Dimethyl sulfoxide in treatment of inflammatory genitourinary disorders

Intravesical dimethyl sulfoxide (DMSO) has been used in the treatment of 213 patients with various inflammatory conditions involving the lower genitourinary tract, including intractable interstitial cystitis, radiation cystitis, chronic prostatitis, and chronic female trigonitis. Significant symptomatic relief has been achieved in the majority of patients so treated, and no systemic or local toxicity has been noted. Some patients failed to respond entirely, and others relapsed after DMSO treatment periods of several months, ultimately coming to augmentation cystoplasty or urinary diversion. However, because of its simplicity and ease of administration, intravesical DMSO therapy is recommended in all noninfectious or non-neoplastic inflammatory conditions presenting initially with severe symptoms, or that have failed to respond to conventional therapy.     

The use of dimethyl sulfoxide in the treatment of intractable urinary frequency

Intravesical instillation of dimethyl sulfoxide (DMSO) was used in the treatment of patients with intractable urinary frequency due to chronic prostatitis, chronic cystitis, tuberculous contracted bladder and interstitial cystitis. Before the application of this therapy, all 4 patients were examined carefully to rule out cases of acute infectious diseases of the urinary tract, active urinary tuberculosis, neurogenic bladder and carcinoma in situ of the bladder. Three of the four patients achieved an excellent response both subjectively and objectively. In the United States, intravesical instillation of DMSO had already been established as the specific method in the treatment of interstitial cystitis and no side effects have been reported so far. Therefore, we recommend the use of intravesical instillation of DMSO more commonly in various forms of intractable urinary frequency.     

Functional results after ileocystoplasty

The functional results after ileocystoplasty were studied in seven patients with interstitial cystitis, irradiated bladder and neurogenic bladder dysfunction. None of the patients had had symptomatic improvement by medical or surgical means. All patients were suffering from urinary frequency and five patients had severe urge incontinence or suprapubic pains. Postoperatively the patients were followed from 8 to 66 months and evaluated by urodynamic examinations and interviews. Urinary frequency was improved in all patients but one with interstitial cystitis who had persisting suprapubic pains. None had residual urine volume greater than 30 ml postoperatively. It is concluded that bladder augmentation by ileocystoplaty is an excellent method of treatment for patients with contracted bladder secondary to interstitial cystitis, irradiated bladder, and detrusor hyperreflexia and sphincter dyssynergia.     

Critical appraisal of dimethyl sulfoxide treatment for interstitial cystitis: discomfort, side-effects and treatment outcome

OBJECTIVE: To evaluate the discomfort and long-term efficacy associated with instillation of dimethyl sulfoxide (DMSO). MATERIAL AND METHODS: A total of 28 patients, 13 (11 females, 2 males) with classic interstitial cystitis (IC) and 15 (13 females, two males) with non-ulcer disease, who had received at least one series of six instillations of DMSO were studied. In addition to studying micturition diaries before and after the treatment, the evaluation included assessments of pain using a visual analog scale and of side-effects after each instillation in every series. Data were obtained by surveying the clinical records. A follow-up telephone interview was conducted for those patients who were treated with DMSO and in whom the treatment was considered successful. DMSO instillations were considered successful if the patient reported symptom amelioration and chose to continue with the treatment. RESULTS: Side-effects were not more common or pronounced in patients with classic compared to non-ulcer IC. For classic IC a significant difference could be seen when comparing side-effects experienced during the first three instillations and the three subsequent instillations. After DMSO instillations, a residual treatment effect lasting 16-72 months could be seen. CONCLUSIONS: Intravesical instillation therapy with DMSO appears to be a feasible treatment option for both subtypes of IC and is associated with a reasonably low degree of discomfort.     

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.     

Increased mast cells of the bladder in suspected cases of interstitial cystitis: a possible disease marker

Mast cells reportedly have been increased in the detrusor muscle bundles of the bladder in patients with interstitial cystitis. In 30 patients with suspected interstitial cystitis quantification of mast cells within the muscularis and submucosa was done. The results were compared to those obtained from a variety of normal bladder specimens removed surgically (16 specimens) and at autopsy (15), and from bladders with a variety of miscellaneous inflammatory conditions (20). In patients with suspected interstitial cystitis the number of mast cells was increased significantly (p less than 0.001) compared to the 3 control groups. This finding suggests that quantification of mast cells in the muscularis may be a useful marker in the histopathological evaluation of bladder biopsies in patients with suspected interstitial cystitis.     

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.     

Comparison of cystoscopic and histological findings in patients with suspected interstitial cystitis

PURPOSE: Although the exact etiology of interstitial cystitis remains elusive, bladder inflammation appears to be common in many patients. The National Institutes of Health (NIH) have established diagnostic criteria for interstitial cystitis based on the presence of irritative voiding symptoms in the absence of other identifiable pathology. Cystoscopic examination with hydrodistention performed in patients under anesthesia is part of the NIH diagnostic criteria. We determine if the severity of cystoscopic findings correlated with histological evidence of inflammation in patients with suspected interstitial cystitis. MATERIALS AND METHODS: A total of 69 patients who met NIH symptom criteria for interstitial cystitis and underwent cystoscopy, hydrodistention and bladder biopsy under anesthesia were reviewed. There were 2 investigators blinded to the histological data who independently reviewed operative reports. A urological pathologist blinded to the clinical data reviewed biopsies for inflammation severity. Cystoscopic and histological findings were then converted to a numeric scale. Numeric data were analyzed using the Pearson correlation coefficient. RESULTS: Cystoscopic examination revealed no evidence of interstitial cystitis in 6 patients (9%), mild changes in 27 (39%), moderate changes in 23 (33%) and severe changes in 13 (19%). Histological examination revealed no inflammation in 21 patients (30%), mild inflammation in 28 (41%), moderate inflammation in 11 (16%) and severe inflammation in 9 (13%). Histological scores correlated poorly with total and scaled cystoscopic severity scores (r = 0.295 and 0.349, respectively). CONCLUSIONS: Severity of cystoscopic findings observed during hydrodistention with anesthesia does not appear to correlate with the degree of inflammation identified histologically in patients with suspected interstitial cystitis.     

The use of dimethyl-sulfoxide (DMSO) in the treatment of interstitial cystitis.

Dimethyl-sulfoxide (DMSO) was used in 17 patients with interstitial cystitis. The diagnosis was made on the basis of clinical and laboratory findings and the characteristic picture with Hunner ulcera. The majority of the patients had responded poorly to other forms of conservative treatment. Subjective symptoms were controlled in 2/3 of the cases but repeated treatment was needed and 5 patients did not respond to the therapy. The DMSO treatment is an alternative worth to try and has in some cases a dramatic and lasting effect.     

Preliminary results of suburothelial injection of botulinum a toxin in the treatment of chronic interstitial cystitis

PURPOSE: Treatment of interstitial cystitis is usually not successful in eradicating bladder pain and increased bladder capacity. This study was designed to evaluate the clinical effectiveness of suburothelial injection of botulinum A toxin in patients with chronic interstitial cystitis. METHODS: Eight women and 2 men with chronic interstitial cystitis who had failed conventional treatments were enrolled in this study. In 5 patients, 100 units of botulinum A toxin was injected suburothelially into 20 sites, and an additional 100 units was injected into the trigone in the other 5 patients. Therapeutic outcome including functional bladder capacity, number of daily urinations, bladder pain, and urodynamic changes were compared between baseline and 3 months after treatment. RESULTS: In 2 patients bladder pain and urinary frequency were improved 3 months after treatment. Mild difficulty in urination was reported by 7 patients. Functional bladder capacity recorded in a voiding diary was significantly increased (155+/-26.3 vs. 77+/-27.1 ml, p<0.001), and the frequency of daily urinations (18+/-7.7 vs. 24.2+/-10.3, p=0.025) and the pain score (2.4+/-1.6 vs. 3.2+/-1.1, p=0.003) were mildly but significantly reduced after treatment. Only the cystometric capacity improved significantly (287+/-115 vs. 210+/-63.8 ml, p=0.05) in urodynamic results. Trigonal injection had no therapeutic effect on symptom or urodynamic improvement. No adverse effect was reported. CONCLUSIONS: The clinical result of suburothelial botulinum A toxin injection was disappointing. None of the patients was symptom free and only a limited improvement in bladder capacity and pain score was achieved in 2 patients.     

The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of interstitial cystitis

PURPOSE: The presence of leukotriene D4 receptors in human detrusor myocytes and increased urinary leukotriene E4 in patients with interstitial cystitis and detrusor mastocytosis imply a role for cysteinyl containing leukotrienes as proinflammatory mediators in this disease. We examined the efficacy of the cysteinyl leukotriene 1 receptor antagonist montelukast for treating patients with interstitial cystitis and detrusor mastocytosis. MATERIALS AND METHODS: Ten women in whom interstitial cystitis was diagnosed according to National Institute of Diabetes and Digestive and Kidney Diseases criteria and who also had detrusor mastocytosis with a minimum of 28 mast cells per mm.2 muscle tissue were included in this study. Patients received a single dose of montelukast daily for 3 months. The efficacy of treatment was determined by 24-hour urinary frequency, nocturia and pain using visual analog scales. RESULTS: After 1 month of montelukast treatment there was a statistically significant decrease in 24-hour urinary frequency, nocturia and pain which persisted during the 3 months of treatment. After 3 months 24-hour urinary frequency had decreased from 17.4 to 12 voidings (p = 0.009), nocturia had decreased from 4.5 to 2.8 (p = 0.019) and pain had decreased from 46.8 to 19.6 mm. on a visual analog scale (p = 0.006). No side effects were observed during treatment. CONCLUSIONS: Montelukast treatment resulted in significant improvement in urinary frequency and pain. Its efficacy for decreasing urinary frequency and pain imply a role of leukotriene receptor antagonists for managing interstitial cystitis but further placebo controlled clinical studies are needed.     

间质性膀胱炎16例的诊断与治疗

目的探讨间质性膀胱炎(IC)的诊断和治疗方法。方法回顾分析16例IC患者的临床资料,患者主要表现为尿频、尿急、耻骨上疼痛和慢性盆腔疼痛,误诊为慢性膀胱炎、盆腔炎、子宫内膜异位症、膀胱结核及尿道综合征,经手术后病理或膀胱镜检查确诊,其中4例行尿流改道,2例行乙状结肠膀胱成形术,10例行药物治疗。结果4例患者行尿流改道治疗后盆腔疼痛完全消失。2例行膀胱成形术后仍有轻微会阴部不适,膀胱容量大于350 m l,分别随访24,33个月无复发。10例非手术治疗患者O′Leary-Sant间质性膀胱炎症状评分和IC问题评分分别由治疗前的(15.4±4.1)和(9.4±2.7)分,降至治疗后的(4.1±2.1)和(5.1±3.9)分。结论对IC的诊断和鉴别诊断应给予充分重视;及早诊断及多种措施联合治疗,可显著改善IC患者的症状,提高生活质量。     

The Intravesical Potassium Sensitivity Test and Urodynamics: Implications in a Large Cohort of Patients with Lower Urinary Tract Symptoms

PURPOSE: Bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH) is the most common diagnosis in older men with lower urinary tract symptoms. However, these symptoms also can occur with interstitial cystitis. We determine whether the potassium sensitivity test is useful for distinguishing BPH from possible intersitial cystitis in patients with lower urinary tract symptoms. We also test the hypothesis that patients with these symptoms who have a positive test will have urodynamic findings consistent with the diagnosis of interstitial cystitis. MATERIALS AND METHODS: The potassium sensitivity test was performed in 526 (95%) males and 25 (5%) females with lower urinary tract symptoms undergoing urodynamic testing. Urodynamic parameters in the positive and negative potassium sensitivity test groups were compared. %Results: Of the patients 16% (89 of 551) had a positive potassium sensitivity test. Compared with patients who had a negative test, those who had a positive test were younger (61 versus 64 years, p = 0.03), had urgency at significantly lower volumes (108 versus 182 cc, p <0.0001), lower bladder capacity (343 versus 436 cc, p <0.0001) and lower post-void residual (49 versus 95 cc, respectively, p <0.001). Urodynamic parameters in the 24% (6 of 25) of women who had a positive potassium sensitivity test were similar to those in men who also had a positive test. CONCLUSIONS: Urodynamic findings in patients with lower urinary tract symptoms who have a positive potassium sensitivity test are significantly different from those in patients who have a negative test, and are similar to those findings characteristic of interstitial cystitis. Interstitial cystitis should be considered in patients with lower urinary tract symptoms who have a positive test. The potassium sensitivity and urodynamic tests may be a useful combination for screening men with lower urinary tract symptoms to identify those symptoms that may be due to interstitial cystitis versus BPH.     

Sacral neuromodulation for the symptomatic treatment of refractory interstitial cystitis: a prospective study

PURPOSE: The efficacy of sacral neuromodulation for the treatment of symptoms in patients with refractory interstitial cystitis was evaluated. MATERIALS AND METHODS: A total of 25 patients with a mean age of 47 years and refractory interstitial cystitis were prospectively evaluated with a trial of sacral nerve stimulation. Patients who demonstrated 50% improvement in frequency, nocturia, voided volume and average pain qualified for permanent sacral nerve stimulator implantation. Treatment success was measured by voiding diary, report of average pain, and response to the Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index. RESULTS: Of the 25 patients 17 qualified for permanent sacral nerve stimulator implantation. At an average of 14 months followup mean daytime frequency and nocturia improved from 17.1 to 8.7 and 4.5 to 1.1, respectively (p <0.01). Mean voided volume increased from 111 to 264 ml. (p <0.01). Report of average pain decreased from 5.8 to 1.6 points on a scale of 0 to 10 (p <0.01). Interstitial Cystitis Symptom and Problem Index scores decreased from 16.5 to 6.8 and 14.5 to 5.4, respectively (p <0.01). Of the 17 patients 16 (94%) with a permanent stimulator demonstrated sustained improvement in all parameters at the last postoperative visit. CONCLUSIONS: Results of this prospective clinical study demonstrate that sacral neuromodulation is a safe and effective treatment for the dysfunctional voiding and pelvic pain in patients with interstitial cystitis who are refractory to other forms of treatment.     

Long-term results of M-VAC for the treatment of advanced urothelial cancer

Total of 37 patients with measurable lesions originating in advanced urothelial cancers received M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) combination chemotherapy and have been followed for a minimum of 12 months. The study included initial diagnoses of 24 bladder cancers and 13 upper urinary tract cancers in patients whose mean age was 62 years. The patients received a mean of three cycles of M-VAC. Clinical complete remission was observed in five of the 37 patients (13.5%) and partial remission was achieved in 10 patients (27.0%) after mean treatment of 2.4 and 2.1 cycles, respectively, for an over-all objective response rate of 40.5%. The mean duration of response was 11.6 +/- 7.1 months and 4.4 +/- 3.5 months for complete and partial remissions, respectively. A mean of 5.2 +/- 1.7 cycles of M-VAC was given for complete remissions and 3.5 +/- 1.4 cycles in partial remissions. An over-all survival rates after one and two years were 28.125% and 5.859%, respectively. Two of the five patients who had once marked complete remissions died after a mean survival time of 14.5 +/- 4.5 months and three survived with a mean duration of 20.3 +/- 5.4 months. Meanwhile, all of the patients who had achieved partial remissions died after a mean survival of 9.1 +/- 5.4 months except for one patient who survived more than 12 months. These results indicate that M-VAC combination chemotherapy for advanced urothelial cancer is extremely efficacious in initial responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

躯体功能及总体健康感在女性间质性膀胱炎治疗过程中的变化

目的探讨间质性膀胱炎（IC）治疗前后躯体功能（PF）及总体健康感（GH）的变化。方法2005年5月-2009年5年,依据症状及膀胱镜检查诊断间质性膀胱炎31例,其中23例符合美国国立糖尿病、消化病和。肾病研究所（NIDDK）的诊断标准。所有患者开始均口服阿米替林25mg,1次／d。治疗一周效果不佳者加服阿米替林至50mg／d,最大不超过100mg／d。对效果不佳或不能耐受阿米替林副作用的患者加用500g／L二甲基亚砜50mL膀胱灌注连续10次（其中4例用500g／L二甲基亚砜50mL＋10000u低分子肝素钠灌注）,总疗程3个月。观察指标：O’Leary间质性膀胱炎症状指数及问题指数、PF及GH。结果31例患者均完成治疗,25例患者取得良好的效果,6例患者效果较差。结论随着女性IC患者病情好转其躯体功能得到改善,患者的总体健康满意度提高。     

THE EFFICACY OF INTRAVESICAL BACILLUS CALMETTE-GUERIN IN THE TREATMENT OF INTERSTITIAL CYSTITIS: LONG-TERM FOLLOWUP

Purpose

Interstitial cystitis is a severe debilitating bladder disease characterized by unrelenting pelvic pain and urinary frequency. A prospective, double-blind, placebo controlled study of the use of intravesical bacillus Calmette-Guerin (BCG) in the treatment of interstitial cystitis was recently completed with a mean followup of 8 months. Results demonstrated a 60% BCG response rate, compared to a 27% placebo response rate. We now report the long-term followup results of those patients who received intravesical BCG.

Materials and Methods

Subjects randomized to receive BCG were followed at routine intervals with questionnaires and voiding diaries identical to those in the blinded study. Adverse events were closely monitored in the treatment and followup phases of the study. Subject baseline values were compared to followup data.

Results

Of the BCG responders mean followup was 27 months (range 24 to 33), and 8 of 9 (89%) continue to have an excellent response in all parameters measured. The global interstitial cystitis survey improved 70%, daily voids decreased 31%, nocturia improved 54%, mean voided volume increased 61%, pelvic pain decreased 81%, vaginal pain decreased 71%, urgency decreased 71% and dysuria decreased 82%. Overall well-being improved 54% and the Rand-36 quality of life survey overall improved 64%. In 86% of the patients (6 of 7) dyspareunia resolved. Of the initial BCG nonresponders there was no significant difference in interstitial cystitis symptomatology from baseline to last followup, suggesting that BCG does not worsen interstitial cystitis symptoms. No long-term adverse events from BCG were noted.

Conclusions

Intravesical Tice^* BCG is safe, effective and durable in the treatment of interstitial cystitis. Of those patients who received only 6 weekly treatments and responded favorably 89% continue to have an excellent response with followup ranging from 24 to 33 months.     

Does the potassium stimulation test predict cystometric,cystoscopic outcome in interstitial cystitis?

PURPOSE: We establish the relationship among symptom duration, cystometric and cystoscopic findings and potassium stimulation test in patients with interstitial cystitis. MATERIALS AND METHODS: A retrospective chart review was performed of 189 patients treated at an ambulatory clinic between 1992 and 1998. Urodynamic parameters, potassium stimulation test results and subjective response to treatment were evaluated. Fisher's exact test was used for statistical analysis. RESULTS: Of the 189 patients diagnosed with interstitial cystitis 173 (92%) were female and 16 (8%) were male. The potassium stimulation test was positive in 105 (83%) patients, negative in 16 (13%) and equivocal in 6 (4%). A cystometrogram and potassium stimulation test were done in 118 patients. Bladder capacity averaged 259 ml. in patients with tests potassium positive and negative, while average bladder volume at first sensation to void was 85 ml. and 148 ml. in those with negative and positive tests, respectively. Among the 102 patients with a positive potassium stimulation test 52 had normal cystoscopic findings. CONCLUSIONS: The potassium stimulation test is not correlated with either bladder capacity or cystoscopic findings.     

膀胱水扩张加膀胱灌注治疗间质性膀胱炎疗效观察

目的膀胱水扩张加膀胱灌注治疗间质性膀胱炎(interstitial cystitis,IC)的临床疗效观察。方法对6例间质性膀胱炎患者行膀胱水扩张及膀胱灌注,分析治疗前、治疗12周后、治疗6个月后间质性膀胱炎症状指数(interstitial cystitissym ptomatic in-dex,ICSI)和问题指数(interstitial cystitis problem index,ICPI)。结果 6例患者均获得满意随访,疗效显著2例、有效3例、无效1例,总有效率为83.3%(5/6)。治疗12周后及治疗6个月后ICSI和ICPI评分均较治疗前明显降低,差异具有统计学意义(P<0.05)。结论膀胱水扩张联合大剂量肝素、碳酸氢钠及利多卡因膀胱灌注治疗间质性膀胱炎具有创伤小、临床疗效显著、价格低廉等优点,具有一定的推广应用价值。