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versión On-line ISSN 1677-6119
Int. braz j urol. vol.37 no.6 Rio de Janeiro nov./dic. 2011
Effects of botulinum toxin type a in the bladder wall of children with neurogenic bladder dysfunction: a comparison of histological features before and after injections
Pascali MP; Mosiello G; Boldrini R; Salsano ML; Castelli E; De Gennaro M
Department of Nephro-Urology, Bambino Gesù Pediatric and Research Hospital, Piazza S. Onofrio 4, Rome, Italy
J Urol. 2011; 185(6 Suppl): 2552-7
PURPOSE: Botulinum toxin type A has gained popularity in urology. Most reported studies have been in adults at urology centers and most have addressed long-term safety. Since botulinum toxin type A treatment for neurogenic bladder dysfunction requires repeat injections, verifying that such treatment does not induce fibrosis in children seems essential.
MATERIAL AND METHODS: The study was approved by the institutional review board and patients were enrolled after we obtained written consent. Patients with neurogenic bladder dysfunction not responding to conventional treatment (anticholinergics and clean intermittent catheterization) were treated with 10 IU/kg botulinum toxin type A up to a maximum of 300 IU. Endoscopic cold cup biopsies were obtained from the posterolateral bladder wall 1.5 to 2 cm above the ureteral orifice. Bladder wall findings were categorized into 3 groups, including inflammatory infiltration, edema and fibrosis. Each criterion was then graded as mild or severe and analyzed by Fisher's exact test (p < 0.05).
RESULTS: A total of 46 bladder wall biopsies were obtained from 40 patients 2 to 18 years old. Biopsies were evaluated in groups 1 and 2, including group 1-20 from patients with no botulinum toxin type A injection and group 2-20 after botulinum toxin type A injection. Group 2 was subdivided into group 3-10 biopsies after 1 injection and group 4-10 after multiple injections. Six patients underwent biopsy twice, that is before the first and second treatments. Histological changes were present in all biopsies. When comparing groups 1 and 2, there was no statistically significant difference in inflammation and edema. However, there was a significant difference in fibrosis between groups 1 and 4 (p < 0.05) with apparently decreased fibrosis after multiple injections.
CONCLUSIONS: In our experience repeat botulinum toxin type A injections into the detrusor in children do not lead to increased fibrosis in the bladder wall. This study confirms the long-term safety of botulinum toxin type A in the pediatric population.
The use of Botox to manage neurogenic bladder dysfunction in the pediatric population has gained ground in recent years as a minimally invasive alternative to bladder augmentation. Much of our information about the use of Botox comes from studies in adult populations whose bladder pathology often differs from the congenital conditions seen in the pediatric population. Concerns have been raised about the long-term use of Botox and the possibility of inducing fibrosis due to repeated injections. The authors in this study performed biopsies in pediatric patients with neurogenic bladder dysfunction both before and after Botox injections. They excluded patients with prior bladder surgery, vesicoureteral reflux, or those with a symptomatic urinary tract infection in the three months prior to biopsy. They biopsied 40 patients total. 20 of these were biopsied prior to a Botox injection and 20 at the time of repeat injection, 10-14 months later. In the second group half of them were biopsied after having received multiple injections (up to 4). Follow-up was performed at threemonth intervals following treatment.
In biopsies performed prior to any injection of Botox, the authors found that patients already had evidence of edema and inflammation as well as some baseline fibrosis. This was typically mild in nature. There were no statistically significant changes noted in the biopsies after injection of Botox. They did note that in the patients who were biopsied after multiple injections there did seem to be a decrease in the severity of fibrosis.
This is a small study with short-term follow-up, but it is certainly encouraging for those seeking an alternative to augmentation cystoplasty, at least in the short term. Questions still remain regarding longterm efficacy and side effects, particularly in the pediatric population. Further studies like this with longer follow-up and a greater number of patients will be valuable in clinical decision-making and counseling of patients and families.
Dr. M. Chad Wallis
Division of Pediatric Urology
University of Utah
Salt Lake City, Utah, USA