US and EUS play an important role in the diagnosis of biliary cancer. Especially, EUS is positioned as a modality for in-depth examination diagnosing T factor (TNM classification). In 2013, general rules for clinical and pathological studies on cancer of the biliary tract (The 6th edition: edited by Japanese Society of Hepato-Biliary-Pancreatic Surgery) was modified and proposed as it was consistent with TNM classification (The 7th edition). I discussed here how US and EUS served in the diagnosis of biliary cancers (bile duct cancer, gallbladder cancer and cancer of ampulla of Vater.) in this situation.

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The diagnosis of sclerosing cholangitis is difficult even with the recent advanced imaging techniques. Especially, it is not easy to discriminate IgG4-related sclerosing cholangitis (IgG4-SC) from those progressive or malignant diseases, such as primary sclerosing cholangitis (PSC), cholangiocarcinoma. Therefore, the Research Committee provided by the Ministry of Health, Labor, and Welfare of Japan and the Japan Biliary Association proposed the new clinical diagnostic criteria of IgG4-SC 2012. We should make a precise diagnosis of sclerosing cholangitis from various aspects of clinical course, serology, ductal imaging, other organ involvement and histological findings. There are several problems remained to be resolved in the therapy of IgG4-SC and PSC. Improvement of diagnostic precision and therapeutic effect of IgG4-SC and PSC are expected with further fundamental and clinical investigations.

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Hepatectomy in biliary disease, such as hilar bile duct carcinoma or gallbladder carcinoma, sometimes cause postoperative hyperbilirubinemia or hepatic failure because of lack of large hepatic parenchyma. We have used Japanese Kampo medicine, Dai-kenchu-to (TU-100) and/or Inchin-ko-to (TU-135), for perioperative management of hepatectomised patients. We estimated effectiveness of combined use of TU-100 and TU-135 in hepatectomised patients with biliary disease from the view point of residual liver circulation. We divided hepatectomised patients with biliary disease into three groups retrospectively, Group A (Control group, n=16), Group B (TU-100, n=9), Group C (TU-100 and TU-135, n=17). Although preoperative KICG in group C shows significantly low level compared to that in group A, there are no significant difference in patient's background, such as age, gender, preoperative hepatic function, parenchymal hepatic resection rate, operative time, amount of intraoperative bleeding. Ratio of KICG on one week after operation to estimated postoperative KICG are 121.3±36.1 in group A, 119.6±23.7 in group B, 161.7±76.1 in group C. Group C shows significantly higher ratio than Group A (p<0.05). A combination use of TU-100 and TU-135 for hepatectomised patients with biliary disease possibly increased residual liver KICG, which indicates improvement of liver micro-circulation.

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Forty six patients with obstructive jaundice who underwent endoscopic nasobiliary drainage (ENBD) using either a 4 Fr or 6 Fr catheter without endoscopic sphincterotomy were enrolled and divided into two groups according to catheter size. Clinical outcomes were compared between the two groups. Bile output, decrease in bilirubin level, and number of days to reduce bilirubin by 50% were similar in the groups. The incidence of pancreatic-type hyperamylasemia was less in 4 Fr group (13.0% versus 34.8%, p=0.10). Post-procedure pancreatitis was seen in 1 patient in 6 Fr group. No patient in the 4 Fr group developed pancreatitis. Nose/throat discomfort on the procedure day scored by a visual analog scale (0, no discomfort; 10, severe discomfort) were 2.5 and 4.4 in the 4 Fr and 6 Fr groups (P=0.030), respectively. The following day, the scores were 2.1 and 3.7 (P=0.056). In conclusion, a 4 Fr ENBD catheter has equal drainage capacity, less adverse effects on the pancreas, and less nose/throat discomfort compared with the 6 Fr catheter.

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Five words, "Forty", "Female", "Fatty", "Fair", "Fertile" are often recognized as the risk factor for gallstone. Also, it is reported that gallstone correlates with lipid abnormalities and diabetes mellitus. Recently, the changes of Japanese basic life style resulted in the increase of obesity, diabetes mellitus and lipid abnormalities, therefore, we attempted to clarify the risk factors for gallstone in this situation. We divided our 205 gallstone patients into three groups by Tsuchiya's gallbladder stone classification, and made the analysis about age, sex, BMI, serum lipids, fasten plasma glucose, HbA1c and insulin. People who have Tsuchiya type 1 gallstone (recognized as cholesterol gallstone) show the features: obese and having insulin resistance, when compared with the other gallstone group and stone free group. Moreover, multivariate statistics shows "age" and "obesity" are the significant risk factors. These results suggest that cholesterol gallstone formation is promoted by obesity or increase of insulin resistance.

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As ultrasound (US) is a simple and less invasive modality, it is widely used for mass screening. Both gallbladder polyps and thickened wall of the gallbladder are common US findings. The US screening is supposed to be extremely useful for the early detection of gallbladder carcinomas. On the other hand, the accuracy of US is strongly affected by both skill and knowledge of sonographers. US images of gallbladder lesions are classified into three types including pedunculated, broad based and wall-thickened ones. This classification is very important not only to make the differential diagnosis but also to evaluate the depth of invasion, since pedunculated lesions can be diagnosed as early carcinomas. To discriminate gallbladder carcinomas from other lesions, we should evaluate their size, internal echo texture, surface structure, layer structure of the gallbladder wall and findings of Doppler assessment. In addition, distention of the gallbladder and the extrahepatic bile duct, debris and slightly thickened wall of the gallbladder are also useful to detect occult lesions of the extrahepatic biliary tract. As the hypoechoic layer includes propria muscle and fibrous part of subserosal layer, the evaluation of the depth of cancer invasion is difficult. So, we should evaluate their morphological feature, size, internal echo texture and findings of enhanced US to make more precise diagnosis.

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The photodynamic therapy (PDT) is an established treatment for the unresectable biliary cancer. As for the photosensitizer used in PDT, Laserphyrin and Foscan has been developed as the next agents from Photofrin. The PDT endoscope becomes slimmer with new functions. Because the PDT for the biliary cancer is not covered by governmental insurance in Japan, fundamental researches and clinical treatments have been performed in limited institutions at present. We reported the history and the present treatment of PDT.

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A 79-year-old man presented with dark urine. Laboratory tests revealed obstructive jaundice and hepatic dysfunction. Distal bile duct carcinoma was diagnosed based on findings of abdominal CT and MRCP. The jaundice improved after PTBD. He underwent pancreatoduodenectomy and local excision of the abdominal wall with the PTBD catheter tract. The histological examination revealed implantation of cancer cells in the catheter tract. He underwent adjuvant chemotherapy with S-1. 18 months after the operation, a tumor was found in the abdominal wall near the site of catheter tract. Aspiration cytology confirmed a recurrence of bile duct carcinoma. 24 months after the operation, follow-up CT showed multiple liver metastases. He underwent systemic chemotherapy with gemcitabine combined with S-1, followed by transcatheter arterial chemoembolization for the liver metastases and local radiation therapy for the abdominal wall tumor. At 32-month follow up, the patient was alive and well. It is suggested that the patients with implantation of bile duct carcinoma in the PTBD catheter tract have a possibility of metachronal peritoneal seeding. Careful observation should be considered for the patients with catheter tract metastasis.

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A 71-year-old woman with a complaint of right hypochondralgia was referred to our hospital and was found to have tumors of the gallbladder and liver by using ultrasonography. She was diagnosed as gallbladder carcinoma with the liver and lymph nodes metastasis by abdominal ultrasonography, CT and MRI. She underwent central bisectionectomy of the liver, as well as cholecystectomy and resection of the extrahepatic bile duct with lymph nodes dissection. Histopathologic examination revealed that the tumor consisted of small, nodular-infiltrative carcinoma cells in the gallbladder and the liver. Immunohistochemical examination revealed that the carcinoma cells were positive for Synaptophysin and that Ki-67 labeling index was 95%. The definitive diagnosis was neuroendocrine carcinoma. Three months after the surgery, CT revealed that she had multiple recurrences in the liver, and she died 1 month later. Neuroendocrine carcinoma of the gallbladder is thought to have a poor prognosis, so effective multidisciplinary treatment including surgery with lymph nodes dissection and adjuvant chemotherapy must be required for this disease.

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We reported a case of early cystic duct cancer with widely spreading carcinoma in situ in the gallbladder. A 78 year-old woman complained of epigastric pain. Abdominal contrast CT showed cystic duct tumors as well as small protruding lesions inside the gallbladder. ERC showed a filling defect shaped like a crab claw in the cystic duct, but did not reveal abnormal findings in the common bile duct. Intraductal ultrasonography showed a hypoechoic tumor inside the cystic duct, which extended into the common bile duct. Based on these findings, papillary cystic duct cancer was diagnosed, and extended cholecystectomy, bile duct resection, and lymph node dissection were performed. The resected specimen contained a 3.5×2.5 cm sized tumor protruding into the cystic duct. The cystic duct was filled with the papillary tumor and some elevated lesions were observed in the mucosa of the gallbladder. Pathological findigs were papillary adenocarcinoma of cystic duct with intramucosal cancer which spread widely in the gallbladder. Intramucosal cancer had spread widely in the gallbladder, but was not continuous, suggesting a multicentric form of carcinogenesis. The patient remains recurrence-free two years after surgery.

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A 71-year-old man who had undergone sigmoid colectomy 6 months before, was found to have dilatation of the left hepatic duct on CT and MRCP. ERC revealed a biliary stenosis of the left hepatic duct and irregular dilatations on peripheral biliary branches (B2, B3), however no mass was detected. On ultra sonography showed a tumor in B3. A left hepatic lobectmy combined with extrahepatic bile duct resection was performed, based on the diagnosis of intra hepatic cholangiocarcinoma or hepatic peribiliary cysts. The resected specimen showed multiple peribiliary cysts located around Glisson sheath and no mass was detected. Hepatic peribiliary cysts are rare and difficult to distinguish from malignant lesions. They should be considered as one of the important lesions in differential diagnoses of biliary stenosis and dilatations.

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A 68-year-old man underwent right hepatectomy with caudate lobectomy and extrahepatic bile duct resection under the preoperative diagnosis of intrahepatic cholangiocarcinoma in August 2011. Histologically the tumor was well differentiated adenocarcinoma with mucin production and diagnosed with intraductal papillary neoplasm of the bile duct (IPNB) with an associated invasive adenocarcinoma. The bile duct margins were negative for cancer. Sixteen months later, another tumor was found at the dilated remnant lower bile duct on abdominal CT scanning. He underwent pancreatoduodenectomy with the preoperative diagnosis of carcinoma of the lower bile duct or ampulla of Vater. Histologically the tumor was invasive papillary adenocarcinoma similar to the first resected tumor. It is generally expected that prognosis after curative resection for IPNB is good, but our case suggests that this tumor has the potential for recurrence at the remnant bile duct. Therefore, surgeons should follow up the patients carefully even after curative operation for IPNB.

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Dilation of the common bile duct was detected by computed tomography (CT) scan in an 80-year-old woman. Upper gastrointestinal endoscopy revealed a tumor of 3 cm in diameter in the papilla of Vater, and a carcinoma was proven by tumor biopsy. Transduodenal ampullectomy was performed, considering the patient's age and the clinical findings for suspecting early carcinoma. Histopathological examination demonstrated adenocarcinoma (tub1- tub2) in tubulovillous adenoma, with partial invasion into Oddi's muscle. Follow-up CT 3 years after surgery showed recurrence in the lymph nodes at the head of the pancreas, and also the para-aortic and upper mediastinal nodes. The patient died four years after initial surgery. Pancreatoduodenectomy is a standard operation for early stage carcinoma of the ampulla of Vater; however, according to clinical practice guidelines for the management of biliary tract and ampullary tumors, limited resection can be considered for intramucosal carcinoma. However, accurate preoperative diagnosis of intramucosal carcinoma is usually difficult and in our case, the tumor invasion to the Oddi's muscle was detected by postoperative histological examination. Therefore, the indication of limited resection should be strictly judged.

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The patient was a 62-year-old female who visited a physician for a chief compliant of jaundice. Increased hepatobiliary enzyme levels and a liver tumor were pointed out, and she was referred to our hospital. On abdominal ultrasonography, an about 70-mm tumorous lesion accompanied by peripheral bile duct dilation was noted in the liver S4/5, and the tumor was ischemic and heterogeneous on abdominal CT. In addition, hypertrophy of the wall was observed in the distal bile duct. On ERC, stenosis of the bilateral hepatic duct-joining region and irregular stenosis and dilation of the right intrahepatic bile duct were observed. Moreover, a filling defect was detected in the distal bile duct, and this region was diagnosed as adenocarcinoma on biopsy. Based on the above findings, the patient was diagnosed with double cancer of intrahepatic and distal cholangiocarcinoma, and right trisegmentectomy+subtotal stomach-preserving pancreatoduodenectomy was performed. On histopathological examination, intrahepatic cholangiocarcinoma was moderately differentiated tubular adenocarcinoma, and distal cholangiocarcinoma was papillary adenocarcinoma. This is the second case of synchronous development of intra- and extrahepatic cholangiocarcinoma in Japan, and so is very rare.

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Intraductal papillary mucinous neoplasm (IPMN) is associated with the incidence of extrapancreatic neoplasms. However, multiple bile duct system tumors associated with IPMN is rare. An 82-year-old woman was admitted to our hospital with jaundice. CT revealed a mass in the middle bile duct, gallbladder wall thickening, and a multilocular cystic lesion in the pancreatic head. ERCP revealed an occluded middle bile duct and a communication between the main pancreatic duct and the cystic lesion. Cytology of the bile juice was class III (suspicion of Adenocarcinoma). Subsequently, the patient was diagnosed with IPMN and biliary neoplasm of middle bile duct. PPPD was performed. Histological analysis demonstrated intraductal papillary mucinous adenoma and tumors in the middle bile duct and gall bladder. Histopathologically, these tumors were completely separate, moderately differentiated tubular adenocarcinomas. CK20 immunostaining was positive in the bile duct and negative in the gall bladder. Thus, we confirmed the diagnosis as double synchronous neoplasm of the common bile duct and gallbladder.

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The recent widespread use of esophago-gastro-duodenoscopy has contributed to early diagnosis of ampullary neoplasm. Although duodenoscopic findings are important for diagnosis, endoscopic biopsy is essential for a definitive diagnosis. Endoscopic ultrasonography-guided fine needle aspiration or endoscopic biopsy after endoscopic sphincterotomy is useful for diagnosis in selected patients with suspected non-exposed-tumor type. Pancreaticoduodenectomy remains a standard treatment for ampullary neoplasm. Reports on the usefulness of reduction treatment such as endoscopic papillectomy have recently increased. Accurate preoperative tumor staging is mandatory for the indication for such treatments. Both EUS and intraductal US of the bile duct can provide useful information for precise tumor staging of ampullary neoplasm. However, even by these modalities differential diagnosis between mucosal cancer and od cancer (depth of tumor: od) remains challenging.

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