The association between pancreatitis and pancreatic cancer is well-established, and it is mostly driven by CP. Over the past few decades, there has been an ongoing debate on whether AP carries the same risk of developing pancreatic cancer, and multiple studies aimed to quantify such risk. Kirkegard et al. conducted a large nationwide matched cohort study in Denmark, which included 40,000 patients with AP. This work concluded that the risk of PDAC in patients with AP was two-fold higher compared to that in the general population over a 5–10-year follow-up period [7]. These observations were similar to the findings from US studies utilizing the VA system database [8,9]. Bansal et al. published a case-control study including about 2600 veterans with PDAC and noncancer controls. This work demonstrated higher likelihood of having a history of AP preceding PDAC (OR 1.76; 95% CI: 1.28–2.41) [8]. Another Taiwanese study assessed AP and PDAC association [10] by evaluating 747 hospitalized patients with AP and 5976 controls. This work observed significantly higher five-year risk of developing PDAC in the AP cohort compared to that in controls (HR 9.10; 95% CI: 3.81–21.76). A large population-based study in Sweden reproduced similar conclusions of elevated PDAC risk in patients with AP in the first few years, but interestingly, this decreased over time [11]. Two meta-analyses were conducted to ascertain the effect of AP and PDAC association. Zhang et al. meta-analysis of four cohort studies estimated a pooled relative risk of 8.30 (95% CI: 4.27–16.13) [12]. Another meta-analysis of 11 observational studies, suggested higher PDAC incidence after AP with estimated pooled relative risk of 7.81 (95% CI: 5.00–12.19) [13]. Although these observations highlighted a robust association between AP and PDAC, the question of whether this is a causal effect or if AP is a presenting symptom of PDAC remains unanswered.

Multiple studies have shown that CP is highly associated with PDAC [8,14,15,16,17,18,19,20]. A multicenter, retrospective cohort study conducted by the International Pancreatitis Study Group showed that the cumulative risk of PDAC in patients with CP is 1.8% and 4% at 10 and 20 years, respectively, a rate which is from 15- to 16-fold greater than that of the general population [14]. Importantly, this risk was independent of sex, ethnicity, and type of pancreatitis (alcoholic and nonalcoholic). A single-center prospective cohort study verified these observations, concluding that CP patients have higher 5- and 10-year cumulative incidence of developing PDAC (1.1% and 1.7%) compared to that in age- and sex-matched controls [15]. Most convincingly, a meta-analysis of six cohort studies and one case-control study showed a pooled relative risk estimate of 13.3 for PDAC among patients with CP [16], which suggested that about five percent of patients with CP will develop PDAC within a 20-year follow-up period. These efforts proposed the higher causative association between long-standing CP and future PDAC development.