Sun Whe Kim

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.

Cyst Growth Rate Predicts Malignancy in Patients With Branch Duct Intraductal Papillary Mucinous Neoplasms

BACKGROUND & AIMSnLittle information is available about the clinico-pathologic characteristics of pancreatic branch duct intraductal papillary mucinous neoplasm (Br-intraductal papillary mucinous neoplasm [IPMN]) because of difficulties in diagnosis based on radiologic and tissue information. We investigated the natural history of Br-IPMN using imaging and surgical pathology data from patients.nnnMETHODSnData were collected from patients admitted to a single tertiary referral institution from January 2000 to March 2009 (median follow up of 27.9 months); 201 patients were diagnosed with Br-IPMN with an initial cyst less than 30 mm without main pancreatic duct dilatation or mural nodules. The patients were followed for more than 3 months and examined by computed tomography (CT) at least twice.nnnRESULTSnThe mean size of the patients initial cysts was 14.7 mm; the mean cyst growth rate was 1.1 mm/year. Thirty-five patients received surgery during follow up and 8 were confirmed to have malignant cysts. The malignant cysts were greater in final size than nonmalignant cysts (24.3 mm vs 16.9 mm; P = .003); they also grew by a greater percentage (69.8% vs 19.4%; P = .046) and at a greater rate (4.1 mm vs 1.0 mm/year; P = .001). The actuarial 5-year risk of malignancy was 41.6% in the group that received surgery and 10.9% for all patients. Cysts that grew more than 2 mm/year had a higher risk of malignancy (5-year risk = 45.5% vs 1.8%; P < .001).nnnCONCLUSIONSnIn combination with cyst size and the presence of mural nodules, cyst growth rate could be used to predict malignancy in patients with Br-IPMN.

A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts

BACKGROUND & AIMSnThe management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients.nnnMETHODSnWe performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers.nnnRESULTSnWe identified molecular markers and clinical features that classified cyst type with 90%-100% sensitivity and 92%-98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%.nnnCONCLUSIONSnWe identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery.

TG13 guidelines for diagnosis and severity grading of acute cholangitis (with videos)

Since the publication of the Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG07), diagnostic criteria and severity assessment criteria for acute cholangitis have been presented and extensively used as the primary standard all over the world. However, it has been found that there are crucial limitations in these criteria. The diagnostic criteria of TG07 do not have enough sensitivity and specificity, and its severity assessment criteria are unsuitable for clinical use. A working team for the revision of TG07 was organized in June, 2010, and these criteria have been updated through clinical implementation and its assessment by means of multi-center analysis. The diagnostic criteria of acute cholangitis have been revised as criteria to establish the diagnosis where cholestasis and inflammation demonstrated by clinical signs or blood test in addition to biliary manifestations demonstrated by imaging are present. The diagnostic criteria of the updated Tokyo Guidelines (TG13) have high sensitivity (87.6xa0%) and high specificity (77.7xa0%). TG13 has better diagnostic capacity than TG07. Severity assessment is classified as follows: Grade III: associated with organ failure; Grade II: early biliary drainage should be conducted; Grade1: others. As for the severity assessment criteria of TG07, separating Grade II and Grade I at the time of diagnosis was impossible, so they were unsuitable for clinical practice. Therefore, the severity assessment criteria of TG13 have been revised so as not to lose the timing of biliary drainage or treatment for etiology. Based on evidence, five predictive factors for poor prognosis in acute cholangitis––hyperbilirubinemia, high fever, leukocytosis, elderly patient and hypoalbuminemia––have been extracted. Grade II can be diagnosed if two of these five factors are present.Free full-text articles and a mobile application of TG13 are available via http://www.jshbps.jp/en/guideline/tg13.html.

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.

Role of postoperative radiotherapy in the management of extrahepatic bile duct cancer

PURPOSEnTo analyze the outcome of postoperative radiotherapy (RT) or chemoradiation for patients with extrahepatic bile duct cancer who had undergone either curative or palliative surgery, and to identify the prognostic factors for these patients.nnnMETHODS AND MATERIALSnBetween March 1982 and December 1994, 91 patients with extrahepatic bile duct cancer underwent RT at the Department of Therapeutic Radiology, Seoul National University Hospital. Of these patients, 84 were included in this retrospective study. The male/female ratio was 3.7:1 (66 men and 18 women). The median age of the patients was 58 years (range 33-76). Gross total surgical resection was performed in 72 patients, with pathologically negative margins in 47 and microscopically positive margins in 25. Twelve patients underwent surgical exploration and biopsy or subtotal resection with palliative bypass procedures. All the patients received >40 Gy of external beam RT after surgery. Concurrent 5-fluorouracil was administered during external beam RT in 71 patients, and maintenance chemotherapy was performed in 61 patients after RT completion. The minimal follow-up of the survivors was 14 months, and the median follow-up period for all the patients was 23 months (range 2-75).nnnRESULTSnThe overall 2- and 5-year survival rate was 52% and 31%, respectively. The 2- and 5-year disease-free survival rate was 48% and 26%, respectively. On univariate analysis using the Kaplan-Meier product limit method, the use of chemotherapy, performance status, N stage, size of residual tumor, stage, and tumor location were significant prognostic factors. However, on multivariate analysis using Coxs proportional hazard model, N stage (N0 vs. N1 and N2, p = 0.02) was the only significant prognostic factor.nnnCONCLUSIONnLong-term survival can be expected in patients with extrahepatic bile duct cancer who undergo radical surgery and postoperative chemoradiation. Regional lymph node metastasis is a poor prognostic factor for these patients.