Biomedical subjects

F H Schroeder

Publications and source records attributed to F H Schroeder.

At least 19 recordsLinked to original sources

PubMed1997

A comparison of disease specific survival of patients who died of and who had newly diagnosed prostate cancer.

PURPOSE: We investigated the validity of calculating prostate specific survival from a population of deaths occurring during a given period. MATERIALS AND METHODS: Stochastic simulation was used to generate a large number of life histories of men with prostate cancer. RESULTS: The investigated method of calculating survival can lead to different outcomes compared to the standard method. In an example with a Dutch population structure the investigated method leads to strong underestimation of 25 years of survival. CONCLUSIONS: The method of calculating survival studied is theoretically not valid. Several probable changes in the population can produce results that are different from the standard method of calculating survival.

Humans↗

PubMed1996

Results of radical prostatectomy in men with clinically localized prostate cancer.

OBJECTIVE: To assess the results of radical prostatectomy in men with early prostate cancer. DESIGN: Retrospective, nonrandomized, multi-institutional pooled analysis. SETTING: Eight university medical centers in the United States and Europe. PATIENTS: A total of 2758 men with stage Tl and T2 prostatic cancer. MAIN OUTCOME MEASURES: Disease-specific and metastasis-free survival rates. RESULTS: Tumor grade was the most important preoperative factor in determining outcome. Disease-specific survival 10 years following surgery and associated 95% confidence intervals were 94% (range, 87%-98%), 80% (range, 74%-85%), and 77% (range, 65%-86%) for those men with grade 1, 2, and 3 tumors, respectively. Metastasis-free survival at 10 years was 87% (range, 78%-92%), 68% (range, 62%-73%), and 52% (range, 38%-64%) for patients with grade 1, 2, and 3 cancers, respectively. CONCLUSIONS: Radical prostatectomy leads to high 10-year disease-specific survival rates in men with all tumor grades. However, caution is needed in comparing these results with similar studies of alternative treatment strategies, such as watchful waiting, due to the inherent potential biases in uncontrolled trials. Nevertheless, these results offer the best currently available estimates of 10-year outcome of radical prostatectomy in men with clinically localized prostate cancer and may be useful in counseling patients with early malignancy.

Europe↗

PubMed1996

Radical prostatectomy: prospective assessment of mortality and morbidity.

OBJECTIVE: To prospectively analyse the morbidity of radical prostatectomy. METHODS: Morbidity data from 188 consecutive radical prostatectomy patients were collected prospectively. Mortality, intraoperative, early postoperative and late postoperative complications were analysed. RESULTS: 1.5% mortality. 3.7% suffered an intraoperative complication. Early postoperative problems were common (43%). Of those with greater than 1 year follow-up, 5.9% remained with some incontinence, and a further 11 patients had artificial sphincters implanted; 32% had narrowing of the anastomosis, requiring at least 1 dilation; 43% of patients retained their potency. CONCLUSIONS: It is concluded that radical prostatectomy can be performed with minimal mortality and acceptable morbidity.

Aged↗

PubMed1995

Prostate cancer.

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Antigens, Neoplasm↗

PubMed1995

The geography of prostate cancer and its treatment in Japan.

The age adjusted death rate from prostate cancer in Japan is one of the lowest in the world but is rising steadily. The vast majority of cases of prostate cancer remain undetected during life, the prevalence of prostate cancer detected at autopsy being 2800 times that of lethal cancer in Japanese in Japan, 570 times in whites in the USA and 470 times in blacks in the USA. A case-control study of prostate cancer carried out in Japan and the Netherlands revealed a number of statistically significant risk factors, including rural residence, more brothers, colon neoplasms in relatives, no morning erections, frequent sexual intercourse in 30s, episodes of sexually transmitted disease, lower plasma testosterone and dihydrotestosterone concentrations and lower beta-carotene intake.

Humans↗

PubMed1994

Frequency and characterization of p53 mutations in primary and metastatic human prostate cancer.

We have studied the frequency of mutations in the p53 gene in human prostate cancer. The investigated material consisted of 20 primary-tumor tissue specimens, obtained by transurethral resection and tissue specimens of 15 lymph-node metastases, obtained at total prostatectomy. The applied methods encompassed immunohistochemistry on frozen sections, using the monoclonal antibody PAb 1801, and single-strand conformation polymorphism (SSCP) analysis, after amplification of single exon sequences by PCR, on exons 5 to 8 of the p53 gene. The mutations, leading to aberrantly migrating bands in the PCR-SSCP analysis, were identified by direct sequencing of the PCR product. Immunohistochemical and PCR-SSCP analysis were completely confirmative. In the primary tumors, mutations were found in 10% of the specimens (codons 232 and 273), and in lymph-node metastases in 15% of the specimens (codons 248 and 273). In one case (codon 273), the same mutation was found both in the primary tumor and in the lymph-node metastasis. Our results show that p53 mutations are infrequent in both primary and metastatic prostate tumors. In addition, they indicate that there is no strict correlation between p53 mutation and tumor metastasis.

Amino Acid Sequence↗

PubMed1994

From laboratory expertise to clinical practice: multidrug-resistance-based gene therapy becomes available for urologists.

Many human tumors such as bladder carcinoma that are initially responsive to chemotherapy eventually fail to respond to treatment. For most drugs, dose escalation that may be required for a cure cannot be achieved because sensitive tissues such as bone marrow limit cytotoxic therapy. Approaches to prevent or circumvent myelosuppression are therefore a high priority of research on dose intensification protocols. One such strategy is to protect bone marrow cells by virtue of expression of the multidrug-resistance (MDR1) gene encoding for P-glycoprotein. In our first set of experiments, we transplanted bone marrow cells derived from transgenic mice that constitutively express MDR1 to lethally irradiated recipients (n = 36). From 6 weeks to 10 months after the transplant, all animals contained MDR1 DNA in spleen and bone marrow specimens as indicated by Southern-blot analysis and expressed MDR1 RNA in bone marrow samples as detected by slot-blot analysis. In addition, these animals were resistant to the myelosuppressive effect of doxorubicin, daunomycin, taxol, vinblastine, vincristine, etoposide, and actinomycin D, whereas control animals that were reconstituted with normal bone marrow reacted with a significant decrease in their white blood counts. In a second set of experiments, we retrovirally transfected a construct consisting of a murine long-terminal repeat (LTR) promoter and the human MDR1 gene into CD34-positive bone marrow stem cells from rhesus monkeys using the same technique as in the ongoing clinical ADA gene-therapy protocol. Upon transplantation, high-level and long-lasting expression of the human MDR1 gene was observed in recipient monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Androgens and androgen-receptors in prostate tissue from patients with benign prostatic hyperplasia: effects of cyproterone acetate.

Testosterone, 5 alpha-dihydrotestosterone and cyproterone acetate (CPA) were estimated in samples of prostate tissue, obtained from benign prostatic hyperplasia (BPH) patients who were or were not pretreated with CPA. Furthermore, these steroids were estimated in various fractions of the BPH tissue, and the number of nuclear androgen-receptor sites was determined. CPA-treatment caused a 4-fold, significant suppression of 5 alpha-dihydrotestosterone levels in total prostate tissue and its subfractions, without affecting testosterone levels or the androgen-receptor contents of the nuclear extracts. Nuclear concentrations of CPA were twice as high as those of 5 alpha-dihydrotestosterone. It is concluded that effects of CPA may have been caused through a combination of the following mechanisms: (1) suppression of peripheral androgen levels; (2) competition with androgens for (nuclear) androgen-receptors; and (3) suppression of prostatic 5 alpha-reductase.

5-alpha Reductase Inhibitors↗

PubMed1992

Physical characteristics and factors related to sexual development and behaviour and the risk for prostatic cancer.

A case-control study of prostatic cancer was carried out to examine the association between selected physical characteristics and factors related to sexual development and behaviour and the risk for this disease. In consideration of an endocrinologic mechanism for these putative risk factors, the association between selected factors and serum hormone level in a comparison group, free of prostate cancer, was also examined. One-hundred cases and 113 controls were included for study. An elevated risk for prostatic cancer was found for those currently married (odds ratio (OR) = 4.0), those who had been married once (OR = 2.8), and those who were currently practising a religion (OR = 2.0). Compared to subjects with one child, those with more than one child and those with no children were more common among cases than controls. Prostatic cancer risk was associated with large body size and, in particular, with greater weight (p < 0.01). Early age at attainment of adult height was also associated with prostatic cancer risk (p < 0.01). Only moderate associations were found between increased frequency of sexual intercourse and prostatic cancer risk. The levels of testosterone (T), dihydrotestosterone, salivary testosterone and T/SHBG (sex hormone binding globulin) did not vary with age. Older men had higher oestradiol levels. Further, little association between hormone levels and risk factors was found, except for married subjects having increased serum androgens (p < 0.05) and heavy subjects having decreased serum androgens (not significant).

Age Factors↗

PubMed1991

Peripheral hormone levels in controls and patients with prostatic cancer or benign prostatic hyperplasia: results from the Dutch-Japanese case-control study.

The possible relationship between changes in peripheral hormone levels and the occurrence of prostatic pathology was studied in a case-control study, involving estimation of various plasma hormones in 368 Dutch and 258 Japanese men, who were grouped as controls and patients with benign prostatic hyperplasia, focal prostatic carcinoma, or clinically evident prostatic carcinoma. Results of a number of previous, smaller studies concerning interrelationships between hormone levels in elderly men were confirmed within the Dutch and Japanese groups. Plasma levels of testosterone and estradiol were significantly lower in the Japanese men, when compared with those in Dutch men. Probably as a result of this difference in testosterone levels, the ratio between serum levels of testosterone and sex hormone-binding globulin (SHBG) was decreased in the Japanese men, while the ratio between the concentrations of dihydrotestosterone and testosterone was increased. These differences were also found when results from Japanese subgroups (controls and patients with prostate pathology) were compared with those from the Dutch subgroups. There were no significant differences in plasma androgen levels between Japanese or Dutch prostate cancer cases and their respective control subgroups. These findings do not support a correlation between the lower plasma testosterone levels and a lower incidence of prostate cancer in the Japanese men. Furthermore, no significant differences were found between salivary levels of testosterone or the ratio between testosterone and SHBG in the various Dutch subgroups. In Japanese benign prostatic hyperplasia patients, the testosterone to SHBG ratio was significantly increased. In conclusion, the results of this retrospective, cross-sectional study do not indicate that hormonal levels play a primary role in the origin or promotion of prostatic abnormalities. The finding of a lower plasma testosterone in the Japanese men, however, remains suggestive, warranting a more extensive prospective study.

Age Factors↗

PubMed1991

Evaluation of prostate-specific antigen and prostatic acid phosphatase in untreated prostatic carcinoma and benign prostatic hyperplasia.

Prostate specific acid phosphatase (PAP) (Abbott, solid-phase enzyme immunoassay) and prostate specific antigen (PSA) (Hybritech, immunoradiometric assay) were determined in 162 newly diagnosed prostatic carcinoma patients, 187 patients with benign prostatic hyperplasia (BPH) and 127 controls. The upper limit of normal in controls for PAP was 2.2 micrograms/l and for PSA 5.0 micrograms/l. In the BPH group PAP was raised in 21%, for PSA in 41%. When the cut-off level of PSA was raised to 10.0 micrograms/l, 20% of BPH patients had an increased level. PSA was superior to PAP for the detection of prostatic cancer in all stages. Of the 162 patients with prostatic carcinoma, 88 had localised diseases and 74 had metastatic spread. PSA and PAP levels increased with each advancing clinical stage. PAP was elevated in 35% of the patients with cancer confined to the prostate. PSA in 69%. (PSA level 10.0 micrograms/l: 57%). In those patients with metastatic spread PAP was elevated in 77% compared with 96% for PSA. (PSA level 10.0 micrograms/l: 92%). The combined use of PSA and PAP does not give a greater accuracy in the screening of prostate cancer when compared with the sole use of PSA. PAP was elevated in only 4 patients when PSA was normal. In the BPH group there was no proven effect of micturition, frequency or residual urine on the SPA level. However, in this group infection may cause a rise in the PSA level.

Acid Phosphatase↗

PubMed1990

Androgen receptor heterogeneity in human prostatic carcinomas visualized by immunohistochemistry.

Expression of the human androgen receptor was examined in 26 primary prostatic carcinomas by immunohistochemical staining with a polyclonal antibody reactive with the N-terminal domain of the human androgen receptor. Eighteen carcinomas showed homogeneous staining for the androgen receptor, whereas in seven cases a considerable heterogeneity in expression of the receptor was found. In one case, only a very limited number of immunoreactive tumour cells were detected. Comparison of androgen receptor expression with the tumour grading score, according to the MD Anderson grading system, revealed that the proportion of immunostained tumour cells and--to a lesser extent--the intensity of immunostaining were decreased in the more aggressive (grade III) tumours. The use of immunohistochemistry for detection of expression of androgen receptor in prostatic carcinomas may become a new and sensitive method for predicting prostatic tumour behaviour under hormonal therapy and prognosis.

Aged↗

PubMed1990

A case-control study of prostatic cancer in Kyoto, Japan: sexual risk factors.

A case-control study on prostatic cancer was conducted in Kyoto, Japan, from 1981-1984, including 100 patients with prostatic cancer (PC) and age, hospital, and date-of-admission matched controls of benign prostatic hyperplasia (BPH) patients and general hospital patients. Analysis of several sexual factors obtained through a self-administered questionnaire revealed the following observations: 1) cancer patients had fewer sex partners before marriage (relative risk, RR = 0.35; 95% confidence interval: 0.13-0.93) than the hospital controls; 2) they had more vigorous sexual activities in the third (RR = 2.89; 1.01-8.28) and fourth decades of life (RR = 2.26: 1.03-4.95) than hospital controls, but no significantly different sexual activities from controls in other decades; 3) they had less frequent orgasms (RR = 2.55; 1.11-5.83) than BPH controls or (RR = 4.96: 1.78-13.9) hospital controls, and sexual intercourse appeared to be less satisfactory (RR = 2.08: 1.05-4.13) than that of hospital controls; and 4) they had less frequent episodes of sexually transmitted diseases (RR = 0.36: 0.16-0.83) than BPH controls. Marital status, fertility, ejaculation, masturbation, nocturnal emission, contraceptive use, and wife's episodes of sexually transmitted disease were not linked to prostatic cancer risk.

Case-Control Studies↗

PubMed1990

Variation of prostate-specific antigen expression in different tumour growth patterns present in prostatectomy specimens.

A series of 55 randomly chosen radical prostatectomy specimens was analyzed for expression of prostate-specific antigen (PSA) by immunohistochemical techniques. Tissue sections were selected in such a manner that in addition to glandular benign prostatic hyperplasia (BPH), one or more different prostatic tumour growth patterns were present. Four monoclonal antibodies, directed against three different PSA epitopes, and one polyclonal anti-PSA antiserum were used. Expression of PSA was compared with that of prostate-specific acid phosphatase (PAP), recognized by two different polyclonal antisera. A critical dilution aimed at a maximum of staining intensity on BPH tissue sections was chosen for all antibodies. Anti-PSA and anti-PAP antisera stained essentially all BPH samples (over 90%). Irrespective of the nature of the antibodies used, PSA expression was found to be decreased in prostatic carcinoma. A clear cut relationship was found between immunoreactivity for PSA and the degree of differentiation of the tumour area. Under the experimental conditions used the PSA monoclonal antibodies stained only 1 out of 10 undifferentiated carcinomas, whereas 50% to 70% of the well- and moderately-differentiated carcinomas showed immunoreactivity. This correlation was less pronounced with the PAP staining pattern. If the PSA antibody titer was raised the percentage of clearly staining undifferentiated carcinomas could be considerably increased (up to 60%-100%), indicating that PSA expression is not absent, but lowered in most (if not all) undifferentiated carcinomas.

Acid Phosphatase↗

PubMed1990

Morphometrically estimated variation in nuclear size. A useful tool in grading prostatic cancer.

At present there are several grading systems for prostatic carcinoma. Most are difficult to reproduce. An objective method of grading seems to be necessary and could make comparisons between various groups of patients easier and grading more reliable. In the present study morphometrically estimated nuclear size and variation in nuclear size are matched with the survival rates of 207 patients who underwent total perineal prostatectomy for cancer. On the basis of morphometrically estimated variation in nuclear size the patients could be divided into two groups with significantly differing survival rates. In this way it was possible to split the group of patients with grade 2 carcinoma (Mostofi's grading system) into two groups of patients with significantly different survival rates. The survival rates in these two groups did not differ significantly from those in the patients with Grade 1 and Grade 3 tumors respectively. The results are discussed in the light of the recent literature on the subject. Morphometry seems to be a valuable tool in grading prostatic cancer.

Cell Nucleus↗

PubMed1990

Prolonged treatment with the GnRH analogue buserelin does not affect alpha-subunit production by the pituitary gonadotroph.

Seven patients with metastatic prostatic cancer were treated with biodegradable implants of the GnRH analogue buserelin and six were treated with buserelin intranasally. After 4-24 weeks of treatment mean serum testosterone concentrations were significantly lower in the patients treated with implants than in those treated intranasally (0.7 vs 1.7 nmol/l respectively; P less than 0.01). Also, serum LH concentrations were significantly lower in the group treated with implants. Serum alpha-subunit concentrations were significantly higher than pretreatment values during buserelin treatment. However, the sum of the concentrations of alpha-subunit present either as free alpha-subunit or as a part of LH did not differ significantly from pre-treatment values after 8 weeks or more of buserelin treatment. During buserelin treatment serum LH concentrations measured by radioimmunoassay (RIA) were higher than those measured by immunoradiometric assay (IRMA). Cross-reactivity of alpha-subunit in the LH RIA accounted for many, but not all, of the observed discrepancies. We conclude that: (1) the principal long-term effect of prolonged buserelin administration on the pituitary gonadotroph is the suppression of LH beta production, while alpha-subunit production is not affected; (2) the serum concentrations of bioactive LH are better reflected by LH concentrations measured by IRMA than by those measured by RIA. (3) Subcutaneous application of biodegradable buserelin implants is more effective in suppressing serum LH and testosterone concentrations than intranasal buserelin application.

Buserelin↗

PubMed1989

Case-control study of prostatic cancer in Kyoto, Japan: demographic and some lifestyle risk factors.

Demographic risk factors for prostatic cancer were examined in a case-control study of 100 triplets of prostatic cancer patients and age-, hospital-, and admission date-matched control series of benign prostatic hyperplasia (BPH) patients and general hospital patients. A higher risk of prostatic cancer was associated with the following factors: 1) long-term occupation in transport or communication (relative risk [RR] = 4.92, 95% confidence interval [CI]: 1.18-20.5) as compared with hospital controls; 2) the wife having a lower educational level (RR = 1.88, 95%CI: 1.02-3.45) as compared with hospital controls; 3) no past episode of hypertension as compared with BPH controls (RR = 2.30, 95%CI: 1.27-4.15); 4) having several sisters (more than four) as compared with both BPH and hospital controls (RR = 3.82, 95%CI: 1.35-10.8 and RR = 2.94, 95%CI: 1.08-8.03 respectively); 5) dense body hair as compared with hospital controls (RR = 4.28, 95%CI: 1.19-15.4). No significant links were found with blood type, daily drug use, head hair, skin color, body type, smoking habits, religion, body weight, and mental characteristics.

Aged↗

PubMed1989

Monoclonal antibody Ki-67 defined growth fraction in benign prostatic hyperplasia and prostatic cancer.

Growth fractions were assessed immunohistochemically in prostatic tissues with benign glandular hyperplasia (BPH) and in specimens of prostatic cancer using the monoclonal antibody Ki-67. This antibody is specific for a proliferation-associated nuclear antigen. In BPH tissues about 0.3% of nuclei of epithelial cells was reactive with Ki-67. The Ki-67 positive nuclei were distributed equally among the basal and luminal cells of the hyperplastic prostatic acini. In prostatic cancer the Ki-67 defined growth fraction ranged from 0.4% to 9.1% (mean value 2.9%). Cancers with a cribriform growth pattern and tumors composed of solid areas of undifferentiated cancer cells showed the highest growth fraction (average values 4.0%, respectively 7.6%). The investigated four tumors composed of undifferentiated solitary tumor cells with diffuse infiltration of the stroma demonstrated an unexpectedly low growth activity (average 1.2%). In cancers with a glandular growth pattern the Ki-67 defined growth fraction of tumor cells varied from 2.2% to 5%. Compared with other epithelial tumors these values are low, but they are in agreement with the earlier findings on prostatic cancer obtained with 3H-thymidine labeling and bromodeoxyuridine incorporation. The observed variation in the level of Ki-67 defined growth activity partly related to the histological tumor pattern suggests that Ki-67 labeling may serve as a prognostic factor additional to the current histopathological grading criteria of prostatic cancer.

Adenocarcinoma↗