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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. [ABSTRACT FROM AUTHOR]

Objective: This study retrospectively investigated the influence of urodynamic parameters and patient characteristics on success rates among patients with overactive bladder (OAB) and urodynamic detrusor overactivity (DO). Materials and Methods: Consecutive patients with OAB and urodynamic DO initially received solifenacin, mirabegron, or combination of both for 1–3 months. If failed, patients were switched to another OAB medication subtype or provided additional OAB medication for a total of 6 months. A successful treatment was defined as an improvement in urgency severity and a global response assessment of ≥1. Success rates after initial or modulated OAB medication were analyzed based on patient and urodynamic characteristics. Results: A total of 453 patients were enrolled, among whom 144, 255, and 54 received solifenacin, mirabegron, and combined medications, respectively. Among the patients, 259 (57.2%) had OAB dry and 194 (42.8%) had OAB wet. Patients receiving mirabegron alone had a significantly higher initial medication success rate compared to that of others. Patients with a phasic DO (50.7%), bladder outlet obstruction (BOO, 52.5%), and no central nervous system (CNS) lesions (47.5%) exhibited higher success rates than those with a terminal DO (42.0%), no BOO (42.7%), and CNS lesions (31.6%), respectively. After switching or modulating the initial OAB medication following treatment failure, 115 (62.2%) of 185 patients still showed improvement in OAB symptoms, with an overall success rate of 70.2% after 6 months of treatment. Conclusion: Initial solifenacin or mirabegron treatment had a success rate of around 50%. In general, patients with a phasic DO, urodynamic BOO, and no CNS lesions have higher success rates than those with a terminal DO, no BOO, and CNS lesions, respectively. Success rates can further be improved by switching or modulating OAB medication. [ABSTRACT FROM AUTHOR]

Detrusor underactivity (DU), an important but under-researched issue, is thought to be complex and multifactorial in etiology, pathophysiology, and diagnosis. Bladder outlet obstruction (BOO) is one of the important known etiologies of DU, with significant morphologic and physiologic changes of the urothelium, suburothelium, and detrusor muscle in the urinary bladder. Chronic urinary bladder ischemia and repeated cycles of ischemia and reperfusion injury cause excessive oxidative stress, and it is thought to be responsible for the development of DU. DU might be the late phase or decompensated status of BOO, with the possible mechanisms of afferent nervous dysfunction, increased inflammation, denervation of the detrusor muscle, and myogenic failure. Prostaglandin E2 (PGE2) involves in the physiological detrusor contraction, and might provide the prognostic value for the recoverability of DU. Neurotrophins, including nerve growth factor and brain-derived neurotrophic factor, involve in the neuroplastic changes in many inflammatory bladder diseases, including BOO and DU. Oxidative stress biomarkers, including 8-hydroxy-2-deoxyguanosine, F2-isoprostane, and the involved pro-inflammatory cytokines, have been applied in BOO due to their involvements in chronic bladder ischemia. PGE2, neurotrophins, inflammatory cytokines, and oxidative stress biomarkers are the potential urine biomarkers in BOO-related DU. [ABSTRACT FROM AUTHOR]

Detrusor underactivity (DU) is a common urodynamic diagnosis in patients with lower urinary tract symptoms and large post-voiding residual volume. Animal and human studies showed the possible etiologies of DU include central or peripheral nerve injury, bladder outlet obstruction, chronic ischemia, aging, diabetes mellitus, and sympathetic inhibition of micturition reflex. Evidence from animal and human DU studies with various etiologies revealed highly similar gross and histological characteristics in the bladders, including increased bladder weight, bladder wall thickening, inflammation, collagen deposition, and fibrosis. In electron microscopy, smooth muscle destruction, swollen mitochondria, decreased nerve innervation, caveolae, and umbrella cell fusiform vesicles were noted in the DU bladders. Most animal DU models demonstrate detrusor contractility changes from compensatory to the decompensatory stage, and the change was compatible with human DU observation. The cystometry in the DU animal studies is characterized by impaired contractility, prolong intercontraction interval, and hyposensation, while in vitro bladder muscle strips experiment may exhibit normal detrusor contractility. Decreased bladder blood flow and increased oxidative stress in bladders had been proved in different animal DU models, suggesting they should be important in the DU pathogenesis pathway. Sensory receptors mRNA and protein expression changes in DU bladders had been observed in both animal and human studies, including muscarinic receptors M2, M3, adrenergic receptor β3, purinergic receptor P2X1, P2X3, and transient receptor potential vanilloid (TRPV) 1 and TRPV4. Although some of the sensory receptors changes remain controversial, it might be the target for further pharmacologic treatments. [ABSTRACT FROM AUTHOR]

Underactive bladder (UAB) is a symptom complex suggestive of detrusor underactivity (DU). Although it implies a primary dysfunction of the detrusor muscle, many other conditions such as advanced age, neurogenic factors, and bladder outlet obstruction also lead to UAB. The current understanding of the pathophysiology directly leading to UAB is limited. We believe that by identifying the morphological changes associated with UAB might shed light on this. Therefore, we searched literature with keywords of electron microscopy, ultrastructure, UAB, and DU to review current ultrastructural evidence concerning UAB. [ABSTRACT FROM AUTHOR]

Lower urinary tract symptoms (LUTS) are complicated and cannot be used alone to diagnose lower urinary tract dysfunctions (LUTDs) and guide treatment. Patients with bladder outlet obstruction (BOO), impaired detrusor contractility, and hypersensitive bladder might present with voiding predominant symptoms, whereas patients with detrusor overactivity (DO), dysfunctional voiding, or BOO might also present with storage symptoms. To clearly identify the pathophysiology of LUTD, a comprehensive urodynamic study (UDS) including pressure flow and image during the storage and emptying phases, naming videourodynamic study (VUDS), is necessary. This study is especially mandatory in the diagnosis of (1) male LUTS refractory to medical treatment for benign prostatic hyperplasia, (2) female voiding dysfunction and urinary retention, (3) diagnosis of overactive bladder syndrome refractory to first-line medication, (4) management of female stress urinary incontinence and postoperative LUTS, (5) diagnosis and management of neurogenic LUTD, (6) pediatric urinary incontinence and enuresis, (7) geriatric urinary incontinence, and (8) recurrent bacterial cystitis. Although VUDS should not be used as a screening test for any LUTS, it should be considered when the initial management cannot relieve LUTS, or when invasive surgical procedure is planning to undertake for patients with refractory LUTS. VUDS should be recommended as the second-line investigation when the initial diagnosis and treatment based on the symptoms alone or noninvasive tests fail to improve LUTS. [ABSTRACT FROM AUTHOR]

Male lower urinary tract symptoms (LUTSs) are highly prevalent in men and the incidence increases with aging. The pathophysiology of male LUTSs might be bladder outlet dysfunctions such as bladder neck (BN) dysfunction, benign prostatic obstruction, and poor relaxation of external sphincter and bladder dysfunctions such as detrusor overactivity (DO), detrusor underactivity, DO, and inadequate contractility. Male LUTSs include voiding and storage symptoms, and precision diagnosis should not be done based on the symptoms alone. Videourodynamic study provides a thorough look at the bladder and bladder outlet and can clearly demonstrate the underlying pathophysiology when the initial medication fails to relieve LUTS. Medical treatment should be given based on the underlying pathophysiology of LUTS, and surgical intervention to remove prostate should only be performed when a definite bladder outlet obstruction due to prostatic obstruction has been confirmed by invasive urodynamic study. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate the efficacy of mirabegron 25 mg daily in patients with nocturia-predominant hypersensitive bladder (HSB). Materials and Methods: This study prospectively investigated 219 consecutive patients with nocturia-predominant HSB and treated with mirabegron 25 mg daily from July 2015 to 2016. Patient with nocturia episode decreased by ≥1/night after treatment was considered successful. The subjective symptom score, such as International Prostate Symptom Score (IPSS), Quality of life index, Overactive Bladder Symptom Score (OABSS), Urgency Severity Scale, patient perception of bladder condition (PPBC), and nocturia episodes per night, was assessed before and 1 month after mirabegron treatment and between successful and failed groups. Results: A total of 219 patients, including 51 women and 168 men, were enrolled. The mean age of the population was 72.3 ± 11.0 years. Totally, 58 (26.5%) of the patients had improvement in nocturia at 1 month after treatment. Among them, 14 (27.5%) women and 44 (26.2%) men had improvement in nocturia episodes after treatment (P = 0.858). Compared the clinical data between successful and failed group, the baseline symptom scores were more severe in successful group, including IPSS-storage subscore (4.84 ± 2.09 vs. 4.11 ± 2.19, P = 0.031), OABSS (3.21 ± 0.67 vs. 2.91 ± 1.00, P = 0.037), and nocturia episodes (3.81 ± 0.95 vs. 3.095 ± 1.32, P = 0.000). Multivariate analysis revealed only a higher nocturia episodes (P = 0.046) predict a successful treatment result. Mirabegron 25 mg daily significantly improved PPBC score along the 3 months' follow-up (P < 0.05), and postvoid residual volume did not increase after mirabegron treatment in overall patients. Conclusions: Mirabegron 25 mg daily treatment showed a limited therapeutic effect on nocturia-predominant HSB patients. The patients with higher OAB symptoms predict a successful result. [ABSTRACT FROM AUTHOR]