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Summary This study examined the immediate effects of wrapped warm footbaths (WW Footbath) on the autonomic, neuroimmunological and psychological activities in healthy middle-aged volunteers. Thirteen subjects were divided into a footbath group ( n =7) and a control group ( n =6). Immediate changes in autonomic activities were recorded with wavelet analysis of heart rate variability. Salivary secretory immunoglobulin A (sIgA) and serum cortisol levels were used as neuroimmunological parameters. Psychological conditions were measured using a Visual Analog Scale. Parasympathetic activity tended to increase and sympathetic activity decrease after footbaths. Results Changes in the relaxation indices, that is, sIgA and serum cortisol levels showed that both lying down and footbath resulted in a relaxed state. Conclusion: WW Footbaths can be an effective method of relaxation, since it induces both a significant increase in parasympathetic activity and significant decrease in sympathetic activity.

Objective The aim of the present study was to examine the association between subjects with self-awareness of fast eating and diagnostic components of metabolic syndrome in Japanese middle-aged male and female. Patients and methods Subjects consisted of 3208 males (average age 50.6 years) and 2055 females (average age 50.0 years). Associations between subjects with self-awareness of fast eating and multiple components of metabolic syndrome (waist circumference, body mass index [BMI], blood pressure, and related blood sample tests) were evaluated. Results Significantly more males (57.7%) acknowledged themselves as "fast eater" than females (46.5%). Self-reported fast eaters showed significantly elevated body weight, BMI, and waist circumference in both genders. However, only male self-reported fast eaters showed high levels of blood pressure, fasting blood glucose, uric acid, and low-density lipoprotein (LDL)-cholesterol. Conclusion Fast eating is associated with diagnostic components of metabolic syndrome. The effect of acknowledging themselves as fast eater presents a higher impact on males than on females in the middle-aged Japanese population. The present study indicates that finding subjects with self-awareness of fast eating may lead to the prevention of developing metabolic syndrome.

Orthostatic hypotension is a hallmark of diabetic autonomic neuropathy and is associated with increased mortality. The serum level of adiponectin is elevated in patients with heart failure or renal failure. In the present study, we measured serum levels of total and high molecular weight adiponectin in patients with Type 2 diabetes and orthostatic hypotension. We also investigated the relationship between the presence of orthostatic hypotension and various clinical variables in patients with Type 2 diabetes.We studied 105 patients with Type 2 diabetes. Orthostatic hypotension was defined as a decrease of 20 mmHg or more in systolic blood pressure and/or 10 mmHg in diastolic blood pressure when blood pressure was measured for 3 min while standing. The brachial-ankle pulse-wave velocity was also measured as an index of arterial stiffness.Orthostatic hypotension was found in 30 patients with diabetes (28.6%). The haematocrit and estimated glomerular filtration rate were significantly lower in patients with orthostatic hypotension than in those without it. Brachial-ankle pulse-wave velocity and serum total and high molecular weight adiponectin were significantly higher in patients with orthostatic hypotension than in those without. Furthermore, the high molecular weight/total adiponectin ratio was higher in patients with orthostatic hypotension than in those without and hypertension was more common in patients with orthostatic hypotension. Plasma prothrombin F1 + 2, a coagulation maker, was higher in patients with orthostatic hypotension than in those without, while there were no differences of fibrinolytic markers between the two groups. Multivariate analysis showed that HDL cholesterol, haematocrit, F1 + 2, brachial-ankle pulse-wave velocity and a decline of systolic blood pressure on standing were independent determinants of high molecular weight adiponectin.Patients with Type 2 diabetes and orthostatic hypotension had an elevated serum level of high molecular weight adiponectin, which was associated with the simultaneous presence of renal dysfunction, anaemia, arterial stiffness and hypercoagulability.

We proposed a new classification of pheochromocytomas according to DNA ploidy patterns. Proliferation index (PI = S% + 4C%) might be an alternative to 4C% which was used as a critical marker of DNA nonaneuploid histograms. The follow-up survey revealed that DNA tetraploid with minimum increase of PI could not rule out the substantial possibility of malignancy and the comparison of DNA diploid histograms disclosed that 22 and 0% showed significant increase of the ratio of 4C% to S% under PI and 4C% criteria, respectively. In conclusion, 4C% was more effective and reliable than PI in order to classify DNA nonaneuploid pheochromocytomas.

The main purpose of the study was to investigate the association between vascular endothelial function and diabetic microangiopathy (nephropathy, retinopathy and neuropathy) in patients with type 2 diabetes. In addition, the association between endothelial function and macroangiopathy evaluated by intimal-medial complex thickness (IMT) was also investigated. Endothelial function was evaluated non-invasively by the measurement of flow-mediated vasodilatation (FMD) of the brachial artery. Diabetic nephropathy and neuropathy were assessed by urinary albumin excretion (UAE) and motor or sensory nerve conduction velocity (MCV, SCV), respectively, and retinopathy was evaluated by an ophthalmologist using the Davis classification. FMD was measured in 102 patients with type 2 diabetes and in 20 control subjects, and showed a tendency to be lower in the diabetic patients. There was a significant decrease in FMD in patients with proliferative diabetic retinopathy, compared with those in patients with no diabetic retinopathy. FMD showed significant positive correlations with MCV and SCV, and significant negative correlations with log UAE, systolic blood pressure and diabetic duration, but no correlation was obtained between FMD and IMT. In stepwise regression analysis, MCV alone showed a significant association with FMD. In conclusion, our results show that in patients with type 2 diabetes FMD is closely associated with all types of microangiopathy, with neuropathy being most strongly associated with FMD; however, FMD is not associated with macroangiopathy evaluated by IMT.

It is recognized that QTc intervals reflect autonomic nerve function. To investigate the clinical usefulness of corrected QT intervals (QTc) in assessing autonomic nerve function in type 2 diabetes, we measured QTc intervals using Bazett's formula in 58 type 2 diabetic patients and 20 age-matched healthy subjects.We examined relationships between QTc intervals and the coefficient of variation of RR intervals (CV(RR)), systolic blood pressure response to standing, and sympathetic skin response (SSR) whose tests reflect autonomic nerve function. We also studied the correlation between QTc and blood pressure or serum lipid concentrations.QTc intervals in diabetic patients were significantly longer than those in healthy subjects and showed a significant but weak negative correlation with CV(RR), as well as systolic blood pressure response to standing. No significant difference in QTc intervals was observed between patients with and without a detectable SSR. QTc intervals showed a significant positive correlation with systolic and diastolic blood pressure although it did not correlate with serum lipid concentrations. QTc also tended to be long in obese diabetic subjects (body mass index25).QTc intervals might also be affected by other factors such as arteriosclerotic macroangiopathy and obesity, and not only autonomic nerve function. Therefore it might be considered as an overall index for complications, and not for pure autonomic impairment.

We investigated the change in low-density lipoprotein receptor activity following the administration of estrogen to patients with hypercholesterolemia (HC). Studies were conducted in 16 patients with HC (total cholesterol (TC)220 mg/dL) and 133 healthy control subjects. LDL-R activity was measured by fluorocytometry. Three of sixteen patients with HC showed low LDL-R activity below 80% together with extremely high serum levels of TC and LDL cholesterol (LDL-C). LDL-R activity showed an inverse correlation with serum levels of TC and LDL-C (p0.05, respectively). Two women with initially low LDL-R activity who showed a marked increase in LDL-R activity exhibited a normalized activity at four and eight weeks after estriol administration, proportional to the reduction in serum levels of TC and LDL-C. One man with an initially extremely low LDL-R activity showed no abnormality at the sites of exons 7, 14, 17 and intron 12 by the PCR-DGGE method, which are common sites for point-mutations of LDL-R among Japanese patients with HC. Estrogen reduced serum levels of TC and LDL-C in patients with HC, at least in part, via an increase in the LDL-R activity of patients with HC and an initially low LDL-R activity.

The majority of patients with localized and some cases of locally advanced prostate cancer undergo radical prostatectomy. However, radical prostatectomy cannot always be selected for those patients. In this situation, primary hormone therapy is an alternative treatment option. We have designed a prospective randomized study of the effects of primary hormone therapy for such patients.A total of 151 patients with T1b, T1c, T2a, T2b or T3a prostate cancer who were not scheduled for radical prostatectomy were enrolled into this study. Patients were randomly allocated into two groups; Group I received luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy (leuprorelin acetate depot, 3.75 mg monthly) and Group II received LH-RH agonist in combination with chlormadinone acetate (100 mg/day). Effects on serum prostate-specific antigen level, progression-free survival and survival were observed for 2 years.The reasons why radical prostatectomy was not scheduled were poor risk for surgery (38%), patient's wish (32%) and physician's recommendation (30%). After 12 weeks of treatment, 49% of the patients in both groups showed a complete response (CR). Of the patients showing a partial response (PR) after 12 weeks of treatment, 25% in Group I and 52% in Group II improved to CR 1 year later (p0.05). Group II showed a longer progression-free survival (p0.05). Progression-free survival rates were 62% (Group I) and 91% (Group II) in T2b patients and 43% (Group I) and 73% (Group II) in T3 patients. Only one patient in each group died from prostate cancer.Early primary hormone therapy is a reasonable treatment option for localized or locally advanced prostate cancer patients if radical prostatectomy was not scheduled. Chlormadinone acetate showed an additive effect with LH-RH agonist, at least in 2 years' observation.

The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade.Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate).There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone.Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.

The effects of preoperative androgen deprivation were explored in the patients who received radical prostatectomy and subsequent adjuvant endocrine therapy for prostate cancer.Stage A2, B or C prostate cancers were randomized to one of two groups: (i) group I (n=90), who received androgen deprivation (leuploride and chlormadinone acetate) for 3 months preoperatively followed by radical prostatectomy and adjuvant endocrine therapy (leuploride only); and (ii) group II (n=86), who underwent the surgery followed by 3 month androgen deprivation and subsequent adjuvant endocrine therapy. The effects of preoperative androgen deprivation on clinical relapse (serum prostate specific antigen (PSA)1.98 ng/mL, local recurrence or distant metastasis) and PSA relapse (PSA0.2ng/mL) were evaluated at 2 years after randomization.There was no significant difference in clinical or PSA relapse-free survival and quality of life measures between the two groups, although relapses occurred significantly more frequently in patients who had more advanced stages, higher pretreatment PSA values or lower histologic differentiation in either group. Subgroup analysis indicated that clinical relapse-free survival in stage C cancer tended to be better in patients with preoperative androgen deprivation than in those patients without it (P0.1).Preoperative androgen deprivation may be beneficial for stage C prostate cancer patients receiving radical prostatectomy and adjuvant endocrine therapy over the 2 year observation period. A longer follow up is needed to clarify the exact extent of benefit in terms of survival and quality of life.

A 52-year-old Japanese male complained of palpitations and excessive sweating. He showed evidence of hyperthyroidism, but without suppression of the serum thyroid-stimulating hormone (TSH). On admission, the serum level of the alpha-subunit of TSH was elevated, but tests for thyroid autoantibodies were negative. The TSH response to thyrotropin-releasing hormone (TRH) was blunted. Imaging studies revealed a pituitary tumor 2 cm in diameter. Administration of methimazole lowered the serum levels of thyroid hormones, and elevated the serum level of TSH. These findings led to the diagnosis of a thyrotropin-secreting pituitary tumor. Immunohistochemical analysis and electron microscopic findings verified the diagnosis.

Two major components of rRNA (18S and 28S rRNA) were separated by electrophoresis in injection-molded acrylic chips with a microchannel 100 microm in width, 40 microm in depth, and with 1 cm of separation distance. Microchannels were filled with 4 g/L hydroxypropylmethylcellulose as sieving polymer and 5 mg/L ethidium bromide for RNA staining. The fluorescent signals were detected by a fluorescent microscope equipped with a photometer and 590 nm emission filter. The assay is rapid (3 min), reproducible, RNase-free, and requires only 1-2 microL of sample. The detection limit was approximately 10 mg/L (10 ng/microL), 100-fold lower than that for conventional agarose gel electrophoresis. Because only 0.1 nL of the loaded sample was used for electrophoresis, the detectable peaks of rRNA in the separation were derived from less RNA than in a single cell. Because the quality of RNA is critical for RNA-related diagnostic tests, disposable plastic chips will be useful for quality assessment of RNA.

To simplify gene expression analysis, oligo(dT)-immobilized polypropylene microplates were used serially to capture mRNA, synthesize cDNA, and amplify specific genes. The amounts of immobilized oligonucleotide, hybridized mRNA, and synthesized cDNA were quantified fluorometrically using either Yoyo-1 or AttoPhos. The immobilized oligonucleotides captured approximately 40-55% of mRNA directly from crude cell lysates. Hybridized mRNA was then amplified by one-step reverse transcription (RT)-PCR with rTth polymerase or two-step PCR with initial cDNA synthesis followed by PCR, where the latter exhibited more sensitivity. In two-step RT-PCR, microplates can be reused for multiple PCRs with the same or different primer sets because synthesized cDNA was covalently attached to the plates at its 5' end. We believe this microplate may be acceptable as a platform for various mRNA expression analyses, including basic research, drug screening, and molecular toxicology, as well as for molecular pathological diagnostics.

Objective To examine the usefulness of serum immunosuppressive acidic protein (IAP) as a predictor for staging renal cell carcinoma (RCC), using receiver-operator characteristic (ROC) analysis, and to compare IAP with other tumour markers. Patients and methods From September 1983 to December 1995, serum IAP was measured in 133 untreated patients with RCC (mean age 60.1 years, sD 11.4, range 31-84). The erythrocyte sedimentation rate (ESR), the levels of fibrinogen, C-reactive protein (CRP), and α2-globulin were also measured. To compare these markers as predictors of local involvement of the renal capsule, lymph node and distant metastasis, the area under the corresponding ROC curve was calculated. Tumour size at the time of resection was added in this analysis for comparison with the levels of these tumour markers. Results The final pathological stage was T1 or T2 in 101 patients and T3 or T4 in 32, while it was NO in 122 patients, N1-3 in seven, M0 in 114 patients and M1 in 19. The area of the ROC curve for tumour size was greatest (0.843) for staging of the local extent (T1/T2 versus T3/T4) and that for IAP was 0.714, similar to the values for fibrinogen, ESR and CRP. For predicting lymph node metastasis, IAP and fibrinogen were the most important (0.864). However, IAP alone (0.894) was the most important predictor of distant metastasis. Using an IAP threshold of 600

Preoperative endocrine therapy has been suggested to improve surgical radicality and/or patient prognosis in prostate cancer.Patients with clinical stage A2, B, and C prostate cancer were randomized to either group I (n = 113) or group II (n = 111). Group I patients were to receive preoperative endocrine therapy consisting of leuprolide and chlormadinone for 3 months, followed by radical prostatectomy with lymph node dissection. Group II patients were to undergo the surgery before endocrine therapy.Group I patients showed a remarkable decrease in prostate-specific antigen (PSA) (mean +/- SE: 41.8 +/- 8.6 ng/mL to 2.7 +/- 0.7 ng/mL) and prostate volume (29.8 +/- 1.7 mL to 21.2 +/- 1.6 mL) during the preoperative therapy. Histopathologic analysis showed a significant difference in the rates of down-staging (19.1% in group I versus 3.3% in group II), positive surgical margins (63.8% versus 81.3%) and positive lymph node metastasis (20.7% versus 36.5%). No significant difference was detected in operating features. Subgroup analyses indicated that beneficial effects were correlated positively with degree of histologic differentiation and negatively with the basal PSA level.Preoperative endocrine therapy reduced local extension of prostate cancer, and the effects depended on histologic differentiation and PSA level. Long-term follow-up data are needed to determine the effects on the patient prognosis.

We report a case of transitional cell carcinoma arising in the fossa navicularis. The patient was a 74-year-old man. He had no history of sexually transmitted disease or urethral stricture. Clinically, the tumor was suspected to be a condyloma acuminatum; however, the pathological diagnosis yielded an unexpected result: transitional cell carcinoma. Radiological examinations and cystoscopy showed no other tumor besides the primary cancer in the fossa navicularis. Partial resection of the urethra was performed and the patient has been without evidence of disease for 3 years.

To investigate the efficacy and safety of bicalutamide (Casodex) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40), 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 mg group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.

A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.

In 1982, Kock and associates, reported their experi- ence based on extensive experimental data in 12 pa- tients in whom a detubularized ileal reservoir was constructed for continent urinary diversion utilizing a catheterizable This report has had a major impact on urinary diversion worldwide.' A number of modifications to Kock's original description have been made to reduce complications and the need for reoperation. Others have developed reservoirs from the right colon, sigmoid, and stomach."*' All have been developed in an effort to improve quality of life and a patient's acceptance of the need for cystectomy as primary treatment of bladder cancer. In the mid 1980s, based on the earlier work of Camey,13 several centers began clinical trials of lower urinary tract re- construction in men, utilizing an ileal reservoir with bilateral ureteroileal urethrostomy or various colonic This obviates the need for a stoma and the need for intermittent catheterization. Thus, they have become attractive alternatives for men.

The localization of 2 isoforms of glucose transporters (GLUT1 and GLUT4) in 75 patients with renal cell carcinoma was examined immunohistochemically. Paraffin sections were immunostained with either anti-GLUT1 or GLUT4 antibody by the avidin-biotin-peroxidase complex method. In 55 of 75 patients, GLUT1 staining was demonstrated at the plasma membrane of the cancer cells. In the clear cell subtype, 44 of 52 (84.6%) patients were positive for GLUT1. We did not detect positive staining for GLUT1 in the spindle cell type. In the mixed cell subtype, positive staining was recognized in only the areas of clear cell carcinomas (10 of 13; 76.9%). Positive staining for GLUT1 did not show any significant correlation with tumor grade or extent. Heterogeneous expression of GLUT1 was observed in tumor cell mass: some tumor cells were positive for GLUT1, while other cells were not. In adjacent normal tissue, GLUT1 staining was only recognized at the plasma membrane of some renal tubules. GLUT4 staining was not recognized in either tumor or normal tissues.

Intravesical instillation therapy of Bacillus Calmette-Guérin (BCG) has become a standard treatment for carcinoma in situ (CIS) of the urinary bladder. However, there have been few reports concerning the direct effect of BCG on existing tumors classified as Ta or T1. In the first stage of this clinical study, 157 patients were treated with BCG intravesical instillation (Tokyo 172 strain [BCG Co. Ltd., Tokyo, Japan]; 80 mg weekly for eight times) by our Study Group. The efficacy on existing tumors was a complete response (CR) rate of 84.4% and 66.4% and a partial response (PR) of 6.3% and 20.8% for 32 cases of CIS and 125 cases of Ta or T1 tumors, respectively.In the second stage of this study, the authors investigated the outcome of the 138 patients who had achieved CR or PR in the first stage. One hundred twenty (87.0%) of the patients were followed fully. Of those patients, 52 were randomized to receive prophylactic (maintenance) therapy consisting of BCG of 40 mg monthly for 12 times (Group A), whereas 55 were randomized to an untreated control group (Group B). Thirteen other patients refused to be randomized and were followed without prophylactic instillation.The median follow-up period was 48 months for Group A and 42 months for Group B. In Groups A and B, the beneficial effect of the BCG therapeutic instillation persisted for a long time, and the 3-year nonrecurrence rate was 77.6% in Group A and 74.2% in Group B. Disease progression was observed rarely.For patients in whom transurethral resection of tumors of the bladder (TUR-Bt) alone is unlikely to eliminate the tumor, intravesical BCG is potentially the treatment of choice.

A double-blind trial was conducted in 138 patients with superficial transitional cell carcinoma of the bladder following transurethral resection to evaluate the prophylaxis of recurrence by an oral Lactobacillus casei preparation (BLP). Patients were stratified into the following 3 subgroups: (A) with primary multiple tumors; (B) with recurrent single tumors, and (C) with recurrent multiple tumors. In each group, patients were randomly allocated to receive BLP or placebo. BLP showed a better prophylactic effect in subgroups A and B than placebo, whereas no significant difference was observed in subgroup C. Cox multivariate analysis showed that the outcome with BLP was significantly better than with placebo (p = 0.01). Slight and tolerable adverse reactions occurred in 3 patients receiving BLP and in 3 of the placebo-treated patients. Oral administration of BLP was thus safe and effective for preventing recurrence of superficial bladder cancer.

A chronological analysis of the clinical features and treatments of advanced prostatic cancer, stages C and D, was performed in 154 cases treated from 1976 through 1991. These cases were divided into two chronological groups: 61 cases treated between 1976 and 1983, and 93 cases between 1984 and 1991. Concerning demographic features and diagnosis, the number of patients with lymph node metastasis was higher in the latter group. There was also increase in cases who were urologically asymptomatic and detected by checkup digital rectal examination or by the elevation of serum prostatic tumor markers. Histopathological differentiation was consistent between the two groups; more than 70% of cancers were moderately and poorly differentiated adenocarcinoma. As for the treatment, total prostatectomy was performed in eight cases in the latter against none in the earlier, but hormonal therapy remained the main treatment throughout the periods: 74.2% in the earlier and 70.7% in the latter. However the methods of the therapy have clearly changed; estrogens and castration were used less often in the latter period, while LH-RH analogues and antiandrogens replaced them although the therapy was equally effective in 82.3% of the cases in the earlier and in 90.4% in the later period and five-year survival rate and the progression-free survival rate at three years showed no significant difference between the two periods. These results showed 1) refined quality of diagnosis 2) a change in mode of hormonal therapy and 3) no detectable improvement of survival in these 16 years. Development of more effective therapies would be warranted for a better survival.

In recent years renal cell carcinomas have been diagnosed as incidental findings. The tumors are usually associated with low stage and good prognosis. To find out if they might have a different malignant potential from suspected tumors, we retrospectively compared 56 cases of incidentally detected tumors with 84 cases of suspected tumors, with regard to tumor stage, nuclear grade, tumor size and DNA ploidy pattern as evaluated by flow cytometry. The incidentally detected tumors were lower in stage (P0.01), smaller in size (P0.01) and higher in probability of survival (P0.02) than the suspected tumors, as other studies have reported. Meanwhile, there was no difference in nuclear grade, DNA ploidy pattern and survival in stage I tumors between the two groups of renal cancers. The results suggest that the better prognosis in incidental renal cancer might be due to early detection rather than lower malignant potential of this specific type of renal cancer.

Age-related changes in the lower urinary tract function were investigated by means of symptomatology and urodynamics. In the symptom study subjectively normal 168 males and 101 females aged over 30 were administered a questionnaire regarding urinary symptoms. The prevalence of symptoms gradually advanced with age and nocturia more than 2 times was dramatically increased up to a half in those aged over 70. In the urodynamic study involving 65 males and 51 females with low symptom scores, significant reduction with advancing age was noted for maximum flow rate in both sexes (males: r = -0.295, p0.05, females: r = -0.591, p0.01) and maximum detrusor pressure in females (r = -0.513, p0.01). There was a significant increase in residual urine in males (r = 0.473, p0.05); otherwise no consistent changes in cystometry and urethral pressure profile related to aging were detected. These results indicate that urinary symptoms and urodynamic variables may change with age even in "normal" subjects, and warrant a careful interpretation of them in the elderly subjects.

An analysis has been undertaken to determine chronological changes that have occurred in the clinical features and treatments of advanced renal cell carcinomas. To accomplish this, 96 renal cell carcinoma cases, handled by the authors' department and at the branch hospital, were divided into two groups: 48 patients treated between 1975 and 1983 (group 1) and 48 patients treated between 1984 and 1991 (group 2). Between the two groups, no differences were seen in the sex ratio, the mean age, and the ratio of those who were found to be advanced cases at the time of diagnosis and those whose cancers had advanced after undergoing a nephrectomy. Concerning treatment, interferon (IFN) and UFT were more frequently used in treating group 2 than group 1, and chemotherapy, radiotherapy, and endocrine therapy less frequently used. No differences were seen in the prognosis between the two groups; however, in those who had advanced after nephrectomy, group 2 cases survived for a significantly longer period than did group 1 cases. Patients who survived for 5 years or longer accounted for two cases in group 1 and 5 cases in group 2 and combination therapies involving surgery, IFN, UFT, or similar medications were used for their treatments. These results suggest that adjuvant therapies, such as surgery, IFN, and UFT, have possibly contributed to prolonging survival, especially for cases that advanced after nephrectomy.

We have conducted a double-blind comparative study of flutamide and chlormadinone acetate (CMA) on patients with stage C or D prostatic cancer and with no prior experience of hormone therapy. This is believed to be the first such trial entered in the medical literature, fifty-four patients were randomly selected to undergo flutamide (p.o.) monotherapy at a daily dose of 375 mg, which was determined as the optimal dose in Japan in our previous phase II study. Forty-nine others were randomly selected to undergo CMA (p.o.) monotherapy at a daily dose of 100 mg, which is the most commonly used dosage in Japan for patients with prostatic cancer. Ultimately, 47 patients from the flutamide group and 40 patients from the CMA group were judged eligible, with efficacy being evaluated after 12 weeks of treatment. Similar objective responses were seen in both groups: 48.9% (95% confidence limits 34.1-63.9%) in the flutamide group, 45% (95% confidence limits 29.3-61.5%) in the CMA group. The response at each organ site was also similar between the groups. Serum prostatic specific antigen decreased by more than 50% of the abnormal pretreatment level in 87.5% of the flutamide group and in 85.7% of the CMA group. Serum luteinizing hormone, follicle-stimulating hormone, testosterone and 5 alpha-dihydrotestosterone decreased significantly in the CMA group, but increased significantly in the flutamide group. The serum testosterone level after 12 weeks of treatment was 0.955 +/- 0.13 ng/ml in the CMA group and 6.64 +/- 0.38 ng/ml in the flutamide group. The serum estradiol level also increased significantly in patients in the flutamide group. The serum prolactin level decreased significantly in the flutamide group, but increased significantly in the CMA group. Eight patients on flutamide manifested gynecomastia. Diarrhea and hepatic toxicity were observed in both groups, but only rarely, and were well tolerated. We have thus concluded that flutamide is as effective as CMA in maintaining libido and potency without decreasing testosterone levels.

The phase II study of flutamide, a pure anti-androgen, was performed to estimate the clinical doses on 165 hormone untreated or treated patients with prostatic cancer. The hormone-untreated patients were given orally flutamide of 90, 375, 750 or 1,125 mg/day in three divided doses daily for 12 weeks. Responses were not observed at the 90 mg/day dose except for improvement of clinical symptoms. However, an objective response rate of 48.8-46.7% was obtained at 375-1,125 mg/day doses. In hormone-treated patients including cases refractory to the previous hormonal treatment, the objective response rates were 13.3 and 8.3% in 375 and 750 mg/day flutamide groups, respectively. Side effects such as gynecomastia, nausea, vomiting, diarrhea, and abnormal laboratory findings such as the elevation of hepatic transaminases were observed. The incidence increased dose-dependently. Determinations of serum hormone levels revealed an increase in testosterone levels by the use of flutamide. In conclusion 375 mg/day of flutamide is the optimal dose in monotherapy for hormone-untreated patients with prostatic cancer, where the quality of life can be maintained compared with therapies involving testosterone suppression. This dose is also expected to show some efficacy in cases refractory to hormone treatment.

A phase I study of orally administered flutamide (a pure anti-androgen) was performed in 26 patients with prostatic cancer. No side effects were observed in 11 patients receiving single doses of either 125, 250, 375 or 500 mg. However, in the daily dosing schedule of 375, 750, 1125 and 1,500 mg/day doses, where medication was taken in three divided doses, discomfort in the stomach, nausea, vomiting and anorexia were experienced in one of the four patients receiving the highest dose of 1,500 mg. Nine patients receiving the other doses did not complain of toxic symptoms. Laboratory values did not change in the three patients receiving the lowest 375 mg/day dose, but elevation of transaminase was observed in five of the nine patients given higher doses. This elevation was observed in all the three patients receiving 1,500 mg/day dose. Among the serum hormone levels, significant increases of luteinizing hormone were observed. As for efficacy, objective responses were observed in two of the three patients in each of the four daily dosing groups. Improvement of pain, voiding obstruction symptoms, and performance status were also observed. Flutamide was found to be absorbed rapidly and to exist as a hydroxylated form (hydroxy-flutamide) in the plasma. The half-life of hydroxy-flutamide was similar in the single and daily administration, but the peak concentration and area under the concentration versus time curve in the daily administration became greater than those in the single administration. In conclusion, flutamide should be examined for efficacy and safety using doses of 375 to 1,125 mg/day in the phase II study.

The results of clinical use of an extracorporeal shock wave lithotripter (Biolithos MARK III) are presented. From May 1991 through February 1992, a total of 50 sessions were carried out on 33 patients with upper urinary tract stones. Treatments were performed on an outpatient basis, and none of the patients needed anesthesia or analgesia. One month after the last session, 18 patients (54.5%) were free from stone fragments and 6 (18.2%) had stone fragments equal to or smaller than 4 mm. The over-all successful rate obtained by these categories was 72.7%. After treatment no serious complications were observed. Although gross hematuria appeared in almost all patients, pain was noted in only 5 patients. Laboratory data after treatments showed slight and transient changes. It is concluded that Biolithos MARK III is useful and safe in the management of upper urinary tract stones on an outpatient basis.

Two cases of papillary ureteral end tumors, treated by transurethral resection are presented. Case 1: A 71-year-old female visited us for asymptomatic macroscopic hematuria. Cystoscopy revealed a papillary pedunculated tumor in the bladder protruding from the right ureteral orifice. Under a diagnosis of superficial tumor at the right ureteral end, transurethral resection was performed using a rigid ureteral resectoscope. Pathological examination revealed transitional cell carcinoma, grade 2 without muscular invasion. There is no evidence of recurrence after 25 months of follow up postoperatively. Case 2: On a routine cystoscopy after transurethral resection of bladder tumor in a 68-year-old male, papillary pedunculated tumors protruding from the right ureteral orifice were found. Under a diagnosis of superficial tumor at the right lower ureter, transurethral resection was performed using cold cup forceps and loop electrocoagulation. The tumor was transitional cell carcinoma, grade 1 without invasion. No evidence of recurrence was detected 15 months postoperatively. Transurethral resection of the ureteral tumor at the lower end appeared to be useful for the selected cases. The indications, complications and follow up for this procedure were discussed.

The results of long-term administration of leuprorelin acetate depot (TAP-144-SR), a sustained-release preparation of luteinising hormone-releasing hormone (LH-RH) agonist, to 40 stage D prostate cancer patients who had had no previous hormonal therapy, have been analyzed. The drug was administered by subcutaneous injection once every four weeks at a dose of 3.75 or 7.5 mg. The mean duration of treatment was 480 (141-1,266) days, and treatment continued for more than one year for 60% of the 40 patients. Objective response was evaluated in accordance with Japanese Response Criteria. The best objective response in the overall evaluation was a partial response in 68.6% of the total patient group (3.75 mg, 64.3%; 7.5 mg, 71.4%). During the administration period, 21 patients were diagnosed as having progressive disease (PD), and the mean time to onset of PD was 308 days. The earliest diagnoses of PD were made on bone metastases (17 cases) and prostatic acid phosphatase levels (12 cases). The survival rate, as determined by Kaplan-Meier's method, was 81.2% (3.75 mg, 80.5%; 7.5 mg, 81.3%) two years after starting the regimen and 66.0% (3.75 mg, 65.1%; 7.5 mg, 66.0%) after three years. There was no dose dependency between either of the two drug doses, which we adopted as functions of the objective response rate, and patients' survival. Serum levels of testosterone, LH and follicle-stimulating hormone (FSH) were monitored from the first-dose until the 148th week of administration. In all patients receiving the drug as scheduled, the testosterone level was maintained at less than 1 ng/ml, and the LH and FSH levels were maintained at levels lower than their respective upper normal limits. There were no particular adverse reactions specific to the long-term administration subsequent to the foregoing 12-week administration study. In conclusion, LH-RH analogue treatment is thought to be a long-lasting, effective, palliative measure for patients with previously-untreated, advanced, prostatic cancer.

We evaluated the efficacy and safety of recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with leukopenia after chemotherapy for urogenital cancers. Recombinant human G-CSF was administered at 100 micrograms./m.2 intravenously in 36 patients and at 75 micrograms. per body weight subcutaneously in 37 for 8 days after methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) therapy or for 14 days after other chemotherapies. Cycle 1 of chemotherapy was given without recombinant human G-CSF, while at cycle 2, recombinant human G-CSF was given additionally. Therefore, cycle 1 of the regimen served as a control to cycle 2 in each patient. An elevation in the median white blood cell nadir was noted: 1,500 versus 3,200 (intravenous) and 2,100 versus 3,200 (subcutaneous) on M-VAC therapy, and 1,800 versus 2,100 (intravenous) and 1,700 versus 2,500 (subcutaneous) on other chemotherapeutic regimens. A shortening of the leukopenic period was observed in cycle 2. There were no significant adverse side effects attributed to the use of recombinant human G-CSF. The results indicate that recombinant human G-CSF may be safely and effectively used against leukopenia after chemotherapy for urogenital cancer. This remedy will become useful for completion of the schedule and dose intensification of chemotherapy in the future. Subcutaneous administration is considered to be the more preferable route.

Laparoscopic nephrectomy was carried out on 6 sows in order to develop the procedures of clinical laparoscopic nephrectomy and the equipment necessary for this operation. Based on the animal experiments, it was shown that (1) retroperitoneal approach was difficult due to narrow space. (2) there must be at least 5 cm distance between each trocar and 4 or 5 trocar 1 cm in diameter were basically required. (3) The procedure consisted of incision and dissection of the peritoneum around the kidney, cutting and ligation of the ureter, dissection along the medial side of the ureter to approach the renal pedicle and clipping and cutting of the renal vessels. (4) The equipment required for this surgery must be functionally equivalent to those used in the open surgery. (5) In addition, the specifically designed equipment, such as a morcellator and an instrument to ligate renal vessels are necessary. The first clinical case of laparoscopic nephrectomy was a 34 years old man with a right non-functioning hydronephrosis due to ureteropelvic junction stricture. The surgery was successfully performed with a 110 ml blood loss. It took 7 and half hours because of abundant peri-renal fatty tissue and large extra-renal pelvis. The convalescence was uneventful. Laparoscopic nephrectomy can be applied on selected cases and the development of equipment will make the surgery more popular.

We investigated the effects of intravesical instillation of BCG Tokyo 172 strain on patients with superficial bladder cancer and CIS of the bladder for tumor ablation and prophylaxis. This is the first controlled multicenter study for governmental approval of BCG Tokyo 172 strain for the treatment of superficial bladder cancer and CIS of the bladder. One hundred-fifty-seven patients (125 with Ta or T1, and 32 with CIS) were treated by 80 mg of BCG diluted in 40 ml of saline, once a week for 8 weeks. The dose and interval adopted in this multicenter study was determined by the previous Phase II study conducted by the same Study Group. Out of 125 superficial tumor Ta, T1, 83 (66.4%) showed complete disappearance of the tumor (CR) and 26 (20.8%) partial disappearance (PR), and out of 32 CIS, 27 (84.4%) showed CR and 2 (6.3%) PR. Among those patients showing CR, and PR who were treated with additional TUR-Bt, 98 patients were randomised for a controlled study of prophylactic BCG instillation. Prophylactic treatment consisted of 40 mg of BCG diluted in 40 ml of saline, monthly for 12 months. Forty-two patients were assigned to the treatment group, whereas the remaining 56 to the control group without any prophylactic instillation. Three cases showed tumor recurrence during the prophylactic phase. Twenty-five cases could not be treated for the whole course of prophylactic instillation mainly due to bladder irritable symptoms. Recurrent free curves were compared till 1050 days after the initiation of the study. However, there was no significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized controlled study was conducted in patients with superficial bladder cancer in order to investigate the safety of an orally administered (3 g/day) Lactobacillus preparation, biolactis powder (BLP), and its preventive effect on the recurrence after transurethral resection of the bladder tumor (TUR-Bt). Of 58 cases enrolled in the study 23 cases in the BLP group and 25 cases in the control group completed the study. There were no significant differences in the patient characteristics for the complete cases between the two groups. Comparison of the disease-free duration by the Kaplan-Meier method revealed that the 50% recurrence-free interval after TUR-Bt was prolonged by BLP treatment (350 days) to 1.8 times that in the control group (195 days). A significant difference between the groups was detected by the long-rank test (p = 0.03). No adverse side effect was observed. The results suggest that oral administration of BLP is useful for the prevention of the recurrence of superficial bladder cancer.

A multicenter cooperative study was conducted to evaluate the clinical efficacy and safety of cis-diammine(glycolato)platinum (254-S), a second-generation anticancer platinum complex, in the treatment of genitourinary cancers. 254-S was given i.v. at 100 mg/m2 at 4-week intervals. As a result, 2 complete responses (CRs) and 8 partial responses (PRs) were obtained in 35 patients with transitional-cell carcinoma (TCC) of the urinary bladder or pyeloureter, 3 PRs were obtained in 16 subjects with prostatic cancer, and 6 CRs and 6 PRs were obtained in 15 patients with testicular cancer, generating objective response rates of 28.6% [95% confidence interval (CI), 14.6%-46.3%], 18.8% (95% CI, 4.0%-45.6%), and 80.0% (95% CI, 51.9%-95.7%), respectively. Bone marrow suppression was the dose-limiting toxicity, although it was reversible. Although no hydration was performed in approx. 40% of the patients, the incidence of nephrotoxic effects was low and most of those encountered were mild, the exception being one patient who showed severe renal insufficiency after the first treatment. Nausea and vomiting occurred in approx. 70% of the patients, but most gastrointestinal toxicities were controlled without antiemetic treatment. In addition, liver-function impairment was rarely observed. We conclude that 254-S is a promising cisplatin analogue for the treatment of genitourinary cancers and is worthy of further investigation in large-scale, randomized comparative studies with other platinum derivatives in both single-agent and combination regimens.

The expert committees, which met in Paris in June 1991 under the patronage of WHO to establish a consensus concerning BPH, adopted the recommendations summarised in this report. Despite certain criticisms which can be made, these recommendations offer the advantage of simplicity and uniformity, thereby constituting a "universal language". This will facilitate comparison of patients and therapeutic results, both in everyday practice and in the course of clinical trials. These recommendations will be periodically re-evaluated in the light of clinical experience and technological progress.

196 cases with vesicoureteral reflux (VUR) from multiple centers were analysed to examine the relationship between VUR and reflux nephropathy. The high correlation (p less than 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 even when reflux did not become worse, which is probably accounted for by the presence of pyelonephritis. Although frequency of pyelonephritis decreased significantly (p less than 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.