Karel Everaert

Efficacy and Safety of OnabotulinumtoxinA for Idiopathic Overactive Bladder: A Double-Blind, Placebo Controlled, Randomized, Dose Ranging Trial

PURPOSE Treatment options for patients with overactive bladder refractory to anticholinergics are limited. We assessed the dose response across a range of doses of onabotulinumtoxinA (BOTOX®) in patients with idiopathic overactive bladder and urinary urgency incontinence whose symptoms were not adequately managed with anticholinergics. MATERIALS AND METHODS In a phase 2, multicenter, randomized, double-blind study, 313 patients with idiopathic overactive bladder and urinary urgency incontinence experiencing 8 or more urinary urgency incontinence episodes a week and 8 or more micturitions daily at baseline received 50, 100, 150, 200 or 300 U intradetrusor onabotulinumtoxinA, or placebo. Symptoms were recorded using a 7-day bladder diary. The primary efficacy variable was weekly urinary urgency incontinence episodes and the primary end point was week 12. RESULTS Demographics and baseline characteristics were balanced across the treatment groups. Durable efficacy was observed for all onabotulinumtoxinA dose groups of 100 U or greater for primary and secondary efficacy measures, including the proportion of incontinence-free patients. When the dose response curves were analyzed, doses greater than 150 U contributed minimal additional or clinically relevant improvement in symptoms. This finding was also reflected in health related quality of life assessments. Dose dependent changes in post-void residual urine volume were observed and the use of clean intermittent catheterization was also dose dependent. The only adverse events significantly greater with onabotulinumtoxinA than with placebo were urinary tract infection and urinary retention. CONCLUSIONS OnabotulinumtoxinA at doses of 100 U or greater demonstrated durable efficacy in the management of idiopathic overactive bladder and urinary urgency incontinence. A dose of 100 U may be the dose that appropriately balances the symptom benefits with the post-void residual urine volume related safety profile.

TRANSCUTANEOUS NEUROMODULATION FOR THE URGE SYNDROME IN CHILDREN: A PILOT STUDY

PURPOSE Neuromodulation has been used to treat voiding dysfunction in adults. Due to its invasiveness it has rarely been used in children until now with the availability of transcutaneous neurostimulation. We evaluated clinical effects of transcutaneous neuromodulation on detrusor overactivity in children with the urge syndrome. MATERIALS AND METHODS Between May 1, 1998 and February 28, 1999, 15 girls (mean age 10.2 years) and 26 boys (mean age 10.7 years) with proved detrusor hyperactivity on videourodynamic study underwent neuromodulation. All children had been given anticholinergic therapy previously. Neurostimulation only was used in children in whom anticholinergics had no effect and those who had significant side effects. Anticholinergics were continued in children in whom they had a partial effect. Stimulation of 2 Hz. was applied for 2 hours every day. Surface electrodes were placed at the level of sacral root S3. After 1 month of trial stimulation those children who responded continued the treatment for 6 months, and were evaluated every 2 months. RESULTS Of the 41 children 15 boys and 13 girls responded after 1 month of trial therapy with an increase in bladder capacity, decrease in urgency, decrease in incontinence and/or better sensitivity. Of the 13 children who did not respond 9 lacked motivation and 4 had no clinical effect despite motivation. After 6 months of therapy a significant increase in bladder capacity, decrease in voiding frequency and decrease in incontinence periods were noted. Adverse effects were not observed. One year after therapy relapse was noted in 7 patients, leaving 21 of 41 children definitively cured. CONCLUSIONS Although preliminary, our results indicate that transcutaneous neuromodulation can improve symptoms of detrusor overactivity, as response to stimulation was noted in 76% of our patients and 56% were cured after 1 year. This therapeutic option is attractive for children because of its noninvasiveness and absence of adverse effects.

The pain cycle: implications for the diagnosis and treatment of pelvic pain syndromes.

Abstract: The aim of the study was to report our results of sacral nerve stimulation in patients with pelvic pain after failed conservative treatment. From 1992 to August 1998 we treated 111 patients (40 males, 71 females, ages 46 ± 16 years) with chronic pelvic pain. All patients with causal treatment were excluded from this study. Pelvic floor training, transcutaneous electrical nerve stimulation (TENS) and intrarectal or intravaginal electrostimulation were applied and sacral nerve stimulation was used for therapy-resistant pain. The outcome of conservative treatment and sacral nerve stimulation (VAS <3/10; >50% pain relief) was related to symptoms of voiding dysfunction and dyschezia, and urodynamic proof of dysfunctional voiding, not to the pain localization or treatment modality. Outcome was inversely related to neuropathic pain. When conservative treatment failed, a test stimulation of the S3 root was effective in 16/26 patients, and 11 patients were implanted successfully with a follow-up of 36 ± 8 months. So far no late failures have been seen. A longer test stimulation is needed in patients with pelvic pain because of a higher incidence of initial false positive tests. Our conclusion is that sacral nerve stimulation is effective in the treatment of therapy-resistant pelvic pain syndromes linked to pelvic floor dysfunction.

A high easy-to-treat complication rate is the price for a continent stoma.

Objective To evaluate the conduit‐related complications and their treatment in Mitrofanoff continent urinary diversion and antegrade colonic enema (ACE) procedures.

A proof‐of‐concept study: Mirabegron, a new therapy for overactive bladder

To evaluate the potential of mirabegron, a selective β3‐adrenoceptor agonist, for treatment of overactive bladder (OAB) symptoms.

Patient Satisfaction and Complications Following Sacral Nerve Stimulation for Urinary Retention, Urge Incontinence and Perineal Pain: a Multicenter Evaluation

Abstract: The aim of the study was to determine the success rate, the complications, the failures and the solutions found in troublesome cases. A retrospective study was performed in three university centers in Belgium. Between March 1994 and April 1998, a quadripolar electrode and a pulse generator were implanted in 53 patients (8 men, 45 women, 43 ± 12 years, mean follow-up 24 ± 8 months, range 13–39 months). During the first few months, 45 (85%) of the 53 patients had an objective response. Eight late failures occurred, with a mean failure delay of 9 ± 5 months. We performed 15 revisions in 12 patients. Major complications were pain and current-related troubles. The outcome was significantly better (P= 0.001) in post-stress incontinence surgery patients. Device-related pain was found more frequently in patients with dysuria and/or retention or perineal pain, and the test stimulation was less reliable (P= 0.025) in patients with a psychiatric history. Sacral nerve stimulation is efficient in treating patients with refractory lower urinary tract symptoms and/or perineal pain.

Chronic prostatitis and male accessory gland infection--is there an impact on male infertility (diagnosis and therapy)?

The aim of this article was to discuss by means of a review of the literature and own study material the multifactorial aetiology of male infertility, extrapolate this hypothesis to male accessory gland infection (MAGI) and relate it to chronic prostatitis and its treatment. Infertility is a multifactorial disease and diagnosis and therapy must be oriented as such. Although the relationship between prostatitis and infertility remains unclear, bacteria, viruses, leucocytes, reactive oxygen species, cytokines, obstruction and immunological abnormalities must be seen as cofactors in the development of infertility in patients with MAGI and prostatitis. Infection, trauma, allergy, neurogenic damage, chemical or mechanical factors can lead to a long‐lasting inflammation of the prostate or pelvic organs even after eradication of the aetiological agent, and is potentially related to infertility through cytokines. In relation to treatment of infertility, antibiotics play a role in bacterial prostatitis whereas in abacterial prostatitis other treatments like antioxidants, sacral nerve stimulation and anti‐inflammatory treatment are worth to be studied in the future.

Urinary tract infections in spinal cord injury: prevention and treatment guidelines.

Abstract Objectives and Methods: The literature on prevention and therapy of urinary tract infection (UTI) in patients with spinal cord injury (SCI) was reviewed using 3 levels of evidence. Results: Antibiotic therapy is only indicated in symptomatic bacteriuria or in symptomatic exacerbations of chronic UTI. During the acute phase of a SCI, UTI’s are more prevalent and bacteria are different and more resistant to antibiotics compared with the chronic phase of SCI. In SCI in general, routine screening urine cultures are not valuable as a high species turn over is seen. Intermittent catheterisation, tapping or Crédé manoeuvre coincide significantly with lower frequency of UTI compared to permanent catheter drainage. No measures are proven efficient in the long term in prevention of bacteriuria or UTI. Methenamine salts are perhaps useful in the prevention of UTI but not in patients with a permanent catheter (level III). Antibiotic prophylaxis was found useful in reducing asymptomatic bacteriuria but not in the prevention of symptomatic infections (level I). However, during prophylaxis a doubling of antibiotic resistance was found. In patients with augmented bladder antibiotic prophylaxis is useless (level II). In chronic SCI the first choice antibiotics are nitrofurantoin or trimethoprim, the second choice are fluoroquinolones (level III) whereas in acute SCI a higher resistance profile to antibiotics is frequent and therefore fluoroquinolones or cefuroxime are suggested (level III). There is no consensus in the literature but we suggest 5 days of antibiotic treatment in UTI during chronic SCI without fever, 7 days in acute SCI without fever and a minimum of 14 days in patients with UTI and fever (level III).

Urinary Tract Infections in Patients with Spinal Cord Injuries

Spinal cord injuries (SCI) result in different lower urinary tract dysfunctions. Because of both the disease and the bladder drainage method, urinary tract infections (UTIs) are one of the most frequent conditions seen in SCI patients. Diagnosis is not always easy due to lack of symptoms. Asymptomatic bacteriuria needs no treatment. If symptoms occur, antibiotherapy is indicated. Duration depends mainly on severity of illness and upper urinary tract or prostatic involvement. Choice of antibiotherapy should be based on local resistance profiles, but fluoroquinolones seems to be an adequate empirical treatment. Prevention of UTI is important, as lots of complications can be foreseen. Catheter care, permanent low bladder pressure and clean intermittent catheterization (CIC) with hydrophilic catheters are interventions that can prevent UTI. Probiotics might be useful, but data are limited.

Bladder neck closure for treating pediatric incontinence

Aims of Study: In order to evaluate the effects of bladder neck closure (BNC) for treatment of pediatric incontinence, on the quality of life of those children, we reviewed the files of 17 children who underwent this procedure during the last 5 years. Information on previous surgery before BNC, continence and complications after BNC and patient satisfaction are gathered.Material and Methods: During the study period, 17 children (9 male, 8 female) underwent BNC with continent diversion. Ten children (5 male, 5 female) suffered neurogenic incontinence in meningomyelocele, 5 children (4 male, 1 female) had bladder exstrophy, 1 girl suffered iatrogenic incontinence after treatment of an ectopic ureterocele and 1 girl suffered structural incontinence after pelvic fracture. Previous surgery for incontinence was done in 12 children with 36 procedures. Primary BNC was done in 5 children. For continent diversion the appendix was used in 13, the ureter in 2, a Monti procedure in 1, and an ileal valve in 1. In 9 children, ileal bladder augmentation was performed at the time of BNC. Four children were augmented before. Mean age at time of operation was 13.5 years. Mean follow–up is 35 months.Results: After BNC, all patients were completely dry. One girl suffered some stomal incontinence during the night. This disappeared after recent bladder augmentation. Patient satisfaction is extremely high after surgery. All patients feel happy with their stoma and do not regret the choice they made. As for complications, urinary tract infections were seen in 9 patients. Stomal complications were seen in 8 patients. Three patients had some difficulty with catheterization, which could be solved with dilatation. Appendiceal polyps, which could be removed under local anesthesia, were seen in 3 and stomal stenosis which needed re–intervention in 2. In 1 patient, three revisions of the stoma were done, in the other patient, two surgical corrections. Out of 8 patients showing stomal complications, only 2 needed revision under anesthesia. All complications are seen in the first 6 months after the continent diversion.Conclusions: We present a series of patients who underwent BNC for treatment of incontinence. BNC is the ultimate bladder neck reconstruction. However, regarding the high success rate, the low complication rate and the high patient satisfaction, we must consider BNC as an important procedure for the reconstructive surgeon. If reconstruction fails, closure must be considered. Compared to most other procedures for bladder neck reconstruction, BNC gives the highest continence rate. Good patient compliance and strict medical follow–up of the upper tract is mandatory in these patients.