Postoperative Hyperamylasemia (POH) Is an Early Predictor of Pancreatic Fistula Occurrence and Severity After Distal Pancreatectomy

Objectives: The aim of this international multicentric study is to characterize postoperative hyperamylasemia (POH) after distal pancreatectomy (DP), with particular focus on its relationship with postoperative pancreatic fistula (POPF) occurrence and severity. Background: The clinical relevance of POH after DP and its relationship with the occurrence and severity of POPF have not been explored yet. Methods: All patients undergoing DP for any indication between 2015 and 2021 at 3 European referral centers for pancreatic surgery were retrospectively analyzed. Drain fluid amylase, C-reactive protein, and serum amylase were examined from postoperative day (POD) 1 to 3. Biochemical leak, POPF, POH, and postpancreatectomy hemorrhage were defined and graded according to ISGPS definitions. Results: In total, 1192 patients were included. Overall rates of POH and POPF were 18% (n= 210) and 29% (n= 344), respectively. The presence of drain fluid amylase ≥2000 U/L on POD 1 (OR=2.11, 95% CI: 1.68-2.86), C-reactive protein ≥200 mg/L on POD 3 (OR=2.19, 95% CI: 1.68-2.86), and POH (OR=1.58, 95% CI: 1.14-2.19) were all independent early predictors of POPF (all P<0.01). The presence of POH almost doubled the rate of POPF (43% vs 26%, P<0.001), and higher POPF severity presented also higher POH rates (no POPF=12%; biochemical leak=19%; B POPF=24%; C POPF=52%). Among patients developing POPF, patients with POH had higher rates of postpancreatectomy hemorrhage (22% vs 9%, P=0.001), sepsis (24% vs 13%; P=0.011), reoperation (21% vs 8%; P< 0.01), and mortality (3% vs 0.3%; P=0.025). Conclusions: The occurrence of POH is an early predictor of POPF and its severity after DP. The diagnosis of POH might define patients at higher risk for a complicated course, targeting them for prevention/mitigation strategies against pancreas-specific complications.