Preoperative Injection of Botulinum Toxin Into the Sphincter of Oddi Does Not Prevent Pancreatic Fistula After Distal Pancreatectomy: The Randomized Controlled PREBOTPilot Trial

OBJECTIVE: To investigate whether preoperative injection of botulinum toxin (BTX) into the sphincter of Oddi (SO) is a safe and feasible strategy to prevent postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). SUMMARY BACKGROUND DATA: POPF remains a common and potentially serious complication following DP, affecting up to 30% of patients. Pharmacologically induced sphincter relaxation by endoscopic injection of BTX into the SO has been described as a new approach to prevent POPF after DP by improved drainage of pancreatic fluid towards the duodenum. METHODS: Patients scheduled for elective primary distal pancreatectomy (DP), irrespective of the underlying disease, were included in this monocenter, randomized controlled, open-label, phase-II trial with 2 parallel arms. Patients randomly assigned to the intervention group received an endoscopic injection of BTX (100 units) into the SO 3-10 days before surgery. Patients in the control group did not undergo any preoperative intervention. The combined primary endpoint was defined as the occurrence of clinically relevant postoperative pancreatic fistula (POPF grades B/C) and/or death due to any cause within 30 days following DP. RESULTS: From March 2020 to August 2023, 50 patients were included in the trial. Subsequent to the analysis of the primary endpoint, which revealed no tendency of a beneficial effect on the rate of POPF after DP following BTX injection, even with the most favorable outcome upon further inclusion of the remaining 10 patients planned for recruitment, the recruitment was prematurely terminated. All 26 patients in the intervention group underwent successful SO BTX injection within a median of 6 (IQR of 5-8) days before surgery. DP was performed in 41 patients (82%). Postinterventional pancreatitis was not detected. Within 30 days, POPF grade B/C occurred in 6 patients in the intervention and 3 patients in the control group (28.6% vs. 15%, P=0.294). One patient in the intervention group died during the trial due to POPF-induced postpancreatectomy hemorrhage (PPH). CONCLUSION: Preoperative injection of BTX into the SO did not reduce clinically relevant POPF or 30-day mortality following DP, and the trial was prematurely terminated for futility. Although the intervention was safe and feasible, these findings do not support its use for the prevention of POPF after DP.