Changes to management influenced by next-generation sequencing of pancreatic duct aspirates among patients with main pancreatic duct dilatation of unclear etiology: a multicenter cohort study.

BACKGROUND AND AIMS: Main pancreatic duct (MPD) dilatation 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 dilatation.

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 dilatation resulted in surgical management for 11 patients with no previous indication. In 6 cases with MPD ≥10 mm, dilatation 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 dilatation, 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 dilatation of unclear etiology.