Polymerase chain reaction in the detection of micrometastases and circulating tumor cells.
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Biomedical subjects
Publications and source records attributed to D Schnorr.
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Recent studies suggest that expression of CD44 splice variants are of prognostic significance for a variety of neoplasias. It was the aim of this study to investigate whether any correlation exists between the concentration of soluble CD44 molecules in serum (CD44 standard form and CD44 splice variants v5 and v6) and the prostate cancer stage. Serum levels of these soluble CD44 isoforms were measured by ELISA tests specific for these proteins in controls (n = 30), patients with benign prostatic hyperplasia (BPH; n = 30), with prostate cancer without metastasis (T1,2,3pN0M0; n = 30) and with locally advanced prostate cancer and/or metastatic disease (T3,4pN1,2M1; n = 19). sCD44std and sCD44v6 concentrations were not significantly different among the four groups studied, with few patients' levels outside the central 95% reference intervals. The mean sCD44v5 concentrations of both prostate cancer and BPH patients were significantly lower than those of the controls. There was no significant difference between the soluble CD44 concentrations of the two groups of prostate cancer patients studied. In contrast to results observed in other carcinomas, the determination of soluble CD44 proteins in serum is not suitable for providing additional prognostic information on patients with prostate cancer.
Using the Tandem-E, Axsym and LIA-mat assays, prostate specific antigen (PSA) was measured in pure PSA solutions of known concentrations of free and complexed PSA and in serum of patients with prostate cancer (n = 31), benign prostate hyperplasia (n = 32) and in healthy controls (n = 27). Measurements of pure PSA solutions showed that the AxSym assay exemplified typical properties of the skewed-response assay reacting more to free PSA than to the complexed PSA forms whereas the other two assays showed an equimolar-response. When PSA was measured in the serum of the tree groups, the AxSym test and Tandem-E gave similar PSA values whereas the LIA-mat test yielded significantly lower values. These results were not related to the amount of free PSA in the samples and proved that discordant PSA values between PSA assays were not mainly caused by the use of skewed- or equimolar assays. Despite these differences, receiver-operation characteristic analysis confirmed that the clinical validity of all three PSA tests did not differ.
In 1243 patients after renal transplantation, 39 malignant tumours were detected in 37 patients. The average latency period between transplantation and tumour disease was 72 months. Tumours included 8 malignant lymphomas, 7 dermatomas and 24 visceral tumours. The patients who developed a tumour had received fewer blood transfusions before transplantation than a tumour-free control group of 60 patients with renal transplants. Rejection crises occurred in a significantly smaller number of tumour patients compared with the control group.
We compared two recently introduced commercial assays (CanAg and Immulite) for measuring free prostate-specific antigen (f-PSA), total PSA (t-PSA), and the ratio of t-PSA/f-PSA (f-PSA%) in control materials and sera of 54 healthy men, 50 patients with benign prostatic hyperplasia (BPH), and 45 patients with prostate cancer (PCa). The lower detection limits for f-PSA were 0.038 microgram/L and 0.004 microgram/L for the CanAg and Immulite assays, respectively. The within-run and between-day precisions of the Immulite assay were < 5%; the CanAg assay showed a poorer precision. Whereas f-PSA values differed between controls and patients but not between BPH and PCa patients, the f-PSA% values were lower in PCa patients than in BPH patients and controls. The receiver-operating characteristic (ROC) curve showed an improved diagnostic power of f-PSA% compared with t-PSA to discriminate between BPH and PCa. Discrimination limits of 16% (CanAg assay), and 15% (Immulite assay) are recommended for f-PSA%.
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We tested the performance of the new immunochemical membrane test BioSign PSA for detecting serum concentrations of prostate-specific antigen > 4 micrograms/l. Measurements were simultaneously performed on 161 serum samples, using the strip test and three quantitative assays of prostate specific antigen (Tandem-E, IMx, LIA-mat). Based on the upper reference limit of 4 micrograms/l, 11-37% of the results obtained with the BioSign test were false-negative and 4-15% were false-positive, compared with the data of the three quantitative assays. It is concluded that the BioSign test in its present form does not satisfactorily differentiate between prostate-specific antigen concentrations above and below 4 micrograms/l, but an improved version of the test would be useful.
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DHEA levels in patients with prostatic cancer were significantly lower, but total and free testosterone (T) significantly higher as those in an age-matched control group. Therefore, the calculated quotients DHEA/free T and DHEA/T were especially different between both groups. DHEA and DHEAS levels in patients with heart diseases were also significantly lower but cortisol (F) levels were significantly higher as those in a control group. The quotients DHEA/F and DHEAS/F were also of greater significance between both groups than the hormone values alone. The response of DHEA and F levels in patients undergoing surgery showed an increase of both steroids under surgery. On the second postoperative day, however, F levels were still significantly higher but DHEA levels were significantly lower as the initial values. The differences between the initial values and those on the second postoperative day of F and DHEA showed a significant correlation, i.e. the higher the elevation of F levels above the initial values the greater was the diminution of DHEA levels below the initial values.
On the background of a continuous increase of knowledge in urologic oncology, the need for actual information and for interdisciplinary cooperation we discuss the diagnostics of prostatic and cystic carcinoma from the standpoint of the required therapy. The threshold of diagnostic detectability of prostatic carcinoma today is approximately the size of a matches head. By transrectal sonography and MRT the anatomic zones of the prostate are imaged and a selective biopsy becomes possible. Morphometric studies of prostatic carcinoma with pathologic-anatomical descriptions of the tumour volume and capsular penetration are described. The requirements for medical imaging for sufficient information on tumour volume, seminal bladder infiltration, capsular infiltration and lymph node diagnostics are derived. For the diagnostics of bladder carcinoma the significance of the lamina propria as a separating membrane between superficial and infiltrating carcinoma is discussed. Possibilities and limitations for the T- and N-determination of infiltrating carcinoma with CT and MRT and new therapy concepts (neoadjuvant chemotherapy) for the muscle-infiltrating cystic carcinoma are discussed.
Treatment of patients with prostatic cancer with a combination of 1-2 mg depot-estrogen (ethinylestradiol sulfonate = Turisteron) per week and 1 mg dexamethasone per day suppressed the mean testosterone (T) level to 2.8% (0.53 nmol/l), the free T to 0.8% (1.9 pmol/l) and the adrenal androgens (AA) -- androstenedione (A), dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) -- to more than 40% of the initial values. Treatment with Turisteron alone (2 mg per week) did not change the DHEA and DHEAS levels but decreased plasma A concentration to 65% (2.96 nmol/l) of the initial values.
Forty-nine patients were treated with either 3 x 75 MBq 89Sr or saline as placebo. Analysis of results 1 to 3 years after therapy revealed the ineffectiveness of 89Sr to relieve pain from metastases. Unexpectedly, a higher survival rate was found after Sr application (46% vs 4% after 2 years). Covariate analysis underlines the effect of 89Sr therapy on life expectation.
Turisteron is an orally highly effective depot estrogen (ethinylestradiol sulfonate) with relatively slight side effects. The treatment with Turisteron is very effective and is well tolerated by the patient. A strong antiandrogenic effect could be produced which had as its sequel a significant increase of the survival rates of patients with carcinoma of the prostate gland. The weekly dosage of 2 mg Turisteron led to a decrease of the biologically active, free testosterone to less than 2% compared with the initial value. The decrease of the total testosterone to castration values and the decrease of the free testosterone still significantly below values of castration are evidences for the strong antiandrogenic effect in exclusive estrogen treatment with Turisteron. From this conclusions relevant to practice were derived and finally therapy recommendation for the conservative treatment of the carcinoma of the prostate gland were given.