Splenic Vein Resection with the Pancreatic Parenchyma Versus Separate Resection After Isolating the Parenchyma During Distal Pancreatectomy (COSMOS-DP Trial): A Multicentre, Randomised, Phase 3 Trial

Background: In distal pancreatectomy (DP), the splenic vein is isolated from the pancreatic parenchyma prior to being ligated and divided, to prevent intra-abdominal haemorrhage from the splenic vein stump with pancreatic fistula (PF). Conversely, dissecting the splenic vein with the pancreatic parenchyma is easy and timesaving. We aimed to establish the safety of combined resection of the splenic vein compared with separate resection of the splenic vein.   Methods: This study was designed as a multicentre prospective randomised phase 3 trial. Patients undergoing DP for pancreatic body and tail tumours were eligible for inclusion. Patients were centrally randomised (1:1) to either separate resection of the splenic vein or combined resection of the splenic vein. The primary endpoint was the incidence of grade B/C PF, and the incidence of intra-abdominal haemorrhage was included as one of the secondary endpoints. All results were analysed using the full analysis set. Findings: Between August 10, 2016 and July 30, 2019, 318 patients were randomly assigned, and two patients were excluded as ineligible. The full analysis population constituted 159 patients in the separate resection group and 157 patients in the combined resection group. In the full analysis set, the proportion of grade B/C PF in the separate resection group was 27·1% vs 28·6% in the combined resection group (adjusted odds ratio: 1·108, 95% confidence interval: 0·847–1·225; P=0·047), demonstrating non-inferiority of the combined resection of the splenic vein against separate resection. The incidence of postoperative intra-abdominal haemorrhage in the two groups was identical at 1·3%.    Interpretation: This study demonstrated non-inferiority of the combined resection of the splenic vein compared with separate resection of the splenic vein regarding safety. Thus, isolating the splenic vein from the pancreatic parenchyma is deemed unnecessary.   Trial Registration: This trial is registered at UMIN000023237 and clinical trials.gov, NCT02871804. Funding Statement: Wakayama Medical University. Declaration of Interests: We declare that we have no conflicts of interest. Ethics Approval Statement: This study was conducted according to the Declaration of Helsinki (Fortaleza, Brazil, October 2013) and the ethical guidelines for medical and health research involving human subjects in Japan. Written informed consent was obtained from all of the enrolled patients. Ethical approval for this study was obtained from the Institutional Review Board of each institution.