Changes to management influenced by next-generation sequencing of pancreatic duct aspirates among patients with main pancreatic duct dilation of unclear etiology: a multicenter cohort study - 03/02/26

Doi : 10.1016/j.gie.2025.11.025

Alex R. Jones, MD ¹, Amudhan Kannan, MBBS ², Dana Ley, MD ³, Oscar Ramirez Ramirez, MD ⁴, Megha Sheth, MD ¹, Gilbert Murimwa, MD ², Ali Abbas, MD ⁵, Abhi Deverakonda, BS ², Christofer Bishop, BSN, RN, OCN ⁶, Veronica Coleman, MPAS, PA-C ⁶, Blake Foley, MPAS, PA-C ⁶, Daniel Ellis, MD ⁶, Deepak Gopal, MD ³, Mark Benson, MD ³, Peter Stadmeyer, MD ³, Gaurav Khatri, MD ⁵, Syed Nabeel Zafar, MD, MPH ⁷, Patricio M. Polanco, MD ², Herbert Zeh, MD ², John Mansour, MD ², Jason Fleming, MD ², Aatur Singhi, MD, PhD ⁸, Rebecca Minter, MD, MBA ⁷, Nisa Kubiliun, MD ⁶, Patrick Pfau, MD ³, Tarek Sawas, MD, MPH ^6,^⁎

¹ Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA

² Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA

³ Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA

⁴ Department of Internal Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA

⁵ Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

⁶ Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA

⁷ Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA

⁸ Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

^∗ Corresponding author: Dr Tarek Sawas, Division of Digestive and Liver Diseases, University of Texas Southwestern, 1801 Inwood Rd, Site 6-102, Dallas, Texas 75235, USA. Division of Digestive and Liver Diseases University of Texas Southwestern 1801 Inwood Rd Site 6-102 Dallas Texas 75235 USA

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Tuesday 03 February 2026

Abstract

Background and Aims

Main pancreatic duct (MPD) dilation of unclear etiology presents a diagnostic challenge because the management of neoplastic and non-neoplastic causes differs significantly. We aimed to assess the clinical utility of next-generation sequencing (NGS) in the management of MPD dilation.

Methods

We retrospectively identified patients with dilated MPD (≥6 mm) of unclear etiology who underwent NGS at 2 academic institutions. The primary outcome was any change to management influenced by NGS compared with previous standard of practice. Adverse event rates of EUS fine-needle aspiration and ERCP were compared.

Results

A total of 62 patients with dilated MPD were identified; they had a mean age of 71.5 ± 12.1 years, and 53.2% were men. The majority had chronic pancreatitis (54.8%). The average MPD diameter was 8.6 ± 2.3 mm. MPD aspiration was performed by EUS fine-needle aspiration in 33 patients (53.2%) and ERCP in 29 patients (46.8%). The adverse event rate was 8.1%, with no difference between aspiration techniques observed. NGS mutations were present in 40 (64.5%) patients. The identification of mutations suggesting a neoplastic cause of MPD dilation resulted in surgical management for 11 patients with no previous indication. In 6 cases with MPD ≥10 mm, dilation was attributed to chronic pancreatitis and surgery was deferred despite previous practice of recommending surgery. Overall, management was changed in 17 (27.4%) patients.

Conclusions

In a multicenter cohort of patients with MPD dilation, NGS of MPD aspirates was safe and changed surgical management for more than one-quarter of patients. Providers should consider MPD sampling with NGS as an ancillary diagnostic modality for patients presenting with MPD dilation of unclear etiology.

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Abbreviations : CP, FNA, IPMN, MPD, NGS, PDAC, UPMC