Pancreatic Fibrosis, Acinar Atrophy and Chronic Inflammation in Surgical Specimens Associated with Survival in Patients with Resectable Pancreatic Ductal Adenocarcinoma

Abstract

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. However, the stromal reaction pathophysiology and its role in PDAC development remain unknown. We aimed to investigate the potential role of histological chronic pancreatitis findings and chronic inflammation on surgical PDAC specimens and disease-specific survival (DSS). Method: Between 2000–2016, we retrospectively enrolled 236 PDAC patients treated with curative-intent pancreatic surgery at Helsinki University Hospital. All pancreatic transection margin slides were re-reviewed. Results: DSS among patients with no fibrosis, acinar atrophy or chronic inflammation identified on pathology slides was significantly better than DSS among patients with fibrosis, acinar atrophy and chronic inflammation [median survival: 41.8 months, 95% confidence interval (CI)26.0–57.6 vs. 20.6 months, 95% CI10.3–30.9; log-rank test p = 0.001]. Multivariate analysis revealed that Ca 19-9 >37 kU/l [hazard ratio (HR)1.48, 95% CI1.02–2.16], lymph node metastases N1–2 (HR1.71, 95% CI1.16–2.52), tumor size >30 mm (HR1.47, 95% CI1.04–2.08), the combined effect of fibrosis and acinar atrophy (HR1.91, 95% CI1.27–2.88) and the combined effect of fibrosis, acinar atrophy and chronic inflammation (HR1.63, 95% CI1.03–2.58) independently served as unfavorable prognostic factors for DSS. However, we observed no significant associations between tumor size (> 30 mm) and the degree of perilobular or (p=0.655) intralobular fibrosis (p=0.587) or acinar atrophy (p=0.584). Conclusions: Our results indicate that the pancreatic stroma is associated with PDAC patients’ DSS. Additionally, the more severe the fibrosis, acinar atrophy and chronic inflammation, the worse the impact on DSS, thereby warranting further studies investigating stroma-targeted therapies.