upper abdominal quadrant. Continued
medical treatment or drainage of the contents of the
swollen gallbladder by percutaneous transhepatic gallbladder drainage or surgical cholecystostomy is preferable,
and a delayed cholecystectomy after the improvement of
inflammation of the gallbladder is indicated. Among
patients with Grade II (Moderate), for those with serious
local complications including biliary peritonitis, pericholecystic abscess, liver abscess or for those with gallbladder
torsion, emphysematous cholecystitis, gangrenous cholecystitis, and purulent cholecystitis, emergency surgery is
conducted (open or laparoscopic depending on experience)
along with the general supportive care of the patient. The
urgent management of Grade III (Severe) acute cholecystitis is always necessary because the patients have organ
dysfunction, and the simultaneous drainage of the gallbladder contents is required to treat the severe
Gallstones are one of the major causes of acute cholecystitis, and cholecystectomy is now being carried out in
many of the patients with cholecystolithiasis. Until the first
half of the 1990s, there were opinions that laparoscopic
surgery was not indicated in patients with acute cholecystitis [3]. Open cholecystectomy was the standard technique.
However, more recently, laparoscopic surgery has also
been introduced for acute cholecystitis, and is now generally considered to be the first option for surgery, similar to
open cholecystectomy. Several reports, including randomized controlled trials (RCTs) comparing laparoscopic
cholecystectomy and open cholecystectomy, have indicated that laparoscopic cholecystectomy is associated with
a significantly shorter postoperative hospital stay and a
lower incidence of complications [47]. A meta-analysis
has also shown that laparoscopic cholecystectomy not only
resulted in treatment effects similar to those produced by
open cholecystectomy, but that it is also a useful surgical
procedure in terms of its low mortality and morbidity[8, 9].
However, the above reports have failed to examine its use
for acute cholecystitis according to the grade of severity.
Laparoscopic cholecystectomy is not recommended for all
cases of acute cholecystitis due to the possibility of patients
in whom cholecystectomy is difficult because of severe
inflammation [10].
On the other hand, there has been a change in the perioperative management of open cholecystectomy patients
in the last few years, and the current management aims to
reduce postoperative pain and encourage early ambulation
and early discharge. These changes show that, in terms of
the postoperative course, open cholecystectomy with miniincision is able to produce as good results as those obtained
by laparoscopic cholecystectomy, although the superiority
of laparoscopic cholecystectomy as a surgical technique for
acute cholecystolithiasis can be recognized [8, 9]. In fact, a
RCT was carried out to reappraise the use of laparoscopic
cholecystectomy and open cholecystectomy by a subcostal
muscle transection incision [11]. This study indicated that
no significant differences were observed between the two
types of cholecystectomies with regard to the rate of
postoperative complications, the degree of pain at discharge, the duration of sick leave, and the direct medical
123
92
cost. At the moment, laparoscopic cholecystectomy is

comprehensively preferred as the surgical treatment for
acute cholecystitis. However, the first priority is the safety
of the patients. With this in mind, open surgery can be
considered to be as effective as laparoscopic surgery.
A cohort study was carried out in a total of approximately 30,000 patients with acute cholecystitis aged
66 years or older concerning the surgical procedures for
acute cholecystitis; 75 % of those patients underwent
cholecystectomy at the time of the initial hospitalization,
with 71 % undergoing laparoscopic cholecystectomy and
29 % undergoing open surgery. The results of the analysis
showed that laparoscopic cholecystectomy is being used as
the first option for surgical procedures that can be performed urgently for acute cholecystitis [12].
Q3. What is the optimal timing of cholecystectomy for
acute cholecystitis?
We recommend that it is preferable to perform cholecystectomy
soon after admission, particularly when less than 72 hours have
passed since the onset of symptoms (recommendation1, level A).
With regard to the timing of the surgery for acute cholecystitis, there are several reports of RCTs conducted in
the 1970s and 1980s that compared early surgery and
elective surgery (from the initial onset until 4 months later)
by open cholecystectomy. The trials failed to find a difference between the surgical procedures in terms of the
amount of bleeding, duration of surgery, and incidence of
complications; however, they were able to show that early
surgery is preferable because it reduces the hospital stay
and leads to an early cessation of pain in the patients [12
17]. In recent years, laparoscopic cholecystectomy has
been actively used for acute cholecystitis and the rate of its
use has been increasing every year since its introduction
[18]. The usefulness of early surgery (rather than delayed
surgery) has been indicated in RCTs [1921] and in metaanalyses in patients with acute cholecystitis [2225].
However, the definition of early surgery differed in each
report, because there were different starting times for the
operations, such as onset of symptoms, time of diagnosis,
and use of randomization. Early surgery was mainly conducted within 7296 h from onset of symptoms. On the
other hand, elective surgery was performed 6 weeks or
more after the onset. Thus, the results of several reports
indicated with a high level of evidence that laparoscopic
cholecystectomy performed during the first admission was
associated with a shorter hospital stay, quicker recovery,
and reduction in overall medical costs compared to open
cholecystectomy. Early laparoscopic cholecystectomy is
now accepted to be sufficiently safe for routine use.
123
After evaluating a patients overall condition and confirmation of the diagnosis by ultrasonography, computed
tomography (CT), and/or magnetic resonance cholangiopancreatography, the timing of the surgical management of
acute cholecystitis patients should be decided by experienced surgeons. Unfortunately, early surgery is performed
less frequently than is recommended at present because of
the scarcity of surgeons [18, 26, 27]. However, the fact that
the above trials excluded patients with pan-peritonitis
caused by perforation of the gallbladder, patients with
common bile duct stones, and those with concomitant
severe cardiopulmonary disease should be kept in mind
when evaluating the results of these trials.
Additionally, each meta-analysis indicated that there
was no statistically significant difference in the incidence
of bile duct injury (BDI). However, these meta-analyses
did not include a large enough number of patients to detect
a difference, because the incidence of BDI in the laparoscopic era is generally less than 1.0 % [2830]. Therefore,
it is impossible to assert that there are no significant differences in the incidence of BDI on the basis of its frequency in these meta-analyses.
Q4. When is the optimal time for conversion from
laparoscopic to open cholecystectomy?
We recommend that surgeons should never hesitate to convert
to open surgery to prevent injuries when they experience
difficulties in performing laparoscopic cholecystectomy
(recommendation 1, level C).
There is a relatively high rate of conversion from laparoscopic cholecystectomy to open cholecystectomy for
acute cholecystitis because of technical difficulties, and
laparoscopic cholecystectomy is associated with a high
complication rate [10, 31]. Although preoperative factors
such as male gender, previous abdominal surgery, the
presence or history of jaundice, advanced cholecystitis, and
infectious complications are associated with a need for
conversion from laparoscopic to open cholecystectomy,
they have limited predictive ability [3234]. Surgeons
assess patients using various factors when deciding whether or not conversion to open cholecystectomy, particularly during laparoscopic cholecystectomy, is necessary.
Therefore, experience not only of the individual surgeons,
but also of the institution where the laparoscopic cholecystectomy is conducted, is required to successfully perform cholecystectomy for all patients with acute
cholecystitis.
The critical view of safety described by Strasberg et al.
[1] in 1995 is of the utmost importance (Fig. 1). Above all,
this critical view is now the ultimate principle for
93
known to be an effective option in critically ill patients,

especially in elderly patients and patients with complications. Cholecystectomy is often performed following
PTGBD after an interval of several days [35, 36]. However,
performing a cholecystectomy 2 weeks later is also common [37]. Overall, early cholecystectomy following
PTGBD is preferable when the patients condition
improves, and if the patient has no complications. Complications of PTGBD sometimes occur, such as intrahepatic
hematoma, pericholecystic abscess, biliary pleural effusion, and biliary peritonitis, which may be caused by
puncture of the liver and the migration of the catheter.
However, such migration should be prevented. On the other
hand, PTGBA (percutaneous transhepatic gallbladder
aspiration) is often used by many facilities, and produces
good treatment outcomes. However, a RCT indicated that
PTGBD was superior to PTGBA in terms of its clinical
effectiveness [38].
Fig. 1 Creation of a critical view of safety. Calots triangle is

dissected free of fat and fibrous tissue and the lower end of the
gallbladder is dissected off the liver bed. It is not necessary to expose
the common bile duct. The critical view of safety is now the ultimate
standard to prevent BDI during laparoscopic cholecystectomy. Failure
to create this view is an indication for conversion to open
cholecystectomy
preventing BDI during laparoscopic cholecystectomy, and

involves conclusive identification of the indicated structures by dissection in Calots triangle. Surgeons who failed
to create this surgical view should consider which procedure is more appropriate for conversion to define the bile
duct anatomy, i.e. conversion to open cholecystectomy or
intraoperative cholangiography.
Since conversion to open cholecystectomy to prevent
intraoperative accidents and postoperative complications is
not disadvantageous for patients, surgeons should never
hesitate to perform such a conversion when they experience difficulty while performing laparoscopic cholecystectomy. A low threshold for the conversion to open
cholecystectomy is important to minimize the risk of major
complications.
Q5. When is the optimal time for cholecystectomy following PTGBD?
The optimal time, however, remains controversial due to a lack
of any strong evidence.
There have been no randomized controlled trials that

have examined the surgical management of patients with
acute cholecystitis undergoing percutaneous transhepatic
gallbladder drainage (PTGBD). However, PTGBD is
Q6. What are the complications to be avoided that are

associated with laparoscopic cholecystectomy?
Bile duct injury, bleeding, and the injury of other organs
(level C).
Complications of laparoscopic cholecystectomy were

reported soon after its introduction, and include BDI,
intraperitoneal hemorrhage needing laparotomy, bowel
injury, and hepatic injury, as well as the commonly
observed complications associated with conventional open
cholecystectomy, such as wound infection, ileus, atelectasis, deep vein thrombosis, and urinary tract infection. Bile
duct injury is considered to be a serious complication.
Bowel and hepatic injuries should also be carefully avoided
as serious complications [28]. These injuries have been
attributable to the limitations of laparoscopic procedures,
such as the narrow view and non-tactile manipulation.
Laparoscopic cholecystectomy is not always associated
with a higher incidence rate compared with open cholecystectomy [3032], but any serious complication that
requires re-operation and/or prolonged hospitalization may
become a serious problem for patients, even those who
firmly believe that laparoscopic cholecystectomy is less
invasive. In spite of many improvements in the technique
and equipment, as well as the surgeons learning curve, the
BDI rate remains high compared to open cholecystectomy.
Table 1 shows the laparoscopic BDI rates in Japan from
biannual questionnaire surveys performed by the Japan
Society of Endoscopic Surgery (JSES) [28]. The incidence
of BDI in the laparoscopic era is higher than that in the
open cholecystectomy era, and is consistently around
0.6 %. Because of this rate, if a RCT is planned, two arms
123
94
Table 1 The complications of laparoscopic cholecystectomy in Japan [28, 48]

19902001
2002
2003
2004
2005
2006
2007
2008
2009
BDI rate (%)
0.66
0.79
0.77
0.66
0.77
0.65
0.58
0.54
0.62
Organ injury (%)
0.25
0.43
0.17
0.17
0.22
0.14
0.14
0.20
0.20
Bleeding (%)
0.65
0.72
0.72
0.72
0.69
0.56
0.58
0.52
0.55
No. of LCs
176,294
19,557
19,084
19,067
20,203
21,550
22,599
25,174
26,140
Japanese annual rates of bile duct injury, organ injury and bleeding to need laparotomy caused by laparoscopic cholecystectomy are shown
LC laparoscopic cholecystectomy
consisting of thousands of patients are required to detect

bile duct injury. There has been no RCT consisting of such
a large number of patients in individual arms. Even the
arms of the meta-analyses of RCTs were not large enough
to detect a difference. Therefore, it is possible that large
population studies would suggest that there are some
severe complications caused by laparoscopic cholecystectomy, whereas smaller studies do not indicate those
problems.
We therefore performed an extensive search of the literature for all types of bile duct injury. The most extreme
bile duct injury seems to be a vasculobiliary injury
involving the major hepatic artery and portal vein. The
incidence of extreme vasculobiliary injury is approximately 2 % of the patients who sustain major biliary
injuries requiring surgical reconstruction during laparoscopic cholecystectomy [39]. Such an extreme vasculobiliary injury is more likely to occur when fundus-down
cholecystectomy is attempted in the presence of severe
inflammation of the gallbladder, usually after the conversion from laparoscopic to open cholecystectomy. This
injury is caused by dissection behind the cystic plate into
the right portal pedicle. To prevent such an injury, the
surgeon involved should recognize the features of severe
inflammation, particularly severe contractive inflammation,
and refrain from using the fundus-down technique when
these symptoms are present.
Q7. When is the optimal time for cholecystectomy following endoscopic stone extraction of the bile duct in
patients with cholecysto-choledocholithiasis?
No definitive conclusions could be made due to the insufficient
evidence.
reports including meta-analysis on combinations of ESE

and laparoscopic cholecystectomy for patients only without
acute cholecystitis. A meta-analysis report showed that
intraoperative endoscopic sphincterotomy is as effective
and safe as postoperative endoscopic sphincterotomy and
resulted in a significantly shorter hospital stay [40], and
there were some reports which mentioned that the interval
between the two procedures was a few days [4144]. The
interval between ESE and laparoscopic cholecystectomy is
therefore left to the individual surgeon. At the moment,
early laparoscopic cholecystectomy following ESE during
the same hospital stay is preferable in some patients
without complications related to ESE.
A report of an analysis of approximately 30,000 patients
who were urgently admitted or admitted through the emergency department for acute cholecystitis demonstrated that a
lack of definitive therapy was associated with a 38 % gallstone-related cumulative readmission rate over the subsequent
2 years [12]. This report also demonstrated that patients with
acute cholecystitis were more likely to have gallstone-related
readmission than patients who had common bile duct stones.
However, common bile duct stones are undoubtedly one of the
factors predicting readmission, including gallstone-related
pancreatitis [4547]. Therefore, obtaining informed consent
concerning readmission is indispensable for the possible risk
for those patients who did not undergo cholecystectomy
during the initial hospitalization.
Biliary Association, the Japan Society for Surgical Infection, and the
Japanese Society of Hepato-Biliary-Pancreatic Surgery, who provided
us with great support and guidance in the preparation of these
Guidelines.
Combining endoscopic stone extraction (ESE) with

laparoscopic cholecystectomy during endoscopic retrograde cholangiography has been found to be a useful means
of treating patients with cholecysto-choledocholithiasis.
However, the optimal timing of laparoscopic cholecystectomy following ESE is still a matter of controversy in
patients with acute cholecystitis. There have been several
123
None.
References
1. Strasberg SM, Hertl M, Soper NJ. An analysis of the problem of
biliary injury during laparoscopic cholecystectomy. J Am Coll
Surg. 1995;180:10125.
2. Tokyo guidelines for the management of acute cholangitis and
cholecystitis. J Hepatobiliary Pancreat Surg. 2007;14:1121.

3. Cushieri A, Dubois F, Mouiel J, Mouiel P, Becker H, Buess G,
et al. The European experience with laparoscopic cholecystectomy. Am J Surg. 1991;161:3857.
4. Kiviluoto T, Siren J, Luukkonen P, Kivilaakso E. Randomized
trial of laparoscopic versus open cholecystectomy for acute and
gangrenous cholecystitis. Lancet. 1998;351:3215.
5. Berrgren U, Gordh T, Grama D, Haglund U, Rastad J, Arvidsson
D. Laparoscopic versus open cholecystectomy: hospitalization,
sick leave, analgesia and trauma responses. Br J Surg. 1994;81:
13625.
6. Zacks SL, Sandler RS, Rutledge R, Brown RS. A populationbased cohort study comparing laparoscopic cholecystectomy and
open cholecystectomy. Am J Gastroenterol. 2002;97:33440.
7. Flowers JL, Bailey RW, Scovill WA, Zucker KA. The Baltimore
experience with laparoscopic management of acute cholecystitis.
Am J Surg. 1991;161:38892.
8. Purkayastha S, Tilney HS, Georgiou P, Athanasiou T, Tekkis PP,
Darzi AW. Laparoscopic cholecystectomy versus mini-laparotomy cholecystectomy: a meta-analysis of randomized control
trials. Surg Endosc. 2007;21(8):1294300.
9. Keus F, de Jong JA, Gooszen HG, van Laarhoven CJ. Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis. Cochrane Database Syst Rev. 2006;18(4):
CD006231.
10. Borzellino G, Sauerland S, Minicozzi AM, Verlato G, Pietrantonj
CD, Manzoni G, et al. Laparoscopic cholecystectomy for severe
acute cholecystitis. A meta-analysis of results. Surg Endosc.
2008;22:815
11. Johansson M, Thune A, Nelvin L, Stiernstam M, Westman B,
Lundell L. Randomized clinical trial of open versus laparoscopic
cholecystectomy for acute cholecystitis. Br J Surg. 2005;92:449.
12. Riall TS, Zhang D, Townsend CM Jr, Young-Fang K, Goodwin
JS. Failure to perform cholecystectomy for acute cholecystitis in
elderly patients is associated with increased morbidity, mortality,
and cost. J Am Coll Surg. 2010;210:66879.
13. Lahtinen J, Alhava EM, Aukee S. Acute cholecystitis treated by
early and delayed surgery. A controlled clinical trial. Scan J
14. Jarvinen HJ, Hastbacka J. Early cholecystectomy for acute cholecystitis: a prospective randomized study. Ann Surg. 1980;191:
5015.
15. Norrby S, Herlin P, Holmin T, Sjodahl R, Tagesson C. Early or
delayed cholecystectomy in acute cholecystitis? A clinical trial.
Br J Surg. 1983;70:1635.
16. van der Linden W, Sunzel H. Early versus delayed operation for
acute cholecystitis. A controlled clinical trial. Am J Surg.
1970;120:713.
17. van der Linden W, Edlund G. Early versus delayed cholecystectomy: the effect of a change in management. Br J Surg.
1981;68:7537.
18. Yamashita Y, Takada T, Hirata K. A survey of the timing and
approach to the surgical management of patients with acute
cholecystitis in Japanese hospitals. J Hepatobiliary Pancreat Surg.
2006;13:40915.
19. Lo CM, Liu CL, Fan ST, Lai EC, Wong J. Prospective randomized study of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Am Surg. 1998;227:4617.
20. Lai PB, Kwong KH, Leung KL, Kwok SP, Chan AC, Chung SC.
Randomized trial of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Br J Surg. 1998;85:7647.
21. Chandler CF, Lane JS, Ferguson P, Thonpson JE. Prospective
evaluation of early versus delayed laparoscopic cholecystectomy for
the treatment of acute cholecystitis. Am Surg. 2000;66(9):896900.
22. Lau H, Lo CY, Patuil NG, Yuen WK. Early versus delayedinterval laparoscopic cholecystectomy for acute cholecystitis.
Surg Endosc. 2006;20:827.
95
23. Shikata S, Noguchi Y, Fukui T. Early versus delayed cholecystectomy for acute cholecystitis: a meta-analysis of randomized
controlled trials. Surg Today. 2005;35:55360.
24. Siddiqui T, MacDonald A, Chong PS, Jenkins T. Early versus
delayed laparoscopic cholecystectomy for acute cholecystitis: a
meta-analysis of randomized clinical trials. Am J Surg.
2008;195:407.
25. Gurusamy K, Samraj K, Glund C, Wilson E, Davidson R. Metaanalysis of randomized control trials on the safety and effectiveness of early versus delayed laparoscopic cholecystectomy for
acute cholecystitis. Br J Surg. 2010;97:14150.
26. Senapati PSP, Bhattarcharya D, Harinath G, Ammori BJ. A
survey of the timing and approach to the surgical management of
cholelithiasis in patients with acute biliary pancreatitis and acute
cholecystitis in the UK. Ann R Coll Surg Engl. 2003;85:30612.
27. Cameron IC, Chadwick C, Phillips J, Johnson AG. Management
of acute cholecystitis in UK hospitals: time for a charge. Postgrad
Med J. 2004;80:2924.
28. Yamashita Y, Kimura T, Matsumoto S. A safe laparoscopic
cholecystectomy depends upon the establishment of a critical
view of safety. Surg Today. 2010;40:50713.
29. The Southern Surgeons Club. A prospective analysis of 1518 laparoscopic cholecystectomies. N Engl J Med. 1991;324:10738.
30. Richardson MC, Bell G, Fullarton GM. Incidence and nature of
bile duct injuries following laparoscopic cholecystectomy: an
audit of 5913 cases. West of Scotland laparoscopic cholecystectomy audit group. Br J Surg. 1996;83:135660.
31. Hugh TB. New strategies to prevent laparoscopic bile duct injury :
surgeons can learn from pilots. Surgery. 2002;132:82635.
32. Eldar S, Sabo E, Nash E, Abrahamso J, Matter I. Laparoscopic
cholecystectomy for acute cholecystitis: prospective trial. World
J Surg. 1997;21:5405.
33. Brodsky A, Matter I, Sabo E, Cohen A, Abrahamson J, Eldar S.
Laparoscopic cholecystectomy for acute cholecystitis: can the
need for conversion and the probability of complications be
predicted? Surg Endosc. 2000;14:75560.
34. Kama NA, Doganay M, Dolapci E, Reis E, Ati M, Kologlu M.
Risk factors resulting in conversion of laparoscopic cholecystectomy to open surgery. Surg Endosc. 2001;15:9658.
35. Kivinen H, Makela JT, Autio R, Tikkakoski T, Leinonen S, Siniluoto T, et al. Percutaneous cholecystostomy in acute cholecystitis in high-risk patients: an analysis of 69 patients. Int Surg.
1998;83:299302.
36. Chikamori F, Kuniyosi N, Shibuya S, Takase Y. Early scheduled
laparoscopic cholecystectomy following percutaneous transhepatic gallbladder drainage for patients with acute cholecystitis.
Surg Endosc. 2002;16:17047.
37. Hyung OK, Byung HS, Chang HY, Jun HS. Impact of delayed
laparoscopic cholecystectomy after percutaneous transhepatic
gallbladder drainage for patients with complicated acute cholecystitis. Surg Laparosc Endosc Percutan. 2009;19:204.
38. Ito K, Fujita N, Noda Y, Kobayashi G, Kimura K, Sugawara T,
et al. Percutaneous cholecystectomy versus gallbladder aspiration
for acute cholecystitis: a prospective randomized controlled trial.
AJR. 2004;183:1936.
39. Strasberg SM, Gouma DJ. Extreme vasculobiliary injuries:
association with fundus-down cholecystectomy in severely
inflamed gallbladders. HPB. 2011;14:18.
40. Gurusamy K, Sahay SJ, Burroughs AK, Davidson BR. Systematic
review and meta-analysis of intraoperative versus preoperative
endoscopic sphincterotomy in patients with gallbladder and suspected common bile duct stones. Br J Surg. 2011;98:90816.
41. Sarli L, Iusco DR, Roncoroni L. Preoperative endoscopic
sphincterotomy and laparoscopic cholecystectomy for the management of cholecystocholedocholithiasis: 10-year experience.
World J Surg. 2003;27:1806.
123
96
42. Basso N, Pizzuto G, Surgo D, Materia A, Silecchia G, Fantini A,
et al. Laparoscopic cholecystectomy and intraoperative endoscopic sphincterotomy in the treatment of cholecysto-choledocholithiasis. Gastrointest Endosc. 1999;50:5325.
43. Tokumura H, Umwzawa A, Hui Cao H, Sakamoto N, Imaoka Y.
Laparoscopic management of the common bile duct stone:
transcystic duct approach and cholecystectomy. J Hepatobiliary
44. Sarli L, Pietra N, Franze A, Colla G, Costi R, Gobbi S, et al.
Routine intravenous cholangiography, selective ERCP and
endoscopic treatment of bile duct stones before laparoscopic
cholecystectomy. Gastrointest Endosc. 1999;50:2008.
123

45. Ranson J. The timing of biliary surgery in acute pancreatitis. Ann
Surg. 1979;189:65463.
46. Frei GJ, Frei VT, Thirlby RC, McClelland RN. Biliary pancreatitis: clinical presentation and surgical management. Am J Surg.
1986;151:1705.
47. DeIorio AV Jr, Vitale GC, Reynolds M, Larson GM. Acute biliary pancreatitis. The roles of laparoscopic cholecystectomy and
endoscopic retrograde cholangiopancreatography. Surg Endosc.
1995;9:3926.
48. Japan Society for Endoscopic Surgery. 10th nationwide survey of
endscopic surgery in Japan (in Japanese). Nihon Naishikyougeka
Gakkaizattshi (J Japan Soc Endosc Surg). 2010;16:565679.

DOI 10.1007/s00534-012-0565-z
GUIDELINE

TG13 miscellaneous etiology of cholangitis and cholecystitis

Ryota Higuchi Tadahiro Takada Steven M. Strasberg Henry A. Pitt Dirk J. Gouma O. James Garden
Markus W. Buchler John A. Windsor Toshihiko Mayumi Masahiro Yoshida Fumihiko Miura
Yasutoshi Kimura Kohji Okamoto Toshifumi Gabata Jiro Hata Harumi Gomi Avinash N. Supe
Palepu Jagannath Harijt Singh Myung-Hwan Kim Serafin C. Hilvano Chen-Guo Ker Sun-Whe Kim

Abstract This paper describes typical diseases and

morbidities classified in the category of miscellaneous
etiology of cholangitis and cholecystitis. The paper also
comments on the evidence presented in the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG 07) published in 2007 and the evidence

article (doi:10.1007/s00534-012-0565-z) contains supplementary
R. Higuchi (&)
Tokyo Womens Medical University, 8-1 Kawada-cho,
Shinjuku-ku, Tokyo 162-8666, Japan
e-mail: higuchi@ige.twmu.ac.jp
T. Takada F. Miura
Department of Surgery, Teikyo University
School of Medicine, Tokyo, Japan
S. M. Strasberg
H. A. Pitt
Department of Surgery, Indiana University School
of Medicine, Indianapolis, IN, USA
D. J. Gouma
O. J. Garden
Clinical Surgery, The University of Edinburgh,
Edinburgh, UK
M. W. Buchler
Heidelberg, Germany
reported subsequently, as well as miscellaneous etiology

that has not so far been touched on. (1) Oriental cholangitis
is the type of cholangitis that occurs following intrahepatic
stones and is frequently referred to as an endemic disease
in Southeast Asian regions. The characteristics and diagnosis of oriental cholangitis are also commented on. (2) TG
07 recommended percutaneous transhepatic biliary drainage in patients with cholestasis (many of the patients have
obstructive jaundice or acute cholangitis and present clinical signs due to hilar biliary stenosis or obstruction).
J. A. Windsor
T. Mayumi
M. Yoshida
Y. Kimura
Sapporo, Japan
K. Okamoto
Department of Surgery, Kitakyushu Municipal
Yahata Hospital, Kitakyushu, Japan
T. Gabata
J. Hata
123
98
However, the usefulness of endoscopic naso-biliary drainage has increased along with the spread of endoscopic
biliary drainage procedures. (3) As for biliary tract infections in patients who underwent biliary tract surgery, the
incidence rate of cholangitis after reconstruction of the
biliary tract and liver transplantation is presented. (4) As
for primary sclerosing cholangitis, the frequency, age of
predilection and the rate of combination of inflammatory
enteropathy and biliary tract cancer are presented. (5) In
the case of acalculous cholecystitis, the frequency of
occurrence, causative factors and complications as well as
the frequency of gangrenous cholecystitis, gallbladder
perforation and diagnostic accuracy are included in the
updated Tokyo Guidelines 2013 (TG13).
Keywords Oriental cholangitis Calculous cholecystitis
Primary sclerosing cholangitis Guidelines Biliary
infection
etiology of cholangitis and cholecystitis included in the

and cholecystitis (TG 07) [1] published in 2007. In view of
the presence of miscellaneous evidence that has not so far
been touched on, we thought it necessary that the updated
Tokyo Guidelines 2013 (TG13) prepare new items, put the
evidence so far collected in its due place, and provide
explanations. Diseases and morbidities classified in this
category include (1) oriental cholangitis, (2) acute cholangitis and cholecystitis associated with pancreaticobiliary
malignancies, (3) biliary tract infections in patients who
underwent previous biliary tract surgery, (4) primary
sclerosing cholangitis, and (5) acalculous cholecystitis.
In this paper, we present comments not only on the
characteristics of miscellaneous etiology of cholangitis and
cholecystitis but also on diagnostic and therapeutic methods, along with the addition of the newly reported
evidence.
Oriental cholangitis (cholangiohepatitis)

Introduction
Characteristics
Along with the addition of the evidence that has been

reported since 2007, we report on the miscellaneous
Oriental cholangitis (Fig. 1, Supplement Fig. 1) is defined

as that type of cholangitis characterized by recurrent right
upper quadrant pain, fever, chill and jaundice induced by
intrahepatic biliary stricture and intrahepatic stones. It is a
pandemic disease observed in Southeast Asian regions,
and people in the low-income group are frequently
affected by the disease. Involvement of b-glucuronidase
due to parasitic and bacterial biliary tract infections is
suggested as a causative factor [27]. In recent years,
however, it is rare that the presence of parasites is confirmed by a resected specimen of the liver [8]. Terms such
as oriental cholangitis, recurrent pyogenic cholangitis and primary hepatolithiasis are frequently used in
Korea, Hong Kong and Japan. They have been referred to
as the terms that describe different aspects of the same
morbidities [9]: emphasis is placed on ethnic predilection
and the mysterious nature of oriental cholangitis,
clinical presentation and suppurative inflammation in
recurrent pyogenic cholangitis, and pathological
changes in primary hepatolithiasis, respectively [9].
Pathologically, oriental cholangitis is characterized by
dilatation and stricture of the extrahepatic/intrahepatic
bile duct accompanying intrahepatic pigment calculi,
and hypertrophy is observed in the bile duct wall
accompanied by intrahepatic pigment calculus and
thickening accompanied by fibrosis and inflammatory cell
invasion [25, 7].
As for parasites related to oriental cholangitis, roundworms and Chinese liver flukes have been reported. Adult
H. Gomi
Tochigi, Japan
A. N. Supe
P. Jagannath
H. Singh
Department of Hepato-Pancreato-Biliary Surgery, Hospital
Selayang, Kuala Lampur, Malaysia
M.-H. Kim
S. C. Hilvano
C.-G. Ker
Yuans General Hospital, Kaohsiung, Taiwan
S.-W. Kim
Department of Surgery, Seoul National University
College of Medicine, Seoul, Korea
123
Fig. 1 Oriental cholangitis: dynamic contrast-enhanced CT shows

inhomogeneous enhancement (especially of the peripheral portion of
the liver: arrowheads) and intrahepatic bile duct dilatation (arrows)
roundworms sometimes enter the bile duct through the

duodenal papilla and give rise to cholangitis in 1656.6 %
of patients [10]. Chinese liver flukes colonize the intrahepatic bile duct and then live there for 2030 years, causing
chronic inflammatory parasitic changes [11].
Q1. What are the imaging findings of oriental
cholangitis?
The imaging findings of oriental cholangitis are follows;
extrahepatic bile duct dilatation, intrahepatic calculi,
localized dilatation / stricture in the biliary tree of the
medial segment of the liver, atrophy of the liver
segment/decreased blood flow, increased echogenicity
(US) of the hepatic portal vein, and liver abscess.
Diagnosis
Ultrasound/computed tomography (US/CT) enables
observation of bile duct dilatation and pneumobilia (Fig. 1,
Supplement Fig. 1), increased US echogenicity in the
portal vein segment of the liver, and atrophy of the liver
segment/decreased blood flow [46, 8]. However, US does
not necessarily depict intrahepatic stones accompanied by
acoustic shadow [8]. Calcium bilirubinate calculi are also
observed as a high-absorption region on CT; however, due
to the low absorption level of cholesterol stones, depiction
of cholesterol stones sometimes becomes difficult [8].
Magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) is able to provide better
imaging without the risk of aggravated sepsis cholangitis
99
and is good at depicting lesions on the proximal side of the

obstruction and stricture and those outside of the biliary
duct [6]. However, when cholestasis is present, a diagnosis
of stones can become impossible or it may be impossible to
visualize the bile duct because of bile concentration and
low signal. Pneumobilia is likely to be mistaken for stones
because it presents a low signal [8]. The rate of correct
diagnosis of the obstructed location by MRI/MRCP is
96100 %, a diagnosis of a cause of obstruction is made in
90 % and one of intrahepatic stones is the same as that by
endoscopic retrograde cholangiopancreatography (ERCP).
Direct cholangiography such as percutaneous transhepatic
cholangiography is an invasive test [6] and it has merits in
that 1it simultaneously enables (1) the removal of intrahepatic stones, (2) biopsy of bile duct lesions, and (3) stent
placement in the bile duct [8]. The reported imaging
findings from direct cholangiography are those of the
dilated bile duct and stones, straightening of the bile duct,
rigidity, decreased arborization, increased branching angle,
acute peripheral tapering and multiple focal strictures
[5, 6]. The diagnostic sensitivity of direct cholangiography
for making a diagnosis of bile duct obstruction is 100 %,
that for stones is somewhat inferior to that of MRCP
(9096 %), and specificity is 98 %. The incidence of liver
abscess in oriental cholangitis is 20 % lower; there is often
a number of partitions. Abscess should therefore be suspected when the limbus is depicted with CT [6].
Acute cholangitis and cholecystitis associated

with pancreaticobiliary malignancy
Characteristics
Biliary drainage is carried out for pancreaticobiliary
malignancies because they are frequently accompanied by
obstructive jaundice. However, patients with morbidities
accompanied by acute cholangitis requiring urgent biliary
drainage are few in number (Supplement Fig. 2). Acute
cholangitis requiring urgent biliary drainage is frequently
observed in the following patients: (1) those who failed to
undergo biliary drainage even if the bile duct at the upper
stream of the liver above the obstructed site of the bile duct
was depicted, and (2) those in whom drainage was
unsuccessful due to catheter obstruction even though a
drainage tube had been placed in the bile duct at the upper
stream of the liver above the obstructed site of the bile duct
due to malignant tumor [1].
The destruction of papillary function due to stent
placement and re-obstruction of the bile duct arising from
tumor enlargement have been reported as a risk factor for
acute cholangitis after metal stent placement for internal
123
100
biliary drainage. Furthermore, cancer progression to the

cystic duct and cystic duct obstruction due to stent
replacement in the bile duct have been reported as risk
factors for the development of acute cholecystitis after
stent placement [1215].
Diagnosis
As for the diagnostic accuracy of diagnostic imaging for
malignant tumors, there is a report showing that the sensitivity/specificity/rate of correct diagnosis of US for
extrahepatic bile duct cancers are 85.6/76.9/84.4 % for
cancers of the hilar bile duct; 59.1/50/57.1 % for cancers of
the middle bile duct; and 33.3/42.8/36.8 % for cancers of
the lower bile duct, respectively [16]. There are reports
showing that about 100 % of the tumors of the biliary
system, except early cancers, are recognized with multidetector CT and a judgment of the usefulness of resection
can be made in 74.591.7 % of the cases [17, 18]. A metaanalysis of MRCP has found that its sensitivity and specificity are 97/88 and 98/95 %, respectively, when the
detection of obstruction/malignancy has been set as the end
point [19].
Q2. How drainage should be carried out for postoperative acute cholangitis following pancreaticobiliary
malignancies?
We suggest a safe and reliable method should be selected
at the facility concerned. When it is difficult, emergency
transportation to an appropriate facility should take
place (recommendation 1, level C).
Treatment
The presence of preoperative cholangitis and cholecystitis
without control of pancreaticobiliary malignancies is an
independent risk factor for postoperative death during
hospital stay and the development of complications, so it is
considered that the control of those morbidities is important [2023]. In recent years, we have occasionally come
across opinions that recommend the use of endoscopic
naso-biliary drainage for hilar cholangiocarcinoma also, in
view of the occurrence of vascular injuries (8 %), peritoneal dissemination (4 %) and recurrence of fistula (5.2 %)
[24, 25]. However, there are so far no reports of randomized controlled trails comparing the modalities of preoperative biliary drainage. Therefore, it is thought that what
matters at this time will be whether or not there are physicians expert in endoscopic or percutaneous drainage at
the facility involved, and the selection of a method
123
enabling safe and reliable emergency biliary drainage

[26]. When the above conditions are not applicable,
patients should be transferred to an appropriate facility to
undergo biliary drainage.
Due to possible risks associated with preoperative percutaneous biliary drainage for fistula recurrence and carcinomatous peritonitis [1], one-stage radical surgery should
be conducted as far as the circumstances allow.
Biliary tract infections in patients who have undergone

previous biliary tract surgery
Q3. What is the frequency of cholangitis after biliary
tract reconstruction?
Cholangitis occurs in about 10% of the patients after biliary
tract reconstruction.
Characteristics
After ERCP and biliary tract surgery, there can be latent
cholangitis and cholecystitis. According to reports that
have examined patients undergoing biliary tract reconstruction, cholangitis occurred during 29129 months
follow-up in 11.3 % of the patients after papilloplasty,
10.310.9 % after choledochoduodenostomy, and 6.411.3 %
after choledochojejunostomy (Supplement Fig. 3), and in
about 4 % of patients in whom cholangitis was recurrent
and severe [27, 28]. Although there are no differences
between perioperative mortality rate and the incidence rate
of complications [28], bile duct carcinomas occurred after
biliary tract reconstruction in 1.97.6 % of the patients,
suggesting the presence of a relationship between inflammatory changes in the bile duct following biliary tract
reconstruction and biliary tract cancer that occurs in the
late stage [27]. According to a report on patients who were
followed up for more than 10 years after surgery for congenital biliary tract dilatation conducted in childhood
(mean age 4.2 years), impairment of the liver occurred in
10.7 % of the patients, bile duct dilatation in 10.7 %, and
repeated cholangitis in 1.8 % [29].
A systematic review of liver transplantation in adult
patients shows that bile duct stricture occurred in 12 % of
patients undergoing brain-dead donor liver transplantation
and in 19 % of patients undergoing live-donor liver
transplantation [30]. According to a discussion of the result
according to the surgical techniques of biliary tract
reconstruction in 51 patients who had undergone liver
transplantation due to primary sclerosing cholangitis
(PSC), there were no differences in the survival rate in
patients who had undergone choledochoduodenostomy,

choledochojejunostomy or choledochocholedochostomy.
However, the incidence of postoperative biliary tract
complications that had occurred more than once was 48, 60
and 17 %, respectively [31].
It is reported that the incidence of cholecystitis differs
(0.0612.6 %) according to underlying diseases other than
biliary tract surgery or surgical techniques and that the
frequency of acalculous cholecystitis is high [3237].
Primary sclerosing cholangitis

Characteristics
Primary sclerosing cholangitis (PSC) (Fig. 2) causes
stricture and obstruction due to progressive and non-specific inflammation of the intra- and extrahepatic bile duct
wall and progresses from cholestasis to liver cirrhosis and
hepatic failure. Its etiology remains unknown [38, 39]. It is
therefore important that secondary sclerosing cholangitis
is excluded [40]. PSC is frequently observed in males,
Caucasians and Northern Europeans [38]; the incidence rate is
0.411.25 patients/100,000 person-years [41, 42], and the
mean age at onset is 42 years [38]. There are reports that
the age distribution is bipolar in shape with one peak at
the 20s and another peak between the 50s and 60s [43, 44].
It is classified into the following 4 stages: (1) small
duct cholangitis, (2) progressive cholestasis, (3) cirrhosis,
and (4) decompensation [38, 45]. Clinical symptoms differ
Fig. 2 Primary sclerosing cholangitis (PSC): ERCP shows stenosis

and beaded appearance
101
according to the stage of the disease. It is detected by blood

test and is often asymptomatic [44]. When the disease has
progressed, cutaneous pruritus following cholestasis,
jaundice, fever due to cholangitis, and abdominal pain
occur. A combination of inflammatory intestinal disease
and biliary tract cancer occurs in 4.316.6 % of PSC cases
[41, 42, 44, 4651].
Diagnosis
ERCP is a standard imaging test. MRCP has shown
promise in recent years as a minimally invasive imaging
test procedure [38]. Imaging findings in the bile duct
include band-like stricture, beaded appearance (Fig. 2),
pruned tree-like appearance, and diverticulum-like outpouching [52]. The Mayo Clinic diagnostic criteria,
which are widely used [40] (Supplementary Table 1),
make much of the imaging findings of intra/extrahepatic
bile duct stricture and the biliary tract. Elevated levels of
serum ALP and T-Bil and an increased leukocyte count
are findings common to acute cholangitis. An increased
eosinophilic count, a serum c-globulin level, an elevated IgG/IgM level, positive anti-nuclear antibody and
positive perinuclear antineutrophil cytoplasmic antibody
(p-ANCA) are useful for differentiation from acute
cholangitis [38, 43, 44]. The positive rates are ALP
88 %, ALT 73 %, T-Bil 39 %, P-ANKA 777 %, and
anti-nuclear antibody 3387 % [38, 44]. According to
meta-analyses, MRCP shows 86 % diagnostic sensitivity
and 94 % specificity, demonstrating that it is somewhat
inferior in terms of the depiction of the intra/extrahepatic
bile duct and a diagnosis of liver cirrhosis and cancer at
the early stage [53, 54]. However, it is considered that
MRCP has sufficient capacity to enable a diagnostic test
for various types of diseases [55]. A diagnosis of cholangiocarcinoma occurring in PSC patients without tumor
formation remains a challenging task, so the diagnosis of
cholangiocarcinoma is made comprehensively by means
of diagnostic modalities such as CA19-9, diagnostic
imaging and scraping cytology [5659]. It is reported
that the diagnostic sensitivity/specificity of US, CT and
MRI for cholangiocarcinoma are about 57/94, 75/80,
63/79 %, respectively [58]. There is a report showing
that positron emission tomography (PET)-CT is useful
for making a diagnosis of cholangiocarcinoma [49].
On the other hand, there are also reports showing that
PET-CT is not useful [60]. Concomitant use of intraductal ultrasound is reported to be associated with the
elevated sensitivity and specificity of endoscopic retrograde cholangiography [61, 62]. The sensitivity and
specificity of scraping cytology for the bile duct are
reported to be about 1873 and 95100 %, respectively
[56, 59, 63, 64].
123
102
mediators such as eicosanoids are involved in the mechanisms for developing such conditions [69, 73].
Acalculous cholecystitis
Characteristics
Diagnosis
Patients with acute acalculous cholecystitis (Fig. 3) account
for 3.714 % of the patients with acute cholecystitis,
1249 % of which occurs after trauma and major surgery
[65, 66]. Acute acalculous cholecystitis occurs in about 1 %
of patients admitted to intensive care units (ICUs) [67],
about 1.2 % of patients with severe burns [68], 5963 % of
patients with gangrenous cholecystitis, and 1520 % of
patients with gallbladder perforation [65, 6971] together
with frequent multiple organ dysfunction. The mortality
rate is 0 % when the patients general status is maintained
[65, 72]; however, it is high (3053 %) in critically ill
patients [6769]. Early and appropriate diagnosis and
treatment are necessary to reduce the mortality rate [69, 71].
Risk factors for the development of acalculous cholecystitis
include surgery, trauma, long-term ICU stays, infections,
burns and parenteral nutrition [67, 68]. It is reported
that ischemia, reperfusion injury and proinflammatory
Patients are under respiratory control and frequently

develop consciousness disturbance arising from the use of
analgesics. Findings such as an elevated leukocyte count,
liver function disorder and clinical symptoms such as
sonographic Murphys sign, right hypochondriac pain and
fever that are highly specific for acute calculous cholecystitis presents are not specific for acute acalculous cholecystitis [66, 71]. US/CT findings include thickening of
the wall ([3.5 mm), pericholecystic fluid, emphysematous
gallbladder, sloughed mucosal membrane, and lack of
gallbladder wall enhancement (only for CT). The sensitivity/specificity of US are 3092/89100 %, and those
of CT are 33100/99100 % [70, 74, 75]. When HIDA
(hepatobiliary iminodiacetic acid) scan fails to visualize the
gallbladder, the case is judged positive. The sensitivity and
specificity of HIDA scan are 68100 and 38100 %,
Fig. 3 Acalculous acute cholecystitis: dynamic CT (ac) shows

gallbladder distention, mucosal enhancement (b, c arrows), and
transient pericholecystic liver enhancement (b arrowheads). MRCP
123
(d) shows gallbladder distension. Gallbladder shows marked hyperintensity (asterisk) on fat-suppressed T1-weighted MR image (e) and
T2-weighted image (f) indicating inspissated bile juice
respectively. HIDA scan is likely to detect positive cases

depending on complications (intravenous hyperalimentation, fasting, hepatic failure) [71]. The rate of correct
diagnosis of diagnostic laparoscopy in critically ill patients
is reported to be 90100 % [76].
Q4. What treatment is being carried out for acute
acalculous cholecystitis?
Cholecystectomy and/or cholecystostomy (drainage of the GB)
are being conducted.
Treatment
Cholecystectomy and/or cholecystostomy (drainage of the
gallbladder) are carried out. However, appropriate timing
and necessity of cholecystectomy and cholecystostomy are
controversial [71]. There are many opinions that cholecystostomy should be conducted in patients with poor
general status and that cholecystectomy should be carried
out after recovery has been achieved [69, 71, 77, 78].
However, there is a group arguing that cholecystectomy
only should be performed [79] and a group asserting that
cholecystostomy is the definitive treatment in patients with
extremely high risk [80].
None.
References
1. Yasuda H, Takada T, Kawarada Y, Nimura Y, Hirata K, Kimura Y,
et al. Unusual cases of acute cholecystitis and cholangitis:
Tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14:98113
(clinical practice guidelines CPGs).
2. Mage S, Morel AS. Surgical experience with cholangiohepatitis
(Hong Kong disease) in Canton Chinese. Ann Surg. 1965;162:
18790.
3. Carmona RH, Crass RA, Lim RC, Trunkey DD. Oriental cholangitis. Am J Surg. 1984;148:11724.
4. van Sonnenberg E, Casola G, Cubberley DA, Halasz NA, Cabrera
OA, Wittich GR, et al. Oriental cholangiohepatitis: diagnostic
imaging and interventional management. Am J Roentgenol.
1986;146:32731.
5. Lim JH. Oriental cholangiohepatitis: pathologic, clinical, and
radiologic features. Am J Roentgenol. 1991;157:18.
6. Heffernan EJ, Geoghegan T, Munk PL, Ho SG, Harris AC.
Recurrent pyogenic cholangitis: from imaging to intervention.
Am J Roentgenol. 2009;192:W2835.
7. Wani NA, Robbani I, Kosar T. MRI of oriental cholangiohepatitis. Clin Radiol. 2011;66:15863.
8. Mori T, Sugiyama M, Atomi Y. Gallstone disease: management
of intrahepatic stones. Best Pract Res Clin Gastroenterol. 2006;20:
111737.
9. Tsui WM, Lam PW, Lee WK, Chan YK. Primary hepatolithiasis,
recurrent pyogenic cholangitis, and oriental cholangiohepatitis: a
tale of 3 countries. Adv Anat Pathol. 2011;18:31828.
103
10. Rana SS, Bhasin DK, Nanda M, Singh K. Parasitic infestations of
the biliary tract. Curr Gastroenterol Rep. 2007;9:15664.
11. Lim JH. Liver flukes: the malady neglected. Korean J Radiol.
2011;12:26979.
12. Okamoto T, Fujioka S, Yanagisawa S, Yanaga K, Kakutani H,
Tajiri H, et al. Placement of a metallic stent across the main
duodenal papilla may predispose to cholangitis. Gastrointest
Endosc. 2006;63:7926.
13. Misra SP, Dwivedi M. Reflux of duodenal contents and cholangitis in patients undergoing self-expanding metal stent placement.
14. Isayama H, Kawabe T, Nakai Y, Tsujino T, Sasahira N,
Yamamoto N, et al. Cholecystitis after metallic stent placement in
patients with malignant distal biliary obstruction. Clin Gastroenterol Hepatol. 2006;4:114853.
15. Suk KT, Kim HS, Kim JW, Baik SK, Kwon SO, Kim HG, et al.
Risk factors for cholecystitis after metal stent placement in
malignant biliary obstruction. Gastrointest Endosc. 2006;64:
5229.
16. Albu S, Tantau M, Sparchez Z, Branda H, Suteu T, Badea R,
et al. Diagnosis and treatment of extrahepatic cholangiocarcinoma: results in a series of 124 patients. Rom J Gastroenterol.
2005;14:336.
17. Choi JY, Kim MJ, Lee JM, Kim KW, Lee JY, Han JK, et al. Hilar
cholangiocarcinoma: role of preoperative imaging with sonography, MDCT, MRI, and direct cholangiography. Am J Roentgenol. 2008;191:144857.
18. Unno M, Okumoto T, Katayose Y, Rikiyama T, Sato A, Motoi F,
et al. Preoperative assessment of hilar cholangiocarcinoma by
multidetector row computed tomography. J Hepatobiliary Pancreat Surg. 2007;14:43440.
19. Romagnuolo J, Bardou M, Rahme E, Joseph L, Reinhold C,
Barkun AN. Magnetic resonance cholangiopancreatography: a
meta-analysis of test performance in suspected biliary disease.
Ann Intern Med. 2003;139:54757.
20. Pitt HA, Postier RG, Cameron JL. Biliary bacteria: significance
and alterations after antibiotic therapy. Arch Surg. 1982;117:
4459.
21. Wells GR, Taylor EW, Lindsay G, Morton L. Relationship
between bile colonization, high-risk factors and postoperative
sepsis in patients undergoing biliary tract operations while
receiving a prophylactic antibiotic. West of Scotland Surgical
Infection Study Group. Br J Surg. 1989;76:3747.
22. Kanai M, Nimura Y, Kamiya J, Kondo S, Nagino M, Miyachi M,
et al. Preoperative intrahepatic segmental cholangitis in patients
with advanced carcinoma involving the hepatic hilus. Surgery.
1996;119:498504.
23. Sano T, Shimada K, Sakamoto Y, Yamamoto J, Yamasaki S,
Kosuge T. One hundred two consecutive hepatobiliary resections
for perihilar cholangiocarcinoma with zero mortality. Ann Surg.
2006;244:2407.
24. Kawakami H, Kuwatani M, Onodera M, Haba S, Eto K, Ehira N,
et al. Endoscopic nasobiliary drainage is the most suitable preoperative biliary drainage method in the management of patients
with hilar cholangiocarcinoma. J Gastroenterol. 2011;46:2428.
25. Takahashi Y, Nagino M, Nishio H, Ebata T, Igami T, Nimura Y.
Percutaneous transhepatic biliary drainage catheter tract recurrence in cholangiocarcinoma. Br J Surg. 2010;97:18606.
26. Nagino M, Takada T, Miyazaki M, Miyakawa S, Tsukada K,
Kondo S, et al. Preoperative biliary drainage for biliary tract and
ampullary carcinomas. J Hepatobiliary Pancreat Surg. 2008;15:
2530 (CPGs).
27. Tocchi A, Mazzoni G, Liotta G, Lepre L, Cassini D, Miccini M.
Late development of bile duct cancer in patients who had biliaryenteric drainage for benign disease: a follow-up study of more
than 1,000 patients. Ann Surg. 2001;234:2104.
123
104
28. Panis Y, Fagniez PL, Brisset D, Lacaine F, Levard H, Hay JM.
Long term results of choledochoduodenostomy versus choledochojejunostomy for choledocholithiasis. The French Association
for Surgical Research. Surg Gynecol Obstet. 1993;177:337.
29. Ono S, Fumino S, Shimadera S, Iwai N. Long-term outcomes
after hepaticojejunostomy for choledochal cyst: a 10- to 27-year
follow-up. J Pediatr Surg. 2010;45:3768.
30. Akamatsu N, Sugawara Y, Hashimoto D. Biliary reconstruction,
its complications and management of biliary complications after
adult liver transplantation: a systematic review of the incidence,
risk factors and outcome. Transpl Int. 2011;24:37992.
31. Schmitz V, Neumann UP, Puhl G, Tran ZV, Neuhaus P, Langrehr
JM. Surgical complications and long-term outcome of different
biliary reconstructions in liver transplantation for primary sclerosing cholangitis-choledochoduodenostomy versus choledochojejunostomy. Am J Transplant. 2006;6:37985.
32. Oh SJ, Choi WB, Song J, Hyung WJ, Choi SH, Noh SH. Complications requiring reoperation after gastrectomy for gastric
cancer: 17 years experience in a single institute. J Gastrointest
Surg. 2009;13:23945.
33. Ito T. Acute noncalculous cholecystitis following gastrectomy for
gastric cancerstudy by ultrasonic examination. Nihon Geka
Gakkai Zasshi. 1985;86:143443.
34. Wagnetz U, Jaskolka J, Yang P, Jhaveri KS. Acute ischemic
cholecystitis after transarterial chemoembolization of hepatocellular carcinoma: incidence and clinical outcome. J Comput Assist
Tomogr. 2010;34:34853.
35. Chen TM, Huang PT, Lin LF, Tung JN. Major complications of
ultrasound-guided percutaneous radiofrequency ablations for
liver malignancies: single center experience. J Gastroenterol
Hepatol. 2008;23:e44550.
36. Tachibana M, Kinugasa S, Yoshimura H, Dhar DK, Ueda S, Fujii
T, et al. Acute cholecystitis and cholelithiasis developed after
esophagectomy. Can J Gastroenterol. 2003;17:1758.
37. Vassiliou I, Papadakis E, Arkadopoulos N, Theodoraki K,
Marinis A, Theodosopoulos T, et al. Gastrointestinal emergencies
in cardiac surgery. A retrospective analysis of 3,724 consecutive
patients from a single center. Cardiology. 2008;111:94101.
38. LaRusso NF, Shneider BL, Black D, Gores GJ, James SP, Doo E,
et al. Primary sclerosing cholangitis: summary of a workshop.
Hepatology. 2006;44:74664.
39. Lee YM, Kaplan MM. Primary sclerosing cholangitis. N Engl J
Med. 1995;332:92433.
40. Linder KD, LaRusso NF. Primary sclerosing cholangitis Schiffs
diseases of the liver. 9th ed. Philadelphia: Lippincott Williams &
Wilikins; 2003. p. 67384.
41. Bambha K, Kim WR, Talwalkar J, Torgerson H, Benson JT,
Therneau TM, et al. Incidence, clinical spectrum, and outcomes
of primary sclerosing cholangitis in a United State community.
42. Card TR, Solaymani-Dodaran M, West J. Incidence and mortality
of primary sclerosing cholangitis in the UK: a population-based
cohort study. J Hepatol. 2008;48:93944.
43. Hirano K, Tada M, Isayama H, Yashima Y, Yagioka H, Sasaki T,
et al. Clinical features of primary sclerosing cholangitis with
onset age above 50 years. J Gastroenterol. 2008;43:72933.
44. Takikawa H, Takamori Y, Tanaka A, Kurihara H, Nakanuma Y.
Analysis of 388 cases of primary sclerosing cholangitis in Japan;
presence of a subgroup without pancreatic involvement in older
patients. Hepatol Res. 2004;29:1539.
45. Bjornsson E, Olsson R, Bergquist A, Lindgren S, Braden B,
Chapman RW, et al. The natural history of small-duct primary
sclerosing cholangitis. Gastroenterology. 2008;134:97580.
46. Burak K, Angulo P, Pasha TM, Egan K, Petz J, Lindor KD.
Incidence and risk factors for cholangiocarcinoma in primary
sclerosing cholangitis. Am J Gastroenterol. 2004;99:5236.
123

47. Claessen MM, Vleggaar FP, Tytgat KM, Siersema PD, van
Buuren HR. High lifetime risk of cancer in primary sclerosing
cholangitis. J Hepatol. 2009;50:15864.
48. Morris-Stiff G, Bhati C, Olliff S, Hubscher S, Gunson B, Mayer
D, et al. Cholangiocarcinoma complicating primary sclerosing
cholangitis: a 24-year experience. Dig Surg. 2008;25:12632.
49. Prytz H, Keiding S, Bjornsson E, Broome U, Almer S, Castedal
M, et al. Dynamic FDG-PET is useful for detection of cholangiocarcinoma in patients with PSC listed for liver transplantation.
Hepatology. 2006;44:157280.
50. Kaplan GG, Laupland KB, Butzner D, Urbanski SJ, Lee SS. The
burden of large and small duct primary sclerosing cholangitis in
adults and children: a population-based analysis. Am J Gastroenterol. 2007;102:10429.
51. Lindkvist B, Benito de Valle M, Gullberg G, Bjornsson E. Incidence and prevalence of primary sclerosing cholangitis in a
defined adult population in Sweden. Hepatology. 2010;52:5717.
52. Nakazawa T, Ohara H, Sano H, Aoki S, Kobayashi S, Okamoto
T, et al. Cholangiography can discriminate sclerosing cholangitis
with autoimmune pancreatitis from primary sclerosing cholangitis. Gastrointest Endosc. 2004;60:93744.
53. Weber C, Kuhlencordt R, Grotelueschen R, Wedegaertner U,
Ang TL, Adam G, et al. Magnetic resonance cholangiopancreatography in the diagnosis of primary sclerosing cholangitis.
Endoscopy. 2008;40:73945.
54. Moff SL, Kamel IR, Eustace J, Lawler LP, Kantsevoy S, Kalloo
AN, et al. Diagnosis of primary sclerosing cholangitis: a blinded
comparative study using magnetic resonance cholangiography
and endoscopic retrograde cholangiography. Gastrointest Endosc.
2006;64:21923.
55. Dave M, Elmunzer BJ, Dwamena BA, Higgins PD. Primary
sclerosing cholangitis: meta-analysis of diagnostic performance
of MR cholangiopancreatography. Radiology. 2010;256:38796.
56. Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM,
Shneider B, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology. 2010;51:66078 (CPG).
57. Levy C, Lymp J, Angulo P, Gores GJ, Larusso N, Lindor KD.
The value of serum CA 19-9 in predicting cholangiocarcinomas
in patients with primary sclerosing cholangitis. Dig Dis Sci.
2005;50:173440.
58. Charatcharoenwitthaya P, Enders FB, Halling KC, Lindor KD.
Utility of serum tumor markers, imaging, and biliary cytology for
detecting cholangiocarcinoma in primary sclerosing cholangitis.
Hepatology. 2008;48:110617.
59. Furmanczyk PS, Grieco VS, Agoff SN. Biliary brush cytology
and the detection of cholangiocarcinoma in primary sclerosing
cholangitis: evaluation of specific cytomorphologic features and
CA19-9 levels. Am J Clin Pathol. 2005;124:35560.
60. Fevery J, Buchel O, Nevens F, Verslype C, Stroobants S, Van
Steenbergen W. Positron emission tomography is not a reliable
method for the early diagnosis of cholangiocarcinoma in patients
with primary sclerosing cholangitis. J Hepatol. 2005;43:35860.
61. Tischendorf JJ, Kruger M, Trautwein C, Duckstein N, Schneider
A, Manns MP, et al. Cholangioscopic characterization of dominant bile duct stenoses in patients with primary sclerosing cholangitis. Endoscopy. 2006;38:6659.
62. Tischendorf JJ, Geier A, Trautwein C. Current diagnosis and
management of primary sclerosing cholangitis. Liver Transpl.
2008;14:73546.
63. Boberg KM, Jebsen P, Clausen OP, Foss A, Aabakken L, Schrumpf E. Diagnostic benefit of biliary brush cytology in cholangiocarcinoma in primary sclerosing cholangitis. J Hepatol.
2006;45:56874.
64. Baskin-Bey ES, Moreno Luna LE, Gores GJ. Diagnosis of
cholangiocarcinoma in patients with PSC: a sight on cytology.
J Hepatol. 2006;45:4769.

cholecystitis. World J Gastroenterol. 2003;9:28213.
67. Laurila J, Syrjala H, Laurila PA, Saarnio J, Ala-Kokko TI. Acute
acalculous cholecystitis in critically ill patients. Acta Anaesthesiol Scand. 2004;48:98691.
68. Theodorou P, Maurer CA, Spanholtz TA, Phan TQ, Amini P,
Perbix W, et al. Acalculous cholecystitis in severely burned patients:
incidence and predisposing factors. Burns. 2009;35:40511.
69. Barie PS, Eachempati SR. Acute acalculous cholecystitis. Curr
Gastroenterol Rep. 2003;5:3029.
70. Kalliafas S, Ziegler DW, Flancbaum L, Choban PS. Acute
acalculous cholecystitis: incidence, risk factors, diagnosis, and
outcome. Am Surg. 1998;64:4715.
71. Huffman JL, Schenker S. Acute acalculous cholecystitis: a
review. Clin Gastroenterol Hepatol. 2010;8:1522.
72. Matsusaki S, Maguchi H, Takahashi K, Katanuma A, Osanai M,
Urata T, et al. Clinical features of acute acalculous cholecystitisnosocomial manner and community-acquired manner. Nihon
Shokakibyo Gakkai Zasshi. 2008;105:174957.
73. Al-Azzawi HH, Nakeeb A, Saxena R, Maluccio MA, Pitt HA.
Cholecystosteatosis: an explanation for increased cholecystectomy
rates. J Gastrointest Surg. 2007;11:83542 (discussion 423).
105
74. Ahvenjarvi L, Koivukangas V, Jartti A, Ohtonen P, Saarnio J,
Syrjala H, et al. Diagnostic accuracy of computed tomography
imaging of surgically treated acute acalculous cholecystitis in
critically ill patients. J Trauma. 2011;70:1838.
75. Mirvis SE, Vainright JR, Nelson AW, Johnston GS, Shorr R,
Rodriguez A, et al. The diagnosis of acute acalculous cholecystitis: a comparison of sonography, scintigraphy, and CT. Am J
Roentgenol. 1986;147:11715.
76. Diagnostic Laparoscopy Guidelines; Practice/Clinical Guidelines
published on 11/2007 by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES, CPG).
77. Sosna J, Copel L, Kane RA, Kruskal JB. Ultrasound-guided
percutaneous cholecystostomy: update on technique and clinical
applications. Surg Technol Int. 2003;11:1359.
78. Owen CC, Bilhartz LE. Gallbladder polyps, cholesterolosis,
adenomyomatosis, and acute acalculous cholecystitis. Semin
Gastrointest Dis. 2003;14:17888.
79. Laurila J, Laurila PA, Saarnio J, Koivukangas V, Syrjala H,
Ala-Kokko TI. Organ system dysfunction following open cholecystectomy for acute acalculous cholecystitis in critically ill
patients. Acta Anaesthesiol Scand. 2006;50:1739.
80. Griniatsos J, Petrou A, Pappas P, Revenas K, Karavokyros I,
Michail OP, et al. Percutaneous cholecystostomy without interval
cholecystectomy as definitive treatment of acute cholecystitis in
elderly and critically ill patients. South Med J. 2008;101:58690.
123

DOI 10.1007/s00534-012-0588-5
ANNOUNCEMENT
Newsletter, January 1, 2013

A-P HPBA activities
Third Congress of Asian-Pacific HPBA
Tadahiro Takada, MD, FACS, FRCS

Founding President of A-P HPBA
The Third Biennial Congress, 2011 A-P HPBA, was held in

Melbourne, Australia, 2730 September 2011 and was
chaired by Professor Christopher Christophi.
The 2011 Congress focused on making a difference
with new technologies and provided an exciting and
innovative scientific program in a unique destination
Melbourne, Australia.
There were postgraduate courses held on 27 September,
followed by three packed days from 28 to 30 September
with a variety of different presentation types including
symposia, debates, video sessions, and case presentations.
To supplement the scientific program, the Congress social
events provided an ideal opportunity for networking with
colleagues and industry associates in an atmosphere of
typical Melbourne hospitality.
Fourth Congress of Asian-Pacific HPBA
Dear Colleagues,
As the founding president of the Asian-Pacific HPBA, I
would like to underline once again that this journal is the
official journal of the following three societies:
The Asian-Pacific Hepato-Pancreato-Biliary Association
(A-P HPBA)
The Japanese Society of Hepato-Biliary-Pancreatic Surgery
(JSHBPS)
The Japan Biliary Association (JBA)
It is my pleasure to inform you of the current activities
of the Asian-Pacific Hepato-Pancreato-Biliary Association
(A-P HPBA).
123
The Fourth Biennial Congress, 2013 A-P HPBA, will take

place in Shanghai, China, 2730 March 2013 with Professor Meng Chao Wu at the helm.
The theme for the A-PHPBA2013 Shanghai Congress will
be Seeking Common Ground While Reserving Differences. This Congress will be unique as our Scientific Committee has prepared an outstanding program combining the
best science and education. It will comprise pre-congress
postgraduate courses and a variety of symposia, debates, video
sessions, and case presentations. As Chinas largest city,
Shanghai is an outstanding conference destination, located at
the hub of this ancient country. There will be no shortage of
activities for delegates and accompanying persons.
Please visit the Congress website http://www.aphpba

2013shanghai.org, where you will find further information.
We look forward to welcoming you to Shanghai in
2013, and we are confident that the event will be a memorable occasion for exchanging knowledge and strengthening friendship.
A-P HPBA officers and councilors (20112013)

President: Palepu Jagannath (India)
President-Elect: Xiao-Ping Chen (China)
Immediate Past-President: Joseph WY Lau (Hong Kong)
Secretary: Sung-Gyu Lee (Korea)
Treasurer: Sheung-Tat Fan (Hong Kong)
Chairman of Scientific Committee: Masao Tanaka (Japan)
Secretary-Elect: Norihiro Kokudo (Japan)
Congress Chairman: Meng-Chao Wu (China)
Members-at-large (20112013)
Christopher Christophi (Australia/New Zealand)
Feng Shen (China)
Avinash Supe (India)
Masakazu Yamamoto (Japan)
Sun-Whe Kim (Korea)
Harjit Singh (Malaysia)
Winston Wei-Liang Woon (Singapore)
Chao-Long Chen (Taiwan)
107
Xiao-Ping Chen,
President-Elect
Tongji Hospital
Tongji Medical College
Department of General
Surgery
Huazhong University of
Science and Technology
Wuhan
China
Joseph WY Lau, Immediate

Past-President
The Chinese University of
Hong Kong
Department of Surgery
Prince of Wales Hospital
Shatin
New Territories
Hong Kong
Sung-Gyu Lee
Secretary
Korea
A-P HPBA officers and councilors (20112013)

Palepu Jagannath, President
Lilavati Hospital and
Research Centre
Department of Surgical
Oncology
Bandra (West)
Mumbai
India
Sheung-Tat Fan
Treasurer
Hong Kong
123
108
Masao Tanaka
Chairman of Scientific
Committee
Japan
Feng Shen
Member-at-Large
China
Norihiro Kokudo
Secretary-Elect
Japan
Avinash Supe
Member-at-Large
India
Meng-Chao Wu
Congress Chairman, Fourth
Congress
Shanghai Eastern
Hepatobiliary Surgery
Hospital
Shanghai
China
Christopher Christophi
Member-at-Large
Australia
123
Masakazu Yamamoto
Member-at-Large
Japan
Sung-Whe Kim
Member-at-Large
Korea
Harjit Singh
Member-at-Large
Malaysia
109
Avinash Supe (Member-at-Large, India)

Masakazu Yamamoto (Member-at-Large, Japan)
Sun-Whe Kim (Member-at-Large, Korea)
Winston WL Woon (Member-at-Large, Singapore)
Harjit Singh (Member-at-Large, Malaysia)
Chao-Long Chen (Member-at-Large, Taiwan)
Development Committee (20112013)
Chairman: Joseph Lau (Hong Kong), Immediate Past-President
Members: Palepu Jagannath (India), President
Sheung-Tat Fan (Hong Kong), Treasurer
Christopher Christophi (Member-at-Large, Australia/New
Zealand)
Winston WL Woon
Member-at-Large
Singapore
Chao-Long Chen
Member-at-Large
Taiwan
Membership Committee (20112013)

Chairman: Palepu Jagannath (President)
Members: Sung-Gyu Lee (Secretary)
Xiao-Ping Chen (China)
Rajeev Joshi (India)
Masakazu Yamamoto (Japan)
Hong Jin Kim (Korea)
Saxon Connor (New Zealand)
Kui Hin Liau (Singapore)
Chao-Long Chen (Taiwan)
Vajarapong Bhudisawasdi (Thailand)
Nominating Committee (20112013)
Chairman: Joseph Lau (Hong Kong), Immediate Past-President
Members: Palepu Jagannath (India), President
Xiao-Ping Chen (China), President-Elect
Publication Committee (20112013)
Chairman: Sheung-Tat Fan (Treasurer)
Members: Palepu Jagannath (President)
Masao Tanaka (Chair of Scientific Committee)
Xiao-Ping Chen (President-Elect)
Sung Gyu Lee (Secretary)
A-PHPBA Committees
Executive Committee (20112013)
Chairman: Palepu Jagannath (India), President
Members: Xiao-Ping Chen (China), President-Elect
Joseph WY Lau (Hong Kong), Immediate Past-President
Sung-Gyu Lee (Korea), Secretary
Sheung-Tat Fan (Hong Kong), Treasurer
Masao Tanaka (Japan), Chairman of Scientific Committee
Education and Training Committee (20112013)
Chairman: Palepu Jagannath (President)
Members: Xiao-Ping Chen (President-Elect)
Christopher Christophi (Member-at-Large, Australia/New
Zealand)
Feng Shen (Member-at-Large, China)
Scientific Committee (20112013)

Chairman: Masao Tanaka (Japan)
Vice-Chairman: Saxon Connor (New Zealand)
Members: Palepu Jagannath (President)
Sung-Gyu Lee (Secretary)
Meng-Chao Wu (Congress Chairman)
Krishnakumar Madhavan (Singapore, next Congress Chairman)
Feng Shen (China)
Zhi-Yong Huang (China)
See-Ching Chan (Hong Kong)
Eric CH Lai (Hong Kong)
Regulagedda A Sastry (India)
Shailesh V. Shrikhande (India)
Itaru Endo (Japan)
Hong-Jin Kim (Korea)
Sun Whe Kim (Korea)
Krishna Raman (Malaysia)
123

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J Hepatobiliary Pancreat Sci (2013) 20:17

TG13: Updated Tokyo Guidelines for acute cholangitis

TG13: Updated Tokyo Guidelines for the management of acute

Published online: 11 January 2013

presence of divergence between severity assessment and

T. Takada (&) F. Miura

J Hepatobiliary Pancreat Sci (2013) 20:17

2012, we held three International Meetings for the Clinical

Keywords Acute cholangitis Acute cholecystitis

Background before Tokyo Guidelines 2007

J Hepatobiliary Pancreat Sci (2013) 20:17

22 countries and Japanese experts in this field attended the

Total number of times of citation

Number of articles citing papers in TG07

Number of journals publishing articles citing papers in TG07

Fig. 1 Annual number of citations of TG07

Citation analysis 20072011 of TG07

Fig. 2 Categories of the journals publishing articles citing papers in

Fig. 3 Geographical origin of authors citing papers in TG07

Need for revision of TG07

J Hepatobiliary Pancreat Sci (2013) 20:17

Develop Clinical Guidelines

Table 2 Types of articles citing TG07

Evidence and consensus based

In 17 articles, patients were diagnosed according to the diagnostic

Fig. 4 Section where cited in original articles (n = 76)

and therapeutic methods. Therefore clinical practice

Process of the development of Tokyo Guidelines 2013

Fig. 5 Annual number of original articles citing papers in TG07

criteria [1, 36] and, at the same time, the presentation of

1. The First International Meeting for the development of

J Hepatobiliary Pancreat Sci (2013) 20:17

(GRADE) systems to provide the levels of evidence and

The GRADE systems

Introduction of bundles for the management of acute

J Hepatobiliary Pancreat Sci (2013) 20:17

Fig. 7 GRADE system (quality

Definition: Overall quality of evidence across studies for the outcome

1. How to judge a Grade of recommendation

Fig. 8 GRADE system (grade of recommendation) [1517]

the guidelines and to provide guidelines for conducting a

J Hepatobiliary Pancreat Sci (2013) 20:17

J Hepatobiliary Pancreat Sci (2013) 20:823

TG13: Updated Tokyo Guidelines for acute cholangitis

TG13 current terminology, etiology, and epidemiology of acute

Published online: 11 January 2013

Abstract While referring to the evidence adopted in the

Electronic supplementary material The online version of this

cholecystitis is the presence of stones. Next to stones, the

J Hepatobiliary Pancreat Sci (2013) 20:823

healthcare-associated infections is important in the current

mortality rate, and recurrence rate are introduced along

Keywords Terminology Etiology Epidemiology

Acute cholangitis is a morbid condition with acute

The onset of acute cholangitis involves two factors: (1)

However, terms such as acute obstructive cholangitis

J Hepatobiliary Pancreat Sci (2013) 20:823

Acute cholangitis/cholecystitis as healthcare-associated

Edematous cholecystitis: 1st stage (24 days) The

Fig. 1 Necrotizing cholecystitis. a Contrast-enhanced CT images

J Hepatobiliary Pancreat Sci (2013) 20:823

Suppurative cholecystitis: 3rd stage (710 days) The

position, pendulum-like movement in the anteflexion

Acalculous cholecystitis: Acute cholecystitis without