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

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

Pioneering drugs for overactive bladder and detrusor overactivity: Ongoing research and future directions

The ongoing research on pioneering drug candidates for the overactive bladder （OAB） aimed to overcome the limitations of currently licensed pharmacotherapies, such as antimuscarinics, β3-adrenergic agents, and botulinum neurotoxin, has been reviewed performing a systematic literature review and web search. The review covers the exploratory agents alternative to available medications for OAB and that may ultimately prove to be therapeutically useful in the future mana-gement of OAB patients based on preclinical and early clinical data. It emerges that many alternative pharmacological strategies have been discovered or are under investigation in disease-oriented studies. Several potential therapeutics are known for years but still fnd obstacles to pass the clinical stages of development, while other completely novel compounds, targeting new pharmacological targets, have been recently discovered and show potential to translate into clinical therapeutic agents for idiopathic and neurogenic OAB syndrome. The global scenario of investigational drugs for OAB gives promise for the development of innovative thera-peutics that may ultimately prove effective as first, combined or second-line treatments within a realistic timescale of ten years.

Significance of preoperatively observed detrusor overactivity as a predictor of continence status early after robot-assisted radical prostatectomy

Several recent studies have reported the involvement of bladder dysfunction in the delayed recovery of urinary continence following radical prostatectomy （RP）. The objective of this study was to investigate the significance of detrusor overactivity （DO） as a predictor of the early continence status following robot-assisted RP （RARP）. This study included 84 consecutive patients with prostate cancer undergoing RARP. Urodynamic studies, including filling cystometry, pressure flow study, electromyogram of the external urethral sphincter and urethral pressure profile, were performed in these patients before surgery. Urinary continence was defined as the use of either no or one pad per day as a precaution only. DO was preoperatively observed in 30 patients （35.7%）, and 55 （65.5%） and 34 （40.5%） were judged to be incontinent 1 and 3 months after RARP, respectively. At both 1 and 3 months after RARP, the incidences of incontinence in patients with DO were significantly higher than in those without DO. Of several demographic and urodynamic parameters, univariate analyses identified DO and maximal urethral closure pressure （MUCP） as significant predictors of the continence status at both 1 and 3 months after RARP. Furthermore, DO and MUCP appeared to be independently associated with the continence at both I and 3 months after RARP on multivariate analysis. These findings suggest that preoperatively observed DO could be a significant predictor of urinary incontinence early after RARP; therefore, it is recommended to perform urodynamic studies for patients who are scheduled to undergo RARP in order to comprehensively evaluate their preoperative vesicourethral functions.

Electroacupuncture at points Baliao and Huiyang (BL35) for post-stroke detrusor overactivity

Acupuncture is used extensively in China for the treatment of stroke and other neurological disorders. The National Institutes of Health recommends acupuncture as an adjunctive therapy for stroke recovery. This study included patients with post-stroke detrusor overactivity who were treated in the Department of Neurology, Fourth Hospital of Harbin Medical University, China. Subjects received either electroacupuncture or sham electroacupuncture at points Baliao [including bilateral Shangliao （BL31）, bilateral Ciliao （BL32）, bilateral Zhongliao （BL33）, and bilateral Xialiao （BL34）] and Huiyang （BL35）. Our results showed that electroacupuncture significantly improved cystometric capacity and bladder compliance, decreased detrusor leak point pressure, ameliorated lower urinary tract symptoms, and decreased the risk of upper urinary tract damage. These findings indicate that electroacupuncture at points Bafiao and Huiyang is an effective treatment for post-stroke detrusor overactivity.

How botulinum toxin in neurogenic detrusor overactivity can reduce upper urinary tract damage?

Intradetrusor injections of botulinum toxin are the cornerstone of medical treatment of neurogenic detrusor overactivity. The primary aim of this treatment is to ensure a low pressure regimen in the urinary bladder, but the mechanisms leading to long-term protection of the urinary tract remain poorly understood. In this paper, we highlight the potential benefts of intradetrusor injections of botulinum toxin regarding local effects on the bladder structures, urinary tract infections, stone disease, vesico ureteral refux, hydronephrosis, renal function based on a comprehensive literature review.

Combined Detrusor and External Urethral Sphincter BTX-A Injections for Detrusor Overactivity and Detrusor External Sphincter Dyssynergia Secondary to Spinal Cord Injury

Objective: To evaluate the efficacy and safety of Combined detrusor and external urethral sphincter BTX-A injections for detrusor overactivity (DO) and detrusor external sphincter dyssynergia (DESD) secondary to spinal cord injury. Study Design: Prospective study. Methods: The study was carried out in 18 SCI patients with detrusor overactivity (DO) and detrusor external sphincter dyssynergia (DESD) receiving Combined detrusor and external urethral sphincter BTX-A injections treatment. Contain 200 U botulinum toxin intradetrusor and 100 U external urethral sphincter injections. The effective outcomes included maximum detrusor pressure at first DO and DESD (PdetmaxDO-DESD), volume at first DO and DESD (VDO-DESD), maximum urethral closure pressure (MUCP), and Incontinence-Specific Quality-of-Life Instrument (I-QoL). Adverse events were recorded. Results: All patients experienced a significant mean reduction in PdetmaxDO-DESD (50.75%), maximum urethral closure pressure (26.34%) and a significant mean increase in VDO-DESD (63.00%) 12-weeks post-injection. Significant (p < 0.001) improvement in mean Incontinence-Specific Quality-of-Life Instrument was also found. No obvious adverse event and toxic effect was observed. Conclusion: Combined detrusor and external urethral sphincter BTX-A injections is a good choice for patients with DO and DESD secondary to spinal cord injury. It could not only protect the upper urinary tract but also improve quality of life.

The role of botulinum toxin in the management of nonneurogenic overactive bladder in children:Highlights for clinical practice.A systematic review

Overactive bladder(OAB)is the most common voiding dysfunction in children;however,nonneurogenic or idiopathic OAB remains poorly studied.First-line treatment includes conservative measures;however,as many patients are refractory,have adverse effects,or are contraindicated for anticholinergics,new options must be explored.This review covers the use of intravesical botulinum toxin(BoNT)for idiopathic OAB treatment in children,emphasizing its efficacy,safety,differences between toxins,doses,and injection tech-niques.Clinical results were promising,with all 8 studies reporting good results.All authors used BoNT type A(BoNT-A),either onabotulinum or abobotulinum toxin A.Response rates were variable,with full-response percentages of 32%-60%.As proven by the full-response rates of 50%,repeated injections are as safe and effective as first injections.Only a few cases of urinary tract infection,transient urinary retention,and hematuria have been reported,with no major local or systemic adverse effects.Despite these limitations,evidence encourages and supports BoNT-A use as a safe and effective treatment modality for refractory idiopathic OAB in pediatric set-tings,regardless of dosage and target toxin.To the best of our knowledge,this is the first systematic review of the use of intravesical BoNT-A for idiopathic OAB treatment in children.

Beyond prostate, beyond surgery and beyond urology: The “3Bs” of managing non-neurogenic male lower urinary tract symptoms

Lower urinary tract symptoms(LUTS),consisting storage,voiding and postmicturition symptoms,is a comprehensive definition involving symptoms that may occur due to several causes.Instead of simply focusing on the enlarged prostate,more attention has to be paid to the entire urinary tract as well as multiple system comorbidities.Therefore,prostate surgery alone does not necessarily provide adequate management and cross-disciplinary collaborations are sometimes required.Based on current literature,this paper proposes the“3Bs”concept for managing non-neurogenic male LUTS,namely,“beyond prostate”,“beyond surgery”and“beyond urology”.The clinical application of the“3Bs”enables urologists to carry out integrated,individualized and precise medical care for each non-neurogenic male LUTS patient.

A Review on Urinary Incontinence after Surgery for Benign Prostatic Hyperplasia

Background: Benign prostatic hyperplasia (BPH) is characterized by the abnormal proliferation of cells, leading to structural changes. It is one of the most common diseases in ageing men. Its clinical presentations are dominated by lower urinary tract symptoms (LUTS). The therapeutic methods can be grouped into two options: the medical option and the surgical option in which prostate enucleation is found. In recent years many studies have reported the onset of urinary incontinence (UI) after prostate enucleation. The management of UI occurring after prostate enucleation is embarrassing for both the practitioner and the patient, and generates additional costs. Purpose: Cite the causes of UI after prostate enucleation for BPH, as well as ways to prevent the onset of UI after this surgery, specifically by the study of the vesicosphincteric system aimed at improving the technique of enucleation;our review will also deal with the therapeutic means of UI. Method: We retrieved studies from Science Direct, Wiley and Pubmed. Results: There are multiple etiologies of UI after prostate enucleation including urethral sphincter insufficiency (USI) and bladder dysfunction (BD). The management of UI after surgery could be conservative, surgical, or use new technologies. Urodynamic assessment before prostate enucleation for BPH is relevant. Conclusion: UI is a common post-operative complication of prostate enucleation. The study of the vesicosphincteric system leads us to believe that prostate enucleation for BPH, partially sparing the mucosa and the external urethral sphincter could decrease the incidence of UI after surgery.

Relationship between urodynamic patterns and lower urinary tract symptoms in Chinese women with a non-neurogenic bladder

Objective:To investigate the urodynamic study(UDS)patterns,obstruction status,continence status,and their correlations among neurologically intact women with lower urinary tract symptoms(LUTS)through an epidemiological and logistic regression analyses.Methods:We retrospectively analyzed the UDS data of 3265 neurologically intact women with LUTS(2002e2014).Five UDS patterns were identified:normo-active detrusor/sphincter(NA,or DSI,detrusor/sphincter intact),idiopathic detrusor overactivity(IDO),idiopathic sphincter overactivity(ISO),IDO+ISO,and detrusor underactivity(DUA).Analyses of UDS pattern distribution and stratification were performed(based on a modification of the European Urological Association-Madersbacher classification system),and their correlations with bladder outlet obstruction(BOO)and stress urinary incontinence(SUI)status were evaluated via logistic regression analysis.Results:NA,IDO,IDO+ISO,ISO,and DUA were noted in 927(28.4%),678(20.8%),320(9.8%),689(21.1%),and 651(19.9%)cases,respectively.Moreover,storage,storage+voiding,and voiding symptoms were noted in 62.4%,21.1%,and 16.5% cases,respectively,whereas BOO and SUI were observed in 12.1%and 29.0%cases,respectively.The risk factors for BOO included NA,IDO,ISO,and IDO+ISO,whereas the protective factors against BOO included storage symptoms,SUI,storage+voiding symptoms,and complaint duration within 1e12 months.NA was the only risk factor for SUI,whereas BOO,storage+voiding symptoms,IDO,and storage symptoms were protective factors for SUI.Conclusion:Five UDS patterns were identified among neurologically intact women with LUTS.Functional abnormalities of the detrusor and/or sphincter were the main causes of LUTS,and were correlated with the BOO or SUI status.Thus,the UDS pattern can provide additional information regarding the risk factors for BOO or SUI status,as compared to symptomatic typing.

Initial Experience with Mirabegron for the Treatment of Neurogenic Lower Urinary Tract Dysfunction

Background: Though anticholinergic drugs are considered the standard treatment for neurogenic detrusor overactivity, it is far from an ideal tool, because of their adverse effects such as Constipation or not respond sufficiently for a substantial proportion of patients. Recently mirabegron has become a commonly used overactive bladder medication in the general population, but few studies about mirabegron for the treatment of neurogenic detrusor overactivity. Objective: To evaluate the efficacy and safety of mirabegron for the treatment of neurogenic lower urinary tract dysfunction. Study Design: Prospective study. Methods: This prospective study included 13 adult patients with neurogenic lower urinary tract dysfunction as a result of spinal cord injury. All patients receiving mirabegron treatment (50 mg once daily) at least 6 weeks. The effective outcomes included the mean urine volume per catheterization, urinary incontinence episodes and Incontinence Specific Quality of Life Instrument. We monitored the blood pressure and heart rate to assess the cardiovascular safety, other adverse events were also recorded. Results: A total of 13 patients were included. After 6 weeks of treatment, all patients experienced a significant increase in the mean volume of per catheterization from 238.46 ± 65.43 ml to 327.69 ± 59.04 ml (p = 0.001). There is a significant reduction in the volume of urine leakage (463.85 ± 247.98 ml VS 180.00 ± 190.96 ml, p = 0.003) and incontinence episodes per 24 h (4.46 ± 2.03 VS 1.92 ± 1.50, p = 0.001). Significant improvement in mean Incontinence Specific Quality of Life Instrument was also found (p = 0.001). No patients reported dry mouth during the study, and the cardiovascular safety were acceptable. Conclusion: Mirabegron is safe and effective in the treatment of neurogenic lower urinary tract dysfunction. It might be a good choice for reducing the cessation of clean intermittent catheterization.

Expressions of voltage-gated K^＋ channel 2.1 and 2.2 in rat bladder with detrusor hyperreflexia

Background Voltage-gated K^＋ channel （Kv） plays a critical role in the modulation of detrusor contraction. This study was conducted to investigate the expressions of Kv2.1 and Kv2.2 in rat bladder with detrusor hyperreflexia （DH）. Methods Thirty adult female Sprague-Dawley rats （200-220 g） were randomly divided into the control group and the experimental group. The experimental group was subjected to spinal cord injury （SCI）. In the controls, the surgical procedure was identical with the exception that dura and spinal cord were transected. Four weeks after SCI, in vivo cystometry and mechanical pulling tests of isolated detrusor strips were performed, mRNA was extracted from the detrusors of normal and DH rats for the detection of expression of Kv2.1 and Kv2.2 by RT-PCR. Differences in expression between normal and overactive detrusors were identified by gel imaging. Results Fourteen rats in the experimental group exhibited uninhibited bladder contraction （〉8 cmH20） before voiding after SCI. One rat died from infection. The frequency of DH in the experimental group was significantly different from that in the control group with or without treatment with 4-aminopyridine （4-AP） （P 〈0.05）, while the amplitude of DH did not change markedly. The rates of variation of the automatic contractile frequency and amplitude were （66.8±12.4）% and （42.6±12.6）% respectively in the control group, and （38.4±9.8）% and （28.0±4.6）% respectively in the DH group. 4-AP increased the automatic contractile frequency apart from the automatic contractile amplitude in both the control and DH groups （P 〈0.05）. 4-AP increased the rate of variation of the automatic contractile frequency more markedly in the control group than in the DH group （P 〈0.05）. Significant expression of Kv2.2 was not detected in bladders in the control group. Compared to the mRNA levels of 13-actin, the mRNA level of Kv2.1 was 1.26±K）.12 in the control group and 0.66±0.08 in the DH group. SCI significantly reduced the mRNA level of Kv2.1 in rat bladders with DH （P 〈0.05）. Conclusions Our study showed that the mRNA level of Kv2.1 decreased significantly in rat bladder with DH, which was one of the important pathogenetic mechanisms for DH, and suggested that Kv2.1 might be one of the therapeutic targets for bladder overactivity.

Efficacy and Safety of OnabotulinumtoxinA in Treating Neurogenic Detrusor Overactivity： A Systematic Review and Meta-analysis

Background： OnabotulinumtoxinA is widely used in treating neurogenic detrusor overactivity （NDO）. We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug for treating NDO. Methods： We searched the following databases： Medline, EMBASE, and the Cochrane Controlled Trials Register. All published randomized double-blind, placebo-controlled trials of onabotulinumtoxinA for the treatment of NDO were identified in the analysis. The reference lists of the retrieved studies were also investigated. Results： Four publications involving a total of 807 patients were identified in the analysis, which compared onabotulinumtoxinA with placebo. The changes of the mean number of urinary incontinence per week （the standardized mean difference [SMD] = -10.91, 95% confidence intervals [C/s] = -14.18-7.63, P 〈 0.0001）; maximum cystometric capacity （SMD = 146.09, 95% CI = 126.19-165.99, P 〈 0.0001） and maximum detrusor pressure （SMD = -32.65, 95% CI = -37.83--27.48, P 〈 0.0001 ） indicated that onabotulinumtoxinA was more effective than the placebo, despite the doses ofonabotulinumtoxinA. Safety assessments primarily localized to the urinary tract indicated onabotulinumtoxinA were often associated with more complications. Urinary tract infections （relative risk [RR] = 1.48, 95% CI = 1.20- 1.81, P = 0.0002）; hematuria （RR = 1.81, 95% CI = 1.00-3.24, P = 0.05） and urinary retention （RR = 5.87, 95% CI = 3.61-9.56, P 〈 0.0001 ）. Conclusions： This meta-analysis indicates that onabotulinumtoxinA to be an effective treatment for NDO with side effects primarily localized to urinary tract.

Multiple factors related to detrusor overactivity in Chinese patients with benign prostate hyperplasia

Background Detrusor overactivity （DO） is a known cause of lower urinary tract symptoms and occurs in 50%-75% of benign prostate hyperplasia （BPH） patients. We sought to investigate the clinical and urodynamic factors that are associated with the presence of DO in Chinese BPH patients.