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

Aatur D. Singhi, Marina N. Nikiforova, Jennifer Chennat, Georgios I. Papachristou, Asif Khalid, Mordechai Rabinovitz, Rohit Das, Savreet Sarkaria, M. Samir Ayasso, Abigail I. Wald, Sara E. Monaco, Michael Nalesnik, N. Paul Ohori, David Geller, Allan Tsung, Amer H. Zureikat, Herbert Zeh, J. Wallis Marsh, Melissa Hogg, Kenneth LeeDavid L. Bartlett, James F. Pingpank, Abhinav Humar, Nathan Bahary, Anil K. Dasyam, Randall Brand, Kenneth E. Fasanella, Kevin McGrath, Adam Slivka

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
JournalGut
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Endoscopic Retrograde Cholangiopancreatography
Bile Ducts
Pathologic Constriction
Sclerosing Cholangitis
Serum
Cholangiocarcinoma
Early Detection of Cancer
Biopsy
Sensitivity and Specificity
Genes
Neoplasms

Keywords

  • ampulla
  • bile duct
  • cholangiocarcinoma
  • dysplasia
  • genomics
  • molecular
  • pancreas
  • pancreatic cancer
  • precision medicine

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures. / Singhi, Aatur D.; Nikiforova, Marina N.; Chennat, Jennifer; Papachristou, Georgios I.; Khalid, Asif; Rabinovitz, Mordechai; Das, Rohit; Sarkaria, Savreet; Ayasso, M. Samir; Wald, Abigail I.; Monaco, Sara E.; Nalesnik, Michael; Ohori, N. Paul; Geller, David; Tsung, Allan; Zureikat, Amer H.; Zeh, Herbert; Marsh, J. Wallis; Hogg, Melissa; Lee, Kenneth; Bartlett, David L.; Pingpank, James F.; Humar, Abhinav; Bahary, Nathan; Dasyam, Anil K.; Brand, Randall; Fasanella, Kenneth E.; McGrath, Kevin; Slivka, Adam.

In: Gut, 01.01.2019.

Research output: Contribution to journalArticle

Singhi, AD, Nikiforova, MN, Chennat, J, Papachristou, GI, Khalid, A, Rabinovitz, M, Das, R, Sarkaria, S, Ayasso, MS, Wald, AI, Monaco, SE, Nalesnik, M, Ohori, NP, Geller, D, Tsung, A, Zureikat, AH, Zeh, H, Marsh, JW, Hogg, M, Lee, K, Bartlett, DL, Pingpank, JF, Humar, A, Bahary, N, Dasyam, AK, Brand, R, Fasanella, KE, McGrath, K & Slivka, A 2019, 'Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures', Gut. https://doi.org/10.1136/gutjnl-2018-317817
Singhi, Aatur D. ; Nikiforova, Marina N. ; Chennat, Jennifer ; Papachristou, Georgios I. ; Khalid, Asif ; Rabinovitz, Mordechai ; Das, Rohit ; Sarkaria, Savreet ; Ayasso, M. Samir ; Wald, Abigail I. ; Monaco, Sara E. ; Nalesnik, Michael ; Ohori, N. Paul ; Geller, David ; Tsung, Allan ; Zureikat, Amer H. ; Zeh, Herbert ; Marsh, J. Wallis ; Hogg, Melissa ; Lee, Kenneth ; Bartlett, David L. ; Pingpank, James F. ; Humar, Abhinav ; Bahary, Nathan ; Dasyam, Anil K. ; Brand, Randall ; Fasanella, Kenneth E. ; McGrath, Kevin ; Slivka, Adam. / Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures. In: Gut. 2019.
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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.",
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TY - JOUR

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

AU - Singhi, Aatur D.

AU - Nikiforova, Marina N.

AU - Chennat, Jennifer

AU - Papachristou, Georgios I.

AU - Khalid, Asif

AU - Rabinovitz, Mordechai

AU - Das, Rohit

AU - Sarkaria, Savreet

AU - Ayasso, M. Samir

AU - Wald, Abigail I.

AU - Monaco, Sara E.

AU - Nalesnik, Michael

AU - Ohori, N. Paul

AU - Geller, David

AU - Tsung, Allan

AU - Zureikat, Amer H.

AU - Zeh, Herbert

AU - Marsh, J. Wallis

AU - Hogg, Melissa

AU - Lee, Kenneth

AU - Bartlett, David L.

AU - Pingpank, James F.

AU - Humar, Abhinav

AU - Bahary, Nathan

AU - Dasyam, Anil K.

AU - Brand, Randall

AU - Fasanella, Kenneth E.

AU - McGrath, Kevin

AU - Slivka, Adam

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

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.

KW - ampulla

KW - bile duct

KW - cholangiocarcinoma

KW - dysplasia

KW - genomics

KW - molecular

KW - pancreas

KW - pancreatic cancer

KW - precision medicine

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U2 - 10.1136/gutjnl-2018-317817

DO - 10.1136/gutjnl-2018-317817

M3 - Article

C2 - 30971436

AN - SCOPUS:85064191910

JO - Gut

JF - Gut

SN - 0017-5749

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