原発性硬化性胆管炎

In a recent publication, Lapitz et al. reported differences in serum levels that predict the development of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis prior to clinical manifestation. We examined whether these biomarkers also predict the risk of gallbladder cancer (GBC) in European prospective plasma samples from 24 GBC cases and 90 control individuals. After logarithmic transformation and quantile normalisation of individual protein levels measured with a timsTOF PRO mass spectrometer, we fitted univariate logistic regression models and applied backward model selection to identify the optimal model for GBC risk prediction. CRP and MASP2, previously reported markers of CCA, were found to be predictive for GBC risk as well (p value < 0.05), and complemented by age at blood sampling, provided an area under the receiver operating characteristic curve of 0.80 (95% confidence interval 0.69-0.92) when combined in a prediction model for GBC risk. We further examined the mRNA expression of CRP and MASP2 in serum samples from 82 GBC cases and 79 control subjects from Chile. CRP mRNA levels were elevated in Chilean GBC cases, but MASP2 showed an opposite trend. While there are considerable differences in the design of the discovery study and ours, the finding that circulating levels of CRP and MASP2 are associated with the risk of both CCA and GBC in Europeans highlights the need for further research into potential shared mechanisms and strategies for the prevention of these two aggressive biliary tumours.

BACKGROUND: Current guidelines recommend pancolonic chromoendoscopy (pCE) over white light endoscopy (WLE) alone for colorectal neoplasia (CRN) detection in individuals with inflammatory bowel diseases (IBD). However, these techniques are poorly adopted due to technical and logistical limitations. Artificial intelligence-based computer-aided detection (CADe) is a promising new technology integrated into modern endoscopy platforms that has been shown to increase CRN detection in the non-IBD population. We aim to compare CADe-guided colonoscopy to chromoendoscopy in a randomized controlled trial (RCT) in individuals with IBD undergoing surveillance colonoscopy. METHODS: This is a pragmatic, multicenter, parallel-group, open-label, non-inferiority RCT comparing CADe-guided colonoscopy (intervention) to pCE (virtual or dye spray) (standard of care). Consenting adults (≥ 18 years) with longstanding (≥ 8 years) IBD (or any duration with primary sclerosing cholangitis) involving ≥ 1/3 of the colorectum, in clinical remission and undergoing surveillance colonoscopy, will be included. Those who undergo a high-quality colonoscopy (adequate preparation, minimal inflammation, complete intubation) will be included in the primary analysis. Patients will be centrally randomized by permuted blocks, stratified by endoscopist. The anticipated CRN rate is 15% in both groups. To demonstrate non-inferiority with a 7.5% margin, at a one-sided alpha of 2.5% and 80% power, and allowing for a 5% loss of eligibility, a total of 752 participants are required. The primary outcome will be visible CRN detected at colonoscopy; secondary outcomes include the mean number of CRN, proportion of individuals with high-risk CRN, procedural time, adverse events, and endoscopist acceptance, with per-protocol (primary) and intention-to-treat (secondary) analyses. This protocol follows the SPIRIT 2025 guidelines. DISCUSSION: AI has shown potential in enhancing CRN detection, but current AI systems are not specifically trained for IBD-related lesions, limiting effectiveness. This multicenter non-inferiority RCT will, for the first time, directly compare CADe-guided colonoscopy to pCE for CRN detection in individuals with IBD. This approach may increase adoption of AI-enhanced endoscopy and improve cancer prevention strategies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) registration number: ACTRN12626000102370. At the time of initial submission (November 2025), recruitment for this study had not started. Participant enrollment began in April 2026, and as of June 8, 2026, 19 out of the target 752 participants have been recruited. The study is currently in the active recruitment phase and has not yet transitioned to follow-up only.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often associated with inflammatory bowel disease (IBD) that can progress to cirrhosis or cholangiocarcinoma (CCA), both carrying a poor prognosis. The mechanisms driving disease progression remain poorly understood. We aimed to identify circulating multi-omic signatures linked to PSC severity (alkaline phosphatase, bilirubin, fibrosis), IBD, and CCA to elucidate underlying biology and discover potential biomarkers for risk stratification and disease monitoring. METHODS: We quantified 737 proteins, 1083 metabolites, and 4573 miRNAs using plasma from 33 patients with PSC with various clinical presentations. We applied machine learning-driven analysis and network-based modeling for the data integration and analysis of associations. Parameters robustly identified in both methods were considered for tailored pathway enrichment analysis. RESULTS: We identified circulating multi-omic profiles associated with PSC disease severity, IBD, and CCA. IBD-specific alterations were subtle; however, we noted associations between microbial-derived metabolites and colorectal cancer-related miRNAs. Severe PSC shared molecular features with PSC-CCA, indicating early activation of malignant pathways in PSC. Severe PSC was characterized by immune-interacting and epithelial-interacting proteins, bile acid and glutathione-related metabolites, and miRNAs regulating fibrosis, inflammation, extracellular matrix remodeling, and cell cycle control, overlapping with PSC-CCA. In established PSC-CCA, we observed coordinated alterations in oncogenic miRNAs, growth factor-related proteins, and depletion of sulfated phenolics and methylxanthines, reflecting extracellular matrix remodeling, inflammatory microenvironment reprogramming, and impaired hepatic detoxification. Overall, pathway enrichment analysis revealed an infection-like and cancer-associated signature defining PSC pathogenesis. CONCLUSIONS: Circulating multi-omic profiles capture the key features of PSC severity and associated CCA. These findings provide mechanistic insights and identify potential biomarkers for cancer risk stratification and disease monitoring using PSC.

BACKGROUND: Vitamin D deficiency has been implicated in cancer risk across several organ systems, but its role in hepatobiliary malignancy (HBM) remains unclear. We evaluated whether vitamin D supplementation (VDS) was associated with a lower risk of HBM specifically in patients with primary sclerosing cholangitis (PSC). METHODS: Patients enrolled in the PSC registry at our quaternary care and liver transplant (LT) center from 2010 to 2020 were analyzed. The primary exposure was VDS, modeled as a time-dependent variable. The primary outcome was HBM. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics, and Cox proportional hazards models were employed to estimate marginal hazard ratios (HRs). Cumulative incidence functionsfor HBM were estimated using a competing risks analysis treating death, and LT was as competing events. RESULTS: A total of 160 patients (mean age 42 years; 66% male) were included, of whom 76 (47.5%) reported baseline VDS. Over a median follow-up of 7 years, 15 patients developed HBM, corresponding to an incidence rate of 12.3 per 1000 person-years. VDS was associated with a significantly lower risk of HBM in both conventional (HR 0.16, 95% CI 0.05-0.57) and IPTW (HR 0.15, 95% CI 0.03-0.41) analyses. This association was consistent across baseline vitamin D strata, including <30 ng/mL (HR 0.12, 95% CI 0.02-0.79) and ≥30 ng/mL (HR 0.18, 95% CI 0.05-0.65). Accounting for competing risks, the 5-year cumulative incidence of HBM was 1.1% among patients receiving VDS versus 11.5% without VDS (p<0.01). DISCUSSION: VDS was associated with a significantly lower risk of HBM in this longitudinally followed cohort of patients with PSC. These findings support the consideration of VDS in all patients with PSC and underscore the need for mechanistic and interventional studies to further evaluate this association.

A rare case of a 26-year-old male presenting with abdominal pain and jaundice was initially suspected to be a gallbladder malignancy based on imaging findings of a gallbladder fossa mass and biliary strictures. Serial imaging, including ultrasound, CT, PET-CT, and endoscopic retrograde cholangiopancreatography (ERCP), revealed a hypermetabolic mass with biliary obstruction but no gallstones. Elevated serum IgG4 levels and a marked clinical response to steroids led to the diagnosis of IgG4-related sclerosing cholangitis (IgG4-SC) and cholecystitis, an uncommon presentation that often mimics malignancy or acute cholecystitis. This case highlights the diagnostic challenges and importance of considering IgG4-related disease (IgG4-RD) in young patients with inflammatory biliary masses and emphasizes multidisciplinary management to avoid unnecessary surgery.