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A new modality is necessary to prevent recurrence of superficial bladder cancer after complete transurethral resection (TUR) because of the high recurrence rate even with current prophylaxis protocols. Prostaglandins (PGs) are known to be produced more in transitional cell carcinoma, and etiologically bladder cancer risk is negatively associated with the intake of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase (COX), the rate-limiting enzyme of the PG production. We have shown the chemopreventive effect of piroxicam, an NSAID, on the N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced rat bladder cancer model. To avoid gastrointestinal side effects of regular NSAIDs, we also showed the chemopreventive effect of nimesulide, a selective inhibitor of the second isoform of COX, COX-2, which does not affect COX-l house-keeping activity in gastrointestinal mucosa on the same model. We also observed induction of COX-2 protein in the rat bladder tumor. In this study, we screened COX-2 protein expression in primary superficial bladder cancer tissues, to elucidate if COX-2 selective inhibitors can be a candidate chemopreventive agent for bladder cancer recurrence. Five and 6 samples of superficial bladder cancer cases with and without recurrence after complete TUR were examined by immunohistochemical analysis. We found more COX-2 protein positive samples in the cases with recurrence than in cases without recurrence. Even though the number of cases examined is small, this result supports our hypothesis that COX-2 contributes to superficial bladder cancer recurrence, thus, selective COX-2 inhibitors can be a candidate chemopreventive agent for the recurrence.

Our previous study demonstrated the clear detection of MN/CA9 mRNA in peripheral blood samples from RCC patients. However, approximately 30 % of control blood samples from healthy volunteers showed MN/CA9 expression. We have developed a new primer set and optimized the PCR conditions, now resulting in a specificity of 100 %. In tissue samples, all clear cell type carcinomas but none of the spindle cell type and pleomorphic cell type tumors expressed the MN/CA9 message. Analysis of MN/CA9 messages in peripheral blood samples from RCC patients gave positive results for 0/2, 1/9, 0/4 and 4/12 of stage I, II, III and IV cases, respectively. RT-PCR analysis using preoperative renal venous blood samples resulted in clear detection of MN/CA9 positive cells in 2/4, 3/13, 2/6 and 1/1 of stage I, II, III and IV cases, respectively. Our results suggest that assessment of MN/CA9 expression by RT-PCR is a promising method for detecting cancer cells in the circulation of patients with RCC.

To compare the efficacy and safety of an incremental-dose regimen of terazosin (1-2 mg daily) and a fixed-dose regimen of tamsulosin (0.2 mg daily), on Japanese patients with symptomatic benign prostatic hyperplasia (BPH).This multicentre, single-blind, randomized trial compared terazosin and tamsulosin over 4 weeks, in 61 patients with symptomatic BPH randomly assigned to terazosin (n = 31) or tamsulosin (n = 30). Terazosin 0.5 mg twice daily was administered for 2 weeks, followed by 1 mg twice daily for 2 weeks. Tamsulosin (0.2 mg) was administered once daily for 4 weeks. Symptoms were evaluated using the International Prostate Symptom Score (IPSS), and quality of life (QOL) was assessed subjectively before treatment, and again after 2 and 4 weeks of treatment. Objective measurements taken before and after the treatment period were the maximum (Qmax) and average (Qave) urinary flow rates, and the percentage residual urine volume. Improvement was defined as a 25% decrease from baseline in IPSS,1 point increase in QOL score, and2.5 mL/s increase in Qmax. Adverse reactions potentially related to the study drugs were recorded throughout the treatment period.Both terazosin and tamsulosin produced statistically significant improvements in subjective and objective variables. Neither treatment affected systolic or diastolic blood pressure or pulse rate. Adverse reactions were noted in four patients (three in the terazosin group and one in the tamsulosin group). However, there was no statistically significant difference in the incidence of adverse effects between the groups.Despite the limitations of small sample size and relatively short treatment periods, terazosin and tamsulosin were equally effective in the treatment of symptomatic BPH in Japanese patients, using relatively lower doses than those used in Western countries.

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 present investigation was conducted to examine the effects of intra-arterial chemotherapy (IAC) for patients with invasive bladder cancer. A total of 37 patients were treated with IAC at Nara Medical University and its affiliated hospitals between January, 1993 and August, 1997. There were 27 patients in the poor risk group. The remaining 10 patients underwent anti-tumor IAC. Thirty of the 37 patients received chemotherapeutic agents via a reservoir, and the remaining 7 patients received a one-shot injection of agents followed by transcatheter arterial embolization (TAE). In the reservoir group, there were 18 patients who received IAC in combination with radiation therapy. As a result, reduction of tumor size was noted in 53%, and the 3-year cause-specific survival rate was 54% in all cases. There was a significant difference in the 3-year survival rate between the radiation-treated group and the group without radiation. The adverse events included anemia, leukopenia, thrombocytopenia and gastrointestinal symptoms, but none of them were severe. The results of the present study indicate that IAC is useful in the treatment of invasive bladder cancer for poor risk patients.

The E-cadherin–catenin complex plays an important role in establishing and maintaining intercellular connections and morphogenesis and reduced expression of its constituent molecules is associated with invasion and metastasis. In the present study, we examined E-cadherin and α-, β- and γ-catenin levels in tumour tissues obtained by radical prostatectomy in order to investigate the relationship with histopathological tumour invasion. Immunohistochemical findings for 45 prostate cancer specimens demonstrated aberrant expression of each molecule to be associated with dedifferentiation and, in addition, alteration of staining patterns for the three types of catenin was significantly correlated with capsular but not lymphatic or vascular invasion. The data thus suggest that three types of catenin may be useful predictive markers for biological aggressiveness of prostate cancer. © 1999 Cancer Research Campaign

A 7-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with superficial bladder carcinoma. Epirubicin-RTU at the dose of 60 mg/30 ml was administered by intravesical instillation once daily for three (3) consecutive days and a 4-day drug-free interval followed; then the above intravesical instillation of Epirubicin-RTU was repeated for three consecutive days. All 20 registered cases were eligible, and 18 cases completed the whole course of the study. In 18 completers, CR was observed in 12 cases and PR was observed in one (1) case, for an efficacy rate of 72.2%. The primary adverse reaction was bladder irritation including pollakiuria 85.0% (17/20), miction pain 85.0% (17/20), and hematuria 80.0% (16/20), which were all reversible and tolerable. In urinalysis, urinary sediment showed leukocytes and erythrocytes, and proteinuria was observed. All were reversible. From the above results, this new formulation of Epirubicin-RTU was considered useful for the treatment of superficial bladder carcinoma.

The objective of this report is to evaluate the upper urinary tract changes of the patients with spina bifida who have been followed up for more than 10 years.We analyzed 228 patients (97 males and 131 females) of spina bifida. Mean patient age was 18.7 years (10 to 51 years) and follow up period ranged from 10 to 27 years (mean 13.4 years). Upper urinary tract deterioration (Hydroureter and/or hydronephrosis), vesicoureteral reflux (VUR) and bladder deformity were investigated by excretory urography and voiding cystourethrography. We compared these 3 parameters in the initial and final examinations.In the initial examinations, upper urinary tract deterioration, VUR and bladder deformity were observed in 32.9%, 33.3% and 40.0%, respectively. During the follow up period, upper urinary tract was improved in 47.3% and VUR in 80.0%. Bladder deformity was disappeared in 14.4%. On the other hand, upper urinary tract was deteriorated in 9.3%. VUR and bladder deformity was newly developed or progressed in 8.0% and 29.3%, respectively. Finally, upper urinary tract deterioration, VUR and bladder deformity were observed in 31.3%, 18.2% and 52.0%, respectively.These results revealed that upper urinary tract and VUR were relatively controlled, however, bladder deformity was increased in its frequency. To prevent upper urinary tract deterioration, further analysis of sequential changes of urinary tract conditions should be demanded.

To evaluate the usefulness of total androgen blockade (TAB) therapy, we retrospectively studied 45 patients with prostate cancer who received TAB therapy as the first-line treatment. The clinical stage was A2 in 1 patient, B1 in 10, B2 in 9, C in 6, D1 in 3 and D2 in 16. Seven, 25 and 13 patients had well, moderately and poorly differentiated adenocarcinomas, respectively. The patients were placed on 1 of 3 TAB regimens: Luteinizing hormone-releasing hormone (LH-RH) agonist and flutamide (group 1), LH-RH agonist and chlormadinone acetate (group 2) and a surgical castration and flutamide (or chlormadinone acetate) (group 3). The therapeutic effect was evaluated at 12 weeks according to the response criteria in the general rules for clinical and pathological studies on prostatic cancer. The overall response was partial response (PR) in 35 patients (77.8%), no change (NC) in 6 (13.3%) and progressive disease (PD) in 4 (8.9%). PR was obtained in 81.3, 79.2 and 60% of the patients in groups 1, 2 and 3, respectively. One patient with PD responded briefly to flutamide withdrawal. None of the patients developed any severe adverse effects. In conclusion, the first-line TAB therapy is effective for prostate cancer with a lower risk than estrogens. Relapsed cases should be followed for flutamide withdrawal syndrome during TAB therapy.

The present investigation was conducted to examine the effects of granisetron alone and a combination of granisetron plus steroids on CDDP-based combination chemotherapy-induced emesis by multi-institutional randomized comparative trial using a central registration method. A total of 62 patients with urological cancer enrolled this study were randomized into two groups: granisetron (40 micrograms/kg) only group and granisetron (40 micrograms/kg) plus steroids (500 mg of methylprednisolone or 8 mg of dexamethasone) group. There were 31 patients eligible in the granisetron only group and 28 in the combination group. The same anti-emetic treatments were given in the recycling courses of chemotherapeutic regimens. Therefore, eligible patients of the second and the third cycle numbered 31 (17 in the granisetron only group, 14 in the combination group) and 21 (11 in the granisetron only group and 10 in the combination group). Significant inhibition of acute emesis in combination group was observed when compared with the granisetron only group in each cycle. Delayed emesis was also significantly inhibited in the combination group on Day 2 and 3 of the first cycle and on Day 2 of the second and third cycle. In addition, appetite loss was significantly reduced in the combination group on Day 2 and 3 of the first and second cycle. No adverse events were seen in either group. These results suggested that a combination of granisetron and steroids was useful for preventing CDDP-based combination chemotherapy-induced emesis.

Since April 1986, a prospective clinical trial for testicular cancer has been underway by our Nara Uro-Oncology Research Group. One hundred and forty-eight cases of germ cell tumor were entered into this study between April, 1986 and August, 1995. They included 99 cases (66.9%) of seminoma and 49 cases (33.1%) of non-seminomatous germ cell tumor (NSGCT). The mean age of seminoma cases (39.7 yrs) was higher than that (30.2 yrs) of NSGCT cases. One hundred and twenty-three cases were treated according to our protocol. In the treatment group, one patient with stage I seminoma died of other diseases and one patient each with stage II and stage III seminoma died of cancer. Three patients with stage III NSGCT died of cancer. The 5-year survival rate was 100% for stage I seminoma, and stage I and stage II NSGCT, 75.0% for stage II seminoma, 0% for stage III seminoma and 66.7% for stage III NSGCT. These findings suggest that new treatment modalities should be introduced into our protocol in the future.

The number of cases of prostate carcinoma (PCA) is steadily inceasing in Japan. The clinical application of a reliable tumor marker, prostate specific antigen (PSA) for the diagnosis, as well as the increasing elderly population in Japan may account for this increase. The subjects were patients at the Nara Medical University and its affiliated hospitals; 1) 687 cases without PCA were evaluated for age-specific PSA and the incidence of abnormal PSA following urological manipulations, 2) 135 cases with histological proven BPH by transurethral resection of prostate (TUR-P) were examined for PSA density (PSAD) and positive PSA rate in BPH, 3) 135 cases receiving a needle biopsy with suspicion of PCA were examined for the efficacy of PSA and PSAD and other parameters, and 4) 459 PCA cases treated between 1988 and 1994, were examined for specific PSA and PSAD values by stage and degree of cell differentiation. The PSA assay used in this study was MARKIT-M PA (normal rangeor = 3.6 ng/ml). The PSA was decreased gradually with age in non-PCA patients, and abnormal PSA was found in 5.5% of these patients following manipulations. The average PSA was 2.95 +/- 2.03 ng/ml in 130 BPH patients (mean age: 71.1 +/- 7.0 years old. and average prostate volume: 32.9 +/- 16.1 ml). And abnormal PSA level (more than 3.61 ng/ml) was found in 22.3%. The mean PSAD was 0.1.0 +/- 0.06, and PSAD was below 0.15 in 86.1% of these BPH cases. Among the 135 cases receiving a needle biopsy, 33 cases had PSA values between 3.61 and 10.0 ng/ml. Of these cases, PCA was found in 18.5% of the 27 cases with a PSAD below 1.5, and in 33.3% of the 6 cases with a PSAD over 1.5. PSA and PSAD were proportionally increased with stage, and a significant difference in the PSA value was observed between stage B1 and B2, and stage C and D (P0.05). However, PSA and PSAD values were not significantly correlated with the cell differentiation in PCA stage A2-C. In total, PSA was 18.1 ng/ml in well, 23.9 ng/ml in moderately and 35.9 ng/ml in poorly differentiated type PCA. The positive rate of PSA was 22.3, 65.4 and 83.5%, that of prostate acid phosphatase (PAP) was 10.0, 17.8 and 45.8%, and that of GSM was 25.0, 14.7 and 68.4%, in BPH, stage A PCA and stage BPCA, respectively. In conclusion, PSA is the most reliable tool in the diagnosis of localized PCA. However, the differential diagnosis of BPH and localized PCA is difficult when the PSA value is between 3.61 and 10.0 ng/ml, and accurate staging of localized PCA is difficult with PSA or PSAD alone. At present, it is necessary to use all possible tools for the early detection of localized PCA, and to perform the needle biopsy in all PCA-suspicious cases.

Screening was performed on 102 patients aged 60 years or older who visited the Outpatient Department of Internal Medicine in Tane General Hospital between June 1994 and May 1995. Of those screened, 36 patients (35.3%) had elevated prostate specific antigen (PSA) values, and 20 of them visited the Urological Department, and underwent digital rectal examination (DRE) and transrectal ultrasonography (TRUS) for further screening. Of the 16 patients who underwent ultrasound guided biopsies of the prostate, 7 patients were found to have prostate cancer. Therefore, the cancer detection rate was 6.9%, which was about 4 times higher than that of mass-screening examinations previously reported in the Japanese literature. These findings suggested that the screening using PSA in outpatients of Internal Medicine may be useful for the early detection of prostate cancer.

The concentrations of pyridinoline (Pyr), a novel marker of bone resorption, were simultaneously measured in both serum and urine samples by ion-paired high-performance liquid chromatography in 27 patients with predialysis chronic renal failure. The patients consisted of 19 males and 8 females, whose creatinine clearance (Ccr) ranged from 2.5 to 47.6 ml/min. The influence of residual renal function on serum Pyr and the clinical significance of serum and urinary Pyr were analyzed in patients with predialysis chronic renal failure. There were significant correlations between serum Pyr and serum Cr (r = 0.76) and between Pyr clearance and Ccr (r = 0.70). In addition, significant correlations were observed serum and urinary Pyr (r = 0.64) and between both serum and urinary Pyr and HS-PTH (r = 0.96 and r = 0.61, respectively) and osteocalcin (r = 0.80 and r = 0.73, respectively). However, serum bone alkaline phosphatase isoenzyme (ALP3) was correlated with neither serum nor urinary Pyr. There was no correlation between the ratio of serum Pyr/serum Cr and the metabolic bone markers (HS-PTH, osteocalcin and ALP3). There was a correlation between Ccr and urinary Pyr, although it was statistically significant (p0.1). These date led to the following conclusions: (1) serum Pyr in patients with oredialysis chronic renal failure is influenced by reduced renal function and (2) urinary pyr shows a state of bone resorption when an adegvafe level of renal function is maintained. This suggests that patients with an advanced stage of renal osteodystrophy are included among cases of predialysis chronic renal failure.

Recently, it has been noted that radical molecules participate in the pathogenesis of some of the complications associated with long-term dialysis therapy, such as amyloidosis. Since allantoin is produced from uric acid almost exclusively by the hydroxy radical, we investigated the plasma concentrations of allantoin in 71 patients with chronic renal failure who were on maintenance hemodialysis. Our specific objective was to investigate the relation of allantoin to the plasma concentrations of beta2-microglobulin and methylguanidine to evaluate the potential of allantoin as a significant parameter of the radical reaction. Although plasma allantoin was not detected in 15 healthy controls, plasma concentrations of allantoin increased markedly in all of the hemodialysis patients (42.6 +/- 37.7 nmol/mL) and wide variation was observed from 4.3 to 185.2 nmol/mL. In addition, we confirmed significant correlations between plasma concentrations of allantoin and beta2-microglobulin as well as serum concentrations of methylguanidine/creatinine and hyaluronic acid (r - 0.456, p0.0005, r = 0.313, p0.005, r = 0.368, p0.01, respectively). Although evidence for a direct link between plasma allantoin levels and amyloidosis was not obtained, the increase in the plasma concentrations of allantoin suggested its clinical significance as a parameter of the radical reaction that is thought to participate closely in the pathogenesis of dialysis-related amyloidosis. From a practical point of view, the measurement of plasma allantoin can be expected to become a significant method of measuring radical members which may be useful in the prophylaxis of some of the complications induced by free radicals.

Androgen ablative treatments for advanced prostatic cancer have achieved great progress with new concepts of therapy in the last decade such as chemical castration with LH-RH analogue and total androgen ablation. However, in treatment for hormone-refractory or relapsing prostatic cancer it remains controversial whether cytotoxic chemotherapy is acceptable or palliative, and whether there is an alternative treatment for this incurable disease. The current status of cytotoxic chemotherapy for advanced prostatic cancer patients in Nara Medical University since 1980 is reported in this paper with the some review of recent advances in hormone-independent prostatic cancer treatment. The overall objective response rate of CDDP-based multi-drug regimens including CDDP monotherapy was 49.6% (CR 0% + PR 49.6%). Response rate of primary chemotherapy group constituted with untreated patient was 67.2%, against 23.9% in the hormone refractory or relapse group. Five-year survival rate was 61.1% in the primary chemotherapy group, 35.5% in the hormone refractory group and 40.6% in the relapse group. Basically, there was no significant difference in response rates and survival rates among the groups of CDDP monotherapy, CDDP+bleomycin+vinblastine, CDDP+cyclophosphamide+adriamycin or CDDP+etoposide. The different response rates among the regimens seemed mainly to depend on the population of refractory or relapsing cases in each group. The important problems remaining unsolved in the research of chemotherapy for prostatic cancer are that there is no effective breakthrough agent and the lack of the harmonization in response criteria. The new agents are under development based on the cellular biology of hormone-refractory prostatic cancer, and there is a bright future in the treatment of this intractable disease.

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.

A series of 180 patients treated with ileal conduit urinary diversion at Nara Medical University and its affiliated hospitals were reviewed. The patients ages at the time of operation ranged from 21 to 79 years old with an average of 60.9 years old and the average postoperative follow-up period was 44.2 months. Early complications occurred in 60 patients (33.3%) and 9 (5.0%) of them resulted in post-operative deaths. Late complications were noticed in 54 (31.6%) of the 171 patients. Frequent late complications included peristomal dermatitis (37.3%), ureteroileal stenosis (17.9%) and urolithiasis (11.9%), for the latter two of which endourological treatments seemed to be effective. To be emphasized is that more attentive care should be paid to the condition of the peristomal skin during follow-up.

Serum concentration of the pyridinium cross-links, pyridinoline (Pyr) and deoxypyridinoline (Dpyr), which are markers of bone resorption, was measured by high-performance liquid chromatography in 56 patients on maintenance hemodialysis. The following analyses were conducted: 1) correlation with known markers of bone metabolism, 2) correlation with findings on bone changes on plain X-ray film, 3) elimination rates by hemodialysis, and 4) increment per day in pyridinoline after hemodialysis (delta Pyr/day). There was a very close correlation found between serum Pyr and Dpyr (r = 0.861). Both serum Pyr and Dpyr showed correlations with known markers of bone metabolism: C-PTH (r = 0.806 and r = 0.747, respectively), M-PTH (r = 0.766 and r = 0.749), osteocalcin (r = 0.717 and r = 0.693), Alp-3 (r = 0.523 and r = 0.441) and tartrateresistant acid phosphatase (r = 0.549 and r = 0.548). In addition, a correlation between the duration of hemodialysis and serum Pyr and Dpyr was observed (r = 0.426 and r = 0.318, respectively). When comparing the mean values of serum Pyr or Dpyr in three groups of patients divided according to bone changes seen on plain X-ray film, there were statistically significant differences between the group without bone changes and the remaining two groups with some bone changes (p0.05). A mean of 45.3% of serum Pyr was removed by hemodialysis. The serum Pyr level returned almost to the original concentration by the following hemodialysis. delta Pyr/day showed a close correlation with C-PTH (r = 0.656).(ABSTRACT TRUNCATED AT 250 WORDS)

Between October 1990 and June 1993, 112 patients underwent fine needle aspiration cytology and core needle biopsy of the prostate under transrectal ultrasonographic guidance. They were suspected of having prostatic cancer from the prostatic antigen level, digital rectal examination and/or transrectal ultrasonography. Twenty seven of the 112 cases (24%) were diagnosed with prostatic cancer. Their cytological diagnoses showed 22 class IV or V, 2 class III, and 3 class I or II. Efficiency, false negative rate and false positive rate were 86%, 11% and 0% in fine needle aspiration cytology. We could obtain sufficient samples for fine needle aspiration cytology in all cases. No severe complication was observed. However, we missed 3 patients, in fine needle aspiration cytology, who were strongly suspected of having prostatic cancer, and reexamination or additional core needle biopsy would have been necessary on 15 of the 112 patients (13%) who showed false negative or class III cytological results, if we had screened prostatic cancer only by fine needle aspiration cytology. In conclusion, fine needle aspiration cytology may not be as useful as core needle biopsy to screen prostatic cancer.

A total of 70 patients with renal trauma were treated at the Department of Urology, Nara Medical University and Nara Prefectural Hospital, including Life-Saving Emergency center, from January 1982 to June 1993. They were between 3 and 79 years old (mean 30.0) and preponded to the younger generation. The main cause of injury was traffic accident in 46 cases (65.7%). According to the Classification of Renal Injury by the Japanese Association for the Surgery of Trauma in Japan, there were 31 cases (44.3%) of type I (subcapsular injury), 18 cases (25.7%) of type II (superficial injury), 15 cases (21.4%) of type III (deep injury), and 6 cases (8.6%) of type IV (pedicle injury). Surgical treatment was performed in 17 cases (24.2%). The major associated injuries were bone fracture in 32 cases (45.7%), lung injury in 17 cases (24.2%), and liver injury in 15 cases (21.4%). Furthermore, hydronephrosis and ureteral tumors were incidentally found in 4 and 1 patient during the course of treatment for renal trauma. Post-traumatic plasma renin activities (PRA) in types III and IV were significantly higher than those in types I and II. Hypertension developed in 1 case of types I and II and 4 cases of types III and IV. The mean level of PRA was significantly decreased 2 years after renal injury in both groups. We should bear in mind that renal trauma may be associated with other urological diseases such as hydronephrosis and urological malignancies, and post-traumatic PRA should be followed carefully.

The current status of treatments for advanced transitional cell carcinoma of the urinary tract with metastasis is reported. A total of 62 patients were treated in Nara Medical University Hospital and its affiliated hospitals between January, 1980 and June, 1993. All patients were divided into two categories; cases in which local recurrence and/or distant metastasis had developed during the followup study (group 1) (n = 32) and fresh cases with distant metastasis (group 2) (n = 30). Most of the metastatic sites were treated with chemotherapy alone or combination therapy including chemotherapy. As for clinical response of each case, CR + PR rate in group 1 (34%) was higher than that in group 2 (13%) (p0.1). As for prognosis, the survival rate in group 1 was significantly higher than that in group 2 (p0.05). In group 1, the survival of CR was significantly higher than that of the non-responders. No adjuvant therapy for invasive bladder cancer and post-operative adjuvant therapy for renal pelvic and/or ureteral cancer can be recommended to prevent local recurrence or distant metastasis. In addition, supporting therapy and dose intensified chemotherapy would lead to good prognosis in advanced urothelial cancer patients.

Ultrasound-guided percutaneous puncture of renal cysts replaced by CO2 was performed on 9 renal cysts of 6 patients from May 1993 through September 1993. Puncture and aspiration of cysts was performed using a 5.5 Fr one-step fluid drain kit (pig tail stent) under ultrasonography inspection. Aspirated volume of cyst contents was 15-292ml (mean 115 ml), and the instilled CO2 volume was 15-150 ml (mean 73 ml). All patients were checked by CT scan. In one month, the reduction rate of cyst volume was 46-84% (mean 69%) and lumbago, their chief complaint, was improved in all patients. No complications were observed in patients treated by CO2 instillation. Although long-term followup is needed to draw a definite conclusion, this therapy may be useful for benign renal cystic lesions.

The preliminary results of a multi-institutional prospective randomized study of the prophylaxis of superficial bladder cancer using epirubicin (protocol NUORG SBT-003) are reported. The subjects were 129 patients with untreated superficial bladder cancer (or = T1b,or = G2) who were randomized into 2 groups: a transurethral resection (TUR)-alone group (63 patients) and a TUR + intravesical epirubicin (20 mg/40 ml, 30 times/2 years) group (66 patients). The nonrecurrence rate observed in the epirubicin group was significantly higher than that seen in the control group. To unify the pathological diagnosis, a central pathology laboratory (CPL) was set up for extramural review. The correspondence of the pathological diagnosis of TUR-Bt specimens between the CPL and the local pathology laboratory (LPL) was 70.5% in grading and 51.9% in staging. There was a tendency for overdiagnosis by the LPL for both the grade and the stage of tumors. However, differing interpretations by pathologists seem to exert little influence on the nonrecurrence rate at interim analysis. Further observation will be necessary to clarify the prophylactic efficacy of low-dose, long-term periodic intravesical epirubicin instillation and the influence of the disagreement in pathological findings between the CPL and the LPL on the analysis of the results.

Current studies have reported that free radical molecules had anticipated intimately with the pathogenesis of some complications specific for a long term hemodialysis. Among substances generated by free radical reaction, methylguanidine (MG) had been well known as most popular parameter in hemodialyzed patient, but allantoin (Alt) had been reported to be generated from uric acid by hydroxyradical, too. In this study, we measured serum level of Alt in long term hemodialyzed patient and analysed in the comparison with serum level of sialic acid, MG, and MG/Cr value. Serum level of Alt in patients group varied from 2.6 to 105.9 nmol/ml, which was significantly higher as compared with exclusively undetectable level in normal volunteers (n = 15). Serum level of Alt in each patient showed a significant correlation with serum level of a sialic acid (r = 0.400 p0.02). Furthermore, although serum level of Alt failed to show a significant correlation with serum level of MG, but showed a significant correlation with MG/Cr value. (r = 0.485 p0.01). In addition, higher level could be found in patient group having higher serum level of MG or MG/Cr value. Based upon those results, we proposed that a measurement of serum level of Alt could be of value in detection of free radical reaction in long term hemodialyzed patient.

Extramedullary plasmacytoma (EMP) is a very rare disease and mainly arises in the head and neck area. We herein reported a case of EMP arising in the retroperitoneal space. A 46-year-old man was referred to our outpatient clinic in November 1989 with the complaint of flank pain on the left side. Radiological examinations showed a tumor formation in the retroperitoneal space, which involved the left kidney, spleen and pancreas. Immunoelectrophoresis showed an elevation of serum IgG level and a spike of M-protein was detected in the serum protein electrophoresis. No bone lesions were detected, and bone marrow aspiration showed no abnormal cells. US-guided needle biopsy of the tumor led to the histological diagnosis as plasmacytoma of the IgG-kappa type. Following three cycles of preoperative chemotherapy (a THP-COP regimen), which resulted in a size reduction of the tumor by 40%, extensive resection of the tumor including extirpation of the left kidney, spleen, and tail of pancreas was performed. Because of tumor extension into the posterior wall of the stomach, however, the surgery resulted in incomplete resection. A total of 11 cycles of postoperative chemotherapy (THP-COP) was performed periodically for the residual tumor in the stomach. Rapid tumor spreading in addition to re-elevation of the serum IgG level, however, developed after the 11th postoperative chemotherapy, which extensively involved the stomach and intestines. The patient died of the disease 33 months after the initiation of treatment.

Thirty-one patients (26 male and 5 female patients) of non-hypercalciuric Ca stone formers were studied concerning their bone metabolism. We measured plasma free gamma-carboxyglutamic acid, plasma hydroxyproline, urinary free gamma-carboxyglutamic acid and urinary hydroxyproline as markers of bone metabolism. Plasma free gamma-carboxyglutamic acid level showed significantly higher in stone formers than normal controls (1.01 +/- 0.37 nmol/ml vs 0.39 +/- 0.13 nmol/ml). But no significant difference were observed in plasma hydroxyproline level (1.99 +/- 0.73 micrograms/ml vs 2.27 +/- 0.92 micrograms/ml), urinary free gamma-carboxyglutamic acid (52.0 +/- 17.6 nmol/mg.Cr vs 45.7 +/- 9.8 nmol/mg.Cr), and urinary hydroxyproline (3.87 +/- 2.02 micrograms/mg.Cr vs 3.33 +/- 1.63 micrograms/mg.Cr). In conclusion, these results suggest that abnormality of bone metabolism may be not a primary event in causing stone formation in these patients.

The current status and controversy of the treatment for renal cell carcinoma are reported. From 1980 to 1990, a total of 283 patients with renal cell carcinoma were treated in Nara Medical University and its affiliated hospitals. All patients were divided into two groups: M0 group (n = 217) and M1 group (n = 66). In addition, the M0 group patients were divided into two groups according to the followup study: M0--M0 group (n = 194) and M0--M1 group (n = 23). There was a significant difference between the survival of the M0 group and that of the M1 group (p0.001). A significant difference was also seen between the survival of M0--M0 group and that of the M0--M1 group (p0.001). The clinical and pathological factors which might be related to prognosis were analyzed. In the M1 group, high stage, high grade, non-surgical treatment for primary site and metastatic sites other than the lungs were found to be poor prognostic factors. In the M0--M1 group, no prognostic factor was seen. These findings indicated that surgical treatment for the primary site in M1 patients should be performed. In addition, development of effective treatment for metastatic sites other than the lungs and effective postoperative adjuvant treatment would be necessary.

The current status of adjuvant chemotherapy for clinically localized but invasive transitional cell carcinoma of the bladder is reported. Since 1986, a prospective randomized study has been conducted to examine the effects of neoadjuvant cyclophosphamide + doxorubicin + cisplatin (CAP) and radiation therapy for T2-3N0-3M0. A total of 47 patients were entered. However, 4 patients were excluded from the study. All eligible patients were randomized into two groups: neoadjuvant CAP plus radiation and control group. In the neoadjuvant treated-group, a 55% complete response plus partial response rate and a 88% downstaging were noted. Both the 12- and 36-month disease-free survival rates of neoadjuvant treated-group were 94.7%, and were higher than those of the control group (p less than 0.1). As for T4N0-3M0 cases, a total of 6 patients were treated with neoadjuvant methotrexate + vinblastine + doxorubicin + cisplatin (M-VAC) therapy. Favorable results were not obtained in this study at this point, because full dose M-VAC and planned recycling were not performed sufficiently. These findings suggests that neoadjuvant CAP plus radiation therapy would be useful for T2-3 invasive cancer of the bladder. Methods to administer full dose M-VAC; such as developments of new chemotherapeutic agents and of new anti-toxic agents, should be developed. In addition, a more successful regimen than M-VAC should be considered for T4 localized invasive bladder cancer.

During the 5 years from January, 1985 to December, 1989, 88 patients with transitional cell carcinoma of the renal pelvis and/or ureter were operated curatively in the Department of Urology, Nara Medical University and the affiliated hospitals. There were 66 males and 22 females (3:1) and the mean age was 66.0 years old ranging from 34 to 82. Staging of the renal pelvic and ureteral cancer of each patient was determined by General Rule for Clinical and Pathological Studies on Renal Pelvic and Ureteral Cancer established jointly by Japanese Urological Association and The Japanese Society of Pathology in 1990. The over-all survival rates at 1 and 3 years were 91.2% and 74.0%, respectively. The 3 year survival rates of TS and TE were 80.5% and 41.7%. As for grading, the 3-year survival rates were 75.0% for G1, 70.1% for G2, and 75.2% for G3, respectively. The stage of the tumors affected the prognosis. Of 88 patients 26 (Group 1) received cisplatin based combination chemotherapy as a postoperative adjuvant therapy, and the remaining 62 (Group 2) received no such cytotoxic adjuvant chemotherapy. The 3-year survival rates were 63.3% in Group 1 and 78.9% in Group 2, however mean age of Group 1 was significantly younger than that of Group 2. In spite of the age matched trial, there were no significant differences in survival rates between both groups. Adverse effects of cisplatin based combination chemotherapy included gastrointestinal symptom, fatigue, alopecia and leukopenia, however no serious toxicity was seen. These results suggest that prospective randomized trial would be clarified the efficacy of postoperative adjuvant chemotherapy for patients with renal pelvic and/or ureteral cancer.

CDDP combined chemotherapy was performed in 55 cases out of 229 prostatic cancer patients who were treated in Nara Medical University and Nara Prefectural Nara Hospital between January 1979 and August 1989. The previously untreated 33 patients received chemotherapy with anti-androgen treatment as an initial treatment, as well as 7 cases of unresponsive to antiandrogen treatment, 14 relapsing cases and one case with recurrence after total prostatectomy. The major regimens of chemotherapy were cis-diammine dichloroplatinum (CDDP) alone in 16 cases, PVB regimen (bleomycin or peplomycin + vincristine + CDDP) in 19 cases, and CAP regimen (cyclophosphamide + adriamycin + CDDP) in 16 cases. Complete response was not achieved or partial response was observed in 20 cases (34%), no change was seen in 20 cases (34%), and progression was seen in 19 cases (32%). Among each evaluable lesion, effects (CR + PR) were observed in 40% in the prostate, in 18% in the bone lesions, in 44% in the soft tissue lesions, and in 42% in the prostatic tumor marker. The 7-year survival rate of the chemotherapy group (35.6%) was better than that of the antiandrogen treatment group (26.6%) in stage D patients, but was not significant statistically When evaluated by the regimen, a partial response was observed in 56% of CDDP alone, in 21% of PVB regimen, and in 38% of the CAP regimen. However, there was no significant difference in survival rate among the regimens. As an adverse effect, myelosuppression and renal toxicity seemed to be dose limiting factors of CDDP combined chemotherapy for advanced prostatic cancer patients.

In the diagnosis of renal osteodystrophy (ROD) and the monitoring of its clinical course, several biochemical parameters have been appreciated as a useful indicators. The present investigations were designed to evaluate the clinical value of serum tartrate resistant acid phosphatase (TRACP) as an additional parameter of osteoclastic activity in ROD based upon the concept that TRACP was marker enzyme specific for osteoclast. Serum TRACP was assayed in 72 patients on long term hemodialysis and compared with conventional parameters of ROD such as ALP, Osteocalcin, Hydroxyproline. Bone change was analyzed according to Jensen's method and categorized into 4 stages. Serum TRACP was exclusively elevated and revealed a evident correlations with each parameters as follows: TRACP v. PTH-C, r = 0.501 p less than 0.01. Hydroxyproline, r = 0.429 p less than 0.05., ALP, r = 0.001., Osteocalcin, r = 0.540 p less than 0.01. In addition, TRACP value in the patients with high stage significantly higher than that in those low stage ROD. These results suggest that measurement of TRACP would be of clinical importance and useful for diagnosis of ROD in chronic maintenance hemodialized patients.

In order to evaluate an inhibitory effect of Al on haem synthesis, erythrocyte uroporphyrinogen-1-synthetase (RBC-Uro-S) activity and erythrocyte level of protoporphyrin (RBC-protoporph) were measured and compared with RBC-Al in 22 patients on maintenance hemodialysis. RBC-Uro-S activity was varied from 38 to 83 nM/ml RBC/hr 37 degrees C (54.18 +/- 12.42 nM/ml RBC/hr 37 degrees C) and a slight elevation could be found no more than in two cases. On the other hand, RBC-protoporph levels showed to be significantly elevated in many cases such as 8 cases out of 22 (36.4%). (normal subjects: 63.25 +/- 27.61 micrograms/dl RBC, HD patients: 90.0 +/- 28.35 micrograms/dl RBC). This study failed to confirm a significant negative correlation between RBC-Al and RBC-Uro-S activity, but a positive significant correlation could be found between RBC-Al and protoporphyrin levels. However we could confirm a negative correlation neither between RBC-Al and Hb values nor between RBC-Uro-S activity and Hb values. Therefore we concluded that Al-intoxication in the patients on long term hemodialysis had a definite inhibitory effect on heme synthesis, but it was by no means a major factor in pathogenesis of anemia associated with chronic dialysis.

The levels of serum Bone Gla Protein (BGP) and plasma free gamma-carboxyglutamic acid (free gamma-Gla) were measured in 36 patients on maintenance hemodialysis and compared with conventional parameters of renal osteodystrophy (ROD), such as C-PTH, intact PTH, Al-PIII and hydroxyproline levels in serum, and sigma GS/D. Even though the values of BGP were significantly elevated in patients group, 64.5 +/- 1.74 ng/ml, but the low values within normal range could be found in 3 of 36 patients, also. On the other hand, plasma levels of free gamma-Gla were markedly elevated in all cases as high as 10.40 +/- 3.10 nmol/ml in average compared to 1.29 +/- 0.37 nmol/ml (n = 15) in healthy controls. Comparative analysis of BGP with other parameters showed exclusively significant correlation as follows, C-PTH: r = 0.833 (p less than 0.01), intact PTH: r = 0.702 (p less than 0.01), Al-PIII: r = 0.771 (p less than 0.01), hydroxyproline: r = 0.462 (p less than 0.01), sigma GS/D: r = -0.407 (p less than 0.05). Respective for its higher levels, comparative analysis of plasma levels of free gamma-Gla with other parameters failed to show a significant correlation except for correlation with C-PTH (r = 0.459, p less than 0.01). Based upon these results, we could confirm a marked elevation in plasma levels of free gamma-Gla in all patients, but couldn't point out its clinical value in ROD in this study.

A multiple center double blind study was performed to study the effectiveness of Cernilton (CN) on benign prostatic hypertrophy in comparison to Paraprost (PP). Among a total of 192 patients, overall effect was studied on 159 patients, overall safety rate on 178 patients and rate of effectiveness on 159 patients. There were no differences between the two groups in the selected patients, criteria for exclusion and drop out cases or background data of the patients. Impression of patients and overall effect by committee and physician judgment were slightly higher in the CN group compared to the PP group, but there was no significant difference between the two groups. For the improvement in subjective symptoms, the rate of moderate improvement or more after 4 weeks by committee judgement was higher in the CN group compared to the PP group. The rate of improvement in protracted miction, which is an effective marker of urinary disturbance, was also higher in the CN group compared to the PP group. An analysis of objective symptoms showed a significant improvement in residual urinary volume, average flow rate, maximum flow rate and prostatic weight in the CN group. A significant improvement in the phased change of residual urinary volume was also seen in the CN group. No side effects or abnormalities in clinical test levels were noted in the CN group. By committee judgement, the rate of more than moderate effectiveness was 49.1% in the CN group compared to 41.2% in the PP group, but there was no significant difference between the two groups. By physician's judgment, the rate of more than moderate effectiveness was 49.4% in the CN group compared to 46.3% in the PP group, but there was also no significant difference between the two groups. These results suggested that Cernilton was an effective drug for benign prostatic hypertrophy.

Hochuekkito was administered in 2.5 g doses three times a day to 162 patients who complained of anorexia or lassitude because of genitourinary cancer. The efficacy rate was 63.0%. The rate of effectiveness on anorexia was 48.4% and that on lassitude was 36.6%. Side effects were observed in 12 patients (7.4%), but most of them were mild gastrointestinal disorders. No severe adverse effects were noted.

A 62-year-old male was admitted to our clinic with the complaints of gross-hematuria and miction pain. Cystoscopic examination revealed non-papillary tumor around the orifice of the left ureter and the left wall. Histopathological findings of the biopsy specimen demonstrated signet-ring cell carcinoma, and the specimen was stained positively by the peroxidase-antiperoxidase technique. No malignant findings in any other organs including gastrointestinal tract and prostate were detected. This patient underwent total cystectomy with ileal conduit and histopathological staging was pT3bNOMO. He was followed with no evidence of local recurrence or metastasis for 29 months after operation. The 45 reported cases with primary signet-ring cell carcinoma of the urinary bladder including our case are reviewed and some characteristics of this entry are discussed.

The following tables show the statistics on the inpatients, diseases and operations at our department during the period from January through December of 1980.

Urinary lactic dehydrogenase (LDH) activity and isozyme pattern were investigated in 38 patients with bladder tumors of various stages and grades and in 10 healthy persons. Urinary LDH activity was markedly elevated and directly correlated with histologic stage and grade of tumors. The urinary LDH isozyme pattern differed significantly from that of normal urine even in early and well-differentiated tumor cases. LDH4 and LDH5 became more prominent as the degree of the histologic stage and grade of the tumor increased. In the patients with tumors more advanced than stage T2, LDH4 and LDH5 were greater than LDH1 plus LDH2, the reverse of what is found in normal urine. As analogous result was obtained in patients with tumors of grade II or higher. No appreciable difference was found in the LDH isozyme pattern of patients with single or multiple tumors although the total activity was greater with multiple tumors. A comparison between LDH isozyme pattern in urine and in tumor tissue was evaluated in 26 patients with a good correlation (r = 0.40, P less than 0.05). Comparison of the results with urine LDH and urine cytology was attempted for each stage and grade. In 5 of 16 cases having negative urine cytology, a positive isozyme index was present and 10 of 13 cases having positive urine cytology had a positive isozyme index. These data suggest that evaluation of urinary LDH combined with urinary cytology might be of value in the diagnosis of bladder tumors and for following patients who have had bladder tumors.

We report a case of infectious cysts of Müllerian duct. A 48-year-old male patient was referred to our department complaining of terminal miction pain on July 19, 1985. The excretory urogram showed right lateral displacement of bladder and pelvic CT-scan demonstrated a large mass containing multiple cysts. A total of 5 percutaneous punctures was performed, but without success. The cysts were removed completely on November 26, 1985. A large volume of pus subsequently yielded a pure culture of Serratia marcescens and multilobular cysts were observed in the incised tumor. Wound healing was delayed because of severe infection. We discussed the difficulty of the management for infectious cysts of the Müllerian duct.

Stimulation of obturator nerve during transurethral electroresection causes violent adductor muscle contraction, and is a major cause of inadvertent bladder perforation. General anesthesia with muscle relaxants is often required when the bladder tumor is in the area where the obturator nerve passes in close proximity to the inferolateral bladder wall. Recently obturator nerve block under spinal anesthesia during transurethral surgery have been reported in several papers, but the blockade is not completely reliable. Obturator nerve block using electrostimulator (neutracer) and insulated electroneedle (pole needle) was performed in 25 patients with bladder tumors during transurethral electroresection from October 1980 to December 1981. We herein describe the technique and results of local obturator nerve blockade. Use of neutracer and pole needle makes the obturator nerve block a completely reliable, safe and easy procedure.

Three hundred seventy cases with calculi in upper urinary tract were treated by endourology, 210 cases were subjects of percutaneous nephrolithotripsy (PNL) and 160 cases of transurethral ureterolithotripsy (TUL), in Nara Medical University Hospital and 13 affiliated hospitals. Of the PNL cases, PNL was completed in 184 cases (87.6%) and not completed in 16 cases (12.4%). 168 cases (80.0%) had successful results by PNL alone, stone-free or stone fragments less than 5 mm, in spite of the stone location and size. No serious adverse effect was experienced throughout the study. However, changes like a scar formation or fibrosis around the nephrostomy tract were revealed as a late complication by excretory urography, computed tomography and renal scanning. Of the 160 TUL cases, TUL was successful in 132 cases (82.5%) and unsuccessful in 28 cases (17.5%). The results of TUL for the calculi above the upper iliac cresta were not favorable, success rate for stone 6-10 mm in diameter was 70.3% and that for stones larger than 11 mm 37.5%. However, the results of TUL for the calculi below the upper ileac cresta were favorable, the success rate for the 6-10 mm calculi was 91.5% and for the calculi larger than 11 mm 88.4%. Of 28 TUL failures, 7 cases underwent PNL and 21 cases received open surgery. Throughout our endourologic treatments, the most problematic stone was calculi impact in the ureter. The indication of endourology for the calculi in upper urinary tract is discussed with consideration of ESWL which is becoming the main stream of stone treatment.

A case of metastasis to the penis and the urethra from superficial bladder tumor of transitional cell carcinoma (TCC), grade 3 is reported. A 52-year-old male patient was diagnosed to have TCC of the urinary bladder (grade 3, stage pT1a) in May, 1985 and was treated initially with transurethral resection followed by adriamycin (ADR) instillation. In February, 1986, urethroscopy showed a papillary tumor in the cavernosal urethra and a metastatic tumor was noted in the corpus spongiosum penis. Biopsy of urethral tumor revealed TCC, grade 3. Therefore partial urethrectomy with resection of penile tumor was performed. Although the patient underwent combination chemotherapy involving CAP (cisplatin + ADR + cyclophosphamide) and M-VAC (methotrexate + vincristine + ADR + cisplatin) regimens, local lesion and metastatic lesions progressed, and he died in June 1986, 20 days after emasculation. The management of superficial bladder tumor with TCC, grade 3 was reviewed and discussed here.

Between April, 1984 and March, 1985 in 14 centers, 33 patients with prostatic cancer of our 14 centers were randomized to subcutaneously receive either 125, 250, or 500 micrograms/day of ICI 118,630, an LH-RH analogue, for 12 weeks, and the clinical efficacy, safety and endocrinal effects of the drug by dose were examined. An objective partial response was obtained in 44.4% of the 125 micrograms-treated group, in 50.0% of the 250 micrograms-treated group, and 42.9% of the 500 micrograms-treated group, showing no significant difference between the groups. General subjective response rates in these three groups were respectively 75.0%, 62.5%, and 85.7%, not differing from each other significantly. No significant difference was observed in endocrinal effect which was seen in 58.3%, 66.7%, and 100% of 125 micrograms, 250 micrograms, and 500 micrograms groups, respectively. Medical castration was attained in 4.1 +/- 2.0 weeks on average. Adverse reactions observed included fever up to 37 degrees C in 1 of the 13 (7.3%) patients treated with 125 micrograms, and hot feeling at the injection site and flare in 1 of the 8 (12.5%) patients treated with 500 micrograms, which were all mild. These patients responded to further ICI 118,630 therapy without requiring any treatment for the adverse reactions.

The anti-emetic effect of corticosteroid during cancer chemotherapy with cis-diamminedichloroplatinum (II) (CDDP) is analyzed retrospectively. From November 1981 to April 1984, 23 of 50 patients receiving CDDP were given corticosteroid as an anti-emetic. Corticosteroids, methylprednisolone (80-500 mg/day) or hydrocortisone (200-480 mg/day), were administered intravenously for 1 to 3 doses. Including 4 patients who had no symptoms, 60% of patients were free from nausea and vomiting. The incidence of gastrointestinal symptoms was significantly lower than that in patients who were not given corticosteroid. Corticosteroid reduced gastrointestinal symptoms in 2 of 3 patients who had prior CDDP treatment. There were no remarkable adverse reactions except acne in 2 patients. A further controlled study is needed to determine the appropriate dose and modality of administration of corticosteroid.

A case of left renal cell carcinoma with a tumor thrombus extending into the vena cava and the right atrium is reported. A 49-year-old female presented with a one month history of palpitation, dyspnea, and leg edema. CT-scanning and angiography revealed a left renal tumor with a tumor thrombus extending into the right atrium. Left nephrectomy and the removal of an intra-atrial tumor thrombus were performed under cardiopulmonary bypass. The postoperative course was unfavorable and the patient died on the 42nd day after the operation because of multiple organ failure in spite of repeated hemoperfusion. Operative procedure and prognosis of renal cell carcinoma with tumor thrombus extending into the right atrium are discussed.

A multicenter randomized clinical trial was carried out between May, 1986 and May, 1987 involving 82 patients with stage B-D prostatic carcinoma from 29 centers. The clinical efficacy, endocrine effect, safety and usefulness of the luteinizing hormone-releasing hormone (LH-RH) analogue and other endocrine manipulations in the treatment of prostatic carcinoma. Zoladex depot containing 3.6 mg of ICI 118,630, an LH-RH analogue, was administered every four weeks 3 times in total. Patients in the control group received either 300 mg of diethylstilbestrol diphosphate orally daily for 12 weeks or orchidectomy. An antitumor effect (CR + PR) was observed in 21 of the 33 patients (63.6%) in the Zoladex group and in 22 of the 33 (66.7%) in the control group, showing no significant difference between the two groups. There was no significant difference in overall subjective response either; 21 of the 24 (87.5%) in the Zoladex group and 24 of the 30 (80.0%) in the control group. In both groups, 100% endocrine effect was obtained as shown by achievement of castration in all patients. Adverse reactions were observed in 14 of the 39 (35.9%) patients treated with Zoladex as compared with 19 of the 34 (55.9%) control patients, resulting in no significant difference in the incidence between the two groups. These adverse reactions were not so severe as to require withdrawal from the study. In both groups, the treatment was assessed as slightly or more useful in 29 of the 33 (87.9%) patients. From these results, it is concluded that Zoladex, 3.6 mg depot, is a useful drug for treatment of prostatic cancer, having clinical efficacy and endocrine effects comparable to those of the conventional endocrine manipulations, being safe, and causing less physiological and psychological pain.