Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis (with videos)

The Tokyo Guidelines 2013 (TG13) for acute cholangitis and cholecystitis were globally disseminated and various clinical studies about the management of acute cholecystitis were reported by many researchers and clinicians from all over the world. The 1^st edition of the Tokyo Guidelines 2007 (TG07) was revised in 2013. According to that revision, the TG13 diagnostic criteria of acute cholecystitis provided better specificity and higher diagnostic accuracy. Thorough our literature search about diagnostic criteria for acute cholecystitis, new and strong evidence that had been released from 2013 to 2017 was not found with serious and important issues about using TG13 diagnostic criteria of acute cholecystitis. On the other hand, the TG13 severity grading for acute cholecystitis has been validated in numerous studies. As a result of these reviews, the TG13 severity grading for acute cholecystitis was significantly associated with parameters including 30‐day overall mortality, length of hospital stay, conversion rates to open surgery, and medical costs. In terms of severity assessment, breakthrough and intensive literature for revising severity grading was not reported. Consequently, TG13 diagnostic criteria and severity grading were judged from numerous validation studies as useful indicators in clinical practice and adopted as TG18/TG13 diagnostic criteria and severity grading of acute cholecystitis without any modification. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included.     

Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis

The initial management of patients with suspected acute biliary infection starts with the measurement of vital signs to assess whether or not the situation is urgent. If the case is judged to be urgent, initial medical treatment should be started immediately including respiratory/circulatory management if required, without waiting for a definitive diagnosis. The patient's medical history is then taken; an abdominal examination is performed; blood tests, urinalysis, and diagnostic imaging are carried out; and a diagnosis is made using the diagnostic criteria for cholangitis/cholecystitis. Once the diagnosis has been confirmed, initial medical treatment should be started immediately, severity should be assessed according to the severity grading criteria for acute cholangitis/cholecystitis, and the patient's general status should be evaluated. For mild acute cholangitis, in most cases initial treatment including antibiotics is sufficient, and most patients do not require biliary drainage. However, biliary drainage should be considered if a patient does not respond to initial treatment. For moderate acute cholangitis, early endoscopic or percutaneous transhepatic biliary drainage is indicated. If the underlying etiology requires treatment, this should be provided after the patient's general condition has improved; endoscopic sphincterotomy and subsequent choledocholithotomy may be performed together with biliary drainage. For severe acute cholangitis, appropriate respiratory/circulatory management is required. Biliary drainage should be performed as soon as possible after the patient's general condition has been improved by initial treatment and respiratory/circulatory management. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included.     

New diagnostic criteria and severity assessment of acute cholangitis in revised Tokyo guidelines

Background

The Tokyo Guidelines for the management of acute cholangitis and cholecystitis were published in 2007 (TG07) and have been widely cited in the world literature. Because of new information that has been published since 2007, we organized the Tokyo Guidelines Revision Committee?to conduct a multicenter analysis to develop the updated Tokyo Guidelines (TG13).

Methods/materials

We retrospectively analyzed 1,432 biliary disease cases where acute cholangitis was suspected. The cases were collected from multiple tertiary care centers in Japan. The ‘gold standard’ for acute cholangitis in this study was that one of the three following conditions was present: (1) purulent bile was observed; (2) clinical remission following bile duct drainage; or (3) remission?was?achieved?by antibacterial therapy alone, in patients in whom the only site of infection was the biliary tree. Comparisons were made for the validity of each diagnostic criterion among TG13, TG07 and Charcot’s triad.

Results

The major changes in diagnostic criteria of TG07 were re-arrangement of the diagnostic items and exclusion of abdominal pain from the diagnostic list.?The sensitivity improved from 82.8?% (TG07) to 91.8?% (TG13). While?the?specificity was similar to TG07, the false positive rate in cases of acute cholecystitis was reduced from 15.5 to 5.9?%. The sensitivity of Charcot’s triad?was?only 26.4?%?but the?specificity?was 95.6?%. However, the false positive rate in cases of acute cholecystitis?was?11.9?% and not negligible. As for severity grading, Grade II (moderate) acute cholangitis is defined as being associated with any two of the significant prognostic factors which were derived from evidence presented recently in the literature. The factors chosen allow severity assessment to be performed soon after diagnosis of acute cholangitis.

Conclusion

TG13 present a new standard for the diagnosis, severity grading, and management of acute cholangitis.     

New diagnostic criteria and severity assessment of acute cholecystitis in revised Tokyo guidelines

Background

The Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07) were published in 2007 as the world’s first guidelines for acute cholangitis and cholecystitis. The diagnostic criteria and severity assessment of acute cholecystitis have since been widely used all over the world. A validation study of TG07 has shown that the diagnostic criteria for acute cholecystitis are highly reliable but that the definition of definite diagnosis is ambiguous. In addition, considerable new evidence referring to acute cholecystitis as well as evaluations of TG07 have been published. Consequently, we organized the Tokyo Guidelines Revision Committee to evaluate TG07, recognize new evidence, and conduct a multi-center analysis to revise the guidelines (TG13).

Methods and materials

We retrospectively analyzed 451 patients with acute cholecystitis from multiple tertiary care centers in Japan. All 451 patients were first evaluated using the criteria in TG07. The “gold standard” for acute cholecystitis in this study was a diagnosis by pathology. The validity of TG07 diagnostic criteria was investigated by comparing clinical with pathological diagnosis.

Results

Of 451 patients evaluated, a total of 227 patients were given a diagnosis of acute cholecystitis by pathological examination (prevalence 50.3?%). TG07 criteria provided a definite diagnosis of acute cholecystitis in 224 patients. The sensitivity of TG07 diagnostic criteria for acute cholecystitis was 92.1?%, and the specificity was 93.3?%. Based on the preliminary results, new diagnostic criteria for acute cholecystitis were proposed. Using the new criteria, the sensitivity of definite diagnosis was 91.2?%, and the specificity was 96.9?%. The accuracy rate was improved from 92.7 to 94.0?%. In regard to severity grading among 227 patients, 111 patients were classified as Mild (Grade I), 104 as Moderate (Grade II), and 12 as Severe (Grade III).

Conclusion

The proposed new diagnostic criteria achieved better performance than the diagnostic criteria in TG07. Therefore, the proposed criteria have been adopted as new diagnostic criteria for acute cholecystitis and are referred to as the 2013 Tokyo Guidelines (TG13). Regarding severity assessment, no new evidence was found to suggest that the criteria in TG07 needed major adjustment. As a result, TG07 severity assessment criteria have been adopted in TG13 with minor changes.     

TG13 flowchart for the management of acute cholangitis and cholecystitis

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 patient’s 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 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. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.     

Urgent ERCP for acute cholangitis reduces mortality and hospital stay in elderly and very elderly patients

BACKGROUND: Acute cholangitis in old people is a cause of mortality and prolonged hospital stay. We evaluated the effects of methods and timing of biliary drainage on the outcomes of acute cholangitis in elderly and very elderly patients.METHODS: We analyzed 331 patients who were older than 75 years and were diagnosed with acute calculous cholangitis. They were admitted to our hospital from 2009 to 2014. Patients' demographics, severity grading, methods and timing of biliary drainage, mortality, and hospital stay were retrospectively obtained from medical records. Clinical parameters and outcomes were compared between elderly(75-80 years, n=156) and very elderly(≥81 years, n=175) patients. We analyzed the effects of methods [none, endoscopic retrograde cholangiopancreatography(ERCP), percutaneous transhepatic biliary drainage, or failure] and timing(urgent or early) of biliary drainage on mortality and hospital stay in these patients.RESULTS: Acute cholangitis in older patients manifested as atypical symptoms characterized as infrequent Charcot's triad(4.2%) and comorbidity in one-third of the patients. Patients were graded as mild, moderate, and severe cholangitis in 104(31.4%), 175(52.9%), and 52(15.7%), respectively. Urgent biliary drainage(≤24 hours) was performed for 80.5%(247/307) of patients. Very elderly patients tended to have more severe grades and were treated with sequential procedures of transient biliary drainage and stone removal at different sessions. Hospital stay was related to methods and timing of biliary drainage. Mortality was very low(1.5%) and not related to patient age but rather to the success or failure of biliary drainage and severity grading of the acute cholangitis.CONCLUSIONS: The methods and timing used for biliary drainage and severity of cholangitis are the major determinants of mortality and hospital stay in elderly and very elderly patients with acute cholangitis. Urgent successful ERCP is mandatory for favorable prognosis in these patients.     

Indications and techniques of biliary drainage for acute cholangitis in updated Tokyo Guidelines 2018

The Tokyo Guidelines 2013 (TG13) include new topics in the biliary drainage section. From these topics, we describe the indications and new techniques of biliary drainage for acute cholangitis with videos. Recently, many novel studies and case series have been published across the world, thus TG13 need to be updated regarding the indications and selection of biliary drainage based on published data. Herein, we describe the latest updated TG13 on biliary drainage in acute cholangitis with meta‐analysis. The present study showed that endoscopic transpapillary biliary drainage regardless of the use of nasobiliary drainage or biliary stenting, should be selected as the first‐line therapy for acute cholangitis. In acute cholangitis, endoscopic sphincterotomy (EST) is not routinely required for biliary drainage alone because of the concern of post‐EST bleeding. In case of concomitant bile duct stones, stone removal following EST at a single session may be considered in patients with mild or moderate acute cholangitis except in patients under anticoagulant therapy or with coagulopathy. We recommend the removal of difficult stones at two sessions after drainage in patients with a large stone or multiple stones. In patients with potential coagulopathy, endoscopic papillary dilation can be a better technique than EST for stone removal. Presently, balloon enteroscopy‐assisted endoscopic retrograde cholangiopancreatography (BE‐ERCP) is used as the first‐line therapy for biliary drainage in patients with surgically altered anatomy where BE‐ERCP expertise is present. However, the technical success rate is not always high. Thus, several studies have revealed that endoscopic ultrasonography‐guided biliary drainage (EUS‐BD) can be one of the second‐line therapies in failed BE‐ERCP as an alternative to percutaneous transhepatic biliary drainage where EUS‐BD expertise is present.     

Elderly patients (≥ 80 years) with acute calculous cholangitis have similar outcomes as non-elderly patients (< 80 years): Propensity score-matched analysis

BACKGROUNDAcute cholangitis (AC) is a disease spectrum with varying extent of severity. Age ≥ 75 years forms part of the criteria for moderate (Grade II) severity in both the Tokyo Guidelines (TG13 and TG18). Aging is associated with reduced physiological reserves, frailty, and sarcopenia. However, there is evidence that age itself is not the determinant of inferior outcomes in elective and emergency biliary diseases. There is a paucity of reports comparing clinical outcomes amongst elderly patients vs non-elderly patients with AC.AIMTo investigate the effect of age (≥ 80 years) on AC''s morbidity and mortality using propensity score matching (PSM).METHODSThis is a single-center retrospective cohort study of all patients diagnosed with calculous AC (January 2016 to December 2016) and ≥ 80 years old (January 2012 to December 2016) at a tertiary university-affiliated teaching hospital. Inclusion criteria were patients who were treated for suspected or confirmed AC secondary to biliary stones. Patients with AC on a background of hepatobiliary malignancy, indwelling permanent metallic biliary stents, or concomitant pancreatitis were excluded. Elderly patients were defined as ≥ 80 years old in our study. A 1:1 PSM analysis was performed to reduce selection bias and address confounding factors. Study variables include comorbidities, vital parameters, laboratory and radiological investigations, and type of biliary decompression, including the time for endoscopic retrograde cholangiopancreatography (ERCP). Primary outcomes include in-hospital mortality, 30-d and 90-d mortality. Length of hospital stay (LOS) was the secondary outcome.RESULTSFour hundred fifty-seven patients with AC were included in this study (318 elderly, 139 non-elderly). PSM analysis resulted in a total of 224 patients (112 elderly, 112 non-elderly). The adoption of ERCP between elderly and non-elderly was similar in both the unmatched (elderly 64.8%, non-elderly 61.9%, P = 0.551) and matched cohorts (elderly 68.8% and non-elderly 58%, P = 0.096). The overall in-hospital mortality, 30-d mortality and 90-d mortality was 4.6%, 7.4% and 8.5% respectively, with no statistically significant differences between the elderly and non-elderly in both the unmatched and matched cohorts. LOS was longer in the unmatched cohort [elderly 8 d, interquartile range (IQR) 6-13, vs non-elderly 8 d, IQR 5-11, P = 0.040], but was comparable in the matched cohort (elderly 7.5 d, IQR 5-11, vs non-elderly 8 d, IQR 5-11, P = 0.982). Subgroup analysis of patients who underwent ERCP demonstrated the majority of the patients (n = 159/292, 54.5%) had delayed ERCP (> 72 h from presentation). There was no significant difference in LOS, 30-d mortality, 90-d mortality, and in-hospital mortality in patients who had delayed ERCP in both the unmatched and matched cohort (matched cohort: in-hospital mortality [n = 1/42 (2.4%) vs 1/26 (3.8%), P = 0.728], 30-d mortality [n = 2/42 (4.8%) vs 2/26 (7.7%), P = 0.618], 90-d mortality [n = 2/42 (4.8%) vs 2/26 (7.7%), P = 0.618], and LOS (median 8.5 d, IQR 6-11.3, vs 8.5 d, IQR 6-15.3, P = 0.929).CONCLUSIONMortality is indifferent in the elderly (≥ 80 years old) and non-elderly patients (< 80 years old) with AC.     

TG13 indications and techniques for biliary drainage in acute cholangitis (with videos)

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-assisted cannulation, wire-guided cannulation, and treatment of duodenal major papilla using endoscopic papillary balloon dilation (EPBD). Furthermore, recently single- or 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 endoscopist’s preference but EST should be selected rather than EPBD from the aspect of procedure-related complications. In terms of BE-BD 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. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.     

Clinical applicability of Tokyo guidelines 2018/2013 in diagnosis and severity evaluation of acute cholangitis and determination of a new severity model

Objective: To determine the diagnostic accuracy of Tokyo guidelines (TG) 2018/2013 (TG18/TG13) and predictors of poor prognosis in acute cholangitis.

Methods: Retrospective 1-year study of consecutive hospital admissions for acute cholangitis. Prognosis was defined in terms of 30 d in-hospital mortality.

Results: Of the 183 patients with acute cholangitis, diagnostic accuracy based on Charcot’s triad, TG07 and TG18/TG13 was 67.8, 86.9 and 92.3% (p?p?p?=?.006), active oncology disease (OR 3.818; p?=?.006) and malignant aetiology of obstructive jaundice (OR 2.224; p?=?.021) were independent predictors of poor prognosis. The discriminative ability of the model with these four variables was high (AUROC 0.842; p?p?=?.005).

Conclusions: TG18/TG13 showed high diagnostic accuracy in acute cholangitis. Compared with TG18/TG13, the simplified severity model ≥2 allows easy selection of patients who will benefit from admission to the intensive care unit and early biliary decompression.     

Tokyo Guidelines 2018: surgical management of acute cholecystitis: safe steps in laparoscopic cholecystectomy for acute cholecystitis (with videos)

In some cases, laparoscopic cholecystectomy (LC) may be difficult to perform in patients with acute cholecystitis (AC) with severe inflammation and fibrosis. The Tokyo Guidelines 2018 (TG18) expand the indications for LC under difficult conditions for each level of severity of AC. As a result of expanding the indications for LC to treat AC, it is absolutely necessary to avoid any increase in bile duct injury (BDI), particularly vasculo‐biliary injury (VBI), which is known to occur at a certain rate in LC. Since the Tokyo Guidelines 2013 (TG13), an attempt has been made to assess intraoperative findings as objective indicators of surgical difficulty; based on expert consensus on these difficulty indicators, bail‐out procedures (including conversion to open cholecystectomy) have been indicated for cases in which LC for AC is difficult to perform. A bail‐out procedure should be chosen if, when the Calot's triangle is appropriately retracted and used as a landmark, a critical view of safety (CVS) cannot be achieved because of the presence of nondissectable scarring or severe fibrosis. We propose standardized safe steps for LC to treat AC. To achieve a CVS, it is vital to dissect at a location above (on the ventral side of) the imaginary line connecting the base of the left medial section (Segment 4) and the roof of Rouvière's sulcus and to fulfill the three criteria of CVS before dividing any structures. Achieving a CVS prevents the misidentification of the cystic duct and the common bile duct, which are most commonly confused. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included.     

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

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 non-inflammatory 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, 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.     

TG13 diagnostic criteria and severity grading of acute cholecystitis (with videos)

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 Murphy’s sign, local inflammatory findings in the gallbladder such as right upper quadrant 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 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. Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.     

Verification of Tokyo Guidelines for diagnosis and management of acute cholangitis

Background

This study aimed to verify diagnostic criteria and severity assessment of the Tokyo Guidelines for acute cholangitis.

Methods

We re-examined whether acute cholangitis was concomitant with gallstones according to the Tokyo Guidelines in 248 patients with choledocholithiasis. Our conventional diagnoses based on physician decision were compared with diagnoses from the Tokyo Guidelines. Problems with severity grade criteria were also evaluated.

Results

In total, 53 cases of acute cholangitis were determined by using the Tokyo Guidelines, including three false-negative and seven false-positive cases (acute cholecystitis or pancreatitis was concomitant with choledocholithiasis). Sensitivity, specificity, and accuracy were 94%, 96%, and 96%, respectively. Forty of the 53 patients underwent biliary drainage (mean interval between admission and drainage, 1.4 days). Severity grades were mild in 10, moderate in 30, and severe in 13 patients. Of these 13 patients with severe disease, 2 had chronic renal failure, 1 had liver cirrhosis, and 1 had severe acute pancreatitis and liver cirrhosis. No patients died, irrespective of severity grade.

Conclusions

Acute cholangitis should be carefully diagnosed when other inflammatory disease is concomitant with choledocholithiasis. A few patients have absolute acute cholangitis even when they do not meet Tokyo Guidelines diagnostic criteria. Classification into mild or moderate grade using the Tokyo Guidelines is difficult when early biliary drainage is routinely performed. When determining severity grade, clinicians must distinguish between organ dysfunction associated with cholangitis itself and that associated with the underlying/concomitant disease. Apart from a few problems like these, the Tokyo Guidelines are mostly acceptable for the diagnosis and management of acute cholangitis.     

TG13 current terminology, etiology, and epidemiology of acute cholangitis and cholecystitis

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/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 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). Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.     

Endoscopic biliary drainage for severe acute cholangitis in biliary obstruction as a result of malignant and benign diseases

BACKGROUND AND AIMS: Endoscopic biliary drainage is an established mode of biliary decompression in patients with acute cholangitis as a result of biliary obstruction secondary to stones and benign strictures. However, there are no reports on endoscopic management of severe acute cholangitis caused by malignant conditions. We prospectively compared the efficacy of the endoscopic drainage for severe acute cholangitis in biliary obstruction as a result of malignant and benign diseases. METHODS: Forty-three patients with severe acute cholangitis requiring urgent biliary drainage were included. Sixteen patients (mean age 58.2 +/- 9.3 years; seven men, nine women) had biliary obstruction as a result of malignant diseases and 27 had benign biliary diseases (mean age 41.6 +/- 14.3 years; nine men, 18 women). Indications for urgent drainage included any one of the following: temperature >38 degrees C (n = 21), septic shock with systolic blood pressure <100 mmHg (n = 9), localized peritonism (n = 21), impaired consciousness (n = 6) and failure to improve within 72 h of conservative management (n = 13). After successful bile duct cannul degrees ation, patients received either a nasobiliary catheter (n = 38) or an in-dwelling stent (n = 5) with or without sphincterotomy for biliary drainage. Outcome measures included complications and clinical response. RESULTS: Endoscopic drainage was established successfully in all the patients in both the groups. Clinical improvement after biliary drainage occurred in 94% patients (15/16) in the malignant group compared with 96% patients (26/27) in the benign group (P = not significant [NS]). Fever subsided at a median of 2.2 days in the malignant group and at 1 day in the benign group (P = NS). Normalization of leukocyte count was seen at a median of 6 days (range 1-17) and 2 days (range 1-5) days in the malignant group and the the benign group, respectively (P = NS). There were no endoscopic retrograde cholangiopancreatography-related complications. The mortality rate as a result of cholangitis was 4.6%, that is two of 43 patients (6.2% of the malignant group vs 3.7% of the benign group; P = NS). CONCLUSIONS: Endoscopic biliary drainage is equally effective in patients with severe acute cholangitis caused by either malignant or benign biliary diseases.     

TG13 miscellaneous etiology of cholangitis and cholecystitis

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 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). 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). Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.     

Thrombomodulin in the management of acute cholangitis-induced disseminated intravascular coagulation

AIM: To evaluate the need for thrombomodulin(r TM) therapy for disseminated intravascular coagulation(DIC) in patients with acute cholangitis(AC)-induced DIC. METHODS: Sixty-six patients who were diagnosedwith AC-induced DIC and who were treated at our hospital were enrolled in this study. The diagnoses of AC and DIC were made based on the 2013 Tokyo Guidelines and the DIC diagnostic criteria as defined by the Japanese Association for Acute Medicine, respectively. Thirty consecutive patients who were treated with r TM between April 2010 and September 2013(r TM group) were compared to 36 patients who were treated without r TM(before the introduction of r TM therapy at our hospital) between January 2005 and January 2010(control group). The two groups were compared in terms of patient characteristics at the time of DIC diagnosis(including age, sex, primary disease, severity of cholangitis, DIC score, biliary drainage, and anti-DIC drugs), the DIC resolution rate, DIC score, the systemic inflammatory response syndrome(SIRS) score, hematological values, and outcomes. Using logistic regression analysis based on multivariate analyses, we also examined factors that contributed to persistent DIC. RESULTS: There were no differences between the r TM group and the control group in terms of the patients' backgrounds other than administration. DIC resolution rates on day 9 were higher in the r TM group than in the control group(83.3% vs 52.8%, P 0.01). The mean DIC scores on day 7 were lower in the r TM group than in the control group(2.1 ± 2.1 vs 3.5 ± 2.3, P = 0.02). The mean SIRS scores on day 3 were significantly lower in the r TM group than in the control group(1.1 ± 1.1 vs 1.8 ± 1.1, P = 0.03). Mortality on day 28 was 13.3% in the r TM group and 27.8% in the control group; these rates were not significantly different(P = 0.26). Multivariate analysis identified only the absence of biliary drainage as significantly associated with persistent DIC(P 0.01, OR = 12, 95%CI: 2.3-60). Although the difference did not reach statistical significance, primary diseases(malignancies)(P = 0.055, OR = 3.9, 95%CI: 0.97-16) and the non-use of r TM had a tendency to be associated with persistent DIC(P = 0.08, OR = 4.3, 95%CI: 0.84-22).CONCLUSION: The add-on effects of r TM are anticipated in the treatment of AC-induced DIC, although biliary drainage for AC remains crucial.     

Predictors for emergency biliary decompression in acute cholangitis

OBJECTIVE: Medical treatment is the first-line management in patients with acute cholangitis but those who fail to respond to antibiotic treatment need urgent biliary decompression. Early prediction of patients with acute cholangitis who require urgent biliary drainage is important because this group of patients has a higher morbidity and mortality from this pathology. This study was undertaken to identify early predictors for emergency biliary decompression in patients with acute cholangitis. METHODS: This is a retrospective analysis of a prospective database of 171 consecutive patients with acute cholangitis managed in a regional hospital in Hong Kong. Emergency biliary drainage was performed when conservative treatment failed. Twenty-four variables that could be assessed upon admission were analyzed for the prediction of the need for emergency biliary decompression. RESULTS: Thirty-one (18.1%) patients needed emergency biliary drainage. Older age (P=0.001), habit of chronic smoking (P=0.04), prolonged prothrombin time (P=0.025), higher blood glucose level (P=0.002), and dilated common bile duct diameter on ultrasonography (P=0.047) predicted the need for urgent biliary drainage. Patients aged older than 75 years had a significantly higher chance of failure of conservative treatment than those aged 75 years or less (26.5% versus 10.2%, P=0.005). CONCLUSIONS: Biliary drainage should be considered early in cholangitic patients aged older than 75 years and/or chronic smoking because they are less likely to respond to conservative treatment. Further studies are required to confirm that the outcome of patients with acute cholangitis can be improved by this selective approach.     

Aeromonas infection in acute suppurative cholangitis: review of 30 cases

OBJECTIVES: Aeromonads, though not common pathogens in biliary sepsis, caused substantial mortality in patients with impaired hepatobiliary function. Our aim was to study the pathogenic role of Aeromonas in acute suppurative cholangitis. METHODS: Between 1996 and 1998, the medical records of patients with a diagnosis of biliary sepsis were reviewed. Those who fulfilled the diagnostic criteria for acute suppurative cholangitis and had positive bile or blood cultures for Aeromonas species were studied. RESULTS: One thousand and forty-five patients were confirmed to have acute suppurative cholangitis. Of these, 30 patients (2.9%) had Aeromonas species isolated from bile; four were complicated by aeromonas septicaemia with simultaneous recovery of the bacteria from blood. All except two isolates were A. hydrophila. Twenty-four patients (80%) had bile duct stones, four (13%) had cholangiocarcinoma and two (7%) pancreatic cancer. Twenty-five cases (83%) had previous exploration of the biliary tract. There was substantial resistance to piperacillin (58%), ceftazidime (30%) and imipenem (15%). Most patients improved after biliary decompression. Only three patients (10%) died, two had terminal malignancy and one had end-stage liver failure. No excess mortality was attributable to Aeromonas infection in biliary sepsis. CONCLUSIONS: Previous instrumentation facilitated ascending Aeromonas infection of the biliary tract from the gastrointestinal tract. Unlike early reports, our results showed that aeromonads did not adversely affect the clinical outcome of acute suppurative cholangitis with successful drainage of biliary obstruction.