Radiologic Features of Implants After Endoscopic Treatment of Vesicoureteral Reflux in Children

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1 Pediatric Imaging Pictorial Essay Cerwinka et al. Implants After Endoscopic Treatment of VUR Pediatric Imaging Pictorial Essay Wolfgang H. Cerwinka 1 Jonathan D. Kaye 1 Hal C. Scherz 1 Andrew J. Kirsch 1 J. Damien Grattan-Smith 2 Cerwinka WH, Kaye JD, Scherz HC, Kirsch AJ, Grattan-Smith JD Keywords: CT, endoscopic injection, MRI, pediatric urology, sonography, vesicoureteral reflux DOI: /AJR Received October 10, 2009; accepted after revision December 21, W. H. Cerwinka, H. C. Scherz, and A. J. Kirsch are consultants for Oceana Therapeutics. 1 Georgia Pediatric Urology, Children s Healthcare of Atlanta, Emory University, 5445 Meridian Mark Rd., Ste. 420, Atlanta, GA Address correspondence to W. H. Cerwinka (wcerwin@emory.edu). 2 Department of Radiology, Children s Healthcare of Atlanta at Scottish Rite, Atlanta, GA. CME This article is available for CME credit. See for more information. AJR 2010; 195: X/10/ American Roentgen Ray Society Radiologic Features of Implants After Endoscopic Treatment of Vesicoureteral Reflux in Children OBJECTIVE. Implants after endoscopic treatment of vesicoureteral reflux (VUR) in children will be more frequently detected on imaging studies and may lead to misinterpretation and unnecessary intervention. This article reviews the radiologic appearance of implants. CONCLUSION. Radiologic findings of implants depend on the imaging technique, bulking agent, and time after injection. A history of VUR or an antireflux procedure and the absence of hydronephrosis in cases of suspected urolithiasis are important clues to suggest implants. E ndoscopic treatment of vesicoureteral reflux (VUR) was introduced as an investigational method in 1981 and was first used to treat patients in As the injection techniques evolved, the cure rates of endoscopic treatment of VUR have significantly improved to rival those of open ureteral reimplantation. A variety of injectable agents have been used and abandoned over time, and several materials are currently under investigation. As the indications for the endoscopic treatment of VUR increase, so does the number of children, and subsequently adults, carrying implants. Many of these patients will undergo imaging studies unrelated to VUR. Visualization of the injected bulking agent at the ureterovesical junction (UVJ) could potentially lead to misdiagnosis and unwarranted intervention. Recent case reports of calcified implants misdiagnosed as urinary calculi and growing interest in the radiology community prompted us to review the appearance of bulking agents on imaging studies after endoscopic treatment of VUR [1 3]. Injectable Agents Polytef (Teflon, DuPont) was the first bulking material used for the treatment of VUR. It is no longer used for urology procedures in pediatric patients in the United States because of the material s propensity to migrate to distant organs and to form granulomas. Silicone also shows distant migration and granuloma formation. Glutaraldehyde crosslinked bovine collagen shows a lower degree of absorption than native collagen, but it may cause allergic reactions even in patients with a negative skin test. Several new bulking agents are currently under investigation, such as inorganic materials and autologous cells. A dextranomer hyaluronic acid copolymer (Deflux, Oceana Therapeutics) has been used as an injectable material in pediatric urology for 15 years. It is easy to inject and biodegradable, with stable implant volume, and its relatively large particle size prevents distant migration. Dextranomer hyaluronic acid copolymer is currently the most commonly used bulking agent and will consequently be most frequently encountered on imaging studies. Injection Technique Most contemporary injection techniques are modifications of the subureteric Teflon injection procedure. The double hydrodistention implantation technique entails the passage of an injection needle under cystoscopic guidance into the ureteral orifice. Sufficient bulking agent is injected submucosally to produce a bulge, which initially coapts the detrusor tunnel. A second implant within the most distal intramural tunnel then leads to coaptation of the ureteral orifice. An average of ml of bulking material is injected per ureter. Radiologic Findings Radiography The copolymer of dextranomer and hyaluronic acid has a radiographic density com- 234 AJR:195, July 2010

2 Implants After Endoscopic Treatment of VUR parable with that of soft tissue, 24 HU, and is not visualized on radiography (Figs. 1 and 2). In a recent study, none of the dextranomer hyaluronic acid copolymer implants was seen on radiographs at a median postoperative time of 24 months and all implants measured less than 400 HU [4]. There is, however, some evidence that dextranomer hyaluronic acid copolymer implant calcification is progressive in nature and may subsequently appear on radiographs several years after injection. Calcium hydroxylapatite (Coaptite, Boston Scientific) has been used for the endoscopic treatment of VUR and because of its composition appears radiodense on radiography and CT immediately after injection. The material s biocompatibility is well documented and no long-term adverse tissue reactions have been reported. Polytef was retrospectively found on radiographs as a faintly increased density in 22% of 57 patients; the implants, however, were never recognized prospectively [5]. Voiding Cystourethrography In a retrospective study, voiding cystourethrography showed dextranomer hyaluronic acid copolymer implants as filling defects similar to ureteroceles at early filling stages in 33% of patients. However, calcifications were not seen on any of the scout images [4] (Fig. 3). Polytef implants produced a filling defect in only 6 9% of studied patients [5, 6]. Sonography In a retrospective study, 27 patients who had undergone endoscopic injection with autologous chondrocytes were followed with serial sonography [7]. Implants with punctate or round hyperechoic foci with or without associated distal shadowing were regarded as calcified. Implant calcifications were detected in 37% patients at a mean of 2.6 years after treatment and none of the patients had concomitant hydronephrosis [7]. The size of dextranomer hyaluronic acid copolymer implants may change over time because of displacement, dissolution, or disruption and is reflected by time-dependent detection rates on ultrasound. Dextranomer hyaluronic acid copolymer implants could be identified with sonography in 83 93% of treated ureters 3 months after injection and in 45 75% 2 3 years after injection [8] (Fig. 4). Dextranomer hyaluronic acid copolymer blebs with tissue density on CT appeared isoechoic on ultrasound, whereas calcified blebs were hyperechoic with postenhancement shadowing on sonography and could be mistaken for distal ureteral calculi [9]. Polytef implants appeared as hyperechoic blebs with distal shadowing on sonography performed immediately after injection and had not changed in echogenicity on follow-up sonography 5 weeks to 1 year postoperatively [10]. These findings were corroborated by retrospective studies in which 85 98% of patients were found to have echogenic polytef implants with variable degrees of acoustic shadowing [5, 6]. Collagen implants appeared hyperechoic without acoustic shadowing in 100% of 36 ureters immediately postoperatively; all implants, however, became hypoechogenic 1 month later [11]. CT In a series of 17 patients who underwent dextranomer hyaluronic acid copolymer injection for VUR, all 33 implants were seen on CT; 36% had calcifications with a median attenuation value of 193 HU (range, HU). Noncalcified implants measured 22 HU (range, HU) (Fig. 5). None of the implants enhanced with IV contrast material. In an attempt to radiographically distinguish UVJ stones from calcified implants, radiographic and demographic characteristics of the 17 patients were compared with 30 patients with UVJ stones. The absence of hydronephrosis and microhematuria, a negative radiograph, and attenuation of less than 400 HU on CT were strongly suggestive of calcified implants. Two patients with bilateral calcified blebs had multiple CT scans. The median attenuation of these implants increased from 193 HU (range, HU) to 387 HU (range, HU) over an average of 17 months (Fig. 6). Patients after endoscopic VUR treatment may develop urolithiasis and present with renal colic (Fig. 7). In these cases, a history of VUR treatment, the side of the injection and flank pain, the presence of hydronephrosis, and the exact location of calcification in relation to the UVJ help to distinguish urinary calculi from calcified implants. Glutaraldehyde cross-linked collagen was used in pediatric urology for antireflux procedures and has shown the potential to calcify. A case report described a symptomatic calcification (hematuria and back pain) that had eroded at the UVJ after injection for VUR treatment 10 years earlier [12]. Polytef was reliably visualized on CT in 100% of 18 patients [5]. The attenuation of polytef ranged from 160 to 466 HU [5]. MRI In a series of 16 patients who had undergone dextranomer hyaluronic acid copolymer injection for VUR, all 27 dextranomer hyaluronic acid copolymer implants were identified on MRI as bright UVJ structures on T2-weighted sequences only including T2-weighted maximum intensity projections [13] (Fig. 8). Although not seen on unenhanced T1-weighted sequences, excretory MR urography depicted the implants as filling defects; dextranomer hyaluronic acid copolymer implants did not enhance with gadolinium (Fig. 9). Polytef showed signal intensity similar to that of surrounding tissue on T1-weighted images and low signal intensity on T2-weighted sequences [14]. Collagen displayed low-to-intermediate signal intensity on T1- and T2-weighted sequences and substantially lower signal intensity than saline on T2-weighted images [15]. References 1. Nelson CP, Chow JS. Dextranomer/hyaluronic acid copolymer (Dx/HA) implants mimicking distal ureteral calculi on CT. Pediatr Radiol 2008; 38: Noe HN. Calcification in a Dx/HA bleb thought to be a ureteral calculus in a child. J Pediatr Urol 2008; 4: Polcari AJ, Kim DY, Helfand BT, Lewis JM, Chaviano AH. Pseudodistal ureteral stone resulting from calcified Deflux implantation. Urology 2009; 74: Cerwinka WH, Qian J, Easley KA, Scherz HC, Kirsch AJ. Appearance of dextranomer/hyaluronic acid copolymer implants on computerized tomography after endoscopic treatment of vesicoureteral reflux in children. J Urol 2009; 181: ; discussion, Gore MD, Fernbach SK, Donaldson JS, Shkolnik A, Zaontz MR, Kaplan WE. Radiographic evaluation of subureteric injection of Teflon to correct vesicoureteral reflux. AJR 1989; 152: Blake NS, O Connell E. Endoscopic correction of vesico-ureteric reflux by subureteric Teflon injection: follow-up ultrasound and voiding cystography. Br J Radiol 1989; 62: Gargollo PC, Paltiel HJ, Rosoklija I, Diamond DA. Mound calcification after endoscopic treatment of vesicoureteral reflux with autologous chondrocytes: a normal variant of mound appearance? J Urol 2009; 181: McMann LP, Scherz HC, Kirsch AJ. Long-term preservation of dextranomer/hyaluronic acid copolymer implants after endoscopic treatment of vesicoureteral reflux in children: a sonographic volumetric analysis. J Urol 2007; 177: AJR:195, July

3 Cerwinka et al. 9. Clark AT, Guerra L, Leonard M. Dextranomer/ hyaluronic acid copolymer implant calcification mimicking distal ureteral calculi on ultrasound. Urology 2009 Aug 14 [Epub ahead of print] 10. Mann CI, Jequier S, Patriquin H, LaBerge I, Homsy YL. Intramural Teflon injection of the ureter for treatment of vesicoureteral reflux: sonographic appearance. AJR 1988; 151: Gudinchet F, Oberson JC, Frey P. Color Doppler ultrasound for evaluation of collagen implants after Fig. 1 Vial of dextranomer hyaluronic acid copolymer. A, Photograph of vial of dextranomer hyaluronic acid copolymer. B, Dextranomer hyaluronic acid copolymer shows low density on radiograph. endoscopic injection treatment of refluxing ureters in children. J Clin Ultrasound 1997; 25: Nepple KG, Knudson MJ, Cooper CS, Austin JC. Symptomatic calcification of subureteral collagen ten years after injection. Urology 2007; 69:982.e1 982.e2 13. Cerwinka WH, Grattan-Smith JD, Scherz HC, Kirsch AJ. Appearance of Deflux implants with magnetic resonance imaging after endoscopic treatment of vesicoureteral reflux in children. J Fig. 2 Attenuation values of dextranomer hyaluronic acid copolymer and its components on CT. A, Attenuation of dextranomer is 204 HU. B, Attenuation of dextranomer hyaluronic acid copolymer is 24 HU. C, Attenuation of hyaluronic acid is 70 HU. A Pediatr Urol 2009; 5: Kirsch MD, Donaldson JS, Kaplan WE. MR appearance of subureteric injection of Teflon to correct vesicoureteral reflux. J Comput Assist Tomogr 1990; 14: Maki DD, Banner MP, Ramchandani P, Stolpen A, Rovner ES, Wein AJ. Injected periurethral collagen for postprostatectomy urinary incontinence: MR and CT appearance. Abdom Imaging 2000; 25: B 236 AJR:195, July 2010

4 Implants After Endoscopic Treatment of VUR Fig. 3 8-year-old boy who underwent imaging 6 weeks after endoscopic treatment with dextranomer hyaluronic acid copolymer (1.5 ml injected at each ureter) for right grade IV and left grade III vesicoureteral reflux. Implants were not seen on radiography (not shown). A C, Implants (arrows, B and C) appear as filling defects at ureterovesical junction on cystograms: scout image (A), oblique view (B), and anteroposterior view (C). Fig. 4 Sonography of 7-year-old girl who underwent imaging 3 months after endoscopic treatment of bilateral grade II vesicoureteral reflux (right ureter, 1.0 ml injected; left ureter, 1.0 ml injected). A and B, Dextranomer hyaluronic acid copolymer appears as iso- to hyperechoic implants (arrows) without postenhancement shadowing on transverse (A) and longitudinal (B) views. AJR:195, July

5 Cerwinka et al. Fig. 5 CT of dextranomer hyaluronic acid copolymer implants. A C, 4-year-old boy 3 years after endoscopic treatment with dextranomer hyaluronic acid copolymer for bilateral grade III vesicoureteral reflux (right ureter, 1.2 ml injected; left ureter, 1.6 ml injected). CT was performed for neuroblastoma surveillance. CT scans show bilateral high-density implants (arrows) at ureterovesical junction (UVJ) with mean attenuation of 398 HU. D F, 6-year-old girl 1 year after endoscopic treatment with dextranomer hyaluronic acid copolymer for right grade II and left grade I vesicoureteral reflux (right ureter, 1.8 ml injected; left ureter, 1.0 ml injected). CT was performed to evaluate right flank pain. CT scans show bilateral low-density implants (arrows) at UVJ with mean attenuation of 20 HU. Fig. 6 2-year-old girl who underwent bilateral dextranomer hyaluronic acid copolymer injection for bilateral grade II vesicoureteral reflux (right ureter, 1.5 ml injected; left ureter, 0.4 ml injected). Multiple CT scans were obtained because of recurrent histiocytosis. A C, CT scans show implants (arrows) at ureterovesical junction with increasing density 26 months (202 HU) (A), 35 months (263 HU) (B), and 43 months (348 HU) (C) after endoscopic treatment. 238 AJR:195, July 2010

6 Implants After Endoscopic Treatment of VUR Fig. 7 6-year-old girl 3 years after left endoscopic injection of 1 ml dextranomer hyaluronic acid copolymer for grade II vesicoureteral reflux. Study was performed to evaluate abdominal pain during emergency department visit. A C, CT scans show calculus (left arrow, A; arrow, B) at right ureterovesical junction (UVJ) and calcified implant (right arrow, A; arrow, C) at left UVJ. Fig year-old girl who had undergone bilateral dextranomer hyaluronic acid copolymer injection for right grade II and left grade IV vesicoureteral reflux (right ureter, 1.3 ml injected; left ureter, 1.5 ml injected) 7 months earlier. MR urography was performed to evaluate bilateral hydronephrosis for obstruction. A, Coronal T2-weighted image shows bilateral bright implants at ureterovesical junction (arrows); bladder is drained by indwelling Foley catheter. B, No implants are visible on coronal T1-weighted image corresponding to A. AJR:195, July

7 Cerwinka et al. Fig year-old girl who had undergone dextranomer hyaluronic acid copolymer injection for bilateral grade III vesicoureteral reflux (right ureter, 1.5 ml injected; left ureter, 2.5 ml injected) 2 months earlier. MR urography was performed to evaluate left hydronephrosis for obstruction. A C, T2-weighted images show bilateral bright implants (arrows) at ureterovesical junction on coronal (A), axial (B), and sagittal (C) views. D F, Implants are not visualized on unenhanced T1-weighted image (D) but appear as filling defects (arrows, E and F) on coronal (E) and sagittal (F) contrast-enhanced T1-weighted images. FOR YOUR INFORMATION This article is available for CME credit. See for more information. 240 AJR:195, July 2010