Redefining postpancreatectomy hemorrhage: Bleeding sources, cryptogenic events, and predictors of severity-analysis of 1,722 consecutive pancreaticoduodenectomies.

Abstract

Postpancreatectomy hemorrhage complicates 3%-10% of pancreaticoduodenectomies and is associated with mortality rates up to 20%. Clinically relevant postoperative pancreatic fistula is a major risk factor. This study aimed to characterize bleeding sources and identify predictors of severe hemorrhage in patients with clinically relevant postoperative pancreatic fistula. We retrospectively analyzed 1,722 consecutive pancreaticoduodenectomies performed between January 2013 and December 2024 at a high-volume tertiary center. Bleeding sources were systematically classified, and microbiological profiles of peripancreatic collections were reviewed. Multivariable logistic regression identified independent predictors of grade B/C postpancreatectomy hemorrhage in patients with clinically relevant postoperative pancreatic fistula. Cryptogenic postpancreatectomy hemorrhage was defined as grade B/C hemorrhage without an identifiable source despite comprehensive evaluation. Postpancreatectomy hemorrhage occurred in 135 patients (7.8%), including 89 cases (5.2%) of grade B/C hemorrhage. The pancreaticojejunal anastomosis was the most frequent bleeding source (15.6%), followed by branches of the superior mesenteric (9.6%) and hepatic (8.1%) arteries; the gastroduodenal artery accounted for only 3.7%. Independent predictors of severe hemorrhage were bile leak (odds ratio, 4.50; 95% confidence interval, 2.01-10.07; P < .001) and gram-negative infection, predominantly Klebsiella pneumoniae (odds ratio, 2.55; 95% confidence interval, 1.18-5.51; P = .017). A nomogram incorporating these factors showed acceptable discrimination (area under the curve, 0.701) with good internal validation (area under the curve, 0.791). Cryptogenic postpancreatectomy hemorrhage occurred in 24.7% of grade B/C cases and was associated with lower mortality than source-identified hemorrhage. In clinically relevant postoperative pancreatic fistula patients, bile leak and K pneumoniae infection independently predict severe postpancreatectomy hemorrhage. The pancreaticojejunal anastomosis was the most common bleeding site, whereas cryptogenic postpancreatectomy hemorrhage appears to represent a lower-mortality subgroup once arterial bleeding is excluded.