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Purpose: The aim of the present study was to determine the clinical usefulness of nuclear matrix protein 22 (NMP22) as a new urinary marker for the screening of urothelial cancer in patients with microscopic hematuria, especially in comparison with that of voided urine cytology. Methods: Patients with microscopic hematuria detected at a health examination, who were advised by a consulted urologist to have a cystoscopical examination, were asked to enter this study. Urine samples were collected before cystoscopy and divided into two portions for a NMP22 test and voided urine cytology. Results: Of the 309 patients with microscopic hematuria, 22 cases (7.1%) of urothelial cancer and one case of prostate cancer were detected. For the other cases, 128 (41.4%) were of benign diseases and 158 (51.1%) were designated as having no evidence of disease (NED). The median NMP22 values for urothelial cancer, other diseases and NED were 35.5, 6.7 and 6.0 U/mL, respectively, with 95% confidence intervals of 19.9–228.2, 5.1–9.3 and 5.4–7.2, respectively. The sensitivity of the NMP22 test for urothelial cancer was 90.9% (20/22), whereas the sensitivity of voided urine cytology was only 54.5% (12/22). Conclusions: The present study indicates that urinary NMP22 is a useful tool for the screening of urothelial cancer in patients with microscopic hematuria.

Cisplatin (CDDP) is one of the most active chemotherapeutic agents but is among the most emetogenic drugs. The emetic side-effects of CDDP-containing intraarterial chemotherapy have not been evaluated in a prospective randomized trial and the efficacy of serotonin antagonists in preventing the emesis associated with this method of CDDP administration has not been assessed.CDDP 50 mg/m2 and methotrexate 30 mg/m2 were administered every 3 weeks through intraarterial catheters placed in the bilateral internal iliac arteries. Patients were classified into two groups: granisetron treatment group (group G) and no treatment group (group NG) with the first course of chemotherapy, crossing over with the second course. The patients in group G received granisetron 40 micrograms/kg by intravenous infusion.Although intraarterial CDDP administration produced less emesis than intravenous CDDP administration, at the same concentration, gastrointestinal toxicity is still the most unpleasant side-effect for patients. Granisetron administration significantly reduced nausea and vomiting during the acute emetic phase (an evaluation of treatment as very effective and effective was made in 89% in group G and 33% in group NG (P0.001). Complete control of emesis was achieved in 68 and 18% of patients in groups G and NG, respectively (P0.0001).A single prophylactic infusion of granisetron was effective in preventing the nausea and vomiting associated with intraarterial CDDP-containing therapy.

The number of nucleolar organizer regions (NOR) of human bladder cancers was evaluated at the light- and electron-microscopic level. The average number of argyrophilic NOR (AgNOR), stained by the one-step silver colloid method, was measured in benign and malignant urothelial cells in the human urinary bladder using a light microscope. The average number of nucleolar fibrillar centers (FC) per nucleus was also calculated by quantitative ultrastructural morphometry in the specimens from the same patients. Statistical evaluations revealed that the average number of AgNOR per nucleus was significantly correlated with the elevation of tumor grade and stage (p < 0.05). An average FC number per nucleus also increased in association with tumor grade and stage (p < 0.05). Although the average number of FC was 5.6 times higher than that of AgNOR, the correlation between the average number of FC and AgNOR was statistically significant. In conclusion, these results suggested that the silver staining method was a useful and convenient tool for the evaluation of the differentiation and invasive potential of bladder cancer cells at the light-microscopic level.

Background: The BTA test is a latex agglutination assay for the qualitative detection in the urine of analytes that are associated with bladder tumor. We compared the results of the BTA test with those of voided urine cytology (VUC) in patients with bladder cancer. Methods: A multicenter trial was performed at 6 institutions. A total of 132 patients with histologically diagnosed bladder cancer were enrolled. Urine samples were split for BTA and VUC testing. Results: The sensitivities of the BTA test and VUC were 57.6% and 37.9%, respectively; this difference was significant (P< 0.001). The BTA test had much higher sensitivity for small, solitary, superficial tumors than did VUC. Conclusion: The BTA test is simple to perform, gives rapid results, and is far more sensitive than VUC for detection of bladder cancer. The BTA test has the potential to become an additional tool for detecting bladder cancer.

Purpose Evaluation of prognostic significance of nucleolar organizer regions (NORs) in renal cell carcinoma (RCC). Materials and Methods Nuclear organizer regions were quantified in a series of 59 cases of RCC by the silver colloid method, and the NOR index was obtained from the ratio between mean NOR counts in each neoplastic nucleus and in normal nucleus. The patients were staged pathologically and divided into 2 groups by average NOR index of all cases, which was 0.76. Correlations between the NOR index and other parameters were statistically analyzed, and the prognostic value of the NOR index was also examined. Results The NOR indices from each group were correlated with the survival curve. In low stage tumors (pT1 or 2 N0M0), the low NOR index group had a survival rate of almost 100 per cent while in those patients with higher NOR indices, there was a significantly increased mortality (p less than 0.01). In patients presenting with high stage tumors (excluding pT1 and 2 NOMO), the survival rate was significantly improved in those patients with a low NOR index (p less than 0.01). On the other hand, the patients with a low NOR index have a better prognosis than those with a high NOR index within each tumor grade (p less than 0.01). Statistical analysis by the log rank test indicated NORs to be a significant predictor of survival over the whole series within low and high pathological stages and within each tumor grade. Analysis of the data with Cox's proportional hazard model showed that NOR index had a stronger hazard ratio than grade or stage of tumor (p = 0.0005). Conclusions Our study has demonstrated that NOR index is a new prognostic indicator for patients with RCC (p = 0.0005).

To confirm the value of the proliferating cell nuclear antigen (PCNA) labelling index in relation to histological grade, stage and prognosis.Tissue specimens from 56 patients (49 men, 7 women; mean age 65 years [range 34-86]) with newly diagnosed transitional cell carcinoma of the urinary bladder were stained by an avidin-biotin peroxidase method using an anti-PCNA monoclonal antibody. Immunohistochemical analysis was performed on ethanol-fixed, paraffin-embedded tissue sections obtained by endoscopic biopsy or transurethral resection (TUR). The PCNA labelling index was determined by counting the number of PCNA-labelled cells in the tissue sections.Grade 1 tumours averaged 5.1 +/- 3.0% labelling versus 10.9 +/- 5.2% in grade 2 tumours, and grade 3 tumours had a PCNA labelling index of 21.8 +/- 10.4%. The average labelling indices for superficial tumour (37 patients) and invasive tumour (19 patients) were 7.5 +/- 5.3% and 20.8 +/- 10.0%, respectively. A distant metastatic bladder tumour showed an average labelling index of 42.3%. To analyse survival, tumours with PCNA indices above and below the median level (12%) were compared. Those patients with an index of12% (the mean of all of the PCNA values) had a worse prognosis than those with an index of12%. The mean PCNA labelling indices in recurrent and non-recurrent tumours were 6.4 +/- 0.7% and 8.2 +/- 1.7%, respectively, statistically not significant.The higher PCNA labelling index may indicate biological malignancy. These results suggest that measurement of the PCNA labelling index in bladder cancer may prove to be an objective and quantitative assay of biological aggressiveness and provide significant prognostic information, though it does not help to select patients at high risk of recurrence in superficial tumours.

Background. Intravesical instillation therapy of Bacillus Calmette-Guerin (BCG) has become a standard treatment for carcinoma in situ (CIS) of the urinary bladder. However, there have been few reports concerning the direct effect of BCG on existing tumors classified as Ta or T1. In the first stage of this clinical study, 157 patients were treated with BCG intravesical instillation (Tokyo 172 strain [BCG Co. Ltd., Tokyo, Japan]; 80 mg weekly for eight times) by our Study Group. The efficacy on existing tumors was a complete response (CR) rate of 84.4% and 66.4% and a partial response (PR) of 6.3% and 20.8% for 32 cases of CIS and 125 cases of Ta or T1 tumors, respectively. Methods. In the second stage of this study, the authors investigated the outcome of the 138 patients who had achieved CR or PR in the first stage. One hundred twenty (87.0%) of the patients were followed fully. Of those patients, 52 were randomized to receive prophylactic (maintenance) therapy consisting of BCG of 40 mg monthly for 12 times (Group A), whereas 55 were randomized to an untreated control group (Group B). Thirteen other patients refused to be randomized and were followed without prophylactic instillation. Results. The median follow-up period was 48 months for Group A and 42 months for Group B. In Groups A and B, the beneficial effect of the BCG therapeutic instillation persisted for a long time, and the 3-year nonrecurrence rate was 77.6% in Group A and 74.2% in Group B. Disease progression was observed rarely. Conclusion. For patients in whom transurethral resection of tumors of the bladder (TUR-Bt) alone is unlikely to eliminate the tumor, intravesical BCG is potentially the treatment of choice. Cancer 1995;75:552-9.

Purpose In several previous reports, it has been suggested that the androgen system is related to bladder carcinogenesis. In this study, to understand the mechanism underlying this relationship, we administered a LH-RH agonist depot (Leuprolide depot), a pure-antiandrogen (flutamide) or a 5 alpha-reductase inhibitor (finasteride) to the mice in the promotion state of bladder carcinogenesis by N-butul-N-(4-hydroxybutyl) nitrosamine (BBN). Materials and methods 177 C3H/He male mice were divided into 7 groups. All mice were treated with 0.05% BBN for 10 weeks and were maintained over the subsequent 12 weeks with the following treatments. Group 1 was a control group; in group 2, castration was performed at the 11th week; in group 3, finasteride was administered starting the 11th week; in group 4, a LH-RH agonist depot was administered starting the 11th week; in group 5, flutamide was administered starting the 11th week; in group 6, both finasteride and a LH-RH agonist depot were administered simultaneously starting the 11th week; and in group 7, both flutamide and a LH-RH agonist depot were administered simultaneously starting the 11th week. Results and conclusions (1) We confirmed that castration significantly suppressed bladder carcinogenesis. (2) Finasteride or flutamide administration as monotherapy had no effect on the results; however, the dosages of these drugs may have been too low, so we are planning a study with higher doses. (3) Conversely, the LH-RH agonist depot significantly promoted bladder carcinogenesis, we believe that the high levels of testosterone immediately after the administration were responsible for this promotion. (4) Simultaneous administration of flutamide suppressed this LH-RH induced promotion of carcinogenesis.

We examined nucleolar organizer region (NOR) indices on 13 bladder tumors on both squash-prepared specimens and paraffin embedded specimens stained by silver-colloid method. It was noted that; 1. The nuclear size was enlarged by squashing, 2. Aggregated NOR dots were dispersed, 3. Uniformity of microscopic phase of the dots was obtained, 4. Squash specimens had more precise countabilities than the paraffin embedded sections for avoidance of nuclear resection. NOR indices (mean +/- S.D.) of those bladder tumors on squash-preparation and paraffin section were 8.64 +/- 4.32 and 6.13 +/- 1.58, respectively, and the former showed good correlation with the tumor stage. When we prepare the squashed specimen from the surgically resected bladder tumor tissue, embedding and sectioning processes which are inevitable for preparation of paraffin embedded section, could be eliminated. Thus, squash-smear technique was considered to be better than the method using paraffin embedded section on the point of shorter duration of examination and accurate countability of the NOR dots.

Biochemical assay and immunohistochemical staining of neutral endopeptidase were performed on bladder cancer cells. In superficial bladder cancer the enzyme activity and immunohistochemical intensity of staining were high, while invasive bladder cancer showed only a low level of activity. This finding suggests that neutral endopeptidase is expressed at a certain stage of cell differentiation, during the neoplastic process in the bladder. Gene expression is assumed to be closely correlated with this mechanism. From the results of this study neutral endopeptidase will serve as a new tumor marker for bladder cancer as well as acute lymphatic leukemia.

Two cases of Fibroepithelial polyp in 47-and 74-year-old males complaining of gross hematuria are described. In the foreign literature, this polyp most commonly occurs in infancy and childhood in the first decade of life, but rarely occurs in aged male. Ten cases of this disease could be accumulated in the Japanese literatures, in which this polyp more commonly occurs in older generation compared with younger one. Urethral polyp should be considered in the differential diagnosis of gross hematuria.

From August, 1989 to December, 1992, 11,386 individuals consisting of 6,981 males and 4,405 females were examined in the general health check at Mito Saiseikai general hospital. Occult blood in dipstick urinalysis was detected in 190 of 6,981 males (2.7%) and 503 of 4,405 females (11.4%). Two renal cell carcinomas and ten bladder carcinomas were found out, but prostatic carcinoma could not be found out. None of these tumors were symptomatic. Two renal cell carcinomas, of which all patients had negative occult blood, were confirmed by computed tomography and angiography. Revealing the locally-confined tumor (Stage I) in the radiologic study, both tumors were resected with radical nephrectomy, and the pathological specimens showed pT2pNOpVO in both tumors. Of 10 bladder carcinomas seven transitional cell carcinomas, of which 6 patients had negative occult blood and one had positive occult blood, were confirmed by cystoscopy and TUR-BT. All of them were low-grade and low-stage tumors. Other three bladder carcinomas were detected by ultrasonography and cystoscopy, but these patient rejected TUR-BT. All of them had negative occult blood. We consider that the transabdominal ultrasonography is a very useful test for detecting the early stage of renal cancer and superficial bladder cancer. We recommend that transabdominal ultrasonography involving the kidney and the lower urinary tract should be performed in the general health check.

The Japanese Urological Cancer Research Group for Adriamycin has conducted a series of clinical trials to investigate the efficacy and safety of prophylactic intravesical chemotherapy for superficial bladder cancer. In the third trial, reported herein, patients with recurrent bladder cancer or multiple primary cancer were selected and randomized to one of four groups using the envelope method after complete resection of the original tumors. Group A was given Adriamycin alone, group B received oral 5-fluorouracil (5-FU), group C was given Adriamycin and oral 5-FU, and group D served as the control group. Of the 544 patients registered, 331 were evaluable for the purpose of this study. The administration of 5-FU (group B) failed to prevent the recurrence of bladder tumors. Although group C (both Adriamycin and 5-FU) did not fare better than group A (Adriamycin only), Adriamycin was effective in preventing the recurrence of tumors, especially in high-risk patients with recurrent and multiple tumors. The risk of recurrence was reduced to 0.21 (95% confidence interval, 0.10–0.44) relative to the control group. There was no indication of a synergistic effect between 5-FU and Adriamycin. As side effects, cystitis syndrome was observed in 23%–30% of the patients in the Adriamycin groups and mild myelosuppression was observed in the 5-FU groups.

M-VAC therapy (methotrexate, vinblastine, Adriamycin, and cisplatin) has improved the treatment results of urothelial cancer patients. However, it is sometimes complicated by drug toxicities, including bone marrow suppression. We analyzed the relative dose intensity in each patient undergoing M-VAC chemotherapy in relation to the chemotherapeutic effect and survival. In addition, the role of granulocyte colony-stimulating factor (G-CSF) in the dose intensity of M-VAC therapy was analyzed. Between June 1988 and March 1993, 29 patients with advanced urothelial cancer were treated with M-VAC therapy in our institution. Of 18 patients with evaluable lesions, 2 (11.1%) showed a complete response (CR) and 7 (38.9%) showed a partial response (PR), and the overall response rate was 50.0%. The median follow-up period for these 18 patients was 14.6 months and the median survival was 8.7 months, with 12 of the 18 patients being alive at the time of analysis. The relative dose intensity (RDI) for these 18 patients was 0.81 for methotrexate, 0.80 for vinblastine, 0.92 for Adriamycin, and 0.91 for cisplatin, for a mean RDI of 0.87. There was no correlation between the chemotherapeutic effect and the RDI. When we calculated the RDI for all 29 patients who underwent M-VAC therapy, G-CSF increased the RDI of Adriamycin significantly. The results of this retrospective study indicate that a dose intensity for M-VAC therapy in the range of 0.61-1.00 is unlikely to correlate with the chemotherapeutic effect, although G-CSF contributes to increasing the RDI of Adriamycin.

Nd:YAG laser irradiation and flexible cystoscopy were used in the outpatient management of 16 cases (21 sessions) with superficial bladder tumors. Irradiation of tumors was accomplished in all cases except 3 in which the visual field was affected by bleeding after the cup biopsy of tumors. Tumors at the bladder neck were easily irradiated through the flexible cystoscope. No tumor recurred at or near the previously irradiated site. This method provided a safe and cost-effective means to treat superficial bladder tumors in selected cases.

A 40-year-old man was admitted to our hospital with a fat-density extrarenal tumor and intrarenal nodules which were detected by ultrasonography (US) and CT scan obtained the general health check. After his admission, US, CT, MRI and angiography were performed. As the final diagnostic procedure, we performed a US-guided percutaneous needle biopsy of the extrarenal tumor, because this tumor was difficult to distinguish from liposarcoma and angiomyolipoma (AML). The pathological study revealed a well-differentiated liposarcoma, and the extrarenal tumor and the left kidney were removed en bloc. Pathologically, the tumor not only invaded into the renal parenchyma directly but also have metastasized independently to the intrarenal region. Postoperatively, he received a tumor dose of irradiation of 50 Gy. Liposarcoma arising in the perirenal space should be considered in the differential diagnosis of exophytic AML. If radiological studies can not confirm the appropriate diagnosis, we consider that biopsy of the tumor should be selected as an alternative diagnostic approach. And, we think that this is the first case report dealing with intrarenal metastases of liposarcoma.

A male aged 20 had been treated for anal and lower abdominal pain after ejaculation for about 2 years under the diagnosis of chronic prostatis. Because of worsening of the pain, he was admitted to our hospital in September 24, 1991. On the rectal examination, a cystic tumor was palbable on the left side of the prostate. The left kidney was not detected by IVP and ultrasonography. CT revealed two retrovesical cystic lesions in the left side. Cystourethroscopy showed an absence of ureteral orifice and ureteral ridge on the left side. Left uretero-seminal vesiculectomy was performed on October 3rd, under the diagnosis of an ectopic ureter entering into the seminal vesicle or ejaculatory duct. Histopathologically, the left ectopic ureter entering into the lower portion of the seminal vesicle or ejaculatory duct and the left renal agenesis were diagnosed. It was remarkable that ureteral epithelium was not transitional but columnar epithelium.

Histopathological comparison of clinical prostatic adenocarcinoma between Japan and the United States (US) has been made with retrospective analyses on 1,037 and 987 cases, respectively. All cases were histologically evaluated by the same pathologist (M.H.) without previous knowledge of clinical information according to application of the Japanese General Rules for Prostatic Cancer (JGRPC) based on the predominant degree of histological differentiation, the nuclear grading by WHO classification and the Gleason grading systems. The age distribution of the patients was slightly different among both groups. However, this difference appeared not to be essential, because there existed difference of the date on diagnosis between two groups. Even though considering this time difference on registration, much more cases from Japan had stage D disease. The observed incidence of the histological differentiation classified by JGRPC among over-all cases did not show significant difference, however, the incidence among the cases with same stage between two groups differed with some statistical significance. Much more cases from the US fell in well differentiated adenocarcinoma and frequency of moderately differentiated adenocarcinoma was higher in the Japanese even in the cases diagnosed at advanced stages. The observed incidence of nuclear grade 3 was also higher in the Japanese. Gleason primary and secondary grade 5 and score 9-10 appeared more frequently in the cases from Japan.(ABSTRACT TRUNCATED AT 250 WORDS)

It has been shown that molecular cytogenetics in interphase nuclei is applicable to paraffin embedded sections from formarin-fixed materials utilizing in situ hybridization (ISH). This allows precise identification of numerical abnormalities of chromosome in tumor cells without disruption of tumor morphology. Thirteen cases of bladder cancer and twenty six cases of prostate adenocarcinoma were evaluated for numerical aberrations of chromosome 1, 7, 10, 11, 17, 18, X and Y utilizing biotinylated probes specific for the alpha satellite region. In two cases from total prostatectomy, one case from total cystectomy and two cases from TUR-P specimen, hybridized chromosomes could not be detected in individual tumor cells. With respect to the appearance of the ISH signal, optical concentration and time for the digestion enzyme has to be established essentially. This technique can now be applied on the detection of biological activity in various types of urological cancer.

Tissue specimens from 12 patients with adenocarcinoma of the prostate and 7 patients with benign prostate hypertrophy were stained by an indirect immunoperoxidase method using antiproliferating cell nuclear antigen (PCNA) monoclonal antibody. The PCNA labeling index was determined by counting the number of PCNA-labeled cells in the tissue sections. Average PCNA labeling index of the benign prostate hypertrophy was 1.2 +/- 0.5%. Poorly differentiated tumors averaged 7.6 +/- 3.9% labeling versus 4.6 +/- 1.3% in moderately differentiated tumors, and well differentiated tumor in the series had a PCNA labeling index of 2.5 +/- 0.9%. The PCNA labeling indices for atypical hyperplasia were 1.9, and 4.1%, respectively. Our preliminary results suggest that the measurement of PCNA labeling index in prostate cancer may prove to be a new objective and quantitative assay of biological potential of individual tumor.

We investigated the effects of intravesical instillation of BCG Tokyo 172 strain on patients with superficial bladder cancer and CIS of the bladder for tumor ablation and prophylaxis. This is the first controlled multicenter study for governmental approval of BCG Tokyo 172 strain for the treatment of superficial bladder cancer and CIS of the bladder. One hundred-fifty-seven patients (125 with Ta or T1, and 32 with CIS) were treated by 80 mg of BCG diluted in 40 ml of saline, once a week for 8 weeks. The dose and interval adopted in this multicenter study was determined by the previous Phase II study conducted by the same Study Group. Out of 125 superficial tumor Ta, T1, 83 (66.4%) showed complete disappearance of the tumor (CR) and 26 (20.8%) partial disappearance (PR), and out of 32 CIS, 27 (84.4%) showed CR and 2 (6.3%) PR. Among those patients showing CR, and PR who were treated with additional TUR-Bt, 98 patients were randomised for a controlled study of prophylactic BCG instillation. Prophylactic treatment consisted of 40 mg of BCG diluted in 40 ml of saline, monthly for 12 months. Forty-two patients were assigned to the treatment group, whereas the remaining 56 to the control group without any prophylactic instillation. Three cases showed tumor recurrence during the prophylactic phase. Twenty-five cases could not be treated for the whole course of prophylactic instillation mainly due to bladder irritable symptoms. Recurrent free curves were compared till 1050 days after the initiation of the study. However, there was no significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term results were analyzed in terms of tumor progression and survival in patients with superficial bladder cancer who were enrolled in the second intravesical chemoprophylactic study of the Japanese Urological Cancer Research Group for Adriamycin, which was started in July 1982. This study was a prospective, randomized, controlled trial conducted on primary tumors treated with a long-term instillation regimen that involved control versus intravesical instillations of Adriamycin or mitomycin C given once a week for the first 2 weeks, once every other week for 14 weeks, once a month for 8 months, and once every 3 months for 1 year, for a total of 21 instillations in 2 years. An analysis of the prophylactic effects of such treatment on bladder tumors after TUR has previously been performed, and the results have been published elsewhere. The present study represents a follow-up of the above trial. Of the 671 cases previously analyzed with regard to tumor prophylaxis, 158 cases (23.5%) were eligible to be followed for tumor progression and survival. A detailed comparison of the background factors between these 158 patients and the other 513 cases revealed no statistically significant difference. Thus, the 158 evaluable cases might reasonably be considered to represent all patients enrolled in the second study, and the results were thought to be reasonable enough to reflect the long-term efficacy of the long-term instillation regimen adopted in this study. The median follow-up for these 158 cases was 6.6 years. Tumor progression in terms of the disease stage and/or grade occurred in 43 of 127 patients who received prophylactic instillations and in 12 of 31 control cases. No significant difference in the incidence of tumor progression was found between the treatment and the control groups. In addition, no difference in survival was observed between the treatment group and the control group. Survival was also compared between patients who showed tumor progression and those who did not. All patients whose tumors did not progress survived, whereas the 7-year survival of those exhibiting tumor progression was less than 90%.

In a cooperative study of the Japanese Urological Cancer Research Group for Adriamycin, the usefulness of chemotherapy with methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC therapy) in treating advanced or recurrent bladder cancer was examined. Evaluation of the clinical responses obtained in 86 evaluable patients revealed 13 complete responses, 29 partial responses, 4 minor responses, 19 cases of no change, and 21 cases of progressive disease. The overall response rate was 48.8% (42/86). The rate of response to M-VAC therapy at each disease site was as low as 21.4% (3/14) in bone lesions but exceeded 40% in the primary lesion, the lymph nodes, the lung, the liver, and other lesions. The clinical response to M-VAC therapy was not significantly influenced by the performance status of the patients, the dose intensity, or previous therapy. The median duration of response for the 42 responders was 22.7 weeks (range, 8.1–134.1 weeks), and the median duration of survival for the 86 evaluable patients was 9.8 months. Side effects were frequently encountered; the patients experienced anorexia, nausea, vomiting, malaise, alopecia, and leukopenia, but all of these symptoms were tolerable.

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)

The authors investigated the influences of recombinant human growth hormone (rh-GH) on rat urinary bladder carcinogenesis induced with N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Rats belonging to the control group (Group I, n = 19) were given 0.05% BBN in drinking water for 9 weeks, and the bladder was excised on the 22nd week after the initiation of BBN administration and inspected. All animals developed visible tumors in the bladder. The mean number of tumors per bladder was 11.26 +/- 5.21, and the mean total volume of tumors per bladder was 126.1 +/- 212.7 microliters. In all but one of the experimental groups (Group V) and in the control group, all animals developed visible tumors in the bladder. When 0.5 units of rh-GH was injected subcutaneously once a week from the week 1 through the week 6 (Group II; n = 20), the mean number of tumors and mean total volume of the tumors were 12.15 +/- 6.59 and 206.6 +/- 318.0 microliters, respectively. When the administration period of rh-GH was changed to between week 7 through the week 12 (Group III; n = 19), the mean number of tumors and mean total volume of the tumors were 16.95 +/- 7.07 and 204.5 +/- 317.7 microliters, respectively. When rh-GH was administered from the week 13 through the week 18 (Group IV; n = 19), the respective values were 16.79 +/- 10.75 and 213.4 +/- 274.6 microliters. In Group V (n = 19), which received only rh-GH from week 1 through the week 6, no tumors were detected. There were statistically significant differences in the mean tumor numbers between Groups I and III, Groups I and IV, and Groups II and III. The mean volume of individual tumor was the greatest in Group II, although the differences were not statistically significant in comparison with the other groups. Histologically, all tumors were transitional cell carcinoma in every group. There were no statistically significant differences in distributions of tumor stage and tumor grade between any groups. These findings suggest that rh-GH enhances the promotion of carcinogenesis of chemically induced rat urinary bladder cancer. It will be necessary to elucidate whether this effect of rh-GH is expressed by the somatostatin hypothesis of GH action, its direct action, or some other mechanisms.

The sonic detection and recording systems of urethral sounds generated during micturition were developed. This procedure was tentatively postulated as "urophonography" and its recording diagram as a "urophonogram". Classification of urophonograms was done on the basis of analyzing normal healthy male volunteers and patients with benign prostatic hyperplasia. Four types of urophonograms were demonstrated according to the shape and characteristics. Types 1, 2, 3 and 4 were characterized by a diamond shape, irregular occurrences of sound spikes, the mixture of Types 1 and 2 and no remarkable sound spikes respectively. Types 1, 2, and 3 were found in BPH, while Type 4 was demonstrated in normal healthy male volunteers. After prostatectomy a high percentage of Type 4 was demonstrated. The frequency (Hz) of these sounds was around 650. Diamond shape sound showed higher value of power gain (dB) than irregular type sound. The wave length was around 0.50 (m). Comparison of urophonographic studies with conventional uroflowmetric investigation was undertaken. Urophonography was useful for investigations of dysfunctional voiding and lower urinary tract obstruction.

A cooperative study of combination of UFT (a compound of FT and Uracil) and human lymphoblastoid interferon (IFN-alpha) was conducted in the cases of metastatic renal cell cancer. IFN-alpha was administered over 3 times a week at a dose of 3 X 10(6) units in combination with UFT at a daily dose of 600 mg FT equivalent. Twenty-eight patients from 16 collaborating institutions were the subjects of the present study. The antitumor effects of the drugs were clinically evaluable in 25 cases according to the response criteria of Japan Society for Cancer Therapy. Complete responses and partial responses were observed in 3 and 2 cases, respectively, showing a response rate of 20 per cent. One complete responder had bone and liver metastases and has been alive for more than 2 years without any evidence of relapse. All of the other responders had lung metastasis. The survival durations of the other two complete responders were 716 days and 255 days. The two partial responders had been alive for more than 819 days and 471 days. The adverse effects of this combination therapy were minimal. Combination of a biological response modifier and a cancer chemotherapeutic agent seems to be a way to increase the treatment efficacy of renal cell cancer.

Fifteen patients with invasive bladder cancer were treated with selective intra-arterial cisplatin and external beam radiotherapy (30.6 Gy over 3 weeks) prior to a planned cystectomy. Cisplatin, in total 200 mg, was administered via bilateral internal iliac artery infusion during the course of radiotherapy. Seven patients were evaluated for local response. Partial response (PR) was revealed in 4, and minor response (MR) in 3. Ten patients received total cystectomy, and pathological effects by the criteria adipted by Japanese Urological Association and The Japanese Society of Pathology, were as follows: Ef. 3 in 1 case, Ef. 2 in 6. Ef. 1b in 1 and Ef. 1a in 2. Down staging was observed in 8 patients from the clinical to the pathological stage. Thirteen patients are alive for 21 months. Two patients have died (1 lung infarction, 1 pancreatic cancer). Though nausea and sciatica-like pain were observed in some cases, there was no severe systemic side effects such as bone marrow suppression and renal toxicity. From these results it is concluded that this therapeutic modality could be effective in the preoperative work-up of candidates for total cystectomy, and also that it could be useful in the treatment of patients in whom total cystectomy is contraindicated.

196 cases with vesicoureteral reflux (VUR) from multiple centers were analysed to examine the relationship between VUR and reflux nephropathy. The high correlation (p less than 0.01) was observed between reflux and renal scarring. Even in cases in whom VUR was not demonstrated at the time of testing, renal scarring of various degrees was recognized, suggesting either co-existed hypoplastic kidney or pre-existed infection. The renal scarring, but not VUR, had a significant correlation with proteinuria and hypertension. Retrospective analysis shows that the surgical treatment was closely related to the degree of renal scarring but not to the degree of reflux. Renal scarring progressed even when reflux did not become worse, which is probably accounted for by the presence of pyelonephritis. Although frequency of pyelonephritis decreased significantly (p less than 0.01) from 0.60 +/- 0.89 to 0.084 +/- 0.305 times/patient. year after anti-reflux surgery, renal scarring progressed in 13 kidneys (5.8%). Seven of the 13 kidneys became worse due to the surgical failure. The scar progression was recognized in the remaining six kidneys (three patients) including adult cases despite the successful surgical correction of reflux. Our study points to the urged need for a prospective clinical trial designed for the study of the pathological and clinical background of progressive renal failure in VUR.

In order to predict the malignant potential of superficial bladder cancer, in 121 patients with this malignancy adenine nucleotide levels (adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate) and energy charge in bladder cancer cells were determined. The nucleotides were analyzed according to the method of Bücher, and the energy charge was calculated by applying the formula of Atkinson. It was clearly pointed out that superficial bladder tumors, which became invasive and/or metastatic, had higher levels of adenylate compounds than those which became not. Our results show that a high correlation exists between adenine nucleotide content and tumor progression.

Forty-six patients with adenocarcinoma of the prostate were given an intravenous infusion of the thymidine analogue, bromodeoxyuridine (BrdU), 200 mg/m2, at the time of needle biopsy or transurethral resection to label tumor cells in the DNA synthesis phase. The tumor specimens were stained by an indirect immunoperoxidase method with anti-BrdU monoclonal antibody. The BrdU labeling index, S-phase fraction, was determined by counting the number of BrdU-labeled cells in the tissue sections. S-phase fraction correlates with the results of histologic tumor grade, Gleason score, and growth patterns. The higher S-phase fraction may indicate biologic malignancy. Moreover, the degree of heterogeneity concerning S-phase fraction distribution within prostate cancer tissue could be evaluated and the findings compared with the morphologic appearance. The authors results suggest that the measurement of BrdU labeling index in prostate cancer may prove to be a new objective and quantitative assay for biologic potential of individual tumors.

Fourteen patients (age range 50-79 mean 64.2) with locally advanced bladder cancer or CIS have been treated with combination of selective intra-arterial infusion of adriamycin (ADM) and/or cisplatin (CDDP) and local hyperthermia, prior to planed surgical resection. The follow-up periods ranged from 33 to 70 months (median 52). Clinical staging was based on biopsy, CT, Echo, chest X-ray, bone scintigraphy, and IVP. The initial tumor stage was Tis in 1 patients, cT2 in 4, and cT3 in 9. Catheterization technique: with the patient in the prone position, the gluteal muscles were dissected to expose the inferior gluteal artery, then catheter was inserted. The tip was wedged in the internal iliac artery below the bifurcation of the superior gluteal artery. ADM 10-20 mg and/or CDDP 10-20 mg were infused once or twice a week, more than eight times during hyperthermia. The total dose of ADM and CDDP were 40-360 mg and 50-360 mg. Local bladder hyperthermia was achieved with a radiofrequency generator. Novatherm IH-500 (Inter-Nova Co. Ltd, Japan). Intravesical temperature was maintained over 40 degrees C for an hour. Surgical resection included total cystectomy (10 patients), partial cystectomy (3) and TUR (1). Of evaluable 8 patients, CR was obtained in 2 patients, PR in 4, NC in 1 and PD in 1. The survival rate (Kaplan Meier method) at 3 years was 71.4% (n = 9) and at 5 years, 62.5% (n = 4). Five patients died, but two of them died of other causes (traffic accident and spinal cord injury). Severe toxicity, consisting of bone marrow suppression (3) perineal erosion (3) and ischialgia (1), was well tolerated. In conclusion, our result suggests combination therapy of intra-arterial chemotherapy and local hyperthermia is safe with minimal systemic side effects, and may prolong survival with invasive bladder cancer.

In order to assess the potential nephrotoxicity of antibiotics, effects of these agents on rat kidney lysosomal membrane were investigated in various conditions. Antibiotics were given to Wistar rats for 5 successive days. After nephrectomy rat lysosomes were separated and their membrane stability was examined by measuring the activities of acid-phosphatase. In addition, after separation of lysosomes from normal untreated Wistar rats, antibiotics were added in the incubation system to assess the in vitro effect of antibiotics. Effects of renal ischemia and the lysosomal membrane stabilizer (cortisol) were also examined. Aminoglycosides antibiotics (streptomycin, kanamycin, gentamycin), doxytetracycline, chloramphenicol, and cephems (cephalothin, cephaloridine, ceftezol, latamoxef) were used for this purpose. It was clearly pointed out that aminoglycosides interfered with the lysosomal stability in vivo and in vitro. After a 60 minutes ischemia of the rat kidneys by clamping the renal arteries, effects of antibiotics on administration of 5 successive days on rat lysosomal stability were investigated. It was demonstrated that aminoglycosides also made the lysosomal membrane more unstable. Effects of the lysosomal stabilizer, cortisol, on rat kidney lysosomes were examined. Use of cortisol simultaneously with an antibiotic was more effective than that before and after it.

In order to evaluate the nephrotoxicity by antibiotics, effects of these agents were investigated in terms of protein synthesis and nucleic acid metabolism in the kidneys of Wistar rats. Aminoglycoside antibiotics (streptomycin, kanamycin, gentamycin), tetracycline (doxytetracycline), chloramphenicol, and cephems (cephalothin, cephaloridine, ceftezol, latamoxef) were used. These antibiotics were given to the rats for 5 successive days. On the 6th day 14C-6-orotic acid and 14C-1-leucine were administered intraperitoneally. Incorporation rates of these tracers into ribonucleic acid and protein fraction in rat kidney ribosomes (polysomes) were measured. Another experiment was undertaken in vitro by separating the polysome fraction from the rat kidneys. In vitro acellular protein synthesis using these polysomes was established. Effects of antibiotics on the incorporation rates of 14C-1-leucine were examined. Marked reduction of incorporation of these tracers into nucleic acid and protein in vivo and in vitro was induced by aminoglycoside antibiotics. These facts suggest that aminoglycoside antibiotics develop nephrotoxicity by interfering with the metabolism of ribosomal RNA and protein.

A group of 8 patients with invasive bladder cancer received fractionated intra-arterial infusions of the thymidine analogue bromodeoxyuridine (BrdU), 150 mg, every 6 to 10 h for 3 days before endoscopic cold cup biopsy to label tumour cells in the proliferative pool (growth fraction). The tumour specimens were fixed and stained by an indirect immunoperoxidase method using anti-BrdU monoclonal antibody. There was an area which could not be stained with anti-BrdU monoclonal antibody surrounding the stained area where diffusion effects could be excluded. This indicates a growth fraction less than 1 and implies that a proportion of the tumour cells in bladder tumours are cycling and contributing to growth. The BrdU labelling index (growth fraction) was determined by counting the number of BrdU labelled cells in the well labelled tissue sections. The average growth fraction of invasive bladder cancer was 38.4 +/- 7.7% (range 26.9-48.1%). Grade 3 tumours averaged 42.8 +/- 5.4% labelling versus 31.0 +/- 4.4% in grade 2. The higher growth fraction may indicate greater biological malignancy. These results indicate that immunohistochemical studies of cell kinetics using BrdU monoclonal antibodies may provide information about the biological characteristics of bladder tumours in situ.

Urodynamic approach to the disorders of the urinary tract has been based on the knowledge of anatomy and neurophysiology of this abnormality. The development of this field included uroflowmetry, cystometry, urethral profilometry, and electromyogram of the external sphincter. In addition to these investigations new trends in urodynamic field were reviewed. With the advent of muscle biochemistry intra-renal urodynamics has been advocated. These researches would be expected to clarify the mechanism of intra-renal reflux. The another investigation was urophonography. When the urine passed through the posterior urethra the urethral sound occurred. The detecting, recording and analyzing systems were developed. This method would be entirely a new method of urodynamic study.

Therapy with proton beam is superior to that with photon beam in concentrating the dose within a lesion. Fifteen patients with urinary malignant tumors were treated by proton irradiation during the period from June, 1985 to March, 1989 at Particle Radiation Medical Center, University of Tsukuba. Four patients were with renal cell carcinoma, five with prostatic cancer and six with bladder cancer. Treatment results were assessed by change in tumor size either three or six months after the irradiation. In all the four cases with renal cell carcinoma, the tumor sizes were found to be unchanged without any enlargement. Of the five cases with prostatic cancer, two showed that the treatment was effective and the tumor sizes in the other three cases were found to be unchanged. In three of the six cases with bladder cancer the tumors disappeared while the treatment was found effective in two other and it did not cause any enlargement of the tumor in the remaining one. Although local control of the tumor was successful in all the cases, one patient with prostatic cancer and three with bladder cancer died of cancer. Various side effects, such as radiation cystitis, were observed. This prospective therapy is expected to replace the conventional photon therapy. However, some improvement is needed to make full use of the advantageous properties in dose distribution. Combination therapy with other general therapy is required for some cases.

Leiomyosarcoma arising from the ovarian vein is extremely rare: only one case was found in the literature. We report a case in a sixty-one-year-old woman who had unexplained attacks of pain in her left lower abdomen and flank for two years.

Myelolipomas are benign tumors composed of mature fat and bone marrow elements. We report a case of adrenal myelolipoma associated with hereditary spherocytosis which was treated with splenectomy seventeen years ago. The hematopoietic stimulus of the hereditary spherocytosis might have been associated with the development of adrenal myelolipoma in the present case.

A case of oncocytoma, the radiological findings of which resembled a hemorrhagic renal cyst, is reported. Cyst fluid analysis demonstrated extremely high levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Preoperatively the lesion was regarded a malignant cyst, and radical nephrectomy was performed. Pathological diagnosis was renal oncocytoma with cystic degeneration. Although cystic change occasionally has been mentioned in oncocytoma, a high level of CEA and CA 19-9 in the cyst fluid of the cystic oncocytoma have not been reported. We discuss the variant forms of oncocytoma and tumor markers in the cyst fluid.

Intravesical Bacillus Calmette-Guérin (BCG) is now a standard treatment for Ta, T1 carcinoma and carcinoma in situ (CIS) of the urinary bladder. In Japan, however, only BCG Tokyo 172 strain is commercially available. We therefore designed a clinical study of PMCJ-9 (BCG Connaught strain) for obtaining approval from Japanese Ministry of Health, Labor and Welfare.In the phase I-II study, PMCJ-9 40.5, 81 (standard dose overseas) or 121.5 mg in saline was instilled into the bladder of patients with Ta, T1 or CIS once weekly for 8 weeks. The recommended dose was decided and similarly administered in the late phase II study.In the phase I-II study, 49 patients were evaluable for efficacy. The complete response (CR) rates were 60.0% (9/15), 68.2% (15/22) and 75.0% (9/12) in the 40.5, 81 and 121.5 mg groups. The incidence of adverse drug reactions (ADRs) was similar in all groups, but four 121.5 mg group patients developed severe ADRs. Thus, 81 mg was the recommended dose for the late phase II study. In that study, 39 patients were evaluable, showing CR rates of 71.8% (28/39) overall and 61.5% (16/26) and 92.3% (12/13) for the Ta, T1 and CIS cases. The safety was assessed in 42 patients and three (7.1%) were discontinued owing to ADRs.The recommended dose for the BCG Connaught strain was decided as 81 mg. PMCJ-9 administration at this dose level weekly for 8 weeks showed a clear antitumor effect and good safety profile against Ta, T1 and CIS transitional cell carcinoma of the bladder.

A randomized, multicenter, double-blind, parallel-group study was conducted in order to evaluate the hormonal kinetics, pharmacokinetics, efficacy and safety of TAP-144-SR (3M) a three-month sustained-release injectable preparation of leuprorelin acetate, a highly active luteinizing hormone-releasing hormone (LH-RH) derivative by comparing the treatment with two subcutaneous doses of the test medication TAP-144-SR (3M) and the treatment with six subcutaneous doses of the reference medication TAP-144-SR (1M), a 1-month sustained-release injectable preparation. Study participants were 103 patients with prostate cancer in whom a stable anti-tumor effect had been obtained with Leuplin Injection 3.75. The hormonal kinetics revealed that the proportion of the patients "maintaining the castration level of serum testosterone (maximum serum testosterone level during treatment below the castration level [100 ng/dl])" was 100% in both treatment groups. With regard to the efficacy, the proportions of the patients in whom the anti-tumor effects (or = Stable) of the baseline treatment prior to the initiation of the treatment with the study medication were maintained during the study treatment period (6 months) were comparable; 84.0% with TAP-144-SR (1M) and 80.4% with TAP-144-SR (3M). On evaluation of the pharmacokinetics, the mean value of AUC1-12w of the serum TAP-144 concentration (including the metabolite M-I) for the treatment with TAP-144-SR (3M) was 77.0% that of the treatment with TAP-144-SR (1M). Adverse events were similar in the subjects on TAP-144-SR (3M) and in those on TAP-144-SR (1M). There existed no big differences in kind, incidence or time of occurrence of adverse events between two groups. TAP-144-SR (3M) showed no clinically relevant findings in particular. These results indicate that one dose of TAP-144-SR (3M) is comparable to three doses of the already approved Leuplin injection 3.75 in serum testosterone level-inhibitory effect, efficacy and safety. Hence, it is considered that TAP-144-SR (3M) is a drug suitable for treatment of prostate cancer over a prolonged period of time.

A total of 465 patients with primary and multiple or recurrent, stages Ta and T1 superficial bladder cancer were included in this randomized multicenter trial to compare the prophylactic effect by 17 times instillation of 40 mg doxorubicin or 40 mg epirubicin with no instillation after transurethral resection of tumor(s). The primary endpoint was first recurrence after transurethral resection. Endoscopic examination as well as urinary cytology was performed in each case every three months. It became evident that the recurrence rate in the doxorubicin or epirubicin instillation arm was lower that in the no instillation arm. Toxicity was mainly restricted to bladder irritation in about 10% of patients in each instillation arm.

A female F344 rat was injected with 2.4 x 10(6) MT-2 cells intravenously at 3 and 4 weeks old, and was mated with a non-infected male rat at the 17th week after injection, when the dam rat contained HTLV-1 provirus in the peripheral blood mononuclear cells as determined by polymerase chain reaction. HTLV-1 provirus was detected in at least 2 out of 9 offspring. This system should be useful for studies on the routes and prevention of vertical transmission and on elimination of once-transmitted HTLV-1.

Thirty-four patients with locally advanced bladder cancer have been treated with selective intra-arterial infusion of CDDP and/or ADM (IA therapy) prior to planned surgical resection. Follow-up ranged from 25 to 108 months (median 61). Initial tumor stage was cT2 in 10 patients, cT3 in 19 and cT4a in 5. Catheterization technique: gluteal muscles were dissected gently along the muscle fiber to expose the inferior gluteal artery with the patients in prone position, then the catheter was inserted. The tip was wedged in the internal iliac artery below the bifurcation of the superior gluteal artery. ADM 10-20 mg and/or CDDP 10-20 mg were infused once or twice a week. Total dose of ADM and CDDP were 40-580 and 60-240 mg. Thirteen patients received IA therapy + hyperthermia and 8 IA therapy + irradiation. Surgical resection included total cystectomy (22 patients), partial cystectomy (3 patients) and transurethral resection of the prostate (5 patients). Survival rate at 5 years is 57.9% (T2 = 90.0, T3 = 52.1, T4 = -). Eighteen patients are alive with no evidence of recurrences, and 11 patients were free of disease for more than 5 years. Side effects were bone marrow suppression (5 patients), vomiting (4), erosion of gluteal skin (7), and neurotoxicity, such as sensory disturbance in lower extremities or ischialgia (2); treatment was well tolerated in others. In conclusion, our results suggest that intra-arterial infusion of ADM and/or CDDP by insertion of catheter from inferior gluteal artery is safe with minimal systemic side effects, and prolongs survival for invasive bladder cancer.

We report a case of nonseminomatous testicular tumor with lymph node involvement and multiple lung and liver metastases. The patient was considered to have a poor prognosis. He received systemic chemotherapy and cytoreductive surgery. Postoperatively a residual metastatic tumor in the liver was treated by intrahepatic arterial cisplatinum-diaminedichloride infusion. Follow-up observation has revealed no evidence of recurrence for 30 months since the last treatment.

Objective It has been reported that blocking of testosterone production inhibits bladder carcinogenesis in various animal models. We investigated how testosterone acts on rat bladder carcinogenesis using an antiandrogen, flutamide, and a 5 alpha-reductase inhibitor, finasteride. Methods Experiment 1: we administered 0.05% BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine] orally to 117 Wistar rats for 10 weeks, divided them into seven groups-control, surgical castration, finasteride (2 mg/kg), luteinizing hormone releasing hormone (LH-RH) agonist (1 mg/kg) flutamide (50 mg/kg), LH-RH agonist plus finasteride, and LH-RH agonist plus flutamide-, and then cystectomized them to investigate the incidence of bladder cancer on week 21; experiment 2: we administered 0.05% BBN to 154 Wistar rats for 7 weeks, divided them into seven groups-control, finasteride 2, 4, and 8 mg/kg, and flutamide 50, 100, and 200 mg/kg-, and then we cystectomized them to investigate the dose-dependent influence on bladder carcinogenesis of these drugs on week 20, and experiment 3: we investigated the presence of androgen receptors in rat and mouse normal bladder mucosa using a monoclonal antibody. Results and conclusions Experiment 1: Surgical castration and LH-RH agonist treatment significantly reduced the occurrence of carcinomas. There was no significant additive effect of coadministered finasteride or flutamide with LH-RH agonist. Finasteride or flutamide monotherapy showed no statistically significant effects on the results of experiment 1 at the doses used. Experiment 2: Flutamide showed a dose-dependent effect on reducing the number of rats with bladder cancer, and at a dosis of 200 mg/kg twice a week, the difference was statistically significant when compared with the control group, whereas finasteride had no statistically significant suppressing effect at any dose. Experiment 3: Mouse and rat bladder urothelium expressed the androgen receptor. Our results indicate that testosterone itself might have a more potent action on bladder carcinogenesis rather than its converting form, 5 alpha-dihydrotestosterone.