Radiotherapeutic effects were studied using human urinary bladder cancer (NM-B-1) and human prostatic cancer (Pro-1) transplantable to nude mice. NM-B-1 is a poorly differentiated transitional cell carcinoma and Pro-1 is a poorly differentiated adenocarcinoma. In both the 24th to 27th passage of NMB-1 and the 35th to 38th passage of Pro-1, the successful transplantation rates were almost 100 per cent and the growth rates were similar and stable. Two weeks after subcutaneous transplantation of the tumor, electron beam irradiation was performed locally using a linear accelerator. The therapeutic effects were evaluated on the tumor growth curve, as well as light and electron microscopic findings. The standard deviations of the tumor volumes were relatively small in all radiated groups and this study seemed applicable to radiosensitivity test. On the tumor growth curve, significant tumor regressive effects were observed statistically in a dose of 12Gy for NM-B-1 and 6Gy or more for Pro-1, respectively, and dose-dependency was seen in the effects. Stromal degeneration and destruction of cancer cells were demonstrated by light and electron microscopy in both NM-B-1 and Pro-1 two weeks after irradiation of 18Gy.

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The effects of combined chemo-radiation therapy were studied using human urinary bladder cancer (NM-B-1) and human prostatic cancer (Pro-1) transplanted into nude mice. NM-B-1 is a poorly differentiated transitional cell carcinoma and Pro-1 is a poorly differentiated adenocarcinoma. In both the 24th to 27th passage of NM-B-1 and the 35th to 38th passage of Pro-1, the successful transplantation rates were almost 100 per cent and the growth rates were similar and stable. The therapies were performed by intraperitoneal administration of anticancer drug combined with single-dose irradiation using a linear accelerator. Since the sensitivity of each single agent used in this study was already known for NM-B-1 and Pro-1, the therapeutic modalities in doses were planned by combination of doses less than the minimal effective dose of each agent. The therapeutic effects were evaluated on the tumor growth curve, as well as light and electron microscopic findings, and the following conclusions were obtained: I) In the studies using NM-B-1, therapeutic potentiation effects were achieved by radiation combined with CDDP, BLM or PEP on the tumor growth curve. II) In the studies using Pro-1, therapeutic potentiation effects were achieved by radiation combined with CDDP, PEP or 5FU on the tumor growth curve, but not achieved by radiation with MMC. III) In all but the groups treated by radiation with MMC or 5FU, the characteristic changes were a vacuolic and/or exudative destruction of cytoplasm with a stromal edemahyalinosis in the light and electron microscopic findings.

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DNA histograms were measured by flow cytometry for 65 bladder tumors (transitional cell carcinoma) using the rapid detergent method with propidium iodide. The ratio of peak channel number of the G1 compartment of the tumor cells to that of the diploid standard (DNA index: DI) was calculated and used for ploidy identification.
1) Diploid tumor cells were observed in 20 patients. Aneuploid cells were observed in 45 patients (69.2%); 6 of these had two tumor cell clones with different ploidy, and one had three clones. Considering the detection limits of used methods for ploidy identification and the restricted number of sampling studied in each patients, the true occurrence of clonal heterogeneity in bladder cancer may be much higher.
2) Based on the flow cytometric data and the pathological criteria, the following data were obtained. a) With grading up, diploid tumors tended to decrease and aneuploid tended to increase. The mean value of DNA index increased significantly with grading up. b) With advancing the stage, diploid tumors tended to decrease and aneuploid tended to increase: The mean value of DNA index was as follows: pTa; 1.24±0.32, pT1; 1.62±0.74, pT2-4; 1.90±0.54. DNA index of pTa was significantly different from that of pT1 (p<0.01) and also from that of pT2-4 (p<0.001). Namely, DI values of invasive tumors were significantly higher than those of non-invasive tumors. This suggest that DNA index might be a marker of the invasive potential of a bladder cancer. It is considered from the results that flow cytometric DNA analysis is a rapid, objective and quantitative method to evaluate the malignant potential of the bladder cancer.

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Congenital megaureter with long narrow segment, in which ureteral dilatation begins some centimeters above the ureterovesical junction, is one of the rare malformations and its pathogenesis remains unclear.
A clinicopathological study was performed on ten megaureters of this type operated on in the past 10 years. We have found that: 1) By the X-ray examinations, the ureteral dilatation was mild in 2 ureters, moderate in 3, and severe in 5. Renal function was almost normal in 2 kidneys, hypofunctioning in 6, and non-functioning in 2. There was no vesicoureteral reflux. 2) The lenght of narrow segments varied from 1 to 6 centimeters. Six ureters were compressed or retracted from outside between the dilated portion and narrow segment. Among them, four ureters were compressed by the umbilical artery, one by the vas deferens, and another by fibrous bands. 3) Operative procedures were: ureterocystoneostomy on 7 ureters, ureteroureteral anastomosis with resection of compressed segment on 2, and ureteroplasty by Davis on 1. 4) On histological examinations of the dilated portion, six ureters showed hypertrophy and hyperplasia of muscle bundles, one showed aplasia of muscle bundles, and one was normal. All specimens from distal narrow segment revealed normal musculature. The junction of one ureter consisted of degenerated circular muscle bundles, and two showed a sudden segmental decrease in muscle bundles.
From these findings, we speculate that this type of megaureter might develop secondary to extrinsic compression by adjoining fetal vessels and/or vas deferens.

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A new method has been developed for the measurement of urinary oxalate by gas-chromatography. 2ml of urine is derivatized by 10% HCl-n-butanol solution after lyophilization. The di-n-buthyl ester of oxalic acid formed is extracted with chloroform and is detected by flame ionization gas chromatography. The separation of chromatogram was remarkably increased comparing with that using 10% HCl- methanol solution. Furthermore, it was confirmed by GC/MS that another compounds did not overlap the peak of di-n-buthyl ester of oxalic acid on chromatogram.
The recovery rate of added oxalate in urine was 97% and the variation coefficient of urinary oxalate (n=8) was 2.3%. The oxalate concentration in urine in healthy volunteers was 34.7±9.3mg/day (mean±SD) (n=35).

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Our previous report has indicated that enhanced anti-tumor effect of liposome entrapped cancer drugs is brought about by the slow release rather than the selective delivery to the tumors. Besides, it is noteworthy that large amounts of the liposome entrapped drugs are selectively taken up by the reticuloendothelial system (RES), such as the spleen, liver and lung. These facts led us to examine the possibility to increase intra-tumor uptake of the liposome entrapped drugs by means of prior RES blockade in cancer bearing nude mice and consequently to accelerate their anti-cancer effect.
Experiment-1. The effect of RES blockade on pharmacokinetics of liposome entrapped Bleomycin (BLM).
Testicular tumor bearing nude mice were treated by intraperitoneal administration of Fesin (saccharated ferric oxide) or drug free liposome for 3 days prior to injection of free (control group) or liposome entrapped BLM (study group). Then the intra-tumor accumulation of BLM was bioassayed at 12 and 24 hours after the injection.
Table 1 shows the results obtained at 12 and 24 hours following intraperitoneal injection of free and liposome entrapped BLM. These results indicate that the concentration of intra-tumor BLM was remarkably increased by RES blockade in the study group. On the other hand, high accumulation of liposome entrapped BLM in the RES was not influenced by RES blockade.
Experiment-2. The effect of RES blockade on in vivo anti-cancer effect of liposome entrapped BLM.
Nine testicular tumor bearing nude mice were divided into two groups, RES blockade and nonblockade groups, which included five and four nude mice, respectively. In RES blockade group (group A), the nude mice were treated by intraperitoneal administration of Fesin 4.5mg/head/day for 3 days and followed by intraperitoneal injection of liposome entrapped BLM, 5mg/head 24 hours after the 3rd shot of Fesin. Then the tumor size was measured every day for 10 days and subsequently individual growth rate was calculated by the formula. In non-blockade group (group B), the nude mice were given a single shot of liposome entrapped BLM, 5mg/head without administration of Fesin in advance. Their tumor size and growth rate were measured for 10 days as with group A. Finally, the daily mean values of the growth rate were compared between the two groups. The average growth rates of groups A and B were 0.77±0.06 and 0.88±0.17, respectively, on day 1, thereby indicating a stronger effect on the tumor size in the former group (statistically not significant). This tendency was observed on day 2. However, it was reversed on day 3, when the average tumor growth rate of group A turned out higher than that of group B, thereby indicating a rebound phenomenon. In both groups, tumors continued to decrease their size by day 5. However, they showed a trend of re-growth from day 6 through day 10, during which period the growth rates of the group A were always higher than those of group B. The average tumor growth rates were 1.02±0.339 in the former and 0.862±0.138 in the latter group on day 10.
One of the five nude mice of group A died on day 6. Autopsy did not disclose the cause of death. The remaining four in either groups showed no clinical illness throughout the period of experiment. In conclusion, clinical application of our system is too early at this moment, considering the limited duration of the effect and the existence of rebound phenomenon. On the other hand, the major impact of RES blockade is likely to be altered pharmacokinetics and drug metabolism. Further efforts to revise the method of RES blockade and to solve the problem of adverse effects could make clinical application of RES blockade possible in the field of sophisticated anti-tumor chemotherapy.

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It is important to perform histopathological examination of the endoscopically normal bladder epithelium of patients with bladder tumor, because carcinoma in situ or precancerous lesions may be sometimes found there. For that purpose, we began to develop a new technique of contact-micro-cystoscopy to observe bladder epithelium with high magnification.
As a basic study, we stained the bladder of dogs with methylen blue, toluidine blue, thionine or cresyl violet acetate, and observed with Storz Contact-Micro-Colpohysteroscope 26156B. It is presumed from this trial that cresyl violet acetate may be the best to stain the bladder epithelium. We also stained the epithelium of the bladder with tumor after total cystectomy with cresyl violet acetate, and observed with this instrument. We could find neoplastic changes in bladder epithelium with the naked eyes.
It is thought that contact-micro-cystoscopy may be used clinically after further improvement of this instrument.

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The heterogeneity in tumorigenicity of cell line KU-2 derived from human renal cell carcinoma was studied utilizing ten clone cell lines (N-2, 3, 5-11 and 13) of KU-2.
As an in vitro study on tumorigenicity, clonogenicity of the clones was determined in a soft agar culture. Single separated cells were inoculated 10⁴ per ml in concentration. The plating efficiency (PE) of KU-2 was 45.7%, while the clones showed variety of PE, ranging from 6.8% to 54.9%. Of these clones, 4 clones, N-7 (PE=21.7%), N-8 (40.0%), N-10 (22.1%), N-13 (6.8%), and KU-2 were studied on their tumorigenicity in vivo. Twenty to fifty million cells of each clone were subcutaneously inoculated in 5-6 nude mice. KU-2, N-8 and N-10 formed visible tumors in 3/5, 2/6 and 3/6 of nude mice within 1-4 months after cell inoculation. However, no tumors grew in the nude mice in which N-7 or N-13 was inoculated. Histological examination of the tumors in nude mice showed some difference in differentiation of adenocarcinoma among 2 clones and KU-2. N-10 was less differentiated in glandular formation than N-8 and KU-2. Finally, to analyze the interaction between tumorigenicity and susceptibility to natural killer (NK) activity, lysis of the clones and KU-2 mediated by NK cells in human peripheral blood lymphocytes (PBL) were determined by ⁵¹Cr-releasing assay. In experiments using PBL of 3 young men activated by 1000IU/ml Interferon-α, N-8 was always most resistant to NK activity, followed by N-10, KU-2, N-7 and N-13. The average total lytic units of PBL against N-8 was about 1/3 of that against N-7.
The results of this study indicate that KU-2 cell line consists of heterogeneous cell populations with different degrees of tumorigenicity and of susceptibility to NK cell mediated cytotoxycity. The clones tumorigenic in nude mice were resistant to NK activity, which suggests acquisition of resistibility to NK activity is required of the cells to be tumorigenic in vivo. In addition, the presence of less tumorigenic and highly NK-sensitive clones in highly tumorigenic and less NK-sensitive cell line indicates that cell differentiation always occurs in a part of the tumor cells.

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Evoked responses of the bulbocavernosus reflex (evoked BCR) were studied with electromyographic methods on 30 males without any neurological problems and 170 male patients with a variety of documented neurological lesions such as spinal cord injury, spinal columnar disorders, cerebrovascular disorders, Parkinson's disease, diabetes mellitus and so on. Square wave stimuli were applied to the penis and acquired responses were recorded with the surface electrodes placed on the anal sphincter. The average response was recorded during 50-150 times of electrical stimulation with a computer averager and the latency was measured. In patients with neurologic lesions, urodynamic studies such as uroflowmetry, cystometry and urethral pressure profilometry were carried out as well.
The results were as follows:
1) The mean latency of control males was 32.2±4.0msec, ranging from 27 to 42msec.
2) Evoked BCR was positive and the latency was within normal values in all of the patients with cervical spinal cord injury. But in 34 patients with lower thoratic, lumbar and sacral spinal cord injury, 9 cases (26%) showed negative evoked BCR and prolongation of the latency was recognized in 2 cases (6%).
3) All of the patients of spinal cord injury with negative evoked BCR demonstrated detrusor areflexia in cystometrogram and the mean value of maximum urethral pressure was statistically lower than that of the patients with positive evoked BCR.
4) In 91 patients with spinal columnar disorders, only 3 cases (3%) had the prolonged latency.
5) All of the patients with cerebrovascular disorders and Parkinson's disease showed positive evoked BCR with normal latency. Remarkable prolongation of the latency was recognized in one case of post operative recurrence of rectal cancer.
Though there are several problems left in evoked BCR for routine clinical application, it is thought to be useful for objective examination of sacral reflex arc and to become an additional diagnostic method to various urodynamic studies.

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From 1975 to 1981, 6520 patients, who attended the urologic clinic of Chiba University Hospital, underwent intravenous pyelography. Thirty-six of these patients (15 males and 21 females) had characteristic features of medullary sponge kidney.
Among these 36 patients, 29 had kidney stones. The number of kidney stone patients in this period was 940, 3.1% of the all patients.
Almost all chief complaints were attributable to kidney stones such as colicky pain. However, macroscopic hematuria was seen in many patients.
Few patients disclosed lowered PSP excretion and creatinine clearance value. Although average renal function remained unchanged after 2 and half years' mean observation period, the creatinine clearence value decreased below 60ml/min in 3 cases. Hypercalciuria and defect in urinary acidification was seen in 5 out of 26 patients tested, and in 3 out of 23, respectively. These low incidence might indicate that these disturbances were rather chance complications, not caused by medullary sponge kidney. Out of 18 cases studied 9 were found to have lowered urine concentration ability. All these 9 patients had kidney stones.
Although the stones in kidneys were not large, the increases of number and/or size were discerned in 10 cases out of 18, which will indicate the need for a follow-up study.

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Human LDH-X(C₄) was isolated from seminal plasma of infertile males by anffinity chromatography, using oxamate-Sepharose and AMP-Sepharose.
Frozen semen samples were thawed and centrifuged for 60 min at 10, 000g and 4°C. About 100ml of seminal plasma was fractionated by (NH₄)₂SO₄ precipitation. The precipitate obtained between 40 and 60% saturation with (NH₄)₂SO₄ was dialysed against 0.05M sodium phosphate buffer (pH 6.8) containing 0.5M NaCl. An oxamate-Sepharose gel which had been used by O'Carra et al (1974) was applied to isolate LDH isoenzymes. In the presence of 500μM NADH, all LDH isoenzymes were bound to the column. Elution with buffer containing 1.6mM NAD⁺ released all LDH isoenzymes. Agar-gel electrophoresis revealed that LDH-5 was dominant in the fraction No. 17, whereas LDH-1 came off of column later. This change of isoenzyme pattern indicates that LDH-1 has higher affinity to the column than LDH-5.
This retardation of LDH-1 on oxamate-Sepharose has been explained with the formation of abortive ternary complex, which is considered to be the cause of the inhibition of the enzymatic activity at high concentrations of pyruvate than LDH-1 activity (Uchijima, 1984), the formatin of abortive ternary complex can not merely explain the only fractions from No. 18 to No. 21 contained LDH-X.
LDH isoenzymes were also bound to AMP-Sepharose when they were added in the presence of the buffer alone. LDH-X could be separated from other isoenzymes with the AMP-Sepharose column, because it did not bind to the column in the presence of 1.6mM NAD⁺.

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Of 52 patients with high stage (T2-4), or high grade and low stage (T1) bladder tumor during the 7 year-period from 1975 to 1981, 23 patients were treated with preoperative irradiation and total cystectomy, 4 with preoperative irradiation and partial cystectomy, and 25 with curative irradiation therapy. The dose of the irradiation was 2000 or 4000rads (whole pelvis) in the preoperative irradiation group, and 5000-6000rads (4000rads to whole pelvis followed by 1000-2000rads to bladder region) in the curative irradiation group. The results were as follows: 1) The three and five year survival rates of patients with T1, T2 and T3 tumor treated with preoperative radiation and surgery were 100%-100%, 80-43% and 45%-23%, whereas those of patients treated with curative irradiation were 73%-62%, 26%-0% and 0%-0%, respectively. 2) Downstaging of tumor was observed in 45% of overall patients. According to histologic growth pattern of tumors, the rate of downstaging was markedly high, (100%-7/7) in non-papillary microinvasive carcinoma compared to superficial papillary carcinoma (50%-4/8) and invasive carcinoma (31%-10/32). 3) The three and five year survival rates of patients with invasive carcinoma (T2-4) were 100% and 57%, respectively, in 6 patients who achieved downstaging of tumor, whereas they were 50% and 11%, respectively, in 16 patients who didn't achieve tumor downstaging by preoperative irradiation. 4) The incidence of local (pelvic) recurrence in the preopeartive irradiation group was low (7%-2/27) compared to the curative irradiation group (32%-8/25). However, the incidence of distant metastasis was high (>20%) in both groups. 58% of distant metastases occurred within one year and 92% within 3 years.

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From May 1974 to Feb. 1984, 290 patients with benign prostate hypertrophy (abbreviated as BPH) underwent surgery at the St. Marianna University School of Medicine.
The method of surgery consisted of transurethral resection (abbreviated as TUR) in 192 cases, open prostatectomy in 54 cases and cryosurgery in 44 cases. Average postoperative catheter indwelling periods and the hospitalization days were 5 and 15 days for the TUR group, 10 and 28 days for the open prostatectomy group and 15 and 38 days for the cryosurgery group, respectively.
The operative complication was high in the open prostatectomy group. The cryosurgery group required reoperation frequently.
The TUR method had least postoperative complications, shortest catheter indwelling periods and shortest hospitalization days.
The TUR method can be recommended on patients with BPH unless the prostate is too big for complete resection on which case open prostatectomy is indicated.
Although cryosurgery was applied relatively frequently in the early few years, we had abandoned crysurgery because of the poor postoperative results.

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1120 patients with bladder tumor treated between 1960 and 1982 were followed up for 2 years or more. Their survival rates were 73% at 2 years, 68% at 3 years, 61% at 5 years and 51% at 10 years, (actuarial method).
Nine factors which may affect survival rates were analyzed and the following results were obtained. Younger than older, male than female patients yielded better survival. As for initial tumor characteristics, single than multiple, small than large, low-T than high-T category, low than high grade tumors yielded better survival. Transitional cell carcinoma yielded better survival than squamous cell or adenocarcinoma. As for treatment modalities, TUR resulted in the most favorable outcome, cystectomy the worst, and cystotomy (partial, segmental or tumor resection) resulted in an intermediate outcome between the above two modalities.
Survival rates were improved progressively from 1960 through 1982. Many factors seem to have contributed to this improvement.

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In many clinical cases of hydronephrosis, obstructive nephropathy, a problem for which conservative treatment or nephrectomy should be undertaken, arise, because functional recovery cannot be predicted in the hydronephrotic condition. In order to clarify the conditions necessary for such recovery, the author performed the following experiment.
Methods: In 50 female mongrel dogs with hydronephrosis induced experimentally by completely ligating the unilateral ureter, changes in urinary components and various parameters of the renal function in the hydronephrotic condition during the period of the obstruction of the ureter were observed. After reopening the ureter, the contralateral ureter was ligated to determine the period of obstruction within which the hydronephrotic kidney could recover functionally to a level permitting maintenance of life with a single kidney. thus, the conditions necessary for functional recovery in the hydronephrotic condition were studied.
Results: 1) Osmotic pressure of hydronephrotic urine, UUN, Cr, and K at dehydration decreased along with the course of the obstruction. The ratio of hydronephrotic urine flow to contralateral kidney's urine flow, free water clearance and osmolar clearance also decreased with the course of occlusion.
2) Significant differences in the urine components and various parameters of the renal function at reopening were determined betwen the groups with and without functional recovery. There were significant differences (p<0.01) in the osmotic pressure of hydronephrotic urine and concentration of K at dehydration, free water clearance and the ratio of hydronephrotic urine flow to contralateral kidney's urine flow between the two groups. In the hydronephrotic condition with more than 320mOsm/l, 16mEg/l, 0.07ml/min and 0.2 of the above parameters, respectively, the function seems to recover to a level allowing maintenance of life even with a single kidney.
3) The function could recover to such a level within five weeks after obstruction.
4) NAG activity of the hydronephrotic kidney was higher than that of the normal kidney, but it was not a parameter showing recoverability.

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A 51-year-old woman visited our hospital because of grosshematuria in July, 1981. Cystoscopy disclosed a papillary tumor protruding from the left ureteral orifice. Excretory urography revealed a large left nephrogram with non-visualization of the excretory system. The diagnosis of left ureteral tumor was made, and left nephroureterectomy was carried out. The tumor invaded through muscle layer to surrounding tissues. Histological examination revealed transitional cell carcinoma grade II-III. Twoport opposing technique radiotherapy which delivered 6000rad to the place of the ureter tumor was carried out.
In February, 1982, large recurrent tumor in the retroperitoneal and subdermal space was noticed. After a dose of 100mg of CDDP had been administered twice, the tumor diminished remarkably in size. By subsequent comformation radiotherapy at a total dose of 5000rad and another administration of 100mg of CDDP, the tumor disappeared completely in April, 1982. No recurrence nor metastasis has been detected until May, 1984.
The radiation-modifying effect of CDDP was discussed.

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