The Tokyo Guidelines for Cholangitis KP Tsui UNITED CHRISTIAN HOSPITAL

Cholangitis Biliary infection associated with partial or complete obstruction of the biliary tree Diagnosis based on clinical findings, such as Charcot’s triad, with laboratory data and imaging findings

Charcot’s triad Fever Jaundice Abdominal pain

Reynold’s Pentad + Hypotension + Mental obtundation

Lai EC, Tam PC, Paterson IA, Ng MM, Fan ST, Choi TK, et al 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.

There was no standard criteria for the diagnosis and severity assessment

Tokyo guidelines Based on a systematic review of literature and consensus of experts at the International Consensus Meeting in Tokyo 2006

TG07 A. Clinical contest and clinical manifestations History of biliary disease Fever and/or chills Jaundice Abdominal pain (RUQ or upper abdominal) B. Laboratory data 5. Evidence of inflammatory response 6. Abnormal liver function tests C. Imaging findings 7. Biliary dilatation, or evidence of an etiology (stricture, stone, stent etc) Suspected diagnosis 2 or more items in A Definite diagnosis Charcot’s triad (2+3+4) Two or more items in A + both items in B and item C Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg (2007) 14:52–58

B-5: abnormal WBC, raised CRP and other changes indicating inflammation B-6: raised ALP, r-GTP (GGT), AST and ALT levels

Severity assessment criteria 2007 Mild (grade I): acute cholangitis which responds to the initial medical treatment

Moderate (grade II) acute cholangitis which does not respond to the initial medical treatment and is not accompanied by organ dysfunction

TG07 Severity assessment criteria Grade III (severe) Associated with onset of dysfunction in at least one of the following organs/ systems 1. Cardiovascular dysfunction Hypotension requiring dopamine >=5ug/kg per min, or any dose of norepinephrine 2. Neurological dysfunction Disturbance of consciousness 3. Respiratory dysfunction PaO2/FiO2 ratio < 300 4. Renal dysfunction Oiguria, serum creatinine > 2.0mg/dl 5. Hepatic dysfunction PT-INR > 1.5 6. Hematological dysfunction Platelet count < 100000/mm3

Because of new information, the Tokyo Guidelines Revision Committee was organized to develop the update Tokyo guidelines (TG13)

Multiple tertiary centers in Japan From Jan 2007 and July 2011 794 patients with cholangitis 794 patients with cholangitis (1) purulent biliary drainage (2) Clinical remission due to bile duct drainage (3) Remission achieved by antimicrobial thearpy alone in patients where the only site of infection was biliary tree

Revision of TG07 The diagnostic criteria was adjusted to achieve the highest sensitivity and specificity

TG07 A. Clinical contest and clinical manifestations History of biliary disease Fever and/or chills Jaundice Abdominal pain (RUQ or upper abdominal) B. Laboratory data 5. Evidence of inflammatory response 6. Abnormal liver function tests C. Imaging findings 7. Biliary dilatation, or evidence of an etiology (stricture, stone, stent etc) Suspected diagnosis 2 or more items in A Definite diagnosis Charcot’s triad (2+3+4) Two or more items in A + both items in B and item C Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg (2007) 14:52–58

New diagnostic criteria and severity assessment of acute cholangitis in revised Tokyo guidelines. J Hepatobiliary Pancreat Sci (2012) 19:548–556

TG13 diagnostic criteria Systemic inflammation A-1. Fever +/- shaking chills A-2. Laboratory data: evidence of inflammatory response Cholestasis B-1. Jaundice B-2. Laboratory data: abnormal liver function tests C Imaging C-1. Biliary dilatation C-2. Evidence of 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 New diagnostic criteria and severity assessment of acute cholangitis in revised Tokyo guidelines. J Hepatobiliary Pancreat Sci (2012) 19:548–556

A-2: abnormal WBC, raised CRP and other changes indicating inflammation B-2: raised ALP, r-GTP (GGT), AST and ALT levels

New diagnostic criteria and severity assessment of acute cholangitis in revised Tokyo guidelines. J Hepatobiliary Pancreat Sci (2012) 19:548–556

With suspected diagnosis, early biliary drainage and source control of infection can be provided

Formulation of new severity assessment TG07 insufficient in separating Grade I and Grade II Need 24 hour observation period Definition of grade II ambiguous Only assessed after observation for initial treatment courses

New diagnostic criteria and severity assessment of acute cholangitis in revised Tokyo guidelines. J Hepatobiliary Pancreat Sci (2012) 19:548–556

TG13 Severity assessment criteria Grade III (severe) Associated with onset of dysfunction in at least one of the following organs/ systems 1. Cardiovascular dysfunction Hypotension requiring dopamine >=5ug/kg per min, or any dose of norepinephrine 2. Neurological dysfunction Disturbance of consciousness 3. Respiratory dysfunction PaO2/FiO2 ratio < 300 4. Renal dysfunction Oiguria, serum creatinine > 2.0mg/dl 5. Hepatic dysfunction PT-INR > 1.5 6. Hematological dysfunction Platelet count < 100000/mm3

Grade II ( moderate ) Any 2 of the following 1. Abnormal WBC count (>12000/mm3, < 4000/mm3) 2. High fever (>=39C) 3. Age (>=75 years) 4. Hyperbilirubinemia (total bilirubin >=5 mg/ dl) 5. Hypoalbuminemia (< STD x 0.7)

Grade I (mild) - Does not meet criteria for Grade II or Grade III at initial diagnosis

TG13 flowchart for the management of acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci (2013) 20:47–54

TG13 management bundles for acute cholangitis and cholecystitis TG13 management bundles for acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci (2013) 20:55–59

Tokyo guidelines Minimal recognition outside Japan Several retrospective studies have validated its diagnostic value Verification of the Tokyo guidelines for acute cholangitis secondary to benign and malignant biliary obstruction: experience from a Chinese tertiary hospital. Hepatobiliary Pancreat Dis Int, Vol 12, No 4, August 1, 2013.

Tokyo guidelines 2007 Based on Japanese studies Sensitivity: 63.9-94% Charcot’s triad < 40% 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;18:250-257.

Tokyo guidelines 2007 Classification into mild or moderate grade using the Tokyo Guidelines is difficult when early biliary drainage is routinely performed. Journal of Hepato-Biliary-Pancreatic Sci, July 2012, Volume 19, Issue 4, pp 487-491. Verification of Tokyo Guidelines for diagnosis and management of acute cholangitis

“Verification of the Tokyo guidelines for acute cholangitis secondary to benign and malignant biliary obstruction: experience from a Chinese tertiary hospital” Verification of the Tokyo guidelines for acute cholangitis secondary to benign and malignant biliary obstruction: experience from a Chinese tertiary hospital. Hepatobiliary Pancreat Dis Int, Vol 12, No 4, August 1, 2013.

First study to verify the application of TG07 for diagnosis and treatment of cholangitis in Chinese patients Verification of the Tokyo guidelines for acute cholangitis secondary to benign and malignant biliary obstruction: experience from a Chinese tertiary hospital. Hepatobiliary Pancreat Dis Int, Vol 12, No 4, August 1, 2013.

At Chinese PLA General Hospital, Beijing 120 patients 82 benign; 38 malignant Retrospective from ERCP database

Verification of the Tokyo guidelines for acute cholangitis secondary to benign and malignant biliary obstruction: experience from a Chinese tertiary hospital. Hepatobiliary Pancreat Dis Int, Vol 12, No 4, August 1, 2013.

Definite diagnosis 68 (82.9%) benign patients 36 (94.7%) malignant 104 (86.7%) overall Charcot’s triad 61 (50.8%) overall Verification of the Tokyo guidelines for acute cholangitis secondary to benign and malignant biliary obstruction: experience from a Chinese tertiary hospital. Hepatobiliary Pancreat Dis Int, Vol 12, No 4, August 1, 2013.

Verification of the Tokyo guidelines for acute cholangitis secondary to benign and malignant biliary obstruction: experience from a Chinese tertiary hospital. Hepatobiliary Pancreat Dis Int, Vol 12, No 4, August 1, 2013.

No significant difference in clinical outcome was observed in patients of different severity grades Conclusion: The TG07 are more reliable than Charcot's triad for the diagnosis of acute cholangitis albeit with limited prognostic values. Verification of the Tokyo guidelines for acute cholangitis secondary to benign and malignant biliary obstruction: experience from a Chinese tertiary hospital. Hepatobiliary Pancreat Dis Int, Vol 12, No 4, August 1, 2013.

Compliance 60842 acute cholangitis patients from the Japanese administrative database associated with the Diagnosis Procedure Combination (DPC) system. Grade III: 7.6 ± 2.1 Grade II: 6.5 ± 3.0 Grade I: 2.9 ± 0.9, p < 0.001 (score 0 = 0% to score 10 = 100%) 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. Journal of Hepato-Biliary-Pancreatic Sciences, January 2011, Volume 18, Issue 1, pp 53-59

Improved prognosis of in-hospital mortality with odds ratio of 0 Improved prognosis of in-hospital mortality with odds ratio of 0.856 among patients with high compliance with the TG07

Take home message The Tokyo guidelines are more sensitive than Charcot’s triad for diagnosis of cholangitis TG13 produces a new standard for diagnosis, severity grading and management of acute cholangitis Awaiting further validation on TG13