The effect of orally administered prazosin hydrochloride was investigated for 2 to 18 weeks in 30 patients with prostatic obstruction. There was a statistically significant reduction in residual urine (p<0.005) and in bladder compliance (p<0.05). The maximum cystometric capacity increased in the majority of patients after treatment. Both the maximum and average urinary flow rates increased significantly (p<0.01 and p<0.005, respectively). There were no significant changes in the maximum urethral closure pressure and in the length of continence zone. Improvement of subjective sympomatology was observed in 77% of cases. Side effects were noted in 33% of cases. The effective maintenance dose of prozosin was 3 to 9mg per day. A classification of prostatic obstruction and a hypothesis of the etiology of unstable bladder were proposed.

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The conduction time of bulbocavernosus reflex was measured in 7 normal controls and 20 patients with neurogenic bladder. This conduction time is calculated as the latency until anal sphincter contracts after electrical stimulation of the penis or clitoris and the posterior urethra. The results are as follows.
1. The conduction time in the normal control group was 32-45msec (average 38.1msec) when electrical stimulation was given to the penis or clitoris and 60-84msec (average 71.1msec) when electrical stimulation was given to te posterior urethra. Accordingly, a conduction time above 50msec in the former and above 90msec in the latter is considered to be abnormal.
2. The conduction time of 12 patients with neurogenic bladder with suprasacral lesions indicated no difference from that of the normal control group. However, prolongation of conduction time of bulbocavernosus reflex was observed in one patient with neurogenic bladder with sacral cord injury and 6 patients with neurogenic bladder with peripheral neuropathy.
3. It is considered that measurememt of conduction time of bulbocavernosus reflex is useful for diagnosis of the type and the site of injury in neurogenic bladder, as an objective and quantitative clinical test.

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In vitro drug-sensitivity of cultured human bladder cancer cells against various anti-cancer agents was measured by the regrowth assay method. The examined anti-cancer agents were Doxorubicin hydrochloride (ADM), Carboquone (CQ), Mitomycin C (MMC), Fluorouracil (5-FU), Cisdiamminedichloroplatinum (CDDP), and Nimustine hydrochloride (ACNU). The cultured human bladder cancer cell lines were T24, MGH-U1, KU-1 and NBT-2. And FL was also used as a control.
After a 2-hour exposure to anti-cancer agents, the growth curve was obtained through the regrowth assay method, and consequently the survival curve and 90% lethal dose (LD₉₀) were determined.
ADM had a high and CQ, MMC, 5-FU had a moderate rate of Therapeutic Index, which is the ratio of MTD (Maximun Tolerance Dose) to LD₉₀. ADM, CQ had a high and 5-FU, CDDP and MMC had a moderate rate of Clinical Index, which is the ratio of LD₉₀ to CUD (Clinically Used Dose). From the viewpoint of the ratio of LD₉₀ to LD₉₀. FL, namely Adverse Index, 5-FU, and ADM were more harmless than CQ, CDDP, MMC and ACNU.
It was proved experimentally that ADM, CQ and 5-FU, which were the drugs clinically well used for the treatment of bladder cancer, had considerable efficacy against cultured humar bladdem cancer cells.

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It is generally believed that intra-arterial infustion of anticancer drugs produces an increase in local drug concentration and a reduction in systemic drug availability. However, in selective intra-arterial infusion chemotherapy the question is still open whether the drug distributed to the target organ effectively. In this report we studied utility of radioisotope (RI) angiography in the evaluation of selective intra-arterial infusion therapy.
In sixteen cases of bladder cancer treated with selective intra-arterial infusion chemotherapy we have performed RI angiography using a small bolus of ^99mTc pertechnetate or ^99mTc-DTPA through the arterial catheter. The RI angiogram showed good visualization of blood supply around the urinary bladder. The cases with a catheter from the inferior gluteal artery indicated high accumulation of RI level in the bladder region (11/20) than the cases with a catheter from superior gluteal artery (2/11). On the other hand, when the RI angiogram showed the RI accumulation in the external area of the urinary bladder, the local complication of anticancer drugs such as hip erosion or pigmentation frequently occured in the region of high RI uptake. The results revealed that the RI angography was helpful to predict the regional complication of anticancer drugs.

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In order to find if carcinomas of the urinary tract should influence the pattern of glycosaminoglycan (GAG) excretion in urine, daily urinary GAG was measured in patients with renal cell carcinoma, bladder carcinoma and prostatic carcinoma, and the result was compared with that of normal adults. Significantly higher levels of urinary GAG were noted in patients with bladder carcinoma and renal cell carrcinoma, whereas in patients with prostatic carcinoma the level was not significantly different from that of normal adults. The urinary GAG distribution pattern examined by two-dimensional electrophoresis did not coincide with that of tissue GAG isolated from renal cell carcinoma. However, in bladder carcinoma, urinary GAG distribution pattern resembled that of tissue GAG isolated from bladder carcinoma; there was prominently large amount of hyaluronic acid both in urine and cancer tissue from the patients with bladder carcinoma. Histochemical study by colloid iron stain demonstrated the presence of GAG in the cytoplasm of the malignant urothelial cells. From these observations, it was suggested that the measurement and demonstration of hyaluronic acid in urine may be of value and used as a marker of bladder carcinoma.

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Nucleic acid metabolism was investigated to know the metabolic activites of the bladder carcinoma cells. Surgically obtained specimens were subjected to this investigation radio-acitve nucleic acid precursors, ¹⁴C-Formate via de novo synthetic pathway, and ¹⁴C-8-Adnine via salvage pathway, were used, Activites of bladder carcinoma cell were determined their incorporation rates. The results were as follows:
1) ¹⁴C-Formate incorporation was much higher in grade II, III and IV of bladder carcinoma cells than in the normal epithelium of the bladder, It was also highest in stage B₂ bladder carcinoma cells.
2) ¹⁴C-8-Ademine was found to be incorporated into nucleic acid bases of bladder carcinoma cell. It was considered that as the grades and stages proceded, the incorporation rates became higher.
3) Comparison between the activites of de novo synthesis and salvage pathway was made. The latter was more active than the former in bladder carcinoma cells.
To select most suitable anti-cancer agents for the surgical adjuvant chemotherapy, a new sensitivity test was developed. The prinicple of this test depends on the inhibitory activites of anti-cancer agents on the nucleic acid metabolism. The procedures were the same as those in the incorporation experiment by adding the agents. The results were applied to the 36 patients who underwent total cystectomy or parital cystectomy
1) Mitomycin C and Adriamycin were the most potent agents than Bleomycin, 5-Fluorouracil, Vincristine and Cyclophosphamide on this sensitivity test.
2) Mitomycin C was used for the post-operative adjuvant chemotherapy. Mitomycin C-sensitive patients showed superior results as to local recurrence and metastases to the Mitomycin C-insensitive patients.
3) This new sensitivity test was considered useful for selection of sutiable anti-cancerr agents for surgical chemotherapy of bladder cancer.

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The pupose of this tudy is to classify the dilated ureters from histological stand point. Ninety-four ureters from 71 children, who showed moderate to severe dilatation of the urters in the urographic studies, were examined under a light microscope. The ureters were divided into 4 groups according to the findings of the muscle layers of the dilated portions as follows:
Group 1: normal muscle layers (42 ureters),
Group 2: hypertrophy and hyperplasia of the muscle bundles (30 urters). Most of the ureters in this group were accompanied with proliferation of interstitial connective tissues.
Group 3: hypoplasia of the muscle bundles (8 ureters). Muscle bundles were thin and muscle cells were also hypoplastic.
Group 4: aplasia of the muscle bundles (14 ureters), in which muscle bundles were not observed. Instead, there were scattered fragments of several atrophic muscle fibers within abundant connective tissues.
According to this classification, the histological features of the dilated ureters were compared with several disorders.
1) Vesico-ureteral reflux (45 ureters): thirty-six ureters (80%) were inclused in the group 1. Among the 8 ureters of the group 2, 7 were moderately to severely dilated on the intravenous pyelogram. One ureter of group 4 was associated with a dysplastic kidney.
2) Primary megaureter (12 ureters): nine ureters (75%) were in the group 2. There was a fairly good correlation between the grade of ureteral dilatation and muscular hypertrophy.
3) Ureterocele (12 ureters) and ectopic ureter (10 ureters): nine of the ureteroceles and 8 of the ectopic ureters showed the findings of either group 3 or group 4. Correlation of the position of the ureteral orifice and the ureteral musculature was investigated. If a ureter opens caudally, the muscle bundles tend to become hypoplastic or aplastic.
4) Prune belly syndrome (4 ureters): three ureters exhibited typical features of group 4. In one of them, the histological difference between the middle and the lower portion of the ureter was examined. In contrast to the previous reports, the muscle cells were proved to be more abundant in the lower portion.
5) Neurogenic bladder (6 ureters), posterior urethral valve (3 ureters): these dialted ureters secondary to the obstruction of the lower urinary tract were included in group 2. In general, the hypertropny of the muscle bundles and the increased amount of connective tissue in these disorders were more prominent than in the primary megaureter. Bacterial infection was remarkably observed in these ureters.
6) Twenty-six kidneys were examined histologically, and 17 were diagnosed as dysplastic. Fourteen ureters (82%) of the dysplastic kidneys had the muscle layers of either group 3 or group 4. This would suggest a coincidence of the abnormal structures of the ureteral muscles and the presence of renal dysplasia in these disorders.
7) Several different portions were examined and compared in 9 ureters. Like normal ureters, 5 of them, irrespective of their histological group, revealed an increase in thickenss and amount of the muscle bundles in the ureter near the ureterovesical junction. Another ureter showed the same histology of group 4 in either portions. In other two ureters, the middle portion was found to be aplastic whereas the upper and lower portions were hypoplastic but muscle bundles could be apparently observed. In one ureter, the muscle layer was normal in the middle portion but it was severely hypoplastic in the upper and lower portions. These observations on pathologic ureters were not described in previous reports.

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In 25 patients with prostatic cancer and 26 patients with benign prostatic hypertrophy, 24 hour urinary hydroxyproline has been measured by the method of Cleary and Saunders. The patients were kept on a diet free of gelatin. Urinary creatinine was estimated. In patients with prostatic cancer serum acid phosphatase, prostatic acid phosphatase, alkaline phosphatase and calcium were measured.
Urinary hydroxyproline excretion and the urinary hydroxyproline/creatinine ratio were both elevated in patients with prostatic cancer with bone metastases when compared to the values in patients with benign prostatic hypertrophy and prostatic cancer without bone metastasis. These were more sensitive indicators of bone metastasis than serum acid phosphatase, prostatic acid phosphatase, alkaline phosphatase and calcium. These results suggest that urinary hydroxyproline is a valuable index of bone metastasis of prostatic cancer.

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A total of 90 dyestuff, workers who were engaged in the production of aromatic amine during the post-war period after the 2nd world war have been examined since 1967 by exfoliative cytologic examiniation. Those identified as class-3 or over by this first screening test were then submitted to a second sereening which consisted of periodic cystscopic examinations and 1 or 2 intravenous pyelographies per year. This system of mass screening has been used for the past 15 years, and we have discovered 13 cases of bladder tumor and 1 case of asynchronous bilateral ureteral tumor.
Out of the 11 cases, bladder tumors were discovered in 5 cases within 3 months after a positive exfoliative cytology result, and in 4 cases within 1 year. The presence of a tumor was confirmed in 81% of those patients within 1 year and in all of them in about 3 years.
Periodic examinations have identified all the tumors when they were about 5mm in size and in stage O through A, demonstrating the usefulenss of systematic examination.
Treatment included intravesical instillation of anticancer agents, mostly mitomycin C, for 7 cases, TUR for 5 cases and partial cystectomy was performed in one case. The patient with an asynchronous bilateral ureteral tumor, who was treated first by right total nephro-ureterectomy with cuff resection of bladder and later by ureter excision and nephrostomy, has been in good health for 7 years.
Recurrence was observed in 3 out of the 7 cases treated with intravesical anticancer agents, and in 4 out of the 5 cases treated by TUR, including two who had more than 2 heterotopic recurrences in 1 year.
Survival of 5, 10 and 15 years was 84%, 55% and 44% respectively. One patient died of post operative peritonitis after a bile duct cancer operation in the first year: the other of cerebral hemorrhage in the 4th year; the third of primary lung cancer in the 7th year; the fourth of primary liver cancer in the 8th year and two more patients died of ileus in the 7th and 11th year.
From the results obtained during the past 15 years by urinary cytology examination routinely applied to 90 ex-workers of a dye factory, we conclude that exfoliative cytology is superior to cystoscopy or histology for early detection of bladder tumors.

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We studied patients with hydronephrosis (11 patients), ureteral calculi (22) and reflux ureter (2) using diuresis renography to assess the dynamic patency of the dilated upper urinary tract. The degree of collecting system dilatation was measured by planimetry on urography films (collecting system area/renal outline area).
Of 11 patients of congenital hydronephrosis 6 demonstrated a complete elimination of radionuclide after injection of furosemide (0.5mg/kg), indicating nonobstruction. Five patients showed no elimination of radionuclide, indicating total obstruction. In the nonobstructive group, retrograde pyelography failed to show positive findings of ureteral obstruction. Urography on these patients showed a minor degree of dilatation of the collecting system witn good cortical width. In the total obstruction group, the collecting system was highly dilated and ureteral stricture of pyeloureteral junction was confirmed in every case.
In patients with ureteral calculi, the diuretic-induced renogram was quantified as the per cent fall during the first 2 minutes. The results of the renographic study were compared with the symptoms calculous size and degree of collecting system dilatation. Of 22 patients 18 demonstrated an elimination of radionuclide at various excretion rates ranging from 0% to 92%. The collecting system dilatation varied in planimetric index from 16.3% to 72.3%, increasing with a decrease in excretion rate of radionuclide. Thus, a significant correlation between the excretion rate and extent of the collecting system dilatation was demonstrated. Stone sizes were increased with the decrease in excretion rate. The remaining 4 patients had ureteral colic at the time of examination. In the 4, no excretion was demonstrated in the diuresis renogram.
Two patients had a reflux ureter with suspected stenosis. The diuresis renography successfully diagnosed these patients by indwelling Foley catheter into the bladder.
It is concluded from these results that diuresis renography can provide information regarding urine drainage of the dilated upper urinary tract. This characteristic may be helpful in the management of these patients.

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Two cases of bladder rhabdomyosarcoma and one case of bladder leiomyosarcoma are reported. One case of rhabdomyosarcoma, 5-year-old boy, has been free of tumor for 91 months after total cystectomy and the other case, 3-year-old boy, died 15 months after total cystectomy followed by radiotherapy and chemotherapy (Actinomycin D). A case of leiomyosarcoma, 26-year-old female, has been free of tumor for 6 months after total cystectomy followed by radiotherapy and chemotherapy (Actinomycin D, Vincristine).
One hundred thirty cases of bladder sarcoma during the past 20 years (1960-1980) were reviwed in the Japanese literature to which 3 new cases were added. We have made a discussion on age distribution, sex, treatment and postoperative course.

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