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.     

Clinical evaluation of 30 patients with interstitial cystitis complicated by fibromyalgia

PURPOSE: Although interstitial cystitis (IC) complicated by fibromyalgia (FM) is yet unreported in Japan, we encountered patients with the complications almost as frequently as in the USA. We report the present status of such patients and the significance of this complication. PATIENTS AND METHODS: We evaluated the clinical findings of 30 patients with IC complicated by FM in the last four years. RESULTS: Average IC symptom index and problem index was 14.9 and 14.6, respectively. Average numbers of tender points for the criteria for FM was 16 locations. Both diseases have some similarities in the decrease in pain threshold, extensive pain, factors exacerbating symptoms and treatment methods. CONCLUSION: Approximately 11% of patients with IC have a complication of FM. They feel isolated due to the lack of understanding of the disease and endure generalized intolerable pain.     

Clinical and urodynamic experience with intravesical hyaluronic acid in painful bladder syndrome associated with interstitial cystitis

Introductionfew studies have been carried out on therapeutic options in patients with painful bladder syndrome associated with interstitial cystitis. The aim is to verify the safety and effectiveness of treatment with sodium hyaluronate through intravesical instillation in patients with painful bladder syndrome.Materials and methodsa series of 18 female patients is presented, with a mean age of 51 years and prior diagnosis of painful bladder syndrome, who were treated by means of the weekly infusion of an intravesical solution of 40 mg of sodium hyaluronate in sterile solution, over a period of eight weeks. The patients were examined clinically and urodynamically prior to their inclusion in the study and eight months after the instillations had concluded.Resultsthere was a statistically significant improvement in the urodynamic parameters and in the symptoms measured quantitatively by means of the questionnaire “Pelvic Pain and Urgency/Frequency” between the baseline situation and after the vesical instillation of sodium hyaluronate in patients with painful bladder syndrome. There was no toxicity arising from the treatment, given that no adverse effects were recorded in relation to it.Conclusionthe clinical use of intravesical hyaluronic acid in patients with painful bladder syndrome possibly associated with interstitial cystitis has been demonstrated. The clinical improvement is also associated both with increased bladder capacity and improved bladder sensitivity. Tolerance was excellent. Clinical tests that more profoundly evaluate the therapeutic potential of this drug in this type of patients are required.     

Lymphocyte function in patients with interstitial cystitis.

To determine whether there is a primary immunological disorder involved in the etiology of interstitial cystitis, we compared the in vitro function of peripheral blood lymphocytes from 10 patients with interstitial cystitis to those from 10 healthy female controls. The lymphocytes were isolated and incubated in either cell culture medium alone, cell culture medium supplemented with the mitogen phytohemagglutinin or cell culture medium with autologous sterile filtered urine, the latter to detect any immunogenic potential of urine in this disease. We studied the relative proliferation of the phenotypes CD2, CD4, CD8, CD19, CD14 and CD56 by immunofluorescence and flow cytometry. To detect activation of T lymphocytes we also studied expression of HLA-Dr and interleukin-2 receptors. There was no difference in the rate of proliferation of the various lymphocyte phenotypes between the 2 groups in any of the culture media. Similarly, there was no difference between the 2 groups in the degree of lymphocytic activation after incubation. Furthermore, incubation in the presence of autologous urine caused no increase in activation above that seen in control cultures. We also assessed the production of the lymphokines interleukin-1, interleukin-2 and interferon-gamma in the supernatant fluid of the cell cultures. There was no difference in the production of these immunoregulatory cytokines between the control and patient groups, and again urine did not act as a mitogen in either group. We conclude from this study that there is no primary immunological disorder evident in patients with interstitial cystitis, and that the urine does not act as a stimulant to the immune system. This finding casts severe doubt on any theory suggesting that interstitial cystitis is an autoimmune disease or that urine contains an autoantigen causing the disease.     

Bladder necrosis following hydrodistention in patients with interstitial cystitis

PURPOSE: Bladder hydrodistention is used to diagnose and treat patients with interstitial cystitis. This procedure has been shown to have minimal morbidity and provide symptomatic relief in a subset of patients with interstitial cystitis. We report our experience with almost total bladder necrosis after hydrodistention at 2 institutions. To our knowledge this rare complication has not been previously reported in the literature. We also reviewed the literature regarding complications of hydrodistention and discuss their possible etiology. MATERIALS AND METHODS: We report 3 cases of bladder necrosis after therapeutic hydrodistention for interstitial cystitis at 2 institutions. All records were reviewed, and the clinical presentation, findings and treatments are discussed. A literature review was performed to evaluate the effectiveness and complications of hydrodistention for interstitial cystitis. RESULTS: There were 2 female and 1 male patient between ages 29 and 46. All patients had a previous diagnosis of interstitial cystitis and had been previously treated with hydrodistention. All patients presented with severe abdominal pain and had necrosis of the entire bladder wall with sparing of the trigone. Two patients were treated with supratrigonal cystectomy. A review of the literature revealed little data on the effectiveness of hydrodistention for interstitial cystitis. CONCLUSIONS: Vesical necrosis is a rare but devastating complication of hydrodistention. It can occur in young patients in the absence of a contracted bladder and it usually presents as severe postoperative abdominal pain. At exploration bladder necrosis with sparing of the trigone was observed. All patients required enterocystoplasty.     

Abnormal urinary potassium metabolism in patients with interstitial cystitis

PURPOSE: If most patients with interstitial cystitis (IC) have epithelial leakage allowing urinary K to penetrate the interstitium and provoke symptoms, urinary K should be lower in untreated patients than in healthy subjects and it should increase with successful heparinoid treatment. This study tested these hypotheses. MATERIALS AND METHODS: Na, K and creatinine (Cr) were determined in spot urine samples from new, symptomatic, untreated patients with IC meeting all National Institute of Diabetes and Digestive and Kidney Diseases clinical diagnostic criteria, returning patients with IC reporting 50% or greater symptom improvement after 4 or greater months of oral heparinoid therapy and control subjects, and in 24-hour urine samples from new untreated patients and controls. RESULTS: In spot urine specimens of 37 new patients with IC K-to-Cr ratios were significantly lower than in 18 controls (0.51 vs 0.88 mg/mg Cr, p = 0.001). A total of 50 successfully treated patients with IC had significantly higher K-to-Cr ratios than those in 37 new patients (0.66 vs 0.51 mg/mg Cr, p = 0.025). Na-to-Cr ratios in the 3 groups were not significantly different. In 24-hour urine specimens 30 new patients had lower average K (31.0 vs 46.2 mEq/l, p = 0.01) and lower K-to-Cr ratios (0.43 vs 0.52 mg K/mg Cr, p = 0.01) than in 47 controls, while Na was not significantly different. CONCLUSIONS: Our finding of lower urinary K in new, untreated patients supports the concept of abnormal epithelial permeability and K absorption in IC. Higher urinary K in successfully treated vs untreated patients may reflect decreasing urinary K absorption due to mucosal repair and a resulting decrease in epithelial permeability. K/mg Cr appears accurate for normalizing urinary K.     

Skin reactions to urine in patients with interstitial cystitis

Eight of 11 patients with interstitial cystitis had positive skin reactions to patch tests with urine (delayed type IV or irritant reactions). The positive reactions were seen to tests with the patients' own urine, but also, although less frequently, to tests with foreign urine as well. Immediate reactions (type I reactions; prick tests, scratch patch tests, and 20-minute patch tests) were not observed. The clinical morphology and the histology of the positive patch tests suggest a toxic rather than an allergic reaction, although the latter could not be totally excluded. The positive skin reactions may be relevant in the pathogenesis of interstitial cystitis suggesting a mucosal hyperreactivity to some component of urine.     

Observations on interstitial cystitis

Interstitial cystitis is more common in young women than previously believed. Findings typical of the disease are a history of diurnal and nocturnal pollakiuria, pelvic discomfort increased with bladder distention, marked bladder tenderness on gentle palpation of the anterior lateral vaginal fornices, less than normal bladder capacity, and a negative urinalysis except for many epithelial cells.     

A referral center's experience with transitional cell carcinoma misdiagnosed as interstitial cystitis

PURPOSE: There has been a recent trend to diagnose interstitial cystitis (IC) in a noninvasive way using a potassium sensitivity test, and a pelvic pain, urgency and frequency questionnaire. The concern is that significant pathology causing the bladder symptoms may be missed, such as transitional cell carcinoma. We present our experience with patients "labeled" as having IC who truly had cancer as the cause of irritative symptoms. MATERIALS AND METHODS: A retrospective review of patient records at our IC center was performed from 1998 to 2002. A total of 600 patients were seen at that time with the diagnosis of interstitial cystitis. RESULTS: Six patients (1%) previously diagnosed as having IC were found to have transitional cell carcinoma as the cause of symptoms, 4 of whom (67%) had no hematuria. Mean time from the diagnosis of IC to diagnosis of transitional cell carcinoma was 29.8 months. Irritative bladder symptoms resolved after identifying and treating the malignancy. CONCLUSIONS: Patients with irritative voiding symptoms require a thorough evaluation which may include cystoscopy, cytology and upper tract imaging. Hematuria was not a good predictor of cancer in our series. In the era before widespread use of minimally invasive means to diagnose IC (ie potassium sensitivity test, pelvic pain, urgency and frequency questionnaire) 1% of patients who were considered to have IC actually had transitional cell cancer as the cause of symptoms. One would expect that this number would increase if the criteria to diagnose IC and initiate treatment were oversimplified. Interstitial cystitis remains a diagnosis of exclusion.     

Psychological profile of Taiwanese interstitial cystitis patients

Objectives:   The correlation between anxiety and interstitial cystitis has, as best we know, not yet been reported on. The present study investigated the psychological profile, including anxiety and depression, of patients suffering from interstitial cystitis (IC).
Methods:   A total of 47 IC patients, all of whom met National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIDDK) criteria, plus a group of 31 age-matched, asymptomatic women received a structured interview on depression (Hamilton Rating Scale for Depression) and also on anxiety symptoms (Hamilton Rating Scale for Anxiety). IC patients also completed questionnaires relating to IC symptom severity, including urgency and frequency (visual analog scale) and O'Leary Sant index.
Results:   A total of 85% of our IC patients featured significant affective symptoms. The average depression scores were 16.6. Fifteen patients (31.9%) featured mild depressive symptoms, five (10.6%) had mild to moderate and 20 (42.6%) had moderate to severe depression symptoms. The mean anxiety score was 21.0, with 21 (44.7%), nine (19.1%) and 17 (36.2%) patients revealing mild, mild to moderate, and moderate to severe anxiety symptoms, respectively. Further, IC patients reported a significantly greater extent of depression and anxiety than was the case for controls. Pain scale and O'Leary Sant index were significantly correlated to anxiety and depression score.
Conclusions:   Most of our IC patients feature significant depression and anxiety. The extent of affective symptoms would appear to correlate well with IC symptom severity.     

Clinical experience of 52 patients undergoing laparoscopic radical prostatectomy

Perioperative results and oncological and functional results were evaluated for 52 patients who underwent laparoscopic radical prostatectomy (LRP). Median operative time was 341 minutes and median blood loss was 828 ml. The intraoperative complications were hemorrhage exceeding 3,000 ml (five cases), ureteral injury (two cases), and rectal injury (one case). The median day of catheter removal was postoperative day 7. Postoperative complications were temporal arrhythmia, mild hydronephrosis, port site hernia, urethral stricture, and a giant lymphocele. When surgical results were compared between the firsthalf cases and second-half cases who were operated on by a single surgeon, median operative time and intraoperative hemorrhage did not differ significantly between the two halves but the day of catheter removal after LRP was significantly earlier for the second-half group. The pathological stage was pT3 in 41.2% of the patients and the negative surgical margin rate was 62.7%. The 3-year PSA-failure-free survival rate was 64. 1%. Pad-free status (0-1 pad/day) was achieved in 84.4% of the patients. Erectile function was preserved in 58.3% of patients undergoing nerve-sparing LRP. Although the complication rate and the quality of operative procedures gradually improved, efforts to improve the oncological and functional outcomes of LRP must continue.     

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.     

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.     

Incidence of Helicobacter pylori in patients with interstitial cystitis.

OBJECTIVE: Chronic gastritis has compelling similarities to interstitial cystitis (IC). It is characterised by chronic pain in a tubular organ. Histologically, epithelial damage, inflammatory response in the lamina propria and epithelial ulcerations are seen. An infective cause was rarely considered until the emergence of Helicobacter pylori over the past 15 years. We have had experience of patients with bladder pain and irritability reporting improvement with antihistamines. It has also been reported that IC symptoms improved dramatically after treatment for H. pylori infection. Previous studies have determined the incidence of H. pylori antibodies in women with IC but we examined bladder material histologically and performed the Campylobacter-like organism (CLO) test on the biopsy specimens. MATERIALS AND METHODS: A prospective controlled study was performed. Patients with urinary symptoms fulfilling the National Institute of Diabetes and Digestive and Kidney Diseases criteria for IC underwent GA cystoscopy at which the macroscopic appearance of the bladder was noted and biopsies were taken. The biopsy material underwent histological examination and CLO test. Control patients who were undergoing cystoscopy for reasons other than investigation of IC also had biopsy taken and the CLO test was performed on these specimens. RESULTS: Five of 15 patients with symptoms and signs of IC had a positive CLO test. Three of 15 patients of the control group had a positive CLO test. With the 2-sided chi(2) test there was no statistical difference between the 2 groups. CONCLUSION: Our small prospective control study does not support the hypothesis that H. pylori is an important component in the pathogenesis of interstitial cystitis.