Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. Different phenotypes of IC/BPS have been explored including Hunner and non-Hunner type IC, hypersensitive bladder, and bladder pain both with and without functional somatic syndrome. Different gene expressions have also been found in different IC phenotypes. Abnormal expressions of uroplakin, chondroitin sulfate and adhesive protein E-cadherin, tight junction protein zonula occludens-1 in IC/BPS bladder suggest abnormal epithelial differentiation in this bladder disease. Analysis of inflammatory proteins, or cytokines in the urine or serum provides another diagnostic foundation forIC/BPS subtypes. The involvement of IC/BPS in systemic functional somatic syndrome and other pelvic organ diseases might also subdivide subtypes of IC/BPS. Chronic inflammation, increased urothelial apoptosis, and abnormal urothelial function are closely associated in IC bladders. This article reviews recent research on the pathomechanisms of IC, which might help us in mapping the heterogeneity of the disease.
Adhesives ; Apoptosis ; Autoimmunity ; Biomarkers ; Cadherins ; Chondroitin Sulfates ; Cystitis ; Cytokines ; Epithelium ; Gene Expression ; Homeostasis ; Inflammation ; Lower Urinary Tract Symptoms ; Mast Cells ; Neurogenic Inflammation ; Nocturia ; Phenotype ; Population Characteristics* ; Tight Junctions ; Urinary Bladder ; Urinary Bladder Diseases ; Urinary Tract Infections ; Uroplakins

PURPOSE: Overactive bladder (OAB) is a symptom syndrome and is usually diagnosed by subjective symptoms of urgency with or without urgency incontinence. However, because urgency symptoms are so subjective, it is difficult to objectively grade symptoms of urgency. Although urodynamic study can detect detrusor overactivity (DO) objectively, not all patients with OAB are found to have DO. Therefore, recent research interests have focused on urinary and image biomarkers in the assessment of OAB. MATERIALS AND METHODS: Investigating articles from the literature and recent published works were reviewed. RESULTS: The urinary nerve growth factor (NGF) level is found to increase in patients with OAB-wet, bladder outlet obstruction, mixed urinary incontinence, and urodynamic DO. NGF levels are correlated with OAB symptoms and return to normal after treatment. However, urinary NGF is not increased only in patients with OAB and DO. It also increases in patients with interstitial cystitis/painful bladder syndrome (IC/PBS) and other lower urinary tract diseases such as urinary tract stones, bacterial infection, and urothelial tumor. Thirty percent of OAB patients have a low urinary NGF level. Nevertheless, antimuscarinic or botulinum toxin treatment can decrease the urinary NGF level, and changes in the NGF level are correlated with the urgency severity scale. CONCLUSIONS: It is therefore possible to use urinary NGF levels as a biomarker for assessment of therapeutic outcome in patients with OAB. Further research on combined multiple biomarkers to differentiate OAB and IC/PBS is necessary.
Bacterial Infections ; Biomarkers ; Botulinum Toxins ; Humans ; Nerve Growth Factor ; Urinary Bladder ; Urinary Bladder Neck Obstruction ; Urinary Bladder, Overactive ; Urinary Calculi ; Urinary Incontinence ; Urodynamics ; Urologic Diseases

Intravesical onabotulinumtoxinA (BoNT-A) injection is an effective treatment for overactive bladder syndrome (OAB) that is refractory to antimuscarinics. An injectable dose of 100 U has been suggested to achieve the optimal balance of benefit and safety in patients with OAB. BoNT-A (total volume of 10 mL) was administered as evenly distributed intradetrusor injections (5 U) across 20 sites approximately 1 cm apart (0.5 mL per site) using a flexible or rigid cystoscope. Treatment with BoNT-A was generally well tolerated by most patients, and most treatment-related adverse events were localized to the urinary tract. The prevalence of OAB increases with age, and elderly patients are more vulnerable to complications. The short-term efficacy of intravesical BoNT-A injection for refractory OAB with no treatment-related complications in the elderly population has been documented. Frail elderly patients can experience the same treatment results, such as significantly improved urgent urinary incontinence and quality of life, as young and nonfrail elderly patients with 100-U BoNT-A injections. However, increased risk of larger postvoid residual (PVR) urine and lower long-term success rates were noted in frail elderly patients; around 11% had acute urinary retention, while 60% had PVR urine volume >150 mL after treatment. In addition, intravesical injection of BoNT-A effectively decreased urgency symptoms in elderly patients with OAB and central nervous system lesions. The adverse effects were acceptable, while the long-term effects were comparable to those in patients with OAB without central nervous system lesions. Nonetheless, the possibility of longstanding urinary retention and chronic catheterization in this vulnerable population requires careful evaluation before treatment with intravesical BoNT-A. In conclusion, the current findings indicate that intravesical BoNT-A is an effective and safe treatment for OAB in elderly patients.
Administration, Intravesical ; Aged ; Botulinum Toxins, Type A ; Catheterization ; Catheters ; Central Nervous System ; Cystoscopes ; Frail Elderly ; Humans ; Muscarinic Antagonists ; Prevalence ; Quality of Life ; Urinary Bladder, Overactive* ; Urinary Incontinence ; Urinary Retention ; Urinary Tract ; Vulnerable Populations

Purpose: We evaluated the therapeutic effects on overactive bladder (OAB) symptoms and sexual function of behavioral therapy with or without mirabegron in sexually active male patients with OAB. Mirabegron, a selective β3 adrenoceptor agonist for the treatment of OAB, has been shown to induce corpus cavernosum relaxation. Methods: In this 4-site, randomized controlled trial, 150 sexually active men with OAB were enrolled between June 2020 and May 2022. Participants were randomly allocated (1:2) into 2 treatment groups: (1) behavioral therapy alone (n = 50) and (2) a combination of mirabegron 50 mg daily and behavioral therapy (n = 100). The evaluation was based on the overactive bladder symptoms score (OABSS), the International Index of Erectile Function, the ejaculatory domain short form, the International Prostate Symptom Score, patient perception of bladder condition, quality of life, and urodynamic parameters. The therapeutic outcomes were assessed at baseline, 4 weeks, and 12 weeks. Results: There were 65 patients (65%) in the combination subgroup and 36 patients in the behavioral therapy who completed all 12 weeks of treatment. Both groups had a statistically significant improvement in OABSS after 12 weeks of treatment. The combination therapy group achieved a statistically significant improvement in all 4 subscores of OABSS, however, the urinary frequency (P = 0.120) and urinary incontinence (P = 0.234) subscores in the behavioral therapy only group did not show a significant change. Additionally, the combination group had a significant improvement in functional bladder capacity, which was not seen in the behavioral therapy group. However, both groups did not have a significant change in erectile or ejaculatory function. Conclusions Behavioral therapy combined with mirabegron had more significant impact on the improvement of OAB than behavior therapy alone. However, both groups did not have significant changes in erectile or ejaculatory function.

PURPOSE: To investigate long-term therapeutic effects and patient adherence to a combination therapy of a 5α-reductase inhibitor and an α-blocker and to identify causes of withdrawal from medication in patients with clinical benign prostatic hyperplasia (BPH). METHODS: BPH patients with lower urinary tract symptoms (LUTS) receiving combination therapy with follow-ups for 1–12 years were retrospectively analyzed. Therapeutic effects were assessed at baseline and annually by measuring International Prostatic Symptoms Score, quality of life index, total prostate volume (TPV), maximal flow rate, voided volume, postvoid residual volume and prostate-specific antigen level. Causes of discontinued combination therapy were also investigated. RESULTS: A total of 625 patients, aged 40–97 years (mean, 73 years) were retrospectively analyzed. All measured parameters showed significant improvements after combination therapy. Three hundred sixty-nine patients (59%) discontinued combination therapy with a mean treatment duration of 2.2 years. The most common reasons for discontinued treatment were changing medication to monotherapy with α-blockers or antimuscarinics (124 patients, 19.8%), receiving surgical intervention (39 patients, 6.2%), and LUTS improvement (53 patients, 8.5%). Only 64 patients (10.2%) were loss to follow-up and 6 (1.0%) discontinued combined treatment due to adverse effects. Smaller TPV after short-term combination treatment caused withdrawal from combination therapy. CONCLUSIONS: BPH patients receiving long-term combination therapy showed significant improvement in all measured parameters. Changing medication, improved LUTS and choosing surgery are common reasons for discontinuing combination herapy. A smaller TPV after short-term combination treatment was among the factors that caused withdrawal from combination therapy.
Adrenergic alpha-1 Receptor Antagonists ; Follow-Up Studies ; Humans ; Lower Urinary Tract Symptoms ; Medication Adherence ; Muscarinic Antagonists ; Patient Compliance* ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia* ; Quality of Life ; Residual Volume ; Retrospective Studies ; Therapeutic Uses

PURPOSE: To investigate the changes in urinary nerve growth factor (uNGF) levels after acute urinary tract infection (UTI) and to assess the role of uNGF in predicting UTI recurrence in women. METHODS: Women with uncomplicated, symptomatic UTIs were enrolled. Cephalexin 500 mg (every 6 hours) was administered for 7-14 days to treat acute UTIs. Subsequently, the patients were randomized to receive either sulfamethoxazole/trimethoprim 800 mg/160 mg daily at bedtime, or celecoxib 200 mg daily for 3 months and were monitored for up to 12 months. NGF levels in the urine were determined at baseline, 1, 4, and 12 weeks after the initiation of prophylactic therapy, and were compared between women with first-time UTIs and recurrent UTIs, sulfamethoxazole/trimethoprim and celecoxib-treated women, and no UTI recurrence and UTI recurrence that occurred during the follow-up period. Twenty women free of UTIs served as controls. RESULTS: A total of 139 women with UTI and 20 controls were enrolled in the study, which included 50 women with a first-time UTI and 89 women with recurrent UTIs. Thirty-seven women completed the study. Women with recurrent UTIs (n=23) had a trend of lower uNGF levels than women with first-time UTIs (n=14). During follow-up, 9 women had UTI recurrence. The serial uNGF levels in women with UTI recurrence were significantly lower than those in women who did not have UTI recurrence during the follow-up period. CONCLUSIONS: The lower levels of uNGF in women with recurrent UTI and the incidence of UTI recurrence during follow-up suggest that lower uNGF might reflect the defective innate immunity in women with recurrent UTI.
Biomarkers ; Celecoxib ; Cephalexin ; Female ; Follow-Up Studies ; Humans ; Immunity, Innate ; Incidence ; Inflammation ; Nerve Growth Factor* ; Recurrence ; Urinary Tract Infections* ; Urinary Tract*

PURPOSE: Augmentation enterocystoplasty (AE) has been shown to improve clinical symptoms in patients with end-stage bladder disease (ESBD). Herein, we report the long-term outcomes of a series of patients with different etiologies of ESBD who received AE. METHODS: We retrospectively reviewed 102 patients with ESBD who received AE at the Hualien Tzu Chi General Hospital from 1992 to 2014. ESBD in this study was defined as including neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI) or myelomeningocele, inflammatory bladder disease (IBD), ESBD occurring after pelvic cancer surgery, and other etiologies. Complications including active lower urinary tract problems and urinary tract infection (UTI), as well as patients’ self-reported satisfaction with the procedure, were evaluated. RESULTS: A total of 102 patients were included in the study. A majority of patients received AE for NLUTD (n=43), followed by IBD (n=38), ESBD after pelvic cancer surgery (n=15), and the other etiologies (n=6). Patients had a mean age of 39.4±18.7 years and were followed for a mean of 78 months. All patients had significantly increased cystometric bladder capacity and compliance at the time of follow-up. Fifty-four patients (52.9%) reported moderate to excellent satisfaction with the outcome, and there were no significant differences among the groups (P=0.430). The most common reason for dissatisfaction was the need for clean intermittent catheterization (CIC; 41.7%), followed by urinary incontinence (25.0%) and recurrent UTI (16.7%). CONCLUSIONS: AE is a safe and effective procedure for patients with ESBD. Postoperative urinary incontinence and UTI as well as the need for CIC may affect quality of life and decrease patient satisfaction.
Compliance ; Cystitis ; Follow-Up Studies ; Hospitals, General ; Humans ; Intermittent Urethral Catheterization ; Lower Urinary Tract Symptoms ; Meningomyelocele ; Patient Satisfaction ; Pelvic Neoplasms ; Quality of Life ; Retrospective Studies ; Spinal Cord Injuries ; Urinary Bladder Diseases* ; Urinary Bladder* ; Urinary Bladder, Neurogenic ; Urinary Incontinence ; Urinary Tract ; Urinary Tract Infections

PURPOSE: To determine the duration of antimuscarinic therapy for overactive bladder syndrome (OAB) appropriate for assessment of the efficacy of treatment, and to evaluate the possible predictive factors for response to therapy. METHODS: All OAB patients who visited a urology outpatient clinic of a tertiary referral center and who were prescribed 5 mg of solifenacin or 4 mg of tolterodine extended release capsules daily were enrolled in the study. Patients were asked to continue therapy for 6 months. All enrolled patients completed the patient perception of bladder condition, overactive bladder symptom score (OABSS), and the modified Indevus Urgency Severity Scale questionnaires. All patients underwent uroflowmetry. RESULTS: A total of 164 patients were enrolled and 125 patients (76%) had at least one follow-up visit. The mean follow-up interval was 1 month (range, 0.5-6 months). Sixty-two patients (49.6%; 95% confidence interval [CI], 40.7-58.5) responded to antimuscarinic treatment. The median time for the onset of response was 3 months (95% CI, 1-6). Multivariate Cox proportional-hazards model revealed that elevated baseline OABSS was an independent predictor of responsiveness to therapy. Receiver operating characteristic (ROC) curve analysis revealed an optimal OABSS cutoff value of > or =7, with an area under the ROC curve of 0.79 (95% CI, 0.70-0.88; sensitivity, 91.9%; specificity, 60.7%). CONCLUSIONS: The median time for a therapeutic response was 3 months, and OABSS was the only predictor for responsiveness. These findings may serve as a guideline when prescribing antimuscarinic treatment for OAB patients.
Ambulatory Care Facilities ; Capsules ; Cholinergic Antagonists ; Follow-Up Studies ; Humans ; ROC Curve ; Sensitivity and Specificity ; Solifenacin Succinate ; Tertiary Care Centers ; Tolterodine Tartrate ; Treatment Outcome ; Urinary Bladder ; Urinary Bladder, Overactive* ; Urology

PURPOSE: Stress urinary incontinence (SUI) in men is a complication secondary to prostatectomy or resulting from neurological lesions. This study presents our experiences with male suburethral slings over the past decade. METHODS: In this study, we considered patients who presented with SUI and were diagnosed with an intrinsic sphincteric deficiency due to postprostatectomy incontinence (PPI) or other causes (non-PPI). Patients who underwent the suburethral sling procedure using a polypropylene mesh and a cardiovascular patch were retrospectively included. An urodynamic study was performed before and after the operation. Global response assessment (GRA) and SUI grading were used for surgical outcome. The revision rate and the infection rate were also evaluated. RESULTS: A total 31 patients were enrolled in this study; the mean patient age was 59.5±18.9 years, and the mean follow-up period was 36.9±29.4 months. Fourteen patients comprised the non-PPI group and 17 were in the PPI group. The preoperative SUI of all patients were categorized as a moderate to severe problem according to the SUI grade, with a mean score of 2.32±0.48 before the operation and 0.48±0.57 after the operation. With a mean score of 2.35±0.71, GRA showed that the patients were satisfied with the treatment. After the sling procedure, 4 patients (13%) reported a mild improvement, 12 (38.7%) a moderate improvement, while 15 (48.4%) reported an excellent improvement. Six patients (19.4%), including 5 from the non-PPI group (35.7%) and 1 (5.9%) from the PPI group (P=0.037), underwent sling removal because of infection. CONCLUSIONS: The male suburethral sling procedure using a polypropylene mesh and a cardiovascular patch is a safe, efficacious, and inexpensive surgical procedure for PPI. In cases of neurological incontinence, however, the higher infection rate in non-PPI patients means that they should be carefully managed.
Follow-Up Studies ; Humans ; Male* ; Multiple Endocrine Neoplasia Type 1 ; Polypropylenes* ; Prostatectomy ; Retrospective Studies ; Suburethral Slings ; Urinary Incontinence* ; Urodynamics

PURPOSE: The aim of this study was to analyze patterns of sensory protein expression and urothelial dysfunction in ketamine-related cystitis (KC) in humans. METHODS: Biopsies of bladder mucosa were performed in 29 KC patients during cystoscopy. Then specimens were analyzed for tryptase, zonula occludens-1 (ZO-1), E-cadherin, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) with immunofluorescence staining and quantification. In addition, 10 healthy control bladder specimens were analyzed and compared with the KC specimens. Another 16 whole bladder specimens obtained from partial cystectomy were also analyzed for the muscarinic receptors M2 and M3, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), β-3 adrenergic receptors (β3-ARs), and the P2X₃ receptor by western blotting. In addition, 3 normal control bladder specimens were analyzed and compared with the KC specimens. RESULTS: The KC bladder mucosa revealed significantly less expression of ZO-1 and E-cadherin, and greater expression of TUNEL and tryptase activity than the control samples. The expression of M3 and β3-AR in the KC specimens was significantly greater than in the controls. The expression of iNOS, eNOS, M2, and P2X3 was not significantly different between the KC and control specimens. CONCLUSIONS: The bladder tissue of KC patients revealed significant urothelial dysfunction, which was associated with mast-cell mediated inflammation, increased urothelial cell apoptosis, and increased expression of the M3 and β3-AR.
Apoptosis ; Biopsy ; Blotting, Western ; Cadherins ; Cystectomy ; Cystitis* ; Cystoscopy ; Fluorescent Antibody Technique ; Humans* ; In Situ Nick-End Labeling ; Inflammation ; Ketamine ; Mucous Membrane ; Nitric Oxide Synthase Type II ; Nitric Oxide Synthase Type III ; Receptor, Muscarinic M2 ; Receptors, Adrenergic ; Tryptases ; Urinary Bladder ; Urothelium