Intraductal papillary neoplasm of the bile duct (IPNB) is a precancerous or early-stage bile duct carcinoma composed of high columnar to cuboidal tumor cells growing in the intrahepatic and extrahepatic bile ducts with a marked papillary to villous structure centered in the thin fibrovascular stalks. IPNB is classified according to the degree of cytoarchitectural atypia into low grade and high grade. High-grade IPNB corresponds to intraepithelial carcinoma. IPNB was reported as a counterpart to pancreatic intraductal papillary mucinous neoplasm (IPMN) and is similar to pancreatic IPMN; it can be classified into four phenotypes according to the mucin-producing expression patterns: pancreatobiliary, intestinal, gastric, and oncocytic types. However, a consensus on the disease concept has not been fully accepted because it occurs less frequently than pancreatic IPMN, has fewer cases with mucus production, and involves two organs (liver and the extrahepatic bile ducts). This review focuses on IPNB's clinicopathological feature and the operational issues faced by clinicians and pathologists.

Background/Aim: Acute colecystitis with unresectable malignant disease is a life-threatening condition. We aimed to investigate the outcome of salvage percutaneous transhepatic gallbladder drainage (PTGBD) in patients with unresectable malignant disease due to failure of management by endoscopic transpapillary gallbladder drainage (ETGBD). Patients and Methods: twenty-one consecutive patients (mean age, 72 years; 62% women) underwent salvage PTGBD between 2013 and 2020. Results: The median overall survival rate was 7.7 months, with a 95% confidence interval (CI) of 3.4-13.1. Independent factors predicting poor outcome were Eastern Cooperative Oncology Group (ECOG) performance status of 4, with a HR of 52.2 (95% CI 1.1-2576.9). Conclusion: Salvage PTGBD has the potential to achieve prolonged survival. Acute cholecystitis in patients with unresectable malignant disease, including those with failure of ETGBD.

We examined 12 patients who were diagnosed pT2 gallbladder cancer after initial cholecystectomy and underwent additional resection. Median age was 75 years. Preoperative diagnosis was cT1 cancer in 2 cases, and benign disease in 10 cases. Usual cholecystomy was selected for 5 cases and whole layer resection was selected for 6 cases, subtotal resection was selected for 1 case. All patients underwent additional resection: 7 hepatectomies, 7 extrahepatic bile duct resections, 11 resional lymph node resections, 11 R0 resections. There were no postoperative complications beyond Clavien-Dindo IIIa, and median postoperative hospital stay was 10.5 days. Histological residual cancer was diagnosed in 3 cases, and postoperative adjuvant chemotherapy was administered in 3 cases. Two cases relapsed, and 5-year RFS was 81.5% and 5-year OS was 91.7%, which were considered equivalent or better than previous reports. Based on the Japanese clinical trial, S-1 is expected to become the standard postoperative treatment and improve the prognosis in the future. At the time of cholecystectomy, gallbladder cancer should always be considered. If pT2 gallbladder cancer is revealed after initial cholecystectomy, two-stage additional resection and proper postoperative adjuvant chemotherapy is considered useful to achieve good prognosis.

Surgical margins in biliary tract cancer include bile duct stumps and radial margin. Even an experienced pathologist may have difficulty diagnosing bile duct stump because of epithelial regeneration/reactive atypia due to inflammation caused by biliary drainage tube, difficulty in the evaluation of frozen sections, and appendage/periductal glands and ducts in the wall mimicking invasive cancer. The outcome for positive invasive cancer in the bile duct stump is poor, and the significance of additional resection is controversial. A positive carcinoma in situ has the same short-term outcomes as a negative margin but may cause recurrence in the medium to long term. In early-stage cholangiocarcinoma without lymph node metastases, additional resection for carcinoma in situ may improve survival. Securing a sufficient margin on the radial margin in the hepatic hilum and hepatoduodenal ligament due to the proximity of the bile duct and blood vessel is challenging, and the outcomes are reported to be poor if the radial margin is positive for invasive cancer. Although reports on the separation of carcinoma in situ and invasive cancer for postoperative treatment in patients with positive resection margins are absent with limited evidence, expectations for chemotherapy and chemoradiotherapy exist.

Perihilar cholangiocarcinoma is an intractable cancer of which complete resection provides the only chance for a cure. Japanese hepatobiliary and pancreatic surgeons have pushed the envelope to improve prognoses by extended liver resection with concomitant vascular resection, pancreatic resection, etc. However, the outcomes of unresectable/borderline resectable patients at diagnosis remain dismal and standard regimen of pharmacological treatments only yields a survival rate of less than 10% at 5 years. Recently, liver transplantation as part of a multidisciplinary treatment for highly selected patients with unresectable disease has been advocated by Western countries. In the U.S., it has been approved as one of the standard indications for liver transplantation and the multicenter collaborative study published in 2012 reported an outstanding result of 65% recurrence-free survival at 5 years. When we deliberately consider perihilar cholangiocarcinoma from a "Transplant Oncology" perspective, an emerging concept we have proposed from Japan, liver resection and liver transplantation are considered to play complimentary roles to achieve "oncological eliminability." Japan is expected to fulfill the mission as a pioneer and leader in this field.

The survival duration of patients with cancer has been improved by advances in chemotherapy. Therefore, the stenting strategy for malignant hilar biliary obstruction (MHBO) needs to be considered with re-intervention after stent occlusion. However, in MHBO, it is difficult to assess lesion extent and drainage area, and the treatment strategy differs from case to case because of the variety of stent types and placements. We believe that exchangeable stents will become the standard treatment modality for MHBO. For re-intervention, the treatment strategy must be reviewed to maximize the patient's quality of life. We present the latest findings on transpapillary and transluminal drainage for MHBO, with a focus on unresectable cases. However, because many matters have not been established, further evidence is needed.

In 2021, the Japanese Gastroenterological Endoscopy Society and the Japanese Biliary Association issued clinical practice guidelines for endoscopic papillectomy (EP), and the European Society of Gastrointestinal Endoscopy (ESGE) also issued guidelines. Both guidelines summarized the indications, techniques, and short- and long-term results of EP in the current situation. EP for papillary adenoma without intraductal extension has been reported with good results, and it is good indication for EP. Efforts are being made to reduce complications, but their frequency is still high. Because relatively high recurrence rates (7-23%) have been reported, long-term follow-up is also necessary. There are still many issues to be resolved, such as treatment strategies for carcinoma in adenoma cases, horizontal extension cases, and cases with intraductal extension. A comprehensive review of the current status and issues of EP will be presented, focusing on the contents of the guidelines and adding the results of recent studies.

A 7X-years old woman had a diagnosis of gallbladder cancer associated with pancreaticobiliary maljunction without bile duct dilatation and performed cholecystectomy (pT2N1M0). Five years later, she was diagnosed with obstructive jaundice and middle bile duct cancer and performed bile duct resection (pT1N0M0). More than 6 years later, she was diagnosed with intrapancreatic bile duct cancer using the EUS-FNA. The case of the metachronous triple biliary tract cancers with pancreaticobiliary maljunction without bile duct dilatation was not found by review of the literature. In patients with pancreaticobiliary maljunction without bile duct dilatation, careful postoperative long-term follow-up should be required for a possible occurrence of metachronous bile duct cancer.

The optimal management of cholecystitis or cholelithiasis after organ transplant is unclear. In this study, ten patients with medical history of heart or lung transplant underwent laparoscopic cholecystectomy in our hospital, and the perioperative managements and surgical outcomes were retrospectively analyzed. The mean age of these patients was 47 years. The transplanted organs were heart (n=8) and lung (n=2). The indications of laparoscopic cholecystectomy were chronic cholecystitis (n=6), common bile duct stones (n=3), symptomatic cholelithiasis (n=2) and acute cholecystitis (n=2). All patients received elective laparoscopic surgery. The operative procedures were multi-ports surgery (n=9) and single-port (n=1). There were no patients with conversion to open surgery. The immunosuppressive regimens consisted of 3 agents (n=9) and 4 agents (n=1), and the main regimen was the combination of cyclosporine or tacrolimus and prednisolone plus mycophenolate mofetil. Eight patients took the immunosuppressive agents in the morning of surgery and 10 patients resumed the baseline immunosuppressive regimen in the evening after surgery. The trough level was monitored in all patients and 5 patients needed to adjust the dose of immunosuppressive agent. All patients discharged without the complications of infection or rejection of the transplanted organs. Elective laparoscopic cholecystectomy for heart or lung transplant recipients were safely conducted without any complications by perioperatively continuing immunosuppressive agents.

A 60-year-old man became aware of itching and jaundice. Blood tests showed elevated hepatobiliary enzymes and he was referred to our hospital. Contrast-enhanced computed tomography revealed a 50-mm tumor in the left lobe of the liver with strong contrast enhancement, extending into the perihilar bile duct. After endoscopic biliary drainage, he underwent left hemihepatectomy with caudate lobectomy combined with middle hepatic vein and extrahepatic bile duct resection. The resected specimen showed a white hepatic tumor, with a size of 50 × 38mm and a well-defined papillary tumor was expanding into the perihilar bile duct, forming tumor thrombus. Histopathologically, the tumor cells comprising round enlarged nuclei and abundant clear cytoplasm proliferated and were positive for chromogranin A and synaptophysin, and the MIB-1 index was 8%, leading to the diagnosis of primary hepatic neuroendocrine tumor (PHNET) G2. Moreover, immunohistochemical examination revealed that tumor cells were positive for CK7 and CK19, markers of biliary epithelium. The present case was considered to be an extremely rare case of PHNET with tumor thrombus in the perihilar bile duct.

A 60s man with jaundice was referred to our hospital. CT scan demonstrated swelling lymph nodes around the head of pancreas, and dilatation of the common bile duct. Cholangiography showed the stenosis of the lower bile duct. Endoscopy showed a tumor of the ampulla of Vater and biopsy results showed neuroendocrine carcinoma. CT just before operation revealed portal vein tumor thrombus (PVTT). A subtotal stomach preserving pancreaticoduodenectomy combined with portal vein resection was performed. Postoperative histological examination revealed neuroendocrine carcinoma of the ampulla of Vater (pT3bN1M0). Post-operative chemotherapy was conducted based on chemotherapy for small-cell carcinoma of the lung. The patient died of multiple liver metastases 19 months after operation. Only 29 cases of neuroendocrine carcinoma of the ampulla of Vater have been reported in Japan in the last 22 years. This was the second report of carcinoma of the ampulla of Vater with PVTT.

A 54-year-old woman was referred to our hospital due to abdominal pain. We performed laparoscopic cholecystectomy for gallblader stone. Preoperatively, there was no indication of cholecystohepatic duct. The white cord-like material connecting the gallbladder neck and bed was detected in calot's triangle area. Considering that this cord consisted of a cystic artery, we divided it. However, bile on the cut end of the cord indicated a cholecystohepatic duct injury (transected biliary injury). We performed biliary abration for cholecystohepatic duct, because of a part of S5 drainage area in cholangiograhy. The postoperative course was uneventful, and the patient was discharged on postoperative day 11. At 6 months of follow-up image, there was lipiodol accumlation and no dilated bile duct or abscess in the liver remnant. We report a case of biliary abration for cystohepatic duct injury during laparoscopic cholecystectomy.

The patient was a 77-year-old female who presented with a mass measuring 90mm long diameter close to the pancreatic head, which was identified incidentally on CT. Based on an EUS-FNA histological examination, the patient was diagnosed with duodenal neuroendocrine carcinoma (NEC), and subtotal stomach-preserving pancreatoduodenectomy was performed. The histopathological assessment showed some lymphatic tissue remaining in the mass, so lymph node metastasis was suspected. The mass consisted mainly of NEC components, and also had adenocarcinomatous and chondrosarcomatous components. The excised specimen showed a nodular lesion was found in the fundus of the gallbladder, and histopathologically it was composed of adenocarcinomatous and chondrosarcomatous components. Metastasis was also found in No.12c lymph node, with only NEC components present. Based on these findings, a diagnosis of gallbladder sarcoma with differentiation to NEC during lymph node metastasis was made. We report this case because it presents an interesting metastatic form and is considered to be a valuable case in terms of tumorigenesis.

Primary sclerosing cholangitis (PSC) comprises 5% of all liver transplantations in Japan. The long-term outcomes of PSC recipients are impaired mainly due to the recurrent disease in the graft, and the disease recurrence has become a matter of debate. To elucidate the outcomes and predictive factors among PSC recipients, a nationwide survey was conducted. The 5- and 10-year patient- and graft-survival rates were 83% and 68%, and 71% and 62%, respectively. The overall PSC recurrence rate was 25% with a 5- and 10-year graft survival rate of 34% and 18%, which was significantly lower than the survival rate of those without recurrence (p<0.001). Univariate analysis identified the following as risk factors for recurrence: donor age (p<0.001), HLA matched number ≥ 4 loci (p=0.016), cyclosporine use (p= 0.004), mono or no immunosuppressive agent (p<0.001), calcineurin inhibitor trough level below the therapeutic range (p<0.001), postoperative biliary complication (p<0.001), and active intestinal bowel disease after LT (p<0.001). Among these factors, donor age ≥ 45 years (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.11-2.25; p=0.002) and mono or no immunosuppressive agent 1-year after LT (HR, 2.05; 95%CI, 1.48-2.6; p=0.005) were identified as independent risk factors in the final multivariate Cox regression model.