Is it Possible to Regenerate the Underactive Detrusor? Part 2 Electrical Stimulation Therapies, Treatment of Bladder Outlet Obstruction, Constipation, and Pelvic Floor Disorders ICI-RS 2024.

INTRODUCTION: Detrusor muscle weakness is commonly noted on urodynamics in patients with refractory voiding difficulty. No clinical therapy has been proven to augment the strength of a detrusor contraction. METHODS: This subject was discussed at a think-tank at the International Consultation on Incontinence-Research Society (ICI-RS) held in Bristol, June 2024. The discussions of the think-tank are being published in two parts. This second part discusses the role of electrical stimulation therapies, treatment of bladder outlet obstruction, constipation, and pelvic floor disorders, in the enhancement of strength of a detrusor contraction. RESULTS: Electrical stimulation therapies, specifically sacral neuromodulation, have long been used in the salvage of patients with refractory nonobstructive voiding dysfunction. Clinical improvements can be noted in men following bladder outlet resistance reduction surgery especially, though not limited to those with demonstrable obstruction. Some patients may also show improvement with pelvic floor relaxation therapies and constipation care. However, there is a lack of high-quality urodynamic data to demonstrate an improvement in the strength of a detrusor contraction with these therapies. The think-tank recommends standards for future clinical studies examining treatments aimed at improving an underactive detrusor. CONCLUSIONS: Studies need to examine whether clinical improvement following treatment of patients with an underactive detrusor is associated with improvement in strength of the detrusor contraction. New therapeutic options should apply specified standards for assessing and reporting the impact on detrusor contraction.

Is Our Limited Understanding of the Effects of Nerve Stimulation Resulting in Poor Outcomes and the Need for Better "Rescue Programming" in SNM and PTNS, and Lost Opportunities for New Sites of Stimulation? ICI-RS 2024.

AIMS: Sacral neuromodulation (SNM) and percutaneous tibial nerve stimulation (PTNS) are strongly recommended by international guidelines bodies for complex lower urinary tract dysfunctions. However, treatment failure and the need for rescue programming still represent a significant need for long-term follow-up. This review aimed to describe current strategies and future directions in patients undergoing such therapies. MATERIALS AND METHODS: This is a consensus report of a Think Tank discussed at the Annual Meeting of the International Consultation on Incontinence - Research Society (ICI-RS), June 6-8, 2024 (Bristol, UK): "Is our limited understanding of the effects of nerve stimulation resulting in poor outcomes and the need for better 'rescue programming' in SNM and PTNS, and lost opportunities for new sites of stimulation?" RESULTS: Rescue programming is important from two different perspectives: to improve patient outcomes and to enhance device longevity (for implantable devices). Standard SNM parameters have remained unchanged since its inception for the treatment of OAB, nonobstructive urinary retention, and voiding dysfunction. SNM rescue programming includes intermittent stimulation (cycling on), increased frequency and changes in pulse width (PW). The effect of PW setting on SNM outcomes remains unclear. Monopolar configurations stimulate more motor nerve fibers at lower stimulation voltage; hence, this could be an option in patients who failed bipolar stimulation in the long term. Unfortunately, there is little evidence for rescue programming for PTNS. However, the development of implantable devices for intermittent stimulation of the tibial nerve may increase long-term adherence to therapy and increase interest in alternative programming. There has been recent promising neurostimulation targeting the pudendal nerve (PNS), especially in BPS/IC. More recently, preliminary data addressed the benefits of high-frequency bilateral pudendal nerve block for DESD and adaptive PNS on both urgency and stress UI in women. CONCLUSION: The exploration of rescue programming and new stimulation sites remains underutilized, and there are opportunities that could potentially expand the therapeutic applications of nerve stimulation. By broadening the range of target sites, clinicians may be able to tailor treatments according to individual patient needs and underlying conditions, thereby improving overall outcomes. However, further studies are still needed to increase the level of evidence, potentially allowing for an individualized treatment both in patients who are candidates for electrostimulation and in those who have already received surgical implants but seek a better outcome.

Is It Possible to Regenerate the Underactive Detrusor? Part 1 Molecular and Stem Cell Therapies Targeting the Urinary Bladder and Neural Axis ICI-RS 2024.

INTRODUCTION: Detrusor muscle weakness is commonly noted on urodynamics in patients with refractory voiding difficulty. No approved therapies have been proven to augment the strength of a detrusor voiding contraction. METHODS: This subject was discussed by a think-tank at the International Consultation on Incontinence- Research Society (ICI-RS) meeting held in Bristol, June 2024. The discussions of the think-tank are being published in two parts. This first part discusses molecular and stem cell therapies targeting the urinary bladder and the neural axis. RESULTS: Senescence of the urothelium and extracellular ATP acting through P2X3 receptors might be important in detrusor underactivity. Several molecules such as parasympathomimetics, acotiamide, ASP8302, neurokinin-2 agonists have been explored but none has shown unequivocal clinical benefit. Different stem cell therapy approaches have been used, chiefly in neurogenic dysfunction, with some studies showing benefit. Molecular targets for the neural axis have included TRPV-4, Bombesin, and serotoninergic receptors and TAC-302 which induces neurite growth. CONCLUSIONS: Several options are currently being pursued in the search for an elusive molecular or stem cell option for enhancing the power of the detrusor muscle. These encompass a wide range of approaches that target each aspect of the contraction mechanism including the urothelium of bladder and urethra, myocyte, and neural pathways. While none of these have shown unequivocal clinical utility, some appear promising. Lessons from other fields of medicine might prove instructive. CLINICAL TRIAL REGISTRATION: Not necessary. Not a clinical trial.

Developing new ways to assess neural control of pelvic organ function in spinal conditions: ICI-RS 2023.

OBJECTIVES: Several central nervous system (CNS) centers affect muscle groups of the lower urinary tract (LUT) and anorectal tract (ART) via autonomic and somatic pathways, working in different modes (storage or expulsion). Hence spinal cord dysfunction can affect the LUT and ART by several possible mechanisms. METHODS: This review reports the discussions of a workshop at the 2023 meeting of the International Consultation on Incontinence Research Society, which reviewed uncertainties and research priorities of spinal dysfunction. RESULTS: Discussion focussed on the levator ani nerve, mechanisms underpinning sensory function and sensation, functional imaging, dyssynergia, and experimental models. The following key research questions were identified. (1) Clinically, how can we evaluate the levator ani muscle to support assessment and identify prognosis for effective treatment selection? (2) How can we reliably measure levator ani tone? (3) How can we evaluate sensory information and sensation for the LUT and the ART? (4) What is the role of functional CNS imaging in development of scientific insights and clinical evaluation? (5) What is the relationship of detrusor sphincter dyssynergia to renal failure? CONCLUSIONS: Spinal cord dysfunction can fundamentally disrupt LUT and ART function, with considerable clinical impact. The evaluation needs to reflect the full scope of potential problems, and new clinical and diagnostic approaches are needed, for prognosis and treatment. The preclinical science evaluating spinal cord function in both LUT and ART storage and elimination remains a major priority, even though it is a challenging experimental context. Without this underpinning evidence, development of new clinical evidence may be held back.

Tradução para o português An International Continence Society (ICS) report on the terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD).

INTRODUÇÃO: A terminologia para disfunção neurogênica do trato urinário inferior em adultos (DNTUIA) deve ser definida e organizada com base clínica em um relatório de consenso. MÉTODOS: Este relatório foi criado por um Grupo de Trabalho sob o endosso e diretrizes do Standardization Steering Committee (SSC) da International Continence Society (ICS), auxiliado em intervalos por julgadores externos. Todas as definições relevantes para DNTUIA foram atualizadas com base em pesquisas nos últimos 14 anos. Um extenso processo de 18 rodadas de revisão interna e externa foi realizado para examinar exaustivamente cada definição, com tomada de decisão pela opinião coletiva (consenso). RESULTADOS: O Relatório de Terminologia para a DNTUIA, englobando 97 definições (42 novas e oito modificadas), foi desenvolvido. Este relatório é clinicamente baseado nos diagnósticos definidos mais comuns. Clareza e facilidade de uso têm sido os principais objetivos para torná-lo interpretável por profissionais e pessoas em treinamento em todos os diferentes grupos envolvidos não só na disfunção do trato urinário inferior, mas também em muitas outras especialidades médicas. CONCLUSÃO: Baseado no consenso, o Relatório de Terminologia para a DNTUIA foi produzido para auxiliar na pesquisa e na prática clínica.

Tradução para o português An International Continence Society (ICS) report on the terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD)

RESUMO Introdução A terminologia para disfunção neurogênica do trato urinário inferior em adultos (DNTUIA) deve ser definida e organizada com base clínica em um relatório de consenso. Métodos Este relatório foi criado por um Grupo de Trabalho sob o endosso e diretrizes do Standardization Steering Committee (SSC) da International Continence Society (ICS), auxiliado em intervalos por julgadores externos. Todas as definições relevantes para DNTUIA foram atualizadas com base em pesquisas nos últimos 14 anos. Um extenso processo de 18 rodadas de revisão interna e externa foi realizado para examinar exaustivamente cada definição, com tomada de decisão pela opinião coletiva (consenso). Resultados O Relatório de Terminologia para a DNTUIA, englobando 97 definições (42 novas e oito modificadas), foi desenvolvido. Este relatório é clinicamente baseado nos diagnósticos definidos mais comuns. Clareza e facilidade de uso têm sido os principais objetivos para torná-lo interpretável por profissionais e pessoas em treinamento em todos os diferentes grupos envolvidos não só na disfunção do trato urinário inferior, mas também em muitas outras especialidades médicas. Conclusão Baseado no consenso, o Relatório de Terminologia para a DNTUIA foi produzido para auxiliar na pesquisa e na prática clínica.

Long-term outcomes of sacral neuromodulation for lower urinary tract dysfunction: A 23-year experience.

AIMS: To evaluate the long-term outcomes of sacral neuromodulation (SNM), and patient characteristics that may predict long-term success or complications. METHODS: A single-center retrospective cohort study was performed of all patients who underwent SNM testing and implantation. Outcome results, resolution of symptoms, and device removal were reported. Multivariable logistic regression was used to identify predictors of success. Cox proportional hazards model was used to identify predictors for device removal. RESULTS: Four hundred and thrity four patients underwent SNM test phase of which 241 (median age 48.0 years, 91.7% [221/241] female) had device implantation and were followed up for median [range] time of 4.0 (3 months-20.5 years) years. Multivariable logistic regression showed that male gender (odds ratio: 0.314; 95% confidence interval: 0.164-0.601, p = .0005) was independently associated with decreased peripheral nerve evaluation success. At final follow-up for patients who originally had device implantation, median (interquartile range) percent of symptoms resolution of all patients was 60.0% (0%-90%) and 69.3% (167/241) had SNM successful outcomes. Cox proportional hazards model showed no difference for time to SNM device removal with respect to patient age, gender, or diagnosis. 69.3% (167/241) patients had at least 1 surgical re-intervention. The most common reason at first surgical re-intervention was lead change only (26.3%, 44/167). CONCLUSION: SNM is a minimally invasive procedure with good long-term success rates. There is a high revision rate but overall, SNM has a good safety profile and excellent long-term outcomes.

The history of sacral neuromodulation in Canada.

Sacral neuromodulation (SNM) has been used for the past 30 years, with significant improvements in the implantation technique and technology over the last several years. Canadian centers were involved with this technique from the very beginning by participating in several multicenter clinical trials and engaging in basic and clinical research. Presently, six Canadian centers continue to have SNM implantation programs.

What developments are needed to achieve less-invasive urodynamics? ICI-RS 2019.

AIMS: To assess the state of technologies for urodynamics that are less invasive than standard cystometry and pressure-flow studies and to suggest areas needing research to improve this. METHODS: A summary of a Think Tank debate held at the 2019 meeting of the International Consultation on Incontinence Research Society is provided, with subsequent analysis by the authors. Less-invasive techniques were summarized, classified by method, and possible developments considered. Discussions and recommendations were summarized by the co-chairs and edited into the form of this paper by all authors. RESULTS: There is a full spectrum of technologies available for less-invasive assessment, ranging from simple uroflowmetry through imaging techniques to emerging complex technologies. Less-invasive diagnostics will not necessarily need to replace diagnosis by, or even provide the same level of diagnostic accuracy as, invasive urodynamics. Rather than aiming for a technique that is merely less invasive, the priority is to develop methods that are either as accurate as current invasive methods, or spare patients from the necessity of invasive methods by improving early triaging. CONCLUSIONS: Technologies offering less-invasive urodynamic measurement of specific elements of function can be potentially beneficial. Less-invasive techniques may sometimes be useful as an adjunct to invasive urodynamics. The potential for current less-invasive tests to completely replace invasive urodynamic testing is considered, however, to be low. Less-invasive techniques must, therefore, be tested as screening/triaging tools, with the aim to spare some patients from invasive urodynamics early in the treatment pathway.

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.

Conception and development of Urinary Tract Infection indicators to advance the quality of spinal cord injury rehabilitation: SCI-High Project.

Context: Urinary tract infections (UTI) are the most frequent secondary health condition following spinal cord injury or disease (SCI/D) that adversely impact overall health and quality of life, and often result in rehabilitation service interruptions, emergency department visits, and urinary sepsis. Methods: Experts in Urohealth and/or UTI recognition and management and the SCI-High Project Team used a combination of evidence synthesis and consensus methods for developing the UTI indicators. A systematic search and a Driver diagram analysis were applied to identify key factors influencing UTI. This Driver diagram guided the UTI Working Group when defining the construct, specifying the aim for the UTI SCI/D quality indicators, and developing the UTI diagnostic checklist and fever definition. Results: The structure indicator was the proportion of patients with a health care professional (i.e. family physician or urologist) able to follow-up with the patient regarding urine culture and sensitivity results within 48-72 h of collection. The Working Group knowingly adopted a single checklist for UTI diagnosis, recognizing the stark contrast in the complexity of diagnosis in acute versus community settings. The process indicator is the proportion of SCI/D rehabilitation inpatients with UTI as defined by the UTI diagnostic checklist. The outcome indicator is the proportion of SCI/D rehabilitation inpatients with inappropriate antibiotic prescription. Conclusion: UTI can be diagnosed using the developed symptoms and signs checklist. These structure, process, and outcome quality indicators will ultimately reduce inappropriate antibiotic therapy for UTI and the rising incidence of antibiotic resistance among community-dwelling individuals with chronic SCI/D.

Canadian consensus algorithm for erectile rehabilitation following prostate cancer treatment.

INTRODUCTION: The present descriptive analysis carried out by a pan-Canadian panel of expert healthcare practitioners (HCPs) summarizes best practices for erectile rehabilitation following prostate cancer (PCa) treatment. This algorithm was designed to support an online sexual health and rehabilitation e-clinic (SHARe-Clinic), which provides biomedical guidance and supportive care to Canadian men recovering from PCa treatment. The implications of the algorithm may be used inform clinical practice in community settings. METHODS: Men's sexual health experts convened for the TrueNTH Sexual Health and Rehabilitation Initiative Consensus Meeting to address concerns regarding erectile dysfunction (ED) therapy and management following treatment for PCa. The meeting brought together experts from across Canada for a discussion of current practices, latest evidence-based literature review, and patient interviews. RESULTS: An algorithm for ED treatment following PCa treatment is presented that accounts for treatment received (surgery or radiation), degree of nerve-sparing, and level of pro-erectile treatment invasiveness based on patient and partner values. This algorithm provides an approach from both a biomedical and psychosocial focus that is tailored to the patient/partner presentation. Regular sexual activity is recommended, and the importance of partner involvement in the treatment decision-making process is highlighted, including the management of partner sexual concerns. CONCLUSIONS: The algorithm proposed by expert consensus considers important factors like the type of PCa treatment, the timeline of erectile recovery, and patient values, with the goal of becoming a nationwide standard for erectile rehabilitation following PCa treatment.

Catheterization for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: A systematic review. A report from the Neuro-Urology Promotion Committee of the International Continence Society (ICS).

AIM: To systematically assess all available evidence on efficacy and safety of catheterization for treating neurogenic lower urinary tract dysfunction (NLUTD) in patients with multiple sclerosis (MS). METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of Embase, Medline, Scopus, Cochrane register (last search March 3, 2018) and by screening of reference lists and reviews. RESULTS: After screening 7'015 articles, we included four studies (one prospective and two retrospective cohort studies, one retrospective cross-sectional study), in which a total of 445 patients were enrolled. No randomized controlled trial was available. Catheterization substantially increased quality of life, post void residual, and incontinence episodes in all included studies. Pooling of data for meta-analysis was not possible due to the heterogeneity of reported outcomes. Adverse events were reported in two studies only. Risk of bias and confounding was intermediate. CONCLUSIONS: Preliminary data suggests beneficial effects of catheterization on the urological outcome in patients with MS. However, although intermittent and indwelling catheterization is used frequently in daily clinical practice in the MS population, the evidence base is very limited and well-designed, properly sampled, and powered studies are urgently needed.

International Continence Society best practice statement for use of sacral neuromodulation.

AIMS: Sacral neuromodulation (SNM) is an accepted therapy for a variety of conditions. However, despite over 20 years of experience, it remains a specialized procedure with a number of subtleties. Here we present the recommendations issued from the International Continence Society (ICS) SNM Consensus Panel. METHODS: Under the auspices of the ICS, eight urologists, three colorectal surgeons and two urogynecologists, covering a wide breadth of geographic and specialty interest representation, met in January 2017 to discuss best practices for neuromodulation. Suggestions for statements were submitted in advance and specific topics were assigned to committee members, who prepared and presented supporting data to the group, at which time each topic was discussed in depth. Best practice statements were formulated based on available data. This document was then circulated to multiple external reviewers after which final edits were made and approved by the group. RESULTS: The present recommendations, based on the most relevant data available in the literature, as well as expert opinion, address a variety of specific and at times problematic issues associated with SNM. These include the use of SNM for a variety of underlying conditions, need for pre-procedural testing, use of staged versus single-stage procedures, screening for success during the trial phase, ideal anesthesia, device implantation, post-procedural management, trouble-shooting loss of device function, and future directions for research. CONCLUSIONS: These guidelines undoubtedly constitute a reference document, which will help urologists, gynecologists, and colorectal surgeons optimize their use of SNM for refractory urinary urgency and frequency, UUI, NOR, and FI.

Neurological lower urinary tract dysfunction essential terminology.

AIMS: To introduce basic concepts and definitions in the International Continence Society (ICS) Standardisation of Terminology in adult Neurogenic Lower Urinary Tract Dysfunction (NLUTD). METHODS: Fundamental terminology in the ICS Standardisation of Terminology of Adult NLUTD was identified and summarized. RESULTS: NLUTD is often associated with impairment of cognitive, motor, sensory, and/or autonomic functions. Lesions are categorized into suprapontine, pontine/suprasacral spinal, sacral spinal, cauda equina/peripheral nerve, or mixed lesions. People affected with neurological disease are also at risk of the conditions seen in the general population, such as benign prostate enlargement. Symptoms of NLUTD include alterations in bladder or urethral sensation and incontinence. Loss of urine can result from incontinence, involuntary passing of urine and factors that impair toilet use, incorporating problems such as impaired cognition urinary incontinence, impaired mobility urinary incontinence, and voiding dysregulation. Signs may be discerned by physical examination and recording of a frequency volume chart or bladder diary. Urodynamic observations during filling cystometry may include altered sensations, neurogenic detrusor overactivity, and reduced bladder compliance. During pressure flow studies, there may be detrusor underactivity or bladder outlet obstruction (BOO). BOO may be caused by various forms poorly co-ordinated muscle activity in the bladder outlet. Symptoms, signs, and urodynamic observations may be useful in diagnosing the presence and specific location of neurological impairment. CONCLUSION: The review provides a succinct summary of symptoms, signs, and urodynamic observations as set out in the ICS Standard on Adult NLUTD.

An International Continence Society (ICS) report on the terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD).

INTRODUCTION: The terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD) should be defined and organized in a clinically based consensus Report. METHODS: This Report has been created by a Working Group under the auspices and guidelines of the International Continence Society (ICS) Standardization Steering Committee (SSC) assisted at intervals by external referees. All relevant definitions for ANLUTD were updated on the basis of research over the last 14 years. An extensive process of 18 rounds of internal and external review was involved to exhaustively examine each definition, with decision-making by collective opinion (consensus). RESULTS: A Terminology Report for ANLUTD, encompassing 97 definitions (42 NEW and 8 CHANGED, has been developed. It is clinically based with the most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in all the different groups involved not only in lower urinary tract dysfunction but additionally in many other medical specialties. CONCLUSION: A consensus-based Terminology Report for ANLUTD has been produced to aid clinical practice and research.

Do we assess urethral function adequately in LUTD and NLUTD? ICI-RS 2015.

INTRODUCTION: Urethral function, as well as anatomy, play a significant role in voiding reflex and abnormalities in one or both contribute to the pathophysiology of Lower Urinary Tract Dysfunction (LUTD). We have several diagnostic tools to assess the urethral function or dysfunction but the question remains, are these adequate? METHODS: This is a report of the proceedings of Think Tank P1: 'Do we assess urethral function adequately in LUTD and NLUTD?' from the annual International Consultation on Incontinence-Research Society, which took place September 22-24, 2014 in Bristol, UK. RESULTS: We have collected and discussed, as a committee, the evidence with regard to the urethra and the available relevant methods of testing urethral function, with the emphasis on female and male voiding dysfunction. We looked into previous research and clinical studies and compiled summaries of pertinent testing related to urethral function. The discussion has focused on clinical applications and the desirability of further development of functional tests and analyses in this field. CONCLUSIONS: There are limitations to most of the urethral function tests. Future perspectives and research should concentrate on further development of functional testing and imaging techniques with emphasis on standardization and clinical application of these tests. Neurourol. Urodynam. 36:935-942, 2017. © 2017 Wiley Periodicals, Inc.