Intrapapillary Botulinum Toxin Injection for PREvention of Post-surgical PAncREactic Fistula

• Status: Not yet recruiting
• Trial end date: 2023-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Surgery is required for the treatment of many pancreatic conditions, either malignant or benign. Mortality of pancreatic surgery can be up to 3% even in expert centers. Morbidity is high, postoperative pancreatic fistula (POPF) being the main postoperative complication. In its current definition (drain output of any measurable fluid >= postoperative day 3 with amylase content >3 times the serum amylase activity and with clinical consequence), the incidence of postoperative PF is between 15 and 30 %. Most POPF resolve spontaneously but when refractory POPF occurs, it may lead to severe complications. POPF severity is graded as follows: grade B in case of change in medical management: infection without organ failure, specific medication (total parenteral nutrition, somatostatin analogs, antibiotics), persistent drainage > 3 weeks, angiographic procedure for bleeding, prolonged hospital stay; grade C in case of reoperation or PF-related organ failure or death.

No specific prophylactic treatment of POPF is currently recommended by clinical guidelines. In clinical research, many prophylactic strategies have been attempted with partial efficacy. Endoscopic pancreatic sphincterotomy with plastic stent placement is effective in pre-and postoperative management of pancreatic fistula but with the need of a highly competent interventional endoscopist. Intrapapillary botulinum toxin injection is believed to induce relaxation of the pancreatic sphincter, leading to a " pharmacological " pancreatic sphincterotomy without any morbidity.

A recent phase I/II prospective study has shown promising results in this indication, with no clinically relevant pancreatic fistula when botulinum toxin was injected. Based on this observation we hypothesize that intrapapillary botulinum toxin injection during an endoscopic procedure before surgery could be effective for the prevention of post-surgical pancreatic fistula

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Botulinum Toxins

Criteria

Inclusion Criteria:

• Patients with scheduled distal pancreatectomy for any indication: open or laparoscopic distal pancreatectomy with or without splenectomy

• Age ≥ 18years

Exclusion Criteria:

• History of myasthenia gravis or Eaton-Lambert syndrome

• Inflammatory myositis <2 years or preexisting motor neuron disease or neuropathies

• ASA score > III

• Pregnancy or lactation

• Altered anatomy of the duodenum and/or the major papilla (prior surgery, prior endoscopic sphincterotomy)

• Scheduled pancreaticoduodenectomy (Whipple procedure)

• Scheduled total pancreatectomy

• Scheduled central pancreatectomy

• Scheduled pancreatic enucleation

• Calcified chronic pancreatitis (suspected on preoperative cross-sectional imaging)

• Pancreas divisum (suspected on preoperative cross-sectional imaging)

• Toxin botulinum contraindications (hypersensitivity to albumin or to saccharose, infection or inflammation at the injection site concerned, generalized muscle weakness)

• Preoperative administration of somatostatin analogs: for long-acting somatostatin analogs, a 1-month washout period is necessary; for short-acting somatostatin analogs, a 24-hours washout period is necessary

• Any kind of surgical method to reinforce the pancreatic stump:

• Use of a bioabsorbable patch

• Use of fibrin glue

• Use of a ligament patch

• Tutorship, trusteeship

• Concurrent participation in other experimental trials

• Not Affiliation to the French social security

• Not Ability to give their consent and not written informed consent

Secondary exclusion criteria: patients who did not have the planned surgery in less than 4 weeks after the botulinum toxin injection.