Impact of surgery for chronic pancreatitis on the risk of pancreatic cancer: Untying the Gordian knot

Pancreatic ductal adenocarcinoma is an aggressive tumor with poor long-term outcomes. Chronic pancreatitis (CP) is considered a risk factor for the development of pancreatic cancer (PC). Persistent pancreatic inflammation and activation of pancreatic stellate cells play a crucial role in the pathogenesis of CP-related PC by activating the oncogene pathway. While genetic mutations increase the possibility of recurrent and persistent pancreatic inflammation, they are not directly associated with the development of PC. Recent studies suggest that early surgical intervention for CP might have a protective role in the development of CP-related PC. Hence, the physician faces the clinical question of whether early surgical intervention should be recommended in patients with CP to prevent the development of PC. However, the varying relative risk of PC in different subsets of CP underlines the complex gene-environment interactions in the disease pathogenesis. Hence, it is essential to stratify the risk of PC in each individual patient. This review focuses on the complex relationship between CP and PC and the impact of surgical intervention on PC risk. The proposed risk stratification based on the genetic and environmental factors could guide future research and select patients for prophylactic surgery.