Fourty-seven patients with advanced stage D adenocarcinoma of the prostate were treated with the combination of vincristine, ifosfamide and peplomycin (VIP therapy).
Of these patients, 34 were refractory to prior hormonal therapy and 22 (64.7%) achieved an objective response (9 partial, 13 stable) using National Prostatic Cancer Project criteria in United States. In the patients of objective response, the response lasted from two to forty-three months with a median duration of 6.3 months.
Disappearance or significant decrease in bone pain was observed in 19 of 26 patients (73.1%). The survival period of the responders was significantly longer than that of the nonresponders (p<0.005). Moreover, among 13 patints who had not previously received hormonal therapy, eleven achieved an objective response (5 partial, 6 stable) for a 84.7 per cent reponse rate. The toxicity of VIP therapy was mild to moderate. We consider that VIP therapy is one of the most useful regimen for the treatment of the advanced adenocarcinoma of the prostate.

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Localization of prostatic acid phosphatase (PAP) in the prostatic tissue was observed by immunohistochemical techniques. Anti-PAP antibody was obtained from rabbits immuninized with purified PAP that was derived from human ejaculate. Immunohistochemical techniques were carried out by direct and indirect immunoperoxidase methods.
In 20 cases of adenomatous prostate, positive reactions against PAP were recognized on glandular epithelial cells and luminal secretions. Positive materials were observed as granularfashioned matters in the cytoplasm of glandular epithelial cell and accumulated at the apical area of cell.
Localization of acid phosphatase (ACP) activity in the adenomatous prostatic tissue was also investgated by the conventional method of Gomori. The site of ACP by enzymatical reactions were the same as that by immunohistochemical findings. But stronger reactions were seen in the basal part of some glandular epithelial cells by Gomori's method. These findings were suggested to represent lysosomal ACP activity.
In 20 cases of prostatic cancer, localization of PAP was observed as granular-fashioned matters in cytoplasm of cancer cells but it differed to the findings of adenomatous tissue. Positive reactions were also detected in the tissue of primary as well as metastatic prostatic cancer fixed by formalin, embedded in paraffin, cancer grades were classified according to the method of Gaeta. These were compared with the pattern of PAP stains. The results were as follows:
In propotion to cancer grade, (1) PAP localization tended to lose its polarity in cancer cell especially at the apical area, (2) concentration of PAP varied increasingly from cell to cell, and (3) irregularity of PAP positive granule was depicted in terms of its size and shape in the cancer cell.

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In order to investigate the abnormality of the coagulation and fibrinolysis system in the bladder tumor, serum fibrinogen, serum FDP and urinary FDP of 44 bladder tumor cases (BT group) were measured and compared with 120 cases of benign urological diseases (control group). Subsequently, 4 bladder tumor cases were histochemicaly examined using FITC conjugated anti human fibrinogen serum in order to investigate local fibrin deposition. The summary of the results is as follows:
1. Mean urinary FDP level was correlated with the degree of pyuria and hematuria in both BT and control groups. When comparing at different degrees of pyuria and hematuria, the mean urinary FDP levels were always higher in the BT group than in the control group. This indicates that a part of urinary FDP originated in the bladder tumor.
2. The positive rate of urinary FDP in relatively clear urine samples was 65.5% in the BT group and 9.1% in the control group. Urinary FDP was proved to be a useful tumor marker for the bladder tumor, especialy in screening and following up after TUR.
3. The mean serum fibrinogen and FDP levels were higher in the BT group than in the control group. But serum fibrinogen or FDP levels were not correlated with urinary FDP levels. It was estimated that urinary FDP in bladder tumor patients did not originate in general abnormality of the coagulation and fibrinolysis system, but in local one.
4. The fibrin deposition was observed in the connective tissue around the bladder tumor. It may explain the origin of urinary FDP.
5. It seemed that the fibrin deposition was most intense at the deep infiltrative parts of the high grade tumor, although further investigation using tumors of different grades, stages or infiltration modes was necessary.

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The effect of fibrinolytic and antifibrinolytic agents on the BBN induced rat bladder tumor was studied. The first experiment was as follows: low grade and low stage bladder tumors were induced in 72 Wister male rats, supplying 0.025% BBN solution ad libitum for 8 weeks. Rats were devided into 6 groups; 1) control group, 2) 1.0% tranexamic acid containing feed group (t-AMCHA group), 3) urokinase 30ou/day×12 weeks i. v. group (UK group), 4) Tegafur 20mg×2/week×12 weeks i. p. group (FT group), 5) FT+t-AMCHA group, 6) FT+UK group. The tumor occurrence rate and the tumor size were compared in the 36th and 45th weeks. As a result, it was suggested that t-AMCHA was supressive and UK was enhancing for occurrence rate and size of the bladder tumor. It was concluded that the fibrin deposition aroud the tumor functioned as supressive for the tumor growth but preventive to infiltration of anti cancer agents to the tumor tissue.
The second experiment was as follows: high grade and high stage bladder tumors were induced in 147 Wister male rats, supplying 0.05% BBN solution ad libitum for 20 weeks. Rats were devided into 6 groups; 1) control group, 2) 1.0% tranexamic acid containing feed group (t-AMCHA group), 3) 0.1% FOY-305 containing feed group (FOY-305 group), 4) Tegafur 20mg×2/week×16 weeksi. p. group (FT group), 5) FT+t-AMCHA group, 6) FT+FOY-305 group. The tumor weight and pathological specimens were compared in the 36th week. As a result, it was suggested that t-AMCHA and Tegafur were not effective in supressing tumor growth but that FOY-305 prevented high grade tumors becoming high stage. It was concluded that the antifibrinolytic agent had an anti-tumor effect for low grade and low stage tumor induced by relatively small amount of BBN, although it had no effect on high grade and high stage tumors induced by large amounts of BBN. In the case of natural bladder tumor which is not induced by BBN, the antifibrinolytic agent may be effective.

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A clinical study was made of children's VUR associated with vesical hilar diverticulum.
Eighteen patients of VUR accompanied by hernias around the ureteric tunnel in the bladder were found during these 10 years. Six of them were required of anti-VUR operation and the remaining were conservatively observed with or without anti-bacterial agents for various periods. They were classified into 2 groups: 11 of them (group A) had paraureteral diverticula and 7 (group B) had periureteral diverticula. Four patients (group C) who had a cystic dilatation of the terminal end of a refluxing ureter with VUR were studied in this series, too.
VUR of group A occurred with a high intravesical pressure and morphological findings of the ureteral orifices being normal except two cases. One case with right complete duplication showed some swelling around the ureteral orifice, which was found to belong to refluxing lower urinary collecting system at the operation and the other had a left large vesical diverticulum including the left ureteral orifice with severe VUR in its bottom.
These cases had VUR of low intravesical pressure type. VUR of group B presented a low intravesical pressure, associating morphological abnomality of the ureteral orifice in the majority of them.
Para and periureteral diverticula were found with a high intravesical pressure or after voiding by VCUG and in some cases cystoscopically. Saccular formation was observed cystoscopically and/or operatively in three patients in group A.
Operative procedures for 11 ureters of the all 7 patients obtained good results by a modified Politano-Leadbetter method in 10 and by Cohen method in one.
15 ureters of 12 individuals except 3 of short following up periods were conservatively observed for 16 to 82 months (average 42.7 months). VUR disappeared in 4 ureters of them, showed grade down in 4 and remained unchanged in the remainder.
The refluxing ureter with either para or periureteral diverticulum lacks in the anti-refluxing mechanism, such as weakness of hilar muscle structure and undergrowth of intramural ureteral muscle bundles in the literatures.
Urinary stasis in the terminal end of the ureter was recognized in many cases (19/31, ureters) but considered to have little influence on the upper urinary tract.
Renal function were kept normal to moderate in all cases. Therefore, operative procedure is not always required for VUR associated with vesical hilar diverticula, if they are followed carefully case by case.

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The cathecholamines, noradrenaline (NA), adrenaline (ADR) and dopamine (DA) were determined in canine upper urinary tract tissues using high-pressure liguid chromatography with electrochemical detection. The NA content was characterized by regional variations in upper urinary tract tissues freed of canine adventitial blood vessels. The NA contents in renal calyces were always highest. Significant differences between renal calyx and renal pelvis, renal pelvis and pelvi-ureteric region, pelvi-ureteric region and upper ureter, upper ureter and lower ureter were demonstrated by the paired t test (p<0.05). No regional variations were seen in the ADR content. The DA content showed the same regional variation pattern as NA, but no significant differences were seen statistically.
To determine the catecholamine contents of only smooth musculer tissues, adventitial and mucosal tissues were resected from the calico-pelviureter. The NA contents of calico-pelvic musculer tissues were significantly higher than those of ureteral musculer tissues.
The left lower ureter was ligated in fifteen dogs, and the right upper urinary tracts were used as controls.
Tissues of various regions were removed after 2 days, 1 week and 1 month. The NA contents of the samples ligated after 2 days were significantly reduced as compared with the controls. Even in the case of a dilated upper urinary tract, the NA content of the calyx was higher than that of other regions. The longer the duration of obstruction, the heavier the tissue weight of dilated upper urinay tract as compared with the control. The NA content of dilated upper urinary tract was not reduced in proportion to obstruction period.

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We have studied on 157 cases of recurrent idiopathic calcium urolithiasis treated at the Department of Urology, Osaka University School of Medicine, and the effect of various therapies on the prevention of the recurrence. In this study, we have defined an estimation method, taking into consideration ipsilateral or bilateral nephrolithiasis and quantitatively representing the appearance frequency of active stone forming enviroment, that is, “evil urine”, that clinical identification was rather simple. According to this estimation method and by comparison of stone episode rate (SER) before and during treatment, we have examined the effect of various therapies on the prevention of the recurrence. The result was as follows:
1) Of the drug therapy groups, in the two groups, allopurinol alone and allopurinol plus thiazide combined therapy group, SER was significantly smaller during treatment than before treatment.
2) In the group of the patients followed up only with water intake and dietary advice, SER was also significantly smaller during follow-up before first visit.
3) In both groups of allopurinol alone and allopurinol plus thiazide combined therapy, we could perform statistical examination of the difference of SER values during two years between before and after treatment. SER value was significantly smaller after treatment.
From the fact that the therapeutic improvement of the pretreatment biochemical abnormalities did not necessarily link with the reduction in the number of stone episodes, and that in the group of the patients followed up only with water intake and dietary advice, SER was significantly smaller during the follow-up period than before first visit, it seems that a double blind study in consideration of “stone clinic effect” is necessary for judgement of true therapeutic effect of a drug for prevention of recurrence.

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The present study deals with F9-like antigens, major histocompatibility antigens (HLA-A, B, C and β₂-microglobulin) and lectin-receptors on the cell surfaces of human embryonal carcinoma (EC) cells. Four cell lines used in the present study were derived from testicular germ cell tumors.
Although the presence of F9-like antigens was suggested in these human EC cells, they also had major histocompatibility antigens. In this point human EC cells differ from mouse EC cells. However, the levels of β₂-microglobulin in the media suggested that HLA was in very small amounts. There are receptors to PNA, UEA-I and DBA on the cell surfaces of human EC cells also. The DBA receptors on human EC cells are far less than on mouse EC cells.
The surface markers of human EC cells do not completely agree with those of mouse EC cells. The expression of surface makers have no connection with the ability of differentiation in human EC cell lines.

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Despite recent progress in the diagnosis and treatment of impotence, a method for evaluating the efficacy of therapy in psychogenic impotence remains to be established. This is attributable to the high rate of subjectivity involved in treatment of this disease, the nature of which makes it virtually im-possible to arrive at an objective criterion for evaluating therapeutic effectiveness.
In an attempt to develop as objective a method of evaluation as possible, the authors assigned numerical values to four parameters considered essential to sexual funtion, namely, libido, erection, ejaculation, and orgasm, and used the sum totals of these scores, collected before and after initiation of therapy, as indicators of over-all sexual function. Numerical values were assigned according to a logarithmic scale, in four 0 to 10, i. e., 0, 1, 3, and 10; a score of 0 signified “normal” and a score of 10, “abnormal”. Numerical values were assigned on a logarithmic scale and not on a proportional scale, because a score of 10 in any given parameter, regardless of scores of 0 in the other parameters, signals a severe impairment of sexual function. By comparing sum totals of scores computed before and after initiation of therapy, the authors were able to evaluate therapeutic efficacy on the basis of changes in these sum totals.
Using this method, the mean total score for a control group of 24 normal subjects was 1.67±0.26 (mean±standard error). For the test group, which consisted of 24 patients of psychogenic impotence, the mean total score prior to initiation of therapy was 16.46±3.55, an extremely high score in comparison with the control group. After four weeks of therapy, the mean total score dropped to 9, 37±1.77, indicating a statistically significant (p<0.05) decrease from the pre-therapy mean total score.
These results show that the method of scoring developed by the authors is useful in objectively delineating the efficacy of therapy in psychogenic impotence.

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From the DNA histogram of bladder irrigation specimens obtained by flow cytometry, percent proliferative compartment (% PC; supradiploid cell compartment in the total cell population) was calculated.
Percent PC was 9.3±5.9 (mean±SD) in the control group. In the bladder cancer patients, high grade or high stage tumors had the tendency to show higher % PC values. Therefore, it is considered to be possible to predict the grade or the stage of the tumor from the % PC in some cases.
Assuming that the normal upper limit of the % PC is 21.1 (mean±2SD of % PC in the control group), 36 bladder tumors were detectable in 39 examinations performed in patients with bladder tumor and the false negative rate was 7.7%. From the above results it is possible to evaluate the presence or absence of tumor cells and this technique could be applied to the automated cytology in patients with bladder tumor.
This technique also provided us with an evaluation of the radicality of TUR-Bt, because the % PC returned to the normal range after curative TUR-Bt while it showed a relatively high value after non-curative TUR-Bt.
In the follow-up examinations of three cases with bladder tumor, the value of % PC was decreased after the effective treatment and was elevated on the occasion of tumor recurrence. Our results suggest that flow cytometry may be a valuable addition to the routine urologic examination to follow up con-servatively treated patients with superficial bladder tumor.

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Effect of antineoplastic agents on cell cycle traverse was investigated using flow cytometry and cultured cell line (OUR-10) originated from human renal cell carcinoma.
Relative DNA contents of tumor cells were determined by flow cytometry and changes of DNA histogram were studied, 24 and 48 hours after 2-hour or continuous exposure of cultured cell line to antineoplastic agents.
Mitomycin C (MMC) led to an accumulation of cells in S and G₂M phase. At concentrations which inhibited cell growth moderately, the rate of cell cycle progression was delayed and cells were blocked in G₂ phase. At higher concentrations, MMC inhibited the progression of cell cycle strongly.
Adriamycin (ADM) resulted in a block in G₂ phase but no accumulation in S phase was observed. At higher concentrations, ADM inhibited cell cycle progression completely.
Bleomycin (BLM) showed no remarkable change of DNA histogram patterns. This was considered to be due to the cytotoxic effect of BLM on tumor cells in G₁ phase.
Exposure of cultured cells to vinblastine (VBL) resulted in an accumulation in G₂M phase, which was consistent with metaphase arrest of VBL.
Accumulation of cells in S and G₂M phases was observed in the treatment with cis-dichlorodiamine-platinum (CDDP). At concentrations which inhibited cell growth strongly, cells were blocked in G₂ phase after the slow progression through S phase. At higher concentrations, the progression of cell cycle was inhibited completely.

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A case of invasive adenocarcinoma of the bladder originated from Gartner's duct in the broad ligament was reported.
A 63-year-old woman was admitted to Department of Urology, Oita National Hospital with com-plaints of micturition pain, cloudy urine and fever attack. Cytologycal examination was conclusive for malignancy. Cystogram revealed a huge shadow defect on the right side of the bladder. Pelvic angiogram and computed tomogram demonstrated a tennis ball sized cyst-like tumor invated into the right side of the bladder wall. Exploratory operation revelaed that the tumor was firmly fixed to the iliac bone, and tumor biopsy was performed. Histologically, the tumor was diagnosed as mesonephric adenocarcinoma. This case was treated effectively with external irradiation and administration of FT-207 and Mitomycin C, however, died about 7 month later of cachexia and pulmonitis.
Gartner's duct cysts are not uncommon. However, malignant cases are rare, especially malignancy of the urinary tract.

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Two patients with Cushing's syndrome due to adrenal adenoma or carcinoma were treated with Trilostane, a competitive inhibitor of 3β-hydroxysteroid dehydrogenase, before surgery. Trilostane therapy decreased plasma levels of aldosterone, progesterone, deoxycorticosterone, 17-OH progesterone, cortisol, Δ⁴-androstenedione and urinary excretion of 17-OHCS.
Conversely, plasma levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate and urinary excretion of 17-KS were increased following this drug administration. One patient with adrenal adenoma or another patient with adrenal carcinoma showed a remarkable or slight improvement in clinical features of this syndrome. No side effects were caused by this drug treatment. Subsequently, trilostane appears to be eligible for the treatment of Cushing's syndrome before surgery.

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Complete disappearance of malignant cells in a 68-year-old male with T₄N₂M₀ bladder cancer by chemotherapy alone is described. The patient was transfered to our clinic in October 1983 because of acute renal failure. Ultrasonography demonstrated left hydronephrosis and right small atrophic kidney. Left nephrostomy resulted in prompt recovery of renal function. Antegrade pyeloureterography disclosed complete ureteral obstruction near the bladder.
Cystoscopy revelaed a sessile tumor posterior to the trigone. Histological examination of the biopsied specimen showed transitional cell carcinoma G3 of the bladder with intramuscular invasion. On rectal examination under epidural anesthesia a hard hen-egg-sized tumor was palpable, which was fixed to the left pelvic wall above the prostate. Lymphangiography disclosed multiple filling defects, 3-10mm in diameter, in bilateral external iliac lymph nodes suggesting nodal metastases. In December 1983 combination chemotherapy with cisplatin (CDDP) and methotrexate (MTX) was begun. The patient received CDDP 70mg/m² i. v. on day 1 and MTX 40mg/m² i. v. on days 8 and 15, every 3 weeks. On day 1, 3000ml of infusion was loaded with mannitol-induced diuresis to protect renal function and 500mg of methylprednisolone was administered to prevent nausea and vomiting. Because of severe stomatitis and thrombocytopenia, combination chemotherapy was discontinued after the third ad-ministration of CDDP. A marked shrinkage of the tumor was observed while a fibrous resistance remained palpable above the prostate. The patient underwent radical cystectomy in February 1984.
Macroscopic examination of the surgical specimen revealed disappearance of the tumor inside the bladder. Histologically no tumor cell could be found in the bladder and pelvic lymph nodes. He is well without recurrence 6 months after the start of the chemotherapy.

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