Risk factors for pancreatic cancer in individuals with intraductal papillary mucinous neoplasms and no high-risk stigmata during up to 5 years of surveillance: a prospective longitudinal cohort study

Background: Cyst size, its growth rate, and diameter of the main pancreatic duct (MPD) are all associated with pancreatic carcinoma prevalence in intraductal papillary mucinous neoplasms (IPMNs). Objective: To examine the above factors in relation to future risk of incident pancreatic carcinoma in individuals with IPMNs harbouring no high-risk stigmata. Design: In a prospective longitudinal cohort, we analysed 2549 patients with IPMNs. A multivariable cause-specific Cox proportional hazards regression model was built to estimate HRs for incident pancreatic carcinoma. Results: IPMN size at baseline and its annual growth rate over 2 years of follow-up were associated with incident pancreatic carcinoma (p_trend<0.001). The multivariable cause-specific HR per 10 mm increase in IPMN size was 1.28 (95% CI 1.10 to 1.50). The annual growth rates of 1.5-2.4 mm/year and ≥2.5 mm/year over 2 years were associated with multivariable cause-specific HRs of 1.91 (95% CI 0.78 to 4.67) and 4.52 (95% CI 2.28 to 8.98), respectively (vs <1.5 mm/year). Neither IPMN size at 5 years nor its maximum growth rate during 5 years was associated with incident pancreatic carcinoma (p_trend>0.07). MPD diameter at 5 years was associated with incident pancreatic carcinoma (multivariable cause-specific HR per 2 mm increase, 2.12; 95% CI 1.72 to 2.63). A predictive nomogram was generated for calculating the risk of incident pancreatic carcinoma. Conclusion: IPMN size and its growth rate predict future pancreatic carcinoma risk only during first 5 years of follow-up. MPD diameter at 5 years may identify patients who still harbour a high risk for pancreatic carcinoma.