Long-term results of intravesical hyaluronan therapy in bladder pain syndrome/interstitial cystitis

Introduction and hypothesis  

While the short-term efficacy of intravesical hyaluronan for bladder pain syndrome/interstitial cystitis (BPS/IC) has been demonstrated, no data exist on the long-term outcome of this therapy.     

Measuring the success of combined intravesical dimethyl sulfoxide and triamcinolone for treatment of bladder pain syndrome/interstitial cystitis

Introduction and hypothesis

The purpose of this study was to investigate change in bladder capacity as a measure of response to combined intravesical dimethyl sulfoxide (DMSO) and triamcinolone instillations for the treatment of newly diagnosed bladder pain syndrome/interstitial cystitis (BPS/IC).

Methods

141 newly diagnosed women were identified retrospectively. 79 were treated with weekly DMSO/triamcinolone instillations. Change in bladder capacity with bladder retrofill, daytime urinary frequency, nocturia episodes per night, and Likert scale symptom scores were reviewed. Wilcoxon signed-rank tests, Wilcoxon rank-sum tests, Spearman’s rank correlations, COX regression analysis, and a Kaplan-Meier survival curve were performed.

Results

Significant changes (median (25^th-percentile to 75^th-percentile) were noted for bladder capacity (75 mL (25 to 130 mL), p?<?0.0001), inter-void interval (0 hrs (0 to 1 hour), p?<?0.0001), nocturia episodes per night (?1 (?2 to 0), p?<?0.0001), and aggregate Likert symptom scores (?2 points (?5 to 0), p?<?0.0001). Percent change in bladder capacity correlated positively with percent change in inter-void interval (p?=?0.03) and negatively with percent changes in nocturia (p?=?0.17) and symptom scores (p?=?0.01). Women without detrusor overactivity (DO) had greater percent changes in capacity than women with DO (62.5 % vs. 16.5 %, p?=?0.02). 61.3 % of patients were retreated with a 36 weeks median time to retreatment and no difference in time to retreatment based upon DO. Greater capacity was protective against retreatment (hazard ratio?=?0.997 [95 % CI 0.994,0.999], p?=?0.02).

Conclusions

Percent change in bladder capacity is a useful objective measure of response to intravesical DMSO/triamcinolone for newly diagnosed BPS/IC. Clinical outcomes do not differ based upon presence of DO.     

Review of intravesical therapies for bladder pain syndrome/interstitial cystitis

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic pain condition characterised by urinary frequency, urgency and pain or discomfort which the patient attributes to the bladder. It is a complex condition to manage and treat and requires a multi-disciplinary and multi-modal approach. As well as lifestyle and behavioural modifications, physical therapy and oral medications, intravesical treatments can be used in the treatment algorithm for BPS/IC. A number of intravesical agents are reviewed in this paper along with the available evidence for their use.     

A systematic review and meta-analysis on the efficacy of intravesical therapy for bladder pain syndrome/interstitial cystitis

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic disease characterised by persistent irritating micturition symptoms and pain. The objective was to compare the clinical efficacy of currently available products for intravesical therapy of BPS/IC and to assess their pharmacoeconomic impact. A Pubmed/Medline database search was performed for articles on intravesical therapy for BPS/IC. A total of 345 publications were identified, from which 326 were excluded. Statistical evaluation was performed with effect size (ES) assessment of symptom reduction and response rates. The final set of 19 articles on intravesical BPS/IC therapy included 5 prospective controlled trials (CTs), the remaining were classified as uncontrolled clinical studies. The total number of patients included was 801, 228 of whom had been evaluated in a CT. For CTs, the largest ES for symptom reduction as well as response rate was observed for high molecular weight hyaluronic acid (HMW-HA), with similar findings in two uncontrolled studies with HMW-HA. The number needed to treat to achieve a response to intravesical therapy was 2.67 for intravesical pentosan polysulphate and 1.31 for HMW-HA which were superior to all other instillates. HMW-HA was significantly superior in cost effectiveness and cost efficacy to all other instillation regimes. The present meta-analysis combined medical and pharmacoeconomic aspects and demonstrated an advantage of HMW-HA over other instillation agents; however, direct comparisons between the different products have not been performed to date in properly designed controlled studies.     

Prospective study of intravesical dimethyl sulfoxide in treatment of suspected early interstitial cystitis

The efficacy of intravesical instillations of dimethyl sulfoxide (DMSO) in the treatment of suspected early interstitial cystitis was investigated in a prospective study. Among 20 patients treated, complete symptomatic remissions were achieved in 3, partial symptomatic remissions were achieved in 16, and 1 had no symptomatic improvement. However, functional bladder capacities following treatment were increased by more than 25 per cent in only 4 cases. Among 16 patients who experienced symptomatic remissions and who have been followed for > four months, 14 had sustained remissions (mean follow-up eleven months) and 2 had unsustained remissions. Clinically apparent toxicity was minimal but transient elevation of the serum lactic acid dehydrogenase was occasionally observed during treatment. DMSO appears to be useful in the management of carefully selected patients with suspected early interstitial cystitis.     

Impact of intravesical hyaluronic acid and chondroitin sulfate on bladder pain syndrome/interstitial cystitis

Introduction and hypothesis

Intravesical instillations of hyaluronic acid (HA) and chondroitin sulfate (CS) may lead to regeneration of the damaged glycosaminoglycan layer in interstitial cystitis/bladder pain syndrome (IC/BPS).

Methods

Twenty-two patients with IC/BPS received intravesical instillations (40?ml) of sodium HA 1.6% and CS 2.0% in 0.9% saline solution (IALURIL?, IBSA) once weekly for 8?weeks, then once every 2?weeks for the next 6?months.

Results

The score for urgency was reduced from 6.5 to 3.6 (p?=?0.0001), with a reduction in pain scores from an average of 5.6 to 3.2 (p?=?0.0001). The average urine volume increased from 129.7 to 162?ml (p?p?p?p?Conclusion The treatment appeared to be effective and well tolerated in IC/BPS in this initial experience.     

Recent developments of intravesical therapy of painful bladder syndrome/interstitial cystitis: a review

PURPOSE OF REVIEW: Painful bladder syndrome/interstitial cystitis is a chronic sterile inflammatory disease of the bladder of unknown cause. It is characterized by bladder pain, urinary frequency, urgency, and nocturia. Although there are plenty of theories, the cause of the condition remains obscure. An abundance of treatments has been suggested, but very few have been subjected to proper controlled trials. This review focuses on the recently published literature on intravesical therapy strategies in painful bladder syndrome/interstitial cystitis. RECENT FINDINGS: Bladder irrigation with different agents has been used during years in an attempt to treat painful bladder syndrome/interstitial cystitis. The background for this is the existing theories about urothelial dysfunction. The 'traditional' agent for glycosaminoglycan substitution is hyaluronic acid. Often used are heparin and dimethyl sulfoxide, the actions of which are not quite clear but supposedly on an anti-inflammatory basis. Other agents for intravesical treatment are Bacillus Calmette-Guerin vaccine and botulinum toxin, and some recent studies have pointed to resiniferatoxin and RDP58. SUMMARY: Painful bladder syndrome/interstitial cystitis persists as a challenging syndrome in urology. Intravesical instillation therapy has basically not changed during the last few years, although some studies have disconfirmed some regimens. Intensive research may hopefully result in more effective treatments in the future.     

Biomarkers for patients with interstitial cystitis/bladder pain syndrome

Interstitial cystitis or bladder pain syndrome (IC/BPS) is a disease of unknown etiology manifested with bladder pain and frequency urgency symptoms. Although several pathophysiologic mechanisms have been proposed, the underlying mechanism of IC/BPS is still unclear. Accumulated evidence supports that IC/BPS is actually a spectrum of clinical phenomena that involves several different genes and environmental factors. Heterogeneous syndromes are seen in patients with IC/PBS, which suggests that the disease should be classified into different subtypes. Abnormal expressions of several bladder epithelial markers, including mast cells, epithelial differentiation proteins, cell membrane proteins, neurotransmitters, and cytokines, are present in IC/BPS. This review discusses the possible biomarkers that may play crucial roles in IC/BPS, and especially focuses on those that have the potential to be used as biomarkers for prognosis and for the determination of the best treatment for patients.     

Risk factors that affect the treatment of interstitial cystitis using intravesical therapy with a dimethyl sulfoxide cocktail

Introduction and hypothesis

Dimethyl sulfoxide (DMSO) bladder instillation is a standard therapy for interstitial cystitis (IC); however, there are varying degrees of success. We hypothesize that first-line intravesical therapy with a DMSO cocktail will optimize treatment outcome.

Methods

Ninety women with newly diagnosed IC were enrolled consecutively for the treatment. The IC symptom and problem index was used as an outcome measure.

Results

Six (6.7%) patients dropped out of the treatment due to intolerable bladder irritation. Fifty-five (65.5%) of the remaining 84 patients, who completed the treatment, experienced ≧50% symptomatic improvement. After a regression analysis, three clinical variables were found to affect treatment adversely, i.e., the presence of advanced cystoscopic glomerulations, microscopic hematuria, and urodynamic detrusor underactivity, respectively.

Conclusions

Our results suggest bladder instillation with a DMSO cocktail may well be considered as first-line therapy for IC patients. However, there exists a subgroup of nonresponders who may have severe disease.     

A combined intravesical therapy with hyaluronic acid and chondroitin for refractory painful bladder syndrome/interstitial cystitis

The aims of this study were to evaluate the efficacy and tolerability of intravesical instillations of high-molecular-weight hyaluronic acid (HA) 1.6% and chondroitin sulfate (CS) 2.0% in patients with refractory painful bladder syndrome/interstitial cystitis (PBS/IC) and to observe their impact on Quality of Life. Twenty-three women were enrolled. They received bladder instillations with HA and CS weekly for 20 weeks and then monthly for 3 months. Mean follow-up after completion of therapy was 5 months. We observed a significant improvement in urinary symptoms on voiding diaries and Visual Analogue Scale for frequency (p = 0.045), urgency (p = 0.005), and pain (p = 0.001). The O'Leary-Sant Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index resulted in a significant improvement in both scores (p = 0.004 and 0.01, respectively). The Pelvic Pain and Urgency/Frequency Symptom Scale only showed significant improvement in the symptom score (p = 0.001). This promising experience seems to offer an additional therapeutic option in patients with refractory PBS/IC.     

Self-administration of dimethyl sulfoxide (DMSO) for interstitial cystitis

Ten patients with biopsy-proved interstitial cystitis were treated with a program of self-administered dimethyl sulfoxide (DMSO) using the technique of intermittent self-catheterization. Nine of the 10 patients responded favorably to the treatment and are on a maintenance program. The technique was well tolerated and without complications.     

Therapeutic effects and predictive factors for successful intravesical hyaluronic acid instillation in patients with interstitial cystitis/bladder pain syndrome

ObjectiveHyaluronic acid (HA) is currently used in Taiwan as intravesical instillation for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). This study investigated the therapeutic effects of HA on IC/BPS in the Taiwanese population.Materials and methodsMen and women aged ≥18 years with documented IC/BPS were initially treated with four weekly intravesical HA instillations (treatment time, 1 month) and then with five monthly instillations (total treatment time, 6 months). Clinical assessments included the evaluation of the Visual Analog Scale (VAS) score of bladder pain, O'Leary–Sant Symptom (OSS) score, IC Symptom Index (ICSI), IC Problem Index (ICPI), functional bladder capacity (FBC), uroflowmetry parameters, and global response assessment (GRA). Therapeutic effects were compared between responders (GRA increased ≥ 2 scales) and nonresponders (GRA increased < 2). Multivariate linear analysis was used to determine predictive factor for successful treatment.ResultsA total of 64 patients (3 men and 61 women) with mean age of 49.4 years (range, 20–79) completed the study. Compared with the baseline data, VAS, ICSI, ICPI, OSS score, daytime frequency, nocturia, and FBC all improved at 1 month or 6 months after starting HA treatment. Significantly more improvements in ICSI, ICPI, OSS score, VAS, and FBC were noted in the responders than in the nonresponders at 6 months of treatment. A low-grade glomerulation was the only predictor for successful treatment response to intravesical HA treatment.ConclusionIntravesical HA administrations improved IC symptoms, decreased bladder pain, and decreased frequency after four instillations, and decreased nocturia and increased bladder capacity after completion of all nine instillations. Low-grade glomerulation predicts successful outcome.     

Long-term outcomes of intravesical therapy for non-muscle invasive bladder cancer

Objectives  

The purpose of the current review was to evaluate the long-term outcomes of intravesical therapy for non-muscle invasive bladder cancer.