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THE INFLUENCE OF INTRAOPERATIVE BLOOD LOSS ON FISTULA DEVELOPMENT FOLLOWING PANCREATODUODENECTOMY
Maxwell T. Trudeau*1, Fabio Casciani1,3, Thomas Seykora2, Laura Maggino3, Charles Vollmer1, Pancreas Fistula Study Group1
1Department of Surgery, Perelman School of Medicine , Philadelphia, PA; 2Georgetown University School of Medicine, Washington DC, ; 3University of Verona, Verona, Italy

Intro
Minimizing blood loss has been shown to decrease transfusions and provide better perioperative outcomes in pancreatoduodenectomy (PD). Additionally, elevated blood loss increases risk for clinically-relevant pancreatic fistula (CR-POPF) and is an essential component, contributing up to 30%, of the 10-point Fistula Risk Score. This study aims to analyze the pivotal role of blood loss on CR-POPF development.
Methods
Pre- and intraoperative factors, along with subsequent outcomes, of 5,534 PDs were accrued from a 17-institution, international collaborative (2003-2018). Four progressive cohorts of estimated blood loss (EBL) were categorized; extremely low (≤150mL; 10 percentile), below median (151-400mL), above median (401-1,000mL), and extremely high (>1,000mL; 90 percentile). Multivariable regression analyses (MVA) were employed to identify factors associated with CR-POPF, and also EBL. Lastly, expected occurrence of CR-POPF was calculated using the FRS, based on hypothetical reductions of risk points attributed to EBL.
Results
CR-POPF developed in 13.6% of patients (N=753; Grade B=11.1%; Grade C=2.5%) and median EBL was 400mL (IQR 250-600mL). Both CR-POPF and Grade C POPF were associated with elevated EBL (median 350 vs. 400mL; p=0.002 and 372 vs. 500mL; p<0.001, respectively). Furthermore, progressive EBL cohorts displayed incremental CR-POPF rates (8.5, 13.4, 15.2, and 16.9%; p<0.001), which was even more substantial in the 55% of patients with soft glands (11.5, 19.7, 26.3, and 31.8%; p<0.001). MVA revealed factors associated with CR-POPF were: soft gland texture (OR 4.38), pancreatic duct diameter (4mm, OR 1.44; 3mm, OR 1.61; 2mm, OR 2.01; 1mm, OR 1.81), high risk pathology (OR 1.62), prophylactic octreotide use (OR 2.42), surgeon experience (0-10yrs, OR 1.58; 11-21yrs, OR 1.38; >21yrs = Ref) and EBL (151-400mL, OR 1.42; 401-1,000mL, OR 2.08; >1000mL OR 2.38). On the other hand, factors associated with EBL≤400 were: age<65 (OR 1.19), and surgeon experience (0-10yrs, OR 4.54; 11-21yrs, OR 3.90). Lastly, hypothetical projections (Figure) demonstrate significant reductions in CR-POPF can be obtained with one-, two-, and three-point decreases in FRS points attributed to EBL risk (12.2, 17.4, and 20.0% reductions, respectively; p<0.001). This is especially pronounced in High Risk (FRS7-10) patients, who demonstrate up to a 31% abrogation (p<0.001).
Conclusion
Blood loss independently contributes significant risk to CR-POPF – particularly in more vulnerable scenarios. Substantial reductions in CR-POPF occurrence are projected by minimizing EBL. Unlike well-recognized, endogenous risk factors for fistula, EBL is associated with surgical experience, and appears to be an actionable target for improvement. Future studies should be directed towards investigating the mechanistic effects governing the interplay between blood loss and CR-POPF occurrence.


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