Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2021; 27(27): 4371-4382
Published online Jul 21, 2021. doi: 10.3748/wjg.v27.i27.4371
Impact of surgery for chronic pancreatitis on the risk of pancreatic cancer: Untying the Gordian knot
Raja Kalayarasan, Sankar Narayanan, Jayaprakash Sahoo, Pazhanivel Mohan
Raja Kalayarasan, Sankar Narayanan, Department of Surgical Gastroenterology, JIPMER, Puducherry 605006, India
Jayaprakash Sahoo, Department of Endocrinology, JIPMER, Puducherry 605006, India
Pazhanivel Mohan, Department of Medical Gastroenterology, JIPMER, Puducherry 605006, India
Author contributions: Kalayarasan R, Narayanan S, Sahoo J and Mohan P did the literature search; Kalayarasan R wrote the first draft of the review; Narayanan S, Sahoo J and Mohan P conceptualized the work, supervised the writing, gave intellectual input, and critically revised the manuscript.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Raja Kalayarasan, MBBS, MCh, MS, Associate Professor, Department of Surgical Gastroenterology, JIPMER, Dhanvnatri nagar, Gorimedu, Puducherry 605006, India.
Received: January 28, 2021
Peer-review started: January 28, 2021
First decision: May 2, 2021
Revised: May 10, 2021
Accepted: June 22, 2021
Article in press: June 22, 2021
Published online: July 21, 2021

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.

Keywords: Chronic pancreatitis, Pancreatic adenocarcinoma, Pancreatic cancer, Surgery, Hereditary pancreatitis, Pancreatitis

Core Tip: Chronic pancreatitis (CP) is a significant risk factor for pancreatic cancer (PC). However, the relative risk is not as high as previously reported. Persistent pancreatic inflammation plays an important role in pancreatic carcinogenesis, and genetic mutations implicated in the pathogenesis of CP are not directly involved in the development of PC. Although surgery for CP reduces the risk of PC, the evidence is not strong enough to recommend routine prophylactic surgery in CP patients. The risk stratification proposed in this review considers the genetic and environmental factors that could guide future prospective studies and select patients for prophylactic surgery.