Incidence Of Bladder Carcinoma Research Articles

Comparison of early re-resection versus standard surgical method for transurethral resection of urinary bladder tumor : A Randomized controlled trial

Incidence of bladder carcinoma is growing all over the world. Transurethral resection of the bladder tumor (TURBT) is gold standard in the managemnet of non muscle invasive bladder cancer, followed by surveillance cystoscopy. But bladder cancer is notorious for recurrance and progression. but it is newly understood that re-resection within 2-6 weeks may be helpful in reducing recurrance and tumor proression.

In Utero Exposure to 3,3',4,4', 5-Pentachlorobiphenyl Dose-Dependently Induces N-butyl-4-(hydroxybutyl) Nitrosamine in Rats With Urinary Bladder Carcinoma.

Polychlorinated biphenyls (PCBs) are fat-soluble environmental pollutants that can accumulate in adipose tissue or be secreted in milk. N-butyl-4-(hydroxy butyl) (BBN), a rat bladder carcinogen, recruits the host metabolism to yield its ultimate carcinogenic form via CYP1s. Since estrogen receptors (ERs) mediate biological responses important for the growth of bladder carcinoma, we investigated PCNA, Cyclin D1, ERs, CYP1s, and AhR expression in BBN rat bladder carcinomas with prenatal PCB exposure. Female SD rats were treated with 7.5 μg, 250 ng, and 2.5 ng of 3,3',4,4',5-pentachlorobiphenyl (PCB126)/kg or vehicle on days 13 to 19 post-pregnancy. Six-week-old male offspring were treated with 0.05% BBN for 10 weeks before being anesthetized and the urinary bladder wall incised to expose the bladder carcinomas. N-butyl-4-(hydroxybutyl) bladder carcinoma incidence increased with prenatal PCB exposure dose-dependently. In bladder carcinoma, PCB126 exposure significantly increased PCNA, D1, ERα, CYPIA1, CYP1B1, and AhR expression dose-dependently, and increased ERα expression was particularly prominent. However, the expression of ERβ was low, independent of the volume of PCB126 given, indicating similarity to the Vehicle group. We conclude that prenatal PCB126 exposure in rats can induce PCB126 to dose-dependently metabolize BBN via CYP1A1, and contribute to bladder carcinogenesis with upregulation of ERα expression.

Pathology outcomes in patients with transurethral bladder tumour resection in a Turkish population: A retrospective analysis.

Transurethral bladder tumour resection (TURBT) is the common surgical method used in the diagnosis, staging and treatment of patients with bladder tumour. Most of the rare tumours other than the urothelial carcinomas of the bladder are in advanced stage on diagnosis and necessitate aggressive treatment. In our study, we aimed to the histologic types of bladder cancer and to determine the regional incidence of rare bladder cancer types in our region. We retrospectively evaluated 815 patients who underwent TURBT surgery between January 2010 and March 2016 in our clinic with a diagnosis of bladder cancer and at least 1 year follow-up. Patients with tumour histopathological examination including histological tumour type, grade and were reported. Thirty-nine patients with an unclear pathology report (neighboring organ invasion, cautery artifact, etc) and 17 patients whose data could not be accessed were excluded from the study. The patients who had received chemotherapy or radiotherapy due to any type of malignancy (23) were also excluded from the study. The outcomes of 736 patients operated in our clinics due to bladder tumour were evaluated. The mean age was 65.2 ± 8.4; 135 were female and 601 were male. Among them 711 patients with urothelial carcinoma were reported (94.2%). According to TNM classification, stage Ta was observed in 270 patients (37.9%), stage T1 in 297 (41.7%), and stage T2 in 144 (20.3%). Non-urothelial cancers were reported in 25 cases (3.3%). The incidence of bladder carcinoma varies between regions. The results of our study are similar to those of the western countries. Increased smoking and exposure to environmental carcinogenetic agents may lead to altered incidences and histological types of bladder tumours. Revision of regional tumour records may be useful to develop and evaluate future treatment strategies.

Urinary bladder carcinoma: impact of smoking, age and its clinico-pathological spectrum.

Urinary bladder carcinoma is common urological malignancy. Although epidemiological evidence favors role of occupational exposure to chemical carcinogen as the aetiological factor of bladder carcinoma, many cases arise with no obvious occupational exposure to chemical carcinogen. Tobacco and cigarette smoking is common in both rural and urban areas of Nepal. The objective of this study was to determine the impact of smoking and age in urinary bladder carcinoma with related clinicopathological correlations. A total of 56 (44 males and 12 females) cases of urinary bladder cancer treated at Dhulikhel Hospital, Kathmandu University Teaching Hospital during time period of January 2004 to December 2013 were included in the study. Data of patients with Urinary bladder cancer were obtained from hospital records and evaluated for age, sex, history of smoking, clinical presentations, cystoscopic findings and histopathological characteristics. Out of 56 cases, 51 (91.1%) of the patients had hematuria. History of smoking was found in 44 patients. Smoking was found much higher in males (88%) than females (41.66%). Transitional cell carcinoma (TCC) was the most common histological variety, which was seen in 51 (91.07%) patients. The significant impact of smoking was found in terms of grade of TCC. The incidence of bladder carcinoma is higher in male and TCC is the most common variety of Urinary bladder malignancy. History of smoking correlated with grade.

Vitamin D Deficiency and Increased Risk of Bladder Carcinoma: A Meta-Analysis

Background/Aims: Vitamin D status in relation to bladder carcinoma risk was still inconsistent. This study was carried out to evaluate the relationship between vitamin D status and bladder carcinoma risk through a meta-analysis approach. Methods: Pubmed, Web of Science, CNKI, and Embase were searched systemically to find eligible studies from the earliest available date to April 16, 2015. The search terms “vitamin D”, “25-hydroxyvitamin D”, “bladder cancer” or “bladder carcinoma” were used to retrieve relevant studies. The exposure of interest was intake of vitamin D or serum vitamin D levels, and the outcome of interest was bladder carcinoma incidence or mortality. The pooled risk ratio (RR) values and their 95%CIs were calculated through meta-analysis. Results: Seven studies with a total of 62,141 participants met the inclusion criteria and were finally included into the meta-analysis. There was no heterogeneity among those included studies (I² = 0%, P = 0.53). The pooled RR of bladder carcinoma for the lowest category versus the highest category of vitamin D was 1.34 (95% CI 1.17-1.53, P < 0.0001). Sensitivity analysis by omitting one study by turns showed all the pooled RRs were statistically significant. Meta-analysis of 5 studies reporting outcomes of serum vitamin D levels also showed that the low serum vitamin D level was associated with increased risk of bladder carcinoma (RR = 1.32, 95%CI 1.15-1.52, P = 0.0001). No obvious risk of publication bias was observed. Conclusion: Vitamin D deficiency is associated with increased risk of bladder carcinoma in present study.

Omega-3 Fatty Acids Inhibit Tumor Growth in a Rat Model of Bladder Cancer

Omega-3 (ω-3) fatty acids have been tested on prevention and treatment of several cancer types, but the efficacy on “in vivo” bladder cancer has not been analyzed yet. This study aimed at evaluating the chemopreventive efficacy of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) mixture in an animal model of bladder cancer. Forty-four male Wistar rats were divided into 4 groups during a 20-week protocol: control; carcinogen—N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN); ω-3 (DHA + EPA); and ω-3 + BBN. BBN and ω-3 were given during the initial 8 weeks. At week 20 blood and bladder were collected and checked for the presence of urothelium lesions and tumors, markers of inflammation, proliferation, and redox status. Incidence of bladder carcinoma was, control (0%), ω-3 (0%), BBN (65%), and ω-3 + BBN (62.5%). The ω-3 + BBN group had no infiltrative tumors or carcinoma in situ, and tumor volume was significantly reduced compared to the BBN (0.9 ± 0.1 mm3 versus 112.5 ± 6.4 mm3). Also, it showed a reduced MDA/TAS ratio and BBN-induced serum CRP, TGF-β1, and CD31 were prevented. In conclusion, omega-3 fatty acids inhibit the development of premalignant and malignant lesions in a rat model of bladder cancer, which might be due to anti-inflammatory, antioxidant, anti-proliferative, and anti-angiogenic properties.

Chemopreventive Efficacy of Atorvastatin against Nitrosamine-Induced Rat Bladder Cancer: Antioxidant, Anti-Proliferative and Anti-Inflammatory Properties

To investigate the anti-carcinogenic effects of Atorvastatin (Atorva) on a rat bladder carcinogenesis model with N-butyl-N-(4-hydroxibutil)nitrosamine (BBN), four male Wistar rat groups were studied: (1) Control: vehicle; (2) Atorva: 3 mg/kg bw/day; (3) Carcinogen: BBN (0.05%); (4) Preventive Atorva: 3 mg/kg bw/day Atorva + BBN. A two phase protocol was used, in which the drug and the carcinogen were given between week 1 and 8 and tumor development or chemoprevention were expressed between week 9 and 20, when the bladders were collected for macroscopic, histological and immunohistochemical (p53, ki67, CD31) evaluation. Serum was assessed for markers of inflammation, proliferation and redox status. The incidence of bladder carcinoma was: control 0/8 (0%); Atorva 0/8 (0%); BBN 13/20 (65%) and Atorva + BBN 1/8 (12.5%). The number and volume of tumors were significantly lower in the Atorva + BBN group, with a marked reduction in hyperplasia, dysplasia and carcinoma in situ lesions. An anti-proliferative, anti-inflammatory and antioxidant profile was also observed in the preventive Atorva group. p53 and ki67 immunostaining were significantly increased in the BBN-treated rats, which was prevented in the Atorva + BBN group. No differences were found for CD31 expression. In conclusion, Atorvastatin had a clear inhibitory effect on bladder cancer development, probably due to its antioxidant, anti-proliferative and anti-inflammatory properties.

The epidemiology of bladder cancer in Russia

This study assessed the epidemiology of bladder cancer in Russia. The available publications in Russian were analysed, as well as information from the database of N. N. Blokhin Cancer Research Center, accumulating non-uniform data from different cities and regions of Russia. In 2006 there were 68 129 patients with bladder cancer in Russia, accounting for 2.8% of all cancer cases, with unknown proportions of males and females. In the same year 11 973 new bladder cancer cases were diagnosed, with morphological confirmation in 82.3% of cases. From 1999 to 2004 the incidence of bladder carcinoma increased by 5.3% in males and by 12.5% in females. In 2006 57.4% of patients with newly diagnosed disease were staged as T1 and T2, 26.8% as T3 and 11.4% as T4 bladder cancer cases. The mortality rate of patients with bladder carcinoma increased by 10.9% in males from 1999 to 2004 and did not change in females. In conclusion, over the past 10 years both the prevalence and incidence of bladder carcinoma have increased in Russia. There was a trend towards detecting less advanced cases of the disease, and stages T3 and T4 are diagnosed less frequently today than in 1996. As a result the mortality rate of bladder cancer patients within the first year from diagnosis has decreased, although the overall mortality rate in males has risen.

Alpha-fetoprotein as a differential marker between bladder cancer and Schistosomiasis among Egyptian patients

Introduction: Schistosomiasis is considered as a widespread problem that affects Egyptians at different ages (WHO, 1993). It is well known that the high incidence of bladder carcinoma in schistosomal patients also represents a great risk to Egyptian society. Objective: This study represents a survey on the changes which took place in Alpha- Fetoprotein (AFP) levels as a differential marker among Egyptian patients suffering from urinary bilharzial infection and bladder cancer. Methodology: A partial study was carried out on four post-operative patients and followed up for sixty three days after chemotherapeutic treatment using immunoenzymatic mediated assay. Results: It was found that bladder cancer leads to obvious significant increase in AFP levels, while schistosomal infection causes a non-significant decrease as compared to healthy control. Although the combination between schistosomal infection and cancer leads to a significant decrease in AFP level compared to non bilharzial cancer cases, there was no significant correlation with healthy cases. Conclusion: It should be pointed out that the somewhat constant level of AFP in the sera of all patients was due to chemotherapeutic treatment. Also, it can be noticed that there is a significant positive correlation with progress of cancer grades.

Alpha-fetoprotein as a differential marker between bladder cancer and Schistosomiasis among Egyptian patients

: Schistosomiasis is considered as a widespread problem that affects Egyptians at different ages (WHO, 1993). It is well known that the high incidence of bladder carcinoma in schistosomal patients also represents a great risk to Egyptian society.

BK virus and carcinoma of the prostate, kidney and bladder

Sir, We read the recent study by Newton et al (2005) with great interest. Presently, we offer a few thoughts on what their results suggest about the role of BK virus in cancer. First, haemorrhagic cystitis and BK nephropathy in transplant patients are the principal disease entities for which BK virus has been implicated (Hirsch, 2005). We ask, how do the antibody titers of the cancer patients and controls compare to transplant patients diagnosed with BK nephropathy or haemorrhagic cystitis? It would be informative to know whether antibody titers in patients with active BK nephropathy are within the range reported for patients with carcinoma. Similarly, how do antibody titers in BK nephropathy patients change with treatment and resolution of BK infection? Perhaps antibody titers decline following resolution of the active BK infection to levels comparable to those reported by Newton et al (2005). Consider a cancer patient with a history of prior BK infection whose antibody titers were previously high, but now have declined. In such an instance, BK virus may be implicated in carcinogenesis, although the antibody titers at the time of this study have returned to the range of normal individuals. Certainly, a study documenting how antibody titers in patients with BK nephropathy change over time would be enlightening. Infection with polyomavirus (PV) may both disrupt the function of tumour-suppressor proteins p53 and pRb (Reich and Levine, 1982; DeCaprio et al, 1988; Bollag et al, 1989; Dyson et al, 1990; Harris et al, 1998; Pipas and Levine, 2001). As the PV infection is cleared, the ability of the cell to respond appropriately to DNA damage may remain impaired. The cells are then transformed, although the active phase of infection has resolved. We suggest, based on this ‘hit-and-run' mechanism, that the absence of elevated titers does not exclude a role for BK virus in carcinogenesis. Nonetheless, the ‘hit-and-run' mechanism is difficult to defend experimentally. How does one find evidence for an infection that has resolved? We anticipate that this may become an area of active research in the near future. Finally, Weinreb et al (2006) identified a population of patients with PV-infected ‘decoy' cells seen on urine cytologic analysis. The incidence of bladder carcinoma in this population was significantly higher than in patients receiving urine cytologic analysis but lacking any such infected cells. Their data suggests an association of PV infection with bladder carcinoma. Did any patients in Dr Newton's study have urine cytologic analyses revealing such ‘decoy' cells? Is there any correlation between the presence of such virally infected cells and antibody titers? The detection of ‘decoy' cells may be more closely associated with carcinoma than antibody titers.

Polyoma virus infection is a prominent risk factor for bladder carcinoma in immunocompetent individuals

Despite various reports of BK viral (BKV) DNA sequences or proteins in tumors of the urogenital tract, there has been no study statistically linking infection by this polyoma virus (PV) to tumor development. All PV are potential transforming viruses, the large T-antigen of which interacts with tumor suppressor proteins. Here, we have performed a cross-sectional study of 3,782 patients having had urine cytologic analyses, comparing those diagnosed with PV infection with those not so diagnosed. In order to focus on immunocompetent individuals, renal transplant patients, for whom a diagnosis of PV infection followed immunosuppressive therapy, were excluded. Among the 133 immunocompetent patients diagnosed with PV infection, the most frequently occurring neoplasms were bladder carcinoma (15.8%) and prostate carcinoma (3.8%). The incidence of bladder carcinoma was sufficient to statistically establish temporality in a two-sided test, linking a prior diagnosis of PV infection to a subsequent diagnosis of bladder carcinoma (odds ratio = 3.419, P < 0.001).

Coexistence of prostate neoplasia in patients undergoing radical cystoprostatectomy due to vesical neoplasia

To assess the incidence of bladder carcinoma infiltrating the prostate and prostate adenocarcinoma in patients undergoing radical cystoprostatectomy due to bladder cancer, as well as to assess if the characteristics of the bladder neoplasia influence the prostatic involvement by this neoplasia. We retrospectively assessed 60 male patients, who underwent radical cystoprostatectomy between July 1997 and December 2003. Mean age was 66.7 years (40 and 93 years). The product of radical cystoprostatectomies was checked for involvement of urethra and prostate parenchyma by the primary neoplasia, and for the presence of associated prostate adenocarcinoma. Bladder neoplasia characteristics, such as localization, size, multifocality, association with in situ carcinoma and histological grade, were studied in order to assess the possibility of using such characteristics as predictive factors of prostate infiltration by bladder urothelial carcinoma. We observed the presence of 20% of patients with bladder carcinoma infiltrating the prostatic urethra, 23.3% of patients with infiltration of the prostate parenchyma and 28.3% of patients with associate prostate adenocarcinoma, resulting in a total of 55% of patients with prostatic involvement (infiltrative bladder carcinoma and/or adenocarcinoma). We also observed a statistically significant correlation between tumor location in the trigone, the presence of in situ carcinoma and the histological grade of the bladder tumor with prostatic infiltration by the vesical neoplasia. The coexistence of prostatic neoplasia in patients operated for bladder neoplasia was frequent in our sample (55%). We observed that the prostatic infiltration by bladder tumors occurs more frequently with tumors located in the trigone, with associated in situ carcinoma and with high histological grade. There was no correlation between neoplastic infiltration of prostate and multifocality or size of the bladder tumor in the studied sample.

Lack of Inhibition of BBN-induced Bladder Carcinogenesis in C57BL/6 Mice by Intravesical Instillation of KRN 7000.

The immunostimulatory α-galactosylceramide, KRN 7000 or (2S, 3S, 4R)-1-0-(α-D-galactopyranosyl)-2-(N-hexacosnoylamino)-1,3,4-octadecatrienol, might be anticipated to have antitumor activity in vivo apart from any direct toxicity to cancer cells. We investigated inhibition of mouse bladder carcinogenesis by intravesically instillated KRN 7000. C57BL/6 mice were divided into 4 groups; all first receiving the carcinogen 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in drinking water for 8 weeks. Next, groups 1 and 2, respectively were administered 10 and 0.1 μg/kg of KRN 7000 intravesically once weekly for 17 weeks. Group 3 received only 0.3 ml of saline (vehicle control). Group 4 did not undergo bladder catheterization. By histologic examination at 26 weeks, the incidence of bladder carcinoma of all types tended to be higher in group 1 than in group 3, but without significance. The incidence of bladder carcinoma in group 4, (no catheterization), was similar to that in group 1. Only one precancerous lesion (papillary or nodular dysplasia) was seen in each of groups 3 and 4. Thus vesical instillation of KRN 7000 did not inhibit bladder carcinogenesis in mice, exposed to the carcinogen studied.

Risk factors for urinary bladder carcinoma in postmenopausal women. The Iowa Women's Health Study.

We evaluated prospectively the association of smoking and other potential risk factors with bladder carcinoma incidence in postmenopausal women. A total of 37,459 women participating in the Iowa Women's Health Study completed baseline questionnaires in 1986 and were followed 13 years for bladder carcinoma incidence (n = 112). Adjusted for potential confounders, the relative risk (RR) of bladder carcinoma in women who were current smokers compared with those who had never smoked was 3.58 (95% confidence interval [CI] = 1.86-6.88). The RR declined as years since quitting increased. Currently, married women, compared with unmarried women, had a RR of 0.66 (95% CI = 0.44-0.99). A 2.46-fold (95% CI = 1.32-4.59) increase in bladder carcinoma risk was identified for women who reported, versus did not report, diabetes. Regular versus no physical activity (RR = 0.66, 95% CI 0.43-1.01) and body mass index were inversely associated (P = 0.06) with bladder carcinoma incidence. We confirmed that cigarette smoking is an important risk factor for bladder carcinoma in women; women who had quit smoking had a reduction of risk. We also identified diabetes as a potential risk factor, which may invite more research on its role in the development of urinary bladder carcinoma.

Etiopathology, risk factors, environmental influences and epidemiology of bladder cancer

The etiology of bladder cancer is well investigated. Bladder carcinogenicity of nitrosamines is proven in animals but not in men, although dimethylnitrosamine in urine of patients with urinary infections or bilharziosis suggest a causative role. Aromatic amines are strong bladder carcinogens. Arsen is proven to be bladder carcinogenic as well as the nitrofurane FANFT. Nitrofurantoin however is not bladder carcinogenic nor are the endogenous metabolites of tryptophan. The influence of papilloma virus on bladder carcinoma induction ist not definitely proven yet. Bilharziosis or chronic urinary infections correlate with bladder carcinomas, nitrosamines being the possible reason. The reason for the increased incidence of bladder carcinomas in balkan nephropathy ist not clear. Arcolein as a metabolite of Cyclophosphamid is a strong bladder carcinogen as well as Phenacetin. Immune suppression and radiotherapy are risk factors, too. About 50% of bladder carcinomas are due to cigaret smoking.

Long-term administration of galactoside-specific mistletoe lectin in an animal model: no protection against N -butyl- N -(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis in rats and no induction of a relevant local cellular immune response

Aqueous extracts from leaves of the European mistletoe (Viscum album L.) are postulated to exert an anticancer efficacy by cytotoxic and/or immunological mechanisms of action. Although popular as an unconventional therapy modality, no controlled randomized clinical trials are available, reliably documenting a clinically beneficial antineoplastic potential of the various commercial mistletoe preparations. Since previous investigations have focused on the purified galactoside-specific lectin (Viscum album L. agglutinin, VAA) as major biological response modifier in the low-dose range, the objective of the present experimental study was to examine its effect on N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced carcinogenesis in the urinary bladder of rats, a suitable animal model for human disease. The carcinogen was fed by gavage in three fractionated low doses (150 mg/kg body weight each) to obtain low-grade and low-stage transitional cell carcinomas. From the onset of the experiment VAA was injected subcutaneously twice a week (1 ng/kg body weight) continuously for either 6 or 15 months. Following an experimental period of 6 months the incidence of bladder carcinomas was 10.2% in rats given exclusively BBN and 6.7% in those additionally treated with VAA. After an experimental time of 15 months 25.8% of the rats fed BBN only and 19.7% of the animals additionally receiving VAA had developed urothelial carcinomas. The differences of the tumor incidences did not reach the level of statistical significance, neither after an experimental duration of 6 (P = 0.88) nor of 15 months (P = 0.71). A difference was found in the size of the transitional cell carcinomas. They proved to be significantly larger (P = 0.02) in the rats additionally treated with VAA for 15 months (mean maximum diameter: 3.31 mm) than in those without lectin treatment (mean maximum diameter: 1.88 mm). Quantitative immunocytochemistry analyzing a panel of immune cells yielded no evidence for the ability of the lectin to provoke a substantial, biologically relevant local cellular immune response in the wall of tumor-free and tumor-bearing bladders. From the current experiment it is obvious that galactoside-specific mistletoe lectin failed to protect against, inhibit, delay or reduce development of chemically induced urothelial carcinomas of the urinary bladder even after long-term administration in the clinically recommended schedule. It seems highly unlikely that adjuvant treatment with mistletoe extracts or VAA might favorably influence bladder cancer in patients by immunological effector mechanisms.

Production of trophoblastic hormones by transitional cell carcinoma of the bladder: Association to tumor stage and grade

Cancer registration statistics of economically advanced countries indicate that bladder carcinoma incidence ranks fourth in men and eighth in women, but a reliable tumor marker for predicting the disease course is still lacking. We designed an immunohistochemical study to comprehensively assess the trophoblastic hormone production profile of transitional cell carcinoma (TCC) of the bladder. Moreover, we correlated histological differentiation and tumor stages with marker expression and, finally, evaluated a potential tumor origin of hCGβ core-fragment (hCGβcf). To this end, formalin-fixed, paraffin-embedded tumor tissues from 104 patients with urothelial neoplasms of various histological grades (23 GI, 24 GII, and 38 GIII) and stage (19pTis, 21pTa, 29pT1, and 35pT2-T4) were analyzed by the immunoperoxidase technique using our own well-characterized monoclonal antibodies against the glycoprotein hormones human chorionic gonadotropin (hCG) and its derivatives hCGα, hCGβ, hCGβcf, luteinizing hormone (LH, LHβ), follicle-stimulating hormone (FSH, FSHβ), and the protein hormones placental lactogen (hPL) and growth hormone (hGH-V/N). Overall, trophoblastic hormone immunoreactivity was found in 36% of TCC. Detailed analysis showed 35% hCGβ, 17% hCGβcf, 9% hCGa, 4% hCG, and 2% hPL-positive cases. The tumors produced neither GH-N, placental GH-V, nor the pituitary gonadotropins FSH/FSHβ and LH/LHβ. Marker positivity significantly increased with high-grade lesions (26% GI- v 55% GIII-TCC) and advanced tumor stages (24% pTa v 63% ≥ pT2). Hormone immunoreactivity was frequently observed in highly proliferating areas. Our findings, together with recent structural and clinical studies, strongly suggest that these hormones, or derivates thereof, might act as local tumor growth factors. Normal urothelium, urothelial papillomas, and carcinoma in situ showed no positive reactions. All tumors producing hCG-derived molecules were negative for the concommitantly analyzed neuroendocrine markers chromogranin A, synaptophysin, and neuron-specific enolase (NSE). In summary, one third of TCC ectopically produce trophoblastic hormones, which is specifically correlated with stage and grade. Apart from hCGβ (97% of the marker-positive cases), the intracellular occurrence of hCGβcf, apparently the second most frequently produced marker, was surprising, and there was also a lesser degree free hCGα and intact holo-hormone expression. The placental protein hormones PL and GH-V are not appropriate tumor marker candidates. Finally, our histogenetic findings support a metaplastic origin of the hCG producing choriocarcinomatous phenotype of some TCC.

Promotive effects of intravesical instillation of dimethylsulfoxide on bladder carcinogenesis in mice

The effect of intravesical instillation of dimethylsulfoxide (DMSO) on bladder carcinogenesis was examined in mice. Experiment 1: Fifty-five female C3H/He mice were administered 0.05% N-butyl-N-(4-hydroxy-butyl) nitrosamine (BBN) in their drinking water for 8 weeks. In week 9 they were divided into two groups consisting of 25 mice each. Then, under nembutal anesthesia the first group was given weekly intravesical inatillations of 0.1 ml DMSO (minimum 99.0%) for 10 weeks. The second group received no treatment except anesthesia. All mice were killed 30 weeks after the begining of the experiment and their urinary bladder resected for histological examination. The incidence of bladder carcinoma was 93.7% (15.16) and 27.7% (6/22) in groups 1 and 2, respectively. These incidences differed significantly between the two groups. Experiment 2: One hundred and twenty female C3H/He mice were divided into two groups. The first group was given 0.05% BBN in their drinking water for 5 weeks and then tap water. The second group was not given BBN. In week 6, the first group was divided again into three groups (1, 2 and 3) consisting of 28, 26, and 27 mice, respectively. The second group was divided into groups 4 and 5 consisting of 21 and 18 mice, respectively. Under nembutar anaesthesia groups 1 and 4 received weekly intravesical instillation of 0.05 ml DMSO (minimum 99.0%) from weeks 6 to 13, Group 2 received weekly intravesical instillation of 0.05 ml distilled water from weeks 6 to 13. Groups 3 and 5 received no treatment except anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of Rat Urinary Bladder Carcinogenesis by α-Difluoromethylornithine

The inhibitory effect of oral administration of α-difhioromethy lornithine (DEMO) on urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BHBN) was explored. Since DEMO in the drinking water at 0.5% and 0.2% had been demonstrated to inhibit tumorigenesis, lower doses (0.2%, 0.1%, 0.03% and 0.01%) of DEMO were examined in the present study. After six-week treatment with the drinking water containing 0.05% BHBN, water containing DFMO at 0.2%, 0.1%, 0.03%, 0.01% or 0% was administered during the subsequent 34 weeks. Incidence of bladder carcinoma was 15/35 (43%), 14/35 (40%), 21/35 (60%), 20/35 (57%) and 27/35 (77%) in the 0.2%, 0.1%, 0.03%, 0.01% and 0% DFMO groups, respectively. Stastistical analysis indicated significant tumor suppression in the 0.2% and 0.1% DFMO groups. Tumor multiplicity and size were not affected by DFMO treatment. No untoward effects were demonstrated in body weight gain or examination of pertinent organs. Our data indicate that bladder carcinogenesis induced by six-week exposure to 0.05% BHBN is significantly inhibited by daily administration of DFMO at the level of 0.1% or higher in drinking water.