Comparative Assessment of Two Strategies for Interpreting Tumor Markers in Ascitic Effusions.

BACKGROUND/AIM: There are two strategies for the interpretation of tumor markers (TM) in fluid effusions: i) high cut-off and ii) fluid/serum ratio (F/S) and low cut-off. The objective of this study is to compare these two strategies and to determine whether diagnostic accuracy improves by the identification of possible false positives using Adenosine deaminase (ADA), C reactive protein (CRP) and % of polymorphonuclear cells (%PN). PATIENTS AND METHODS: We studied 157 ascitic fluids, 74 of which were malignant. ADA, CRP and %PN were determined in ascitic fluid, and Carcinoembryonic antigen (CEA), Cancer antigen 72-4 (CA72-4), Cancer antigen CA19-9 and Cancer antigen 15-3 (CA15-3) in both fluid and serum. RESULTS: The strategy of high cut-off showed 59.5% sensitivity at 100% specificity. The F/S strategy showed 75.7% sensitivity at 95.2% specificity. Subclassifying cases with ADA, CRP and %PN negative showed 67.5% sensitivity at 100% specificity for high cut-off and for the F/S strategy was 81.7% sensitivity at 98.7% specificity. CONCLUSION: The strategy of F/S with negative ADA, CRP and %PN allow the best interpretation for TM in the ascitic fluid.

Evaluation of two strategies for the interpretation of tumour markers in pleural effusions.

BACKGROUND: Pleural effusions present a diagnostic challenge. Approximately 20% are associated with cancer and some 50% require invasive procedures to perform diagnosis. Determination of tumour markers may help to identify patients with malignant effusions. Two strategies are used to obtain high specificity in the differential diagnosis of malignant pleural effusions: a) high cut-off, and b) fluid/serum (F/S) ratio and low cut-off. The aim of this study is to compare these two strategies and to establish whether the identification of possible false positives using benign biomarkers - ADA, CRP and % of polymorphonuclear cells - improves diagnostic accuracy. METHODS: We studied 402 pleural effusions, 122 of them malignant. Benign biomarkers were determined in pleural fluid, and CEA, CA72-4, CA19-9 and CA15-3 in pleural fluid and serum. RESULTS: Establishing a cut-off value for each TM for a specificity of 100%, a joint sensitivity of 66.5% was obtained. With the F/S strategy and low cut-off points, sensitivity was 77% and specificity 98.2%, Subclassifying cases with negative benign biomarkers, both strategies achieved a specificity of 100%; sensitivity was 69.9% for single determination and 80.6% for F/S ratio. CONCLUSIONS: The best interpretation of TM in the differential diagnosis of malignant pleural effusions is obtained using the F/S ratio in the group with negative benign biomarkers.

Diagnostic Accuracy of Tumor Markers CYFRA21-1 and CA125 in the Differential Diagnosis of Ascites.

BACKGROUND: The usefulness of tumor markers in the differential diagnosis of cancer in patients with ascites remains a matter of controversy. Few studies have reported the measurement of cancer antigen 125 (CA125) and cytokeratin 19 soluble fragments (CYFRA21-1) in ascitic fluid. The aim of the present study was to evaluate the diagnostic accuracy of these tumor markers in the detection of malignant ascites. MATERIALS AND METHODS: We analyzed CA125 and CYFRA21-1 from 143 consecutive undiagnosed patients with ascitis. RESULTS: Use of CA125 gave a sensitivity of 39.7% and a specificity of 98.8%, and CYFRA21-1 a sensitivity of 50.0% and a specificity of 97.6% in differential diagnosis of malignant ascites. For combined use of CA125 plus CYFRA21-1, sensitivity was 65.5% and specificity 96.5%. In patients with negative cytology, these two tumor markers had a sensitivity of 50% and a specificity of 96.5%. CONCLUSION: The determination of tumor markers in ascitic fluid could be useful for the diagnostic assessment of patients with ascites.

A prognostic score based on clinical factors and biomarkers for advanced non-small cell lung cancer.

AIMS: The objective of the present study is to determine the prognostic value of clinical variables and biomarkers in patients with advanced stages of NSCLC and establish a prognostic classification of these patients. METHODS: For 135 patients with advanced NSCLC we determined their clinical variables and their levels of CEA, CA 125, CYFRA 21-1, albumin, LDH, erythrosedimentation and leukocytes. RESULTS: Multivariate analysis identified PS (ECOG) >1, metastases, no anti-neoplastic treatment, CA 125 >35 U/mL, CYFRA 21-1 >3.3 ng/mL and leukocytes >10'000/µL, as independent prognostic factors for survival. Patients were classified into 3 groups according to the number of adverse prognostic factors (APF). One point was assigned for each APF, except for chemotherapy treatment. Patients with 0-1 APF represented our reference group: patients with 2-3 APF had HR=2.7 (95% CI: 1.5-4.6), while patients with 4-5 APF had HR=8.8 (95% CI: 4.6-16.8). This "score" maintained the differences between risk groups both in patients who received antineoplastic treatment and in those who did not. CONCLUSION: The application of a score that includes clinical data and biomarkers may improve the prognostic classification of NSCLC patients.

Diagnostic accuracy of tumour markers in serous effusions: a validation study.

The utility of tumour markers (TM) in the differential diagnosis of cancer in serous effusion (fluid effusion (FE)) has been the subject of controversy. The aim of this study was to prospectively validate our previous study and to assess whether the addition of adenosine deaminase (ADA), C-reactive protein (CRP) or percentage of polymorphonuclear cells (%PN) allows the identification of false positives. In this study, carcinoembryonic antigen, cancer antigen 15-3, cancer antigen 19-9, ADA, CRP and %PN in FE were determined in 347 patients with 391 effusions. Effusions were considered as malignant effusion when at least one TM in serum exceeded the cutoff and the ratio FE/S was higher than 1.2. Also, cases with values of ADA, CRP and %PN above the established cutoffs in serous effusion were considered as potential false positives. The combined sensitivity and specificity of the three TM was 76.2 % (95 % confidence intervals (CI) 67.8-83.3 %) and 97.0 % (95 % CI 94.1-98.7), respectively. Subanalysis of the 318 cases with previous criteria and negative ADA, CRP and %PN obtained sensitivities of 78.4 % (95 % CI 69.4-85.6) and a specificity of 100 % (95 % CI 98.2-100). The results obtained validate our previous study and are improved with the addition of ADA, CRP and %PN. TM in serous effusions and serum could be useful for the diagnostic assessment of patients with serous effusions.

Determination of the biological variation of S100ß and lactate dehydrogenase in disease-free patients with malignant melanoma.

BACKGROUND: Biological variation is important for determining analytical goals and for establishing the magnitude of change between two consecutive measurements. The aim of this study was to determine the biological variation for S100ß and lactate dehydrogenase in patients diagnosed with malignant melanoma but without evidence of disease recurrence. METHODS: The biological variation of S100ß and lactate dehydrogenase was estimated from a mean of four consecutive measurements in 32 patients diagnosed with malignant melanoma but without evidence of disease recurrence, 3 months after tumor resection or 4 months after finishing adjuvant treatment. The mean sampling interval was 3 months. RESULTS: Mean concentrations of S100ß and lactate dehydrogenase were 0.0557 µg/L and 6.3 µkat/L, respectively. Between-run analytical variation was 3.5% at 0.181 µg/L for S100ß and 3.5% at 2.83 µkat/L for lactate dehydrogenase. Biological variations obtained for S100ß and lactate dehydrogenase were 14.2% and 8.2%, respectively. The analytical goals (defined as 50% of biological variation) were 7.1% for S100ß and 4.1% for lactate dehydrogenase. CONCLUSIONS: The estimation of biological variation allows us to calculate analytical goals and reference change values. These are necessary tools for the correct interpretation of serial measurements in patient follow-up.

Determination of biological variation of α-fetoprotein and choriogonadotropin (ß chain) in disease-free patients with testicular cancer.

BACKGROUND: Knowledge of biological variation (BV) is important for determining analytical goals and for establishing the magnitude of change between two consecutive measurements which indicate change in a patients' health status. The aim of this work is to determine the BV for total choriogonadotropin (ß chain) (ß-hCG) and α-fetoprotein (AFP) in patients diagnosed with testicular cancer but with no evidence of recurrence of disease. METHODS: We estimated BV from a mean of five consecutive measurements in 28 patients diagnosed with testicular cancer, 3 months after tumor resection or 4 months after complete treatment with chemotherapy. The mean sampling interval was 3 months. RESULTS: The mean concentrations of α-fetoprotein and choriogonadotropin (ß chain) were 3.9 µg/L and 0.79 IU/L, respectively. Between-run analytical variation was 7.1% at 4.1 µg/L for α-fetoprotein, and 19% at 0.65 IU/L for choriogonadotropin (ß chain). BV obtained for α-fetoprotein and choriogonadotropin (ß chain) was 12.4% and 16.7%, respectively, and the reference change value (RCV) for one-tail showed 38.2% and 60.7% for α-fetoprotein and choriogonadotropin (ß chain), respectively. CONCLUSIONS: The estimation of BV allows us to calculate analytical goals and RCVs, necessary tools for the correct interpretation of serial measurements in the follow-up of patients.

Nt-proBNP in haemodialysis patients: a preliminary study.

OBJECTIVE: N-terminal pro-brain natriuretic peptide (Nt-proBNP) is a marker of left ventricular function. Although many factors can increase left ventricular dysfunction in haemodialysis patients, the role of Nt-proBNP is uncertain. MATERIAL AND METHODS: Serum concentrations of Nt-proBNP and troponin T were measured by electrochemiluminescence and C-reactive protein by immunoturbidimetry in 52 dialysis patients followed-up for 36 months. RESULTS: Nt-proBNP correlated (p<0.05) with time on haemodialysis (rho=0.345), left ventricular mass index (r=0.596), troponin T level (r=0.605) and age (r=0.296). Patients with a history of heart disease showed higher levels of Nt-proBNP (median; minimum-maximum ngl/L) (15,571; 1,553-209,451) than those without (4,535; 751-115,078) (p<0.01). Sensitivity and specificity of Nt-proBNP in the detection of left ventricular dysfunction (ventricular ejection fraction < 45%) were 1.0 and 0.782, respectively. In the univariate analysis, patients with Nt-proBNP levels > or = 33,314 ng/L, CRP > or = 5 mg/L or troponin T > or = 0.1 microg/L had poorer probabilities of 1-year, 2-year and 3-year survival than patients with lower levels. Unfavourable prognostic factors in the multivariate analysis were CRP > 5 mg/L and Tn T > 0.1 microg/L. CONCLUSIONS: Nt-proBNP showed good diagnostic performance for detecting left ventricular dysfunction and was an important predictor of mortality in haemodialysis patients in the univariate analysis. In the multivariate analysis, Nt-proBNP lost its prognostic value, whereas for CRP and Tn T it was maintained.