Study data published in JAMA Surgery indicate that combined division of the splenic vein is non-inferior to separate division, with regards to safety. Per these findings, investigators advised that isolating the splenic vein from the pancreatic parenchyma may be unnecessary during distal pancreatectomy (DP).
Mechanical staplers are increasingly utilized to dissect the pancreas during DP. Compared with customary DP, in which the splenic vein is ligated and divided after separation from the pancreatic parenchyma, the use of mechanical staplers favors the dissection of the splenic vein with the pancreatic parenchyma. The relative safety of these 2 techniques remains unclear. To elucidate the potential risk of complications in combined vs separate division of the splenic vein during DP, investigators conducted a multicenter, prospective, randomized phase 3 trial at multiple hospitals in Japan.
Eligible patients were scheduled to undergo DP for pancreatic body and tail cancer. Patients were centrally randomized in a 1:1 ratio to either separate or combined division of the splenic vein during DP. Patient procedures took place between 2016 and 2019. The primary endpoint was the incidence of grade B/C pancreatic fistula (PF) within 6 months of surgery.
Patients were also followed for the development of additional complications, including intra-abdominal hemorrhage. Based on prior studies, investigators set the assumed incidence rate of B/C PF in the cohort to 10%. In comparing incidence rates between the combined and separate division groups, the noninferiority margin was set at 9%. Logistic regression models were used to assess the relative risk for complications in the combined vs separate groups.
The intent-to-treat cohort consisted of 316 patients, among whom 159 (50.3%) underwent separate division and 157 (49.7%) underwent combined division. Preoperative characteristics were comparable between groups. Overall, the proportion of grade B/C PF in the separate division group was 27.1%, compared with 28.6% in the combined division group. As such, the risk of grade B/C PF was slightly higher in the combined division group, though the odds ratio was not significantly elevated (odds ratio [OR], 1.108; 95% confidence interval [CI], 0.847-1.225).
When analyses were restricted to patients who underwent treatment according to protocol, the proportions of grade B/C PF were 27.4% and 27.1% in the separate and combined division groups, respectively (OR, 1.003; 95% CI, 0.827-1.217). In both analyses, combined division of the splenic vein was noninferior to separate division with respect to the incidence of grade B/C PF.
Complication rates were also similar between groups. While the rates of hemostasis of the stasis line and pancreatic injury were slightly higher in the combined vs separate division groups, the differences were not statistically significant. Postoperative intra-abdominal hemorrhage was observed in 1.3% of patients in both groups. Per these data, investigators concluded that combined division of the splenic vein is noninferior to separate division in terms of safety signals.
In terms of study limitations, investigators acknowledged that intra-abdominal hemorrhage may have been a more clinically relevant primary endpoint. However, its low incidence overall would have required a much larger study cohort to approach sufficient statistical power. Additionally, post-DP hemorrhage is thought to be a result of grade B/C PF, and thus PF was selected as a relevant proxy for hemorrhage and other complications.
“In conclusion, [our] trial successfully demonstrated the noninferiority of combined division of the splenic vein compared with separate division…in terms of the incidence of grade B/C PF,” investigators wrote. “Thus, the safety of this procedure was established such that it could be recommended with more confidence.”
Disclosure: Two study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Yamada S, Fujii T, Sonohara F, et al. Safety of combined division vs separate division of the splenic vein in patients undergoing distal pancreatectomy: a noninferiority randomized clinical trial. JAMA Surg. Published online March 3, 2021. doi: 10.1001/jamasurg.2021.0108