Multimodal endoscopic diagnosis in biliary oncology: integrating EUS-guided tissue acquisition and cholangioscopy for personalized cancer care.

The diagnosis of biliary malignancies remains challenging because of the heterogeneous growth patterns of cholangiocarcinoma, the limited sensitivity of conventional tissue acquisition techniques, and the growing need for molecular profiling in the era of precision oncology. Over the past decade, endoscopic ultrasound (EUS) and digital single-operator cholangioscopy have transformed the diagnostic approach by providing complementary information. EUS enables high-resolution imaging, locoregional staging, and tissue acquisition from primary tumors and regional lymph nodes, while cholangioscopy offers direct intraductal visualization and targeted biopsy of suspicious biliary lesions. This review summarizes the current evidence on the diagnostic performance, strengths, and limitations of EUS-guided tissue acquisition and cholangioscopy, emphasizing their complementary role within contemporary diagnostic algorithms. We also discuss emerging technologies, including molecular profiling, next-generation sequencing, artificial intelligence, radiomics, digital pathology, and liquid biopsy, which are shaping the future of biliary oncology. In addition to the available evidence, we present our institutional experience comparing EUS-guided tissue acquisition and cholangioscopy-directed biopsy in patients with suspected malignant biliary strictures. Our institutional experience supports the complementary use of EUS-guided tissue acquisition and cholangioscopy within a multimodal diagnostic approach. In the subgroup of patients who underwent both procedures, we observed high diagnostic sensitivity while maintaining an acceptable safety profile, supporting the potential value of a multimodal diagnostic approach. Integrating advanced endoscopic techniques with precision diagnostics is likely to optimize diagnostic accuracy and guide personalized management of biliary malignancies.