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Context: Nocturia is among the most common and bothersome lower urinary tract symptoms (LUTS), but there is no clear consensus on how to identify and manage this symptom in the neurological population., Objective: To systematically review the literature about nocturia in neurological patients., Evidence Acquisition: Studies were identified by electronic search of Cochrane and Medline databases. The studies were included if their participants had acquired neurological pathology among multiple sclerosis (MS), Parkinson's disease (PD), stroke, spinal cord injury (SCI), and reported data on the epidemiology, aetiology, diagnosis, or treatment of nocturia. An independent extraction of the articles was performed by two authors using predetermined datasets, including quality-of-study indicators., Evidence Synthesis: A total of 132 studies were included; 46 evaluated the epidemiology of nocturia, 28 the possible aetiologies, 10 the diagnostic tools, and 60 the treatments. Nocturia prevalence ranged from 15% to 96% depending on the pathology and definition used. It was one of the most frequently reported LUTS in PD and stroke patients. Several validated questionnaires were found to screen for nocturia in this population. Causalities were numerous: LUT, renal, sleep, cardiovascular dysfunctions, etc. Treatments targeted these mechanisms, with an overall risk of bias assessed as high or serious. The highest level of evidence was seen in MS patients: pelvic floor muscle training, cannabinoids, and desmopressin were effective, but not melatonin. In stroke patients, transcutaneous sacral and transcutaneous tibial nerve stimulation (TTNS) improved nocturia; in PD patients, TTNS, solifenacin, and rotigotine did not., Conclusions: Nocturia is highly prevalent in patients with neurological disorders. Causalities and treatments are not different from the general population, but are poorly studied in neurological patients., Patient Summary: In this report, we looked at the published studies about nocturia-the fact of waking to void during the hours of sleep-in patients with neurological diseases. We found that nocturia is very frequent in this population, that the causes are the same as in the general population but may be combined, and that treatments are also the same but have an overall weak level of evidence. We conclude that more research is needed on this topic., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: We evaluated the 3-year safety and efficacy of the BlueWind Medical RENOVA™ iStim system for the treatment of overactive bladder syndrome., Materials and Methods: All patients who previously underwent implantation with the RENOVA system were offered continued participation. The primary long-term study end point was to evaluate the safety profile based on incidence of serious adverse events (system and/or procedure related), which was measured by the impact and frequency of serious adverse events. The secondary end points included clinical improvement compared to baseline and quality of life improvement compared to baseline at 36 months, which was measured by 3-day voiding diary and quality of life questionnaires at certain time points., Results: Of the 34 patients with overactive bladder syndrome who previously underwent implantation with the RENOVA system 20 consented to continuation in this 3-year followup study. Mean patient age was 56.1 years and 80% (16) of the study cohort was female. The overall treatment success rate was 75% at 36 months in the per protocol (16) and the intent to treat (20) analyses. In total, 73% of the patients reported improvement in health related quality of life scores above the minimal important difference of 10 points., Conclusions: This 3-year followup study using the BlueWind RENOVA iStim system for the treatment of overactive bladder syndrome symptoms confirms the long-term good safety profile with no technical failures reported. Lasting treatment efficacy is mirrored by a sustained positive impact on patient quality of life.

Introduction: Detrusor underactivity (DU) is currently a topic that receives major attention within functional urology. Urologists are often confronted with men who present with voiding dysfunction without bladder outlet obstruction (BOO) or after desobstructive or neuromodulation treatment. Their impaired bladder emptying is suspected to be related to failure of detrusor contractile function. Earlier research indicated that patients with non-obstructive urinary retention (NOR), for example, detrusor underactivity (DU), have a lower success rate after sacral neuromodulation (SNM) compared to patients treated with SNM for storage dysfunction. However, predicting factors for treatment success in the NOR group have not yet been defined., Methods and Evidence: The aim of this study was to assess whether the use of the new BOO-contractility (Maastricht-Hannover) nomogram can identify and predict SNM non-responders. Our results in 18 men showed that only 20% of patients below the 10th percentile, but 86% of men between the 10 and 25th percentiles of the nomogram can be treated successfully with SNM. All successfully treated patients voided without needing self- catheterisation., Conclusions: This pilot study showed for the first time that SNM treatment response in male patients with impaired bladder emptying can be predicted with the BOO-contractility (Maastricht-Hannover) nomogram. Men below the 10th percentile are likely to be treatment non-responders, whereas the majority of men above the 10th percentile are responders. Neurourol. Urodynam. 36:808-810, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Aim: Increased afferent fibre activity contributes to pathological conditions such as the overactive bladder syndrome. Nerve fibres running near the urothelium are considered to be afferent as no efferent system has yet been described. The aim of this study was to identify sub-types of afferent nerve fibres in the mouse bladder wall based on morphological criteria and analyse regional differences., Materials and Methods: 27 bladders of six month old C57BL/6 mice were removed and tissues were processed for immunohistochemistry. Cryostat sections were cut and stained for Protein Gene Product 9.5 (PGP), calcitonin gene related polypeptide (CGRP), neurofilament (NF), vesicular acetylcholine transporter (VAChT) and neuronal nitric oxide synthase (nNOS)., Results: In the sub-urothelium, different types of afferent nerve fibre were found, i.e. immunoreactive (IR) to; CGRP, NF, VAChT, and/or nNOS. At the bladder base, the sub-urothelium was more densely innervated by CGRP-IR and VAChT-IR nerve fibres, then at the lateral wall. NF- and nNOS nerves were sparsely distributed in the sub-urothelium throughout the bladder. At the lateral wall the inner muscle is densely innervated by CGRP-IR nerve fibres. NF, VAChT and nNOS nerves were evenly distributed in the different muscle layers throughout the bladder. Nerve fibre terminals expressing CGRP and NF were found within the extra-mural ganglia at the bladder base., Conclusions: Different types of afferent nerve fibres were identified in the sub-urothelium of the mouse bladder. At the bladder base the sub-urothelium is more densely innervated than the lateral wall by CGRP-IR and VAChT-IR afferent nerve fibres. CGRP and NF afferent nerve fibres in the muscle layer probably relay afferent input to external ganglia located near the bladder base. The identification of different afferent nerves in the sub-urothelium suggests a functional heterogeneity of the afferent nerve fibres in the urinary bladder., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Cycling has gained increased popularity among women, but in contrast to men, literature on urogenital overuse injuries and sexual dysfunctions is scarce., Aim: To determine the prevalence and duration of urogenital overuse injuries and sexual dysfunctions in female cyclists of the largest female cycling association in The Netherlands., Methods: A cross-sectional questionnaire survey was sent to 350 members of the largest female Dutch cycling association and 350 female members of a Dutch athletics association (runners)., Main Outcome Measures: The prevalence and duration of urogenital overuse injuries and sexual complaints were assessed using predefined international definitions., Results: Questionnaire results of 114 cyclists (32.6%) and 33 runners (9.4%) were analyzed. After at least 2 hours of cycling, dysuria, stranguria, genital numbness, and vulvar discomfort were present in 8.8%, 22.2%, 34.9%, and 40.0%, respectively (maximum duration 48 hours). These complaints are not present in the controls (P < .001). In multivariable logistic regression analysis, increased saddle width was significantly associated with the presence of dysuria and stranguria. Older age was significantly associated to the presence of vulvar discomfort. Of the cyclists, 50.9% has at least one urogenital overuse injury. Insertional dyspareunia was present in 40.0% of cyclists and lasted until 48 hours after the effort. The latter complaint was not present in runners (P < .001). Uni- or bilateral vulvar edema was reported by 35.1% of cyclists. As for general complaints, 18.4% of cyclists reported a change in sexual sensations and 12.8% reported difficulties in reaching orgasm owing to cycling-related complaints. Limitations include population size and the use of non-validated questionnaires., Conclusions: The results of this study suggest that urogenital overuse injuries and sexual complaints are highly prevalent in female cyclists who are active participants in riding groups., (Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Nitric oxide-stimulated cGMP synthesis represents an important signalling pathway in the urinary bladder. Inhibitors of the PDE1 and PDE5 enzyme have been studied to treat storage and voiding disorders in clinical settings. The distribution of PDE2 in the bladder is unknown. This study focuses on the distribution and site of action of PDE2 within the guinea pig urinary bladder wall., Methods: Six male guinea pig bladders were dissected and treated in 2 ml Krebs' solution and 10 µM of the specific PDE2 inhibitor, Bay 60-7550 at 36 °C for 30 min. After stimulating tissues with 100 µM of diethylamine-NONOate for 10 min, the tissues were snap frozen and cut in 10 µm sections which were examined for cGMP immune-reactivity, co-stained with either vimentin, synaptic vesicle protein 2, calcitonin gene-related protein and protein gene product 9.5., Results: PDE2 inhibitor Bay 60-7550 inhibits cGMP breakdown the most in the urothelial and suburothelial layers, as well as on the nerve fibres. After inhibition by Bay 60-7550, cGMP was mainly expressed in the intermuscle interstitial cells and the nerve fibres of the outer muscle layers of lateral wall, indicating the presence of PDE2 activity., Discussion and Conclusion: Our study is the first to show the distribution of PDE2 in the bladder which was shown to be present in the urothelium, mainly umbrella cells, the interstitial cells of the suburothelium and the outer muscle, as well as in nerve fibres.

Intramural ganglia are present in the bladder wall of several species including human, pig, and guinea-pig. It has been suggested that there is a network of intramural ganglia in the bladder of these species that may be part of a motor-sensory system and receive afferent input. Prostaglandins (PG) have been suggested to play a role in this afferent signalling mechanism. To investigate the distribution of the prostaglandin E2 receptors EP1 and EP2 in and around intramural ganglia of the guinea pig, bladders of 6 guinea pigs were dissected, and processed for immunohistochemistry. Sections were examined for prostaglandin E2 receptor EP1- and EP2-immuno-reactivity and co-stained for vimentin, a marker for interstitial cells (IC) and cyclo-oxygenase 1 (COX I), the enzyme responsible for PG synthesis. Immunoreactivities for EP1 and EP2 were found in intramural ganglion cells. These cells were observed in between muscle bundles and on, or close to the serosal surface of the bladder. Furthermore, COX I was present in interstitial cells close to ganglion cells, indicating the possibility of a local synthesis of prostaglandins near the ganglia. The co-staining of EP1 or EP2 with vimentin showed that processes of interstitial cells run through the ganglia, often encircling or ensheathing cells. Therefore, it can be concluded that there is a close relationship between the intramural ganglia and the network of interstitial cells in the muscular layers of the bladder. EP1 and EP2 receptors are expressed on the ganglia and this arrangement suggests that intramural ganglia are involved in (pre)processing afferent information., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aims: To investigate urologists' referral attitude for sacral neuromodulation (SNM) for treating refractory idiopathic overactive bladder syndrome (OAB) and to quantify the weight they attribute to clinical parameters to refrain from SNM referral., Methods: We set up a vignette study using a discrete-choice design. The questionnaires were distributed at two national urological meetings., Results: One hundred eight urologists completed the questionnaire. Three parameters were significantly associated with the decision to refrain from referral: absolute contraindications for SNM (anatomical low bladder compliance, current urinary tract infection, progressive neurological disease, urinary tumors) had the strongest association (0.78, 95% CI 0.58 to 0.97; P < 0.001), followed by cardiac pacemaker (0.24, 95% CI 0.08 to 0.39; P = 0.003), and diabetes mellitus (0.19, 95% CI 0.06 to 0.32; P = 0.006). On the other hand, urologists considered fecal incontinence as an important parameter for referral (-0.16, 95% CI -0.29 to -0.04; P = 0.011). Current medication with antimuscarinics and polyuria played no role in the decision. Results in a subgroup of 24 neuro-urologists/functional urologists were similar but non-critical parameters were not associated with the decision to refrain from SNM referral., Conclusions: Besides absolute contraindications, other non-critical parameters such as cardiac pacemaker or diabetes mellitus influence urologists' decision to refrain from referral for SNM. We believe that the use of decision tools will help urologists identifying patients benefiting from SNM and therefore we call for broad dissemination of such tools into clinical practice., (© 2013 Wiley Periodicals, Inc.)

Objective: To present and describe a non-invasive method to study the origin and development of bladder filling sensation and to evaluate the repeatability of the method., Method: Eighteen volunteers participated in the study and were given a water loading protocol consisting of 1,000 ml water intake 1 hr before the session and 200 ml every 10 min during the session. Protocol 1: To evaluate diuresis rate, seven participants were asked to void every 15 min and the voided volume was measured. Protocol 2: Eleven volunteers graded bladder sensation on regular time points, on an empty graph with time on the X-axis and intensity of sensation on the Y-axis. The protocol ended at absolute need to void (maximal intensity) and voided volumes were measured. This protocol was conducted three times with a 10 days interval., Results: Protocol 1: The diuresis rate was not different during the sessions and showed no variation over the studied time period (P = 0.2). Protocol 2: For an individual, the diuresis rate was not different between the sessions. The curves in all patients showed a continuously increasing bladder intensity. In seven participants the curve was convex, in the other four, the curve was sigmoidal. For each individual the pattern was constant during the three sessions., Conclusion: A strict water loading protocol induces a constant diuresis. This allows individuals to draw an introspection bladder sensation curve with a specific shape, which can be used as a method to study the development of bladder sensation non-invasively., (© 2013 Wiley Periodicals, Inc.)

Introduction: Lower urinary tract symptoms (LUTS) are highly prevalent, cause an enormous economic burden on healthcare systems and significantly impair the quality of life (QoL) of affected patients. The dependence of the LUT on complex central neuronal circuits makes it unique in comparison to other visceral functions, such as the gastrointestinal tract, but also more vulnerable to neurological diseases., Methods and Analysis: This is a prospective neuroimaging study investigating the supraspinal control of LUT function in healthy controls and in patients with non-neurogenic LUTS. The clinical assessment will include medical history, neuro-urological examination, bladder diary, urine analysis, urodynamic investigations, as well as standardised questionnaires regarding LUTS and QoL. The acquisition of neuroimaging data will include structural assessments (T1-weighted imaging and diffusion tensor imaging) as well as functional investigations using blood-oxygen-level dependent sensitive functional MRI (fMRI) in a 3 T MR scanner. The fMRI will be performed during four different bladder tasks using an automated MR-compatible and MR-synchronised pump system. The first three task-related fMRIs will consist of automated, repetitive filling of 100 mL warm (37°C) saline starting with (1) an empty bladder, (2) a low prefilled bladder volume (100 mL) and (3) a high prefilled bladder volume (persistent desire to void). The fourth task-related fMRI will comprise of automated, repetitive filling of 100 mL cold (4-8°C) saline starting with an empty bladder., Ethics and Dissemination: The local ethics committee approved this study (KEK-ZH-Nr. 2011-0346). The findings of the study will be published in peer-reviewed journals and presented at national and international scientific meetings., Trial Registration Number: This study has been registered at clinicaltrials.gov (http://www.clinicaltrials.gov/ct2/show/NCT01768910)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To present a straightforward, reproducible technique with the basic principle of preserving all available outer penile shaft skin and using this to cover the dorsal side of the penis. The DOuble LOngitudinal Megapreputium Incision TEchnique is presented in a step-by-step fashion., Materials and Methods: Six consecutive patients with a mean age of 13.3 months (range, 7-25) underwent this reconstruction between 2006 and 2011. The technique starts with 2 longitudinal incisions, the first on the ventral side, and the second on the dorsal side of the penis. After hinging the penile skin to the dorsal side, redundant inner preputial tissue is resected using diagonal incisions. Dartos is spared. A comparison with previously reported techniques and a concise review of existing literature are provided., Results: The final cosmetic results, after an initial period of edematous swelling of the ventral aspect of the penis, were good in all patients. The bilateral diagonal scars on the penile shaft became inconspicuous over time. Voiding normalized. No complications occurred., Conclusion: The DOuble LOngitudinal Megapreputium Incision TEchnique provides a straightforward and reproducible surgical correction for congenital megaprepuce., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: We evaluated whether patients with overactive bladder and incontinence who discontinued intravesical botulinum toxin therapy can be successfully treated with sacral neuromodulation., Materials and Methods: All patients who were referred to our center after discontinuation of botulinum toxin-A between 2005 and 2010 were included in this observational study. All patients underwent test stimulation with sacral neuromodulation and were evaluated with voiding diaries. Success was defined as more than 50% improvement in leakage episodes. Successful test stimulation was subsequently followed by a definitive implant. Patient satisfaction with sacral neuromodulation therapy was evaluated 1 year after the definitive implant., Results: A total of 20 patients were included in the study. Of these patients 17 (85%) had discontinued botulinum toxin-A because of lack of efficacy and 3 had been treated successfully with botulinum toxin-A but requested a more permanent solution. The mean interval between the botulinum toxin-A and the sacral neuromodulation test stimulation was 23 months. In 14 patients (70%) the test stimulation was successful and they received a definitive implant. Of the 14 patients 5 even showed a decrease of greater than 90% in leakage episodes. One year after implantation 11 patients (79%) were satisfied with the sacral neuromodulation treatment., Conclusions: Despite the small sample size, this study indicates that patients who are dissatisfied with or in whom botulinum toxin-A treatment fails can respond successfully to sacral neuromodulation. The success rate of the test stimulation was comparable to that of patients who have never been treated with botulinum toxin-A. The 1-year satisfaction rate was comparable that of patients without a history of botulinum toxin-A treatment., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

In this paper a general discussion of the available data on the role of prostaglandin (PG) and phosphodiesterase is discussed. Functional studies would be a next step to understand the functional meaning of the data described in this paper. The data presented are a basis for further research on selective modulation of the EP1 and EP2 receptor which could be a therapeutic target in functional bladder disorders such as OAB. PDE inhibitors are closer to clinical use, as these drugs have been studied and registered for other indications such as erectile dysfunction in men. Therefore, in vivo studies in human subjects can be conducted on short term. However, from a scientific point of view, it is very important to unravel the exact site of action and role of PDE inhibition with in vitro and in vivo studies as is the case with PG. In this way, a combination of drugs targeting different mechanisms involved in bladder physiology such as PG, cGMP, cAMP, and muscarinic receptors, could reduce side effects and improve efficacy.

In this paper, a general introduction is given, presenting the overactive bladder syndrome (OAB) and its impact on the quality of life and economical burden in patients affected. Moreover, the anatomy, physiology and histology of the lower urinary tract are discussed, followed by a brief overview on the possible role of prostaglandin (PG) and phosphodiesterase type 5 (PDE5) in the urinary bladder. The current literature on the role and distribution of PGE2 and its receptors in the urinary bladder is discussed. In both animal models and in human studies, high levels of signaling molecules such as PG and cGMP have been implicated, in decreased functional bladder capacity and micturition volume, as well as in increased voiding contraction amplitude. As a consequence, inhibition of prostanoid production, the use of prostanoid receptor antagonists, or PDE inhibitors might be a rational way to treat patients with detrusor overactivity. Similarly, prostanoid receptor agonists, or agents that stimulate their production, might have a function in treating bladder underactivity.

Objective: To study PDE5 localisation by visualising the product of phosphodiesterase type 5 (PDE5) inhibition, namely cGMP, to determine the site of action of inhibitors in the urinary bladder., Materials and Methods: Bladders of nine male guinea pigs were dissected and treated in wells containing 2 mL Krebs' solution and 1 μM of the specific PDE5 inhibitor vardenafil at 36 °C for 30 min. After stimulating tissues with 100 μM of the nitric oxide (NO) donor diethylamine-NONOate for 10 min, the tissues were snap-frozen and 9-10 μm sections were cut. Sections were examined for cGMP immunoreactivity and also stained for vimentin, a marker for interstitial cells and the neuromarkers protein gene product 9.5 (PGP9.5), synaptic vesicle protein 2 (SV2), neurofilament (NF) and calcitonin gene-related peptide (CGRP), using the two-step indirect immunohistochemistry technique., Results: After PDE5 inhibition, cGMP was found to be present in the urothelium, suburothelial interstitial cells and endothelium of blood vessels. cGMP was not expressed in nerves positive for CGRP, NF and SV2, and was expressed only in very few efferent nerves positive for PGP9.5., Conclusion: Our data show that the possible sites of action of PDE5 inhibition in the bladder are the urothelium, suburothelial interstitial cells and blood vessels, rather than the bladder nerve fibres., (© 2013 BJU International.)

A consensus statement published in 2011 summarised current research, clinical approaches, and treatment options for nocturia. Since that time, new research has refined our understanding of nocturia in clinically important ways and new evidence has been presented on the efficacy and outcomes of several treatment methods for this underreported, infrequently recognised, and undertreated problem in adults. This paper provides updated guidance to clinicians in light of recent advances in the field., (© 2013 BJU International.)

Background: To investigate the effect of prostaglandin depletion by means of COX-inhibition on cholinergic enhanced spontaneous contractions., Methods: The urethra and bladder of 9 male guinea pigs (weight 270-300 g) were removed and placed in an organ bath with Krebs' solution. A catheter was passed through the urethra through which the intravesical pressure was measured. The muscarinic agonist arecaidine, the non-selective COX inhibitor indomethacin, and PGE2 were subsequently added to the organ bath. The initial average frequency and amplitude of spontaneous contractions in the first 2 minutes after arecaidine application were labelled F(ini) and P(ini), respectively. The steady state frequency (F(steady)) and amplitude (P(steady)) were defined as the average frequency and amplitude during the 5 minutes before the next wash out., Results: Application of 1 μM PGE2 increased the amplitude of spontaneous contractions without affecting frequency. 10 μM of indomethacin reduced amplitude but not frequency.The addition of indomethacin did not alter F(ini) after the first application (p = 0.7665). However, after the second wash, F(ini) was decreased (p = 0.0005). F(steady), P(steady) and P(ini) were not significantly different in any of the conditions. These effects of indomethacin were reversible by PGE2 addition.., Conclusions: Blocking PG synthesis decreased the cholinergically stimulated autonomous contractions in the isolated bladder. This suggests that PG could modify normal cholinergically evoked response. A combination of drugs inhibiting muscarinic receptors and PG function or production can then become an interesting focus of research on a treatment for overactive bladder syndrome.

Aims: Glycosaminoglycan (GAG) layer replenishment is a cornerstone in the therapy of interstitial cystitis (IC). During the last years intravesical GAG layer replenishment has proven to be an effective treatment for overactive bladder (OAB), radiation cystitis, and recurrent urinary tract infections (UTIs)., Methods: Examination of different substances available for intravesical GAG replenishment and evaluation of the evidence for the treatment of the above-mentioned conditions., Results: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) database for studies on intravesical GAG replenishment. A total of 27 clinical studies remain relevant to this topic, many of them with mixed patient selection and suboptimal definition of symptom improvement/success. Two placebo controlled studies with hyaluronic acid failed to show superiority and have not been published. One active controlled randomized study has been published showing that chondroitin sulphate 0.2% has a clear benefit for OAB patients. Another study with chondroitin sulphate 2.0% failed to show statistically significant evidence, but was underpowered., Conclusions: A short number of randomized controlled studies confirm efficacy of intravesical GAG layer replenishment therapy. Concluded from the study background (which comprises also uncontrolled studies), so far chondroitin sulphate 0.2% is in favor for intravesical GAG layer replenishment therapy. In general, large-scale trials are urgently needed to underline the benefit of this type of therapy., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: To explore the distribution of prostaglandin E receptor type 2 (EP2) in the bladder muscle layers and its spatial relationship to cyclo-oxygenase type 1 (COX I)., Materials and Methods: Twelve male guinea pigs were killed by cervical dislocation, the bladders removed and fixed in 4% paraformaldehyde in PBS. Frozen sections of 10 μm were cut and stained with antibodies to EP2, COX I and vimentin., Results: EP2 receptor immunoreactivity is located on the smooth muscle cells as well as on vimentin positive surface muscle and intramuscular interstitial cells. EP2 expression on interstitial cells is highly localized. Discrete regions of intense staining were observed on the interstitial cell processes. COX I is expressed in the muscle interstitial cells and was found to be located on discrete regions of the cell and cell processes. Double staining with EP2 and COX I suggests that the regions of a cell expressing EP2 are different from those expressing COX I., Conclusions: The presence of COX I, prostaglandin E receptor type 2 (EP2) immune-reactivity in the network of interstitial cells suggests a role of this network in the propagation of signals. Due to a cAMP coupling of the EP2 receptor in many other tissues and a lower dissociation constant of EP2, it is suggested that a rise in PG levels may gradually push the balance from a relaxant EP2 effect towards a contractile effect. Hence, PG could have a modulatory role on the non-voiding bladder contractions by changing the threshold level for excitability of the interstitial cell network., (Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.)

The benefit that patients with overactive bladder (OAB) experience with conservative management is an important aspect in the evaluation of this therapy. The first-line options include behavioral interventions, and several techniques are available. Clinical research indicates amelioration of individual symptoms with these techniques, but few studies have shown a positive effect on health-related quality-of-life parameters. After failure of behavioral therapy or in combination with a training program, pharmacological therapy with anticholinergics is the next step. Extensive clinical research into different pharmacological compounds has shown significant effects on the symptomatic elements of OAB. The clinical relevance and the effects on quality-of-life parameters with pharmacological therapy have also been evaluated and show a significant effect on specific aspects. Recently, clinical research in conservative management of patients with OAB has focused more on evaluating patients' perceptions of their condition and the effects of treatment with patient-reported outcome instruments. Future studies should include these tools in the evaluation of any therapy in OAB.

Objectives: To review the technique, indications, results and working mechanisms of sacral neuromodulation (SNM) for lower urinary tract dysfunction., Methods: The available literature on SNM for lower urinary tract dysfunction was searched. Based on the information available in the literature and also based on personal experience, the urological indications, technique, mechanisms of action and results of SNM are presented and discussed., Results: SNM for lower urinary tract dysfunction involves stimulation of the 3rd sacral nerve with an electrode implanted in the sacral foramen and connected to a pulse generator. The technique is accepted by the FDA since 1997. Currently, SNM for lower urinary tract dysfunction has been successfully used in about 26,000 patients with various forms of lower urinary tract dysfunction, including urgency, frequency and urgency incontinence as well as non-obstructive urinary retention. The actual procedure of SNM consists of a minimal invasive technique and is effective in about 70% of the patients who have been implanted with a permanent system. Also, in pelvic pain, interesting results have been described. SNM modulates the micturition reflexes at different levels in the central nervous system., Conclusions: Sacral neuromodulation is a safe and effective therapy for various forms of lower urinary tract dysfunction, including urgency, frequency and urgency incontinence as well as non-obstructive urinary retention. It should be the first choice after failure of maximal conservative therapy.

Aims: To describe the terminology and pattern of bladder sensations experienced during non-invasive rapid bladder filling in a controlled setting in patients with OAB and to compare these results with a previous study conducted in healthy volunteers., Methods: Three groups of patients with OAB, in total 10 patients, participated in three consecutive focus group sessions. Before each session a strict water loading protocol was given. During the first two sessions, participants described how they experienced their bladder sensations in daily life and during a non-invasive bladder filling with constant focus on their bladder. The third session focused on verifying the interpretation of the data gathered and describing the pattern of sensations., Results: Patients describe their bladder sensations as a pressure or a tingling sensation and the pattern can be described by terms ranging from no sensation to an absolute need to void. The absolute need to void may develop suddenly or more slowly progressive. The mean development of bladder sensation is significantly different between patients and healthy volunteers as well as their average diuresis., Conclusions: Patients with OAB describe their bladder sensations as a pressure or a tingling sensation. There appear to be two types of urgency: a sudden absolute need to void and a slowly developing absolute need to void. Furthermore bladder sensation develops significantly different in volunteers than in OAB patients., (Copyright © 2012 Wiley Periodicals, Inc.)

The following is a report of the proceedings of the Nocturia Think Tank sessions of the annual International Consultation on Incontinence-Research Society, which took place June 13-15, 2011 in Bristol, UK. The report is organized into sections pertaining to the main topics of discussions having occurred at that meeting, centering on the relationship of nocturnal polyuria (NP) and nocturia but also synthesizing more current evidence advancing our knowledge of the diagnosis and management of nocturia. This article is not meant to be a comprehensive review on the subject of nocturia, a number of which are available in the recent literature. All authors were physically present during, or in a preliminary session just prior to, the meeting in Bristol., (Copyright © 2012 Wiley Periodicals, Inc.)

Neuromodulation is used as a treatment for overactive bladder syndrome, if conservative management is ineffective or only partially effective. Sacral neuromodulation is now a minimally invasive treatment as a result of improvements in surgical technique, and it has good long-term results. Nevertheless the risk of complications such as pain and decreasing effect is still present. Developments in alternative neuromodulation treatments, such as posterior tibial nerve stimulation, pudendal nerve stimulation and intravesical injection therapy with botulinum neurotoxin, have extended the role of neuromodulation. Intravesical injection therapy with botulinum toxin, along with sacral neuromodulation, has been included in the treatment algorithm of overactive bladder syndrome if this does not respond to conservative therapy. When choosing for a neuromodulation therapy, the side-effects and complications of the treatments should be considered alongside the specific patient situation and evidence for effectiveness and long-term effectiveness.

Objectives: To evaluate technical aspects and outcome of robotic laparoscopic extravesical anti-reflux surgery in the treatment of high-grade vesicoureteral reflux (VUR) with associated complicating conditions., Materials and Methods: Retrospective database and chart reviews were performed to identify a subgroup of patients with high-grade VUR who underwent robot-assisted anti-reflux surgery using the extravesical Lich-Gregoir repair and who additionally had preoperatively known complicating factors. Five such patients were operated on from 2005 to 2009. All had bilateral VUR, bladder dysfunction, breakthrough infections, renal scarring or at least one of the following complicating factors: posterior urethral valve bladders, duplex systems or para-ostial diverticula. Outcome and surgical aspects were assessed., Results: At follow-up 9 of 10 ureters were free of reflux and diverticulae had disappeared completely. No lasting urinary retentions occurred but two boys needed reinsertion of a catheter for 24 h after surgery. No further complications were noted. There were no signs of obstruction, infections did not persist and there was no negative effect on bladder function. Dissection of para-ostial diverticula seemed the only additional technical challenge., Conclusions: Robot-assisted extravesical anti-reflux surgery seems a promising technique in the operative management of this unfavorable subset of patients. Reflux cure rate is higher than expected using injection therapy and at the same time morbidity seems lower than with open surgery. Further experience is needed to confirm these first impressions., (Copyright © 2011 S. Karger AG, Basel.)

Unlabelled: What's known on the subject? and What does the study add? Sacral neuromodulation (SNM) is a well-established treatment for patients with chronic LUTS. The selection of eligible candidates could be improved by identifying factors that can predict a successful response. In the present study, we evaluated the role of various psychological and psychiatric factors in relation to SNM treatment., Objective: • To evaluate if psychological and psychiatric factors can predict the outcome of test stimulation or permanent treatment with sacral neuromodulation (SNM)., Patients and Methods: • Between 2006 and 2009, patients with overactive bladder syndrome or non-obstructive urinary retention who were eligible for test stimulation were included. • All patients completed the Amsterdam Biographic Questionnaire (ABQ), which measures the personality traits of the patient, and the Symptom Check-List-90-Revised (SCL-90-R), which is a screening instrument for neuroticism, and for current level of complaints. • The results of the questionnaires were compared with the outcomes of test stimulation and permanent treatment. • In addition to the questionnaires, we also included the psychiatric history as a potential predictive factor., Results: • On univariate analysis there was no relationship between the psychological characteristics and the outcome of test stimulation or the occurrence of adverse events (AEs) with permanent treatment. • A history of psychiatric disease was not related to the outcome of test stimulation, but was shown to be a positive predictor for the occurrence of AEs with permanent SNM treatment., Conclusions: • In the present study there was no evidence that psychological screening with the ABQ or SCL-90-R can predict the outcome of SNM treatment. • Patients with a medical history of psychiatric disease appear to be more likely to encounter AEs with permanent SNM treatment., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Introduction: Sacral neuromodulation (SNM) of the lower urinary tract has proven to be safe and effective in patients with complaints of OAB syndrome who are not responding to conservative therapy. After 5 years of treatment the implanted system is still effective in 56-71% of patients. The loss of effect could be caused by adaptation of the nerve system to prolonged stimulation of the sacral nerves., Materials and Methods: We set up a pilot intervention study. After a run-in period of 2 weeks patients were randomized into two groups: one group with on-demand neuromodulation (intervention group) and one group with continuous neuromodulation (control group). Patients in the intervention group were instructed to switch their INS off by default and to switch it on again when they felt recurrent symptoms, patients in the control group were asked to use their system as normally., Results: After 2 weeks 10 out of 16 subjects reported a comparable symptom score during on-demand use of their neuromodulation system. Patients appreciated the comfort of being self-determent in the need for therapy., Conclusions: Possible benefits for patients could be: more autonomy, longer battery life of the implanted INS, decreasing the chance of adaptation by the nervous system., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: Nocturnal polyuria is a common but often overlooked cause of nocturia. We investigated the proportion of adults with 2 or greater voids nightly who had nocturnal polyuria in 2 cohorts from the United States and Europe., Materials and Methods: Data on nocturnal polyuria were obtained from 3 or 7-day frequency-volume charts completed by patients as part of screening for inclusion in subsequent trials of nocturia therapy. Patients recorded the time and volume of each void. Nocturnal polyuria was defined as nocturnal urine volume greater than 33% of 24-hour volume, including the first morning void., Results: In the first cohort 1,003 patients were screened, of whom 846 provided evaluable diary data, including 641 (76%) with nocturnal polyuria. Of the total screened population of 1,003 patients 641 (64%) had confirmed nocturnal polyuria. The prevalence of nocturnal polyuria increased with age but was high in all age groups. In the second cohort 1,412 patients were screened, of whom 917 provided evaluable diary data, including 806 (88%) with nocturnal polyuria. Of the total screened population of 1,412 patients 806 (57%) had confirmed nocturnal polyuria. The prevalence of nocturnal polyuria increased with age but was high in all age groups. Of 158 patients receiving benign prostatic hyperplasia and/or overactive bladder medication 141 (89%) had nocturnal polyuria. In each cohort the nocturnal polyuria prevalence was high in all ethnic groups (63% or greater)., Conclusions: In this large study nocturnal polyuria was present in most patients with nocturia regardless of gender, age, ethnicity, country and concomitant benign prostatic hyperplasia/overactive bladder therapy., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the reliability of the degree of urge and perception of bladder fullness scales, the relationship between the scales and bladder volume, and possible differences between bladder sensations experienced in a controlled or an uncontrolled setting., Materials and Methods: Volunteers and patients with overactive bladder symptoms participated in the protocols. They were asked to grade bladder sensation on a 4-point urge scale of no sensation to need to void now and assess the perception of fullness on a visual analog scale of empty to full bladder. This was assessed in a 3-day bladder diary and during controlled, noninvasive bladder filling., Results: Each scale was reliable and significantly related to bladder volume (p <0.001). Agreement between the scales and voided volume was poor. Patients and volunteers grade bladder fullness and degree of urge higher in an uncontrolled than in a controlled setting., Conclusions: The perception of bladder fullness and the degree of urge have a significant relation to bladder volume in controlled and uncontrolled settings. Due to poor agreement between the scales and actual voided volume these scales cannot replace measuring voided volume. The perception of bladder sensation depends on the setting. Bladder sensation at the hospital might underestimate the bother of symptoms experienced by a patient in daily life., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Aims: To compare the patient's response rate to the Percutaneous Nerve Evaluation test (PNE) and the 1st stage tined-lead placement test (FSTLP) for sacral neuromodulation therapy (SNM)., Methods: Single center study on patients with refractory idiopathic overactive bladder syndrome (OAB) or non-obstructive urinary retention, screened with both PNE and FSTLP. Patients were followed prospectively and their response rate based on bladder diary after PNE was compared to that after FSTLP. More than 50% improvement in at least two relevant urinary symptoms was considered a positive response. A Wilcoxon paired test was done to compare the rates of the two screening options and logistic regression to determine possible associations. A follow-up was conducted to determine the long-term failure rate., Results: One hundred patients were included (82 female, 69 OAB). The mean age was 55 years (SD 13). The positive response rate on PNE was 47%. FSTLP showed a 69% positive response rate, which was negatively related to age. The 22% gain in positive response was statistically significant (P < 0.001) and positively associated with female gender and younger age. All 69 patients with a positive response to FSTLP received SNM treatment. Failure rate after an average of 2 years was 2.9%., Conclusions: This study suggests that FSTLP may be a more sensitive screening method than PNE to identify patients eligible for SNM therapy, warranting randomized trials., (Copyright © 2011 Wiley-Liss, Inc.)

Aims: To describe the bladder sensations experienced during non-invasive rapid bladder filling in a controlled setting in healthy volunteers., Methods: Three groups of healthy volunteers, total 11 subjects (4 men, 7 women), participated in three consecutive focus group sessions. Before each session a strict water loading protocol was given. The first two sessions focused on how participants described and experienced bladder sensations in daily life and during a physiological bladder filling with constant focus on their bladder. The third session focused on verifying the interpretation of the data gathered so far and describing the pattern of sensations., Results: During the focus group sessions with constant focus on their bladder, all participants experienced their bladder sensation as a continuous progression. Healthy subjects describe their bladder sensation(s) as a "pressure" and a "tingling" sensation, but a terminology ranging from no sensations to an absolute need to void is used by all participants and better describes the pattern in which the need to void develops in healthy volunteers., Conclusions: By means of focus group research it is possible to describe the development of normal bladder sensation and to refine terminology used by healthy participants. The findings show that two types of bladder sensations are reported spontaneously by healthy uninitiated volunteers, pressure and a tingling sensation, of which the first develops in a continuous manner. The pattern in which the absolute need develops is described by the terms: no sensation, weak awareness, stronger awareness, weak need, stronger need and absolute need to void., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose: Detrusor nonvoiding contractions occur in up to 70% of healthy individuals. These contractions increase in those with pathological detrusor function and may be associated with afferent activity. We examined nonvoiding contractions in the urethane anesthetized guinea pig bladder and studied the effect of filling rate and intravesical volume., Materials and Methods: A total of 14 guinea pigs were anesthetized and underwent bladder catheterization at the dome. In 6 guinea pigs bladder infusion was continuous and 2 physiological filling rates were used, including 25 (0.75 HD) and 50 μl per minute (1.5 HD). In another 8 guinea pigs isovolumetric cystometry was done by filling the bladder incrementally and recording at low, medium and high intravesical volume., Results: Nonvoiding contractions were apparent in all animals. Contractions increased in frequency and amplitude as the bladder filled. Different phases were identified. Immediately after a void no nonvoiding contractions were observed, followed by continuous activity, first with small contractions, and later with small and large contractions. Small nonvoiding contractions showed a phasic pattern in frequency while the frequency of large nonvoiding contractions slowly increased or remained stable. The frequency and amplitude of nonvoiding contractions were higher at a faster filling rate and a higher intravesical volume., Conclusions: Nonvoiding contractions are present in the anesthetized guinea pig. Under normal physiological conditions they increase in amplitude and frequency with the increase in the filling rate and in intravesical volume. Small and large nonvoiding contractions differ in frequency pattern and occur at different bladder filling periods. This may illustrate different afferents functioning during bladder filling, which could be important for understanding bladder pathology., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Study Type - Therapy (economic analysis)., Level of Evidence: 1b., Objective: To assess and compare the costs and effects value of either starting with sacral neuromodulation (SNM) or botulinum toxin A (BTX) treatment in patients with refractory idiopathic overactive bladder from a societal perspective., Materials and Methods: An economic model comparing SNM with BTX was developed. A clinical relevant effect (i.e. success) was defined as 50% or greater reduction in incontinence episodes or urgency frequency symptoms. Information on the clinical effectiveness of the two treatments and on the course of the disease with the two treatments were based primarily on published literature and, when required, on expert opinion. Both treatments were assumed to be performed under general anaesthesia and, for SNM treatment, first-stage tined lead test was used. All costs were based on national data from the year 2008. Analyses from the societal perspective were conducted for a 5-year duration. Costs were discounted at 4% and effects at 1.5%. In addition, different modelling scenarios were used to see determine any changes in the results obtained., Results: Starting with SNM resulted in a higher quality adjusted life year (QALY) gain (difference of 0.23) and a higher cost (difference of €6428) compared to starting with BTX. The corresponding incremental cost-effectiveness ratio was €27,991/QALY. The probability of this ratio being cost effective (e.g. under €40,000/QALY) is 88%. SNM starts to be cost-effective after 4 years. SNM was not cost-effective in some other scenarios, such as when BTX was conducted under local anaesthesia or when peripheral nerve evaluation or bilateral testing was used for SNM., Conclusions: Starting with SNM, treatment is cost-effective after 5 years compared to BTX. However, in some scenarios, such as the use of local anaesthesia for BTX treatment and SNM peripheral nerve evaluation or bilateral test, SNM was not cost-effective., (© 2010 THE AUTHORS; BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

What's known on the subject? and What does the study add? Nocturia is currently defined by the International Continence Society (ICS) as the complaint that an individual has to wake at night one or more times to void. It is, however, an underreported, understudied, and infrequently recognized problem in adults. Many factors may contribute to nocturia which are treatable, yet patients do not seek care or the condition may not be identified by providers. This paper aims to help healthcare providers better serve patients who are experiencing nocturia by summarizing current research, clinical approaches, and treatment options. The results of the conference provide a balanced evaluation of the full treatment armamentarium capable of meeting the needs of patients with the manifold causes of nocturia such as nocturnal polyuria, overactive bladder, or benign prostatic hyperplasia., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Purpose: We evaluated the effect of pulse rate changes on the clinical response to and stimulation related pain symptoms of sacral neuromodulation treatment., Materials and Methods: In this pilot study we evaluated the effect of 4 pulse rates, including 5.2, 10, 21 and 40 Hz, in patients with a suboptimal response to sacral neuromodulation. The effect of each frequency was evaluated during a 6-day test period. To avoid the carryover effect stimulation was discontinued for 24 hours between consecutive test periods. On the last 3 days of each test period a voiding diary and questionnaire were completed. Changes in the clinical response and pain symptoms were compared between the 4 pulse rates using multivariate analysis., Results: Of the 50 patients included in the study 40 (80%) were female. Mean ± SD age was 55.5 ± 12.3 years. Of the patients 41 (82%) had overactive bladder symptoms and 9 (18%) were in chronic nonobstructive urinary retention. No significant difference was found in clinical outcome on the voiding diary and questionnaire between the pulse rates and none of the 4 rates was significantly related to sacral neuromodulation associated pain. However, individuals appeared to benefit from changing the pulse rate in terms of treatment efficacy and stimulation related pain., Conclusions: On the group level none of the 4 pulse rates appeared to have a significantly different effect on clinical outcome or sacral neuromodulation related pain. However, an individualized approach to optimize treatment efficacy by changing the pulse rate appears to be useful., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Aims: To determine the effects on Quality of Life (QoL) of a Brindley procedure, which combines a sacral dorsal root rhizotomy to treat neurogenic detrusor overactivity with sacral anterior root stimulation to enable micturition, defecation, and penile erections in complete spinal cord injury (SCI) patients compared to a matched Control Group., Methods: Cross-sectional study. The Qualiveen questionnaire, SF-36 questionnaire, and multiple choice questions about urinary continence and urinary tract infections were sent to 93 patients who had a Brindley stimulator implanted in the Netherlands and a matched Control Group of 70 complete SCI patients with neurogenic detrusor overactivity. Primary study outcomes were Specific Impact of Urinary Problems score and general QoL index of the Qualiveen., Results: Response rates were 78% and 40% for patients with a Brindley stimulator and controls, respectively. Stimulators were still used for micturition in 46 (63%). These patients had a significant better Specific Impact of Urinary Problems score, general QoL index (Qualiveen), and continence rate, and less urinary tract infections compared to the Control Group. Patients also benefited of the rhizotomy with regard to QoL and continence rate if the stimulator was not used anymore. The subscales of the SF-36 had better scores for the patients who used their stimulator as compared to those who did not use the stimulator and compared to the Control Group., Conclusions: The Brindley stimulator for complete spinal cord injury patients improves Quality of Life, continence, and urinary tract infection rate compared to a matched Control Group., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose: We evaluated whether bilateral sacral nerve stimulation can be effective to restore treatment efficacy in patients in whom unilateral sacral neuromodulation fails., Materials and Methods: Patients in whom unilateral sacral neuromodulation failed were included in analysis. The percutaneous nerve evaluation test was used to evaluate the effect of contralateral and bilateral stimulation. The stimulation electrode was placed in the contralateral S3 foramen and symptoms were self-recorded using a 3-day voiding diary. Clinical success was defined as more than 50% improvement in at least 1 relevant voiding diary parameter vs baseline., Results: The 15 study patients underwent test stimulation with percutaneous nerve evaluation. In 3 patients lead migration was suspected and, thus, they were not included in analysis. Four of the remaining 12 patients had a successful response to percutaneous nerve evaluation, of whom 3 were eventually implanted with a contralateral lead. After 12 months of treatment 2 of the 3 patients had a successful outcome., Conclusions: In this pilot study only a select group of patients appeared to benefit from bilateral stimulation after unilateral therapy failure. Further investigation is needed to determine the predictive factors and cost-effectiveness of this treatment., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We systematically assessed long-term satisfaction and patient experience with sacral nerve modulation therapy., Materials and Methods: All patients who received sacral neuromodulation between 1990 and 2007 at our center and who still had the implant were included in the survey. All received a postal questionnaire regarding satisfaction and experiences with the system, such as side effects, complications, burden, impact on sexuality and defecation changes., Results: Of the 275 questionnaires sent 207 were returned for a 75% response rate. The population was 83% female. Overall treatment was done for overactive bladder syndrome, nonobstructive urinary retention, combined overactive bladder and retention, and pelvic pain in 55%, 24%, 20% and 1% of patients, respectively. Overall satisfaction with sacral neuromodulation was high at 90%. No correlations were found between the satisfaction rate, and pretreatment age, gender, complaint type, sexual dysfunction or therapy duration. However, 56% of patients reported side effects, such as pain at the internal nerve stimulator site and due to stimulation. However, 89% of these patients did not seek further therapy. Of patients with additional defecation problems 47% experienced relief of complaints., Conclusions: This study shows a high satisfaction rate in patients with sacral neuromodulation. There was no relation between patient age, complaint type, therapy duration or side effects and the satisfaction rate. The number of side effects was limited but further analysis in prospective cohorts should identify patients who are likely to have side effects or stop sacral neuromodulation treatment., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We explored the structural relationship between enzymes producing prostaglandin (cyclooxygenase I) and 1 of the receptor families that respond to prostaglandin (prostaglandin E receptor 1) in the bladder muscle., Materials and Methods: Nine male guinea pigs were sacrificed by cervical dislocation. Bladders were removed and fixed in 4% paraformaldehyde in phosphate buffered saline. Frozen sections (10 μm) were cut and stained with antibodies to prostaglandin E receptor type 1, cyclooxygenase I and vimentin., Results: Prostaglandin E receptors 1 was identified on smooth muscle cells, and vimentin positive surface muscle and intramuscular interstitial cells. Muscle staining was less intense than on interstitial cells and had a punctuate appearance. Prostaglandin E receptor 1 expression on interstitial cells was highly localized. Discrete regions of intense staining were noted on interstitial cell processes. Cyclooxygenase I was also expressed in muscle interstitial cells. Cyclooxygenase I positive interstitial cells were more prevalent in the muscle bundles of the inner muscle than in the outer muscle layers. Cyclooxygenase I staining was noted on discrete regions of the cell or cell processes. Double staining with prostaglandin E receptor 1 and cyclooxygenase I suggested that cell regions expressing the former are different from those expressing the latter., Conclusions: The discovered arrangement of prostaglandin E receptor 1 and cyclooxygenase I may have the potential to facilitate the propagation of signals in the interstitial cell network. Such a signaling system may have a role in coordinating events, as in bladder pathology, facilitating the global coordinated changes associated with bladder wall remodeling., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Sacral neuromodulation has been developed to treat chronic lower urinary tract symptoms, resistant to classical conservative therapy. The suspected mechanisms of action include afferent stimulation of the central nervous system and modulation of activity at the level of the brain. Typical neuromodulation is indicated both in overactivity and in underactivity of the lower urinary tract. In the majority of patients, a unilateral electrode in a sacral foramen and connected to a pulse generator is sufficient to achieve significant clinical results also on long term. In recent years, other urological indications have been explored.

Purpose: We present long-term followup data on the outcome of sacral neuromodulation using the tined lead procedure., Materials and Methods: We conducted a single center study including all patients who received an implantable neurostimulator between 2002 and 2005 using the tined lead technique. Treatment efficacy was evaluated by comparing the data of a 3-day voiding diary filled out in May 2009 to the data before the onset of sacral neuromodulation treatment (baseline). Clinical success was defined as more than 50% improvement in at least 1 of the relevant voiding diary parameters., Results: A total of 64 patients underwent implantation with an implantable neurostimulator using the tined lead procedure. Mean followup was 53 months (range 35 to 77). Five patients died of causes unrelated to sacral neuromodulation and they were not included in analysis. The implantable neurostimulator was removed from 7 patients and 3 stopped using the neurostimulator. Voiding diary analysis showed that 38 of 59 patients (64%) were successfully treated. There were 21 patients (33%) who underwent a surgical revision due to an adverse event and 1 (1.6%) who underwent lead revision because of suspected lead migration., Conclusions: Sacral neuromodulation with the tined lead procedure is a safe and effective treatment for patients with overactive bladder symptoms or urinary retention., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the advantages of scrotal incision in the treatment of undescended testis. Undescended testis is a common pediatric condition and is conventionally managed surgically by orchidopexy. A single scrotal incision orchidopexy has become accepted as a valid approach for patients with palpable undescended testicles. Because this approach also allows easy detection of atrophic testes or testicular remnants, it recently has also emerged as an alternative initial surgical approach to impalpable undescended testicles., Methods: All orchidopexies performed between 2004 and 2008 at our university hospital were prospectively included in this study. A total of 194 scrotal orchidopexies were performed in 154 patients (mean age, 71 months; range, 4-229 months). In all cases a scrotal approach was chosen irrespective of the initial position or presence of an open processus vaginalis. Testicular position was examined at follow-up after a mean period of 10 months (3-22 months)., Results: Overall, 36 of the 46 impalpable testicles (78%) could be diagnosed and treated accordingly, using only a scrotal incision. Conversion to laparoscopy was needed in 4 cases. A limited number of postoperative complications were seen. In all cases, the testes were palpable and remained in the scrotum on follow-up., Conclusions: Initial single scrotal incision can be recommended for orchidopexy, even in the more difficult cases of impalpable undescended testes. Advantages seem to include shorter operative time, a cosmetically appealing single incision, and possibly less pain. The scrotal incision technique significantly reduces the need for laparoscopy in impalpable testes. Surprisingly, it even allows successful orchidopexy of abdominal testes, provided an open processus is present., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objectives: The aim of this review is to evaluate the place of transurethral resection of the prostate (TURP) in patients with elevated and/or rising prostate specific antigen (PSA). The role of TURP in these patients is assessed in symptomatic as well as in asymptomatic patients., Methods: Current literature (1987-2009) was reviewed with regard to this specific population. This research was performed using the Medline online search tools., Results: Initially, possible therapeutic strategies other than TURP could be used in patients with elevated and/or rising PSA values and no sign of proven prostate cancer. Consequently, the value of TURP in patients with elevated and/or rising PSA and no proven prostate cancer is discussed. In this setting, TURP can be executed with or without concomitant prostate biopsies. Furthermore, TURP can be proposed to patients with and without lower urinary tract symptoms., Conclusions: In this review, we evaluated the role of TURP in patients with elevated and/or rising PSA values and no proven prostate cancer. We believe TURP has a place in this particular population even in patients without lower urinary tract symptoms. This strategy is well founded on solid ground after an extensive review of the available literature. In most cases, a TURP will result in a normalization of PSA as well as a symptomatic benefit. Additionally, this procedure will allow histological evaluation which might show a possible life threatening prostate cancer in some patients.

Aim: The aims of this study were to compare the structure of bladders from a transgenic mouse model of Alzheimer's disease with age matched control animals and to explore the idea that any structural differences might be related to functional bladder changes associated with the condition., Materials and Methods: Two groups of mice were used. Transgenic animals in which the murine Amyloid Precursor Protein (APP) gene has been partly replaced by the human APP including both the Swedish and London mutations and that overexpress a mutant of the human Presenilin 1 gene (PS1M146L) driven by the PDGF promoter. The transgenic mice (App(SL)/PS1(M146L)) aged 24+/-3 months were used. The second group was an age matched control group of C57 black mice. The bladders from each group were isolated, fixed in 4% paraformaldehyde and prepared for immunohistochemistry. Antibodies to the vesicular acetylcholine transporter (VAChT) and neuronal nitric oxide synthase (nNOS) were used to identify neural structures., Results: Cholinergic nerves (VAChT(+)) were observed in the inner and outer muscle bundles of App(SL)/PS1(M146L) and control mice. No major differences were noted in the distribution of these fibres. In contrast, there was a distinct difference in the innervation of the sub-urothelial layer. In App1(SL)/PS1(M146L) mice there were numerous VAChT and nNOS positive fibres in sharp contrast to the paucity of similar nerves in control animals. VAChT and nNOS did not appear to co-localise in the same nerve fibres within the lamina propria. Pairs of nerve fibres, nNOS(+) and VAChT(+), were observed to be intertwined and run in close proximity. A particularly unusual feature of the App(SL)/PS1(M146L) mouse bladder was the presence of neurones within the bladder wall. These nerve cell bodies were seen in all App(SL)/PS1(M146L) mouse bladders. The neurones could be found singly or in small ganglion like groups of cells and were located in all layers of the bladder wall (sub-urothelium, in the lamina propria adjacent to the inner muscle and within the inner muscle and outer muscle layers). No nerve cells or small ganglia were noted in any of the control bladders studied., Conclusions: There are structural differences in the bladders of App(SL)/PS1(M146L) mice compared to control animals. These differences are associated with sub-urothelial nerves which, because of their location, are likely to be sensory fibres. This may lead to a changed sensory processing from the App(SL)/PS1(M146L) bladders. The physiological role of the intra-mural neurones and ganglia is not known. It is speculated that they may be associated with peripheral motor/sensory mechanisms linked to the generation and modulation of sensation., (Copyright (c) 2009 Elsevier B.V. All rights reserved.)

Aims: To determine (using structured brain storm sessions), which treatments should be used if drugs fail for OAB and to determine priority research questions in relation to this issue., Methods: A frame work for discussion was prepared by the chairman of the session; this included a brief summary of the currently existing evidence. Several experts had been asked to prepare a presentation of their personal treatment algorithm and to identify the [lack of] evidence for such an algorithm. These presentations were summarized by the chairman. Next, this summary was discussed with a large group of experts and opinion leaders and audio-recorded. The proceedings of this process are the basis for this manuscript., Results: The structured sessions resulted in detailed statements about: possible reasons for failure of conservative treatment, the evaluation of outcomes of RCT's, the use of botulinum toxin A in refractory OAB patients, the relative place of neuromodulation or sacral nerve stimulation and botulinum toxin A in the treatment of refractory OAB., Conclusions: A list of 10 unanswered questions and research topics was compiled. Additionally, 5 top priority research topics were identified., ((c) 2010 Wiley-Liss, Inc.)

Aims: The aim of this study was to assess the long-term safety, tolerability and efficacy of fesoterodine treatment in subjects with overactive bladder (OAB) symptoms., Methods: This was an open-label extension study of a 12-week, double-blind fesoterodine study. During open-label treatment, all subjects received fesoterodine 8 mg for an initial 4 weeks, after which subjects could elect dose reduction to 4 mg or subsequent reescalation to 8 mg during clinic visits (dose reduction and reescalation each permitted once annually). The maximum allowable duration of open-label fesoterodine treatment ranged from 24 to 32 months across study sites. Safety and tolerability were evaluated via discontinuations, fesoterodine exposure, treatment-emergent adverse events (TEAEs) and subject-reported treatment tolerance. Three-day bladder diaries and other patient-reported outcomes (PROs) were assessed during the first 24 months of open-label treatment. PROs included evaluations of health-related quality of life [HRQL; King's Health Questionnaire (KHQ), and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF)], severity of bladder-related problems and treatment satisfaction. Subjects completed 3-day diaries before open-label baseline and months 1, 4, 8, 12 and 24; the ICIQ-SF and measures of bladder-related problems and treatment satisfaction at open-label baseline and months 4, 12 and 24; and the KHQ at open-label baseline and months 12 and 24., Results: Of the 417 eligible subjects who enrolled in the open-label extension, 61% continued fesoterodine treatment for > or = 24 months and 71% elected to maintain the fesoterodine 8-mg dose throughout treatment. No unexpected safety signals were observed. Most subjects rated treatment tolerance as at least 'good' throughout the study (> or = 88%). Dry mouth was the most commonly reported TEAE (34%) during open-label treatment, resulting in discontinuation in 2% of subjects (n = 8). Improvements from open-label baseline in OAB symptoms, HRQL and bladder-related problems were statistically significant at the earliest point measured and maintained through month 24. Treatment satisfaction rates were high throughout the study (> or = 84%)., Conclusions: Long-term fesoterodine treatment was well tolerated and associated with sustained improvements in OAB symptoms and HRQL.