Marcus J. Drake

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

EAU guidelines on urinary incontinence

CONTEXT The first European Association of Urology (EAU) guidelines on incontinence were published in 2001. These guidelines were periodically updated in past years. OBJECTIVE The aim of this paper is to present a summary of the 2009 update of the EAU guidelines on urinary incontinence (UI). EVIDENCE ACQUISITION The EAU working panel was part of the 4th International Consultation on Incontinence (ICI) and, with permission of the ICI, extracted the relevant data. The methodology of the 4th ICI was a comprehensive literature review by international experts and consensus formation. In addition, level of evidence was rated according to a modified Oxford system and grades of recommendation were given accordingly. EVIDENCE SUMMARY A full version of the EAU guidelines on urinary incontinence is available as a printed document (extended and short form) and as a CD-ROM from the EAU office or online from the EAU Web site (http://www.uroweb.org/guidelines/online-guidelines/). The extent and invasiveness of assessment of UI depends on severity and/or complexity of symptoms and clinical signs and is different for men, women, frail older persons, children, and patients with neuropathy. At the level of initial management, basic diagnostic tests are applied to exclude an underlying disease or condition such as urinary tract infection. Treatment is mostly conservative (lifestyle interventions, physiotherapy, physical therapy, pharmacotherapy) and is of an empirical nature. At the level of specialised management (when primary therapy failed, diagnosis is unclear, or symptoms and/or signs are complex/severe), more elaborate assessment is generally required, including imaging, endoscopy, and urodynamics. Treatment options include invasive interventions and surgery. CONCLUSIONS Treatment options for UI are rapidly expanding. These EAU guidelines provide ratings of the evidence (guided by evidence-based medicine) and graded recommendations for the appropriate assessment and according treatment options and put them into clinical perspective.

EAU Guidelines on the Assessment of Non-neurogenic Male Lower Urinary Tract Symptoms including Benign Prostatic Obstruction

CONTEXT Lower urinary tract symptoms (LUTS) represent one of the most common clinical complaints in adult men and have multifactorial aetiology. OBJECTIVE To develop European Association of Urology (EAU) guidelines on the assessment of men with non-neurogenic LUTS. EVIDENCE ACQUISITION A structured literature search on the assessment of non-neurogenic male LUTS was conducted. Articles with the highest available level of evidence were selected. The Delphi technique consensus approach was used to develop the recommendations. EVIDENCE SYNTHESIS As a routine part of the initial assessment of male LUTS, a medical history must be taken, a validated symptom score questionnaire with quality-of-life question(s) should be completed, a physical examination including digital rectal examination should be performed, urinalysis must be ordered, post-void residual urine (PVR) should be measured, and uroflowmetry may be performed. Micturition frequency-volume charts or bladder diaries should be used to assess male LUTS with a prominent storage component or nocturia. Prostate-specific antigen (PSA) should be measured only if a diagnosis of prostate cancer will change the management or if PSA can assist in decision-making for patients at risk of symptom progression and complications. Renal function must be assessed if renal impairment is suspected from the history and clinical examination, if the patient has hydronephrosis, or when considering surgical treatment for male LUTS. Uroflowmetry should be performed before any treatment. Imaging of the upper urinary tract in men with LUTS should be performed in patients with large PVR, haematuria, or a history of urolithiasis. Imaging of the prostate should be performed if this assists in choosing the appropriate drug and when considering surgical treatment. Urethrocystoscopy should only be performed in men with LUTS to exclude suspected bladder or urethral pathology and/or before minimally invasive/surgical therapies if the findings may change treatment. Pressure-flow studies should be performed only in individual patients for specific indications before surgery or when evaluation of the pathophysiology underlying LUTS is warranted. CONCLUSIONS These guidelines provide evidence-based practical guidance for assessment of non-neurogenic male LUTS. An extended version is available online (www.uroweb.org/guidelines). PATIENT SUMMARY This article presents a short version of European Association of Urology guidelines for non-neurogenic male lower urinary tract symptoms (LUTS). The recommended tests should be able to distinguish between uncomplicated male LUTS and possible differential diagnoses and to evaluate baseline parameters for treatment. The guidelines also define the clinical profile of patients to provide the best evidence-based care. An algorithm was developed to guide physicians in using appropriate diagnostic tests.

Autonomous Activity in the Isolated Guinea Pig Bladder

Phasic changes in pressure have been reported to occur in the bladder which are not associated with micturition. Spontaneous intravesical pressure changes can be recorded from bladders in vitro or bladders in vivo isolated from the central nervous system suggesting that the bladder itself is capable of autonomous activity. Experiments using isolated cells and muscle strips indicate that the smooth muscle can generate spontaneous activity. Whether this is the origin of phasic changes in the intact organ remains unknown. The present study set out to establish the presence and characteristics of autonomous activity in the isolated guinea pig bladder. Multiple‐point motion analysis and concurrent intravesical pressure recording were used to identify and quantify spontaneous and evoked activity. Highly complex autonomous activity was observed in unstimulated bladders. This activity comprised localised micro‐contractions in single or multiple discrete regions, waves of activity and micro‐stretches. Low‐amplitude phasic ‘micro‐transients’ were seen in the intravesical pressure trace in association with micro‐contractions. Incremental increases in the intravesical volume recruited additional areas of activity. Atropine and tetrodotoxin had no effect on the micro‐transients or micro‐contractions. Exposure to the muscarinic agonist arecaidine (10‐300 nM) initially increased the incidence of micro‐contractions which subsequently became co‐ordinated into phasic pressure rises and contraction waves, interspersed with periods of total quiescence. The findings describe the generation and co‐ordination of autonomous activity in the bladder wall and also demonstrate complex phasic activity. This approach has shown the importance of assessing the integrative properties of the entire organ in studies of the physiology and patho‐physiology of the bladder.

The Artificial Urinary Sphincter After a Quarter of a Century: A Critical Systematic Review of Its Use in Male Non-neurogenic Incontinence

CONTEXT The artificial urinary sphincter (AUS) has historically been considered the gold standard for the surgical management of non-neurogenic stress urinary incontinence (SUI) in men. As new surgical alternatives attempt to offer alternatives to treat male SUI, a contemporary assessment of the evidence supporting the use of AUS appears mandatory for clinical decision making. OBJECTIVE To conduct a critical systematic review of long-term outcomes after AUS implantation in male patients with non-neurogenic SUI. EVIDENCE ACQUISITION A literature search was conducted in PubMed/Medline and Embase databases using the keywords urinary incontinence and urinary sphincter, artificial and male, restricted to articles published in Dutch, English, French, and German between 1989 and 2011. Studies were included if they reported outcomes after AUS implantation in patients with non-neurogenic SUI with a minimum follow-up of 2 yr. Studies with heterogeneous populations were included if information about non-neurogenic patients was displayed separately. EVIDENCE SYNTHESIS Twelve reports were identified, gathering data about 623 patients. Only three studies were prospective. Continence, evaluated only by patient-reported pad use and various questionnaires, was achieved in 61-100% of cases (no pad or one pad per day). Dry rates (no pad) were only available in seven studies and varied from 4% to 86%. A pooled analysis showed that infection or erosion occurred in 8.5% of cases (3.3-27.8%), mechanical failure in 6.2% of cases (2.0-13.8%), and urethral atrophy in 7.9% (1.9-28.6%). Reoperation rate was 26.0% (14.8-44.8%). Patient satisfaction was evaluated in four studies with four different tools and seems to improve after AUS implantation. CONCLUSIONS Quality of evidence supporting the use of AUS in non-neurogenic male patients with SUI is low, based on heterogeneous data, low-quality studies, and mostly out-of-date efficacy outcome criteria. AUS outcomes need to be revisited to be compared with new surgical alternatives, all of which should be prospectively evaluated according to current evidence-based medicine standards.

Model of peripheral autonomous modules and a myovesical plexus in normal and overactive bladder function

Normal bladder function is controlled by the central nervous system (CNS) and any peripheral contribution to bladder control is believed to be small. Nevertheless, anatomically and functionally, such a contribution might exist. Taking account of this evidence, we propose that the detrusor muscle is arranged into modules, which are circumscribed areas of muscle active during the filling phase of the micturition cycle. These modules might be controlled by a peripheral myovesical plexus, consisting of intramural ganglia and interstitial cells. Detrusor overactivity is the occurrence of abnormal increases in pressure during bladder filling, which the patient cannot inhibit. This disorder is thought to be a consequence of abnormal expression of the micturition reflex or changes in the properties of the smooth muscle. We propose that detrusor overactivity results from exaggerated symptomatic expression of peripheral autonomous activity, resulting from a shift in the balance of excitation and inhibition in smooth muscle modules. These structures responsible for origin and spread of peripheral autonomous activity could be targeted to help develop new therapeutic strategies.

Localized contractions in the normal human bladder and in urinary urgency

To describe an observational study to establish whether localized activity arises in the normal human bladder, and whether there is any correspondence between changes in such activity and reported sensation.

Neural Control of the Lower Urinary Tract: Peripheral and Spinal Mechanisms

This review deals with individual components regulating the neural control of the urinary bladder. This article will focus on factors and processes involved in the two modes of operation of the bladder: storage and elimination. Topics included in this review include: (1) The urothelium and its roles in sensor and transducer functions including interactions with other cell types within the bladder wall (“sensory web”), (2) The location and properties of bladder afferents including factors involved in regulating afferent sensitization, (3) The neural control of the pelvic floor muscle and pharmacology of urethral and anal sphincters (focusing on monoamine pathways), (4) Efferent pathways to the urinary bladder, and (5) Abnormalities in bladder function including mechanisms underlying comorbid disorders associated with bladder pain syndrome and incontinence. Neurourol. Urodynam. 29: 128–139, 2010.

The human urinary microbiome; bacterial DNA in voided urine of asymptomatic adults

The urinary microbiome of healthy individuals and the way it alters with ageing have not been characterized and may influence disease processes. Conventional microbiological methods have limited scope to capture the full spectrum of urinary bacterial species. We studied the urinary microbiota from a population of healthy individuals, ranging from 26 to 90 years of age, by amplification of the 16S rRNA gene, with resulting amplicons analyzed by 454 pyrosequencing. Mid-stream urine (MSU) was collected by the “clean-catch” method. Quantitative PCR of 16S rRNA genes in urine samples, allowed relative enumeration of the bacterial loads. Analysis of the samples indicates that females had a more heterogeneous mix of bacterial genera compared to the male samples and generally had representative members of the phyla Actinobacteria and Bacteroidetes. Analysis of the data leads us to conclude that a “core” urinary microbiome could potentially exist, when samples are grouped by age with fluctuation in abundance between age groups. The study also revealed age-specific genera Jonquetella, Parvimonas, Proteiniphilum, and Saccharofermentans. In conclusion, conventional microbiological methods are inadequate to fully identify around two-thirds of the bacteria identified in this study. Whilst this proof-of-principle study has limitations due to the sample size, the discoveries evident in this sample data are strongly suggestive that a larger study on the urinary microbiome should be encouraged and that the identification of specific genera at particular ages may be relevant to pathogenesis of clinical conditions.

Neural control of the lower urinary and gastrointestinal tracts: supraspinal CNS mechanisms.

Normal urinary function is contingent upon a complex hierarchy of CNS regulation. Lower urinary tract afferents synapse in the dorsal horn of the spinal cord and ascend to the midbrain periaqueductal gray (PAG), with a separate nociception path to the thalamus. A spino‐thalamo‐cortical sensory pathway is present in some primates, including humans. In the brainstem, the pontine micturition center (PMC) is a convergence point of multiple influences, representing a co‐ordinating center for voiding. Many PMC neurones have characteristics necessary to categorize the center as a pre‐motor micturition nucleus. In the lateral pontine brainstem, a separate region has some characteristics to suggest a “continence center.” Cerebral control determines that voiding is permitted if necessary, socially acceptable and in a safe setting. The frontal cortex is crucial for decision making in an emotional and social context. The anterior cingulate gyrus and insula co‐ordinate processes of autonomic arousal and visceral sensation. The influence of these centers on the PMC is primarily mediated via the PAG, which also integrates bladder sensory information, thereby moderating voiding and storage of urine, and the transition between the two phases. The parabrachial nucleus in the pons is also important in behavioral motivation of waste evacuation. Lower urinary tract afferents can be modulated at multiple levels by corticolimbic centers, determining the interoception of physiological condition and the consequent emotional motor responses. Alterations in cognitive modulation, descending modulation, and hypervigilance are important in functional (symptom‐based) clinical disorders. Neurourol. Urodynam. 29: 119–127, 2010.