• Elisa Bannone, Giovanni Marchegiani, Charles Vollmer, Giampaolo Perri, Giuseppa Procida, Gaetano Corvino, Sara Peressotti, Pier Giuseppe Vacca, Roberto Salvia, and Claudio Bassi.
• Department of General and Pancreatic Surgery-The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy.
• Ann. Surg. 2023 Aug 1; 278 (2): e293e301e293-e301.

ObjectiveTo evaluate whether postoperative serum hyperamylasemia (POH), with drain fluid amylase (DFA) and C-reactive protein (CRP), improves the Fistula Risk Score (FRS) accuracy in assessing the risk of a postoperative pancreatic fistula (POPF).Summary Background DataThe FRS predicts POPF occurrence using intraoperative predictors with good accuracy but intrinsic limits.MethodsOutcomes of patients who underwent pancreaticoduodenectomies between 2016 and 2021 were evaluated across FRS-risk zones and POH occurrence. POH consists of serum amylase activity greater than the upper limit of normal (52 U/l), persisting within the first 48 hours postoperatively (postoperative day -POD- 1 and 2).ResultsOut of 905 pancreaticoduodenectomies, some FRS elements, namely soft pancreatic texture (odds ratio (OR) 11.6), pancreatic duct diameter (OR 0.80), high-risk pathologic diagnosis (OR 1.54), but not higher blood loss (OR 0.99), were associated with POH. POH was an independent predictor of POPF, which occurred in 46.8% of POH cases ( P <0.001). Once POH occurs, POPF incidence rises from 3.8% to 42.9%, 22.9% to 41.7%, and 48.9% to 59.2% in patients intraoperatively classified at low, moderate and high FRS risk, respectively. The predictive ability of multivariable models adding POD 1 drain fluid amylase, POD 1-2 POH and POD 3 C-reactive protein to the FRS showed progressively and significantly higher accuracy (AUC FRS=0.82, AUC FRS-DFA=0.85, AUC FRS-DFA-POH=0.87, AUC FRS-DFA-POH-CRP=0.90, DeLong always P <0.05).ConclusionsPOPF risk assessment should follow a dynamic process. The stepwise retrieval of early, postoperative biological markers improves clinical risk stratification by increasing the granularity of POPF risk estimates and affords a possible therapeutic window before the actual morbidity of POPF occurs.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

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