The in vivo anticancer effects of high energy shock waves (HESW), on bladder cancer induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), were studied in the rat using the Siemens lithotriptor (Lithostar). There was no significant difference in the anticancer effects in delaying tumor growth, measured as the whole bladder weight including the weight of the cancer, between the groups with and without exposure to HESW. However, light microscopic examination revealed extensive submucosal bleeding and exfoliation of mucosa, and electron microscopic examination revealed degeneration of pleomorphic microvilli, swelling of mitochondria, and destruction of mitochondorial cristae in the cancer cells in bladders exposed to HESW. Flow cytometric determination of DNA content in the cancer cells exposed to HESW indicated a selective diminution of cells in the G2 and M phases and an increase of cells in the G0 and G1 phases of the cell cycle.
While the mechanism of HESW-induced anticancer effect could not be determined on the basis of this study, these changes in the morphology and the cell cycle of cancer cells induced by HESW exposure suggest some kind of biological effects following exposure to HESW.
It is expected that HESW be an effective method for the treatment of human cancer in combination with chemotherapy and radiation.

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Renal adenocarcinoma was induced in CBA/H/T6J mice by a single intraperitoneal injection of 250mg/kg of streptozotocin (STZ). Light and electron microscopic examination revealed that the carcinoma was a granular cell type-adenocarcinoma with abundant microvilli, basal lamina and intermediate junction indicating an epithelial cell origin.
In histopathological analysis of the process of this carcinogenesis, all of the kidneys examined had a dilatation of proximal tubules in the second month and thereafter. In the fifth month, one of eight kidneys developed an adenoma. The adenoma was found in all the kidneys after the ninth month. An adenocarcinoma developed in one of the 14 kidneys in the twelfth month and in all others in the fifteenth month.
In vivo labeling of bromodeoxyuridine on the cells in various stages demonstrated an increase of the labeling index which paralleled with progression of the carcinogenesis process. This finding in in vivo analysis of cell proliferation also supports the idea that serial changes of the kidney which are histopathologically proven correspond to the carcinogenesis process.
The original carcinoma (STZ-RCC) has serially been passed in vivo at the present. Intrasplenic injection of STZ-RCC yielded multiple macroscopic foci of metastasis in the liver. This indicates that STZ-RCC has a malignant potential.
Thus, STZ-induced mouse renal adenocarcinoma can be applied to the model system to investigate carcinogenesis and biological behaviors of renal cell carcinoma.

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We selected highly metastatic lines from mouse renal adenocarcinoma (STZ-RCC) chemically induced with streptozotocin.
At eight weeks after an intrasplenic injections (IS injection) of original STZ-RCC, this procedure yielded metastasic foci in the liver, which we transplanted serially in syngeneic mice (STZ-HM1). STZ-HM1 was then injected into the spleen of a syngeneic mouse, which provided a source for further cycles of hepatic metastasis selection. Three cycles of selection for hepatic metastasis yielded a high hepatic metastasis line (STZ-HM3). Intravenous injection of the parent line (original STZ-RCC) yielded metastatic foci in the lung eight weeks later, which we also transplanted serially in syngeneic mice (STZ-PM1).
The repeated IS injection of the cells was clearly responsible for the increase in the frequency of hepatic metastasis and the number of its nodules. In particular, STZ-HM3 was revealed to have more metastatic nodules in the liver ranging from 293 to 432 (median; 368) in all five mice at eight weeks after IS injection. STZ-PM1 had a significantly higher rate of pulmonary metastasis and more pulmonary metastatic nodules after intravenous injection than the parent line. These results confirm that the parent line, STZ-RCC, has a heterogeneity in the metastatic phenotype.
In vitro invasion assay for STZ-RCC, STZ-HM1, -HM2 and -HM3 demonstrated that in vitro invasive potential was paralleled with in vivo hepatic metastasis potential. The result suggests that the invasion potential revealed by in vitro invasion assay is important in metastasis formation.

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Immunomodulatory effects of cholera toxin (CT) were investigated in a rat model, and the effects of CT on rat renal allograft (from Lewis rat to WKAH rat) were also examined. The results are: 1) The number of lymphocytes in the thymus, spleen and peripheral blood was remarkably decreased after 7 day administration of CT (0.1 and 0.2mg/kg/day), but the number of red blood cells and neutrophils was not decreased. 2) CT suppressed mixed lymphocyte reaction (MLR) in a dose dependent fashion, and %suppression reached 97% at the concentration of 10μg/ml. The later the time of addition of CT to MLR, the less became this effect. 3) In the control group, the mean survival time (MST) after transplantation was 8.5±0.3 (Mean ± SE) days. CT, given 1 day before transplantation, did not prolong MST. In the group to which CT was given daily for 14 days from the day of transplantation, MST was prolonged with the increase of CT. CT at the dosage of 0.2mg/kg/day prolonged MST (16.2±3.2 days) significantly (p<0.05), where treated with CT from the 3rd day after transplantation, MST (10.3±1.3 days) was not significantly prolonged. From the above findings, CT seems to act mainly on the early phase of acute rejection and prolongs rat renal allograft survival.

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We studied whether or not prophylactic use of antibiotics following transurethral resection of prostate (TUR-P) was needed. The subjects were 152 patients preoperatively passing sterile urine who underwent TUR-P. They were divided into three groups: 35 with no use of antibiotics (no prophylaxis group), 70 with one day use of antibiotics (one day-prophylaxis group) and 47 with use of antibiotics untill pyuria disappeared (long term-group). The three groups did not differ in their rates of fever episodes (≥38.0°C) during the first two weeks nor in the time of disappearance of pyuria. The no prophylaxis group and the one day-group differed statistically in their cumulative rates of bacteriuria (≥10⁴CFU/ml) on the postoperative third day: 4 patients (11.4%) in the no prophylaxis group and none in the one day group (p<0.01). On the 90th day, however, no significant difference was found in that rate: 22 patients (62.9%) in the no prophylaxis group and 32 patients (45.7%) in the one day group. 70% of the bacteria isolated from urine during the follow up were Gram positive cocci. The time to the elimination of pyuria was not influenced by the use of antibiotics. Our study suggests that postoperative antibiotics for patients passing sterile urine is not necessary following TUR-P.

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Whether or not recurrence is related to the results of urinary cytology examined within 10 days after transurethral resection of bladder tumour was studied retrospectively in 47 patients with superficial bladder tumour. Of 7 cases with positive cytology during the postoperative 10 day period, 4 cases had a later recurrence of tumour and 2 cases had a residual tumour due to incomplete resection of original tumour.
By microscopic chromocystoscopy, in 11 patients concurrent urothelial atypia (carcinoma in situ or dysplasia) was found in the apparently normal mucosa. Nine of the 11 cases had a later recurrence of tumour or a residual tumour.
Of in total 15 patients combined with abnormal cytology and concurrent urothelial atypia, 12 (80%) were found with recurrence of tumor cystoscopically 4-64 months (mean; 20.6 months) after TUR. This recurrence rate was significantly (p<0.05) higher than that (42.4%) in patients without positive cytology and concurrent urothelial atypia.
These results suggest that positive urinary cytology during 10 days subsequent to TUR and/or association with concurrent urothelial atypia are indicative of later tumour recurrence, incomplete resection of tumour or presence of additional occult tumour foci.

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Cell population of urinary leucocytes of 22 patients (intestine group) who underwent operations using intestinal segments for the urinary tract was compared with that of 26 complicated UTI patients without surgical intervention (control group). Eosinophils were recognized in 15.5 per cent of urinary leucocytes of the intestine group. However, in the control group, urine eosinophils were recognized only in 0.15 per cent. Although in sterile urines of the intestine group eosinophils were recognized in 30.8 per cent, in infected urines, the percentage of eosinophils decreased. Conversely, the percentage of neutrophils increased to 91.9 per cent. These findings suggest that neutrophils play an important role in infected urines of the intestine group as in urines of the control group.
Significant differences were found in the values of urinary secretory IgA, IgG, IgM and urinary osmolarity. To evaluate the influence of these differences on the activity of phagocytosis of urinary leucocytes, the activity of phagocytosis of polymorphonuclear leucocytes (PMN), isolated from the peripheral blood, was investigated in immersion in urines of both groups. The mean rate of phagocytosis of E. coli in urines of both groups showed no statisticaly significant differences. However, urinary osmolarity of the intestine group was within the suitable range for phagocytosis and the activity of phagocytosis in urine was correlated with the value of IgG, which suggests that IgG has the opsonic effect. In contrast, the activity of phagocytosis in urine of the control group was strongly correlated with the value of urinary osmolarity.
The growth of Providencia, Streptococcus, P. aeruginosa, whose frequency of isolation from urine of both groups was different in our previous study, and E. coli was studied in urine of the two groups. No significant difference in the growth of all bacteria was found, however. This finding suggests that the difference in the frequency of isolation of these bacteria from urine possibly depends on the adhesion of bacteria to intestinal epithelium.

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Based on the frequency volume chart, 215 patients who complained of pollaksuria were clinically investigated. The subjects were divided into 2 groups: the elderly group was composed of 85 patients more than 65 years of age (mean of 72) and the adult group comprised 130 patients less than 64 years old (mean of 47). The elderly group was characterized by the fact that, during nighttime (after sleep), their urinary volume was larger, each voided volume was smaller and the number of voiding was greater than the other group. Clinical analysis of the causes of pollakisuria enabled us to subdivide them into 6 diagnostic categories. Among the elderly patients polyuria during sleep and unstable bladder were prevalent and among adult patients unstable bladder and over hydration were common. Medication was made in 80 patients (37%), while 108 (50%) needed neither medication nor surgery. It is stressed that the frequency volume chart is one of the important diagnostic tools to evaluate the cause of pollakisuria and to select appropriate treatment.

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A clinico-pathological study was conducted on 69 patients with bladder cancer who underwent total cystectomy. The one, three and five-year actuarial survival rates for the 69 patients were 73.3%, 48.6% and 44.1%, respectively. Survival rate was not significantly associated with sex, the number of tumors or the size of tumors. The survival rate in those aged 70 years or more was slightly worse than in those who were much younger. Patients with papillary tumors had a more favorable survival rate than those with non-papillary tumors but we could find no significant difference between those with pedunculated tumors and those with sessile tumors. The actuarial 5-year survival rates by grade were 71.9% in G1+G2, 22.6% in G3 and 32% in non-transitional cell carcinoma; the rates by stage were 86.5% in pTa+pT1, 85.7% in pT2, 20.8% in pT3a, 18.2% in pT3b and 0% in pT4. When the stage reached pT3a, the survival rate fell remarkably. The rate of INFα (93.8%) was significantly better than that of INFβ (28.1%) and INFγ (15.2%). The rate of ly₀ (76.2%) was also significantly better than that of ly₁(25.5%) and ly₂ (18.8%) . There was no significant difference in survival between v(-) (50.7) and v(+) (25.9%). We could find no significant difference between patients who underwent pelvic lymph nodes dissection and those who did not. The patients were divided into those who were alive and those dead within 2-years and 5-years after total cystectomy and the degree of involvement of clinico-pathological factors was assessed by multivariate analysis (Quantification II method), using 12 factors as predictor variables. The factor with the greatest influence on prognosis was pathological stage followed by mode of infiltration. Discrimination between the living and the dead was achieved at an 87.9% success rate (2 years) and an 88.5% success rate (5 years) by this analysis. These results suggest that systemic adjuvant treatment should be carried out to improve the prognosis of patients with bladder cancer after total cystectomy when the pathological stage is judged as pT3a-pT4 and when the mode of infiltration is INFβ or INFγ even if the stage is pT2.

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We attempted to produce a maignant urinary bladder carcinoma in mice by transplanting MBT-2 cells. MBT-2 carcinoma about 3.0×10³ cells/0.02ml were succesfully transplanted into the bladder wall with an incidence of 80% (20/25) after three exprimental weeks. Inoculated tumor cells grew expansively into the bladder cavity from the bladder submucosa, and invaded the muscle layer. We observed that tumors caused gross hematuria and bilateral hydronephrosis.
This malignant tumor model in which a tumor is implanted into its original organs seems to be useful for predicting clinical effectiveness in experimental cancer therapy.

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Extracorporeal shock wave lithotripsy (ESWL) treatment was performed on 17 patients with a solitary or sole functioning kidney from August 1986 to April 1988. Some patients with renal stone had a double pig tail catheter to protect the stone street and those with ureteral stones had a ureteral balloon occlusion catheter to raise the efficiency of fragmentation placed prior to ESWL as much as possible. Combined manipulation with such an instrument as nephrostomy tube to wash out residual stone fragments or endoscopic operation were performed. Despite of these devices, ESWL treatments for staghorn calculi and cystine stones were troublesome in solitary kidneys. After follow up ranged from 9 to 602 days (mean 87.6 days), 10 patients (58.8%) were stone free. ESWL treatment is safe and effective for solitary kidneys. We recommended premedication and pretreatment by ureteral stenting in patients with a solitary kidney.

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Using new criteria for histological effects of anti-cancer treatment, the effects of hormono-chemotherapy on 10 patients with prostatic cancer not previously treated were compared with those on 10 patients who received conventional hormone therapy. Marked effects were observed in 4 (40%) patients received hormono-chemotherapy but not observed in patients who received conventional hormone therapy (x² test, p<0.05). All four cases who showed marked effects were in stage B at the beginning of treatment. Hormonal effects were more obvious in well differentiated cancer, and the effects of chemotherapy were observed in some cases with moderately and poorly differentiated cancer. Therefore, the addition of chemotherapy is recommended as the initial therapy on prostatic cancer to reduce the relapsing rate, especially for patients with poorly and moderately differentiated cancer.

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Voiding cystourethrography (VCU) of 407 children with vesicoureteral reflux (VUR) at our hospital during 1969-1990 was reviewed and 7 cases (8 ureters) of intrarenal reflux (IRR) were found. All the children were male and had had an episode of febrile urinary infection under one year of age. One child had a left flank mass, which was later proven a urinoma. VUR was moderate (grade III) in 3 and massive (grade IV and V) in 5. VUR was estimated as primary in one child and as secondary in 6 (anterior urethral ring 2, posterior urethral valve 2, neurogenic bladder 2). IRR was localized to the upper area in 3, to the lower area in 2, and to the whole kidney in 3. Sixty percent of those with IRR in the polar areas was associated with moderate VUR, whereas all of those in the whole kidney was with massive one. Renal scarring was assessed by excretory urography (IVP) and/or ^99mTc-DMSA renoscintigraphy. Seven kidneys were evaluable; polar scars in 5, dwarf with polar scar in 1 and dwarf with poor function (suspected hypodysplasia) in 1. In 4 kidneys new scar formation was observed. It was noted, however, that IRR did not necessarily accompany renal scars of the corresponding areas and IRR to the whole kidney did not always lead to multiple scars in the whole kidney. The nature and problems of IRR, renal scars and ^99mTc-DMSA renoscintigraphy were discussed. It was suggested that urinary infection played a greater part in renal scar formation.

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Human external urethral sphincters (n=13) were studied histochemicaly, using ATP-ase staining. The proportions of constituent muscle fiber types (slow twitch type 1 fibers: 35.6-97.7%, mean 65.7%, SD 16.6) were different among the individuals. There were no ignifiscant relationships between the percentage of type 1 fibers and the sex or the age.
As for the mean muscle fiber diameter of 13 cases, the sizes of type 2 fibers (19.2-42.4um, mean 27.8um) were significantly (p<0.05, t-test) larger than those of type 1 fibers (15.7-30.3um, mean 22.3um). In analyses of individual cases, 10 male cases had significantly larger type 2 fibers than type 1. Two of 3 female cases had no significant difference in diameter between the two fiber types and the remaining 1 female case, in contrast with male cases, had significantly larger type 1 fibers than type 2.
There was no significant relationship between the proportions and the diameters of constituent muscle fiber types.
Our study thus showed extreme interindividual variation and implicated the presence of sexual difference in human external urethral sphincter muscle.

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Quantification of argyrophilic nucleolar organizer regions (AgNORs) stained by the silver colloid method in urinary exfoliative cells from 36 benign urological diseases and 33 transitional cell carcinomas (TCC) of the urinary bladder was carried out. Also, AgNORs of these cells were measured by means of the computer-assisted image analysis system. There was a significant correlation between AgNORs numbers of cells from voided or wash-out smears and those from touch smears (p<0.01). The mean AgNOR numbers per nucleus showed a stepwise increase from non-infected benign urological diseases (mean±SD: 3.33±0.60) through infected urological diseases (3.88±0.58), grade 1 of TCC (5.23±1.39) and grade 2 of TCC (6.34±0.86), to grade 3 of TCC (8.09±1.19). The maximum number of AgNORs in each group indicated almost the same results. The estimation of the distribution of the maximum AgNOR number might be of great value for rapid and reliable detection of bladder cancers. Moreover, the computer-assisted image analysis of AgNORs could offer an objective index for the cytological assessment of urinary bladedr diseases including TCC.

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The patient was a female aged 18. Hematuria was discovered at an examination two years previously at which time the patient was complaining of right lumbar pain. The patient visited our hospital with a chief complaint of right abdominal tumor in June, 1988.
A retroperitoneal tumor, 77×45mm in size, was observed by CT and ultrasonic examination, and the right kidney was in hydronephrosis. An operation was performed in September, 1988, based on a diagnosis of retroperitoneal tumor and hydronephrosis. The tumor was seen to have involved the right ureter. Subsequently the tumor was surgically removed; right total nephroureterectomy and partial cystectomy were performed at that time. The removed tumor was 90×70mm in size and 120g in weight; it was histopathologically diagnosed as extraskeletal Ewing sarcoma. A systemic examination was carried out postoperatively, but no abnormalities were observed. As of September, 1990, the patient had had no recurrence and was being kept observation on an outpatient basis.
There have been a total of 210 case reports regarding extraskeletal Ewing sarcoma published worldwide, including our case and 26 cases in Japan, so far as we know. However those of a lesion of retroperitoneal origin are extremely rare, numbering only 11 cases worldwide and 2 in Japan. Herein we report our case of extraskeletal Ewing sarcoma with reference to the other 209 cases reported in the literature to date.

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Two cases of eosinophilic cystitis are reported. Case 1 was a 7-year-old boy with pollakisuria and case 2 was a 20-year-old man with right lower abdominal pain. They were suspected of bladder sarcoma after the examinations by cystoscopy, IVP, ultrasonography, CT and NMR-CT. Transurethral, percutaneous and open biopsies were performed and histloogical examination revealed massive infiltration of eosinophils mainly in the vesical muscle layer without malignant cells. We could establish the diangosis only by biopsy. In case 1, IgE RAST was positive for tick and case 2 seemed to be allergic to rare beef. We presumed that they caused eosinophilic cystitis.

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