To clarify the association between DNA damage response in tumor specimens of ductal resection margins and local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma. A retrospective analysis was conducted of 11 patients with positive ductal margins with carcinoma in situ. To evaluate the early DNA damage response, the nuclear staining pattern of p53-binding protein 1 (53BP1) was examined by immunofluorescence. Of the 11 tumor specimens of carcinoma in situ, 10 showed diffuse localization of 53BP1 in nuclei (53BP1 inactivation) and 4 showed discrete nuclear foci of 53BP1 (53BP1 activation); the apoptotic index was significantly decreased in the 7 tumor specimens with 53BP1 inactivation compared to the 4 with 53BP1 activation (median apoptotic index, 1% vs. 22%; p=0.003). Cumulative probability of local recurrence was significantly higher in patients with 53BP1 inactivation than in patients with 53BP1 activation (cumulative 5-year local recurrence rate, 60% vs. 0%; p=0.019). These data suggest that local recurrence is associated with 53BP1 inactivation and decreased apoptosis.

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We studied the clinicopathological findings and immunohistochemical study. 12 patients combined with adenomyomatosis of the gallbladder had been resected for gallbladder cancer were enrolled for the present study; 11 patients had segmental type, 1 patient had localized type. The specimens were from 9 men and 3 women. The average age was 56.6 years. Two patients had symptoms. Tumor maker was raised in five patients. Six patients had gallstone. Carcinoma was synthetically diagnosed in 7 (58.3%) patients. In diagnosis by form, we could diagnose 1 flat type and 6 protrude type.
Immunohistochemical study was examined in 8 patients: 6 patients could been examined about fundal compartment. All patients had pyloric gland metaplasia and hyperplasia. Index of MIB-1 and p53 in the fundal compartment was not significantly different from those of neck compartment.
Conclusion: 1. Flat type carcinoma associated with adenomyomatosis of the gallbladder was difficult to diagnose. 2. It was not certain whether segmental type adenomyomatosis of the gallbladder could develop gallbladder cancer.

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We studied the clinical evaluations of the severity assessment criteria in Japanese evidenced-based guidelines for acute obstructive suppurative cholangitis (AOSC) that was still used routinely. On the severity assessment criteria, 79% of AOSC group (19/24), 46.5% of non-AOSC group (89/191) were classified in the moderate grade. In both groups of moderate grade, the case having jaundice was 100% of AOSC group (19/19), and 96.6% of non-AOSC group (86/89). In addition, the case having only jaundice was 100% of AOSC group (5/5), and 97.4% of non-AOSC group (74/76). Jaundice had become a major factor which increased moderate grade. The case having more than two criterional factors was 73.7% of AOSC group (14/19), and 14.6% of non-AOSC group (13/89). How to extract a severe case in wide moderate grade is a future problem. When case having more than two criterional factors and having high WBC, CRP levels, in a moderate grade in Japanese guideline, it is desirable to deal as an associate severe grade.

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Only two prospective studies on adjuvant treatment for resected biliary cancer have been reported. In one study, postoperative adjuvant chemotherapy with mitomycin C and 5-fluorouracil for pancreaticobiliary carcinomas significantly improved overall survival only in patients with gallbladder cancer who underwent noncurative resection compared to surgery alone. The other study on postoperative radiotherapy for perihilar cholangiocarcinoma showed no effect of this treatment on either survival or late toxicity. Some retrospective studies suggested survival benefit of postoperative chemotherapy with gemcitabine for biliary carcinoma or adjuvant radiotherapy for noncuratively resected biliary cancer. Well-designed prospective trials in this field should be organized by Japanese researchers.

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Essential thrombocythemia (ET) is rare disease. We report a case of a common bile duct cancer with ET. A 61-year-old man with ET treated by oral administration of aspirin for 20 years complained epigastralgia and was found to have a common bile duct cancer at another hospital. On admission, his platelet was 153.1×104 /μl. He was given hydroxyurea and when the platelet decreased to 67.7×104 /μl, pylorus preserving pancreatoduodenectomy was performed. Intraoperative intravenous infusion of heparin was performed and hydroxyurea was resumed on post operative day 1.Post operative courses was uneventful without ET-related complication. Adequate control of platelet count and anticoagulant therapy through the perioperative period are very important for surgical patients with ET.

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A 73-year-old woman was referred to our hospital due to the elevation of serum transaminase levels and dilatation of intrahepatic bile duct revealed with ultrasonography. Serum bilirubin level was within normal range on admission, however it elevated up to 8.8 mg/dl during the hospital stay. She underwent endoscopic retrograde cholangiography (ERC). ERC revealed severe stenosis at the hilar bifurcation of bile duct, extending to the common duct. Although the results of brush cytology and bile cytology were negative, endoscopic retrograde forceps biopsy specimen showed nuclear enlargement and strong positivity of MIB-1 staining in epithelium. Extended left hemihepatectomy was conducted after percutaneous transhepatic portal embolisation under the diagnosis of suspected cholangiocarcinoma. Histologically, no malignant cells were detected in the resected specimen, and, infiltration of inflammatory cells and thick fibrous tissue around the bile duct. The final diagnosis was primary sclerosing cholangitis.

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Carcinoid tumors are generally considered to possess low grade malignancy and show slow progressions. We present two treated cases of carcinoid tumor of duodenal papilla. Case 1. An asymptomatic 66 year old female was found with 12 mm size ulceration of duodenal papilla during gastrointestinal endoscopy. Pathological exam revealed carcinoid cells. Case 2: A forty year-old female without any symptom. During evaluation of IPMN by EUS, a 5 mm SMT-like lesion was found at papilla of duodenum. Biopsy revealed carcinoid cells. No pancreatic duct invasion was found, and endoscopic papillectomy was performed. The patient has no sign of recurrence after one year. The carcinoid tumors are usually treated by surgical resection. Recently, a few successful cases have been reported in which endoscopic resection was performed. Because of carcinoid tumor's slow growing nature which may present as metastasis or recurrence in long term, a close observation is recommended after treatment.

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Adenoendocrine cell carcinomas in the extrahepatic bile duct are rare. A 64 years old man suffering from general malaise and icterus was admitted. Abdominal computed tomographic scan revealed a tumor in the lower bile duct. ERCP demonstrated a filling defect in the lower bile duct and we repeatedly obtained biopsies from the tumor. The results revealed adenoendocrine cell carcinoma of the bile duct. A pancreatoduodenectomy was performed with the preoperative diagnosis of adenoendocrine cell carcinoma. Histologically, the tumor consisted of solid nests of eosinophilic atypical cells with adenocarcinoma. Immunohistochemically, staining was positive for CD56. The definitive diagnosis was adenoendocrine cell carcinoma. The patient had multiple liver metastases 3 months after the operation and died 5months after the operation.

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A 64-year-old woman with upper abdominal pain was diagnosed as having an advanced stage gallbladder cancer with significant hepatic invasion and metastasis to paraaortic lymph nodes. We initiated chemotherapy using S-1, since a curative operation was considered impossible. S-1 (100 mg/day) was orally administered for 4 weeks every 6 weeks. After 3 courses of the treatment, marked reduction in size of the primary tumor and its hepatic invasion and disappearance of the lymph node metastasis was observed on CT. The marked effects of S-1 therapy were maintained for 1 year. Curative resection of the gallbladder, extrahepatic bile ducts and regional lymph nodes was then carried out. The pathology of the resected specimen revealed that the resection was definitely curative (pT2, pN0, pM0, pinf0, Stage II). The patient remains cancer-free for more than 1 year after the operation. This case demonstrates the potential of S-1 chemotherapy in allowing curative resections for unresectable advanced gallbladder cancers.

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Today, endoscopic treatment has become a standard treatment for choledocholithiasis. In addition, endoscopic bile duct drainage is considered to be recommended degree A in the choice of the drainage method in "The clinical practice guidelines for the management of acute cholangitis and cholecystitis". However, there are some cases of difficult transpapillary biliary access. In two patients of choledocholithiasis with difficult biliary cannulation, we performed lithotripsy using the rendezvous technique, which is a combination of interventional radiology and endoscopic treatment. The Rendezvous technique is useful as one of the choices for difficult biliary cannulation.

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A 66-year-old man with past histories of chronic renal failure, prostate cancer, hyperparathyroidism and postoperative rectal cancer. He was referred to our hospital due to onset of fever and acute abdominal pain. From when, endoscopic therapy was undergone due to cholangitis accompany with biliary stones. At that time, Papilla of Vater was discoverd at the anal and posterior of a large diverticulum, middle endoscopic sphincterotomy (EST) was performed. The endoscopic nasobiliary drainage and dropped out type catheter pancreatic duct drainage were performed post pre-cutting procedure. Four days after EST, GI bleeding with hypovolemic shock was presented. Blood transfusion were given and emergent endoscopical hemostasis were performed three times but the treatments were in vain. The patient was then referred to our department. He was then underwent surgical hemostasis by transduodenal papilloplasty, lithotomy of the biliary stones, cholecystectomy and C tube drainage. His condition was improved postoperatively. He was discharged 22 days after operation. There are only few reports about surgical procedure effecting hemorrhage which was difficult to endoscopically hemostasis in Japan.

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A 74-year-old man, who had undergone gastrectomy for gastric cancer 10 years previously, was shown by ultrasonography to have a gallbladder tumor, the tumor was subsequently confirmed by computed tomography.
As malignant tumor could not be excluded on the basis of its growth observed over a three-month period, cholecystectomy was performed. Macroscopic observation of the resected specimen demonstrated no evidence of direct invasion to the liver. The mildly elevated tumor was located in the body of the gallbladder, and histological analysis revealed a storiform pattern consisting of many spindle cells with large neoplastic nuclei.
Immunostaining demonstrated positivity for vimentin, α-SMA, p53, CD68, and α1-antitrypsin, and negativity for cytokeratin, EMA, CD34, c-kit, S-100, NSE, and NCAM. The final diagnosis of the tumor was malignant fibrous histiocytoma of the gallbladder. The present case is only the 12th of its kind to have been reported in Japan.

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During surgery for hilar intrahepatic cholangiocarcinoma (HIHC), combined vascular resection and reconstruction is frequently required to obtain negative surgical margins. A 57-year-old man had a tumor occupying S1 and S4 of the liver which was detected by CT. ERCP demonstrated severe invasion of the left hepatic duct and right anterior branch of the bile duct by the tumor. Angiography showed encasement of the right portal vein, right hepatic artery, and inferior vena cava (IVC). Left trisegmentectomy of the liver was performed. For combined vascular resection, after resection of the tumor-involved vessels, the IVC was closed by continuous suture under total hepatic vascular exclusion (THVE), the portal vein was reconstructed using an umbilical vein graft, and the right hepatic artery was reconstructed by end to end anastomosis. Although lymph nodes #8,12,13 were positive for metastasis and the tumor stage was classified as stageIV, R0 resection was performed. Gemcitabine was administered weekly as adjuvant chemotherapy. With this treatment, post-operative survival of 39 months was achieved. For the surgical treatment of HIHC, extended hepatectomy with combined vascular resection is recommended whenever curative resection (R0) may be achieved.

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Complication of endoscopic therapeutic lithotripsy including EST, EPBD and ESWL were reviewed. In general, complication was divided into two periods. The early complications that were occurred in a couple of days, were composed with acute pancreatitis, bleeding and duodenal rupture. The occurrence rate of these therapeutic procedures were twice compared with diagnostic ERCP. The serious issue was acute pancreatitis and regarding this point, EST was superior to EPBD. The latter complication were consist of stone recurrence, cholecystitis, cholangitis and biliary malignancy. Regarding the stone recurrence, EPBD was superior to EST. However, it is still controversial which technique was better procedure.

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The choice of treatment for bile duct stones is either by endoscopic approach; endoscopic sphincterotomy (EST) and endoscopic papilla balloon dilation (EPBD), or surgical approach; open and laparoscopic bile duct exploration. The bleeding and perforation in the EST group and pancreatitis in the EPBD group are frequent complications. These complications induce critical conditions, thus careful procedures and follow-up are necessary. The reported recurrent rates of bile duct stones in the EST group tend to be higher than in the EPBD group, however further long-term follow up study after EPBD is mandatory. The number of laparoscopic common bile duct explorations increases, however its advantage should be considered when the incidences of postoperative complications and long-term prognosis after laparoscopic surgery are evaluated. At present, the most preferable treatment procedure can be selected at each institution to decrease the short-term and long-term morbidities. Since the bile duct stone and acute cholangitis are closely related and the initial treatment for moderate/severe cholangitis is endoscopic biliary drainage, both surgical and endoscopic approach should be provided for patients with bile duct stones.

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The skill needed for management of bile duct stones is summarized according to a series of recent reviews. Biliary specialists are to be skillful for diagnostic and therapeutic techniques to treat bile duct stones along with highly qualified knowledge of their epidemiology, patho-physiology and prognosis. Such a management skill should be primarily based upon professionalism.

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