Endoscopic Treatment with Dextranomer-Hyaluronic Acid for Vesicoureteral Reflux: Histological Findings

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Abstract
Purpose: Dextranomer-hyaluronic acid co-polymer is the first endoscopic bulking agent approved for vesicoureteral reflux in the United States. We evaluated the histopathological changes associated with this treatment in children with vesicoureteral reflux. Materials and Methods: Children 1 to 11 years old in whom treatment with dextranomer-hyaluronic acid co-polymer for grades III or greater vesicoureteral reflux had failed were eligible for the study. Failure was defined as persistent vesicoureteral reflux on voiding cystourethrography done approximately 3 months after implantation. At ureteral reimplantation the implant and surrounding ureteral tissue were resected and fixed for histopathological analysis. Tissue sections (4 to 5 μm.) were stained for routine histology and examined under a light microscope. Patients with a similar grade of vesicoureteral reflux who had not undergone endoscopic treatment served as the control group. Results: The study population comprised 23 patients with vesicoureteral reflux, of whom 13 with a mean age of 2 years 8 months at diagnosis underwent 1 to 3 treatments with dextranomer-hyaluronic acid co-polymer. The remaining 10 patients with a mean age of 1 year 10 months at diagnosis did not receive the bulking agent before ureteral reimplantation. The implant remained in situ 13 to 39 months (mean 22). On ureteral reimplantation the implant was located at the site of injection in 12 of the 13 patients. Histologically a granulomatous inflammatory reaction indicated by giant cell infiltration was observed at the implantation site. At ureteral reimplantation 9 implants were pseudo-encapsulated. Calcification was present in 9 ureters, while the eosinophil count was greater than 5 cells per 0.125 mm.2 in 7 ureters treated with dextranomer-hyaluronic acid co-polymer. Mast cell infiltration was similar in the treatment and control groups. Conclusions: Endoscopic treatment with dextranomer-hyaluronic acid co-polymer for vesicoureteral reflux is associated with a granulomatous reaction of the giant cell type, inflammatory cell infiltration and implant pseudo-encapsulation. They are typical histological findings associated with implantation of a foreign material. Dextranomer-hyaluronic acid co-polymer remains safe and effective for vesicoureteral reflux in children.