From detailed investigations of the vascular structure of the penis, it has been proposed that there exists a valvular structure, consisting of smooth muscle, located at a point immediately before the helicine artery, bifurcated from the deep artery, opens to the cavernous sinuses, an area where autonomic nerves are densely distributed, participating in opening and closing the valve. On the other hand, there is said to be no valvular structure in the vein outflowing from the cavernous sinuses, and blood flows into the dorsal penile vein by penetrating the albuginea obliquely or vertically after running parallel in the region immediately below the albuginea. It is considered that, when the valve of the helicine artery opens, blood flows into the cavernous sinuses, expanding them, and as a result the outflowing vein is compressed between the sinuses and the albuginea, or the albuginea itself, acting like a valve and therefore assuming an important function in maintaining erection by disturbing the reflux of blood flow. It is also presumed that the contracting of ishiocavernous muscle plays a part in developing the rigidity of the penis. It is considered, moreover, that the trabecula of the cavernous body consisting of smooth muscle also plays a part in the promotion and disappearance of erection.
It is very important to run functional tests of erection when diagnosing impotence, and today many tests are availble for differential diagnosis; including papaverine test, dynamic cavernosometry and cavernosography. As for therapy, treatments involving vasoactive agent infusion, such as papaverine or prostaglandin E₁ into the cavernous body, have become common. For cases with venous impotence, ligation of the penile deep vein and crus of the penile cavernous body have come to be attempted. Furthermore, revascularization of penile artery can be performed to treat arterial impotence. For cases in whom these methods are not effective, implantation of various penile prostheses into the penis has been shown to be successful.

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Although the adverse effects of vesicoureteral reflux on the renal function and renal growth have been well documented, there is still controversy regarding the factors for spontaneous cure of reflux and the time required for the resolution. We performed a retrospective analysis of 829 ureters in 541 children who have been followed for more than 3 years since 1973. Reflux was judged as spontaneously cured only after 2 micturition cystourethrograms (MCU) had shown no reflux. In total reflux resolved in 220 ureters (26.5%) of 182 children (33.6%). Resolution rate was 39.5% in boys and 28.0% in girls, and there was statistically significant difference between both sexes. In chilren who had underwent urethrotomy on congenital urethral stenosis, e. g. bulbous urethral stenosis in the boy and distal urethral stenosis in the girl, resolution rate was 43% in boys and 23% in girls.
Resolution rate according to VUR-grade was 85.5% in grade I and II reflux, 45.8% in grade III, and 6.7% in grade IV and V. Of 92 children who underwent urodynamic evaluations, 37% showed findings of unstable bladder. Renal scarring was observed in 7.3% of renal units which was significantly less frequent than the incidence among total renal units with reflux. Reflux was resolved in 30% of renal units without scarring and 10% of renal units with scarring. The incidence of small kidney in the spontaneously resolved group was 3.6%, which was significantly lower compared to the total renal units with reflux.
The mean age at resolution of reflux was 5.7 years in boys and 7.5 years in girls. Boys who had been diagnosed before 1 year of age showed a higher rate of resolution than any other age group. The mean duration of reflux was 1.9 years. The relationship between the initial grade of reflux and the duration of reflux was studied, and there was no statistically significant difference among the different grades of reflux. A decay curve for spontaneous cure by grade showed about 50% of resolution in the first year of the follow-up periods. About 90% of any grade of reflux resolved during the first 3 years in patients with spontaneously resolved reflux.
We conclude from this study that the conditions under which one can anticipate spontaneous resolution of reflux with non-surgical approach are: patients with grade I to III reflux, boys under 1 year of age, patients with normal renal growth without scars, and patients without mechanical or functional abnormalities in the lower urinary tract.

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A study was conducted in a total of 51 patients with urinary bladder tumor who had received surgical operation associated with removal of regional lymphnodes after lymphography. Abnormal findings were observed in lymphogram of 22 patients. The other 29 patients showed no such abnormality. After the operation pathological metastasis was confirmed in 7 patients. Lymphograms of these patients ith positive lymphatic metastasis revealed filling defects in 85.7% and collaterals in 57.4%. There as correlation between the occurrences of these two findings based on quantification analysis III of multivariate analysis. Lymphography before operation showed 87.5% of sensitivity, 65.1% of specificity and accuracy of 68.6%, not having higher accuracy compared to other studies. These results suggest that lymphography, which may have clinical sigtnificance, is not a decisive method in exploration of bladder tumor. Comprehensive analysis of diagnostic imaging should be performed, including CT after lymphography.

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To evaluate the genetic difference in induction of bladder cancer by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), BBN was given to two different strains of mice, i. e. A/J (BCG resistant) strains and C57BL/6 (BCG susceptible) strains. The influence of Freund complete adjuvant (FCA), which includes BCG, was similarly examined along with associated cellular immunity as evaluated by footpad reaction (FPR).
The results were as follows:
1. The incidence of bladder cancer was significantly higher in C57BL/6 strains (90.0%) than A/J strains (54.5%).
2. FCA reduced the incidence of bladder cancer significantly in C57BL/6 strains.
3. FPR, which reflects the delayed type hypersensitivity, was activated significantly in FCA treated C57BL/6 strains.
These data suggest that the strain differences in mice probably explains the inhibition of carcinogenesis by FCA and cellular immunity.

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We report the results of prospective randomized study which was designed to evaluate prophylactic effects of intravesical bacillus Calmette-Guerin (BCG) in the treatment of superficial transitional cell carcinoma of the bladder. A total of 44 cases who had no previous treatment of bladder cancer were randomly assigned to BCG or control groups after TUR. BCG group (23 cases) received intravesical instillation of 80mg BCG (Tokyo strain) at one week intervals for 6 weeks, at two week intervals for 12 weeks, and at one month intervals for 20 months. In BCG groups, 3 cases had recurrence at 6 months and 1 case at 9 months, while the other 19 cases had no recurrent disease for 3 to 34 months (average 20.3 months) of follow-up. Control group (21 cases) had no further treatment after TUR. In control gorup, recurrence was seen at 3 months in 3 cases, at 6 months in 5 cases, at 9 months in 2 cases, at 12 months in 3 cases and at 21 months in 1 case. Only 7 cases in the control group were free of recurrence for 8 to 45 months (average 32.3 months) of follow-up. One and two year. recurrence rates in BCG group (18.4%, 18.4%) was significantly (p<0.01) lower than those in control group (63.2%, 68.9%). Among the complications of intravesical BCG were cystitis (76.2%), low grade fever (13.0%), and several days' persistent gross hematuria (13.0%). Most of these signs were self-limited and only in 2 cases instillation of BCG was discontinued. These results suggest that intravesical BCG is effective for prophylaxis of recurrence of superficial bladder cancer after TUR.

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47 cases including 24 renal pelvic tumors, 20 ureteral tumors and 3 renal pelvic and ureteral tumors treated in our hosptial from January, 1980 to December, 1987, were studied clinico-histopathologically. The patients ranged in age from 38 to 81 years (average 65 years) the sex ratio was 3:1 with male predominance over female. Tumor occurred on the right side in 19 cases, on the left side in 27 cases and bilaterally in 1 case. The most frequent sign was hematuria which was observed in 40 cases (85%). The interval from the onset of initial symptoms to the first visit was within one month in 9 cases (19.1%). The major findings of excretory urograms were filling defect in 21 cases (47.1%) and non-visualizing kidney in 15 cases (33.8%). Positive urinary cytology was obtained in 21 cases (44.7%). Operative therapy as performed in 45 cases, namely, nephroureterectomy and partial cystectomy in 30 cases (66.7%) and nephroureterectomy in 9 cases (20%). Histopathologically, all cases but two cases of squamous cell carcinoma and to cases of mixed type carcinoma ere transitional cell carcinoma. Subsequent bladder tumors were found in 8 cases (17.7%). The overall survival rate at 1, 3 and 5 years were 80.2%, 41.1% and 41.1%, respectively by Kaplan-Meier method. In this series, the interval from the onset of initial symptoms, the grade and stage of tumor and metastasis of lymph nodes were to be considered in developing prognosis.

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The serum levels of α-fetoprotein (AFP) are known to undergo acute changes (paradoxical elevation) after effective chemotherapies for testicular germ cell tumors. In order to understand the clinical significance, the changes of the serum AFP levels after PVB therapy for testicular germ cell tumors were analyzed, and their relationship to the treatment effects was investigated in this retrospective study.
Thirty-one patients with testicular germ cell tumors (11 with stage I, 7 with stage II, and 13 with stage III) which had been treated by PVB therapy were evaluated.
The measurement of the serum AFP levels was performed by radioimmunoassay on Day 1 (the initiation day of the PVB therapy), thereafter on Day 8 and Day 22. The half-life (t_1/2) or doubling time (t₂) of the serum AFP were calculated.
In patients with stage I disease, the serum AFP levels declined nearly according to its biological half-life between Day 1 and Day 22 after termination of chemotherapy (t_1/2=6.2 days).
In patients with stage II or III disease, the changes of the serum AFP levels were not consistent with the treatment results between Day 1 and Day 8. Namely, complete responders revealed a prolonged decline of the serum AFP levels (t_1/2=63.0 days), partial responders a transient rise of the serum AFP levels (t₂=49.5 days) and non-responders a sudden rise of the serum AFP levels (t₂=9.9 days). On the contrary, the serum AFP levels changed in accordance with the treatment effects between Day 8 and Day 22.
Early changes of the serum AFP levels were seen in patients with stage II or III disease between Day 1 and Day 8 after chemotheapy. It was indicated that the measurements of the serum AFP levels during this period were not useful for the evaluation of the treatment effects in these patients. Furthermore, it was suggested that the early changes of the serum AFP levels possibly correlate with the poor response. The mechanism of the early changes of the serum AFP was also discussed.

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This study was designed to evaluate the functional changes of Sertoli cells following the administration of clomiphene citrate for male infertility.
Sperm count and seminal transferrin level were measured before and after the treatment in 22 cases of oligozoospermia (sperm count: less than 20×10⁶/ml) and 14 cases of subnormal sperm count group (sperm count: 20-30×10⁶/ml). Clomiphene citrate was administered per os for more than 3 months consecutively in a dose of 25mg/day. Seminal transferrin concentration increased more than 1.5 times compared with pre-treatment level in 6 cases (16.7%). Among these patients, sperm count markedly increased (20×10⁶/ml or more than the pre-treatment level) in 3 cases (50%) and slightly increased (10×10⁶/ml or more than pre-treatment) in 1 case (16.7%). In 30 cases, in which seminal transferrin level did not increase, sperm count markdly increased in 6 cases (20%) and slightly increased in 6 cases (20%). Thus, sperm count was improved more frequently in the cases in which seminal transferrin level remained elevated than the cases with no elevation of serum transferrin level.
Serum FSH level of patients whose seminal transferrin level remained elevated after the treatment was significantly higher than that of patients with no elevation of serum transferrin level (mean±SD=32.8±18.0mIU/ml v. s. 14.4±11.7mIU/ml, respectively).
These data suggested that the activation of Sertoli cells may contribute to the increase of sperm count following the administration of clomiphene citrate and the elevated seminal trasferrin secretion may be related to the increase of serum FSH level following this treatment.

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The amount of autonomic receptors in the old and young rabbit prostate homogenate was measured in order to study the effect of age on the autonomic receptors of the prostate using radioligand binding techniques. For measuring the adrenergic alpha-1, alpa-2, beta-receptors and cholinergic muscarinic receptors, ³H-Prazosin (³H-PZ), ³H-Yohimbine (³H-YOH), ³H-Quinuclidinylbenzilate (³H-QNB) were used, respectively.
It was found that both the young and old rabbit prostate has a single class of binding sites for each ligand examined. There was an age-related difference in the distribution of these autonomic receptors (young: α1=muscarinic>α2>β, old: α1>muscarinic>α2>β). There were more alpha-1 and alpha-2 receptors in the old rabbit prostate, although these differences were not statistically significant. There was no age-related differences in the amount of beta adrenergic and muscarinic receptors. These results demonstrate that the age may affect the distribution of autonomic receptors but not significantly the amount of autonomic receptors of rabbit prostate.

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A total of 50 cases of primary tumors in the renal pelvis and ureter were treated in Tokyo University Branch Hospital (20 cases in 1966-1982) and in Tranomon Hospital (30 cases in 1977-1987). They were composed of 42 men and 8 women (5.3:1) with a mean age of 61 years. 31 patients suffered from renal pelvic tumors, 15 ureteral tumors and 4 tumors in both sites. The tumors were located in the left side in 33 cases, right in 16, and both sides in 1.86% of patients showed gross hematuria. The findings on IVP were filling defect (42%) and nonvisualization (33%). Positive urine cytology was obtained in 12 of 25 cases (48%). Surgery was performed in 47 cases. The remaining 3 cases were with advanced diseases. The surgeries were total nephroureterectomy plus ipsilateral retroperitoneal lymphnode dissection in 26 cases, total nephroureterectomy without node dissection in 7, total nephroureterectomy and total cystrectomy in 3, nephrectomy in 9, partial nephrectomy in 1 and segmental excision of ureter with ureteroureterostomy in one. Histologically, all tumors were transitional cell carcinoma. Over-all survival rates (Kaplan-Meier's method) of the operated patients at 1, 3, 5 years were 84.2%, 73.1% and 69.4%, respectively. The stage and grade of the tumors affected the prognosis. N fatter at lymphnode dissection was the most determinating fatter of prognosis. 3 advanced cases who did not receive surgery for primary site were treated with 5FU in 2, and with CAP in 1.2 of them died of the disease within 1 year after diagnosis, one patient was lost in follow up. Nine patients received systemic chemotherapy: 1 with CDDP, 7 with CAP and 1 with CAP and MVAC. Of 3 patients with metastatic tumors, 1 showed NC and 2 showed PD. All patients died of the disease with survival periods of 6 months to 18 months. One patient with bilateral tumor received CAP and 5FU after partial nephrectomy in one side and was alive with disease (NC) for 3 years and 8 months. The remaining 5 patients received adjuvant chemotherapy after surgery. All of them were alive and free of disease for a mean period of 3 years. Recurrence of tumor in the bladder was seen in 11 of 44 patients. 55% of the recurrence was observed within 1 year.

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The interrelation among urinary incontinence (nocturnal enuresis, urge incontinence), history of urinary tract infection and renal function was investigated in 153 children with primary vesicoureteral reflux who were more than three years old.
Of them, 98 children (64%) had the chief complaint of urinary tract infection (UTI) and 43 children (28%), urinary incontinence. Of the children whose chief complaint was UTI, 44 (45%) had incontinence. Thus, 87 children (57%) with VUR had urinary incontinence.
Almost all the children who had urinary incontinence and no previous UTI had good renal function. Renal dysfunciton was found in children with previous UTI history.
These studies on children with primary VUR more than three years old indicate that, although urinary incontinence could be a factor for recurrence of UTI and a probable cause of worsening of renal function, there is no direct correlation between urinary incontinence and renal dysfunction accompanied by VUR.

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We retrospectively reviewed 38 patients with primary penile squamous cell carcinoma (stage 1 in 22, stage 2 in 7 and stage 3 in 9) who were treated in our institution from 1963 through 1987. The incidence of regional nodal metastasis was correlated with tumor category, local infiltration and tumor grade. The incidence rate of nodal metastasis of G2 and G3 tumors was statistically higher than that of G1 tumors. Of 27 patients initially treated by radiotherapy and/or chemotherapy, 11 patients achieved complete response. G1 tumors and T1 to 2 tumors had such high response rates as 58 and 50 per cent, respectively, but 5 patients (45 per cent) had local recurrence at an average of 74 months after initial treatment. The 5-year survival rates of over-all, stage 1, 2 and 3 were 73, 90, 75 and 25 per cent, respectively. Patients with stage 3 disease had a statistical lower survival rate than those with stage 1 or 2 disease. Among 13 patients with regional nodal metastasis, none with G2 tumor survived three years, although 3 patients (60 per cent) of those with G1 tumor survived five years. These results suggest that tumor grade is the most prognostic factor for the regional nodal metastasis, the response of conservative treatment and the survival of metastasized patients.

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The immune responses in patients with renal cell carcinoma were evaluated from the production of interleukin-2 (IL-2), the expression of IL-2 receptors and the activity of lymphokine activated killer (LAK) cells. In addition, the effect of the patient's serum on the expression of IL-2 receptors and LAK activity were investigated.
The production of IL-2 by peripheral blood mononuclear cells (PBM) from patients with renal cell carcinoma was not suppressed, when compared with that in controls. However, the expression of IL-2 receptors tended to decrease with the progression of clinical stage. The LAK cells generated by PBM of patients with renal cell carcinoma had significant cytotoxic activity against Daudi cells, ACHN cells and autologous tumor cells, while autologous serum suppressed the expression of IL-2 receptors and the induction of LAK cells in patients with renal cell carcinoam. Furthermore, serum from patients with renal cell carcinoma suppressed the cytotoxic activity of LAK cells generated by PBM from a normal volunteer. These results indicated the presence of immunosuppressive factors in the serum of patients with renal cell carcinoma which impaired the clinical effect of treatment using IL-2 or LAK cells.

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The existence of immunosuppressive factors which impair the clinical effect of treatment using IL-2 or lymphokine activated killer (LAK) cells has been reported in the serum of patients with renal cell carcinoma. For the purpose of eliminating these immunosuppressive factors, plasmapheresis combined with adoptive immunotherapy using LAK cells was performed in ten patients with stage IV renal cell carcinoma. Immunological examinations revealed that the number of peripheral blood lymphocytes, NK activity and the ratio of Leu 11 positive cells were increased during the treatment. Of the 9 evaluable patients, one has a partial response, 5 showed no change and 3 had progressive disease. In addition to the one partial response, the size of some metastatic lesions in the lungs decreased in 2 patients during the treatment. As serious side effects, brain edema progressed in 2 patients with brain metastases and acute hepatitis due to plasmapheresis was noted in one patient. Moreover, transient and reversible renal dysfunction developed in most patients. These reuslts indicated that plasmapheresis combined with adoptive immunotherapy using LAK cells is a useful therapy for patients with advanced renal cell carcinoma.

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The effect of glycosaminoglycans on calcium oxalate crystal formation in the supersaturated solution was studied by examining the size and shape of calcium oxalate crystals generated under an optical microscope. It was found that heparan sulfate and heparin were more effective growth inhibitors than chondroitin sulfate and hyaluronic acid at concentrations within their respective urinary range. With increasing calcium and/or glycosaminoglycans concentration in the solution, the degree of growth inhibition caused by glycosaminoglycans was enhanced. Calcium oxalate crystal shapes generated with various glycosaminoglycans varied with glycosaminoglycan species. One of the causes of those differences in the shape and degree of growth inhibition might be the structural differences between them, that is, the number of sulfate residue and O- or N-form they contain. Calcium oxalate crystal shapes in the presence of heparin or heparan sulfate at higher concentrations were similar to those of calcium oxalate monohydrate crystals in the urinary sediments of hyperoxaluric patients. These facts might suggest the possibility that heparin and/or heparan sulfate were present in the crystal forming region.

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Voiding parameters on the Uroflow Diagnostic Interpretation (UDI) were analysed in relation to the voided volume in 58 micturitions of 36 helathy adult females. The maximum flow rate (Qmax) and the mean flow rate during central 90% of the voided volume (QM90) increased linearly up to the voided volume of 400ml. The voiding time (T100) took a value within a certain range independently of the voided volume from 100 to 400ml and never exceeded 21 seconds in all micturitions. Voiding time for the central 90% of the voided volume (T90), time to Qmax (TQmax) and time from Qmax to 95% of the voided volume (Tdesc) were independent of the volume voided. The maximum rate of increase of flow rate (dQ/dT max) and the estimated bladder wall contraction velocity at 40ml bladder contents (dL/dT 40) showed a tendency to increase depending on the volume voided. T100 showed a prolongation in 84.0% of 25 micturitions in 20 neurogenic bladder patients and in 66.7% of 27 in 21 chronic cystitis patients, always accompanied by a prolongation of T90. No other parameters were clearly different between healthy women and patients and/or between the two groups of patients. Voiding time is a useful parameter representing female micturition.

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Products of major histocompatibility complex (MHC) play important roles in immune reaciton. Class II MHC antigens serve as restriction elements for cells presenting antigens to CD4-positive helper T cells and also as histocompatibility antigens responsible for graft rejection. Furthermore, it was reported that expression of class II antigens on tumor cells increases immunogenicity in the murine system. In an attempt to investigate the relationship between renal cell cancer (RCC) and host's immune responses, we examined the expression of class II MHC antigens on RCC tissues of 30 cases and tumor cell lines. Immunohistochemical study showed that class II antigens were detected on 29 out of 30 RCC tissues to various dagrees with an order of positivity DR>DP>DQ but not normal renal tubular cells. Significant correlation was found between the expression of DQ or DP and the degree of lymphocyte infiltration. Three lines of RCC were examined by flowcytometric analysis, and were found to lack class II antigens. In KRC/Y and ACHN, however, HLA-DR-positive cells and in KRC/Y a smaller number of HLA-DP-positive cells were found when these cells were treated with interferon-γ but not inteferon-α. The result suggests that the expression of class II antigens on RCC might be modified by interferon-γ which is produced by tumor infiltrating lymphocytes or administrated for cancer treatment. Their expression is considered to affect host's immune response to RCC.

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In patients with either bilateral renal malignancies or with carcinoma occurring in a solitary kidney, the principle of en bloc removal of the tumor-bearing kindey cannot be applied.
Recently we have performed surgical enucleation in two cases of asynchronous bilateral renal cell carcinoma.
Case 1. A 60-year-old woman was hospitalized with diangosis of left renal tumor 10 years tumor 10 years after right nephrectomy for renal cell carcinoma. The tumor was enucleated while occluding the renal vessles. Pathological examination revealed that the tumor (a nodule of 35g) was renal cell carcinoma of grade I and perfectly covered by pseudocapsule. Hemodialysis was not required. The patient has been well for more than 11 months postoperatively and Ccr is 65ml/min.
Case 2. A 62-year-old man with slight elevation of serum GOT and GPT level was examined by CT, which revealed a space occupying lesion in the left kidney. He had undergone nephrectomy for renal cell carcinoma of right kindey 11 years ago. Three nodules of 56g, 6g and 3g were removed by in situ enucleation. They were renal cell carcinoma of grade II and there was no malignant penetration of the pseudocapsule pathologically. After surgery hemodialysis was required 10 times for 21 days. Renal function has been refined gradually and the patient is well with 47.3ml/min of Ccr at 4 months postoperatively.
Before this report of 2 cases there were 22 cases of asynchronous bilateral renal cell carcinoma in Japanese literature. Of the 24 cases with renal cell carcinoma in the residual sole kidney, enucleation and partial nephrectomy for conserving renal tissue were performed in 8 and 2 cases, respectively. These 10 cases were alive from 3 to 42 months postoperatively. Hemodialysis after radical nephrectomy was done in 5 patients and various kinds of treatment, such as irradiation, chemotherapy and immunotherapy, were given to 9 cases, but the results were not satisfactory.
Our experience and the satisfactory results achieved after surgical enucleation and partial nephrectomy suggest that these techniques have significant applicability in these patients.
Although radical nephractomy must be considered as the optimum curative therapy for patients wiht localized renal cell carcinoma and a normal opposite kidney, enucleation and partial nephrectomy are the treatment of choice when localized low grade renal cell carcinoma is present in a solitary kidney.

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Congenital neurogenic bladder dysfunction with spina bifida nad sacral dysgenesis manifested itself at middle age is reported.
A 48-year-old male who had urinary retention and suprapubic cystostomy one year and a half before in another hospital was seen, asking for removal of the cystostomy. He had never had any neurologic or bladder dysfunction in his childhood and adulthood.
X-ray examination revealed a bifid spine and sacral dysgenesis, bilateral hydronephrosis, bilateral VUR and urethral stricuture. Uroflowmetry showed a severe dysuric pattern (voided volume 5ml, residual urine 230ml) and the cystometrogram revealed a hyperactive bladder.
Optical urethrotomy for stricture yeiled some improvement i. e. recovery of voluntary voiding with large amount of residual urine. TUR of the bladder neck resulted in almost complete voiding. Cohen's antireflux operation yielded favorable improvement of hydronephrosis. The bladder and renal function remained favorable in the follow-up period of about two years.
The clinical course of this patient suggested that his bladder dysfunction was due to late manifestation of congenital neurogenic bladder.

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