Gallstone disease is quite common in Japan and Western countries. Its therapeutic strategy has been discussed with mainly focusing on the indication of surgical and nonsurgical treatment. Also, clinical queries are how to manage; 1) asymptomatic cases and colic pains, 2) cholecystitis/cholangitis complication, 3) biliary cancers. In this regard, the recent understanding of gallstone pathogenesis and clinical implication in association with cholestasis and biliary oncogenesis is reviewed in the main light of our original research work. First, cholesterol gallstone formation process is mainly addressed as well as challenging therapeutic strategies based upon such scientific products. Second, a breakthrough in molecular understanding of biliary excretory mechanisms is interpreted with summarizing the progress in handling of various cholestasis. Finally, biliary oncogenesis based upon metabolic defects is elaborated in the aspect of future therapeutic strategy. Taken together, the author would sincerely like to appreciate for this attractive field, and to strongly hope the further progress by members of Japan Biliary Association.

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Biliary intraepithelial neoplasia (BilIN) for microscopical flat intraepithelial neoplasm and intraductal papillary neoplasm (IPN) for grossly visible papillary intraepithelial neoplasm of the biliary tract including the gallbladder are known. These lesions are thought to be followed by invasive cholangiocarcinoma and gallbladder carcinoma. BilIN is classifiable into BilIN-1 (low grade), BilIN-2 (intermediate grade) and BilIN-3 (high grade), and BilIN-3 includes intraepithelial carcinoma of the biliary tract. These intraepithelial lesions are described in New WHO classification of tumours of the digestive system (2010). In this classification, mucinous cystic neoplasm (MCN) of the liver and biliary tract is recommended to replace hepatobiliary cystadenoma/adenocarcinoma. Cystic variant of IPNB and peribiliary cysts should be differentiated from hepatobiliary MCN. New approach by using this standard classification expects new horizon of clinical practice and research of the biliary tract neoplasm.

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In surgery for hilar cholangiocarcinoma, additional resection of >5 mm in the proximal duct is difficult after maximal or near maximal transection of the duct. Such limited resection of margin-positive proximal duct does not improve survival, even when negative margin is achieved with additional resection. To achieve R0 resection, we, hepatobiliary surgeons should always consider feasibility of more extended radical resection when general condition and liver functional reserve are stable.
Several authors reported that a positive ductal margin with carcinoma in situ, unlike with invasive carcinoma, did not have a strong adverse effect on survival. In many cases of cholangiocarcinoma with superficial spread, the survival does not depend on the complete resection of all the superficial spread but on the stage of the main lesion. Therefore, the resection of all the superficial spread does not lead to an improvement in survival in patients with advanced cholangiocarcinoma, but it may improve survival in early staged cancer such as noninvasive or minimally invasive papillary cancer.

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Since computed Tomography (CT) progressed from helical CT to multidetector-row CT (MDCT), it became possible to diagnose fine lesions by thin-slice examination. Thus, the precision of imaging diagnosis has greatly improved, and imaging diagnostic systems of the biliary tract have changed dramatically. Previously, before MDCT, the diagnosis of a longitudinal extension was performed by cholangiography, and the diagnosis of vertical extension was mainly performed by angiography. After the development of MDCT, such imaging provided enough data for the diagnosis of both longitudal and vertical extension. Three-dimensional (3D) construction using MDCT ensures that understanding the 3D imaging of artery, portal vein and bile duct can be easy. Therefore, MDCT became an indispensable tool for judging indications for surgery.
Since 1999, MDCT has been used for the diagnosis in our department. MDCT is very useful for the diagnosis of vertical spreading and longitudinal extension of cholangiocarcinoma from pathological findings. Therefore, the treatment strategy is easily planned and promptly decided.
Here, we show several typical imagings of MDCT, and comment on the basic and abilities of MDCT.

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PURPOSE: Forty-one patients with biliary cancer (22 extrahepatic bile duct cancer, 11 gall bladder cancer, 8 ampullary cancer) who underwent ¹⁸F-fluorodeoxy-glucose positron emission tomography (FDG-PET) before treatment were enrolled in the present study. We investigated the clinical significance of PET for primary tumor, metastases and the other cancers. We also analyzed the relationship between the maximum standardized uptake value (SUVmax) and clinicopathologic factors. RESULTS: The accumulation of FDG to primary tumor was observed in 28 of 41 patients (68.3%). The sensitivity of FDG-PET was 100% for gallbladder cancer, 87.5% for ampullary cancer, and 45.4% for bile duct cancer, respectively. The SUVmax levels in primary tumor were significantly correlated with M-category in TNM classification (p=0.033). Meanwhile, 21 patients (51%) showed the FDG accumulation except for the primary tumor. The sensitivity for lymph node metastasis, liver metastasis, and peritoneal dissemination was 89%, 75%, and 100%, respectively. In the abnormal accumulations of the other regions in 8 patients, colon cancer was newly found in 3 patients. CONCLUSIONS: FDG-PET has a low sensitivity for detecting the primary tumor in biliary cancer, but it is useful for detection of distant metastasis and occult malignant disease.

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The prognostic factors for patients with ampullary cancer were examined, and the possibility of indications for limited surgery was investigated. The clinicopathological factors of 80 resected cases are analyzed, and moreover, five patients who underwent PHRSD for pT1 cancer were compared with 11 patients who underwent pancreatoduodenectomy (PD). Multivariate analyses of the resected cases revealed that positive histopathological lymph node metastasis was an independent prognostic factor. Analyses of preoperative factors revealed that a macroscopic appearance of the tumor other than the superficial protruding type, positive macroscopic pancreatic invasion, and positive macroscopic duodenal invasion were significantly correlated with positive histopathological lymph node metastasis. In patients who underwent PHRSD, the operation time and associated blood loss were comparable with those of PD, and neither recurrence nor death from cancer was found. However, given the insufficient accuracy rate of the imaging diagnostic techniques, PD should be considered as the standard operation for ampullary cancer, even for T1 cases, at the present time.

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Autoimmune pancreatitis (AIP) and its various extrapancreatic lesions are currently considered to represent manifestations of organs involved IgG4-related systemic sclerosing disease. Although most cases of IgG4-related sclerosing cholangitis are associated with AIP, there are some cases with no apparent pancreatic lesions compatible with AIP. Considering the age of onset, associated diseases, cholangiography, serum IgG4 levels, and steroid responsiveness, IgG4-related sclerosing cholangitis differs from primary sclerosing cholangitis. To diagnose IgG4-related sclerosing disease, it is most important to differentiate from bile duct cancer. IgG4-related sclerosing cholangitis should be diagnosed on the basis of combinations of cholangiography, serum IgG4 levels, endoscopic biopsy from the bile duct, and steroid responsiveness.

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The guidelines, Evidence-based clinical guidelines for the management of biliary tract carcinoma, were published in Japanese by Igaku-Tosyo Suppan in 2007. Because three years has passed from the publication, the revision of the guidelines are about to begin. We reviewed the endoscopic role in the management of biliary tract carcinoma on guidelines revision. The main topics are as follows; 1) immunogloblin G4-related sclerosing cholangitis that mimics infiltrating hilar cholangiocarcinoma, 2) clinical utility of cholangioscopy for the preoperative assessment of bile duct carcinoma, 3) drainage methods for malignant hilar biliary obstruction.

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An 85-year-old woman with right hypo-chondralgia was admitted to our hospital for a close examination. Samples obtained during abdominal paracentesis showed bile-like ascites. Emergent laparoscopy was performed to test for duodenal or gallbladder perforation. No signs of inflammation or apparent perforation were found in the gallbladder; however, there was bile leakage from the gallbladder fundus. The patient, who was diagnosed with biliary peritonitis due to transudation of bile from the gallbladder, underwent laparoscopic cholecystectomy. Upon identifying a thrombus formed in the branch of a subserosal vein, we hypothesized that ischemia may have also contributed to the pathogenesis of the peritonitis. In similar cases, prognosis using a laparoscopic approach is favorable if peritonitis is due to non-infected bile. Although leakage of bile from the gallbladder is difficult to diagnose, we recommend it be considered in cases of acute abdomen, and appropriate operative procedures discussed.

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The present cases were 62, 63, and 72-year-old males. Duodenal perforation was developed on ERCP for the evaluation of choledocholithiasis and chronic pancreatitis. Perforated site of 2 cases was duodenal second portion and the other was superior duodenal angle. ERCP of all cases was undergone by the operators with less than 40 times of experiences. Although 2 cases whose peritoneal irritation sign appeared immediately required the operation, 1 case with mild abdominal symptoms and lack of inflammatory response in blood findings was cured by only conservative medical management. Duodenal perforation was considered to be caused by stretching manipulation of endoscope. We suggest that operator of ERCP should pay attention to duodenal perforation at the time of stretching manipulation of endoscope, and that conservative management could be acceptable when the abdominal findings are mild, while immediate surgery is required when especially abdominal symptoms got worse or peritoneal perforation developed.

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A 73-year-old woman was admitted to our hospital for the right hypochondrial pain. Abdominal computed tomogram (CT) showed gallbladder cancer with invasion of the liver and portal vein. Extended right hemihepatectomy was planned but she had severe mitral valve regurgitation. At first mitral valve replacement was perfomed. Repeated abdominal CT showed the reduction of gallbladder cancer about the invasion of the liver and portal vein. Under the diagnosis of gallbladder cancer with cholecystitis, hepatectomy of segment 4a+5, extrahepatic bile duct resection and hepaticojejunostomy was perfomed. Microscopic findings was gallbladder cancer with xanthogranulomatous cholecystitis. We report a rare case of the gallbladder cancer with xanthogranulomatous cholecystitis which showed the change in the image by progress of time.

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Familial occurrence of congenital biliary dilatation (CBD) has been reported, but that in adult cases is rarely reported. Although CBD is sometimes associated with bile duct cancer, coexistence of cancer, dysplasia and hyperplasia of the bile duct has never been documented. We experienced a case of mother and daughter with CBD who were diagnosed at adult age. A 70-year-old woman presented with jaundice and underwent extrahepatic bile duct resection for Todani Type IV CBD and anomalous pancreatobiliary junction. Pathological examination revealed cancer, dysplasia and hyperplasia in the dilated bile duct. Her daughter had undergone surgery for Todani Type I CBD without biliary neoplasia at the age of 37 years. In 32 reported cases of CBD from 16 families, only two cases from one family were diagnosed at adult age and none had biliary tract cancer. Because biliary tract cancer associated with CBD has poor prognosis, CBD should be treated before cancer develops. Screening for CBD is recommended to relatives with family history of CBD.

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A 73 year old man visited to his family doctor complaint of fever and abdominal pain. Diagnostic imagings revealed cholecystitis and choledochitis with gallstone and gallbladder tumor. He had laparoscopic cholecystectomy. Immuno-hisitochemical examination of the gallbladder tumor revealed Cynaptophysin (+), Chromogranin A (-), CD56 (-) and LCA (-), which comfirmed small cell carcinoma. He had moved to our hospital to have second operation, wedge resection of gallbladder bed and regional lymphadenectomy. However, adjuvant chemotherapy of gemcitabine and TS-1 was given second operation, he died of the disease 8 months after first operation. Small cell carcinoma of the gallbladder is very rare and its prognosis is extremely poor. Operative method or chemotherapy for the disease has not been established. One case was reported long survived after pancreaticoduodenectomy, another was reported to have good response by chemotherapy for lung small cell carcinoma. Further research is needed.

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Pancreaticobiliary maljunction (PBM) is a congenital anomaly defined as a union of the pancreatic and biliary ducts that is located outside the duodenal wall, and this anormaly occur various pathology including carcinogenesis due to reflux and stasis of bile mixed with pancreatic juice. We herein review epidemiology and clinical features of PBM, in particular, based on nationwide survey (n=2,561) of Japanese study group of PBM.
Almost cases had clinical symptoms. Particularly, acute pancreatitis was most frequent complication in pediatric patients. Regarding cancer occurrence, in pediatric patients, only one case with biliary dilatation was combined with a bile duct cancer. In adult patients, the occurrence rates of biliary cancers were 21.6% in patients with biliary dilatation and 42.4% in patients without biliary dilatation. Overall incidence of biliary cancers with PBM is from 1,000 to 3,000 times higher comparing to the risk in the general population.
Further evaluation and follow-up survey were still necessary for the elucidation of pathology and adequate diagnosis and treatment of PBM.

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