Experimental bladder tumor was reviewed in this paper. Many investigators have been studying on the bladder carcinogenesis since occupational bladder cancers were reported. Main object in research for bladder cancer was to identify and remove environmental causes and various factors related to the development of bladder cancer.
Human bladder cancers can be classified into papillary non-invasive and nodular invasive cancer. The establishment of an animal model of bladder cancer similar to human bladder cancer is important to clarify the natural history of this disease and obtain basic data on its clinical diagnosis and treatment.
Bladder carcinogenesis has been known to occur in a two-stage process: initiation and promotion. Recently inhibitory effects on the bladder carcinogenesis were also studied.
In this paper we described the results that have been obtained in our laboratory concerning animal bladder carcinomas.

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The effect of the streptococcal preparation OK-432, which is one of the biological response modifiers, was examined in BALB/c mice using a transplantable murine renal cell carcinoma (Renca) of spontaneous origin, and an analysis of effector cells was performed. The tumor grew progressively and metastasized consistently to the abdominal lymph nodes and then to distant organs following the inoculation of Renca cells in the left renal subcapsular site in BALB/c mice, and the survival time of the mice was under 42 days. In this tumor model, i. p. administration of OK-432 after tumor inoculation significantly extended the survival time and significantly inhibited the formation of the inoculated tumor itself. Removal of the left kidney on the 7th day after tumor inoculation neither extended the survival time nor augmented the effect of OK-432. Splenic cells obtained on the 7th day after tumor inoculation from Renca-bearing mice treated with OK-432 were capable of lysing syngeneic Renca cells, NK-sensitive allogenic YAC-1 cells, and LAK-sensitive EL-4 cells in a 4-hour ⁵¹Cr-release assay in vitro. Those obtained from healthy mice treated with OK-432 also showed cytotoxic activity against Renca cells. The cytotoxicity of splenic cells from Renca-bearing mice treated with OK-432 was lost almost completely for both Renca and YAC-1 cells after in vitro treatment with anti-asialo GM1 antibody, and was partially lost after in vitro treatment with anti-Thy-1, 2 antibody. Additionally, in vivo i. p. administration of anti-asialo GM1 antibody significantly counteracted the effect of OK-432 on survival. These findings demonstrated that Renca cells were NK-sensitive and that the i. p. administration of OK-432 was beneficial for the prevention of the spontaneous metastasis of Renca carcinoma. As the effectors, NK cells played a dominant role and activated T cells were also involved.

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The effect of experimental unilateral torsion of the testis on the contralateral intrascrotal testis in Wistar rats was evaluated histologically and immunohistochemically.
The results were summarized as follows.
1) Histological damage of the seminiferous tubules in the contralateral testis was present only in adult rats.
2) The histological change 3-5weeks after the experimental torsion consisted of marked decrease of spermatocytes, loss of spermatids and spermatozoa and numerous Sertoli-cell only tubules. Hyperplasia of the interstitial cells was demonstrated without thickness of the basement membrane and infiltration of the inflammatory cells. The tubular diameter and the ratio of contralateral testicular weight to rat body weight were significantly decreased (p<0.05) in torsion group.
3) Using an indirect immunofluorescent method, the positive immunohistochemical staining on spermatid and spermatozoa of normal testicular tissue was demonstrated using only the serum of rat with histological damage on the contralateral testis. Therefore, the phenomenon may be ascribable to the presence of antisperm antibody.
It is concluded that the mechanism of the damage in seminiferous tubules of the contralateral testis with experimental torsion in adult Wistar rats is related to the humoral immunity producing antisperm antibody.

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The clinical courses of bone metastases in 81 cases of prostatic cancer were examined using conventional X-ray. All patients received endocrine therapy as the initial treatment; castration and estrogen were given to 46 cases, castration and antiandrogen to 19, LH-RH analog to 11, flutamide to 5. The response to endocrine therapy was evaluated every 6 months after the start of the treatment according to National Prostatic Cancer Project criteria. The prognosis was calculated by cause-specific survival.
The types of untreated bone metastases on X-ray were classified into five: sclerotic in 12 cases (15%), mixed but mainly sclerotic in 25 (31%), mixed but mainly lytic in 14 (17%), lytic in 8 (10%) and undetermined with positive scintigraphy in 22 (27%). Two mixed types showed more spread metastases and tendency of elevated prostatic acid phosphatase when compared with other types. Temporary enlargement of sclerotic area within 6 months after start of the treatment did not correlate with deterioration of disease. Remodeling of metastaic areas occured 6-36 months after start of the treatment showed curative course and the prognosis of these groups were favorable. Most of lytic areas tended to sclerotic finding following endocrine therapy regardless of effects by endocrine therapy. Sclerotic and two mixed types showed better and worse tendencies, respectively. On viewpoint of remodeling, change of metastatic area and newly appearance of metastases, an evaluation criteria of response to the therapy was proposed, which showed good correlation with prognosis.
From these observations, it was concluded that bone metastases tended from lytic to sclerotic changes and that lytic-sclerotic cycles occured repeatedly along with disease progression regardless of effect to therapy. Remodeling seemed to be curative signs of metastatic area.

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The testicular function after orchiopexy for unilateral cryptorchism was examined for fertile state with the relation to the age at operation and the testicular size.
Sperm concentration decreased with the age at operation, accompanying a rise of gonadotropins and a decrease of the testicular size. The testicular size decreased with the age at operation. sperm deterioration was correlated more with the testicular size in the normally descending side than that of the operated one. The gonadotropin level was inversely correlated with the size of the contralateral normally descending testis.
These results indicate that fertility after unilateral orchiopexy is influenced by the age at operation as well as the development of the normally descending contralateral testis.

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We performed transluminal re-canalization by needle puncture under fluoro-endoscopic control on a total of ten patients (membranous urethra, 8; bulbous urethra, 2) with complete obliteration after traumatic urethral disruption. The re-canalized tract was created by balloon dilation, internal urethrotomy or endoscopic resection of the scar tissue. The patient age ranged from 10 to 57 years (mean age; 37.9±15.3 years). A transluminal puncture was attempted in three patients by transperineal-transurethral approach and in seven by transurethral approach. In one of them, who sustained a complete membranous disruption 5 weeks ago, transluminal pucture failed because of the movable proximal urethra. The remaining nine patients voided without difficulty for the mean follow-up period of 18.1±14.3 months (range: 2-46). Three patients had mild stress urinary incontinence. A transluminal puncture is less invasive, safe and reliable for re-establishment of the true proximal part of the disrupted urethra. It can be recommended as a useful technique for endourological reestablishment for a completely obliterated urethra. Although this endoscipic re-establishment requires urethral sounding or internal urethrotomy for 6 months postoperatively, it may be an alternative to conventional surgical repair.

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Serum γ-Seminoprotein (γ-Sm) of 33 patients suffering from urinary retention due to BPH was evaluated. In acute urinary retention γ-Sm was 17.1±54.9ng/ml (N=33) and its positive rate was 72.7%. After indwelling urethral catherization for one week γ-Sm fell to 3.7±3.6ng/ml (N=17) and its positive rate was 42.8%. γ-Sm measured after one month was negative on all cases.
It was showed that γ-Sm in acute urinary retention increased and after releasing from urinary retention it was rapidly normalized. It is necessary to take into account the above mentioned findings on evaluation of γ-Sm as a tumormarker of prostatic carcinoma.

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Renal cell cancer (RCC) cell lines, ACHN and KRC/Y, with or without exposure to interferons (IFNs), were examined for their susceptibility to lymphokine-activated killer (LAK) cells in relation to modulation of major histocompatibility complex (MHC) class I antigens on tumor cells. Flow cytometric analysis demonstrated constitutional expression of class I antigen on both cell lines, which was enhanced by IFN-α and -γ, and was reduced by acid treatment at pH3. A 4-h ⁵¹Cr-release cytotoxicity assay demonstrated that pretreatment of both cell lines with IFN-α and -γ decreased their susceptibility to LAK cells. Although an inverse correlation between class I antigen expression and susceptibility to LAK cells has been reported by others, IFN and acid treatment demonstrated that the degree of class I antigen expression did not correlate with the susceptibility to LAK cells. These results suggest that clinically administered IFNs might induce protection of RCC to LAK cells, and that decrease of susceptibility might depend upon a mechanism different from the enhancement of class I antigens which is frequently expressed on RCC.

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Invasion of renal cell carcinoma to veins is known to have a close relation with pulmonary metastasis. We speculated that a tumor thrombus would lodge in the pulmonary artery before establishment of a clinically apparent pulmonary metastasis. This may be particularly true in patients with renal vein or vena cava involvement of renal cell carcinoma. In this instance, it is crucial to know the clinical consequence of tumor thrombi in the pulmonary artery. Thus, we investigated these issues with the aid of lung-perfusion imaging in 22 renal cell carcinoma patients with and without vein involvement.
The lung-perfusion imaging revealed positive in 8 of the patients examined prior to treatment. The incidence of positive finding was well correlated with an extensive vein invasion. Patients with positive imaging prior to treatment were associated with pulmonary metastasis at a higher rate than those with negative findings. These findings have indicated that vein invasion should be related with tumor thrombus formation in the pulmonary artery, and such a status in the lung would, in part, result in pulmonary metastasis.
Two different clinical courses were found by an analysis of patients with the positive imaging prior to treatment. One is the clinical course in which positive findings were correlated with a newly developed metastasis in the lung. Thus, care should be taken in development of the metastasis during the follow-up when patients show the positive lung-perfusion imaging prior to treatment. On the other hand, we found two patients in whom the positive findings disappeared during the follow-up. Although the short follow-up period should be taken into consideration, this finding might suggest that establishment of pulmonary metastasis requires not only mechanical trapping of carcinoma cells in pulmonary microvasculature, but an invasive potential of the cells themselves (“seed”) and appropriate microenvironment (“soil”) to enhance the local growth of cells.

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196 cases with vesicoureteral reflux (VUR) from multiple centers were analysed to examine the relationship between VUR and reflux nephropathy. The high correlation (p<0.01) was observed between reflux and renal scarring. Even in cases in whom VUR was not demonstrated at the time of testing, renal scarring of various degrees was recognized, suggesting either co-existed hypoplastic kidney or pre-existed infection. The renal scarring, but not VUR, had a significant correlation with proteinuria and hypertension. Retrospective analysis shows that the surgical treatment was closely related to the degree of renal scarring but not to the degree of reflux.
Renal scarring progressed in 7 of 111 cases (6.3%) during an average of 3.3 years of conservative treatment. Renal scarring progressed even when reflux did not become worse, which is probably accounted for by the presence of pyelonephritis. Although frequency of pyelonephritis decreased significantly (p<0.01) from 0.60±0.89 to 0.084±0.305 times/patient·year after anti-reflux surgery, renal scarring progressed in 13 kidneys (5.8%). Seven of the 13 kidneys became worse due to the surgical failure. The scar progression was recognized in the remaining six kidneys (three patients) including adult cases despite the successful surgical correction of reflux.
Our study points to the urged need for a prospective clinical trial designed for the study of the pathological and clinical background of progressive renal failure in VUR.

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The efficacy of modified M-VAC chemotherapy was evaluated in twenty-two patients with advanced urothelial carcinoma (18 cases of transitional cell carcinoma, 3 of transitional cell associated with squamous cell carcinoma and 1 of squamous cell carcinoma). Among the 22 patients, 14 underwent two or more courses of modified M-VAC chemotherapy and had lesions suitable for the evaluation. Three of the 14 patients achieved complete response and 6 partial response, resulting in a 64.3% response rate. With regard to the direct effect according to the site of the lesion, the response rate was 75% for the urinary bladder, 100% for lung, 100% for subcutaneous tissues, and 75% for lymph nodes metastasis, whereas the chemotherapy was ineffective for metastasis in the bone and muscle. With this neoadjuvant chemotherapy the primary tumor of the urinary bladder was downstaged from T2 to T0 in one patient who showed complete response. In 4 of 5 patients achieving partial response, the primary tumors were downstaged from T2 to T1. Of 9 patients given this chemotherapy for metastatic lesions, 2 achieved complete response and are alive, whereas all 3 without response died of cancer within the 1 year following the chemotherapy.
Since most of the cases associated with the squamous cells carcinoma component showed no response to the therapy, it seems that the level of serum squamous cell carcinoma-associated antigen may be helpful for predicting the efficacy of modified M-VAC chemotherapy.
Side effects related to this chemotherapy and their incidences were as follows: leukocytopenia (less than 1, 000/mm³) 18.2%, thrombocytopenia (less than 100, 000/mm³) 27.2%, nausea and vomiting 100%, hair loss 90.9% and renal dysfunction (Ccr 50l/day or less) 13.6%. No serious side effects were found in our series.

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Prostate thermotherapy consisting of 6 sessions of intrarectal 60min irradiation of 915MHz microwave generated by a prostathermer (Blodan, Israel) was performed once or twice a week on 30 patients with benign prostatic hyperplasia. Excluding 2 cases who refused further therapy at the first session because of rectal discomfort, 28 cases were evaluated for the efficacy of the treatment. Good or fair improvement in subjective symptons was observed in 24 (85.7%) of the cases. Nocturia was significantly relieved from 2.9 to 2.0 a night. Among the objective responses, no improvement was achieved as to residual urine or prostate size, while a significant increase of maximum or average flow rate on uroflowmetry was observed. Adverse effects were minor or moderate, including 2 cases of urethral bleeding and rectal discomfort, 2 cases of lower urinary tract infection and 1 case of hypotension, which occurred at the 5th session. The scoring criteria taking into account of both subjective and objective responses showed that the efficacy is good in 10 cases (33.3%) and fair or good in 20 cases (66.7%). These results indicated the usefulness of the prostathermer as one of non-surgical therapies for benign prostatic hyperplasia.

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Because human urine contains various substances which can affect each other, it is quite difficult to clarify the mechanism of formation of calcium oxalate (CaOx) crystal in urine. The authors recently determined CaOx crystalline content and the concentrations of other substances in urine specimens from patients with urolithiasis and healthy volunteers, and subjected the data to multi-regressive analysis for the purpose of assessing the effect of these urinary substances on CaOx crystal formation.
1. In analysis of urine from patients with urolithiasis, the partial correlation coefficients of CaOx crystal formation with oxalic acid, sodium, calcium, uric acid magnesium were 0.67, 0.28, 0.18, and -0.10, respectively. The formula of regression was as follows:
Amount of CaOx crystal (×10⁶μm³/ml)=3.59×10^-2Ox(mM/L)+4.72×10^-3Ca(mM/L)+4.52×10^-3Na(mM/L)+2.51×10^-4UA(mM/L)-2.39×10^-2Mg(mM/L)-1.65
The multiple correlation coefficient was 0.759. Thus, in patients with urolithiasis, urinary crystal formation was most dependent on the oxalic acid level. sodium, calcium, and uric acid were found to promote crystal formation, while magenesium to suppress it.
2. In analysis of urine from healthy volunteers, the partial correlation coefficients of CaOx crystal formation with oxalic acid and inorganic phosphorus were 0.51 and -0.24, respectively. The formula of regression was as follows:
Amount of CaOx crystal (×10⁶μm³/ml)=1.91×10^-2Ox(mM/L)-3.43×10^-4P(mM/L)+0.29
The multiple correlation coefficient was 0.525. Thus, also in urine from healthy volunteers, crystal formation was dependent on the oxalic acid level, but no other factors promoting crystal formation was identified. Inorganic phosphorus was found to suppress crystal formation in urine from healthy volunteers.
The low multiple correlation coefficient in healthy volunteers as compared to that in patients with urolithiasis suggests that many unknown substances are involved in crystal formation.

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Prognosis of 114 patients treated for renal cell carcinoma from 1972 to 1988 was investigated to evaluate intravenous tumor extension as a prognostic factor. Those in whom presence or absence of macroscopic tumor thrombus was not confirmed were not included in the current patient group. Tumor stages were evaluated according to TNM criteria except that intravenous tumor thrombus was not counted for local staging. Incidence of T3 and T4 tumors, distant metastasis and grade 3 anaplasia (G3) were higher in V+group (V1+V2) than in V0 group, which appeared to be a major difference of background making 5-year actuarial survival rates in V1 and V2 patient groups worse than in V0. Therefore, 5-year actuarial survival rates in N0 and M0 cases receiving radical nephrectomy were compared and found 83.3% in V2 group, 54.4% in V1 and 87.3% in V0. Since V1 group included G3 tumors more frequently than the other two groups, 5-year survival rates were further compared after excluding those with G3 tumors and found to be identical among V0, V1 and V2 groups. The current results indicate that macroscopic intravenous extension of renal cell carcinoma is an accompanied phenomenon secondary to high grade and invasive tumors and therefore, not a primary risk factor for prognosis. Accordingly, it is questionable to regard macroscopic tumor thrombus itself as a risk factor for clinical staging.

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As a prospective study on asymptomatic microhematuria, complete urological examinations including cystoscopy, IVP, ultrasound and urinary cytology were performed on 422 patients over 40 years old between January 1987 and December 1988 (group A). The results of group A was compared with that of retrospective study on 266 patients, who had incomplete urological examination between January 1984 and December 1985 (group B). Cystoscopy was performed on 321 patients (87.2%) in group A and on 108 patients (40.6%) in group B. Bladder tumor was found in 10 cases (2.4%) in group A, including 7 cases of male patients (5.7%), but in only 1case (0.4%) in group B. Since the negative rate of abnormal urinary cytology was 50% and that of abnormal IVP was 90% in 10cases of bladder tumor in group A, cystoscopy was considered to be an essential examination for the screening of patients with asymptomatic microhematuria over 40 years old patients.

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Thirty-four patients with renal pelvic and ureteral cancers received regional lymphadenectomy since 1980. The patients consisted of 21 with renal pelvic cancers, 10 with ureteral and 3 with renal pelvic and ipsilateral ureteral. Fifteen patients (44.1%) had metastatic nodes: 13 with renal hilar or para-aortic metastases and 2 with pelvic nodal involvements only. Thirteen of these 15 patients with nodal metastasis had high grade tumors and 14 had high stage tumors. The 5-year survival rate of these 15 patients was 26.3% which was considerably poor when compared with 19 patients without metastasis. Twenty patients with high grade and high stage tumors who received respective operations with regional lymphadenectomy had significantly better prognosis compared with the historical control group (15 patients, from 1961 to 1979).
Additional regional lymphadenectomy for renal pelvic and ureteral cancers appears to be a valuable operation for improving prognosis.

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Fifty-five female C3H/He mice were given 0.05% N-bytyl-N-(4-hydroxybutyl) nitrosamine in their drinking water for 18 weeks. In week 19, eleven mice (group 3) were sacrificed to confirm that they all had bladder carcinoma. The remaining mice were divided into two groups. Group 1 received 20Gy of proton irradiation over the whole pelvis, while group 2 received no treatment as a control. After 3 weeks all the animals were sacrificed and their bladders were resected to weigh and to examine histologically. The average weight of the bladder, as an index of the tumor volume, was 67.7mg in group 1, 120.6mg in group 2 and 106.5mg in group 3. There was a significant differences (p<0.05) between group 1 and group 2. The incidences of superficial (pT1) and deeply invasive (pT2-3) bladder carcinomas were [10/18 (56%) and 8/18 (39%)] in group 1, [3/17 (18%) and 14/17 (82%)] in group 2 and [2/11 (18%) and 9/11 (82%)] in group 3, respectively. These rates of incidence were significantly different (p<0.05) between group 1 and group 2. However, there was no significant difference (p=0.068) between group 1 and group 3. These results indicate that proton irradiation is effective for treatment of invasive bladder carcinoma in mice.

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We performed combination therapy with cyclophosphamide, Vincristine and Dacarbazine (CVD) regimen and transarterial embolization (TAE) in 2 cases of malignant pheochromocytoma with matastases.
Case 1: 59-year-old female. After primary left adrenal lesion had been removed, recurrence at the left renal hilar region and metastases to the right iliac bone and 5th cervical vertebra occurred. We took 3 courses of CVD regimen after TAE for the lesions in the right iliac bone. Her endocrinological data has been normal for more than 1 year after treatment.
Case 2: 29-year-old male. Total cystectomy, ileal conduit and pelvic lymphadenectomy had been performed for the primary lesion of the urinary bladder. 2 years after the 1st operation, metastases to the right obturator nodes and multiple bones occurred. We gave 3 courses of CVD regimen followed by TAE for the lesions in the right obturator nodes. Just after treatment, we could stop insulin and reduce anti-hypertension drugs, but the effect of treatment was temporary. In conclusion, combination of CVD regimen and TAE is effective for malignant pheochromocytoma with metastases.

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We report a case of an extragonadal germ cell tumor in the retrovesical region. The patient complained of a perineal and micturition pain. Urethrography, CT and MRI showed a retrovesical tumor protruding into the bladder. Alfa-fetoprotein was increased to 12, 170ng/ml.
Bilateral testes did not contain any palpable mass by careful palpation. No tumor was detected by ultrasonography, either. Clinically, he was diagnosed as having a retrovesical extragonadal germ cell tumor associated with paraaortic lymph-nodes and bilateral pulmonary metastases.
Although he was treated by combination chemotherapy (PVB and VAB-6 regimen) and irradiation, he died of carcinomatosis about 6 months after the admission.
There was no evidence of tumor in bilateral testes on autopsy. This case was a second case of extragonadal germ cell tumor originating from the retrovesical lesion in the literature.

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