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Enhancing effect of diethylstilbestrol on urinary bladder carcinogenesis in neonatally castrated male rats.

The effects of diethylstilbestrol (DES) on the development of urinary bladder cancer induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in neonatally castrated rats and on metaplastic changes of the coagulating glands and ejaculatory ducts were studied. Pretreatment with DES during infancy increased the incidence of preneoplastic lesions, papillomas, and cancers of the urinary bladder in BBN-treated males. Pretreatment with DES was more effective in castrated males than in uncastrated males. BBN did not induce tumors of the coagulating glands or ejaculatory ducts, in which metaplastic changes were observed in DES-treated rats.

Animals↗

Reversibility of proliferative lesions and induction of non-papillary tumors in rat urinary bladder treated with phenylethyl isothiocyanate.

Phenylethyl isothiocyanate (PEITC), generally thought to be a chemopreventive agent for various kinds of genotoxic carcinogens, has been found to induce rat urinary bladder carcinomas in our laboratory. To cast light on the underlying mechanisms, the reversibility of urothelial proliferative lesions and the frequencies of H-ras and p53 mutations in the induced rat urinary bladder tumors were investigated. F344 male rats were given diet containing 0.1% PEITC for 48 weeks and then killed, or for 32 weeks and then returned to normal diet without supplement for 1, 3, 7 days or 16 weeks before death. At 7 days after withdrawal of PEITC treatment, carcinomas were observed in only two of 24 rats but a high incidence of dysplasias was evident. Furthermore, 16 weeks after withdrawal, seven of 12 (58.3%) rats had carcinomas. In addition, carcinomas were induced in 11 of 12 (91.7%) rats continuously receiving PEITC for 48 weeks. Most of the carcinomas were characterized as of non-papillary transitional cell type with occasional squamous cell differentiation and/or glandular components. Bromodeoxyuridine labeling indices (LIs) were increased by PEITC administration even in normal-looking epithelium. After withdrawal of treatment, LIs in simple and papillary or nodular (PN) hyperplasias were markedly decreased and these lesions gradually disappeared, while values for dysplasias and carcinomas, which persisted, were only slightly decreased. A silent point mutation was found in H-ras in one of 12 tumor samples (8.3%), whereas seven (58.3%) had mutations in p53. These results indicate that PEITC itself is a carcinogen for the rat urinary bladder, and that while the simple and PN hyperplasia induced by PEITC are reversible, dysplasia is irreversible with the potential to give rise to non-papillary carcinomas with frequent p53 mutations.

Animals↗

Vascular and morphological changes in the urinary bladder wall after irradiation.

Twelve adult rabbits were used to study radiation-induced changes in the urinary bladder by angiographic, microangiographic, light microscopic and scanning electron microscopic methods. Angiographic, microangiographic and light microscopy examinations were performed on 2 animals in which the urinary bladders were not irradiated and on 4 animals in which parts of the bladders received high radiation doses of 60Co. The bladders irradiated in this manner exhibited advanced changes within a shorter time after irradiation than those in an earlier study. In this study a lower dose of irradiation was given over the entire bladder. Otherwise, the radiation changes were similar. Light and scanning electron microscopic studies were carried out on 2 normal and 4 irradiated bladders. In the latter, atrophy of the mucosa, epithelial desquamation, cellular atypisms and ulcerations were observed.

Animals↗

Urinary fibronectin in diagnosis and follow-up of patients with urinary bladder cancer.

The levels of fibronectin in urine from 106 patients with urinary bladder cancer, from 13 patients with benign urological disease and from 24 healthy control individuals were determined by an enzyme-linked immunosorbent assay (ELISA). The fibronectin levels in urine from patients with bladder cancer were higher than in patients with benign urothelial disease and in healthy controls. In 9 patients with bladder cancer, sampling was done both pre- and post-operatively. In these cases the fibronectin levels after operation were significantly lower than they had been before. Among 14 patients treated with BCG intravesically for superficial bladder tumours, those with complete remission of disease had less urinary fibronectin than those who did not respond to treatment. The data suggest that urinary fibronectin may be a useful marker for detecting urinary bladder cancer and for selecting patients for BCG treatment.

Albuminuria↗

Eosinophil peroxidase increases membrane permeability in mammalian urinary bladder epithelium.

Eosinophil peroxidase (EPO), a cationic protein found in eosinophils, has been reported to be cytotoxic independent of its peroxidase activity. This study investigated with electrophysiological methods whether EPO is toxic to mammalian urinary bladder epithelium. Results indicate that EPO, when added to the mucosal solution, increases apical membrane conductance of urinary bladder epithelium only when the apical membrane potential is cell interior negative. The EPO-induced conductance was concentration dependent, with a maximum conductance of 411 microseconds/cm2 and a Michaelis-Menten constant of 113 nM. The EPO-induced conductance was nonselective for K+ and Cl-. The conductance was partially reversed using voltage but not by removal of EPO from the bulk solution. Mucosal Ca2+ reversed the EPO-induced conductance by a mechanism involving reversible block of the conductance. Prolonged exposure (up to 1 h) to EPO was toxic to the urinary bladder epithelium, as indicated by an irreversible increase in transepithelial conductance. These results suggest that EPO is indeed toxic to urinary bladder epithelium via a mechanism that involves an increase in membrane permeability.

Animals↗

Coexistence of papillary and nodular carcinomas in the urinary bladder.

Of 203 patients with transitional cell carcinoma of the urinary bladder which had been cystectomized and examined by step-sectioning during the period between 1969 and 1986, 33 had coexistent papillary, papillonodular and/or nodular carcinomas in the bladder. Of them, 12 (36%) had a history of papillary carcinomas, 26 (79%) had multiple tumors and 22 (67%) had a concomitant carcinoma in situ, and/or mucosal dysplasia. Moreover, microscopic papillary structures were identified in 32 out of the 33 (97%) cases with papillonodular and/or nodular carcinomas, indicating some of the nodular invasive carcinomas in the bladder to have developed from papillary carcinomas.

Adult↗

Concurrent malakoplakia and papillary urothelial carcinoma of the urinary bladder.

A case of malakoplakia and papillary urothelial carcinoma of the urinary bladder is reported. In this case, malakoplakia was an incidental finding in a biopsy of the urinary bladder of a 74-yr old female, who presented with hematuria. The biopsy showed a low-grade papillary urothelial carcinoma in close association with malakoplakia. This is a rare association of these lesions.

Aged↗

[Urinary bladder carcinoma was induced in a patient treated with cyclophosphamide for malignant lymphoma].

A case of urinary bladder carcinoma in a patient with malignant lymphoma (ML) involving the thyroid gland, gastrointestinal tract and the gallbladder is reported. The histological type of ML from the biopsy specimens of the thyroid gland and the stomach was non-Hodgkin's, diffuse large cell lymphoma of B cell origin. The patient had been treated for ML with cyclophosphamide (CPM), doxorubicin, vincristine and prednisolone effectively then maintained with low dose CPM. Two and a half years after the initial therapy, urinary bladder tumor diagnosed transitional cell carcinoma histologically was found. The patient had received 55 gr. of CPM totally. The dose of CPM was relatively smaller than the one in the other second cancer cases reported induced by CPM previously. It may be suggested that the urinary bladder carcinoma induced by CPM is related not only total dose of CPM but also the other factors. Thus usage of CPM must be cautious because of the secondary disease.

Carcinoma, Transitional Cell↗

M4 muscarinic autoreceptor-mediated inhibition of -3H-acetylcholine release in the rat isolated urinary bladder.

A pharmacological analysis was carried out in the rat urinary bladder to assess the nature of muscarinic receptors subtypes functionally involved in the negative feedback mechanism regulating acetylcholine (ACh) secretion from postganglionic cholinergic nerve terminals and in smooth muscle contraction. Bladder strips were preincubated with 3H-choline, and the electrically evoked [3H]ACh release was detected simultaneously with contraction in the absence of acetylcholinesterase inhibitors. The effects were compared of seven muscarinic antagonists on [3H]ACh secretion (prejunctional effect) and muscle contraction (postjunctional effect). The rank order of postjunctional potencies (-log EC50) for the seven antagonists (atropine > 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) > hexahydrosiladiphenidol hydrochloride (HHSiD) > tripitramine > pirenzepine > AF DX-116 > methoctramine) as well as their postjunctional affinity estimates (pA2) are in keeping with the notion that muscarinic receptors responsible for bladder contraction belong to the M3 subtype. The M3 subtype-preferring 4-DAMP and HHSiD did not discriminate between prejunctional and postjunctional effects. The M2/M4 subtype-preferring antagonists tripitramine, methoctramine and AF-DX 116 were more potent in facilitating the evoked [3H]ACh release than in inhibiting the contractile response. The rank order of prejunctional potencies was atropine > 4-DAMP > tripitramine > HHSiD > methoctramine > AF-DX 116 > pirenzepine, indicating the involvement of M4 receptors. Furthermore, when potency relationship was determined by correlating prejunctional-log EC50 values with published constants for cloned and natives muscarinic receptor subtypes, the correlations were significant for both M4 and M5 subtypes, but the best correlation found (P < .001) was for the M4 subtype. These findings suggest that the negative feedback mechanism inhibiting the release of ACh in the rat urinary bladder is mediated by prejunctional autoreceptors of the M4 subtype.

Acetylcholine↗

Isolation of large sheets of apical material from frog urinary bladder epithelial cells by freeze-fracture.

In the amphibian urinary bladder, water permeability is correlated with the insertion of intramembrane particle aggregates (IMPAs) into the apical plasma membrane (AM) of the granular cells. These aggregates are believed to contain water channels. Characterization of the IMPAs by comparing AM fractions of antidiuretic hormone (ADH)-treated and resting epithelia requires isolation and purification of AM-rich material, free of other cytoplasmic aggregate-containing organelles, in both cases. A technique derived from freeze-fracture was chosen to isolate large sheets of apical membrane material from frog (Rana esculenta) urinary bladder epithelium. The apical side was plated on a polylysine-coated glass slide, frozen with liquid nitrogen, and fractured. A nylon mesh was inserted between the glass slide and the bladder, in order to bring the fracture plane back to the AM periodically. Fluorescent markers were used to characterize the material having fractured with the glass slide. Samples were observed by fluorescence and phase contrast microscopy. We obtained evidence that numerous patches of fractured AM remained on the glass surface without nuclei. A phase contrast picture was obtained only at a high magnification, indicating a low thickness of the recovered material. Further characterization was made with SDS-PAGE. Protein contents of samples were extracted under various experimental conditions and the patterns of ADH-treated, resting AM samples, or whole epithelial cell crude homogenates, were compared. Staining of some bands increased under certain conditions, whereas many others disappeared. Both morphological and biochemical approaches demonstrate that the recovered material was apical in origin.

Animals↗

Comparative predictive values of urinary cytology, urinary bladder cancer antigen, CYFRA 21-1 and NMP22 for evaluating symptomatic patients at risk for bladder cancer.

PURPOSE: We study the potential diagnostic use of urinary bladder cancer antigen, CYFRA 21-1 and NMP22*; for evaluating symptomatic patients who present with microscopic hematuria and are at risk for bladder cancer. MATERIALS AND METHODS: Urinary tumor markers were determined in 187 samples from 112 patients symptomatic of bladder cancer (group 1), and 75 with benign and other urological conditions (group 2). Immunoassays were used to measure the 3 selected biomarkers. Sensitivity and specificity were established by previously defined cut points. Biomarker results were reported as corrected and uncorrected for urinary creatinine. Urinalysis was performed in all samples. RESULTS: Positive and negative predictive values were 85.5%, 80.5% and 81.1%, and 80.8%, 79.2% and 76.5% for urinary bladder cancer antigen, CYFRA 21-1 and NMP22, with the cutoffs 9.7 microg./l., 5.4 microg./l and 10.0 units per ml., respectively. These predictives values were 85.2% and 72.5%, respectively, for urinary cytology. The combination of biomarkers decreased the positive predictive values to 72.3% to 78.6% and increased negative predictive values to 84.2% to 86.1%. Urinary tract infection, inflammation and malignancy associated with other genitourinary organs were the primary cause for false-positive test results in the 3 assays evaluated. CONCLUSIONS: With a single biomarker, around 80% of the positive results would have correctly identified symptomatic patients for cystoscopy. Of the negative results 75% would have correctly reduced the number of cystoscopies. Sensitivity and negative predictive values could be improved with the combination of biomarkers but with a loss of specificity and positive predictive values. Urinary tract inflammation and other genitourinary malignancies might contribute to the reduction in specificity of these tests.

Adult↗

Lymphoepithelioma-like carcinoma of urinary bladder: (LELCA).

Lymphoepithelioma-like carcinoma of the bladder (LELCA) is an uncommon neoplasm of the urinary bladder and up till now only 49 cases have been reported in the English literature. It is imperative to distinguish between lymphoepithelioma-like carcinoma and malignant lymphoma as primary bladder lymphoma is extremely rare. We report a case of a 55 year old lady who presented with the complaint of burning micturition and gross hematuria for the past 5 months. There were no other known comorbids. Pelvic ultrasound was normal. Cystoscopy showed a 4x4 cm sessile mass in the bladder. Histopathological examination was consistent with the diagnosis of lymphoepithelioma like carcinoma of the urinary bladder.

Carcinoma, Squamous Cell↗

Primary granulocytic sarcoma of the urinary bladder: case report and review of the literature.

We report a case of granulocytic sarcoma of the urinary bladder, with no evidence of hematologic involvement. The patient was initially misdiagnosed and was treated with chemotherapy for transitional carcinoma grade 3. Despite this treatment, the clinical features of the patient progressed, and a repeated biopsy yielded the correct diagnosis. Three cases of granulocytic sarcoma of the urinary bladder have been reported in published studies, with only one of these primary. To our knowledge, ours is the second case of granulocytic sarcoma of the urinary bladder presenting with urologic symptoms but without hematologic findings.

Adult↗

Urinary bladder neoplasms induced in BALB/c female mice with low doses of 2-acetylaminofluorene.

Large numbers of female BALB/c mice were exposed to low levels of 2-acetylaminofluorene (2-AAF) in the diet. The dose response for urinary bladder neoplasms exhibited a shallow trend to low doses which increased sharply at the higher doses. The dose response over the entire dosage range gave the impression of a "threshold" type response below the mid-doses. Since the tumor incidence at the lower doses was less than 1.0 percent, relatively few urinary bladder tumors occurred. Thus, it was deemed advisable to re-examine noninvasive or early invasive bladder carcinomas and to study the dose response for only the "unequivocal" urinary bladder tumors. Examination of the dose response curves for "unequivocal" urinary bladder tumors showed a positive trend over the low end of the dose range. As a further check, an analysis was conducted on only invasive or metastasizing bladder carcinomas. In this case, there was no significant low dose trend. Thus, the shape of the low dose response curve for bladder carcinomas remains uncertain.

2-Acetylaminofluorene↗

Immunopathologic analysis of human urinary bladder cancer. Characterization of two new antigens associated with low-grade superficial bladder tumors.

The authors have further characterized the normal human tissue distribution and tumor expression of two highly restricted tumor-associated antigens, detected by mouse monoclonal antibodies M344 and 19A211, which are primarily expressed on low-grade superficial urinary bladder tumors. This study was conducted using immunohistochemical staining of frozen and deparaffinized sections of human normal and tumor tissues. The antigens are stable and well preserved on deparaffinized tissue sections. M344 antibody identifies a high-molecular-weight determinant on a cytosolic protein component of over 300,000 Mr. This antigen was not detected on any normal tissue analyzed, including 14 specimens of normal urothelium and 22 cases of cystitis; however, M344 was positive in 74.5% of Ta-T1 tumors and 11% of T3-T4 tumors. 19A211 antibody identifies a sialylated epitope on a cytoplasmic protein complex of 100,000 to 200,000 Mr. This antigen also was expressed preferentially on low-grade superficial bladder tumors (77% Ta-T1) and less frequently on deeply infiltrating tumors (10% T3-4). 19A211 was negative on all normal cells tested, with the exception of umbrella cells, in approximately 25% of the normal urothelium and cystitis specimens studied. Either one or both of these tumor-associated antigens are detected in approximately 80% of low-grade papillary superficial tumors and carcinoma in situ of the urinary bladder. The expression of these antigens on a subset of low-grade bladder tumors, known to progress in only about 10% of cases, suggests that phenotypic differences may reflect biologic potential. Beyond their possible biologic significance, antibodies M344 and 19A211 may provide clinically useful probes for early detection and stratification of urinary bladder tumors.

Antibodies, Monoclonal↗

Squamous cell carcinoma of the bilharzial and non-bilharzial urinary bladder: a review of etiological features, natural history, and management.

Squamous cell carcinoma of the urinary bladder, though uncommon in Europe and the United States, is the most common variety of bladder tumor in countries where urinary bilharziasis prevails. A great controversy still exists regarding its natural history and management. Here, we review the literature of bilharzial and nonbilharzial squamous cell carcinoma of the urinary bladder, focusing on large series. Our aim was to gather most of the published data about this disease entity, report it in a systematic comparative review, and attempt to identify the adverse features and variables behind its dismal outcome. The conclusions are that squamous cell carcinoma, whether bilharzial or nonbilharzial, has distinctive clinicopathological features, different from those of the transitional cell variety. These tumors usually present in advanced (muscle-invasive) stages. Pelvic nodal metastases are not common, and the incidence of distant metastases is less than that reported with transitional cell carcinoma. Local treatment, including cystectomy and adjunctive radiotherapy, is the most acceptable way of treating such tumors.

Carcinoma, Squamous Cell↗

Lactate dehydrogenase activity and isoform distribution in the rat urinary bladder: effects of outlet obstruction and its removal.

The rat urinary bladder responded to infravesical obstruction by an increased weight. The weight began to increase after 3 days of obstruction. After 10 days the weight gain had become significant, but increased further with time. At 90 days the bladders weighed 12 times the initial weight. Lactate dehydrogenase (LDH) activity per unit bladder weight increased with the duration of the obstruction. The increase was significant in the 90 day group. The isoform pattern of LDH was determined. For the control group the M3H form was dominant, with M4 second; M4 became the dominant isoform after 3 days of obstruction. The relative amount of M4 had increased by 80% after 90 days. In one group, which was first obstructed for 10 days and then had the obstruction removed for 4 weeks, bladder weight and LDH isoform pattern were normal. We suggest that the changes in isoform pattern in the obstructed bladder reflect a metabolic adaptation to the prolonged voiding time and the increased detrusor pressure, with a consequently compromised oxygen supply, and that the changes are reversible if the outlet conditions are normalized.

Animals↗

Fibrosarcoma of the urinary bladder. Study of a case showing extensive chondroid differentiation.

A case of primary fibrosarcoma of the urinary bladder showing extensive chondroid differentiation was studied by light microscopy and immunofluorescent microscopy using tissue-specific antibodies against intermediate filaments. The tumor cells were uniformly and positively labeled with vimentin antibodies and were negative for desmin and keratin, thus confirming the nonmuscle mesenchymal origin of the neoplasm. The value of intermediate filament typing in the differential diagnosis of spindle cell tumors of the urinary bladder is discussed, and a review of the literature on the subject is presented. It is postulated that the retained capacity for continued differentiation displayed by this tumor may account for the relatively better prognosis observed for this patient.

Aged↗