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Special Issue "Botulinum Toxin A on Lower Urinary Tract Dysfunction"

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (31 January 2016)

Special Issue Editor

Guest Editor
Prof. Hann-Chorng Kuo

Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien Taiwan
Website | E-Mail
Interests: neurourology; urodynamics; female urology; stress urinary incontinence; LUTS

Special Issue Information

Dear Colleagues,

Botulinum toxin A is a potent protein that can selectively modulate neurotransmission from nerve endings, resulting in blocking of neurotransmitter release and causing muscular paralysis. Recent evidence also revealed that botulinum toxin A has mechanism acting on sensory receptors and an anti-inflammatory effect. Injection of onabotulinumtoxinA into the urethral sphincter results in a reduction of urethral resistance and improves voiding efficiency. Detrusor overactivity is also suppressed by intravesical onabotulinumtoxinA injections, which results in reduction in detrusor pressure and decreased urinary incontinence and daily frequency. In lower urinary tract dysfunction, onabotulinumtoxinA has recently received regulatory approval for the treatment of adult patients with neurogenic detrusor overactivity due to spinal cord lesions, multiple sclerosis, and idiopathic overactive bladder. Although unapproved, onabotulinumtoxinA has been widely used to treat patients with neurogenic or non-neurogenic voiding dysfunction, male lower urinary tract symptoms due to benign prostatic hyperplasia or bladder-neck dysfunction. Other indications to which urologists have applied onabotulinumtoxinA in recent decades include interstitial cystitis/bladder pain syndrome, bladder oversensitivity, and chronic pelvic pain syndrome. This review focuses on recent clinical trials and researches on the therapeutic effects of onabotulinumtoxinA on lower urinary tract dysfunction. The basic science which support the clinical application of onabotulinumtoxinA on lower urinary tract dysfunction will be covered in this Special Issue. The technical points, adverse events, and patients’ satisfaction and adherence to this novel treatment will also be discussed.

Prof. Hann-Chorng Kuo, M.D.
Guest Editor

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Keywords

  • lower urinary tract dysfunction
  • overactive bladder
  • BPH
  • interstitial cystitis
  • neurogenic bladder

Published Papers (9 papers)

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Research

Jump to: Review

Open AccessArticle
Efficacy and Safety of Intravesical OnabotulinumtoxinA Injection in Patients with Detrusor Hyperactivity and Impaired Contractility
Received: 15 February 2016 / Revised: 7 March 2016 / Accepted: 11 March 2016 / Published: 18 March 2016
Cited by 5 | PDF Full-text (597 KB) | HTML Full-text | XML Full-text
Abstract
We investigated the efficacy and safety of intravesical onabotulinumtoxinA injection in patients with detrusor hyperactivity and impaired contractility (DHIC). Twenty-one patients with urodynamically proven DHIC and 21 age-matched patients with overactive bladder (OAB) with urodynamic detrusor overactivity were treated with intravesical injections of [...] Read more.
We investigated the efficacy and safety of intravesical onabotulinumtoxinA injection in patients with detrusor hyperactivity and impaired contractility (DHIC). Twenty-one patients with urodynamically proven DHIC and 21 age-matched patients with overactive bladder (OAB) with urodynamic detrusor overactivity were treated with intravesical injections of 100 U of onabotulinumtoxinA. The overactive bladder symptom score, urgency severity score, patient perception of bladder condition, global response assessment, voiding diary, and procedure-related adverse events (AE) at baseline, two weeks, one, three, and six months after treatment were assessed. The results showed that the subjective symptom scores improved significantly in both groups, and the scores did not differ between the groups. The decrease in urgency episodes and urgency urinary incontinence were noted in OAB patients but not in DHIC patients. Although the incidence of AEs was comparable between the groups, the therapeutic efficacy lasted for a mean of 4.9 ± 4.8 months in DHIC patients and 7.2 ± 3.3 months in OAB patients (p = 0.03). We concluded that the efficacy of intravesical onabotulinumtoxinA injection for DHIC patients was limited and short-term. Nevertheless, AEs did not increase in DHIC. Intravesical onabotulinumtoxinA might not be a good indication in patients with DHIC and high post-voiding residual urine. Physicians should inform patients of the potential benefits and risks of onabotulinumtoxinA injection for treatment of DHIC. Full article
(This article belongs to the Special Issue Botulinum Toxin A on Lower Urinary Tract Dysfunction)
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Open AccessArticle
Adverse Events of Intravesical OnabotulinumtoxinA Injection between Patients with Overactive Bladder and Interstitial Cystitis—Different Mechanisms of Action of Botox on Bladder Dysfunction?
Received: 17 January 2016 / Revised: 29 February 2016 / Accepted: 7 March 2016 / Published: 16 March 2016
Cited by 4 | PDF Full-text (959 KB) | HTML Full-text | XML Full-text
Abstract
Intravesical onabotulinumtoxinA (BoNT-A) injections have been proposed to treat both overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS) in patients with refractory conditions. We compared adverse events (AEs) after BoNT-A treatment between IC/BPS and OAB in women. IC/BPS patients who failed conventional [...] Read more.
Intravesical onabotulinumtoxinA (BoNT-A) injections have been proposed to treat both overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS) in patients with refractory conditions. We compared adverse events (AEs) after BoNT-A treatment between IC/BPS and OAB in women. IC/BPS patients who failed conventional treatments were enrolled to receive suburothelial injections of BoNT-A (100 U) followed by hydrodistention. Age matched OAB female patients refractory to antimuscarinic agents underwent BoNT-A (100 U) injections. The bladder capacity, maximum flow rate (Qmax), post-void residual (PVR), and voiding efficiency (VE) at baseline, 3 and 6 months, and the post-treatment AEs were analyzed between groups. Finally, 89 IC/BPS and 72 OAB women were included. In the OAB group, the bladder capacity and PVR increased, and VE decreased significantly at three and six months after BoNT-A treatment. In the IC/BPS group, the Qmax increased significantly at six months. There were significant differences in changes of capacity, Qmax, PVR and VE between the two groups. Moreover, OAB patients suffered more frequently from events of hematuria, UTI, and large PVR (>200 mL), but less frequently from events of straining to void. In conclusion, OAB women had higher PVR volume and lower VE than those in IC/BPS after BoNT-A injections. These results imply that the bladder contractility of OAB patients are more susceptible to BoNT-A, which might reflect the different mechanisms of action of Botox on bladder dysfunction. Further investigations to confirm this hypothesis are warranted. Full article
(This article belongs to the Special Issue Botulinum Toxin A on Lower Urinary Tract Dysfunction)
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Open AccessArticle
Does Reduction of Number of Intradetrusor Injection Sites of aboBoNTA (Dysport®) Impact Efficacy and Safety in a Rat Model of Neurogenic Detrusor Overactivity?
Toxins 2015, 7(12), 5462-5471; https://doi.org/10.3390/toxins7124896
Received: 9 October 2015 / Revised: 3 December 2015 / Accepted: 10 December 2015 / Published: 17 December 2015
PDF Full-text (1146 KB) | HTML Full-text | XML Full-text
Abstract
Intradetrusor injections of Botulinum toxin A—currently onabotulinumtoxinA—is registered as a second-line treatment to treat neurogenic detrusor overactivity (NDO). The common clinical practice is 30 × 1 mL injections in the detrusor; however, protocols remain variable and standardization is warranted. The effect of [...] Read more.
Intradetrusor injections of Botulinum toxin A—currently onabotulinumtoxinA—is registered as a second-line treatment to treat neurogenic detrusor overactivity (NDO). The common clinical practice is 30 × 1 mL injections in the detrusor; however, protocols remain variable and standardization is warranted. The effect of reducing the number of injection sites of Dysport® abobotulinumtoxinA (aboBoNTA) was assessed in the spinal cord-injured rat (SCI). Nineteen days post-spinalization, female rats received intradetrusor injections of saline or aboBoNTA 22.5 U distributed among four or eight sites. Two days after injection, continuous cystometry was performed in conscious rats. Efficacy of aboBoNTA 22.5 U was assessed versus aggregated saline groups on clinically-relevant parameters: maximal pressure, bladder capacity, compliance, voiding efficiency, as well as amplitude, frequency, and volume threshold for nonvoiding contractions (NVC). AboBoNTA 22.5 U significantly decreased maximal pressure, without affecting voiding efficiency. Injected in four sites, aboBoNTA significantly increased bladder capacity and compliance while only the latter when in eight sites. AboBoNTA significantly reduced NVC frequency and amplitude. This preclinical investigation showed similar inhibiting effects of aboBoNTA despite the number of sites reduction. Further studies are warranted to optimize dosing schemes to improve the risk-benefit ratio of BoNTA-based treatment modalities for NDO and further idiopathic overactive bladder. Full article
(This article belongs to the Special Issue Botulinum Toxin A on Lower Urinary Tract Dysfunction)
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Review

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Open AccessReview
Botulinum Toxin A for Bladder Pain Syndrome/Interstitial Cystitis
Received: 31 January 2016 / Revised: 24 June 2016 / Accepted: 28 June 2016 / Published: 1 July 2016
Cited by 6 | PDF Full-text (204 KB) | HTML Full-text | XML Full-text
Abstract
Botulinum neurotoxin A (BoNT-A), derived from Clostridium botulinum, has been used clinically for several diseases or syndrome including chronic migraine, spasticity, focal dystonia and other neuropathic pain. Chronic pelvic or bladder pain is the one of the core symptoms of bladder pain syndrome/interstitial [...] Read more.
Botulinum neurotoxin A (BoNT-A), derived from Clostridium botulinum, has been used clinically for several diseases or syndrome including chronic migraine, spasticity, focal dystonia and other neuropathic pain. Chronic pelvic or bladder pain is the one of the core symptoms of bladder pain syndrome/interstitial cystitis (BPS/IC). However, in the field of urology, chronic bladder or pelvic pain is often difficult to eradicate by oral medications or bladder instillation therapy. We are looking for new treatment modality to improve bladder pain or associated urinary symptoms such as frequency and urgency for patients with BPS/IC. Recent studies investigating the mechanism of the antinociceptive effects of BoNT A suggest that it can inhibit the release of peripheral neurotransmitters and inflammatory mediators from sensory nerves. In this review, we will examine the evidence supporting the use of BoNTs in bladder pain from basic science models and review the clinical studies on therapeutic applications of BoNT for BPS/IC. Full article
(This article belongs to the Special Issue Botulinum Toxin A on Lower Urinary Tract Dysfunction)
Open AccessReview
Intraprostatic Botulinum Neurotoxin Type A Injection for Benign Prostatic Hyperplasia—A Spotlight in Reality
Received: 18 December 2015 / Revised: 19 April 2016 / Accepted: 20 April 2016 / Published: 26 April 2016
Cited by 6 | PDF Full-text (216 KB) | HTML Full-text | XML Full-text
Abstract
Botulinum toxin is a neurotoxin produced by the bacterium Clostridium botulinum. It inhibits the release of acetylcholine and other neurotransmitters from the nerve terminal. Botulinum toxin, specifically toxin type A (BoNT-A) has been used since the 1970s to reduce the muscular hypercontraction disorders. [...] Read more.
Botulinum toxin is a neurotoxin produced by the bacterium Clostridium botulinum. It inhibits the release of acetylcholine and other neurotransmitters from the nerve terminal. Botulinum toxin, specifically toxin type A (BoNT-A) has been used since the 1970s to reduce the muscular hypercontraction disorders. The application of BoNT-A in urology field started from intra-bladder injection for overactive bladder, which has been recognized as third line therapy in many countries. Since prostate gland as well as bladder is under the influence of autonomic innervation, theorectically, injection of BoNT-A into the prostate induces chemo-denervation and modulation of prostate function, and reduces lower urinary tract symptoms (LUTS). This article reviews the application of BoNT-A in patients with LUTS/ benign prostatic hyperplasia (BPH) from mechanisms of action to clinical results. BoNT-A has been shown to induce prostate apoptosis, downregulation of alpha 1A receptors, and reduce contractile function of prostate in animal studies. Open studies of intraprostate BoNT-A injection have demonstrated promising results of reducing LUTS and improvement of voiding function in human LUTS/BPH, however, intraprostatic BoNT-A injection did not perform better than the placebo group in recent publications of placebo controlled studies. We suggested that BoNT-A prostate injection might benefit selected population of BPH/LUTS, but it is unlikely to be an effective therapy for general population of male LUTS/BPH. Full article
(This article belongs to the Special Issue Botulinum Toxin A on Lower Urinary Tract Dysfunction)
Open AccessReview
Intravesical OnabotulinumtoxinA Injection for Overactive Bladder Patients with Frailty, Medical Comorbidities or Prior Lower Urinary Tract Surgery
Received: 2 February 2016 / Revised: 16 March 2016 / Accepted: 18 March 2016 / Published: 25 March 2016
Cited by 6 | PDF Full-text (237 KB) | HTML Full-text | XML Full-text
Abstract
Overactive bladder (OAB) symptoms increase with age and involve several comorbidities. OnabotulinumtoxinA (BoNT-A) intravesical injection is a treatment choice for patients who are intolerant of or refractory to antimuscarinics. However, the increased risk of urinary tract infection and elevated post-void residual (PVR) volume [...] Read more.
Overactive bladder (OAB) symptoms increase with age and involve several comorbidities. OnabotulinumtoxinA (BoNT-A) intravesical injection is a treatment choice for patients who are intolerant of or refractory to antimuscarinics. However, the increased risk of urinary tract infection and elevated post-void residual (PVR) volume post-treatment require resolution. Male sex, baseline PVR > 100 mL, and comorbidities are independent risk factors of adverse events (AEs) such as acute urinary retention (AUR). Intravesical BoNT-A injection is safe and effective for OAB patients with frailty, medical comorbidities such as Parkinson’s disease (PD), chronic cerebrovascular accidents (CVA), dementia, or diabetes, or a history of prior lower urinary tract surgery (prostate or transvaginal sling surgery). Post-treatment, 60% of frail elderly patients had a PVR volume > 150 mL and 11% had AUR. Although intravesical BoNT-A injection is safe for PD patients, CVA patients had higher strain voiding rates. Diabetic patients were at increased risk of large PVR urine volume and general weakness post-treatment. Treatment results were similar between patients with and without a history of prostate or transvaginal sling surgery. Possible AEs and bladder management strategies should be conveyed to patients before treatment. Careful patient selection is important, and therapeutic safety and efficacy should be carefully balanced. Full article
(This article belongs to the Special Issue Botulinum Toxin A on Lower Urinary Tract Dysfunction)
Open AccessFeature PaperReview
Use of Botulinum Toxin A in the Treatment of Lower Urinary Tract Disorders: A Review of the Literature
Received: 27 January 2016 / Revised: 10 March 2016 / Accepted: 15 March 2016 / Published: 23 March 2016
Cited by 9 | PDF Full-text (262 KB) | HTML Full-text | XML Full-text
Abstract
Botulinum neurotoxin (BoNT) is used to treat a variety of ailments, and its therapeutic application in lower urinary tract disorders (LUTDs) is well studied. Robust evidence supporting the efficacy and tolerability of BoNT in the treatment of neurogenic detrusor overactivity (NDO) and non-neurogenic [...] Read more.
Botulinum neurotoxin (BoNT) is used to treat a variety of ailments, and its therapeutic application in lower urinary tract disorders (LUTDs) is well studied. Robust evidence supporting the efficacy and tolerability of BoNT in the treatment of neurogenic detrusor overactivity (NDO) and non-neurogenic overactive bladder (OAB) has led to regulatory approval for these conditions. Use of BoNT in the treatment of interstitial cystitis/bladder pain syndrome, chronic pelvic pain, and detrusor sphincter dyssynergia has demonstrated some promise, but is still evolving and off-label for these indications. Trials to date do not support the use of BoNT for benign prostatic hyperplasia. This comprehensive review outlines the mechanisms of BoNT in the treatment of LUTDs in adults and presents background and updated data examining the efficacy and adverse events associated with the use of BoNT in common urologic applications. Full article
(This article belongs to the Special Issue Botulinum Toxin A on Lower Urinary Tract Dysfunction)
Open AccessFeature PaperReview
Potential Effect of Liposomes and Liposome-Encapsulated Botulinum Toxin and Tacrolimus in the Treatment of Bladder Dysfunction
Received: 3 February 2016 / Revised: 26 February 2016 / Accepted: 29 February 2016 / Published: 18 March 2016
Cited by 3 | PDF Full-text (2288 KB) | HTML Full-text | XML Full-text
Abstract
Bladder drug delivery via catheter instillation is a widely used treatment for recurrence of superficial bladder cancer. Intravesical instillation of liposomal botulinum toxin has recently shown promise in the treatment of overactive bladder and interstitial cystitis/bladder pain syndrome, and studies of liposomal tacrolimus [...] Read more.
Bladder drug delivery via catheter instillation is a widely used treatment for recurrence of superficial bladder cancer. Intravesical instillation of liposomal botulinum toxin has recently shown promise in the treatment of overactive bladder and interstitial cystitis/bladder pain syndrome, and studies of liposomal tacrolimus instillations show promise in the treatment of hemorrhagic cystitis. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core that can encapsulate hydrophilic and hydrophobic drug molecules to be delivered to cells via endocytosis. This review will present new developments on instillations of liposomes and liposome-encapsulated drugs into the urinary bladder for treating lower urinary tract dysfunction. Full article
(This article belongs to the Special Issue Botulinum Toxin A on Lower Urinary Tract Dysfunction)
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Open AccessReview
Botulinum toxin A for the Treatment of Overactive Bladder
Received: 29 January 2016 / Revised: 20 February 2016 / Accepted: 24 February 2016 / Published: 29 February 2016
Cited by 10 | PDF Full-text (236 KB) | HTML Full-text | XML Full-text
Abstract
The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical [...] Read more.
The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder. Full article
(This article belongs to the Special Issue Botulinum Toxin A on Lower Urinary Tract Dysfunction)
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