Routine staple-line clip reinforcement during laparoscopic distal pancreatectomy does not reduce clinically relevant pancreatic fistula: a multicenter randomized clinical trial

Background: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains a leading cause of morbidity after laparoscopic distal pancreatectomy (LDP), with rates plateauing at 20%–30%. Staple-line clip reinforcement is a widely used technical adjunct intended to reduce CR-POPF, but multicenter randomized evidence supporting its routine use is lacking. This study aimed to evaluate whether routine clip reinforcement reduces CR-POPF incidence and whether its effect is influenced by pancreatic texture or friability. Materials and methods: This multicenter, open-label, randomized clinical trial was conducted at three tertiary referral centers in the Republic of Korea between June 2021 and February 2025. A total of 190 adult patients undergoing elective LDP were randomized 1:1 to stapled transection with metallic clip reinforcement (clip group, n = 96) or standard stapled transection alone (no-clip group, n = 94). The primary outcome was CR-POPF incidence (ISGPS grade B or C). Prespecified subgroup analyses assessed treatment-by-subgroup interactions according to pancreatic texture, friability, body mass index, and operation time. Results: In the intention-to-treat analysis, CR-POPF occurred in 21 of 96 patients (21.9%) in the clip group and 26 of 94 patients (27.7%) in the no-clip group [risk difference, −5.8% (95% CI, −17.5%–6.0%); P = 0.45]. No grade C fistulas occurred. Per-protocol analysis yielded consistent results. No significant treatment effect modification was observed in any prespecified subgroup. Multivariable analysis identified prolonged operation time as the only independent risk factor for CR-POPF [adjusted OR, 1.012 per minute (95% CI, 1.004–1.020); P = 0.004]. Conclusion: Routine staple-line clip reinforcement during LDP did not significantly reduce CR-POPF incidence. These findings do not support its routine use in an unselected LDP population and suggest that operative efficiency may be a more relevant target for CR-POPF prevention than additional technical reinforcement.