Abstract
IMPORTANCE: The progression of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas to malignant disease is still poorly understood. Observational and surgical series have failed to provide comprehensive information. OBJECTIVE: To identify dynamic variables associated with the development of malignant neoplasms by combining pathological features with data from preoperative repeated observations. DESIGN, SETTING, AND PARTICIPANTS: The Crossover Observational Multicentric Study included a retrospective cohort of patients with branch-duct IPMNs (BD IPMNs) enrolled in a surveillance program from January 1, 2000, to December 31, 2019. Patients were enrolled from 5 referral centers: the Pancreas Institute, Verona, Italy; Seoul National University Hospital, Seoul, South Korea; Singapore General Hospital, Singapore; Johns Hopkins School of Medicine, Baltimore, Maryland; and University of Texas MD Anderson Cancer Center, Houston. Patients underwent a minimum of 12 months of preoperative surveillance (median, 37 [interquartile range (IQR), 20-68] months). MAIN OUTCOMES AND MEASURES: Dynamic variables associated with malignant disease were explored to estimate the presence of high-grade dysplasia (HGD) and invasive cancer at final pathological examination. RESULTS: A total of 292 patients were included in the analysis (137 women [46.9%] and 155 men [53.1%]; median age, 64 [IQR, 56-71] years). During surveillance, 27 patients (9.2%) developed a worrisome feature after 5 years, and 46 of 276 (16.7%) developed high-risk stigmata (HRS). At final pathological evaluation, 107 patients (36.6%) had HGD or invasive cancer, and 16 (5.5%) had IPMNs with concomitant pancreatic ductal adenocarcinoma. Rates of HGD and invasive cancer at pathological evaluation significantly differed between those without worrisome features and those developing HRS from a previous worrisome feature (9 [27.3%] vs 13 [61.9%]; P < .001). Developing an additional worrisome feature during surveillance (odds ratio [OR], 3.24 [95% CI, 1.38-7.60]; P = .007) or an HRS from a baseline worrisome feature (OR, 2.87 [95% CI, 1.01-8.17]; P = .048) was associated with HGD at final pathological evaluation. Among HRS, development of jaundice on a low-risk cyst was independently associated with invasive cancer (OR, 16.04 [95% CI, 2.94-87.40]; P = .001). CONCLUSIONS AND RELEVANCE: These findings suggest that in BD IPMNs under surveillance, harboring a stable worrisome feature carries the lowest risk of malignant disease. Development of additional worrisome features or HRS is associated with the presence of HGD, whereas the occurrence of jaundice is associated with invasive cancer.