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Published on: July 28, 2022
Dextranomer hyaluronic acid copolymer effects on gastroesophageal junction
Kathryn Martin1, Sherif Emil, Chantal Bernard
1*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.
Insights
Dextranomer hyaluronic acid (DxHA) copolymer shows potential for treating gastroesophageal reflux disease by creating a bulking effect at the gastroesophageal junction without causing functional complications in rabbits.
Area of Science:
- Gastroenterology
- Surgical Innovation
- Biomaterials Science
Background:
- Fundoplication outcomes for pediatric gastroesophageal reflux disease (GERD) are often suboptimal, necessitating alternative treatments.
- Dextranomer hyaluronic acid (DxHA) copolymer, effective for vesicoureteral reflux, was investigated for its effects on the gastroesophageal junction (GEJ).
Purpose of the Study:
- To evaluate the safety and efficacy of Dextranomer hyaluronic acid (DxHA) copolymer injection into the gastroesophageal junction (GEJ) as a potential treatment for GERD.
- To assess the histological and functional effects of DxHA injection at the GEJ in a rabbit model.
Main Methods:
- Twelve New Zealand white rabbits received injections of saline (control), low-dose DxHA, or high-dose DxHA into the muscular layer of the GEJ.
- Lower esophageal sphincter pressure was measured before and after a 12-week survival period, followed by histological examination of GEJ tissues.
Main Results:
- All rabbits survived the procedure with comparable weight gain across groups.
- No significant changes in mean lower esophageal sphincter pressure were observed post-injection.
- Histological analysis revealed an intramural implant with foreign body giant cell reaction and fibroblastic infiltration, but no mucosal injury or stenosis.
Conclusions:
- Dextranomer hyaluronic acid (DxHA) injection at the GEJ resulted in a histological bulking effect without significant functional complications in this rabbit model.
- These findings suggest that DxHA copolymer may represent a promising new therapeutic option for managing gastroesophageal reflux disease.
Objective:
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).
Methods:
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.
Results:
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.
Conclusions:
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.
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