ArticleJHEP reports : innovation in hepatology2026
Molecular endoscopy with next-generation sequencing improves diagnosis of cholangiocarcinoma in patients with extrahepatic biliary strictures.
Article in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND &
aimsDifferentiating benign from malignant extrahepatic biliary strictures remains a diagnostic challenge, despite advances in sampling techniques and ancillary tests. Next-generation sequencing (NGS) may improve diagnostic performance and enable essential molecular profiling for malignancies. We aimed to assess the diagnostic performance of targeted NGS compared to cytohistology and fluorescence in situ hybridization (FISH), using samples exclusively collected via optimized single-operator cholangioscopy.
methodsWe prospectively enrolled 104 patients with extrahepatic biliary strictures or suspected cholangiocarcinoma. A definitive diagnosis was established through cytohistology and clinical follow-up. In total, 445 samples (265 brushings and 180 biopsies) were collected. Targeted DNA sequencing was performed using a custom-designed 50-gene panel. FISH was retrospectively performed in a subgroup of 42 patients. The diagnostic performance of all three modalities was compared.
resultsNGS achieved a sensitivity of 82.2% for malignancy, significantly higher than cytohistology alone (59.2%, p = 1.9x10
conclusionsThe combination of cytohistology and NGS significantly improves diagnostic performance for cholangiocarcinoma in patients with extrahepatic biliary strictures using specimens obtained via single-operator cholangioscopy. This approach also enables early molecular profiling of low-cellularity specimens and may reduce diagnostic delays while optimizing therapeutic decision-making. IMPACT AND IMPLICATIONS: Differentiating benign from malignant extrahepatic biliary strictures remains a major clinical challenge, justifying the need for more sensitive and specific diagnostic tools beyond conventional cytohistology. Our findings show that combining next-generation sequencing with cytohistology significantly improves diagnostic performance, enables early molecular profiling, and is easily applicable in clinical laboratories. These results are especially relevant for patients with suspected cholangiocarcinoma and patients with primary sclerosing cholangitis, where timely and accurate diagnosis is critical and often difficult. Integrating next-generation sequencing into routine diagnostic workflows could reduce diagnostic delays and guide therapeutic decisions in patients with biliary tract lesions.
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