RT Journal Article
SR Electronic
T1 Next-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary strictures
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1141
OP 1151
DO 10.1136/gutjnl-2021-325178
VO 71
IS 6
A1 Maria Arechederra
A1 María Rullán
A1 Irene Amat
A1 Daniel Oyon
A1 Lucia Zabalza
A1 Maria Elizalde
A1 M Ujue Latasa
A1 Maria R Mercado
A1 David Ruiz-Clavijo
A1 Cristina Saldaña
A1 Ignacio Fernández-Urién
A1 Juan Carrascosa
A1 Vanesa Jusué
A1 David Guerrero-Setas
A1 Cruz Zazpe
A1 Iranzu González-Borja
A1 Bruno Sangro
A1 Jose M Herranz
A1 Ana Purroy
A1 Isabel Gil
A1 Leonard J Nelson
A1 Juan J Vila
A1 Marcin Krawczyk
A1 Krzysztof Zieniewicz
A1 Waldemar Patkowski
A1 Piotr Milkiewicz
A1 Francisco Javier Cubero
A1 Gorka Alkorta-Aranburu
A1 Maite G Fernandez-Barrena
A1 Jesus M Urman
A1 Carmen Berasain
A1 Matias A Avila
YR 2022
UL http://gut.bmj.com/content/71/6/1141.abstract
AB 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.Data sharing not applicable as no datasets are generated and/or analysed for this study. Our data are not in a repository. Deidentified participant data are all included in the submission.