Effectiveness of Methods for Pyloric Drainage in esophagecTomY: Botox vs. Pyloromyotomy

Official title

Comparative Effectiveness of Intrapyloric Botulinum Toxin Injection Versus Pyloromyotomy for Pyloric Drainage During Esophagectomy: A Registry-Based, Pragmatic Randomized Noninferiority Trial

Overview

The goal of this pragmatic, registry-based, randomized clinical trial is to find out if using botulinum toxin (Botox) to help drain the stomach during an esophagectomy works as well as a pyloromyotomy in patients undergoing elective esophagectomy for benign or malignant esophageal disease. Both methods are intended to prevent problems with food emptying too slowly from the stomach (delayed gastric emptying), which can cause discomfort after surgery. The main question it aims to answer is: Is intrapyloric Botox injection as a drainage procedure during esophagectomy non-inferior in preventing symptoms of delayed gastric emptying at 6 months postoperatively compared to pyloromyotomy? Researchers will compare intrapyloric Botox injection to pyloromyotomy to see if Botox is non-inferior to pyloromyotomy in easing symptoms of delayed gastric emptying. Participants will: Be randomized to one of two treatment groups-either intrapyloric Botox injection or pyloromyotomy-during their esophagectomy. Complete surveys assessing digestive symptoms at standard postoperative follow-up intervals (3 months, 6 months, 1 year, and 2 years postoperatively). Undergo a standard gastric emptying study at 6 months after surgery.

Detailed description

This is a single institution, pragmatic, registry-based, prospective, single-blinded, randomized, double-arm, noninferiority clinical trial comparing outcomes of two standard-of-care alternative intraoperative methods of pyloric drainage during esophagectomy. One arm of the study will be patients receiving intervention 1, intrapyloric Botox injection (Botox Group), and the other arm will be patients receiving intervention 2, pyloromyotomy (Pyloromyotomy Group). Participants will be allocated equally to the interventions being compared (allocation ratio 1:1).

Patients randomized for intrapyloric Botox injection will undergo our standard procedure as follows: 100 units of Botox is dissolved in 10 mL normal saline. After identifying the pylorus during esophagectomy, 10 mL of the Botox solution is injected intramuscularly at the anterior pyloric ring in 2 separate areas and in 1 area on each side of the pyloric ring (total 4 areas). Patients randomized for pyloromyotomy will undergo standard pyloromyotomy through a transabdominal, anterior approach.

This study will occur at Cleveland Clinic Foundation in Cleveland, OH. Three staff surgeons will perform these operations.

Interventions

• Biological Botulinum Toxin A (Botox )
  Patients randomized for intrapyloric Botox injection will undergo the following standard procedure: 100 units of Botox are dissolved in 10 mL normal saline. After identifying the pylorus, the 10 mL of Botox solution is injected intramuscularly at the anterior pyloric ring in 2 separate areas and in 1 area on each side of the pyloric ring.
• Procedure Pyloromyotomy
  Patients randomized for pyloromyotomy will undergo standard pyloromyotomy as follows: after identifying the pylorus, a 2-cm longitudinal incision is made with Metzenbaum or Mayo scissors on the anterior pylorus, centered on the pyloric ring. The incision extends through the serosa and muscular layers to expose the submucosa and mucosa, which is left intact. The cut muscle is spread apart until the submucosa bulges up to the level of the cut serosa. Care is taken to avoid perforation, and the sur

Primary outcome measures

• Gastroparesis Cardinal Symptom Index (GCSI) total score at 6 months postoperatively or prior to the first reintervention (which ever comes first) [Time frame: 6 months postoperatively or prior to the first pyloric reintervention to treat symptoms of delayed gastric emptying postoperatively (whichever comes first)]

Secondary outcome measures (4)

• Complications in the immediate post-operative period (within 30 days post-operatively) [Time frame: 30 days postoperatively or until discharge from the index hospitalization (whichever duration is greater)]
• Gastric emptying at 6 months postoperatively, measured by gastric emptying scintigraphy study (GES) [Time frame: 6 months postoperatively]
• Cleveland Clinic Esophageal Questionnaire (CEQ) domain scores at 6-months postoperatively or prior to the first reintervention (whichever comes first) [Time frame: 6 months postoperatively or prior to the first pyloric reintervention to treat symptoms of delayed gastric emptying postoperatively (whichever comes first)]
• Pyloric reinterventions by 24 months post-operatively [Time frame: 24 months postoperatively]

Eligibility criteria

Inclusion criteria

• 18 years of age or older
• Undergoing elective esophagectomy (thoracoabdominal, Ivor-Lewis, McKeown)
• Receiving a gastric conduit for alimentary reconstruction
• Technically able to receive either intrapyloric Botox injection or pyloromyotomy as ultimately determined intraoperatively
• Willing and able to provide informed consent
• Willing and able to participate in long-term follow up including study visits and surveys

Exclusion criteria

• Undergoing emergent esophagectomy (e.g., for esophageal perforation)
• Patients with underlying neuromuscular disease as Botox would be contraindicated (amyotrophic lateral sclerosis, myasthenia gravis, muscular dystrophies, Lambert-Eaton syndrome)
• Patients undergoing left thoracoabdominal without left cervical neck incision (i.e., Sweet esophagectomy) - excluded due to the extent of gastric resection
• Pregnancy
• Allergy or hypersensitivity to botulinum toxin
• Cannot feasibly receive both pyloric interventions as determined intraoperatively (e.g., patients with central obesity undergoing thoracoabdominal esophagectomy makes for a technically difficult pyloromyotomy)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Prevention

Study locations

United States · 1 center

• Cleveland Clinic — Cleveland

Publications

• Khan OA, Manners J, Rengarajan A, Dunning J. Does pyloroplasty following esophagectomy improve early clinical outcomes? Interact Cardiovasc Thorac Surg. 2007 Apr;6(2):247-50. doi: 10.1510/icvts.2006.149500. Epub 2006 Dec 18. PMID 17669829
• Urschel JD, Blewett CJ, Young JE, Miller JD, Bennett WF. Pyloric drainage (pyloroplasty) or no drainage in gastric reconstruction after esophagectomy: a meta-analysis of randomized controlled trials. Dig Surg. 2002;19(3):160-4. doi: 10.1159/000064206. PMID 12119515
• Fok M, Cheng SW, Wong J. Pyloroplasty versus no drainage in gastric replacement of the esophagus. Am J Surg. 1991 Nov;162(5):447-52. doi: 10.1016/0002-9610(91)90258-f. PMID 1951907
• Deng B, Tan QY, Jiang YG, Zhao YP, Zhou JH, Chen GC, Wang RW. Prevention of early delayed gastric emptying after high-level esophagogastrostomy by "pyloric digital fracture". World J Surg. 2010 Dec;34(12):2837-43. doi: 10.1007/s00268-010-0766-z. PMID 20734044
• Arya S, Markar SR, Karthikesalingam A, Hanna GB. The impact of pyloric drainage on clinical outcome following esophagectomy: a systematic review. Dis Esophagus. 2015 May-Jun;28(4):326-35. doi: 10.1111/dote.12191. Epub 2014 Feb 24. PMID 24612489
• Sutcliffe RP, Forshaw MJ, Tandon R, Rohatgi A, Strauss DC, Botha AJ, Mason RC. Anastomotic strictures and delayed gastric emptying after esophagectomy: incidence, risk factors and management. Dis Esophagus. 2008;21(8):712-7. doi: 10.1111/j.1442-2050.2008.00865.x. Epub 2008 Oct 1. PMID 18847448
• Benedix F, Willems T, Kropf S, Schubert D, Stubs P, Wolff S. Risk factors for delayed gastric emptying after esophagectomy. Langenbecks Arch Surg. 2017 May;402(3):547-554. doi: 10.1007/s00423-017-1576-7. Epub 2017 Mar 21. PMID 28324171
• Hajibandeh S, Hajibandeh S, McKenna M, Jones W, Healy P, Witherspoon J, Blackshaw G, Lewis W, Foliaki A, Abdelrahman T. Effect of intraoperative botulinum toxin injection on delayed gastric emptying and need for endoscopic pyloric intervention following esophagectomy: a systematic review, meta-analysis, and meta-regression analysis. Dis Esophagus. 2023 Oct 27;36(11):doad053. doi: 10.1093/dote/doad PMID 37539558

Identifiers

NCT: NCT06721520 · 24-898

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗