Effects of Blood Collection Conditions on Ovarian Cancer Serum Markers

Evaluating diagnostic and early detection biomarkers requires comparing serum protein concentrations among biosamples ascertained from subjects with and without cancer. Efforts are generally made to standardize blood processing and storage conditions for cases and controls, but blood sample collection conditions cannot be completely controlled. For example, blood samples from cases are often obtained from persons aware of their diagnoses, and collected after fasting or in surgery, whereas blood samples from some controls may be obtained in different conditions, such as a clinic visit. By measuring the effects of differences in collection conditions on three different markers, we investigated the potential of these effects to bias validation studies.We analyzed serum concentrations of three previously studied putative ovarian cancer serum biomarkers-CA 125, Prolactin and MIF-in healthy women, women with ovarian cancer undergoing gynecologic surgery, women undergoing surgery for benign ovary pathology, and women undergoing surgery with pathologically normal ovaries. For women undergoing surgery, a blood sample was collected either in the clinic 1 to 39 days prior to surgery, or on the day of surgery after anesthesia was administered but prior to the surgical procedure, or both. We found that one marker, prolactin, was dramatically affected by collection conditions, while CA 125 and MIF were unaffected. Prolactin levels were not different between case and control groups after accounting for the conditions of sample collection, suggesting that sample ascertainment could explain some or all of the previously reported results about its potential as a biomarker for ovarian cancer.Biomarker validation studies should use standardized collection conditions, use multiple control groups, and/or collect samples from cases prior to influence of diagnosis whenever feasible to detect and correct for potential biases associated with sample collection

Rates of study completion with single versus split daily dosing of antidepressants: a meta-analysis

Objective: To examine the tolerability of single versus multiple daily dosing (SDD vs. MDD) of antidepressant drugs in clinical practice. Method: Studies comparing single versus multiple daily dosing of antidepressants were reviewed. Since there were no numeric data available on the rates of adverse events for the SDD versus MDD arms, meta-analyses were carried out to compare rates of study completers (or rates of drop-outs) with single versus multiple daily dosing. Results: The review process identified 22 studies meeting our inclusion criteria. This meta-analysis found no difference in the rates of study completers with SDD or MDD regime of antidepressants. Conclusion: Our analysis on rates of completers (or rates of drop-outs) gives us an estimation of the overall acceptability of treatment and of course, but has limited utility when compared to the rates of adverse events. Yet, the present analyses suggest that adverse events which are significant enough to result in drop-outs, are not more frequent with SDD than MDD. MDD strategy of antidepressants does not seem to be more advantageous for the acceptability of treatment and obviously is disadvantageous for compliance. Thus, a simplified treatment regimen may be practical to increase treatment success rates in depression. (C) 2004 Elsevier B.V. All rights reserved

evolving role of serum biomarkers in the management of ovarian cancer

The availability of an ideal serum tumor marker would be of great clinical benefit for both the diagnosis and management of patients with epithelial ovarian cancer. Serum cancer antigen 125 assay significantly increases the diagnostic reliability of ultrasound in discriminating a malignant from a benign ovarian mass, especially in postmenopausal women, and it is the only well validated tumor marker for monitoring disease course. Several other tumor-associated antigens have been assessed, including glycoprotein antigens other than cancer antigen 125, soluble cytokeratin fragments, kallikreins, cytokines and cytokine receptors, vascular endothelial growth factor, D-dimer, and lisophosphatidic acid. This article assesses the potential diagnostic and prognostic role of these novel biomarkers, both alone and in combination with cancer antigen 125. The future for serum tumor marker research is represented by the emerging technology of proteomics, which may allow scientific advances comparable to those achieved ..

ESGO/ISUOG/IOTA/ESGE Consensus Statement on preoperative diagnosis of ovarian tumours.

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the preoperative diagnosis of ovarian tumours, including imaging techniques, biomarkers and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the preoperative diagnosis of ovarian tumours and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the preoperative diagnosis of ovarian tumours and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement