乌鸦传媒

Patients who develop acute pancreatitis are at increased risk of subsequent pancreatic cancer, with the highest rates in the first years after the acute episode but remaining elevated beyond 5 years, a Danish population-based study found.

During the first 2 years after admission for acute pancreatitis, the risk for these patients compared with the general population was increased 20-fold, with an adjusted hazard ratio for pancreatic cancer diagnosis of 19.52 (95% CI 14.81-25.73), according to Jakob Kirkegård, an MD, PhD student at Aarhus University Hospital in Aarhus, and colleagues.

From 2 to 5 years after the initial acute episode, the risk of pancreatic cancer was more than twice as high (HR 2.43, 95% CI 1.73-3.51), and beyond 5 years, the risk remained double that of the general population (HR 2.02, 95% CI 1.57-2.61), the researchers reported online in

Some experimental evidence suggests that pancreatitis can trigger pancreatic cancer, but data from previous studies have been limited and inconclusive, the team noted. For instance, in one of more than 2,500 U.S. veterans with pancreatic cancer, an association was seen between acute pancreatitis and cancer, but the analysis excluded only patients whose malignancy was diagnosed during the first year after the acute episode. This may not have been sufficient time to avoid confounding by surveillance bias or reverse causation, as pancreatic cancers typically evolve over years, Kirkegård et al said.

Therefore, to help clarify a potential association, he and his colleagues conducted a nationwide study utilizing data from the Danish National Patient Registry, the Civil Registration System, and the Danish Cancer Registry. The team received financial support from the Danish Cancer Society.

The investigators identified 41,669 patients admitted for acute pancreatitis from 1980 to 2012, and matched them with 208,340 individuals in the general population. Included cases were only those diagnosed after a 3-year washout period since the initiation of the patient registry (in 1977), to avoid the possibility of including prevalent cases.

The analysis was adjusted for alcohol- and smoking-related illnesses and comorbidity burden.

The median age of both cases and controls in the study was 56, and slightly more than half were men. Median follow-up time was 5.3 years among cases and 5 years for controls.

Compared with the comparison group, patients with pancreatitis had more relevant comorbidities, including obesity, diabetes, gallstones, and smoking/alcohol-related diseases.

A total of 937 cases of pancreatic cancer were found. During the first 2 years after the acute episode, the adjusted hazard ratios were high both for women (HR 20.52, 95% CI 13.09-30.95) and men (HR 19.28, 95% CI 13.26-27.60).

Elevated risks persisted after 5 years for both women (HR 2.23, 95% CI 1.58-3.17) and men (HR 1.87, 95% CI 1.28-2.71).

The absolute 2-year and 5-year risks of developing pancreatic cancer were 0.68% (95% CI 0.61-0.77) and 0.85% (95% CI 0.76-0.94).

The researchers also performed several sensitivity analyses to determine the robustness of their findings. In two analyses that were restricted to patients with at least 1 year of follow-up and more than 10 years of follow-up, respectively, the adjusted hazard ratios were 2.40 (95% CI 1.99-2.88) and 2.21 (95% CI 1.56-3.13).

In another sensitivity analysis that stratified according to pancreatitis etiology, the highest risks for pancreatic cancer were seen among those with idiopathic pancreatitis (HR 2.52, 95% CI 1.83-3.47) and biliary pancreatitis (HR 1.80, 95% CI 1.13-2.89).

Kirkegård cautioned that the study showed only an association, which does not establish causality: "However, we do consider our study to have eliminated the majority of confounding that could have caused an association between acute pancreatitis and pancreatic cancer," he told 乌鸦传媒.

"As such, our study suggests that we should start to consider acute pancreatitis as an actual risk factor for subsequent pancreatic cancer. Identification of risk factors is of immense importance, as this may facilitate earlier diagnosis, which is probably the way to improve survival from this fatal cancer."

As for potential mechanisms by which pancreatitis might lead to cancer, he noted that pancreatitis can activate stellate cells in the pancreas, "which in turn can lead to fibrosis and increased cell turnover." This can lead to activation of the Kras oncogene, which is mutated early in approximately 90% of cases of pancreatic cancer.

A limitation of the study, the researchers noted, was the assumption of accuracy of pancreatitis diagnoses in the national patient registry.

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