Impact of reinforced pancreaticojejunostomy with or without tissue adhesive glue modified cyanoacrylate following pancreaticoduodenectomy: a randomized controlled clinical trial

Abstract Background Postoperative pancreatic fistula (POPF) remains the most significant complication following pancreaticoduodenectomy (PD). This randomized controlled trial evaluated the efficacy of reinforcing the pancreaticojejunostomy (PJ) with Glubran ® 2, a modified N-butyl-2-cyanoacrylate adhesive, in reducing the rate of clinically relevant POPF. Methods This single-center randomized controlled trial with blinded patients and blinded outcome assessors enrolled 100 consecutive patients undergoing open PD for pancreatic head or periampullary cancer between 15 January 2025 and 15 January 2026. Patients were randomized 1:1 to Glubran ® 2-reinforced PJ (Glubran ® 2 group) or conventional PJ (Control group). The primary endpoint was the rate of POPF (Grade B/C per ISGPS 2016) within the 90-day postoperative period. Operating surgeons were not blinded; ward physicians, outcome assessors and statisticians were blinded. Results POPF (Grade B/C) occurred in 3 patients (6%) in the Glubran ® 2 group versus 11 patients (22%) in the Control group ( p = 0.041; Fisher’s exact test). Grade B POPF was 4% versus 16% ( p = 0.092) and Grade C POPF was 2% versus 6% ( p = 0.617); individual-grade comparisons were prespecified as exploratory. Overall morbidity (any complication) was 18% versus 54% ( p < 0.001) and severe complications (Clavien-Dindo ≥ IIIa) were 10% versus 36% ( p = 0.004). The Glubran ® 2 group had earlier drain removal (median 6 [IQR 5–7] vs. 14 [IQR 9–18] days, p < 0.001) and shorter hospital stay (10.8 ± 3.2 vs. 19.2 ± 7.1 days, p < 0.001). On multivariable analysis, Glubran ® 2 use was an independent protective factor (adjusted OR 0.18, 95% CI 0.06–0.54, p = 0.002), after adjustment for soft pancreatic texture and main pancreatic duct ≤ 3 mm. The effect was consistent on per-protocol and surgeon-clustered sensitivity analyses. Conclusions In this single-center randomized trial, reinforcement of pancreaticojejunostomy with Glubran ® 2 was associated with a significantly lower rate of POPF (Grade B/C), shorter time to drain removal, lower overall morbidity, and shorter length of hospital stay, with an acceptable safety profile. These hypothesis-generating findings warrant confirmation in an adequately sized, multicenter trial with operator-independent application before any recommendation for routine clinical adoption. Trial registration ClinicalTrials.gov NCT06756074. Registered 24 December 2024 (prospective). https://clinicaltrials.gov/study/NCT06756074 .