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.     

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.     

Clinical comparison of intravesical hyaluronic acid and chondroitin sulfate therapies in the treatment of bladder pain syndrome/interstitial cystitis

Introduction

Intravesical glucosaminoglycan (GAG) replacement therapies are commonly used in the treatment of bladder pain syndrome (BPS)/interstitial cystitis (IC). Different intravesical glucosaminoglycan products are currently available. In this prospective study, clinical efficacy of chondroitin sulfate and hyaluronic acid are compared in patients with BPS/IC.

Methods

Patients were randomized to CS and HA groups. All patients were evaluated for visual analogue pain scale (VAS), interstitial cystitis symptom index (ICSI), interstitial cystitis problem index (ICPI), voiding diary for frequency/nocturia, and mean urine volume per void at the beginning of the therapy and after 6 months. All patients had a potassium sensitivity test (PST) initially. Wilcoxon and Mann‐Whitney U tests were used for statistical analysis.

Results

There were 21 patients in both groups. Mean age of patients in CS and HA groups were 47.10 and 48.90, respectively(P > 0.05). Before treatment, Parson's test was positive in 64.3% of patients (27/42) with no difference between groups. VAS of pain, ICSI, ICPI, frequency at 24 h and nocturia results have improved significantly at both treatment arms. Intravesical CS was also found superior to intravesical HA in terms of 24 h frequency, nocturia and ICPI (P < 0.05). No severe adverse effects were reported.

Conclusions

Data comparing clinical efficiencies of different GAG therapies are very limited. In this study, intravesical CS was found superior to intravesical HA in terms of 24 h frequency, nocturia and ICPI in patients with BPS/IC in short term follow‐up. To provide a definitive conclusion on superiority of one GAG therapy to others, further evaluation with long term follow up is required.     

Intravesical hyaluronic acid and alkalinized lidocaine for the treatment of severe painful bladder syndrome/interstitial cystitis

Introduction and hypothesis

Intravesical instillation of hyaluronic acid (HA) may restore the integrity of glycosaminoglycan layer in patients with painful bladder syndrome/interstitial cystitis (PBS/IC), and the benefit may be improved with addition of alkalinized lidocaine (AL).

Methods

48 women with severe PBS/IC who failed oral medications were enrolled and divided into one trial and two control groups. The trial group received intravesical 40?mg HA, 10?ml of 2?% lidocaine and 5?ml of 8.4?% sodium bicarbonate on a weekly basis for 8?weeks and then monthly for 4?months with a subsequent follow-up of 24?weeks, while the two control groups received 40?mg HA and mixture of 10?ml of 2?% lidocaine and 5?ml of 8.4%sodium bicarbonate respectively following the same procedure. Response to therapy was evaluated by Global Response Assessment, voids per day, Visual Analogue Scale for pain, frequency and urgency, O??leary-Sant Interstitial Cystitis Symptom Index and Problem Index, cystoscopy and bladder capacity.

Results

Overall 45 patients finished this study protocol. The HA + AL group and the AL group showed significant improvement at week 2 (P?<?0.01), while the HA group began to show effect at week 4 (P?<?0.01). There was no improvement in the AL group at week 24 and these patients quitted the study without follow up. Contrarily, the HA + AL and HA group kept on improving till the end of the study without significant difference between the two groups.

Conclusions

Intravesical instillation of HA and AL may provide both immediate and sustained relief of symptoms in severe PBS/IC in this preliminary study.     

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.     

Pregnancy and interstitial cystitis/painful bladder syndrome

Painful bladder syndrome (PBS) and interstitial cystitis (IC) often affect women of child-bearing age. This article includes information of interest to PBS/IC patients who are pregnant or contemplating pregnancy, and to the clinicians who care for them. One topic is how pregnancy affects PBS/IC symptoms, although little is known at this time. The article also describes the pregnancy risks associated with the most commonly used PBS/IC treatments. Finally, the current knowledge regarding genetic factors in IC is discussed.     

Increased bladder permeability in interstitial cystitis/painful bladder syndrome

The definition of interstitial cystitis (IC) has evolved over the years from being a well-defined entity characterized by diagnostic lesion (Hunner’s ulcer) in the urothelium to a clinical diagnosis by exclusion [painful bladder syndrome (PBS)]. Although the etiology is unknown, a central theme has been an association with increased permeability of the bladder. This article reviews the evidence for increased permeability being important to the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBS) and in treating the disorder. Recent work showing cross-communication among visceral organs is also reviewed to provide a basis for understanding IC/PBS as a systemic disorder of a complex, interconnected system consisting of the bladder, bowel and other organs, nerves, cytokine-responding cells and the nervous system.     

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.     

Urodynamic testing and interstitial cystitis/painful bladder syndrome

Introduction and hypothesis

The objective of this study is to evaluate the relationship between symptom severity in interstitial cystitis/painful bladder syndrome, urodynamic testing (UDT), and cystoscopy.

Methods

Charts of subjects who underwent cystoscopy and bladder overdistention (BOD) from January 2006 to July 2007 were reviewed for data points, questionnaires, UDT, and BOD findings. The independent T test and Mann–Whitney U test were performed between questionnaires, urodynamic data, and cystoscopic findings.

Results

Significantly lower volumes on all UDT parameters and higher scores on the interstitial cystitis problem index and pain Likert scale were found in subjects who felt pain with filling on UDT. Significantly lower median volumes for certain urodynamic parameters were found in subjects with high pain Likert scores and O'leary–Sant indices and those with grade 3 glomerulations and anesthetic bladder capacities of less than 600 mL on BOD.

Conclusion

UDT may be a useful adjunctive test in the evaluation of patients with irritative voiding symptoms.     

Intravesical hyaluronic acid for interstitial cystitis/painful bladder syndrome: A comparative randomized assessment of different regimens

Objectives: To compare the clinical effectiveness of different regimens of intravesical hyaluronic acid instillation for patients with interstitial cystitis/painful bladder syndrome. Methods: A total of 60 patients (age 16–77 years) diagnosed with interstitial cystitis/painful bladder syndrome were enrolled in this prospective, randomized study. A total of 30 patients were assigned to receive four weekly intravesical instillations of 40 mg of hyaluronic acid followed by five monthly instillations (hyaluronic acid‐9 group). Another 30 patients received 12 intravesical instillations of 40 mg hyaluronic acid every 2 weeks (hyaluronic acid‐12 group). Symptomatic changes after hyaluronic acid treatments were assessed using Interstitial Cystitis Symptom and Problem Indexes, pain visual analog scale, functional bladder capacity, frequency and nocturia in voiding diary, maximum flow rate, voided volume, postvoid residual volume, and Quality of Life Index at 1, 3 and 6 months. Results: Of the 60 patients, 59 were evaluable at the end of the study. The Interstitial Cystitis Symptom Index, Interstitial Cystitis Problem Index and total score, pain visual analog scale, functional bladder capacity, maximum flow rate, and Quality of Life Index improved significantly after 6 months in both groups. The frequency and voided volume improved significantly only in the hyaluronic acid‐12 group. However, patients with moderate and marked improvement were clinically similar in both groups. The measured variables did not differ between the two groups over the course of the study. Conclusion: No significant difference was noted in the therapeutic effect between two hyaluronic acid instillation regimens for treatment of interstitial cystitis/painful bladder syndrome patients. Both groups showed significant improvement in symptom scores and Quality of Life Index.     

Hyaluronan treatment of interstitial cystitis/painful bladder syndrome

The aim of this study is to evaluate the efficacy of intravesical hyaluronan therapy in interstitial cystitis/painful bladder syndrome (IC/PBS). One hundred twenty-six patients with IC/PBS and an average disease duration of 6.1 years were treated with weekly instillations of a 50-cm³ phosphate-buffered saline solution containing 40 mg sodium hyaluronate. To be eligible for hyaluronan treatment, a positive modified potassium test was requested as a sign of a urine–tissue barrier disorder. Data were obtained by a visual analogue scale (VAS) questionnaire rating from 0 to 10 that asked for global bladder symptoms before and after therapy. Additional questions evaluated the therapeutic impact on quality of life. A positive and durable impact of hyaluronan therapy on IC/PBS symptoms was observed—103 (85%) of the patients reported symptom improvement (≥2 VAS units). The mean initial VAS score of 8.5 decreased to 3.5 after therapy (p < 0.0001). Out of 121 patients, 67 (55%) remained with no or minimal bladder symptoms after therapy (VAS 0–2). The majority (101, 84%) reported significant improvement of their quality of life. Intravesical therapy had to be initiated again with good success in 43 patients (34.5%) as symptoms recurred after discontinuation of treatment, while the rest stayed free of symptoms for up to 5 years. In general, hyaluronan therapy was well tolerated and, with the exception of mild irritative symptoms, no adverse reactions were reported for a total of 1,521 instillations. Timely hyaluronan instillation therapy may lead to complete symptom remission or even cure in part of the IC/PBS patients, while some responders need continuous intravesical therapy. The present results suggest that selection of patients for hyaluronan therapy by potassium testing improves the outcome of intravesical therapy with a response rate of >80%.     

膀胱疼痛综合症／间质性膀胱炎研究进展

膀胱疼痛综合症／间质性膀胱炎（painful bladder syndrome／interstitial cystitis,PBS／IC）是一种基于尿频、尿急、膀胱或盆底疼痛的的慢性疼痛综合症。1836年美国费城外科医生JOSEPH PARRISH报告了3例病因不明的有严重下尿路症状的患者并将此疾病命名为“膀胱三叉神经痛”。     

Voiding urges perceived by patients with interstitial cystitis/painful bladder syndrome

AIMS: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a symptom-based diagnosis. We studied the IC/PBS symptom commonly referred to as "urgency" and its relationship to IC/PBS pain in a group of women with recent onset of the disease. METHODS: As part of a case control study to identify risk factors for IC, cases completed a questionnaire including two statements regarding the perceived cause of their urge to void. One was related to fear of incontinence and the other was linked with relief of pain. A Likert scale indicating level of agreement/disagreement comprised the response options. RESULTS: Most respondents (65%) agreed with the statement linking urge with pain relief. A minority (21%) concurred with the fear of incontinence statement. Disagreement for both was found in 19%. A substantial proportion (46%) agreed with pain relief but also disagreed that urge is related to fear of incontinence. Those who reported urge to relieve pain were significantly more likely to report worsened pain with bladder filling and/or improved pain with voiding. There were no such associations with urge to prevent incontinence. Overactive bladder or diabetes prior to IC onset did not confound these results. CONCLUSIONS: At least two distinct experiences of urge to urinate are evident in this population. For most, urge is linked with pain relief and is associated with bladder filling/emptying. About 1/5 reported urge to prevent incontinence. A similar portion did not agree with either urge, indicating that they may experience something altogether different, which requires further inquiry.     

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.     

Morbidity rate and medical utilization in interstitial cystitis/painful bladder syndrome

Introduction and hypothesis

The objective was to calculate the morbidity rate and medical utilization of interstitial cystitis/painful bladder syndrome (IC/PBS) over 12 years using a nationwide database of Taiwan.

Methods

This was a cohort study of the Longitudinal Health Insurance Database 2010 with new diagnoses of IC/PBS from 2002 through 2013. The morbidity rate was adjusted for age, sex, and calendar date using density methods. Moreover, medical utilization during the study period was measured.

Results

It was observed that the incidence of IC/PBS was 21.8/100,000 in 2002 and 21.1/100,000 in 2013. The prevalence of IC/PBS was 21.8/100,000 in 2002 and 40.2/100,000 in 2013. In 2003, the incidence and prevalence of women was 28.6/100,000 and 63.5/100,000 respectively. The incidence and prevalence of men was 12.3/100,000 and 19.4/100,000 respectively. In 2002, the incidence was 45.5/100,000, 32.4/100,000, and 9/100,000 in the age groups above 65, 40–65, and under 40 years respectively. The prevalence in 2003 was 86.3/100,000, 63.1/100,000, and 16.4/100,000 in age groups above 65, 40–65, and under 40 years respectively. This pattern was similar until 2013. The mean outpatient and inpatient visit time was 4.8 and 1.8 times per year respectively. The mean surgical fee (US$ 246.6?±?304.5) was 23.6% of the total fee.

Conclusions

The morbidity rate of IC/PBS showed a higher incidence and prevalence in women and older patients. A new drug for the treatment of IC/PBS may be a factor of the peak in the morbidity rate. The increase in medical utilization could be explained by the awareness of physicians and patients seeking medical help.