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[Florid glandular cystitis of the intestinal type with mucin extravasation: a lesion simulating a tumor].

A wide spectrum of glandular epitheliales metaplastic changes may be seen in the bladder. Extensive replacement of the urotelium with an epithelium resembling intestinal mucosa is recognised as a premalignant condition. However, the natural history of intestinal metaplasia of the urinary bladder and long-term outcome are unknown. We report a case of glandular cystitis with intestinal metaplasia in a young patient. Cystoscopy revealed a tumour well circumscribed measuring 4 cm on the trigone. Microscopic examination showed numerous glands lined by intestinal type epithelium without atipia, conforming to the appearance of the intestinal variant of cystitis glandularis. This case had prominent foci of basophilic mucin in the stroma. Rounded aggregates of mucin were occasionally surrounded by compressed connective tissue cells, simulating mucinous cyst. This case illustrates the extent to which cystitis glandularis may mimic a neoplasm on gross evaluation and the propensity of mucin extravasation to cause diagnostic difficulty, a finding documented only rarely previously, and we discuss its biologic significance.

Adult↗

Cystitis and interstitial nephritis related to the use of tiaprofenic acid (Surgam).

We describe a case of concurrent presentation of severe haemorrhagic cystitis and acute interstitial nephritis with eventually lethal outcome, associated with the use of tiaprofenic acid (Surgam), a propionic acid-derived non-steroidal anti-inflammatory drug (NSAID). Although interstitial nephritis and haemorrhagic cystitis are caused by all types of NSAIDs, a higher incidence of interstitial nephritis and especially haemorrhagic cystitis has been described related to propionic acid derivatives. Awareness of this serious adverse effect is important.

Aged↗

Sex, time-of-day and estrous variations in behavioral and bladder histological consequences of cyclophosphamide-induced cystitis in rats.

This study examined how cyclophosphamide (CP)-induced cystitis related manifestations (bladder inflammation and behavioral impairment) differed in female and male Sprague-Dawley rats. Under transient halothane-O2-N2O gas anesthesia, a single dose of CP was injected (100 mg/kg i.p. in 1 ml saline) and the animal's behaviors analyzed for a period of 4 h using a protocol that permits quantitative analysis of behavioral impairment. The rats were then sacrificed and their bladders removed for histological quantification of inflammation. All CP-injected, but not control rats, exhibited a range of impairment behaviors that increased rapidly over a period of 2 h, gradually reaching plateau levels over the next 2 h. Female rats initially developed behavioral responses faster than male rats, but reached the same mean peak values overall as males. No sex differences were observed in CP-induced bladder inflammation. Influences of time-of-day and estrous stage were further examined in females. Time-of-day had no effect on the degree of bladder inflammation. Although there were also no significant time-of-day differences in behavioral impairments, impairment scores from 90 min after the injection consistently tended to be lower for rats injected 5 h versus 9 h after lights on. Overall, the effects of estrous stage were also insignificant. However, a subset of rats who were in the estrous stage of their cycle early in the morning of the experimental day developed the most severe degree of bladder inflammation, but failed to develop the severe behavioral impairments shown by all the other rats. These results show that there are seemingly only minor sex differences in the overall behavioral and inflammatory consequences of CP injections, as evidenced by similar final degrees of behavioral impairment and inflammation. These results also suggest, however, that there are sex differences in the etiology of the disease process. These differences are evidenced by the more rapid development of behavioral symptoms in females and the susceptibility of some of those having shown morning estrous smears to develop very severe bladder inflammation in absence of corresponding behavioral impairment. The multiple influences of sex and estrous condition on CP-induced cystitis related manifestations observed here underline the complexity of the etiological factors associated with the cystitis disease process.

Animals↗

A hypothesis for the etiology of interstitial cystitis based upon inhibition of bladder epithelial repair.

Interstitial cystitis (IC) is a chronic bladder disease characterized by distinct bladder mucosal abnormalities, for which the etiology is unknown. Although the epidemiology of this disorder is similar to that of bacterial cystitis, prospective studies using sensitive culture techniques and polymerase chain reaction assay for a variety of microorganisms have failed to identify a specific infectious etiology for IC. We have identified a low-molecular-weight peptide in the urine of IC patients that inhibits the proliferation of normal bladder epithelial cells in vitro. We therefore propose a model of IC, in which this peptide inhibits bladder epithelial regeneration following damage (such as that caused by bacterial cystitis). The chronically damaged epithelium is prone to colonization with various microorganisms, and the resulting exposure to these microorganisms, other urinary antigens, and/or damaged epithelial cells prompts the low-level inflammatory response commonly seen in this disorder.

Cystitis, Interstitial↗

The prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in young women.

Four hundred and fifty-two urine isolates from women with acute uncomplicated cystitis and a positive urine culture presenting to a sexually transmitted disease clinic were collected during 1989-1991, and 213 specimens were collected over 1995-1997. The predominant species was Escherichia coli, representing 68% of the isolates; others included Staphylococcus saprophyticus (8%), Group B streptococci (7%), Proteus spp. (6%), Klebsiella spp. (4%) and Enterococcus spp.(3%). More than 10% of the E. coli isolates were resistant to ampicillin, cephalothin, tetracycline and trimethoprim sulfamethoxazole (TMP SMX ) during both study periods, with the greatest increase in resistance to ampicillin and TMP/SMX between the two periods. Six hundred and four urinary tract infection isolates, including 83% E. coli, 7% S. saprophyticus, 3%, Klebsiella spp. 2% Proteus spp., 2% enterococci, 1% Enterobacter spp. and 2% other organisms, were collected from women with acute cystitis attending a university student health service during 1995. Among E. coli isolates, 25% were resistant to ampicillin, 24% to tetracycline and 11%, to TMP SMX. Resistance to fluoroquinolones was essentially absent among gram-negative pathogens. Continued evaluation of susceptibility patterns of pathogens causing acute uncomplicated cystitis to traditional as well as new antimicrobials in well defined populations is necessary to ascertain the optimal empiric therapy.

Acute Disease↗

Comparison of PCR, enzyme immunoassay and conventional culture for adenovirus detection in bone marrow transplant patients with hemorrhagic cystitis.

BACKGROUND: Adenovirus-associated hemorrhagic cystitis (HC) has become a recognized sequel of immunosuppression. The diagnosis of viral infection is usually determined by viral cultures. OBJECTIVES: Analysis of different diagnostic methods for adenovirus (AdV) detection in bone marrow transplant patients with hemorrhagic cystitis. STUDY DESIGN: We describe a prospective study for AdV detection in the urine of patients with hematuria in the first 100 days after bone marrow transplant (BMT), comparing different laboratory techniques, PCR, enzyme immunoassay (EIA) and conventional culture. RESULTS: A total of 143 urine samples were analyzed, 75 collected in the pre-transplant period with and without hematuria and 68 post-transplant, only with microscopic or macroscopic hematuria. After BMT, hematuria occurred in 38.9% of patients, being more frequent in unrelated donor transplants. AdV was isolated in one pre-transplant patient without symptoms and in three post-transplant patients with HC grades 3 and 4 (severe), who were in month 2 or 3 post-transplant. Compared to culture as the gold standard, the accuracy, specificity and sensitivity of EIA were 95, 30 and 100% and for PCR were 63, 100 and 60%, respectively. CONCLUSIONS: We concluded that despite technical difficulties and the long time that elapsed before results were obtained, cell culture still remains the best method for adenovirus detection in the urine of patients with hemorrhagic cystitis.

Adenovirus Infections, Human↗

Emphysematous cystitis, a rare complication of urinary tract infection in a male diabetic patient: a case report.

Emphysematous cystitis is a rare complication of urinary tract infection, characterized by spontaneous gas formation in the urinary bladder due to bacterial fermentation. Approximately 50 to 80% of patients with this disease are diabetic, and there is a higher incidence in females. We report a case of emphysematous cystitis in a diabetic male who was admitted under the impressions of hypoglycemia, acute bronchitis, and chronic renal failure. Treatment of the emphysematous cystitis consisted of adequate urinary drainage, empirical antibiotic therapy, and strict blood sugar control. The patient recovered satisfactorily after 9 days of hospitalization.

Cystitis↗

Intravesical antisense therapy for cystitis using TAT-peptide nucleic acid conjugates.

The present study investigated the potential of intravesical instillation for localized reduction of NGF (nerve growth factor) expression in the urinary bladder. Overexpression of NGF has been linked to the pathogenesis of interstitial cystitis (IC). A minimum free energy algorithm was used to predict suitable regions in mRNA of rat betaNGF, which can be targeted for an antisense approach. The candidate antisense oligos were evaluated for their ability to reduce NGF expression in vitro by cotransfecting HEK293 cells with NGF cDNA. A single oligonucleotide ODN sequence was chosen for testing in an acute cystitis model in rat induced by cyclophosphamide. Overexpression of NGF is known to mediate inflammation of bladder in this model. For improved stability, antisense ODN was replaced with antisense peptide nucleic acid (PNA) and its penetration into bladder was facilitated by tethering TAT peptide sequence. Rat bladders were instilled with either antisense or its scrambled control prior to cystitis induction. Cystometrograms performed on rats under urethane anaesthesia exhibited bladder contraction frequency that was significantly decreased in the antisense treated rats than rats treated with the control. NGF immunoreactivity was also decreased in the urothelium of the antisense treated bladders. Our findings demonstrate the feasibility of using TAT-PNA conjugates for intravesical antisense therapy.

Administration, Intravesical↗

Alkaline encrusted cystitis associated with malakoplakia.

Alkaline encrusted cystitis is a rare inflammatory condition of the bladder which has been reported sporadically over the past 80 years. It is caused by infection with urea splitting organisms leading to the deposition of inorganic salts on to the surface of the bladder. We present three cases of alkaline encrusted cystitis. In two cases the encrusted area was associated with foci of malakoplakia. The third case occurred in a patient who had received chemotherapy for acute lymphoblastic leukaemia. To our knowledge, these are the first cases of malakoplakia associated with alkaline encrusted cystitis. These two conditions have a number of clinical and aetiological similarities, and may have more in common than has been previously thought.

Adolescent↗

Xanthogranulomatous cystitis associated with malignant neoplasms of the bladder.

AIMS: Two cases of xanthogranulomatous cystitis in conjunction with malignant neoplasms of the bladder are described. METHODS AND RESULTS: A partial cystectomy [corrected] specimen from a 55-year-old man showed a urachal adenocarcinoma partly surrounded by a large xanthogranulomatous inflammatory mass. Multiple resections of the locally recurring tumour over the subsequent 10 years did not show further xanthogranulomatous changes. In the second case, a 76-year-old woman, a focus of xanthogranulomatous cystitis was present near a moderately differentiated transitional-cell carcinoma of the vesico-ureteric junction. CONCLUSIONS: Xanthogranulomatous inflammation is associated with malignant neoplasms in the bladder as it is in the kidney and extra-urinary sites, as well as with benign neoplasms and non-neoplastic conditions such as urachal diverticula. The presence of a concomitant neoplasm should therefore be considered when the diagnosis of xanthogranulomatous cystitis is made.

Adenocarcinoma↗

Supratrigonal cystectomy and ileocystoplasty in management of interstitial cystitis.

BACKGROUND: Interstitial cystitis is a chronic non-infectious inflammatory disease of the bladder of unknown aetiology which is characterized by irritative voiding symptoms and suprapubic pain related to bladder filling. Surgical treatment is indicated in severely symptomatic patients when medical therapies have failed, usually after a period of several years. The authors' experience with a modified technique of ileocystoplasty following supratrigonal cystectomy performed in five patients with interstitial cystitis is presented here. METHODS: A modified technique of bladder augmentation using ileum following supratrigonal bladder resection is described. RESULTS: All patients experienced relief from their symptoms. No patient had residual bladder pain and urinary frequency settled down in all. Bladder capacity was increased significantly. Three patients voided spontaneously postoperatively and two required clean intermittent self-catheterization. CONCLUSIONS: Supratrigonal cystectomy and ileocystoplasty can be a satisfactory option in refractory cases of interstitial cystitis. A simplified technique of ileal bladder construction that provides satisfactory bladder capacity is presented. Most urologists are familiar with ileal surgery, having used the ileum as a conduit after cystectomy for urinary diversion.

Aged↗

Urothelial cytoprotective activity of Tamm-Horsfall protein isolated from the urine of healthy subjects and patients with interstitial cystitis.

PURPOSE: Tamm-Horsfall protein (THP) is a ubiquitous urinary protein with essentially no known function. We propose that THP is a cytoprotective agent that protects the urothelium from cationic species. To test this hypothesis we isolated THP from normal and interstitial cystitis urine to see if it could protect cultured cells from damage induced by the polyamine, protamine sulfate (PS). METHODS: Tamm-Horsfall protein was extracted from the urine of interstitial cystitis (IC) patients (N=28) and normal volunteers (N=5). Urothelial target cells (T24) were radiolabeled with 51Cr and then exposed to PS (0-1.0 mg/mL) for either 1.5 or 20 h. The resulting cytotoxicity data (dose-response curves) were then compared with the data obtained when PS was preincubated with 0-0.5 mg/mL of THP (IC vs normal), the semisynthetic polysaccharide, pentosan polysulfate (Elmiron), or human serum albumin. RESULTS: Toxicity of PS was significantly reduced by incubation with THP (or Elmiron) prior to evaluation by the chromium release assay, but not reduced by incubating with another protein, albumin. Tamm-Horsfall protein from IC patients' urine was less protective than an equal quantity of THP from normal urine. CONCLUSIONS: These experiments suggest that THP has an important role in bladder mucosal defense mechanisms, protecting the bladder surface from injury. Inability of THP to prevent cytotoxic damage by urinary polyamine or other urinary toxins (cationic species) may be relevant in the etiology of interstitial cystitis, as putative urinary toxic components have been described in the urine of some patients.

Adjuvants, Immunologic↗

Bladder replacement by ileocystoplasty: the final treatment for interstitial cystitis.

OBJECTIVE: To develop and improve the technique of bladder replacement with ileum in patients with interstitial cystitis. PATIENTS AND METHODS: A consecutive series of 27 patients (23 women and four men, median age 61 years, range 40-79) with chronic severe interstitial cystitis refractory to conservative therapies underwent cystectomy and bladder replacement using an ileal pouch. The relief of pain was assessed over a median follow-up of 30 months (range 2-48). RESULTS: Pain relief was complete in all patients and the median neo-bladder capacity was 520 mL (range 350-700). Only four patients required intermittent self-catheterization to drain post-micturition residual urine. Bladder calculi formed in two patients and were removed successfully at cystoscopy. CONCLUSION: Bladder replacement with ileum in the form of the Kock pouch is an effective surgical treatment for intractable interstitial cystitis.

Adult↗

Effect of sucralfate on induced chemical cystitis in rabbits.

OBJECTIVE: To study the histological effect of locally applied sucralfate on the urinary bladder in rabbits with chemically induced cystitis. MATERIALS AND METHODS: Sucralfate (1 g dissolved in 10 mL saline) was instilled into the bladders of six rabbits, while four controls had no instillation. The procedure was repeated 4 days later and followed immediately by 10 mL of 2% formaldehyde infused into the bladder and retained for 10 min in all 10 rabbits. After careful flushing with saline, 10 mL sucralfate solution was again instilled in the study group and 10 mL of saline only in the control group. On day 6, the sucralfate instillation was repeated in the six treated animals. All the rabbits were then killed on day 8-9, their bladders removed and examined macroscopically and histologically. RESULTS: Formaldehyde instillation was quickly followed by gross haematuria in all animals. It subsided in the group treated with sucralfate, but not in the controls. Examination revealed only slight changes in the former group, but severe inflammatory lesions in the latter. CONCLUSIONS: Intravesically instilled sucralfate protected rabbit bladder urothelium against chemically induced cystitis. Clinical trials of intravesical sucralfate seem warranted in patients irradiated for pelvic cancer or with severe cystitis caused by cytotoxic drugs.

Administration, Intravesical↗

Emphysematous cystitis: a radiographic diagnosis.

Emphysematous cystitis is a somewhat uncommon entity in which early diagnosis and treatment play a key role in avoiding potentially high morbidity and mortality. An elderly woman with emphysematous cystitis and no comorbid factors, except advanced age, is presented. This case illustrates the key features in the radiographic diagnosis of this unusual disease. Discussion of the cause, diagnosis, and treatment of emphysematous cystitis emphasizes prompt recognition, drainage of the bladder and use of appropriate broad spectrum antibiotic therapy.

Age Factors↗

'An empty and happy feeling in the bladder.. .': health changes experienced by women after acupuncture for recurrent cystitis.

OBJECTIVE: The aim of this study was to explore changes in health as reported by cystitis-prone females after having received prophylactic acupuncture treatment for recurrent cystitis. DESIGN: A qualitative study based on written free text answers on the women's own experience of changes related to health after completion of TCM acupuncture treatment. Data were analyzed using Giorgi's phenomenological approach. SETTING: Subjects living in the Bergen area, Norway, were recruited by advertisement in local newspapers and included provided they had had three or more episodes of lower UTI during the previous 12 months. RESULTS: The main topics reported were related to improved pressure during micturition and more complete bladder emptying; more normal bowel movement and less abdominal discomfort; more energy, reduced stress level, and better sleep. Only a few reported feeling worse. CONCLUSION: The symptoms described as relieved by the women in our study seem to fit TCM theory for diagnoses of their vulnerability to cystitis. Qualitative methods have a role in TCM research that may enrich our knowledge in other ways than traditional quantitative methods may.

Acupuncture Therapy↗

The prevalence of interstitial cystitis in gynecologic patients with pelvic pain, as detected by intravesical potassium sensitivity.

OBJECTIVE: The purpose of this study was to determine the prevalence of interstitial cystitis in a large number of gynecologic patients with pelvic pain versus control subjects, as indicated by a positive result on a potassium sensitivity test. STUDY DESIGN: Gynecologists at four US medical centers administered the potassium sensitivity test to consecutive unselected patients with pelvic pain and control subjects. Before testing, each patient with pelvic pain was given an initial clinical diagnosis on the basis of the chief symptomatic complaint(s) and was surveyed for urologic symptoms. RESULTS: Of 244 patients with pelvic pain, 197 patients (81 %) had a positive result from a potassium sensitivity test. Positive potassium sensitivity test rates were comparable across all four sites and all clinical diagnoses that included endometriosis, vulvodynia (vulvar vestibulitis), and pelvic pain. Urologic symptoms were reported by 84% of patients, but only 1.6% of the patients had received an initial diagnosis of interstitial cystitis. None of the 47 control subjects were tested positive with the potassium sensitivity test. CONCLUSION: Interstitial cystitis may be a common unrecognized cause of pelvic pain in gynecologic patients and deserves greater, if not primary, consideration in the differential diagnosis of pelvic pain.

Administration, Intravesical↗

An antiproliferative factor from interstitial cystitis patients is a frizzled 8 protein-related sialoglycopeptide.

Approximately 1 million people in the United States suffer from interstitial cystitis, a chronic painful urinary bladder disorder characterized by thinning or ulceration of the bladder epithelial lining; its etiology is unknown. We have identified a glycosylated frizzled-related peptide inhibitor of cell proliferation that is secreted specifically by bladder epithelial cells from patients with this disorder. This antiproliferative factor (APF) profoundly inhibits bladder cell proliferation by means of regulation of cell adhesion protein and growth factor production. The structure of APF was deduced by using ion trap mass spectrometry (MS), enzymatic digestion, lectin affinity chromatography, and total synthesis, and confirmed by coelution of native and synthetic APF derivatives on microcapillary reversed-phase liquid chromatography (microRPLC)/MS. APF was determined to be an acidic, heat-stable sialoglycopeptide whose peptide chain has 100% homology to the putative sixth transmembrane domain of frizzled 8. Both synthetic and native APF had identical biological activity in normal bladder epithelial cells and T24 bladder cancer cells. Northern blot analysis indicated binding of a probe containing the sequence for the frizzled 8 segment with mRNA extracted from cells of patients with interstitial cystitis but not controls. APF is therefore a frizzled-related peptide growth inhibitor shown to contain exclusively a transmembrane segment of a frizzled protein and is a potential biomarker for interstitial cystitis.

Antineoplastic Agents↗