To investigate the expression of c-H-ras (p21), c-erb B₁ (EGFR) and c-erb B₂ (p185) gene products in human bladder cancer, immunohistochemical studies using monoclonal antibodies to these proteins were performed on formaline fixed (within 15 hours)-paraffin sections of tumor tissues from 20 patients with bladder cancer, normal appearing adjacent bladder (non-tumor) tissues from 11 of the 20 patients, and normal bladder tissues from 3 patients who died of non-cancerous diseases as control.
p21 Positive staining was demonstrated in the superficial cells of urothelium in 1 of 3 controls, also in 5 of 20 tumor tissues compact cells without vacuole in cells which have an increased nuclear/cytoplasmic ratio. Seven of 11 non-tumor tissues indicated positive staining either in superficial layer only or in whole layers of urothelium, and 1 of the latter group reacted with the monoclonal antibody to human bladder cancer produced in our laboratory. EGFR was found in 5 of 20 tumor tissues and 7 of 11 non-tumor tissues, but not in controls. Most EGFR positive tissues also indicated p21 positivity except in 1 of the tumor tissues. p185 Positive staining was demonstrated in 9 of 20 tumor tissues and 5 of 11 non-tumor tissues, but not in the controls. Furthermore, 5 of 6 tumor tissues from the patients with lymph node metastasis indicated p185 positivity.
These results suggest that both p21 and EGFR may have a role in transformation and that p185 has a role in the development of metastasis in some urotherial malignancies.

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Urodynamic evaluation was performed in 11 male patients, who underwent radical cystectomy with pelvic lymph node dissection for bladder cancer followed by bladder replacement with a urethral Kock pouch, 3 to 21 months after the operation. Frequency of micturition were 4.9±1.5 times (mean±S. D.) during the day-time and 1.5±1.2 times during the night-time. Tidal volume of micturition ranged from 300 to 550ml and residual volume from 10 to 30ml. Urinary continence was completely preserved in all patients (100%) during the day-time and 8 (72.7%) during the night-time. On pouchmetry, maximum capacity of the pouch was 429.2±82.4ml, and intra-pouch pressure was 16.2±5.4cmH₂O at the capacity of 200ml and 38.7±11.5cmH₂O at the maximum capacity. Maximum intra-pouch pressure on voiding was 80.0±19.4cmH₂O. Uroflowmetry demonstrated intermittent voiding curves in all the patients, with maximum flow rate of 15.2±6.5ml/sec, voided volume of 405.9±80.7ml and residual rate of 4.5±2.6%. Maximum intra-urethral pressure at the external urethral sphincter was 28.0±11.3cmH₂O when the pouch was empty and increased in response to pouch filling up to 64.7±27.0cmH₂O. Maximum urethral closing pressure and total profile length on the urethral pressure profile were 30.2±12.4cmH₂O and 20.9±9.0mm, respectively, with the pouch empty, and 23.2±14.5cmH₂O and 20.0±7.6mm, respectively, with the pouch full.
The bladder replacement using the urethral Kock pouch is a valuable alternative for continent urinary reconstruction provided creation of a low pressure reservoir and preservation of the urethral sphincter function are achieved. On the other hand, long term effects of the high intra-pouch pressure by abdominal strain on the reservoir have not been determined. It is conceivable that this high pressure may cause functional and/or organic changes of the pouch and jeopardize the anti-reflux mechanism at the afferent limb. In a case with high intra-pouch pressure on voiding, evacuation of urine by an intermittent catheterization instead of abdominal strain may be advocated, irrespective of the residual volume.

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With the use of a newly developed and convenient enzymatic method, tissue, urine and blood polyamine (diamine, spermidine and spermine) levels were evaluated as a tumor marker of renal cell carcinoma (RCC) in 50 cases with the disease. Furthermore, blood and urine polyamines were periodically determined and evaluated as a follow-up marker. The pretreatment three polyamine levels in tissue, blood and urine of the patients were all significantly higher than those of the controls. However, because of their low sensitivities, they were not always decisive for biochemical diagnosis of RCC. Tissue spermidine levels were increased with the advance of the stages. Tissue diamine level also showed a good correlation with the pathological grade. Tissue diamine was found to predict distant metastasis. Blood spermidine and urine diamine were useful as follow-up markers. In conclusion, combined determination of tissue, blood and urine polyamine levels was thought to be useful as tumor markers of RCC.

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We reviewed 12 patients who had undergone curative or non-curative nephrectomy for renal cell carcinoma invading adjacent organs (stage T4). 83 patients with renal cell carcinoma confined within the perirenal fascia (T1-T3) who had undergone nephrectomy served as controls. Of the 12 patients with T4 tumor 6 had undergone simultaneous excision of involved adjacent organs (hemicolectomy in 4, resection of the tail of pancreas in 5, splenectomy in 2). At operation 6 patients with T4 tumor had distant metastasis, 3 had fixed lymph node metastases, and 4 had tumor extention into the main renal vein or vena cava. Although T4 tumor had distant or fixed lymph node metastasis more frequently than T1-T3 tumors, the incidence of gross tumor thrombus showed no such difference between T3 and T4 tumors. Postoperative follow-up of patients with T4 tumor showed that local recurrence developed within 9 months in 3 of 5 patients who had undergone curative excision, new distant metastasis developed within 6 months in 5 patients, 1 patient died of acute renal failure in the early convalescence, 10 patients died of the disease within 12 months and 1 died of the disease in 31 months. Pathological examination showed that T4 tumors tended to be classified as grade 3, to extend in an infiltrating fashion and to have a sarcomatoid structure. Patients who had a tumor where these three histological features were dominant died to tumor within 3 months after nephrectomy. These results indicate that curative excision of T4 renal cell carcinoma is not only difficult, but frequently associated with early local recurrence and new distant metastasis. A more effective adjuvant therapy is required to improve the prognosis of T4 renal carcinoma.

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A total of 174 cases that consulted due to chance proteinuria and/or hematuria (CPH) were studied as to its clinical course, in particular patients' prognosis. They were selected from 311 patients on whom renal biopsy was performed from December, 1975 to December, 1985 in our institute. Furthermore, IgA nephropathy which occupied the major part of the CPH group was also studied as a prognostic factor. The CPH group showed 81% of disease stabilizing rate in 10 years' follow-up. In various data such as chemical analysis of blood and urine, immunoglobulin levels, and renal function at the time of biopsy, daily urinary protein excretion (>1g/day) statistically showed a significant correlation to deterioration of the renal function during the follow up. However, hematuria was not found correlated. Of CPH group, 48% was diagnosed to be with IgA nephropathy. The patients with IgA nephropathy with CPH, comparing with the cases without CPH, were younger and had better renal function and milder change of renal mesangial proliferation. The 10 years-disease stabilizing rates of the disease were 81% in CPH and 63% in non CHP group. In conclusion, prognostic factors affecting renal function in the CPH group was found to be daily urinary protein excretion and, if diagnosed as IgA nephropathy by biopsy, pathological changes were also shown to be prognostic factors. Therefore, CPH patients having proteinuria over 1g/day must be examined by renal biopsy and when IgA nephropathy is diagnosed, long time follow-up is necessary and re-biopsy for examination of pathological change during the interval is recommended.

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In the present paper, we have reported the purification procedures of N-acetyl-β, D-glucosaminidase (NAG) A from human renal tissue as well as the enzymatic properties of NAG A. NAG A was purified to homogeneity by gel filtration methods using Sephacry S-400 and S-200, followed by affinity chromatography with TSK DEAE 5-PW. The final activity of the enzyme was 1001U/ml protein which was 506.6-fold that of the crude extract (supernatant of 20, 000×G of the homogenate). The molecular weight of NAG A was 140kDa, consisting of two subunits of 30kDa and 57kDa. The isoelectric point of the enzyme was 5.60. The optimal pH of the enzyme was between 4.7 and 4.9. The Km value of the enzyme for sodio-m-cresol sulfophtaleinyl-N-acetyl-β, D-glucosaminide was found 0.177×10^-3mol/l. Lectin affinity chromatographies using concanavalin A and wheat germagglutinin have demonstrated that major sugar-chains of the enzyme were the high mannose type and hybrid type with a fucose residue, and that a small amount of the complex type was contained.

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To clarify prognostic factors for progression of superficial transitional cell carcinoma of the bladder (Ta, T1 and G1, G2), 159 patients, treated by transurethral resection from 1975 to 1988, were analysed concerning clinical findings, laboratory data, endoscopic findings and histopathological findings of the tumor. Histopathological findings included ABH blood group isoantigen (ABH) and Thomsen-Friedenreich antigen (T-ag) as well as other result. Twenty two cases in the series showed progression; 10 with up-grading and up-staging, 12 with either one of them.
Advanced age, positive urinary cytology, multiple or broad base tumor, G2 or T1 tumor, negative ABH and abnormal T-ag were closely associated with progression.
By multivariate analysis of these factors, ABH, stage of the tumor, T-ag and form were shown to be important prognostic factors in this order. ABH and T-ag were not correlated with other cliniocopathological factors in predicting tumor progression. Therefore we concluded that ABH and T-ag were much important for prediction concerning potential for progression of the superficial bladder cancer.

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From January 1982 to December 1989, we experienced seven multilocular cystic renal cell carcinomas (MLCRCCs) in 36 asymptomatic renal cancers incidentally diagnosed, and none in 23 symptomatic renal cancers (p<0.05). No multilocular cystic nephromas (MLCNs) appeared in either group.
Though MLCRCCs have been considered to be, in general, extremely rare, they do occur in asymptomatic renal cancers. A multiloculated renal mass with thick septum discovered in an adult by ultrasonography or CT scan should be suspected as being a MLCRCC rather than a MLCN.

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Blood collected from irrigating fluid in TURP was studied if it was appropriate blood as autologous transfusion or not. TURP was performed aided by continuous irrigation through suprapubic cystostomy. The cystostomy tube was connected to the Shiley STAT or Haemonetics Cell Saver in 15 patients. The average weight of resected adenoma was 36g per patient. The product of washed blood gave an average yield of 440ml per patient with an average RBC count of 469×10³/mm³, hemoglobin of 14.6g/dl, hematocrit of 44.8%, platelets of 15400/mm³. The half-life of collected red blood cells tagged with ⁵⁵Cr was 22 days. The urine in 10 patients (67%) were contaminated with bacteria before TURP, and 3 of collected blood were contaminated with bacteria (20%). As for carcinoma cells, cultured urinary bladder carcinoma cells (T24) and renal carcinoma cells (ACHN) were completely eliminated after filtration through leukocyte removal filter Sepacell^® or Pall RC^®. As results, the intxaoperatively collected blood from irrigating fluid in TURP was useful and safe as autologous blood transfusion.

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We treated seventy venogenic impotents with ligation of the deep dorsal vein of the penis. Their corporal veno-occlusive function was evaluated by dynamic infusion cavernosometry and cavernosography (DICC). Under local anesthesia, we made a longitudinal skin incision at the base of the penis. The deep dorsal vein was ligated and also a portion of this vein of 1.5cm long was resected together with branches surrounding the vein. After the operation, the infusion rate determined by DICC was confirmed to be decreased in almost all patients.
Thirty nine out of seventy cases had their erectile capability restored and reported that they could achieve sexual intercourse. Sixty one of the seventy cases showed full erection together with an intracavernous papaverine injection. However fifty percent of the sixty one patients who became capable of obtaining erection with the treatment had lost their erectile capability again within one year of the operation, however the other fifty percent were shown to maintain their erectile capability for up to three years. As four years after the treatment only thirty percent of those who had achieved the initial erectile capability still remained potent.
This operation is easy to perform without any major complications, and its outcome is as good as that achieved by other more invasive venous ligation in the treatment of patients with venogenic impotence. We therefore conclude that penile deep dorsal vein ligation and partial resection of the vein one of the most useful treatments currently available for venogenic impotence and should be the treatment of choice.

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A survey on urinary incontinence in 161 (41 male, 120 female) institutionalized elderly was independently performed by urologists and attending nurses. Urinary incontinence was found in 107 cases (66%), with 76 cases (47%) suffering from severe leakage (more than 5 times a day and needs diaper). The prevalences of incontinence and severe leakage were 63% and 52% at geriatric hospitals, 59% and 29% at intermediate care centers and 78% and 63% at nursing homes, respectively. The risk factors for incontinence were consciousness disturbance, urinary urgency, impaired mobility and dementia, and those for severe leakage were apathy, loss of urinary sensation, dementia and impaired mobility. The type of incontinence was considered functional one in 81% of cases. The agreement of the incontinence type evaluated by urologists and that by nurses was found in 90% of incontinent cases. Incontinence was estimated “incurable” in 54% of cases by attending nurses. These observations indicate a high prevalence of severe and “incurable” incontinence in the institutionalized elderly, urgently warranting an effective remedy for the increasing aged society.

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The aim of this study is to clarify the physiology and pathophysiology of two striated urethral sphincters, the periurethral striated sphincter (PUS) and the external urethral sphincter (EUS), in the voiding cycle, using a selective and semi-quatitative electromyographic technique.
Under ultrasonic guidance, two needle-electrodes were inserted into the two sphincters of 31 males (7 neurologically normal, 13 with nuclear and/or infranuclear lesions, 11 with supranuclear lesions), and EMGs recorded during the whole cystometric course were analysed by the aid of Turns-Amplitud Diagram (TAD). The results obtained were as follows:
1) In neurologically normal cases, the increment of turns as well as amplitudes in EMGs of both the sphincters were observed with the bladder filling, and they were completely diminished at the onset of than voiding.
2) The increment of turns were more obvious than that of amplitues in EMGs of both the sphincters.
3) More voluntary function could be assumed on EUS than PUS.
4) The functional sphincteric responsibility corresponding to the voiding cycle could be expressed by the direction and the length of the vectors obtained from TAD.
5) In neurogenic bladder cases, various abnormal sphincteric responsibility, such as the shortening and/or abnormal directions of the vectors, were found.
With the results described above, this semi-quantitative assessment of sphincter EMG was thought to be useful to evaluate the abnormal activity of the urethral sphincter in neurogenic bladder cases.

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A randomized prospective study was conducted for the purpose of investigating the efficacy of intravesical chemoprophylaxis of superficial bladder cancers. Eligible patients were randomized into three groups: 1) adriamycin (ADM) group; intravesical instillation with 50mg of ADM dissolved in 100ml physiological saline, 2) mitomycin C (MMC) group; intravesical instillation with 30mg of MMC dissolved in 100ml of physiological saline, 3) control group; transurethral resection or transurethral coagulation only.
The characteristic features of our protocol consisted of frequent (six times) instillations of the drugs within two weeks after transurethral resection, followed by instillations on two consecutive days at four-week intervals for two years. Furthermore, large quantities (100ml) of instillation fluid containing relatively low concentrations of the drugs (500μg/ml for ADM or 300μg/ml for MMC) were employed.
One hundred and forty-four patients have been submitted to the study; 110 patients were fully evaluable for recurrence and 34 patients were eliminated as non-evaluable patients. The cumulative five-year non-recurrence rates of the patients with multiple tumors were 32% in the MMC group, 25% in the ADM group and 7% in the control group. The cumulative non-recurrence rates of the ADM and MMC groups were significantly higher than that of the control group.
It is considered that this instillation therapy with ADM and MMC is useful for preventing the recurrence of superficial bladder cancers.

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The effects of a single administration of ethane dimethane sulphonate (EDS), which has a direct cytotoxic effect on Leydig cells, was assessed for its spermatogenic damage and intratubular androgen level in SD male adult rats. The protective effect of human chorionic gonadotropins (hCG) (s. c.), testosterone propionate (TP) (s. c.) and intratesticular administration of testosterone microcrystal suspension (Tmcs) against the spermatogenic damage in rats EDS given was also evaluated.
EDS caused a decrease of the seminiferous tubular diameter and impaired spermatogenesis remarkably; moreover, it also caused significant decreases in intratubular androgen levels.
These results suggest that EDS-treated SD male adult rats may be suitable as a model for hormone dependent infertility. The administration of hCG and intratesticular Tmcs prevented tubular damage and increased the intratubular T level. On the other hand, the administration of TP prevented tubular damage while remarkably decreasing intratubular androgen level.
In this connection, it was inferred that priming of rats with TP caused an increase in intratubular androgen binding protein, which would stimulate spermatogenesis.
The fact that a single injection of Tmcs caused no tubular damage suggests that intratubular T level is one of the factors playing an important role in spermatogenesis and that an intratesticular injection of Tmcs may be useful for the treatment of some cases of idiopathic male infertility.

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Primary tumor in the ureteral stump is rare. A 66-year-old woman visited our hospital because of microscopic hematuria. She had undergone right nephrectomy for the contracted kidney 36 years ago. Intravenous pyelography and cystoscopy showed no positive findings for hematuria. But urine cytology indicated class V. The flexible ureterorenoscopy disclosed a nonpapillary sessile tumor in the ureteral stump. We also did the biopsy of the tumor under the direct vision before open surgery. The specimen showed transitional cell carcinoma, grade 3. The ureteral stump was successfully removed. The flexible ureterorenoscopy was most useful for the diagnosis in this case.

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A 70-year-old man had a history of total laryngectomy for laryngeal cancer and bilateral inguinal hernia repair 5 years previously. The patient had suffered from difficulty with urination since then and had been treated for prostatic hypertrophy at our department. He developed microscopic hematuria from June 1991, and was admitted because a bladder tumor was detected by cystoscopy. Cystography showed a scrotal bladder hernia with filling defects in the bladder per se and the bladder hernia as well. Cystoscopy revealed tumors in the hernia and in the vicinity of the ureteral orifice. Biopsy indicated transitional cell carcinoma. Voiding cystourethrography showed normal urination and no residual urine. Excision of the tumor-containing hernia, partial cystectomy with right ureteral orifice, and reconstruction of the right inguinal canal were performed on October 25, 1991. The postoperative course was favorable and he was discharged on the 40th postoperative day. The tumors were respectively stage as TCC, G1, and pT1a, and TCC, G1>G2, and pT1b.
Thirty five cases of bladder hernia that have been reported in Japan. Eight cases of accompanied by cancer have been reported in Japanese (3 cases) and foreign (5 cases) literatures. These are reviewed and discussed.

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