The diagnosis of perihilar cholangiocarcinoma (CCA) remains challenging, with conventional cytology, brushing, transpapillary biopsies and imaging providing limited sensitivity.⁽¹⁾ Endoscopic ultrasound (EUS)-guided fine-needle biopsy (FNB) is typically performed in the presence of a mass or suspicious portal lymph nodes. ⁽²⁾ In contrast, cholangioscopy-directed biopsies are increasingly used for evaluating indeterminate biliary strictures. ⁽³⁾ Comparative real-world data on their diagnostic yield are scarce. We aimed to assess the diagnostic performance, safety, and clinical impact of these modalities.

We retrospectively analyzed 117 consecutive patients with hilar strictures evaluated for suspected biliary malignancy between 01.2020-09.2025. The final diagnosis was based on surgical histology when available, or on a multidisciplinary consensus with radiological and clinical follow-up. Sensitivity analysis was restricted to the 96 patients with confirmed malignancy. A test was considered positive when histology confirmed malignancy (EUS-FNB or cholangioscopy guided biopsy) or when visual features were interpreted as malignant. True positives (TP) were malignant cases with diagnostic confirmation, and false negatives (FN) were malignant cases with negative or non-diagnostic results. Combined sensitivity was defined as positivity in at least one modality in patients who underwent both procedures.

Of 117 patients, 96 (82%) had malignancy. Median age was 66 years (IQR 58–73), 53% were male, ECOG 0–1 in 94%, and the comorbidity burden was moderate. Malignant lesions were hilar in 78% and Bismuth I in 20%, with Bismuth–Corlette III–IV predominating. EUS-FNB was performed in 40 of these cases, yielding a sensitivity of 65% (26/40; 95% CI: 46.3–76.3). Cholangioscopy-directed biopsies were performed in 72 malignant cases, with a sensitivity of 72.2% (52/72; 95% CI: 60.5–82.9). Visual impression during cholangioscopy suggested malignancy in 61 of 72 cases, corresponding to a sensitivity of 84.7% (95% CI: 74.3–92.3). In the subgroup of 26 malignant patients who underwent both procedures, the combined sensitivity increased to 96.2% (25/26; 95% CI: 81.1–99.9). Adverse events were more frequent after cholangioscopy (cholangi­tis 13.5%, pancreatitis 3.4%, bleeding 2.2%) than EUS (pancreatitis 4.5%); all were mild and managed conservatively.

EUS-FNB and cholangioscopy each demonstrated moderate sensitivity, with visual cholangioscopy yielding the highest single-modality performance. Although cholangioscopy carried more complications, the combination of EUS and cholangioscopy achieved near-complete sensitivity and remained safe, underscoring their complementary role in the diagnostic algorithm of suspected CCA.