Pii: s0090-4295(02)01903-9

Objectives. To compare, in a prospective study, the efficacy of a single injection of polydimethylsiloxane
(Macroplastique) or dextranomer/hyaluronic acid copolymer (Deflux), a new biodegradable substance, and
to assess the short-term and 1-year clinical effects concerning reflux resolution and the safety of these two
bulking agents. Subureteral injection of bulking agents has recently demonstrated good success rates for
endoscopic treatment of vesicoureteral reflux. Macroplastique has been one of the most popular bulking
agents during the past years. Nevertheless, considering the synthetic property, new biodegradable sub-
stances have become more relevant.
Methods. From January 2000 to June 2001, 16 boys and 56 girls (total of 114 ureters) with a mean age
of 34.5 months were treated endoscopically for vesicoureteral reflux. A single subureteral Macroplastique
or Deflux injection was performed in 34 children (58 ureters) and 38 children (56 ureters), respectively. Both
groups were comparable in terms of baseline parameters. Vesicoureteral reflux was grade II in 52, grade III
in 57, and grade IV in 5 ureterorenal units. The procedure was performed on an outpatient basis, with the
children under general anesthesia. In addition to the routine parameters, the follow-up evaluation consisted
of renal ultrasonography and voiding cystourethrography at 3 and 12 months postoperatively.
Results. Endoscopic treatment was performed without any complications in all cases. At the 3-month
follow-up visit, reflux was corrected in 50 (86.2%) of 58 refluxing ureters in the Macroplastique group and
in 40 (71.4%) of 56 refluxing ureters in the Deflux group. At 1 year of follow-up, reflux correction was
maintained in 80.9% of ureters in the Macroplastique group and in 67.6% of ureters in the Deflux group. No
postoperative complications were observed in either group.
Conclusions. A single subureteral injection of either polydimethylsiloxane (Macroplastique) or dextrano-
mer/hyaluronic acid copolymer (Deflux) is an effective treatment modality for children with vesicoureteral
reflux. The procedure was well tolerated, safe, and associated with low morbidity. Deflux, a new biocom-
patible, biodegradable substance, seems to be an alternative modality to other bulking agents for treating
vesicoureteral reflux in children, with acceptable short-term and 1-year results. UROLOGY 60: 894–898,
2002. 2002, Elsevier Science Inc.
The conservative treatment of children with urinary tract infections to minimize the risk of re-
vesicoureteral reflux using long-term antibi- nal scarring and possible long-term consequen- otic prophylaxis aims to prevent reflux-associated ces.1,2 This treatment modality relies on the spon-taneous resolution of reflux, which may take years.
Additionally, excellent compliance is necessary From the Department of Urology, University of Innsbruck, Inns-bruck; and Department of Pediatric Urology, KH Barmh Schwest- and requires long-term surveillance with interven- ing voiding cystourethrograms. Continuous anti- Reprint requests: C. Radmayr, M.D., Department of Urology, biotic prophylaxis is difficult to monitor and is as- University of Innsbruck, Anichstrasse 35, Innsbruck A-6020, sociated with increasing compliance problems, as Submitted: March 11, 2002, accepted (with revisions): June 4, well as the risk of developing antibiotic resis- tance.3,4 Approximately one third of children 894 ALL RIGHTS RESERVED
treated nonoperatively will be lost to follow-up and TABLE I. Distribution of reflux grades before
will remain untreated after medical treatment has treatment
been started.5,6 Therefore, increasing numbers ofparents prefer endoscopic treatment to avoid long- VUR Grade
Macroplastique (n)
Deflux (n)
term antibiotic management. Pediatric urologists generally agree that an injectable biomaterial can be an effective way to correct reflux, although the ideal agent has not yet been identified.7,8 Endo- scopic treatment is based on the principle of creat- KEY: VUR ϭ vesicoureteral reflux. ing a solid support behind the intravesical ureter,elongating the intramural length of the ureter.9,10Hence, the injectable biomaterial must be stable daily) was administered to all patients. The preoperative urine without migration and should be encapsulated by fibrous tissue within a short time. Therefore, poly-dimethylsiloxane (Macroplastique) is one of the METHODS
most popular bulking agents fulfilling these crite- The treatment was performed as an outpatient procedure.
ria and is used extensively in medical applications, The ureteral orifices were visualized using the pediatric 9.5F especially for endoscopic management of vesi- Wolf cystoscope with a 5F working channel. A flexible 5F coureteral reflux.11 Macroplastique consists of pediatric endoscopic needle prepared with EZ-Gel surgicallubricant was used with the Macroplastique Administration fully vulcanized solid polydimethylsiloxane parti- Gun, and a 3.5F polytetrafluoroethylene-coated needle was cles (40% of volume) in a bio-excretable hydrogel used to inject dextranomer/hyaluronic acid copolymer (De- carrier (non-iodine povidone). Macroplastique has flux) as described previously.20 A single endoscopic subu- good bulking properties, requiring less material, reteral Macroplastique or Deflux injection was performed in with limited or nonexistent migration of the com- 58 and 56 ureters with grade II to IV vesicoureteral reflux,respectively. The differences in the injected volumes between paratively large, inert microparticles (median min- the two groups were not statistically significant (Macroplas- imal diameter 140 ␮m) created as an elas- tique: range 0.6 to 1 mL, mean 0.8; Deflux: range 0.5 to 1 mL, tomer.12–14 In 1995, the first experimental and mean 0.7; P Ͼ0.05). Bilateral reflux was present in 24 children short-term results of a new bioimplant were pub- in the Macroplastique group and in 18 children in the Deflux lished.15 This new biodegradable substance (De- group. One week after the injection, control renal ultrasonog-raphy was performed to recognize urinary obstruction. Void- flux) consists of dextranomer microspheres in a ing cystourethrography (VCUG), ultrasonography, and urine sodium hyaluronan solution and may serve as a culture were done in all patients 3 months after discharge. The new alternative to Macroplastique for the endo- routine parameters, including medical history, physical con- scopic treatment of reflux.16 The Deflux system dition, and adverse events, were recorded at 3 and 12 months represents a new biocompatible material without of follow-up. Successful reflux correction was defined as ab-sent or grade I reflux on follow-up VCUG and no de novo immunogenic properties and a lack of distant mi- hydroureteronephrosis on renal ultrasonography. At 12 gration.17 In our prospective study using a single months of follow-up, VCUGs were available for only 24 pa- injection of either substance, we compared the ef- tients in the Macroplastique and only 22 in the Deflux group.
ficacy of these two agents for the endoscopic treat- Antibiotic prophylaxis was stopped if vesicoureteral reflux ment of reflux in children. The short-term and was absent or grade I. If reflux persisted, repeated treatmentwith the previous bulking agent was offered to the parents.
1-year clinical effects concerning reflux resolutionand safety were evaluated.
The Z test for significance of a single proportion (normal MATERIAL AND METHODS
test, two sided) was applied for statistical analysis, with deter-mination of confidence intervals of the proportion of positive PATIENTS
outcomes at 3 months after the procedure for patients treated Children with vesicorenal reflux were randomly assigned to the two groups. During the 18-month study period, 72 chil-dren (16 boys and 56 girls) with 114 ureterorenal units un- derwent subureteral injection of Macroplastique (34 children;24 girls and 10 boys; mean age 33 months) or Deflux (38 All procedures were performed as planned on an children; 32 girls and 6 boys; mean age 36 months). The reflux outpatient setting under general anesthesia with grades were grade II in 52, grade III in 57, and grade IV in 5 no intraoperative complications. At 3 months of (Table I), according to the reflux grading system recom-mended by the International Reflux Study.18 The exclusion follow-up, reflux was corrected in 50 (86.2%) of criteria were duplicated refluxing ureters, Hutch diverticu- the 58 ureteral units in the Macroplastique group lum, failed surgical reimplantation, neurogenic bladder deter- and in 40 (71.4%) of the 56 ureteral units in the mined by history and multichannel urodynamics, and voiding Deflux group (Table II). The confidence intervals dysfunction diagnosed by history and uroflowmetry with sur- of the proportion of positive outcomes after 3 face electromyography in children with bladder control.19 An-tibiotic prophylaxis using either trimethoprim (1 to 2 mg/kg months are shown in Figure 1. At the 95% confi- daily) or co-trimoxazole (sulfamethoxazole 5 to 10 mg/kg dence interval, no statistically significant differ- UROLOGY 60 (5), 2002
been seen in either group to date. Two children TABLE II. Reflux resolution (ureters) after a
after Macroplastique injection and three after De- single injection
flux injection underwent bilateral repeated injec- VUR Grade
Macroplastique (n)
Deflux (n)
KEY: VUR ϭ vesicoureteral reflux. The debate about the ideal bulking agent in en- doscopic therapy for children with vesicoureteralreflux still remains controversial.21,22 The sub-stance should be nontoxic, biocompatible, nonmi-gratory, nonantigenic, and cause minimal local in-flammation. To our knowledge, we report the firstprospective trial comparing two different bulkingagents with regard to efficacy and 1-year outcome.
We limited our protocol to a single injection ofMacroplastique or Deflux, in contrast to previousstudies using multiple injections. This unique as-pect of a single injection allowed us to comparedifferent bulking agents in a much more standard-ized manner. Previous studies have indicated a Difference in proportion of positive out- success rate of 81% to 93% by endoscopic injection comes. CI ϭ confidence interval. using Macroplastique.23,24 The 86.2% success rate3 months after a single injection observed in our ence (P ϭ 0.0536) was observed. No difference in Macroplastique group confirmed this published outcome according to gender was observed in ei- data. In contrast to prior studies describing particle ther group. Defining the success rate as no evi- migration of less cross-linked silicone gels or non- dence of reflux, the response rate after Macroplas- cross-linked silicone oils with a particle diameter tique and Deflux injection decreased to 75.8% and of less than 100 ␮m, Macroplastique is created as 62.5%, respectively. No significant dilation of the an elastomer, minimizing the risk of migration.13,22 upper urinary tract was observed in either group.
Nonetheless, one has to take into consideration the However, a temporary mild dilation of the collect- possible risks of autoimmune reactions25 and ma- ing system was found in 23 ureterorenal units lignancy in the long term, which has been demon- (40%) after Macroplastique injection and 12 (21%) after Deflux injection. Contralateral de novo grade In 1995, Stenberg and Lackgren15 introduced a I reflux developed in 1 patient in both groups but new bioimplant consisting of dextranomer micro- did not require additional treatment. Neither ad- spheres and hyaluronic acid (dextranomer/hyal- verse reactions nor any signs of toxicity in either uronic acid copolymer or Deflux). The short and group were observed. Six and four patients had long-term success rate of 68% to 75% in treating postoperative afebrile urinary tract infection after grade II or greater vesicoureteral reflux was re- Macroplastique and Deflux injection, respectively.
ported after a single injection.27,28 The success rate At 1 year of follow-up, 46 children (24 with 41 of 71.4% in our study was again consistent with the ureters in the Macroplastique group, 22 with 32 published data. At 1 year of follow-up, reflux res- ureters in the Deflux group) were available for re- olution rates decreased gradually to 80.9% (Mac- peated VCUG. Additional follow-up VCUGs of the roplastique) and to 67.6% (Deflux). The trend to- remaining patients were in progress at last follow- ward higher success rates in the Macroplastique up. The reflux resolution rate decreased gradually group may be explained by the higher viscosity and to 80.5% in the Macroplastique group and 68.8% in absence of retraction of the substance. Because the the Deflux group. On follow-up VCUG, initial efficacy of Deflux compared with Macroplastique grade III reflux in 2 patients (1 patient in either showed no statistically significant differences with group) had decreased to grade II reflux. Of a total regard to reflux resolution, one can recommend of 7 patients who had grade I reflux at 3 months of the Deflux system as a reliable, new, alternative follow-up (4 with 6 ureters in the Macroplastique biodegradable bulking agent that permits defini- group and 3 with 5 ureters in the Deflux group), 1 tive treatment in most children with vesicoureteral patient with two ureterorenal units in the Macro- reflux. Additionally, Deflux fulfills most of the cri- plastique group and 2 patients with four uretero- teria required for the ideal implantable bulking renal units in the Deflux group developed grade II agent and is advantageous over autologous agents reflux after 12 months. No adverse reactions have because it is inherently stable. Additionally, the UROLOGY 60 (5), 2002
safety profile is highly satisfactory. Compared with 10. O’Donnell B, and Puri P: Endoscopic correction of pri- many years of antibiotic prophylaxis, endoscopic mary vesico-ureteral reflux: results in 94 ureters. Br Med J treatment using either substance offers an immedi- 293: 1404 –1406, 1986.
11. Schulman CC: Use of particulate silicone microim- ate cure of reflux in most cases,29 consistent with plants for the endoscopic correction of vesicoureteric reflux in our results. In contrast to the Macroplastique sys- children. Dialogues Pediatr Urol 17: 6 –7, 1994.
tem, which requires specific equipment, including 12. Solomon LZ, Birch BR, Cooper AJ, et al: Nonhomolo- an administration gun to ensure high pressure dur- gous bioinjectable materials in urology: “size matters”? BJU
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UROLOGY 60 (5), 2002

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