Plasma testosterone in patients receiving diethylstilbestrol

With accurate, inexpensive plasma testosterone assays now available it is possible to monitor the efficacy of hormonal manipulation in the patient with adenocarcinoma of the prostate. We monitored plasma testosterone in our patients receiving diethylstilbestrol (DES) 1 mg. per day. We found no statistical difference in mean plasma testosterone between patients with adenocarcinoma of the prostate and castrated patients with prostatic carcinoma, all receiving DES, 1 mg. per day. We recommend that plasma testosterone be closely monitored in patients receiving hormonal therapy for adenocarcinoma of the prostate.     

Plasma Neuroendocrine Markers in Patients with Benign Prostatic Hyperplasia and Prostatic Carcinoma

Purpose

Approximately 50 percent of all malignant prostatic tumors contain neuroendocrine cells, which cannot be attributed to small cell prostatic carcinoma or carcinoid-like tumors, and which represent only 1 to 2 percent of all prostatic malignancies. Only limited data are available concerning the plasma levels of neuroendocrine markers in patients with prostatic tumors. Therefore, we determined the incidence of high plasma levels of neuroendocrine markers in patients with benign and malignant prostatic disease.

Materials and Methods

The presence of elevated plasma neuropeptide levels was investigated in 135 patients with prostatic carcinoma and 28 with benign prostatic hyperplasia. Plasma chromogranin A, neurone-specific enolase, substance P, calcitonin, somatostatin, neurotensin and bombesin levels were analyzed by immunoassays, and were compared to clinical and pathological stages of disease. Plasma prostatic acid phosphatase and prostate specific antigen levels were also determined. All patients were followed for at least 2 years after inclusion in the study.

Results

Significantly elevated levels of chromogranin A were detected in 15 percent of patients with prostatic carcinoma before any treatment. During hormone resistant prostate cancer progression plasma chromogranin A and neuron-specific enolase levels were elevated in 55 percent and 30 percent of the patients, respectively. In patients with stage D3 disease survival curves were generated by the Kaplan-Meier method, and log rank analysis revealed a statistically significant difference between groups positive and negative for chromogranin A. Substance P and bombesin were also occasionally elevated in prostatic tumors. Determination of neuroendocrine differentiation by neuron-specific enolase or chromogranin A immunoassays was not helpful in the prediction of progressive localized prostatic carcinoma.

Conclusions

Future studies of plasma neuropeptide levels should confirm whether these parameters can be used as prognostic markers during late progression of prostatic carcinoma or for the selection of patients suitable for evaluation of new antineoplastic drugs known to be active against neuroendocrine tumors.     

Bromocriptine and prostatic carcinoma: testosterone metabolism in relation to tumor grading (author's transl)]

Since Prolactin has intra- and extrapostatic effects on growth and function of the prostate, the influence of the anti-prolactin bromocriptine (PRAVIDEL) was investigated in 15 patients with untreated prostatic carcinoma of various grades of differentiation in vivo. A five-days treatment with 15 mg Pravidel daily significantly suppressed prostatic androgen uptake, unrelated to tumor grading. 5 alpha-Reductase was favored in poorly differentiated lesions with a decreased testosterone/dihydrotestosterone ratio. The pretherapeutic accumulation of 5 alpha-androstanediol was diminished after Pravidel and the tissue/plasma ratio decreased. The 17 beta-hydroxy-pathway of testosterone is predominant as compared to the 17-keto pathway; both pathways are favored after Pravidel in poorly differentiated tumors. Intraprostatic metabolic effects of Pravidel are not related to peripheral androgen levels nor are they dependent on altered prostatic hormone uptake. In the poorly differentiated prostatic tumors Pravidel initiates a metabolic situation as observed in prostate cancer responding to androgen depletion or estrogen therapy.     

The intraprostatic spiral: clinical results in 150 consecutive patients.

The clinical results of treatment of infravesical prostatic obstruction with an intraurethral coil in 150 consecutive patients are reported. A total of 80 patients had urinary retention and 70 had severe prostatism. Median observation time was 8.2 months, with a range of 0 to 40 months. In 75 patients the spiral was removed after a median of 4 months (range 0 to 30 months) because of planned prostatectomy in 17, urinary retention in 16, incontinence in 10, local discomfort in 7, no symptomatic improvement in 13 and causes not related to the spiral (stroke and so forth) in 7. Migration occurred 55 times in 42 patients but this only led to coil removal in 5. A total of 23 patients died with the coil in situ. Voiding symptoms improved considerably in the majority of the patients. Approximately two-thirds of the patients had no or few symptoms, while a fourth had moderate symptoms, leaving only approximately 10% with severe prostatism. Chronic bacteriuria was noted in 52 patients but was not a clinical problem. Calcification on the top and inside of the coil was noted mainly after long-term treatment, and probably necessitated exchange of the coil after 2 to 3 years. We conclude that the prostatic spiral is a useful alternative to an indwelling catheter. However, life-long followup is necessary in most patients.     

Prostatic biopsy in selected patients with carcinoma in situ of the bladder: preliminary report

Transitional cell carcinoma was found in biopsies of grossly normal-appearing prostates in 4 of 40 patients with recurrent carcinoma in situ of the bladder. In selected patients prostatic biopsy may be warranted if conservative therapy does not control the bladder tumors and if cystectomy is contemplated.     

Prostatic capsule- and seminal-sparing cystectomy for bladder carcinoma: initial results for selected patients

OBJECTIVE: To evaluate the oncological outcome and functional results of prostate-sparing cystectomy (PSC), proposed for treating bladder cancer, used since 1999 in our institution in an attempt to preserve male sexuality and to increase continence after cystectomy. PATIENTS AND METHODS: Between January 1999 and December 2001, 111 men were candidates for cystectomy; 42 were selected for a prostatic capsule- and seminal-sparing cystectomy with orthotopic urinary diversion. All patients had clinically organ-confined tumours (clinical stage 相似文献   

Prostatic acid phosphatase in serum and bone marrow in patients with prostatic carcinoma

Sixty-two per cent of 61 patients with prostatic carcinoma showed elevated levels of serum acid phosphatase, analysed by radioimmunoassay (RIA). Enzymatically determined serum acid phosphatase was raised in only 38% of the same patients. Bone marrow acid phosphatase determined by RIA was raised in 41%. In untreated metastatic patients with prostatic carcinoma, radioimmunologically determined serum acid phosphatase was elevated in 12 of 13 patients, whereas bone marrow acid phosphatase (RIA) and enzymatically determined serum prostatic acid phosphatase were increased only in about half of the patients. In a control group the upper reference limit of bone marrow acid phosphatase determined by RIA was significantly raised above that obtained by serum analyses. This indicates that nonprostatic acid phosphatases (possibly from bone marrow cells) cross-react with prostatic acid phosphatase in an unpredictable way, even when using a specific radioimmunoassay. In patients with metastatic carcinoma of the prostate, the results of bone marrow acid phosphatase determinations, analysed by RIA, seem to lack diagnostic and/or prognostic information additional to that obtainable by serum acid phosphatase (RIA) analysis.     

Prostatic carcinoma: complications of megavoltage radiation therapy

Megavoltage radiation therapy and radical prostatectomy are at present the only curative treatments for prostatic carcinoma. Because a high complication rate appeared to follow radiotherapy, all patients with prostatic carcinoma presenting to a Danish provincial hospital between 1975 and 1980 were reviewed. Of 31 radiation-treated patients, 23 had serious complications. No recurrence was noted in eight patients. Twenty-three had a recurrence despite radiotherapy but 11 of these patients had no local recurrence. In view of the high level of complications following radiation therapy and the high incidence of latent carcinomas in the prostate gland, a cautious approach to radiotherapy is recommended.     

Bromocriptine and prostatic carcinoma: plasma kinetics, production and tissue uptake of 3H-testosterone in vivo

The influence of the anti-prolactin bromocriptine on plasma kinetics, production rate and tissue uptake of testosterone was investigated in 15 patients with newly diagnosed stages C and D prostatic carcinoma. Bromocriptine was given for 5 days in a daily dose of 15 mg. orally. The studies were performed with the single injection technique using the 2-compartment model. Plasma testosterone, serum prolactin, and luteinizing and follicle-stimulating hormones were determined initially. Blood samples were drawn up to 5 hours after the injection of 3H-testosterone. For tissue studies a transrectal needle biopsy was done 3 hours post-injection. Bromocriptine suppressed prolactin and the endogenous testosterone level. Furthermore, it favored the elimination of 3H-testosterone, lowered the production rate of testosterone and hampered the in vivo uptake of the 3H-label into prostatic carcinoma tissue. Finally, the grading of the tumor lesions affected only the pre-bromocriptine uptake of radioactive androgens and not the uptake in response to bromocriptine. The potential clinical impliications of these observations are discussed.     

Prostatic carcinoma: histological and immunohistological factors affecting prognosis

Neuro-endocrine or paracrine cells of the human prostate and urethra have been identified by various methods, predominantly silver stains and immunocytochemistry. The incidence of neuro-endocrine differentiation in prostatic carcinoma has varied considerably from 10 to 100%, but has not been studied previously as an independent factor affecting prognosis. Nucleolar organiser regions (NORs) are loops of ribosomal RNA occurring in the nucleoli of cells which ultimately process RNA genes. NORs have been demonstrated by silver (Ag) staining techniques and have been studied in numerous malignant tumours. A pilot study from this laboratory has shown a distinct and significant difference in AgNOR staining between prostatic carcinoma and benign prostatic epithelial hyperplasia. A retrospective study was performed with at least 6 years' follow-up. This confirmed the presence of neuro-endocrine cells in more than half of the patients under investigation. A significant correlation between survival and the absence of neuro-endocrine cells was demonstrated. AgNOR staining was shown to be of no prognostic value.     

Plasma testosterone in adult normoglycaemic men: impact of hyperinsulinaemia

This study analysed the relationship of plasma testosterone with β‐cell secretion, insulin sensitivity and other pituitary‐target gland hormones in normoglycaemic adult men. The sample frame was the ‘Offspring of individuals with diabetes study’ database. A total of 358 offspring of individuals with type‐2 diabetes (T2DM) and 287 individuals without known family history of T2DM were recruited for the study. Normoglycaemic men aged ≥18 years (maximum 55) were selected for this analysis. All participants underwent 75 g oral glucose tolerance test (OGTT); blood samples were collected at 0, 30, 60 and 120 min for plasma insulin and C‐peptide. Total testosterone, cortisol, adrenocorticotropic hormone, thyroid stimulating hormone and thyroxine (T4) were measured in the fasting sample. A total of 164 men (age 28 ± 7.7 years) were included in analysis. Testosterone correlated negatively with BMI, waist to hip ratio (WHR), area under curve (AUC) of C‐peptide and insulin (during OGTT) and was positively correlated with insulin sensitivity (r ~ 0.4). Cortisol and T4 positively correlated (weak) with testosterone (r ~ 0.2). In multivariate analysis, AUC C‐peptide, BMI, WHR (negatively) and cortisol (positively) were related to testosterone. Concluding, testosterone correlated negatively with BMI and β‐cell secretion. There was a positive association of testosterone with insulin sensitivity, cortisol and T4.     

Plasma testosterone and estradiol levels in unilateral cryptorchidism

This research was conducted to investigate the relationship between plasma hormone level during activation of hypothalamic-pituitary-testicular axis at the postnatal period and at puberty in unilateral cryptorchidism. Plasma testosterone and estradiol levels of 80 patients with unilateral cryptorchidism at different ages (range: 6 months-12 years) were measured. The mean plasma testosterone level is 40 (15-60) pg/ml at 6 months of age, 55 (30-120) at ages between 9 and 12 years, and 20 (11-22) at ages between 1 and 9 years. The mean plasma estradiol level is 12, 11 and 11 (5-24) pg/ml, respectively, in these groups. The patients with unilateral cryptorchidism do not have similar peaks of plasma estradiol level as plasma testosterone level at the postnatal period and at puberty. Peak of plasma testosterone at puberty occurs if the patients were not operated on.     

Testosterone metabolism in patients with advanced carcinoma of the prostate: A comparative in vivo study of the effect of oestrogen and anti-prolactin

Summary In the light of the high incidence of cardiovascular side effects with oestrogen therapy in patients with prostatic cancer, other medications altering androgen metabolism are under investigation. The influence of the anti-prolactin bromocriptine (CB154) on plasma kinetics of testosterone and on endogenous hormones was studied and compared with the effect of ethinyl oestradiol in 25 patients with prostatic carcinoma. Bromocriptine significantly suppressed both prolactin and testosterone, inhibited the transfer of androgen from the inner pool into the deep compartment and favoured its degradation. Ethinyl oestradiol decreased testosterone, LH and FSH, and prolonged the biological half-life of testosterone. The effects of bromocriptine on androgen metabolism might be of therapeutic value in patients with prostatic carcinoma.