The clinical significances of ultrasound-related procedures for biliary tract diseases are detection of lesions, differential diagnosis, tumor staging and therapeutic applications. Transabdominal ultrasonography, which can evaluate the gallbladder wall and the intra/extra hepatic bile duct, is widely accepted as a noninvasive modality for diagnosis of abdominal diseases. The distal bile duct and the ampulla of Vater cannot be generally estimated by this method. EUS is useful for diagnosis of biliary diseases. The tumor staging for biliary cancer can be determined by the correlation between the tumor echo and the structure of the wall or the surrounding organs. EUS can detect a small stone in the gallbladder or the bile duct without the artifact from air in the GI tract. Furthermore, EUS is also useful for detection of small lesions, differential diagnosis, tumor staging for biliary cancer such as gallbladder cancer, cholangiocarcinoma, and ampullary cancer. In cases of difficult differential diagnosis, EUS-FNA has been reported to provide useful information. Further studies including new methods, e.g. enhanced ultrasonography, are warranted for improvement of diagnosis for biliary diseases.

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Although the primary therapeutic strategy for bile duct cancer is surgical resection, around 60% of resected cases have any kinds of prognostic factors, such as positive lymph node metastasis and positive surgical margins. Thus, these patients may be potential candidates for adjuvant therapy. Many clinical trials seeking feasibility and clinical benefits of adjuvant therapy were conducted. However, most of them were single-center clinical trial consisting of small number of patients with tumors existing in different anatomical sites. There was no firm evidence of clinical usefulness of adjuvant therapy until now. Publication of multi-center prospective randomized study is long-awaited. Concerning neoadjuvant and down-staging chemotherapy for initially unresectable or borderline resectable bile duct cancer, its clinical benefits have not yet been proven. In the near future, development of multi-drug regimen using cytotoxic agents and targeted therapies based on particular biomarkers are expected.

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Recently, ERCP and associated procedures are widely used for the management of pancreatobiliary disorders, because of the increasing needs for minimal invasive procedures. Novel protective lead shield can significantly reduce the radiation exposure, leading to avoid unnecessary radiation exposure to medical staff. Deep cannulation of the desired duct is a prerequisite for successful therapy at ERCP. Achieving deep biliary cannulation can be challenging at times for experts and novices alike. Endoscopists should not repeat the same approach. They should try to use alternative techniques which are tailored to the individual papillary and ductal anatomy of each patient. A new insertion method using balloon endoscope enables easier access to the afferent duodenal loop in a patient with Roux-en-Y anastomosis. ERCP and associated procedures are much less invasive and involve much less manpower, preparation, and procedure time. However, procedure-related complications occur occationary. It is necessary to be aware of the fundamental knowledge and techniques of these procedures in order to avoid unexpected results.

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This retrospective study investigated the outcomes of chemoradiotherapy (CRT) for local recurrence of biliary tract cancer (BTC) after surgery. Thirteen patients with isolated local recurrence of BTC received CRT in our hospital. Primary cancer lesions were intrahepatic bile duct (n=1), extrahepatic bile duct (n=9), gallbladder (n=2) and ampulla of Vater (n=1). The dominant recurrence sites were in resected margin of bile duct (n=7), tissues around the hepatoduodenal ligament (n=5) and lymph nodes (n=3). External radiotherapy was delivered in ten patients and intra-ductal irradiation using ¹⁹²I in three patients. 5-Fu, Gemcitabine or S-1 was administered as concomitant chemotherapy. We analyzed the adverse effect, local response and survival time after the therapy. Although twelve patients were completed the scheduled CRT, adverse effects in Grade 2 or 3 was observed in six patients. Local progression occurred in four patients. The median of progression free survival time was 9.7 months. The 1 and 2-year overall survival rates after the CRT was 38% and 19%. The suppression of local growth after CRT was favorable prognostic factor for overall survival after the treatment. The CRT for local recurrence of BTC was feasible and safe with contribution in prolong of survival by local disease control.

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To begin with, one should attempt a bloodless operational procedure (interventional radiology). An operative procedure can be considered to result when a guide wire is not passed through the stricture or accessed through a fistula. As for surgical method, the best option is a physiologic bile duct-bile duct anastomosis, while a bile duct-jejunum anastomosis should be the final option, and ought not to be readily adopted. As for measures to prevent the recurrence of the stricture, superior surgical technique is the most important factor, with the duration of the detention of the splint tube and perfect timing of the tube control being important; a longitudinal hepatic insertion of the tube is also more effective than an insertion into the left hepatic duct.

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Intraductal papillary neoplasm of the bile duct (IPNB) has been described as a primary biliary neoplasm characterized by intraductal papillary growth. However, a lot of discussion have recently been made in terms of its definition and concept. Someone argues that IPNB is not a distinct entity but belongs to the spectrum of conventional bile duct cancers, while others raise the possibility that IPNB is a unique tumor possibly accounting for more than 10% of primary biliary neoplasms. Although there are various opinions, they can be categorized into three groups. In this article, I try to introduce the three major proposed standards regarding IPNB by demonstrating representative cases.

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Recent advances in molecular biology have revealed existence of specific receptors for bile acids, and the roles of bile acids as signaling molecules have attracted increasing attention. It has been revealed that conjugated bile acids specifically activate sphingosine-1-phosphate (S1P) receptor type 2 (S1PR2). The activation of S1PR2 by conjugated bile acids stimulates SphK2, one of two sphingosine kinases which produces S1P. It has been reported that conjugated bile acids and S1P signaling via S1PR2 and SphK2 regulate lipid and glucose metabolism in the liver, and promote progression of cholangiocellular carcinoma. These findings suggest that bile acids and S1P signaling associate with variety of pathophysiology. Here, we introduce the roles of bile acid signaling and its interactions with S1P signaling via S1PR2 and SphK2 in the pathophysiology of hepatobiliary diseases.

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We present a case of gall stone ileus caused by unresectable perihilar cholangiocarcinoma (pCCA). The patient was a 75-year-old-man who had had the diagnosis of pCCA which was considered to be unresectable due to peritoneal metastases. Thus the patient was treated by chemotherapy consisting of gemcitabine and S-1. Eleven months after the diagnosis of pCCA, the patient suffered from gallstone ileus. Findings of celiotomy for gallstone ileus showed that peritoneal metastases were eradicated, suggesting that chemotherapy was markedly effective. Thus we considered early resumption of chemotherapy was preferred. Remaining gallstones in the gallbladder were small and considered to be unlikely to cause ileus thereafter. Hence, cholecystoduodenal fistula causative of gallstone ileus was left untreated and we only performed removal of impacted gallstone. After surgery, the patient recovered uneventfully. Therefore, chemotherapy was recommenced early postoperatively. The patient is currently doing well and receiving chemotherapy 48 months after the initial diagnosis of pCCA. Efficacy of chemotherapy for unresectable cholangiocarcinoma has been improved and thus number of long-term survivors with this dismal condition will increase. Because coexistence of gallstone and cholangiocarcinoma is common, gallstone ileus is rare but should be taken into consideration of long-term complication accompanying patients with unresectable cholangiocarcinoma.

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Portal vein thrombosis is one of the fetal complications after surgery for hilar chlangiocarcinoma. Some factors are considered to cause post operative portal vein thrombosis. We evaluated the relation between branch angle of portal vein and post operative portal vein thrombosis in this literature. We encountered two cases of portal vein thrombosis after right hemi-hepatectomy. Case1 is 78 year old man. The hilar cholangioma was Bismuth type II. The left branch angle of portal vein was 18 degree. Case2 is 74 year old man. The hilar cholangioma was Bismuth type IV. The left branch angle of portal vein was 95 degree. We examined the left branch angle of portal vein in 9 cases of right hemi-hepatectomy for hilar cholangioma from Octorber 2005 to June 2014. The branch angle of portal vein was obviously acute in cases of portal vein thrombosis. We considered that acute left branch angle of portal vein would be one of the risk factors of postoperative portal vein thrombosis.

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A 77-year-old man was referred to our hospital following the diagnosis of advanced gallbladder cancer with multiple para-aortic lymph node metastases and a single liver metastasis. He underwent combination therapy of gemcitabine and cisplatin. After eight courses, abdominal computed tomography indicated volume reduction of the main tumor and para-aortic lymph nodes and disappearance of the liver metastasis. This remarkable response to neoadjuvant chemotherapy enabled the performance of curative surgery. Pancreatoduodenectomy combined with partial liver resection and lymph node dissection was performed. The patient survived for 53 months from the diagnosis without recurrence.

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A female in her seventies was admitted because of weight loss and high fever. CT of the abdomen showed a low density tumor in the S4, S5 and S8. ¹⁸F-fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT) showed a high accumulation of ¹⁸F-FDG in the tumor of the liver and diffusely increased accumulation in the bone marrow. Because of high WBC count and serum granulocyte colony-stimulating factor (G-CSF) level, preoperative diagnosis was G-CSF producing cholangiocarcinoma. Following right anterior and left medial sectionectomy, the serum G-CSF level as well as the WBC count dropped down to normal range. Histologically, the tumor was composed of squamous cell carcinoma which was stained with anti-G-CSF antibody. Postoperative FDG-PET/CT showed no accumulation in the bone marrow.

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Case 1 and 2 underwent cholecystectomy for gallbladder stone, and case 3 and 4 underwent pancreatoduodenectomy for pancreatic head cancer. All cases had type F2 communicating accessory bile ducts (CABD) based on the Goor classification. CABD was diagnosed preoperatively in three cases, and intraoperatively in one case. In cholecystectomy cases, CABD was preserved to maintain the bile drainage. However, CABD was sacrificed in pancreatic cancer cases because of lymph node dissection. None of the patients developed postoperative biliary complications. In 26 cases that have been reported in Japan, 17 cases (65.4%) were diagnosed preoperatively. CABD were preserved in the most of the cases in cholecystectomy. CABD should be diagnosed preoperatively because CABD injury has high risk of bile leakage and stenosis. Intraoperative careful treatment for avoiding bile duct injury was crucial whether CABD was preserved or not.

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A 69 year-old woman was diagnosed as advanced stage gall bladder cancer with hilar and peripancreatic lymph nodes metastasis. It was suspected that those lymph nodes would invade to hepatic artery and portal vein. Chemo-radiation therapy was initiated because curative resection was considered impossible. After administration of S-1 combined with radiation (65Gy) therapy followed by GEM/CDDP chemotherapy, she was diagnosed as partial response, and then she was referred to our hospital for surgery. CT scan revealed no tumor mass in the gallbladder and necrotic changes suspected in the lymph node. We performed gallbladder bed resection, pancreatoduodenectomy and lymph node dissection. Histopathological examination revealed atypical cells formed irregular glandular structures in a small section of the gallbladder, diagnosed well-differentiated tubular adenocarcinoma. A few residual atypical cells were also present in lymph node No. 13a. Final diagnosis was T1b N1 M0 (stage IIIB). She is alive without recurrence at 24 months after surgery. Although advanced gallbladder cancer has a poor prognosis, multidisciplinary treatment including surgery may help improve pateints' outcomes.

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The patient was a 78-year-old man admitted to our hospital because of ampullary carcinoma. Surgery was not feasible and thus he underwent stenting using a covered metal stent (CMS). A second CMS was added 4 months later due to tumor ingrowth and sludge formation at the duodenal end of the first stent. The duodenal end of the second CMS was placed toward the inferior duodenal angle, and the stent was patent for 3 years and 6 months.

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A 73-year-old woman consulted our department for prolonged liver dysfunction following cholangitis. Although upper abdominal CT and MRI revealed no abnormalities, an irregular low-echo nodule of 10mm was detected in the duodenal papillary area by EUS. Abnormal wall findings were apparent in the papillary area bile duct by ERCP, wherein IDUS disclosed the presence of a nodule. A poorly differentiated adenocarcinoma was diagnosed based on the results of EST and biopsy. As no signs of tumor were noted in the papillary opening, a diagnosis of ampullary carcinoma of non-exposed protruded type was made, necessitating pylorus-preserving pancreaticoduodenectomy. Pathological findings indicated an adenocarcinoma with invasive micropapillary carcinoma (IMPC). The size of the lesion was 9mm, which had marked lymphatic vessel invasion and lymph node metastasis. Based on these observations, careful lymph node dissection is recommended when encountering IMPC in biopsy tissue samples.

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Neuroendocrine carcinoma (NEC) rarely occurs in gallbladder. We report one case of NEC in gallbladder treated with chemotherapy. It was difficult to performe definitive operation because of multiple lymph node swelling. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was useful for histological diagnosis of NEC. For definite diagnosis, the patient underwent cholecystectomy and biopsy of enlarged lymph node by opening abdomen. Pathological examination revealed there was not any adenocarcinoma lesion, but only NEC lesion. In MRI, high b-value diffusion weighted image (DWI) revealed high intensity, which may reflect high cellular density of NEC. This patient was recieved etoposide plus cisplatin therapy, and stable disease was achieved. Accumulation of cases is necessary for establishment of the guidline of diagnosis and chemotherapy in NEC of gallbladder.

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Umbilical metastasis of malignant tumor which is known as Sister Mary Joseph's nodule (SMJN) is rare, especially from biliary cancer. Here, we report a case of metachronous SMJN after resection of a cancer of the ampulla of Vater. A 64-year-old woman underwent pancreatoduodenectomy for a cancer of the ampulla of Vater. 1-year and 3-months later, she had the elevation of serum Ca19-9 level, and celiac lymph node metastasis was detected by CT. After systemic chemotherapies, CT demonstrated umbilical mass in a diameter of 1cm in addition to the celiac lymph node metastasis. FDG-PET showed a positive finding in the umbilical mass. We diagnosed the mass as SMJN. She could not continue the chemotherapy due to pancytopenia, and then she underwent radiotherapy for the celiac lymph node metastasis. SMJN increased in size and a pain of the umbilical part developed. We performed resection of SMJN for palliative therapy 2-years and 4-months after the initial surgery. After the resection, the pain disappeared and her quality of life was improved.

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Sclerosing cholangitis is a disease with diffuse stenosis and wall thickness in intra- and extrahepatic biliary tracts. We performed a nationwide survey in Japan of primary sclerosing cholangitis (PSC) and IgG4-related sclerosing cholangitis (IgG4-SC) in 2015, and 428 cases with PSC and 521 cases with IgG4-SC were registered. In PSC, we noticed that there were two peaks in the distribution of the age at presentation, especially in male. IBD was complicated in 39.6% overall but in 69.4% in younger patients. Five-year liver-transplantation free survival rates were 77.0%, and older age, presence of symptoms, and serum albumin at diagnosis were significantly associated with mortality. In IgG4-SC, male to female ratio was 4:1, and 60's were at risk for developing in both male and female. There were 16.1% of patients with serum IgG4 levels within normal range. Type 1 of cholangiographic classification in which stenosis was located at distal biliary tract was the most common. Only three cases were complicated with cholangiocarcinoma. Prednisolone was used in 88.5% of patients and the treatment efficacy was excellent; 5-year survival was 95.2%.

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