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Number of worrisome features is associated with increasing risk of malignancy in Intraductal Papillary Mucinous Neoplasm (IPMN).
Piotr Zelga1, Yasmin Hernandez-Barco2, Motaz Qadan1, Cristina R. Ferrone1, Avinash Kambadakone4, Asif Jah3, Andrew L. Warshaw1, Keith D. Lillemoe1, Anita Balakrishnan3, Carlos Fernandez-del Castillo1
1Department of Surgery, Massachusetts General Hospital / Harvard Medical School, Boston, Massachusetts, United States, 2Division of Gastroenterology, Massachusetts General Hospital / Harvard Medical School, Boston, Massachusetts, United States, 3Department of Surgery, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom, 4Department of Radiology, Massachusetts General Hospital / Harvard Medical School, Boston, Massachusetts, United States

Objective: The 2017 revised International Association of Pancreatology guidelines for management of IPMN describe worrisome features (WF) and high-risk stigmata (HRS), recommending resection in the latter and further workup and close surveillance for patients with WF. The effect of multiple WF on the likelihood of malignancy has not been evaluated.
2. Design: Retrospective cross-sectional review of prospective databases
3. Setting: Two high-volume tertiary referral centers for HPB surgery
4. Patients 810 patients who underwent pancreatic resection for IPMN. Patients were retrospectively categorized into subgroups according to the number of worrisome features or high-risk stigmata.
5. Main Outcome Measure: presence of high-grade dysplasia (HGD) or invasive cancer on final pathology.
6. Results 379 (47%) patients had HRS, 370 (46%) had one or more WF, and 61 patients (7%) had neither. Malignancy was present in 70% (n=267) of patients with HRS and in 30% (n=127) of those with WF. Only 3/61 patients without WF/HRS had malignancy, and all only in the form of HGD. The risk of malignancy increased in a stepwise fashion with the number of WF, was 23%, 32%, and 59%, with 1, 2, and 3 WF, respectively (p= 0.001), and reached 100% in patients with 4 or more. Although the likelihood ratios differed for particular WF, the areas under the curve were not statistically different.
7. Conclusions We confirm that presence of HRS in IPMN is associated with a very high likelihood of malignancy. The presence of a single WF has a malignancy risk of 23%, and additional WF increase this risk significantly. When 3 or more are present, the risk is similar to that of HRS.


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