Second-line Test Research Articles

Elevation of multiple serum markers in patients with stage I ovarian cancer.

The high overall mortality from ovarian cancer (> 60%) relates, in part, to delays in diagnosis. When ovarian cancer is detected in stage I (International Federation of Gynecology and Obstetrics staging), up to 90% of patients can be cured. Transvaginal sonography can detect early-stage disease with great sensitivity, but it is expensive and lacks specificity. Although serum marker assays could provide a less expensive and more convenient initial screening test, the sensitivity of assays varies. Measurement of serum CA 125 in conjunction with ultrasound screening as a second-line test confers high specificity but detects only about one half of early stage ovarian carcinomas. The purpose of this retrospective study was to determine whether assays of multiple serum markers would improve sensitivity by detecting a higher percentage of stage I ovarian cancers than the CA 125 assay alone. Using immunoradiometric assays, we measured preoperative serum levels of CA 125 tumor-associated antigen, macrophage colony-stimulating factor (M-CSF), and OVX1 in 46 patients with stage I ovarian cancer of different histologies and 237 patients with benign pelvic masses. We also assayed sera from 204 apparently healthy women who had participated in a screening trial and remained free from cancer at 1 year of followup. All specimens were obtained from cryopreserved aliquots. Marker levels were considered to be elevated when levels of CA 125 were greater than 30 U/mL, M-CSF levels were greater than 3.1 ng/mL, or OVX1 levels were greater than 12.1 U/mL. At least one of the serum markers was elevated in 98% of patients with stage I ovarian cancer; CA 125 levels were elevated in 67%. By the same criteria, 11% of healthy individuals and 51% of patients with benign pelvic masses had at least one elevated marker value. Thus, the sensitivity of the combination of assays for the three serum markers was significantly greater than the sensitivity of the CA 125 assay (P < .0005) and specificity was moderate. A panel of these three tumor markers can identify early-stage ovarian cancer with extremely high sensitivity and moderate specificity. Elevation of one or more serum markers should be evaluated further as an indication for transvaginal sonography in apparently healthy women. Such a strategy might substantially reduce the expense and improve the specificity of screening compared to the use of ultrasound alone. Prospective studies with a large cohort of patients at high risk for ovarian cancer will be required to confirm these findings.

Assessment of hemolytic and hemorrhagic anemias in preclinical safety assessment studies.

The general characteristics of anemia and the distinguishing features of hemolytic, hemorrhagic, hypoproliferative, maturation abnormality, and iron-deficiency anemias are described. Hemolytic anemias are differentiated initially from hemorrhagic anemias by excluding hemorrhage on clinical, necropsy, or histologic examination. Next, they are distinguished from the remaining types of anemia on the basis of higher reticulocyte counts or, in some instances, by the very rapid rate of decline of the PCV. Hemolytic anemias are distinguished from each other on the basis of incidence and the presence or absence of a dose-response (idiosyncratic vs toxic) and by the cause of hemolysis (oxidative, nonoxidative, or immune-mediated). Hemorrhagic anemias are subclassified on the basis of single- and multiple-site hemorrhage. The causes of multiple-site hemorrhage (hemostasis dysfunction) are established by first- and second-line tests, the type of bleeding, clinical data, and the information gained from an evaluation of the structure, activity, and metabolism of the compound.