RT Journal Article SR Electronic T1 Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 52 OP 61 DO 10.1136/gutjnl-2018-317817 VO 69 IS 1 A1 Aatur D Singhi A1 Marina N Nikiforova A1 Jennifer Chennat A1 Georgios I Papachristou A1 Asif Khalid A1 Mordechai Rabinovitz A1 Rohit Das A1 Savreet Sarkaria A1 M Samir Ayasso A1 Abigail I Wald A1 Sara E Monaco A1 Michael Nalesnik A1 N Paul Ohori A1 David Geller A1 Allan Tsung A1 Amer H Zureikat A1 Herbert Zeh A1 J Wallis Marsh A1 Melissa Hogg A1 Kenneth Lee A1 David L Bartlett A1 James F Pingpank A1 Abhinav Humar A1 Nathan Bahary A1 Anil K Dasyam A1 Randall Brand A1 Kenneth E Fasanella A1 Kevin McGrath A1 Adam Slivka YR 2020 UL http://gut.bmj.com/content/69/1/52.abstract AB Objective Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens.Design We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens.Results The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response.Conclusions The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.