Urine biomarker could be a useful tool for differential diagnosis of a lower urinary tract dysfunction.

A precision diagnosis of lower urinary tract dysfunctions (LUTD) such as bladder outlet obstruction, detrusor overactivity (DO), interstitial cystitis/bladder pain syndrome (IC/BPS), dysfunctional voiding (DV), or detrusor underactivity (DU) needs invasive videourodynamic study. Exploring non-invasive tools to help screening LUTD is necessary for clinicians in their daily practice. This article reviews recently clinical studies of using urinary inflammatory proteins and oxidative stress biomarkers in the identification of specific LUTD among men and women with lower urinary tract symptoms (LUTS). Some important findings have been reported: (1) Using urine chemokines CXCL-1 and interleukin-8 (IL-8), we may discriminate overactive bladder (OAB) symptoms in women between DO and urinary tract infection. (2) Urinary levels of oxidative stress biomarkers such as 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane have a potential being used as a tool to identify women with mixed DO and stress urinary incontinence. (3) Urine levels of total antioxidant capacity (TAC), and prostaglandin E2 (PGE2) are positively correlated with voiding detrusor pressure in patients with DU. (4) Urine levels of brain-derived neurotrophic factor (BDNF) and PGE2 were significantly higher in the DU patients with detrusor function recovery. (5) Women with DV had higher urinary levels of tumor necrosis factor-alpha (TNF-α) and 8-OHdG, and urinary IL-2 level was significantly lower. (6) Urine level of 8-isoprostane was higher in the patients with idiopathic DO and neurogenic DO. (7) Higher urine cytokine levels of monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted (RANTES), CXCL-10, IL-7, and eotaxin-1 in patients with IC/BPS than controls. (8) The urine levels of IL-8, CXCL-10, BDNF, IL-6, and RANTES were significantly higher in patients with Hunner's IC than non-Hunner's IC. (9) Male patients with IC/BPS had a significantly higher level of eotaxin, MCP-1, TNF-α, 8-OHdG, and TAC. Combining a higher eotaxin and a higher TNF-α can provide a satisfactory diagnostic value in discriminating IC/BPS from other LUTD in men. These studies provide evidence that measurement of cluster of urine biomarkers could be used as a diagnostic tool to differentiate different LUTD in patients with similar LUTS.

Combination of urinary biomarkers and machine-learning models provided a higher predictive accuracy to predict long-term treatment outcomes of patients with interstitial cystitis/bladder pain syndrome.

PURPOSE: To identify predictive factors for satisfactory treatment outcome of the patients with IC/BPS using urine biomarkers and machine-learning models. METHODS: The IC/BPS patients were prospectively enrolled and provide urine samples. The targeted analytes included inflammatory cytokines, neurotrophins, and oxidative stress biomarkers. The patients with overall subjective symptom improvement of ≥ 50% were considered to have satisfactory results. Binary logistic regression, receiver-operating characteristic (ROC) curve, machine-learning decision tree, and random forest models were used to analyze urinary biomarkers to predict satisfactory results. RESULTS: Altogether, 57.4% of the 291 IC/BPS patients obtained satisfactory results. The patients with satisfactory results had lower levels of baseline urinary inflammatory cytokines and oxidative biomarkers than patients without satisfying results, including interleukin-6, monocyte chemoattractant protein-1 (MCP-1), C-X-C motif chemokine 10 (CXCL10), oxidative stress biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHDG), 8-isoprostane, and total antioxidant capacity (TAC). Logistic regression and multivariable analysis revealed that lower levels of urinary CXCL10, MCP-1, 8-OHDG, and 8-isoprostane were independent factors. The ROC curve revealed that MCP-1 level had best area under curve (AUC: 0.797). In machine-learning decision tree model, combination of urinary C-C motif chemokine 5, 8-isoprostane, TAC, MCP-1, and 8-OHDG could predict satisfactory results (accuracy: 0.81). The random forest model revealed that urinary 8-isoprostance, MCP-1, and 8-OHDG levels had the most important influence on accuracy. CONCLUSION: Machine learning decision tree model provided a higher accuracy for predicting treatment outcome of patients with IC/BPS than logistic regression, and levels of 8-isoprostance, MCP-1, and 8-OHDG had the most important influence on accuracy.

Cystoscopic characteristic findings of interstitial cystitis and clinical implications.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disease of unknown etiology, characterized by bladder pain and frequency urgency symptoms. Based on the cystoscopic findings after hydrodistention under anesthesia, the phenotype of IC/BPS includes no glamerulation, characteristic glomerulation, and with Hunner's lesion. IC is specifically defined if there are characteristic Hunner's lesion appeared in cystoscopy or after hydrodistention. If there are glomerulations without Hunner's lesion, BPS should be considered. The definition of Hunner's lesion and glomerulations differs based on different definition and observations. Currently, there has been no clear description and grading of the glomerulations and Hunner's lesion. Because the classification of IC/BPS has an impact on the treatment strategy and associated with therapeutic outcome, it is unmet to have a clear definition and consensus on the characteristic cystoscopic findings of IC/BPS. This article reviews the literature and presents the figures of Hunner's lesions and description of different mucosal lesions after cystoscopic hydrodistention.

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.

Multimodal therapies and strategies for the treatment of interstitial cystitis/bladder pain syndrome in Taiwan.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease characterized by bladder pain, frequency, and nocturia. The most common pathologies include chronic inflammation and bladder urothelium dysfunction. According to the bladder condition with or without Hunner's lesions, IC/BPS can be divided into "IC" in patients with Hunner's lesion (HIC) and "BPS" in those without Hunner's lesion (NHIC). Previous studies have reported greater central sensitization and interorgan cross-talk in patients with NHIC. Multimodal treatments have been recommended in clinical guidelines under the biopsychosocial model. The bladder-gut-brain axis has also been speculated, and multimodal therapies are necessary. Unfortunately, currently, no treatment has been reported durable for IC/BPS. Patients with IC/BPS usually experience anxiety, depression, holistic physical responses, and even threats to social support systems. The lack of durable treatment outcomes might result from inadequate diagnostic accuracy and differentiation of clinical phenotypes based on the underlying pathophysiology. Precision assessment and treatment are essential for optimal therapy under definite IC/BPS phenotype. This article reviewed currently available literature and proposed a diagnosis and treatment algorithm. Based on bladder therapy combined with suitable physical and psychological therapies, a well-grounded multimodal therapy and treatment algorithm for IC/BPS following a diagnostic protocol are indispensable.

Use of Urinary Biomarkers in Discriminating Interstitial Cystitis/Bladder Pain Syndrome from Male Lower Urinary Tract Dysfunctions.

To analyze the urinary biomarkers in men with lower urinary-tract symptoms (LUTS) and identify interstitial cystitis/bladder pain syndrome (IC/BPS) from the other lower urinary-tract dysfunctions (LUTDs) by the levels of characteristic urinary biomarkers. In total, 198 men with LUTS were prospectively enrolled and urine samples were collected before intervention or medical treatment. Videourodynamic studies were routinely performed and the LUTDs were diagnosed as having bladder-outlet obstruction (BOO) such as bladder-neck dysfunction, benign prostatic obstruction, or poor relaxation of external sphincter (PRES); and bladder dysfunction such as detrusor overactivity (DO), hypersensitive bladder (HSB), and IC/BPS. Patients suspicious of IC/BPS were further confirmed by cystoscopic hydrodistention under anesthesia. The urine samples were investigated for 11 urinary inflammatory biomarkers including eotaxin, IL-6, IL-8, CXCL10, MCP-1, MIP-1ß, RANTES, TNF-α, NGF, BDNF, and PGE2; and 3 oxidative stress biomarkers 8-OHdG, 8-isoprostane, and TAC. The urinary biomarker levels were analyzed between LUTD subgroups and IC/BPS patients. The results of this study revealed that among the patients, IC/BPS was diagnosed in 48, BOO in 66, DO in 25, HSB in 27, PRES in 15, and normal in 17. Patients with BOO had a higher detrusor pressure and BOO index than IC/BPS, whereas patients with IC/BPS, BOO, and DO had a smaller cystometric bladder capacity than the PRES and normal subgroups. Among the urinary biomarkers, patients with IC/BPS had significantly higher levels of eotaxin, MCP-1, TNF-α, 8-OHdG, and TAC than all other LUTD subgroups. By a combination of different characteristic urinary biomarkers, TNF-α, and eotaxin, either alone or in combination, had the highest sensitivity, specificity, positive predictive value, and negative predictive value to discriminate IC/BPS from patients of all other LUTD subgroups, BOO, DO, or HSB subgroups. Inflammatory biomarker MCP-1 and oxidative stress biomarkers 8-OHdG and TAC, although significantly higher in IC/BPS than normal and PRES subgroups, did not have a diagnostic value between male patients with IC/BPS and the BOO, DO, or HSB subgroups. The study concluded that using urinary TNF-α and eotaxin levels, either alone or in combination, can be used as biomarkers to discriminate patients with IC/BPS from the other LUTD subgroups in men with LUTS.

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.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

Pelvic Floor Myofascial Pain Might Influence Treatment Outcome of Interstitial Cystitis/Bladder Pain Syndrome: A Prospective Study.

BACKGROUND: In patients with interstitial cystitis or bladder pain syndrome (IC/BPS), 85% were found to have pelvic floor myofascial pain (PFMP) and hypertonicity (PFH). However, they physicians are not typically trained to consider or assess PFMP as a contributing factor to patients' IC/BPS symptoms. OBJECTIVE: This study aimed to explore the relationship between PFMP and treatment outcomes in women with IC/BPS. STUDY DESIGN: A prospective study. SETTING: Department of Urology, Medical Center, Hualien, Taiwan. METHODS: Patients with IC/BPS who received any type of treatment were prospectively enrolled. They underwent vaginal digital examination at baseline. PFMP severity was quantified on the visual analog scale (VAS). Subject assessment items included O'Leary-Sant symptom score (OSS), Global Response Assessment (GRA), and Beck's anxiety inventory. Object assessment items included bladder computed tomography (CT), urodynamic parameters, maximum bladder capacity, and grade of glomerulation. RESULTS: A total of 65 women with IC/BPS (mean age, 57.1 ± 11.3 years) were enrolled in the study. Patients with more severe PFMP had significantly higher rate of dyspareunia (P = 0.031); more comorbidities (P = 0.010); higher number of PFMP sites (P < 0.001); and higher OSS (P = 0.012). PFMP severity was not significantly correlated with bladder conditions, whether subjective or objective. Moreover, PFMP severity (VAS) was significantly negatively associated with the GRA score. LIMITATIONS: There was a small sample size and short follow-up duration, the patients in this study are all women, and the applicability to other populations is uncertain. CONCLUSION: PFMP might affect the subjective results of IC/BPS treatment but not the bladder condition. Therefore, in the future treatment of patients with IC/BPS, digital vaginal examinations of pelvic floor muscles should be performed and focused more on the PFM-related conditions, and necessary PFM treatments, such as the vaginal pelvic floor muscle message, should be scheduled.

Multimodal Treatment with Cognitive Behavioral Therapeutic Intervention Plus Bladder Treatment Is More Effective than Monotherapy for Patients with Interstitial Cystitis/Bladder Pain Syndrome-A Randomized Clinical Trial.

(1) Background: Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) not only induces physiological damage but also greatly affects psychological stress. Multidisciplinary therapy has been recommended for IC/BPS treatment, but clinical trial data of combined bladder therapy and cognitive behavioral therapy (CBT) are lacking. This study evaluated CBT efficacy in patients with IC/BPS. (2) Methods: Patients with IC/BPS were randomized to the bladder monotherapy (BT) or combined CBT (CBT) group. The primary endpoint was the self-reported outcome by global response assessment (GRA). Secondary endpoints included IC symptoms and problem index, bladder pain score, Beck's anxiety inventory (BAI), and depression inventory, and objective parameters were also compared. (3) Result: A total of 30 patients receiving BT and 30 receiving CBT therapy were enrolled. Significant improvement of the BAI at 8 (p = 0.045) and 12 weeks (p = 0.02) post-treatment was observed in the CBT group, with significantly greater GRA scores at 12 weeks (p < 0.001). Repeated measures analysis of variance showed a significant effect within the CBT group on IC/BPS patients' self-reported treatment outcomes (p = 0.001) and anxiety severity BAI scores (p = 0.033). (4) Conclusion: A multimodal treatment of CBT combined with suitable bladder treatment more effectively improves anxiety severity and treatment outcomes in patients with IC/BPS.

Clinical presentation, videourodynamic characteristics, and treatment outcome in men with interstitial cystitis-like lower urinary tract symptoms.

PURPOSE: In men, lower urinary tract symptoms (LUTS) similar to interstitial cystitis/bladder pain syndrome (IC/BPS) are difficult to diagnose, and treatment outcomes are poor. This study investigated clinical characteristics and videourodynamic study (VUDS) parameters, pathophysiology, and treatment outcomes in men with IC-like LUTS. METHODS: Men with frequency, urgency, dysuria, and bladder pain initially diagnosed as IC/BPS by ESSIC criteria were assessed to rule out other lower urinary tract diseases (LUTD) by voiding diary, digitorectal examination, urinalysis, VUDS, and cystoscopic hydrodistention. Subsequent treatments for LUTD and specific treatment for IC/BPS were based on VUDS and cystoscopic findings. Clinical VUDS characteristics and treatment outcomes were compared with those of women with IC/BPS. RESULTS: Seventy consecutive men (median age 54.5 years) were enrolled. The median maximum bladder capacity under cystoscopic hydrodistention was 650 mL (IQR 495-763) and glomerulation grade was 2 (1.0-2.0). The patients had moderate anxiety and depression severity; 49% had improved treatment outcomes. On VUDS, 42 (60%) patients had variable LUTD, including detrusor overactivity (n = 14), bladder neck dysfunction (n = 15), dysfunctional voiding (n = 3), and poor relaxation of the external sphincter (n = 24); also, 22 (31.4%) had a previous bladder outlet procedure. The self-reported treatment outcome was significantly better for patients with vs. without LUTD (p = 0.014). CONCLUSIONS: Men with IC-like LUTS diagnosed as IC/BPS may have bladder outlet dysfunction as well as bladder dysfunction, causing a hypersensitive and painful bladder. The IC-like symptoms in the patients with LUTD might, in part, originated from bladder outlet dysfunction rather than the bladder alone.

Use of Urinary Cytokine and Chemokine Levels for Identifying Bladder Conditions and Predicting Treatment Outcomes in Patients with Interstitial Cystitis/Bladder Pain Syndrome.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition causing bladder inflammation. Urinary biomarkers have been assessed as suitable for the diagnosis and treatment. This study aimed at investigating the role of urinary biomarkers in identifying bladder conditions and predicting the treatment outcome of IC/BPS. METHODS: A total of 309 patients with IC/BPS and 30 controls were enrolled in this study. All patients underwent a comprehensive urological workup of symptoms, pain severity, and cystoscopic hydrodistention findings including maximal bladder capacity (MBC) and glomerulation grade. Urine samples were collected to investigate the levels of urinary cytokines and chemokines. According to MBC and glomerulation grade, patients with IC/BPS were further classified into the Hunner's IC (HIC) and non-HIC groups. The urinary biomarkers between IC/BPS and control groups and HIC and non-HIC groups were compared. Moreover, the treatment response was graded according to global response assessment (GRA) scores, and urinary biomarker levels were analyzed based on different GRAs. RESULTS: Patients with IC/BPS had significantly high urinary monocyte chemoattractant protein-1, eotaxin, tumor necrosis factor -alpha (TNF-α), and prostaglandin E2 levels. Significantly higher levels of urinary interleukin-8, C-X-C motif chemokine ligand 10 (CXCL 10), brain-derived neurotrophic factor, eotaxin, and regulated-on-activation, normal T-cell expressed and secreted (RANTES) were noted in HIC than those with non-HIC and controls. Among all biomarkers, TNF-α had the best sensitivity, specificity, positive predictive value, and negative predictive value. There was a significant correlation between biomarker levels and GRA. CONCLUSIONS: Significantly higher urine cytokines and chemokine levels were found in patients with IC/BPS. Most urinary biomarkers were significantly associated with MBC, glomerulation grade, and treatment outcome.

Usefulness of videourodynamic study in the decision-making of surgical intervention and bladder management for neurogenic lower urinary tract dysfunction among patients with myelomeningocele.

PURPOSE: Neurogenic lower urinary tract dysfunction (NLUTD) is common among children with myelomeningocele (MMC). If NLUTD is not appropriately managed, recurrent urinary tract infection (UTI) can persist and may affect upper urinary tract function. This study investigated the usefulness of videourodynamic study (VUDS) in the urological management of MMC. METHODS: We retrospectively analyzed 57 patients with MMC who underwent VUDS and received urological treatments at the hospital, including surgeries, minimally invasive therapies, and conservative management. The baseline VUDS parameters of patients who received different treatments were evaluated, and the treatment outcomes of the different treatment subgroups were compared. RESULTS: There were 29 male and 28 female patients with a mean age of 24.1 ± 15.9 years upon enrollment. Patients had dysuria or urinary retention (n = 42, 73.7%), urinary incontinence (n = 40, 70.2%), recurrent UTI (n = 35, 61.4%), hydronephrosis (n = 27, 47.4%), and vesicoureteral reflux (n = 26, 45.6%). VUDS revealed detrusor sphincter dyssynergia in 32 (56.1%) patients, bladder neck dysfunction in 13 (22.8%), and intrinsic sphincter deficiency in 20 (35.1%). Among them, 21 (36.8%) received surgical intervention, 17 (29.8%) minimally invasive therapy, and 19 (33.3%) conservative management. After a mean follow-up of 8.5 years, the incidence rates of recurrent UTI (61.4% vs 31.6%, p = 0.001), hydronephrosis (47.4% vs 14.0%, p < 0.0001), urinary incontinence (70.2% vs 35.1%, p < 0.0001), and vesicoureteral reflux (45.6% vs 21.1%, p < 0.001) decreased. The overall global response assessment rate was 73.7%, and patients who underwent surgery had the best rate (90.5%). The predictive value of bladder compliance for treatment selection was > 20.5 ml/cm H2O. CONCLUSION: VUDS can be used to comprehensively assess lower and upper urinary tract dysfunction among patients with MMC. To improve NLUTD and prevent complications, minimally invasive therapies or surgical procedures should be recommended to patients with MMC who have low bladder compliance.

Possible Association between Bladder Wall Morphological Changes on Computed Tomography and Bladder-Centered Interstitial Cystitis/Bladder Pain Syndrome.

This study aimed to evaluate the clinical significance of urinary bladder wall thickening on computed tomography (CT) among patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Patients with IC/BPS were prospectively enrolled and classified into three groups according to bladder CT finding: smooth bladder wall, focal bladder thickening, and diffuse bladder thickening. Among the 100 patients with IC/BPS, 49, 36, and 15 had smooth bladder wall, focal bladder thickening, and diffuse bladder thickening on CT, respectively. Patients with Hunner's lesion showed a higher proportion of diffuse and focal bladder thickening compared to those without the same (p < 0.001). Patients with diffuse bladder thickening displayed smaller first sensation of filling, cystometric bladder capacity, and voided volume compared to the rest (all p < 0.001). Patients with focal and diffuse thickening had a higher proportion of inflammatory cell infiltration, uroepithelial cell denudation, and granulation tissue compared to those with smooth bladder wall (p = 0.045, 0.002, and 0.005, respectively). Bladder wall thickening on CT was correlated with clinical phenotypes of IC/BPS, including histopathological findings. Focal or diffuse bladder wall thickening on CT might indicate the presence of chronic bladder wall inflammation and fibrosis and could be used to differentiate bladder-centered IC/BPS.

Voiding dysfunctions in patients with non-Hunner's ulcer interstitial cystitis/bladder pain syndrome do not affect long-term treatment outcome.

PURPOSE: The role of urodynamic study in the diagnosis and prognostication of interstitial cystitis/bladder pain syndrome (IC/BPS) is still controversial. This study evaluated the correlation of the baseline voiding dysfunctions and long-term treatment outcome in patients with non-Hunner's ulcer IC (NHIC). MATERIALS AND METHODS: A total of 211 NHIC patients were enrolled. All patients underwent videourodynamic (VUDS) examination at baseline to identify their voiding conditions and received subsequent treatments. The primary endpoint was Global Response Assessment (GRA) at the interview. Secondary endpoints included O'Leary-Sant symptom score (OSS), Visual Analogue Scale (VAS) for pain and the rate of IC symptom flare-up. RESULTS: The mean age was 56.8 ± 12.8 years, and mean duration of IC was 16.0 ± 9.9 years. At baseline, 83 (39.3%) patients had a voiding dysfunction and 132 (62.7%) had 1 to 3 co-morbidities. The duration, co-morbidities, treatments, changes in OSS and VAS, maximum bladder capacity (MBC), glomerulations, GRA and flare-up rate showed no significant difference among different subgroups. When we divided patients by their storage and voiding conditions, patients with non-hypersensitivity bladder (HSB) (n = 32) had significantly greater MBC (P = .002) whereas those with HSB with (n = 76) or without (n = 103) voiding dysfunction had higher glomerulation (P = .021). When we analysed voiding dysfunction subgroups by GRA, patients with a GRA of ≥2 had a significantly shorter duration of disease (13.9 ± 8.6 years, P = .021). There were also significant associations between GRA and the changes of OSS (P < .001) and VAS (P < .001). CONCLUSIONS: VUDS can disclose voiding dysfunction in 39.3% of NHIC patients. With adequate therapy, the voiding dysfunctions in NHIC patients do not affect long-term treatment outcome.

Cystoscopic hydrodistention characteristics provide clinical and long-term prognostic features of interstitial cystitis after treatment.

To evaluate the correlations of clinical symptoms, urodynamic parameters, and long-term treatment outcomes with different findings of cystoscopic hydrodistention (HD) in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). This retrospective analysis of 486 patients with IC/BPS investigated baseline clinical symptoms, disease duration, medical comorbidities, urodynamic findings, cystoscopic characteristics [including maximal bladder capacity (MBC) and the presence of glomerulations and Hunner's lesions], and outcomes according to the five IC/BPS HD subtypes based on the glomerulation grade, MBC, and the presence of Hunner's lesions. Receiver operation characteristic analysis identified an optimal cutoff value of MBC ≥ 760 ml as a predictor of satisfactory outcomes. Glomerulation grade and MBC were significantly correlated (r = - 0.403, P < 0.001), and both were significantly associated with IC Symptom Index scores. The rate of satisfactory outcomes was better for the patients with low glomerulation grade and MBC ≥ 760 ml (64.2%), and significantly worse for those with Hunner's lesions (36.8%); no significant differences were noted among the other groups. The results suggested that IC/BPS patients can be classified into the following three distinct subgroups: (1) those with low glomerulation grade and MBC ≥ 760 ml; (2) those with low glomerulation grade and MBC < 760 ml, or with high glomerulation grade regardless of MBC; and (3) those with Hunner's lesions. The results showed that three IC/BPS subgroups had distinct bladder characteristics and treatment outcomes. The patients with high MBC and low glomerulation grade after HD had more medical comorbidities but a significantly higher rate of satisfactory treatment outcome.IRB: 105-25-B.

Therapeutic Effect of Botulinum Toxin A on Sensory Bladder Disorders-From Bench to Bedside.

Bladder oversensitivity arises from several different conditions involving the bladder, bladder outlet, systemic or central nervous system diseases. Increase of the bladder sensation results from activation of the sensory receptors in the urothelial cells or suburothelial tissues. Medical treatment targeting the overactive bladder (OAB) or interstitial cystitis (IC) might relieve oversensitive bladder symptoms (frequency, urgency and pain) in a portion of patients, but a certain percentage of patients still need active management. Botulinum toxin A (BoNT-A) has been demonstrated to have anti-inflammatory and antinociceptive effects in bladder sensory disorders and has been shown effective in the reduction of bladder oversensitivity and the increase of functional bladder capacity. For patients with OAB, urgency and urinary incontinence improved, while in patients with IC, bladder pain could be relieved in association with reduction of bladder oversensitivity after BoNT-A intravesical injection. Histological evidence has confirmed the therapeutic mechanism and clinical efficacy of intravesical BoNT-A injection on patients with OAB or IC. Bladder oversensitivity can also be relieved with the instillation of liposome encapsulated BoNT-A or low energy show waves (LESWs), which enable the BoNT-A molecule to penetrate into the urothelium and suburothelial space without affecting the detrusor contractility. Liposome encapsulated BoNT-A or combined LESWs and BoNT-A instillation might be future treatment alternatives for bladder oversensitivity in sensory bladder disorders.

Predictive Factors for a Satisfactory Treatment Outcome with Intravesical Botulinum Toxin A Injection in Patients with Interstitial Cystitis/Bladder Pain Syndrome.

A botulinum toxin A (BoNT-A) intravesical injection can improve the symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS). Patients with IC/BPS have different clinical characteristics, urodynamic features, and cystoscopic findings. This study assessed the treatment outcomes of a BoNT-A intravesical injection and aimed to identify the predictive factors of a satisfactory outcome. This retrospective study included IC/BPS patients treated with 100 U BoNT-A. The treatment outcomes were assessed by global response assessment (GRA) at 6 months. We classified patients according to different clinical, urodynamic, and cystoscopic characteristics and evaluated the treatment outcomes and predictive factors. A total of 238 patients were included. Among these patients, 113 (47.5%) had a satisfactory outcome (GRA ≥ 2) and 125 (52.5%) had an unsatisfactory outcome. Improvements in the IC symptom score, IC problem score, O'Leary-Sant symptom score, and visual analog scale score for pain were significantly greater in patients with a satisfactory outcome than in patients with an unsatisfactory outcome (all p = 0.000). The IC disease duration and maximal bladder capacity (MBC) were significantly different between patients with and without a satisfactory outcome. Multivariate analysis revealed that only the MBC was a predictor for a satisfactory outcome. Patients with a MBC of ≥760 mL and glomerulations of 0/1 (58.7%) or glomerulations of 2/3 (75.0%) frequently had a satisfactory outcome. We found that BoNT-A intravesical injection can effectively improve symptoms among patients with IC/BPS, with a remarkable reduction in bladder pain. A MBC of ≥760 mL is a predictive factor for a satisfactory treatment outcome.

Anxiety severity does not influence treatment outcomes in patients with interstitial cystitis/bladder pain syndrome.

AIMS: Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) typically experience anxiety mood status, which is closely connected with physical and psychological status and treatment outcome. This study aimed to evaluate the impact of anxiety severity on therapeutic results in IC/BPS patients. METHODS: We prospectively enrolled IC/BPS patients who had previously undergone any kind of treatment for their disease. The primary endpoint was a change in Beck Anxiety Inventory (BAI) scores at 3 months after treatment. Secondary endpoints included changes in the Global Response Assessment (GRA), O'Leary-Sant symptom score (OSS), and Numerical Rating Scale (NRS) at 3 months after treatment. Urodynamic studies were also compared with the clinical symptom scores. RESULTS: Overall, 85 IC/BPS patients (mean age, 53.1 ± 12.4 years) were included in the study. At 3 months, changes in the GRA were not significantly different among the different anxiety severity groups. At baseline, 55 (64.7%) patients had moderate or severe anxiety. We observed a significant positive correlation between the change in BAI and the change in OSS after treatment and a significantly negative correlation with GRA at 3 months. Moreover, improvements in OSS and NRS were associated with the change in GRA. Changes in IC symptoms, but not physiological outcomes, were associated with improved anxiety status after treatment. In addition, the change in BAI was significantly associated with age, baseline BAI, and changes in OSS and GRA after treatment. CONCLUSIONS: Baseline anxiety severity does not influence treatment outcomes of IC/BPS. Patients should receive active treatment regardless of their baseline anxiety status.