Risk Factors for Pancreatic Fistula Grade C after Pancreaticoduodenectomy: A Large Prospective, Multicenter Japan-Taiwan Collaboration Study

Abstract

Background: Postoperative pancreatic fistula (POPF) is a harmful complication after pancreaticoduodenectomy (PD). Grade C POPF, as defined by International Study Group of Pancreatic Fistula (ISGPF), is the most life-threatening complication. This study aims to evaluate risk factors for Grade C POPF after PD. Methods: This is a prospective, multicenter collaboration study based in Japan and Taiwan. Between 2014 and 2017, 3,022 patients were enrolled in this study and 2,762 patients were analysed after 260 patients were excluded (discontinuation of protocol treatment: n=241, incomplete information: n=19). We analysed risk factors of Grade C POPF based on the 2005 ISGPF scheme (sepsis, organ dysfunction, haemorrhage, reoperation, and/or death) and then separately by the updated 2016 ISGPF scheme (organ failure, reoperation, and/or death). Findings: Among 2,762 patients that underwent PD, 93 patients (3∙4%) developed Grade C POPF as defined by 2005 ISGPF and 46 patients (1∙7%) developed Grade C POPF as defined by 2016 ISGPF. We found eight independent risk factors associated with Grade C POPF as defined by 2005 ISGPF on multivariate analyses; male sex, body mass index (BMI) ≥25∙0 kg/m2, chronic steroid use, preoperative serum C-reactive protein ≥1∙0 mg/dL, soft pancreas, main duct size <3 mm, operative time ≥480 min, and intraoperative blood loss ≥1000 mL. Six independent risk factors for Grade C POPF as defined by 2016 ISGPF were found; BMI ≥25∙0 kg/m2, chronic steroid use, preoperative serum albumin <3∙0 mg/dL, soft pancreas, operative time ≥480 min, and intraoperative transfusion. When we developed Grade C POPF risk scoring models using these risk factors, the c-statistic of the risk model for Grade C POPF in 2005 ISGPF scheme was 0∙79, and that in 2016 ISGPF scheme was 0∙77. Interpretation: We identified risk factors for Grade C POPF after PD. These factors might assist surgeons to adopt intraoperative and postoperative strategies. Trial Registration: The study was registered on ClinicalTrials.gov (NCT02322424), and the University Hospital Medical Information Network Clinical Trials Registry (UMI15942). Funding Statement: This study was supported by the Japanese Society of Hepato-Biliary-Pancreatic Surgery and Taiwan Society of Gastrointestinal Surgery. Declaration of Interests: The authors declare no financial interests or potential conflicts of interest. Ethics Approval Statement: The study was initially approved by the Ethical Committee on Clinical Investigation of Wakayama Medical University Hospital (WMUH) (No. 1420), and then by the ethical committees of each participating institution.