Biomedical subjects
A Van Dalen
Publications and source records attributed to A Van Dalen.
Structural homologies in immunoglobulins.
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Prognostic significance of CEA and CA 19-9 in colorectal cancer in Kuwait.
Preoperative CEA and CA 19-9 levels have been used in the past as prognostic indicators in colorectal cancer, but Dukes' stage is still considered to be the most important prognostic factor. Recent survival estimates may have been influenced by the fact that in the last decade adjuvant chemotherapy and postoperative irradiation have been included in the routine management of advanced-stage disease. In a heterogeneous Kuwaiti population higher reference levels (95th percentile) of CEA and CA 19-9 have been found than those usually employed. In the present study 62 patients with Dukes' stage B + C could be analyzed for two-year disease-free survival (DFS). Relapse was observed in 19 patients, 28 patients were disease free and 15 patients with censored observations were included. No significant difference in DFS was observed in Dukes' B (69%) versus Dukes' C (48%) patients (p = 0.09). On the other hand, Dukes' stage B + C patients with elevated preoperative levels of CEA or CA 19-9 had a significantly poorer DFS than patients with normal levels. For CEA levels below or above the cutoff the DFS was 74% versus 23% (p = 0.003); for CA 19-9 levels below or above the cutoff the DFS was 71% versus 33% (p = 0.004). In 54 patients with Dukes' stage B + C for whom preoperative levels of both CEA and CA 19-9 were available multivariate analysis revealed a decreasing risk of relapse in the following order: CEA and/or CA 19-9 elevated (chi-square 7.09; p = 0.008), CA 19-9 elevated (chi-square 6.27; p = 0.01), CEA elevated (chi-square 5.47; p = 0.02), and Dukes' C (chi-square 2.08; p = 0.15 n.s.). Hence, novel treatment protocols may have improved the disease-free survival, but the use of adjuvant chemotherapy and/or radiotherapy is of questionable benefit in patients who have elevated levels of CEA and/or CA 19-9 prior to treatment.
The prognostic significance of increasing marker levels in metastatic breast cancer patients with clinically complete remission, partial remission or stable disease.
TPS, CA 15-3 and CEA were determined in metastatic breast cancer patients during treatment. After six months of follow-up the patients were divided into four groups according to the UICC criteria for treatment response. Forty-six patients with a more favorable prognosis (complete remission, partial remission or stable disease) were followed for an extended period. In 30 of the 46 patients at least one marker had increased at the end of the six-month period by at least 25% (TPS in 54%, CA 15-3 in 20%, CEA in 20%). All these 30 patients subsequently developed progression. The prognostic sensitivity was 83%, 30% and 30%, respectively, for TPS, CA 15-3 and CEA. The combination of TPS and CA 15-3 showed a sensitivity of 96%. The median lead time was about 8 months for TPS and CA 15-3, but less than 50% of the patients showed a lead time for CA 15-3 as compared to TPS. We conclude that TPS and CA 15-3 determinations are helpful for the prediction of progression during the follow-up of breast cancer patients.
Performance characteristics of IMMULITE TPS: a comparison with TPS IRMA.
This paper describes an automated immunoassay for the measurement of TPS developed for the IMMULITE. The IMMULITE system is a fully automated continous random access analyzer, which uses enzyme-amplified chemiluminiscent as the detection system. The IMMULITE TPS assay is a sequential, two-site chemiluminiscent enzyme immunometric assay designed for the quantitative measurement of TPS in serum. The IMMULITE TPS assay covers a clinical concentration range of 20-2400 U/L, with a lower detection limit of 6 U/L. A serum method comparison (n = 340) to the TPS IRMA assay demonstrates a correlation coefficient of 0.961 and a slope of 1.04. Samples run on IMMULITE TPS assay exhibit linearity upon dilution where recovered values fall within 15% of the theoretical sample value. The intra-assay precision of the IMMULITE TPS assay ranged from 3.3-4.7%, while the interassay precision ranged from 3.9-6.0%. By using different methods (immunoradiometric assay vs chemiluminiscent enzyme-labeled immunometric assay, one-step procedure vs sequential two-step procedure, manual vs fully automated procedure) the two TPS tumor marker tests used in this study gave quite comparable determinations for the sera from the cancer patients.
Multicentre tumour marker reference range study.
BACKGROUND: The array of antibodies and assay formats utilised by kit manufacturers contribute to different values being quoted as clinically "normal". Kit-specific reference range limits will maximise the clinical utility of tumour marker assays. MATERIALS AND METHODS: Serum samples (approximately 800) were obtained from volunteers, age 20-70 years, in France, Germany, The Netherlands and Portugal. Each sample was assayed with a number of DPC tumour markers kits. IMMULITE assays were carried out in The Netherlands; Coat-A-Count IRMA, IRMA-Count, Double Antibody and Milenia assays at EURO/DPC Ltd. Analytes included, BR-MA, OM-MA, GI-MA (for the determination of CA 15-3, CA 125 and CA 19-9, respectively), CEA, PSA, PAP and HCG. RESULTS: The median and 95th percentiles for each analyte in each assay format were estimated; where appropriate, data subsets were considered. CONCLUSION: Kit-specific reference range data generated for important tumour marker analytes will help clinicians interprete their assay results.
A profile of tumor markers in the population of Kuwait.
The tumour markers CEA, AFP, CA 125 and CA 199 were analyzed in a group of apparently healthy subjects in Kuwait. The sample (n = 394) included both genders in the population with a mean age of 38 (S.d. 12.0) years. The distribution of CEA levels values was significant different (Mann-Whitney U test) between Kuwaiti and non-Kuwaiti. The distribution of AFP levels was found to be the same in all groups. The distribution of CA 125 levels was significantly higher in females than in males, both in Kuwaiti and non-Kuwaiti. The distribution of CA 19-9 values was found to be significantly higher in the Kuwaiti female group when compared to the males. The upper reference level was defined as the 95 percentile of the normal values in each group. In the total population the reference level of AFP was 5.6 micrograms/l and of CA 19.9 43 kU/l. The reference level of CA 125 was 16 U/l in males and 24 kU/l in females, respectively. The CEA reference level in Kuwaitis was 6.9 micrograms/l and in non-Kuwaitis 4.4 micrograms/l. The results indicated the importance of determining the reference levels of tumour markers for each individual laboratory. It was also emphasized that care should be taken on the impact of 95 percentiles of normal and benign disease groups.
Serum levels of CA 125 and TPS during treatment of ovarian cancer.
Two hundred and sixty ovarian cancer patients (including all FIGO stages) were enrolled in a prospective multicentre study. In this interim study we analyzed 206 patients receiving combined chemotherapy for at least 3 courses for two-year overall survival (OS). CA 125 and TPS were applied for monitoring treatment and the relationship between marker levels, marker changes and clinical assessments was established. Preoperative CA 125 or TPS levels were not correlated with OS in FIGO stage I and II patients. After 3 chemotherapy courses the marker levels were not correlated with OS in stage I and II. Partial debulking in stage II patients was a bad prognostic factor. CA 125 or TPS levels (using a CA 125 discrimination level of 25 kU/l and a TPS discrimination level of 100 U/l) after 3 courses of chemotherapy were highly significantly correlated with OS in FIGO stages III and IV patients: CA 125 two-year OS 67% versus 26% (p < 0.0001) and TPS two-year OS 55% versus 22% (p < 0.0001). The prognostic value of CA 125 levels after 3 chemotherapy courses could be further increased by combining CA 125 and TPS levels. When both CA 125 and TPS levels were below their respective discrimination levels, the two-year overall survival was 75%. When both levels were above the discrimination level, the two-year overall survival was only 17%.
Automated data collection and presentation in the operating room.
An 'Operating Room Data Integration System', is described which is used to collect, present and archive all important physiological parameters during open heart surgery. The system requires very little attention, and provides an easy to understand and coherent interface to the user. The system is adaptable to a large extend and thus data can be presented to the user in a manner, with which he or she is already familiar. Simple drivers can be written to enable connection of the system to almost any other piece of medical equipment, if the latter provides an analog or digital, output signal. Automatic logging of the acquired signals is then possible.
TPS and CA 125 levels in serum, cyst fluid and ascites of patients with epithelial ovarian neoplasms.
The serum markers TPS and CA 125 were determined in serum, cyst fluid and ascites in ovarian carcinoma patients and in patients with benign ovarian neoplasms. The levels of TPS and CA 125 were significantly higher in malignant and benign tumor cysts and ascitic fluids than in corresponding patients sera (p < 0.005 for TPS, p < 0.0001 for CA 125). The concentrations of cyst fluid TPS and CA 125 were also usually higher in cancer patients than in patients with benign ovarian neoplasms. TPS and CA 125 were elevated in a higher proportion of ovarian cancer patients sera than in benign ovarian patients' sera (p < 0.001 for both markers). Serum preoperative TPS and CA 125 levels were significantly higher in patients with advanced disease (FIGO stage III/IV) than in patients with early stage disease (FIGO stage I/II, p = 0.002, p < 0.05 respectively). When histology was considered, small differences in the marker signals were noted for TPS and CA 125 with the exception of mucinous neoplasms, where TPS showed a markedly higher signal. These results suggest that the combined use of TPS and CA 125 could be of additive value for the identification of epithelial ovarian neoplasms. Postsurgical TPS sera levels achieved the normal values faster than CA 125 suggesting that determination of TPS concentration before and 3 days after surgery seems to be valuable for the evaluation of radical surgery.