Next-generation Sequencing Improves The Detection of Malignant Biliary Strictures and Changes Management

Olgert Bardhi; Alex Jones; Daniel Ellis; Thomas Tielleman; Anna Tavakkoli; Dutch Vanderveldt; Markus Goldschmiedt; Aatur Singhi; Nisa Kubiliun; Tarek Sawas

doi:10.1016/j.gie.2024.12.024

Next-generation Sequencing Improves The Detection of Malignant Biliary Strictures and Changes Management

Gastrointest Endosc. 2024 Dec 21:S0016-5107(24)03828-8. doi: 10.1016/j.gie.2024.12.024. Online ahead of print.

Authors

Affiliations

¹ Department of Medicine, University of Texas Southwestern, Dallas, TX.
² Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, TX.
³ Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA.
⁴ Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, TX. Electronic address: tarek.sawas@UTsouthwestern.edu.

PMID: 39716538
DOI: 10.1016/j.gie.2024.12.024

Abstract

Background and aims: Malignant biliary strictures (MBS) pose diagnostic and therapeutic challenges due to the frequent indeterminate results after initial sampling. Next generation sequencing (NGS) panel (BiliSeq) offers promise in MBS detection, but real-world performance remains uncertain. This study aimed to assess standard sampling techniques alone and with BiliSeq for malignancy detection in biliary strictures, and to evaluate management changes based on NGS.

Methods: This retrospective cohort study included 77 biliary stricture patients undergoing BiliSeq during ERCP. Sensitivity, specificity, PPV, and NPV were calculated, and sensitivity compared between tests using McNemar's test. Clinical impact was defined by identifying MBS patients with negative cytology/pathology correctly identified by BiliSeq.

Results: Among 77 patients (28 malignant, 49 benign) who underwent BiliSeq testing during ERCP. Primary sclerosing cholangitis (PSC) was present in 24 patients (31.2%). A mass was detected in 35.7% of MBS vs. 6.1% of benign cases (P=0.001). BiliSeq sensitivity for malignancy was 75% (95% CI: 55.1%-89.3%), surpassing the combination of cytology and biopsy 42.9% (95% CI: 24.5%-62.8%), p=0.03. Combining BiliSeq with cytology/biopsy improved sensitivity from 42.9% to 85.7%, P<0.001. Among MBS patients with negative cytology/biopsy (n=16), BiliSeq altered management in 75%.

Conclusion: NGS and pathological evaluation enhances MBS detection sensitivity, leading to management changes in 75% of cases when pathology testing is negative.

Keywords: biliary stricture; endoscopy; next-generation sequencing.