Pancreatic fibrosis, acinar atrophy and chronic inflammation in surgical specimens associated with survival in patients with resectable pancreatic ductal adenocarcinoma

BMC Cancer

Ari Ristimäki¹  Leena Kylänpää²  Marianne Udd²  Tiina Vuorela²  Taija Korpela²  Harri Mustonen³  Hanna Seppänen³  Caj Haglund³ 

[1] Department of Pathology, HUSLAB, HUS Diagnostic Center, Helsinki University Hospital and Applied Tumor Genomics Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland;Gastroenterological Surgery, Abdominal Center, Helsinki University Hospital and University of Helsinki, Haartmaninkatu 4, 00029, PL 340, Helsinki, HUS, Finland;Gastroenterological Surgery, Abdominal Center, Helsinki University Hospital and University of Helsinki, Haartmaninkatu 4, 00029, PL 340, Helsinki, HUS, Finland;Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland;

关键词: Pancreatic cancer;    Stroma;    Tumor–stroma interactions;    Chronic pancreatitis;   

DOI  :  10.1186/s12885-021-09080-0

来源: Springer

【 摘 要 】

BackgroundPancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies, is increasing in incidence. However, the stromal reaction pathophysiology and its role in PDAC development remain unknown. We, therefore, investigated the potential role of histological chronic pancreatitis findings and chronic inflammation on surgical PDAC specimens and disease-specific survival (DSS).MethodsBetween 2000 and 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 and histological findings were evaluated applying international guidelines.ResultsDSS 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% CI 10.3–30.9; log-rank test p = 0.001]. Multivariate analysis revealed that Ca 19–9 > 37 kU/l [hazard ratio (HR) 1.48, 95% CI 1.02–2.16], lymph node metastases N1–2 (HR 1.71, 95% CI 1.16–2.52), tumor size > 30 mm (HR 1.47, 95% CI 1.04–2.08), the combined effect of fibrosis and acinar atrophy (HR 1.91, 95% CI 1.27–2.88) and the combined effect of fibrosis, acinar atrophy and chronic inflammation (HR 1.63, 95% CI 1.03–2.58) independently served as unfavorable prognostic factors for DSS. However, we observed no significant associations between tumor size (> 30 mm) and the degree of perilobular fibrosis (p = 0.655), intralobular fibrosis (p = 0.587), acinar atrophy (p = 0.584) or chronic inflammation (p = 0.453).ConclusionsOur 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.

【 授权许可】

CC BY