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hyaluronic acid copolymer (Deflux®) injection for grade I vesicoureteral reflux
Journal of Pediatric Urology (2012) 8, e27ee30
CASE REPORT
Asymptomatic chronic partial obstruction of a normal ureter following dextranomer/hyaluronic acid copolymer (Deflux) injection for grade I vesicoureteral reflux Angela M. Arlen a, Brittany L. Pakalniskis b, Christopher S. Cooper a,* a b
Department of Urology, University of Iowa, 200 Hawkins Dr., 3 RCP, Iowa City, IA 52242-1089, United States Department of Pathology, University of Iowa, 200 Hawkins Dr., 3 RCP, Iowa City, IA 52242-1089, United States
Received 25 October 2011; accepted 8 December 2011 Available online 29 December 2011
KEYWORDS Vesicoureteral reflux; Ureteral obstruction; Child
Abstract Endoscopic management of vesicoureteral reflux with dextranomer/hyaluronic copolymer (Deflux, Oceana Therapeutics, Inc., Edison, NJ, USA) has gained widespread acceptance with increasing success rates and minimal morbidity. Formation of a pseudocapsule and calcification are known histologic changes at the injection site. Postoperative ureteral obstruction has been reported in cases of severe voiding dysfunction, neurogenic bladder and abnormal ureteral anatomy. We present a case of chronic asymptomatic obstruction in a normal ureter following injection of 0.7 ml Deflux. ª 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Introduction Endoscopic injection of dextranomer/hyaluronic acid copolymer (Deflux) has been established as a safe and effective management option for vesicoureteral reflux (VUR) [1]. Success rates as high as 90% have been reported for VUR grade IeIV; however, complex cases involving
* Corresponding author. Tel.: þ1 319 384 8299; fax: þ1 319 356 3900. E-mail address: [email protected] (C.S. Cooper).
ureteral duplication, ureteroceles after puncture, paraureteral diverticula and neurogenic bladder have significantly lower resolution rates [2]. We present a case of chronic asymptomatic obstruction in a normal ureter following injection of Deflux.
Case report An infant girl presented locally at 9 weeks of age with a febrile urinary tract infection and pyelonephritis. Workup included a voiding cystourethrogram (VCUG), which
1477-5131/$36 ª 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jpurol.2011.12.006
e28 revealed grade II vesicoureteral reflux (VUR) on the right. Ultrasound did not demonstrate any hydronephrosis or evidence of duplication. The child was placed on prophylactic antibiotics after an appropriate treatment course. Repeat VCUG at 15 months of age demonstrated persistent grade I reflux on the right. She was referred to us at 18 months of age with recurrent breakthrough febrile urinary tract infections despite prophylactic antibiotics. Review of VCUG confirmed right-sided grade I VUR, with reflux into the distal third of the ureter during the filling phase. There was no evidence of ureteral dilation or duplication and the bladder wall appeared smooth. Retroperitoneal ultrasound did not reveal any evidence of hydroureteronephrosis or anatomic anomaly. After a review of treatment options with the parents, the patient remained on prophylactic antibiotics and planned annual surveillance with ultrasound and VCUG. The child developed three infections including an episode of pyelonephritis in the ensuing 6 months. Given the occurrence of multiple febrile breakthrough infections, all documented with catheterized specimens, her parents elected to proceed with endoscopic intervention. The patient underwent cystoscopy and 0.7 ml Deflux (Oceana Therapeutics, Inc., Edison, NJ, USA)was injected beneath the right ureteral orifice via the hydrodistentioneimplantation technique (HIT), resulting in a standard subureteric mound. The right ureteral orifice did not appear grossly patulous but did hydrodistend. At the time of Deflux injection, the child was not yet toilet-trained and had no signs of voiding dysfunction. Mild hydroureteronephrosis was detected on initial postprocedure ultrasound at 6 weeks. A repeat ultrasound was obtained 6 weeks later, which demonstrated mildly increased hydroureteronephrosis. Subsequent MAG-3 renal scan with furosemide revealed a differential function of 55% on the left and 45% on the right, with delayed washout on the right (T½ 24 min). Interval ultrasound and renal scan at 6 months were relatively stable. Repeat ultrasound at 6 months (approximately 15 months post Deflux) revealed progressive hydroureteronephrosis. At this time, ureteral dilation could be seen from the kidney to the level of the subureteric mound at the ureterovesical junction (Fig. 1). A repeat renal scan revealed a decrease in relative function from 45% to 27% (Fig. 2), with delayed washout on the right
A.M. Arlen et al. (T½ 28 min). Creatinine remained within normal limits, and the child did not experience urinary tract infections postoperatively. She was toilet-trained uneventfully with normal voiding habits. The child underwent an open right ureteral reimplantation for chronic partial ureteral obstruction. Intraoperatively, the bladder appeared to be of normal thickness and capacity. A 7mm nodule located anterolateral to the right ureteral orifice was visualized. The orifice accommodated a 5-Fr feeding tube. A second loculated area of walled-off Deflux was identified inferior to the ureter. The Deflux pseudocapsule was removed and each of the individual Deflux beads was noted to be enlarged and of a yellowish color. In addition to the visual increase in the size of the Deflux beads, subjectively the volume removed was much larger than 0.7 ml. The distal ureter was excised and a Cohen cross-trigonal ureteral reimplantation was performed without complication. The child’s postoperative course was uneventful. Ultrasound at 6 weeks post reimplant demonstrated resolution of hydronephrosis. Pathological analysis revealed foreign material with fibrin and calcification. The distal ureter was noted to have adjacent foreign material with foreign body giant cell reaction (Fig. 3).
Discussion Relatively few Deflux injection-related complications have been reported, and surgically relevant obstruction is rare. In 2004, Snodgrass reported a case of obstruction attributed to the dysmorphic nature of the injected ureter [3]. Vandersteen et al. reported a 0.6% incidence of ureteral obstruction; 80% occurred in children with severe voiding dysfunction or myelomeningocele and one patient had a complete ureteral duplication [4]. Histologic studies of the distal ureter have been performed, and demonstrated the formation of a pseudocapsule with granulomatous inflammation and calcification at the injection site [5]. Calcifications within the Deflux bleb have been previously reported [6,7]. Broderick et al. reported diffuse foreign body giant cell reaction within the lamina propria of an excised distal ureter in a child undergoing
Figure 1 Ultrasound at 15 months post Deflux demonstrating interval increase in right-sided hydroureteronephrosis (A) and evident Deflux mound at ureterovesical junction (B).
Ureteral obstruction post Deflux injection
Figure 2
e29
Renal scan demonstrating decreased relative right renal function and delayed washout indicative of partial obstruction.
Figure 3 Abundant granulomatous inflammation with foreign body giant cells in soft tissue adjacent to ureter (A). Abundant pale staining foreign material surrounded by a rim of necrosis and foreign body giant cells (B).
e30 ureteral reimplantation with persistent VUR following Deflux injection on two occasions, consistent with our pathologic analysis [8]. The Deflux was found to have migrated cephalad along the ureter, and it was postulated that phagocytosis may play a role in loss of injected volume and subsequent Deflux failure. In our case, the volume of foreign material excised at the time of open surgery appeared significantly greater than the injected volume of 0.7 ml. It is hypothesized that the volume of foreign material was greater than the injected volume in this child secondary to calcification and exaggerated local tissue reaction. This case serves as an important example that ureteral obstruction may occur after Deflux injection, even in a normal ureter following a low volume injection.
Conflict of interest None.
Funding None.
A.M. Arlen et al.
References [1] Peters CA, Skoog SJ, Arant BS, Copp HL, Elder JS, Hudson RG, et al. Summary of the AUA guideline on management of primary vesicoureteral reflux in children. J Urol 2010;184:1134e44. [2] Molitierno JA, Scherz HC, Kirsch AJ. Endoscopic treatment of vesicoureteral reflux using dextranomer hyaluronic acid polymer. J Pediatr Urol 2008;4:221e8. [3] Snodgrass WT. Obstruction of a dysmorphic ureter following dextranomer/hyaluronic acid copolymer. J Urol 2004;171: 395e6. [4] Vandersteen DR, Routh JC, Kirsch AJ, Scherz HC, Ritchey ML, Shapiro E, et al. Postoperative ureteral obstruction after subureteral injection of dextranomer/hyaluronic acid copolymer. J Urol 2006;176:1593e5. [5] Stenberg A, Larsson E, La ¨ckgren G. Endoscopic treatment with dextranomer/hyaluronic acid for vesicoureteral reflux: histologic findings. J Urol 2003;169:1109e13. [6] Noe HN. Calcification in a Deflux bleb thought to be a ureteral calculus in a child. J Pediatr Urol 2008;4:88e9. [7] Palagiri AV, Dangle PP. Distal ureteral calcification secondary to Deflux injection: a reality or myth? Urology 2011;77:1217e9. [8] Broderick K, Thompson JH, Khan AR, Geenfield SP. Giant cell reaction with phagocytosis adjacent to dextranomer/hyaluronic acid (Deflux) implant: possible reason for Deflux failure. J Pediatr Urol 2008;4:319e21.
CASE REPORT
Asymptomatic chronic partial obstruction of a normal ureter following dextranomer/hyaluronic acid copolymer (Deflux) injection for grade I vesicoureteral reflux Angela M. Arlen a, Brittany L. Pakalniskis b, Christopher S. Cooper a,* a b
Department of Urology, University of Iowa, 200 Hawkins Dr., 3 RCP, Iowa City, IA 52242-1089, United States Department of Pathology, University of Iowa, 200 Hawkins Dr., 3 RCP, Iowa City, IA 52242-1089, United States
Received 25 October 2011; accepted 8 December 2011 Available online 29 December 2011
KEYWORDS Vesicoureteral reflux; Ureteral obstruction; Child
Abstract Endoscopic management of vesicoureteral reflux with dextranomer/hyaluronic copolymer (Deflux, Oceana Therapeutics, Inc., Edison, NJ, USA) has gained widespread acceptance with increasing success rates and minimal morbidity. Formation of a pseudocapsule and calcification are known histologic changes at the injection site. Postoperative ureteral obstruction has been reported in cases of severe voiding dysfunction, neurogenic bladder and abnormal ureteral anatomy. We present a case of chronic asymptomatic obstruction in a normal ureter following injection of 0.7 ml Deflux. ª 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Introduction Endoscopic injection of dextranomer/hyaluronic acid copolymer (Deflux) has been established as a safe and effective management option for vesicoureteral reflux (VUR) [1]. Success rates as high as 90% have been reported for VUR grade IeIV; however, complex cases involving
* Corresponding author. Tel.: þ1 319 384 8299; fax: þ1 319 356 3900. E-mail address: [email protected] (C.S. Cooper).
ureteral duplication, ureteroceles after puncture, paraureteral diverticula and neurogenic bladder have significantly lower resolution rates [2]. We present a case of chronic asymptomatic obstruction in a normal ureter following injection of Deflux.
Case report An infant girl presented locally at 9 weeks of age with a febrile urinary tract infection and pyelonephritis. Workup included a voiding cystourethrogram (VCUG), which
1477-5131/$36 ª 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jpurol.2011.12.006
e28 revealed grade II vesicoureteral reflux (VUR) on the right. Ultrasound did not demonstrate any hydronephrosis or evidence of duplication. The child was placed on prophylactic antibiotics after an appropriate treatment course. Repeat VCUG at 15 months of age demonstrated persistent grade I reflux on the right. She was referred to us at 18 months of age with recurrent breakthrough febrile urinary tract infections despite prophylactic antibiotics. Review of VCUG confirmed right-sided grade I VUR, with reflux into the distal third of the ureter during the filling phase. There was no evidence of ureteral dilation or duplication and the bladder wall appeared smooth. Retroperitoneal ultrasound did not reveal any evidence of hydroureteronephrosis or anatomic anomaly. After a review of treatment options with the parents, the patient remained on prophylactic antibiotics and planned annual surveillance with ultrasound and VCUG. The child developed three infections including an episode of pyelonephritis in the ensuing 6 months. Given the occurrence of multiple febrile breakthrough infections, all documented with catheterized specimens, her parents elected to proceed with endoscopic intervention. The patient underwent cystoscopy and 0.7 ml Deflux (Oceana Therapeutics, Inc., Edison, NJ, USA)was injected beneath the right ureteral orifice via the hydrodistentioneimplantation technique (HIT), resulting in a standard subureteric mound. The right ureteral orifice did not appear grossly patulous but did hydrodistend. At the time of Deflux injection, the child was not yet toilet-trained and had no signs of voiding dysfunction. Mild hydroureteronephrosis was detected on initial postprocedure ultrasound at 6 weeks. A repeat ultrasound was obtained 6 weeks later, which demonstrated mildly increased hydroureteronephrosis. Subsequent MAG-3 renal scan with furosemide revealed a differential function of 55% on the left and 45% on the right, with delayed washout on the right (T½ 24 min). Interval ultrasound and renal scan at 6 months were relatively stable. Repeat ultrasound at 6 months (approximately 15 months post Deflux) revealed progressive hydroureteronephrosis. At this time, ureteral dilation could be seen from the kidney to the level of the subureteric mound at the ureterovesical junction (Fig. 1). A repeat renal scan revealed a decrease in relative function from 45% to 27% (Fig. 2), with delayed washout on the right
A.M. Arlen et al. (T½ 28 min). Creatinine remained within normal limits, and the child did not experience urinary tract infections postoperatively. She was toilet-trained uneventfully with normal voiding habits. The child underwent an open right ureteral reimplantation for chronic partial ureteral obstruction. Intraoperatively, the bladder appeared to be of normal thickness and capacity. A 7mm nodule located anterolateral to the right ureteral orifice was visualized. The orifice accommodated a 5-Fr feeding tube. A second loculated area of walled-off Deflux was identified inferior to the ureter. The Deflux pseudocapsule was removed and each of the individual Deflux beads was noted to be enlarged and of a yellowish color. In addition to the visual increase in the size of the Deflux beads, subjectively the volume removed was much larger than 0.7 ml. The distal ureter was excised and a Cohen cross-trigonal ureteral reimplantation was performed without complication. The child’s postoperative course was uneventful. Ultrasound at 6 weeks post reimplant demonstrated resolution of hydronephrosis. Pathological analysis revealed foreign material with fibrin and calcification. The distal ureter was noted to have adjacent foreign material with foreign body giant cell reaction (Fig. 3).
Discussion Relatively few Deflux injection-related complications have been reported, and surgically relevant obstruction is rare. In 2004, Snodgrass reported a case of obstruction attributed to the dysmorphic nature of the injected ureter [3]. Vandersteen et al. reported a 0.6% incidence of ureteral obstruction; 80% occurred in children with severe voiding dysfunction or myelomeningocele and one patient had a complete ureteral duplication [4]. Histologic studies of the distal ureter have been performed, and demonstrated the formation of a pseudocapsule with granulomatous inflammation and calcification at the injection site [5]. Calcifications within the Deflux bleb have been previously reported [6,7]. Broderick et al. reported diffuse foreign body giant cell reaction within the lamina propria of an excised distal ureter in a child undergoing
Figure 1 Ultrasound at 15 months post Deflux demonstrating interval increase in right-sided hydroureteronephrosis (A) and evident Deflux mound at ureterovesical junction (B).
Ureteral obstruction post Deflux injection
Figure 2
e29
Renal scan demonstrating decreased relative right renal function and delayed washout indicative of partial obstruction.
Figure 3 Abundant granulomatous inflammation with foreign body giant cells in soft tissue adjacent to ureter (A). Abundant pale staining foreign material surrounded by a rim of necrosis and foreign body giant cells (B).
e30 ureteral reimplantation with persistent VUR following Deflux injection on two occasions, consistent with our pathologic analysis [8]. The Deflux was found to have migrated cephalad along the ureter, and it was postulated that phagocytosis may play a role in loss of injected volume and subsequent Deflux failure. In our case, the volume of foreign material excised at the time of open surgery appeared significantly greater than the injected volume of 0.7 ml. It is hypothesized that the volume of foreign material was greater than the injected volume in this child secondary to calcification and exaggerated local tissue reaction. This case serves as an important example that ureteral obstruction may occur after Deflux injection, even in a normal ureter following a low volume injection.
Conflict of interest None.
Funding None.
A.M. Arlen et al.
References [1] Peters CA, Skoog SJ, Arant BS, Copp HL, Elder JS, Hudson RG, et al. Summary of the AUA guideline on management of primary vesicoureteral reflux in children. J Urol 2010;184:1134e44. [2] Molitierno JA, Scherz HC, Kirsch AJ. Endoscopic treatment of vesicoureteral reflux using dextranomer hyaluronic acid polymer. J Pediatr Urol 2008;4:221e8. [3] Snodgrass WT. Obstruction of a dysmorphic ureter following dextranomer/hyaluronic acid copolymer. J Urol 2004;171: 395e6. [4] Vandersteen DR, Routh JC, Kirsch AJ, Scherz HC, Ritchey ML, Shapiro E, et al. Postoperative ureteral obstruction after subureteral injection of dextranomer/hyaluronic acid copolymer. J Urol 2006;176:1593e5. [5] Stenberg A, Larsson E, La ¨ckgren G. Endoscopic treatment with dextranomer/hyaluronic acid for vesicoureteral reflux: histologic findings. J Urol 2003;169:1109e13. [6] Noe HN. Calcification in a Deflux bleb thought to be a ureteral calculus in a child. J Pediatr Urol 2008;4:88e9. [7] Palagiri AV, Dangle PP. Distal ureteral calcification secondary to Deflux injection: a reality or myth? Urology 2011;77:1217e9. [8] Broderick K, Thompson JH, Khan AR, Geenfield SP. Giant cell reaction with phagocytosis adjacent to dextranomer/hyaluronic acid (Deflux) implant: possible reason for Deflux failure. J Pediatr Urol 2008;4:319e21.