Paracrine changes in the peritoneal environment of women with endometriosis.
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During the past decade, macrophage-derived substances such as prostanoids, cytokines, growth factors and angiogenic factors have been detected in the peritoneal fluid of women with endometriosis. In particular, growth-promoting and angiogenic factors are considered to be substantially involved in the pathogenesis of endometriosis. In this study, vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-beta) and intercellular adhesion molecule 1 (ICAM-1), substances recently detected in the peritoneal fluid of women with endometriosis, were assessed with regard to their concentrations in different stages of endometriosis and changes of the peritoneal paracrine activity after medical treatment with a gonadotrophin releasing hormone agonist (GnRHa). Peritoneal fluid was obtained from patients with endometriosis during laparoscopy before and after a 4-month treatment with a GnRHa. VEGF, TGF-beta and ICAM-1 could be detected in all women presenting with various stages of active endometriosis. After GnRHa therapy, all patients showed significant decreases in mean concentrations of VEGF (194+/-77 pg/ml), TGF-beta (902+/-273 pg/ml) and ICAM-1 (157+/-52 ng/ml). Patients with stage III and IV endometriosis (according to the rAFS score) had much higher concentrations of VEGF and TGF-beta before treatment compared with those patients with mild endometriosis (rAFS stages I and II). The most striking decrease in concentration was for TGF-beta, from 902 pg/ml before to 273 pg/ml after therapy. These results indicate an important role for paracrine activity in the establishment and maintenance of endometriosis. Indeed, treatment with a GnRHa may reduce paracrine activity in the peritoneal cavity via hypo-oestrogenism and provide proof of successful therapy. (+info)
Comparison of standard and CA-125 response criteria in patients with epithelial ovarian cancer treated with platinum or paclitaxel.
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PURPOSE: To assess CA-125 as a measure of response in patients treated with paclitaxel. PATIENTS AND METHODS: One hundred forty-four patients treated with paclitaxel derived from four different trials and 625 patients treated with platinum from two trials were analyzed using precisely defined 50% and 75% reductions in CA-125. The standard and CA-125 response rates to paclitaxel and platinum were compared. In addition, we analyzed individual patient groups in which there was a difference in response according to the two response criteria. RESULTS: Patients with stable disease as determined by standard criteria who were treated with platinum and responded according to CA-125 criteria have an improved median progression-free survival compared with patients with stable disease who did not respond according to CA-125 criteria (10.6 v 4.8 months; P<.001). Standard and CA-125 response rates for patients treated with platinum (58.93% v 61.31%, respectively) and paclitaxel (30.65% v 31.67%, respectively) were very similar, as were rates of false-positive prediction of response by CA-125 (platinum 2.2% and paclitaxel 2.9%). Responders to paclitaxel had a significantly improved progression-free survival compared with non-responders by both standard criteria (median progression-free survival, 6.8 v 2.5 months; P<.001) and CA-125 criteria (median progression-free survival, 6.8 v 3.4 months; P<.001). CONCLUSION: Forassessing activity of therapy for ovarian cancer, these data show that precise 50% or 75% CA-125 response criteria are as sensitive as standard response criteria. We propose that they may be used as a measure of response in lieu of or in addition to standard response criteria in clinical trials involving epithelial ovarian cancer. Sensitivity is maintained whether patients are treated with platinum or paclitaxel. (+info)
Fluctuations in CA 125 and CA 15-3 serum concentrations during spontaneous ovulatory cycles.
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The aim of this study was to investigate cycle dependent changes of serum CA 125 and CA 15-3 concentrations during spontaneous ovulatory cycles. Twenty apparently healthy women with spontaneous menstrual cycles attending our infertility clinic were included. Of these women, 18 had occluded tubes as a result of sterilization. Ovulation was confirmed by luteinizing hormone test and ultrasonography and, to exclude endometriosis, a laparoscopy was performed. Serum samples for CA 125, CA 15-3, 17 beta-oestradiol and progesterone determinations were taken every second day starting on the 2nd day of the cycle until the 7th day of the next cycle. After correction for inter-individual variation in serum concentrations, highest CA 125 concentrations were found during the menstruation. During the follicular and peri-ovulatory phase CA 125 serum concentrations were lowest. For CA 15-3, serum concentrations were not statistically different throughout the cycle. CA 125 and oestradiol concentrations were negatively correlated, CA 15-3 and oestradiol concentrations were positively correlated. Absolute serum concentrations of both CA 125 and CA 15-3 vary among females. Within the female, fluctuations of CA 125 are phase related. In the population studied most of the patients had tubal obstruction and high CA 125 serum concentrations during menstruation, which revokes the theory that the menstrual rise of CA 125 is due only to retrograde menstruation. (+info)
Artificial neural network models for the preoperative discrimination between malignant and benign adnexal masses.
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OBJECTIVE: The aim of this study was to generate and evaluate artificial neural network (ANN) models from simple clinical and ultrasound-derived criteria to predict whether or not an adnexal mass will have histological evidence of malignancy. DESIGN: The data were collected prospectively from 173 consecutive patients who were scheduled to undergo surgical investigations at the University Hospitals, Leuven, between August 1994 and August 1996. The outcome measure was the histological classification of excised tissues as malignant (including borderline) or benign. METHODS: Age, menopausal status and serum CA 125 levels and sonographic features of the adnexal mass were encoded as variables. The ANNs were trained on a randomly selected set of 116 patient records and tested on the remainder (n = 57). The performance of each model was evaluated using receiver operating characteristic (ROC) curves and compared with corresponding data from an established risk of malignancy index (RMI) and a logistic regression model. RESULTS: There were 124 benign masses, five of borderline malignancy and 44 invasive cancers (of which 29% were metastatic); 37% of patients with a malignant or borderline tumor had stage I disease. The best ANN gave an area under the ROC curve of 0.979 for the whole dataset, a sensitivity of 95.9% and specificity of 93.5%. The corresponding values for the RMI were 0.882, 67.3% and 91.1%, and for the logistic regression model 0.956, 95.9% and 85.5%, respectively. CONCLUSION: An ANN can be trained to provide clinically accurate information, on whether or not an adnexal mass is malignant, from the patient's menopausal status, serum CA 125 levels, and some simple ultrasonographic criteria. (+info)
Combined inhibin and CA125 assays in the detection of ovarian cancer.
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BACKGROUND: The reproductive hormone inhibin has been used as a diagnostic marker of ovarian mucinous and granulosa cell cancers. The aims of this study were to develop a new inhibin immunofluorometric assay (alphaC IFMA) to replace an inhibin RIA as a diagnostic marker of these ovarian cancers and to assess whether the alphaC IFMA in combination with CA125, which detects serous cancers, leads to an improved biochemical diagnosis of all ovarian cancers. METHODS: Serum inhibin concentrations were determined in healthy postmenopausal women (n = 165) and women with ovarian cancers (n = 154), using an inhibin RIA and an alphaC IFMA, which detects inhibin forms containing the alphaC subunit as well as the free alphaC subunit. RESULTS: The alphaC IFMA gave a similar or better discrimination of mucinous (90% vs 71%) and granulosa cell (100% vs 100%) cancers compared with the inhibin RIA. Combination of CA125 and alphaC IFMA values by canonical variate analysis or by multiROC analysis showed that the percentage of all ovarian cancers detected was significantly increased compared with either CA125 or alphaC IFMA alone. CONCLUSIONS: The alphaC IFMA shows a similar or better specificity compared with the RIA, but with increased sensitivity. In combination with CA125, the alphaC IFMA provides an effective dual test for the detection of the majority (90%) of ovarian cancers. (+info)
Intraperitoneal hyaluronan production in stable continuous ambulatory peritoneal dialysis patients.
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OBJECTIVE: Several cytokines and proteins are excreted intraperitoneally during the course of peritonitis and stable states in continuous ambulatory peritoneal dialysis (CAPD) patients. Dialysate hyaluronan (HYA) is also regarded as a marker of peritoneal healing during bacterial peritonitis. We examined here, intraperitoneal HYA production in stable CAPD patients and compared the results to those of the peritoneal equilibration test (PET), the length of time on dialysis, and other marker proteins. DESIGN: We determined the concentration of HYA and other marker proteins in the 4-hour-dwell dialysate at 1-year intervals. SETTING: CAPD unit in Hitachi General Hospital. PATIENTS: The subjects were 46 stable CAPD patients who underwent 104 PETs. RESULTS: A correlation was found between the length of time on dialysis and the amount of HYA excretion in the 4-hr-dwell dialysate (r = 0.403, p < 0.001). A positive but weak correlation was found between the dialysate-to-plasma ratio of the creatinine concentration and dialysate HYA excretion (r = 0.229, p < 0.05). Seven patients were over the 90th percentile in both the concentration of HYA (>349.2 ng/mL) and the amount of HYA (>743.6 microg/4-hr dwell). Five patients exceeded 1000 microg of HYA excretion in the 4-hr-dwell dialysate, 4 of whom showed an abrupt increase of HYA excretion to more than 1000 microg/4-hr dwell, and discontinued CAPD within 6 months due to ultrafiltration failure. Two of these 4 patients were diagnosed with sclerosing encapsulating peritonitis at autopsy. CONCLUSION: Intraperitoneal HYA production increased with both higher permeable membrane and the length of time on CAPD. Monitoring of HYA in the peritoneal dialysate may be useful as a marker to assess functional and morphological changes in the peritoneum in long-term CAPD patients. (+info)
Serum CA-125 values on the day of oocyte retrieval are not predictive of subsequent pregnancy with in-vitro fertilization.
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In the clinical management of in-vitro fertilization (IVF) patients it would be very useful to know, before the embryo transfer, whether or not there is a significant chance of pregnancy in that cycle. If low, it would be better to freeze the embryos and postpone the embryo transfer to a subsequent cycle. For this reason, a retrospective study was carried out to investigate the correlations between the serum CA-125 values before embryo transfer and the clinical outcome of that IVF cycle. Women aged <40 years undergoing a complete infertility evaluation including laparoscopy and receiving gonadotrophin-releasing hormone analogue (GnRHa) suppression followed by purified follicle stimulating hormone (FSH) for IVF-embryo transfer were entered into the study. Ninety-seven cycles qualified for evaluation (26 pregnant and 71 non-pregnant cycles). CA-125 concentrations on the day of oocyte retrieval were significantly lower in the pregnant versus non-pregnant cycles in both non-endometriosis and endometriosis patients. To evaluate the existence of a cut-off value of CA-125 which would allow the prediction of a possible pregnancy with sufficient specificity and sensitivity, a receiver operating characteristic curve analysis was performed. This analysis demonstrated the absence of any predictive value of the subsequent pregnancy for CA-125 concentrations. For this reason, and in contrast with previous findings, CA-125 determinations before the embryo transfer in IVF patients do not appear to be a useful tool for clinicians to use in predicting the outcome of IVF in any given cycle. (+info)
Ultrasound assessment of ovarian cancer risk in postmenopausal women with CA125 elevation.
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We have previously shown that, in asymptomatic post-menopausal women, serum CA125 elevation is associated with a 36-fold increase in risk of ovarian cancer. This study was undertaken to assess the value of pelvic ultrasound for further stratification of ovarian cancer risk. Of 22,000 post-menopausal women, aged > or = 45 participating in an Ovarian Cancer Screening Trial, 741 with a CA125 > or = 30 U ml(-1) underwent pelvic ultrasonography. Twenty index cancers (primary invasive epithelial carcinomas of the ovary and fallopian tube) were diagnosed amongst these 741 women during a median follow-up of 6.8 years. Ultrasound results separated the women with CA125 elevation into two groups. Those with normal ovarian morphology had a cumulative risk (CR) of index cancer of 0.15% (95% confidence interval (CI) 0.02-1.12) which is similar to that of the entire population of 22,000 women (0.22%, 95% CI 0.18-0.30). In contrast, women with abnormal ovarian morphology had a CR of 24% (15-37) and a significantly increased relative risk (RR) of 327 (156-683). Ultrasound can effectively separate post-menopausal women with raised CA125 levels into those with normal scan findings who are not at increased risk of index cancer and those with abnormal findings who are at substantially increased risk of index cancer. (+info)