Long-term follow-up of intravesical abobotulinumtoxinA (Dysport®) injections in women with idiopathic detrusor overactivity.

Objective: Only a few numbers of studies have been published on the use of abobotulinumtoxinA (Dysport®) in idiopathic detrusor overactivity (IDO). This study reported the long-term follow-up of women with IDO who were treated with intravesical Dysport® injections. Methods: Two hundred and thirty-six patients with IDO who had failed first-line conservative and antimuscarinic therapy received 500-900 units of Dysport® between April 2014 and July 2015. All patients were followed up for 5 years after their initial injection and interviewed on the phone. Results: A total of 236 women with IDO aged from 18 years to 84 years (mean±standard deviation: 49.6±15.9 years) were included in our study. The median follow-up time for patients was 36.5 (range: 10-70) months, and the median recovery time after injection was 18.5 (range: 0-70) months. A total of 83 (35.2%) patients stated that they had subjective improvement of their symptoms whereas 84 (35.6%) patients did not report any improvement in symptoms. The initial International Consultation on Incontinence Questionnaire Overactive Bladder mean score was 6.9 (standard deviation 3.4). There was a positive association between the median recovery time and the components of the International Consultation on Incontinence Questionnaire Overactive Bladder questionnaire. Conclusion: In a sub-population of overactive bladder patients with IDO who have failed first-line therapy, a single intravesical Dysport® injection can resolve patient symptoms completely or reduce the symptoms to an acceptable level that can be controlled with antimuscarinics or re-injection on demands.

Intravesical Injection of Abobotulinumtoxin-A in Patients with Bladder Pain Syndrome/Interstitial Cystitis.

OBJECTIVE: This study aimed to evaluate retrospectively the outcomes of Abobotulinumtoxin-A (Dysport®) intravesical injection in refractory interstitial cystitis/ bladder pain syndrome patients to first- and second-line treatment. MATERIALS AND METHODS: From March 2016 to 2021, 44 adult patients with bladder pain syndrome who were refractory to first- and second-line treatment were enrolled in our study. The Bladder Pain/Interstitial Cystitis Symptom Score questionnaire was filled out for every patient before and 1-3 months after intervention in addition to urodynamic evaluation. Patient satisfaction was evaluated using a scoring system that was defined as high or >80% improvement (highly satisfied), intermediate 40%-79% (intermediate satisfaction), and poor 0%-39% improvement. RESULTS: The mean age of our study population was 57 years, including 41 females and 3 males. The mean follow-up time was 9 months. According to the results of urodynamics, 68% of cases had low capacity, and detrusor overactivity, while 18% had only low capacity. In terms of the endpoint outcome, half of the patients (52%) had intermediate satisfaction, whereas 41% reported a good response. Only 3 cases had no response or felt (7%) any improvement after the intervention (poor response). The paired t-test analysis revealed that the mean Bladder Pain/Interstitial Cystitis Symptom Score was reduced after injection (P = .001). CONCLUSION: Our results showed the efficacy and safety of intravesical injections with Abobotulinumtoxin-A (Dysport®) in patients with interstitial cystitis/bladder pain syndrome. Further randomized controlled trials are recommended to investigate its superiority over placebo considering the need for anesthesia, the occurrence of local complications, risks of urinary retention, and a large post-void residual (PVR) volume.

Differences in the Urinary Microbiome of Patients with Overactive Bladder Syndrome with and without Detrusor Overactivity on Urodynamic Measurements.

INTRODUCTION: It has been hypothesized that the urinary microbiome might play an important role in OAB. Studies have been conducted on the association between OAB symptoms and the microbiome, although a possible causality still has to be determined. MATERIAL AND METHODS: In this study, 12 female patients, ≥18 years of age, with 'OAB DO+' and 9 female patients with 'OAB DO-' were included. Patients were excluded if they met one of the following exclusion criteria: bladder tumors and previous bladder operations; sacral neuromodulation; injection of Botox in the bladder; and TOT or TVT operations. Urine samples were collected and stored with patient informed consent and with the approval of the Hospital Ethical Review Board (Arnhem-Nijmegen). All OAB patients underwent urodynamics before collecting urine samples, and the diagnosis of detrusor overactivity was confirmed by two individual urologists. In addition, samples from 12 healthy controls who did not undergo urodynamic evaluation were analyzed. The 16S rRNA V1-V2 region amplification and gel electrophoresis were used to determine the microbiota. RESULTS: 12 of the OAB patients had DO shown on their urodynamic studies; the remaining 9 patients had a normoactive detrusor on their urodynamic measurements. Overall, there were no substantial differences among the demographic characteristics of the subjects. The samples were classified as the following: 180 phyla, 180 classes, 179 orders, 178 families, 175 genera, and 138 species. The least commonly observed phyla were Proteobacteria, with an average presence of 10%, followed by Bacteroidetes with 15%, Actinobacteria with 16%, and Firmicutes with 41%. Most of the sequences could be classified according to the genus level for each sample. DISCUSSION: Significant differences were observed in the urinary microbiome of patients with overactive bladder syndrome who have detrusor overactivity on urodynamics compared to OAB patients without detrusor overactivity and matched controls. OAB patients with detrusor overactivity have a significantly less diverse microbiome and show a higher proportion of Lactobacillus, particularly Lactobacillus iners. The results imply that the urinary microbiome could be involved in the pathogenesis of a specific phenotype of OAB. The urinary microbiome could be a new starting point to study the causes and treatments of OAB.

Microbiome in Lower Urinary Tract Symptoms (LUTSs): Mapping the State of the Art with Bibliometric Analysis.

BACKGROUND: The main objective of this study is to provide the first characterization of the current research field of the clinical microbiome in LUTSs. METHODS: First-of-its-kind scientometric insight into the historical development and structural state of the discipline is provided by a field analysis, mapping, and sub-analysis of articles for future research. On 22 December 2022, the entire Scopus database was searched without language or date restrictions. Search terms included "Chronic prostatitis", OR "Interstitial cystitis", OR "Lower urinary tract symptoms", OR "Lower urinary tract dysfunction", OR "Overactive bladder", OR "Incontinence", OR "Urolithiasis", OR "Urothelium", OR "Urine", OR "Urology", OR "urinary disorder", OR "Pathophysiology", OR "Benign prostatic hyperplasia", OR "Benign prostatic enlargement", AND "Microbiota", OR "Microbiome", OR "Urobio-ma", OR "Urobiota; microflora". The author and institutional data were transformed using the analytical tool Biblioshiny (a Shiny app for Bibliometrix), which took into account variations in author spelling as well as institutional naming and subgroups. RESULTS: The specified search strategy was able to locate 529 documents from 267 sources published from 1981 to 2022. The average number of years from publication was 4.59 years. The authors with the most publications were Wolfe AJ and Brubaker I. The top three most collaborative networks were Loyola University Chicago, Loyola University Medical Center, and the University of California San Diego. The most frequently occurring words among the 50 nodes were: human, humans, nonhuman, female, adult, article, microbiology, microflora, microbiota, and controlled study. Frontiers in Cellular and Infection Microbiology and the International Urogynecology Journal, followed by Nature Reviews Urology, were the top three most relevant sources in microbiome research in urology. CONCLUSIONS: One of the most crucial requirements for developing research policies and anticipating the scientific requirements of researchers is paying attention to the evolution of various scientific fields. Understanding research gaps and future needs in microbiome research in urology can be effectively understood by paying attention to the models, maps, and visualizations used in this research, which are the results of systematic analysis of scientific products in the most esteemed scientific journals in the world.

Efficacy of percutaneous and transcutaneous posterior tibial nerve stimulation on idiopathic overactive bladder and interstitial cystitis/painful bladder syndrome: A systematic review and meta-analysis.

OBJECTIVES: Percutaneous and transcutaneous posterior tibial nerve stimulation (PTNS and TTNS) showed a promising effect on overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome. We aimed to give a systematic review and meta-analysis on the efficacy and safety of these therapeutic methods as well. METHODS: We searched studies available on PubMed, Embase, Cochrane, Scopus, Web of Science, and ProQuest on March 31, 2021, to find both published and unpublished studies. The retrieved articles were screened by two independent researchers and then the selected studies were critically appraised by Cochrane risk-of-bias tool for randomized trials, and Joanna Briggs Institute's checklist for quasi-experimental studies. Finally, the results of studies were synthesized using Review Manager (RevMan) 5.4 statistical software when the data were homogenous. The meta-analysis was performed by calculating the effect size (mean difference) and their 95% confidence intervals (CIs). RESULTS: Of the total 3194 publications, 68 studies were included in our qualitative evaluation and 9 studies (11 trials) in the quantitative stage. When TTNS or PTNS were compared to sham, placebo, no treatment, or conservative management, a decrease in frequency of urination was observed in both TTNS (mean difference [MD]: -3.18, 95% CI: -4.42 to -1.94, and p < 0.00001), and PTNS (MD: -2.84, 95% CI: -4.22 to -1.45, and p < 0.00001), and overall TTNS or PTNS (MD: -2.95, 95% CI: -4.01 to -1.88, and p < 0.00001). Significant improvements in mean voiding volume (MVV) and decreasing nocturia were also observed. CONCLUSIONS: Nerve stimulations either PTNS or TTNS appear to be effective interventions in treating refractory idiopathic OAB in terms of daily voiding frequency, MVV, urgency episodes, and nighttime voiding frequency. However, our result did not show any improvement in terms of urinary incontinence, postvoid residual volume or urge incontinence, and maximum cystometric capacity which emphasized the efficacy of these modalities on dry-OAB rather than wet-OAB.

The Scientific Value of Abstracts on Prostate Cancer Presented at the European Association of Urology Congresses.

Background: Scientific congresses are an important medium for presenting recent clinical findings. Publication of abstracts allows wider dissemination. Objectives: To determine the publication rates of prostate cancer abstracts presented at the annual congress of the European Association of Urology (EAU). Design, Setting, and Participants: All abstracts with the term prostate cancer or carcinoma presented at the congress of the European Association of Urology from 2015 to 2018 were analyzed. We captured their publication rate, journal impact factor and time to publication. Moreover, we formulated a scoring system to determine the grade of discrepancy between the conclusions mentioned in the congress abstract and published abstract. Results: A total of 834 abstracts presented at EAU annual meeting included prostate cancer or carcinoma in their title. We recorded a publication rate of 56.8% with 474 of the 834 abstracts being published with a mean time of 12.5 months. Conclusion: Approximately, 57% of the prostate cancer abstracts presented at the EAU congress are published in peer reviewed journals. This acceptance rate indicates the high distribution and dissemination of these abstracts.

Lower urinary tract signs and symptoms in patients with COVID-19.

BACKGROUND: The type of pneumonia that is caused by the new coronavirus (SARS-CoV-2) has spread across the world in a pandemic. It is not clear if COVID-19 patients have any lower urinary tract signs or symptoms. METHODS: The effect of COVID-19 on lower urinary tract function was studied in a prospective multi-centre, observational study including 238 patients who were admitted with symptoms caused by COVID-19 to the university hospital of Aachen in Germany and Tabriz in Iran. RESULTS: None of the patients reported to have any lower urinary tract symptoms. SARS-CoV-2 was found in the urine of 19% of the tested patients. The mortality rate in COVID-19 infected patients with microscopic haematuria together with white blood cells in their urine, was significantly increased from 48 to 61% in the Tabriz cohort (p-value = 0.03) and from 30 to 35% in the Aachen cohort (p-value =0.045). Furthermore, in the group of patients with SARS-CoV-2 urine PCR, the mortality rate rose from 30 to 58%. (p-value =0.039). CONCLUSION: Patients admitted with COVID-19 did not report to have any lower urinary tract symptoms, even those patient who had a positive Urine SARS-CoV-2 PCR. In addition, hematuria, WBC in urine as well as SARS- CoV-2 presence in urine, were found to be strong negative prognostic factors in admitted COVID-19 patients.

Can the predictive value of multiparametric MRI for prostate cancer be improved by a liquid biopsy with SelectMDx?

BACKGROUND: SelectMDx is a urinary biomarker test for determining prostate cancer risk. AIM: In a group of patients with a biopsy proven prostate cancer (PCa) who had undergone a multi parametric Magnetic Resonance Imaging (mpMRI) and urinary biomarker test with SelectMDx, we studied the additive value of SelectMDx to mpMRI and correlated that to the radical prostatectomy histology. METHODS AND RESULTS: Thirty-nine consecutive patients with a positive prostate biopsy were included in the study. They all had mpMRI and SelectMDx and underwent a radical prostatectomy. Overall, the mpMRI showed a PIRADS ≤3 lesion in seven cases out of the 39 patients. Significant lesions (PIRADS ≥4) were found in 32 cases (82%), that is, in 17 cases a PIRADS 5 lesion and in 15 cases a PIRADS 4 lesion. The mpMRI missed significant PCa in seven cases (18%) who had a PIRADS ≤3 lesion but had a significant PCa on final histology after RP. In our study, the positive predictive values of mpMRI were 97% and that of the SelectMDx was 100%. CONCLUSION: In this real-life selected group of consecutive patients with a confirmed positive PCa biopsy and available mpMRI, the liquid biopsy test with SelectMDx, did not provide an additional information about the PCa clinical significance. The addition of SelectMDx was only found valuable in those patients who had a very high-risk PCa (ie, GS ≥8) who had a positive SelectMDx test outcome despite of a negative mpMRI outcome.

Urinary Microbiome and its Correlation with Disorders of the Genitourinary System.

PURPOSE: Until recently, the urine of healthy individuals was assumed to be sterile. However, improvement of bacterial detection methods has debunked this assumption. Recent studies have shown that the bladder contains microbiomes, which are not detectable under standard conditions. In this review, we aimed to present an overview of the published literature regarding the relationship between urinary microbiota and functional disorders of the genitourinary system. METHODS: We searched Medline, PubMed, Embase, The Cochrane library and Scopus to identify RCTs published, with MeSH and free keywords including microbiota, bladder pain syndrome, prostatitis, kidney stone disease, and bladder cancer until September 2020. Randomized controlled trials investigating microbiome and lower urinary tract symptoms were included. Non-randomized trials, cross-over trials and pooled studies were excluded. The articles were critically appraised by two reviewers. CONCLUSION: The urine microbiome is a newly introduced concept, which has attracted the attention of medical researchers. Since its recent introduction, researchers have conducted many fruitful studies on this phenomenon, changing our perspective toward the role of bacteria in the urinary tract and our perception of the genitourinary system health. RESULT: A deeper understanding of the urinary microbiome can help us to develop more efficient methods for restoring the microbiota to a healthy composition and providing symptom relief. Modification of the urinary microbiome without antibiotic use can be a possible venue for future research.

Bladder Pain Syndrome and Interstitial Cystitis Beyond Horizon: Reports from the Global Interstitial Cystitis/Bladder Pain Society (GIBS) Meeting 2019 Mumbai - India.

PURPOSE OF THE MEETING: Bladder pain syndrome/interstitial cystitis is a prevalent but underserved disease. At the Global Interstitial Cystitis/Bladder Pain Syndrome Society (GIBS) meeting, the organization and participants were committed to delivering word-class expertise and collaboration in research and patient care. Under the umbrella of GIBS, leading research scholars from different backgrounds and specialties, as well as clinicians, from across the globe interested in the science and art of practice of Bladder Pain Syndrome (BPS)/Interstitial Cystitis (IC) were invited to deliberate on various dimensions of this disease. The meeting aimed to have global guidelines to establish firm directions to practicing clinicians and patients alike on the diagnosis and treatment of this disease entity. Chronic Pelvic Pain Syndrome (CPPS) is defined by pain in the pelvic area that can have different etiologies. This can be due to urologic, gynecologic, musculoskeletal, gastrointestinal, neurologic, and autoimmune or rheumatologic diseases. At the GIBS meeting held in Mumbai, India, in August 2019, a multidisciplinary expert panel of international urologists, gynecologists, pain specialists, and dietitians took part in a think tank to discuss the development of evidence-based diagnostic and treatment algorithms for BPS/IC. SUMMARY OF PRESENTED FINDINGS: The diagnosis of BPS/IC is difficult in daily clinical practice. Patients with BPS/IC present with a variety of signs and symptoms and clinical test results. Hence, they might be misdiagnosed or underdiagnosed, and the correct diagnosis might take a long time. A good history and physical examination, along with cystoscopy, is a must for the diagnosis of IC/BPS. For the treatment, besides lifestyle management and dietary advice, oral medication and bladder instillation therapy, botulinum toxin, and sacral neuromodulation were discussed. The innovation in bladder instillation applicators, as well as battery-free neuromodulation through the tibial nerve, was discussed, as well. RECOMMENDATION FOR FUTURE RESEARCH: As BPS/IC is complex, for many patients, several treatments are necessary at the same time. This was presented at GIBS 2019 as the piano model. In this way, a combination of treatments is tailored to an individual patient depending on the symptoms, age, and patients' characteristics. In the art of medicine, especially when dealing with BPS/IC patients, pressing the right key at the right time makes the difference.

Botulinum toxin A for refractory OAB and idiopathic urinary retention: Can phenotyping improve outcome for patients: ICI-RS 2019?

AIMS: Botulinum toxin A (BTX-A) is a well-established treatment for refractory idiopathic overactive bladder (OAB). It has also been used with short-term success in treating idiopathic urinary retention. However, efficacy and complication rates are variable and predicting those likely to benefit most from treatment would enable personalization of therapy and optimization of outcomes. At the International Consultation on Incontinence-Research Society (ICI-RS) meeting in 2019 a Think Tank addressed the question of how we can improve the way we phenotype patients undergoing BTX-A treatment. METHODS: The Think Tank conducted a literature review and expert consensus meeting focussing on how advances in basic science research of the mechanism of action of BTX-A, as well as assessment of psychological comorbidity, can be translated into clinical practice to improve patient selection for therapy. RESULTS: Idiopathic OAB and idiopathic urinary retention are heterogenous conditions encompassing several phenotypes with multiple potential pathophysiological mechanisms. Animal models have demonstrated a central nervous system mechanism of action of intravesically injected BTX-A and this has been confirmed in human functional MRI studies, but whether this tool can be used to predict outcome from treatment remains to be determined. Phenotyping based on psychological comorbidity using validated screening tools should be studied as a way to potentially optimize patient selection for therapy. CONCLUSIONS: Advances in basic science research into the mechanism of action of BTX-A have improved our understanding of the pathophysiology of OAB and may lead to novel ways to phenotype patients. Psychological assessment is another way in which phenotyping may be improved. Areas for further research are proposed.

Neuromodulation for functional bladder disorders in patients with multiple sclerosis.

The function of the lower urinary tract is mainly storage and voiding of urine, which is coordinated by the nervous system. Various diseases of the nervous system may cause neuro-urological symptoms. Neuro-urological symptoms depend on the localization of the disease and the extension of the neurological lesion. About 80% of multiple sclerosis (MS) patients have neuro-urological symptoms within 10 years after diagnosis. In addition, 10% of MS patients may even present with voiding dysfunction at disease onset. In this review, different types of neuromodulation are discussed. The available studies suggest that sacral neuromodulation (SNM) and percutaneous tibial nerve stimulation (PTNS) may be helpful in the neuromodulation of MS-related overactive bladder symptoms. These techniques may not only decrease the severity of symptoms but also significantly improve the quality of life of affected patients. Exploring the role of implantable tibial nerve stimulation devices in patients with MS could open new doors in the management of urgency and urgency incontinence in this patient group.

How can we improve the diagnosis and management of bladder pain syndrome? Part 2:ICI-RS 2018.

BACKGROUND: This paper summarises the discussion in a think tank at the International Consultation on Incontinence-Research Society (ICI-RS) 2018 about the treatment of bladder pain syndrome. AIMS: To review the treatments of bladder pain syndrome from behavioural treatments to surgical interventions. MATERIALS AND METHODS: Review the literature in the light of the think tank discussions. RESULTS: All guidelines recommend different levels of treatment starting with conservative behavioral treatments then introducing oral treatments followed by intravesical instillations. If these treatments fail then more invasive treatments such as botulinum toxin injections, neuromodulation, or surgery could be suggested. CONCLUSION: Unfortunately for all treatments, the numbers are limited and, therefore, the evidence base is not strong. Further suggestions for research are suggested.

Are there different patterns of detrusor overactivity which are clinically relevant? ICI-RS 2018.

INTRODUCTION: Different patterns of detrusor overactivity (DO) have been described and included in several standardization terminology documents. However, it is unclear if these different patterns have any clinical significance. METHODS: This is a report of the proceedings of Proposal 3: "Are there different patterns of detrusor overactivity which are clinically relevant?" from the annual International Consultation on Incontinence-Research Society (ICIRS) meeting, which took place from 14 to 16 June 2018, in Bristol, UK. RESULTS: We have collected and discussed, as a committee, the evidence about different urodynamic (UD) patterns of detrusor overactivity and their potential clinical significance. We reviewed the important previous basic research and clinical studies and compiled summaries. The discussion focused on clinical relevance of different UD patterns of DO and what further research is required. CONCLUSIONS: There are several UD definitions of patterns of detrusor overactivity, however the clinical relevance of these definitions remains unclear. Future research should concentrate on defining the pattern of DO in relation to clinical diagnosis, gender, age, and treatment outcomes.

How can we improve the diagnosis and management of bladder pain syndrome? Part 1: ICI-RS 2018.

BACKGROUND: This paper summarizes the discussion in a think tank at the ICI-RS 2018 about the diagnosis of bladder pain syndrome (BPS). AIMS: To review the guidelines, investigations and subtypes of BPS. MATERIALS AND METHODS: Review of literature in the light of the think tank discussion. RESULTS: All guidelines recommend completing history, physical examination, urine analysis, urine culture, and urine cytology to define the BPS phenotype but there are differences on further investigations. In those guidelines which recommend cystoscopy, the identification of Hunner's lesions (HLs) is recommended as this changes the treatment plan and outcome. CONCLUSION: We propose that the differentiation of Hunner's ulcers is an important step in the assessment of these patients. Further suggestions for research are suggested.

Pathophysiological mechanisms in detrusor underactivity: Novel experimental findings.

Underactive bladder (UAB) is a multifactorial symptom complex often related to detrusor underactivity (DU). Although recognized as a common cause of lower urinary tract symptoms and with significant effects on quality of life, UAB/DU is largely underresearched. Herein, we review up-to-date knowledge on the pathophysiological mechanisms of UAB/DU, with an emphasis on the relationship between UAB and bladder outlet obstruction (BOO). Original articles and reviews concerning UAB/DU were identified through a search of the PubMed/Medline and Scopus databases. DU can result from several pathological mechanisms, which can be categorized as idiopathic, neurogenic, myogenic, or functional. The main etiological factors of UAB/DU are aging, diabetes mellitus, neurogenic disorders, and BOO. Although conventional models focus primarily on efferent nerve and myogenic mechanisms, contemporary views highlight the importance of the afferent pathway. Specifically, recent findings in BOO showed that afferent dysfunction, such as altered expression of muscarinic and purinergic P2X3 receptors or diminished urothelial ATP may play a role in the initial and reversible stages of DU, with potential diagnostic and therapeutic implications.

Oral Pharmacologic Management of Overactive Bladder Syndrome: Where Do We Stand?

Overactive bladder syndrome (OAB) is a prevalent disorder with a significant impact on quality of life. Despite this high prevalence, there is significant underdiagnosis and undertreatment due to several barriers, including embarrassment, poor communication and low patient adherence. Currently, various antimuscarinic are available in the treatment of OAB. The introduction of mirabegron has broadened the therapeutic approach and combination therapy of both agents can be valuable in clinical practice. Yet, patient adherence to most drugs for OAB is still relatively poor. Healthcare providers need to identify and utilise strategies to improve treatment adherence by defining clear treatment goals, implement educational methods and frequently communicate with patients to identify problems with adherence. The elderly population form need special attention as in these patients, anticholinergics should be prescribed with care and adequate knowledge regarding pharmacokinetics and drug interactions in essential. Furthermore, patient expectations should be clearly discussed. In this narrative review, the current advances in oral pharmacotherapy are evaluated and the most important factors involved in the management of OAB are discussed.

The Role of the Periaqueductal Gray Matter in Lower Urinary Tract Function.

The periaqueductal gray matter (PAG), as one of the mostly preserved evolutionary components of the brain, is an axial structure modulating various important functions of the organism, including autonomic, behavioral, pain, and micturition control. It has a critical role in urinary bladder physiology, with respect to storage and voiding of urine. The PAG has a columnar composition and has extensive connections with its cranially and caudally located components of the central nervous system (CNS). The PAG serves as the control tower of the detrusor and sphincter contractions. It serves as a bridge between the evolutionary higher decision-making brain centers and the lower centers responsible for reflexive micturition. Glutamatergic cells are the main operational neurons in the vlPAG, responsible for the reception and relay of the signals emerging from the bladder, to related brain centers. Functional imaging studies made it possible to clarify the activity of the PAG in voiding and filling phases of micturition, and its connections with various brain centers in living humans. The PAG may be affected in a wide spectrum of disorders, including multiple sclerosis (MS), migraine, stroke, Wernicke's encephalopathy, and idiopathic normal pressure hydrocephalus, all of which may have voiding dysfunction or incontinence, in certain stages of the disease. This emphasizes the importance of this structure for the basic understanding of voiding and storage disorders and makes it a potential candidate for diagnostic and therapeutic interventions.

Management of Idiopathic Overactive Bladder Syndrome: What Is the Optimal Strategy After Failure of Conservative Treatment?

CONTEXT: A considerable number of patients affected by the overactive bladder syndrome (OAB) do not respond to pharmacotherapy and bladder training due to unsatisfactory response or intolerability. OBJECTIVE: To review the available literature assessing therapeutic effect of the available third-line treatment modalities for OAB. EVIDENCE ACQUISITION: PubMed, Medline, and Cochrane databases were searched for all studies comparing outcomes of the available third-line treatment modalities for OAB. EVIDENCE SYNTHESIS: Several minimally invasive surgical procedures are available for patients with refractory OAB. These therapies include intravesical botulinum toxin type A, posterior tibial nerve stimulation, and sacral neuromodulation. CONCLUSIONS: None of the mentioned therapeutic modalities shows strong superiority over another. If the results of one therapy are not satisfactory, switching to another third-line treatment can be attempted. The treatment algorithm is dependent on several factors, including age, comorbidity, patient preference, surgical expertise, and financial concerns. All these factors should be taken into consideration before initiation of treatment. PATIENT SUMMARY: In the management of drug-resistant overactive bladder syndrome, the different minimally invasive treatments that are available are equal. If the results of one therapy are not satisfactory, switching to another treatment can be attempted. The treatment algorithm is dependent on several factors, including age, comorbidity, patient preference, surgical expertise, and financial concerns.

Overactive bladder syndrome and the potential role of prostaglandins and phosphodiesterases: an introduction.

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.