Neuro-Urology: Call for Universal, Resource-Independent Guidance.

Neurogenic lower urinary tract dysfunction (NLUTD), the abnormal function of the lower urinary tract in the context of neurological pathology, has been the subject of multiple efforts worldwide for the development of clinical practice guidelines. These guidelines are based on the same body of evidence, and are therefore subject to the same gaps. For example, sexual and bowel dysfunction in the context of NLUTD, optimal renal function assessment in those who are non-ambulatory or with low muscle mass, optimal upper tract surveillance timing, and modification of diagnostic and treatment modalities for low-resource nations and communities are inadequately addressed. In addition, many aspects of the conclusions and final recommendations of the guidelines are similar. This duplicative work represents a large expenditure of time and effort, which we believe could be focused instead on evidence gaps. Here, we call for a global unified approach to create a single, resource-independent, comprehensive guidance on NLUTD, neurogenic sexual, and neurogenic bowel dysfunction. Targeted research addressing the evidence gaps should be called for and pursued. This will allow for focus to shift to filling the gaps in the evidence for future guidelines.

Randomised Controlled Trials Assessing the Clinical Value of Urodynamic Studies: A Systematic Review and Meta-analysis.

Context: The role of urodynamic studies (UDSs) in the diagnosis of lower urinary tract symptoms (LUTS) is crucial. Although expert statements and guidelines underline their value for clinical decision-making in various clinical settings, the academic debate as to their impact on patient outcomes continues. Objective: To summarise the evidence from all randomised controlled trials assessing the clinical usefulness of UDS in the management of LUTS. Evidence acquisition: For this systematic review, searches were performed without language restrictions in three electronic databases until November 18, 2020. The inclusion criteria were randomised controlled study design and allocation to receive UDS or not prior to any clinical management. Quality assessment was performed by two reviewers independently, using the Cochrane Collaboration's tool for assessing the risk of bias. A random-effect meta-analysis was performed on the uniformly reported outcome parameters. Evidence synthesis: Eight trials were included, and all but two focused on women with pure or predominant stress urinary incontinence (SUI). A meta-analysis of six studies including 942 female patients was possible for treatment success, as defined by the authors (relative risk 1.00, 95% confidence interval: 0.93-1.07), indicating no difference in efficacy when managing women with UDS. Conclusions: Although UDSs are not replaceable in diagnostics, since there is no other equivalent method to find out exactly what the lower urinary tract problem is, there are little data supporting its impact on outcomes. Randomised controlled trials have focussed on a small group of women with uncomplicated SUI and showed no added value, but these findings cannot be extrapolated to the overall patient population with LUTS, warranting further well-designed trials. Patient summary: Despite urodynamics being the gold standard to assess lower urinary tract symptoms (LUTS), as it is the only method that can specify lower urinary tract dysfunction, more studies assessing the clinical usefulness of urodynamic studies (UDSs) in the management of LUTS are needed. UDS investigation is not increasing the probability of success in the treatment of stress urinary incontinence.

Diagnosis and treatment of urethral stricture in men with neurogenic lower urinary tract dysfunction: A systematic review.

AIM: To summarize available data focused on diagnosis and management of urethral stricture in men with neurogenic lower urinary tract dysfunction by a systematic review of the literature. MATERIALS AND METHODS: A systematic review of the literature was carried out through an extensive electronic database search performed in PubMed/MEDLINE and Scopus databases for full texts, and International Continence Society, American Urology Association, and European Association of Urology abstracts for citations related to urethral structure. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. RESULTS: A total of 316 articles were identified, 48 of which were selected for this review. Different strategies are currently being used for the management of urethral strictures, such as clean intermittent catheterization (CIC) which reduces stricture by up to 68%; direct vision internal urethrotomy which shows lower rates of renarrowing; urethroplasty which shows a success rate up to 70%; urinary diversion is the treatment of choice when reconstruction is not possible. CONCLUSIONS: Further studies are needed in this population because of the heterogeneity of the outcomes and the lack of a standardized definition and classification of this population.

Botulinum toxin for treating overactive bladder in men: A systematic review.

PURPOSE: We sought to systematically review the literature on the use of botulinum toxin (BTX-A) injections in the bladder to treat overactive bladder (OAB) in men. MATERIALS AND METHODS: A systematic review was performed to identify clinical trials on efficacy and safety of BTX-A injections in the detrusor for treatment of OAB in men published from inception to October 2020. Quality assessment was performed using the Cochrane Collaboration's tool for assessing risk of bias and study characteristics were extracted by two reviewers independently. RESULTS: After screening 75 abstracts, 12 trials were included in the qualitative synthesis, of which 6 were conducted exclusively in men (mean age: 66.7 years). Only two were randomized controlled studies and the remaining were observational studies, mostly case series. Total number of participants in each study ranged from 28 to 146. Therapeutic response to intravesical BTX-A injection was assessed differently across the studies, which used quality-of-life symptom questionnaires and voiding diary parameters. Urodynamics findings were reported separately for men before and after intravesical injection of BTX-A in two studies only. Pooling of outcome data was possible with adverse events reported after BTX-A by seven studies, which showed urinary tract infection, urinary retention, increased postvoid residual, de novo interstitial cystitis, and hematuria rates of 29.8%, 20.0%, 37.3%, 28.3%, and 12.4%, respectively. CONCLUSIONS: Limited information regarding the efficacy and safety of BTX-A bladder injections for male OAB from relatively low evidence is available. Further research is needed to better understand the risk-benefit profile of BTX-A in the male population.

Is coronavirus disease 2019 associated with indicators of long-term bladder dysfunction?

OBJECTIVE: Early reports have suggested that coronavirus disease 2019 (COVID-19) can present with significant urinary frequency and nocturia, and that these symptoms correlate with markers of inflammation in the urine. We evaluated surrogate markers of chronic urinary symptoms to determine if they were more frequent after COVID-19 infection. METHODS: Routinely collected data from the province of Ontario was used to conduct a matched, retrospective cohort study. We identified patients 66 years of age or older who had a positive COVID-19 test between February and May 2020 and survived at least 2 months after their diagnosis. We matched them to two similar patients who did not have a positive COVID-19 test during the same time period. We measured the frequency of urology consultation, cystoscopy, and new prescriptions for overactive bladder medications during a subsequent 3-month period. Proportional hazard models were adjusted for any baseline differences between the groups. RESULTS: We matched 5617 patients with COVID-19 to 11,225 people who did not have COVID-19. The groups were similar, aside from a higher proportion of patients having hypertension and diabetes in the CoVID-19 cohort. There was no significantly increased hazard of new receipt of overactive bladder medication (hazards ratio [HR]: 1.04, p = 0.88), urology consultation (HR: 1.40, p = 0.10), or cystoscopy (HR: 1.14, p = 0.50) among patients who had COVID-19, compared to the matched cohort. CONCLUSION: Surrogate markers of potential bladder dysfunction were not significantly increased in the 2-5 months after COVID-19 infection.

Prevalence of self-reported complications associated with intermittent catheterization in wheelchair athletes with spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To identify the prevalence of complications associated with intermittent catheterization in wheelchair athletes with spinal cord injury (SCI). SETTING: International and national sporting events. METHODS: A total 130 competitive wheelchair athletes living with SCI completed a self-reported questionnaire during international or national sporting events. The questionnaire collected information regarding demographics, injury characteristics, method of bladder emptying, and complications related to intermittent catheterization. RESULTS: Overall, 84% (109/130) of wheelchair athletes used intermittent catheterization. Within this group, 77% of athletes (84/109) experienced at least one complication associated with intermittent catheterization. Twenty-seven percent (29/109) sustained urethral injuries and 63% (69/109) had at least one episode of urinary tract infection during the last 12 months. Almost one-fourth of male athletes (22/95, 23%) had a history of inflammation / infection of genital organs associated with intermittent catheterization. CONCLUSIONS: Here we report a high prevalence of self-reported complications associated with intermittent catheterization in wheelchair athletes with SCI. Considering their potential impact on lower urinary tract function, athletic performance, and health, further studies are needed to assess the role of preventative strategies to reduce complications related to intermittent catheterization in wheelchair athletes with SCI. SPONSORSHIP: Coloplast Brazil and Instituto Lado a Lado pela Vida (a nongovernmental, nonprofit organization based in São Paulo) and Wellspect provided funding for this study.

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.

Impact of LUTS on treatment-related behaviors and quality of life: A population-based study in Brazil.

AIMS: To report on the impact of lower urinary tract symptoms (LUTS) on treatment-related behaviors and quality of life in Brazilian adults greater than or equal to 40 years. METHODS: Data were from a computer-assisted telephone survey conducted in Brazil between 1 September and 31 December 2015 (Brazil LUTS study). Participants were adults greater than or equal to 40 years with landlines living in major cities from five geographical regions in Brazil. Participants rated how often they experienced individual LUTS during the previous month and associated bother, and the impact on quality of life (QoL), treatment seeking, treatment, treatment satisfaction, and treatment discontinuation. Multiple logistic regression models were adjusted to analyze the simultaneous effects of predictor variables on each dependent variable. RESULTS: When the presence of LUTS was defined as symptoms occurring less than half the time or more, one-quarter of respondents sought treatment but 6% fewer actually received treatment. Of these, around 25% reported dissatisfaction with treatment and almost 10% reported treatment discontinuation. The occurrence of some symptoms and, in particular, the resultant bother were significantly related to worse QoL and to treatment-related outcomes, such as treatment seeking, actual treatment, treatment dissatisfaction, and treatment discontinuation. Symptoms of all three categories were associated with all these domains for both sexes. CONCLUSIONS: This is the first population-based study carried out in South America showing that treatment seeking and treatment rates for LUTS are low. Since the LUTS prevalence is high, this reinforces the importance of a comprehensive medical assessment, focusing on the resulting bother, for more appropriate and personalized patient management.

Surgical treatment of post-prostatectomy stress urinary incontinence in adult men: Report from the 6th International Consultation on Incontinence.

AIMS: To report the recommendations of the 6th International Consultation on Incontinence (ICI) on post-prostatectomy urinary incontinence. METHODS: The 6th ICI committee on surgical treatment of urinary incontinence in men assessed and reviewed the outcomes of surgical therapy and updated the prior recommendations published in 2013. Articles from peer-reviewed journals, abstracts from scientific meetings, and literature searches by hand and electronically formed the basis of this review. The resulting guidelines were presented at the 2016 ICI meeting in Tokyo, Japan. RESULTS: Voiding diary and pad tests are valuable for assessing quantity of leakage. Cystoscopy and/or urodynamics may be useful in guiding therapy depending on the type of incontinence and presumed etiology. Artificial Urinary Sphincter (AUS) is the preferred treatment for men with moderate to severe stress urinary incontinence (SUI) after RP. Male slings are an acceptable approach for men with mild to moderate SUI. Much discussion centers on the definition of moderate SUI. Injectable agents have a poor success rate in men with SUI. Options for recurrent SUI due to urethral atrophy after AUS implantation include changing the pressure balloon, downsizing the cuff and increasing the amount of fluid in the system. Infection and/or erosion demand surgical removal or revision of all or part of the prosthesis. CONCLUSIONS: Although there are several series reporting the outcomes of different surgical interventions for PPUI, there is still a need for prospective randomized clinical trials. Recommendations for future research include standardized workup and outcome measures, and complete reporting of adverse events at long-term.

Current controversies in urinary tract infections: ICI-RS 2017.

AIMS: The current definition of urinary tract infection (UTI) relies on laboratory and clinical findings, which may or may not be relevant, depending upon the patient group under consideration. This report considers the utility of current definitions for UTI in adults with and without underlying neurological conditions in order to identify gaps in current understanding and to recommend directions for research. METHODS: This is a consensus report of the proceedings of Think Tank TT3: "How do we define and when do we treat UTI in neurological and non-neurological adult patients?" from the annual International Consultation on Incontinence-Research Society (ICI-RS), June 8-10, 2017 (Bristol, UK). RESULTS: Evidence considering the definitions of UTI in patients with and without neurological diseases was reviewed and synthesized. We examined research on laboratory methods and clinical definitions, focusing on specific cut-off values for the quantification of significant bacteriuria, and leucocyturia. Several areas were identified, mostly related to the lack of evidence-based definitions of significant bacteriuria for different patient groups, as well as uncertainties about the role of inflammatory biomarkers, and non-specific symptoms and signs. CONCLUSIONS: One of the biggest challenges in clinical practice is to discriminate between asymptomatic bacteriuria and symptomatic UTI. Future research should concentrate on risk factors for developing symptomatic UTI in different patient groups. Targeted investigations for specific populations, such as the frail elderly, and patients with neurogenic bladder dysfunction, are still needed.

What is the utility of urodynamics, including ambulatory, and 24 h monitoring, in predicting upper urinary tract damage in neuro-urological patients and other lower urinary tract dysfunction? ICI-RS 2017.

AIMS: This article focuses on how, and if, urodynamics can help to identify which kidneys are in danger of deteriorating in function and also gives recommendations for future research. METHODS: At the International Consultation on Incontinence-Research Society (ICI-RS) in 2017, a multi-disciplinary group presented a literature search of what is known about the utility of Urodynamics, including ambulatory, and 24 h monitoring, in predicting upper urinary tract damage in neuro-urological patients and other lower urinary tract dysfunctions. Wider discussions regarding knowledge gaps, and ideas for future research ensued and are presented in this paper along with a review of the evidence. RESULTS: The current treatment strategy both in congenital and acquired neurogenic bladder is rather aggressive and successful when addressing hazards to kidney function. This article has highlighted uncertainties concerning the use of 40 cmH2O DLPP and even the lower value of 20. The current literature suggests that patients with spina bifida and those with spinal cord injury have a higher risk of developing upper urinary tract damage and kidney function impairment than those with multiple sclerosis. CONCLUSIONS: Future research should focus on less invasive methods to assess the risk to the upper and lower urinary tract such as urine and serum measurements of cytokines that are involved in the pathophysiology of urinary tract impairment.

Non-surgical urologic management of neurogenic bladder after spinal cord injury.

PURPOSE: To review the available data on non-surgical management for neurogenic bladder in patients with spinal cord injury (SCI). Before the introduction of urinary catheters and antibiotics, neurogenic bladder was one of the main culprits for death in those patients with SCI. Currently, the management of neurogenic bladder is focused in improving quality of life and preserving renal function. METHODS: A literature review was performed and therapeutic management for neurogenic bladder was divided in six sections: (1) intermittent bladder catheterization; (2) indwelling catheters; (3) condom catheter drainage; (4) reflex voiding and bladder expression with Valsalva or Credé; (5) oral drug therapy of the spinal cord injured bladder; and (6) botulinum neurotoxin (BoNT). RESULTS: Intermittent catheterization is recommended as the preferable method for management of neurogenic bladder in patients with SCI based on limited high-quality data. However, this may not be feasible or available to all and other alternative options include condom catheter drainage or indwelling catheters such as urethral catheters or suprapubic tube, reflex voiding, and bladder expression with Valsalva or Credé. Non-invasive medical therapies are the key to improve incontinence, urodynamic parameters, and quality of life in this population. Botulinum neurotoxin has revolutionized the management of neurogenic bladder in the last two decades decreasing the need for reconstruction or diversion. CONCLUSION: The Joint SIU-ICUD (Société Internationale d'Urologie) (International Consultation on Urological Diseases) International Consultation reviewed the available presented data and provided specific conclusions and recommendations for each non-surgical urologic method to address neurogenic bladder after SCI.

An initial study on the effect of functional electrical stimulation in erectile dysfunction: a randomized controlled trial.

Erectile dysfunction (ED) affects approximately 150 million men worldwide. Functional electrical stimulation (FES) therapy has shown a high regenerative capacity for smooth muscle cells and, therefore, is being increasingly adopted. FES can be a beneficial treatment option when the cause of ED is related to degeneration of cavernous smooth muscle. To evaluate the impact of FES on erectile function in men with erectile dysfunction. Twenty-two patients with ED participated in this randomized clinical trial. Participants were randomly assigned to two groups: intervention (IG) or control (CG). IG participants underwent FES therapy (50 Hz/500 µs) for a total of 4 weeks, divided into two weekly sessions lasting 15 min each, with intensity lower than the motor threshold. CG participants were treated with placebo FES and followed the same routine as the IG. Erectile function was assessed by the validated International Index of Erectile Function (IIEF-5) and Erection Hardness Score (EHS), applied before and after treatment, and quality of life, by the WHOQOL questionnaire. Statistically significant differences in IIEF-5 and EHS were found between the IG and CG after treatment (p < 0.05), as well as a within-group difference in the IG when comparing the post-treatment periods (p < 0.0001) The WHOQOL revealed a significant difference between CG and IG after treatment (p < 0.05), as well as a within-group difference in the IG after treatment (p < 0.0001), except in the Environment domain, in which there was no difference between the pre- and post-treatment periods (50.9 ± 2.8 pre vs. 52.3 ± 3.1 post). This trial showed that FES therapy may improve erectile function and quality of life in men with ED.

The effects of Pilates method on pelvic floor muscle strength in patients with post-prostatectomy urinary incontinence: A randomized clinical trial.

AIMS: To assess the effects of a Pilates exercise program compared to conventional pelvic floor muscle training (PFMT) protocol on pelvic floor muscle strength (PFMS) in patients with post-prostatectomy urinary incontinence. METHODS: Patients were randomized into three treatment groups (G1: Pilates, G2: electrical stimulation combined with PFMT, and G3: control group). Duration of therapy was 10 weeks. Baseline assessment included the 24 h pad-test and the ICI-Q questionnaire. PFMS was measured using a manometric perineometry device at baseline and 4 months after radical prostatectomy (RP). The level of significance was P < 0.05. RESULTS: One hundred twenty three patients were randomized and 104 patients completed the study protocol (G1: n = 34; G2: n = 35; G3: n = 35). Post-treatment assessment showed statistically significant improvements in maximum strength in G2, increased endurance in G1 and G2, and increment of muscle power in all three groups (P < 0.05). However, there were no significant differences in the mean changes of maximum strength, endurance, and muscle power between groups after treatment (P > 0.05). G1 and G2 achieved a higher number of fully continent patients than G3 (P < 0.05). At the end of treatment, 59% of patients in G1, 54% in G2, and 26% in G3 were continent (no pads/day). CONCLUSIONS: Improvements in PFMS parameters were distinct among active treatment groups versus controls, but did not predict recovery of urinary continence at final assessment. The Pilates method promoted similar outcomes in the proportion of fully continent patients when compared to conventional PFMT 4 months after RP.

Collagen content in the bladder of men with LUTS undergoing open prostatectomy: A pilot study.

AIMS: To evaluate the collagen content in the bladder wall of men undergoing open prostate surgery. METHODS: From July 2014 to August 2016, men aged ≥ 50 years, presenting LUTS and undergoing open prostate surgery due to benign prostatic enlargement (BPE) or prostate cancer were prospectively enrolled. Preoperative assessment included validated questionnaires (IPSS and OAB-V8), lower urinary tract ultrasound, and urodynamics. Bladder biopsies were obtained during open prostatectomy for determination of collagen content (sirius red-picric acid stain; polarized light analysis). Collagen to smooth muscle ratio (C/M) in the detrusor was measured and its relationship with preoperative parameters was investigated. The level of significance was P < 0.05. RESULTS: Thirty-eight consecutive patients were included in this pilot study. Mean age was 66.36 ± 6.44 years and mean IPSS was 11.05 ± 8.72 points. Men diagnosed with diabetes mellitus (DM2) were found to have higher collagen content in the bladder wall when compared to non-diabetic patients (17.71 ± 6.82% vs 12.46 ± 5.2%, respectively; P = 0.024). Reduced bladder compliance was also marker for higher collagen content (P = 0.042). Bladder outlet obstruction (BOO) was not a predictor of increased collagen deposition in the bladder wall (P = 0.75). Patients with PVR ≥ 200 mL showed a higher collagen to smooth muscle ratio in the bladder wall (P = 0.036). CONCLUSIONS: DM2 and urodynamic parameters, such as increased PVR and reduced bladder compliance, were associated with higher collagen content in the bladder wall of men with LUTS.