Elham Afghani, MD, on Pancreatitis and Pancreatic Cancer

The incidence and mortality rate of pancreatic cancer is increasing despite advancements in treatment and surgical techniques. It is expected to be the second leading cause of cancer-related deaths by 2030.  It has a 5-year survival rate of 10% in the United States and 3% in Europe. According to the Surveillance, Epidemiology, and End Results (SEER) database, more than 50% of the cases are being diagnosed at late stages; only approximately 10% are being diagnosed at earlier stages, when the cancer is localized and resectable. Early detection provides the best opportunity to identify lesions in hopes of reducing mortality. However, there are no screening guidelines for pancreatic cancer in the United States.

Chronic inflammation seems to be a predisposing factor for carcinogenesis and associated with cancer development. Chronic pancreatitis (CP) is an inflammatory disease leading to destruction of acinar cells and fibrosis. Incidence rates of CP range from 5 to 12 per 100,000; the incidence rate of pancreatic cancer is around 13 per 100,000. A recent systematic review and meta-analysis found that the risk of pancreatic cancer in patients with chronic pancreatitis is 16-fold. However, whether this is secondary to tobacco and alcohol exposure— which are risk factors for both chronic pancreatitis and pancreatic cancer—or whether it is the activation of pancreatic stellate cells as a link, as stellate cells lead to carcinogenesis, or the combination heightens the risk, remains a question.

The strongest relationship between pancreatitis and pancreatic cancer has been found between hereditary pancreatitis, which is due to an underlying PRSS1 mutation (mutations of the cationic trypsinogen). This has been associated with a 40-fold lifetime risk of pancreatic cancer. The association between acute pancreatitis, chronic pancreatitis, and pancreatic cancer has been evaluated by several studies.

However, one must not also forget the instances in which acute pancreatitis may be an early clinical manifestation of pancreatic cancer. This occurs either through a tumor causing obstruction of the pancreatic duct or through an inflammatory process in general. The latter has been observed in mice expressing oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS). In a multicenter study of patients who were followed over a median follow-up time of 55 months after an initial episode of acute pancreatitis, researchers found that there was a 0.7% overall risk of pancreatic cancer. While a small proportion of patients with pancreatitis develop pancreatic cancer, this provides an opportunity for early detection in patients with pancreatitis.

References

1. Rijkers AP, Bakker OJ, Ahmed Ali U, et al. Risk of pancreatic cancer after a primary episode of acute pancreatitis. Pancreas; 2017;46(8):1018-1022. DOI: 10.1097/MPA.0000000000000879

2. Carriere C, Young AL, Gunn JR, et al. Acute pancreatitis accelerates initiation and progression to pancreatic cancer in mice expressing oncogenic Kras in the nestin cell lineage. PloS one 2011;6(11): e27725. doi: 10.1371/journal.pone.0027725

3. Weiss FU. Pancreatic cancer risk in hereditary pancreatitis. Front Physiol; 2014:5(70). DOI: 10.3389/fphys.2014.00070

4. Kirkegard J, Mortensen FV, Cronin-Fenton D. Chronic pancreatitis and pancreatic cancer risk: A systematic review and meta-analysis. Am J Gastroenterol. 2017;112(9):1366-1372. DOI: 10.1038/ajg.2017.218

5. Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology 2013;144(6):1252-1261. DOI: 10.1053/j.gastro.2013.01.068