Neutrophil-to-Lymphocyte Ratio Is Associated with Disease Progression in a Surveillance Cohort of Patients with Branch-Duct IPMN.

Background

A Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) are common pancreatic precursor lesions requiring varying duration of surveillance because of their potential for malignant transformation. Current risk stratification relies predominantly on imaging-based criteria defined by the Kyoto guidelines, while reliable blood-based biomarkers are lacking. The neutrophil-to-lymphocyte ratio (NLR) has been associated with invasive IPMN in surgical resected cases, but its role in routine BD-IPMN surveillance has not been investigated. This study investigated the association between NLR and disease progression in a large surveillance cohort of patients with BD-IPMN.

Methods

This retrospective two-center study included patients with image-based diagnosis of BD-IPMN who underwent at least one further follow-up endoscopic ultrasound (EUS) examination between 2006 and 2026 and had an available differential blood count. Disease progression was defined as the development of new worrisome features (WFs), high-risk stigmata (HRS), pancreatic resection for progressive disease, or IPMN-associated carcinoma.

Results

A total of 285 patients undergoing 2207 EUS examinations were included, with a mean EUS surveillance duration of 4.8 years. During follow-up, 63 patients (22.1%) developed at least one WF, 4 (1.4%) developed HRS, 11 (3.9%) underwent pancreatic resection, and 2 (0.7%) developed IPMN-associated carcinoma. NLR was significantly elevated in patients who developed WFs (p = 0.0023), HRS (p < 0.0001), underwent pancreatic resection (p = 0.0006), or had high-grade dysplasia (p = 0.0002). Baseline continuous NLR showed no significant discriminatory ability for subsequent disease progression (AUC, 0.563; 95% CI, 0.482-0.635; p = 0.136). Patients with an NLR above the cohort median (>2.36) had approximately twofold higher odds of subsequent disease progression (OR, 2.02; 95% CI, 1.02-3.98). Longitudinal analyses demonstrated significant increases in NLR preceding the development of WFs (p < 0.0001), HRS (p = 0.0265), and pancreatic resection (p = 0.0272). Rising NLR was particularly associated with cyst growth, cyst size ≥30 mm, and main pancreatic duct dilation.

Conclusions

Elevated and increasing NLR was associated with BD-IPMN progression and correlated with established markers of higher-risk disease. Longitudinal NLR assessment may represent a simple and widely available complementary biomarker for surveillance; however, its modest discriminatory performance warrants prospective validation before clinical implementation.