Validation of the diagnostic accuracy of probe-based confocal laser endomicroscopy for the characterization of indeterminate biliary strictures: results of a prospective multicenter international study

Background: Characterization of indeterminate biliary strictures remains problematic. Tissue sampling is the criterion standard for confirming malignancy but has low sensitivity. Probe-based confocal laser endomicroscopy (pCLE) showed excellent sensitivity in a registry; however, it has not been validated in a prospective study. Objective: To prospectively validate pCLE in real time during ERCP for indeterminate biliary strictures. Design: Prospective, international, multicenter study. Setting: Six academic centers. Patients: A total of 136 patients with indeterminate biliary strictures. Interventions: Investigators provided a presumptive diagnosis based on the patient history, ERCP impression, and pCLE during the procedure before and after tissue sampling results were available. A presumptive diagnosis also was made separately by a blinded investigator during ERCP and after tissue sampling to estimate care without pCLE. Follow-up was at least 6 months. Main Outcome Measurements: Accuracy, sensitivity, and specificity during ERCP alone, ERCP with pCLE, and ERCP with pCLE and tissue sampling. Results: A total of 112 patients were evaluated (71 with malignant lesions). Tissue sampling alone was 56% sensitive, 100% specific, and 72% (95% confidence interval [CI], 63%-80%) accurate. pCLE with ERCP was 89% sensitive, 71% specific, and 82% (95% CI, 74%-89%) accurate. After tissue sampling returned, strictures could be characterized with 88% (95% CI, 81%-94%) accuracy. Limitations: No randomization of care maps. pCLE not blinded. Conclusion: pCLE provided a more accurate and sensitive diagnosis of cholangiocarcinoma compared with tissue sampling alone. Incorporation of pCLE into the diagnostic armamentarium of patients with indeterminate biliary strictures may allow for a more accurate assessment, potentially reducing delays in diagnosis and costly repeat testing.