Multiple intravesical instillations of low-dose resiniferatoxin in the treatment of refractory interstitial cystitis

BACKGROUND: Current medications used in the treatment of interstitial cystitis (IC) have limited efficacy. This prospective study investigated the efficacy of multiple intravesical instillations of resiniferatoxin (RTX) at the concentration of 10 nM. METHODS: Patients with proven IC previously treated with traditional medications for more than 6 months without clinical benefit were enrolled. They were excluded if bladder outlet obstruction or urinary tract infection was present. Intravesical instillation of low-dose RTX (10 nM) once weekly for 4 weeks was performed at the outpatient department. International Prostate Symptom Score (IPSS), 5-Point Pain Scale, and Quality of Life Index (QOL Index) were recorded. A videourodynamic study was done at baseline and 3 months after treatment. RESULTS: The therapeutic results and urodynamic parameters were compared between baseline and 3 months. Thirteen patients, including 10 women and 3 men, were enrolled in this study. The mean duration of IC symptoms was 4.4 +/- 2.5 years. The mean duration of active treatment was 15.3 +/- 8.6 months. One female patient dropped out due to severe bladder pain after RTX instillation. Among the 12 patients who completed the study treatment, subjective assessment revealed that 2 had an excellent therapeutic result, 5 had an improved result and 5 remained unchanged from baseline. The overall satisfactory rate was 58.3%. IPSS, 5-Point Pain Scale, and QOL Index were significantly decreased after RTX treatment. There was no significant increase in mean functional bladder capacity or change in urodynamic parameters. No serious adverse event occurred after RTX treatment. CONCLUSIONS: This study suggests that multiple intravesical instillations of RTX at the concentration of 10 nM are effective in relieving lower urinary tract symptoms in patients with refractory IC. The treatment is tolerable and suitable for use on an outpatient clinic basis.     

Intravesical instillation of resiniferatoxin for the patients with interstitial cystitis

Although hydrodistention of the bladder is accepted as the initial treatment for patients with interstitial cystitis (IC), second-line treatment for worsening symptoms is not concretely established. Resiniferatoxin (RTX) desensitizes bladder afferent c-fibers and its intravesical instillation is effective for patients with detrusor overactivity. We studied the clinical relevance of intravesical treatment with RTX for patients with IC. The treatment was performed for 3 patients with incomplete improvement after hydrodistention. All 3 patients were free of bladder pain posttreatment and had slight improvement of the maximum voided volume. Though RTX treatment requires general anesthesia against severe bladder pain it is effective for selected patients with interstitial cystitis and can be potentially used as one of the treatment options.     

Clinical experience with multiagent intravesical therapy in interstitial cystitis patients unresponsive to single-agent therapy

Summary A total of 25 patients with the diagnosis of interstitial cystitis (IC) were involved in this study. All patients had been previously diagnosed with interstitial cystitis and had received treatment with single intravesical agents. Patients were divided into two groups according to their bladder capacity. The bladder capacity was >350 ml in group I patients and <350 ml in group II patients. For our study, dimethylsulfoxide (DMSO), methylprednisolone, and heparin sulfate were given every week for a total of 6 weeks. When symptoms recurred, supportive oral pharmacotherapy consisting of anticholinergics and/or tricyclic antidepressants was given. Under anesthesia, patients in group I showed a 99% increase in their bladder capacity; whereas those in group II showed an increase of only 19%. Cystoscopically, Hunner's ulcers were present in 60% of the group II patients but were seen in only 5% of the group I patients. Histopathological examination showed that the inflammatory changes were more frequent and severe in group II than in group I. Mast-cell hyperplasia was present in 100% of the patients in group II, versus only 61% of those in group I. A total of 23 patients (92%) achieved an initial remission averaging 8.1 months. In all, 9 patients (35%) had 1 or more relapses, and all achieved a subsequent remission averaging 8 months. By this combined multiagent approach, the majority of patients with IC obtained relief from their incapacitating symptoms and were socially rehabilitated.     

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.     

Abnormal sensitivity to intravesical potassium in interstitial cystitis and radiation cystitis

The urgency-frequency syndrome (UFS) (non-bacterial cystitis, interstitial cystitis) may well represent a heterogenous group with several etiologies. This study was based on the hypothesis that one subset of UFS patients has a leaky (to solutes) epithelium and cations such as potassium could thereby diffuse subepithelially and provoke symptoms. It was also hypothesized that normal impermeable transitional epithelium would not allow cations to diffuse across the cells during the K + provocation test and no symptoms would be experienced. If the epithelium was permeable (“leaky”), diffusion would occur and provoke symptoms. Water or 0.4 M KCl was placed intravesically into normal volunteers and interstitial cystitis (IC) patients. Water did not provoke symptoms in either group but KCl provoked 45% of normals and 70% of IC patients. Differences were significant (P < 0.0001). This test provides a valuable diagnostic tool for UFS and a valuable research tool to separate epithelial permeability problems from other subsets of patients. A third group, consisting of 11 IC patients in remission on heparinoid therapy, was also tested and only 18% were provoked by KCl. Four patients with radiation cystitis were also examined and all four (100%) were provoked by the potassium. © 1994 Wiley-Liss, Inc.     

膀胱水扩张联合灌注树胶脂毒素治疗间质性膀胱炎的疗效分析

目的 评价使用腰麻下膀胱水扩张联合灌注树胶脂毒素(RTX)治疗间质性膀胱炎(IC)的疗效.方法 回顾性分析16例间质性膀胱炎患者,均使用腰麻下行水扩张加RTX膀胱灌注.评价治疗前、后1个月以及6个月的排尿次数,排尿量以及临床症状比较.结果 所有患者治疗前与治疗后1个月以及6个月的排尿频率、最大膀胱容量以及临床症状评分相比,均有明显改善差异有统计学意义(P＜0.05).16例患者中14位患者有不同程度的症状改善.2例患者的临床症状消失或明显改善.结论 RTX膀胱灌注以及膀胱水扩张对于间质性膀胱炎是短期内安全有效改善症状的治疗方法.     

膀胱水扩张联合灌注树胶脂毒素治疗间质性膀胱炎的疗效分析

目的 评价使用腰麻下膀胱水扩张联合灌注树胶脂毒素(RTX)治疗间质性膀胱炎(IC)的疗效.方法 回顾性分析16例间质性膀胱炎患者,均使用腰麻下行水扩张加RTX膀胱灌注.评价治疗前、后1个月以及6个月的排尿次数,排尿量以及临床症状比较.结果 所有患者治疗前与治疗后1个月以及6个月的排尿频率、最大膀胱容量以及临床症状评分相...     

Prospective, randomized, double-blind study of safety and tolerability of intravesical resiniferatoxin (RTX) in interstitial cystitis (IC)

Objective: To determine the safety and tolerability of intravesical resiniferatoxin (RTX) in interstitial cystitis (IC) patients. Materials and Methods: IC patients were instilled with 50 cc of test solution containing either placebo, 0.05 M or 0.10 M RTX in the bladder. Plasma concentration of RTX and its degradant resiniferonol 9-, 13-, 14-orthophenylacetate was measured. Immediate post-treatment blood sampling and cystoscopy were performed. Symptoms were evaluated before treatment, at 4- and at 12-week follow-ups, using VAS indicator for pain, voiding diary, and OLearys IC symptom/problem indices. Results: Among 22 patients observed (ten in 0.10 M RTX, eight in 0.05 M RTX, and four in placebo groups), the most commonly reported adverse event was pain during instillation (80.0%, 87.5%, and 25.0%). No serious adverse events were reported. Conclusions: Use of intravesical RTX in IC patients is associated with important tolerability issues but safe at 0.10 M and 0.05 M.     

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.     

Successful therapy of interstitial cystitis with pentosanpolysulfate

Sodium pentosanpolysulfate (Elmiron) is a synthetic, sulfated polysaccharide available in an oral form that is excreted into the urine. This drug was used in a double-blind fashion to evaluate its efficacy in the management of symptoms of interstitial cystitis. A dose of 100 mg. 3 times daily was used for a minimum of 4 months and was continued for longer than 18 months in some individuals. A total of 62 patients was evaluated from 2 different medical centers. Subjective improvements were greater in all parameters when the drug was compared to placebo therapy, with significant improvement in pain, urgency, frequency and nocturia. Objective improvement in average voided volumes was greater with the drug than with placebo (p equals 0.009). No significant difference was found between drug and placebo groups in the average number of daily voiding episodes.     

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.     

膀胱内灌注治疗在间质性膀胱炎中的应用

膀胱内灌注治疗已广泛应用于间质性膀胱炎的治疗,能用作膀胱内灌注的药物种类繁多,其作用机理、疗效及副反应表现不一,本文就目前常用的几类药物的应用情况作一综述.     

膀胱内灌注治疗在间质性膀胱炎中的应用

膀胱内灌注治疗已广泛应用于间质性膀胱炎的治疗,能用作膀胱内灌注的药物种类繁多,其作用机理、疗效及副反应表现不一,本文就目前常用的几类药物的应用情况作一综述.     

Current management of interstitial cystitis

The management of patients with IC remains a challenge because no single agent has proven universally effective. DMSO and PPS have been evaluated through early placebo-controlled trials, and these two agents are FDA approved treatments for IC. BCG is currently undergoing a large placebo-controlled trial, and hyaluronic acid is receiving similar clinical evaluation. Sacral nerve root stimulation shows promise with early favorable results. As with any treatment algorithm, it is reasonable to begin with conservative treatment using time-dependent milestones, allowing adequate trials of successive therapy while ensuring an appropriate pace for timely symptom resolution.