Intra-Detrusor Botulinum Neuro-Toxin A Injection Prevents Rat Bladder Fibrosis Secondary to Bladder Outlet Obstruction (original) (raw)
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European Urology, 2006
e u r o p e a n u r o l o g y 5 0 ( 2 0 0 6 ) 1 0 5 8 -1 0 6 4 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Abstract Objectives: To study histological features and morphological differences in bladder wall specimen from patients with and without botulinum toxin A injections and to compare those issues in responders and non-responders to the toxin therapy. Material and methods: Bladder wall specimen obtained from cystectomy in 45 patients with neurogenic overactive bladders with and without injection of botulinum toxin A into the detrusor muscle for treatment of neurogenic incontinence were evaluated concerning the histological criteria inflammation, oedema and fibrosis of the bladder wall. Results: Bladder wall specimen obtained from patients suffering from neurogenic detrusor overactivity showed important histological alterations. Generally, inflammatory infiltration, oedema and fibrosis of the bladder wall were frequently observed. When comparing specimen from patients who had received botulinum toxin injection to those from patients who had not, there was no difference concerning inflammation and oedema. However, patients who had received botulinum toxin injection showed significantly less fibrosis of the bladder wall than those who had not received the toxin injection ( p < 0.00073). When comparing specimen from responders and non-responders to the botulinum toxin therapy, there was no difference in inflammation.
European Urology, 2008
e u r o p e a n u r o l o g y 5 3 ( 2 0 0 8 ) 1 2 4 5 -1 2 5 3 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Abstract Background: We examined, for the first time in a prospective study, the histological changes in the urothelium and suburothelium of patients with neurogenic (NDO) or idiopathic detrusor overactivity (IDO) after one or repeat treatments with intradetrusor BoNTA. Methods: Flexible cystoscopic bladder biopsies were obtained from patients with urodynamically proven intractable spinal NDO or IDO before and 4 and 16 wk after one or repeat treatments with intradetrusor injections of BOTOX1 (NDO 300 U, IDO 200 U). Specimens were stained for haematoxylin-eosin and analysed blindly for inflammatory changes, fibrosis, hyperplasia, and dysplasia in the urothelium and suburothelium. Statistical comparisons were significant at p values less than 0.05. Results: Signs of chronic inflammation were found in 59.1% of baseline biopsies (65.6% of NDO vs. 50% of IDO, p = 0.049), 67.6% of post-first biopsies and 86.4% after repeat injections. The two groups were comparable for degree of baseline inflammation, which did not change significantly after first injection and up to 16 wk after a third injection. Mild fibrosis was found in 2.2% of biopsies examined, equally before and after treatment, but not after repeat injections. No dysplasia or hyperplasia was identified. Eosinophils were identified more frequently in biopsies taken after repeat injections compared with the post-first injection and baseline biopsies (x 2 = 8.23, p = 0.018). No difference existed between NDO and IDO bladders. Conclusions: BoNTA injections do not appear to be producing significant inflammatory changes, fibrosis, or dysplastic changes in human bladder urothelium/suburothelium after a single injection and in a limited number of repeat treatment biopsies. The presence of eosinophils might be treatment-related, because they were mostly found in post-treatment biopsies.
European urology, 2008
e u r o p e a n u r o l o g y 5 3 ( 2 0 0 8 ) 1 2 4 5 -1 2 5 3 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Abstract Background: We examined, for the first time in a prospective study, the histological changes in the urothelium and suburothelium of patients with neurogenic (NDO) or idiopathic detrusor overactivity (IDO) after one or repeat treatments with intradetrusor BoNTA. Methods: Flexible cystoscopic bladder biopsies were obtained from patients with urodynamically proven intractable spinal NDO or IDO before and 4 and 16 wk after one or repeat treatments with intradetrusor injections of BOTOX1 (NDO 300 U, IDO 200 U). Specimens were stained for haematoxylin-eosin and analysed blindly for inflammatory changes, fibrosis, hyperplasia, and dysplasia in the urothelium and suburothelium. Statistical comparisons were significant at p values less than 0.05. Results: Signs of chronic inflammation were found in 59.1% of baseline biopsies (65.6% of NDO vs. 50% of IDO, p = 0.049), 67.6% of post-first biopsies and 86.4% after repeat injections. The two groups were comparable for degree of baseline inflammation, which did not change significantly after first injection and up to 16 wk after a third injection. Mild fibrosis was found in 2.2% of biopsies examined, equally before and after treatment, but not after repeat injections. No dysplasia or hyperplasia was identified. Eosinophils were identified more frequently in biopsies taken after repeat injections compared with the post-first injection and baseline biopsies (x 2 = 8.23, p = 0.018). No difference existed between NDO and IDO bladders. Conclusions: BoNTA injections do not appear to be producing significant inflammatory changes, fibrosis, or dysplastic changes in human bladder urothelium/suburothelium after a single injection and in a limited number of repeat treatment biopsies. The presence of eosinophils might be treatment-related, because they were mostly found in post-treatment biopsies.
BMC Urology
Background Botulinum toxin A (BoNT-A) is a new treatment modality in various causes of bladder dysfunction; like neurogenic detrusor overactivity and overactive bladder. The best technique of administrating BoNT-A in patients is unknown. A validated in vitro model could be used to investigate newer intravesical administration techniques of BoNT-A. In this study, we describe the development and validation of in vitro model to measure inhibitory effects of BoNT-A on bladder strip contractions. Methods Rat bladder strips were mounted in organ baths filled with Krebs’ solution. The strips were stimulated chemically (80 mM potassium chloride, 1 μM carbachol) and electrically (Electrical Field Stimulation (EFS) 100 shocks, 50 V, 20 Hz, every 3 minutes). The viability of the strips was measured by carbachol stimulation at the beginning and at the end of the experiments. The strips were incubated in various concentrations of BoNT-A (0.03, 0.2, 0.3 nM). Controls were incubated in Krebs’ solu...
Current Status of Botulinum Toxin for Neurogenic Bladder Dysfunction
Current Bladder Dysfunction Reports, 2010
With 10 years of use completed since the first bladder injection, an increasing body of evidence supports the efficacy of intradetrusally injected botulinum neurotoxin type A to treat intractable symptoms of neurogenic detrusor overactivity in adults. Highly significant improvements in patients' symptoms, urodynamic parameters and quality of life, sustained with repeat injections and with few transient side effects have been consistently reported, leading to high-grade recommendations for its use in refractory adult neurogenic detrusor overactivity. Cautions have been raised when it is used in children, in whom efficacy has been shown in open-label studies. Large, placebo-controlled trials are awaited, as is further investigation into long-term safety.
Botulinum toxin type A may improve bladder function in a rat chemical cystitis model
Urological research, 2003
The purpose of this study was to investigate the effect of botulinum toxin type A on bladder function and histology in a rat chemical cystitis model. The study included 41 female Sprague-Dawley rats with chemical cystitis induced by intravesical instillation of hydrochloric acid. The acid instillation was repeated monthly to maintain chronic inflammation. The treatment group (n=21) received 2-3 units of botulinum toxin type A injected into the bladder detrusor at the 3, 6, 9 and 12 o'clock positions, and the control group (n=20) underwent saline injection into the bladder detrusor at the same positions. Urodynamic studies were performed in all rats before the treatment and at death. The rats were killed at 1 week, 2 weeks, 1 month and 2 months after treatment. The bladders were removed and examined histologically for mast cells and inflammatory changes. The cystometric findings showed that, at the beginning and end of the experiment, the increases in the maximum bladder capacity...