Argyrophilic Nucleolar Organizer Regions (AgNORs) were examined in 96 patients with renal cell carcinoma undergoing nephrectomy at Department of Urology, Chiba University Hospital during 1985-1990. Silver staining was performed with one-step method described by Ploton, and average numbers of grains in a cell were obtained by counting 100 cells.
Numbers of AgNORs were increased along with up grading. When AgNORs were compared in various cell types, the number in pleomorphic and spindle types and that in Bellini duct carcinomas were more than that in common types. The number of AgNORs correlated with pT and pV factors, but no relationship was shown between the number and these factors when compared in the same grade. The tumor size correlated with the number of AgNORs. The number of AgNORs in the primary legion showed a reversed correlation with doubling times calculated from either primary, recurrent or metastatic legions examined in 22 cases. In all cases it tended that the number of AgNORs correlated with survival, however survival in G3 cases was not influenced due to worse prognosis.
It was concluded that the number of AgNORs in renal cell carcinoma was an additional factor for estimating the properties of tumor cells.

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We established four renal cell carcinoma (RCC) cell lines (HANKS), namely the primary tumor (HANKS-Pr), metastasized to the lung (HANKS-Lu), liver (HANKS-Li) and lymph node (HANKS-LN) derived from a patient with advanced RCC, and analyzed their characters. Each had an epithelial morphology and exhibited multilayering. These cell lines have been maintained for more than 36 months and over 100 in vitro passages. In karyotype analysis, the common aberration in the four cell lines was marker chromosome t(3;18)(p13;q21). In soft agar culture, HANKS-Pr showed the lowest growth. Furthermore, we found high level expression of major histocompatibility complex (MHC) class I antigen on HANKS-Pr and HANKS-Lu, and low expression of MHC class II antigen on four cell lines. HANKS-LN had transplantability in nude mice.
We determined the different biological properties among HANKS cell lines stemming from the same origin.

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An evaluation was made of the long-term results and risk factors of tumor recurrence in patients with superficial bladder cancer who were treated with intravesical bacillus Calmette-Guerin (BCG) and who had a mean follow-up period of 57 months.
Eligible for the study were a total of 102 patients who were treated by transurethral resection of tumors and were considered to be free from tumor from 1984 to 1989. A suspension containing 80mg Tokyo 172 strain BCG in 50ml normal saline was given intravesically to 50 patients once a week for six weeks without further maintenance instillation. To the other 52 patients was additionally given monthly intravesical BCG instillation for 12 months.
The actuarial nonrecurrent rates according to sex, different BCG treatment protocol, tumor grade, tumor status including primary or recurrent tumors, and solitary or multiple tumors were estimated by Kaplan-Meier method. The estimated three-, five- and seven-year actuarial nonrecurrent rates in all 102 cases were 77.3%, 68.5% and 60.6%, respectively. When nonrecurrent rates were compared to tumor characteristics, no statistically significant differences were observed between primary and recurrent tumors or between solitary and multiple tumors estimated by generalized Wilcoxon method. On the other hand, when nonrecurrent rates were compared with tumor grades, grade 3 tumor showed a 40.0% three-year nonrecurrent rate. The differences between grade 3 and grade 1 and between grade 3 and grade 2 were statistically significant (p<0.05).
When the efficacies of BCG therapies incorporating different BCG treatment protocols were compared, the 50 cases of the weekly instillation group presented 58.4% five-year nonrecurrent rate compared to 74.4% for the 52 cases treated by maintenance instillation. However, the difference was not statistically significant. The mean tumor-free periods compared between the weekly treatment group and the maintenance group revealed 41.7±18.7 months and 53.1±21.3 months, respectively, with the difference being significant (p<0.01).
Multivariate analysis using Cox's proportional hazards model was performed to identify the most significant factors for tumor recurrence. The single most important factor for tumor recurrence was found to be tumor grade (risk ratio 9.694, p<0.05). No other factor was chosen as a statistically significant factor for tumor recurrence.
These results indicate that efficacy of intravesical BCG instillation for high-grade bladder cancer is not sufficiently satisfactory, and that maintenance instillation probably contributes to a tumor-free period and to delayed tumor recurrence.

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The following experiment was performed to estimate PAH clearance of chronic unilateral and completely obstructed kidney and to explore its change during obstruction period. Thirty adult male mongrel dogs were used. Unilateral complete ureteral obstruction was made by ligation of the left ureter proximal to the bladder. After 3, 5, 10, 20 and 40 days of obstruction, an experiment was performed. Under laparotomy, the left kidney was exposed and polyethylene catheter was inserted into the renal pelvis. Intrapelvic pressure was monitored by pressure transducer. In a condition that PAH (p-aminohippurate) was constantly infused intravenously, intrapelvic urine of the obstructed kidney was exchanged for physiological saline. After the exchange, intrapelvic PAH concentration was measured at hourly intervals for 4 hours. At each midpoint of the measurements, plasma PAH concentration was measured. At the end of the experiment, the obstructed kidney was resected and pelvic capacity was measured.
PAH of the obstructed pelvis increased at hourly intervals after the exchange. The result showed that the clearance ability was maintained in the completely obstructed kidney. PAH clearance values were 16.3, 13.6, 1.0, 0.9, 0.9ml/hr/kg b. w. at 3, 5, 10, 20 and 40 days obstruction respatively. PAH clearance decreased sharply during early stage of obstruction and tended to reach a fixed low value at over 10 days of obstruction. Our experimental method seemed to be available to estimate the clearance ability of chronicaly, unilaterally and completely obstructed kidney.

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We evaluated 18 patients with renal pelvic and ureteral carcinoma focusing on the operative treatment. All the patients underwent nephroureterectomy and partial cystecotomy, except for two patients, with CIS of the ureter and renal insufficiency, and one with invasive bladder carcinoma, in whom partial ureterectomy and total cystectomy were performed, respectively. Lymphadenectomy were performed in all the patients and resected lymph nodes were from renal hilus, para-aorta or vena cava, according to the affected side, intra aorto-caval and all the pelvic nodes in the affected side. Lymph node metastases were found in 4 patients (22%), 2 in the primary and distant nodes and the other in the regional nodes only. Skipped lesion of the lymph node metastasis was not rare and lymph node dissection from the renal hilus to the pelvis on the affected side should be included in the operative treatment of renal and ureteral carcinoma.

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Alkali therapy is widely accepted as a treatment for recurrent calcium stone patients with distal renal tubular acidosis (dRTA).
Nine patients, five with complete and four with incomplete type of dRTA, were treated with alkali agents for more than three years; an average period of 10.8 years. In five patients, new stone formation and stone growth were completely prevented by this treatment. Among the four failed cases, three did not take enough alkali agents (in spite of our medication), and the other had recurrent urinary tract infection resulting in infectious stone formation.
In conclusion, the long-term efficacy of alkali therapy for prevention of recurrent stone formation with dRTA is confirmed when the patient takes enough alkali agents and the urinary tract infection is well controlled.

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Granulocyte-Colony Stimulating Factor (G-CSF) was administered to patients with bladder cancer, ureteral cancer and testicular cancer following chemotherapy. Chemotherapy included 23 courses of M-VAC (Methotrexate, Vinblastine, Adriamycin, Cisplatin) therapy to patients with bladder cancer or ureteral cancer and 10 courses of EP (Etoposide, Cisplatin) therapy to patients with testicular cancer. During M-VAC chemotherapy, about a half of the patients experienced leukopenia below 3000/mm³ until the 11th day. Leukopenia failed to improve promptly when G-CSF was started after leukocytes decreased below 3000/mm³. On the other hand, 5-days of prophylactic administrations of G-CSF from the 9th day of M-VAC therapy were able to increase leukocytes promptly.
In EP chemotherapy against testicular tumor, G-CSF was started on the 9th day and continued for 5 days. Leukocytes increased immediately and the average duration of leukopenia below 3000/mm³ was only 1.2 day.
These results indicate that a short term of prophylactic administration of G-CSF following these chemotherapies is able to accelerate a recovery from leukopenia and decrease a risk of bacterial infection.
G-CSF is proposed to be enrolled in the treatment of urological cancer for the improvement of safety and the outcome of therapy.

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One hundred and five patients with renal pelvic and ureteral tumor entered our treatment program between 1982 and 1991. Of 105 patients, 81 had resectable transitional cell carcinoma and were treated with radical or total nephroureterectomy (57 vs. 24) and/or lymph node dissection (66). Adjuvant chemotherapy was added in 26 patients with high stage disease and with lymph node disease. There were 61 male and 20 female patients. Their ages ranged from 36 to 86 years, with a mean of 62 years. The follow-up period was 3 to 114 months, with a mean of 31 months. The estimated 5-year survival was 67% in all 81 patients. Classified according to the pathological stage, 5-year survival was 70% in pTis+pTa disease group, 91% in pT1 group, 88% in pT2 group, 53% in pT3 group, and 27% in pT4 group. Under the grading system, 5-year survival was 100% in grade 1 disease, 74% in grade 2, and 26% in grade 3. It was 78% in 52 patients with negative node disease and 26% in 15 with positive node disease. There were 51 patients (61%) with no recurrent disease. Seventeen patients (21%) had recurrence in the bladder after a median latent period of 8-month, and 15 (19%) patients had recurrence in the retroperitoneum, liver, lung and (or) other site after a median latent period of 8 months. The results of this series were quite similar to those of previous reports. The efficacy of lymph node dissection and adjuvant chemotherapy could not be confirmed.

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A survey by questionnairs was performed to understand the present conditions of urinary incontinence in the aged. The objects were 748 persons who were residing in eight geriatric nursing homes locating in Nara Prefecture. The answers from 183 males and 565 females ranging from 57 to 101 years old were collected and analyzed.
The answers were interpreted as follows: (1) Of these 748 persons 422 (56%) were incontinent, 94 males (51%) and 330 females (58%). (2) The higher age group tends to show the higher rate of incontinence. (3) The rate of incontinence seems to highly correlate with the degree of dementia and impaired mobility. (4) Sixty-nine persons (16%) had consulted a nursing home doctor and/or other medical doctors, only 20 of whom had been medicated for incontinence. (5) An institution where a behavioral therapy program had been employed showed a lower rate of incontinent persons.
From these results, it is considered that not only an increase of nursing staff but also aggressive participation of medical specialists including urologists are needed to improve their quality of life.

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Human chorionic gonadotropin (hCG) is a highly specific tumor marker for trophoblastic neoplasmas. Also in patients with non-trophoblastic tumors, hCGβ-related material has been frequently demonstrated in their urine. This material was termed β-core fragment (β-CF) since it is recognized by hCGβ-core directed antisera but not by hCGβ-carboxyterminal peptide (CTP) directed antisera.
We measured the concentration of β-CF in the urinary samples from patients with urotherial tumors and studied its clinical usefulness as a tumor marker. The concentration of β-CF was expressed as ng/mg of creatinine in the urine and the cut-off value was 0.1ng/mg·Cr. Thirty (61.2%) of 49 patients with bladder carcinoma had raised β-CF levels and the positive rates were dependent upon pathological grade (25.0, 33.3 and 82.8% at G1, G2 and G3, respectively). The elevated urinary β-CF were also detected in 5 of 7 patients with upper urinary tract carcinoma. However, there was no elevated urinary β-CF level in prostate carcinoma. Serial determination in 13 patients with elevated β-CF level prior to therapy showed that 12 patients had decreased concentrations after successful treatment, but 1 patient with persistently elevated urinary β-CF level after treatment subsequently relapsed.
The determination of urinary β-CF may provide a useful tool in identifying and monitoring the response to treatment in patients with carcinomas of the bladder and the upper urinary tract.

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Nd:YAG laser irradiation and flexible cystoscopy were used in the outpatient management of 16 cases (21 sessions) with superficial bladder tumors. Irradiation of tumors was accomplished in all cases except 3 in which the visual field was affected by bleeding after the cup biopsy of tumors. Tumors at the bladder neck were easily irradiated through the flexible cystoscope. No tumor recurred at or near the previously irradiated site. This method provided a safe and cost-effective means to treat superficial bladder tumors in selected cases.

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We investigated the alterations of urodynamic parameters of reflex micturition evoked by filling the bladder with physiological saline prior to and after the administration of midodrine (alpha 1 agonist), terazosin (alpha 1 antagonist), clonidine (alpha 2 agonist) and yohimbine (alpha 2 antagonist) in 28 male decerebrate dogs. The significant finding produced by midodrine was an increase in contraction pressure, while terazosin produced a significant decrease in threshold pressure, contraction pressure and urethral pressure. Clonidine produced a decrease in threshold pressure, urethral pressure and external urethral sphincter activity, while yohimbine produced a significant increase in bladder volume and urethral pressure. It seems that alpha 1 adrenergic activity modulates urethral closing pressure via postsynaptic alpha 1 receptors, and that alpha 2 adrenergic activity mainly modulates urethral closing pressure via presynaptic alpha 2 receptors in the lower urinary tract function.

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The tissues consisted of adenocarcinoma of the prostate were examined by immunohistochemical study with monoclonal antibody (43-21-1-1) against γ-seminoprotein (γSm). The degree of staining regarding any correlation with the histological grade was evaluated. The prostatic tissues were obtained by transurethral resection or by fine needle biopsy from untreated 38 patients. The avidinbiotin peroxidase complex technique was used to stain on 3μm-sections of 10% formalin fixed, paraffin embedded tissue. In addition, immunohistochemical staining with the commercialized antibodies to prostate-specific antigen (PSA; polyclonal, DAKO) and to prostatic acid phosphatase (PAP; polyclonal, DAKO) was done simultaneously for a comparative study. The degree of immunoperoxidase stain was classified into two categories, namely location and pattern, and was graded from 0 to 3, respectively. The product of the degree of location and the degree of pattern was noted as the total score. The mean of score was calculated in each histological grade. Then the means of total scores were compared and evaluated as having any statistical difference by Student's t test among 3 histological grades as well as among 3 primary antibodies used in this study.
When the monoclonal antibody to γ-Sm was used for immunoperoxidase staining, the means of total scores and the rates of negative reactions (% Negative) in 3 histological grades were 6.8±1.8 (M±SD) and 0% in well (N=9), 4.4±2.4 and 14% in moderately (N=22), and 1.8±2.3 and 54% in poorly differentiated lesions (N=11), respectively. There were statistically significant differences (P<0.05) among 3 histological grades. The means of total scores and % Negative by PAP staining were 7.1±1.5 and 0% in well (N=8), 6.1±2.5 and 9% in moderately (N=22), and 4.3±3.2 and 30% in poorly differentiated lesions (N=10) respectively. However, no statistical differences were noted among 3 histological grades. The PSA staining demonstrated almost the same findings as did PAP staining. The means of total scores and % Negative by PSA staining were 7.1±1.5 and 0% in well (N=8), 5.9±2.5 and 9% in moderately (N=21), and 3.8±2.5 and 10% in poorly differentiated lesions (N=10), respectively. There was no statistical difference between the moderate and the poor, but between well and moderately differentiated lesions (p<0.05).
In conclusion, the degree of immunoperoxidase staining with the monoclonal antibody to γ-Sm correlated well with histological grade. The monoclonal antibody to γ-Sm may have an important role to distinguish between moderately and poorly differentiated adenocarcinoma of the prostate.

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Early changes of sugar chain detected by binding with lectines on luminal cell membrane of rat bladder epithelium treated with N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) were immunohisto-chemically examined with a transmission electron microscopy using ferritin-labeling lectins.
BBN was given to male Wistar rats at the concentration of 0.05W/V% in drinking water, and the rats were sacrificed at 4, 8, 16, 20 weeks, respectively, after the beginning of the BBN treatment. The bladder was treated with Half Karnovsky's solution via intra aortic canulation for 20 minutes, and then removed. A part of bladder was examined grossly and by a light microscopy. The other part was cut into 3×3mm squares and fixed with 2.5% glutaraldehyde solution and washed with 0.1M cacogyl buffer with 10% sucrose. The tissue was sectioned and then incubated with ferritin-labeling lectins; concanavalin A (Con A), ulex europeaus agglutinin (UEA-1), peanut agglutinin (PNA) and dolichos biflorus agglutinin (OBA), respectivley. These specimens were examined under a transmission electron microscopy.
In cell membrane of the normal bladder, binding of Con A was found occasionally and binding of PNA was found focally, but binding of UEA-1 and DBA occurred incompletely on the cell membrane.
The plaque and ridge on cell surface of bladder epithelium found to be obscured at 8 weeks after the treatment with BBN, and microvilles were barely observed under an electron microscope, but they increased gradually and could be seen by the microscope at the time of 16 weeks after the BBN treatment. The transitional cell carcinoma of rat bladder epithelium was diagnosed by light microscopic examination at 20 weeks.
Furthermore, particles of the ferritin concomitant with Con A and PNA, respectively increased intensively on the whole cell membrane of the bladder epithelium at 20 weeks, and binding site of PNA increased mainly around microvilli, although the DBA and UES-1 were not changed during the entire period of the BBN treatment. These results suggest that the differences of lectin binding patterns on the luminal cell membrane were associated not only with malignant transformation of the epithelium but also induced by the polarity in the cells of the bladder epithelium with the BBN administration.

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The mechanisms of relaxing effect of papaverine on the phenylephrine (10^-6M)-or the high K⁺ (30mM)-induced contracture were studied on the isolated canine corpus cavernosum. Rod shaped preparation of the corpus cavernosum without the tunica albuginea was mounted in a tissue bath, immersed in Tyrode solution and the isometric tension was recorded. Cumulative applications of papaverine (10^-6-3×10^-5M) relaxed the phenylephrine (10^-6M)- or the high K⁺ (30mM)-induced contracture with a dose-dependent manner. A pretreatment with papaverine (10^-510^-4M) dose-dependently reduced the magnitude of the phenylephrine (10^-6M)-induced contracture, more prominently in the tonic than in the phasic component, while reduced that of the high K⁺ (30mM)-induced contracture in both components. The relaxing effect of papaverine (5×10^-6M) on the high K⁺ (30mM)-induced contracture was antagonized by an increase in extracellular Ca⁺⁺ concentration. A reintroduction of Ca⁺⁺ after perfusion of Ca⁺⁺ free and high K⁺ (30mM) solution containing 1mM EGTA failed to bring about normal contractile activity in the presence of papaverine (10^-4M), Papaverine, even if its high concentration (10^-4M), could not completely abolish the transient phasic contraction evoked norepinephrine (10^-5M) which was abolished by ryanodine (3×10^-6M), in Ca⁺⁺ free solution. Isoproterenol (10^-8-10^-6M) or dibutyryl cyclic-AMP (10^-5-10^-3M) relaxed the phenylephrine (10^-6M)- and the high K⁺ (30mM)-induced contracture. The relaxing effect of isoproterenol (10^-8-10^-6M) or dibytyryl cyclic-AMP (10^-5-10^-3M) on the phenylephrine (10^-6M)- or the high K⁺ (30mM)-induced contracture was promoted by low concentration (10^-6M) of papaverine. These results suggest that the mechanisms of relaxing action of papaverine on the isolated canine corpus cavernosum are an inhibition of the voltage-dependent and receptor-operated influx of Ca⁺⁺, depression of Ca⁺⁺ store sites and an increase in cellular cyclic-AMP level.

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The effect of unilateral hydronephrosis on the growth of contralateral kidney were evaluated with weanling rats of which kidneys were in growing stage (body weighed between 80g and 90g). These rats underwent complete unilateral ureteral obstruction (CUUO) on day 0. They were divided into 3 groups and went through second operations on day 3 (CUUO-3) as follows; a) CUUO released, b) nephrectomy performed and c) CUUO continued. Sham-operation was performed on day 0 and on day 3 to the controls. Wet weights and bromodeoxy-uridine (BrdU) labeling index (L. I.) (index for cell proliferation in the uriniferous tubules) of the contralateral kidneys were measured for the evaluation.
The wet weights were significantly higher in all the groups than that of the controls throughout the observation period on and after the day 3.
The group that underwent nephrectomy demonstrated a sharp rise in L. I. after the day 7. In the group that was continued in CUUO, the L. I. started to rise later than its rise in nephrectomised group but the index caught up at the time when the blood flow completely disappeared in the kidneys of the ligated side. L. I. in the group of which CUUO was released became significantly higher than that of controls on the day 7 and remained its significance until the day 21 in spite of resolusion of the hydronephrosis.
To reveal the effect of length of obstructed term, the same trial was carried out that rats endured in CUUO for 5 days (CUUO-5) till the second operation. This turned out lower L. I. in the CUUO-5 than the CUUO-3.
These results suggest that the presence of hydronephrosis made by CUUO suppress the growth (cell proliferation) of contralateral kidney and also duration of obstruction can be critical on the renal growth that shorter obstructed period turns out preferable for cell proliferation after relief of CUUO.

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During the past thirty-five years, we treated 221 patients with stage 1 renal cell carcinoma. We classified these patients into two groups: 175 patients who did not show recurrence and 45 patients who showed recurrence (excluding one patient who died of other disease). We investigated factors which affect the recurrence after nephrectomy and the survival after recurrence in these two groups.
We found two major factors such as tumor diameter and tumor grade which affected the recurrence of renal cell carcinoma. Of these two factors, the grade of malignancy affected the prognosis of the patients with stage 1. Furthermore, as a result of long-term observation, we found that patients with grade I showed good prognosis compared with these with grade II, III and IV.
The patients who showed weight loss constituted the majority of recurrent patients. Anaemia, erythrocyte sedimentation rate and positive reaction of C-reactive protein in addition to weight loss were major factors affecting the prognosis of stage 1 patients. In an effort to analysing the features of recurrent patients, there observed that no significant difference of the non-recurrent rate was detected between the patients who showed cancer death after nephrectomy and the patients who were aliving after nehrectomy.
In analysing metastatic lesions and numbers of metastatic foci, we detected relatively long-term survival especially in patients with less than 3 foci of metastases in the lung, compared to those with multiple foci. Furthermore, we found dimension of the metastasis depended on the grade of the primary lesion.

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Pseudolymphoma is reactive extranodal lymphocytosis, and it's lymphocytes are so minimally atypical that it is basically benign. The patient was a 68-year-old female with pain in the left back and lower abdomen. Plain CT (computerized tomogram) of the kidney revealed a mass in the left kidney. It had a smooth surface and higher density than parenchyma. Similarly a left orbital mass was revealed by CT. We could not deny the mass to be a malignant tumor, so we took specimens from these lesions by an open biopsy. Histological examination of these specimens showed pseudolymphoma. Pseudolymphoma of the left kidney was reduced in its size by treatment with prednisolone. The patient is continuously followed up to date.

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It is a fact that there are few effective drugs available except for interferon for that treatment of renal cell carcinoma, and the efficacy rate of interferon is less than 10% even if multiple drug regimens are included. We have experienced a case of renal cell carcinoma in whom interferon therapy was successful in reducing the primary lesion and tumor thrombus extending into the inferior vena cava.
A 57-year-old man was admitted to our department with a complaint of macroscopic hematuria. Computed tomography and magnetic resonance imaging revealed a right renal tumor and the tumor thrombus. Because of the past history of his myocardial infarction, a radical operation was considered risky. So we started interferon therapy. Four months after the start of interferon therapy, the primary lesion and the tumor thrombus markedly reduced in their size, and the clinical response was evaluated as partial response by response criteria for urological cancer treatment. Therefore, radical nephrectomy and tumor thrombectomy were performed with extracorporeal circulation.
Histopathologically, necrosis and lymphocyte infiltration into the cancer cell focus were seen, and these immunologic reactions were considered at the affection of interferon. In some case, interferon therapy is a useful and safe in the treatment of the primary lesion of renal cell carcinoma, and further investigation must be studied.

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