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Background and Aims: Although EUS is highly accurate for the evaluation of common bile duct (CBD) dilation, the yield of EUS in patients with incidental CBD dilation is unclear., Methods: Serial patients undergoing EUS for incidental, dilated CBD (per radiologist, minimum of >6 mm objectively) from 2 academic medical centers without active pancreaticobiliary disease or significantly elevated liver function test results were evaluated. Multivariable logistic regression identified predictors of EUS with significant findings and a novel prediction model was derived from one center, internally validated with bootstrapping, and externally validated at the second center., Results: Of 375 patients evaluated, 31 (8.3%) had significant findings, including 26 choledocholithiasis, 1 ampullary adenoma, and 1 pancreatic mass. Predictors of significant findings with EUS included age of ≥70 years (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5-10.0), non-biliary-type abdominal pain without chronic pain (OR, 6.1; 95% CI, 2.3-17.3), CBD diameter of ≥15 mm or ≥17 mm with cholecystectomy (OR, 6.9; 95% CI, 2.7-18.7), and prior ERCP (OR, 6.8; 95% CI, 2.1-22.5). A point-based novel clinical prediction model was created: age of ≥70 years = 1, non-biliary-type abdominal pain without chronic pain = 2, prior ERCP = 2, and CBD dilation = 2. A score of <1 had 93% (development) and 100% (validation) sensitivity and predicted a <2% chance of having a significant finding in both cohorts while excluding the need for EUS in ∼30% of both cohorts. Conversely, a score of ≥4 was >90% specific for the presence of significant pathology., Conclusions: Less than 10% of patients undergoing EUS for incidental CBD dilation had pathologic findings. This novel, externally validated, clinical prediction model may reduce low-yield, invasive evaluation in nearly one-third of patients., Competing Interests: Disclosure The following authors disclosed financial relationships: V. Chandrasekhara: Consultant for Boston Scientific and Covidien LP, research funding from STARmed and Micro-tech, and equity interest in Nevakar Corporation. A. C. Storm: Research grant from Apollo Endosurgery, Boston Scientific, Endogenex, Endo-TAGSS, Enterasense, MGI Medical, OnePass, and SofTac; consultant for Ambu, Boston Scientific, Envision Endoscopy, Intuitive, Medtronic, Microtech, and Olympus. E. Rajan: Coinvestigator for Medtroic and Ruhoff and consultant for Olympus and Johnson & Johnson. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: To describe the MR features and prognosis of patients with an uncommon complication of primary sclerosing cholangitis (PSC) characterized by a spontaneous perforation of the common bile duct (CBD) resulting in a peri-biliary collection and a pseudo-cystic appearance of the CBD., Methods: A single-center cohort of 263 patients with PSC who had at least two MRIs between 2003 and 2022 and a minimum follow-up of 1 year was retrospectively analyzed. MRI data (characteristics of CBD perforation and MR features of PSC) and clinical data were assessed. Analysis of survival without liver transplantation according to type of PSC (classical or CBD spontaneous perforation) was performed according to the Kaplan-Meier method and the curves were compared using the Log-Rank test., Results: A total of nine (3.4%) PSC patients (5 males) had perforation of the CBD with a median age at diagnosis of 18 years compared to 33 years for the control group (p = 0.019). The peri-biliary collections were variable in appearance (fusiform or pedunculated), with a diameter ranging from 5 to 54 mm. All nine patients showed intra- and extra-hepatic bile duct involvement, dysmorphia, and high ANALI scores. The clinical course was characterized by numerous complications in most patients, and five patients (56%) underwent liver transplantation at a median time of 5 years from diagnosis, compared to 40 patients (16%) in the control group (p = 0.02)., Conclusion: The spontaneous perforation of the common bile duct is an uncommon complication of primary sclerosing cholangitis that affects young patients and is associated with a poor prognosis., Clinical Relevance Statement: This uncommon complication of primary sclerosing cholangitis with perforation of the common bile duct resulting in a peri-biliary collection and a pseudo-cystic appearance of the common bile duct is characterized by a poor prognosis in younger patients., Key Points: • Among 263 patients with primary sclerosing cholangitis (PSC), nine patients (3.6%) had an uncommon complication characterized on MRI by perforation of the common bile duct (CBD). • This perforation of the CBD was responsible in all nine cases for the formation of a peri-biliary collection, giving a pseudo-cystic appearance to the CBD. • The spontaneous perforation of the common bile duct is an uncommon complication of primary sclerosing cholangitis that affects young patients with a poor prognosis., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Biliary dilatation without obvious etiology on cross sectional imaging warrants further investigation. This study aimed to assess yield of endoscopic ultrasound in providing etiologic diagnosis in such situation., Methods: Prospective cohort of consecutive patients with biliary dilatation & non diagnostic computed tomography (CT) and /or magnetic resonance imaging (MRI) underwent endoscopic ultrasound (EUS) with/without fine needle aspiration cytology (FNAC) and were followed clinically, biochemically with/without radiology for up to six months. The findings of EUS were corroborated with histopathology of surgical specimens and endoscopic retrograde cholangiography (ERCP) findings in relevant cases., Results: Median age of 121 patients completing follow up was 55 years. 98.2% patients were symptomatic and median common bile duct (CBD) diameter was 13 mm. EUS was able to identify lesions attributable for biliary dilatation in (67 out of 121) 55.4% cases with ampullary neoplasm being the commonest (29 out of 67 i.e. 43%). Multivariate logistic regression analysis identified jaundice as the predictor of positive diagnosis on EUS, of finding ampullary lesion and pancreatic lesion on EUS. EUS had sensitivity, specificity, positive predictive value and diagnostic accuracy of 95.65%, 94.23%, 95.65% and 95.04% respectively in providing etiologic diagnosis. Threshold value for baseline bilirubin of 10 mg%, for baseline CA 19.9 of 225 u/L and for largest CBD diameter of 16 mm were determined to have specificity of 98%, 95%, 92.5% respectively of finding a positive diagnosis on EUS., Conclusion: EUS provides considerable diagnostic yield with high accuracy in biliary dilatation when cross sectional imaging fails to provide etiologic diagnosis., (© 2024. The Author(s).)

Background: Dilatation of common bile duct (CBD) is mostly pathological and mainly occurs secondary to mechanical causes. We aimed to explore the prevalence of CBD dilatation in Intraductal Papillary Mucinous Neoplasms of the pancreas (IPMN) among patients referred to EUS., Methods: A retrospective study of all patients who had an EUS diagnosis of IPMN from 2011 to 2019 at Galilee Medical Center were extracted. Control group including patients with other types of pancreatic cysts., Results: Overall, 2400 patients were included in the study, of them 158 patients were diagnosed with pancreatic cysts, 117 patients (74%) diagnosed with IPMN (group A), and 41 patients (26%) diagnosed with other pancreatic cysts (group B). Univariate analysis showed significant association of IPMN (OR 3.8, 95% CI 1.3-11.5), resected gallbladder (GB) (OR 7.75, 95% CI 3.19-18.84), and age (OR 1, 95% CI 1.01-1.08) with CBD dilatation. Classifying IPMN to sub-groups using adjusted multivariate logistic regression analysis, only main duct-IPMN (MD-IPMN) significantly correlated with CBD dilatation compared to branch duct (BD)-IPMN and mixed type-IPMN (OR 19.6, 95% CI 4.57-83.33, OR 16.3, 95% CI 3.02-88.08)., Conclusion: MD-IPMN was significantly correlated with dilated CBD. Assessment of the pancreas is warranted in encountered cases of dilated CBD without obvious mechanical cause., (© 2024. The Author(s).)

A 65-year-old woman was diagnosed with an 8 cm large common bile duct stone and multiple stones in both intrahepatic ducts because of abnormal liver function tests. After a multidisciplinary approach, surgical removal was considered, and primary closure after laparoscopic removal of the common bile duct stone was performed. The patient recovered without complications and was discharged on the fourth postoperative day. Endoscopic removal of common bile duct stones is the standard treatment, but surgical removal through laparoscopic common bile duct exploration is also a safe and effective treatment method for such huge gallstones.

A 10-year-old American Shorthair cat presented with anorexia and jaundice, and echogenic evaluation revealed diffuse thickening of the common bile duct (CBD) wall. An exploratory laparotomy was conducted, the lesion was evaluated as difficult to remove, and the cat was euthanized and autopsied. Histologically, round neoplastic cells proliferated in the mucosa of the CBD and infiltrated the hepatic lobe, pancreas, and duodenum. Immunohistochemistry revealed that the neoplastic cells were positive for cytoplasmic-CD3 and granzyme B, and TCR-gamma clonal rearrangement was detected. Based on these findings, the neoplasia was diagnosed as a primary CBD lymphoma originating from cytotoxic T or natural killer cells. To the best of our knowledge, this is the first reported case of feline primary CBD lymphoma. Although rare, lymphoma of the CBD should be considered in cats with jaundice and thickening of the CBD.

A potbelly pig was evaluated for anorexia and icterus. Clinicopathologic abnormalities suggested an active inflammatory hepatobiliary process. Ultrasound and CT of the abdomen revealed an extrahepatic biliary obstruction of the common bile duct (CBD). Surgical exploration and choledochotomy revealed a markedly dilated CBD containing a large volume of intraluminal inspissated biliary material. This case report describes the imaging findings of an extrahepatic biliary obstruction secondary to abscessation within the CBD in a pig., (© 2024 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.)

Spindle and giant cell type undifferentiated carcinoma of the extrahepatic bile duct is an uncommon malignancy. We report a case involving the common bile duct in a 72-year-old male with jaundice who was admitted to our hospital. Diagnostic imaging, including abdominal computed tomography and magnetic resonance imaging, revealed a mass in the distal common bile duct, accompanied by dilatation of both intra- and extrahepatic bile ducts and regional lymph node enlargement. Endoscopic retrograde cholangiography demonstrated stenosis in the distal common bile duct, with a biopsy confirming adenocarcinoma. The patient underwent endoscopic retrograde biliary drainage followed by a subtotal stomach-preserving pancreaticoduodenectomy with regional lymphadenectomy. Microscopic examination revealed that the tumor predominantly comprised spindle and giant atypical cells within the stroma. Immunohistochemical analysis showed the tumor cells expressing cytokeratins and mesenchymal markers, confirming the diagnosis of spindle and giant cell type undifferentiated carcinoma of the common bile duct. Ki-67 labeling index was observed to be above 80%. Postoperatively, intra-abdominal lymph node recurrence was noted at two months, and multiple liver metastases were identified at three months. The patient died seven months post-surgery. The literature pertaining to this rare disease is reviewed and discussed., (© 2024. Japanese Society of Gastroenterology.)

Depression frequently occurs in patients with liver cirrhosis, yet the reasons for this correlation are not fully understood. Dysbiosis of gut microbiota has been implicated in depression through the gut-brain axis via the vagus nerve. This study explored the potential role of the gut-liver-brain axis via the vagus nerve in depression-like phenotypes in mice with liver cirrhosis. These mice underwent common bile duct ligation (CBDL), a method used to stimulate liver cirrhosis. To assess depression-like behaviors, behavioral tests were conducted 10 days following either sham or CBDL surgeries. The mice with CBDL displayed symptoms such as splenomegaly, elevated plasma levels of interleukin-6 and tumor necrosis factor-α, depression-like behaviors, decreased levels of synaptic proteins in the prefrontal cortex (PFC), disrupted gut microbiota balance, and changes in blood metabolites (or lipids). Additionally, there were positive or negative correlations between the relative abundance of microbiome and behavioral data or blood metabolites (or lipids). Significantly, these changes were reversed in CBDL mice by performing a subdiaphragmatic vagotomy. Intriguingly, depression-like phenotypes in mice with CBDL were improved after a single injection of arketamine, a new antidepressant. These results suggest that CBDL-induced depression-like phenotypes in mice are mediated through the gut-liver-brain axis via the subdiaphragmatic vagus nerve, and that arketamine might offer a new treatment approach for depression in liver cirrhosis patients., Competing Interests: Declaration of competing interest Dr. Hashimoto is the inventor of filed patent applications on “The use of R-ketamine in the treatment of psychiatric diseases”, “(S)-norketamine and salt thereof as pharmaceutical”, “R-ketamine and derivative thereof as prophylactic or therapeutic agent for neurodegeneration disease or recognition function disorder”, “Preventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases”, and “R-ketamine and its derivatives as a preventive or therapeutic agent for a neurodevelopmental disorder” by the Chiba University. Dr. Hashimoto has also received speakers' honoraria, consultant fee, or research support from Abbott, Daiichi-Sankyo, Meiji Seika Pharma, Seikagaku Corporation, Dainippon-Sumitomo, Taisho, Otsuka, Murakami Farm and Perception Neuroscience. Other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We present a combination of distal cholangiocarcinoma of the intrapancreatic common bile duct and intraductal papillary mucinous tumor associated with ductal adenocarcinoma of the pancreatic tail. This clinical case is unique. When analyzing the literature, we found no any case of similar primary multiple malignant tumor. Importantly, final diagnosis of simultaneous malignant pancreatobiliary neoplasia is possible only via intraoperative biopsy after adequate morphological dissection and research of resected organ complex including molecular genetic analysis due to identical histological and immunohistochemical picture of ductal neoplasia.

The authors present differential diagnosis of parasitic invasion of the common bile duct. A 52-year-old patient admitted with malignant bile duct obstruction, mechanical jaundice, cholestatic hepatitis and cholangitis. Bile duct tumor was preliminary diagnosed according to anamnesis, complaints, physical, laboratory and instrumental data. Retrograde cholangiopancreatography, endoscopic papillotomy and revision of the common bile duct were performed. There was occlusion at the level of the upper third of the common bile duct. Retrograde cholangioscopy was performed to clarify the nature of obstruction and tumor. Cholangioscopy revealed parasites in the common bile duct that required extraction. The patient was sent to the infectious disease hospital.

Objectives: We aimed to determine whether inflammatory indexes (II), including the neutrophil-lymphocyte ratio (NLR), the C-reactive protein (CRP) to albumin ratio (CAR), the CRP-lymphocyte ratio (CLR), and the systemic immune-inflammation index (SIII) can be diagnostic for common bile duct stones (CBDSs) excretion before endoscopic retrograde cholangiopancreatography (ERCP)., Backgrounds: Because of the spontaneous clearance, it is mandatory to ascertain the presence of CBDSs before ERCP., Methods: Retrospectively, we evaluated two groups. Group A included 96 records in which CBDSs existed in magnetic resonance cholangiopancreatography (MRCP) and ERCP. Group B included 36 records in which CBDSs existed in MRCP but not ERCP. IIs were calculated on presentation and before ERCP., Results: Stone detection in ERCP had a 3.992-fold (95% 1.769-9.007) higher probability with a stone larger than 3.25 mm in MRCP. Before ERCP, CAR, and CLR values were higher in group A than in group B (3.88 [1.25-14.14] and 1.24 [0.50-9.66], p  =  0.027 versus 8.79 [2.19-35] and 2.67 [1.02-20.05], p  =  0.029 , respectively). Higher CRP, CAR, and CLR values were considered significant for detecting a stone in ERCP (AUC: 0.627 [0.519-0.739], 0.625 [0.513-0.737], and 0.624 [0.514-0.734], respectively)., Conclusion: Low CRP, CAR, and CLR values might associate with the spontaneous migration of CBDS.

Objective: Changes of the pancreaticobiliary ducts herald disease. Magnetic resonance cholangiopancreatography (MRCP) allows accurate duct visualisation. Data on reliable upper reference ranges are missing., Design: Cross-sectional whole body MRI data from the population-based Study of Health in Pomerania were analysed. The width of the common bile duct (CBD) and the pancreatic duct (PD) was determined. We aimed to describe the distribution of physiological duct diameters on MRCP in a population of healthy subjects and to identify factors influencing duct size., Results: After excluding pre-existing pancreaticobiliary conditions, CBD and PD diameters from 938 and 774 healthy individuals, respectively, showed a significant increase with age (p<0.0001) and exceeded the conventional upper reference limit of normal in 10.9% and 18.2%, respectively. Age-dependent upper reference limits of duct diameters were delineated with non-parametric quantile regression, defined as 95th percentile: for CBD up to 8 mm in subjects <65 years and up to 11 mm in subjects ≥65 years. For the PD reference diameters were up to 3 mm in subjects <65 years and up to 4 mm in subjects ≥65 years., Conclusions: This is the first population-based study delineating age-adjusted upper reference limits of CBD and PD on MRCP. We showed that up to 18.2% of healthy volunteers would have needed diagnostic workup, if the conventional reference values were used. The utilisation of the adapted reference levels may help to avoid unnecessary investigations and thus to reduce healthcare expenditure and test-related adverse events., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Secondary pancreatic neoplasms account for less than 5% of all pancreatic malignancies, with renal cell carcinoma (RCC) being one of the most common primary tumors. Here, we present the case of a patient with obstructive jaundice secondary to an isolated metastatic RCC, to the intrapancreatic portion of the common bile duct, ampulla of Vater, and pancreatic parenchyma. Patient had a history of a left radical nephrectomy due to a primary RCC 10 years prior to presentation, and eventually underwent a pylorus-sparing pancreaticoduodenectomy (PD) with minor morbidity. While metastases of RCC to the pancreatic body and tail have been reported, isolated metastasis to the pancreatic bile duct comprises an even rarer subgroup., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To determine the effect of flushing of the common bile duct (CBD) on hepatobiliary markers and short-term outcome in dogs undergoing cholecystectomy for the management of gallbladder mucocele (GBM)., Study Design: Randomized, controlled, prospective study., Animals: Thirty-two client-owned dogs., Methods: Dogs were allocated randomly to either a "flush" group or a "non-flush group." Flushing was performed in a normograde fashion, followed by a routine cholecystectomy. Data collected included presenting clinical signs, preoperative and 3-day postoperative hepatobiliary markers (alkaline phosphatase, ALP; alanine aminotransferase, ALT; gamma glumatyl-transferase, GGT; bilirubin; cholesterol; triglycerides), duration of hospitalization, and complications. These data were compared between groups., Results: Sixteen dogs were enrolled in each group. One dog (in the flush group) was excluded following diagnosis of hepatic lymphoma. Border terriers were overrepresented (20/31). Overall, there were marked reductions from preoperative to 3 days postoperative in serum bilirubin (p = .004), ALP (p = .020), ALT (p < .001), GGT (p = .025), and cholesterol (p < .001) values. There was no difference in any marker between groups. Survival to discharge was 90.3% (28/31 dogs)., Conclusion: Cholestatic markers decreased significantly 3 days postcholecystectomy. No short-term clinical or clinico-pathological benefits were identified when flushing the CBD in dogs undergoing cholecystectomy for GBM., Clinical Significance: The findings of the study do not support routine flushing of the CBD during cholecystectomy for GBM in dogs., (© 2023 The Authors. Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Rationale: Adenomyoma is a rare reactive, hamartomatous benign tumor-like lesion. Although adenomyoma can occur anywhere in the gastrointestinal tract, including the gallbladder, stomach, duodenum, and jejunum, it is very rarely observed in the extrahepatic bile duct and ampulla of Vater (AOV). The preoperative accurate diagnosis of adenomyoma of the Vaterian system, including the AOV and common bile duct, is significant to appropriate patient management. However, discriminating between benign and malignancy is highly challenging. Patients are frequently mistaken as having periampullary malignancy, thereby leading to unnecessary extensive surgical resection with a high risk of complications., Patient Concerns: A 47-year-old woman visited a local hospital owing to epigastric and right upper-quadrant abdominal pain for 2 days., Diagnoses: Abdominal ultrasonography performed in the local hospital revealed suspicious of a distal common bile duct malignancy. She was transferred to our hospital for further evaluation and management., Interventions: After consulting with the patient, a multidisciplinary team, including a gastroenterologist, finally decided to perform surgery under the impression of an ampullary malignancy, and pylorus-preserving pancreatoduodenectomy was performed without any complications. She was histopathologically diagnosed with an adenomyoma of the AOV., Outcomes: At the 5-year follow-up, she was well and did not develop further symptoms or complications., Lessons: Although adenomyoma is very rare, it should be included in the differential diagnosis of mass-like lesions of the AOV to avoid unnecessary surgeries., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Intracholecystic papillary neoplasm (ICPN) is one of the precursors of gallbladder cancer defined in the 2010 World Health Organization classification of tumors. We herein report ICPN with pancreaticobiliary maljunction (PBM), which is a high-risk factor for biliary cancer., Case Presentation: A 57-year-old female presented with abdominal pain. Computed tomography showed a swollen appendix and gallbladder nodules with bile duct dilatation. Endoscopic ultrasonography revealed a gallbladder tumor spreading into the cystic duct confluence accompanying PBM. Based on papillary tumors around the cystic duct detected using the SpyGlass DS II Direct Visualization System (SpyGlass DS), ICPN was suspected. We performed extended cholecystectomy, extrahepatic bile duct resection, and appendectomy with a diagnosis of ICPN and PBM. The pathological diagnosis was ICPN (90 × 50 mm) with high-grade dysplasia spreading into the common bile duct. The absence of residual cancer in the resected specimen was pathologically confirmed. P53 staining was totally negative in both the tumor and normal epithelium. The overexpression of CTNNB1 was not observed., Conclusions: We encountered a patient with a very rare gallbladder tumor, ICPN with PBM. SpyGlass DS contributed to a precise assessment of the extent of the tumor as well as a qualitative diagnosis., (© 2023. Japanese Society of Gastroenterology.)

Adenomyomatous hyperplasia, a common non-neoplastic lesion in the gallbladder, is rarely identified in the extrahepatic bile duct. Typically, these lesions appear as a nodule or mural thickening/elevation. However, in exceptional circumstances, pedunculated/polypoid adenomyomatous lesion occurs in the biliary tract; two cases in the gallbladder and only one case in the common bile duct have been reported. Despite their benign nature, adenomyomatous lesions, especially those with a polypoid appearance, are clinically difficult to exclude a possibility of malignant neoplasms. We describe a case of polypoid-type adenomyomatous lesion of the cystic duct in a 72-year-old man, which was considered as a cystic duct neoplasm preoperatively. Gross examination of the resected specimen revealed that the 9 mm-sized cystic duct polyp. Histologically, the polypoid lesion consisted of glands without atypia, fibrous stroma, smooth muscle bundles, and accompanying stromal inflammation, leading to the diagnosis of benign adenomyomatous lesion. The lesion might be considered as adenomyomatous hyperplasia arising in the valve of Heister, while true nature of the lesion is uncertain. Recognition and accumulating for this rare disease will contribute to better clinical management in the future.

Synchronous primary cancer of the gall bladder and distal common bile duct is rare. There are only few case reports and case series available of these synchronous cancers. Management of this tumor is individualized in these case reports and series based upon the presentation. We present a case of a patient who had multifocal adenocarcinoma involving distal common bile duct and gall bladder. Keywords: Distal common bile duct cancer; gall bladder cancer; synchronous primary.

Abstract: Neuroendocrine tumors (NETs) are heterogeneous group of tumors arising from enterochromaffin cells. Neuroendocrine tumors are most commonly found in bowel and pancreatic tissue. Because of paucity of enterochromaffin cells in biliary tract, NETs of bile duct are very rare. Most of the neoplasms in the extrahepatic bile duct are adenocarcinomas; only 0.2% to 0.3% of NETs arise from the bile duct. Cases reported in the literature of biliary carcinoid are diagnosed postoperatively on histopathologic evaluation. We hereby demonstrate a rare presentation of CBD NET identified preoperatively on somatostatin receptor but not on glucose transporter imaging, confirmed by histopathology and immunohistochemistry to be grade 2 NET (Ki-67, 20%)., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare that they have no conflict of interest.

Objective: To determine the associations of pancreatobiliary maljunction (PBM) in the West., Background: PBM (anomalous union of common bile duct and pancreatic duct) is mostly regarded as an Asian-only disorder, with 200X risk of gallbladder cancer (GBc), attributed to reflux of pancreatic enzymes. Methods: Radiologic images of 840 patients in the US who underwent pancreatobiliary resections were reviewed for PBM and contrasted with 171 GBC cases from Japan., Results: Eight % of the US GBCs (24/300) had PBM (similar to Japan; 15/ 171, 8.8%), in addition to 1/42 bile duct carcinomas and 5/33 choledochal cysts. None of the 30 PBM cases from the US had been diagnosed as PBM in the original work-up. PBM was not found in other pancreatobiliary disorders. Clinicopathologic features of the 39 PBM-associated GBCs (US:24, Japan:15) were similar; however, comparison with non-PBM GBCs revealed that they occurred predominantly in females (F/M = 3); at younger (<50-year-old) age (21% vs 6.5% in non-PBM GBCs; P = 0.01); were uncommonly associated with gallstones (14% vs 58%; P < 0.001); had higher rate of tumor-infiltrating lymphocytes (69% vs 44%; P = 0.04); arose more often through adenoma-carcinoma sequence (31% vs 12%; P = 0.02); and had a higher proportion of nonconventional carcinomas (21% vs 7%; P = 0.03). Conclusions: PBM accounts for 8% of GBCs also in the West but is typically undiagnosed. PBM-GBCs tend to manifest in younger age and often through adenoma-carcinoma sequence, leading to unusual carcinoma types. If PBM is encountered, cholecystectomy and surveillance of bile ducts is warranted. PBM-associated GBCs offer an invaluable model for variant anatomy-induced chemical (reflux-related) carcinogenesis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The aim of this study was to establish an automatic classification model for chronic inflammation of the choledoch wall using deep learning with CT images in patients with pancreaticobiliary maljunction (PBM)., Methods: CT images were obtained from 76 PBM patients, including 61 cases assigned to the training set and 15 cases assigned to the testing set. The region of interest (ROI) containing the choledochal lesion was extracted and segmented using the UNet++ network. The degree of severity of inflammation in the choledochal wall was initially classified using the ResNeSt network. The final classification result was determined per decision rules. Grad-CAM was used to explain the association between the classification basis of the network and clinical diagnosis., Results: Segmentation of the lesion on the common bile duct wall was roughly obtained with the UNet++ segmentation model and the average value of Dice coefficient of the segmentation model in the testing set was 0.839 ± 0.150, which was verified through fivefold cross-validation. Inflammation was initially classified with ResNeSt18, which resulted in accuracy = 0.756, sensitivity = 0.611, specificity = 0.852, precision = 0.733, and area under curve (AUC) = 0.711. The final classification sensitivity was 0.8. Grad-CAM revealed similar distribution of inflammation of the choledochal wall and verified the inflammation classification., Conclusions: By combining the UNet++ network and the ResNeSt network, we achieved automatic classification of chronic inflammation of the choledoch in PBM patients and verified the robustness through cross-validation performed five times. This study provided an important basis for classification of inflammation severity of the choledoch in PBM patients., Advances in Knowledge: We combined the UNet++ network and the ResNeSt network to achieve automatic classification of chronic inflammation of the choledoch in PBM. These results provided an important basis for classification of choledochal inflammation in PBM and for surgical therapy.

Background: Choledochal cysts should be treated with complete surgical resection, or, rarely liver transplantation. Treated patients can remain at risk of developing metachronous cholangiocarcinomas and lifelong follow up is indicated. However, there is no agreement on what constitutes an acceptable follow up strategy. This review was undertaken to develop an evidenced based surveillance strategy., Methods: A systematic review of MEDLINE, EMBASE, PubMed, Web of Science, and Google Scholar was undertaken for reports (published up to 10 September 2021) describing late biliary complications and development of metachronous cholangiocarcinoma following choledochal cyst resection., Results: Twenty-five publications described 74 metachronous cholangiocarcinomas occurring in 3911 patients (overall incidence 2%). Cancers developed commonly at the hepatic hilus and were diagnosed after a median interval of 92 months (range 9-249 months) after the initial resection. While reporting is incomplete, the majority of cholangiocarcinomas developed following resection of type I and type IV cysts with few metachronous cancers recorded after treatment of type II or III cysts. Peak age range for presentation with metachronous cholangiocarcinoma is in the twenties following cyst resection in childhood suggesting that patients are at greatest risk for metachronous tumour development for up to 20 years (240 months)., Conclusion: A surveillance strategy is proposed for patients treated primarily for cyst types I and IV and unresected type V using annual liver function tests, Ca 19-9 measurement and biannual ultrasound assessment for 20 years post cyst resection, with biannual liver function testing, Ca 19-9 measurement and three yearly ultrasound assessment thereafter., (© 2022 Royal Australasian College of Surgeons.)

Recently, "polypoid invasive carcinoma (PICA)" showing grossly visible polypoid, invasive carcinoma with no adenoma component was proposed as a neoplastic polyp of the gallbladder. Herein, we report four cases of PICA of the bile duct. PICA cases of bile duct showed single, sessile polypoid growth grossly, and polypoid components were composed of invasive carcinoma of papillary/tubular patterns with active desmoplasia, and invaded directly and continuously into the bile duct wall and periductal tissue. While PICA and other intraductal papillary neoplasm of bile duct (IPNB) shared several features, PICA showed an invasive carcinoma growing in the duct lumen and also invading into the bile duct wall, thus different from IPNB which is the intraluminal polypoid, preinvasive epithelial neoplasia with back-to-back epithelial units. Taken together, PICA and IPNB could be differentiated from each other., (© 2022. Japanese Society of Gastroenterology.)

Acute cholangitis caused by migrating clips is a possible complication following laparoscopic cholecystectomy. In this case report, a 50-year-old woman was admitted to the hospital with fever, icterus, and epigastric pain. Blood samples and blood cultures showed cholestasis, signs of infection and three different types of bacteria in the blood stream. Magnetic resonance cholangiopancreatography showed a migrating clip in the common bile duct and was extracted using endoscopic retrograde cholangiopancreatography. Migrating clip following laparoscopic cholecystectomy is a cause of cholangitis and should be considered in patients presenting with relevant symptoms.

Abstract: Recurrent stone detection is common after endoscopic treatment of common bile duct stones (CBDS). This study aimed to identify the risk factors for recurrence of CBDS.We retrospectively evaluated 14 patients who underwent endoscopic treatment for CBDS. Risk factors for single and multiple recurrent CBDSs were evaluated using logistic regression analysis.Endoscopic and needle-knife precut sphincterotomy was performed in 506 and 112 patients, respectively. There was 1 recurrence in 85 patients (13.8%), 2 recurrences in 23 patients (3.7%), and 3 recurrences in 9 patients (1.5%). According to the multivariate analyses, being older than 65 years (odds ratio [OR] 1.084, P = .000), concomitant heart disease (OR 2.528, P = .002), concomitant lung disease (OR 1.766, P = .035), a large common bile duct diameter (OR 1.347, P = .000), presence of cholelithiasis (OR 1.752, P = .018), stent (OR 1.794, P = .023), or T-tube placement in the common bile duct (OR 47.385, P = .000), and prolongation of the procedure (OR 1.037, P = .000) increased the risk of recurrence, while having undergone cholecystectomy due to gallstones (OR 1.645, P = .042). The mean stone diameter (P = .059), nitroglycerin use (P = .129), and periampullary diverticulum (P = .891) did not increase the risk of recurrent CBDS.The probability of multiple recurrences after the first recurrence of CBDS increased with age >65 years, concomitant heart/lung diseases, stent/T-tube placement in the common bile duct, a wide common bile duct (≥10 mm), and cholelithiasis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The aims of the study were to evaluate the yield of magnetic resonance imaging (MRI) in patients with common bile duct (CBD) dilatation without a sonographic evident cause and to investigate sonographic and laboratory findings at presentation that might predict identification of underlying pancreaticobiliary pathology., Methods: Included were consecutive patients in whom MRI was performed for further evaluation of CBD dilatation detected on ultrasound (US), without a sonographic evident cause, from January 1, 2014, to December 31, 2014. Magnetic resonance imaging and clinical data were retrospectively reviewed. Patients were divided into two groups: patients with and without identified underlying causative pancreaticobiliary pathology. Ultrasound findings and laboratory results at presentation were compared between groups to identify findings suggestive of underlying pancreaticobiliary pathology., Results: Fifty-seven patients, with a mean age of 54 ± 16 years including 37 females (65%), underwent MRI. Specific pancreaticobiliary causes for CBD dilatation were identified in 38 patients (66%, 31 benign and 7 malignant). In the remaining patients, no cause was identified in 17 (30%) and MRIs were nondiagnostic in 2 patients. Magnetic resonance imaging accuracy for correctly identifying the underlying cause of CBD dilatation was 91%. Patients with associated intrahepatic bile duct dilatation on US and elevated alanine aminotransferase and alkaline phosphatase were more likely to have underlying pancreaticobiliary pathology (P < 0 .05). No patient with initial negative MRI had pancreaticobiliary malignancy., Conclusions: Magnetic resonance imaging seems to be an accurate noninvasive method for identifying the underlying cause in most patients with CBD dilatation on US and in excluding pancreaticobiliary malignancy. Patients with associated intrahepatic bile duct dilatation and/or elevated liver enzymes are at higher risk of harboring underlying pancreaticobiliary pathology., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Conflict of interest No conflicts of interest to declare.

Methods: Two hundred and forty seven of 480 patients with naïve papilla undergoing therapeutic ERCP between April 2013 and March 2018 were enrolled for the study. The following patient characteristics were investigated: age, sex, body mass index, previous diseases (heart disease, renal failure, cerebrovascular disorders, coexisting malignancy and pulmonary disease), history of PEP, common bile duct diameter, diverticula and volume of fluid infused 24 hours after the procedure. All ERCP cases had naïve papilla and had undergone treatment., Results: The incidence of PEP was 8.5%. Significant differences were observed in the volume of fluid infused between patients without and with a history of heart disease (1,380 vs. 1,755 mL). The mean volume of the infused fluid was significantly lower in the PEP than non-PEP group (1,483 vs. 1,688 mL, P = 0.02). Moreover, PEP incidence differed according to a fluid infusion cutoff of 1,000 mL (7 vs. 11 cases of PEP in those with ≦1,000 mL and >1,000 mL fluid volume, respectively, P < 0.001)., Conclusion: Restricted fluid volume was a newly identified risk factor for PEP, particularly in patients with heart and renal diseases as comorbidities., Competing Interests: None

Intraoperative delineation of tumor margins is critical for effective pancreatic cancer surgery. Yet, intraoperative frozen section analysis of tumor margins is a time-consuming and often challenging procedure that can yield confounding results due to histologic heterogeneity and tissue-processing artifacts. We have previously described the development of the MasSpec Pen technology as a handheld mass spectrometry-based device for nondestructive tissue analysis. Here, we evaluated the usefulness of the MasSpec Pen for intraoperative diagnosis of pancreatic ductal adenocarcinoma based on alterations in the metabolite and lipid profiles in in vivo and ex vivo tissues. We used the MasSpec Pen to analyze 157 banked human tissues, including pancreatic ductal adenocarcinoma, pancreatic, and bile duct tissues. Classification models generated from the molecular data yielded an overall agreement with pathology of 91.5%, sensitivity of 95.5%, and specificity of 89.7% for discriminating normal pancreas from cancer. We built a second classifier to distinguish bile duct from pancreatic cancer, achieving an overall accuracy of 95%, sensitivity of 92%, and specificity of 100%. We then translated the MasSpec Pen to the operative room and predicted on in vivo and ex vivo data acquired during 18 pancreatic surgeries, achieving 93.8% overall agreement with final postoperative pathology reports. Notably, when integrating banked tissue data with intraoperative data, an improved agreement of 100% was achieved. The result obtained demonstrate that the MasSpec Pen provides high predictive performance for tissue diagnosis and compatibility for intraoperative use, suggesting that the technology may be useful to guide surgical decision-making during pancreatic cancer surgeries., Competing Interests: Competing interest statement: M.E.K., J.Z., R.J.D., J.Q.L., C.L.F., J.S., and L.S.E. are inventors in US Patent 10,643,832 and/or in other patent applications related to the MasSpec Pen technology licensed by the University of Texas to MS Pen Technologies, Inc. J.Z., J.S., and L.S.E. are shareholders in MS Pen Technologies, Inc. J.S., L.S.E., and C.L.F. serve as chief medical officer, chief scientific officer, and a consultant, respectively, for MS Pen Technologies, Inc.

Background: Common bile duct (CBD) stone is one of the most prevalent gastroenterological diseases, but the role played by biliary microbiota in the pathogenesis of CBD stones remains obscure. The aim of this study was to investigate the characteristics of the biliary tract core microbiome and its potential association with the formation of pigment stones., Methods: Twenty-eight patients with biliary obstruction of various causes were enrolled. Thirteen had new-onset pigment CBD stone. Of the remaining 15, four had benign biliary stricture, four had gallbladder cancer, three had pancreatic cancer, 3 had distal CBD cancer, and one had hepatocellular carcinoma. Endoscopic retrograde cholangiopancreatography was used to collect bile samples for DNA extraction, 16S ribosomal RNA gene sequencing, and bile microbiota composition analysis., Results: Proteobacteria (61.7%), Firmicutes (25.1%), Bacteroidetes (5%), Fusobacteria (4.6%), and Actinobacteria (2.6%) were the most dominant phyla in the bile of the 28 study subjects. A comparison between new-onset choledocholithiasis and other causes of biliary obstruction (controls) showed Enterococcus was found to be significantly abundant in the CBD stone group at the genus level (linear discriminant analysis score = 4.38; P = 0.03). However, no other significant compositional difference was observed., Conclusion: This study demonstrates an abundance of microbiota in bile juice and presents a biliary microbiome composition similar to that of duodenum. The study also shows Enterococcus was significantly abundant in the bile juice of patients with a brown pigment stone than in controls, which suggests Enterococcus may play an important role in the development of pigment stones., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Abstract: To evaluate the effectiveness of percutaneous removal of common bile duct (CBD) stones using a modified balloon technique (balloon catheter sphincteroplasty and expulsion of the stones using half-captured balloons within the sheath) in patients difficult to treat with endoscopy.Fifty patients underwent a modified balloon technique (balloon group), and 53 patients underwent CBD stone removal by the basket method (stone basket group) between 2016 and 2019. We compared the balloon and stone basket groups to evaluate the effectiveness of the modified balloon technique. Outcome variables such as demographics, technical success rates, procedural details, and complications were analyzed. Statistical analysis was performed using Student t test, Fisher exact test, or the χ2 test.The technical success rate in the balloon group was 66% (33/50) in 1 session, 32% (16/50) in 2 sessions, and 2% (1/50) in 3 sessions. That of the stone basket group was 45% (24/53) in 1 session, 38% (20/53) in 2 sessions, and 17% (9/53) in 3 sessions.The total procedure time was significantly shorter in the balloon group (29.5 ± 15.1 minutes) than in the stone basket group (41.7 ± 20.2 minutes) (P < .01), whereas the number of stones was higher in the balloon group than in the stone basket group (P = .03). Maximal stone size, balloon size, pancreatitis, and hospitalization stay did not show statistical differences between the 2 groups. Most complications (9 patients, balloon group; 8 patients, stone basket group) were mild and transient. Major complications occurred in one patient in the stone basket group, who experienced hemobilia due to arterial injury caused by percutaneous transhepatic biliary drainage, which was treated by endovascular embolization without mortality.The modified balloon technique is an effective and safe treatment method for CBD stone removal in patients presenting difficulties in the endoscopic approach., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The alimentary limb has been proposed to be a key driver of the weight-loss-independent metabolic improvements that occur upon bariatric surgery. However, the one anastomosis gastric bypass (OAGB) procedure, consisting of one long biliary limb and a short common limb, induces similar beneficial metabolic effects compared to Roux-en-Y Gastric Bypass (RYGB) in humans, despite the lack of an alimentary limb. The aim of this study was to assess the role of the length of biliary and common limbs in the weight loss and metabolic effects that occur upon OAGB. OAGB and sham surgery, with or without modifications of the length of either the biliary limb or the common limb, were performed in Gottingen minipigs. Weight loss, metabolic changes, and the effects on plasma and intestinal bile acids (BAs) were assessed 15 days after surgery. OAGB significantly decreased body weight, improved glucose homeostasis, increased postprandial GLP-1 and fasting plasma BAs, and qualitatively changed the intestinal BA species composition. Resection of the biliary limb prevented the body weight loss effects of OAGB and attenuated the postprandial GLP-1 increase. Improvements in glucose homeostasis along with changes in plasma and intestinal BAs occurred after OAGB regardless of the biliary limb length. Resection of only the common limb reproduced the glucose homeostasis effects and the changes in intestinal BAs. Our results suggest that the changes in glucose metabolism and BAs after OAGB are mainly mediated by the length of the common limb, whereas the length of the biliary limb contributes to body weight loss. NEW & NOTEWORTHY Common limb mediates postprandial glucose metabolism change after gastric bypass whereas biliary limb contributes to weight loss.

Background: Balloon-assisted stone extraction (BASE) can be applied to remove the common bile duct (CBD) stones during laparoscopic CBD exploration (LCBDE). This study aimed to analyze the efficacy of BASE. Methods: A retrospective analysis of patients with CBD stone who underwent LCBDE using BASE from 2001 to 2017 was conducted. The outcomes of BASE and potential factor for failure of technique were also evaluated. Results: A total of 163 patients underwent LCBDE using BASE were enrolled. Success rate of BASE was 88.3% (144/163) and 19 (11.7%) patients with failed BASE underwent basket for lithotripsy additionally. The reason for aborting BASE were stone impaction ( n  = 6), small stone ( n  = 4), migration into intrahepatic duct (IHD) ( n  = 3), and others ( n  = 6). The overall success rate of stone clearance was 98.2% (160/163). The mean CBD diameter was 15.8 mm (range 7-34 mm), and the largest stone size was 13.8 mm (range 3-36 mm). The overall rate of complication related with procedure was 4.9% (8/163), including bile leakage in 2 patients (1.2%), bleeding in 2 patients (1.2%), and pancreatitis in 4 patients (2.4%). There was no procedure-related mortality. Conclusions: BASE for CBD stone is safe and effective technique for the treatment of CBD stones.

Substance-P (SP) is a neuropeptide that modulates immune responses and accelerates tissue repair in critical inflammatory disease. Liver fibrosis and cirrhosis are the ultimate outcomes of almost all chronic liver diseases caused by viral infection, steatohepatitis, autoimmune, and cholestatic injury. Despite the development of new drugs, liver transplantation is still the only fundamental treatment; thus, new therapeutic approaches to mitigate liver fibrosis and chronic inflammation are constantly being needed. The aim of this study was to examine the effect of SP on liver damage due to cholestatic stress. To induce cholestatic injury, common bile duct ligation (CBDL) was attempted, followed by systemic application of SP. SP treatment increased IL-10 and decreased TNF-α in serum with increasing levels of circulating regulatory T cells (Tregs) from the early stage of CBDL. Moreover, SP decreased CBDL-induced TGF-β1 expression in the circulation. This could create anti-inflammatory/anti-fibrotic environment under CBDL, which might ameliorate the progression of liver fibrosis in CBDL. Histological and molecular analysis revealed that SP treatment reduced ductular reaction, hepatic damage, and apoptotic hepatocytes, accompanied by diminishing type I collagen and upregulating MMP-9. These studies found that SP is a promising therapeutic candidate for immune-related liver disease as well as cholestatic liver disease, by providing hepatic protective effects via immune suppression., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Rationale: Biliary cysts (BC) are rare dilatations of various parts of a biliary tract. They account for approximately 1% of all benign biliary diseases. Total cyst excision and Roux-Y hepaticojejunostomy is the treatment method of choice in most patients. In this paper, a novel surgical treatment with the use of internal biliary and pancreatic catheters was presented., Patient Concerns: A 21-years-old woman with a giant choledochal cyst of Todani IA type presenting with abdominal pain, nausea, fever and palpable abdominal mass. It had been previously drained as a misdiagnosed pancreatic cyst in another hospital., Diagnosis: A very high amylase level (107140,0 U/l) in drain fluid was noted in laboratory tests. Endoscopic retrograde cholangiopancreatography revealed a biliary cyst located in the distal common bile duct and a pancreaticobiliary anomaly was suggested. A cholangiography per catheter inserted to the biliary cyst showed a large round contrast-filled cyst. A cholangiography following cyst decompression revealed a very long, tortuous bile duct entering the duodenum., Interventions: Cholecystectomy, cyst resection, Roux-Y hepaticojejunostomy, and implantation of catheters into pancreatic and bile duct were performed. The postoperative course was uneventful and she was discharged on 12th day without any complications. Histopathology revealed a cyst wall partially lined with biliary-type and mucinous epithelium, with dysplasia ranging from low to high grade (biliary intraepithelial neoplasia, high grade), without invasion., Outcomes: The biliary and pancreatic catheters were removed during endoscopic retrograde cholangiopancreatography 8 weeks following surgery without any complications. Fourteen months later, the patient reported good health., Lessons: Diagnosis of the abdominal cyst should be very precise in order to avoid misdiagnosis and inadequate management. The early diagnosis and proper treatment of BC are needed in order to avoid serious complications. The cholangiocarcinoma is the most dangerous potential complication of BC due to dysplasia within the cyst wall as in our young female patient., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Intraductal papillary mucinous neoplasms (IPMNs) are mucin-secreting cystic neoplasm of pancreas. They have a malignant potential. They are usually localised to the pancreas but occasionally can involve surrounding structures (1.9%-6.6%), like bile duct and duodenum, and are labelled as IPMN with invasion. Jaundice as a manifestation of IPMN is not common (4.5%). It can present as jaundice as a result of invasion of common bile duct (CBD) resulting in stricture formation or uncommonly as a result of fistulising to CBD with resultant obstruction of CBD by thick mucin secreted by this tumour. As only few cases (around 23) of mucin-filled CBD are reported in the literature. We are presenting our experience in dealing a rare case of obstructive jaundice caused by IPMN fistulising into CBD, highlighting the difficulties faced in managing such case, especially with regards to biliary drainage and what can be the optimum management in such cases., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)