We had been evaluated the long-term outcome of endoscopic papillotomy for patients with bile duct stones and clarified that prior cholecystectomy, calculus gallbladder and pneumobilia are risk factors of bile duct stone recurrence after endoscopic papillotomy. However, major cause of death in our cohorts after endoscopic treatment are cardiovascular disease and other organ cancer, because gallstones disease is strongly associated with diabetes and hyperlipidemia. We should educate the patients about importance of diet and excise to improve their prognosis. This article shows the chairman-lecture at 54^th Japan biliary association annual meeting and the open lecture on gallstone diseases.

Endoscopic retrograde cholangiopancreatography (ERCP) is the mainstay of endoscopic diagnosis and treatment of biliary tract diseases but recently endoscopic ultrasound (EUS) including intraductal ultrasound (IDUS) plays an important role in clinical practice. The diagnostic yield of EUS for bile duct stones is superior to CT and MRI. IDUS is utilized in the diagnosis of cholangiocarcinoma and EUS-FNA is increasingly reported for pathological diagnosis of biliary tract diseases. EUS-guided biliary drainage (EUS-BD) was first reported in cases with failed or difficult ERCP but recent clinical trials demonstrated similar efficacy of EUS-BD and transpapillary drainage by ERCP in the management of malignant biliary obstruction as a first line treatment. Development of dedicated devices is warranted for further spread of EUS-BD in clinical practice.

IgG4-related sclerosing cholangitis (IgG4-SC) is recognized as a biliary manifestation of IgG4-related disease. IgG4-SC can be carefully diagnosed based on the clinical diagnostic criteria for IgG4-SC including following four criteria: characteristic biliary imaging findings, elevation of serum IgG4 levels, coexistence of IgG4-related disease, except those of the biliary tract, and characteristic histologic features. Recently clinical practice guidelines for IgG4-SC have been developed. Cholangiographic classification of IgG4-SC is useful for making the differential diagnosis between IgG4-SC and other diseases. When intrapancreatic bile duct stenosis is detected, pancreatic cancer and cholangiocarcinoma (CC) must be ruled out. If stenosis is demonstrated in the hilar region, primary sclerosing cholangitis, cholangiocarcinoma, and follicular cholangitis should be ruled out. Steroid therapy is standard treatment. Oral prednisolone therapy is started at 0.6mg/kg/d for 2 or 4 weeks, and the dose is then gradually tapered. Although the outcome of most IgG4-SC patients has been reported to be good based on the strong responsiveness of IgG4-SC to steroid therapy, further study is needed to elucidate the long-term outcome.

Nowadays, endoscopic biliary drainage (EBD) is the first choice biliary drainage technique. EBD should be classified on the basis of resectability of tumor and the site of biliary tract obstruction (distal or perihilar bile duct). For resectable cases, Japanese guidelines recommend EBD for distal biliary obstruction. On the other hand, endoscopic nasobiliary drainage was recommend for perihilar biliary obstruction. For unresectable cases, Japanese guidelines recommend self-expandable metallic stent placement. However, unilateral or bilateral biliary drainage and stent-in-stent or side-by-side remains unresolved. We should understand various differences between Japanese and others guidelines. We also should perform biliary drainage based on patient's general condition (age, performance status, underlying disease and severity). In near future, we also should conduct high quality studies regarding biliary drainage for cholangiocarcinoma in the real clinical setting.

Surgical resection is the only curative treatment for biliary tract cancers. However, there are many unresectable or recurrent patients who need systemic therapy. The standard first-line chemotherapy is combination of gemcitabine and cisplatin. Several new regimens are now under investigation to improve the treatment outcomes. For postoperative adjuvant chemotherapy, several large-scale clinical trials have been conducted, and the evidence is accumulating. On the other hand, preoperative treatments and conversion surgery have been attempted, but the evidence is not yet sufficient. As a different approach from conventional cytotoxic agents, great expectation is given to precision medicine using molecular targeted agents. Immunotherapy including immune checkpoint inhibitors is also a promising field. With these various approaches, it is hoped that the treatment outcomes for patients with biliary tract cancers who received medical treatment will be improved in the near future.

It is well known that there are many anatomical variations in bile duct and hepatic artery at hepatic hilus. Preoperative anatomical evaluation of the branching pattern and running course of the bile duct and hepatic artery in relation to the portal vein is not only crucial for safe biliary surgery, but also important for achieving R0 resection, especially for perihilar cholangiocarcinoma (PHC). Clinical significance of infraportal running course of the right posterior sectional bile duct and supraportal running course of the right posterior hepatic artery has been well recognized in PHC surgery. However, there is other several anatomical variations that have a possibility of affecting curability and/or causing serious postoperative complication, even if that variant is extremely rare. With recent technical advances in diagnostic imaging, the detailed three-dimensional (3D) anatomy at hepatic hilus can be easily evaluated with a workstation using 3D image analysis software. Herein, anatomical variations of bile duct and hepatic artery that biliary surgeon should recognize before surgery are demonstrated in comparison to the standard 3D surgical anatomy, and clinical significance of these variations is discussed.

Pancreaticoduodenectomy is a standard treatment for ampullary carcinoma. Among biliary carcinoma, this tumor shows the highest R0 resection rate and favorable outcomes after resection. From results of pathological studies, when ampullary carcinoma is limited to mucosa of the ampulla of Vater and does not invade the sphincter of Oddi, the possibility of lymph node metastasis is extremely low, suggesting that local excision is theoretically indicated for such tumor. However, because current preoperative imaging cannot accurately make a diagnosis of invasion to the sphincter of Oddi, in principle, local excision should not be indicated for ampullary carcinoma. For ampullary adenoma, local excision could be applied, but detailed pathological examination is mandatory after resection. Pancreatic invasion is an important prognostic factor; if the tumor invades into the pancreas, perineural invasion is frequently observed and the tumor might have malignant biological potential similar to pancreatic carcinoma. Lymph node metastasis is a strong prognostic factor and the number of positive lymph nodes could better stratify patient outcomes after resection.

While normal bile juice show hypointensity on T1-weighted MR imaging (T1WI), concentrated bile juice within the gallbladder may show hyperintensity on T1WI and hypointensity on MR cholangiopancreatography (MRCP). So MRCP sometimes cannot clearly illustrate the gallbladder with concentrated bile juice. The hepatic segment having biliary cholestasis by intrahepatic bile duct obstruction may show hyperintensity on T1WI. Imaging diagnosis by ultrasound and CT of intrahepatic bile duct stones is frequently difficult if lacking calcium deposition. Intrahepatic stone is frequently bilirubin calcium calculus shows hyperintensity on T1WI. MRI is useful for the correct diagnosis of intrahepatic stone. The most characteristic imaging feature of acute cholangitis is transient inhomogeneous hepatic contrast enhancement on arterial dominant phase of dynamic CT and dynamic MRI. Other findings of acute cholangitis are bile duct wall thinking wit contrast enhancement, periportal hyperintensity on T2-weighted imaging, inhomogeneous hyperintensity of the hepatic parenchyma on diffusion weighted imaging.

Selective bile duct cannulation is one of the most important technique for all endoscopic biliary therapeutic interventions. In endoscopic retrograde cholangiopancreatography (ERCP), selective bile duct cannulation by the standard technique has been reported to fail even in experienced hands. First of all, training for biliary cannulation must be performed in safety. Trainees should perform as an assistant under the guidance of experts at first, and should be recommended to experience the training using simulators. Before confronting real patients, we should confirm the strategy for bile duct cannulation. When unintentional pancreatic approach is repeated, there are two ways to assist bile duct cannulation with pancreatic guidewire placement. One is the pancreatic guidewire technique, and the other is transpancreatic pre-cut papillotomy. Both of which can be followed by prophylactic pancreatic stents insertion to avoid post-ERCP pancreatitis. If both bile duct approach and pancreatic duct approach cannot be achieved, needle knife precutting can be selected. Instructors have to confirm how they manage to teach trainees in adequate manners, and have to be familiar with various techniques without sticking to only one technique.

Background: Surgical outcome of laparoscopic cholecystectomy (LC) in cases with history of upper abdominal surgery is not well investigated. Thus, we aimed to investigate the outcome of LC in patients with the history in this study. Patients and Methods: A total of 48 patients with history of upper abdominal surgery undergoing LC in our hospital were enrolled in this study. Surgical outcome of LC in the patients were investigated. Results: The history of the upper abdominal surgery was as follows; gastrectomy in 33 cases, colectomy in 3, and surgery for liver injury in 3. LC was indicated for gallbladder stone in 39 cases, acute cholecystitis in 6, and gallbladder polyp in 3. Eight cases (16.7%) required conversion from LC to open cholecystectomy due to dense adherence. Mean intraoperative blood loss was 41ml and operation time was 111 min. Postoperative complications greater than III of Clavien-Dindo classification developed in 2 cases (4.2%). Average duration postoperative hospital stay was 6 days. Conclusion: This study clarified surgical outcome of LC in patients with history of upper abdominal surgery. While the outcome seems favorable, further studies would be required to determine whether LC is better than open cholecystectomy in the patients.

We performed PTGBD for moderate to severe acute cholecystitis (AC) with high-risk factors for surgery prior to laparoscopic cholecystectomy (Lap-C). So far, the propriety of preoperative PTGBD for AC are unclear and still controversial. Herein, merits and démerits of PTGBD was evaluated. Of 146 cases with AC, there were 61 cases of moderate AC and 18 cases of severe AC. Backgrounds, laboratory data at admission, recovery period, days of restart diet, hospital stay days, and the outcomes of surgery were surveyed. PTGBD was performed in 25 cases of moderate, and in 9 cases of severe AC. There were no significant differences between with- and without PTGBD groups in length of hospital stay and outcome in moderate group. However, recovery period from AC, days of restart oral diet and hospital stay were significantly longer in non-surgery group than surgery group with PTGBD. In severe AC, Lap-C could be performed safely in all of PTGBD cases, while a half of non-PTGBD cases underwent open laparotomy. Three patients in non-PTGBD group needed blood transfusion during the surgery. Preoperative PTGBD could yield a certain clinical benefit, which is the capability of safe Lap-C, for the patients with high-risk factors, especially in severe AC.

Endoscopic papillary large balloon dilation (EPLBD) has already been a popular technique, which enabled easy removal of common bile duct stones even in cases with large and multiple stones. Originally, this technique has been attempted in cases after failed stone removal following endoscopic sphincterotomy (EST). Therefore, it has been a standard technique to perform EST prior to EPLBD. On the other hand, the technique of EPLBD without EST was recently introduced and the several study results have been reported. The previous studies suggested that the efficacy and safety were comparable regardless of performing EST. However, there have been only a few randomized controlled trials to compare the treatment outcomes between the two techniques. Therefore, further evaluation is requested to conclude whether EST is necessary prior to EPLBD.

Endoscopic papillary large balloon dilation (EPLBD) is a treatment method that has recently become widely used for choledocolithiasis. It is important to establish clinical guidelines to perform EPLBD safely and accurately. The Japan Gastroenterological Endoscopy Society has developed the 'EPLBD Clinical Practice Guidelines' as fundamental guidelines based on new scientific techniques. The working committee established 21 clinical questions (CQ) from 6 sections including indications, techniques, special cases, complications, outcomes, and postoperative observation according to the 'EST Clinical Practice Guidelines'. The guidelines are consisted with statements and comments regarding each CQ.

A 81-year-old man saw his doctor with complaints of tiredness and bilirubinuria. Blood test showed the elevation of total bilirubin and hepatobiliary enzymes. CT scan showed obstruction and wall thickening at distal bile duct. He was referred to our hospital for treatment of obstructive jaundice and further examination. He was diagnosed as distal bile duct cancer. There was no abnormal macroscopic finding at the papilla of Vater. He underwent subtotal stomach-preserving pancreaticoduodenectomy. Pathological diagnosis showed poorly differentiated adenocarcinoma at the bile duct and well differentiated adenocarcinoma at the papilla of Vater. Although atypical epithelium as BilIN1-2 presented between the two lesions, he was diagnosed as double cancer of the distal bile duct and papilla of Vater because of the difference of histological and immunostaining results. This was a rare case of double cancer of the bile duct and papilla of Vater.

Gallbladder metastasis from renal cell carcinoma (RCC) is rare, and reports on metastasis to gallbladder alone is ever rarer. We herein report a case of gallbladder metastasis from RCC. A 65-year-old male underwent right nephrectomy for RCC six years earlier. At a urology outpatient clinic, ultrasonography (US) demonstrated a gallbladder tumor, and he was referred to our department. US, CT, MRI and EUS revealed a tumor with a diameter 10mm in the neck of the gallbladder.

He underwent open cholecystectomy with resection of gallbladder bed. Permanent pathological diagnosis demonstrated gallbladder metastasis from RCC (clear cell type). Metastasis to gallbladder alone seems extremely rare. Gallbladder metastasis of RCC should be considered in patient with gallbladder tumor with a past medical history of RCC for which good prognosis can be expected by cholecystectomy.

A 53 year-old woman was referred to our hospital with complaints of hypogastrium pain. Abdominal computed tomography revealed a huge tumor which measured 7cm in maximal diameter in the hepatic hilum of the right lobe. Branches of hepatic artery, portal vein and bile duct pass through in the tumor. The tumor biopsy specimen revealed the findings of adenocarcinoma. We diagnosed it as intrahepatic cholangiocellular carcinoma. We performed extended right hepatectomy with caudate lobectomy and extrahepatic bile duct resection. Macroscopically, the tumor was solid and whitish in cut surface and the normal portal canal was seen in the center of the tumor. The lesion was diagnosed as cholangiolocellular carcinoma histologically. She had developed benign stenosis of choledochojejunostomy 7 months after surgery. We dilated the anastomosis by a biliary stent via PTBD fistula. She has been in good health with no recurrence for seven years and six months after surgery.

An 81-year-old man presented with stenosis in the distal bile duct that was diagnosed using endoscopic retrograde cholangiopancreatography. Bile duct biopsy detected a carcinoma in situ (BilIN-3). A computed tomography scan revealed wall thickening of the distal bile duct, which showed a contrast effect. The contrast effect of the biliary duct wall was observed up to the right hepatic artery branch. The patient was diagnosed with distal bile duct cancer. A subtotal stomach preserving pancreatoduodenectomy was performed. Histopathological examination revealed a well differentiated mucinous adenocarcinoma, and the tumor was accompanied by extensive perineural invasion. Mucinous adenocarcinoma of the common bile duct is rare in literature. Our case provides a characterization of extensive perineural invasion.

We reviewed biliary drainage methods and the timing for acute cholangitis according to Tokyo Guidelines 2018 (TG18). The diagnostic and severity grading criteria for acute cholangitis in the 2013 Tokyo Guidelines were verified and adopted in the TG18. Many of cases with acute cholangitis occurred due to choledocholithiasis and the TG18 guidelines recommend endoscopic drainage first. We showed new biliary drainage methods (balloon enteroscopy assisted ERCP and endoscopic ultrasound assisted biliary drainage), however, those new ways should be performed at the tertiary referral hospitals with experienced hands.

Acute cholecystitis, i.e. acute inflammation of the gallbladder, is caused by gallstones in 85% to 95% of cases. The first stage in the course is edematous (stasis and dilation of lympatics). The next is necrotizing (hemorrhagic necrosis). The last is suppurative (abscess formation). Diagnosis is based on clinical, laboratory, and imaging findings. Physical signs include Murphy's sign and right upper quadrant abdominal mass, pain, or tenderness. Laboratory abnormalities include nonspecific inflammatory markers such as leukocytosis and elevated C-reactive protein; hepatic enzymes and bilirubin may be mildly elevated. Possible sonographic findings are gallbladder enlargement, wall thickening, stone impaction, echogenic debris, sonographic Murphy's sign, fluid surrounding the gallbladder, intramural hypoechoic layer, and hypoechoic areas showing various irregular structures and Doppler signals. Contrast computed tomography is useful when diagnosis is difficult and when pericholecystic abscess or gallbladder perforation is suspected.

In this article we summarized treatment for acute cholecystitis focusing on the revision of Tokyo Guidelines 2018 (TG18). The flowchart for the management of acute cholecystitis was revised based not only on the severity grading but also the surgical risk. It is recommended that the Charlson co-morbidity index (CCI) and American Society of Anesthesiologists physical status classification (ASA-PS) be used to assess a patient's surgical risk. Early laparoscopic cholecystectomy (LC) should ideally be performed for patients with mild and moderate cholecystitis patients with low surgical risk. For severe cholecystitis patients with low surgical risk and favorable organ system failure (cardiovascular or renal organ system failure which is rapidly reversible after admission), urgent or early LC can be performed by a specialist surgeon with extensive experience in a setting that allows for intensive care management. For patients with high surgical risk, elective cholecystectomy should be considered after the improvement of the acute inflammatory process. If a patient does not respond to the initial medical treatment, urgent or early gallbladder drainage is required.