Bile Ducts

The biliary epithelial cells, also known as cholangiocytes, line the intra- and extrahepatic bile ducts, forming a barrier between intra- and extra-ductal environments. Cholangiocytes are mostly known to modulate bile composition and transportation. In hepatobiliary diseases, bile duct injury leads to drastic alterations in cholangiocyte phenotypes and their release of soluble mediators, which can vary depending on the original insult and cellular states (quiescence, senescence, or proliferation). The cholangiocyte-secreted cytokines (also termed cholangiokines) drive ductular cell proliferation, portal inflammation and fibrosis, and carcinogenesis. Hence, despite the previous consensus that cholangiocytes are bystanders in liver diseases, their diverse secretome plays critical roles in modulating the intrahepatic microenvironment. This review summarizes recent insights into the cholangiokines under both physiological and pathological conditions, especially as they occur during liver injury-regeneration, inflammation, fibrosis and malignant transformation processes.

ImportanceRecent evidence suggests higher bile duct injury rates for patients undergoing robotic-assisted cholecystectomy compared with laparoscopic cholecystectomy. Proponents of the robotic-assisted approach contend that this may be due to selection of higher-risk and more complex patients being offered robotic-assisted cholecystectomy.ObjectiveTo evaluate the comparative safety of robotic-assisted cholecystectomy and laparoscopic cholecystectomy among patients with varying levels of risk for adverse postoperative outcomes.Design, setting, and participantsThis retrospective cohort study assessed fee-for-service Medicare beneficiaries aged 66 to 99 years who underwent cholecystectomy between January 1, 2010, and December 31, 2021. Data analysis was performed between June and August 2024. Medicare beneficiaries were separated into model training and experimental cohorts (60% and 40%, respectively). Random forest modeling and least absolute shrinkage and selection operator techniques were then used in a risk model training cohort to stratify beneficiaries based on their risk of a composite outcome of postoperative adverse events consisting of 90-day postoperative complications, serious complications, reoperations, and rehospitalization in an independent experimental cohort.ExposuresRobotic-assisted vs laparoscopic cholecystectomy.Main outcomes and measuresThe primary outcome of interest was bile duct injury requiring operative intervention after cholecystectomy. Secondary outcomes were composite outcomes from cholecystectomy composed of any complications, serious complications, reoperations, and readmissions.ResultsA total of 737 908 individuals (mean [SD] age, 74.7 [9.9] years; 387 563 [52.5%] female) were included, with 295 807 in an experimental cohort and 442 101 in a training cohort. Bile duct injury was higher among patients undergoing robotic-assisted compared with laparoscopic cholecystectomy in each subgroup (low-risk group: relative risk [RR], 3.14; 95% CI, 2.35-3.94; medium-risk group: RR, 3.13; 95% CI, 2.35-3.92; and high-risk group: RR, 3.11; 95% CI, 2.34-3.88). Overall, composite outcomes between the 2 groups were similar for robotic-assisted cholecystectomy compared with laparoscopic cholecystectomy (RR, 1.09; 95% CI, 1.07-1.12), aside from reoperation, which was overall higher in the robotic-assisted group compared with the laparoscopic group (RR, 1.47; 95% CI, 1.35-1.59).Conclusions and relevanceIn this cohort study of Medicare beneficiaries, bile duct injury rates were higher among low-, medium-, and high-risk surgical candidates after robotic-assisted cholecystectomy. These findings suggest that patient selection may not be the cause of differences in bile duct injury rates among patients undergoing robotic-assisted vs laparoscopic cholecystectomy.

BackgroundIschemia of the bile duct is a common feature in liver disease and transplantation, which represents a major cause of morbidity and mortality, especially after liver transplantation. Detailed knowledge of its pathogenesis remains incomplete due to the lack of appropriate in vitro models.MethodsTo recapitulate biliary damage induced by ischemia and reperfusion in vitro, human intrahepatic cholangiocyte organoids (ICOs) were grown at low oxygen levels of 1% up to 72 h, followed by re-oxygenation at normal levels.FindingsICOs stressed by ischemia and subsequent re-oxygenation represented the dynamic change in biliary cell proliferation, upregulation of epithelial-mesenchymal transition (EMT)-associated markers, and the evocation of phase-dependent cell death programs similar to what is described in patients. Clinical-grade alpha-1 antitrypsin was identified as a potent inhibitor of both ischemia-induced apoptosis and necroptosis.InterpretationThese findings demonstrate that ICOs recapitulate ischemic cholangiopathy in vitro and enable drug assessment studies for the discovery of new therapeutics for ischemic cholangiopathies.FundingDutch Digestive FoundationMLDS D16-26; TKI-LSH (Topconsortium Kennis en Innovatie-Life Sciences & Health) grant RELOAD, EMC-LSH19002; Medical Delta program "Regenerative Medicine 4D"; China Scholarship Council No. 201706230252.

Background/objectivesPost-cholecystectomy syndrome (PCS) remains diagnostically challenging due to overlapping biliary and non-biliary causes. This study aimed to evaluate whether common bile duct (CBD) diameter measured by MRCP can serve as a practical triage parameter in symptomatic PCS patients and to define a data-supported threshold for predicting clinically relevant biliary pathology. Secondary objectives included assessing correlations between MRCP findings and upper endoscopic features.MethodsIn this retrospective single-center study, symptomatic adults undergoing upper endoscopy and MRCP were analyzed. Demographic, clinical, biochemical, radiologic, and endoscopic variables were recorded. Diagnostic performance was assessed using ROC analysis, and independent predictors of biliary dilatation were evaluated with multivariable logistic regression.ResultsWe analyzed 141 symptomatic post-cholecystectomy patients (mean age 58.2 ± 16.3 years; 67.4% female; median time since surgery 18 [9-36] months). Major symptoms: abdominal pain 84.9%, dyspepsia/bloating 47.5%, nausea/vomiting 22.3%, diarrhea 15.1%. CBD diameter measurements were available in the MRCP subgroup (n = 45); ERCP was performed selectively (n = 12). MRCP findings: CBD ≥ 7 mm 31.9%, biliary dilatation 14.9%, stricture 2.8%, suspected Oddi dysfunction 11.3%, postoperative complications 39.7%. Endoscopy: mucosal inflammation 91.5%; normal 8.5%. Significant correlations included CBD diameter vs. mucosal inflammation (r = 0.32, p = 0.001), dilatation vs. bile reflux (r = 0.28, p = 0.004), and Oddi dysfunction vs. papillary edema (r = 0.41, p = 0.001). CBD diameter showed the best diagnostic performance (AUC 0.82, 95% CI 0.74-0.90; cut-off ≥ 8.0 mm; sensitivity 78.3%; specificity 81.5%; p p = 0.007).ConclusionsIn symptomatic post-cholecystectomy patients, MRCP-measured CBD diameter provides a useful metric for risk stratification, with a threshold of ≥8 mm identifying patients more likely to harbor biliary pathology. These findings support a structured diagnostic approach that prioritizes noninvasive imaging while reserving ERCP for selected cases. Further prospective validation is warranted.