The effects of a high fat diet on progression of minimal cancerous lesions to manifest ones were investigated using a chemo-endocrinical carcinogenesis model of rat prostate. Male Fischer 344 rats were alternatively given a diet containing 0.75ppm of ethinyl estradiol (EE) for 3 weeks and the basal diet without EE for the following 2 weeks, and subcutaneously administered with 3, 2′-dimethyl-4-aminobiphenyl (DMAB) at 50mg/kg body weight 2 days after the diet with EE was changed to the basal one. This sequential treatment was repeated 10 times in 50 weeks, and the animals were fed with either normal fat diet (NF) or high fat diet (HF) during the following 30 weeks. At week 80, all the rats were sacrificed for histological examination of the prostate. Atypical hyperplasia and adenocarcinoma were induced in 15.4% (4/26) and 34.6% (9/26) in the rats fed NF and 44.8% (13/29) and 20.7% (6/29) in those group fed HF, respectively. The incidence of adenocarcinoma was significantly higher in the group fed NF than in the other. However, the number of rats with either atypical hyperplasia or adenocarcinoma was not significantly different between the two groups. These observations provided no supporting evidence that high fat content in diet has enhancing effects on prostatic carcinogenesis. Using different species or strain of rats, C3H/He mice and ACI/Seg rats, additional experiments were also conducted by a slightly modified protocol without changing on fat contents. Although ACI/Seg rats were known to spontaneously develop prostate cancer, the histopathological examinations revealed atypical hyperplaisa at 25% (16/64) in mice and microadenocarcinoma at 8.1% (6/74) in rats. Apparently further studies are needed until a more useful and efficient model of prostate carcinogenesis is established.

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We experienced 32 cases of occupational uroepithelial cancer at Jichi Medical School Hospital from 1974 to 1990. All of them were dyestuff workers who had been engaged in production or handling of benzidine, β-naphthylamine or α-naphthylamine. In these 32 cases, upper urinary tract tumors were found in 7 cases, one of these having bilateral lesions.
The mean age when the tumor of the urinary tract was first disclosed was 48 years old, with a range of 36 to 66 years old. The mean age of this occupational group was about 16 years younger than that of the spontaneous urinary tract tumor group in our hospital.
We divided our cases into two groups according to duration of carcinogen exposure; less than 5 years and 5 years or more. However we did not obtain significant difference in the grade of tumors or prognosis between the two groups.
But when we divided them into two groups according to the type of work; production group and handling group, 18 of 21 production workers had high grade tumors. On the other hand, only 3 of 11 handling workers had high grade tumors, which was a significant difference. Besides, 10 of 21 production workers or only one of 11 handling workers were fatal. The difference was also significant.
There was no significant correlation among the type of work, the duration of exposure and the age of onset.
In our study, we showed that the type of work was quite important to predict the grade of tumors and the prognosis in occupational uroepitherial cancer patients.
Our data indicate that close observation is necessary especially for the group of workers who had been engaged in production of carcinogenic aromatic amines.

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Recently it has been known that the active form of vitamin D, 1α, 25-dihydroxyvitamin D (1α, 25-(OH)₂D), plays some immunological roles in controlling cell differenciation and carcinogenesis. Moreover, 1α, 25-(OH)₂D is said to have some effects in the changes of several numbers of oncogenes.
In this study, the serum concentrations of 1α, 25(OH)₂D and 25-hydroxyvitamin D (25-(OH)₂D) were measured in 30 patients with renal cell carcinoma. The two vitamin D metabolites were separated and purified using high performance liquid chromatography, and each fraction was subjected to competitive protein binding assay using vitamin D deficient rat serum for 25-(OH)₂D and chick embryo intestinal receptors for 1α, 25-(OH)₂D as the binder.
The average concentration of serum 1α, 25-(OH)₂D was 28.9±5.2pg/ml for controls whereas the average in patients with renal cell carcinoma was 19.7±5.9pg/ml. The concentration of 1α, 25-(OH)₂D was significantly lower in the patients with renal cell carcinoma compared to in the controls (p<0.01). The average concentrations of serum 25-(OH)₂D had no significant differences between the two groups.
Comparison between the stage I+II and stage III+IV, T1+T2 and T3+T4, rapid type and slow type groups showed that the average serum 1α, 25-(OH)₂D concentrations was significantly lower in the stage III+IV, T3+T4, and rapid type groups compared to the other groups (p<0.01, p<0.05, p<0.01). And besides there were no significant correlations between the concentration of serum 1α, 25-(OH)₂D and creatinine clearance in patients with renal cell carcinoma.
Taken together, it is suggested that the serum concentration of 1α, 25-(OH)₂D is in some way correlated with the progression of renal cell carcinoma.

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We treated ten patients with carcinoma in situ of the bladder (primary type, 6 and secondary type, 4) by intravesical bacillus Calmette-Guerin therapy. All patients received 8 weekly instillation, and among them 3 patients were followed by additional instillation monthly for 7 months. Complete regression (negative biopsies and cytology study) was observed after 8 weekly instillation in all patients.
To elucidate the mechanism of action of BCG on carcinoma in situ, the biopsied specimens after BCG instillation were examined light and electronmicroscopically. It was speculated that BCG might act on cancer cells in two ways: one was sloughing and denudation of the cancer cells by acute tuberculous cystitis, and the other was a role of the macrophages through immune reaction.
In our study, the toxicity and complications seemed to be much severer than previously reported. Vesicoureteral reflux was observed in 6 patients. Decreased bladder capacity noted in all patients, among them radical cystectomy and colocystoplasty were performed in 2 patients under the diagnosis of bladder contracture.
Although complete regression was observed in all patients after 8 weekly BCG instillation, the duration being free from cancer cells was variable. And we also discussed on the additional therapy in such patients in the literature.

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Our induction immunosuppressive therapies were carried out on patients split into three groups. The first group of 25 recipients were treated with regimen I [cyclosporin (CsA); 12mg/kg/day and prednisolone (Pred)]. The second group of 16 recipients were treated with regimen II [CsA; 6mg/kg/day, Pred and mizoribine (MIZ) or azathioprine (AZA)]. The third group of 14 recipients were treated with regimen III [CsA; 10mg/kg/day, Pred and MIZ or AZA].
There was no significant difference among the three groups in renal function three months after renal transplantation. The frequency and grade of rejection were significantly higher in Group II than in the other groups. One of group I had CsA nephrotoxicity and none of group III had liver dysfunction three months after renal transplantation. Group I had a higher incidence of posttransplant hypertension. Hypertension of group I was very severe.
We concluded that the triple-drung therapy on group III was the best induction immunosuppressive therapy after renal transplantation of the above three.

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We report our experience with the endourological treatment of 4 patients with 5 benign ureteroileal anastomotic strictures after ileal conduit urinary diversion. The treatment was successful in 4 of the 5 renal units without restenosis with a mean follow up of 10 months. The strictures were dilated by ureteral dilators and/or balloon dilation catheters using guide wires through percutaneous nephrostomies in an antegrade fashion. A 9 or 12 Fr. percutaneous splint catheter or a 12 Fr. double pig tail catheter was placed for 3-8 weeks after a successful dilation. Two renal units underwent repeated dilations. In 1 renal unit, a guide wire was hardly passed through the stricture and the treatment was unsuccessful. No serious complications were encountered. Percutaneous endourological managements of ureteroileal anastomotic strictures seemed to be quite versatile techniques which should be tried as the initial approach in many cases.

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Experiments were performed to elucidate the effects of stimulation of the olfactory tubercle on the urinary bladder and external urethral sphincter in 31 dogs anesthetized with ketamine and α-chrolarose and immobilized with gallamine. The hypogastric nerve was severed in all dogs, and the bladder was filled with Tyrode's solution under constant pressure (15-20cmH₂O).
The outflows of the pelvic vesical branch (PV) and the pudendal urethral branch (PU) and isotonic vesical contractions were recorded simultaneously.
Stimulation (5-100Hz, 3msec, 0.2mA) was applied through a unipolar platinum electrode (50μm, in diameter) inserted into the olfactory tubercle from the ventral surface.
Olfactory tubercle stimulation elicited PV excitation (bladder contraction) and concomitant PU inhibition (urethral relaxation), but no reverse effect.
Electrical stimulation was applied to the excitatory points at varied frequencies (5-100Hz). PV excitation and bladder contraction were produced at 10, 20, 50 and 100Hz, but not at 5Hz.
In another group, the vesicopressor pathway from the tubercle was investigated by partial sectioning of the brain stem in dogs from which the left fore- and mid-brain had been previously removed. The vesicopressor response induced by tubercle stimulations was not abolished by sectioning of the medial preoptic area, medial hypothalamus or periaqueductal grey, but was abolished by sectioning of the lateral preoptic area, lateral hypothalamus or ventral mesencephalic tegmentum, respectively. At the rostral pontine level, the response was abolished by partial sectioning of the lateral part of the pontine reticular formation ipsilateral to the stimulation.

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We studied 31 patients with bidimensionally measurable metastases of urothelial cancer who were treated with a planned regimen (20mg/m² methotrexate, 0.6mg/m² vincristine, 500mg/m² cyclophosphamide, 20mg/m² adriamycin, and 30mg bleomycin on day 1, and 50mg/m² cisplatinum on day 2) in cycles given every 3 weeks. CR was achieved in 4 patients (13%) and PR in 17 patients (55%). The response rates according to the disease characteristics were 71% for TCC, 33% for SCC, 67% for renal pelvis tumors, 67% for bladder tumors, 73% for lung metastases, 67% for liver metastases, and 67% for lymph node metastases. The median response duration and the number of cycles of therapy were 32 months/3 cycles for patients with a CR and 6 months/6 cycles for those with a PR. The median duration of survival was 32 months (range: 3-46) in CR, 11 months (range: 1-37) in PR, and 6 months (range: 2-10) in non responders (NC+PD). A significant prolongation of survival was noted in patients with either CR (p<0.01) or PR (p<0.05). Then main toxic effects were pulmonary fibrosis and myelosuppression. Two patients aged 73 and 81 died of pulmonary fibrosis. However, it was possible to prevent pulmonary fibrosis by not administering bleomycin to patients over 70 years of age, or to patients with pulmonary dysfunction. WBC count nadirs of <2, 000/m³ were noted in 22 patients (71%). Platelet count nadirs of <5×10⁴/mm³ were noted in 7 patients (23%). However, there were no deaths due to myelosuppression.

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Topography and histological types of main tumor and satellite tumor nodules (STN) were investigated on 60 cases of renal cell carcinoma by gross and microscopic study by making whole area histological sections.
30-100 histological slides were made from the median sagital section and multiple horizontal sections of renal cell carcinoma.
STN were observed in 28 cases of the 60 cases (46.7%) and could be classified into 3 types according to their location relative to the main tumor. STN could not be observed in some cases despite the large main tumor of 10cm or more, while STN were observed in some cases with the main tumor of only 2.5cm or less. High grade and high stage cases showed a high incidence of STN. It is considered that, only in cases, with the tumors of low grade, low stage and has only 1 STN or less, conservative surgery on renal parenchyma is possible. When the case is of low grade and low stage and has a possibility of preserving normal renal parenchyma, conservative surgery on renal parenchyma may be justified even if the tumor is large.
But the question has been raised whether the conservative surgery of renal parenchyma should be done at the risk of operative difficulty compared with nephrectomy, postoperative management, and local recurrence of the tumor.
Meanwhile further study may be required as to whether or not tumor thrombus should be dealt with similarly to STN.

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The clinical state of bacteriuria and its correlation with pyuria and symptomatic genitourinary tract infection (GUTI) were studied in 42 renal transplantation recipients who were followed up in the Kidney Center of Tokyo Women's Medical College over 6 months and who showed bacteriuria more than 3 times between January and December in 1987.
The results were as follows.
1) Of the 42 recipients, bacteriuria was found less than 5 times in 19 patients, 6 to 10 times in 18 patients and more than 11 times in 5 patients. There was a tendency for the same bacteria to be isolated several times from the same patient. The most commonly isolated bacterias were Enterobacter, Enterococcus, Serratia and E. coli.
2) Bacteriuria was accompanied by pyuria in 33 patients (79%) and by symptomatic GUTI in 12 patients (29%). Bacteriuria without pyuria was shown in 9 patients (21%) without symptomatic GUTI and it was suggested that bacteriuria did not result in graft hypofunction after two years.
3) Of 16 patients with bacteriuria accompanied by pyuria, symptomatic GUTI occurred in 9 patients (56%). Of these, one patient was found to have VUR of the transplanted kidney, another was found to have VUR of the native kidney, and a third patient died due to interstitial pneumonitis presumably as a result of overimmunosuppression.
Transplantation recipients with bacteriuria accompanied by pyuria develop symptomatic GUTIs frequently and should be treated with proper antibacterial agents. When bacteriuria continues, further examination should be performed for an organic disease of the urinary tract or an overimmunosuppressed state. When a patient shows bacteriuria without pyuria, chemotherapy is not needed and it is sufficient to observe the course carefully.

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Continuous monitoring of penile rigidity and tumescence has been proved to be of use for accurate diagnosis of erectile impotence, since it provides objective recording of penile rigidity as well as circumferential expansion. Prior to clinical use of this procedure in Japan, a study was performed to clarify normal features of nocturnal penile tumescence of Japanese and to ensure safety of this procedure. The subjects consisted of 16 normal volunteers, aged from 24 to 44 years. With fully informed consent of the volunteers, nocturnal penile rigidity and circumferential expansion were simultaneously measured for three consecutive nights by means of RigiScan at the base of the penis (base) and at about five milimeters proximal to the coronary sulcus (tip). The minimum circumference of the penis was 62.7±4.6mm (mean±SD) at the tip and 65.4±9.3mm at the base. The maximum circumference, which meant full erection in the normal volunteers, was 102.5±14.2mm at the tip and 108.6±14.7mm at the base. The mean duration of tumescence, i. e. circumference expansion more than 10mm, was 23.0±6.9 minutes at the tip and 38.3±12.0 minutes at the base. The mean rate of episodes of circumference expansion more than 10mm was 0.75±0.27 per hour at the tip and 0.70±0.26 per hour at the base. The maximum rigidity lasting more than 10 minutes was 82.9±10.1% at the tip and 85.4±8.4% at the base. Out of the 16 volunteers, 10 felt discomfort at the last episode of full erection on the penis where the loops were placed. Since the discomfort followed after several episodes of full erection, it did not disturb the assessment of penile rigidity and tumescence. None of the subjects made an error in operating the instrument. With its ambulatory character and safety, the RigiScan will be of use for diagnosis and treatment of patients with erectile impotence.

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Intracavernous administration of papaverine is now commonly employed for diagnosis and therapy of impotence. To assess the pharmacokinetics of papaverine, we recorded its concentration in peripheral blood and also in cavernous blood after intravenous and intracavernous injection of 40mg of papaverine. Peripheral blood was sampled serially after injection. Plasma was immediately extracted and then kept at at -40°C until analysis. High pressure liquid chromatography was used to record the concentration of papaverine.
The maximum serum concentration of papaverine measured after intracavernous injection was 7.7ng/ml, which was considerably lower than the average serum concentration of 24.0ng/ml after intravenous injection. Peak serum concentration was reached 1min after intravenous injection and 10min after intracavernous injection. It is clear that the corpus cavernosum constitutes a separate pharmacokinetic compartment. Therefore there was no significant difference between the papaverine concentration in peripheral blood of patients who showed full erection after intracavernous injection and that of patients who did not achieve erection. The concentration of papaverine in the intracavernous blood of a fully erected penis was only about 1 microgram/ml after 20min. This concentration is similar to that in cavernous blood of those who showed excessively persistent erection.
Our results imply that papaverine administered into the cavernous space relaxes smooth muscle, and is then washed out to general circulation, and the concentration in the cavernous space reaches a low level of about 1 microgram/ml. The low concentration level is maintained for several hours during erection. Therefore, we presume that papaverine acts on both the inflow system and smooth muscle of cavernous tissue in the phase of producing erections. However, in the phase of maintaining erection, papaverine acts on the smooth muscle of cavernous tissue to reduce the outflow. We can not evaluate the inflow function or corporeal veno-occlusive function of the penis by the papaverine test a lone.

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Most of the previous publications have focused mainly on structural atypism (SAT) or differentiation in the studies on histopathological findings of prostate carcinoma. We studied nuclear anaplasia (NAN) as well as SAT in prostate carcinoma, comparing with differentiation grade or Gleason's pattern, to find NAN's clinical implication. We also compared histopathological findings of prostate carcinoma in our cases with those in U. S. A.
Analysis of NAN grade and SAT grade distribution in stages revealed a correlation between the grades and the stages, in which SAT1 or NAN1 decreased while SAT3 or NAN3 increased in their frequencies as stage progressed. A similar correlation was found between ‹SAT+NAN› grade and stage.
While NAN grade and SAT grade agreed with each other in 70% of the patients with prostate carcinoma, that was not the case in the remaining patients. This suggested a complementary relationship between NAN grade and SAT grade in some patients. A similar relationship was found between NAN grade and Gleason's pattern. These results suggest that, in a non-negligible number of patients, the NAN grade does not agree with the SAT grade or Gleason's pattern which is defined by atypism in the glandular structure.
Disease-specific survival in each SAT grade could be further defined by the NAN grade. For example, in both SAT2 and SAT3, NAN3 tended to have a poorer prognosis than NAN2. Thus, NAN grading system would furnish more accurate information to predict the patients' clinical course.
Prostate carcinomas in our series had a higher frequency of moderately or poorly differentiated type or Gleason's sum than those in the ACS study or the VACURG study. These results indicate a more malignant tendecny of prostate carcinoma in Japan

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During 2 years and 7 months from June, 1985 to December, 1987, a randomized multi-center trial of PVB, VAB-6, BVP regimen (group A) without etoposide versus PEB chemotherapy (bleomycin, etoposide and cisplatinum) (group B) was given to patients with disseminated testicular tumors. Of 34 patients registered, 10 patients were with minimal disease in stages IIA, IIIO and IIIA and 24 with extensive disease in IIB, IIIB2 and IIIC. Seminomas were found in 10 patients, while non-seminomatous tumors in 24. Among groups A and B, there was no statistical difference in clinico-pathological profiles. A group patients were given either PVB, VAB-6 or BVP according to the physician's discretion.
In groups A and B, 35% and 43% of the patients achieved complete response, and 45% and 50% achieved partial response, respectively. The difference in CR rates among both groups was not statistically significant even when calculated according to the stage or histologic grouping. Salvage treatments mainly with surgical resection of residual tumors after the chemotehrapy, however, were more successful in group B (88%) than group A (61%). It appears likely that the higher response of induction chemotherapy in patients with extensive disease made the salvage surgery more successful in group B than in group A. The 3 year survival rate was 100% in group B, whereas it was 76% in group A. Although the incidence of myelosuppression and alopecia was significantly higher in group B, neuropathy was significantly more frequent in group A. From the above results, PEB seems to be a better induction chemotherapy than the conventional one for advanced testicular tumors.

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Fibronectin (FN) is a high molecular weight glycoprotein widely distributed in the body and has a number of biological activities. Recently, there have been reports on the relationship between plasma fibronectin (pFN) levels and malignant diseases, but the significance of pFN is still unclear.
Using immunoturbidimetric assay, we measured pFN levels of 24 healthy controls and 61 patients with urological malignant diseases, and obtained the following results.
1. pFN levels before treatment.
1) pFN level was 379±60.6μg/ml and 356±123.7μg/ml in the healthy controls and patients, respectively. There was no significant difference.
2) pFN level in patients with metastases was 320±92.9μg/ml and had no statistical difference as compared with patients without metastases (371±132.7μg/ml) and controls, despite the decrease in the mean value.
3) pFN level in patients with poor prognosis (300±107.8μg/ml) was significantly lower than that in patients with good prognosis (410±157.2μg/ml) and controls (p<0.05).
2. pFN levels during conservative treatments for advanced disease.
pFN level in patients with a rapid progressive disease (287±64.4μg/ml) was significantly lower than that in patients with a slow progressive disease (327±43.3μg/ml) (p<0.01).
These data suggest that low pFN level predicts rapid progression of the disease and poor prognosis in patients with a urological malignant disease.

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We present a case of bilateral synchronous renal cell carcinoma treated with surgical enucleation.
Urological consultation was asked to evaluate masses of the kidneys, which were detected during a diagnostic imaging on a 58-year-old man with hepatic disorder.
Excretory urograms showed definite bilateral upper pole renal masses. Bilateral selective renal angiograms disclosed neovascularity in the small masses.
Surgical enucleation of the left renal tumor by a flank approach was performed. The surgical specimen being 3.5 by 2.5 by 2cm (29g) was pseudoencapsulated and was identified renal cell carcinoma of the clear cell type, grade 1. INF_α, pathologically.
Seven weeks after, a pseudoencapsulated tumor of 3 by 2.5 by 2cm (16g) in the right upper pole was removed by simple enucleation. The pathological diangosis was renal cell carcinoma of clear cell type, grade 2, INF_α.
The patient is well without evidence of recurrent or any residual disease at 21 months after the second operation. Renal function remains with in normal limits (CCr 110ml/min).
Of our collected cases of bilateral synchronous renal cacinomas treated by bilateral conservative surgery, clinical data are available for 11. Includingour case, a total of 12 cases are reviewed.

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Menkes' kinky hair disease is a poor prognostic congenital disease with X-linked recessive inheritance. This disease is clinically characterized by seizures, friable hair, growth failure, mental retardation and others. Recently it has been known that this disease is also characterized by multiple diverticula of the bladder and other urological abnormalities. A 6-year-old boy was diagnosed as having Menkes' kinky hair disease at another hospital several weeks after birth because of seizures, friable hair and low serum copper level. He voided by Credè's maneuver by the nurse because he could not void for himself. He was referred to our hospital for macrohematuria and micturition pain on October 8, 1989.
Right renal staghorn calculus and multiple diverticula of the bladder were found by roentgenographic examination. He has been treated conservatively after discharge because of his poor condition.

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