[Invasive neurostimulation in neuro-urology: state of the art]. / Invasive Neurostimulation in der Neuro-Urologie: State of the Art.

Modulation or stimulation of the nerves supplying the lower urinary tract is a possible treatment option for dysfunction of the lower urinary tract, pelvic floor and rectum if conservative or minimally invasive treatment approaches fail. This overview shows the possibilities and limitations of sacral neuromodulation, sacral deafferentation with sacral anterior root stimulation and conus deafferentation.Sacral neuromodulation (SNM) is a procedure for the treatment of refractory pelvic floor dysfunction of various origins (idiopathic, neurogenic or post-operative), such as overactive bladder, non-obstructive retention and faecal incontinence. A particular advantage of SNM is the possibility of prior test stimulation with a high prognostic value. The procedure is minimally invasive, reversible and associated with relatively low morbidity rates.Following the introduction of MRI-compatible SNM systems, there has been renewed interest in the treatment of neurogenic bladder dysfunction. A recent meta-analysis reports similar success rates as in the idiopathic patient population.Sacral deafferentation with implantation of a sacral anterior root stimulator (SARS/SDAF) is an excellent therapeutic option for patients with spinal cord injury, which can significantly improve the quality of life of those affected and, in addition to treating neurogenic lower urinary tract dysfunction, can also have a positive effect on neurogenic bowel dysfunction, neurogenic sexual dysfunction or autonomic dysreflexia. If conservative or minimally invasive treatment fails, it is crucial for the success of this procedure to consider SDAF/SARS at an early stage in order to avoid irreversible organic damage.Conus deafferentation (KDAF) is a less invasive surgical treatment option for patients with spinal cord injury for whom sacral deafferentation would be indicated but who would not benefit from the simultaneous implantation of a sacral anterior root stimulator. In principle, these patients also have the option of being subsequently treated with an extradural implant and thus utilising the advantages of anterior root stimulation. Indications for KDAF are autonomic dysreflexia, therapy-refractory detrusor overactivity, recurrent urinary tract infections, urinary incontinence and spasticity triggered by detrusor overactivity. With KDAF, we have a safe and efficient procedure with great potential for improving the spectrum of paraplegiological and neuro-urological treatment.

[Therapeutic value of neuromodulation in women]. / Stellenwert der Neuromodulation bei der Frau.

BACKGROUND: Neuromodulative treatment for the treatment of overactive bladder has been used in clinical practice since its introduction in the early 1980s. OBJECTIVES: Description and update of the various neuromodulative techniques (tibial nerve stimulation, sacral and pudendal neuromodulation), presentation of their effectiveness and safety, and evaluation of their evidence for clinical practice. MATERIALS AND METHODS: Literature search in PubMed and Embase, inclusion of studies according to the following criteria: evidence level, timeliness, length of follow-up and number of female patients according to the author's preference. RESULTS: The efficacy and safety of both percutaneous tibial nerve stimulation (PTNS) and sacral neuromodulation (SNM) has been proven by studies with an evidence level of 1. Long-term data of up to 20 years are available for SNM, while long-term data for PTNS are limited. Permanent implants for tibial nerve stimulation are promising new developments. Pudendal neuromodulation (PNM) is suitable for more complex indications but is surgically more challenging. CONCLUSIONS: Both PTNS and SNM are suitable for broad application in clinical practice. PTNS can be offered as an alternative to pharmacotherapy, while SNM provides the most convincing clinical data of all neuromodulative therapies.

Supratrigonal cystectomy and augmentation cystoplasty with ileum or ileocecum in the treatment of ulcerative interstitial cystitis/bladder pain syndrome: a 14-year follow-up.

INTRODUCTION AND HYPOTHESIS: This study analyzes the long-term results of supratrigonal cystectomy and augmentation cystoplasty in patients with severe ulcerative interstitial cystitis/bladder pain syndrome (IC/BPS) and reduced bladder capacity. METHODS: Outcome data were retrospectively and prospectively collected and analyzed in women who underwent supratrigonal cystectomy and augmentation cystoplasty for ulcerative IC/BPS at Muenster University Hospital between 1991 and 2006. We used cross-tabulation and Pearson's Chi-squared test to examine how outcome is influenced by age, preoperative functional bladder volume, and choice of augmentation material. RESULTS: After a median 171-month follow-up, analysis could be done in 26 of 27 patients. Persistent pain necessitated early revision in 2 patients (7.7%). Mean postoperative O'Leary Sant IC Score was 12.7 in the prospectively questioned patients. Responses to Patient Global Impression of Improvement (PGI-I) were: "very much better" in 15 cases (65.2%) and "much better" in 7 (30.4%). Twelve patients (52.2%) emptied their augmented bladder voluntarily, whereas 7 (32%) needed intermittent self-catheterization (ISC). The rate of patients requiring ISC tended to be lower when detubularized ileocecal bowel was used. All 5 patients (19.2%) with late relapse of ulcerative IC/BPS needed ISC. CONCLUSIONS: Severe ulcerative IC/BPS can be curatively treated in some patients by supratrigonal cystectomy and augmentation, which is associated with a high satisfaction rate and few long-term complications even over a very long follow-up. In our analysis, the need for ISC is a risk factor for late relapse, although ileocecal augmentation could increase the proportion of patients with sufficient voluntary micturition.

Systematic Literature Review and Meta-Analysis of Sacral Neuromodulation (SNM) in Patients with Neurogenic Lower Urinary Tract Dysfunction (nLUTD): Over 20 Years' Experience and Future Directions.

INTRODUCTION: Sacral neuromodulation (SNM) has been used in carefully selected patients with neurogenic lower urinary tract dysfunctions (nLUTD) for over two decades. METHODS: The aim of the current work was to perform a systematic literature review and meta-analysis of studies reporting the safety and effectiveness of SNM in patients with nLUTD (neurogenic detrusor overactivity, non-obstructive urinary retention, or a combination of both). For this purpose a systematic literature research was conducted using Embase (OvidSP), MEDLINE (OvidSP), MEDLINE In-Process Citations & Daily Update (OvidSP), MEDLINE (OvidSP) e-Pub ahead of print, Cochrane Central Register of Controlled Trials (CENTRAL), NIH Clinicaltrials.gov, and WHO International Clinical Trials Registry Platform (ICTRP) between 1998 and March 2020, supplemented by a hand search. RESULTS: Forty-seven studies were included in the systematic literature review. Twenty-one studies comprising a total of 887 patients were included in the meta-analysis of test SNM. The pooled success rate of SNM test stimulation was 66.2% (95% CI 56.9-74.4). Depending on neurogenic conditions test success rates varied greatly. Twenty-four studies with a total of 428 patients were included in the meta-analysis of permanent SNM. The success rate of pooled permanent SNM was 84.2% (95% CI 77.8-89.0). Among the identified studies, the most common adverse events (AEs) were loss of effectiveness, infection, pain at implant site, and lead migration with AE rates of 4.7%, 3.6%, 3.2%, and 3.2%, respectively. Limitations entail lower level of evidence (Oxford classification 3-4) of included studies, significant risk of bias, small sample sizes in some studies, the inclusion of retrospective case series, substantial between-study heterogeneity, heterogeneous patient populations, insufficient disease classification, and variations in terms of outcome parameters as well as techniques. Furthermore, long-term data are limited. CONCLUSION: This meta-analysis supports not only the benefits of permanent SNM for various nLUTDs but also high overall success rates, similar to idiopathic patients. Current data of the analyzed studies showed that SNM is safe for these patients. However, more vigorous studies and/or registries are needed before definitive conclusions can be drawn.

Efficacy of pentosan polysulfate for the treatment of interstitial cystitis/bladder pain syndrome: results of a systematic review of randomized controlled trials.

Background: Among the numerous therapeutic approaches used in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) few have been assessed with a sufficient level of evidence. The safety and efficacy of pentosan polysulfate sodium (PPS) has been shown in several open-label and comparative clinical trials with different populations including two meta-analyses. In the context of the approval procedure of PPS for the treatment of IC/BPS by the European Medicines Agency we updated the findings of the previous analyses by incorporating the results of the latest studies.Method: Relevant studies based on a systematic review of PubMed/Medline and the Cochrane Library in June 2018 were identified. For completeness control, clinical trial registries were also searched. Only randomized, placebo-controlled clinical trials providing sufficient information to estimate at least one relevant effect size measure to compare the efficacy of PPS versus placebo were included in the analysis.Results: Of the studies identified in the literature search, six randomized placebo-controlled studies met the pre-defined eligibility criteria. Analyses showed no indication of heterogeneity or publication bias. Treatment with PPS led to a statistically significant improvement in the patient's overall response assessment (p < .001), pain (p = .009) and urgency (p = .005).Conclusions: Our meta-analyses confirmed the results of preceding meta-analyses showing that PPS is efficacious compared to placebo in the treatment of bladder pain, urinary urgency and frequency of micturition and thus an evident option for the treatment of IC/BPS symptoms.

Botulinumtoxin for bladder disorders.

An overactive neurogenic detrusor and an non-neurogenic overactive bladder both exhibit symptoms such as urgency and frequency, both with and without urinary incontinence, and are often accompanied by nocturia. OnabotulinumtoxinA-Detrusorinjection has become well established as a second line therapy in cases where anticholinergic medication has failed. The procedure can be performed under general or local anesthesia, in both in- and outpatient settings. The side effects of the procedure are primarily urinary tract infections and - especially in neurogenic bladder patients - urinary retention. This article focuses on the approved indications and summarizes the current scientific data.

[Sacral neuromodulation for refractory overactive bladder]. / Sakrale Neuromodulation bei refraktärer überaktiver Blase.

Sacral neuromodulation (SNM) is a minimally invasive, established treatment modality for overactive bladder (OAB) as well as for other pelvic functional disorders, such as non-obstructive urinary retention and fecal incontinence. A pacemaker implanted in the upper buttocks delivers mild electrical pulses to the sacral nerves thereby modulating pathological afferent signals from pelvic end organs. The current article conveys the current knowledge on the indications, contraindications, mechanism of action, implantation technique, efficacy and complications of SNM for the treatment refractory OAB.

De novo neurogenic bladder dysfunction after salvage lymph node dissection in patients with nodal recurrence of prostate cancer.

AIMS: To examine the impact of Salvage lymph node dissection (SLND) on bladder function and oncological outcome in hormone naïve patients with nodal recurrence of prostate cancer (PCa) after radical prostatectomy (RP). METHODS: In a prospective study between October 2015 and November 2016, 20 patients underwent transperitoneal SLND for nodal recurrence of PCa after RP at our institution. Standardized urodynamics were performed pre- and postoperatively after 6 weeks, 3, and 6 to 12 months. Prostate-specific antigen (PSA) levels were used to monitor the oncological outcome. Perioperative outcomes encompassed, among others, type of complications after surgery classified to Clavien-Dindo. RESULTS: The proportion of patients with neurogenic bladder dysfunction was postoperative at 6 weeks, 3, and 6 to 12 months 78.5%, 70%, and 45.5%, respectively. Compared to preoperative urodynamics, follow-ups revealed a statistical significant cleavage of bladder wall compliance until six to twelve months after SLND (34.5 vs 22 mL/cmH2 O, P = 0.044). Referring to the oncological outcome all patients experienced a PSA progression, 10 patients (50%) within 11 weeks after surgery. Overall, four patients (20%) suffered from a postoperative complication after SLND, which comprises Clavien grade I-IIIa. CONCLUSIONS: Transperitoneal SLND, as a treatment option for patients with nodal recurrence of PCa after RP reveals additional potential pitfalls than previously reported. Urodynamics reveal a significant impact of SLND on postoperative functional bladder dysfunctions. Therefore, informed consent prior to SLND should include the risk of persistent low compliance bladder.

Urodynamic results, clinical efficacy, and complication rates of sacral intradural deafferentation and sacral anterior root stimulation in patients with neurogenic lower urinary tract dysfunction resulting from complete spinal cord injury.

AIMS: To investigate the outcome and complications of sacral deafferentation (SDAF) and sacral anterior root stimulation (SARS) in patients with neurogenic lower urinary tract dysfunction (NLUTD) resulting from complete spinal cord injury (SCI). METHODS: Retrospective chart analysis of 137 patients who underwent SDAF/SARS at a single institution. Patients were categorized as being at risk of renal damage when the maximum detrusor pressure was >40 cmH2 O or detrusor compliance was <20 ml/cmH2 O. RESULTS: After a mean follow-up time of 14.8 ± 5.3 years, SDAF/SARS treatment significantly (P < 0.001) reduced the number of patients suffering from elevated detrusor pressure from 65 to 2, and from low detrusor compliance from 62 to 13, respectively. Mean bladder capacity significantly (P < 0.001) improved from 272.4 ± 143.0 to 475.0 ± 82.7 ml. The mean number of symptomatic UTI also decreased significantly (P < 0.001) from 6.2 ± 4.5 to 2.5 ± 2.6 per year. The number of patients suffering from incontinence had significantly (P < 0.001) decreased from 70 to 44. At the last follow-up visit, 107 (78.1%) patients were still using the stimulator. A total of 84 complications requiring surgical revision were observed. Defects of the stimulator cables or the receiver plate were the most common events (n = 38). The retrospective design pertains to the limitations of the study. CONCLUSIONS: Sacral deafferentation and SARS are an effective treatment option for refractory NLUTD in patients with complete SCI, despite a substantial long-term complication rate.

The 2013 EAU guidelines on chronic pelvic pain: is management of chronic pelvic pain a habit, a philosophy, or a science? 10 years of development.

CONTEXT: Progress in the science of pain has led pain specialists to move away from an organ-centred understanding of pain located in the pelvis to an understanding based on the mechanism of pain and integrating, as far as possible, psychological, social, and sexual dimensions of the problem. This change is reflected in all areas, from taxonomy through treatment. However, deciding what is adequate investigation to rule out treatable disease before moving to this way of engaging with the patient experiencing pain is a complex process, informed by pain expertise as much as by organ-based medical knowledge. OBJECTIVE: To summarise the evolving changes in the management of patients with chronic pelvic pain by referring to the 2012 version of the European Association of Urology (EAU) guidelines on chronic pelvic pain. EVIDENCE ACQUISITION: The working panel highlights some of the most important aspects of the management of patients with chronic pelvic pain emerging in recent years in the context of the EAU guidelines on chronic pelvic pain. The guidelines were completely updated in 2012 based on a systematic review of the literature from online databases from 1995 to 2011. According to this review, levels of evidence and grades of recommendation were added to the text. A full version of the guidelines is available at the EAU office or Web site (www.uroweb.org). EVIDENCE SYNTHESIS: The previously mentioned issues are explored in this paper, which refers throughout to dilemmas for the physician and treatment team as well as to the need to inform and engage the patient in a collaborative empirical approach to pain relief and rehabilitation. These issues are exemplified in two case histories. CONCLUSIONS: Chronic pelvic pain persisting after appropriate treatment requires a different approach focussing on pain. This approach integrates the medical, psychosocial, and sexual elements of care to engage the patient in a collaborative journey towards self-management.

Disability in women suffering from interstitial cystitis/bladder pain syndrome.

OBJECTIVES: To examine a biopsychosocial framework of patient disability in patients suffering from interstitial cystitis/bladder pain syndrome (IC/BPS). To evaluate the impact of psychosocial factors on the relationship between pain and disability within women with IC/BPS. PATIENTS AND METHODS: Women with IC/BPS completed questionnaires including demographics, symptoms and problems (IC Symptom and Problem Indices), pain (McGill Pain Questionnaire), quality of life (Medical Outcomes Study - Short Form 12), disability (Pain Disability Index) and psychosocial variables (Center for Epidemiological Studies - Depression Scale; State Trait Anxiety Inventory; Pain Catastrophizing Scale; Multidimensional Scale of Perceived Social Support). Exploratory and confirmatory factor analyses were employed to determine the factor structure and composition of the measured variables. Structural equation modelling was used to examine model fit and the mediation effect of the psychosocial factors (negative affect, catastrophizing and social support) on impairments and functional disability. RESULTS: Questionnaires completed by 196 women with IC/BPS provided data for the present study. The measurement model showed good fit to the data. Negative affect (P < 0.001) and catastrophizing (P < 0.001) were significant in explaining the relationship between impairments and functional disability, whereas social support did not. CONCLUSIONS: Disability in patients suffering from IC/BPS is partially explained by the impact of negative affect and catastrophizing. As a result of the refractory nature of IC/BPS, patient management within a biopsychosocial framework represents an essential area of investigation. Decreases in negative affect and catastrophizing will probably lead to improvements in pain-related disability.

GAG layer replenishment therapy for chronic forms of cystitis with intravesical glycosaminoglycans--a review.

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

Bladder Pain Syndrome Committee of the International Consultation on Incontinence.

AIMS OF STUDY: The Bladder Pain Syndrome Committee of the International Consultation on Incontinence was assigned the task by the consultation of reviewing the syndrome, formerly known as interstitial cystitis, in a comprehensive fashion. This included the topics of definition, nomenclature, taxonomy, epidemiology, etiology, pathology, diagnosis, symptom scales, outcome assessment, principles of management, specific therapies, and future directions in research. STUDY DESIGN, MATERIALS, METHODS: The emphasis was on new information developed since the last consultation 4 years previously. Where possible, existing evidence was assessed and a level of recommendation was developed according to the Oxford system of classification. RESULTS: The consultation decided to refer to the condition as "bladder pain syndrome" (BPS) because the designation is more descriptive of the clinical condition and better fits standard classification taxonomy. Reasonable definitions of BPS include the definition of the ESSIC European group and a slight modification made at a SUFU sponsored Miami meeting in early 2008. Males or females with pain, pressure, or discomfort that they perceive to be related to the bladder with at least one urinary symptom, such as frequency not obviously related to high fluid intake, or a persistent urge to void should be evaluated for possible BPS. The initial assessment consists of a frequency/volume chart, focused physical examination, urinalysis, and urine culture. Urine cytology and cystoscopy are recommended if clinically indicated. Treatment progresses from conservative management through various oral and intravesical therapies, with most surgical therapies reserved for unresponsive cases. Pain management is critical throughout the treatment process. The consultation believes that the disorder is best viewed as one of a group of chronic pain syndromes, rather than as primarily an inflammatory bladder disorder. Recommendations for future research pathways are suggested.

Intravesical glycosaminoglycan replenishment with chondroitin sulphate in chronic forms of cystitis. A multi-national, multi-centre, prospective observational clinical trial.

Effectiveness, safety, and tolerability of instillation therapy with chondroitin sulphate (CAS 9082-07-9, Gepan instill) was investigated in a non-interventional study. 286 patients with clinically diagnosed chronic forms of cystitis, such as bladder pain syndromelinterstitial cystitis, radiation cystitis, overactive bladder syndrome and chronically-recurring cystitis were included. The course of symptoms was documented over 8 instillations at maximum, covering a period of approximately three months. All main symptoms of chronic cystitis declined consistently and statistically significantly (p < 0.0001). Both daytime and nighttime micturition frequencies as well as the score levels of urgency and pain declined significantly during the course of treatment. The functional bladder capacity as indicated by the volume of first morning voiding increased from 157.9 ml +/- 7.5 to 186.7 ml +/- 6.9 (mean +/- SE; p < 0.0001). The level of urgency decreased from 6.8 +/- 0.1 to 3.4 +/- 0.2 (mean +/- SE; numerical rating scale (11-point box scale); p < 0.0001) and nocturia decreased from 4.0 +/- 0.2 to 2.1 +/- 0.1 times (mean +/- SE; p < 0.0001). Chondroitin sulphate instillation was effective and well tolerated in the therapy of chronic forms of cystitis associated with a possible GAG layer deficit (GAG layer: mainly composed of the glycosaminoglycans chondroitin sulphate, dermatan sulphate and heparan sulphate), but the results need to be confirmed in a controlled study.

What is new in bladder pain syndrome/interstitial cystitis?

PURPOSE OF REVIEW: Bladder pain syndrome/interstitial cystitis is an important and poorly understood disorder. This review highlights current research findings that may be of benefit to the clinician who is responsible for the diagnosis and treatment of patients who suffer from this condition. RECENT FINDINGS: The perspective from which we view bladder pain syndrome/interstitial cystitis is evolving, as is apparent in the literature this year. It is best perceived as one of many chronic pain syndromes, some of which may be related. International efforts aimed at consistent definition and nomenclature are ongoing. Some new treatments have been reported that may be of benefit. SUMMARY: In the age of the internet, it is incumbent upon the clinician to keep up with current ideas, epidemiology, and treatment findings to be able to discuss these with well informed patients who come to clinics around the world. In this review we hope to bring practicing healthcare providers up to date with the literature on bladder pain syndrome/interstitial cystitis, and the implications for their patients.

The prognostic impact of pelvic lymph node metastasis and lymphovascular invasion on bladder cancer.

OBJECTIVES: To present long-term results of a single-center series of patients undergoing bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer and to analyze the impact of pelvic lymph node metastasis and lymphovascular invasion on clinical outcome. METHODS: Between 1986 and 2005 833 patients were treated with bilateral pelvic lymphadenectomy and radical cystectomy at our institution. 614 of them with valid clinical follow-up information and no neoadjuvant therapy could be evaluated. RESULTS: Disease-free and overall survival in the entire cohort was 56.7% and 49.5% at 5 years and 52.4% and 38.2% at 10 years, respectively. 28.1% of all patients had pelvic lymph node metastasis. We found organ-confined tumor stages (or=pT3) and positive pelvic lymph nodes had a significantly shorter overall survival than those without lymph node metastasis (P < 0.0001). In the subgroup of or=pT3) (P = 0.004) and lymphovascular invasion (P = 0.001) were independent prognostic parameters. CONCLUSIONS: According to the present series, survival for patients with