Second trimester amniocentesis in twin pregnancies: maternal haemoglobin as a dye marker to differentiate diamniotic twins

Objective To review the use of a membrane-free haemolysate prepared from maternal blood to distinguish the amniotic sacs at amniocentesis in twin gestation. Setting University Hospital, Groningen. Method Haemoglobin solution prepared from maternal blood. Subjects 63 twin pregnancies having amniocentesis. Results The fetal loss before 28 weeks was 4%. There was no perinatal mortality. Dye was detected in the second sac in 9 of 24 women tested before 1985 and none of the 39 women since, no malformations could be ascribed to the use of the haemolysate. Conclusion The use of the membrane-free haemolysate is safe, but the technique will probably gradually become redundant because of improved ultrasound

Higher levels of interleukin-6 in cystic fluids from patients with malignant versus benign ovarian tumors correlate with decreased hemoglobin levels and increased platelet counts

Background. Recently, high pretreatment platelet counts and low pretreatment hemoglobin levels were found to be negative prognostic factors in patients with ovarian cancer. Interleukin-6 (IL-6) is a multifunctional cytokine with a diversity of functions leading to the induction of C-reactive protein (CRP), increased platelet counts, and low hemoglobin levels. Different epithelial ovarian cancer cell lines are found to produce varying amounts of IL-6. In this study, a possible relationship between IL-6 levels in cystic fluids of benign and malignant ovarian tumors and pretreatment serum CRP, platelet counts, and hemoglobin levels was evaluated. Methods, A bioassay and enzyme-linked immunosorbent assay (ELISA) were performed to determine the IL-6 levels in cystic fluids and serum from 42 patients with benign and malignant ovarian tumors. Results. The median IL-6 level was higher in cystic fluids of malignant tumors (n = 21) when compared with cystic fluids of benign tumors (n = 21) (P <0.01 for bioassay and ELISA). Serum IL-6 levels in patients with malignant tumors were not significantly higher compared with IL-6 levels in patients with benign tumors, whereas CRP levels were higher in patients with malignant tumors (P <0.01). Cystic fluid IL-6 levels were related to serum CRP levels (r = 0.60, P <0.01 [bioassay]; r = 0.62, P <0.01 [ELISA]), platelet counts (r = 0.60, P <0.01 [bioassay]; r = 0.41, P <0.01 [ELISA]), and were related inversely to hemoglobin levels (r = -0.57, P <0.01 [bioassay]; r = 0.54, P <0.01 [ELISA]). Conclusions. IL-6 levels are higher in cystic fluids of malignant ovarian tumors compared with benign tumors. The relationship of cystic fluid IL-6 levels with CRP, platelet counts, and hemoglobin levels suggests a possible causative role of tumor-derived IL-6 in the appearance of general side effects of ovarian cancer, which recently have been recognized as prognostic factors

Preoperative sensitivity and specificity for early-stage ovarian cancer when combining cancer antigen CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor using mixtures of multivariate normal distributions

Purpose In CA-125–based ovarian cancer screening trials, overall specificity and screening sensitivity of ultrasound after an elevated CA-125 exceeded 99.6% and 70%, respectively, thereby yielding a positive predictive value (PPV) exceeding 10%. However, sensitivity for early-stage disease was only 40%. This study aims to increase preoperative sensitivity for early-stage ovarian cancer while maintaining the annual referral rate to ultrasound at 2% by combining information across CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor (M-CSF). For direct comparisons between marker panels, all sensitivity results correspond to a 98% fixed first-line specificity (referral rate 2%). Patients and Methods Logistic regression, classification tree, and mixture discriminant analysis (MDA) models were fit to a training data set of preoperative serum measurements (63 patients, 126 healthy controls) from one center. Estimates from the training set applied to an independent validation set (60 stage I to II patients, 98 healthy controls) from two other centers provided unbiased estimates of sensitivity. Results Preoperative sensitivities for early-stage disease of the optimal panels were 45% for CA-125II; 67% for CA-125II and CA 72-4; 70% for CA-125II, CA 72-4, and M-CSF; and 68% for all four markers (latter two results using MDA). Conclusion Efficiently combining information on CA-125II, CA 72-4, and M-CSF significantly increased preoperative early-stage sensitivity from 45% with CA-125II alone to 70%, while maintaining 98% first-line specificity. Screening trials with these markers using MDA followed by referral to ultrasound may maintain previously high levels of specificity and PPV, while significantly increasing early-stage screening sensitivity. MDA is a useful, biologically justified method for combining biomarkers

Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer

Early detection remains the most promising approach to improve long-term survival of patients with ovarian cancer. In a five-center case-control study, serum proteomic expressions were analyzed on 153 patients with invasive epithelial ovarian cancer, 42 with other ovarian cancers, 166 with benign pelvic masses, and 142 healthy women. Data from patients with early stage ovarian cancer and healthy women at two centers were analyzed independently and the results cross-validated to discover potential biomarkers. The results were validated using the samples from two of the remaining centers. After protein identification, biomarkers for which an immunoassay was available were tested on samples from the fifth center, which included 41 healthy women, 41 patients with ovarian cancer, and 20 each with breast, colon, and prostate cancers. Three biomarkers were identified as follows: (a) apolipoprotein A1 (down-regulated in cancer); (b) a truncated form of transthyretin (down-regulated); and (c) a cleavage fragment of inter-alpha-trypsin inhibitor heavy chain H4 (up-regulated). In independent validation to detect early stage invasive epithelial ovarian cancer from healthy controls, the sensitivity of a multivariate model combining the three biomarkers and CA125 [74% (95% CI, 52-90%)] was higher than that of CA125 alone [65% (95% CI, 43-84%)] at a matched specificity of 97% (95% CI, 89-100%). When compared at a fixed sensitivity of 83% (95% CI, 61-95%), the specificity of the model [94% (95% CI, 85-98%)] was significantly better than that of CA125 alone [52% (95% CI, 39-65%)]. These biomarkers demonstrated the potential to improve the detection of early stage ovarian cancer

Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer

Early detection remains the most promising approach to improve long-term survival of patients with ovarian cancer. In a five-center case-control study, serum proteomic expressions were analyzed on 153 patients with invasive epithelial ovarian cancer, 42 with other ovarian cancers, 166 with benign pelvic masses, and 142 healthy women. Data from patients with early stage ovarian cancer and healthy women at two centers were analyzed independently and the results cross-validated to discover potential biomarkers. The results were validated using the samples from two of the remaining centers. After protein identification, biomarkers for which an immunoassay was available were tested on samples from the fifth center, which included 41 healthy women, 41 patients with ovarian cancer, and 20 each with breast, colon, and prostate cancers. Three biomarkers were identified as follows: (a) apolipoprotein A1 (down-regulated in cancer); (b) a truncated form of transthyretin (down-regulated); and (c) a cleavage fragment of inter-alpha-trypsin inhibitor heavy chain H4 (up-regulated). In independent validation to detect early stage invasive epithelial ovarian cancer from healthy controls, the sensitivity of a multivariate model combining the three biomarkers and CA125 [74% (95% CI, 52-90%)] was higher than that of CA125 alone [65% (95% CI, 43-84%)] at a matched specificity of 97% (95% CI, 89-100%). When compared at a fixed sensitivity of 83% (95% CI, 61-95%), the specificity of the model [94% (95% CI, 85-98%)] was significantly better than that of CA125 alone [52% (95% CI, 39-65%)]. These biomarkers demonstrated the potential to improve the detection of early stage ovarian cancer