Nocturia and obstructive sleep apnoea.

Nocturia, the need to urinate at night, is a common symptom in patients with obstructive sleep apnoea (OSA). Continuous positive airway pressure treatment can reduce nocturia in some patients, but the underlying mechanisms are complex and not fully understood. OSA affects the autonomic nervous system, oxidative stress and endothelial damage. Furthermore, the commonly held theory attributing polyuria to a false signal of cardiac overload and response natriuresis has limitations. A comprehensive approach to the management of nocturia in OSA, considering factors such as comorbidities, medication use, alcohol consumption and lifestyle, is needed. Effective management of nocturia in OSA requires a multidisciplinary approach, and urologists should be aware of the potential effect of OSA on physiology and refer patients for further testing at a sleep centre. In addition to continuous positive airway pressure, other interventions such as oral appliances and surgical obstruction treatment could be beneficial for some patients. Overall, understanding the complex interplay between OSA and nocturia is crucial for optimizing patient outcomes.

Targeted multiparametric magnetic resonance imaging/transrectal ultrasound-guided (mpMRI/TRUS) fusion prostate biopsy versus systematic random prostate biopsy: A comparative real-life study.

BACKGROUND: Patients with suspected prostate cancer usually undergo transrectal ultrasound-guided (TRUS) systematic biopsy, which can miss relevant prostate cancers and lead to overtreatment. AIMS: The aim of this study was to evaluate the detection rate for prostate cancer in MR-guided targeted biopsy (TB) and systematic biopsy (SB) in comparison with mpMRI of the prostate. METHODS AND RESULTS: Three hundred and eight men who underwent mpMRI due to elevated PSA values between 2015 and 2020 were studied at university hospital Aachen, Germany. MRI-images were divided into cohorts with suspicious findings (PI-RADS ≥ 3) and negative findings (PI-RADS < 3). In patients with PI-RADS ≥ 3 TB combined with SB was performed. A part of this group underwent RP subsequently. In patients with PI-RADS < 3 and clinical suspicion SB was performed. In the PI-RADS ≥ 3 group (n = 197), TB combined with SB was performed in 194 cases. Three cases were lost to follow-up. Biopsy yielded 143 positive biopsies and 51 cases without carcinoma. TB detected 71% (102/143) and SB 98% (140/143) of the overall 143 carcinoma. Overall, 102 carcinomas were detected by TB, hereof 66% (67/102) clinically significant (Gleason ≥ 3+4) and 34% (35/102) clinically insignificant carcinoma (Gleason 3+3). SB detected 140 carcinomas, hereof 64% (90/140) csPCA and 36% (50/140) nsPCA. Forty-one of the overall 143 detected carcinoma were only found by SB, hereof 46% (19/41) csPCA and 54% (22/41) nsPCA. Tumor locations overlapped in 44% (63/143) between TB and SB. In 25% (36/143), SB detected additional tumor foci outside the target lesions. 70/143 patients subsequently underwent RP. The detection of tumor foci was congruent between mpMRI and prostatectomy specimen in 79% (55/70) of cases. Tumor foci were mpMRI occult in 21% (15/70) of cases. In the group with negative mpMRI (n = 111), biopsy was performed in 81 cases. Gleason ≥ 3+4 carcinoma was detected in 7% and Gleason 3+3 in 24% cases. CONCLUSION: There was a notable number of cases in which SB detected tumor foci that were mpMRI occult and could have been missed by TB alone. Therefore, additional systematic random biopsy is still required. A supplemental random biopsy should be considered depending on the overall clinical suspicion in negative mpMRI.

Between-subject similarity of functional connectivity-based organization of the human periaqueductal gray related to autonomic processing.

The periaqueductal gray (PAG) is a brain stem area designated to play an essential role in lower urinary tract (LUT) control. Post-mortem human and animal studies have indicated that the PAG is symmetrically organized in functionally and anatomically distinct columns which are involved in sympathetic or parasympathetic autonomic control of the LUT. The current study aims to find consistency across subjects and identify homologous clusters between subjects. Here, we evaluated data from 10 female participants. During a bladder filling protocol, we ran a resting-state functional magnetic resonance imaging (fMRI) scan while participants experienced a strong desire to void. A voxel-by-voxel correlation matrix of the PAG was created and parcellated using the Louvain module detection algorithm. Resulting in a map of the PAG in which each voxel is assigned to a cluster as determined by the Louvain module detection algorithm. The spatial similarity of resulting clusters between participants was assessed by computing the Dice similarity coefficient for all cluster comparisons. Next, we designed a permutation test to create randomized parcellation maps which enabled us to statistically test the similarity values observed across participants. We observed several significantly similar clusters between subjects compared to permutations (p ≤ 0.05). These results show that the PAG can be parcellated into distinct clusters which show a similar spatial distribution at the group level. This analysis is a crucial step to determine the agreement between in vivo PAG parcellations and the functional and anatomical columnar organization of the PAG which is known from previous research. These advancements may enable us to identify the relationship between LUT symptoms, such as urgency, and activity patterns in the PAG in normal and pathological states.

Association between lower urinary tract symptoms (LUTS) and obsessive-compulsive disorders (OCD) in women: A study based on urodynamic findings and micturition problem.

AIM: This study focused on women with chronic lower urinary tract symptoms (LUTS) who simultaneously suffered from obsessive-compulsive disorder (OCD) to evaluate the association between micturition abnormality and OCD. METHODS: A cohort case study was conducted on 128 women with chronic LUTS who visited the academic clinic from 2012 to 2018. The participants with a history of OCD were grouped together, whereas the other group consisted of those with no psychiatric issues. Data were analyzed using the Kolmogorov-Smirnov test and also the nonparametric Kruskal-Wallis and χ2 tests. RESULTS: The participants with OCD had a lower mean age (41.7 vs. 48.8 years) and longer symptom duration than the control group. Moreover, voiding phase problems were more prevalent among OCD patients (mean voiding score: 9.3 vs. 6.9). Urge urinary incontinence (UUI) was the most common type of urinary incontinence in OCD patients, and the most important urodynamic study finding was bladder outlet obstruction (45% and 17% in the OCD and control groups, respectively). Voiding disorders resulted in chronic renal failure in two patients (3.12%). It was shown that bladder outlet obstruction (odds ratio (OR) 4.43, 95% confidence interval [CI] 1.53-12.78, p = 0.006] was the strongest predictor of OCD and stress urinary incontinence (OR 0.20, 95% CI 0.07-0.53, p < 0.001) was the best protector against OCD. CONCLUSION: The findings revealed that chronic LUTS was related to voiding dysfunction and urodynamic abnormality in OCD patients. These disorders may be categorized as somatoform disorder that requires appropriate treatments.

Current Management of Post-radical Prostatectomy Urinary Incontinence.

Prostate cancer is the second most common cancer in men worldwide. Radical prostatectomy and radiation beam therapy are the most common treatment options for localized prostate cancer and have different associated complications. The etiology of post prostatectomy incontinence is multifactorial. There is evidence in the literature that anatomic support and pelvic innervation are important factors in the etiology of post-prostatectomy incontinence. Among the many surgical and technical factors proposed in the literature, extensive dissection during surgery, damage to the neurovascular bundle and the development of postoperative fibrosis have a substantial negative impact on the continence status of men undergoing RP. Sparing of the bladder neck and anterior, and possibly posterior, fixation of the bladder-urethra anastomosis are associated with better continence rates. Overactive bladder syndrome (OAB) is multifactorial and the exact role of prostate surgery in the development of OAB is still under debate. There are several variables that could contribute to detrusor overactivity. Detrusor overactivity in patients after radical prostatectomy has been mainly attributed to a partial denervation of the bladder during surgery. However, together with bladder denervation, other hypotheses, such as the urethrovesical mechanism, have been described. Although there is conflicting evidence regarding the importance of conservative treatment after post-prostatectomy urinary incontinence, pelvic floor muscle training (PFMT) is still considered as the first treatment choice. Duloxetin, either alone or in combination with PFMT, may hasten recovery of urinary incontinence but is often associated with severe gastrointestinal and central nervous side effects. However, neither PFMT nor duloxetine may cure male stress urinary incontinence. The therapeutic decision and the chosen treatment option must be individualized for each patient according to clinical and social factors. During the recent years, the development of new therapeutic choices such as male sling techniques provided a more acceptable management pathway for less severe forms of urinary incontinence related to radical prostatectomy. Following this perspective, technological improvements and the emergence of new dedicated devices currently create the premises for a continuously positive evolution of clinical outcomes in this particular category of patients.

An International Continence Society (ICS) report on the terminology for pelvic floor muscle assessment.

INTRODUCTION: The terminology for female and male pelvic floor muscle (PFM) assessment has expanded considerably since the first PFM function and dysfunction standardization of terminology document in 2005. New terms have entered assessment reports, and new investigations to measure PFM function and dysfunction have been developed. An update of this terminology was required to comprehensively document the terms and their definitions, and to describe the assessment method and interpretation of the finding, to standardize assessment procedures and aid diagnostic decision making. METHODS: This report combines the input of members of the Standardisation Committee of the International Continence Society (ICS) Working Group 16, with contributions from recognized experts in the field and external referees. A logical, sequential, clinically directed assessment framework was created against which the assessment process was mapped. Within categories and subclassifications, each term was assigned a numeric coding. A transparent process of 12 rounds of full working group and external review was undertaken to exhaustively examine each definition, plus additional extensive internal development, with decision making by collective opinion (consensus). RESULTS: A Terminology Report for the symptoms, signs, investigations, and diagnoses associated with PFM function and dysfunction, encompassing 185 separate definitions/descriptors, has been developed. It is clinically based with the most common assessment processes defined. Clarity and user-friendliness have been key aims to make it interpretable by clinicians and researchers of different disciplines. CONCLUSION: A consensus-based Terminology Report for assessment of PFM function and dysfunction has been produced to aid clinical practice and be a stimulus for research.

Parcellation of human periaqueductal gray at 7-T fMRI in full and empty bladder state: The foundation to study dynamic connectivity changes related to lower urinary tract functioning.

AIMS: The periaqueductal gray (PAG) is a brain stem area involved in processing signals related to urine storage and voiding. The PAG is proposed to be responsible for projecting afferent information from the bladder to cortical and subcortical brain areas and acts as a relay station projecting efferent information from cortical and subcortical areas to the pons and spinal cord. Here, we use 7-Tesla functional magnetic resonance imaging to parcellate the PAG into functionally distinct clusters during a bladder filling protocol. METHODS: We assess the similarity between parcellation results in empty and full bladder states and show how these parcellations can be used to create dynamic response profiles of connectivity changes between clusters as a function of bladder sensations. RESULTS: For each of our six healthy female participants, we found that the agreement between at least one of the clusters in both states resulting from the parcellation procedure was higher than could be expected based on chance (p ≤ .05), and observed that these clusters are significantly organized in a symmetrical lateralized fashion (p ≤ .05). Correlations between clusters change significantly as a function of experienced sensations during bladder filling (p ≤ .05). CONCLUSIONS: This opens new possibilities to investigate the effects of treatments of lower urinary tract symptoms on signal processing in the PAG, as well as the investigation of disease-specific bladder filling related dynamic signal processing in this small brain structure.

Can we harness the placebo effect to improve care in lower urinary tract dysfunction? ICI-RS 2019.

The proposal "Can we harness the placebo effect to improve care in lower urinary tract dysfunction?" was discussed at the International Consultation on Incontinence-Research Society (ICI-RS) 2019 meeting. The placebo effect can change the treatment outcome whether the treatment is an active treatment or placebo. The total active treatment outcome is a combination of the placebo and the active treatment effect which is seen in placebo-controlled trials. The placebo effect plays an important role in the treatment of lower urinary tract dysfunction in overactive bladder, bladder pain syndrome, and stress urinary incontinence. In clinical practice, a number of factors can be employed to use the placebo effect to maximize its effect on patients receiving an active treatment, such as having the same environment for review such as the same appointment time, same room, and same clinician. Clinicians should also be aware of the nocebo effect which is increased with an overemphasis on side effects or negative outcomes.

The effect of continuous positive airway pressure on nocturia in patients with obstructive sleep apnea syndrome.

OBJECTIVE: The prevalence of nocturia in patients with obstructive sleep apnea syndrome (OSAS) who received continuous positive airways pressure (CPAP) treatment was studied as well as the effect of CPAP treatment on nocturia. METHODS: All patients that were referred to the pulmonology department of a large teaching hospital in the Netherlands and received a CPAP mask for OSAS were interviewed and invited to take part in the study (N = 274). After informed consent, all patients were asked about the number of nocturia episodes before and after CPAP. RESULTS: In this prospective analysis, 274 patients (190 male and 84 female) were included. The mean age was 60.3 years (SE = 0.7). Sixty-four patients (23.4%) reported no nocturia episodes before CPAP and 210 patients (76.4%) reported ≥1 nocturia episode(s). Treatment of OSAS with CPAP reduced nocturia with one or more episodes per night in 42.3% of the patients. Clinically relevant nocturia (≥2 voids per night) was reduced from 73.0% to 51.5%. There were no statistically significant gender differences. CONCLUSION: The prevalence of nocturia in patients diagnosed with OSAS is 75.8% in both sexes. After treatment with CPAP, almost half of patients experienced a decrease in the nocturia frequency of one or more voids. Clinically relevant nocturia was reduced with one-third after CPAP. CPAP not only reduced the number of voids during the night but also improved the associated quality of life.

ICI-RS 2019 nocturia think tank: How can experimental science guide us in understanding the pathophysiology of nocturia?

INTRODUCTION: The following is a report on the proceedings of the 2019 International Consultation on Incontinence-Research Society nocturia think tank (NTT). OBJECTIVES: The objectives of the 2019 NTT were as follows: (a) to evaluate the role of urothelium in the pathophysiology of nocturia; (b) to determine whether nocturia is a circadian disorder; (c) to discuss the role of melatonin in nocturia; (d) to consider ambulatory urodynamic monitoring in evaluating patients with nocturia; (e) to explore studies of water handling in human compartments utilizing heavy water; and (f) to explore whether basic science is the key to understanding the treatment options for diminished bladder capacity in patients with nocturia. METHODS: A compendium of discussions of the role of experimental science in understanding the pathophysiology of nocturia is described herein. RESULTS AND CONCLUSIONS: Translational science will play an increasing role in understanding the pathophysiology of nocturia, which may result in improved treatment strategies.

How can we prevent postprostatectomy urinary incontinence by patient selection, and by preoperative, peroperative, and postoperative measures? International Consultation on Incontinence-Research Society 2018.

AIMS: To review current prevention strategies for urinary incontinence among patients undergoing radical prostatectomy (RP). METHODS: This is a consensus report of the proceedings of a research proposal from the annual International Consultation on Incontinence-Research Society (ICI-RS), 14 to 16 June 2018 (Bristol, UK): "How can we prevent postprostatectomy incontinence by patient selection, and by preoperative, peroperative, and postoperative measures?" RESULTS: Several baseline parameters were proposed as predicting factors for postprostatectomy urinary incontinence (PPUI), including age, tumor stage, prostate volume, preoperative lower urinary tract symptoms, maximum urethral closure pressure, and previous transurethral resection of the prostate. More recently, magnetic resonance imaging has been used to measure the membranous urethral length and sphincter volume. Peroperative techniques include preservative and reconstructive approaches. Bladder neck preservation improved early (6 months), as well as long-term (>12 months) continence rates. Several prospective studies have reported earlier return of continence following preservation of puboprostatic ligaments, although no long-term data are available. Preservation of the urethral length yielded controversial outcomes. Concerning postoperative strategies, it is probably optimal to remove the catheter in a window between 4 and 7 days if clinically appropriate; however, more research in this regard is still required. Postoperative PFME (preoperative pelvic floor muscle exercise) appears to speed up the recovery of continence after RP. CONCLUSIONS: Conservative strategies to prevent PPUI include proper patient selection and PFME. Peroperative techniques have largely shown benefit in the short term. Postoperative complications and timing of trial without catheter can influence continence status. Future research initiatives must assess peroperative and postoperative measures, with longer-term follow-up.

How can we better manage drug-resistant OAB/DO? ICI-RS 2018.

AIMS: Botulinum toxin A (BTX-A), sacral nerve stimulation (SNM), and posterior tibial nerve stimulation (PTNS) are established treatments for idiopathic overactive bladder (OAB) refractory to oral drug therapy. At the ICI-RS meeting in Bristol in 2018 a think tank was convened to address the question of how to better manage drug-resistant OAB/DO (detrusor overactivity). METHODS: The think tank conducted a literature review and an expert consensus meeting focusing on the evidence for predicting response and adverse events (AEs) with the current therapies for drug-resistant idiopathic OAB. RESULTS: Several factors have been associated with poor outcomes using BTX-A including increasing age, body mass index, male sex, and frailty. Voiding dysfunction with BTX-A also appears to be more prevalent in those with increasing age, male sex, higher baseline postvoid residual and with poorer contractility as assessed by urodynamic parameters. SNM full implantation appears to be higher with the first stage tined lead placement procedure compared to percutaneous nerve evaluation. Urodynamics do not appear to predict outcomes with SNM. Patients with psychiatric comorbidity are more likely to experience AEs with SNM. Outcomes related to lead positioning and the number of active electrodes are mixed in predicting long term success. Patients with increased daytime frequency and lower first sensation of bladder filling were independent factors associated with success with PTNS. CONCLUSIONS: Further research is required to optimize these procedures and to better understand which patients will benefit from the various options available in managing refractory OAB.

What are the origins and relevance of spontaneous bladder contractions? ICI-RS 2017.

INTRODUCTION: Storage phase bladder activity is a counter-intuitive observation of spontaneous contractions. They are potentially an intrinsic feature of the smooth muscle, but interstitial cells in the mucosa and the detrusor itself, as well as other muscular elements in the mucosa may substantially influence them. They are identified in several models explaining lower urinary tract dysfunction. METHODS: A consensus meeting at the International Consultation on Incontinence Research Society (ICI-RS) 2017 congress considered the origins and relevance of spontaneous bladder contractions by debating which cell type(s) modulate bladder spontaneous activity, whether the methodologies are sufficiently robust, and implications for healthy and abnormal lower urinary tract function. RESULTS: The identified research priorities reflect a wide range of unknown aspects. Cellular contributions to spontaneous contractions in detrusor smooth muscle are still uncertain. Accordingly, insight into the cellular physiology of the bladder wall, particularly smooth muscle cells, interstitial cells, and urothelium, remains important. Upstream influences, such as innervation, endocrine, and paracrine factors, are particularly important. The cellular interactions represent the key understanding to derive the integrative physiology of organ function, notably the nature of signalling between mucosa and detrusor layers. Indeed, it is still not clear to what extent spontaneous contractions generated in isolated preparations mirror their normal and pathological counterparts in the intact bladder. Improved models of how spontaneous contractions influence pressure generation and sensory nerve function are also needed. CONCLUSIONS: Deriving approaches to robust evaluation of spontaneous contractions and their influences for experimental and clinical use could yield considerable progress in functional urology.

The efficacy of botulinum toxin A and sacral neuromodulation in the management of interstitial cystitis (IC)/bladder pain syndrome (BPS), what do we know? ICI-RS 2017 think thank, Bristol.

AIMS: This manuscript aims to address the evidence availale in the literature on the efficacy of Botulinum Toxin A (BoNT-A) and sacral neuromodulation (SNM) in patients suffering from Interstitial Cystitis (IC)/BPS and propose further research to identify mechanisms of action and establish the clinical efficacy of either therapy. METHODS: At the International Consultation on Incontinence-Research Society (ICI-RS) in 2017, a panel of Functional Urologists and Urogynaecologists participated in a Think Tank (TT) discussing the management of IC/BPS by BoNT-A and SNM, using available data from both PubMed and Medicine literature searches. RESULTS: The role of BoNT-A and SNM in the treatment of IC/BPS are discussed and mechanisms of actions are proposed. Despite the available randomized trial data on the effect of intravesical BoNT-A treatment on symptoms of IC/BPS, a consistent conclusion of a positive effect cannot be drawn at the moment, as the published studies are small and heterogeneous in design. There is substantive evidence for the positive effects of SNM on symptoms of IC/BPS patients however, during patient selection, it is important to distinguish the degree and the location of pain in order to tailor the best therapy to the right patients. CONCLUSIONS: Both intravesical BoNT-A treatment and SNM have been shown to have positive effects in patients with IC/BPS. However, firm conclusions cannot yet be drawn. Patient-reported outcomes and quality of life should be assessed in addition to urinary and pain symptoms. Since current treatments mainly focus on symptomatic relief, future research should also focus on clarifying the pathogenic mechanisms involved in IC/BPS.

ICI-RS 2015-Is a better understanding of sleep the key in managing nocturia?

AIMS: Nocturia, or waking up at night to void, is a highly prevalent and bothersome lower urinary tract symptom. However, the applied treatment modalities do not improve symptoms in about half of the patients. The aim of this report is to generate new ideas for future nocturia research, with special emphasis on the role of sleep physiology and sleep disorders. METHODS: The following is a report of the presentations and subsequent discussion of the Nocturia Think Tank session at the annual meeting of the International Consultation on Incontinence Research Society (ICI-RS), which took place in September 2015 in Bristol. General information about the organization of the ICI-RS meeting can be found on the website "www.ici-rs.org." An overview of challenges within the existing evidence, future research ideas, and results of research with regard to nocturia and sleep were presented. RESULTS AND CONCLUSION: In order to optimize the management of nocturia and nocturnal polyuria (NP), future research has to focus on the development of unambiguous terminology regarding nocturia and NP, the role of renal function profiles and simplified frequency volume charts as guidance of individualized therapy and the role of sleep disorders such as periodic limb movements during sleep and habitual voiding as a response to awakening. Neurourol. Urodynam. 37:2048-2052, 2018. © 2016 Wiley Periodicals, Inc.

The urinary microbiome and its contribution to lower urinary tract symptoms; ICI-RS 2015.

AIMS: The microbiome is the term used for the symbiotic microbial colonisation of healthy organs. Studies have found bacterial identifiers within voided urine which is apparently sterile on conventional laboratory culture, and accordingly there may be health and disease implications. METHODS: The International Consultation on Incontinence Research Society (ICI-RS) established a literature review and expert consensus discussion focussed on the increasing awareness of the urinary microbiome, and potential research priorities. RESULTS: The consensus considered the discrepancy between findings of conventional clinical microbiology methods, which generally rely on culture parameters predisposed towards certain "expected" organisms. Discrepancy between selective culture and RNA sequencing to study species-specific 16S ribosomal RNA is increasingly clear, and highlights the possibility that protective or harmful bacteria may be overlooked where microbiological methods are selective. There are now strong signals of the existence of a "core" urinary microbiome for the human urinary tract, particularly emerging with ageing. The consensus reviewed the potential relationship between a patient's microbiome and lower urinary tract dysfunction, whether low-count bacteriuria may be clinically significant and mechanisms which could associate micro-organisms with lower urinary tract symptoms. CONCLUSIONS: Key research priorities identified include the need to establish the scope of microbiome across the range of normality and clinical presentations, and gain consensus on testing protocols. Proteomics to study enzymatic and other functions may be necessary, since different bacteria may have overlapping phenotype. Longitudinal studies into risk factors for exposure, cumulative risk, and emergence of disease need to undertaken. Neurourol. Urodynam. 36:850-853, 2017. © 2017 Wiley Periodicals, Inc.

Long-term compliance and results of intravesical botulinum toxin A injections in male patients.

INTRODUCTION: Intravesical injections with botulinum toxin A (BoNT-A) is an established treatment for patients with overactive bladder (OAB) symptoms. However, most studies have evaluated the efficacy of this treatment in women and report short-term results. In this study, we evaluated the long-term compliance of BoNT-A in a heterogeneous group of male patients. MATERIALS AND METHODS: This is a retrospective, single-centre study. We evaluated all male patients who have been treated with BoNT-A from 2004 until 2010 in a large teaching hospital. Patients received 100-300 U of onabotulinum toxin-A in 20 intravescial injections. Some patients received dose adjustment with repeated injections. RESULTS: In total, 88 male patients were included. The mean follow-up was almost 6 years (69 months). Of all patients, 22 (25%) continued BoNT-A treatment at last follow-up (success). Of the patients who discontinued treatment, 35 had insufficient effect and 27 had tolerability issues (eg, urinary retention, self-catheterisation, voiding LUTS). Four patients abandoned treatment due to other reasons that were not related to BoNT-A. Of all patients, 24% had to use intermittent catheterisation (de novo) or indwelling catheters at some point during the follow-up. DISCUSSION: In this real-life, heterogeneous cohort of men, the long-term compliance with BoNT-A was 25%. Patients with neurogenic OAB symptoms appear to have the best results in our study with 36% of patients who were still on active treatment during last follow-up. Intravesical BoNT-A can be an effective treatment for men with OAB symptoms. In our study, only 25% of patients continued treatment during long-term follow-up. Larger, prospective trials are needed to confirm these results.

Do we understand how botulinum toxin works and have we optimized the way it is administered to the bladder? ICI-RS 2014.

AIMS: The use of botulinum toxin A (BoNT/A) is commonplace now in the management of refractory overactive bladder and neurogenic detrusor overactivity (NDO). Despite one formulation now having a license, the full mechanism of action is not fully understood. Furthermore practice varies worldwide in the way the toxin is delivered to the bladder. At the ICI-RS 2014 Meeting in Bristol, UK a Think Tank session was conducted on the topic of "Do we understand how botulinum toxin works and have we optimized the way it is administered to the bladder?" This manuscript reflects the Think Tank's summary and opinion. METHODS: An overview of the existing evidence and consensus regarding mechanism of action and practical aspects of BoNT/A administration was presented. Further avenues of potential research were suggested. RESULTS: BoNT/A effect in the bladder is complex with likely effects on both efferent and afferent nerves. The site of action is controversial with the relative contribution of the detrusor as opposed to the suburothelial effects remaining unclear and open to further studying. The classical concept of prevention of acetylcholine release in the bladder is not supported by a wealth of evidence on neurotransmitters although co-localization studies have suggested cholinergic nerves are the most affected by BoNT/A. There is more robust evidence for effects on the purinergic system and afferent desensitization and emerging evidence for central effects. A variety of technique studies were presented. OnabotlinumtoxinA has recently been studied in large phase III trials and with this there is a standardized injection technique which is trigone-sparing. The evidence for altering location of injection is mixed with some studies suggesting less voiding dysfunction in bladder base injections alone but others suggesting location of injection does not affect outcomes. Early pilot data and evidence of instillation either with electromotive drug administration (EMDA) or in liposomes were also presented as an alternative to injections. CONCLUSIONS: The mechanism of action of BoNT/A in the bladder is complex and not fully understood. There is emerging support for its role on afferent mechanisms. The technical aspects of the injection procedure have been standardized to a certain extent but further study is required in larger scale studies to assess minimizing voiding dysfunction, improving tolerability, and assessing alternatives to injections.

Evidence for prostaglandin E2 receptor expression in the intramural ganglia of the guinea pig urinary bladder.

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.

Differentiation of lower urinary tract dysfunctions: The role of ambulatory urodynamic monitoring.

OBJECTIVES: To determine the value of ambulatory urodynamic monitoring in the assessment of patients with lower urinary tract symptoms. METHODS: This was a cross-sectional study including patients who underwent both conventional urodynamic and ambulatory urodynamic assessment at our Center between December 2002 and February 2013. The ambulatory urodynamic studies were interpreted in a standardized way by a resident experienced with urodynamic measurements, and one staff member who specialized in incontinence and urodynamics. RESULTS: A total of 239 patients (71 male and 168 female) were included in the present study. The largest subgroup of patients, 79 (33%), underwent ambulatory urodynamic monitoring based on suspicion of an acontractile bladder. However, 66 of these patients (83.5%) still showed contractions on ambulatory urodynamics. Other groups that were analyzed were patients with suspected storage dysfunction (47 patients), inconclusive conventional urodynamic studies (68 patients) and incontinence of unclear origin (45 patients). Particularly in this last group, ambulatory urodynamics appeared to be useful for discrimination between different causes of incontinence. CONCLUSIONS: Ambulatory urodynamic monitoring is a valuable discriminating diagnostic tool in patients with lower urinary tract symptoms who have already undergone conventional urodynamics, particularly in the case of patients with suspected bladder acontractility and incontinence of unclear origin during ambulatory urodynamics. Further study is required to determine the clinical implications of the findings and their relationship with treatment outcome.