Massimo Porena

Botulinum-A Toxin Injections Into the Detrusor Muscle Decrease Nerve Growth Factor Bladder Tissue Levels in Patients With Neurogenic Detrusor Overactivity

PURPOSE We investigated the effects of BTX-A on visceral afferent nerve transmission by measuring bladder tissue NGF levels in patients with neurogenic detrusor overactivity before and after intravesical treatment with BTX-A. We also compared the bladder tissue NGF content with clinical and urodynamic data. MATERIALS AND METHODS A total of 23 patients underwent clinical evaluation and urodynamics with detection of the UDC threshold, maximum pressure and maximum cystometric capacity before, and at the 1 and 3-month followups. Endoscopic bladder wall biopsies were also obtained at the same time points. NGF levels were measured in tissue homogenate by enzyme-linked immunosorbent assay (Promega, Madison, Wisconsin). RESULTS At 1 and 3 months mean catheterization and incontinent episodes were significantly decreased (p <0.05 and <0.001, respectively). On urodynamics we detected a significant increase in the UDC threshold and maximum cystometric capacity, and a significant decrease in UDC maximum pressure at the 1 and 3-month follow-ups compared to baseline (each p <0.001). At the same time points we detected a significant decrease in NGF bladder tissue content (each p <0.02). CONCLUSIONS BTX-A intravesical treatment induces a state of NGF deprivation in bladder tissue that persists at least up to 3 months. As caused by BTX-A, the decrease in acetylcholine release at the presynaptic level may induce a decrease in detrusor contractility and in NGF production by the detrusor muscle. Alternatively BTX-A can decrease the bladder level of neurotransmitters that normally modulate NGF production and release.

Six-Year Follow-Up of Botulinum Toxin A Intradetrusorial Injections in Patients with Refractory Neurogenic Detrusor Overactivity: Clinical and Urodynamic Results

BACKGROUND Most reports in the literature on botulinum toxin A (BoNTA) therapy for neurogenic detrusor overactivity (NDO) are based on the results of a single injection. Because most patients may require retreatment, the efficacy and safety of multiple injections must be addressed clearly. OBJECTIVE To investigate the effectiveness and safety of BoNTA intradetrusorial injections in a group of spinal cord-injured (SCI) patients with refractory detrusor overactivity (DO). DESIGN, SETTING, AND PARTICIPANTS Seventeen SCI patients were prospectively included in the study and followed up to 6 yr. INTERVENTION All patients received repeat intradetrusorial injections of BoNTA 300 units (Botox, Allergan, Irvine, CA) under cystoscopic control on an inpatient basis. MEASUREMENTS The preliminary assessment included voiding diary, urodynamics, kidney and bladder ultrasound, and cystourethrography. Patients also completed a standardised quality-of-life (QoL) questionnaire. Clinical evaluation, urodynamics, urinary tract imaging, and QoL assessment were repeated every year throughout the follow-up. RESULTS AND LIMITATIONS Before treatment, all patients complained of urinary incontinence and had DO. Bilateral and monolateral renal pelvis dilatation were detected in six and five patients, respectively, and a monolateral and third-grade vesicoureteral reflux was observed in three. At 6-yr follow-up, a significant decrease in the frequency of daily incontinence episodes (p<0.01), a significant increase in first uninhibited detrusor contraction and in maximum bladder capacity (p<0.001 for both), and a significant decrease in maximum pressure of these contractions (p<0.01) were observed. Fifteen patients (88.2%) were completely continent. Renal pelvis dilatation and vesicoureteral reflux resolved in all cases, and the QoL index significantly increased. Limitations of the study are related to the small number of included patients. CONCLUSIONS In SCI patients with refractory NDO who do not want or are unfit for invasive reconstructive surgery, BoNTA intravesical treatment represents a valid alternative to control DO and urinary incontinence and to preserve upper urinary tract function over a long-term follow-up.

Botulinum A toxin intravesical injection in patients with painful bladder syndrome: 1-year followup

PURPOSE We evaluated the 1-year efficacy and tolerability of botulinum A toxin intravesically injected in patients with painful bladder symptoms associated with increased urinary frequency, refractory to conventional treatments. MATERIALS AND METHODS Three men and 12 women were prospectively included in the study. Under short general anesthesia the patients were given injections of 200 U commercially available botulinum A toxin diluted in 20 ml 0.9% NaCl. Injections were performed submucosally in the bladder trigone and lateral walls under cystoscopic guidance. A voiding chart and the visual analog scale for pain were used, and urodynamics were performed before treatment, and 1, 3, 5 and 12 months later. RESULTS Overall 13 patients (86.6%) reported subjective improvement at the 1 and 3-month followups. The mean visual analog scale score, and daytime and nighttime urinary frequency were significantly decreased (p <0.05, <0.01 and <0.05, respectively). At the 5-month followup the beneficial effects persisted in 26.6% of cases but increased daytime and nighttime urinary frequency, and an increased visual analog scale score were observed compared to baseline. At 12 months after treatment pain recurred in all patients. Nine patients complained of dysuria 1 month after treatment. Dysuria persisted in 4 cases at the 3-month followup and in 2 at the 5-month followup. CONCLUSIONS Intravesically injected botulinum toxin A is effective for short-term management of refractory painful bladder syndrome. The beneficial effects decreased progressively within a few months after treatment. Thus, repeat injections of the neurotoxin are required for efficacious treatment in patients with the disease.

Intravesical Capsaicin Versus Resiniferatoxin In Patients With Detrusor Hyperreflexia: A Prospective Randomized Study

PURPOSE Capsaicin and resiniferatoxin (Sigma Chemical Co., St. Louis, Missouri) administered intravesically are attractive options for treating detrusor hyperreflexia. Because the 2 agents differ in chemical structure and relative potency, possible differences in their clinical and urodynamic effects were investigated in this prospective comparative study. MATERIALS AND METHODS A group of 24 spinal cord injured patients with refractory detrusor hyperreflexia were randomly assigned to receive a single dose of 2 mM. capsaicin in 30 ml. ethanol plus 70 ml. 0.9% sodium chloride or 100 nM. resiniferatoxin in 100 ml. 0.9% sodium chloride. Dwell time was 40 minutes with urodynamic monitoring. Urodynamics were performed at baseline before treatment, and after followups of 30 and 60 days. The frequency of daily catheterizations, incontinence episodes and side effects was recorded. RESULTS There was no significant urodynamic or clinical improvement in the capsaicin arm at 30 and 60 days of followup. In the resiniferatoxin arm the mean uninhibited detrusor contraction threshold plus or minus standard deviation increased from 176 +/- 54 to 250 +/- 107 ml. at 30 days (p <0.05) and to 275 +/- 98 ml. at 60 days (p <0.01). Mean maximum bladder capacity increased from 196 +/- 75 to 365 +/- 113 ml. at 30 days (p <0.001) and to 357 +/- 101 ml. at 60 days (p <0.001). Daily catheterizations and incontinent episodes were significantly decreased at 30 and 60 days of followup. Autonomic dysreflexia, limb spasms, suprapubic discomfort and hematuria developed in most patients who received capsaicin but in none who received resiniferatoxin. CONCLUSIONS Intravesical administration of resiniferatoxin is superior to that of capsaicin in terms of urodynamic results and clinical benefits in spinal cord injured patients and it does not cause the inflammatory side effects associated with capsaicin.

Botulinum Toxin A for Overactive Bladder and Detrusor Muscle Overactivity in Patients With Parkinson's Disease and Multiple System Atrophy

PURPOSE Urinary disturbances are common in patients with Parkinsons disease and multiple system atrophy. We investigated the effectiveness and safety of botulinum toxin type A injected into the detrusor muscle in patients with Parkinsons disease and multiple system atrophy who had refractory overactive bladder symptoms and detrusor overactivity. MATERIALS AND METHODS All participants underwent clinical and urodynamic assessment, and completed a quality of life questionnaire before botulinum toxin type A treatment, and 1 and 3 months thereafter. Four patients with Parkinsons disease and 2 with multiple system atrophy were enrolled in the study. All patients received 200 U botulinum toxin type A injected into the detrusor muscle at 20 sites under cystoscopic guidance at a single session on an inpatient basis. Outcome measures were clinical assessment (a voiding diary including daytime and nighttime urinary frequency, and episodes of urgency and urge urinary incontinence), urodynamic assessment (including first volume and maximum pressure of uninhibited detrusor contractions, and maximum cystometric capacity) and pressure flow studies. RESULTS One and 3 months after botulinum toxin type A injection all patients reported that daytime and nighttime urinary frequency had decreased and quality of life scores improved. No patients had further episodes of urgency and urge urinary incontinence during the 5-month followup. Urodynamics showed improvement in all urinary function variables tested. No systemic side effects were recorded during or after treatment. In all patients post-void urinary residual volume increased and intermittent catheterization was required only in those with multiple system atrophy. CONCLUSIONS The new beneficial effect that we report in a small study sample encourages larger trials to confirm botulinum toxin type A injection into the detrusor muscle as an effective and safe treatment for refractory overactive bladder symptoms and detrusor overactivity related to Parkinsons disease and multiple system atrophy.

Colposacropexy with Gore-Tex Mesh in Marked Vaginal and Uterovaginal Prolapse

This study focusses on abdominal sacral colpopexy which appears to provide the most anatomically correct restoration and secure and durable support for advanced vaginal or uterovaginal prolapse. 21 patients underwent colposacropexy or hysterocolposacropexy using Gore-tex mesh. All patients referred symptoms of vaginal heaviness and urinary dysfunctions. Five presented with complete vaginal vault prolapse, 7 with third-degree anterior colpoceles and 9 with uterovaginal prolapse. Hydronephrosis was present in 4. Five patients had previously undergone total hysterectomy, and underwent only sacropexy; 9 underwent standard total abdominal hysterectomy before sacropexy; 7 underwent hysterocolposacropexy, preserving the uterus. In colposacropexy anchorage was designed to provide a large vagina-mesh contact area thus reducing the risk of suspension failure. Hysterocolposacropexy was performed using 3 stitches to anchor the synthetic mesh to the vagina and the uterine isthmus. Postoperative follow-up times range from 12 to 68 months. Overall results for 19/21 patients were satisfactory. In all 21 patients the descensus was markedly reduced. Hydronephrosis was completely resolved. Slight incontinence persisted in 3, but protection was not required. Slight dysuria persisted in 2. First-degree cystoceles recurred only in 3 patients who underwent hysterocolposacropexy. Sacropexy with synthetic mesh seems to be the most valid support of uterovaginal prolapse as the physiological vaginal axis is restored and vaginal function is preserved. Our success rate and the overall satisfaction expressed by 19/21 patients have encouraged us to continue in this surgical approach.

Botulinum toxin type A in patients with Parkinson's disease and refractory overactive bladder

PURPOSE In this 6-month followup study we investigated the effect of intradetrusor injection of 100 U botulinum toxin type A in patients with Parkinsons disease and refractory detrusor overactivity. MATERIALS AND METHODS Eight patients with Parkinsons disease and detrusor overactivity refractory to anticholinergics were injected with 100 U botulinum toxin type A. Daytime and nighttime urinary frequency, and urinary incontinence episodes were recorded. Patients also completed a standardized quality of life questionnaire on incontinence and a visual analog scale on the impact of bladder problems on daily life activities, and underwent urodynamic assessment, including pressure flow studies. Clinical and urodynamic assessment was performed before, and 1, 3 and 6 months after injection. RESULTS In all patients 100 U botulinum toxin type A induced decreased daytime and nighttime urinary frequency, a decreased number of urinary incontinence episodes, increased quality of life scores and, as shown by increased maximum cystometric capacity, improved urodynamic findings. In 2 patients with Parkinsons disease post-void residual urine volume developed. CONCLUSIONS Intradetrusor injection of 100 U botulinum toxin type A induced clinical and urodynamic improvement in overactive bladder symptoms that lasted at least 6 months in patients with Parkinsons disease.

BIOFEEDBACK SUCCESSFULLY CURES DETRUSOR-SPHINCTER DYSSYNERGIA IN PEDIATRIC PATIENTS

PURPOSE We assessed the efficacy of voiding and bladder biofeedback for achieving perineal synergy and curing symptoms in children with detrusor-sphincter dyssynergia MATERIALS AND METHODS A total of 16 boys and 27 girls 4 to 14 years old with detrusor-sphincter dyssynergia diagnosed by uroflowmetry and electromyography underwent biweekly voiding biofeedback therapy consisting of perineal floor electromyography during uroflowmetry. The 6 patients with enuresis and an unstable bladder also underwent bladder biofeedback training during cystometry. Biofeedback continued until detrusor-sphincter dyssynergia resolved. Followup consisted of electromyography and uroflowmetry 1 month after completing biofeedback training, and telephone interviews after 2 and 4 years. RESULTS Biofeedback resolved detrusor-sphincter dyssynergia in all children, although the condition disappeared significantly sooner in girls (p <0.02). Secondary enuresis disappeared significantly earlier than primary enuresis (p <0.0001). The 2-year success rate of 87.18% for enuresis decreased to 80% at the 4-year followup. CONCLUSIONS Voiding and bladder biofeedback achieves perineal synergy and cures symptoms in children with detrusor-sphincter dyssynergia

Uterus preservation in pelvic organ prolapse surgery

Attitudes to sexuality and the psychological value of reproductive organs have changed in Western countries over the last few decades. Nevertheless, repair of pelvic support defects with concomitant hysterectomy is still considered the standard treatment for pelvic organ prolapse. Over the last 10 years, however, interest has been growing in uterus-sparing surgery, which can be divided into vaginal, abdominal, and laparoscopic procedures. The majority of studies on uterus-sparing surgery, with the exception of abdominal techniques, report few cases with short follow-up. Sacrospinous hysteropexy is the most studied vaginal technique for uterus preservation and favorable results have been demonstrated, although the majority of studies are flawed by selection and information bias, short follow-up and lack of adequate control groups. Abdominal and laparoscopic procedures are promising, providing similar functional and anatomical results to hysterectomy and sacrocolpopexy. Consensus is growing that the uterus can be preserved at the time of pelvic reconstructive surgery in appropriately selected women who desire it. The results of comparison trials and prospective studies confirm that uterus-sparing surgery is feasible and is associated with similar outcomes to hysterectomy, as well as shorter operating times. Surgeons should be ready to respond to the wishes of female patients who want to preserve vaginal function and the uterus.

Visually Directed Transrectal High Intensity Focused Ultrasound for the Treatment of Prostate Cancer: A Preliminary Report on the Italian Experience

PURPOSE High intensity focused ultrasound is a minimally invasive treatment option for prostate cancer. Data from the literature show promising early oncological outcomes and a favorable side effect profile. This study is a preliminary report of the Italian experience (Perugia and Turin) of patients treated with the Sonablate(R)500 high intensity focused ultrasound device. MATERIALS AND METHODS Between 2004 and 2007, 163 consecutive men with T1-T3 N0M0 prostate cancer underwent high intensity focused ultrasound with the Sonablate 500. Followup included prostate specific antigen tests at 1 month and then every 3 months after treatment, and a random prostate biopsy at 6 months. Failure was defined according to prostate specific antigen nadir, positive findings on followup biopsy and biochemical failure according to Phoenix criteria. RESULTS Median patient age was 72 years old, median baseline prostate specific antigen was 7.3 ng/ml, and disease stage was T1 in 44.1%, T2 in 42.5% and T3a in 13.4% of patients. Median followup was 23.8 months. After high intensity focused ultrasound treatment prostate specific antigen decreased to a median nadir of 0.15 ng/ml. Median prostate specific antigen at 3 and 6 months was 0.30 and 0.54 ng/ml, respectively. At 6 months the negative biopsy rate was 66.1%. There was no biochemical evidence of disease in 71.9% overall. On multivariate analysis prostate specific antigen nadir became the only independent predictor of no biochemical evidence of disease and positive biopsy at a cutoff of 0.40 ng/ml. CONCLUSIONS A favorable outcome of high intensity focused ultrasound is associated with lower baseline prostate specific antigen, lower prostate specific antigen nadir, lower Gleason score and lower tumor stage. As with any novel technology long-term data will be required before this technique gains widespread clinical acceptance.