Design: Single-centre, open-label, randomised phase 2 trial, stopped for futility
Population: 50 patients scheduled for elective distal pancreatectomy
Primary outcome: Grade B/C postoperative pancreatic fistula and/or death within 30 days
Effect: Fistula 28.6% with botulinum toxin vs 15% control (P = 0.294)

Clinically relevant pancreatic fistula follows up to three in ten distal pancreatectomies. The PREBOTPilot trial tested whether relaxing the sphincter of Oddi with endoscopic botulinum toxin, given 3 to 10 days before surgery, would improve drainage into the duodenum and reduce fistula.

Fifty patients were randomised before the single-centre phase 2 trial was stopped for futility. Grade B or C fistula occurred in 28.6% of the botulinum group and 15% of controls (P = 0.294). One patient in the injection group died of haemorrhage secondary to fistula. The injection itself caused no pancreatitis.

The trial was small and open-label, but the direction of the result was against the intervention. There is no case for using it outside a trial.

Do not use preoperative sphincter of Oddi botulinum toxin to prevent fistula after distal pancreatectomy.
Continue standard fistula risk assessment and drain management after distal pancreatectomy.
Watch for sentinel bleeding in any patient with a grade B or C fistula, given the risk of haemorrhage.

Why it matters

A plausible, already-described prevention strategy failed its first randomised test.

The statistics, in plain English

With 50 patients the trial could not reliably detect small differences; a P value of 0.294 means the higher fistula rate with botulinum toxin may be chance. What matters is that the result showed no trend towards benefit, which is why it was stopped.