[Clinical study of interstitial cystitis. I-(I). The clinical and pathological observations of the contracted bladder caused by interstitial cystitis and tuberculosis].
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Bladder biopsy samples from 17 interstitial cystitis patients and 20 controls were evaluated for urothelial cell activation using a panel of monoclonal antibodies to HLA-DR, intercellular adhesion molecule 1, interleukin 1 alpha and tumor necrosis factor alpha. Urothelial cells in the majority (13 of 16, 81%) of the biopsies from patients with interstitial cystitis showed increased expression of HLA-DR, while fewer samples were positive for intercellular adhesion molecule 1 (3 of 16, 19%), interleukin 1 alpha (2 of 17, 12%) or tumor necrosis factor alpha (1 of 15, 7%). No urothelial cell expression of intercellular adhesion molecule 1, interleukin 1 alpha or tumor necrosis factor alpha was detected in the controls, and only 1 of 20 control samples contained HLA-DR positive urothelial cells. These results suggest that an unusual type of cellular activation is present in interstitial cystitis. In vitro studies with cultured normal urothelial cells indicated that cells activated with gamma interferon and tumor necrosis factor alpha expressed intercellular adhesion molecule 1 and HLA-DR, although increases in intercellular adhesion molecule 1 expression occurred earlier. Urothelial cells in interstitial cystitis patients may be defective in ability to express intercellular adhesion molecule 1. Alternatively, the differential expression of HLA-DR and intercellular adhesion molecule 1 in interstitial cystitis specimens may represent a functional subset of interstitial cystitis or reflect different stages of the disease. Urothelial cell activation in interstitial cystitis may result in aberrant immune responses and immune activation within the bladder. Because HLA-DR can be detected in paraffin-embedded tissues, evaluation of urothelial cell HLA-DR expression, although not specific for interstitial cystitis, may become a useful tool in the pathological evaluation of biopsy tissues from patients with this disease.
PURPOSE: Interstitial cystitis is a disorder of the bladder characterized by urgency and frequency of urination, and pelvic pain. The classic type of interstitial cystitis is characterized by Hunner's ulcers, which are focal regions of severe bladder inflammation. Patients with Hunner's ulcers tend to have more severe symptoms and are often refractory to medical management. We present a prospective series of patients who underwent ablative therapy of Hunner's ulcers using a neodymium (Nd):YAG laser. MATERIALS AND METHODS: A total of 24 patients with interstitial cystitis underwent ablative therapy for Hunner's ulcers. Medical therapy had failed in all cases. Using regional or general anesthesia the Nd:YAG laser under cystoscopic control was used to ablate the ulcers. The power setting was 15 W. with a firing duration of between 1 and 3 seconds. The procedure was performed on an outpatient basis. Symptoms were noted preoperatively and postoperatively. RESULTS: All patients had symptom improvement within 2 to 3 days. The mean pain scores decreased from 9.1 to 1.2 (p <0.003), the mean urgency score decreased from 8.2 to 1.9 (p <0.003), the mean voiding interval increased from every 30 minutes to every 102 (p <0.0001) and nocturia decreased from a mean of 7.9 voids per night to 2.9 (p <0.0001). There were no complications. Mean followup was 23 months. However, relapse in 11 patients required 1 to 4 additional treatments. The re-treatment response was similar to the initial treatment. CONCLUSIONS: Nd:YAG laser ablation of Hunner's ulcers is an excellent, minimally invasive method of treating interstitial cystitis. While it is not a cure, it offers patients an opportunity to have decreased symptoms for an extended period and it may be repeated as necessary.
OBJECTIVES: To determine whether interstitial cystitis is associated with the increased release of substance P from the bladder wall into urine, by measuring urinary excretion rates of substance P and its metabolites in women with interstitial cystitis and in a control group of women with stress incontinence and normal bladder function. PATIENTS AND METHODS: Catheter urine was collected from 13 patients and 10 controls during a water diuresis ( approximately 10 mL/min) before and after instilling the bladder with 100 mL of water. The contribution of the bladder wall to urinary substance P peptides was assessed by measuring the change in substance P peptide levels after 2 min of bladder stasis before and after instillation. RESULTS: Absolute substance P excretion rates were similar in patients with interstitial cystitis and controls; 2 min of bladder stasis reduced the substance P excretion rate (P = 0.03) and increased the excretion rate of substance P metabolites (P = 0.01). CONCLUSIONS: The release of substance P from the bladder wall was not increased in patients with interstitial cystitis.
Interstitial cystitis (IC) is a predominantly female condition with the presenting symptoms of frequency of micturition and pain. The diagnosis is confirmed by bladder visualization at cystoscopy during filling, emptying, and redistension. The epidemiology, proposed etiologies, and current therapies for interstitial cystitis are discussed. The condition of IC is poorly understood and has no specific histological characteristics. However, there is much that can be offered to the IC sufferer to relieve or cure her symptoms. It is hoped that the recent decade of increasing research activity will be fruitful in answering questions of etiology and pathogenesis, and offering hope for new therapies and ultimately cure.
Interstitial cystitis (IC) is a syndrome consisting of severe refractory bladder symptoms of unknown etiology. The disease tends to affect Caucasian women with a mean age of 40 years, with 25% of patients under the age of 30. Few population based epidemiological studies of IC have been performed. We analyzed a case of interstitial cystitis in a 42-year-old non-smoker woman. In two biopsy samples the presence of viral DNA of human polyomavirus BK (BKV), human herpes virus type 1 and type 2 (HHV- 1 and HHV-2), adenovirus, human papillomavirus (HPV) and bacterial DNA (Chlamydia trachomatis and Mycoplasma genitalium) were evaluated by means of polymerase chain reaction (PCR). Both samples resulted positive only for BKV and HPV DNA. HPV genotyping revealed the presence of HPV-66 that is associated with a high risk of cancer development. Thus the finding of a viral co-infection could support the hypothesis of the multi-factorial origin of this pathology.
Interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome are clinical syndromes characterized by pelvic pain with or without voiding symptoms such as urgency and frequency. There are many similarities in their epidemiology, adverse effect on quality of life, etiology/pathophysiology, natural history, and response to similar treatments. However, overlapping clinical definitions and similar entrance criteria for large-scale cohort studies make comparisons problematic. Newer efforts to classify pelvic pain syndromes should help in our recognition that interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome likely are not organ-specific syndromes but urogenital manifestations of regional or systemic abnormalities.
Thirteen patients with interstitial cystitis diagnosed by the NIH criteria were treated with intravesical electromotive administration of lidocaine and dexamethasone followed by cystodistention. After a mean follow-up of 10 (range 3-22) months, 8/13 (62%) of the patients reported complete resolution of bladder symptoms lasting an average 4.5 (range 0.75-17) months. Partial or short-term improvement of bladder symptoms was observed in three patients, while two patients reported aggravation of pain for several days after therapy. A significant increase in bladder capacity, to an average 166% of the pretreatment capacity, was observed in all patients. Whenever symptoms recurred after initially effective therapy, retreatments were performed with equal efficacy in 11 patients. This promising new therapeutic approach, performed on an outpatient basis, may become first-line treatment for patients with interstitial cystitis.
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.
Urine from patients with interstitial cystitis has been reported to be more cytotoxic than urine from healthy subjects when tested in vitro against cells from a normal urothelial cell line. The purpose of the present study was to develop a method to measure urinary cytotoxicity and so make it possible to estimate the toxicity of urine from interstitial cystitis patients. The study included 10 women with interstitial cystitis and 10 healthy controls. Urine specimens were obtained from both groups and urine cytotoxicity was measured by a modified 51Cr-release assay: A range of urine dilutions was added to suspensions of target cells with intracellular bound 51Cr, and cellular death was recorded by measuring the 51Cr-release from the target cells. The transitional cell bladder cell lines T24 and Hu609 and the erythroleukemia K562 cell line were used as target cells. There was no difference in urine cytotoxicity between interstitial cystitis patients and healthy controls. Urine cytotoxicity was increased by dilution in both groups.
BACKGROUND: It has been postulated that interstitial cystitis can be induced by an allergy. This is partly based on the observation that many patients with interstitial cystitis also have allergic diseases. In this study, an allergic evaluation was conducted on patients with interstitial cystitis complicated by bronchial asthma, a typical allergic disease. METHODS: Clinical histories were obtained and biopsy specimens from the vesical walls of the study patients were examined histologically. Cutaneous tests and IgE radioallergosorbent tests (RAST) were performed. Further, intravesical provocation tests were carried out using IgE RAST-positive antigens, and histamine release assays were performed on the vesical biopsy specimens using anti-IgE antibodies. RESULTS: Five of 6 patients alternately exhibited symptoms of allergic disease and bladder symptoms. The eosinophil and mast cell counts in the vesical biopsy specimens of these 5 patients were increased. Furthermore, an intravesical provocation test performed using the IgE RAST-positive antigen was positive in 4 patients. The mean vesical biopsy specimen histamine release was 17.7% for patients with interstitial cystitis with bronchial asthma which was significantly higher than that for interstitial cystitis patients without bronchial asthma (8.9%) or the control group (4.5%). The prognosis of patients with interstitial cystitis with allergic complications was relatively good. CONCLUSION: Patients with bronchial asthma exhibited hypersensitivity both generally and locally in the bladder. The alternation phenomenon was observed between the hypersensitive organs.
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OBJECTIVE: To evaluate the Interstitial Cystitis Symptom Index and Problem Index as a screening tool for interstitial cystitis, and to estimate the prevalence and risk factors for interstitial cystitis in women with chronic pelvic pain. METHODS: Forty-five women scheduled to undergo laparoscopy for chronic pelvic pain were recruited. Women were questioned about lower urinary tract symptoms, administered the Interstitial Cystitis Symptom Index and Problem Index, and rated pain symptoms on a 0-10 visual analogue scale. Cystoscopy with hydrodistension and bladder biopsy was performed at the time of laparoscopy. Interstitial cystitis was diagnosed if women had a combination of: 1) urgency, 2) frequency or nocturia, and 3) positive cystoscopic findings. RESULTS: Seventeen women (38%) were diagnosed with interstitial cystitis. A score of 5 or more on the Symptom Index had 94% sensitivity (95% confidence interval [CI] 71%, 99.8%) and 93% negative predictive value (95% CI 68%, 99.8%) in diagnosing interstitial cystitis. On multivariable analysis, an elevated Symptom Index score of 5 or more (odds ratio [OR] 9.4; 95% CI 1.01, 88.1) and an elevated dyspareunia score of 7 or more (OR 5.5; 95% CI 1.10, 27.1) were risk factors for interstitial cystitis. CONCLUSION: In our sample of women with chronic pelvic pain, the prevalence of interstitial cystitis was 38%. The Interstitial Cystitis Symptom Index was a useful screening tool. Independent risk factors for the diagnosis of interstitial cystitis were an elevated Symptom Index score and an elevated dyspareunia pain score. For women with chronic pelvic pain, screening for interstitial cystitis should be performed.
It has been suggested that interstitial cystitis is an autoimmune disease. The evidence for this hypothesis, based on studies of humoral immune factors, has been contradictory. We assessed the immune response in interstitial cystitis by evaluating lymphocyte populations in the peripheral blood and bladder tissue of interstitial cystitis patients. The lymphocyte phenotypes in peripheral blood were entirely normal, including the CD4 (cluster designation nomenclature) and CD8 subsets, and the CD4:CD8 ratio. Bladder lamina propria showed a predominance of CD4 over CD8 lymphocytes in interstitial and other forms of cystitis. Bladder epithelium showed a similar pattern in bacterial or mechanical cystitis but specimens from patients with interstitial cystitis had a predominance of CD8 cells. The findings of normal lymphocyte populations in the peripheral blood are not supportive of an autoimmune mechanism in the disease. The findings in bladder tissue show that the urothelium is not involved in the inflammatory reaction, as is the lamina propria, and they would suggest, therefore, that the initiating factor does not originate from the bladder lumen. The CD8 predominance in the urothelium along with a CD4 predominance in the lamina propria may form a characteristic pattern for the diagnosis of interstitial cystitis and merits further study.
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.
PURPOSE: Based on the assumption that interstitial cystitis results from a defective mucous lining of the bladder epithelium, we investigated the activity of hyaluronic acid in the treatment of this disease. Hyaluronic acid is an important glycosaminoglycan present in all connective tissues, including the glycosaminoglycan layer of the vesical mucosa. It exhibits a variety of pharmacological properties that enhance its appeal for the therapy of interstitial cystitis. MATERIALS AND METHODS: A total of 25 patients with characteristic findings of interstitial cystitis refractory to other medical treatments participated in a trial of intravesical hyaluronic acid at a dose of 40 mg. weekly for 4 weeks and then monthly. Response to therapy was evaluated by symptom score, voiding diaries and visual analog scales. RESULTS: An initial 56% positive (complete plus partial) response rate at week 4 increased to 71% by week 12 and response was maintained until week 20. Beyond week 24 there was a moderate decrease in the effectiveness of the medication. There was no significant toxicity attributable to hyaluronic acid in the bladder. CONCLUSIONS: The response of patients with refractory interstitial cystitis to the intravesical administration of hyaluronic acid was gratifying. In the past many therapies for interstitial cystitis which were initially considered promising failed the test of a controlled study. Such a study to determine the activity of hyaluronic acid in patients with interstitial cystitis is currently under way.
Interstitial cystitis, a sterile bladder condition, is characterized by urinary frequency, urgency, burning and suprapubic pain. Increasing evidence indicates that interstitial cystitis is a heterogeneous syndrome that reflects an immune response to a variety of triggers. More than 50% of the patients have allergies, 30% have the irritable bowel syndrome and almost 20% suffer from migraine headaches. Increased numbers of mast cells have been reported in interstitial cystitis. Mast cell activation, which is critical if these cells were to be implicated in this syndrome, has been investigated by electron microscopy, which definitively shows mast cell secretion. Recently, methylhistamine, the major metabolite of histamine, and the specific mast cell marker, tryptase, were shown to be significantly elevated in urine of interstitial cystitis patients. Bladder biopsies from 53 patients were analyzed blindly for the number and degree of activation of mast cells using 4 different stains for light microscopy, as well as electron microscopy. Controls included 16 patients with incontinence and chronic bacterial cystitis. Mast cells in controls were less than 10/mm.2 and were all nearly intact. Surprisingly, mast cells from 11 cancer patients averaged 50/mm.2 but almost all were intact. In contrast, mast cells from 26 interstitial cystitis patients averaged 40/mm.2 and more than 90% were activated to various degrees. Therefore, bladder mast cell activation is a characteristic pathological finding in at least a subset of patients with interstitial cystitis.
PURPOSE: We determined how interstitial cystitis progresses from initial symptoms to diagnosis. MATERIALS AND METHODS: We retrospectively analyzed the records of 45 patients to determine the dates of symptom onset and diagnosis, and sequence of urgency/frequency, nocturia and pain. We also documented alternate and previous diagnoses, and previous surgical treatments. RESULTS: Of the patients 89% presented with only 1 symptom. Median time from the initial symptom to all symptoms was 2 years (mean 5.5). The most common previous diagnoses were urinary infection in 19 cases, a gynecologic diagnosis in 14 and urethral diagnoses in 6. A previous urinary infection was documented in only 1 of 19 patients, while 11 had undergone hysterectomy and 5 diagnosed with endometriosis had no pathological documentation available. CONCLUSIONS: Early interstitial cystitis presents variably and usually with only a single symptom of urgency/frequency, nocturia or pain. Clinicians may fail to appreciate the symptoms of early interstitial cystitis, which leads to delayed diagnosis until the patient is more symptomatic. With time multiple symptoms manifest. Bacterial cystitis, prostatitis, endometriosis and chronic pelvic pain are common initial misdiagnoses. Interstitial cystitis should be considered when laboratory documentation of alternate diagnoses is lacking or when patients fail to respond to therapy for alternate diagnoses.