The absorption and disappearance of adriamycin (ADM) through the bladder epithelium in the rat was investigated using a fluorescence microscope. In the absorption study in vitro, ADM permeated through the epithelium into the lamina propria or the inner layer of the muscle within 15 minutes after instillation, showing no further infiltration into the deeper part of the bladder wall. In addition, fluorescence histological evidence for the uptake of ADM by the endothelial cells of the blood vessels in the lamina propria suggested a systemic diffusion of ADM to the whole blood by blood circulation. These data coincided well with the absorption study in vivo. On the other hand, ADM once absorbed in the bladder wall disappeared from the lamina propria or the inner layer of the muscle and was confined only in the epithelium at 60min after the excretion of ADM. The intensity of ADM fluorescence then decreased gradually with time elapsed. No ADM fluorescence was recognized in the bladder tissue 48hr later. In the absorption study with the BBN induced rat bladder tumor, ADM permeated into all the cells of papillary tumor within 5 minutes of instillation.
The fluorescence histological method used in the present study is harmless and may readily be applicable to the pharmacodynamic study of ADM in human bladder tumors. This method proves to be a promising approach to the development of an ideal instillation therapy effective on bladder tumor cells without side-effects.

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Multivariable analysis (quatification method I and II) was used to investigate the relationship between survival rates and prognostic factos. The items studied were age, stage, pathological differentiation, gait disturbance, acid phosphatase and erythrocyte sedimentation rate (ESR). The data were available for 353 patients for all items.
The significance of each item was evaluated in all patients-group, subgroup stratified by their cause of death, and subgroup stratified by their stage. The significance of age and gait disturbance which represent the general condition was proven in all patients, non-cancer death group and stage ABC group. In the cancer death group, stage D group was the most significant as prognostic factor. ESR was the most significant in the stage D group and the significance was gradually increased with the observation time.

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Seven elderly patients, 79-88 years old, with bladder cancer were treated by transvesical tumorectomy with intraoperative radiation therapy (IORT). The cancers appeared to be of high grade and high stage by cystoscopy and other examinations, and consequently they were diagnosed to be over stage T₂. Therefore, all patients were thought to be candidates for total cystectomy. But their ages and complications precluded this treatment, so we decided to carry out the “palliative” IORT.
The operation of IORT required less than two hours and required less than 200ml of blood loss. There were no complications such as hematuria, irritable bladder, and rectal symptoms.
The postoperative stage diagnoses coincided with the preoperative ones in 5 cases, but two cases were overdiagnosed. Five patients died after more than one year and 11 months, but four patients died due to other diseases, without cancer. One patient died due to pulmonary cancer confirmed by autopsy. Recurrence was seen in one case.
These results confirmed that IORT was effective for local control of bladder cancer and partially prophylactic for recurrence. Furthermore, this treatment seemed to be even curative for some cases. We recommend this modality of treatment for some of aged patients and patients with complications who are unable to undergo cystectomy.

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Bladder and urethral functions were evaluated urodynamically in 114 patients with lumbar disorders including prolapsed lumbar intervertebral disc (66 patients), lumbar canal stenosis (19 patients), lumbar spondylolysis and/or spondylolisthesis (21 patients), lumbar spondylosis deformans (5 patients) and ossification of the yellow ligament of the lumbar spine (3 patients). The patients consisted of 88 males and 26 females with an average age of 47 years (range 17 to 73 years). Symptomatic organic infravesical obstruction was excluded by physical and radiographic examination.
Cystometry revealed preoperative neurogenic bladder in 23 patients (20%); normal detrusor with overactive sphincter in 2 (9%), underactive in 8 (36%), overactive in 5 (23%) and equivocal in 7 (32%). One patient not receiving cytometry revealed abnormal uroflowmetry with 140ml residual urine. Twenty of them underwent electromyographic examination of the external sphincter and 15 (75%) had an overactive sphincter. Nine (39%) of them complained no urological symptoms. Neurogenic bladder seemed to highly associate in those having abnormal tendon reflex in the lower extremities, decreased bulvocavernosus reflex and sensory disturbance in the perineal area, but there was no statistical significance.
Of twenty-three neurogenic bladder patients, eighteen underwent a lumbar vertebral operation and fifteen received postoperative urodynamic evaluation. Uroflowmetry was improved in more than half of the patients within 3 months after the operation and cystometry was normalized in 4 of 7 patients who underwent cystometry over 6 months after the operation. Preoperative overactive detrusor remained unchanged in two of three patients who underwent cystometry over 6 months after the operation.

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Hyperthermia was induced for the treatment of invasive bladder carcinoma in order to study it's usefulness.
The subjects were 12 cases of invasive bladder cancer; including 5 cases of T2, 3 cases of T3, 2 cases of T4, and 2 cases of recurrence after total cystectomy. As previous treatment, 4 patients received radiotherapy and the other received TUR, systemic chemotherapy, and intravesical injection of anticancer drugs. For hyperthermia treatment, a Thermotron RF-8 was used for heating a deep seated tumor. Each case recieved hyperthermia 2 to 10 times. Combined therapy included injection of HPC-adriamycin into the urinary bladder in 5 cases, immunotherapy in 3 cases, M-VAC therapy in one case, rediotherapy in one case, radiotherapy and intra-arterial injection in one case, and Peplomycin and OK-432 local injection in one case.
The treatment results showed a 75% effectiveness; with CR in 4 cases, PR in 5 cases, MR in 2 cases and PD in one case. Three patients died and 9 survived. Of four patients who had received radiotherapy as a previous treatment 3 cases obtained CR and one case MR. Therefore, it was considered that a favorable treatment effect with hyperthermia could be obtained after radiotherapy.

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Activated carbon characteristically shows an extremely high transmigration to the lymph node, as well as a sustained release of the adsorbed drugs. Therefore, several attempts to use activated carbon as a carrier in cancer chemotherapy have been done. In the present study, we first introduced a new drug-dosage form of cisplatin (CDDP) adsorbed to activated carbon particles (CDDP-CH), and examined its characteristics and anti-cancer effect against human bladder cancer cell lines.
CDDP solution of varied concentrations (Randa^®) was mixed with activated carbon particles (Norit^®A) and examined for adsorption and discharge by atomic absorption spectrophotometry and high performance liquid chromatography. Total CDDP adsorption increased in proportion to the amount of activated carbon. CDDP-CH was successfully prepared at an efficient concentration for cancer chemotherapy and CDDP-CH slowly discharged CDDP, indicating it as a useful means for the anti-cancer drug.
Using cultured human bladder cancer cell lines (KU-1, HTB9), the anti-cancer effect was compared between CDDP and CDDP-CH by MTT-assay and double layer soft agar colony assay. CDDP-CH revealed an inhibitory effect agaisnt human bladder cancer cell lines.
In view of the fact that activated carbon readily migrates to the lymph node, clinical application of this drug dosage form may be useful in cases of malignant tumor metastasis to the lymph node.

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We reviewed 157 patients retrospectively with incidental carcinoma of the prostate who had been treated at our collaborating hospitals during the past ten years.
Of 5212 patients with benign prostatic hyperplasia who received subcapsular prostatectomy or transurethral resection of the prostate (TUR-P), 157 (3.0%) were diagnosed as having an incidental carcinoma of the prostate, which was somewhat lower than that in previously published reports. Of these, 30 and 127 patients were in stage A1 and A2, respectively.
Well, moderately and poorly differentiated carcinomas were found in 44.6%, 36.7% and 18.5% of the patients, respectively. The incidence of poorly differentiated carcinoma in the study seemed to be higher than that in the previous reports. A positive correlation was identified in TUR-P specimens between the carcinoma differentiation and its extension which was evaluated by cancer-positive chip ratio.
Atypical adenomatous hyperplasia and intraductal dysplasia were identified in 36.9% and 85.3% of the patients with incidental carcinoma, respectively. These incidences tended to become lower as the carcinoma became less differentiated or more extended. Further studies will be necessary to define the significance of these pathological findings as a direct biological precussor of prostatic carcinoma.
Six out of the 157 patients with incidental carcinoma showed a progression during the follow-up period. All of these patients were in stage A2 and all but one showed a histology of moderately or poorly differentiated carcinoma at the time of diagnosis. Radical prostatectomy or radiation therapy as well as endocrine therapy should be considered as treatment modalities for stage A2 patients, when staging lymphadenectomy shows no pelvic lymph node metastasis.

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Ten patients with urinary stress incontinence were treated by suburethral sling procedure using a polytetrafluoroethyrene tube as the sling. The tension of suspension was determined by the post-urethrovesical angle measured by transrectal ultrasonography in each patient. In nine patients, the post-urethrovesical angle ranged from 90 to 110 degrees, and urinary continence of the patients was completely obtained. The remaining one patient whose post-urethrovesical angle was determined as 120 degrees could not obtain complete continence. Noen of the patients had subjective post-operative disturbance in urination and the peak flow rate of post-operative uroflowmetry hardly decreased in 7 patients in whom this was performed. Although post-urethrovesical angles reduced as the tension which suspended the bladder neck increased, the tension reforming the post-urethrovesical angle was various in each patient. Since one of the aims of suspension of the bladder neck for patients with stress incontinence is reform of the post-urethrovesical angles, correct and reasonable tension of suspension is to be obtained by measuring the post-urethrovesical angle.

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Twenty cases of advanced testicular tumors treated primarily by PVB therapy were reviewed. PVB therapy induced CR in 9 patients (45%). PR in 3 (15%), MR in 3, NC in 3 and PD in 2. The practical doses of the three drugs (cisplatin, vinblastine, bleomycin) were calculated for the initial three couses, and there was very little difference in the mean doses of the drugs per couse between good responders (CR+PR, n=12) and poor responders (MR+NC+PD, n=8). The interval of each course for good responders was unexpectedly longer than that for poor responders (p<0.02).
The prognosis based on several clinical factors was studied. The five-year survival rate (Kaplan-Meier) was 100% in stage II (n=6) and 68.6% in stage III (n=14) (statistically significant) and 90% in non-bulky cases (n=10) and 58.3% in bulky cases (n=10) (statistically insignificant). The two-year survival rate of 5 cases containing choriocarcinoma element was 40.0%, which was statistically worse than that (86.8%) of other histological types (p<0.05). These results suggest that the PVB therapy is not sufficient to cure the cases with choriocarcinoma element or bulky metastasis.

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We treated in total 795 patients with primary transitional cell carcioma of the urinary bladder between April, 1964 and December, 1988. Eighteen patients of them had upper urothelial cancer during the follow-up period.
Thirteen of the 18 patients had received transurethral resection for the initial bladder cancer, while 3 total cystectomy and 2 segmental resection. The over-all incidence of bladder cancer patients who subsequently developed upper urinary tract tumors was 2.3 per cent. The interval between initial treatment of the bladder cancer and treatment for the upper urinary tract tumor ranged from 2 to 74 months (median 20 months).
The five-year survival rate after treatment for the upper urinary tract tumor was 31.7 per cent. We conclude that the following are high risk patients for development of upper urinary tract recurrences: 1) patients with bladder cancer near orifices, 2) patients with recurrent bladder cancer under bladder preserving treatment for a long time, 3) patients with G2 multifocal bladder cancer.

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From March 1989 through December 1989, 123 patients, 9 to 78 years old, were treated by extracorporeal shock wave lithotripsy (ESWL) with the Wolf Piezolith device. Outpatient treatment was performed routinely. Anesthesia was not required in all of the patients. No analgesia or sedation was given routinely. When pyuria had been found before treatment, a course of prophylactic oral antibiotics was given. Treatment consisted of 2000 to 6000 shocks in adults. The need for re-treatment was decided on the basis of the follow up X-rays.
Fragmentation into particles 5mm in size or less occurred in 144 of the 149 renoureteral units (96.6%). Unfragmented stones were treated successfully by the combination therapy of ESWL and fiberoptic transurethral nephroureterolithotripsy (f-TUL).
Of 144 renoureteral units, 3-month follow-up data are available for 96. Among the 96 units, the rate of being free of stones was 67 per cent for renal stones and 96 per cent for ureteral stones treated in situ. The over-all rate of being free of stones was 80.2 per cent.
There were no significant complications.
Ultrasound imaging has proved to be as effective as X-ray imaging.
Outpatient ESWL with the Wolf Piezolith device is considered to be safe and efficient for the initial treatment of urinary stones.
On the other hand, ESWL monotherapy is not sufficient for the treatment of complete staghorn calculi or long-term impacted ureteral calculi. We think that the combination use of ESWL and f-TUL is the most effective procedure for treatment of complicated stones.

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Transurethral incision of the prostate and bladder neck (TIPBn) was compared with transurethral resection of the prostate (TURP) followed by bladder neck incision in the treatment of 22 patients with outflow obstruction caused by a small prostate adenoma (below 15gm). Eleven patients underwent TIPBn and another 11 TURP. An evaluation of the urodynamic findings and subjective symptoms was undertaken before the operation and 3 months afterwards. Urodynamic findings were evaluated, based upon uroflowmetry, i. e., in terms of maximum flow rate, average flow rate, voiding time, initiation time and residual rate. All patients in the TIPBn group revealed an improvement in every urodynamic parameter (MFR: from 6.1 to 10.8ml/sec, AFR: from 3.1 to 5.8ml/sec, Voiding time: from 95.5 to 24.2sec/100ml, Initiation time: 34.3 to 10.2sec, Residual rate: 31.6 to 17.8%, in mean value). Ten out of the 11 in the TIPBn group subjectively considered the result to be good. The improvements in the urodynamic parameters in the TIPBn group were statistically comparable to those in the TURP. The improvements in voiding time and initiation time, however, tended to be much better in the TIPBn group.
We conclude that TIPBn can be the operation of choice in the treatment of outflow obstruction caused by a small prostate.

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We evaluated 32 patients with urinary calculi under 16 years of age over the past 14 years since the founding of the Department of Urology, Kinki University School of Medicine. They comprised 0.8% of the total urolithiasi patients. They consisted of 18 boys and 14 girls with a male-to-female ratio of 1.29. The average age was 8.7 years for boys and 10.4 years for gils without any marked peak. The most frequently chief complaint was hematuria which was present in 15 cases (47%). Although pyuria was seenin seven cases (22%), urinary bacterial culture was positive only in 5. The underlying diseases could be diagnosed in 13 cases (41%), of which eight cases (62%) developed metabolic disorder. The sites of caluculi were determined in 29 cases (91%), of which 28 had stones in the upper urinary tract. Surgical teatment was performed on 16 cases in 17 sessions. Ureterolithotomy was done in as many as five cases, followed by pyeloplasty in four cases. Nephrectomy was performed in only one case. There was only one case which had been treated with extracorporeal shock-wave lithotripsy (ESWL). The composition of calculi was found in 21 cases (66%), the majority or 13 cases (57%) of which had calcium-containing stones. Nevertheless, there was no case of hypercalciuria.
When compared to the previous reports in Japan, it was worthy of note that calculi in the upper urinary tract and calcium-containing stones had higher incidences. It is expected that more patients will be treated with ESWL in the future. On the other hand, it is required that standardized criteria be established for the diagnosis of hypercalciuria in Japan.

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Clinical courses of 293 patients with superficial papillary bladder tumors were analysed on the basis of tumor number at the first presentation. The follow-up period ranged from 6 to 266 months with a median of 59 months. 171 patients (58%) had a single tumor, while 122 (42%) had multiple tumors. Those older than 60 years occupied 68% in the latter group and 51% in the former (p<0.01). High grade tumors were more frequent in the latter than the former (p<0.05). The five-year recurrence rate was 68% for the latter and 39% for the former single tumor group (p<0.01). Malignant progression was observed in 3.6% of patients with a single tumor and 13.4% of those with multiple tumors (p<0.01). The results would offer a theoretical background to the finding of a poor ten-year actuarial survival rate of 54% for multiple tumor group compared with 76% for the single tumor group (p<0.05). However, the rate of primary cancer death was similar in both groups.

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Of 8 tumors surgically extirpated from 8 patients with renal cell carcioma, 7 were successfully processed in short-term culture by collagenase method, and 130 metaphases were extacted from these 7 tumors and were subjected to chromosomal analysis according to the G banding technique. As for karyotype, 4, 2 and 1 cases were mainly diploid, hypodiploid and aneuploid, respectively. The highest incidence of chromosome aberration was marked by #3 chromosome (5 of 7 cases of which 4 and 1 showed monosomy as clonal aberration and trisomy as non-clonal aberrtion, respectively). The commonest gain of chromosome was noted for #7 trisomy (4 of 7 cases). Two cases had already had metastases at the time of surgery, each showing #7 trisomy. Marker chromosome was noted in 6 of 7 cases. Structural chromosome aberration had a lesser incidence compared with numerical aberration; only clonal aberrations were long-arm aberrations (2q⁺, 6q⁺) of #2 and #6 chromosomes. Short-arm aberrations (3p^-, 8p^-) of #3 and #8 chromosomes were noted in one case each. 3p deletion, which is reported to be predominant in the liteature, was noted only in one case. This was observed in triploid cells. However, all of metaphases showing 2q⁺ and 6q⁺ had concomitant #3 monosomy, and excess portions of #2 and #6 chromosomes were in good agreement with the band pattern of #3 chromosomal long-arm. Therefore, translocation of 3q12-qter in #2 and #6 chromosomes is supposed to lead to 3p deletion. A similar mechanism seems to be involved in the formation of marker chromosomes, suggesting the involvement of deleted #3 chormosome in marker chromosomes.

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Histological and flow cytometry (FCM) analyses were performed of carcinogenesis of rat prostate cancer induced with N-Nitroso-N-methylurea (NMU). Ten-week-old rats were inoculated intravenously (i. v.) with twice injections of NMU (30mg/kg body weight) and then, divided into 3 groups; Group 1: the rats were injected subcutaneously with LH-RH analogue (100μg/kg b. w.) every 4 weeks. Group 2: the rats were injected subcutaneously with testosterone enanthate (10mg/body) every 2 weeks and Group 3: the rats were untreated to serve as controls. We further divided Groups 1 and 2 into (+) and (-) subgroups at 34 weeks after initial injection. Group 1 (+) or 2 (+) rats were continuously given the drug and in Group 1 (-) or 2 (-) rats the drug was suspended. At 44 or 53 weeks after initial injection, we removed the prostate and seminal vesicles of all rats and performed histological and FCM analyses of them. Histological analysis of rat prostates revealed hyperplasia in each group, and both Groups 2 (+) and 2 (-) showed an incidence as high as 87.5%. Atypical hyperplasia was sometimes observed in each group and its incidence was not significantly different between any 2 groups. At 51 weeks after initial injection, a macroscopic adenocarcinoma (weighing about 11g) was found in the prostate of a dead rat of Group 2 (+). Histological analysis of rat seminal vesicles revealed hyperplasia in each group, in particular in Groups 2 (+) and 2 (-). In these groups all rats showed hyperplasia. At 53 weeks after initial injection, two rats of Group 2 (+) showed atypical hyperplasia and another rat of Group 2 (+) showed a macroscopic adenocarcinoma. In FCM analyses of the prostates and the seminal vesicles, aneuploid pattern was observed in each group with insignificant difference between any 2 groups. There was no meaningful correlation between histological analyses and FCM analyses of the prostates and the seminal vesicles.

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One hundred patients with carcinoma of the urinary bladder were treated with preoperative intra-arterial anticancer drug infusion in combination with an active carbon-based artificial liver or preoperative radiotherapy (400 rad ×5 days, total 2000 rad) in order to alleviate systemic side effects after preoperative adjuvant therapy and to perform radical cystectomy as soon as possible. Five-year survival was 69.8% in the artificial liver combined preoperative intra-arterial anticancer drug infusion group, and that of the no-pretreatment group and the preoperative irradiated group was 48.6% and 45.8%, respectively. In particular, the CDDP treated group had a higher 5-year survival of 77.4% than did the without CDDP treated group. This was attributable mostly to improved prognosis of T₂, whereas either of these preoperative adjuvant therapies failed to ameliorate the prognosis of T₃ or T₄ stage patients. Therefore, systemic preoperative anticancer chemotherapies such as M-VAC are necessary to destroy “micrometastases” and to improve the prognosis of highly advanced bladder cancer.

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The patient was a 61-year-old male who had undergone right nephrectomy for nephrolithiasis 35 years before. He had been on hemodialysis for 6 years for chronic renal failure caused by left renal staghorn calculus and hydronephrosis. He was admitted to our hospital because of macroscopic hematuria and sense of residual urine which had persisted for 3 months. Cystoscopic examination showed an extensive papillary tumor in the urinary bladder, which histologically was an adenocarcinoma.
Giant left hydronephrosis associated with staghorn calculus noted by KUB and CT scan. Total cystectomy, intraoperative radiotherapy, and left nephrostomy were performed under the diagnosis of adenocarcinoma of the urinary bladder and left hydronephrosis.
The bladder tumor was found to be a mucinous adenocarcinoma. The patient died from a cerebral hemorrhage on the 17th postoperative day. At autopsy, tumors were found in the pelvis of the left kidney and the middle and lower regions of the ureter, which were adenocarcinoma like the bladder tumor.
Adenocarcinoma occurring simultaneously in the renal pelvis and bladder has not been previously reported to our knowledge, in Japan or elsewhere.

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