Circulating Cytokine Model Allows for Identification of Malignant Intraductal Papillary Mucinous Neoplasms

Abstract

Introduction: Intraductal papillary mucinous neoplasms (IPMNs) are the precursor lesions of pancreatic cancer. The objective of this study is to assess the discriminatory performance of circulating cytokines containing TNF-α, IL-2R, IL-6 and IL-8, and then build a novel predictive model to improve the diagnostic accuracy. Method: The demographic and clinical characteristics of consecutive patients histologically confirmed as IPMNs between March 2016 and December 2019 were retrospectively collected and analyzed for model establishment. Then, another prospective consecutive cohort was enrolled from March 2020 to January 2021 for further validation. Results: The circulating TNF-α, IL-2R, IL-6 and IL-8 levels were significantly elevated in malignant IPMNs compared to benign IPMNs (p<0.001), and all four circulating cytokines were verified as independent predictors (p<0.05). Then, based on the Logistic algorithm, a novel circulating cytokine score (CCS) was calculated and proved to be an independent predictive indicator (p<0.001). Besides CSS, two high-risk stigmata features containing presence of solid component (PSC) and main pancreatic duct (MPD) dilation ≥ 10 mm were also confirmed as independent indicators for predicting malignant IPMNs. Finally, a novel nomogram incorporating CCS with these two high-risk stigmata features showed a remarkable diagnostic performance both in the training and validation cohorts with AUCs of 0.928 and 0.873, respectively. Conclusion: CCS can be considered as a novel independent predictive indicator for malignant IPMNs, and the formulated nomogram model integrating CCS, PSC and MPD ≥ 10 mm will be a valuable and promising tool for predicting the probability of malignant IPMNs to implement appropriate managements.