G. Karsenty

Recommendations on the Use of Botulinum Toxin in the Treatment of Lower Urinary Tract Disorders and Pelvic Floor Dysfunctions: A European Consensus Report

CONTEXT The increasing body of evidence and number of potential indications for the use of botulinum neurotoxins (BoNTs) in the lower urinary tract (LUT) underlines the pressing need for evidence-based guidelines. OBJECTIVE A European expert panel consensus conference was convened with the main aim of evaluating the evidence and clinical considerations for the use of BoNTs in the treatment of urologic and pelvic-floor disorders and to propose relevant recommendations. EVIDENCE ACQUISITION The quality of evidence from fully published English-language literature in the PubMed and EMBASE databases was assessed using the European Association of Urology (EAU) levels of evidence (LoE). Recommendations were graded and approved by a unanimous consensus of the panel. EVIDENCE SYNTHESIS The use of botulinum neurotoxin type A (BoNTA) is recommended in the treatment of intractable symptoms of neurogenic detrusor overactivity (NDO) or idiopathic detrusor overactivity (IDO) in adults (grade A). Caution is recommended in IDO because the risk of voiding difficulty and duration of effect have not yet been accurately evaluated. Repeated treatment can be recommended in NDO (grade B). The depth and location for bladder injections should be within the detrusor muscle outside the trigone (grade C). Dosage in children should be determined by body weight, with caution regarding total dose if also being used for treatment of spasticity, and minimum age (grade B). Existing evidence is inconclusive for recommendations in neurogenic detrusor-sphincter dyssynergia, bladder pain syndrome, prostate diseases, and pelvic-floor disorders. The use of BoNTA in the LUT with the current dosages and techniques is considered to be safe overall (grade A). CONCLUSIONS The consensus committee recommends larger placebo-controlled and comparative trials to evaluate the efficacy of single and repeat injections, the duration of effect, the optimal dosage and injection technique, the timing for repeat injection, and the short- and long-term safety of the treatment in LUT and pelvic-floor disorders.

Summary of European Association of Urology (EAU) Guidelines on Neuro-Urology

CONTEXT Most patients with neuro-urological disorders require life-long medical care. The European Association of Urology (EAU) regularly updates guidelines for the diagnosis and treatment of these patients. OBJECTIVE To provide a summary of the 2015 updated EAU Guidelines on Neuro-Urology. EVIDENCE ACQUISITION Structured literature searches in several databases were carried out to update the 2014 guidelines. Levels of evidence and grades of recommendation were assigned where possible. EVIDENCE SYNTHESIS Neurological disorders often cause urinary tract, sexual, and bowel dysfunction. Most neuro-urological patients need life-long care for optimal life expectancy and quality of life. Timely diagnosis and treatment are essential to prevent upper and lower urinary tract deterioration. Clinical assessment should be comprehensive and usually includes a urodynamic investigation. The neuro-urological management must be tailored to the needs of the individual patient and may require a multidisciplinary approach. Sexuality and fertility issues should not be ignored. Numerous conservative and noninvasive possibilities of management are available and should be considered before a surgical approach is chosen. Neuro-urological patients require life-long follow-up and particular attention has to be paid to this aspect of management. CONCLUSIONS The current EAU Guidelines on Neuro-Urology provide an up-to-date overview of the available evidence for adequate diagnosis, treatment, and follow-up of neuro-urological patients. PATIENT SUMMARY Patients with a neurological disorder often suffer from urinary tract, sexual, and bowel dysfunction and life-long care is usually necessary. The update of the EAU Guidelines on Neuro-Urology, summarized in this paper, enables caregivers to provide optimal support to neuro-urological patients. Conservative, noninvasive, or minimally invasive approaches are often possible.

Efficacy and Safety of Low Doses of OnabotulinumtoxinA for the Treatment of Refractory Idiopathic Overactive Bladder: A Multicentre, Double-Blind, Randomised, Placebo-Controlled Dose-Ranging Study

BACKGROUND In the treatment of patients with idiopathic overactive bladder (iOAB), high doses of botulinum toxin type A (BoNTA) were often associated with complications resulting from high postvoid residuals (PVR), leading to clean intermittent catheterisation (CIC) and urinary tract infections (UTI). OBJECTIVE Evaluate the efficacy and tolerability of low doses of onabotulinumtoxinA compared to placebo in patients with iOAB. DESIGN, SETTING, AND PARTICIPANTS Between 2005 and 2009, adults with persistent iOAB were included in a prospective, randomised, double-blind, placebo-controlled comparative trial. INTERVENTION Patients were randomised to undergo a single intradetrusor injection procedure of either placebo or onabotulinumtoxinA (50 U, 100 U or 150 U). MEASUREMENTS The initial evaluations (ie, clinical and urodynamic variables as well as quality of life [QoL]) were repeated at day 8 and months 1, 3, 5, and 6. RESULTS AND LIMITATIONS Ninety-nine patients were included in the efficacy analysis. Three months after the procedure, we observed>50% improvement versus baseline in urgency and urge urinary incontinence (UUI) in 65% and 56% of patients who respectively received 100 U (p=0.086) and 150 U (p=0.261) BoNTA injections and >75% improvement in 40% of patients of both groups (100 U [p=0.058] and 150 U [p=0.022]). Complete continence was observed in 55% and 50% patients after 100 U and 150 U BoNTA treatment, respectively, at month 3. Frequency symptoms and QoL improved up to the 6-mo visit. We observed only three patients with a PVR>200 ml in the 150 U group and a few UTIs. CONCLUSIONS 100 U and 150 U BoNTA injections were well tolerated and have both shown to improve symptoms and QoL in patients with iOAB. Nevertheless, 100 U injections showed a reasonable efficacy, with a lower risk of high PVR. TRIAL REGISTRATION ClinicalTrials.gov NCT00231491.

Ureteral and Multifocal Tumours Have Worse Prognosis than Renal Pelvic Tumours in Urothelial Carcinoma of the Upper Urinary Tract Treated by Nephroureterectomy

BACKGROUND It is not known whether the primary tumour location of upper urinary tract urothelial carcinoma (UUT-UC) is associated with prognosis. OBJECTIVE To evaluate the impact of initial primary tumour location on survival in patients who had undergone radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS Using a multi-institutional, retrospective database, we identified 609 patients with UUT-UC who had undergone RNU between 1995 and 2010. Tumour location was categorised as renal pelvis, ureter, or multifocal. INTERVENTION All patients had undergone RNU. MEASUREMENTS Tumour location was tested as a prognostic factor for survival through univariate and multivariable Cox regression analysis. RESULTS AND LIMITATIONS Tumour location was renal pelvis in 317 cases (52%), ureter in 185 cases (30%), and multifocal in 107 cases (18%). Compared to renal pelvic and ureteral tumours, multifocal tumours were more likely to be associated with advanced stages (pT3/pT4; 39%, 30%, and 54%, respectively; p<0.001) and high-grade disease (53%, 56%, and 76%, respectively; p<0.001). On multivariable analysis, tumour location was an independent prognostic factor for cancer-specific death, disease recurrence, and metastasis (p<0.05). The 5-yr cancer-specific death-free survival probability was 86.8% for renal pelvic tumours, 68.9% for ureteral tumours, and 56.8% for multifocal tumours (p<0.001). The retrospective design of this study was its main limitation. CONCLUSIONS Ureteral and multifocal tumours had a worse prognosis than renal pelvic tumours. These findings are not in line with recently published data and should be investigated in a prospective assessment to obtain a definitive statement regarding this matter.

Botulinum toxin-A (Botox) intradetrusor injections in children with neurogenic detrusor overactivity/neurogenic overactive bladder: a systematic literature review.

OBJECTIVES Describe and discuss the efficacy and safety of botulinum toxin type A (BTX-A) intradetrusor injections in children with neurogenic detrusor overactivity (NDO) and urinary incontinence or overactive bladder symptoms of neurogenic origin (NOAB). METHODS A MEDLINE and EMBASE search for clinical studies involving BTX-A injected into the detrusor of children with NDO or NOAB was performed, prior to data analysis. RESULTS A total of six articles evaluating the efficacy and safety of Botox in patients with NDO and incontinence/NOAB were selected. The underlying neurological disease was myelomeningocele in 93% of patients. Most were over 2 years of age. The most common amount of Botox injected was 10-12 U/kg with a maximal dose of 300 U, usually as 30 injections of 10 U/ml in the bladder (excluding the trigone) under cystoscopic guidance and general anaesthesia. Most of the studies reported a significant improvement in clinical (65-87% became completely dry) as well as urodynamic (in most studies mean maximum detrusor pressure was reduced to <40 cm H(2)O and compliance was increased >20 ml/cm H(2)O) variables, without major adverse events. CONCLUSIONS Botox injections into the detrusor provide a clinically significant improvement and seem to be very well tolerated in children with NDO and incontinence/NOAB refractory to antimuscarinics.

Impact of laparoscopy simulator training on the technical skills of future surgeons in the operating room: a prospective study

BACKGROUND The efficacy of laparoscopy simulators remains controversial. METHODS This was a comparative prospective study that evaluated the impact of simulator training on technical competence during a real surgical procedure. Residents were divided into 3 groups: the Mcgill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS) group, training on a simple simulator; LAP Mentor group, training on a virtual simulator; and control group. An initial evaluation was made by a validated score during a laparoscopic cholecystectomy. Each resident was then trained for 1 month. A second evaluation was then performed. RESULTS Before/after scores were significantly improved in the MISTELS (P = .042) and LAP Mentor (P = .026) groups. It was not the case in the control group. There was a better progression in the MISTELS (P = .026) and LAP Mentor (P = .007) groups than in the control group. There was no significant difference between the MISTELS and LAP Mentor groups. CONCLUSIONS Simulator training provides a more rapid acquisition of competence in surgical technique.

Sperm cryopreservation before cancer treatment: a 15-year monocentric experience

Sperm banking is an important procedure to preserve fertility before cancer therapy. The aim of this study was to comprehensively analyse cryopreservation activity retrospectively for 1080 patients referred to the sperm bank for sperm cryopreservation before cancer treatment. This study included 1007 patients diagnosed with testicular cancer (TC) (41.7%), lymphoma (26%), other haematological cancers (9.4%) or other types of cancer (22.8%); of these, 29 patients did not produce any semen sample and cryopreservation was impossible for 67 patients. Semen characteristics before treatment were within normal ranges, except moderate asthenospermia. Sperm concentration was significantly lower in TC than in non-TC. Straws from 57 patients (6.3%) were used in assisted reproductive technologies, which led to a 46.8% cumulative birth rate. Straws were destroyed for 170 patients (18.7%) and 140 patients performed semen analyses after cancer therapy. After an average delay of 22.5 months after the end of therapy, 43 patients (30.7%) exhibited azoospermia. This study of a large population of cancer patients revealed a high level of successful sperm storage. Utilization of cryopreserved spermatozoa led to good chances of fatherhood. Nevertheless, sperm banks should be aware of the low rates of straw use and straw destruction by cancer patients.

Tibial Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review.

CONTEXT Tibial nerve stimulation (TNS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option for patients with an underlying neurological disorder. OBJECTIVE We systematically reviewed all available evidence on the efficacy and safety of TNS for treating neurogenic lower urinary tract dysfunction (NLUTD). EVIDENCE ACQUISITION The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. EVIDENCE SYNTHESIS After screening 1943 articles, 16 studies (4 randomized controlled trials [RCTs], 9 prospective cohort studies, 2 retrospective case series, and 1 case report) enrolling 469 patients (283 women and 186 men) were included. Five studies reported on acute TNS and 11 on chronic TNS. In acute and chronic TNS, the mean increase of maximum cystometric capacity ranged from 56 to 132mL and from 49 to 150mL, and the mean increase of bladder volume at first detrusor overactivity ranged from 44 to 92mL and from 93 to 121mL, respectively. In acute and chronic TNS, the mean decrease of maximum detrusor pressure during the storage phase ranged from 5 to 15cm H2O and from 4 to 21cm H2O, respectively. In chronic TNS, the mean decrease in number of voids per 24h, in number of leakages per 24h, and in postvoid residual ranged from 3 to 7, from 1 to 4, and from 15 to 55mL, respectively. No TNS-related adverse events have been reported. Risk of bias and confounding was high in most studies. CONCLUSIONS Although preliminary data of RCTs and non-RCTs suggest TNS might be effective and safe for treating NLUTD, the evidence base is poor, derived from small, mostly noncomparative studies with a high risk of bias and confounding. More reliable data from well-designed RCTs are needed to reach definitive conclusions. PATIENT SUMMARY Early data suggest tibial nerve stimulation might be effective and safe for treating neurogenic lower urinary tract dysfunction, but more reliable evidence is required.

Efficacy and safety of onabotulinumtoxinA therapy are sustained over 4 years of treatment in patients with neurogenic detrusor overactivity: Final results of a long‐term extension study

To present final efficacy/safety results from a prospective, long‐term extension trial of onabotulinumtoxinA for urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO); patients received treatment for up to 4 years.

Technical aspects of botulinum toxin type A injection in the bladder to treat urinary incontinence: Reviewing the procedure

Standardise the injection technique with botulinum toxin type A (BoNT A) in the bladder of patients with overactive bladder (OAB) [idiopathic overactive bladder (iOAB) or neurogenic overactive bladder (nOAB) with urinary incontinence], using a literature review and a survey of an International expert panel.