Acute pancreatitis is a sudden-onset inflammatory disease of the pancreas. Although acute pancreatitis promotes development of pancreatic cancer in mouse models, there have been conflicting findings from epidemiology studies. This could be partly because the studies did not include adequate lag periods from acute pancreatitis to pancreatic cancer, or report associations at different follow-up times.
Jakob Kirkegård et al conducted a nationwide population-based matched cohort study in Denmark to determine the risk of pancreatic cancer in 41,669 patients with acute pancreatitis compared with an age- and sex- matched comparison cohort from the general population (controls, n=208,340).
They followed the patients with acute pancreatitis and controls from their respective index dates until pancreatic cancer (recorded in the Danish Cancer Registry), chronic pancreatitis/other exocrine pancreatic disease, pancreatic resection or transplantation, death, emigration, or November 1, 2013 (whichever came first).
The median follow-up time for the pancreatitis cohort was 5.3 years and for the controls was 5.0 years. Patients with acute pancreatitis had higher burdens of comorbidity, including alcohol- and smoking-related diseases, gallstones, obesity, and diabetes, than controls.
After accounting for these, Kirkegård et al found that patients with acute pancreatitis had an increased risk of pancreatic cancer compared with controls.
In total, 937 cancers occurred in the study population. Patients with acute pancreatitis had increased risk of pancreatic cancer compared with the comparison subjects within the first 2 years of follow-up (adjusted hazard ratio, 19.28; 95% CI 14.62–25.41).
The risk decreased over time but remained high after more than 5 years of follow-up (adjusted hazard ratio, 2.02; 95% CI 1.57–2.61). Patients followed for more than 5 years after an initial episode of acute pancreatitis still had a higher risk of pancreatic cancer than controls (adjusted hazard ratio, 2.02; 95% CI 1.57–2.61).
The 2-year and 5-year absolute risks of pancreatic cancer among patients with acute pancreatitis were 0.70% (95% CI 0.62%–0.78%) and 0.87% (95% CI 0.78%–0.97), respectively (see figure).
When Kirkegård et al stratified patients according to etiology, a sensitivity analysis found patients with idiopathic pancreatitis have the highest risk of pancreatic cancer, followed by patients with biliary pancreatitis. The authors could not make meaningful interpretations of data from patients with alcohol-associated or endoscopic retrograde cholangiopancreatography (ERCP)-related pancreatitis.
Although Kirkegård et al did not have information on potential confounders, such as tobacco smoking and alcohol consumption, they adjusted their estimates for smoking- and alcohol-related conditions.
The authors explain that previous studies did not report risk estimates by follow-up time, which are essential for interpretation and comparison of findings from different studies, because pancreatic cancer takes years to develop. Kirkegård et al state that a pancreatic cancer observed shortly after the start of a follow up (within 2 years) was likely present at the time of acute pancreatitis diagnosis. The authors did in fact find a 20-fold increased risk of pancreatic cancer within the first 2 years after acute pancreatitis diagnosis, consistent with previous studies.
Chronic pancreatitis also increases risk for pancreatic cancer. Studies are needed to determine the mechanisms of these processes.