Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures.


Journal

Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R

Informations de publication

Date de publication:
01 2020
Historique:
received: 29 10 2018
revised: 25 03 2019
accepted: 27 03 2019
pubmed: 12 4 2019
medline: 18 12 2019
entrez: 12 4 2019
Statut: ppublish

Résumé

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. 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. 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 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.

Identifiants

pubmed: 30971436
pii: gutjnl-2018-317817
doi: 10.1136/gutjnl-2018-317817
pmc: PMC6943248
doi:

Substances chimiques

Biomarkers, Tumor 0
CA-19-9 Antigen 0

Types de publication

Evaluation Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

52-61

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 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.

Déclaration de conflit d'intérêts

Competing interests: ADS has received an honorarium from Foundation Medicine, Inc.

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Auteurs

Aatur D Singhi (AD)

Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA.

Marina N Nikiforova (MN)

Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA.

Jennifer Chennat (J)

Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Georgios I Papachristou (GI)

Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Asif Khalid (A)

Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Mordechai Rabinovitz (M)

Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Rohit Das (R)

Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Savreet Sarkaria (S)

Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

M Samir Ayasso (MS)

Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Abigail I Wald (AI)

Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA.

Sara E Monaco (SE)

Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA.

Michael Nalesnik (M)

Department of Pathology, Division of Transplant Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

N Paul Ohori (NP)

Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA.

David Geller (D)

Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Allan Tsung (A)

Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Amer H Zureikat (AH)

Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Herbert Zeh (H)

Department of Clinical Sciences, Surgery, University of Texas Southwestern, Dallas, Texas, USA.

J Wallis Marsh (JW)

Department of Surgery, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.

Melissa Hogg (M)

Department of Surgery, NorthShore University Health System, Evanston, Illinois, USA.

Kenneth Lee (K)

Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

David L Bartlett (DL)

Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

James F Pingpank (JF)

Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Abhinav Humar (A)

Department of Transplant, Thomas E Starzl Transplant Instiute University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Nathan Bahary (N)

Division of Hematology and Oncology, UPMC Cancer Centers, Pittsburgh, Pennsylvania, USA.

Anil K Dasyam (AK)

Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Randall Brand (R)

Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Kenneth E Fasanella (KE)

Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Kevin McGrath (K)

Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Adam Slivka (A)

Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

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