Papaverine hydrochloride was administered to the cavernous body of the penis in a total of 262 patients who were diagnosed as impotent at our Reproduction Center, Toho University, during the 5 years' period from 1984 to 1988. The condition of erection was accurately recorded by the use of both a mercury strain gauge and rubber strain gauge to classify the erection curve, and papaverine hydrochloride outflow into the peripheral blood was concurrently measured in some of the cases in order to assess its relation with the erection curve pattern.
As for the concentration of papaverine hydrochloride in the peripheral blood, it was found that the better the state of erection, the smaller the outflow of peripheral blood. An assessment of the relationship of the concentration of papaverine hydrochloride with the classification of erection pattern showed that the amount of outflow was smaller in the N type (normal) pattern and that the amount of outflow was increasingly larger in the following order: A type (arterial), N′ type (arterial and venous) and V type (venous).
The distribution of the erection curve patterns, in the 262 cases was: N type, 45%; A type, 10%; N′ type, 22.5%; and V type, 22.5%.
From the above findings, it is presumed that classification of erection curve pattern under papaverine hydrochloride loading is useful for the differentiation of vascular impotence, particularly for the diagnosis of disorders in the outflow system.

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Hyperthermic treatment was performed in 31 patients with benign prostatic hypertrophy (BPH). Eight patients of them had a urethral catheter because of urinary retention. The prostate was heated transrectally to 43-45°C. The treatment consisted of 10 sessions of 60min. each. To evaluate this treatment, the following parameters were determined before, during and one week after the last hyperthermia session: subjective symptoms score, and residual urine volume, uroflowmetry and transrectal ultrasound of the prostate as objective data. Symptoms score improve in all patients. Of 8 patients with a catheter, the catheter could be removed from 4 patients. There was no significant change in prostate volume, but significant decreases of residual urine volume, and increases of maximum flow rate and mean flow rate were observed. No adverse reactions were seen. Judging from the above results, this treatment is considered to be useful for patients with BPH.

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To our knowledge, the action of estradiol which is produced from testosterone by aromatase on human spermatogenesis has not been fully clarified. In oligozoospermia, with high values of E₂/T ratio, it is considered that the role of estradiol is suppressive to spermatogenesis. In this study, alteration of spermatogenesis was evaluated when serum estradiol levels were decreased by suppression of aromatase activity.
Nine male infertile patients were treated with testolactone (Teslac^®: 1.0g/day, for 3 months), one of the aromatase inhibitors. Four of them had an increase in sperm count (more than 10×10⁶/ml relative to base line).
In endocrinological findings, serum estradiol levels and E₂/free T ratio were significantly decreased after treatment. Serum free testosterone levels were significantly increased in all cases, presumably from decreased sex hormone binding globulin (SHBG) levels. These findings suggested the effectiveness of the administrated aromatase inhibitor. In particular four patients whose sperm counts were improved after testolactone treatment had high values of basal serum estradiol levels and E₂/free T ratio before treatment, and these values were normalized after treatment.
In conclusion we suggest that an aromatase inhibitor may be effective to male infertile patients with high serum estradiol levels.

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Our previous report has shown that the shapes of calcium oxalate crystals formed in a supersaturated solution with glycosaminoglycan varied with glycosaminoglycan species. The present study was conducted to demonstrate the effect of magnesium on the shapes of calcium oxalate crystals with glycosaminoglycan by optical and scanning electron microscopy. In the presence of magnesium, the phenomenon of the plate- or sheet-like crystals parallel growing on the surface of other crystals was observed with each glycosaminoglycan and was enhanced with hyaluronic acid, chondroitin sulfate, heparan sulfate or heparin, more marked in this order. On the other hand, with heparan sulfate or heparin the stratification of the plate-like crystals was observed, whereas with hyaluronic acid or chondroitin sulfate it was not observed. Moreover, the stratification of the crystals with heparin was stimulated more markedly with increasing magnesium concentrations, and the lamella-shaped crystals at low heparin concentrations in the presence of magnesium was similar to the crystals at high heparin concentrations. These results suggest that magnesium stimulates the effect of glycosaminoglycan on calcium oxalate crystal shapes.

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Twenty-two patients with renal cell carcinoma subjected to radical nephrectomy were divided into 2 groups. The first group consisted of patients who received nephrectomy alone, and the second of 10 patients who received pre-operative IFN-gamma. Using monoclonal anti-bodies of each subset of lymphocytes, immunological distributions of tumour infiltrating lymphocytes (TIL) were evaluated by means of immunohistochemical staining and the peripheral blood lymphocytes (PBL) were evaluated by flow-cytometry. Furthermore, immunological effects of IFN-gamma on these immuno-competent cells were investigated.
The effect of IFN-gamma on TIL was an increase in CD3 (pan-T cells), in particular an increase in CD8 (suppressor/cytotoxic-T cells). On the other hand, a significant increase in CD16 alone was found on PBL. As to the TIL according to stages, all subset ratios tended to be higher in high stage patients without administration of IFN-gamma. With pre-admininstration of IFN-gamma, a marked increase in CD3 was found among low stage patients. In examining these cells according to grades, no specific trend was observed between low and high grade patients without having IFN-gamma administration. With pre-administration of IFN-gamma, an increase in CD3 and CD8 was observed in low grade patients. As to PBL, a significant increase in CD16 alone was observed with pre-administration of IFN-gamma, and no correlation was found between stage and grade.
We draw the conclusions that the subsets of TIL were quite different from those of PBL. And in our study with regard to subsets of TIL, its increase of CD3, in particular of CD8 was observed in low Stage and low grade patients after the administration of IFN-gamma. On the basis of these phenomena, it is assumed that IFN-gamma acts for enhancement of antigenecity of renal cell carcinoma with special relationship to TIL, also depending on its stage and grade.

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We reviewed 9 children with unilateral massive (III and IV, Dwoskin-Perlmutter) vesicoureteral reflux associated with congenital mechanical obstruction of the lower urinary tract. Four children with bilateral reflux with bilateral difference of severity more than 2 grades were also included. Obstruction was attributed to posterior urethral valve in 5, anterior urethral stricture in 3 and megaurethra in 1. The chief complaints were febrile episodes and urinary infection, followed by voiding difficulty, bed wetting and/or urinary incontinence and voiding through anus. All 4 children with troubles other than posterior urethral valve had either anorectal anomaly or H-type rectourethral fistula without imperforate anus.
Of the 9 children 8 had massive reflux on the left side. The majority of these left ureters with massive reflux were associated with ipsilateral severe renal hypofunction on scintigraphy. After prompt resolution of obstruction, the majority of these massive reflux did not disappear. Decompression appeared to salvage none of such kidneys. The orifice positions of such ureters were far craniolateral and the resected kidneys showed dysplasia or severe hypoplasia. The prognosis was generally excellent except one child with massive reflux on the right side who progressed to an end-stage renal disease.
The embryogenesis of this “VURD syndrome” was discussed in its relation to the “bud theory” of renal hypodysplasia. It was showed that this syndrome was observable in obstructions other than the posterior urethral valve. Massive reflux appeared to serve as a “pop-off” mechanism to buffer high pressure and to lead to preservation of better renal function. Reflux in children with congenital mechanical obstruction may be the result of 2 different mechanisms. In 1 group that consists mainly of cases with lower grade reflux, due primarily to high intravesical pressures, reflux will resolve following release of the obstruction alone. In the other group that includes cases with abnormal orifice position, reflux will persist following reduction of intravesical pressure. Early nephroureterectomy is advocated.

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Major histocompatibility complex (MHC) antigens and intercellular adhesion molecule-1 (ICAM-1) play important roles in immune response. In order to investigate the association between renal cell cancer (RCC) and host's immune system, expression of MHC antigens and ICAM-1 was examined on RCC. Immunohistochemical analysis revealed a positive correlation between the expression of MHC antigens and ICAM-1. In general, tumor with higher degree of mononuclear cell infiltration expressed MHC antigens and ICAM-1 more frequently and intensely. Among cytokines which were reported to be potent inducers of ICAM-1 on malignant melanoma cell lines, interferon (IFN)-γ and tumor necrosis factor (TNF)-α augmented the expression of ICAM-1 on ACHN cells whereas ICAM-1 and class I antigens on KRC/Y cells. IFN-α enhanced MHC class I antigens but not ICAM-1. Class II antigen expression of both cell lines was augmented by only IFN-γ. These results suggest that cytokines which could be produced by tumor-infiltrating mononuclear cells, especially IFN-γ and TNF-α, might modulate expression of MHC antigens and ICAM-1, and influence host immune response against RCC.

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The DNA ploidy of testicular seminomas was studied by flow cytometry using paraffin embedded samples. The mitotic count and DNA index (DI) for 27 seminomas were analyzed in 80 samples with a mean of 3.0 samples per case. Six anaplastic seminomas which were with 3 or more mitoses per a high power field were distinguished from 21 typical seminomas.
DNA ploidy pattern was aneuploid in all seminomas except one case of anaplastic seminoma, and clonal heterogeneity in DNA content was found in 3 of 20 (15%) cases of which 2 or more samples were analyzed.
Although the DI had no significant difference between those two groups of seminomas classified by mitotic count, the DI in anaplastic seminomas was ranged from 1.5 to 2.0 (median DI=1.70), otherwise the DI in typical seminomas ranged from 1.5 to 3.5 (median DI=1.89), particularly 9 cases in 21 (43%) typical seminomas distributed in hypertetraploid region. The median DI of stage I seminomas was 1.88 and that of stages II+III seminomas was 1.75, though there was also no significant correlation between DI and clinical stages.
In general, it is postulated that the higher DI is paralleled to the more malignant nature of neoplasms, nevertheless this study suggested that the higher DI in seminomas is not always related to high malignant potentiality determined by histological type and clinical stage.

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Concerning with the inhibitory activity of sodium pentosan polysulphate (SPP) on calcium oxalate stone formation, the following three experiments were carried out. 1) The inhibitory activities for calcium oxalate crystal formation, aggregation and growth in vitro, 2) the effects on the deposition of calcium oxalate crystals in rats treated with ethylene glycol, and 3) the effects of oral administration to human subjects on the metastable limit of urinary calcium oxalate and on the inhibitory activity of the urine for calcium oxalate crystal growth.
The results were as follows:
1. The degree of the calcium oxalate crystal formation measured by an aggregometer was decreased by addition of more than 1mM of SPP.
2. The inhibitory activity of SPP on calcium oxalate crystal aggregation was measured using a Coulter Counter. The aggregation was inhibited at a low concentration of SPP (0.02μM).
3. Calcium oxalate crystal growth was measured using a seeded crystal method with [¹⁴C] oxalic acid. SPP inhibited the crystal growth proportionally to the concentration of SPP (0.1μM-100μM).
4. Renal tubular deposition of calcium oxalate crystals was marked in rats that orally received ethylene glycol (0.4%), which was expected to be suppressed by intramuscular administration of SPP (30mg/kg/day or 60mg/kg/day).
5. Oral administration of SPP (500mg/day) to five healthy male subjects for five days resulted a tendency to increase of the metastable limit of the urinary calcium oxalate as measurement by an aggregometer, but the inhibitory activity of the urine for calcium oxalate crystal growth, which was measured by seeded crystal method with [¹⁴C] oxalic acid, showed no variable changes.

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Our method of exfoliative cytology using a prostatic fluid collecting catheter is effective in detecting prostatic carcinoma. To presume histological diagnosis by means of the cytology we analyzed cytological findings of 62 cases of prostatic carcinoma in relation with their biopsy findings, clinical stages and clinical courses.
In cases in which cellular atypism was low in the cytology the carcinoma was mostly well or moderately differentiated. Conversely, in cases in which the carcinoma was well differentiated atypism was mostly low in the cytology. In cases in which the cellular atypism was high the carcinoma was poorly differentiated, and vice versa. The poorer histological differentiation and the higher cytological atypism, the more advanced carcinoma and the higher death rate from the carcinoma. The tendency seemed to be more related with the cellular atypism than with the histological differentiation.
Thus the cytological findings reflect the histology well and the degree of the histological differentiation can be presumed by the cytological atypism. The cellular atypism is not a less important factor than the histologic differentiation degree for determining the clinical stage and the prognosis.

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We reviewed retrospectively the medical records of 70 patients treated for prostate cancer who were followed for more than 10 years or until they died. All patients were treated by hormonal therapy and 54 of 70 patients (77per cent) were combined with castration. Of 70 patients 10 (14.3per cent) are alive now with an average follow up for 180.5 months. Of 60 patients with stage A and B only 3 died of the tumor. Of 56 patients with stage C and D, 10 and 18 patients died of the tumor, respectively. From the point of pathology, none of the patients with well differentiated adenocarcinoma died of the tumor. And in patients with stage A and B, pathologically well and moderately differentiated adenocarcinoma, there were no cancer death. On the other hand, a group of patients of poorly differentiated adenocarcinoma had a poor prognosis. In cases with well differentiated adenocarcinoma who discontinued hormonal medication (diethylstibestrol diphosphate) no patients died of the tumor. From these observations we consider that, after long term hormonal medication, we can stop the hormonal medication for patients who have no positive prostate biopsy results for 4 years with well differentiated adenocarcinoma of stage A and B.

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A chemosensitivity test was carried out on superficial bladder cancers using the trypan blue dye exclusion assay for the purpose of screening chemosensitive drugs for intravesical chemotherapy.
Transplantable murine bladder tumor cells (MBT-2) were incubated, in vitro, in the presence of adriamycin (4, 40, 400, 1000μg/ml) as well as verapamil (3, 30, 100, 500μg/ml) at 5% CO₂, 37°C for two hours. After cellular viabilities were calculated, MBT-2 cells were inoculated into the hind limbs of mice. The cellular viability was correlated well with the ratio of tumor appearance, tumor growth inhibition and prolongation of survival, and was dose dependant in the adriamycin treated groups. On the other hand, a reduction of cellular viability, tumor growth inhibition and prolongation of survival were seen in the high dose verapamil (100, 500μg/ml) treated groups.
Human superficial bladder cancer cells were incubated in the presence of adriamycin, 4′-0-tetrahydropyranyladriamycin, mitomycin C and pepleomycin (1000μg/ml) and/or verapamil (500μg/ml). The reduction rates of cellular viability markedly varied with the kind of anticancer drugs. A reduction of cellular viability of human tumor cells as well as MBT-2 cells was seen in the verapamil treated groups.
This rapid and handy assay seems to be useful for the purpose of screening chemosensitive drugs for intravesical chemotherapy.

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The characteristics of urinary tract infections (UTI), secretory IgA and urine composition of 24 patients (intestine group) who underwent operations using intestinal segments in urinary tract were compared with those of 26 complicated UTI patients without surgical intervention (control group).
No significant differences were found in the frequency of either mono or polymicrobial infections between both groups. However, the frequency of bacterial isolation was different in the two groups, Streptococcus spp. and Providencia spp. were frequently isolated and P. aeruginosa was rarely isolated from the urine of the intestine group compared with from the urine of the control group. Furthermore, in polymicrobial infections of the intestine group with indwelling catheters, E. faecalis and Providencia spp. were frequentry isolated simultaneously.
The mean value of urinary secretory IgA was 94.0μg/dl in the intestine group and 25.0μ/dl in the control group (p<0.0001). The mean urinary osmolarity was 370mOsm/kg in the intestine group and 500mOsm/kg in the control group (p<0.005). The other parameters, including urinary pH and urea N concentration, showed no statisticaly significant differences.
These findings suggest that urinary tract constructed from intestinal segments differs from the urinary tract without surgical intervention in the feature of UTI and anti-bacterial defense mechanisms.

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Clinicopathological studies were made on 105 patients with renal cell carcinoma who visited us from January 1978 to August 1989. The results were as follows:
1. Overall 3, 5 and 10-year survival rates were 60.4%, 49.8% and 44.5%, respectively.
2. Patients in Robson stage I survived longer than those in stage III, and patients in stage II survived longer than those in stage IV with a significant difference.
3. A significant difference did not exist between patients in stages lower than pT2 and those in pT3a, while patients in pT3a survived longer than those in stages higher than pT3b.
4. Patients with grade 1 tumors survived longer than those with grade 2 tumors, and patients with grade 2 tumors survived longer than those with grade 3 tumors with a significant difference.
5. Patients with clear cell subtype survived longer than those with granular cell subtype and mixed subtype with a significant difference, while a significant difference did not exist between patients with granular cell subtype and those with mixed subtype.
6. Patients with INFα tumors survived longer than those with INFβ tumors with a significant difference. There was the same significant difference in patients with grade 2 tumors.

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The efficacy of maintenance bacillus Calmette-Guerin (BCG) instillations for superficial bladder tumors was studied by prospective randomized trial. From June 1985 to October 1988, 42 newly diagnosed patients with superficial bladder carcinoma (pTa or pT1) were treated by transurethral tumor resection and subsequent five daily instillations of mitomycin C. Then they were divided into non-maintenance group (22 patients) and maintenance group (20 patients) by randomization. The patients received six weekly instillations of 80mg of BCG, Tokyo strain (Japan BCG manufacturing Co., Tokyo, Japan), suspended in 40ml of physiological saline, and the patients in the maintenance group received four additional instillations of BCG every three months. We could not complete the six-week course of BCG Instillations in three patients due to adverse effects (two in non-maintenance group and one in maintenance group) and we lost six patients from follow-up within one year (one in non-maintenance group and five in maintenance group). The mean follow-up period of the remaining 33 patients was 28.1 months. Of these 33 patients, six patients had been found to have recurrent tumors, and the over-all three-year non-recurrence rate was 82%. Before employing BCG, when we used only mitomycin C after TUR-Bt, the three year non-recurrence rate was 58%. This indicates prophylactic effect of BCG instillations. The stage of the initial tumor of the six recurrent cases were all pT1b. The non-recurrence rate of the patients with pT1b tumor was significantly lower than that of the patients with pTa and pT1a tumor. However, multiplicity and grade of tumors did not affect the non-recurrence rate. In the 33 patients two had recurrent tumors at the initial cystoscopy just after the six-week BCG instillations, and were excluded from the study between the non-maintenance and maintenance groups. The three-year non recurrence rate of the non-maintenance group (18 patients) was 83%, while the rate of the maintenance group (13 patients) was 94%. There was no significant difference in non-recurrence rate between these two groups. These results indicate that maintenance BCG instillation have little additional prophylactic effect after the six-week BCG instillations.

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Testicular germ cell tumors obtained from 44 patients were immunohistochemically studied using anti-neuron specific enolase (NSE) antibody. The level of NSE in the serum was also measured in 9 patients before and after extirpation of the tumor.
As for tumor cells of seminoma, 19 of 20 pure seminomas and all 9 of mixed type were positive for NSE. On the contrary, a spermatocytic seminoma was NSE-negative. As for embryonal carcinomas, some tumor cells were NSE-positive in 13 of 15 of mixed type. In yolk sac tumor, a few tumor cells were also NSE-positive in 8 of 21 of both pure and mixed types. Some NSE-positive cells were found in teratomatous components of 10 of 14 mature and immature teratomas of both pure and mixed types. These were in neural cells, chondrocytes, and glandular epithelial cells. Spermatogonia in 5 normal testes were NSE-positive.
NSE level in the serum was elevated before extirpation and decreased after extirpation in 4 of 5 cases of seminoma of pure type and in 1 of 2 of mixed type which included seminomatous elements. All of these cases were either in the advanced stage or had a rather large primary tumors.
Immunohistochemical study of testicular germ cell tumors using anti-NSE antibody may facilitate histological diagnosis, and serum NSE level may be useful for monitoring the clinical course as well as for clinical diagnosis of seminoma.

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This paper describes a new technique and preliminary clinical results of remote after-loading transurethral irradiation for cancer of the prostate. As of January 1986, twelve patients with adenocarcinoma of the prostate have been treated by our radiotherapy technique. Clinically, 3 patients were in stage B2, 3 in stage C, 3 in stage D1 and 3 in stage D2. These patients have been followed up for 13 to 33 months with a median follow-up period of 20.6 months. The dose of transurethral irradiation was 9-10Gy. to the prostatic capsule and about 2Gy. to the rectum in one procedure. We repeated this radiotherapy 3 to 4 times within an about 1-month period. Three patients in stage D1 and one patient in stage C received an additional external beam radiation (40Gy.) to the entire pelvis. A needle biopsy was also performed every 4-6 months after irradiation.
Local tumor response proved rapid and satisfactory as verified by a rectal examination and ultrasonography. The biopsies revealed a 70% negative rate within one year. The most common side effect was transient frequency observed in 7 patients. Severe complications such as incontinence, urethral stricture, or proctitis were not evident. This study suggests that intracavitary irradiation of cancer of the prostate is effective and safe. This method may have wider application.

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A case of malignant fibrous histiocytoma (MFH) of the urinary bladder was presented. A 59-year-old man visited our hospital with a chief complaint of gross hematuria with clots. Intravenous urography revealed a filling defect on the left side of the bladder. CT scan demonstrated that the tumor invaded the bladder wall deeply. The histology of the biopsy specimens obtained by TUR was suspected to be transitional cell carcinoma. Bleeding from the bladder was so severe that a lot of units of blood transfusion were required in order to compensate for anemia before total cystectomy was performed. The tumor was hemispheric, moderately demarcated, measuring 5.5cm×4.0cm×5.5cm, and located at the posterior wall. The histological diagnosis was malignant fibrous histiocytoma, inflammatory type, with venous invasion of tumor cells. Postoperatively, the patient received 5 courses of combination chemotherapy of adriamycin (100mg/body, day 1) and dacarbazine (400mg/body, day 1-5). He is alive with no evidence of local and metastatic disease 24 months after operation, in spite of the poor prognosis predicted from the histological findings.
MFH of the urinary bladder is very rare. We also made a brief review of prior reports on this disease.

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