Urinary Incontinence

Reviewing the Literature

RIU0314_02-13.qxd 2/14/07 6:06 PM Page 44 Pediatric Urology continued aids in the counseling of parents after initial treatment failure and demonstrates the high success rate of a second Dx/HA injection for the treatment of persistent VUR. References 1. 2. Elder JS. This month in pediatric urology. J Urol. 2006;175:807-808. Kirsch AJ, Perez-Brayfield M, Smith EA, Scherz HC. The modified STING procedure to correct vesicoureteral reflux: improved results with submucosal implantation within the intramural ureter. J Urol. 2004;171:2413-2416. Urinary Incontinence Botulinum Toxin A in the Treatment of Neurogenic and Idiopathic Urinary Incontinence Reviewed by Shelby N. Morrisroe, MD, Michael B. Chancellor, MD Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, PA [Rev Urol. 2007;9(1):44-45] © 2007 MedReviews, LLC nticholinergic therapy has long been considered the “gold standard” for treating urinary incontinence (UI) of both neurogenic and idiopathic origins. However, for those who fail this conservative measure for lack of efficacy or intolerable side effects, secondline treatments such as intradetrusor injections of botulinum toxin type A (BoNTA) have been studied. Initial studies have shown BoNTA to be of benefit clinically, as demonstrated by improvement in incontinence urodynamically as well as by quality-of-life (QOL) assessment. A definitive explanation of how BoNTA exerts its effect on the overactive bladder is still unavailable. It does cause a reversible chemodenervation by inhibition of neuronal acetylcholine secretion but seems to have a different mechanism of action in smooth muscle than in skeletal muscle. Clinical data suggest that there are similar responses to BoNTA for patients with neurogenic and idiopathic causes of UI. However, more studies are needed to further delineate the optimal treatment regimen for both patient populations. A This randomized clinical trial evaluated the effectiveness of focal injections of BoNTA in relieving symptoms of UI and reducing elevated detrusor pressures associated with the risk of renal complications as evaluated in both adults and children with neurogenic UI. Study 1 included 59 adults who received either placebo or BoNTA (200 U or 300 U BOTOX; Allergan, Irvine, CA) via 30 intradetrusor injections. Study 2 included 24 children with neurogenic UI at risk of kidney impairment who were given injections with BoNTA at 12 U/kg (maximum: 300 U) at approximately 40 sites in the detrusor. In the first study, changes in UI frequency, urodynamic parameters including maximum detrusor pressure and maximum bladder capacity, and QOL were assessed throughout the 24 weeks following injection. Results showed that BoNTA at doses of 200 U and 300 U reduced the incidence of UI episodes by 50% and were associated with improvements in urodynamic parameters and QOL. There were no marked differences between the 2 BoNTA doses administered. However, the study was not powered to detect differences between the 2 doses. The efficacy was maintained for the 24-week duration of the study, suggesting that the duration of effect is greater than 6 months. In the second study, cystometric measures and incontinence scores were assessed before and at 1, 3, and 6 months after BoNTA treatment in children who required regular clean intermittent catheterization (CIC) and were at a high risk of impaired kidney function. The incontinence score decreased at 1, 3, and 6 months by 46%, 15%, and 13%, respectively. Maximum detrusor pressure had decreased by 41% at 1 month and by 22% at 3 months (and had increased nonsignificantly by 4% at 6 months). Maximum bladder capacity had increased by 35%, 23%, and 36%, respectively. To assess the long-term success of repeated injections, data were also reviewed for 4 children who received at least 5 injections. There was no evidence of drug resistance, and bladder compliance was increased by 109% 6 months after the fifth injection. These results suggest that BoNTA therapy may reduce the risk of vesicoureteric reflux and subsequent renal impairment and may also postpone or reduce the necessity for bladder augmentation surgery. Both studies add to the increasing evidence for the efficacy of BoNTA in the management of neurogenic UI in children and adults. Botulinum Toxin in the Treatment of Neurogenic Bladder in Adults and Children Efficacy of Botulinum Toxin A in the Treatment of Female Idiopathic Detrusor Overactivity Incontinence: Long-Term Results of a Prospective Nonrandomised Study Schurch B, Schulte-Baukloh H. Werner M, Kuschel S, Schmid DM, Schuessler B. Eur Urol Suppl. 2006;5:679-684. Eur Urol Suppl. 2006;5:685-690. 44 VOL. 9 NO. 1 2007 REVIEWS IN UROLOGY RIU0314_02-13.qxd 2/14/07 6:06 PM Page 45 Urinary Incontinence This ongoing, prospective, nonrandomized trial investigated BoNTA for the treatment of patients with idiopathic detrusor overactivity and subsequent UI in whom anticholinergic drugs have failed. Twenty-six women received 100 U BoNTA as 30 injections into the detrusor, sparing the trigone and base. Clinical and urodynamic evaluations were performed before and at 4, 12, and 36 weeks after injection. Results showed that continence was achieved by 69%, 96%, and 73% of patients, respectively. Maximum bladder capacity and bladder compliance were significantly increased, and cystometric detrusor contractions were significantly decreased at each follow-up compared with baseline. Mean postvoid residual volume was significantly increased at the 4-week follow-up visit (63 mL compared with 18 mL at baseline), and 2 patients required temporary CIC for postvoid residual volume greater than 100 mL. QOL was significantly improved at all follow-up visits. Efficacy had attenuated by 9 months in all patients. BoNTA treatment demonstrated good tolerability, with no patients withdrawing from the study because of adverse events. During the 36 weeks of follow-up, 9 urinary tract infections were found in 26 patients (34%), an incidence similar to that reported after CIC or urodynamic procedures. Accumulating data indicate that BoNTA is an effective and well-tolerated treatment of UI in patients with idiopathic detrusor overactivity in whom anticholinergic medication has failed. Further, it seems to have a similar benefit in UI secondary to neurogenic detrusor overactivity in both adult and child populations. In contrast to the daily oral intake of anticholinergics, BoNTA injections have a longlasting effect (up to 9 months), and patients experience few or no adverse effects. These factors are likely to contribute to the improvement found in patients’ QOL. Effectiveness of treatment does not seem to be markedly affected by the large range of BoNTA doses used in these studies. A standardized dosage and treatment protocol has yet to be determined. Further studies are needed to explore the effect of dose, volume, and pattern of injection on efficacy, safety, and duration of action. VOL. 9 NO. 1 2007 REVIEWS IN UROLOGY 45