Intravesical Botulinum Toxin A Research Articles

Lower urinary tract dysfunction in the central nervous system neurogenic bladder and the real-life treatment outcome of botulinum toxin A.

Neurogenic lower urinary tract dysfunction (NLUTD) is common in patients with central nervous system (CNS) lesions. Cases of cerebrovascular accidents (CVA), Parkinson's disease, dementia, and other intracranial lesions develop poor bladder control with or without urinary difficulty due to loss of cortical perception of bladder filling sensation and poor coordination of urethral sphincter relaxation during reflex micturition. Patients with CNS lesions usually have overactive bladder (OAB) symptoms, including urgency, frequency, incontinence, voiding symptoms of dysuria, large postvoid residual volume, and retention. In elderly patients with severe CNS disease the OAB symptoms are usually difficult to adequately relieve by medical treatment, and thus, their quality of life is greatly. Botulinum toxin A (BoNT-A) is currently licensed and has been applied in patients with idiopathic and neurogenic OAB due to spinal cord injury or multiple sclerosis. However, the application of BoNT-A in the treatment of urinary incontinence due to NLUTD in chronic CNS lesions has not been well-documented. Although cohort studies and case series support BoNT-A treatment for neurogenic OAB, chronic urine retention after intravesical BoNT-A injection for OAB and exacerbated urinary incontinence after urethral BoNT-A injection for voiding dysfunction have greatly limited its application among patients with NLUTD due to CNS lesions. This article reviews the pathophysiology and clinical characteristics of NLUTD in patients with CNS lesions and the clinical effects and adverse events of BoNT-A injection for patients with NLUTD. A flowchart was created to outline the patient selection and treatment strategy for neurogenic OAB.

Intravesical Botulinum Toxin Injection Plus Hydrodistention Is More Effective in Patients with Bladder Pain-Predominant Interstitial Cystitis/Bladder Pain Syndrome.

Intravesical botulinum toxin A (BoNT-A) injections are included in the interstitial cystitis/bladder pain syndrome (IC/BPS) treatment guidelines. However, the IC phenotype suitable for treatment with BoNT-A has not been clarified. Therefore, we identified the factors influencing treatment outcomes for intravesical BoNT-A injections in patients with non-Hunner IC/BPS (NHIC). This retrospective study included patients with NHIC who underwent 100 U BoNT-A intravesical injections over the past two decades. Six months after treatment, treatment outcomes were assessed using the Global Response Assessment (GRA). Outcome endpoints included GRA, clinical symptoms, urodynamic parameters, urine biomarkers, and the identification of factors contributing to satisfactory treatment outcomes. The study included 220 patients with NHIC (42 men, 178 women). The satisfactory group (n = 96, 44%) had significantly higher pain severity scores and IC symptoms index, larger maximum bladder capacity (MBC), and lower 8-isoprostane levels at baseline. Logistic regression revealed that larger MBC (≥760 mL) and bladder pain predominance were associated with satisfactory outcomes after BoNT-A injection. Subjective parameters and pain severity scores improved significantly in patients with bladder pain-predominant IC/BPS after BoNT-A injection. Thus, NHIC patients with bladder or pelvic pain are more likely to experience satisfactory outcomes following intravesical BoNT-A injections.

Examining the Role of Frailty on Treatment Patterns and Complications Among Older Women Undergoing Procedure-Based Treatment for Urinary Incontinence.

Aging beyond 65 years is associated with increased prevalence of urinary incontinence (UI), frailty, and increased complication rate with UI treatments. To investigate this relationship, we examined frailty as a predictor of procedure-based UI treatment patterns and urologic complications in Medicare-eligible women. We identified women undergoing procedures for UI between 2011 and 2018 in the 5% limited Medicare data set. A claims-based frailty index (CFI) using data from the 12 months prior to the index procedure defined frailty (CFI ≥0.25). Urologic complications were assessed during the 12 months following the index procedure. We used unadjusted logistic regression models to calculate odds of having a specific type of UI procedure based on frailty status. Odds of postprocedure urologic complications were examined with logistic regression adjusted for age and race. We identified 21783 women who underwent a procedure-based intervention for UI, of whom 3826 (17.5%) were frail. Frail women with stress UI were 2.6 times more likely to receive periurethral bulking (95% confidence interval [CI] 2.26-2.95), compared to nonfrail. Conversely, frailty was associated with lower odds of receiving a Sling or Burch colposuspension. Among women with urgency UI or overactive bladder, compared to nonfrail, frailty was associated with higher odds of both sacral neuromodulation (odds ratio [OR] = 1.21, 95% CI: 1.11-1.33) and intravesical Botox (OR = 1.16, 95% CI: 1.06-1.28), but lower odds of receiving posterior tibial nerve stimulation. Frailty was associated with higher odds of postprocedure urologic complications (OR = 1.64, 95% CI: 1.47-1.81). Frailty status may influence treatment choice for treatment of stress or urgency UI symptoms and increase the odds of postprocedural complications in older women.

Long term safety outcomes and continuation rates of repeated Intravesical Botulinum Toxin A injections for Detrusor Overactivity: 16 year’s experience of a Tertiary Centre in the UK

Introduction:Overactive bladder (OAB) affects 27% of women in the UK with an adverse impact on quality of life. Medical treatment with anticholinergics has a high discontinuation rate due to side effects. OnabotulinumtoxinA (BOTOX ®) is an established treatment for refractory OAB, although there are little published data regarding safety with long term use. Objective:To report the long-term safety and continuation rates of intravesical Botox for OAB. Methods:This was a retrospective cohort study of patients treated with botulinum toxin A for OAB in a tertiary centre from 2007–2023. Data were collected retrospectively from medical records. Results:132 patients were identified, with a total of 574 episodes of intravesical Botox. Mean age at first treatment was 55 years. After 1st Botox treatment, 21% of patients developed urinary tract infections. Clean intermittent self-catheterisation (CISC) was performed in 33% of patients, 5% of whom were performing CISC prior to treatment. The range of number of Botox treatments per patient was 1–18; 74% had more than one treatment. 52% of patients were lost to follow-up and 30% are ongoing patients. Recurrent UTIs developed in 23%. Conclusion:Repeated Botox injections appear to be a safe form of treatment for refractory OAB. Long term complications include recurrent UTIs, which affects 1 in 4 women, and voiding dysfunction, which affects 1 in 5. Only 1 in 3 women continue long term Botox treatment.

Predictors for adverse events following intravesical botulinum toxin injections in men.

Intravesical botulinum toxin A (BTX-A) has been long established as treatment for overactive bladder and neurogenic bladder dysfunction. However, most published data are reported amonga female cohort. Adverse events such as intermittent self-catheterization (ISC) and urinary tract infections (UTIs) play a large role in discontinuation of therapy. There is currently limited information regarding predictive factors to appropriately counsel male patients. We retrospectively collected data on male patients undergoing their first intravesical BTX-A therapy from January 2016 to July 2021 in two high-volume centers. Data included demographics, past medical and surgical history, and urodynamic parameters. Patients were excluded if they had a long-term catheter or ISC before initiation of therapy. A total of 69 men were included in the study with a median age of 66 years. There were 18 patients with neurogenic bladder dysfunction. Thirty men had urge incontinence secondary to radical prostatectomy or bladder outflow surgery. Overall rates of ISC were 43.5%. Predictors for ISC included a baseline postvoid residual (PVR) ≥ 50 mL (odds ratio [OR]: 4.2, 95% confidence interval [CI]: 1.36-13.03, p = 0.01), BTX-A dose >100 units (OR: 4.2, 95% CI: 1.36-13.0, p = 0.01). Stress urinary incontinence was protective against ISC (OR: 0.20, 95% CI: 0.04-1.00, p = 0.049) as well as history of prostatectomy/bladder outflow obstruction (BOO) surgery (OR: 0.16, 95% CI: 0.05-0.47, p < 0.001). A multivariable logistic regression model with these factors yielded a c-statistic of 0.80 (optimism-adjusted = 0.75). An enlarged prostate was the only predictor for UTI amongour male cohort (OR: 8.0, 95% CI: 2.03-31.5, p = 0.003). This is the first study assessing risk factors of adverse events amongmen following BTX-A injection. High PVR and BTX-A dose of >100U were predictors of requiring ISC after BTX-A. Stress incontinence, previous radical prostatectomy, and BOO surgery were all protective against needing ISC post-BTX-A. An enlarged prostate was associated with development of UTI. These factors can be used to assist in counseling male patients regarding their risk of ISC and UTI.

Treating Neurogenic Lower Urinary Tract Dysfunction in Chronic Spinal Cord Injury Patients-When Intravesical Botox Injection or Urethral Botox Injection Are Indicated.

Lower urinary tract symptoms (LUTS), such as urgency, urinary incontinence, and/or difficulty voiding, hamper the quality of life (QoL) of patients with spinal cord injury (SCI). If not managed adequately, urological complications, such as urinary tract infection or renal function deterioration, may further deteriorate the patient's QoL. Botulinum toxin A (BoNT-A) injection within the detrusor muscle or urethral sphincter yields satisfactory therapeutic effects for treating urinary incontinence or facilitating efficient voiding; however, adverse effects inevitably follow its therapeutic efficacy. It is important to weigh the merits and demerits of BoNT-A injection for LUTS and provide an optimal management strategy for SCI patients. This paper summarizes different aspects of the application of BoNT-A injection for lower urinary tract dysfunctions in SCI patients and provides an overview of the benefits and drawbacks of this treatment.

MP74-02 MEDIUM TO LONG-TERM OUTCOMES OF VENTRAL-ONLAY BUCCAL MUCOSA GRAFT SUBSTITUTION URETHROPLASTY FOR FEMALE URETHRAL STRICTURE

You have accessJournal of UrologyCME1 Apr 2023MP74-02 MEDIUM TO LONG-TERM OUTCOMES OF VENTRAL-ONLAY BUCCAL MUCOSA GRAFT SUBSTITUTION URETHROPLASTY FOR FEMALE URETHRAL STRICTURE Elizabeth Day, Helena Gresty, Anthony Noah, Richard Nobrega, Jeremy Ockrim, and Tamsin Greenwell Elizabeth DayElizabeth Day More articles by this author , Helena GrestyHelena Gresty More articles by this author , Anthony NoahAnthony Noah More articles by this author , Richard NobregaRichard Nobrega More articles by this author , Jeremy OckrimJeremy Ockrim More articles by this author , and Tamsin GreenwellTamsin Greenwell More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003348.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Female urethral stricture (FUS) is rare. Urethroplasty is becoming increasingly popular however there is little to guide choice of technique as all series to date contain small numbers with limited follow-up. We report the medium to long-term outcomes of ventral-onlay buccal mucosa graft substitution urethroplasty (VOBMGSU) in treating FUS. METHODS: A retrospective review of a prospectively acquired database of 52 consecutive women (median age 51 years, range 31-71) with urethral stricture having VOBMGSU since June 2012 and a median follow up 38.2 months, range 8.1-111.9). Data was analysed for stricture recurrence, change in peak free flow rate (Qmax), post-void residuals (PVR) and Patient Global Impression of Improvement (PGII) using a 7-point Likert scale where 1=very much better and 7=very much worse). Short and longer-term complications of surgery were noted. Persistent or de-novo lower urinary tract symptoms (LUTS) were investigated to delineate their cause – and this is detailed. Statistical analysis was performed with the Wilcoxon signed rank test, Students T Test and Mann-Whitney U Test. RESULTS: At last follow-up 46/52 (88.5%) of women were stricture free. Mean Qmax significantly improved from 6 ml/s (range 0-24) to 14 ml/s (range 5-31) (p<0.05). Mean PVR significantly reduced from 112 mls (range 0-609) to 38 mls (range 9-86) (p<0.05). Short and longer-term complication rates were low. 1/48 (2.1%) patients developed mild de novo SUI, which settled with conservative measures by 6 months post urethroplasty. Frequency persisted in 6/52 (9.7%) and was managed with intravesical Botox in 2 and Sacral Neuromodulation in 1. Stricture recurrence was managed by meatotomy in 1, meatal dilatation in 2, redo-VOBMG urethroplasty in 2 and vaginal flap meatoplasty in 1 with resolution of stricture in 5. Median PGII at 12 months post VOBMG urethroplasty was 1 (1-4) and this was maintained at 36 months post-surgery. CONCLUSIONS: Medium term results in the largest series of VOBMG female urethroplasty to date are excellent with stricture free rates of 88.5%, median PGII of 1 and significantly improved Qmax and PVRs. Source of Funding: Nil © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1069 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elizabeth Day More articles by this author Helena Gresty More articles by this author Anthony Noah More articles by this author Richard Nobrega More articles by this author Jeremy Ockrim More articles by this author Tamsin Greenwell More articles by this author Expand All Advertisement PDF downloadLoading ...

PD05-05 THE REAL-LIFE PRACTICE OF INTRAVESICAL BOTULINUM TOXIN A INJECTION FOR INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME - SATISFACTION RATE AND PREDICTIVE FACTORS

You have accessJournal of UrologyCME1 Apr 2023PD05-05 THE REAL-LIFE PRACTICE OF INTRAVESICAL BOTULINUM TOXIN A INJECTION FOR INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME - SATISFACTION RATE AND PREDICTIVE FACTORS Wei-Hsin Chen, Wan-Ru Yu, Jia-Fong Jhang, Yuan-Hong Jiang, and Hann-Chorng Kuo Wei-Hsin ChenWei-Hsin Chen More articles by this author , Wan-Ru YuWan-Ru Yu More articles by this author , Jia-Fong JhangJia-Fong Jhang More articles by this author , Yuan-Hong JiangYuan-Hong Jiang More articles by this author , and Hann-Chorng KuoHann-Chorng Kuo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003229.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Botulinum toxin A (BoNT-A) has been demonstrated to have anti-inflammatory and antinociceptive effects on bladder sensory disorders and has been shown effective in reducing bladder oversensitivity and increasing functional bladder capacity, however, the real-world treatment outcome on interstitial cystitis/bladder pain syndrome (IC/BPS) is still lacking. This study investigated the real-life practice of intravesical BoNT-A injection for patients with IC/BPS. METHODS: This retrospective study included IC/BPS patients treated with 100U BoNT-A intravesical injection in the past twenty years. The treatment outcomes were assessed by the global response assessment (GRA) at 6 months post treatment. The treatment outcome was assessed by classification according to the GRA, clinical symptoms, urodynamic parameters, cystoscopic characteristics, and urine biomarkers, and the predictive factors for a satisfactory outcome were investigated. RESULTS: Of a total of 220 patients (180 females, 40 males) enrolled in this study who received the BoNT-A injection, only 87 (40%) of patients had significantly satisfactory treatment outcomes; the satisfactory group has a significantly larger voided-volume, a lower urinary inflammatory protein MCP-1, and oxidative stress biomarker 8-isoprostane than the unsatisfactory group (Table 1). The IC severity and detrusor pressure are predictive factors to affect treatment outcomes under BoNT-A injection (Figure 1). CONCLUSIONS: IC/BPS patients with less inflammation in the bladder have a satisfactory outcome to intravesical BoNT-A injection. Patients with higher grade of bladder inflammation might need more intravesical BoNT-A injections to achieve a satisfactory outcome. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e150 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wei-Hsin Chen More articles by this author Wan-Ru Yu More articles by this author Jia-Fong Jhang More articles by this author Yuan-Hong Jiang More articles by this author Hann-Chorng Kuo More articles by this author Expand All Advertisement PDF downloadLoading ...

Efficacy of Intravesical Botulinum Toxin A Injection in the Treatment of Refractory Overactive Bladder in Children.

This study aimed to evaluate the efficacy of intravesical botulinum toxin A (BoNT-A) injections for the treatment of pediatric overactive bladder (OAB) by exploring the differential treatment outcomes in children with different OAB etiologies and those who received additional intrasphincteric BoNT-A injections. We performed a retrospective review of all pediatric patients who received intravesical BoNT-A injections between January 2002 and December 2021. All patients underwent a urodynamic study at baseline and three months after BoNT-A administration. A Global Response Assessment (GRA) score of ≥2 at three months after BoNT-A injection was defined as successful treatment. Fifteen pediatric patients (median age, 11 years), including six boys and nine girls, were enrolled in the study. A statistically significant decrease in detrusor pressure from baseline to three months postoperatively was observed. Thirteen (86.7%) patients reported successful results (GRA ≥ 2). The cause of OAB and additional intrasphincteric BoNT-A injections did not affect the improvement in urodynamic parameters and treatment success. The study demonstrated that intravesical BoNT-A injection is effective and safe for the treatment of neurogenic and non-neurogenic OAB in children refractory to conventional therapies. Additionally, intrasphincteric BoNT-A injections do not provide additional benefits in the treatment of pediatric OAB.

The Comparative Effectiveness of Botulinum Toxin-A Injection Therapy Versus Augmentation Uretero-Enterocystoplasty for the Treatment of Lower Urinary Tract Dysfunction.

We investigated the effectiveness of intravesical botulinum toxin-A (BTX-A) injection therapy in patients with lower urinary tract dysfunction (LUTD) and upper urinary tract (UUT) deterioration and evaluated whether BTX-A injection therapy could substitute for augmentation uretero-enterocystoplasty (AUEC). Data from a prospective, single-center cohort from 2017-2021 were analyzed. Patients were divided into 2 treatment groups: AUEC and BTX-A (i.e., patients who declined AUEC). Bladder and UUT functions were assessed by comparing clinical information, urodynamic data, laboratory results, and imaging records. In total, 121 patients were enrolled (BTX-A group: 41 patients; AUEC group: 80 patients). The BTX-A group showed a reduced maximum detrusor pressure and increases in the maximum bladder volume and bladder compliance (P<0.05). However, in follow-up evaluations, significantly smaller improvements (all P<0.05) in urodynamic parameters were found in the BTX-A group than in the AUEC group. Notably, there was no significant improvement in vesicoureteral reflux (VUR; P=0.66) or upper urinary tract dilatation (UUTD; P=0.75) in the BTX-A group, and no statistically significant difference in serum creatinine (Scr) levels or the estimated glomerular filtration rate (eGFR) was observed in the follow-up evaluations (all P>0.05). Both VUR and UUTD improved significantly in the AUEC group, and the Scr and eGFR levels significantly improved after AUEC relative to baseline levels (P<0.05). The reduction in the Scr level was significantly lower in the BTX-A group than in the AUEC group during 0-15 months of follow-up (Scr reduction differences, -1.36; P<0.01). Although BTX-A injection therapy was effective for improving bladder function, BTX-A injections did not alleviate UUT deterioration in this study, particularly in patients with advanced-stage LUTD. Conversely, AUEC for LUTD has a well-established role in improving UUT function. Hence, BTX-A injection therapy should not replace AUEC to ameliorate UUT impairment and protect UUT function.

Comparison of the Clinical Efficacy and Adverse Events between Intravesical Injections of Platelet-Rich Plasma and Botulinum Toxin A for the Treatment of Interstitial Cystitis Refractory to Conventional Treatment.

Intravesical injection of Botulinum toxin A (BoNT-A) and platelet-rich plasma (PRP) have been reported to alleviate bladder pain and decrease nocturia in patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS). Both treatments are novel and there has no comparison between them. This study compared the therapeutic effects and adverse events between IC/BPS patients receiving PRP or BoNT-A injections. This study retrospectively analyzed female patients with IC/BPS who were refractory to conventional treatment and received BoNT-A (n = 26) or PRP (n = 30) injections within the previous two years. Patients were arbitrarily treated with four monthly injections of PRP or a single injection of 100 U of BoNT-A. All injections were followed by cystoscopic hydrodistention. The primary endpoint was the global response assessment (GRA), and secondary endpoints were changes in the O'Leary-Sant IC symptom score, visual analog score (VAS) of bladder pain, voiding diary, and uroflow measures from baseline to six months after the first injection day. The baseline demographics revealed no significant difference between groups. The GRA at one, three, and six months was similar between groups. A significant improvement in IC symptom scores was noted in both groups. Although VAS was significantly improved in overall patients, no significant difference was noted between the PRP and BoNT-A groups at 6 months. Only half of the study cohort had a GRA ≥2 at six months. An increase in the post-void residual was noted one month after the BoNT-A injection, but there was no difference between groups at three and six months. More patients reported dysuria (19.2% vs. 3.3%, p = 0.086) and urinary tract infection (UTI, 15.4% vs. 0%, p = 0.041) after BoNT-A injection than after the PRP injections. The time from the first injection to receiving alternative treatment was similar between groups. Both intravesical PRP and BoNT-A injections have similar efficacy in IC symptom improvement. However, only half of the study cohort had a GRA of ≥2 at the six-month follow-up BoNT-A injection carries a potential risk of UTI after treatment.

Sexual dysfunction in women with interstitial cystitis/bladder pain syndrome: Do onabotulinum toxin-A injections improve sexual function?

Interstitial cystitis/bladder pain syndrome (IC/BPS) has a negative impact on female sexual function. We aimed to evaluate the effect of intravesical botulinum toxin-A (BTX-A) injection on the improvement of sexual dysfunction and urinary symptoms using the multi-domain female sexual function Index (FSFI), interstitial cystitis symptom index (ICSI), and interstitial cystitis problem index (ICPI). The data of the 23 patients (study group) who received intravesical BTX-A with the diagnosis of IC/BPS were reviewed. Twenty-three age-matched healthy, sexually active women were determined as the control group. Patients received 100 U BTX-A submucosally injections, including the trigone. One hundred units of BTX-A were diluted to 20 cc0.9% saline, and 1 cc was then applied submucosally on 20 different points of the bladder wall (5 U/1 mL per site). The study group was asked to fill out FSFI, ICSI,andICPI, as well as the visual analog scale (VAS) and bladder diary before and 3 months after the treatment. Patients in the control group completed the same questionnaires once. The pre- and post-treatment questionnaire scores were compared in the study group. The study group's data were also compared to the control group. Compared to the pretreatment period, the study group showed statistically significant improvement in the total FSFI score and each domain of the FSFI after BTX-A injection. The mean total FSFI score and three domains of FSFI (desire, lubrication, pain) reached to the score of the control group following BTX-A injection. Statistically significant improvements were also shown in scores of ICSI, ICPI, and VAS. (p < 0.05). IC/BPS is associated with a very high incidence of sexual dysfunction. Intravesical BTX-A injection may provide significant improvement in sexual dysfunction in women with IC/BPS.

The clinical application of intravesical botulinum toxin A injection in patients with overactive bladder and interstitial cystitis.

Botulinum toxin A (BoNT-A) has been widely used in several urological functional disorders including neurogenic detrusor overactivity (NDO), overactive bladder (OAB), lower urinary tract dysfunction, and interstitial cystitis/bladder pain syndrome (IC/BPS). Chronic inflammation is found in a large proportion of patients with OAB and IC/BPS. The chronic inflammation activates sensory afferents which resulting in central sensitization and bladder storage symptoms. Because BoNT-A can inhibit the sensory peptides released from the vesicles in sensory nerve terminals, the inflammation can be reduced and symptom subsided. Previous studies have demonstrated that the quality of life improved after BoNT-A injections, both in neurogenic and non-NDO. Although the use of BoNT-A in treatment of IC/BPS has not been approved by FDA, intravesical BoNT-A injection has been included in the AUA guideline as the fourth line therapy. Generally, intravesical injections of BoNT-A are well tolerated, though transient hematuria and urinary tract infection can occur after the procedure. In order to prevent these adverse events, experimental trials have been conducted to test if BoNT-A can be delivered into the bladder wall without intravesical injection under anesthesia such as using liposomes encapsulated BoNT-A or application of low energy shock wave on the bladder to facilitate BoNT-A penetrating across the urothelium and treat OAB or IC/BPS. This article reviews current clinical and basic researches of BoNT-A on OAB and IC/BPS.

Treatment Outcomes of Intravesical Botulinum Toxin A Injections on Patients with Interstitial Cystitis/Bladder Pain Syndrome.

Botulinum toxin A (BoNT-A) is effective in reducing bladder hypersensitivity and increasing capacity through the effects of anti-inflammation in the bladder urothelium; however, studies on the treatment outcome of interstitial cystitis/bladder pain syndrome (IC/BPS) are lacking. We investigated the treatment outcome in IC/BPS patients receiving intravesical BoNT-A injections. This retrospective study included IC/BPS patients who had 100U BoNT-A intravesical injections in the past 20 years. The treatment outcomes at 6 months following the BoNT-A treatment were evaluated using the global response assessment (GRA) scale. The treatment outcomes according to the GRA scale include clinical symptoms, urodynamic parameters, cystoscopic characteristics, and urinary biomarkers, and it was these predictive factors for achieving satisfactory outcomes which were investigated. Among the 220 enrolled patients (180 women, 40 men) receiving BoNT-A injections, only 87 (40%) had significantly satisfactory treatment outcomes. The satisfactory group showed significantly larger voided volumes, and lower levels of both the urinary inflammatory protein MCP-1 and the oxidative stress biomarker 8-isoprostane in comparison to the unsatisfactory group. The IC severity and detrusor pressure are predictive factors of BoNT-A treatment outcomes. IC/BPS patients with less bladder inflammation showed satisfactory outcomes with intravesical BoNT-A injections. Patients with severe bladder inflammation might require more intravesical BoNT-A injections to achieve a satisfactory outcome.

Intravesical Botulinum toxin-A injection in pediatric overactive neurogenic bladder with Detrusor overactivity: Radiologic and clinical outcomes.

The neurogenic bladder is one of the most serious and painful disorders seen in pediatric urology clinics. The upper urinary tract can be impaired by increased bladder pressure. Botulinum toxin-A (BTX-A) is one of the new therapeutic interventions for this disease. Thus, this research was designed to determine the clinical as well as radiological outcomes intravesical BTX-A injections in patients with overactive neurogenic bladder with Detrusor over activity. From March 2012 to March 2019, this cohort study was conducted at Shahid Labbafinejad hospital in Tehran, Iran. Thirty-five pediatric patients with a neurogenic bladder and Detrusor overactivity who fulfilled the eligibility criteria received BTX-A injections. Demographic data, including spinal cord lesions or congenital malformations, upper and lower urinary tract nuclear scans, evidence of vesicoureteral reflux (VUR) and its severity, and hydronephrosis and 72 h voiding diary before and after intervention were all recorded. The mean ± standard deviation age of participants was 9.47 ± 4.61 years. After injection, nocturia and urination frequency as general symptoms of the overactive neurogenic bladder improved (p < 0.05). Also, the severity of hydronephrosis was decreased in 33% of patients following injection. In our study, 32 out of 35 patients had vesicoureteral reflux. Of those, there was complete resolution and downgrading of VUR in 17 (53.12%) and 13 (40.62%) respectively. In the evaluation of voiding cystourethrography (VCUG) before and after the injection, downgrading of VUR was seen in 53% of the cases. In the 99mTc-DMSA nuclear scan before and after the injection, the appearance of a new parenchymal scar and uptake reduction was not observed, which indicates the cessation of scar formation in all patients. Although Enuresis, Urgency, Frequency, Nocturia, and UUI significantly improved after injection.

Step-wise Treatment of Bladder Pain Syndrome: Case Report

Bladder pain syndrome/interstitial cystitis is a condition characterized by chronic pelvic and bladder pain (lasting longer than 6 months) accompanied by urinary symptoms (urinary frequency, urgency and nocturia). It can have a highly negative effect on the quality of life. The treatment of this disease is impeded by lack of understanding of its etiology. Therefore, treatment recommendations and information about their efficacy are scarce. The American Urological Association recommends a step-wise therapeutic approach starting from mere patients’ lifestyle modification to pharmacological therapy or to even more complex methods, such as intravesical botulinum toxin-A injections. We present here a case of a 60-year old woman, who presented in 2020 with tiresome symptoms characteristic to bladder pain syndrome lasting for two years. Previous treatments with antibiotics, anti-inflammatory, analgesic and anticholinergic medications were unsuccessful; urine culture was negative. During the cystoscopy in our center small bladder capacity and minute glomerulations were observed. Urodynamic tests (cystometry) were performed showing hypersensitive bladder with small capacity. Bladder hydrodistention procedure was performed twice; however the positive effects only lasted up to one month each time. Therefore, it was decided to perform an intravesical botulinum toxin-A injection into bladder trigonal area after which the patient experienced a significant relief in bladder pain, reduced urinary frequency during the day and night and improved quality of life.

Current Concepts in Endoscopic Bladder Neck Injection: Combined Antegrade and Retrograde Endoscopic Injection of the Bladder Neck in Children with Neurogenic Bladder.

Introduction: Urinary incontinence is common in patients with neurogenic bladder, and efficient management is an ongoing challenge. Besides open surgical procedures like bladder neck reconstruction, artificial sphincter implantation, or sling procedures, endoscopic bladder neck injections of bulking agents enable minimally invasive access with promising results. Several studies report on the effect of antegrade vs. retrograde endoscopic injection techniques. We report our preliminary experience of combined antegrade and retrograde endoscopic injection of the bladder neck in children with neurogenic bladder, in selected cases combined with intravesical Botox® injection. Methods: With the patient in lithotomy position, antegrade urethrocystoscopy was performed using a 9.5 Fr cystoscope. In parallel, percutaneous suprapubic bladder access introducing a second 9.5 Fr. cystoscope was accomplished. Four quadrant Dx/H injections were performed, with the two surgeons guiding each other by parallel endoscopy to the optimal localization for injection. In selected patients, the procedure was completed with transurethral intravesical Botox® injection. Results: A total of 6 children underwent the combined procedure (2/6 patients including intravesical Botox® injection). The mean follow-up was 15 months (range 3 to 48). 5 Patients experienced a significant improvement of urinary incontinence, however one patient demonstrated complete failure. Conclusions: Even if we present only preliminary results with a limited number of patients, we present a minimally invasive technique with encouraging results. In carefully selected patients, combined antegrade and retrograde endoscopic injection of the bladder neck is a useful tool to treat urinary incontinence.

Frailty impacts on treatment trends and perioperative urologic morbidity among older women undergoing procedure-based treatment for urinary incontinence

Frailty increases with aging and may be a predictor of urologic complications after procedures for urinary incontinence (UI) treatment. We aim to explore the association between frailty and treatment trends and perioperative urologic morbidity among older women after procedure-based UI treatments. We analyzed claims data from a 5% national random sample of Medicare beneficiaries provided by the Centers for Medicare and Medicaid Services to include women undergoing a procedure-based intervention for UI between 2011-2018. Procedures included were midurethral/fascial slings, periurethral bulking, and Burch colposuspension for stress urinary incontinence (SUI); and sacral neuromodulation, intravesical Botox, and posterior tibial nerve stimulation for urgency urinary incontinence (UUI) and the overactive bladder (OAB) syndrome. A Claims-based Frailty Index (CFI) was applied to identify frailty within the 12 months prior to the date of the intervention. The CFI score was dichotomized: ‘Frail’ defined by CFI score ≥0.25 and ‘Non-Frail’ by CFI score <0.25. Demographic and clinical characteristics were abstracted from the analytical file on the date of the intervention. Post-procedure urologic and surgical outcomes that occurred within the 12-month period after the index procedure were also abstracted. Univariate and bivariate analyses stratified by frailty status evaluated differences in demographic and clinical characteristics. Trends of UI interventions performed were compared based on frailty status. Multivariable analyses were performed to identify the relationship of frailty on post-intervention urologic/surgical outcomes and the independent effects of age, race, and region. 21,783 women had a CFI-score and underwent a UI intervention between 2011-2018. The mean age was 72±11 years. The majority of women were White (90.5%). 3,826 had CFI ≥ 0.25 and thus classified as ‘Frail’; 17,957 had CFI<0.25 and was classified as ‘Non-frail’. Slings were the most common procedure performed in this cohort (44%). Frail women with stress urinary incontinence have 2.5 higher odds of having periurethral bulking compared to other SUI interventions. Frail women with UUI/OAB have 1.2 higher odds of having sacral neuromodulation in comparison to other inventions. Urologic complications within 1 year of surgery were identified in 18,198 (83.5%) of subjects. Frail women had 1.63 higher odds of having a urologic complication, 95% CI [1.47, 1.82], p<0.0001. The significant impact of frailty on presence of urology complications of UI procedures did not change after considering age, race, or region. Frailty pre-existed procedure-based treatments for urinary incontinence in 17% of older women. While minimally invasive procedures were most commonly performed, pre-existing frailty resulted in higher rates of urologic complications.

Low-Energy Shock Wave Plus Intravesical Instillation of Botulinum Toxin A for Interstitial Cystitis/Bladder Pain Syndrome: Pathophysiology and Preliminary Result of a Novel Minimally Invasive Treatment.

Low-energy shock wave (LESW) therapy is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. LESW treatment has been demonstrated to be effective in treating chronic prostatitis and pelvic pain syndrome as well as overactive bladder, and it has a potential effect on interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. LESW reduces pain behavior, downregulates nerve growth factor expression, and suppresses bladder overactivity by decreasing the expression of inflammatory proteins. Previous rat IC models have shown that LESW can increase urothelial permeability, facilitate intravesical delivery of botulinum toxin A (BoNT-A), and block acetic acid-induced hyperactive bladder, suggesting that LESW might be a potential therapeutic module for relieving bladder inflammatory conditions, such as bladder oversensitivity, IC/BPS, and overactive bladder. A recent clinical trial showed that LESW monotherapy was associated with a significant reduction in pain scores and IC symptoms. BoNT-A detrusor injection or liposome-encapsulated BoNT-A instillation could also inhibit inflammation and improve IC symptoms. However, BoNT-A injection requires anesthesia and certain complications might occur. Our preliminary study using LESW plus intravesical BoNT-A instillation every week demonstrated an improvement in global response assessment without any adverse events. Moreover, an immunohistochemistry study revealed the presence of cleaved SNAP25 protein in the suburothelium of IC bladder tissue, indicating that BoNT-A could penetrate across the urothelial barrier after application of LESW. These results provide evidence for the efficacy and safety of this novel IC/BPS treatment by LESW plus BoNT-A instillation, without anesthesia, and no bladder injection. This article reviews the current evidence on LESW and LESW plus intravesical therapeutic agents on bladder disorders and the pathophysiology and pharmacological mechanism of this novel, minimally invasive treatment model for IC/BPS.

Impact of intravesical onabotulinumtoxinA (Botox) on sexual function in patients with overactive bladder syndrome: a systematic review and meta-analysis.

The association between overactive bladder (OAB) syndrome and sexual dysfunction is well documented. Intra-detrusor onabotulinumtoxinA (Botox) has proven to be effective treatment for OAB syndrome. Our aim was to examine the impact of intravesical Botox injection on sexual function in patients with OAB, by systematically reviewing the literature. We reviewed the literature for studies that reported a change in sexual function after Botox treatment in patients suffering from OAB. This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement using pre-agreed keywords, from database inception to December 2020. Statistical analyses were performed using Review Manager (RevMan; v.5.4). Initial results yielded 455 citations. Seven articles met our inclusion criteria. One article was double-reported, leaving 6 studies in the systematic review. Three observational before-and-after studies used the Female Sexual Function Index (FSFI) with sufficient information, and therefore were included in our meta-analysis. The pooled number of participants in all studies was 119 patients. In the meta-analysis, there was significant improvement in the following domains of the FSFI after Botox injection; desire (mean difference (MD) -0.51, p = 0.02), arousal (MD -0.86, p = 0.02), lubrication (MD -0.57, p = 0.03), orgasm (MD -0.65, p = 0.0003) and satisfaction (MD -0.46, p = 0.05). Pain was the only domain that did not show improvement (MD -0.07, p = 0.79). The total FSFI score was reported in 88 patients (two studies) showing significant improvement (MD -0.77, p = 0.006). We report a systematic review of the effect of Botox treatment on sexual function in patients with OAB. Although studies are small, the results indicate a positive effect in patients with OAB.