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HYALURONIC ACID COPOLYMER: THE EFFICACY OF BLADDER NECK INJECTION FOR URINARY INCONTINENCE
0022-5347/05/1744-1691/0 THE JOURNAL OF UROLOGY® Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 174, 1691–1694, October 2005 Printed in U.S.A.
DOI: 10.1097/01.ju.0000179253.13807.82
ALTERNATIVE USES OF DEXTRANOMER/HYALURONIC ACID COPOLYMER: THE EFFICACY OF BLADDER NECK INJECTION FOR URINARY INCONTINENCE ROSALIA MISSERI,* ANTHONY J. CASALE,† MARK P. CAIN
AND
RICHARD C. RINK
From the Department of Pediatric Urology, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana
ABSTRACT
Purpose: Urinary continence in children with neuropathic bladder and other urological disorders depends on a bladder with adequate low pressure storage capacity and a competent outlet. Various procedures are performed with the goal of achieving continence in these patients. Recently, dextranomer/hyaluronic acid copolymer (Dx/H) has been introduced for the correction of vesicoureteral reflux. We evaluated the efficacy of submucosal bladder neck (BN) injection of Dx/H for urethral incontinence in children. Materials and Methods: We retrospectively reviewed continence status after Dx/H injection into the BN for incontinence. Parameters examined include gender, underlying disease, prior BN surgery and means of emptying the bladder. Continence was described by the patients and/or their parents as unchanged (no change in requirements for diapers or pads), improved (longer dry intervals or requiring fewer pads/diapers) or dry (requiring no pads and dry in underwear). Results: A total of 6 males and 10 females underwent injections for treatment of incontinence. Mean followup was 9.5 months (range 3 to 24). Volumes injected ranged from 0.8 to 4.4 ml (mean 1.88). Of the patients 3 achieved dryness after injection, all of whom had catheterizable urinary stomas and two-thirds had undergone bladder augmentations. All 5 patients who improved had undergone augmentation and had catheterizable channels. No improvement was seen in 8 patients. Conclusions: Injection at the BN is well tolerated and relatively easy to perform. Success rates may be better in females and in patients with neuropathic incontinence. Despite limited success it remains an option for all patients who are poor surgical candidates and those who want to avoid extensive BN reconstruction. KEY WORDS: urinary incontinence, injections, dextranomer-hyaluronic acid copolymer
One of the major goals in the treatment of children with neuropathic voiding dysfunction or anatomical abnormalities such as exstrophy or epispadias is continence. When conservative therapy with clean intermittent catheterization and pharmacological therapy fails only surgical options remain. Procedures such as bladder neck (BN) reconstruction, BN sling surgery, artificial urinary sphincter placement and BN closure are used to achieve the goal of continence. To be successful any bladder outlet enhancing procedure must be performed in a bladder with good capacity and normal compliance. Perhaps the reason why so many techniques exist is that no single surgery is as effective as one might hope. Recently, endoscopic injection of the bladder neck has been described as a means of achieving continence. Materials such as polydimethylsiloxane, polytetrafluoroethylene particles, collagen, carbon-coated zirconium oxide beads, autologous fat and implantable microballoons have been used to help increase bladder outlet resistance.1– 6 Dextranomer/hyaluronic acid copolymer (Dx/H) has recently been introduced for the treatment of vesicoureteral reflux with favorable results.7 We evaluated the efficacy of Dx/H injection to the bladder neck of incontinent children and attempt to define parameters that predict success. * Current address: Weill Medical College of Cornell University, Children’s Hospital of New York Presbyterian, Institute for Pediatric Urology, New York, New York 10021. † Correspondence: University of Louisville, 234 East Gray St., Suite 662, Louisville, Kentucky 40202.
MATERIALS AND METHODS
We retrospectively reviewed the charts of patients who underwent bladder neck injection therapy with Dx/H for urinary incontinence during a 16-month period. The procedure was offered to patients with refractory urinary incontinence despite adequate bladder capacity without urodynamic evidence of bladder instability or diminished compliance. With the patient under general anesthesia, Dx/H was injected in an antegrade fashion through a continent catheterizable channel if available or transurethrally in a retrograde fashion with the aid of a 10Fr offset pediatric cystoscope. The offset cystoscope allowed for Dx/H to be delivered through a 3.7Fr needle. The needle was then manipulated to penetrate the submucosa of the bladder neck. Once the needle was positioned a small volume of Dx/H was injected to confirm positioning. The tracking pattern of the material was observed as more of the material was injected. After allowing approximately 15 seconds to lapse after completion of the injection the needle was withdrawn. The needle was then placed in the submucosa approximately 180 degrees from the original injection site. Again positioning was confirmed and additional Dx/H was injected until the bladder neck appeared to coapt (see figure). Patients were instructed to continue catheterizing as scheduled through the catheterizable channel or per urethra for those without a channel. Alternately a catheter may be left indwelling through a catheterizable channel for 2 days. Continence was described by the patients and/or their parents as unchanged (no change in requirements for diapers or
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BLADDER NECK INJECTION FOR URINARY INCONTINENCE
Antegrade appearance of bladder neck before (A) and after (B) treatment (note coaptation).
pads), improved (longer dry intervals, fewer diapers or pads) or dry (requiring no pads and dry in underwear). Parameters examined to compare patients who improved with those who remained incontinent include gender, underlying disease, prior BN surgery and means of emptying the bladder. RESULTS
A total of 6 males and 10 females 4 to 18 years old underwent a single Dx/H BN injection for incontinence. All procedures were performed in an outpatient setting by 1 of 3 surgeons (AJC, MPC and RCR). Median followup was 8 months (mean 9.5, range 3 to 24). The etiology of the incontinence included neuropathic bladder in 12 cases, exstrophyepispadias complex in 3 and bilateral ectopic ureters in 1. The volume injected ranged from 0.8 to 4.4 ml (mean 1.88). No urodynamic evidence of impaired compliance or instability was noted preoperatively. Pretreatment detrusor leak point pressures available in 12 patients with neuropathic bladders ranged from 25 to 31 cm H2O. Overall 3 of 16 (18.75%) patients achieved dryness after injection. Each of these injections was performed in an antegrade fashion through catheterizable urinary stomas. Incontinence was due to myelodysplasia in these 3 patients. Ileocystoplasty had been performed previously in 2 females with myelodysplasia, and prior continence procedures had been performed in 2 (1 Pippi-Salle bladder neck repair, 1 small intestinal submucosal sling). Average volume injected in this group was 2.13 ml (range 2 to 2.4). Improvement was noted in 5 of the 16 (31.25%) patients. This group included 1 patient with exstrophy-epispadias complex, who had undergone 2 prior Young-Dees-Leadbetter bladder neck repairs, and 4 with myelodysplasia. Of the 4 patients with myelodysplasia incontinence developed in 1 after augmentation despite normal postoperative bladder capacity and compliance, a prior small intestine submucosa (SIS) bladder neck sling failed in 1, a Young-Dees-Leadbetter repair with SIS sling as well as a subsequent attempt to achieve continence with collagen as a bulking agent failed in 1 and prior BN repair with SIS sling failed in 1. All of these patients had previously undergone augmentation and had catheterizable channels. Three injections were performed in retrograde fashion and 2 in an antegrade fashion. Average volume injected in this group was 1.76 ml (range 0.8 to 3). Of the 16 patients 8 (50%) had no improvement in continence status after Dx/H injections. This group included 4 children with myelomeningocele, 2 with the exstrophyepispadias complex, 1 with the VATER syndrome and 1 with ectopic ureters. Prior surgical attempts at continence in-
cluded sling in 2 cases and bladder neck repair in 1. One patient with myelomeningocele failed to become continent after 2 bladder neck surgeries (failed sling followed by BNR with sling). In the patient with bilateral ectopic ureters a prior BNR with sling failed. Of the 8 patients 6 had undergone augmentation and they had catheterizable channels. Average volume injected in this group was 1.77 ml (range 0.8 to 4.4). Injections were antegrade in 3, retrograde in 4, and antegrade and retrograde in 1. Of the 16 patients 3 catheterize per urethra and the remainder catheterize via a catheterizable channel. All patients who achieved dryness or improved empty the bladder through a catheterizable channel. Of the 12 patients with neuropathic bladder (myelomeningocele 11, VATER syndrome 1) 3 (25%) were dry after 1 injection, 4 (33%) had improved continence and 5 (42%) were unchanged. None of the 4 patients with nonneuropathic bladder achieved continence, 1 (25%) improved and 3 (75%) had no change. With respect to gender, none of the 6 males was dry, 3 (50%) improved and 3 (50%) were unchanged. The 3 male patients with improvement in continence had myelodysplasia and a history of a bladder neck sling (1), a previously failed BN repair and subsequent collagen injection at the bladder neck (1) and a failed BN repair with SIS sling (1). Of the 10 females 3 (30%) were dry, 2 (20%) improved and 5 (50%) were unchanged. The table shows success rates by prior bladder neck procedures to achieve continence. When questioned, all 5 patients with improvement in continence would repeat the procedure if the physician thought it appropriate, and 7 of the 8 who did not have durable results would also consider a second attempt. No case has been complicated by allergic reaction, wound infection or urinary tract infection. No patient in whom the procedure failed has presented for bladder neck repair or sling procedure. DISCUSSION
Treatment of incontinence in the pediatric population remains a challenge. Despite nonsurgical management with pharmacological agents and/or clean intermittent catheterization, some children remain incontinent and require surgical therapy to increase bladder capacity, improve bladder compliance and increase bladder outlet resistance. The injection of bulking agents at the bladder outlet for continence in children was first reported in 1985.8 Results using polytetrafluoroethylene were reasonable but the material fell out of favor with concerns over particle migration and granuloma formation.9 Since then the options for bulking materials have expanded to include other agents such as polydimethylsiloxane and collagen.1, 3 With success defined as improvement or dryness, success rates using these materials have ranged from 5% to 88% in children.10, 11 Given the efficacy of Dx/H for treatment of vesicoureteral reflux we sought to assess its role in the treatment of urinary incontinence in children. Our overall continence rate of 18.25% with moderate improvement in an additional 31.25% of patients injected with Dx/H is promising. Our results are similar to the long-term results recently reported by Lottman et al.12 Due to our small sample size, it is unclear whether children who have undergone prior bladder neck procedures fare
TABLE 1. Prior bladder neck procedure and success rates Continence Procedure None Bladder Bladder Bladder Bladder
neck neck neck neck
slings repairs repair with sling sling with collagen
No. Pts
No. Dry (%)
No. Improved (%)
No. Failed (%)
5 3 3 4 1
1 (20) 1 (33) 1 (33) 0 (0) 0 (0)
1 (20) 1 (33) 1 (33) 2 (50) 0 (0)
3 (60) 1 (33) 1 (33) 2 (50) 1 (100)
BLADDER NECK INJECTION FOR URINARY INCONTINENCE
better or worse than those who have not. Some studies have reported higher success rates in patients who undergo secondary collagen injections, while in a study using polydimethylsiloxane others contend that prior bladder neck surgery creates scarring that may hinder effective submucosal injection.1, 10, 13, 14 None of the patients who catheterize per urethra had improved continence after this procedure. Prior studies in which suprapubic cystostomy was performed in children who performed intermittent catheterizations before injection yielded continence rates of 76%.15 This high success rate was attributed to the cystostomy as catheterization may cause molding of the material. In our study failures in this group may be due to molding or migration of the implanted material due to catheterization. Longer followup may elucidate the impact of migration, absorption and molding of the material on the success of the technique. Although all patients who became dry after Dx/H injection were injected in an antegrade fashion, again due to small sample size, it is unclear whether the direction in which the material is injected is predictive of success. Larger volumes of material may need to be injected to improve continence. A visual end point for bladder neck coaptation is used to determine when bladder neck bulking is sufficient. Although difficult to devise, more objective means to determine when the correct amount of bulking agent has been injected would be helpful. As with other injection techniques, such as the STING procedure, a learning curve may exist. Each surgeon has had limited experience with bladder neck bulking using collagen. While technique and its associated learning curve may be important in the success of the procedure, we must also continue to develop and examine newer and possibly more suitable injectable materials for the treatment of incontinence. None of our patients in whom the procedure failed has presented for a formal bladder neck repair or bladder neck sling procedure. However, prior Dx/H injection has not presented additional technical difficulties when such procedures have been attempted.16 Several variables may have affected our surgical outcomes, including injection technique, patient characteristics (gender), etiology of the incontinence and prior surgical procedures. To better study the efficacy of bladder neck injection with Dx/H prospective studies of a larger patient population are necessary. CONCLUSIONS
Injection at the bladder neck is a well tolerated procedure that is relatively easy to perform. It should be considered an option for patients who are poor surgical candidates and those who want to avoid extensive bladder neck reconstruction. Patients with poor outlet resistance secondary to myelodysplasia may be the best candidates for this procedure. REFERENCES
1. Halachimi, S., Farhat, W., Metcalfe, P., Bagli, D. J., McLorie, G. A. and Khoury, A. E.: Efficacy of polydimethylsiloxane injection to the bladder neck and leaking diverting stoma for urinary continence. J Urol, 171: 1287, 2004 2. Berg, S.: Polytef augmentation urethroplasty: correction of surgically incurable urinary incontinence by injection technique. Arch Surg, 107: 379, 1973 3. Shortliffe, L. M. D., Freiha, F. A., Kessler, R., Stamey, T. A. and Constantinou, C. E.: Treatment of urinary incontinence by periurethral injection of glutaraldehyde cross-liked collagen. J Urol, 141: 538, 1989 4. Gonzalez de Garibay, A. S., Castillo-Jimeno, J. M. and Villanueva-Perez, P. I.: Treatment of urinary stress incontinence using paraurethral injection of autologous fat. Arch Esp Urol, 44: 595, 1991 5. Pycha, A., Klingler, C. H., Haitel, A., Heinz-Peer, G. and Marberger, M.: Implantable microballoons: an attractive alter-
6. 7.
8. 9.
10. 11. 12.
13. 14. 15. 16.
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native in the management of intrinsic sphincter deficiency. Eur Urol, 33: 469, 1998 Madjar, S., Covington-Nichols, C. and Secrest, C. L.: New periurethral bulking agent for stress urinary incontinence: modified technique and early results. J Urol, 170: 2327, 2003 Lackgren, G., Wahlin, N., Skoldenberg, E. and Stenberg, A.: Long term followup of children treated with dextranomer/ hyaluronic acid copolymer for vesicoureteral reflux. J Urol, 166: 1887, 2001 Vortsman, B., Lockhart, J., Kaufman, M. R. and Politano, V.: Polytetrafluoroethylene injection for urinary incontinence in children. J Urol, 133: 248, 1985 Malizia, A. A., Reiman, H. M., Myers, R. P., Sande, J. R., Barham, S. S., Benson, R. C. et al: Migration and granulomatous reaction after periurethral injection of polytef (Teflon). JAMA, 251: 3277, 1984 Wan, J., McGuire, E. J., Bloom, D. A. and Ritchey, M. L.: The treatment of urinary incontinence in children using glutaraldehyde cross-linked collagen. J Urol, 148: 127, 1992 Sundaram, C. P., Reinberg, Y. and Aliabadi, H. A.: Failure to obtain results with collagen implantation in children with urinary incontinence. J Urol, 157: 2306, 1997 Lottman, H. B., Margaryan, M., Bernuy, M., Grosz, A., Aigrain, Y. and Lortat-Jacob, S.: Long-term effect of dextranomer endoscopic injections for treatment of urinary incontinence: an update of a prospective study of 30 patients. Presented at Section on Urology, American Academy of Pediatrics, San Francisco, California, October 9 –11, 2005 Cole, E. E., Adams, M. C., Brock, J. W. and Pope, J. C.: Outcome of continence procedures in the pediatric patient: a single institutional experience. J Urol, 170: 560, 2003 Eckford, S. D. and Abrams, P.: Para-urethral collagen implantation for female stress urinary incontinence. Br J Urol, 68: 586, 1991 Bomalaski, M. D., Bloom, D. A., McGuire, E. J. and Panzl, A.: Glutaraldehyde cross-linked collagen in the treatment of urinary incontinence in children. J Urol, 155: 699, 1996 Lackgren, G.: Personal communication, October 2004 EDITORIAL COMMENT
Bulking agents initially found to be useful in subureteral injections for reflux seem destined to audition as bladder neck injections to cure incontinence. Dx/H is now the latest agent to be investigated for bladder neck injections. The authors should be commended for their interest in presenting their patients an endoscopic alternative to complex reconstructive surgery in the hopes of achieving continence. Unfortunately they found that there was “limited success” with this technique. Only 3 of 16 patients were dry and 5 showed improvement in incontinence. Quantifying this improvement (ie length of dry intervals) would allow the reader a better appreciation of the significance of the improvement. The authors acknowledge the need for a larger study. For instance, only 3 of their 16 patients catheterize per urethra. Only 5 patients who had not undergone prior continence procedures were available for review, and only 1 of these 5 was continent following injection. The study may have benefited from analysis of pretreatment urodynamic data, which can be helpful in predicting which children would have a successful outcome.1 In regard to technique, the injection was done by the retrograde transurethral approach or alternatively by the antegrade approach (ie via a catheterizable stoma). There has been discussion about injecting the bladder neck submucosa via antegrade and retrograde approaches simultaneously, allowing 2 perspectives for optimal coaptation.2 Additionally, the authors injected Dx/H at 2 separate sites 180 degrees apart. One wonders if injection in all 4 quadrants would improve coaptation and increase the success rate. Due to concerns of bulking agent migration, absorption and compression, longer followup would more strongly validate any successful results. Future studies should include the effect of a repeat injection on success rates as we have seen in description of success rates of subureteral injections for reflux. Overall, this experience with Dx/H injection of the bladder neck serves the purposes of offering patients options for the treatment of incontinence along with realistic expectations of the outcome of this treatment. If a larger study confirmed the findings of the current study, our incontinent patients would benefit in 2 ways: 1) patients more inclined to successful treatment with Dx/H would have a minimally invasive option for the treatment of incontinence and 2) identification of the poor performers would allow us to spare them a
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BLADDER NECK INJECTION FOR URINARY INCONTINENCE
procedure that has little chance of helping them. Richard N. Schlussel Division of Pediatric Urology Morgan Stanley Children’s Hospital of New York-Presbyterian New York, New York
1. Chernoff, A., Horowitz, M., Combs, A., Libretti, D., Nitti, V. and Glassberg, K.: Periurethral collagen injection for the treatment of urinary incontinence in children. J Urol, 157: 2303, 1997 2. Dean, G.: Personal communication
DISCUSSION Dr. Joao L. Pippi-Salle. When you inject the bladder neck with Dx/H or other materials, how difficult is it to get back either to do a bladder neck reconstruction or a bladder neck closure? Dr. Rosalia Misseri. To date, we have not had to go back on any of these cases. We have reimplanted some ureters that were previously injected with Dx/H, and in those patients what you see is that the Dx/H material often just extrudes out. There are some histological changes that we have seen in the distal ureter that was injected, and so perhaps it might just extrude out as it does in the ureter or the tissue reaction may be more substantial at the bladder neck.
Vol. 174, 1691–1694, October 2005 Printed in U.S.A.
DOI: 10.1097/01.ju.0000179253.13807.82
ALTERNATIVE USES OF DEXTRANOMER/HYALURONIC ACID COPOLYMER: THE EFFICACY OF BLADDER NECK INJECTION FOR URINARY INCONTINENCE ROSALIA MISSERI,* ANTHONY J. CASALE,† MARK P. CAIN
AND
RICHARD C. RINK
From the Department of Pediatric Urology, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana
ABSTRACT
Purpose: Urinary continence in children with neuropathic bladder and other urological disorders depends on a bladder with adequate low pressure storage capacity and a competent outlet. Various procedures are performed with the goal of achieving continence in these patients. Recently, dextranomer/hyaluronic acid copolymer (Dx/H) has been introduced for the correction of vesicoureteral reflux. We evaluated the efficacy of submucosal bladder neck (BN) injection of Dx/H for urethral incontinence in children. Materials and Methods: We retrospectively reviewed continence status after Dx/H injection into the BN for incontinence. Parameters examined include gender, underlying disease, prior BN surgery and means of emptying the bladder. Continence was described by the patients and/or their parents as unchanged (no change in requirements for diapers or pads), improved (longer dry intervals or requiring fewer pads/diapers) or dry (requiring no pads and dry in underwear). Results: A total of 6 males and 10 females underwent injections for treatment of incontinence. Mean followup was 9.5 months (range 3 to 24). Volumes injected ranged from 0.8 to 4.4 ml (mean 1.88). Of the patients 3 achieved dryness after injection, all of whom had catheterizable urinary stomas and two-thirds had undergone bladder augmentations. All 5 patients who improved had undergone augmentation and had catheterizable channels. No improvement was seen in 8 patients. Conclusions: Injection at the BN is well tolerated and relatively easy to perform. Success rates may be better in females and in patients with neuropathic incontinence. Despite limited success it remains an option for all patients who are poor surgical candidates and those who want to avoid extensive BN reconstruction. KEY WORDS: urinary incontinence, injections, dextranomer-hyaluronic acid copolymer
One of the major goals in the treatment of children with neuropathic voiding dysfunction or anatomical abnormalities such as exstrophy or epispadias is continence. When conservative therapy with clean intermittent catheterization and pharmacological therapy fails only surgical options remain. Procedures such as bladder neck (BN) reconstruction, BN sling surgery, artificial urinary sphincter placement and BN closure are used to achieve the goal of continence. To be successful any bladder outlet enhancing procedure must be performed in a bladder with good capacity and normal compliance. Perhaps the reason why so many techniques exist is that no single surgery is as effective as one might hope. Recently, endoscopic injection of the bladder neck has been described as a means of achieving continence. Materials such as polydimethylsiloxane, polytetrafluoroethylene particles, collagen, carbon-coated zirconium oxide beads, autologous fat and implantable microballoons have been used to help increase bladder outlet resistance.1– 6 Dextranomer/hyaluronic acid copolymer (Dx/H) has recently been introduced for the treatment of vesicoureteral reflux with favorable results.7 We evaluated the efficacy of Dx/H injection to the bladder neck of incontinent children and attempt to define parameters that predict success. * Current address: Weill Medical College of Cornell University, Children’s Hospital of New York Presbyterian, Institute for Pediatric Urology, New York, New York 10021. † Correspondence: University of Louisville, 234 East Gray St., Suite 662, Louisville, Kentucky 40202.
MATERIALS AND METHODS
We retrospectively reviewed the charts of patients who underwent bladder neck injection therapy with Dx/H for urinary incontinence during a 16-month period. The procedure was offered to patients with refractory urinary incontinence despite adequate bladder capacity without urodynamic evidence of bladder instability or diminished compliance. With the patient under general anesthesia, Dx/H was injected in an antegrade fashion through a continent catheterizable channel if available or transurethrally in a retrograde fashion with the aid of a 10Fr offset pediatric cystoscope. The offset cystoscope allowed for Dx/H to be delivered through a 3.7Fr needle. The needle was then manipulated to penetrate the submucosa of the bladder neck. Once the needle was positioned a small volume of Dx/H was injected to confirm positioning. The tracking pattern of the material was observed as more of the material was injected. After allowing approximately 15 seconds to lapse after completion of the injection the needle was withdrawn. The needle was then placed in the submucosa approximately 180 degrees from the original injection site. Again positioning was confirmed and additional Dx/H was injected until the bladder neck appeared to coapt (see figure). Patients were instructed to continue catheterizing as scheduled through the catheterizable channel or per urethra for those without a channel. Alternately a catheter may be left indwelling through a catheterizable channel for 2 days. Continence was described by the patients and/or their parents as unchanged (no change in requirements for diapers or
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BLADDER NECK INJECTION FOR URINARY INCONTINENCE
Antegrade appearance of bladder neck before (A) and after (B) treatment (note coaptation).
pads), improved (longer dry intervals, fewer diapers or pads) or dry (requiring no pads and dry in underwear). Parameters examined to compare patients who improved with those who remained incontinent include gender, underlying disease, prior BN surgery and means of emptying the bladder. RESULTS
A total of 6 males and 10 females 4 to 18 years old underwent a single Dx/H BN injection for incontinence. All procedures were performed in an outpatient setting by 1 of 3 surgeons (AJC, MPC and RCR). Median followup was 8 months (mean 9.5, range 3 to 24). The etiology of the incontinence included neuropathic bladder in 12 cases, exstrophyepispadias complex in 3 and bilateral ectopic ureters in 1. The volume injected ranged from 0.8 to 4.4 ml (mean 1.88). No urodynamic evidence of impaired compliance or instability was noted preoperatively. Pretreatment detrusor leak point pressures available in 12 patients with neuropathic bladders ranged from 25 to 31 cm H2O. Overall 3 of 16 (18.75%) patients achieved dryness after injection. Each of these injections was performed in an antegrade fashion through catheterizable urinary stomas. Incontinence was due to myelodysplasia in these 3 patients. Ileocystoplasty had been performed previously in 2 females with myelodysplasia, and prior continence procedures had been performed in 2 (1 Pippi-Salle bladder neck repair, 1 small intestinal submucosal sling). Average volume injected in this group was 2.13 ml (range 2 to 2.4). Improvement was noted in 5 of the 16 (31.25%) patients. This group included 1 patient with exstrophy-epispadias complex, who had undergone 2 prior Young-Dees-Leadbetter bladder neck repairs, and 4 with myelodysplasia. Of the 4 patients with myelodysplasia incontinence developed in 1 after augmentation despite normal postoperative bladder capacity and compliance, a prior small intestine submucosa (SIS) bladder neck sling failed in 1, a Young-Dees-Leadbetter repair with SIS sling as well as a subsequent attempt to achieve continence with collagen as a bulking agent failed in 1 and prior BN repair with SIS sling failed in 1. All of these patients had previously undergone augmentation and had catheterizable channels. Three injections were performed in retrograde fashion and 2 in an antegrade fashion. Average volume injected in this group was 1.76 ml (range 0.8 to 3). Of the 16 patients 8 (50%) had no improvement in continence status after Dx/H injections. This group included 4 children with myelomeningocele, 2 with the exstrophyepispadias complex, 1 with the VATER syndrome and 1 with ectopic ureters. Prior surgical attempts at continence in-
cluded sling in 2 cases and bladder neck repair in 1. One patient with myelomeningocele failed to become continent after 2 bladder neck surgeries (failed sling followed by BNR with sling). In the patient with bilateral ectopic ureters a prior BNR with sling failed. Of the 8 patients 6 had undergone augmentation and they had catheterizable channels. Average volume injected in this group was 1.77 ml (range 0.8 to 4.4). Injections were antegrade in 3, retrograde in 4, and antegrade and retrograde in 1. Of the 16 patients 3 catheterize per urethra and the remainder catheterize via a catheterizable channel. All patients who achieved dryness or improved empty the bladder through a catheterizable channel. Of the 12 patients with neuropathic bladder (myelomeningocele 11, VATER syndrome 1) 3 (25%) were dry after 1 injection, 4 (33%) had improved continence and 5 (42%) were unchanged. None of the 4 patients with nonneuropathic bladder achieved continence, 1 (25%) improved and 3 (75%) had no change. With respect to gender, none of the 6 males was dry, 3 (50%) improved and 3 (50%) were unchanged. The 3 male patients with improvement in continence had myelodysplasia and a history of a bladder neck sling (1), a previously failed BN repair and subsequent collagen injection at the bladder neck (1) and a failed BN repair with SIS sling (1). Of the 10 females 3 (30%) were dry, 2 (20%) improved and 5 (50%) were unchanged. The table shows success rates by prior bladder neck procedures to achieve continence. When questioned, all 5 patients with improvement in continence would repeat the procedure if the physician thought it appropriate, and 7 of the 8 who did not have durable results would also consider a second attempt. No case has been complicated by allergic reaction, wound infection or urinary tract infection. No patient in whom the procedure failed has presented for bladder neck repair or sling procedure. DISCUSSION
Treatment of incontinence in the pediatric population remains a challenge. Despite nonsurgical management with pharmacological agents and/or clean intermittent catheterization, some children remain incontinent and require surgical therapy to increase bladder capacity, improve bladder compliance and increase bladder outlet resistance. The injection of bulking agents at the bladder outlet for continence in children was first reported in 1985.8 Results using polytetrafluoroethylene were reasonable but the material fell out of favor with concerns over particle migration and granuloma formation.9 Since then the options for bulking materials have expanded to include other agents such as polydimethylsiloxane and collagen.1, 3 With success defined as improvement or dryness, success rates using these materials have ranged from 5% to 88% in children.10, 11 Given the efficacy of Dx/H for treatment of vesicoureteral reflux we sought to assess its role in the treatment of urinary incontinence in children. Our overall continence rate of 18.25% with moderate improvement in an additional 31.25% of patients injected with Dx/H is promising. Our results are similar to the long-term results recently reported by Lottman et al.12 Due to our small sample size, it is unclear whether children who have undergone prior bladder neck procedures fare
TABLE 1. Prior bladder neck procedure and success rates Continence Procedure None Bladder Bladder Bladder Bladder
neck neck neck neck
slings repairs repair with sling sling with collagen
No. Pts
No. Dry (%)
No. Improved (%)
No. Failed (%)
5 3 3 4 1
1 (20) 1 (33) 1 (33) 0 (0) 0 (0)
1 (20) 1 (33) 1 (33) 2 (50) 0 (0)
3 (60) 1 (33) 1 (33) 2 (50) 1 (100)
BLADDER NECK INJECTION FOR URINARY INCONTINENCE
better or worse than those who have not. Some studies have reported higher success rates in patients who undergo secondary collagen injections, while in a study using polydimethylsiloxane others contend that prior bladder neck surgery creates scarring that may hinder effective submucosal injection.1, 10, 13, 14 None of the patients who catheterize per urethra had improved continence after this procedure. Prior studies in which suprapubic cystostomy was performed in children who performed intermittent catheterizations before injection yielded continence rates of 76%.15 This high success rate was attributed to the cystostomy as catheterization may cause molding of the material. In our study failures in this group may be due to molding or migration of the implanted material due to catheterization. Longer followup may elucidate the impact of migration, absorption and molding of the material on the success of the technique. Although all patients who became dry after Dx/H injection were injected in an antegrade fashion, again due to small sample size, it is unclear whether the direction in which the material is injected is predictive of success. Larger volumes of material may need to be injected to improve continence. A visual end point for bladder neck coaptation is used to determine when bladder neck bulking is sufficient. Although difficult to devise, more objective means to determine when the correct amount of bulking agent has been injected would be helpful. As with other injection techniques, such as the STING procedure, a learning curve may exist. Each surgeon has had limited experience with bladder neck bulking using collagen. While technique and its associated learning curve may be important in the success of the procedure, we must also continue to develop and examine newer and possibly more suitable injectable materials for the treatment of incontinence. None of our patients in whom the procedure failed has presented for a formal bladder neck repair or bladder neck sling procedure. However, prior Dx/H injection has not presented additional technical difficulties when such procedures have been attempted.16 Several variables may have affected our surgical outcomes, including injection technique, patient characteristics (gender), etiology of the incontinence and prior surgical procedures. To better study the efficacy of bladder neck injection with Dx/H prospective studies of a larger patient population are necessary. CONCLUSIONS
Injection at the bladder neck is a well tolerated procedure that is relatively easy to perform. It should be considered an option for patients who are poor surgical candidates and those who want to avoid extensive bladder neck reconstruction. Patients with poor outlet resistance secondary to myelodysplasia may be the best candidates for this procedure. REFERENCES
1. Halachimi, S., Farhat, W., Metcalfe, P., Bagli, D. J., McLorie, G. A. and Khoury, A. E.: Efficacy of polydimethylsiloxane injection to the bladder neck and leaking diverting stoma for urinary continence. J Urol, 171: 1287, 2004 2. Berg, S.: Polytef augmentation urethroplasty: correction of surgically incurable urinary incontinence by injection technique. Arch Surg, 107: 379, 1973 3. Shortliffe, L. M. D., Freiha, F. A., Kessler, R., Stamey, T. A. and Constantinou, C. E.: Treatment of urinary incontinence by periurethral injection of glutaraldehyde cross-liked collagen. J Urol, 141: 538, 1989 4. Gonzalez de Garibay, A. S., Castillo-Jimeno, J. M. and Villanueva-Perez, P. I.: Treatment of urinary stress incontinence using paraurethral injection of autologous fat. Arch Esp Urol, 44: 595, 1991 5. Pycha, A., Klingler, C. H., Haitel, A., Heinz-Peer, G. and Marberger, M.: Implantable microballoons: an attractive alter-
6. 7.
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13. 14. 15. 16.
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native in the management of intrinsic sphincter deficiency. Eur Urol, 33: 469, 1998 Madjar, S., Covington-Nichols, C. and Secrest, C. L.: New periurethral bulking agent for stress urinary incontinence: modified technique and early results. J Urol, 170: 2327, 2003 Lackgren, G., Wahlin, N., Skoldenberg, E. and Stenberg, A.: Long term followup of children treated with dextranomer/ hyaluronic acid copolymer for vesicoureteral reflux. J Urol, 166: 1887, 2001 Vortsman, B., Lockhart, J., Kaufman, M. R. and Politano, V.: Polytetrafluoroethylene injection for urinary incontinence in children. J Urol, 133: 248, 1985 Malizia, A. A., Reiman, H. M., Myers, R. P., Sande, J. R., Barham, S. S., Benson, R. C. et al: Migration and granulomatous reaction after periurethral injection of polytef (Teflon). JAMA, 251: 3277, 1984 Wan, J., McGuire, E. J., Bloom, D. A. and Ritchey, M. L.: The treatment of urinary incontinence in children using glutaraldehyde cross-linked collagen. J Urol, 148: 127, 1992 Sundaram, C. P., Reinberg, Y. and Aliabadi, H. A.: Failure to obtain results with collagen implantation in children with urinary incontinence. J Urol, 157: 2306, 1997 Lottman, H. B., Margaryan, M., Bernuy, M., Grosz, A., Aigrain, Y. and Lortat-Jacob, S.: Long-term effect of dextranomer endoscopic injections for treatment of urinary incontinence: an update of a prospective study of 30 patients. Presented at Section on Urology, American Academy of Pediatrics, San Francisco, California, October 9 –11, 2005 Cole, E. E., Adams, M. C., Brock, J. W. and Pope, J. C.: Outcome of continence procedures in the pediatric patient: a single institutional experience. J Urol, 170: 560, 2003 Eckford, S. D. and Abrams, P.: Para-urethral collagen implantation for female stress urinary incontinence. Br J Urol, 68: 586, 1991 Bomalaski, M. D., Bloom, D. A., McGuire, E. J. and Panzl, A.: Glutaraldehyde cross-linked collagen in the treatment of urinary incontinence in children. J Urol, 155: 699, 1996 Lackgren, G.: Personal communication, October 2004 EDITORIAL COMMENT
Bulking agents initially found to be useful in subureteral injections for reflux seem destined to audition as bladder neck injections to cure incontinence. Dx/H is now the latest agent to be investigated for bladder neck injections. The authors should be commended for their interest in presenting their patients an endoscopic alternative to complex reconstructive surgery in the hopes of achieving continence. Unfortunately they found that there was “limited success” with this technique. Only 3 of 16 patients were dry and 5 showed improvement in incontinence. Quantifying this improvement (ie length of dry intervals) would allow the reader a better appreciation of the significance of the improvement. The authors acknowledge the need for a larger study. For instance, only 3 of their 16 patients catheterize per urethra. Only 5 patients who had not undergone prior continence procedures were available for review, and only 1 of these 5 was continent following injection. The study may have benefited from analysis of pretreatment urodynamic data, which can be helpful in predicting which children would have a successful outcome.1 In regard to technique, the injection was done by the retrograde transurethral approach or alternatively by the antegrade approach (ie via a catheterizable stoma). There has been discussion about injecting the bladder neck submucosa via antegrade and retrograde approaches simultaneously, allowing 2 perspectives for optimal coaptation.2 Additionally, the authors injected Dx/H at 2 separate sites 180 degrees apart. One wonders if injection in all 4 quadrants would improve coaptation and increase the success rate. Due to concerns of bulking agent migration, absorption and compression, longer followup would more strongly validate any successful results. Future studies should include the effect of a repeat injection on success rates as we have seen in description of success rates of subureteral injections for reflux. Overall, this experience with Dx/H injection of the bladder neck serves the purposes of offering patients options for the treatment of incontinence along with realistic expectations of the outcome of this treatment. If a larger study confirmed the findings of the current study, our incontinent patients would benefit in 2 ways: 1) patients more inclined to successful treatment with Dx/H would have a minimally invasive option for the treatment of incontinence and 2) identification of the poor performers would allow us to spare them a
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procedure that has little chance of helping them. Richard N. Schlussel Division of Pediatric Urology Morgan Stanley Children’s Hospital of New York-Presbyterian New York, New York
1. Chernoff, A., Horowitz, M., Combs, A., Libretti, D., Nitti, V. and Glassberg, K.: Periurethral collagen injection for the treatment of urinary incontinence in children. J Urol, 157: 2303, 1997 2. Dean, G.: Personal communication
DISCUSSION Dr. Joao L. Pippi-Salle. When you inject the bladder neck with Dx/H or other materials, how difficult is it to get back either to do a bladder neck reconstruction or a bladder neck closure? Dr. Rosalia Misseri. To date, we have not had to go back on any of these cases. We have reimplanted some ureters that were previously injected with Dx/H, and in those patients what you see is that the Dx/H material often just extrudes out. There are some histological changes that we have seen in the distal ureter that was injected, and so perhaps it might just extrude out as it does in the ureter or the tissue reaction may be more substantial at the bladder neck.