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PubMed2003

Pathology of interstitial cystitis.

In this workshop the participants were asked to consider the role of pathology in the diagnosis and management of interstitial cystitis (IC). Currently, the NIDDK definition of IC is made on clinical criteria; bladder biopsy is not required for the clinical work-up and histology is not used as a diagnostic criterion. The literature review described the most common pathological findings to be epithelial denudation or ulceration, mononuclear inflammation, edema, congestion, hemorrhage, and mast cell activation. These pathological changes were not universal or specific with 55% of IC subjects in one study having histology that was normal and indistinguishable from control subjects. Presentations were made which generally confirmed an association between abnormal pathology and more severe disease as determined by symptoms, cystoscopic capacity, and prognosis. During the workshop it was clear that whether or not a biopsy was performed depended on a number of factors, for example, country of origin, the research interest of the unit, and the desire to exclude malignancy on histological grounds. The consensus, which was not unanimous, was that bladder biopsy was a-non-mandatory test in the clinical work-up of the patient with IC but that urine cytology should be performed. It was discussed that bladder biopsy be an optional test and particularly relevant when one was suspicious of other conditions and in IC research. It was hoped that bladder biopsy pathology will give clues to contributory pathogenic processes such as epithelial dysfunction and inflammation; and in the future, with the help of molecular biology, may help determine etiology.

Biopsy↗
PubMed2003

The place of cystoscopy and hydrodistension in the diagnosis of interstitial cystitis: a potpourri of opinions emanating from an International Consultation on IC in Kyoto, Japan, March 28-30, 2003.

The place of cystoscopy and hydrodistension in the diagnosis of interstitial cystitis (IC) was discussed by an international and Japanese panel of IC researchers. Cysto and hydrodistension (HD) has been traditionally regarded as pivotal to the diagnostic process. To assess the experts' opinions a questionnaire was circulated which revealed that 20 of the 31 responders regarded cysto and HD to remain as an important inclusion criterion in the diagnosis of IC (with 8 undecided and 3 against the inclusion). The questionnaire further demanded opinions about the specificity of the known IC changes at cysto and HD, correlation with the clinical picture, false positives, and methodology of the examination.

Cystitis, Interstitial↗
PubMed2003

Current and future directions in diagnostic markers in interstitial cystitis.

Interstitial cystitis (IC) is a chronic bladder disorder of unknown etiology that is often diagnosed by symptom criteria with or without cystoscopic findings. Several potential diagnostic markers have recently been described that may facilitate diagnosis of this disorder. A summary of the literature and a discussion regarding these biomarkers is provided, along with a brief discussion of new biomarkers presented at the meeting.

Biomarkers↗
PubMed2000

A case of eosinophilic cystitis in a 5-year-old boy.

Eosinophilic cystitis (EC) is rather an uncommon disease in childhood. A case of EC in a 5-year-old boy, in which open biopsy was needed for final diagnosis, is reported. After diagnosis, he was treated with pemirolast potassium followed-up with eosinophil cationic protein (ECP) in serum and urine. Eosinophil cationic protein is an appropriate marker of EC.

Child, Preschool↗
PubMed2000

Subtypes of bladder mast cells in interstitial cystitis.

BACKGROUND: Because the types of mast cells present in the bladder of patients with interstitial cystitis (IC) have not been elucidated, we have used immunohistochemical techniques to determine which of the mast cell types is present in biopsy specimens. METHODS: For all patients diagnosed with IC (n = 10; female) their symptoms satisfied the criteria proposed by the National Institutes of Health criteria of IC and six patients suffering from bladder tumors were selected as control patients. Adjacent sections of paraffin-embedded tissues that had been fixed in Carnoy's solution were reacted with either antitryptase or antichymase antibodies. RESULTS: In detrusor and in mucosa, the number of tryptase-positive and chymase-negative mast cells (MC(T)) was 146+/-25 and 81+/-31 cells/mm2, respectively, and the number of tryptase-positive and chymase-positive mast cells (MC(TC)) was 124+/-50 and 54+/-20 cells/mm2, respectively. These numbers were significantly greater than those of the control group. A significant negative correlation (P<0.005; R = 0.943) was observed between the number of MC(TC) and the bladder capacity. The number of mast cells obtained by toluidine blue staining in detrusor and in mucosa was 95+/-68 and 71+/-39 cells/mm2, respectively, suggesting that staining with toluidine blue underestimated the number of mast cells. CONCLUSIONS: Mast cells were significantly increased in number in both the mucosa and detrusor of bladder specimens from IC patients compared with those from control. The MC(TC) may be the type of mast cell dominantly present in the bladder of IC patients. The MC(TC) in detrusor increased with the progression of contracted bladder.

Adult↗
PubMed2001

Prognosis of conservative therapy of advanced interstitial cystitis: experience of five cases.

BACKGROUND: It is generally believed that surgical procedures, particularly the more invasive ones, should be reserved for patients who fail to respond to conservative therapy by several established modalities. We studied whether conservative therapy was applicable to patients with interstitial cystitis (IC) in which an individual's awake bladder capacity decreases to 100 mL or less with vesicoureteral reflux (VUR). METHODS: Five cases that satisfied the criteria proposed by the National Institutes of Health were examined. The maximum awake bladder capacity was 50-100 mL (average, 74 mL). The bladder capacity under anesthesia was 70-300 mL (average, 199 mL). Only conservative treatments were carried out. RESULTS: The observation period ranged from 3 to 16 years with an average of 9 years. The awake bladder capacity ranged from 200 to 300 mL (average, 250 mL). The symptom index total score, which was previously 18.5, decreased to 5.5 and the problem index total score, which was previously 14.3, decreased to 3.5. Symptoms of bladder irritation improved. In four cases, VUR disappeared as the bladder capacity increased. Vesicoureteral reflux persisted in one case although its severity decreased and there was no fever. CONCLUSION: The patients treated with conservative therapy were able to maintain an awake bladder capacity that was sufficient for acceptable quality of life and their symptoms of bladder irritation improved. This suggests that we should regenerate the original remaining bladder using conservative therapy, even if IC is in a late stage.

Administration, Intravesical↗
PubMed2003

Adjuvant hydrodistension under epidural anesthesia for interstitial cystitis.

BACKGROUND: Hydrodistension is the first choice of treatment for interstitial cystitis because it allows for diagnosis, bladder biopsy and treatment. However, the method and efficacy of hydrodistension are variable. We performed adjuvant hydrodistension and examined the efficacy and factors that influence prognosis. METHODS: Fifty-two patients participated in the present study as subjects; they satisfied the diagnostic inclusion and exclusion criteria established by the National Institute of Diabetes, Digestive and Kidney Disease (NIDDK) in 1987, USA. Under epidural anesthesia, the bladder was repeatedly distended up to the maximal bladder capacity for treatment, diagnosis and biopsy. Hydrodistension was performed again on the following day for approximately 30 min under epidural anesthesia in a ward until macroscopic hematuria disappeared. RESULTS: Five patients were classified into the good, 30 into the moderate and 17 into the poor response group. In the good response group, three patients had type I allergy and one patient did not fulfil all of the positive factors in the NIDDK criteria. The poor response group included one patient with collagen disease. The poor response group was further divided into two subgroups based on bladder capacity. One subgroup included eight patients with a bladder capacity of less than 100 mL and vesicoureteral reflux (VUR). The other subgroup included nine patients with a bladder capacity of more than 100 mL. Among these nine patients there were five patients who lacked one or two positive factors in the NIDDK criteria. CONCLUSION: Adjuvant hydrodistension under epidural anesthesia is effective for about 70% of patients for more than 3 months. It can be performed in a ward without any serious complications. It was observed that patients lacking one or two positive factors were included in the good and poor response groups.

Anesthesia, Epidural↗
PubMed2003

Xanthogranulomatous cystitis.

Xanthogranulomatous cystitis (XC) is a rare benign chronic inflammatory disease of unknown etiology. Herein we report a case of a 70-year-old woman who presented with frequent, postmicturition pain and lower abdominal discomfort. Cystoscopy revealed a mass at the dome of the bladder near the left wall. Enhanced computed tomography (CT) demonstrated a mass with a central cavity. The patient underwent partial cystectomy because the presence of bladder neoplasm could not be ruled out. She had has no recurrence of XC 29 months after the operation. The present case of XC is the 20th to be reported in the world.

Aged↗
PubMed2001

A study to detect Gardnerella vaginalis DNA in interstitial cystitis.

OBJECTIVE: To investigate the possible role of Gardnerella vaginalis in interstitial cystitis (IC), using molecular methods to avoid difficulties with the culture and recovery of viable organisms, and the problems associated with the recovery of low numbers of culturable organisms. MATERIALS AND METHODS: Thirty-three bladder biopsy samples (29 paraffin-embedded and four freshly frozen) from patients with IC, diagnosed according to National Institute of Diabetes, Digestive and Kidney Diseases criteria, were assessed. Biopsy samples were used as urine samples may be contaminated by normal vaginal flora. A positive control comprised a 'normal' biopsy sample from a patient with a previous bladder tumour, seeded with G. vaginalis NCTC 10915. Microbial DNA was extracted from all paraffin-embedded and fresh specimens, and subjected to in vitro amplification by polymerase chain reaction (PCR) with G. vaginalis-specific primers. RESULTS: The anticipated PCR product of 333 base pairs was obtained with the positive control, whereas none of the other biopsy samples showed positive amplification specific for G. vaginalis. CONCLUSION: As there was no G. vaginalis DNA in any of the samples from patients with IC, it is an unlikely candidate in the pathogenesis of IC.

Cystitis, Interstitial↗
PubMed1996

Interstitial cystitis--an update.

Interstitial cystitis is a rare chronic debilitating condition predominantly affecting middle-aged women. The diagnosis, made from the combination of symptoms, cystoscopic findings and bladder biopsies, is often delayed because GPs are often unaware of the condition. The precise aetiology remains obscure and it is clear that there is much research that needs to be undertaken to shed any light on the various current aetiological theories. There is a wide assortment of therapies already available and many more currently under trial. Until there is further progress in the pathogenesis of IC, it seems unlikely that non-operative treatment will consist of anything but palliation. The only potential cures currently available are cystectomy and urinary diversion or surgical replacement of the bladder by enterocystoplasty.

Cystitis, Interstitial↗
PubMed1996

Detrusor myopathy: an accurate predictor of bladder hypocompliance and contracture in interstitial cystitis.

OBJECTIVE: To determine whether any histological characteristics within the detrusor in cases of early interstitial cystitis (IC) predict the subsequent development of severe symptoms due to bladder contracture. PATIENTS AND METHODS: The detrusor muscle component of bladder biopsies from 21 patients with IC was examined in sections stained with haematoxylin and eosin. Videocystometrography was performed at least 2 months after the biopsy and the patients were then followed up clinically for at least 3 years. RESULTS: The detrusor appeared normal in 13 patients; in eight there was evidence of detrusor myopathy. Patients with biopsies confirming detrusor myopathy were significantly more likely to have hypocompliant bladders than those with normal detrusor muscle histology (P < 0.02). Over the following 3 years, six of the eight patients with detrusor myopathy developed progressively severe symptoms and required subtotal cystectomy and enterocystoplasty. None of the 13 patients without detrusor myopathy required bladder substitution. CONCLUSION: In IC, detrusor myopathy is associated with bladder hypocompliance. Patients with detrusor myopathy appear to have more severe disease and are more likely to progress to bladder contracture requiring substitution enterocystoplasty.

Contracture↗
PubMed1996

Intragranular activation of bladder mast cells and their association with nerve processes in interstitial cystitis.

OBJECTIVE: To investigate the presence of progesterone receptors and the extent and type of degranulation exhibited by the increased numbers of mast cells (MCs) found in interstitial cystitis (IC), a painful bladder disorder which occurs almost exclusively in women, worsens perimenstrually and is characterized by increased numbers of oestradiol receptor (OR)-positive MCs. PATIENTS AND METHODS: The state of MC degranulation was analysed blindly using electron microscopy of bladder biopsies from 26 patients with IC and six control patients which included five women with incontinence, with none of the established characteristics of IC, and one man with transitional carcinoma of the bladder. Emphasis was placed on preserving the secretory granule ultrastructure. The presence of progesterone receptors (PRs) in five patients with IC and three controls was investigated using commercially available antibodies against PRs. RESULTS: Over 85% of bladder MCs expressed high affinity PRs, but the number of PR-positive MCs in patients with IC did not differ significantly from that of controls despite the overall increase in MCs seen in IC. MCs were activated to various degrees and were often near to neuronal processes. The secretory granule content of MCs from patients with IC was in different stages of dissolution, ranging from heterogeneous loss of electron density to the appearance of crystalline substructure and target forms containing only remnants of the original material. Typical degranulation by compound exocytosis was not observed. MCs from control patients contained secretory granules with mostly intact, electron-dense granules. CONCLUSION: These findings indicate that the symptoms of IC may depend on an imbalance of the relative number of oestrogen receptors (ORs) to PRs on bladder MCs resulting in a 'progesterone deficient' state. This possibility is strengthened by demonstration that oestradiol augments the secretion of MC histamine in response to the neuropeptide substance P, which is pro-inflammatory, nociceptive and overexpressed in bladders with IC. Intragranular activation of bladder MCs is a characteristic pathological finding in patients with IC. The lack of extensive degranulation, typically seen in anaphylaxis, may indicate a unique mode of stimulation and/or differential release of mediators.

Adult↗
PubMed1997

A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis.

OBJECTIVE: To evaluate the therapeutic efficacy of intravesical pentosanpolysulphate (PPS) compared with placebo in patients with interstitial cystitis (IC). PATIENTS AND METHODS: Twenty patients who fulfilled the diagnostic criteria for IC participated in a double-blind placebo-controlled study; 10 received intravesical PPS (300 mg in 50 mL of 0.9% sodium chloride) applied twice a week for 3 months and the other 10 received a placebo. Symptomatic relief and objective variables (bladder capacity voiding volumes and urinary frequency) were assessed after 3 months and the long-term outcome of those continuing treatment was determined. RESULTS: Of the patients treated with PPS, four gained significant symptomatic relief compared with only two receiving placebo. Only the urodynamic bladder capacity showed a statistically significant increase in patients treated with PPS (P = 0.047). At 18 months from the start of the study, the symptoms were relieved in eight patients while still receiving PPS instillations and in four without treatment. CONCLUSIONS: These results suggest that intravesical PPS is an effective option for the treatment of IC and shows that the intravesical application of PPS is a safe treatment with no important side-effects.

Administration, Intravesical↗
PubMed1998

Increased expression of substance P receptor-encoding mRNA in bladder biopsies from patients with interstitial cystitis.

OBJECTIVES: To determine whether substance P (SP, also known as neurokinin 1, NK1) receptors are differentially expressed in bladder biopsies from patients with interstitial cystitis (IC) compared with matched controls. MATERIALS AND METHODS: Cold-cup biopsies were taken during routine diagnostic cystoscopy. NK1-receptor expression was assessed using a quantitative analysis of NK1-receptor-encoding mRNA in bladder biopsies from patients and controls using in situ hybridization histochemistry (ISHH) combined with autoradiographic image analysis. RESULTS: Autoradiographic signal indicating the presence of NK1-encoding mRNA was localized to detrusor muscle, urothelium and vascular structures. In the bladder vasculature, the signal was predominantly associated with endothelial cells. NK1 receptor-encoding mRNA within the vascular endothelium was increased in the biopsies obtained from patients with IC. CONCLUSION: Increased levels of NK1 receptor-encoding mRNA within the bladder vascular endothelium suggests the up-regulation of NK1 receptor as a putative factor in the pathogenesis of pain related to IC. Increased responsiveness to SP released from the perivascular sensory terminals may result in a local cascade of neurogenic inflammatory responses which trigger the pathophysiological changes, including pain, characteristic of IC.

Adult↗
PubMed2000

A randomized double-blind placebo-controlled crossover trial of the efficacy of L-arginine in the treatment of interstitial cystitis.

OBJECTIVES: To determine, in a double-blind placebo-controlled crossover study, whether L-arginine improves the symptoms of interstitial cystitis (IC), a chronic condition in which nitric oxide (NO) may be important, as previous open pilot studies suggested that L-arginine reduced the pain and frequency associated with IC. PATIENTS AND METHODS: Patients fulfilling the standard diagnostic criteria for IC were randomized to receive L-arginine (2.4 g/day) or placebo for one month. After a 2-week 'washout' period they received the other medication. Patients were assessed at each stage using a validated symptom index, a voiding diary, urine analysis and records of adverse events. Patients were asked about overall efficacy at the close of the study. The results were compared using a t-test, with significance indicated at P<0.05. RESULTS: Sixteen (16) patients (mean age 51.3 years) were enrolled; the mean duration of IC was 5.4 years, the IC symptom index score 29.1, their nocturnal frequency 3.5 (voided volume 182 mL) and daytime frequency 12.7 (124 mL). Patients on placebo showed no differences in any recorded variable over the baseline values. L-arginine caused a statistically significant reduction in the overall symptom score of 2.2 over baseline, but there was no difference in voided volume, frequency or nocturia. As there was no significant difference for any variable between L-arginine and placebo, this reduction in score should be regarded with caution. Three patients withdrew because of side-effects (severe headaches, night sweats and flushing). CONCLUSION: Oral L-arginine produces a statistically significant improvement in the IC symptom index in patients with IC, but the effect is small. This effect may not be clinically significant as there were no improvements in the other variables assessed and no significant difference between the response to L-arginine and placebo. From these results the use of L-arginine cannot be recommended for treating IC.

Adult↗
PubMed2002

Effects of dimethyl sulphoxide and heparin on stretch-activated ATP release by bladder urothelial cells from patients with interstitial cystitis.

OBJECTIVE: To determine whether dimethyl sulphoxide (DMSO) and heparin reduce the greater stretch-activated ATP release in interstitial cystitis (IC), as ATP serves as a nocio-neurotransmitter in the bladder, and thus explain their beneficial effects in patients with IC (a disease characterized by hypersensory bladder symptoms). MATERIALS AND METHODS: Bladder epithelia in IC release more ATP in response to stretch than do control samples. Both DMSO and heparin are used intravesically to treat IC; such agents can modulate urothelial function because they directly contact bladder urothelium. Biopsies taken from patients with IC and from control subjects were grown in primary cultures using established cell-culture techniques. Cultured urothelial cells were stretched with the Flexcell device (Flexcell International Corp., McKeesport, PA, USA) and supernatant ATP was measured, using a luciferin-luciferase assay. DMSO (0.1%, 0.5% and 1%) or heparin (50, 200, 800 and 1600 U) was added to the cells at the start of the stretch experiments and the ATP released into the supernatant measured. Cell viability was also determined using Trypan Blue staining. RESULTS: IC cells released significantly more ATP in response to stretch than did control cells. This increased release of ATP by stretched IC cells was significantly blocked by adding DMSO or heparin at all concentrations used. Heparin appeared to have a greater dose-dependent effect on ATP release than did DMSO. CONCLUSIONS: These findings are consistent with the hypothesis that the urothelium provides sensory input via ATP release and that this process is increased in IC. Furthermore, stretch-activated ATP release was blocked by adding DMSO and heparin, both intravesical agents commonly used to treat the symptoms of IC. This study supports the notion that purinergic-targeted therapy is warranted in treating IC. Further studies are needed to determine the mechanisms of increased ATP release by IC urothelial cells.

Adenosine Triphosphate↗
PubMed2003

A study to detect Helicobacter pylori in fresh and archival specimens from patients with interstitial cystitis, using amplification methods.

OBJECTIVES: To detect Helicobacter pylori DNA in fresh and paraffin-embedded bladder biopsy specimens, and thus determine any possible role in interstitial cystitis (IC). MATERIALS AND METHODS: Thirty-three bladder biopsy samples were examined from patients with IC (29 paraffin-embedded and four freshly frozen) diagnosed according to National Institute of Diabetes, Digestive and Kidney Disease criteria. The positive control was a gastric biopsy sample from a patient with a known gastric ulcer caused by H. pylori infection. RESULTS: The anticipated polymerase chain reaction product size of 109 base pairs was obtained with the positive control, whereas none of the other biopsy samples (paraffin embedded or fresh) showed positive amplification specific for H. pylori. CONCLUSIONS: As there was no H. pylori DNA in any of the samples from patients with IC, it is an unlikely candidate in the pathogenesis of IC.

Biopsy↗
PubMed2003

The role of self-help groups in educating and supporting patients with prostate cancer and interstitial cystitis.

OBJECTIVES: To identify and compare the needs of patients with prostate cancer or interstitial cystitis (IC), and to evaluate the role of self-help groups (SHGs) in meeting those needs, as SHGs are thought to be an important source of information and social support for such patients. METHODS: The authors attended SHG meetings for prostate cancer and IC from September 2000 to May 2001. Issues related to SHGs were addressed by combining their experiences with those published previously. RESULTS: Patients with prostate cancer appear to use SHGs primarily as a medium for advocacy and information sharing about the disease, whereas patients with IC seem to use SHGs for social support and coping skills. Patients perceive SHGs as being useful, but many do not attend these meetings. Urologists' attitudes toward SHGs are identified as a potential factor contributing to the under-use of SHGs by both groups of patients. CONCLUSIONS: The inherent differences in disease and patient characteristics result in both groups of patients using SHGs for different reasons. The differences in therapeutic objectives are reflected in the format and content of SHG meetings. Issues related to not participating in SHGs and areas of future research are discussed.

Aged↗