Long-term outcome of randomized clinical trial between polyacrylate-polyalcohol copolymer (PPC) and dextranomer-hyaluronic acid copolymer (Dx/HA) as bulking agents for endoscopic treatment of primary vesicoureteral reflux (VUR).

OBJECTIVE: The aim of our study is to compare long-term outcome of endoscopic treatment of VUR using PPC or Dx/HA. PATIENTS AND METHODS: From October 2014 to April 2017 patients with VUR grades from 3 to 5 that needed endoscopic treatment were eligible for this RCT. Patients were randomized in two groups: PPC and Dx/HA. A VCUG was performed at 6 months; if VUR > 3 was still present a second ET was performed. We included for this long-term follow-up study those patients that were successfully treated at short-term follow-up. At 36 months postoperative VCUG was performed to assess outcome. Success was considered if postoperative VUR grade was 0 at 36 months, and there was no ureteral obstruction. RESULTS: In the previous study, 60/73 ureters were successfully treated in 36/44 patients, and then we have analyzed 60 ureters in 36 patients. Three patients were lost in long-term follow-up, and then we analyzed 57 ureters in 33 patients divided. PPC group 18 patients (28 ureters); and Dx/HA group 15 patients (29 ureters). After 3 years of follow-up the VCUG showed a success rate of 26/28 of RU in PPC and 26/29 of DX/HA. Two RU in PPC group had ureteral obstruction, and then the successful rate for PPC group dropped to 24/28. The overall successful rate at long-term was 72.7% of the RU in PPC group and 70.3% in Dx/HA group. CONCLUSION: PPC and Dx/HA has similar long-term outcome in VUR resolution, but ureteral obstruction could be present at long-term follow-up in PPC group.

Comparison of polyacrylate polyalcohol copolymer (PPC) and dextranomer/hyaluronic acid (Dx/HA) for treatment of vesicoureteral reflux. A systematic review and meta-analysis.

PURPOSE: Our study aimed to compare the efficacy of polyacrylate polyalcohol copolymer and Dextranomer-Hyaluronic Acid for endoscopic treatment of vesicoureteral reflux. MATERIAL AND METHODS: MEDLINE, EMBASE, Scopus, Web of science, Ovid, Cochrane databases, Google scholar have been searched for studies published until January 2022 in any language. Studies that compared the success rate for endoscopic treatment of vesicoureteral reflux in children with two bulking agents, namely, "polyacrylate polyalcohol copolymer." and "Dextranomer-Hyaluronic Acid" were included for this analysis. RESULTS: Nine studies were included in data synthesis for this meta-analysis. Pooled data with a total of 763 ureters in PPC group and 718 ureters in Dx/HA group indicated that ureters in PPC group were more likely to undergo complete reflux resolution than Dx/HA (OR 3.80, 95% CI: 2.71; 5.31). Among subgroup of patients with high grade reflux, PPC injection had more resolution rate compared to Dx/HA patients (OR: 2.92, 95% CI: 1.19-7.16). In total, 95.81% of the PPC group and 86.52% of the Dx/HA group experienced success after the third injection. However a concerning complication of endoscopic treatment which is ureterovesical junction obstruction (UVJO) was more prevalent in PPC group. So the possible benefits arising from endoscopic treatment with PPC could be offset by the costs of re-implantation surgery or stenting in the case of UVJO. CONCLUSION: These data indicate that PPC injection for vesicoureteral reflux treatment was associated with a higher success rate, but concerningly, UVJO incidence was higher in the PPC group which might negate the possible benefits of PPC injection However, due to the lack of studies with long-term follow-up, we couldn't reach a definitive conclusion about the superiority of one of the bulking agents over the other.

Endoscopic treatment of vesicoureteral reflux after kidney transplantation: outcomes and predictive factors of clinical and radiological success.

PURPOSE: This study aimed to identify and describe the outcomes of different endoscopic treatments and the predictive factors affecting success in the treatment of symptomatic vesicoureteral reflux (VUR) after kidney transplantation. METHODS: Patients who had undergone endoscopic injection treatment for symptomatic VUR detected by VCUG with at least 1-year follow-up were included in the study. Patients with dysfunctional and/or obstructive voiding patterns were excluded from the study. We retrospectively evaluated the patient's characteristics, operative information about the type of injection (one, two, or four-point) and the bulking agent (DX-HA, PPC), and perioperative data. Clinical success was defined as no febrile UTI, and radiological success was defined as the absence of VUR in VCUG 3 months after the operation. Clinical success, radiological success, and encountered complications were statistically analyzed. RESULTS: A total of 76 patients were included in this study. The one-point, two-point, and four-point injection technique was applied to 32 (42.1%), 13 (17.1%), and 31 (40.7%) of patients, respectively. PPC and DX-HA were used as bulking agents in 54 (71.1%) and 22 (28.9%) patients, respectively. The clinical success rate was 73.7% (n = 56). In logistic regression analysis, a significant efficacy of the four-point technique was observed in the univariate analysis of clinical success (p = 0.042). The radiological success rate was 40.8% (n = 31). In the logistic regression analysis, DX-HA and PPC radiological success was attained in 4 (18.1%) and 27 (50%) patients, respectively (p = 0.01). Ureterovesical junction (UV) stricture developed in 5 (6.5%) patients. There was no difference between injection techniques and bulking agents in terms of the development of UV stricture (p = 0.32; p = 0.08). CONCLUSION: The success of endoscopic treatment in patients with VUR after kidney transplantation can be increased by multiple injections. Furthermore, PPC can be used to obtain a higher radiological success.

A systematic review & meta-analysis comparing outcomes of endoscopic treatment of primary vesico ureteric reflux in children with polyacrylate poly alcohol copolymer versus dextranomer hyaluranic acid.

BACKGROUND & AIMS: There are conflicting reports on the efficacy of bulking agents for vesico ureteric reflux (VUR). In this meta-analysis we have compared the outcomes of endoscopic treatment with polyacrylate polyalcohol copolymer (PPC) and dextranomer hyaluronic acid (DxHA). METHODS: A systematic review of publications between 2010 and 2020 was conducted covering databases like PUBMED, MEDLINE etc. for (endoscopic treatment) AND (VUR) AND (PPC OR DxHA) AND (recurrence OR complications). PRISMA guidelines were followed and only comparative studies were included. Outcomes were early success defined as absence of VUR in voiding cystourethrogram at 3-months followup, urinary tract infections (UTI) and occurrence of vesico-ureteric-junction obstruction (VUJO). Risk of bias was analysed with Robvis tool and odds-ratios were compared with Revman-3.0. RESULTS: Among nine studies (heterogeneity; I 2 69-79%) all cleared the risk of bias assessment. There was no significant difference in high grade VUR (p = 0.94) between PPC (40%) and DxHA (43%). Success rate after single injection was significantly higher (p = 0.0001) at 86% (477/555) for PPC vs 69% (474/685) for DxHA. UTI rate between PPC (12%) and DxHA (14.6%) was not statistically significant (p = 0.54). VUJO rate between PPC (3.9%) and DxHA (0.8%) was also not significantly different (p = 0.47). Significantly lesser volume (p = 0.02) was used for PPC (0.7 ml) compared to DxHA (0.9 ml). CONCLUSION: Reflux resolution was significantly higher with PPC than DxHA. Postinjection UTI/VUJO incidence was not significantly different between them. Limitation of this meta-analysis was heterogeneity & small number of articles. Further studies should focus on long-term outcomes and cost-effectiveness.

Endoscopic treatment of primary vesicoureteral reflux in children with two different bulking agents, high success and low complication rates: Comparison of Dexell and Vantris.

INTRODUCTION AND OBJECTIVES: To compare the results in terms of efficacy and safety of the endoscopic management for vesicoureteral reflux (VUR) in two different standardized primary VUR cohorts treated with Dexell and Vantris. PATIENTS: 128 refluxing renal units (RRU) in 87 patients with primary VUR (64 females, 23 males). Patients with secondary VUR and severe bladder and bowel dysfunction were excluded. A total of 22 continent children with mild bladder-bowel dysfunction underwent bladder-bowel training before the implantation. All procedures were performed in the presence of sterile urine using a conventional subureteral transurethral injection technique. RESULTS: There were no statistically significant differences between groups in terms of mean age, sex, RRU side, 99mTc-DMSA uptake, and reflux grade. The overall resolution rates based on the number of RRUs for up to three endoscopic treatments were 80% (56/70) in Dexell group and 94.8% (55/58) in Vantris group (P = .012). No postoperative recurrences or vesicoureteral junction obstructions were seen in any group. CONCLUSIONS: Dexell and Vantris provided an effective and safe endoscopic VUR treatment in the early and mid-term follow up of children with primary VUR. The effectiveness of these substances, which can produce different mass effects with different particle sizes, in safe VUR resolution, needs further investigations.

Endoscopic treatment of primary vesicoureteral reflux in children with two different bulking agents, high success and low complication rates: comparison of Dexell and Vantris. / Tratamiento endoscópico del reflujo vesicoureteral primario en niños con dos materiales diferentes. Tasa de éxito alta y tasa de complicaciones baja: comparación entre Dexell y Vantris.

INTRODUCTION AND OBJECTIVES: To compare the results in terms of efficacy and safety of the endoscopic management for vesicoureteral reflux (VUR) in two different standardized primary VUR cohorts treated with Dexell and Vantris. PATIENTS: 128 refluxing renal units (RRU) in 87 patients with primary VUR (64 females, 23 males). Patients with secondary VUR and severe bladder and bowel dysfunction were excluded. A total of 22 continent children with mild bladder-bowel dysfunction underwent bladder-bowel training before the implantation. All procedures were performed in the presence of sterile urine using a conventional subureteral transurethral injection technique. RESULTS: There were no statistically significant differences between groups in terms of mean age, sex, RRU side, 99mTc-DMSA uptake, and reflux grade. The overall resolution rates based on the number of RRUs for up to three endoscopic treatments were 80% (56/70) in Dexell group and 94.8% (55/58) in Vantris group (p = 0.012). No postoperative recurrences or vesicoureteral junction obstructions were seen in any group. CONCLUSIONS: Dexell and Vantris provided an effective and safe endoscopic VUR treatment in the early and mid-term follow up of children with primary VUR. The effectiveness of these substances, which can produce different mass effects with different particle sizes, in safe VUR resolution, needs further investigations.

Randomized clinical trial between polyacrylate-polyalcohol copolymer (PPC) and dextranomer-hyaluronic acid copolymer (Dx/HA) as bulking agents for endoscopic treatment of primary vesicoureteral reflux (VUR).

OBJECTIVE: To compare the radiological and clinical outcomes of endoscopic treatment of primary VUR using polyacrylate-polyalcohol copolymer (PPC-Vantris®) or dextranomer-hyaluronic acid copolymer (Dx/HA-Deflux®). MATERIALS AND METHODS: From October 2014 to April 2017, patients with primary VUR grade III to V that needed endoscopic treatment (ET) were eligible for this randomized clinical trial. We excluded toilet-trained patients with lower urinary tract symptoms. Patients were randomized and allocated into two groups: PPC group and Dx/HA group. After endoscopic treatment a voiding cystourethrography (VCUG) was performed at 6 months; if VUR was still present a second ET was performed. Radiological success was considered if postoperative VUR grade was 0 and clinical success rate was considered if no more fUTI appeared during follow-up. RESULTS: Forty-six patients were eligible but 2 did not accept the trial. Forty-four patients with 73 refluxing ureters were included. PPC: 34 refluxing ureters; and Dx/HA: 39 refluxing ureters. Both groups were statistically homogeneous and comparable. Mean follow-up was 27.6 months. Radiological success rate (82.2%) and clinical success rate (92.3%) were similar in both groups (p > 0.05). The volume of bulking agent used in those successfully treated was greater in Dx/HA group (p < 0.05). Distal ureter was excise in all cases of ureteral reimplantation after PPC treatment; however, distal ureter was preserved in all ureters reimplanted after Dx/HA injection. CONCLUSION: PPC and Dx/HA had similar outcomes, but we must warn that ureteral reimplantation after endoscopic treatment with PPC is difficult because of the periureteral fibrosis.

Comparison of histopathological characteristics of polyacrylate polyalcohol copolymer with dextranomer/hyaluronic acid after injection beneath the bladder mucosa layer: a rabbit model.

OBJECTIVES: To compare short- and long-term local tissue reaction of polyacrylate polyalcohol copolymer (PPC) with dextranomer/hyaluronic acid (DHA) in rabbits. METHODS: Eight healthy New Zealand rabbits were randomly divided into two groups. In group I (control group), DHA was injected just beneath the mucosal layer of the bladder wall, while PPC was injected in group II. Subcutaneous injection of both bulking agents was also performed in nude mice. Histological evaluations with leukocyte common antibody (LCA), CD68, CD31, and CD34 were conducted on biopsies 1 and 6 months postoperatively. Scanning electron microscopy (SEM) and MTT assay were also performed for these two bulking agents. RESULTS: SEM images revealed larger particle size of PPC. LCA and CD68 staining was significantly higher in group II as compared with group I in both short- and long-term follow-ups. However, in groups I and II, expression of CD31 (101 ± 0.5 vs. 92 ± 0.25, p > 0.05) and CD34 (115 ± 0.75 vs. 103 ± 0.5, p > 0.05) was not significantly different in long-term follow-up. Remarkably, severe fibrosis was observed in group II as compared to mild fibrosis in group I one month after injection. The results of in vivo application of these bulking agents in nude mice were in accordance with the results obtained from rabbit model. MTT assay revealed that cell proliferation was significantly higher in the presence of DHA as compared with PPC. CONCLUSION: Severe inflammation and fibrosis in PPC may be due to continued foreign body reaction, presence of alcohol polymers, or larger particle sizes.

Endoscopic treatment of grades IV and V vesicoureteral reflux with two bulking substances: Dextranomer hyaluronic acid copolymer versus polyacrylate polyalcohol copolymer in children.

PURPOSE: We aimed at evaluating the efficacy and complications of two bulking substances: dextranomer/hyaluronic acid copolymer(Dx/Ha;Dexell®) versus polyacrylate polyalcohol copolymer(PPC;Vantris®) in subureteric injection treatment of children with high grades (grades IV-V) vesicoureteral reflux(VUR). METHODS: Data of patients undergoing endoscopic treatment of high grade VUR (January 2009-August 2015) were retrospectively investigated. Patients with high grade VUR caused by posterior urethral valve, duplex system, paraureteral diverticula and neurogenic bladder were excluded. Classical subureteric injection method (STING) was used. Seventy-three children (45 girls and 28 boys) who had 88 refluxing renal units (RRUs) with grades IV-V VUR (n=64/n=24) underwent endoscopic treatment using Dx/Ha (n=63 RRUs) and PPC (n=25 RRUs). RESULTS: Mean age of patients in Dx/Ha and PPC groups were 6 (3) and 6 (3.75) year (p=0.81), and volumes of these substances given were 1.3 (1) and 1 (0.5) mL (p=0.003), respectively. Overall, for the first endoscopic injection, success rate of grades IV-V VUR per RRU was 53.9% with Dx/Ha, compared to 80% in PPC-injected group, (p=0.024). Late ureterovesical junction obstruction developed only in one patient in PPC-injected group. No ureteral obstruction was observed in Dx/Ha-injected group. CONCLUSIONS: Endoscopic injection of PPC resulted in significantly higher success rate, compared to Dx/Ha in subureteric injection treatment of children with high grade VUR. However, the development of late ureterovesical junction obstruction should also be taken into account in PPC injection.

Open ureteroneocystostomy after failed endoscopic injection with three different bulking agents for the treatment of vesicoureteral reflux.

BACKGROUND/PURPOSE: To evaluate the success rate of open ureteroneocystostomy (UNC) after failed endoscopic treatment of vesicoureteral reflux (VUR) in children and to discuss the reasons for failure under the light of histopathological findings. METHODS: The clinical data of 371 patients who underwent endoscopic injection for VUR at our institution for the treatment of VUR between January 2008 and January 2014 were reviewed. Patients who were submitted to open ureteral reimplantation following failed endoscopic injection were included in the study. RESULTS: Among 371 patients, 34 (49 ureters) were submitted to open UNC (9.1%). There were 22 female and 12 male patients. Three different injection materials were used; dextranomer/hyaluronic acid in 29, carbon-coated beans in 7 and polyacrylate polyalchohol copolymer in 13. Histological study revealed that the injected material was identified in 34 ureters as malpositioned. Control VCUG 6 months after UNC showed complete resolution in 46 of 47 ureters (97.87%). CONCLUSIONS: Previous endoscopic injection, although causing difficulty in dissection to some degree, does not alter the success rate of UNC. According to the histopathological findings, the cause of failure of injection seems to be attributable to incorrect plane of injection or leakage of the agent after injection.

The influence of ureteral orifice configuration on the success rate of endoscopic treatment of vesicoureteral reflux.

BACKGROUND: To investigate the effect of polyacrylate polyalcohol copolymer (Vantris) injection for the correction of VUR in children according to ureteral orifice shape and VUR grade. MATERIALS AND METHODS: Forty children (29 girls and 11 boys) with 61 renal refluxing units (RRU) and primary VUR underwent endoscopic correction of their reflux, using Vantris. Under general anesthesia, routine cystoscopy was performed and ureteral orifice configuration and dynamic hydro distention grade were determined. The injection technique was STING, HIT or a combination of them. Ultrasound scan was performed one and 3 months after injection and radionuclide cystography (RNC) was performed 3 months after the operation. RESULTS: The mean volume of injected Vantris was 0.62 cc. Reflux was corrected in 52 (85.2%) of the 61 RRU after single injection and this equates reflux correction in 37 of the 40 patients. No significant correlation was observed between ureteral orifice shape and VUR correction rate. CONCLUSIONS: Our results showed that there was no correlation between the ureteral orifice configuration and the success rate of endoscopic surgery for VUR in short term.

Prospective study using a new bulking agent for the treatment of vesicoureteral reflux: polyacrylamide hydrogel.

PURPOSE: Vesicoureteral reflux is frequently diagnosed in the pediatric population. Endoscopic treatment has become a popular form of first-line therapy. Available products offer good short-term success rates. However, the cost of these injected implants is an issue. We evaluated the success of endoscopic treatment for vesicoureteral reflux using polyacrylamide hydrogel. MATERIALS AND METHODS: We performed a single center, single surgeon, prospective, off-label study using polyacrylamide hydrogel to treat vesicoureteral reflux. All patients underwent endoscopic subureteral double hydrodistention implantation technique injection followed by renal ultrasound and voiding cystourethrogram at 3 months postoperatively to confirm the absence of de novo hydronephrosis and correction of vesicoureteral reflux (grade 0). RESULTS: A total of 40 patients (69 refluxing ureters) underwent polyacrylamide hydrogel injection. Median age at surgery was 50 months. Bilateral reflux was identified in 29 patients (73%). Nine patients had duplex systems, 2 with reflux into both moieties. Reflux was graded using the International Reflux Study in Children grading system, with grade I seen in 9 ureters, II in 17, III in 20, IV in 18 and V in 5. Mean volume injected was 1.1 ml. Success rate for grade I to III vesicoureteral reflux at 3 months after a single treatment was 87%, and the overall success for all grades was 81.2%. CONCLUSIONS: Off-label use of polyacrylamide hydrogel injection therapy for primarily low grade vesicoureteral reflux demonstrates that the technique and short-term success rates are comparable to the most popular bulking agent, dextranomer/hyaluronic acid. These results suggest that further trials comparing polyacrylamide hydrogel and dextranomer/hyaluronic acid would be worthwhile.

Results of Treatment of Grades IV and V Vesicoureteral Reflux with Endoscopic Injection of Polyacrylate Polyalcohol Copolymer.

PURPOSE: Here we report the results of a review of a prospectively maintained database of the use polyacrylate polyalcohol copolymer (PPC) injection to correct grades IV and V VUR. MATERIALS AND METHODS: All children with grades IV and V primary VUR that presented with febrile urinary tract infection while on prophylaxis, in a 3-year period, were treated with a sub-ureteral injection of PPC. Institutional ethical approval was obtained. Exclusion criteria were incomplete bladder emptying documented on videourodynamic study, ureteral duplication, paraureteral diverticula, and poor ureteral emptying observed during fluoroscopy and previous open surgical or endoscopic treatment. Pre- and post-operative evaluation included urinalysis, renal and bladder ultrasonography, DMSA scan, and videourodynamic studies. RESULTS: Thirty-three children [36 renal units (RU)] were included with a median age of 57 months (range 7-108). There were 18 boys and 15 girls. Thirty RU had grade IV and 6 grade V VUR. Median follow-up time was 32 months (range 7-58). Reflux was cured in 32/36 RU with the first injection, but another two patients were reimplanted because of dilatation. Complications included early urinary tract infection in seven children, transient lower urinary tract symptoms in five children. Progressive ureteral dilatation was noted in four children and was treated with insertion of a double J stent. Two of these children eventually required an ureteroneocystostomy. CONCLUSION: The use of PPC to treat grades IV and V vesicoureteral reflux in young children has an overall success rate of 83.3%. Persistent ureteral dilatation was present in 11% associated with high injection volume. Future studies will attempt to maintain a high success rate reducing the volume of injection and the incidence of dilatation.