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PubMed2005

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

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

Administration, Intravesical↗
PubMed2005

What is the pain of interstitial cystitis like?

To describe the characteristics of pain experienced by patients with interstitial cystitis (IC) in terms of pain site, severity, and character, we performed a secondary analysis of data from the IC database (ICDB), which was a prospective, longitudinal, cohort study of IC patients. We analyzed the cross-sectional baseline data from 629 patients who had a completed baseline symptom questionnaire. Patients answered questions about whether they had pain or discomfort associated with urinary symptoms over the past 4 weeks and if so, about the location, characteristics, intensity, and frequency of their pain. Logistic regression examined associations between pain location and the presence of urinary symptoms. Analyses were performed using SAS version 8.2 (SAS Institute, Cary, NC, USA) and considered significant at the 5% level. Five hundred and eighty-nine (94%) patients with a mean age of 45 years (SD 14 years) reported baseline pain or discomfort associated with their urinary symptoms. The most common baseline pain site was lower abdominal (80%), with urethral (74%) and low back pain (65%) also commonly reported. The majority of patients described their pain as intermittent, regardless of the pain site. Most patients reported moderate pain intensity, across all pain sites. There was a statistically significant link between pain in the urethra, lower back, and lower abdomen, and urinary symptoms. Patients with IC report pain at several sites other than the bladder, possibly arising from the previously well-described myofascial abnormalities of pelvic floor and abdominal wall present in patients with IC and other chronic pelvic pain syndromes.

Cystitis, Interstitial↗
PubMed2006

There is a low incidence of recurrent bacteriuria in painful bladder syndrome/interstitial cystitis patients followed longitudinally.

The objective of this paper was to establish whether patients with confirmed painful bladder syndrome/interstitial cystitis (PBS/IC) presenting with symptoms of UTI have actual bacteriuria vs a flare of their PBS/IC symptoms. One hundred and six (n = 106) consecutive female patients (mean age 39.8 +/- 14 years) with newly diagnosed IC were identified and followed longitudinally for 24 months. At the initial visit and at all subsequent visits, urinary specimens were obtained by sterile catheterization (Bard 14Fr female) and cultured for bacteria. Eight patients had an initially positive urine culture, and repeat cultures 8 weeks after treatment were all negative. Once sterile urine was established, the diagnosis of PBS/IC was confirmed. A pelvic pain/urgency/frequency (PUF) questionnaire score was obtained from 89 patients. After the diagnosis of PBS/IC, all patients received multimodal treatment. Patients were instructed to present to the office whenever they developed symptoms of UTI, at which time a sterile catheter specimen was obtained and sent for culture. Greater than 10(3) colonies were considered positive. Patients who did not report flares were contacted to establish whether unreported treatments were given. Seventy-two patients (68%) had no UTI episodes or flares. The remaining 34 patients (32%) presented with 54 flares, of which 44 were culture-negative and 10 were culture-positive. A single flare was reported by 21 patients during the 24 months, with three positive cultures (14.3%). Recurrent UTI symptoms (two to four flares) were seen in a small group (n = 13) for a total of 33 flares. Of these, seven had two flares each (12 negative, 2 positive), five had three flares each (12 negative, 3 positive), and one patient had four flares (two negative, two positive). Therefore, within the group with recurrent symptoms, seven positive cultures were obtained for a rate of recurrent bacteriuria of 6.6% (7/106). Nine of the 10 positive bacterial cultures were due to gram-negative bacteria: Escherichia coli (n = 6), Proteus mirabilis (n = 1), Klebsiella pneumonia (n = 1), and Citrobacter sp. (n = 1). One grew Streptococcus sp. There was no difference between the flare group and nonflares in regards to age or PUF scores between groups. This study is the first to report on the low incidence of confirmed UTIs in a large group of PBS/IC patients followed longitudinally. These data suggest that only a small number of PBS/IC patients with UTI symptoms have positive urine cultures (9.4%; 10/106). Although the symptoms of recurrent UTI are prevalent in IC patients, the incidence of confirmed recurrent UTIs is only 6.6%. Because the flares of IC are usually self-limiting, treatment response to antibiotics may be misleading in light of the low incidence of positive urine cultures. These data suggest that the symptom flares of IC are not usually associated with recurrent UTI and, therefore, are likely due to a triggering of the other painful mechanisms involved in IC patients who are culture-negative.

Adult↗
PubMed2000

Treatment guidelines for classic and non-ulcer interstitial cystitis.

Interstitial cystitis (IC) is a chronic disease of as yet unknown etiology. It commonly affects females, presenting with symptoms of pain on bladder filling, and urinary frequency. Accumulated evidence indicates that IC is a heterogeneous syndrome. Compared to classic IC, the non-ulcer type appears different concerning symptomatic, endoscopic and histological findings, as well as the response to various forms of treatment. This review gives an introduction to the syndrome of IC, concerning epidemiology, clinical characteristics, diagnostic criteria and etiological considerations. A variety of treatment modalities have been suggested and are assessed and reviewed, such as hydrodistension of the bladder, intravesical instillation therapy, oral medication, transcutaneous electrical nerve stimulation, transurethral resection of diseased bladder tissue, and supratrigonal cystectomy followed by enterocystoplasty and urinary diversion. Our algorithm on non-surgical and surgical treatment for classic and non-ulcer IC is presented.

Anti-Inflammatory Agents↗
PubMed2000

Surgical treatment of interstitial cystitis in women.

Interstitial cystitis is a clinical entity that has been known for a century, but its pathophysiology remains largely unknown and the optimal treatment is a matter of ongoing discussion. A successful strategy for treatment relies on precise appraisal of symptoms, clinical findings and histology, as well as on the patient's individual personality. The least invasive treatment possible should be chosen, and only after conservative options have been exhausted should a surgical solution be considered. In this respect, anatomical bladder capacity plays an important role. A large capacity indicates the potential for conservative treatment and may be regarded as a negative predictor for the outcome of orthotopic bladder substitution. In contrast, a small anatomical capacity is unlikely to respond to conservative therapy, but is associated with a high probability of successful orthotopic bladder substitution.

Cystitis, Interstitial↗
PubMed2003

NF-kappaB-dependent gene expression of proinflammatory cytokines in T24 cells: possible role in interstitial cystitis.

Our previous report of predominant activation of nuclear transcription factor NF-kappaB in the bladder urothelium of interstitial cystitis (IC) patients suggests a potential role for this nuclear factor in the pathogenesis of the disease. Although NF-kappaB has been implicated in the pathogenesis of several inflammatory diseases, the downstream mechanism(s) by which it can mediate its effects are still fragmentary. In this study, we examined the role of this nuclear factor on the induction of proinflammatory cytokine gene expression in human bladder carcinoma T24 cells and further examined their corresponding protein levels in the urine of IC patients. T24 cells transduced with a dominant-negative super-repressor IkappaB mutant (pAxCAmIkappaB-M) or wild-type adenoviral vectors in the presence or absence of rhTNF-alpha. Transduction efficiency and ability of pAxCAmIkappaB-M to inhibit NF-kappaB activation were monitored by in situ reporter beta-galactosidase and gel mobility shift assays, respectively. Expression profile analysis of proinflammatory cytokines was measured in cells and urine of IC patients using RT-PCR and ELISA, respectively. The activation of NF-kappaB by rhTNF-alpha was associated with 27, eight, ten and sevenfold increases in the TNF-alpha, IL-1beta, IL-6 and IL-8 transcripts, respectively. In contrast, abrogation of the TNF-alpha-induced cytokine gene expression by an adenovirus super-repressor IkappaB mutant vector demonstrate that these effects were NF-kappaB-dependent. Interestingly, the NF-kappaB-induced expression of these transcripts correlates with increased protein levels of NF-kappaB-regulated proinflammatory factors in the urine of IC patients in comparison to controls. That these factors are capable of activating NF-kappaB in urothelial cells suggests a pivotal role for this nuclear transcription factor in the pathophysiology of the disease, possibly by inducing aberrant immune and inflammatory responses within the bladder of IC patients.

Cystitis, Interstitial↗
PubMed2004

Detection of Helicobacter pylori in bladder biopsy specimens of patients with interstitial cystitis by polymerase chain reaction.

The cause of interstitial cystitis (IC) is still unknown. Several features suggest that it may be an infectious disease and it has compelling similarities to chronic gastritis. The identification of Helicobacter pylori as the cause of chronic gastritis focused attention on this organism. Many studies have been done investigating the role of H. pylori in the etiology of IC. Previous studies mostly determined the presence of H.pylori with antibodies in the serum samples of IC patients, but these methods may lead to false positive or negative results. We therefore investigated the presence of H.pylori in bladder biopsy specimens by using polymerase chain reaction (PCR), which is accepted as the most sensitive and specific test for detecting this organism. A total of 32 patients with IC were enrolled into the study. The PCR assay was performed on cold cup bladder biopsies of IC patients. Both positive and negative controls were included in each set of PCR reactions. Gastric biopsy specimens of peptic ulcer patients with proven H. pylori infection were used as positive controls. Bladder biopsies of all IC patients were negative for H. pylori DNA. PCR showed the presence of H. pylori in the positive controls in each cycle demonstrating that the PCR assay was working properly. Thus, there is no evidence that IC is the result of H. pylori infection. This study does not negate the possibility that other infectious agents may play a role in the etiology of IC.

Biopsy↗
PubMed2006

Amifostine and glutathione prevent ifosfamide- and acrolein-induced hemorrhagic cystitis.

INTRODUCTION: Ifosfamide (IFS) is an antineoplastic alkylating agent whose major side effect is hemorrhagic cystitis (HC). This toxicity is attributed to the renal excretion of acrolein (ACR), a highly urotoxic IFS metabolite. Despite the clinical use of mesna to prevent HC, a significant percent ( approximately 33%) of patients present with at last one feature of HC, mainly hematuria. AIM: To investigate the use of two antioxidants-amifostine and glutathione-for the prevention of experimental IFS- and ACR-induced HC. MATERIALS AND METHODS: Male Swiss mice were treated intraperitoneal (i.p.) with saline (control), glutathione (125, 250 or 500 mg/kg) or amifostine (25, 50 or 100 mg/kg), and 30 min later they received a single i.p. injection of IFS at a dose of 400 mg/kg. To investigate the systemic effects of the antioxidants on ACR-induced HC, the animals were treated with saline, amifostine (50 mg/kg, i.p.) or glutathione (500 mg/kg, i.p.), and 30 min afterward with 75 mug ACR intravesically (i.ve.). In another set of experiments, the antioxidants were injected directly into the bladder, where the mice received a single i.ve injection of ACR (75 mug) plus amifostine (1.5 mg/kg) or glutathione (2 mg/kg). HC was measured 3 h after IFS or ACR injection according to bladder wet weight, macroscopic (edema and hemorrhage) and microscopic changes, i.e., edema, hemorrhage, cellular infiltration, fibrin deposition and urothelial desquamation. RESULTS: Pretreatments with amifostine or glutathione prevented IFS-induced HC in a dose-dependent manner. Furthermore, ACR-induced HC was also prevented by systemic (i.p.) or local (i.ve.) pretreatment with glutathione or amifostine. The greatest protective effect was seen with local amifostine treatment (2 mg/kg i.ve.) (P < 0.05). CONCLUSIONS: Glutathione and amifostine show a beneficial effect in experimental IFS- and ACR-induced HC. Thus, they should be investigated as an alternative treatment to prevent HC observed in patients undergoing IFS treatment.

Acrolein↗
PubMed1997

A case of veno-occlusive disease complicated by severe hemorrhagic cystitis successfully treated with recombinant plasminogen activator.

Recombinant tissue plasminogen activator (rt-PA) is an effective treatment for veno-occlusive disease (VOD) after bone marrow transplantation (BMT). However rt-PA therapy is limited by the risk of hemorrhagic complications. There is little guidance about the use of rt-PA for patients with severe VOD and severe hemorrhage. We report the case of a 16-year-old woman who developed severe VOD associated with life-threatening hemorrhagic cystitis (HC). A dramatic improvement in VOD was obtained after administration of recombinant tissue plasminogen activator (rt-PA). HC was managed with continuous bladder irrigation and blood transfusions. Administration of rt-PA was followed by a moderate increase in blood transfusion requirement but rt-PA did not cause dramatic aggravation of the HC. We conclude that severe HC might not be a contraindication to rt-PA therapy and such patients can be included in randomized trials conducted to determine the efficacy and risk benefit of rt-PA therapy for VOD.

Adolescent↗
PubMed2002

Interstitial cystitis, pelvic pain, and the relationship to myofascial pain and dysfunction: a report on four patients.

Treatment of chronic pelvic pain (CPP), interstitial cystitis (IC), prostatodynia, and irritative voiding symptoms can be frustrating for both patients and physicians. The usual approaches do not always produce the desired results. We found that when we treated myofascial trigger points (TrP) in pelvic floor muscles as well as the gluteus, piriform, infraspinatus, and supraspinatus muscles, symptoms improved or resolved. Various palpation techniques were used to isolate active myofascial TrPs in these muscles of four patients with severe CPP, IC, and irritative voiding symptoms. Injection and stretch techniques for these muscles were performed. Visual twitch responses at the skin surface and in the muscles were used to verify successful needle piercing of a TrP. The patients were asked to verbally describe exactly where the flash of distant pain was felt, a process that permitted an accurate recording of the precise pattern of pain referred by that TrP. The findings involved with the four patients substantiate the need for myofascial evaluation prior to considering more invasive treatments for IC, CPP, and irritative voiding symptoms. Referred pain and motor activity to the pelvic floor muscles (sphincters), as well as to the pelvic organs, can be the sole cause of IC, CPP, and irritative voiding dysfunction and certainly needs further investigation.

Adult↗
PubMed2003

Etiology: where does prostatitis stop and interstitial cystitis begin?

Male chronic pelvic pain syndrome (MCPPS) and interstitial cystitis (IC) patients show striking similarities in clinical presentation, diagnostic evaluation, purported pathogenesis, and even response to therapy. This makes the distinction between them very difficult. This review aims to show just how easy it is for the clinician to miss the features of IC in the MCPPS patient (and conversely). Misdiagnosis can result in the rejection of various potentially helpful therapies while accurate early diagnosis will lead to appropriate therapies and a better quality of life for the patient.

Chronic Disease↗
PubMed1998

Chronic interstitial cystitis and systemic lupus erythematosus in an 8-year-old girl.

An 8-year-old girl with systemic lupus erythematosus (SLE) and diffuse proliferative glomerulonephritis had chronic interstitial cystitis (CIC) early in the course of SLE. The early occurrence of CIC, the lack of intestinal symptoms, the association with vesicoureteric reflux, and the improvement of CIC during therapy with cyclosporin A were the prominent features of the patient reported here.

Brain↗
PubMed2003

Giant botryoid fibroepithelial polyp of bladder with myofibroblastic stroma and cystitis cystica et glandularis.

A 3-year-old boy presented with a single episode of gross hematuria and no history of previous urinary tract disorder. Imaging studies revealed a large complex polypoid filling defect in the bladder lumen. Several attempts at transurethral biopsy and cytological examination of the urine revealed clumps of benign epithelial cells, but suspicion of a malignant neoplasm such as rhabdomyosarcoma remained high and the lesion was resected. The specimen measured 15 cm, had a narrow zone of attachment to the bladder mucosa, and was grossly botryoid. Changes typical of cystitis cystica et glandularis were present at and near all surfaces. Myxoid stroma contained scattered benign fibroblasts, myofibroblasts, and smooth muscle cells. Inexplicably, one of two karyotyped stromal cells demonstrated a translocation usually associated with rhabdomyosarcoma. This child is well without evidence of bladder abnormality 1.5 years after surgery.

Child, Preschool↗
PubMed2000

Chronic cystitis caused by Corynebacterium urealyticum detected by polymerase chain reaction.

The case of a 73-year-old man with chronic cystitis due to Corynebacterium urealyticum was complicated by hematuria and urinary stone formation. The diagnosis was based on an amplification product obtained using polymerase chain reaction for mycobacterial species on urine and a bladder biopsy specimen. A specific 212 bp amplification fragment that did not hybridize with a Mycobacterium-specific probe was recognized. Sequence analysis of the fragment revealed Corynebacterium urealyticum. Routine urine cultures were negative, but prolonged culture on sheep blood agar led to the isolation and identification of Corynebacterium urealyticum. Identification was confirmed by polymerase chain reaction on the colonies. The patient was treated successfully with vancomycin. Integration of molecular laboratory diagnostics with conventional microbiology and pathology was synergistic for the diagnosis.

Aged↗
PubMed2007

Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic cystitis; implication of reactive oxygen and nitrogen species as well as PARP activation.

Cyclophosphamide (CP) and ifosfamide (IF) are widely used antineoplastic agents, but their side-effect of hemorrhagic cystitis (HC) is still encountered as an important problem. Acrolein is the main molecule responsible of this side-effect and mesna (2-mercaptoethane sulfonate) is the commonly used preventive agent. Mesna binds acrolein and prevent its direct contact with uroepithelium. Current knowledge provides information about the pathophysiological mechanism of HC: several transcription factors and cytokines, free radicals and non-radical reactive molecules, as well as poly(adenosine diphosphate-ribose) polymerase (PARP) activation are now known to take part in its pathogenesis. There is no doubt that HC is an inflammatory process, including when caused by CP. Thus, many cytokines such as tumor necrosis factor (TNF) and the interleukin (IL) family and transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) also play a role in its pathogenesis. When these molecular factors are taken into account, pathogenesis of CP-induced bladder toxicity can be summarized in three steps: (1) acrolein rapidly enters into the uroepithelial cells; (2) it then activates intracellular reactive oxygen species and nitric oxide production (directly or through NF-kappaB and AP-1) leading to peroxynitrite production; (3) finally, the increased peroxynitrite level damages lipids (lipid peroxidation), proteins (protein oxidation) and DNA (strand breaks) leading to activation of PARP, a DNA repair enzyme. DNA damage causes PARP overactivation, resulting in the depletion of oxidized nicotinamide-adenine dinucleotide and adenosine triphosphate, and consequently in necrotic cell death. For more effective prevention against HC, all pathophysiological mechanisms must be taken into consideration.

Acrolein↗
PubMed2004

A case of severe hemorrhagic cystitis following bone marrow transplantation.

Hemorrhagic cystitis (HC) is a common adverse effect caused by the preparative regimens for bone marrow transplantation. Unfortunately, an effective therapy for HC has not yet been established. Here we report a case of severe HC in which the upper as well as the lower urinary tract were severely affected, resulting in right ureteral obstruction and a contracted bladder. Hyperbaric oxygen therapy was effective in suppressing the severe HC, but the cause of HC could not be identified. Five years after the bone marrow transplantation the patient underwent augmentation ileocystoplasty with ileal ureteral replacement.

Adult↗
PubMed2006

Eosinophilic cystitis simulating invasive bladder cancer: a real diagnostic challenge.

OBJECTIVES: To report our experience with eosinophilic cystitis (EC) presented as invasive bladder cancer. MATERIALS AND METHODS: We recently treated three patients with bladder masses mimicking neoplasms and biopsy proved the diagnosis of EC. Data from our three patients were presented. RESULTS: There were two females and one male with ages of 14, 43 and 38 years. All the three patients had irritative bladder symptoms, suprapubic pain and hematuria. Bladder mass was detected by pelvic examination in the three patients and confirmed by radiologic tests and cystoscopy. In one patient, the mass caused bilateral hydroureteronephrosis while the upper tract was normal in the other two. Elevated serum leukocytes was evident in the three cases while peripheral eosinophilia was observed in one. Biopsy showed EC in all the three patients who were treated by transurethral resection of the lesions followed by a combination of corticosteroids, antibiotics and antihistaminics. All patients experienced marked improvement during a follow-up duration up to 30 months. CONCLUSION: EC is a rare disease. In addition to symptoms of frequency, dysuria, hematuria and suprapubic pain, the disease may present with a bladder mass mimicking invasive bladder cancer. Resection of the lesion is mandatory with systemic treatment of corticosteroids, antihistaminics and antibiotics. Early detection and prompt treatment usually result in a good prognosis.

Adolescent↗
PubMed2000

Interstitial cystitis: the painful bladder syndrome.

Interstitial cystitis (IC) is an enigmatic and frustrating condition to manage as a physician and to cope with as a patient. Many patients are declared as drug addicted and neurotic. Social status and number of sexual partners showed no correlation with incidence. Patients report moderate to excruciating pain in the suprapubic or vaginal area, urgency and frequency (up to 50 micturitions/d), and disruption of their social life. Diagnosis of IC is made by exclusion. Different pathophysiologic mechanisms have been proposed: changes in epithelial permeability, pelvic floor dysfunction, mastocytosis, activation of c-fibers, and increase of nerve growth factors and bradykinin. No single theory can explain IC.

Adaptation, Psychological↗