Jean Jacques Wyndaele

Fourth international consultation on incontinence recommendations of the international scientific committee: Evaluation and treatment of urinary incontinence, pelvic organ prolapse, and fecal incontinence†‡§¶‖

P. Abrams , K.E. Andersson, L. Birder, L. Brubaker, L. Cardozo, C. Chapple, A. Cottenden, W. Davila, D. de Ridder, R. Dmochowski, M. Drake, C. DuBeau, C. Fry, P. Hanno, J. Hay Smith, S. Herschorn, G. Hosker, C. Kelleher, H. Koelbl, S. Khoury,* R. Madoff, I. Milsom, K. Moore, D. Newman, V. Nitti, C. Norton, I. Nygaard, C. Payne, A. Smith, D. Staskin, S. Tekgul, J. Thuroff, A. Tubaro, D. Vodusek, A. Wein, and J.J. Wyndaele and the Members of the Committees

Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: pathophysiology and mechanism(s) of action.

The PDE5 inhibitor tadalafil is investigation for the treatment of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Several clinical studies of tadalafil and other PDE5 inhibitors have reported significant symptom reduction but limited urinary flow rate improvement. This manuscript reviews the published literature describing the pathophysiology of male LUTS, with an emphasis on mechanisms that may be modulated or improved by phosphodiesterase type 5 (PDE5) inhibition.

Inflammation in Prostate Biopsies of Men without Prostatic Malignancy or Clinical Prostatitis

Objective: Inflammation is a frequent histological finding in prostate biopsies, performed on men without prostatic malignancy or clinical prostatitis. We investigated the relationship between morphological parameters of inflammation in prostatic tissue and total serum prostate–specific antigen (PSA) and prostate–specific antigen density (PSAD) levels to determine if subclinical inflammation can cause elevation of PSA and PSAD.Methods: We reviewed 268 prostate biopsies, performed on 238 men with elevated PSA and/or abnormal digital rectal examination of the prostate. All premalignant and malignant biopsies and cases of clinical prostatitis were excluded. The inflammation in the remaining 145 prostate biopsies was scored for extent of inflammation and aggressiveness of inflammation, using the four–point scale designed by Irani and co–workers. In this prostatic inflammation scoring system, extent of inflammation is graded from 0 up to 3 according to the degree of invasion of inflammatory cells in prostatic tissue. Aggressiveness of inflammation is graded from 0 up to 3 according to the degree of contact or disruption of prostatic glandular epithelium by inflammatory cells.Results: Each of the studied biopsies showed inflammatory cells. Median PSA levels in grades 1, 2 and 3 of extent of inflammation were, respectively, 5.7, 6.8 and 13.0. Median PSAD levels in these groups were 0.13, 0.16 and 0.33. There was no significant difference between these grades for PSA nor for PSAD. Median PSA levels in grades 0, 1 and 2 of aggressiveness of inflammation were, respectively, 3.9, 5.9 and 8.9. Median PSAD levels in these groups were 0.12, 0.18 and 0.17. For both parameters, there was a significant difference between grades (respectively, p = 0.0028 and p = 0.0330).Conclusion: Inflammation of the prostate is a histological finding in almost every set of prostate biopsies, even when there are no signs of clinical prostatitis. This subclinical inflammation can cause PSA elevation. Not the extent of inflammation is of importance, but the disruption of epithelial integrity caused by the inflammatory infiltrate. When confronted with a patient with an elevated PSA level whose prostate biopsies reveal no malignancy but only inflammation, this concept can help in determining the need for quick repeat biopsies.

Voiding Habits and Wetting in a Population of 4332 Belgian Schoolchildren Aged Between 10 and 14 Years

Objective: To determine the prevalence of daytime- with/without night-time wetting, in Belgium, in a group of 10 to 14 year old schoolchildren, and to study the voiding habits. Subjects and methods: A questionnaire of 41 questions was developed and completed by 4332 parents at home. Results: Wetting or soiling episodes were reported by a total of 528 (12%) of the children: monosymptomatic nocturnal enuresis by 62 (1%), daytime wetting with/without night-time wetting by 343 (8%), and faecal soiling by 123 (3%). We found significantly more girls in the wetting group, and the capacity to regularly postpone the voiding was significantly lower in this group. Significantly more children had nocturia in the group with wetting. Conclusions: Children with daytime wetting with/without night-time wetting have very often bladder-sphincter dysfunctions, which is in turn correlated with recurrent urinary tract infections. Eight percent of the 10 to 12 year old schoolchildren report daytime wetting with/without night-time wetting with some frequency. Surprisingly few parents, especially in the daytime wetting group, searched for medical help. Physicians and paediatricians should be encouraged to be more attentive to wetting in children and initiate discussion about urinary en faecal problems with parents and children.

Contemporary Management of the Painful Bladder: A Systematic Review

CONTEXTnDifferent types of behavioural, dietary, interventional, pharmacologic, and surgical therapies have been used to treat painful bladder syndrome/interstitial cystitis (PBS/IC). Because of the paucity of randomised placebo-controlled studies on different treatments, an evidence-based management approach has not yet been developed.nnnOBJECTIVEnTo critically review and synthesize data from a wide range of current therapeutic approaches to PBS/IC, to quantify the effect size from randomised controlled trials (RCTs), and to reach clinical agreement on the efficacy of treatments for PBS/IC.nnnEVIDENCE ACQUISITIONnWe performed a systematic review of the literature to identify articles published between 1990 and September 2010 on the management of PBS/IC. We included articles restricted to the English language published since 1990 to date that reported on oral and intravesical treatment, multimodal or combined treatment, and surgical treatment. For all RCTs, standardised mean differences (SMDs) were extracted and combined in a meta-analysis applying a random-effect model that incorporated the heterogeneity of effects. The four outcomes assessed in all studies were a change in the Interstitial Cystitis Symptom Index (ICSI), pain, urgency, and frequency. Non-RCTs (nRCTs) were analysed with a narrative synthesis of the evidence from all research designs.nnnEVIDENCE SYNTHESISnWe included 7709 adult patients from 29 RCTs and 57 nRCTs. Meta-analysis of RCTs showed that only cyclosporine A provided a simultaneous great effect size of SMD on ICSI, pain, and frequency. Amitriptyline at different dosages showed a great effect size of SMD on pain and urgency or on ICSI and frequency. The remaining RCTs showed sporadic significant changes in only one of the four considered parameters. The attributed levels of evidence for treatments reported in RCTs were 1b; grades of recommendations ranged from A to C. According to the Jadad score, 11 RCTs were high-quality studies. Meta-analysis of RCTs showed a great heterogeneity in the applied methodologies, clinical outcomes assessed, and the obtained results in different studies. The results from the nRCTs showed that the most frequently adopted treatment is oral pentosan polysulfate and that the use of botulinum A toxin intradetrusorial injections in PBS/IC is increasing. A high heterogeneity in drugs and treatment modalities, clinical outcomes, and obtained results was also found for nRCTs.nnnCONCLUSIONSnLimited evidence exists for the few treatments for PBS/IC. The lack of definitive conclusions is due to the great heterogeneity in methodology, symptoms assessment, duration of treatment, and follow-up in both RCTs and nRCTs.

Adverse events after botulinum A toxin injection for neurogenic voiding disorders

Objectives:To review the side effects of local injections of botulinum A toxin (BTX-A).Methods:A medline search for publications about adverse events after injection of BTX-A for lower urinary tract dysfunctions.Results:We found four publications that report generalised side effects after BTX-A injection for detrusor overactivity (two) and detrusor–sphincter dyssynergia (two). The causes of generalised adverse events are not clear, but spread outside the target organ and into the systemic circulation may contribute. The dose used, the injection volume and the injection technique can all play a role.Conclusion:Generalised side effects after BTX-A injection for voiding disorders are rare but they can be very disabling for spinal cord-injured patients. Although no long-term side effects are reported so far, urologists should be aware that these effects of BTX-A injections are unknown.

A phase II dose-ranging study of mirabegron in patients with overactive bladder

Introduction and hypothesisMirabegron is a potent and selective β3-adrenoceptor agonist that may represent an alternative treatment option in place of antimuscarinics for patients with overactive bladder.MethodsPatients completed a single-blinded, 2-week placebo run-in period followed by 12xa0weeks of randomized (nu2009=u2009928) double-blinded treatment with mirabegron oral controlled absorption system (OCAS) 25, 50, 100, or 200xa0mg once-daily (QD), placebo or tolterodine extended release (ER) 4xa0mg QD. The primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes/24xa0h. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes/24xa0h; severity of urgency; nocturia; and quality of life measures. Safety parameters included vital signs, adverse events, laboratory tests, electrocardiogram measurements and post-void residual volume.ResultsMirabegron 25, 50, 100, and 200xa0mg resulted in dose-dependent reductions (improvements) from baseline to end-of-treatment in micturition frequency of 1.9, 2.1, 2.1, and 2.2 micturitions/24xa0h respectively, versus 1.4 micturitions/24xa0h with placebo (pu2009≤u20090.05 for the mirabegron 50-, 100-, and 200-mg comparisons). There was a statistically significant improvement with mirabegron compared with placebo for most secondary endpoints including quality of life variables. While there was a significant (pu2009<u20090.05) increase from baseline in pulse rate in the mirabegron 100-mg and 200-mg groups, this was not associated with an increased incidence of cardiovascular adverse events.ConclusionsThe favorable efficacy and tolerability of mirabegron in this phase II dose-finding study has led to its successful advancement into a phase III clinical development program.

Clean intermittent catheterization and urinary tract infection: review and guide for future research.

Whats known on the subject? and What does the study add?

Researching bladder afferents—determining the effects of β3‐adrenergic receptor agonists and botulinum toxin type‐A

A substantial portion of the current research on lower urinary tract dysfunction is focused on afferent mechanisms. The main goals are to define and modulate the signaling pathways by which afferent information is generated, enhanced and conveyed to the central nervous system. Alterations in bladder afferent mechanisms are a potential source of voiding dysfunction and an emerging source for drug targets. Established drug therapies such as muscarinic receptor antagonists, and two emerging therapies, β3‐adrenergic receptor agonists and botulinum toxin type‐A, may act partly through afferent mechanisms. This review focuses on these two new principles and new and established methods for determining their sites of action. It also provides brief information on the innervation of the bladder, afferent receptors and transmitters and how these may communicate with the urothelium, interstitial cells and detrusor smooth muscle to regulate micturition. Peripheral and central mechanisms of afferent sensitization and myogenic mechanisms that lead to detrusor overactivity, overactive bladder symptoms and urgency sensations are also covered. This work is the result from ‘Think Tank’ presentations, and the lengthy discussions that followed, at the 2010 International Consultation on Incontinence Research Society meeting in Bristol, UK. Neurourol. Urodynam. Neurourol. Urodynam. 30:684–691, 2011.

Neurologic urinary incontinence

This manuscript summarizes the work of Committee 10 on neurologic bladder and bowel of the International Consultation on Incontinence in 2008–2009. As the data are very large the outcome is presented in different manuscripts. This manuscript deals with neurologic urinary incontinence.