Brief review on the topic of Acute cholangitis, focussing on the Tokyo Guidelines

1. Pratap Sagar Tiwari, MD, Internal Medicine,
DM Resident, Hepatology,
NAMS, Bir Hospital, Nepal
Total Slides:38

2. INTRODUCTION
• Acute cholangitis is a clinical syndrome characterized by fever, jaundice,
and abdominal pain that develops as a result of stasis and infection in the
biliary tract.
• Cholangitis was first described by Charcot as a serious and life-threatening
illness; however, it is now recognized that the severity can range from mild
to life-threatening [1].
1. Boey JH, Way LW. Acute cholangitis. Ann Surg 1980; 191:264.
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3. PATHOGENESIS
• In Acg there is biliary infection a/with partial or complete obstruction of
the biliary system caused by any of various etiologies including
choledocholithiasis, benign and malignant strictures, biliary-enteric
anastomotic malfunction, and indwelling biliary stent malfunction.
• Biliary infection alone does not cause clinical cholangitis unless biliary obstruction
raises the intraductal pressure a central pathogenetic event. ↑ pressure promotes the
migration of bacteria from the portal circulation into the biliary tract and subsequent
colonization. It also favors migration of bacteria from bile into the systemic circulation,
resulting in a higher incidence of septicemia [1].
• Thus, acute cholangitis progresses from local biliary infection to the SIRS,
and advanced disease leads to sepsis with or without organ dysfunction.
1. Sung JY, Costerton JW, Shaffer EA. Defense system in the biliary tract against bacterial infection. Dig Dis Sci 1992; 37:689. 3/38

4. Mechanism of bacterial entry into the biliary tract
The sphincter of Oddi: forms an effective mechanical barrier to duodenal reflux and
ascending bacterial infection.
The continuous flushing action of bile plus the bacteriostatic activity of bile salts:
help to maintain bile sterility.
Secretory IgA and biliary mucous: function as antiadherent factors, preventing
bacterial colonization.
BARRIER MECHANISM
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5. Mechanism of bacterial entry into the biliary tract
• When the barrier mechanism is disrupted, as occurs after endoscopic
sphincterotomy, choledochal surgery, or biliary stent insertion, pathogenic
bacteria enter the biliary system at high concentrations.
• The presence of a foreign body, such as a stone or stent, can then act as a
nidus for bacterial colonization.
• Bile taken from pts without obstruction is sterile or nearly sterile [1]. In
comparison, approx 70 % of all pts with gallstones have evidence of bacteria
in the bile [1,2].
1. Csendes A, Becerra M, Burdiles P, et al. 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; 160:363.
2. Ohdan H, Oshiro H, Yamamoto Y, et al. Bacteriological investigation of bile in patients with cholelithiasis. Surg Today 1993; 23:390. 5/38

6. Bacteriology
• Culture of bile, ductal stones, and blocked biliary stents are positive in
over 90 % of cases, yielding a mixed growth of Gm negative and Gm positive
bacteria. [1]:
• Escherichia coli is the major Gm -tive bacterium isolated (25-50 %),
followed by Klebsiella (15-20 %) and Enterobacter species (5-10 %).
• The MC Gm +tive bacteria are Enterococcus species (10-20 %).
• Anaerobes, such as Bacteroides and Clostridia, may be present as a mixed
infection.
1. van den Hazel SJ, Speelman P, Tytgat GN, et al. Role of antibiotics in the treatment and prevention of acute and recurrent cholangitis. Clin Infect Dis 1994; 19:279.
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7. • Clinical manifestations are an important factor in making the DX of ACg.
• In 1877,[1] Charcot was the first to describe the clinical triad of fever,
jaundice and abdominal pain as a clinical manifestation of ACg, and in 1959,
Reynolds and Dragan[2] were the first to describe a severe form of
cholangitis that included Charcot’s triad plus septic shock and mental
status change (Reynold’s Pentad).
• Fever and abdominal pain are the MC observed clinical manifestations in ACg,
with an incidence of each of up to 80% or more, whereas jaundice is observed in
60%–70% of cases.
• The incidence of Charcot’s triad is reported in not more than 72% (15.4-
72%) of pts with ACg, and Reynolds’ pentad is extremely rare, reported in
only 3.5–7.7% of the pts.
1. Charcot M. De la fievre hepatique symptomatique. Comparaison avec la fievre uroseptique. Lecons sur les maladies du foie des voies biliares et des reins. Paris: Bourneville et Sevestre; 1877. p.176–85.
2. Reynolds BM, Dragan EL. Acute obstructive cholangitis. A distinct syndrome. Ann Surg 1959;150:299–303.
Charcot’s triad + septic shock and mental status change =Reynold’s Pentad
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8. Incidence of clinical manifestation of acute cholangitis
References are at the end of the slides.
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9. Diagnostic criteria for Acute Cholangitis
• A variety of different names and definitions of acute cholangitis are found
in the literature, depending on the authors.[6,8,10–17 ]
• Some authors defined Acg based on clinical sign’s such as Charcot’s triad
(fever and/or chills, abdominal pain, and jaundice),[6,16–17] while others
emphasized the presence of biliary obstruction or the properties of the
bile (suppurative cholangitis),[10,13–14] as a result, there were no standard
DX criteria for ACg.
6. 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;211:55–9.
8. Chijiiwa K, Kozaki N, Naito T, Kameoka N, Tanaka M. Treatment of choice for choledocholithiasis in patients with acute obstructive suppurative cholangitis and liver cirrhosis. Am J Surg
1995;170:356–60.
10. Csendes A, Diaz JC, Burdiles P, Maluenda F, Morales E. Risk factors and classification of acute suppurative cholangitis. Br J Surg 1992;79:655–8.
11. Thompson JE Jr, Tompkins RK, Longmire WP Jr. Factors in management of acute cholangitis. Ann Surg 1982;195:137–45.
12. Gigot JF, Leese T, Dereme T, Coutinho J, Castaing D, Bismuth H. Acute cholangitis. Multivariate analysis of risk factors. Ann Surg 1989;209:435–8.
13. Boey JH, Way LW. Acute cholangitis. Ann Surg 1980;191:264–70.
14. O’Connor MJ, Schwartz ML, McQuarrie DG, Sumer HW. Acute bacterial cholangitis: an analysis of clinical manifestation. Arch Surg 1982;117:437–41.
15. Haupert AP, Carey LC, Evans WE, Ellison EH. Acute suppurative cholangitis. Experience with 15 consecutive cases. Arch Surg 1967;94:460–8.
16. Welch JP, Donaldson GA. The urgency of diagnosis and surgical treatment of acute suppurative cholangitis. Am J Surg 1976;131: 527–32.
17. Saharia PC, Cameron JL. Clinical management of acute cholangitis. Surg Gynecol Obstet 1976;142:369–72. 9/38

10. Development of guideline
• No guidelines focusing on the MX of Acute cholangitis had been published
prior to 2007, and no worldwide criteria existed for diagnostic and severity
assessment.
• Acute cholangitis has long been DX on the basis of Charcot’s triad, which
relies on clinical signs [2]. However, these criteria were first proposed in
1877, more than 100 years ago.
• Although Charcot’s triad provides highly specific diagnostic criteria [3],
studies have reported its SN to be on the order of 50 to 70% [3-10].
• More multicenter case series studies showed Charcot’s triad DX rates to be
much lower (26.4% [1] and 21.2% [11]).
• Thus, the ability of this method to diagnosis AC is severely limited.
References are at the end of the slides.
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11. Tokyo Guideline development
• A working group to establish practical Guidelines for the MX of
Cholangitis was organized in 2003 (chief researcher, Tadahiro Takada).
• This project was funded by a grant from the Japanese Ministry of Health, Labour, and Welfare, and was supported by the Japanese Society for Abdominal
Emergency Medicine, the Japan Biliary Association, and the Japanese Society of Hepato-Biliary-Pancreatic Surgery.
• Finally, an International Consensus Meeting took place in Tokyo, on 2006,
to obtain international agreement on diagnostic criteria, severity
assessment, and MX. And the TG07 flowchart was established on the
basis of the consensus.
• The TG07 flowchart has been cited in numerous publications and has had a major
impact on everyday clinical practice and clinical research.
• The Tokyo Guidelines were revised in 2013, and in 2018 (TG18) which is
the third revised version.
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12. TG007: Diagnostic criteria for acute cholangitis
A multi-center analysis found that the SN was 82.6 % and the SP was 79.8 % [1].
1. 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;19:548–56.
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13. TG 1 8 ／TG13 Diagnostic criteria for Acute Cholangitis
Note: Other factors which are helpful in DX of acute cholangitis include abdominal pain (RUQ or upper abdominal) and a
HX 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 DD is difficult.
A multi-center analysis found that the SN was 91.8 %
and the SP was 77.7 %. TG13 showed similar
specificity to TG07 but showed markedly ↑sensitivity.
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14. NOTE:
• Jaundice, one of the symptoms in Charcot’s triad, is only observed in
60 to 70% of pts with AC [1-8].
• With the TG18/TG13 diagnostic criteria for AC, a diagnosis of AC can
still be made in the absence of jaundice, based on elevated ALP,
gamma-GTP, LAP, and transaminases (AST, ALT) in the blood test
results.
1. Csendes A, Diaz JC, Burdiles P, Maluenda F, Morales E. Risk factors and classification of acute suppurative cholangitis. Br J Surg 1992;79:655-658.
2. Welch JP, Donaldson GA. The urgency of diagnosis and surgical treatment of acute suppurative cholangitis. Am J Surg 1976;131:527-532.
3. Thompson JE Jr, Tompkins RK, Longmire WP Jr. Factors in management of acute cholangitis. Ann Surg. 1982;195:137-145.
4. Gigot JF, Leese T, Dereme T, Coutinho J, Castaing D, Bismuth H. Acute cholangitis. Multivariate analysis of risk factors. Ann Surg 1989;209(4):435-438.
5. Boey JH, Way LW. Acute cholangitis. Ann Surg 1980;191: 264-27.
6. O'Connor MJ, Schwartz ML, McQuarrie DG, Sumer HW. Acute bacterial cholangitis: an analysis of clinical manifestation. Arch Surg 1982;117:437-441.
7. Lai EC, Tam PC, Paterson IA, Ng MM, Fan ST, Choi TK, Wong J. Emergency surgery for severe acute cholangitis. The high-risk patients. Ann Surg 1990;211:55-59.
8. Haupert AP, Carey LC, Evans WE, Ellison EH. Acute suppurative cholangitis. Experience with 15 consecutive cases. Arch Surg 1967;94:460-468. 14/38

15. Retrospective comparison of various DX criteria of
Acute Cholangitis in a multi-center study in Japan
CHARCOT’S TRIAD % TG07 TG13
SN 26.4 82.6 91.8
SP 95.9 79.8 77.7
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;19:548–56.
Note: In terms of diagnostic criteria, sensitivity is more important than specificity for this disease, which can be life
threatening if not diagnosed rapidly and treated appropriately.
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16. TG007. Criteria for severity assessment of Acute Cholangitis
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.
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17. TG007: Definitions of severity assessment criteria for acute cholangitis
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 DX has been made.
In TG07, Grades II and I were only assessed after observation of the RX courses.
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18. TG 1 8 ／TG13 Severity assessment criteria for ACg
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19. TG 1 8 ／TG13 Severity assessment criteria for ACg
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20. Imaging ; USG OR CT ?
• Abdominal ultrasound can readily detect abnormal dilation of the bile duct and,
at the same time, be used to identify the cause .
• Bile duct stones present as highly echoic nodular lesions that cast an acoustic shadow, whereas with
malignant stenosis of the bile duct, the mass around the stenosed bile duct can be identified as a normal,
low-echo region.
• According to a meta-analysis by Abboud et al., USG has SN of 42% and SP of 96%
for dilated CBD and a SN of 38% and a SP of 100% for all bile duct stones. These
results show that USG has high SP but insufficient SN [1].
• There are various disadvantages relating to the accuracy of USG such as the
greater likelihood of being affected by technician experience and clinical
condition of the pt compared to CT scans [2], but USG should be performed
initially in pts with suspected AC given its minimal invasiveness, wide availability,
convenience, and cost effectiveness.
1. Abboud P-AC, 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(4):450-7.
2. Rickes S1, Treiber G, Mönkemüller K, Peitz U, Csepregi A, Kahl S, et al. Impact of the operator's experience on value of high -resolution transabdominal ultrasound in the diagnosis of choledocholithiasis: a
prospective comparison using endoscopic retrograde cholangiography as the gold standard. Scand J Gastroenterol. 2006;41(7):838-43. 20/38

21. Imaging ; USG OR CT ?
• Unlike abdominal ultrasound, CT imaging is not affected by intestinal gas
and thus can be used to objectively identify high-attenuated nodules in the
bile duct .
• However, because the CT value of bile duct stones depends on the amount
of calcium phosphate or calcium carbonate in the stones [1], the detection
SN of CT range from 25 to 90% [2].
• CT imaging can clearly identify bile duct dilatation and can contribute to
much better DX of the cause of biliary stenosis (e.g., biliary carcinoma,
pancreatic cancer, or sclerosing cholangitis). CT imaging is also useful for
diagnosing local complications (e.g., liver abscess or portal vein thrombosis)
[2–5].
1. Lee JK, Kim TK, Byun JH, Kim AY, Ha HK, Kim PN, et al. Diagnosis of intrahepatic and common duct stones: combined unenhanced and contrast -enhanced helical CT in 1090 patients. Abdom Imaging.
2006;31(4):425-32.
2. Patel NB, Oto A, Thomas S. Multidetector CT of emergent biliary pathologic conditions. Radiographics. 2013;33(7):1867-88.
3. Yoon K -H, Ha HK, Lee JS, Suh JH, Kim MH, Kim PN, et al. Inflammatory Pseudotumor of the Liver in Patients with Recurrent Pyogenic Cholangitis: CT -Histopathologic Correlation 1. Radiology. 1999;211(2):373-9.
4. 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 Am J Roentgenol. 2001;176(3):675-9.
5. 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(3):528-35.
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22. CT demonstrating ACg with gallstone and CBD stone
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. 22/38

23. Dynamic CT : ACg
• On the arterial phase, inhomogeneous hepatic parenchymal enhancement
(nodular, patchy, wedge-shaped or geographic) is frequently seen in pts with
ACg.
• Hepatic parenchymal changes seen at imaging in Acg are likely to be related to the extension of the
inflammatory process into the periportal tissues causing a decreased portal blood flow and an increased
arterial blood flow.
• This inhomogeneous hepatic enhancement of contrast-enhanced dynamic
CT appears in the arterial phase only, and disappears in the portal and
equilibrium phases.
23/38

24. MRI/MRCP
• MRCP is a non-invasive method that can delineate the bile duct and is a
good option for identifying malignant disease or bile duct stones causing a
biliary obstruction [1].
• Although MRI/MRCP are objective imaging methods with sufficient
diagnostic capabilities, they are usually not the first-choice test method for
reasons of availability and convenience.
1. Watanabe Y, Nagayama M, Okumura A, Amoh Y, Katsube T, Suga T, et al. MR Imaging of Acute Biliary Disorders 1. Radiographics. 2007;27(2):477-95.
24/38

25. • Research comparing the diagnostic accuracy of MRI/MRCP, CT, and USG in
obstructive jaundice showed MRCP to have the best diagnostic capabilities,
with benign and malignant disease being identified in 98% and 98% of
cases, respectively, with MRI/MRCP, 82.86% and 91.43% of cases with CT,
and 88% and 88% of cases with USG[1].
• Imaging findings with AC include ↑ signal around the bile duct on T2-
weighted images and heterogeneous enhancement of the bile duct wall,
abscesses, and PVT on CET1-weighted images, underlining the utility of
this method in the DX of AC and complications [2].
• MRI/MRCP tests are therefore recommended when abdominal ultrasound
or CT imaging do not provide a definite diagnosis.
1. Singh A, Mann HS, Thukral CL, Singh NR. Diagnostic Accuracy of MRCP as Compared to Ultrasound/CT in Patients with Obstructive Jaundice. J Clin Diagn Res. 2014;8(3):103- 7
2. Eun HW, Kim JH, Hong SS, Kim YJ. Assessment of acute cholangitis by MR imaging. Eur J Radiol. 2012;81(10):2476-80. 25/38

26. Is procalcitonin useful for DX and severity assessment for acute
cholangitis?
• ACg occurs when biliary stenosis results in bile backing up and becoming
infected. This blockage elevates pressure within the biliary system and
results in the infected bile being flushed into systemic circulation, inducing
a systemic inflammatory response.
• The pt can develop septicemia if this situation continues. Severe ACg can
lead to organ failure due to septicemia; a recent report has suggested that
measurement of serum procalcitonin, a serum marker for septicemia, can
provide a simpler and faster method to assess the severity of AC.
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27. Serum procalcitonin levels: studies
• Three case series studies have investigated the relationship between
serum procalcitonin levels and the severity of AC.
• These studies reported that serum procalcitonin levels ↑ with severity
based on the TG07[1],TG13 guidelines [2,3].
• These results suggest that serum procalcitonin levels are useful when
assessing the severity of AC.
• However, as this research only includes small-scale case series studies in
single institutions and the current body of evidence remains small, further
clinical research is needed to evaluate the usefulness of this method.
1. Hamano K, Noguchi O, Matsumoto Y, Watabe T, Numata M, Yosioka A, Ito Y, Hosoi. Usefulness of procalcitonin for severity assessment in patients with acute cholangitis. Clin Lab 59(1-2): 177-83, 2013.
2. Shinya S, Sasaki T, Yamashita Y, Kato D, Yamashita K, Nakashima R, Yamauchi Y, Noritomi. Procalcitonin as a useful biomarker for determining the need to perform emergency biliary drainage in cases of acute
cholangitis. J Hepatobiliary Pancreat Sci 21(10)：777-85, 2014.
3. Umefune G1, Kogure H1, Hamada T1,2, Isayama H3, Ishigaki K1, Takagi K1, Akiyama D1, Watanabe T1, Takahara N1, Mizuno S1, et al. Procalcitonin is a useful biomarker to predict severe acute cholangitis: a
single -center prospective study. J Gastroenterol. 2016 Oct 25. 27/38

28. Initial treatment
• Once a definitive DX of Acg has been reached, initial RX including the infusion of
sufficient fluids and antibiotic and analgesic administration is started, with
careful monitoring of BP, HR, and urine volume.
• Despite the concern that analgesic administration may mask physical signs and
cause a mistaken DX, a RCT comparing IV morphine and an IV placebo for pts
examined in the emergency room complaining of abdominal pain found no
difference between them in the rate of DX [1,2], and analgesics should therefore
be administered proactively at an early stage.
• Opioid analgesics such as morphine hydrochloride and other similar types of
drug (such as non-opioid analgesics and pentazocine) cause the SOD to contract,
which may ↑biliary pressure, and must therefore be administered with caution.
1. Thomas SH, Silen W, Cheema F, Reisner A, Aman S, Goldstein JN, et al. Effects of morphine analgesia on diagnostic accuracy in Emergency Department patients with abdominal pain: a prospective, randomized
trial. J Am Coll Surg. 2003;196:18-31 14.
2. Gallagher EJ, Esses D, Lee C, Lahn M, Bijur PE. Randomized clinical trial of morphine in acute abdominal pain. Ann Emerg Med. 2006;48:150-60, 60 e1-4 28/38

29. TG18 Flow chart for initial assessment in Acute Cholangitis
Initiate medical treatment and orfgan support as necessary
Suspected Acute
biliary infection
Acute Cholangitis
• Measurement of
Vital signs
• Examination
• Diagnostic Criteria
Assessment
of Severity
grading
Transfer to Advance CenterOther Disease
Treatment
According to
TG18
FLOWCHART
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30. Transfer criteria
• If a hospital is not equipped to perform endoscopic or percutaneous
transhepatic biliary drainage or provide intensive care, pts with moderate
or severe cholangitis should preferably be transferred to a hospital capable
of providing these treatments, irrespective of whether or not they are
actually required[1].
1. The revision committee for the guidelines of acute cholangitis and cholecystitis. Guidelines of acute cholangitis and cholecystitis 2013 Tokyo: Igakutosho-shuppan Ltd.; 2013 in Japanese.
30/38

31. 31/38

32. TG18 Flow chart for Mx in Acute Cholangitis
*Blood culture should be taken into consideration before antibiotics are started.Bile samples should be taken during
biliary drainage and cultured.
ꬹPrinciples of Rx for Acg consist of Antimicrobial administration, biliary drainage and RX of the etiology.
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33. MX: Grade I (mild acute cholangitis)
• In most cases initial RX including antibiotics is sufficient, and most pts do
not require biliary drainage.
• However, biliary drainage should be considered if a pt does not respond
to initial treatment.
• EST and subsequent choledocholithotomy may be performed at the same
time as biliary drainage.
• Postoperative cholangitis usually improves with antibiotic RX alone, and
biliary drainage is not usually required [1].
• Miura F, Takada T, Strasberg SM, Solomkin JS, Pitt HA, Gouma DJ, et al. TG13 flowchart for the management of acute cholangitis and cholecystitis. Journal of hepato-biliary-pancreatic sciences. 2013
33/38

34. MX: Grade II (moderate acute cholangitis)
• Moderate acute cholangitis is cholangitis that is not severe but requires
early biliary drainage.
• Early endoscopic or percutaneous transhepatic biliary drainage is
indicated.
• If the underlying etiology requires RX, this should be provided after the
pt’s general condition has improved[2], and EST and subsequent
choledocholithotomy may be performed together with biliary drainage.
1. Yokoe H. TG18 Diagnostic criteria and severity grading of acute cholecystitis.Journal of hepato-biliary-pancreatic sciences. 2018
2. Miura F, Takada T, Strasberg SM, Solomkin JS, Pitt HA, Gouma DJ, et al. TG13 flowchart for the management of acute cholangitis and cholecystitis. Journal of hepato-biliary-pancreatic sciences. 2013 34/38

35. MX: Grade III (severe acute cholangitis)
• Severe acute cholangitis is cholangitis with sepsis-induced organ damage.
• As the pnt’s condition may deteriorate rapidly, a swift response is
essential including appropriate respiratory/circulatory management
(tracheal intubation followed by artificial ventilation and the use of
hypertensive agents).
• Endoscopic or percutaneous transhepatic biliary drainage should be
performed as soon as possible after the pt’s condition has been improved
by initial RX and respiratory/circulatory management.
• If treatment for the underlying etiology is required, this should be
provided after the pt’s general status has improved [1].
• Miura F, Takada T, Strasberg SM, Solomkin JS, Pitt HA, Gouma DJ, et al. TG13 flowchart for the management of acute cholangitis and cholecystitis. Journal of hepato-biliary-pancreatic sciences. 2013
35/38

36. Role of antimicrobial therapy
• Acute cholangitis is still fatal diseases if not appropriately treated in a
timely fashion.
• A recent large scale study indicated the morality rate (30-day all-cause
mortality rate) of 2.4%, 4.7%, 8.4% by TG 13 Severity Grade I, II, and, III,
respectively [1].
• The primary goal of antimicrobial therapy in Acg 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 [2].
1. Gomi H, Takada T, Hwang TL, Akazawa K, Mori R, Endo I, et al. Updated comprehensive epidemiology, microbiology, and outcomes among patients with acute cholangitis. J Hepatobiliary Pancreat Sci. 2017
Jun;24(6):310-318.
2. 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;19:279-86.
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37. Recommended duration of antimicrobial therapy
37/38

38. Representative oral antimicrobial agents for acute cholangitis with
susceptible isolates (Endorsed from Tokyo Guidelines 2013]
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39. End of Slides
• Wada K. Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat
Surg. 2007;14(1):52-8. Epub 2007 Jan 30.
• Takada T. Background: Tokyo Guidelines for the management of acute cholangitis and cholecystitis. J Hepatobiliary
Pancreat Surg. 2007;14(1):1-10. Epub 2007 Jan 30.
• Kiriyama S. TG13 guidelines for diagnosis and severity grading of acute cholangitis. J Hepatobiliary Pancreat Sci. 2013
Jan;20(1):24-34. doi: 10.1007/s00534-012-0561-3.
• Takada T. TG13: Updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis.J Hepatobiliary
Pancreat Sci. 2013 Jan;20(1):1-7. doi: 10.1007/s00534-012-0566-y.
• Miura F. Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. J
Hepatobiliary Pancreat Sci. 2018 Jan;25(1):31-40. doi: 10.1002/jhbp.509. Epub 2018 Jan 8.
• Kiriyama S. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis. J Hepatobiliary
Pancreat Sci. 2018 Jan;25(1):17-30. doi: 10.1002/jhbp.512. Epub 2018 Jan 5.
• Gomi H. Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis. J Hepatobiliary Pancreat
Sci. 2018 Jan;25(1):3-16. doi: 10.1002/jhbp.518. Epub 2018 Jan 9.
TG 2007 TG 2018TG 2013
39

40. References: Incidence of clinical manifestation of acute cholangitis
6. 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;211:55–9.
8. Chijiiwa K, Kozaki N, Naito T, Kameoka N, Tanaka M. Treatment of choice for choledocholithiasis in patients with acute
obstructive suppurative cholangitis and liver cirrhosis. Am J Surg
1995;170:356–60.
9. Charcot M. De la fievre hepatique symptomatique. Comparaison avec la fievre uroseptique. Lecons sur les maladies du
foie des voies biliares et des reins. Paris: Bourneville et Sevestre; 1877. p.176–85.
10. Csendes A, Diaz JC, Burdiles P, Maluenda F, Morales E. Risk factors and classification of acute suppurative cholangitis.
Br J Surg 1992;79:655–8.
11. Thompson JE Jr, Tompkins RK, Longmire WP Jr. Factors in management of acute cholangitis. Ann Surg 1982;195:137–
45.
12. Gigot JF, Leese T, Dereme T, Coutinho J, Castaing D, Bismuth H. Acute cholangitis. Multivariate analysis of risk factors.
Ann Surg 1989;209:435–8.
13. Boey JH, Way LW. Acute cholangitis. Ann Surg 1980;191:264–70.
14. O’Connor MJ, Schwartz ML, McQuarrie DG, Sumer HW. Acute bacterial cholangitis: an analysis of clinical
manifestation. Arch Surg 1982;117:437–41.
15. Haupert AP, Carey LC, Evans WE, Ellison EH. Acute suppurative cholangitis. Experience with 15 consecutive cases. Arch
Surg 1967;94:460–8.
16. Welch JP, Donaldson GA. The urgency of diagnosis and surgical treatment of acute suppurative cholangitis. Am J Surg
1976;131: 527–32.
17. Saharia PC, Cameron JL. Clinical management of acute cholangitis. Surg Gynecol Obstet 1976;142:369–72. 40

41. References: Development of guideline
1. 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;19:548–56.
2. Charcot M. De la fievre hepatique symptomatique. Comparison avec la fievre uroseptique. Lecons sur les maladies du foie des voies
biliares et des reins. Paris: Bourneville et Sevestre; 1877. p. 176–85.
3. Csendes A, Diaz JC, Burdiles P, Maluenda F, Morales E. Risk factors and classification of acute suppurative cholangitis. Br J Surg
1992;79:655-658.
4. Welch JP, Donaldson GA. The urgency of diagnosis and surgical treatment of acute suppurative cholangitis. Am J Surg 1976;131:527-532.
5. Thompson JE Jr, Tompkins RK, Longmire WP Jr. Factors in management of acute cholangitis. Ann Surg. 1982;195:137-145.
6. Gigot JF, Leese T, Dereme T, Coutinho J, Castaing D, Bismuth H. Acute cholangitis. Multivariate analysis of risk factors. Ann Surg
1989;209(4):435-438.
7. Boey JH, Way LW. Acute cholangitis. Ann Surg 1980;191: 264-27.
8. O'Connor MJ, Schwartz ML, McQuarrie DG, Sumer HW. Acute bacterial cholangitis: an analysis of clinical manifestation. Arch Surg
1982;117:437-441.
9. Lai EC, Tam PC, Paterson IA, Ng MM, Fan ST, Choi TK, Wong J. Emergency surgery for severe acute cholangitis. The high-risk patients. Ann
Surg 1990;211:55-59.
10. Haupert AP, Carey LC, Evans WE, Ellison EH. Acute suppurative cholangitis. Experience with 15 consecutive cases. Arch Surg 1967;94:460-
468.
11. Kiriyama S, Takada T, Tsann-Long Hwang, Akazawa H, Miura F, Gomi H, Mori R,Endo I, Itoi T, Masamichi Yokoe Miin-Fu Chen, Yi-Yin Jan, et
al. Clinical application and verification of the TG13 diagnostic and severity grading criteria for acute cholangitis: An international
multicenter observational study. J Hepatobiliary Pancreat Sci. 2017
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