Gallbladder

Roux-en-Y gastric bypass (RYGB) is highly effective in reversing obesity and associated diabetes. Recent observations in humans suggest a contributing role of increased circulating bile acids in mediating such effects. Here we use a diet-induced obesity (DIO) mouse model and compare metabolic remission when bile flow is diverted through a gallbladder anastomosis to jejunum, ileum or duodenum (sham control). We find that only bile diversion to the ileum results in physiologic changes similar to RYGB, including sustained improvements in weight, glucose tolerance and hepatic steatosis despite differential effects on hepatic gene expression. Circulating free fatty acids and triglycerides decrease while bile acids increase, particularly conjugated tauro-β-muricholic acid, an FXR antagonist. Activity of the hepatic FXR/FGF15 signalling axis is reduced and associated with altered gut microbiota. Thus bile diversion, independent of surgical rearrangement of the gastrointestinal tract, imparts significant weight loss accompanied by improved glucose and lipid homeostasis that are hallmarks of RYGB.

The clinical and economic importance of fasciolosis has been recognised for centuries, yet diagnostic tests available for cattle are far from perfect. Test evaluation has mainly been carried out using gold standard approaches or under experimental settings, the limitations of which are well known. In this study, a Bayesian no gold standard approach was used to estimate the diagnostic sensitivity and specificity of five tests for fasciolosis in cattle. These included detailed liver necropsy including gall bladder egg count, faecal egg counting, a commercially available copro-antigen ELISA, an in-house serum excretory/secretory antibody ELISA and routine abattoir liver inspection. In total 619 cattle slaughtered at one of Scotland's biggest abattoirs were sampled, during three sampling periods spanning summer 2013, winter 2014 and autumn 2014. Test sensitivities and specificities were estimated using an extension of the Hui Walter no gold standard model, where estimates were allowed to vary between seasons if tests were a priori believed to perform differently for any reason. The results of this analysis provide novel information on the performance of these tests in a naturally infected cattle population and at different times of the year where different levels of acute or chronic infection are expected. Accurate estimates of sensitivity and specificity will allow for routine abattoir liver inspection to be used as a tool for monitoring the epidemiology of F. hepatica as well as evaluating herd health planning. Furthermore, the results provide evidence to suggest that the copro-antigen ELISA does not cross-react with Calicophoron daubneyi rumen fluke parasites, while the serum antibody ELISA does.

TGR5 activation of enteroendocrine cells increases glucagon-like peptide 1 (GLP-1) release, which maintains glycemic homeostasis. However, TGR5 activation in the gallbladder and heart is associated with severe side effects. Therefore, intestinally-targeted TGR5 agonists were suggested as potential hypoglycemic agents with minimal side effects. However, until now no such compounds with robust glucose-lowering effects were reported, especially in diabetic animal models. Herein, we identify a TGR5 agonist, 26a, which was proven to be intestinally-targeted through pharmacokinetic studies. 26a was used as a tool drug to verify the intestinally-targeted strategy. 26a displayed a robust and long-lasting hypoglycemic effect in ob/ob mice (once a day dosing (QD) and 18-day treatment) owing to sustained stimulation of GLP-1 secretion, which suggested that robust hypoglycemic effect could be achieved with activation of TGR5 in intestine alone. However, the gallbladder filling effect of 26a was rather complicated. Although the gallbladder filling effect of 26a was decreased in mice after once a day dosing, this side effect was still not eliminated. To solve the problem above, several research strategies were raised for further optimization.

BACKGROUND: Despite cultural preferences for organ preservation in East Asia, choledochoscopic gallbladder-preserving surgery (CGPS) remains controversial given high recurrence rates. This study objectively quantified the increased technical complexity of laparoscopic cholecystectomy (LC) for recurrent cholecystolithiasis after prior CGPS using the Tokyo Guidelines 2018 (TG18). METHODS: In this propensity-matched study (1:1, n = 220) conducted between 2020 and 2025, patients requiring LC due to recurrent cholecystolithiasis after prior CGPS were compared with patients with primary cholecystolithiasis undergoing LC. Investigators matched groups for TG18 severity grading, BMI, and biliary anomalies. Two blinded surgeons assessed the intraoperative findings using TG18 Delphi scoring (7-point scale). Primary outcomes included difficulty scores, critical view of safety (CVS) achievement, and bile duct injury. RESULTS: The CGPS group demonstrated significantly higher median TG18 scores (34 [IQR 30–39] vs. 21 [18–24]; adjusted mean difference: Δ 14.0 points, 95% CI: 11.2–16.8; p 25 predicted a fivefold increased conversion risk (aOR = 4.9, 95% CI: 2.3–10.6). CONCLUSIONS: Prior CGPS induces irreversible fibrosis that significantly increases reoperative difficulty (Δ 14 TG18 points), highlighting the need for careful patient selection in organ-preserving procedures. Definitive management with primary cholecystectomy remains the gold standard.