Botulinum Toxin Injections May Not Prevent Delayed Gastric Emptying After Esophagectomy

Intraoperative botulinum toxin (BOTOX^® Cosmetic) injections may not reduce the likelihood of postesophagectomy complications, such as delayed gastric emptying or need for endoscopic pyloric intervention, according to study findings published in Diseases of the Esophagus.

Gastric dysmotility and pyloric dysfunction are thought to result from damage to branches of the vagus nerve and the neuromuscular structure of the stomach during esophagectomy for resectable esophageal cancer. Prophylactic techniques to prevent complications due to esophagectomy include botulinum toxin injections and pyloric drainage procedures.

While intraoperative pyloric interventions have demonstrated potential to decrease the risk for delayed gastric emptying after esophagectomy, the evidence supporting the use of botulinum toxin injections to prevent delayed gastric emptying and the need for endoscopic pyloric interventions was not well analyzed.

Researchers conducted a systematic review, meta-analysis, and meta-regression up until February 4, 2023. They searched the medical literature for randomized controlled trials, cohort studies, case control studies, and case studies in which the researchers analyzed the risk for delayed gastric emptying and the need for pyloric intervention after intraoperative botulinum toxin injections.

The researchers included 9 studies (1 randomized controlled trial and 8 retrospective cohort studies) in which outcomes were assessed in a total of 1,070 participants. Of these, 406 received intraoperative botulinum toxin injections, 346 underwent intraoperative surgical pyloroplasty, and 318 received no intervention during esophagectomy.

Of the 406 participants who received botulinum toxin injections, 276 (68%) underwent Ivor Lewis esophagectomy, 92 (23%) underwent McKeown esophagectomy, and 38 (9%) underwent transhiatal esophagectomy with 58% of these procedures performed using open approaches and the remaining 42% performed using minimally invasive approaches. Botulinum toxin injection doses ranged from 20 to 200 units.

The researchers calculated the risk for delayed gastric emptying after intraoperative botulinum toxin injections to be 13.3% (95% CI, 7.9-18.6%) based on data from 365 participants in 8 studies. Similarly, the researchers calculated the risk for needing endoscopic pyloric intervention following intraoperative botulinum toxin injections to be 15.2% (95% CI, 7.9-22.5%) based on data from 308 participants in 7 studies.

Botulinum toxin injections did not decrease risk for delayed gastric emptying (odds ratio [OR], 0.57; 95% CI, 0.20-1.61; P =.29) or need for pyloric interventions (OR, 1.73; 95% CI, 0.42-7.12; P =.45) compared with no botulinum toxin injections. Intraoperative botulinum toxin injections also did not prove more effective than pyloroplasty in decreasing risk for delayed gastric emptying (OR, 0.85; 95% CI, 0.35-2.08; P =.73) or endoscopic pyloric intervention (OR, 8.20; 95% CI, 0.63-105.90; P =.11).

Following a meta-regression analysis, the researchers discovered that male biological sex decreased risk for delayed gastric emptying (coefficient: -0.007; P =.003). In contrast, age, surgical technique, cancer type, and botulinum toxin dose did not significantly affect delaying gastric emptying risk. None of these factors significantly affected the likelihood of the need for endoscopic pyloric intervention.

“Level 2 evidence suggests that intraoperative BT [botulinum toxin] injection may not improve the risk of DGE [delayed gastric emptying] and NEPI [need for pyloric intervention] in patients undergoing esophagectomy,” the study authors noted.

Study limitations include the retrospective design, risk for selection bias, and small sample sizes of heterogenous, included studies of moderate statistical power and quality that contained insufficient information about outcomes regarding the need for pyloric intervention after esophagectomy. Additionally, the need for more recent studies is required, since advancements in pyloric draining techniques and subsequent revisions in the definition of DGE may affect results.