Postoperative Serum Hyperamylasemia (POH) Adds Sequential Value to the Fistula Risk Score (FRS) in Predicting Pancreatic Fistula after Pancreatoduodenectomy

Objective: To 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 data: The FRS predicts POPF occurrence using intraoperative predictors with good accuracy but intrinsic limits. Methods: Outcomes of patients who underwent pancreaticoduodenectomies (PD) 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). Results: Out of 905 PDs, some FRS elements, namely soft pancreatic texture (OR 11.6), pancreatic duct diameter (OR 0.80), high-risk pathological 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). Conclusions: POPF risk assessment should follow a dynamic process. The stepwise retrieval of early, postoperative biologic 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.