Diagnosing ‘indeterminate’ biliary strictures remains a clinical challenge. The gold standard is a histological or cytological diagnosis. Conventional endoscopic sampling methods include brush cytology, fluoroscopy-guided endobiliary biopsies, and bile aspiration. These are limited by low sensitivity with frequent false-negative results. These limitations often delay definitive diagnosis and appropriate management. Cholangioscopy-guided biopsies using digital single-operator systems offer direct visual targeting of abnormal mucosa and may improve diagnostic accuracy. This study evaluates the diagnostic performance of cholangioscopy-guided biopsies in patients with biliary strictures previously deemed suspicious for malignancy on cross-sectional imaging.

This was a retrospective, single-center study including consecutive patients who underwent Endoscopic Retrogade Cholangiopancreatography (ERCP) and cholangioscopy with biopsy between January 2024 and November 2025. All patients had biliary strictures considered suspicious for malignancy based on cross-sectional imaging. Cholangioscopy was performed using the SpyGlass DS II system (Boston Scientific), and all biopsies were obtained under direct visual guidance. Final diagnosis was based on histopathology from cholangioscopy-guided biopsies, or in cases of negative endoscopic sampling, from tissue obtained intraoperatively or through image-guided percutaneous biopsy.

A total of 44 patients were included, with a median age of 62 years. 30 (68%) were male and 14 (32%) were female. The majority had hilar strictures (n=30, 68%), followed by common hepatic duct (CHD) strictures (n=11, 25%) and common bile duct (CBD) strictures (n=3, 7%). All strictures appeared suspicious for malignancy on cross-sectional imaging. All patients were discussed in malignant Hepatopancreatobiliary multidisciplinary team (HPB MDT). Cholangioscopy with targeted biopsies was performed using the SpyGlass DS II system (with the use of SpyBite Max Biopsy Forceps). Final diagnosis was available for 42 patients; two were excluded due to unknown outcome. Among the 29 patients with a final diagnosis of cholangiocarcinoma, cholangioscopy guided biopsy confirmed malignancy in 20 cases, yielding a sensitivity of 69%. 5 cases were falsely negative, with malignancy confirmed later via surgical or other sampling. The remaining 4 cases were considered to have malignancy from progressive changes on imaging.

Of the 13 patients without malignancy, biopsy was negative in all, corresponding to complete concordance with the final diagnosis. Median surveillance for patients that were diagnosed with benign disease was 15.3 months.

The overall clinical diagnostic accuracy of cholangioscopy-guided biopsies in this case series was 78.6% with a sensitivity of 69% and a specificity of 100%. These figures compare favorably with conventional ERCP brush cytology, for which large series and meta-analyses consistently report pooled sensitivities in the order of 40–45% and specificities approaching 100% for malignant biliary strictures(1-3).

These findings reflect a consistently high diagnostic yield for visually targeted cholangioscopy-guided biopsy in the evaluation of extrahepatic biliary strictures.

Cholangioscopy-guided biopsies demonstrate a good diagnostic yield and accuracy in the evaluation of biliary strictures that are suspicious for malignancy. Our findings support the routine use of cholangioscopy-guided biopsy as a reliable tissue acquisition method in the diagnostic work-up of suspected cholangiocarcinoma, while acknowledging that cholangioscopy is likely to be best used as one component of a multimodality endoscopic work-up for indeterminate biliary strictures.