Svensson Emma, Zvara Peter, Qvist Niels, Hagander Lars, Möller Sören, Rasmussen Lars, Schrøder Henrik Daa, Hejbøl Eva Kildall, Bjørn Niels, Petersen Súsanna, Larsen Kristine Cederstrøm, Krhut Jan, Muensterer Oliver J, Ellebæk Mark Bremholm
Pediatric surgery, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University. Skane University Hospital Lund, 221 84 Lund, Sweden.
Research Unit for Urology, Department of Clinical Research, University of Southern Denmark, J. B. Winsløws Vej 4, 5000 Odense C, Denmark.
Int J Surg Protoc. 2021 Aug 11;25(1):171-177. doi: 10.29337/ijsp.156. eCollection 2021.
Esophageal atresia (EA) is a congenital malformation affecting 1:3000-4500 newborns. Approximately 15% have a long-gap EA (LGEA), in which case a primary anastomosis is often impossible to achieve. To create continuity of the esophagus patients instead have to undergo lengthening procedures or organ interpositions; methods associated with high morbidity and poor functional outcomes. Esophageal injections of Botulinum Toxin Type A (BTX-A) could enable primary anastomosis and mitigate stricture formation through decreased tissue tension.
In this randomized controlled blinded animal trial, 24 pigs are divided into a long- or short-gap EA group (LGEA and SGEA, respectively) and randomized to receive BTX-A or isotonic saline injections. In the LGEA group, injections are given endoscopically in the esophageal musculature. After seven days, a 3 cm esophageal resection and primary anastomosis is performed. In the SGEA group, a 1 cm esophageal resection and primary anastomosis is performed, followed by intraoperative injections of BTX-A or isotonic saline. After 14 days, stricture formation, presence of leakage, and esophageal compliance is assessed using endoscopic and manometric techniques, and in vivo and ex vivo contrast radiography. Tissue elongation is evaluated in a stretch-tension test, and the esophagus is assessed histologically to evaluate anastomotic healing.
The study complies with the ARRIVE guidelines for animal studies and has been approved by the Danish Animal Experimentation Council. Results will be published in peer-reviewed journals and presented at national and international conferences.
The optimal management of long-gap esophageal atresia remains controversialPrimary anastomosis could improve functional outcomes and reduce complicationsBotulinum Toxin Type A decreases tissue tension and could facilitate anastomosisReduced tension could further abate the risk for anastomotic stricture and leakageWe present a model to evaluate the method in long- and short-gap esophageal atresia.
食管闭锁（EA）是一种先天性畸形，发病率约为1/3000 - 4500新生儿。约15%的患者为长间隙食管闭锁（LGEA），这种情况下往往无法进行一期吻合。为建立食管连续性，患者不得不接受延长手术或器官植入术；这些方法与高发病率和不良功能结局相关。注射A型肉毒杆菌毒素（BTX - A）可实现一期吻合，并通过降低组织张力减轻狭窄形成。
在这项随机对照双盲动物试验中，24头猪被分为长间隙或短间隙食管闭锁组（分别为LGEA和SGEA），并随机接受BTX - A或等渗盐水注射。在LGEA组，通过内镜在食管肌层进行注射。7天后，进行3厘米食管切除术和一期吻合。在SGEA组，进行1厘米食管切除术和一期吻合，然后术中注射BTX - A或等渗盐水。14天后，使用内镜和测压技术以及体内和体外造影X线摄影评估狭窄形成、渗漏情况和食管顺应性。在拉伸 - 张力试验中评估组织伸长情况，并对食管进行组织学评估以评估吻合口愈合情况。
该研究符合动物研究的ARRIVE指南，并已获得丹麦动物实验委员会的批准。结果将发表在同行评审期刊上，并在国内和国际会议上展示。
长间隙食管闭锁的最佳治疗方法仍存在争议一期吻合可改善功能结局并减少并发症A型肉毒杆菌毒素可降低组织张力并有助于吻合降低张力可进一步降低吻合口狭窄和渗漏的风险我们提出了一个模型来评估长间隙和短间隙食管闭锁的治疗方法。
