Moderate dose diethylstilbestrol diphosphate therapy in hormone refractory prostate cancer.

OBJECTIVE: To examine the efficacy and toxicity of a moderate dose (250 mg/day) of diethylstilbestrol diphosphate (DES-DP) intravenously administered to patients with hormone refractory prostate cancer (HRPC) as well as the influence of this agent on the endocrine system. PATIENTS AND METHODS: Sixteen patients with HRPC were treated with a daily intravenous injection of 250 mg of DES-DP for 28 days. Eastern Cooperation Oncology Group (ECOG) performance status and pain score were used for subjective evaluation and PSA was used for objective evaluation. Testosterone, free testosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were used for hormonal parameters. RESULTS: Fourteen patients were eligible. The mean patient age was 75.2 years. With respect to the ECOG pain score, 5 patients scored 1 or higher, in 4 patients, the pain completely disappeared, and in 1 patient, the pain score improved from 4 to 1. The PSA level decreased significantly from 528 +/- 556 ng/ml (mean +/- SD) to 154 +/- 197 ng/ml. The DHEA level was not changed during DES-DP administration. The DHEA-S level decreased significantly from 882 +/- 430 ng/ml to 480 +/- 236 ng/ml. Testosterone and free testosterone were in the castration level before and during the treatment. Toxicity was minimal. None of the patients developed cardiovascular disorder. CONCLUSION: A moderate dose (250 mg/day) of DES-DP decreased PSA levels and relieved pain without causing serious toxicity in patients with HRPC. It is suggested that the mechanism of the DES-DP effect on the decrease in PSA and pain relief involves a decrease in DHEA-S.

Pheochromocytoma of the urinary bladder: a case report.

We present a 66-year old female patient with pheochromocytoma of the urinary bladder. We performed transabdominal needle biopsy of the tumor without suspicion of pheochromocytoma because of her well-controlled blood pressure and no characteristic symptoms following administration of antihypertensive medication. Hypertensive crisis (260/130 mmHg) occurred just after the needle insertion. The diagnosis was pheochromocytoma. The norepinephrine level in the serum and her blood pressure normalized without antihypertensive medication after partial cystectomy. Pheochromocytoma should be suspected in cases of intramural bladder tumors, especially in a normotensive patients receiving antihypertensive medication.

[PSA doubling time in prostate cancer relapsed after endocrine therapy].

PURPOSE: The PSA level of prostate cancer patients generally declines after endocrine therapy, but elevates when the cancer relapses in most cases. However, the rate of elevation differs with the case. We investigated the PSA doubling time (PSA-DT) of the prostate cancer patients whose PSA declined after endocrine therapy and later re-elevated, and investigated the relationship with other parameters. PATIENTS AND METHODS: We investigated 55 prostate cancer patients who underwent endocrine therapy between 1991 and 1998. Their PSA re-elevated continuously after their PSA fell below 10 ng/ml after the endocrine therapy as the first line treatment. First, the correlation coefficients with time and PSA were calculated in order to decide whether their PSA elevation was exponential or linear. PSA-DT was calculated thereafter, and compared with the clinical stage, pathological differentiation, clinical relapse style, time from the beginning of the therapy to PSA relapse, pre-treatment PSA value, and prognosis. The relationship between PSA-DT and each clinical parameter was tested using the Kruskal-Wallis test. Differences in survival rates and PSA-DT were calculated using the log-rank test. RESULTS: PSA elevated exponentially after cancer relapsed. PSA-DT in all cases ranged from 0.5 to 26.3 months, with an average of 4.4 +/- 4.8 (S.D.) months and the median was 2.5 months. PSA-DT was significantly (p < 0.01) short when the pre-treatment clinical stage was high, the time from the beginning of the therapy to PSA relapse was short, or the pre-treatment PSA value was high. PSA-DT tended to be short when the pre-treatment pathological differentiation was low, but not significantly. PSA-DT tended to be short when the cancer relapsed as distant metastasis rather than regional relapse, but not significantly. Prognosis from the initial treatment and PSA relapse was significantly poor when the PSA-DT was short. CONCLUSIONS: PSA elevated exponentially in the relapsed prostate cancer patients after the endocrine therapy. PSA-DT was distributed in a very wide range, and this value was considered to reflect the malignant potential and prognosis of the cancer. PSA-DT may be useful for determining the strategy after relapse.

[The result of mass screening of 1997 for prostatic cancer in Isesaki City].

PURPOSE: Screening by only prostate specific antigen (PSA) for prostate cancer was started since PSA had been added to mass screening as one of check lists in 1997 in Isesaki city, Gunma pref. We expected PSA screening to be introduced into other areas. We therefore studied how to perform a screening procedure for prostate cancer as well as discussed our result of the screening conducted lately. MATERIALS AND METHODS: 1,382 out of 1,423 Isesaki citizens who took mass screening aged 40 to 64 were chosen. Regardless of age, men with a serum PSA level equal or larger than 4.1 ng/ml (Tandem R) were selected for second screening since we determined it was a cut-off level for further check-up. Of those men, 38 were requested for second screening and actually only 24 took it. All these men took PSA check-up again, furthermore 23 took transrectal examination (TRE) and/or transrectal ultra sonography (TRUS) except for one of them. The next screening was requested for sixteen of them. Prostate biopsy was conducted for all of them. RESULTS: More old men took screening and were diagnosed prostate cancer. The findings derived from such diagnosis showed one of them aged 50 to 59 and six of them aged 60 to 64 had the cancer. Moreover, four out of twenty with PSA level ranging 4.1 to 10.0 ng/ml and all of three with PSA level over 20.0 ng/ml had the cancer. Five out of sixteen with a positive sign for further PSA check-ups had the cancer. All the three suspect of the cancer by TURS and DRE had prostate cancer. Two of seven with PSA negative showed suspicion of prostate cancer and had the cancer. No neo-adjuvant and total prostatectomy was conducted for four with 4.0 to 10.0ng/ml diagnosed T2N0 M0. One of them with PSA equal or over 20.0 ng/ml was diagnosed T3N0M0. After hormone therapy its PSA decreased to that equal or under 0.5 ng/ml. Total prostatectomy was conducted for it. CONCLUSION: It is not proved that only PSA mass screening for prostatic cancer contributes to detect early cancer and better prognosis cure case. For the proof, it will be nessary that PSA mass screening is examined more people in the wide area. We conclude men aged 65 to 69 also should take PSA check-up based on epidemiological feature of prostatic cancer.

[A case of pure leiomyoma of the prostate].

Pure leiomyoma of the prostate is very rare. A 67-year-old man was hospitalized with gross hematuria and urinary retention. Drip infusion pyelography revealed a defect of the urinary bladder. By radiological examinations, submucosal tumor of the bladder neck was diagnosed. Transrectal biopsy suggested a benign prostatic tumor histologically. Open resection of the tumor was performed. Histological findings were pure leiomyoma of the prostate. The postoperative course was good and urinary retention was improved remarkably.

[Prostate specific antigen doubling time in prostate cancer before treatment and in refractory status].

Prostate-specific antigen(PSA) increases exponentially in prostate cancer patients before treatment and in refractory status. PSA increases in 68-86% of prostate cancer patients before treatment, and that of the remaining 14-32% of the patients is stable. Those patients with a higher pre-treatment PSA level are more likely to have a shorter PSA-doubling time(PSA-DT). The relationship between pre-treatment stage, grade and PSA-DT is controversial. PSA-DT in biochemical failure patients predicts the risk of clinical recurrence. PSA-DT was correlated well with time to clinical recurrence after biochemical failure. Distant recurrence was associated with short PSA-DT. Higher clinical stage and lower differentiation before treatment correlated with shorter PSA-DT in recurrent cancer patients. PSA-DT is an important parameter for judging malignant potential of each cancer.

Transitional cell carcinoma in the fossa navicularis of the male urethra: a case report.

We report a case of transitional cell carcinoma arising in the fossa navicularis of the male urethra. The patient was 87-years-old and noticed intermittent urethral bleeding. We could see a tumor protruding from the urethral meatus, removed it successfully, and irradiated the base of the tumor with Nd:YAG laser. The histologic finding was grade 2 transitional cell carcinoma, pTa. There was no other tumor in the urinary bladder or upper urinary tract. The postoperative course was uneventful and the patient showed no evidence of disease for 4 months after treatment but died from other causes.

[Fundamental and clinical study of the anti-prostatic effect of allylestrenol].

The anti-androgen activity of allylestrenol was studied in the rat, and it was found to have an activity which was equivalent to that of chlormadinone acetate. The direct anti-prostatic activity is the result of the following mechanism: inhibition of serum testosterone uptake into the prostate, inhibition of testosterone-5 alpha-reductase activity and inhibition of 5 alpha-DHT . receptor complex formation. Large doses of allylestrenol administered to normal mature rats, inhibit the hypothalamus-pituitary-gonadal axis, and atrophy of the prostate will be more marked due to an indirect effect as a result of the reduction in the serum testosterone level. Based on this finding, we performed a clinical trial with allylestrenol in patients with hypertrophy of the prostate and cancer of the prostate. We administered 45 mg a day allylestrenol to 19 patients with prostatic hypertrophy and obtained satisfactory clinical results in so far as improvement of micturition and reduction in prostate mass was concerned. We also administered 90 mg a day of allylestrenol to 4 patients with cancer of the prostate and obtained a cytostatic effect.

Analysis of Estramustine binding protein (EBP) in rat dorsal prostate by means of high pressure liquid chromatography.

High pressure liquid chromatography (HPLC, Toyo Soda TSK-GEL G3000 SW column) was used to analyse the properties of Estramustine binding protein (EBP) in the cytosol of rat dorsal prostate. There exist in the cytosol of rat dorsal prostate two binding components having a high affinity for Estramastine. When estimated by HPLC, the molecular weights of these Estramustine binding components are 45,000-50,000 and 25,000-30,000 daltons, respectively. The binding of 3H-Estramustine to a macromolecule with a molecular weight of 25,000-30,000 is more heat labile than binding of 3H-Estramustine to a macromolecule with a molecular weight of 45,000-50,000. The present study also demonstrates that the HPLC method offers higher resolution, smaller sample size and faster analysis than other methods used in binding studies.