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ABSTRACTIntroductionOveractive bladder (OAB) is a common syndrome in adults. Current pharmacologic treatment includes antimuscarinic agents and β-3 adrenoceptor agonists. For non-responders to oral medication, intravesical injection of botulinum toxin A (BoNT-A) is an effective option. However, these treatments have potential adverse events and should be cautiously selected for appropriate patients. This review presents the recently published results of clinical trials and studies for patients with OAB and the underlying pathophysiology of OAB. Appropriate medical therapy based on pathophysiology of OAB is also presented.Areas coveredLiterature search from Pubmed from 2001 to 2023 including clinical background, pharmacology, and clinical studies for OAB medications.Expert opinionTreatment of OAB syndrome with any antimuscarinic or β-3 adrenoceptor agonist is feasible as a first-line approach. For patients with suboptimal therapeutic effect to full-dose antimuscarinics or mirabegron, combination with both drugs can improve efficacy. Intravesical BoNT-A 100-U injection provides therapeutic effects for refractory OAB. Patients who are refractory to initial pharmacotherapies should be investigated for the underlying pathophysiology; then an appropriate medication can be added, such as an α1-blocker or anti-inflammatory agents. Patient education about behavioral modification and therapies should always be provided with oral medication or BoNT-A injection for OAB patients.

The objective of the present study was to investigate the diagnostic values of urine cytokines in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) and to identify their correlations with clinical characteristics. Urine samples were collected from 127 patients with IC/BPS [European Society for the Study of Interstitial Cystitis (ESSIC) types 1 and 2] and 28 controls. Commercially available multiplex immunoassays (MILLIPLEX map kits) were used to analyze 31 targeted cytokines. Cytokine levels between patients with IC/BPS and controls were analyzed using ANOVA. Receiver-operating characteristic curves of each cytokine to distinguish IC/BPS from controls were generated for calculation of the area under the curve. Patients with IC/BPS had urine cytokine profiles that differed from those of controls. Between patients with ESSIC type 1 and 2 IC/BPS, urine cytokine profiles were also different. Among cytokines with high diagnostic values (i.e., area under the curve > 0.7) with respect to distinguish patients with ESSIC type 2 IC/BPS from controls, regulated upon activation, normal T cell expressed and presumably secreted (RANTES), macrophage inflammatory protein (MIP)-1β, and IL-8 were of higher sensitivity, whereas macrophage chemoattractant protein (MCP)-1, chemokine (C-X-C motif) ligand 10 (CXCL10), and eotaxin-1 were of higher specificity. In multivariate logistic regression models controlling for age, sex, body mass index, and diabetes mellitus, the urine cytokines with high diagnostic values (MCP-1, RANTES, CXCL10, IL-7, and eotaxin-1) remained statistically significant in differentiating IC/BPS and controls. MCP-1, CXCL10, eotaxin-1, and RANTES were positively correlated with glomerulation grade and negatively correlated with maximal bladder capacity. In conclusion, patients with IC/BPS had urine cytokine profiles that clearly differed from those of controls. Urine cytokines might be useful as biomarkers for diagnosing IC/BPS and mapping its clinical characteristics.

Overlapping symptoms of overactive bladder (OAB) and urinary tract infection (UTI) often complicate the diagnosis and contribute to overprescription of antibiotics. Inflammatory response is a shared characteristic of both UTI and OAB and here we hypothesized that molecular differences in inflammatory response seen in urine can help discriminate OAB from UTI. Subjects in the age range of (20–88 yr) of either sex were recruited for this urine analysis study. Urine specimens were available from 62 UTI patients with positive dipstick test before antibiotic treatment. Six of these patients also provided urine after completion of antibiotic treatment. Subjects in cohorts of OAB (n= 59) and asymptomatic controls (n= 26) were negative for dipstick test. Urinary chemokines were measured by MILLIPLEX MAP Human Cytokine/Chemokine Immunoassay and their association with UTI and OAB was determined by univariate and multivariate statistics. Significant elevation of CXCL-1, CXCL-8 (IL-8), and CXCL-10 together with reduced levels for a receptor antagonist of IL-1A (sIL-1RA) were seen in UTI relative to OAB and asymptomatic controls. Elevated CXCL-1 urine levels predicted UTI with odds ratio of 1.018 and showed a specificity of 80.77% and sensitivity of 59.68%. Postantibiotic treatment, reduction was seen in all CXC chemokines with a significant reduction for CXCL-10. Strong association of CXCL-1 and CXCL-10 for UTI over OAB indicates mechanistic differences in signaling pathways driving inflammation secondary of infection in UTI compared with a lack of infection in OAB. Urinary chemokines highlight molecular differences in the paracrine signaling driving the overlapping symptoms of UTI and OAB.

Botulinum toxin subtype A (BoNT-A) is a potent neurotoxin that can selectively modulate neurotransmitter release from nerve endings, resulting in muscular paralysis. BoNT-A might also act on sensory nerves, and have an anti-inflammatory effect. In the first urological use of BoNT-A, injection into the urethral sphincters of patients with detrusor–sphincter dyssynergia resulted in a reduction of urethral resistance and improved voiding efficiency. Subsequently, intravesical BoNT-A injections have received regulatory approval for treatment of neurogenic detrusor overactivity owing to spinal cord lesions or multiple sclerosis, and idiopathic overactive bladder in adults. BoNT-A has also been widely used to treat patients with the off-label indications of neurogenic or non-neurogenic voiding dysfunction and male lower urinary tract symptoms owing to BPH and bladder-neck dysfunction. Other indications for which urologists have applied BoNT-A injections include interstitial cystitis/bladder pain syndrome, bladder oversensitivity and chronic pelvic pain syndrome. BoNT-A is currently delivered as an intravesical injection; however, use of liposome encapsulated formulations is also beginning to show some therapeutic potential.

Interstitial cystitis/bladder pain syndrome is characterized by bladder pain associated with urgency, frequency, nocturia, dysuria and sterile urine. Recent studies revealed that these bladder dysfunctions could originate from chronic inflammation or urothelial insult and proceed to a cascade of tissue reactions, which finally ascends to the CNS. The principles for treatment of interstitial cystitis/bladder pain syndrome are based on controlling the dysfunctional epithelium by continual replenishment of the glycosaminoglycan layer, inhibiting neurological hyperactivity by administration of amitriptyline or imipramine, suppression of allergies with antihistamines, and pain control with nonsteroidal anti-inflammatory drugs, COX-2 inhibitors or tranquilizers. Intravesical treatment with heparin, hyaluronic acid, chondroitin sulfate, Bacillus Calmette–Guérin, dimethylsulfoxide, resiniferatoxin, or botulinum toxin A has shown early effectiveness in some patients. Surgical treatment should be reserved for those who have no response to medical therapy.

Dysfunctional voiding is an abnormality of bladder emptying in neurologically normal individuals where the external sphincter activity increases during voiding, and it is difficult to diagnose by symptoms alone. Videourodynamic study could provide great help in differentiating dysfunctional voiding and other voiding disorder. In this retrospective study, we analyze the videourodynamic parameters of the patients with dysfunctional voiding.

Objectives:Intravesical injection of onabotulinumtoxinA (i.e. Botox) provides effective treatment for overactive bladder. However, treatment‐related adverse events (AEs) remain problems. This study investigated the effect of AEs after onabotulinumtoxinA injection on the success rate for idiopathic detrusor overactivity (IDO).

Overactive bladder syndrome (OAB) is highly prevalent bladder disorder in men and women. About 10–15% of the population suffers from urgency frequency with or without urgency urinary incontinence. It is estimated that 50–75% of patients with OAB may have urodynamic detrusor overactivity (DO). Urodynamic study invasive and most of the OAB patients might not accept it as a routine assessment. Therefore, a more objective and non‐invasive test for diagnosis and assessing DO from OAB patients is needed. Recently, urinary nerve growth factor (NGF) has gained great interest in detecting DO in patients with OAB. Urinary NGF level was found to increase in OAB and urodynamic DO. Urinary NGF levels correlated with severity of OAB symptoms. Patients with either idiopathic or neurogenic DO may have increased urinary NGF levels. Urinary NGF levels have been shown to decrease in patients with patients with OAB and DO who have been well treated with antimuscarinics or botulinum toxin injection, but not in those with persistent OAB after treatment. Not all patients with OAB can have an elevated urinary NGF level; it may also be increased in patients with interstitial cystitis/painful bladder syndrome and other lower urinary tract diseases, suggesting urinary NGF expression could be a product of bladder inflammation and a limited specificity of urinary NGF for diagnosing DO. The source of urinary NGF has not yet been fully explored yet. Nevertheless, urinary NGF level is likely to be a promising biomarker for diagnosis of DO from OAB patients, to monitor therapeutic outcome and predict disease progression.

Objectives:To measure urinary nerve growth factor (NGF) levels in patients with several urinary tract diseases under different conditions and compare with NGF levels in patients with overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS).

Botulinum neurotoxin (BoNT) is well–known for its ability to modulate neurotransmission and treat muscular hypercontractility. In addition, recent studies also suggest that BoNT affects the modulation of sensory function and inflammation. We hereby review the mechanism by which it modulates overactive bladder and interstitial cystitis.

The traditional medication for overactive bladder (OAB) is antimuscarinic agent, which targets muscarinic receptors. Recent investigations have revealed that muscarinic receptors are present in the urothelium and suburothelial sensory fibers, as well as in the detrusor. Urothelial dysfunction and abnormality of sensory receptor expression or transmitter release in suburothelial nerves could contribute to OAB refractory to antimuscarinics. Intravesical treatment to inhibit abnormal receptor expression or transmitter release in the sensory nerve terminals in the suburothelial space might provide beneficial therapeutic effects in the treatment of OAB. Intravesical resiniferatoxin (RTX) instillation and intravesical botulinum toxin A (BoNT‐A) injection are two promising treatment alternatives for refractory OAB. RTX at a high dose may cause undesired adverse events, such as hematuria, bladder pain or autonomic dysreflexia. RTX at a low concentration can decrease sensory urgency without influencing detrusor contractility; multiple instillations of low‐dose RTX may be required to achieve adequate desensitization of OAB. BoNT‐A, however, has a beneficial effect on detrusor contractility and causes large post‐void residual after injection in some patients. Therefore, careful dosage and injection site adjustment is mandatory to achieve satisfactory results using intravesical therapy.

Urethral injection of botulinum A toxin (BoNT-A) has therapeutic effects on voiding dysfunction. However, the optimal dose remains to be determined. This study compared the therapeutic results of urethral injections of 50 U and 100 U of BoNT-A.

Evidence suggests that unmyelinated C fibers become predominant in the mediation of the detrusor reflex in patients with chronic spinal cord lesions and possibly in idiopathic detrusor hyperactivity. Intravesical vanilloid therapy might be effective in treating refractory detrusor overactivity due to nonspinal cord lesion. This study investigated the clinical effect of intravesical resiniferatoxin in treating detrusor overactivity of nonspinal cord lesions refractory to anticholinergics.

This study investigates the effectiveness of botulinum A toxin in the treatment of various types of lower urinary tract dysfunction and determines the predictive factors for a successful outcome.

Video urodynamic changes were compared after the pubovaginal sling procedure using rectus fascia or polypropylene mesh in women with stress urinary incontinence.

Objectives:To investigate the relationships between urethral and paraurethral anatomy and urethral pressure measurements in women with stress urinary incontinence (SUI).Materials and Methods:A total of 83 women with SUI and 33 with frequency urgency syndrome but not SUI were included in the study. The parameters of transrectal sonography of the urethra and urethral pressure profilometry were compared among the subjects with each of four types of SUI and non–SUI subjects.Results:Videourodynamic study revealed that 26 women had type 0 SUI, 39 had type 1 SUI, 19 had type 2 SUI and 9 had type 3 SUI. The urethral striated muscular area was significantly smaller in subjects with type 3 SUI than in subjects with type 0 SUI and in non–SUI subjects. The thickness of the urethropelvic ligaments was thinner in subjects with SUI than in non–SUI subjects. Maximal urethral closure pressure (MUCP) was also significantly smaller in subjects with SUI than in non–SUI subjects. Pressure transmission ratio (PTR) was lower in subjects with type 1, 2 and 3 SUI than in subjects with type 0 SUI and no SUI. Pelvic floor contractility was significantly lower for subjects with type 3 SUI than for the other groups of subjects. Leak point pressure (LPP) showed a significantly progressive decrease from type 1 to 3 SUI subjects.Conclusions:This study found that SUI in women is a condition in which the urethral and paraurethral structures become progressively deficient. The intrinsic and extrinsic structural deficiencies result in a lower MUCP, smaller PTR, insufficient pelvic floor contractility on the urethra, and a lower LPP in SUI patients.

Objectives. To determine the influence of surgery on bladder and urethral function by performing a videourodynamic study in female patients with stress urinary incontinence (SUI) before and after a pubovaginal sling procedure. Methods. A total of 14 women with type II SUI, 7 with type III SUI, and 3 with mixed type II/III SUI were included in the study. The pubovaginal sling procedure was carried out using a modified method that minimized interference with the endopelvic fascia. Videourodynamic study was performed before the procedure, within 7 to 14 days postoperatively, and at 3 to 6 months postoperatively. Results. Videourodynamic study within 7 to 14 days postoperatively revealed no change in the mean voiding detrusor pressure (Pdet), cystometric capacity, or maximal flow rate (Qmax) compared with the preoperative data. The bladder neck opening time and residual urine amount were significantly increased. Within 3 to 6 months after surgery, Pdet, Qmax, bladder neck opening time, and residual urine amount returned to preoperative levels. An elevation of the bladder neck was noted during coughing in 7 patients. After surgery, de novo detrusor instability was noted in 2 patients (8.3%). No infection or sling failure was noted at a mean follow-up time of 12 months. The success rate was 96%. Conclusions. The pubovaginal sling procedure is an effective method for the treatment of type II or type III SUI. The postoperative videourodynamic results show that this procedure can re-establish a "hammock effect" on the proximal urethra during abdominal straining without compromising urethral resistance.

Objectives. To establish a clinical prostate score based on the parameters of uroflowmetry and prostate measurements to provide a better prediction of benign prostatic obstruction (BPO) in men with lower urinary tract symptoms (LUTS) and small prostate volume. Methods. From October 1997 to September 1998, a prospective study of 324 consecutive men with LUTS was conducted in a community hospital in Taiwan. All patients were first evaluated by uroflowmetry and transrectal sonography of the prostate, and a videourodynamic study (VUDS) was performed before any medication was given. Patients were grouped as obstructed or unobstructed according to the results of the VUDS. Parameters from uroflowmetry and prostate measurements were evaluated for their sensitivity in predicting BPO. A clinical prostate score was established by summing scores on seven prostatic and uroflowmetric items: maximal flow rate (Qmax), flow pattern, voided volume, residual urine amount, total prostate volume (TPV), transition zone index (TZI), and prostatic configuration. Each of these items had a score representing the grade of sensitivity of BPO. Results. Among the 324 men examined, only 65.4% were found to have obstruction by VUDS. A value of Qmax 10 mL/s or less had a sensitivity of only 75.4% and specificity of only 63.7% for BPO. A constrictive flow pattern had 87.2% sensitivity, residual urine 100 mL or greater had 86.1%, TPV 40 mL or greater had 94.6%, TZI 0.5 or greater had 87.8%, and the presence of a median lobe had 87.1% sensitivity; the presence of any of these factors added 2 points to the score. The other parameters were scored as 1, 0, and −1, representing their sensitivity as slightly superior or inferior to that of LUTS. A prostate score of 3 or greater had a sensitivity of 87.2% and a specificity of 60.8% for BPO. On the basis of this prostate score, 148 patients (46%) would have been treated for BPO without the need for further investigation, of whom 19 (5.9%) would have been misdiagnosed. The remaining 176 patients (54%) would have undergone a VUDS and 93 of these patients (28.7%) were unobstructed. Conclusions. By combining uroflowmetry and transrectal sonography of the prostate, patients with LUTS can be diagnosed with a good sensitivity and specificity. Using the parameters in the uroflow and prostate measurements, a prostate score could be established and used as an indicator of BPO for selecting patients with LUTS who require further treatment or invasive VUDS.

In a series of 229 lower ureteral calculi manipulated with either extracorporeal shock wave lithotripsy (ESWL††Dornier Medical System, Inc., Marietta, Georgia.) or ureteroscopy the stone clearance rate 7 days after treatment was 40.6% and 90%, respectively. Only 17 of 32 patients (53.1%) treated with ESWL were rendered stone-free at 4-week followup. In addition to concern about stone clearance, other medical and social factors, and the availability of health insurance coverage must be considered. Since the differences of living standards between highly developed and developing countries are great, the selection of ESWL or ureteroscopy as primary treatment of lower ureteral calculi must be based on the socioeconomical status of a specific country. Because ESWL devices are not readily available in most developing countries and ureteroscopy is cost-effective, highly efficacious (greater than 92%) and involves minimal morbidity (less than 10%) for calculi removal in experienced hands, we recommend ureteroscopy as the treatment of choice for lower ureteral stones, with ESWL as the alternative, in developing countries.

Objective:Motor cycle accidents are the major cause of head injury and spinal cord injury (SCI) in Taiwan. The incidence of SCI in Hualien county is the highest in the world. In a community hospital in Hualien, active urological management was carried out for SCI patients with voiding dysfunctions and urological complications. This study was conducted to assess the success of active urological management. Methods:From 1988 to 1996, in the urological department, 251 SCI patients with varying voiding dysfunctions or urological complications were managed with various surgical or nonsurgical procedures according to their underlying pathologies. The satisfaction rate and quality of life index were assessed before and after active urological treatment. Results:There were 118 patients with cervical SCIs, 93 patients with thoracic or lumbar SCIs, and 40 patients with sacral SCIs or infrasacral neuropathy. After initial managements, 174 patients were able to pass urine by themselves, by clean intermittent self-catheterization (CISC) or with an indwelling Foley catheter. The remaining 77 patients suffering from severe dysuria, urinary incontinence, hydronephrosis and frequent urinary tract infections were managed with various surgical procedures. The procedures included external sphincterotomy (n = 30), enterocystoplasty (n = 28), autoaugmentation (n = 6), continent urinary diversion (n = 7), periurethral Teflon injection (n = 3), and transurethral resection of the prostate (n = 3). After treatment, hydronephrosis resolved in 100% of the kidney units; frequent symptomatic urinary tract infection improved in 83.3% after external sphincterotomy and 75% after enterocystoplasty and continent diversion; while urinary incontinence disappeared or improved in 93% after enterocystoplasty and autoaugmentation. The total satisfaction rate was 84.4% after the surgical procedures. The mean quality of life index improved from –1.27 ± 0.39 to +1.54 ± 0.38 after management. However, some complications such as mucus secretion (76.5%), abdominal pain (20.6%), loose stool (23.5%) and frequent stone formation (11.8%) still bothered the patients undergoing enterocystoplasty and continent diversion. Repeat sphincterotomy was necessary in 16.7% of patients, and 50% were not satisfied with total incontinence after external sphincterotomy. During the follow-up period, 87% of all patients had ≥1 yearly episode of urinary tract infection after spinal injury and 11 patients died of urosepsis. Conclusions:Active urological management to improve quality of life and to treat urological complications in SCI patients is mandatory. After long-term follow-up, SCI patients can be free of indwelling catheters, hydronephrosis usually resolves and urinary tract infections are infrequent.

Clinical diagnosis of overactive bladder (OAB) varies greatly and is based on subjective symptoms. A better way to diagnose and assess therapeutic outcome in patients who present with OAB needs to be developed. Evidence has shown that urinary proteins, such as nerve growth factor (NGF) and prostaglandin E2(PGE2) levels increase in patients with OAB, bladder outlet obstruction (BOO) and detrusor overactivity (DO). Urinary NGF level increases physiologically in normal subjects at urge to void, but increases pathologically in OAB patients at small bladder volume and at urgency sensation. Patients with OAB dry and OAB wet have significantly higher urinary NGF levels compared to controls and patients with increased bladder sensation. Urinary NGF levels decrease after antimuscarinic therapy and further decrease after detrusor botulinum toxin injections in refractory OAB. A higher urinary NGF level could be a biomarker for sensory nerve‐mediated DO. Urinary NGF levels could be a potential biomarker for diagnosis of OAB and serve for the assessment of the therapeutic effect of antimuscarinic therapy. Another potential biomarker for the diagnosis of OAB is detrusor wall thickness. It has been hypothesized that the bladder wall increases in thickness in patients with OAB. The thickened detrusor wall might decrease in response to antimuscarinic treatment, and measurement of detrusor wall thickness might be a useful biomarker for the evaluation of OAB. However, current investigations do not yet provide a uniform observation among various studies.