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Between 1980 and June, 2002, transurethral resection of prostate was performed against 3294 cases of benign prostatic hyperplasia, and 144 cases of stage A cancer were detected (4.4%). Among these cases, 136 cases which had complete records of examination were studied. Annual number of stage A and A1:A2 ratio were not influenced by introducing PSA determination from 1991, although the number of T1c has been increasing gradually. Since subclassification of stage A is different between Japanese rules (A1; 3 chips of cancer with well-differentiated adenocarcinoma, A2; others) and TNM (T1a; 5% of less number of chips with cancer, T1b; others), two criteria were compared. Coincidence was found with 93.7%, and disagreement was due to ratio of number of chips with cancer to whole number resected, or different grade. The former difference was caused by a larger or smaller prostate. Most cases of A1 and A2 were subjected to watchful waiting or subsequent therapy. PSA was elevated in 10 cases (7%), two of which died from progression of cancer. Other cases were disease-free. Individual pathological findings are important for subclassification of stage A.

A randomized, multicenter, double-blind, parallel-group study was conducted in order to evaluate the hormonal kinetics, pharmacokinetics, efficacy and safety of TAP-144-SR (3M) a three-month sustained-release injectable preparation of leuprorelin acetate, a highly active luteinizing hormone-releasing hormone (LH-RH) derivative by comparing the treatment with two subcutaneous doses of the test medication TAP-144-SR (3M) and the treatment with six subcutaneous doses of the reference medication TAP-144-SR (1M), a 1-month sustained-release injectable preparation. Study participants were 103 patients with prostate cancer in whom a stable anti-tumor effect had been obtained with Leuplin Injection 3.75. The hormonal kinetics revealed that the proportion of the patients "maintaining the castration level of serum testosterone (maximum serum testosterone level during treatment below the castration level [100 ng/dl])" was 100% in both treatment groups. With regard to the efficacy, the proportions of the patients in whom the anti-tumor effects (> or = Stable) of the baseline treatment prior to the initiation of the treatment with the study medication were maintained during the study treatment period (6 months) were comparable; 84.0% with TAP-144-SR (1M) and 80.4% with TAP-144-SR (3M). On evaluation of the pharmacokinetics, the mean value of AUC1-12w of the serum TAP-144 concentration (including the metabolite M-I) for the treatment with TAP-144-SR (3M) was 77.0% that of the treatment with TAP-144-SR (1M). Adverse events were similar in the subjects on TAP-144-SR (3M) and in those on TAP-144-SR (1M). There existed no big differences in kind, incidence or time of occurrence of adverse events between two groups. TAP-144-SR (3M) showed no clinically relevant findings in particular. These results indicate that one dose of TAP-144-SR (3M) is comparable to three doses of the already approved Leuplin injection 3.75 in serum testosterone level-inhibitory effect, efficacy and safety. Hence, it is considered that TAP-144-SR (3M) is a drug suitable for treatment of prostate cancer over a prolonged period of time.

Patients with Stage D2 prostate cancer were treated with surgical or medical (LHRH analog) castration combined with either estrogen, chlormadinone acetate or flutamide as initial therapy. The effect of each medication was compared. The overall survival, cause-specific survival and relapse-free survival were not different among the three medications. Patients given each medication were divided into two groups each according to grade, extent of diseases on bone metastases, and levels of tumor marker. Survivals of the corresponding two groups were compared with each other among different medications. No differences were revealed with any medication. There were no serious side effects in whole patients, except that grade 2 liver dysfunction was accompanied in 12% of flutamide-treated group. It is concluded that the three drugs used with castration did not make any difference in the survival of stage D2 patients, and differences between medications were seen in the frequency of side effects.

Patients with prostate cancer treated during 1986-95 were divided into two groups: the first five years as early period and the recent five years as late period. Background factors, therapeutic modality and prognosis were compared between these two groups. The number of patients during the late period (245) was about 1.5 fold that during the early period (161). The average age for each stage are similar within the same period, and also similar between early and late periods. Almost the same ratios were noticed on stage distribution and on histological grade between early and late periods. Therefore, the increase in the number of patients in recent years was due mainly to expansion with the same proportion of background factors. Patients with T2 and T3 during the late period received more aggressive treatments with/without endocrine therapy. Subsequently these patients seemed to show better prognosis than the patients during the early period. No differences in survival of patients with metastosis was revealed between these two periods. Therefore, the outcome was not improved by recent endocrine therapy.

Thirty seven patients complaining of voiding disturbance who showed gray zone total prostate-specific antigen (t-PSA) level (upper limit of normal approximately 10 ng/ml) but did not reveal apparent cancerous findings in the prostate were examined for free PSA (f-PSA) and prostate volume. According to histological diagnosis, 9 were cancer cases and the other 28 were non-cancer cases. The free/total (F/T) ratio was 0.10 and 0.16 in the cancer and non-cancer groups, respectively (t-PSA; DPC kit, p = 0.03). The t-PSA (DPC and Dinabott kits), f-PSA and PSA density alone did not distinguish these two groups. For diagnosis of cancer, the ratio seemed to be F/T, the most reliable followed by PSA density and t-PSA. When using a 13% F/T, the sensitivity and specificity for cancer detection were 88.9 and 70.8%, respectively. t-PSA measured with the Dinabott kit, showed a similar tendency except that the F/T ratio showed a slight variation. Prostate volume and patient age influenced the F/T slightly, but these factors may not impair the usefulness of F/T.

Clinical effects of estramustine phosphate (EMT) on hormone refractory prostate cancer were studied. Prostate cancer relapsed in 70 of the 259 patients with stage C and D diseases who had initially responded to endocrine therapy. After cancer relapse, endocrine therapy was changed to oral administration of EMT in 21 patients, while initial endocrine therapy was continued in 14 and additional radiation therapy was given in 35. A partial response or no change was observed in 11 of the 21 patients (52%) given EMT therapy, the mean duration of the response being 14.2 months. The 21 patients given EMT therapy survived significantly longer than the 14 patients with continued on endocrine therapy, and those responding to EMT therapy tended to have a better survival than those unresponsive. Side effects of EMT included loss of appetite in 2 patients and edema of the lower limb in 1, but they were not severe enough to require discontinuation of the drug. EMT may be a useful drug for patients with advanced prostate cancer with relapse after endocrine therapy.

We report a case of cavernous hemangioma of the urinary bladder treated with transurethral resection (TUR). A 58-year-old woman was admitted to our department with the chief complaint of macroscopic hematuria. Cystoscopy revealed a red sessile tumor 2 cm in diameter, at the internal urethral orifice. The tumor had a mostly low signal intensity, partly high signal intensity, on T1-weighted, coronal magnetic resonance (MR) images. Computed tomography and T2-weighted MR images did not delineate the tumor. TUR was performed, and the specimen was pathologically diagnosed as cavernous hemangioma of the urinary bladder. A brief description of the case is provided and the literature is reviewed.

We report a case of bilateral renal cell carcinoma with extension into the inferior vena cava associated with von Hippel-Lindau (VHL) disease. A 52-year-old woman was referred to our hospital for further examination of bilateral renal masses which were found on abdominal ultrasound examination. The diagnosis was confirmed with renal angiography, abdominal computed tomography (CT), abdominal magnetic resonance-CT (MRI), cavography and head MRI. Right adjunctive nephrectomy and removal of the tumor thrombus were performed. She has been treated with interferon-alpha after the operation. The analysis of her DNA by using single strand conformational polymorphism revealed a VHL gene abnormality.

To evaluate prognostic factors in stage D2 prostate cancer, 235 patients who had been treated with endocrine therapy were investigated. With univariate analysis, performance status, hemoglobin concentration, serum alkaline phosphatase, LDH, histological grade, extent of disease (EOD), and response of tumor markers at 3 months were shown to be significant prognostic factors. To compare these 7 factors, multivariate analyses was performed in 196 cases. Cox proportional hazard model demonstrated that LDH, followed by response of tumor markers at 3 months, histological grade, and EOD were significant for predicting prognosis. We concluded that the patients whose serum LDH was above the normal range and/or whose tumor markers were not or had not been normalized 3 months after the onset of endocrine therapy were in the high risk group, and should be given more aggressive treatment.

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.

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.

Clinical evaluation of TANDEM PSA which is the most frequently used prostate specific antigen (PSA) assay method in the world and a comparison with other methods were performed in Japanese cases in a cooperative research fashion. The minimum detectable level of the method was found to be 0.50 ng of PSA in one ml of serum and 1.9 ng/ml was regarded as the upper normal value in Japanese males. The distribution of serum PSA showed a significant difference between the benign prostate hypertrophy (BPH) cases and patients with stage C or D prostate cancer. The sero-diagnosis prostate cancer at an early stage with the TANDEM PSA was difficult. The correlation to other methods of PSA detection was very high. Furthermore, the clinical use of the method in following-up the clinical course of prostate cancer patients was very useful. These findings suggested that the PSA detection using TANDEM PSA is applicable even in Japanese cases although the upper cut-off level is decreased.

Fundamental and clinical studies of serum prostatic acid phosphatase (PAP) detected by a Delfia PAP kit were performed. The system is a time-resolved fluoroimmunoassay using europium as a tracer. The lower limit of detection was 0.2 ng/ml. Sera from 54 patients with prostate cancer, 20 with benign prostatic hypertrophy, 20 with urological malignancies other than prostate cancer and 140 adult males over 46 years old were determined. From the mean + 2 S.D. of serum PAP values obtained on the adult males, 1.5 ng/ml was considered as the upper normal level of adult males. By calculating the efficiency and ROC curve using the PAP values of prostate cancer and benign prostatic cancer, 2.5 ng/ml was decided as a cut-off value of this kit. The positive rates of adult males, prostate cancer, benign prostatic cancer and urological malignancies other than prostate cancer were 0.7%, 65%, 20% and 10%, respectively. The sensitivity of stage A2, B2, C and D1 + D2 was, 0%, 0%, 64% and 83%, respectively. The efficiency of the Delfia PAP kit was 52% and that of the Markit M PA kit was 71%. The correlation between the values assayed with the Delfia PAP kit and the Dinabot PAP kit was very high; the value obtained with the Delfia PAP kit was about 80% of that obtained with the Dinabot PAP kit.

To clarify the effects and limitation of medical treatment for benign prostatic hyperplasia (BPH), 2,476 patients with BPH were analyzed in terms of symptoms, objective findings, treatment modality and whether surgery was required during the course of medical treatment. As initial therapy, 1,320 cases (53.3%) were treated with medicine and 783 cases (31.6%) underwent surgery. In the group of patients initially treated with medicine, 264 cases (20.0%) required surgery and most operations were performed within six months from the start of medical treatment. Those who required surgery had a larger prostate and more residual urine than those who continued medical treatment. This tendency was also observed in the patients treated with antiandrogen. Therefore, medical therapy might be inappropriate to treat the patients with more than 50 ml of residual urine or significantly large prostate such as goose egg sized or larger. In conclusion, medical treatment possessed potential usefulness for the management of BPH, however, there seemed to be limitation of the effects of medical treatment.

We report a patient who developed a fistula between the right ureter and the right common iliac artery aneurysm. He had had replacement of a synthetic graft for abdominal aortic aneurysm sixteen years previously. The diagnosis was confirmed by angiography, retrograde pyelography and computed tomography. The fistula was treated by right nephroureterectomy and resection of right common iliac artery aneurysm. A brief description of the case is provided and the review of the literature is described.

A study of the clinical utility of the IMx PA Dainapack, a new kit for detection of serum prostate specific antigen (PSA) by a fully automated enzyme immunoassay (EIA) system, was conducted. Results concerning reproducibility, dilution linearity and sensitivity were good. The excellent assay performance of this kit, particularly in terms of its high sensitivity (0.1 ng/ml), was confirmed. The upper limit of normal was determined to be 4.0 ng/ml from the mean +/- 3 S.D. (3.79 ng/ml) in healthy male controls (n = 244). Using 4.0 ng/ml as the upper limit of normal, 6 of 244 healthy male controls (2%) were positive. In various urinary diseases, 173 of 192 prostatic cancer (90%) and 46 of 112 benign prostatic hypertrophy (BPH) (41%) cases were positive. In prostatic cancer, the positive rates increased with the advance in clinical stage and in stage A the positive rate was especially high (8 of 12 (67%) were positive). On the other hand, using the BPH group as a negative control, the maximum accuracy rate for prostatic cancer had a cut-off value of 8.0 ng/ml. Thus, 8.0 ng/ml is an appropriate cut-off value differentiating prostatic cancer from BPH while 4.0 ng/ml is the cut-off value between the normal group and those with prostatic cancer (including stage A) and BPH. In the follow-up patients with prostatic cancer, serum PSA values measured by this kit reflected the effectiveness of treatment. The correlations between values obtained with the IMx PA Dainapack and 6 current kits were good (r = 0.93 to 0.99) but the values differed with the kit.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Semen quality and endocrine parameters after spermatic cord torsion were investigated. Of 24 patients evaluated following spermatic cord torsion 12 were treated with bilateral orchiopexy (orchiopexy group), and 12 were treated with ipsilateral orchiectomy and contralateral orchiopexy (orchiectomy group). The average sperm density and the average total sperm count in the orchiectomy group were significantly lower than those in the orchiopexy group (p < 0.05, p < 0.05, respectively). The mean serum follicle stimulating hormone level in the orchiectomy group was significantly higher than that in the orchiopexy group (p < 0.05). These findings suggest a significant decrease in testicular function in the orchiectomy group. All the patients in the orchiopexy group demonstrated a normal semen quality and endocrine parameters during followup. Four of the 8 patients in the orchiectomy group whose duration of followup was more than two years still demonstrated oligozoospermia (< 20 x 10(6)/ml, one of 4 was azoospermia). The average age at operation of these four patients with abnormal semen quality was significantly higher than that of the other 4 patients with normal semen quality (p < 0.05), whereas no significant difference in duration of torsion preceding surgical therapy was observed between these two groups. These findings suggest that subsequent semen quality is likely to remain within normal limits with early surgical treatment by bilateral orchiopexy. Ipsilateral orchiectomy in the younger generation seems to result in less damage of the contralateral testis than in the older generation.

A 66-year-old female was admitted to Chiba University Hospital for the evaluation of a left adrenal mass which was incidentally discovered by computerized tomography. The patient had no clinical signs of Cushing's syndrome. Although the plasma ACTH level was suppressed, serum cortisol and urinary 17-OHCS levels were normal. Serum cortisol was not suppressed by dexamethasone and loss of diurnal rhythm of cortisol was observed. Uptake of 131I-aldosterone in the left adrenal gland was noted, but no accumulation was observed in the right one. Left adrenalectomy was performed. The tumor resected was 20 x 22 x 26 mm in size. Pathological diagnosis was adreno-cortical adenoma. Whether slight abnormality of adrenocortical function without clinical symptoms observed in the present case would develop into a clinically typical Cushing's syndrome remains to be solved.

Twenty-one cases of inverted papilloma of the renal pelvis have been described in the literature. A 71-year-old man was admitted to our hospital to examine a right renal mass. We diagnosed a right renal tumor on the basis of the findings from excretory urogram (IVP), computerized tomography (CT) and magnetic resonance imaging (MRI). Surgical material revealed an inverted papilloma in the renal pelvis. We report on the first case of an invested papilloma of the renal pelvis associated with renal cell carcinoma.

A 20-year-old man was admitted on February 2, 1990 with the chief complaint of pollakisuria, miction pain and macrohematuria. Urinalysis revealed numerous leukocytes and Enterobacter was identified by urine culture. Cystoscopy revealed an edematous region. Contrast film of small intestines demonstrated vesicoileal fistula. Judging from these and the radiographic findings, we made the diagnosis of vesicoileal fistula with Crohn's disease. After medical therapy between February 22 and May 25, urinalysis became normal and we assumed that the fistula had closed. Now, it is about a year since the therapy began, the patient remains well, without urinary and enteric symptoms. Cystoscopy and urinalysis did not reveal recurrence of the fistula. Despite previous reports that vesicoenteric fistulas complicating Crohn's disease require surgical treatment, this case responded to medication, and required no surgical treatment. This case is a reminder of the importance of the principle of therapy.

We have already pointed out by the use of multivariate analysis that local response of the prostate is one of the important prognostic factors in patients receiving endocrine therapy. Herein, we investigated how the local response to endocrine therapy affects the survival rate or the survival period. We also studied the relationship between the local response and histopathological findings. The local response of prostate was not correlated with the stage progression. Sixty-seven percent of the patents in each stage had an initially favorable local response of the prostate, in which the primary tumor became flattened or reduced by endocrine therapy. By contrast, the local response of the prostate was well correlated with the prognosis in each stage. Patients with a flattened or reduced primary lesion following endocrine therapy showed a higher survival rate or a longer survival period than those with the unchanged lesion. This result has confirmed that the local response of prostate to endocrine therapy is useful in predicting clinical courses of patients. Grade of structural atypism (SAT), one of the pathological findings, had a correlation with local response of the prostate. With an elevation of the SAT grade, the proportion of patients with unchanged primary lesion was increased.

Prostate carcinomas are well known to be initially responsive to endocrine therapy. However, a significant number of the patients experience a relapse from endocrine therapy during the follow-up period. We clinically analyzed various aspects of the relapse which indicate a limitation in the effectiveness of endocrine therapy for prostate carcinoma. In a total of 372 patients, 117 (31.5%) had some evidence of local relapse such as regrowth of the primary lesion, or a generalized relapse such as re-elevation of total acid phosphatase, reactivation of previously present metastasis or the new appearance of metastasis, during endocrine therapy. Of these, one-fourth had local relapse alone and the remainder showed generalized relapse. The interval from the start of the treatment to the time of relapse tended to become shorter; 45.9 months (mean) in stage B, 36.8 in stage C and 29.3 in stage D, according to the stage progression. As to the non-relapse rate of the primary lesion, no differences were found among the stage, with the rate being approximately 90% at the fifth year in each stage. However, the generalized relapse-rate tended to increase with the stage progression. In the generalized relapse, the patients of stage C or D showed a non-relapse rate of 71.7% or 67.4%, respectively. Most of the generalized relapse appeared within five years following start of endocrine therapy in these advanced stages. The interval from relapse to prostate carcinoma-related death in patients with the generalized relapse was 9 approximately 21 months, and those in stage D tended to show a a poorer prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Between January, 1975 and December, 1989, 86 patients with renal cell carcinoma received radical nephrectomy associated with lymphadenectomy at our institutions. Pathological examination revealed lymph node metastasis in 15 patients (17.4%). The incidence of lymph node metastasis increased in accordance with the aggravation of tumor stage (p less than 0.01) and grade (p less than 0.05). Patients with a rapidly growing tumor showed higher incidence of lymph node metastasis than patients with a slow growing tumor (p less than 0.01). Regional lymph node metastases were found in 3 of the 41 patients with a slow growing tumor. Since these 3 patients are surviving with no evidence of disease for 38.7 months on average, the regional lymphadenectomy was considered to have been effective for their survival. Nine of the 25 patients with a rapid growing tumor had progressive lymph node metastasis. Four of them had apparent tumor thrombi as well as lymph node metastasis, and 2 of them had distant metastasis. These patients showed poor prognosis even after operation. Lymphadenectomy was of no value to the patients with apparent tumor thrombi and/or distant metastasis.

A 65-year old man presented with a seven-month history of macrohematuria and left back pain. Abdominal ultrasonography, enhanced computed tomographic (CT) scanning, magnetic resonance imaging (MRI), selective renal angiography and vena cavography revealed a left renal tumor extending into the inferior vena cava and right atrium. Surgery was performed using the cardiopulmonary bypass and the whole tumor was resected grossly except for the tumor invading into the lumbar vein. The patient recovered promptly but died from cancer metastasis six months after operation.

Forty-one patients with adenocarcinoma of the prostate localized in the pelvis (stage A2, NX; 3, A2, pN0; 5, B, NX; 5, B, pN0; 1, C, NX; 13, C, pN0; 7, C, pN1; 7) underwent curative external radiotherapy. Thirty-two cases were treated by fast neutron combined with or without Liniac X-ray and 9 cases were treated by Liniac X-ray. Twenty-six cases were well controlled by radiotherapy, but 15 cases recurred and were followed by endocrine therapy. The types of recurrence were local growth in 3, distant metastases in 11, and both in 1. These recurrences occurred in the cases of large prostatic carcinoma, small radiation field in NX cases or low radiation dose. The five-year disease-free survival rates of stage A2, B, C were 86, 66, and 47%, respectively and the five-year overall survival rates were 100, 100, and 53%, respectively. The cases with well differentiated carcinoma had better prognosis than those with poorly differentiated carcinoma (p less than 0.05). As 58% of the cases which were given concomitant endocrine therapy were controlled for over 2 years, endocrine therapy seems to be effective in the cases of failure after radiotherapy. Most of the complications were slight and only one case with complication of sacral decubitus needed surgical treatment. It was concluded that external radiotherapy was a good modality for prostatic carcinoma localized in the pelvis.

A 66-year-old female visited our university hospital with the chief complaint of right lower abdominal pain in July, 1984. Kidney-ureter-bladder roentgenograms disclosed the right ureter stone and several left renal stones. She passed the right ureter stone composed of calcium oxalate. Thereafter, she passed small stones twice and sand stones twice until September, 1985. The stone analysis revealed two of them as silica. Although most patients with silica stones reported in Japan had a history of long-term medication of magnesium trisilicate, this patient had not taken this drug. Silica stones are rare and fifteen cases including the present case have been reported in Japan.

To investigate the efficacy and the safety of RU23908 for the treatment of prostatic cancer, an early phase 2 study with the oral administration of 150 or 300 mg daily was performed in 47 patients with stage C or D prostatic cancer at 15 institutions from April 1987 to June 1988. Forty patients were evaluable for efficacy. Concerning the effect on the object lesion, the results of the overall evaluation revealed that complete or partial response (CR + PR) was obtained in 34 of the 40 cases (85.0%). As to the effect classified by site, CR + PR were observed in 35 out of the 40 cases with primary lesion (87.5%), in 10 of the 22 cases with bone metastasis (45.5%), in 5 of the 6 cases with lymph node metastasis (83.3%) and CR was observed in one case with lung metastasis. In the PAP evaluation, 33 out of the 34 cases were judged to be CR + PR (97.1%). The improvement rate of clinical symptoms was 88.9% for bone pain, 83.3% for dysuria and 45.5% for performance status. Adverse reactions were observed in 29 of the 47 cases (61.7%) investigated and 7 cases (14.9%) were withdrawn. During the study period of 12 weeks and the subsequent period of continued administration, 6 cases (12.8%) and 2 possible cases of interstitial pneumonia were diagnosed. From the above results, the treatment of prostatic cancer with RU23908 150 mg/day or 300 mg/day in combination with surgical castration showed an excellent clinical effect compared to conventional endocrine therapy, but has a problem of safety. Therefore, this drug may be expected to be a highly useful therapeutic drug, if safely is improved in the future by reviewing the dose.

Serum gamma-seminoprotein (gamma-Sm) was evaluated as a new marker for prostatic cancer in comparison with prostatic acid phosphatase (PAP). The sensitivity of gamma-Sm and PAP for untreated prostatic cancer was 81% and 67%, respectively. gamma-Sm showed a higher positive rate over all stages than in benign prostatic hypertrophy (BPH). There was no correlation between gamma-Sm and PAP in prostatic cancer. Improved sensitivity was obtained by simultaneous measurement of gamma-Sm and PAP. Specificity of gamma-Sm and PAP for BPH was 87% and 90%, respectively. gamma-Sm normalized after endocrine therapy for stage D2 more often than did PAP. These results indicate that gamma-Sm is another useful marker to evaluate prostatic cancer.

Effects of chemotherapy to endocrine therapy (castration with estrogen/antiandrogen)-relapsed (24 cases) or endocrine therapy-resistant (14 cases) prostate cancer were compared. Pretreatment clinical stages in these groups were stage D1 (3 cases) and D2 (35 cases). Regimens of chemotherapy in this study were as follows: cis-platinum (CDDP) (1 case), phosphamide (3 cases), combination of vincristine, phosphamide and peplomycin (5 cases), combination of cyclophosphamide, adriamycin (ADM) and CDDP (8 cases) and combination of phosphamide, ADM, and CDDP (21 cases). Response to chemotherapy and subsequent survival in these two groups were examined. When evaluated at 3 months after the start of the chemotherapy, partial response and stable cases were 50% and 36% in endocrine therapy-relapsed and -resistant groups, respectively. Because the worse performance status contained more cases in the endocrine therapy-resistant group, the response was compared at the same base of performance status, and the response was almost equal in the two groups. Survival in the endocrine therapy-relapsed group was better than that in the therapy-resistant group. When compared at the same base of performance status, the difference in survival time between the two groups was not evident. In conclusion, the response of chemotherapy was similar between endocrine therapy-relapsed and -resistant patients, and performance status was a main factor influencing the prognosis of endocrine therapy-refractory prostate cancer.

The therapeutic utility of bunazosin hydrochloride was evaluated by a multi-center (67 hospitals) double-blind controlled study in patients who complained of voiding disturbances due to neurogenic bladder. For means of comparison, bethanechol chloride and placebo were used as reference drugs. Bunazosin hydrochloride was orally administered 1.5 mg per day for the first week and 3.0 mg per day for two weeks thereafter (Group E). Bethanechol chloride 15 mg (Group B) and placebo (Group P) were orally administered three times daily for three weeks. Three hundred and twenty-three cases were subjected to this study. The global improvement rating was analyzed for 244 cases (83 in Group E, 78 in Group B and 83 in Group P). The global utility rating (GUR) was analyzed for 252 cases (84 in Group E, 81 in Group B and 87 in Group P). Three hundred and twenty cases (107 in Group E, 104 in Group B and 109 in Group P) were analyzed with respect to overall safety rating (OSR). The global improvement ratings (excellent and good) were 32.5% in Group E, 28.2% in Group B and 21.2% in Group P. In the evaluation of GUR, Group E was superior to Group P. In addition, the incidence judged to be useless in Group E was significantly lower than that in Group B. There were no differences in OSR among these three groups. In the total evaluation of the subjective symptoms, the rates of improvement were not different among these three groups. In the total evaluation of the objective findings, the improvement rate in Group E was significantly higher than that in Group P. In addition, the deterioration rate in Group E was significantly lower than that in Group B. In objective findings before and after administration of bunazosin hydrochloride (Group E), the volume of residual urine, the rate of residual urine and the average flow rate improved significantly However, the bladder capacity, the maximum resting bladder pressure and the maximum urethral pressure did not change significantly. Bunazosin hydrochloride improved the objective findings regardless of the bladder capacity and the maximum resting bladder pressure. These significant improvements were marked in the neurogenic bladder patients who were able to urinate and in the patients whose urethral pressure was high. There were no differences in the incidence of side effects or in the appearance of abnormal values of laboratory findings in these three groups. Neither specific signs nor serious clinical side effects except those reported previously were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Between 1975 and 1989, 90 patients with prostate cancer in clinical stage A2 to C underwent pelvic lymphadenectomy. Median follow-up period was 38 months. Almost all of the patients with pN0-1 (49) and 4 of pN2 were treated by curative treatment, such as radical prostatectomy (7) or radiation therapy (45). The remaining pN2 (26), pN3 (4) and pM1 LYM (6) received endocrine therapy. Pelvic lymph node metastasis were noticed in 50 cases (56%). Rates of positive node and degree of nodal extension were related to clinical stage and histological grade. Disease-free survival of the patients with pN0-1 was better than that of the patients with more than pN2. There was no difference in disease-free survival between the patients with pN0 and pN1. We concluded that the patients with pN0 and pN1 were the candidates for curative therapy and recommend that the patients with more than pN2 be treated with endocrine therapy.

Prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate specific antigen (PSA) were examined on 120 cases of stage D2 prostate cancer between 1979 and 1989. All patients received endocrine therapy as the first treatment; castration and immediate administration of estrogen or antiandrogen (101), LH-RH analogs (13), estrogen (3) and antiandrogen (3). The actuarial survival rates were calculated by the cause-specific survival method. Pretreatment levels of PAP, gamma-Sm and PSA did not influence prognosis. After start of treatment, the relationship between the changes of the markers and prognosis were examined. At 1 month after the start of the treatment, normalization of PAP or gamma-Sm was not reflected in the following course. On the contrary, at 3 and 6 months, groups with normalization of PAP or gamma-Sm showed better prognosis than those with elevated levels. The same tendency of PSA was obtained at 6 months after start of treatment. In patients with normalized PAP at 3 months, abnormal gamma-Sm showed worse prognosis than normalized gamma-Sm. Therefore, the significance of determination on the two markers was manifested. As histological grade influenced the following course, poorly differentiated adenocarcinoma with normalized PAP at 3 months showed better prognosis than those with elevated levels. In conclusion, it is worthwhile to measure multiple markers for predicting the prognosis of stage D2 prostate cancer treated with endocrine therapy.

To clarify factors affecting prognosis following endocrine therapy, stage D2 patients who died from prostatic cancer within 3 years and those under well-controlled state longer than 5 years were compared with respect to background factors and response to endocrine therapy. Thirty-five and 18 cases, respectively, were studied. Differences between the two groups were bone pain, anemia, tumor grade, number of bone metastasis, and response to endocrine therapy. Performance status in long-term survival groups tended to be better than that in short-term cancer death groups.

Of 572 patients with prostatic carcinoma, 497 received endocrine therapy as the initial treatment. These patients were surveyed in a cooperative research study by members from five universities. Prognosis, causes of death and side effects of estrogen therapy were studied. The prognosis of patients who had received endocrine therapy became worse, as the stage progressed. The prognosis of those who had received a combination of estrogen therapy with castration tended to be better than that of those who had received estrogen therapy alone. Similarly, the prognosis of those who had received a combination of progesterone therapy with castration tended to be better than that of those who had had progesterone therapy alone. No relationship was found between estrogen doses (low, medium and high) and prognosis, although a precise comparison among the three could not be made because of the smaller number of patents with low doses. A high dose of estrogen may not always be the indication, rather a medium dose such as 300 mg diethylstilbestrol diphosphate may be clinically appropriate. The cause of death could be identified in 303 patients who had received endocrine therapy. Cancer-related death was the most frequent (63.7%), and cardio- or cerebrovascular death accounted for only 14.2% of the cases. When this analysis was confined to the patients who had received estrogen therapy, estrogen administration seemed to be the cause of cardio- or cerebrovascular death of 16.1% of the patients. Daily dosing of estrogen was not definitely related to the incidence, or the interval to cardio- or cerebrovascular death. However, among the patients who had died of cardio- or cerebrovascular disease, 50% of the patients who had received a medium or high dose of estrogen tended to die within two years after treatment, while 50% of those who had received a low dose died within three years.

The general trend on the treatment for prostatic carcinoma has been changing from endocrine therapy alone to an alternative type according to stage. We evaluated clinically the favorable and unfavorable outcome of endocrine therapy in Japan, so that others will be appropriately evaluated. In a cooperative study made by members of five universities, 572 patients with clinically or histologically reconfirmed prostatic carcinoma were entered in this retrospective study. We studied the true influence of prognostic factors on the prognosis of 497 patients with prostatic carcinoma who had received endocrine therapy, employing multivariate analyses, such as quantification method II, multiple regression analysis and Cox's proportional hazard model. Twelve factors were considered in the study; "age", "stage", "histological findings (structural atypism = SAT, nuclear anaplasia = NAN, Gleason's primary and secondary pattern)", "pretreatment level of total acid (ACP) and of alkaline phosphatase (ALP)", "castration performed or not performed", "doses of estrogen", "type of response of local prostatic tumor and of ACP to endocrine therapy". Analysis of the "importance" of a prognostic factor by a partial correlation determined by quantification method II, revealed "stage" to have the greatest "importance" on prognosis throughout the entire period. "Response of local prostatic tumor", "response of ACP" and "Gleason's primary pattern" tended to be important factors for prognosis, in particular, in the first half period, and "age" and "Gleason's secondary pattern" were important in the latter half. Multiple regression analysis revealed the "stage", once again to be the most influential factor on the prognosis for the entire observation period. Also "response of local prostatic tumor", "SAT" and "Gleason's primary pattern" affected the patients' prognosis in the first half of the observation period. In the latter half, "age" became more of an influential factor than "histological findings". Analysis with Cox's proportional hazard model revealed that "response of ACP", "stage", "age", "Gleason's primary and secondary pattern", and "response of local prostatic tumor" were definitely the more influential prognostic factors, of which chi-square values (or t values) were statistically significant. Comparison of the significant factors in each multivariate analysis revealed that common influential prognostic factors, such as "age", "stage", "histological findings (mainly Gleason's primary and secondary pattern)", "response of local prostatic tumor" and "response of ACP" were coincident to the clinical impression. The clarification of these factors would be clinically beneficial when treating patients with endocrine therapy.

We investigated how histopathological features, such as structural atypism (SAT), nuclear anaplasia (NAN) and Gleason's pattern, influence the prognosis of patients receiving endocrine therapy. Patients with SAT 3 or NAN 3 clearly had a lower survival rate and a shorter survival period than those with other grades of SAT or NAN and this tendency was more prominent in the high stage than low stage. Patients with a higher grade of SAT or NAN had a poorer prognosis as well, when only cancer-related death was considered in the calculation of survival and survival period. The results described above suggest that the grade of SAT and NAN is one of most influential factors for prognosis. In the analysis for the prognosis of patients according to grade of mean value of SAT + NAN, there were differences in prognosis among mean value of SAT + NAN 2-4, 5 and 6. This indicated that the combined grading system would provide more information to the prediction of prognosis. Patients with Gleason's primary (or secondary) pattern 1 and 2, or 3 and 4 had a better survival than those with pattern 5 in the analysis when only cancer-related death was considered. This was coincident with the result that the survival rate for each Gleason's sum 2-3, 4-5, 6, 7-8 and 9-10 was different. Consequently, Gleason's pattern influenced the rate of cancer-related deaths, and this pattern may be another important factor for predicting the prognosis.

A total of 49 patients complaining of pollakisuria and incontinence; 20 patients with overactive neurogenic bladder and 29 patients with stress incontinence, were treated with clenbuterol, and the effects of the drug were studied. Subjective symptoms were improved markedly in 8 patients (17%), moderately in 14 patients (29%), and slightly in 10 patients (21%). The symptoms were unchanged in 15 patients (31%) and aggravated in 1 patient (2%). In objective observation, the volume at first desire to void (P less than 0.01) and the maximum urethral closure pressure (P less than 0.05) significantly increased. The objective symptoms were improved markedly in 2 patients (5%), moderately in 12 patients (27%), and slightly in 11 patients (25%). The symptoms were unchanged in 15 patients (34%) and aggravated in 4 patients (9%). Overall improvement was graded as marked in 7 patients (15%), moderate in 17 patients (35%), slight in 11 patients (23%), unchanged in 13 patients (27%) and aggravated in none. In neurogenic bladder, the overall improvement was graded as marked in 2 patients (11%), moderate in 4 patients (21%), slight in 4 patients (21%), unchanged in 9 patients (47%) and aggravated in none. In stress incontinence, the overall improvement was graded as marked in 5 patients (17%), moderate in 13 patients (45%), slight in 7 patients (24%), unchanged in 4 patients (14%) and aggravated in none. Side effects were noted in 12 patients (25%) and they were all not serious. Finger tremor was the most common side effect (5 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

We have investigated the clinical significance of urinary tissue polypeptide antigen (TPA) as a tumor marker for urothelial cancers. Urinary TPA levels were determined by the immunoradiometric assay of Prolifigen TPA Kit "Daiichi"-II in 486 healthy controls and 1835 patients with various diseases including 526 with urothelial cancers and 140 with prostatic cancer. The mean value of urinary TPA was 199 +/- 213 (1SD)U/1 in 486 healthy controls. 95% of them having a level below 600 U/l. Therefore, 600 U/l was applied as a cut-off level. Positive rates of urothelial cancers and reactivated prostatic cancer were 57.6% (148 of 248 cases) and 45.5% (5 of 11 cases) respectively. On the other hand, the false positive rate of most urological benign diseases was only about 20% except for the acute stage of urinary tract infections and upper urinary tract stones with hydronephrosis. There was no significant difference in the positive rate between urinary TPA level and urinary cytology in urothelial cancers. The combination of both tests raised the positive rate to 73.1%. Therefore, urinary TPA may be useful in the monitoring of urothelial cancers, and the combination of urinary TPA and urinary cytology may increase the diagnostic accuracy.

Percutaneous transluminal angioplasty (PTA) was done in a 58-year-old man with hypertension due to a left-sided renal artery stenosis. Hypertension was cured dramatically and plasma renin activity was within the normal range after the operation. This non-traumatic procedure seems to be excellent and recommendable as a first treatment of renovascular hypertension.

A 65-year-old male visited the Sawara Hospital with the chief complaint of right intrascrotal mass. The mass without tenderness, in which right testis and spermatic cord appeared to be involved, reached the right inguinal region. Right high orchiectomy was performed under the diagnosis of a testicular tumor. Histological diagnosis was malignant lymphoma. Intravenous pyelogram revealed right hydronephrosis and 67Ga-scintigram showed an abnormal accumulation of radioisotopes in the pelvic and paraaortic region. Chemotherapy with vincristine, cyclophosphamide, 6-mercaptopurine and prednisolone was performed under the diagnosis of stage IV lymphoma. Two months after chemotherapy, right hydronephrosis disappeared and no abnormal accumulation in 67Ga-scintigram was found. He has been doing well three months after treatment.

A 52-year-old woman was admitted, complaining of an abdominal mass and jaundice. The abdominal mass was revealed to be myoma uteri. We explored her hormonal data for her virilizing signs. Urinary 17KS and pregnanetriol levels were elevated and decreased by cortisol administration. She was diagnosed to have 21-hydroxylase deficiency and has been well controlled at our out-patient clinic.

The present study was undertaken to assess the efficacy of single agent chemotherapy with alpha A-interferon or alpha 2-interferon for metastatic renal cell carcinoma. alpha A and alpha 2-Interferon were administered i.m. at a primary dose of 3 X 10(6) units/day to 13 patients. Two patients (15%) showed partial response; 1 patient (8%), minor response; 5 patients (38%), no change; 6 patients (46%), progressive disease. These preliminary observations indicate that these interferons are active antitumor agents in patients with renal cell carcinoma.

We performed circle tube nephrostomy in 17 patients using a newly designed catheter. The catheter which we called 'Chiba Nephrostomy Circle tube' consisted of a silicon tube which has three holes in the middle portion, and a metal connector. The renal function recovered to normal in 12 of the 17 patients (recovery rate 71%), improved in 4 (24%), and remained unchanged in only one patient. Although temporal urinary leakage occurred in 5 patients (29%), there were no serious complications with this newly designed tube. Furthermore, pyelonephritis, renal bleeding and urolithiasis, which occasionally occur by single nephrostomy, did not occur with this method. Thus, we proved the clinical usefulness of the newly designed circle tube.

Prostatic acid phosphatase was determined with Merck-Kanto's test kit on the cases of prostatic cancer experienced at our University Hospital from August in 1983 to February in 1985. Untreated cases were 4 stage A cases, 1 stage B case, 3 stage C cases, 3 stage D1 cases and 12 stage D2 cases. Nine cases were determined before and after hormonal treatment. From 67 controlled cases and 19 recurrent cases, 144 and 56 samples were selected, respectively. This method showed good reproducibility and even the serum stored at -80 degrees C after separation could be used for determination by addition of tartrate just before the measurement. The occurrence of abnormal values in untreated prostatic cancer cases, was 0% for stage A, 1 case for stage B, 33% for stage C and D1 and 75% for stage D2. Hormonal treatment decreased the high values of 5 cases and 1 case returned to normal. Compared to the recurrent cases, controlled cases showed a significantly larger ratio of negative, and it suggests that the test is useful for follow-up. Prostatic hypertrophy showed the increase of the value in 6% of the cases. Both prostatitis and urinary tract stone cases remained in the normal range.

The serum prostate specific antigen (PA) of the patients with prostatic cancer were determined with 3 assay kits, the Diagnostic Products Cooperation (DPC) kit, the Eiken kit and the Dainippon Pharmaceutical Co. (MARKIT F) kit. The first 2 assay kits involve radioimmunoassay and the latter EIA. For comparison, prostatic acid phosphatase (PAP) and gamma-seminoprotein (gamma-Sm) were determined using an Eiken kit and Chugai kit. Efficiency of the DPC kit, Eiken kit and the MARKIT F kit for untreated prostatic cancer was 26, 25 and 36%, respectively. The PA level measured using the Eiken kit and the MARKIT F kit both well correlated to the PAP level, but with the DPC kit correlation was slightly low. The PA level measured using the 3 different kits correlated poorly with the gamma-Sm level. The PA values obtained with 3 different assays from patients with prostatic cancer were highly correlated, but showed great differences in the values measured. When the standards used in the DPC kit were analyzed by the Eiken kit, the DPC standards as measured by the Eiken kit had only about half of their assigned values. The same standards were analyzed by the MARKIT F kit, the standards yielded measured values about one third of their assigned values. When the standards used in the MARKIT F kit were analyzed by the Eiken kit, the MARKIT F standards yielded measured values about 2.5 fold of their assigned values. The differences between the values obtained with the 3 assay kits presented a serious problem in clinical use of PA. Standardization of these assay kits will be awaited.

LH-RH analog (Buserelin) was administered in 10 cases of untreated prostatic cancer in our hospitals. All 10 cases had stage D2 disease. Five cases were of moderately differentiated carcinoma and 5 cases were of poorly differentiated carcinoma. The levels of luteinizing hormone and follicle stimulating hormone in blood plasma tended in decrease four weeks after treatment except for one case. The levels of testosterone in blood plasma reached the castrated level four weeks after administration except for the above one case. In adjacent effect by National Prostatic Cancer Project Criteria, the LH-RH proved to be effective in 6 of the 10 cases. The flush of face appeared in two cases, but it disappeared spontaneously. One case had a slight temporal macrohematuria one week after treatment.

Seventy of the 205 patients treated for bladder cancer in the past 8 years were over 70 years old (older group). The male to female ratio was 2.2 in older group, and that for the younger group was 4.1. The incidence of high grade cancer was larger in the older group than in the younger group. The 5-year survival rate was 42% for the older group and 66% for the younger group. The older patients with superficial cancer died mostly because of other causes and those with invasive cancer died of cancer. Eight cases of high grade, low stage cancer were treated by TUR or radiation, and they were well-controlled.

To reduce urinary calcium excretion, 50 mg of hydrochlorothiazide per day was given to 35 patients with hypercalciuria. Urinary calcium decreased significantly after 4 weeks of drug administration, but urinary magnesium did not change. Magnesium calcium ratio increased significantly. Although serious side effects were not seen, serum potassium decreased and serum uric acid increased significantly. From these results thiazide seems to be a useful and safe medicine to reduce urinary calcium excretion. The dose and method of administration require further examination because the patients have to take the drug for a long time.

From August, 1981 to May, 1984, we measured gamma-seminoprotein in the serum of 51 untreated patients with prostatic cancer in the Chiba University Hospital. Prostatic acid phosphatase (radioimmunoassay) in serum was also measured in these patients. We also measured gamma-seminoprotein and prostatic acid phosphatase in serum of patients under control by hormonal treatment and of reactivated patients. In untreated stage B and stage C cases, positive rate of gamma-seminoprotein in serum was larger than that of prostatic acid phosphatase. Therefore the measurement of gamma-seminoprotein in serum is considered to be useful in the diagnosis of early prostatic cancer. Four weeks after hormonal treatment, gamma-seminoprotein in the serum of 74% of the patients returned to the normal level. The positive rate of gamma-seminoprotein in the serum of reactivated patients is significantly larger than that of the patients under control by hormonal therapy.