Journal
GUT
Volume 71, Issue 6, Pages 1141-1151Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/gutjnl-2021-325178
Keywords
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Categories
Funding
- Instituto de Salud Carlos III (ISCIII) cofinanced by ' Fondo Europeo de Desarrollo Regional' (FEDER) 'Una manera de hacer Europa' [PI16/01126, PI19/00163]
- Gobierno de Navarra Salud [58/2017, 55/2018]
- AGATA Strategic Project from Gobierno de Navarra [0011-1411-2020-000010]
- Fundacion Mario Losantos [2020/101]
- AMMF [2018/117]
- Cholangiocarcinoma Charity
- COST Action [CA181122]
- Ramon y Cajal Program
- [RYC-2014-15242]
- [RYC-2018-024475-1]
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The NGS mutational analysis of bile cfDNA, named Bilemut, showed a sensitivity of 96.4% and specificity of 69.2% for detecting malignancy in patients with suspicious biliary strictures. Implementation of Bilemut at the initial diagnostic stage can significantly improve detection of malignancy, reduce delays in clinical management, and assist in selecting patients for targeted therapies.
Objective Despite significant progresses in imaging and pathological evaluation, early differentiation between benign and malignant biliary strictures remains challenging. Endoscopic retrograde cholangiopancreatography (ERCP) is used to investigate biliary strictures, enabling the collection of bile. We tested the diagnostic potential of next-generation sequencing (NGS) mutational analysis of bile cell-free DNA (cfDNA). Design A prospective cohort of patients with suspicious biliary strictures (n=68) was studied. The performance of initial pathological diagnosis was compared with that of the mutational analysis of bile cfDNA collected at the time of first ERCP using an NGS panel open to clinical laboratory implementation, the Oncomine Pan-Cancer Cell-Free assay. Results An initial pathological diagnosis classified these strictures as of benign (n=26), indeterminate (n=9) or malignant (n=33) origin. Sensitivity and specificity of this diagnosis were 60% and 100%, respectively, as on follow-up 14 of the 26 and eight of the nine initially benign or indeterminate strictures resulted malignant. Sensitivity and specificity for malignancy of our NGS assay, herein named Bilemut, were 96.4% and 69.2%, respectively. Importantly, one of the four Bilemut false positives developed pancreatic cancer after extended follow-up. Remarkably, the sensitivity for malignancy of Bilemut was 100% in patients with an initial diagnosis of benign or indeterminate strictures. Analysis of 30 paired bile and tissue samples also demonstrated the superior performance of Bilemut. Conclusion Implementation of Bilemut at the initial diagnostic stage for biliary strictures can significantly improve detection of malignancy, reduce delays in the clinical management of patients and assist in selecting patients for targeted therapies.
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