The significance of symptomes, digital rectal examination (DRE), transrectal ultrasonography (TRUS) and prostatic specific antigen (PSA) as aids in the early detection of prostate cancer was investigated. In number of studies, sensitivity of DRE is lower than that of TRUS but specificity of DRE is adversely higher than that of TRUS. PSA was an excellent means to observe clinical course of prostate cancer patients but have proven to be insensitive and nonspecific to detect early stage prostate cancer. There is certainly no single test that can be applied reliable to detect the presence of prostate cancer at present. The use of three screening modalities must be recommended to improve the detection rate.
Mass screening program in Gunma Prefecture has been being studied since 1981. In this paper, we demonstrated that this screening program is successful to detect early prostate cancer with high detection rate (0.8%), improves the survival rates comparing to those of patients detected by out-patient clinics and the tests applied in this program prove relatively high specificity and sensitivity. To prove the significance of mass screening program, pilot studies in well excuted randomized prospective protocols are urgently needed. To acheive this purpose, it is necessary to organize a cooperative study group since approximate 50, 000 to 100, 000 subjects should be examined in this protocol.

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Three hundred thirty-six patients with superficial bladder cancers underwent their initial surgery at the Department of Urology of Okayama University School of Medicine from 1961 to 1985.
They have been followed-up until December 1988. (the median: 68 months) Among the 336 cases, excluding 9 cases which were treated initially with total cystectomy or incomplete resection, the remaining 327 cases were reviewed in order to study the pattern of their local recurrences in the bladder.
Major factors affecting recurrences of superficial bladder cancer were evaluated by the multivariate analysis using Cox's proportional hazard model. The examined factors included age on admission, sex, tumor's number, size, stage, histological grade and shape, operative method, intravesical chemotherapy, systemic chemotherapy, radiotherapy, frequency of recurrences and the date of operation.
During the follow-up period, 179 cases out of the 327 cases did not show any recurrences. The remaining 148 cases recurred from once to 11 times, therefore, a total number of recurrences was counted to be 406. In the 406 recurrences, 338 recurrences were treated by TUR, SVR, or SR. The remaining 68 recurrences were treated with total cystectomy or untreated. Fifty-seven cases out of the 148 cases demonstrated recurrences more than 3 times. Only 4 cases were free from recurrences more than 24 months following the surgery for their last recurrences.
The analysis in the 327 primary cases showed that the number of tumors was the most important factor. On the other hand the analysis in 338 recurrences showed that the second most important factor was the frequency of recurrences, following the number of tumors. This result suggested that tumor multiplicity and time interval of recurrence were important factors to determine the prognosis of recurrent superficial bladder cancer.

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We investigated changes of urinary and renal γ-glutamyl transpeptidase (γ-GPT) activities in rat with renal damages caused by nephrotoxic agents in order to clarify the onset and the course of these nephrotoxicities.
Cisplatin (CDDP) which is an antitumor agent, cephaloridine (CER) which is the first-generation cephem, and gentamicin (GM) which is an aminoglycoside were employed as tested nephrotoxic agents.
We administered three fourth of LD₅₀ of each agent to male Fischer 344 rats, intra-peritoneally. And the time-course changes of serum creatinine (s-Cr) value, creatinine clearance (Ccr) and urinary γ-GTP activity were observed after administration of each agent. Finally, we measured renal γ-GTP activities and observed pathological changes of the kidneys.
The elevation of s-cr values and the reduction of Ccr appeared 3 days and 12 hours after the administration of CDDP and CER, respectively. And the peak appeared 7 days and 3 days after the administration of CDDP and CER, respectively. Increase of urinaly γ-GTP activities occurred earlier than the peak of s-cr value and Ccr in each group and as early 12 hours after the administration. In CER groups, the peak of urinary γ-GTP activities was observed within 12 hours after the administration. And the peak of urinaly γ-GTP activities was observed at 24 hours and in 3 days after the administration of GM and CDDP, respectively. In addition, renal γ-GTP activities reduced around 40% of those of control. On the other hand, we found anatomically preferential sites for lesions in the kidney induced by different agents; namely the proximal tubules in outer stripe of the outer medulla by CDDP, proximal tubules beneath renal capusule by CER and diffuse pattern by GM.
These results suggest that the excretion of γ-GTP into urine can be a sensitive marker for the proximal tubul an damage induced by nephrotoxicagents.

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Twenty-one patients with superficial bladder cancer entered an analysis of single dose (2′R)-4′-0-tetrahydropyranyladriamycin (THP) or adriamycin (ADM) administration. The patients in each group that have been or not have been treated previously with anti-cancer drugs were randomized into two groups, one was given THP and the other ADM. Thirty-mg of THP or ADM dissolved in 30ml of physiologic saline was instilled into the bladder, and retained for 1 hour. After 1 hour retention of the drugs, tumor tissues and normal mucosas were removed by punch biopsy forceps transurethrally. The tissue concentrations of THP and ADM were estimated by high performance liquid chromatography.
The tissue concentrations of THP and ADM in the tumors were significantly greater (p<0.05) than those in the normal bladder mucosas. The tissue concentration of THP in the tumors were greater than that of ADM. The tissue concentrations of THP and ADM in the tumor of patients who have been treated with anti-cancer drugs priviously were less than those of patients who have not. This results demonstrated that prior therapy with anti-cancer drug may cause a resistance for intravesical instillation chemotherapy. However in patients with prior therapy, the tissue concentration of THP in the tumors were greater than that of ADM.
Based on these findings, THP has been shown to be were effective as an intravesical instillating agent expecially, in cases with prior chemotherapy.

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A new human testicular cancer cell line (TCam-2) was established. The original material of TCam-2 was a primary lesion of a left testicular seminoma (typeical pure type seminoma) from a 35 aged male patient. TCam-2 produced neither AFP nor β-HCG, It showed strong immunoreactivities for 5G9 (anti testicular cancer MoAb), 4B3 (anti PTHrP MoAb) and PALP (placental alkaline phosphatase). The chromosomal analysis revealed 92 modal number and loss of Y chromosome. Histochemical, morphological and chromosomal analysis supported that TCam-2 is from classical seminoma. TCam-2 was trasplanted subcutaneously to the back of 6 weeks old scid mice (CB-17 strain), and grew a caassical seminomatous tissue.

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With the purpose to avoid the risk of transfusion mediated infection and complication, predeposited autologous blood transfusion was performed.
From April 1990 to March 1991, transurethral resection of the prostate (TUR-P) were performed in 27 patients (mean age: 72.5 years) with benign prostatic hypertrophy (BPH). Autologous blood (200-400ml, mean 244ml) was predeposited 3 weeks prior to TUR-P in 18 patients (mean age: 73.9 years) and transfused during or just after the operation in 16 (five patients required some homologous blood in addition to their own banked blood). Another three patients were transfused with homologous blood only. The mean values for hemoglobin concentration were 13.7±0.4g/dl before blood deposition and 12.8±0.5g/dl on the day of operation (recovery rate: 92.5±2.7%). Although no complication was found in autologous blood transfusion group (11 patients), one case of systemic exanthema and one case of type C hepatitis were observed in homologous blood transfusion group (8 patinets).
In TUR-P, positive correlations were observed among resected prostate weight (Pro-wt.), blood loss (B.) and operation time (Op-T.). Correlation efficient between Pro-wt. and B. was 0.80, that of B. and Op-T. was 0.77 and that of Pro-wt. and Op-T. was 0.85. From these results and ultransomographic measurement of the prostate weight, the amount of blood loss can be calculated preoperatively, there by the amount of blood needed for transfusion will be estimated.
Since surgical operation for BPH is usually carried out on an elective basis and the amount of blood necessary for transfusion is estimable, TUR-P is one of the best indication of autologous blood transfusion.

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We analyzed the current status and problems of a screeing for prostatic cancer (PCa) through a health examination in 12 hospitals in Fukuoka prefecture. From 1987 to 1991, a total of 16, 126 subjects received this. The number of subjects who received this increased every year. In 5 hospitals in which such a screening is optional, however, only about 20% of subjects through a health examination received it each year. Furthermore, most of the subjects were in their 50s or 40s. Those in their 70s or more who are at higher risk for PCa rarely received such screening. PCa was detected in 6 subjects (0.04%) (well differentiated adenocarcinoma: 3, moderate differentiated adenocarcinoma: 3) in 5 years. Five were in stage B and treated with radical prostatectomy and one was in stage C and hormonal therapy was performed. The mean age of the 6 patients was 57.7 year old ranging from 51 to 66. The incidence of PCa detected by a screening in dock increased with age. Prostate specific antigen (PSA) was considered to be more useful for detecting prostate cancer in dock as compared with digital examination (DRE), transrectal ultrasonography or prostatic acid phosphatase because of its relatively high sensitivity (83.3%) and specificity (84.8%). The incidence of PCa detected with combination of DRE and determination of PSA was 0.15% and significantly higher than that detected with DRE alone, 0.01%.
These results suggest the need for enlightenment on PCa and the significance of a screening with combination of DRE and determination of PSA through a health examination for detecting early stage of PCa.

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Two hundred and thirty-four patients who visited the urology clinic in Kitasato University Hospital were evaluated with digital rectal examination (DRE), serum prostate specific antigen (PSA) study and prostate ultrasonography. Of 71 men who underwent ultrasound-guided transrectal biopsy 19 (26.8%) were found to have prostate cancer, accounting for 8.1% (19/234) of the whole population. When PSA levels were arbitrarily divided into 0 to 2, 2.1 to 10 and greater than 10ng/ml, the positive DRE was associated with cancer detection rate of 3.3%, 77.8% and 100%, respectively, with an overall detection rate of 32.6%. However, a normal DRE (benign-feeling gland) is associated with much less cancer detection rate of 5.9%, 28.6% and 100%, respectively, with an overall rate of only 16.0%. The positive biopsy rate was 30% (18/60) in the presence of hypoechoic lesions on sonography, but 9.1% (1/11) if absent. The positive predictive value of DRE (32.6%, 15/46) increased to 36.6% (15/41) if a hypoechoic lesion was identified sonographically and to 87.5% (14/16) if PSA levels were abnormal. One patient was found to have a microfocus of well differentiated adenocarcinoma in one of the 6 biopsy cores. Radical retropubic prostatectomy was performed in 9 of the 19 patients with clinically localized prostate cancer. On pathologic examination of the prostatectomy specimens 5 of them were upstaged to positive seminal vesicle or lymph node metastasis.
The spectrum of prostate cancer detected by these modern techniques is broad and extends from tiny clinically insignificant cancer to advanced disease in its incurable stage. The detection rate of clinical cancer may be increased by the liberal use of these techniques, however, further efforts should be focused on the detection of clinically important, biologically active cancer still in its early stage.

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Phenotypic difference of lymphocytes circulating in tumorous renal artery and renal vein in patients with renal cell carcinoma was studied.
Fifteen patients with no prior treatment were studied, from whom blood samples were taken at the time of radical nephrectomy. Mononucler cells separated from tumorous renal arterial and venous blood were analyzed for cell surface markers. CD3, CD4, CD8, CD11b, CD16, CD25, CD57, Leu8 HLA-DR were compared. CD25 positive cells were significantly increased in venous blood than in arterial blood in the kidneys with tumor. No significant difference was found regarding the other surface markers.

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We designed a following experiment to appraise the effect of unilateral hydronephrosis on the contralateral kidney using weanling rats whose kidneys were in a growing stage.
Rats were divided into 4 groups. Complete unilateral (left) ureteral obstruction (CUUO) was made on the experiment rats, and these went through the following procedures on the day 3 after CUUO; 1) Group R: CUUO released, 2) Group N: left nephrectomy performed, 3) Group S: CUUO continued. Sham-operations were performed on the days 0 and 3 to the controls. Renal cortical blood flow and glomerular volume of the contralateral (right) kidneys were determined on the days 5, 7, 9, 14 and 21.
Blood flow to the renal cortex per unit volume (ml/min/100cm³; measured with Laser blood perfusion monitor) in the contralateral kidneys increased gradually in the all groups, but statistical significance was not confirmed in the observed period between any groups. Increases in total renal blood flow (wet kidney weight times renal cortical blood flow per unit volume; g×ml/min/100cm³) were proportional to the measured wet kidney weight in the all groups. Notably in the group N, a significant increase was noted compared to the group R and the controls.
Glomerular volume (GV) of the contralateral kidneys did not show significant changes on the day 3 compared to the controls. GV significantly grew up during the day 5 to the day 14 (2 to 11 days after the relief of CUUO) in the group R and then it settled to the level of the controls on the day 21. In contrast, GV in the group N and the group S still continued to grow up (statistically significant) on the day 21. GV in the group R did not correlate to total renal blood flow after the day 14 although total renal blood flow continued to increase gradually. Proprotional increases in total renal blood flow and GV were observed in group N and group S.
These results suggest that some factors, other than increase of renal blood flow, are playing roles on enlargement of glomerular volume after a relief of CUUO.

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The subtypes of the muscarinic cholinergic receptor in human detrusor muscle were studied using radioligand binding techniques. It was found that there were significant amount of M1, M2 and M3 receptors labeled by ³H-pirenzepine, ³H-AFDX and ³H-4DAMP, respectively, in human detrusor muscle. The rank order of the amount of these receptors was M3>M1≥M2. The amount of M3 receptors was about 10-fold of M1 or M2. In the inhibition experiment of ³H-QNB binding to human detrusor muscle, the Ki values of pirenzepine or AFDX was 50-100 fold of that of 4DAMP and the rank order of Ki values was pirenzepine>AFDX>4DAMP. The M3 selective drug, 4DAMP showed smallest Ki value among the three drugs studied, indicating that the affinity of M3 receptor was highest among the three muscarinic subtypes. These data suggest that M3 receptors are predominant in human detrusor muscle biochemically.

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The in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the number and function of peripheral neutrophils were studied in time sequence in 9 cancer patients receiving anticancer cytotoxic chemotherapy; 6 patients with transitional cell carcinoma of urothelium treated with CAP (the combination of cyclophosphamide, adriamycin and cisplatin) and the other 3 with testicular tumor treated with PEB (the combination of cisplatin, etoposide and bleomycin). The neutrophil function was evaluated by superoxide production, measuring chemiluminescence of the neutrophil suspension by a photometer.
In the 1st course, when no rhG-CSF was administered, the neutrophil function declined significantly (p<0.01) as the peripheral neutrophil count (PNC) decreased, reached the minimum almost at the same day as PNC reached the nadir, and returned to the normal level at the beginning of the next course. In the 2nd course, when rhG-CSF (75μg/body) was administered subcutaneously daily for 14 consecutive days beginning at 72 hours after the chemotherapy, the nadir of neutropenia was elevated (p<0.01), the period of neutropenia (<1, 000/mm³) was shortened (p<0.01), the recovery from neutropenia (>1, 500/mm³) was accelerated (p<0.01) as compared to the 1st course, and an marked increase of PNC (p<0.01) to the peak on the next day of the last administration of rhG-CSF was observed. In addition, deterioration of neutrophil function was alleviated (p<0.05) and the neutrophil function was enhanced (p<0.01-0.05) during rhG-CSF administration, even at the nadir of neutropenia.
The study shows that rhG-CSF appears to enhance the function of peripheral mature neutrophils, even if they were impaired by cytotoxic chemotherapy in the bone marrow during the process of their maturation and that rhC-CSF would be effective against the impaired antimicrobial defense mechanism in cancer patients receiving chemotherapy by improving not only chemotherapy-induced neutropenia but also the deteriorated neutrophil function.

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Between January 1985 and November 1992, 12 patients with renal cell carcinoma involving the inferior vena cava were evaluated and treated at this hospital. In 4 of the 12 patients (33%), the tumors extended into the right atrium. These 4 patients underwent radical nephrectomy with tumor thrombus extraction. Of the 4 patients one had metastases to regional lymph nodes, but no patient had distant metastases. We used a cardiopulmonary bypass and a right atriotomy in all patients for the removal of thrombus under direct vision. We also performed in the intra-operative transesophageal ultrasonography for monitoring of intra-atrial thrombus. The average blood loss during operation was 10, 430ml. One of these patients died in the postoperative period and the other patient died from inferior vena caval emboli without long term sequelae. However, the remaining 2 patients of this group are free of disease, with a mean follow-up of 21 months. Although the numbers are small, these results suggest that patients with intra-atrial tumor thrombus had a worse prognosis than those with other types of vena cava tumor thrombus. One reason for this poor prognosis is due to the complicated surgical management and we believe that a complete removal of tumor thrombus and a complete vascular control are key points of this operation.

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Twelve pediatric patients with antenatal diagnosed urinary tract anomalies from 1988 to 1992 in Niigata University Hospital were clinically examiend.
1: All patients were diagnosed by ultrasonography. Eleven cases did not have any abnormal pregnancy and other had oligohydramnious.
2: Postnatal surgical treatments were performed in 11 cases, but antenatal therapy was not performed in any case.
3: Temporary percutaneous nephrostomy (PNS) were carried out on 7 kidneys in 6 cases during infantile period seemes to be effective in preserving function of congenital obstructed kidneys.

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Submucosonography to stage tumors of the esophagus and stomach is well reported. Here we report our experience with a modified procedure to evaluate the stage of bladder tumor cystoscopically and compare the results of staging by other methods. The evaluation was carried out on accuracy 10 patients (10 bladder tumors). A water soluble contrast medium (CM: lohexol 33mg/ml) was injected into the submucosa of the bladder cystoscopically. Usually the injected point was one centimeter to the urethral margin of the tumor and up to three points were selected. Within 30 minutes after the injection, the lateral and frontal X-ray pictures were taken. The accuracies of staging by submucosonography were compared with the results of other methods, i. g., ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI). By submucosonography, three categories depending on the diffusion of CM were classified as follows. Type I: (diffuse type) without disturbance of diffusion. Type II: (borderline type) between type I and III. Type III: (defect type) local disturbance of diffusion. Overall accuracies of each were 70.0% (submucosonography), 62.5% (US), 44.4% (CT), 66.7% (MRI) respectively.
The accuracies of submucosonography were high in stage Ta, above stage T2 and low in stage T1.

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Specific progesterone-binding protein (P₄-BP) is demonstrated in adrenocortical nuclei of the guinea pig, but, not in nuclei of other animals. We tried to demonstrate the progesterone-binding activity in nuclei of human normal adrenals and adrenal tumors. Normal adrenals were obtained from six patients with renal cell carcinomas undergoing radical nephrectomy. Seven adrenocortical adenomas were obtained: five tumors from patients with Cushing's syndrome, one tumor from nonfunctioning adenoma, and one from aldosteronoma. Nuclei were purified from the tissues, and progesterone binding assay was performed.
We could not demonstrated progesterone-binding activity in nuclei of six normal human adrenals. However, we demonstrated progesterone-binding activity in nuclei purified from human adrenocortical adenomas associated with Cushing's syndrome. Saturation analysis revealed a Kd of 13.85±1.99 nM (mean±SD, n=5) and a binding capacity of 1.95±0.37pmol/mg DNA (mean±SD, n=5). A Kd of progestrerone-binding activity in human adrenocortical adenoma was similar to that of guinea pig P₄-BP, and a binding capacity was about one-fifteenth of guinea pig P₄-BP. However, nuclei purified from a non-functioning adrenocortical adenoma and an aldosteronoma failed to demonstrate progesterone-binding activity. The binding activity was specific for progesterone. 5α-pregnane-3, 20-dione was a modest competitor, while, 17β-estradiol, testosterone, cortisol, and other related steroids were poor competitors. Thus the progesterone-binding activity in human adrenals was similar to guinea pig P₄-BP in the affinity and specificity of binding. Furthermore, we demonstrated [³H] progesterone bound to nuclei from normal human adrenals, as well as, from adrenocortical adenomas associated with Cushing's syndrome by means of thin layer chromatography. It is possible that the progesterone-binding activity is too low to be detected by the classical steroid binding assay.

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Incidentally discovered prostatic cancer can pursue a benign clinical course or it can rapidly progress. For the purpose of this study, we summarized pathological and clinical results of 107 (5.3%) stage A prostatic cancer patients in 2008 transurethral resection of the prostate for clinically diagnosed benign prostatic hyperplasia. For each patient, 3.9 slides, 13.6 tissue chips per slide and 52.5 tissue chips per patient (from 16 to 140 chips) were examined microscopically.
The survival rates of patient with well, moderately and poorly differentiated groups were 62, 37 and 12% at 10 years, and those with Gleason score 2 to 4, 5 to 7 and 8 to 10 group were 63, 42 and 0% respectively. The survival rates in stage A1 (well differentiated or Gleason score 4 or less in less than 5% of the tissue removed during transurethral resection of the prostate) and stage A2 (anything other than stage A1) were 63 and 41% at 10 years, respectively. And cancer specific survival rates in stage A1 and stage A2 were 96% and 64% at 10 years, respectively. The number of cancer specific death were 1 in 30 (3.3%) in stage A1 group and 14 in 77 (18.2%) in stage A2 group.
Our results indicated that tumors with low potential for aggressive behavior had a volume extent of less than 5% and a well differentiated group. Aggressive treatments should be recommended to all patients who were diagnosed stage A2 prostatic cancer.

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Mechanism of action of Deoxyspergualin (DSG) in vitro has not been clarified, because it is unstable in solution. I studied its mechanism in vitro using Deoxymethylspergulin (MeDSG) that is stable in solution. Action of MeDSG was studied using human lymphocyte and a human T cell clone which was established in our laboratory. MeDSG showed dose dependent inhibition of blastogenesis in MLR. MeDSG inhibited the response by about 50% at the concentration of 10μg/ml. It is a very intresting point that MeDSG added at 3 days later suppressed MLR. But MeDSG did not suppress MLR added at 4 days later or 2nd MLR. MeDSG did not have effects on the production of IL-1, IL-2 and the expression of IL-2 receptor on stimulated lymphocyte by mitogen. But MeDSG suppressed IFN-γ production induced stimulation of alloantigen at only concentration of 1μg/ml. MeDSG did not suppress proliferation of helper T cell clone. On the other hand, CsA suppressed IL-2 receptor expression and proliferation of helper T cell clone. These results showed MeDSG act on relatively late phase of immunoreaction. From in vitro results, when we use DSG for clinical acute rejection, it is more appropriate to use DSG and Methylprednisolone at the same time to get early recovery.

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Testicular tumor tissues and various normal tissues were examined by immunohistochemical techniques for expression of globotriaosylceramide (Gb₃) using anti-Gb₃ monoclonal antibody (1A4). In formalin fixed paraffin-embedded specimens (31 cases), Gb₃ was positive for every kind of elements of tesicular germ cell tumors, especially it's incidence of positive staining were 100% in seminomas (16/16) and embryonal carcinomas (6/6). On the other hand, four cases of testicular malignant lymphoma were all negative for Gb₃, and some normal testicle, liver, kidney, pancreas, spleen, ileum and rectum showed very weak reactivity with 1A4. In frozen materials (10 cases), similar incidence of positive staining with that of paraffin-embedded specimens were observed in drying only manner, 4% parafolm-aldehyde fixation following drying and 10min. of acetone fixation following drying. Incidence of very strong staining in testicular germ cell tumors were as follows, 7/10 in 4% parafolm-aldehyde fixation, 6/10 in drying only, 4/10 in 10min. of acetone fixation and 7/22 in paraffinembedded specimens. Fixation with 30min. of acetone fixation and 10min. of 90% ethanol and treatment with 10min. of chloroform: methanol (2:1, v/v) extreamly decreased the reactivity with 1A4, suggesting that Gb₃ exists mainly as glycolipid.
Gb₃ may thus be a useful histological marker for testicular germ cell tumor, and the tissue should be treated with the process of freezing followed by 4% parafolm-aldehyde fixation, drying only or 10min. of acetone fixation, and formalin fixed paraffin-embedded specimens were also available enough.

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

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