Fumihiko Miura

Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines

Because acute cholangitis sometimes rapidly progresses to a severe form accompanied by organ dysfunction, caused by the systemic inflammatory response syndrome (SIRS) and/or sepsis, prompt diagnosis and severity assessment are necessary for appropriate management, including intensive care with organ support and urgent biliary drainage in addition to medical treatment. However, because there have been no standard criteria for the diagnosis and severity assessment of acute cholangitis, practical clinical guidelines have never been established. The aim of this part of the Tokyo Guidelines is to propose new criteria for the diagnosis and severity assessment of acute cholangitis based on a systematic review of the literature and the consensus of experts reached at the International Consensus Meeting held in Tokyo 2006. Acute cholangitis can be diagnosed if the clinical manifestations of Charcot’s triad, i.e., fever and/or chills, abdominal pain (right upper quadrant or epigastric), and jaundice are present. When not all of the components of the triad are present, then a definite diagnosis can be made if laboratory data and imaging findings supporting the evidence of inflammation and biliary obstruction are obtained. The severity of acute cholangitis can be classified into three grades, mild (grade I), moderate (grade II), and severe (grade III), on the basis of two clinical factors, the onset of organ dysfunction and the response to the initial medical treatment. “Severe (grade III)” acute cholangitis is defined as acute cholangitis accompanied by at least one new-onset organ dysfunction. “Moderate (grade II)” acute cholangitis is defined as acute cholangitis that is unaccompanied by organ dysfunction, but that does not respond to the initial medical treatment, with the clinical manifestations and/or laboratory data not improved. “Mild (grade I)” acute cholangitis is defined as acute cholangitis that responds to the initial medical treatment, with the clinical findings improved.

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.

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.

Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines

This article discusses the definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis. Acute cholangitis and cholecystitis mostly originate from stones in the bile ducts and gallbladder. Acute cholecystitis also has other causes, such as ischemia; chemicals that enter biliary secretions; motility disorders associated with drugs; infections with microorganisms, protozoa, and parasites; collagen disease; and allergic reactions. Acute acalculous cholecystitis is associated with a recent operation, trauma, burns, multisystem organ failure, and parenteral nutrition. Factors associated with the onset of cholelithiasis include obesity, age, and drugs such as oral contraceptives. The reported mortality of less than 10% for acute cholecystitis gives an impression that it is not a fatal disease, except for the elderly and/or patients with acalculous disease. However, there are reports of high mortality for cholangitis, although the mortality differs greatly depending on the year of the report and the severity of the disease. Even reports published in and after the 1980s indicate high mortality, ranging from 10% to 30% in the patients, with multiorgan failure as a major cause of death. Because many of the reports on acute cholecystitis and cholangitis use different standards, comparisons are difficult. Variations in treatment and risk factors influencing the mortality rates indicate the necessity for standardized diagnostic, treatment, and severity assessment criteria.

Guidelines for the management of biliary tract and ampullary carcinomas: surgical treatment

The only curative treatment in biliary tract cancer is surgical treatment. Therefore, the suitability of curative resection should be investigated in the first place. In the presence of metastasis to the liver, lung, peritoneum, or distant lymph nodes, curative resection is not suitable. No definite consensus has been reached on local extension factors and curability. Measures of hepatic functional reserve in the jaundiced liver include future liver remnant volume and the indocyanine green (ICG) clearance test. Preoperative portal vein embolization may be considered in patients in whom right hepatectomy or more, or hepatectomy with a resection rate exceeding 50%–60% is planned. Postoperative complications and surgery-related mortality may be reduced with the use of portal vein embolization. Although hepatectomy and/or pancreaticoduodenectomy are preferable for the curative resection of bile duct cancer, extrahepatic bile duct resection alone is also considered in patients for whom it is judged that curative resection would be achieved after a strict diagnosis of its local extension. Also, combined caudate lobe resection is recommended for hilar cholangiocarcinoma. Because the prognosis of patients treated with combined portal vein resection is significantly better than that of unresected patients, combined portal vein resection may be carried out. Prognostic factors after resection for bile duct cancer include positive surgical margins, especially in the ductal stump; lymph node metastasis; perineural invasion; and combined vascular resection due to portal vein and/or hepatic artery invasion. For patients with suspected gallbladder cancer, laparoscopic cholecystectomy is not recommended, and open cholecystectomy should be performed as a rule. When gallbladder cancer invading the subserosal layer or deeper has been detected after simple cholecystectomy, additional resection should be considered. Prognostic factors after resection for gallbladder cancer include the depth of mural invasion; lymph node metastasis; extramural extension, especially into the hepatoduodenal ligament; perineural invasion; and the degree of curability. Pancreaticoduodenectomy is indicated for ampullary carcinoma, and limited operation is also indicated for carcinoma in adenoma. The prognostic factors after resection for ampullary carcinoma include lymph node metastasis, pancreatic invasion, and perineural invasion.

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.

Surgical treatment of patients with acute cholecystitis: Tokyo Guidelines

Cholecystectomy has been widely performed in the treatment of acute cholecystitis, and laparoscopic cholecystectomy has been increasingly adopted as the method of surgery over the past 15 years. Despite the success of laparoscopic cholecystectomy as an elective treatment for symptomatic gallstones, acute cholecystitis was initially considered a contraindication for laparoscopic cholecystectomy. The reasons for it being considered a contraindication were the technical difficulty of performing it in acute cholecystitis and the development of complications, including bile duct injury, bowel injury, and hepatic injury. However, laparoscopic cholecystectomy is now accepted as being safe for acute cholecystitis, when surgeons who are expert at the laparoscopic technique perform it. Laparoscopic cholecystectomy has been found to be superior to open cholecystectomy as a treatment for acute cholecystitis because of a lower incidence of complications, shorter length of postoperative hospital stay, quicker recuperation, and earlier return to work. However, laparoscopic cholecystectomy for acute cholecystitis has not become routine, because the timing and approach to the surgical management in patients with acute cholecystitis is still a matter of controversy. These Guidelines describe the timing of and the optimal surgical treatment of acute cholecystitis in a question-and-answer format.

Antimicrobial therapy for acute cholecystitis: Tokyo Guidelines.

Acute cholecystitis consists of various morbid conditions, ranging from mild cases that are relieved by the oral administration of antimicrobial drugs or that resolve even without antimicrobials to severe cases complicated by biliary peritonitis. Microbial cultures should be performed by collecting bile at all available opportunities to identify both aerobic and anaerobic organisms. Empirically selected antimicrobials should be administered. Antimicrobial activity against potential causative organisms, the severity of the cholecystitis, the patient’s past history of antimicrobial therapy, and local susceptibility patterns (antibiogram) must be taken into consideration in the choice of antimicrobial drugs. In mild cases which closely mimic biliary colic, the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is recommended to prevent the progression of inflammation (recommendation grade A). When causative organisms are identified, the antimicrobial drug should be changed for a narrower-spectrum antimicrobial agent on the basis of the species and their susceptibility testing results.

TG13 surgical management of acute cholecystitis

BackgroundLaparoscopic 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-and-answer format using the evidence concerning surgical management of acute cholecystitis.Methods and materialsForty-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 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.ResultsThere 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.ConclusionSurgical 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 surgeon’s attention to the need to reduce the incidence of bile duct injury.Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.

Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines.

Diagnostic and therapeutic strategies for acute biliary inflammation/infection (acute cholangitis and acute cholecystitis), according to severity grade, have not yet been established in the world. Therefore we formulated flowcharts for the management of acute biliary inflammation/infection in accordance with severity grade. For mild (grade I) acute cholangitis, medical treatment may be sufficient/appropriate. For moderate (grade II) acute cholangitis, early biliary drainage should be performed. For severe (grade III) acute cholangitis, appropriate organ support such as ventilatory/circulatory management is required. After hemodynamic stabilization is achieved, urgent endoscopic or percutaneous transhepatic biliary drainage should be performed. For patients with acute cholangitis of any grade of severity, treatment for the underlying etiology, including endoscopic, percutaneous, or surgical treatment should be performed after the patient’s general condition has improved. For patients with mild (grade I) cholecystitis, early laparoscopic cholecystectomy is the preferred treatment. For patients with moderate (grade II) acute cholecystitis, early laparoscopic or open cholecystectomy is preferred. In patients with extensive local inflammation, elective cholecystectomy is recommended after initial management with percutaneous gallbladder drainage and/or cholecystostomy. For the patient with severe (grade III) acute cholecystitis, multiorgan support is a critical part of management. Biliary peritonitis due to perforation of the gallbladder is an indication for urgent cholecystectomy and/or drainage. Delayed elective cholecystectomy may be performed after initial treatment with gallbladder drainage and improvement of the patient’s general medical condition.