Ettore Mearini

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.

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

Open Prostatectomy in Benign Prostatic Hyperplasia: 10-Year Experience in Italy

This study reports the experience of 47 Italian urology units together with the urology unit at the University of Perugia concerning open surgery in the management of benign prostatic hyperplasia (BPH). Until 20–25 years ago, open surgery was the most common approach. In the late 1970s the development of endoscopes and their methodology has led to a gradual reduction in open surgery operations, which decreased rapidly with the introduction of mini-invasive endoscopic techniques. Therefore, open surgery for BPH is declining, though still performed. Skill in traditional surgery is mandatory because, until an alternative is devised, indications for open surgery still exist and cannot be ignored. The survey shows the indications and contraindications, complications and results of a 10-year nationwide experience. Guidelines for open surgery in patients with BPH have been drawn up.

Lichen Sclerosus of the Male Genitalia and Urethral Stricture Diseases

Introduction: The true incidence of urethral involvement in patients with genital lichen sclerosus (LS) is unknown. We review the epidemiology and discuss the pathogenesis of LS and urethral stricture diseases. Materials and Methods: During the period 1991–2002, of 925 patients who underwent urethroplasty for anterior urethral stricture, 130 patients (14%) received the diagnosis of LS. In all patients with LS the histology was re-examined to confirm the clinical diagnosis. Retrograde and voiding urethrography was used to establish urethral involvement in the disease. Results: In 106 patients (82%) the histology provided the classical features of LS, and 24 patients (18%) showed some histological variations. In 49 patients (37%) the LS involved the pendolous urethra (meatus-navicularis-penile), and in 53 cases (41%) a panurethral stricture was evident. Conclusions: LS urethral involvement appears to be a much more common and extensive disease than previously reported, and requires particular care in its early diagnosis.

Testosterone Levels in Benign Prostatic Hypertrophy and Prostate Cancer

Introduction: Although hormones play fundamental roles in prostate growth, their clinical significance is not completely clear. In the present study we assessed whether serum hormone levels are markers of prostate disease. Patients and Methods: In 128 patients with benign prostatic hypertrophy or prostate cancer, testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin levels were correlated with disease. In patients with prostate cancer, the hormone levels were also correlated with prognostic factors. Predictive values were assessed for prostate-specific antigen and testosterone levels only, using multiple logistic regression analysis and receiver operating characteristic curves. Results: The testosterone concentrations were significantly lower in patients with prostate cancer than in those with benign prostatic hypertrophy and were also significantly lower in patients with advanced-stage disease than in patients with organ-confined disease. Testosterone appears to be an independent predictor of disease and enhances the predictive accuracy for benign prostatic hypertrophy and prostate cancer. Conclusions: This study supports experimental findings that prostate cancer is frequently associated with low testosterone concentrations. In the diagnostic workup for prostate cancer, associating prostate-specific antigen and testosterone levels may improve the predictive accuracy of prostate disease tests.

Role of glyoxalase I in the proliferation and apoptosis control of human LNCaP and PC3 prostate cancer cells

Glyoxalase I (GLOI) detoxifies reactive dicarbonyls, as methylglyoxal (MG) that, directly or through the formation of MG‐derived adducts, is a growth inhibitor and apoptosis inducer. GLOI has been considered a general marker of cell proliferation, but a direct link between the two has yet to be demonstrated. The aim of the present work was to clarify whether GLOI was involved in the proliferation control of LNCaP and PC3 human prostate cancer cells or might play a different role in the growth regulation of these cells.

Two-year efficacy and safety of botulinum a toxin intravesical injections in patients affected by refractory painful bladder syndrome.

INTRODUCTION AND AIM We report the 2-year efficacy and tolerability of intravesical botulinum A toxin (BoNT/A) injections in patients with painful bladder syndrome (PBS) associated with increased urinary frequency refractory to conventional treatments. MATERIALS AND METHODS Thirteen women were prospectively included in the study. The preliminary assessment included voiding diary, urodynamics, urinary tract ultrasound and the visual analog scale (VAS) for pain quantification. All patients received multiple injections of 200 U commercially available BoNT/A diluted in 20 ml 0.9% NaCl, under cystoscopic guidance. Clinical evaluation, urodynamics, urinary tract ultrasound and VAS were repeated at least two times per year throughout the follow-up. RESULTS A total of 58 injections were administered with a mean of 4.8 +/- 0.8 injections per patient. The mean interval between two consecutive injections was 5.25 +/- 0.75 months. At 1 and 4 mo follow up ten patients reported a subjective improvement. Mean VAS scores, mean daytime and night-time urinary frequency decreased significantly. Nine patients at 1 month and seven at the 4-month check-up complained of dysuria. The three non-responders to the first intravesical treatment session underwent another three months later with satisfactory results. At 1 and 2 years follow up the beneficial effects persisted in all patients. We did not observe any systemic side effects during the observation time. CONCLUSIONS Intravesically injected BoNT/A is effective and safe in the medium-term management of patients with PBS. As the beneficial effect decreased progressively within a few months after treatment, repeat injections of the neurotoxin were needed over time.