@article{23a300e26a834eb0aeea038b78744b90,
title = "Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures",
abstract = "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.",
keywords = "ampulla, bile duct, cholangiocarcinoma, dysplasia, genomics, molecular, pancreas, pancreatic cancer, precision medicine",
author = "Singhi, {Aatur D.} and Nikiforova, {Marina N.} and Jennifer Chennat and Papachristou, {Georgios I.} and Asif Khalid and Mordechai Rabinovitz and Rohit Das and Savreet Sarkaria and Ayasso, {M. Samir} and Wald, {Abigail I.} and Monaco, {Sara E.} and Michael Nalesnik and Ohori, {N. Paul} and David Geller and Allan Tsung and Zureikat, {Amer H.} and Herbert Zeh and Marsh, {J. Wallis} and Melissa Hogg and Kenneth Lee and Bartlett, {David L.} and Pingpank, {James F.} and Abhinav Humar and Nathan Bahary and Dasyam, {Anil K.} and Randall Brand and Fasanella, {Kenneth E.} and Kevin Mcgrath and Adam Slivka",
note = "Funding Information: 2Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USa 3Department of gastroenterology, Hepatology, and nutrition, University of Pittsburgh Medical center, Pittsburgh, Pennsylvania, USa 4Department of Pathology, Division of transplant Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USa 5Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USa 6Department of clinical Sciences, Surgery, University of texas Southwestern, Dallas, texas, USa 7Department of Surgery, West Virginia University Health Sciences center, Morgantown, West Virginia, USa 8Department of Surgery, northShore University Health System, evanston, illinois, USa 9Department of Surgery, University of Pittsburgh Medical center, Pittsburgh, Pennsylvania, USa 10Department of transplant, thomas e Starzl transplant instiute University of Pittsburgh Medical center, Pittsburgh, Pennsylvania, USa 11Division of Hematology and Oncology, UPMc cancer centers, Pittsburgh, Pennsylvania, USa 12Department of radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USa Acknowledgements the authors would like to thank Mrs Kate Smith for outstanding administrative assistance. this study was supported in part by the institute for Precision Medicine at the University of Pittsburgh, the UPMc Hillman cancer center, Shear Family Foundation, the Pittsburgh liver research center at the University of Pittsburgh and the University of Pittsburgh Medical center, and the Sky Foundation (to aDS). Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",
year = "2020",
month = jan,
day = "1",
doi = "10.1136/gutjnl-2018-317817",
language = "English (US)",
volume = "69",
pages = "52--61",
journal = "Gut",
issn = "0017-5749",
publisher = "BMJ Publishing Group",
number = "1",
}