*Division of Pediatric General and Thoracic Surgery †Division of Pediatric Pathology ‡Division of Pediatric Gastroenterology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
J Pediatr Gastroenterol Nutr. 2014 May;58(5):593-7. doi: 10.1097/MPG.0000000000000259.
The outcomes of fundoplication for gastroesophageal reflux disease are suboptimal in many children, and alternatives are clearly needed. Dextranomer hyaluronic acid (DxHA) copolymer, an agent with proven efficacy in vesicoureteral reflux, was studied with respect to its effects on the gastroesophageal junction (GEJ).
Twelve New Zealand white rabbits underwent measurement of lower esophageal sphincter pressure followed by laparotomy and injection into the muscular layer of the GEJ (controls, 1.0 mL saline; low-dose DxHA [0.5 mL]; high-dose DxHA [1.0 mL]). After a 12-week survival period, the animals underwent manometry, sacrifice, and necropsy. Organs were examined histologically by pathologists blinded to the injection delivered.
All animals survived. Weight gain was equal in the 3 groups. There was no significant difference in mean lower esophageal sphincter pressure from baseline in any group (control 2.3 mmHg [95% confidence interval, CI -3.3 to 7.9]; low-dose group 3.2 mmHg [95% CI -0.8 to 7.2]; high-dose group -4.0 mmHg [95% CI -18.95 to 10.95]). Histologically, DxHA injection produced an intramural implant, with a foreign body giant cell reaction, and fibroblastic infiltration with collagen deposition. High-dose injection did not consistently result in a qualitative increase in the magnitude of the reaction. There was no mucosal injury or luminal stenosis.
In this first study evaluating the effects of DxHA injection at the GEJ, a histologic bulking effect was observed without obvious functional complications. The agent may have a role in the treatment of gastroesophageal reflux disease.
胃食管反流病患儿行胃底折叠术的疗效并不理想，显然需要替代方案。葡聚糖-透明质酸（DxHA）共聚物在治疗膀胱输尿管反流方面已被证实有效，本研究旨在探讨其对胃食管交界处（GEJ）的影响。
12 只新西兰白兔行食管下括约肌压力测量后行剖腹术，并于 GEJ 肌层注射（对照组 1.0 mL 生理盐水；低剂量 DxHA [0.5 mL]；高剂量 DxHA [1.0 mL]）。12 周存活期后，行测压、处死和尸检。病理学家对注射情况不知情，对器官进行组织学检查。
所有动物均存活。3 组动物的体重增加均无差异。从基线来看，各组平均食管下括约肌压力均无显著差异（对照组 2.3 mmHg [95%置信区间，CI -3.3 至 7.9]；低剂量组 3.2 mmHg [95% CI -0.8 至 7.2]；高剂量组 -4.0 mmHg [95% CI -18.95 至 10.95]）。组织学上，DxHA 注射导致了一个黏膜下植入物，伴有异物巨细胞反应和纤维母细胞浸润伴胶原沉积。高剂量注射并未始终导致反应程度的质的增加。未见黏膜损伤或管腔狭窄。
本研究首次评估了 DxHA 注射于 GEJ 的效果，观察到了组织学上的增容效应，而无明显的功能并发症。该药物可能在胃食管反流病的治疗中具有一定作用。
