Evaluation of ovarian cancer biomarkers HE4 and CA-125 in women presenting with a suspicious cystic ovarian mass

Objective

Women presenting with a large or complex ovarian cyst are referred to extensive surgical staging to ensure the correct diagnosis and treatment of a possible epithelial ovarian cancer. We hypothesized that measurement of the biomarkers HE4 and CA-125 preoperatively would improve the assignment of these patients to the correct level of care.

Methods

Patients diagnosed with a cystic ovarian mass and scheduled for an operation at our center of excellence for ovarian cancer surgery from 2001 to 2010 were prospectively included (n=394) and plasma was collected consecutively. Cut-off for HE4 was calculated at 75% specificity (85 pM and 71.8 pM for post and premenopausal women). For CA-125, 35 U/mL cut-off was used. The study population included women with malignant (n=114), borderline (n=45), and benign (n=215) ovarian tumors.

Results

Receiver operator characteristic (ROC) area under the curve (AUC) in the benign versus malignant cohorts was 86.8% for CA-125 and 84.4% for HE4. Negative predictive value was 91.7% when at least one of the biomarkers was positive, with only early stage epithelial ovarian cancer showing false negative results. Sensitivity at set specificity (75%) was 87% for risk of ovarian malignancy algorithm (ROMA) in the postmenopausal cohort (cut-off point, 26.0%) and 81% in the premenopausal cohort (cut-off point, 17.3%). ROC AUC in the benign versus stage I epithelial ovarian cancer was only 72% for HE4 and 76% for CA-125.

Conclusion

In our study, population HE4 did not outperform CA-125. Based on our data a prospective trial with patients already diagnosed with an ovarian cyst may be conducted.     

The cost of the menstrual cycle in young Swedish women.

The purpose of this study was to evaluate the cost of the menstrual cycle for young Swedish women aged 14-20 years. The young women were randomly selected and interviewed by a trained female psychologist; a total of 68 young women completed the interviews. Twenty of the girls used oral contraceptives, while 48 had natural periods. The oral contraceptive users had a lighter menstrual flow and shorter periods (1 day less) than the girls with natural menstruation. The oral contraceptive users experienced less menstrual pain, used fewer painkillers and did not stay at home during their periods as often as the girls with natural periods. The cost of sanitary protection products was about US$1 per month less for the oral contraceptive users. Girls taking oral contraceptives also avoided stained underwear and soiled bedlinen significantly more often than the non-oral contraceptive users. The study design did not allow for cost estimates on soiled underwear, bedlinen or lost work- or schooldays. The results of the study indicate that expenditures related to the menstrual cycle are considerable for young Swedish women.     

The sensitivity of the premature infant pain profile - PIPP to measure pain in hospitalized neonates

AIM: The present study uses an Icelandic translation of the original version of the Premature Infant Pain Profile (PIPP) in order to assess its accuracy and sensitivity to the measure of pain in hospitalized neonates in Iceland. The PIPP is a composite tool developed to assess acute pain in preterm and term neonates. METHODS: A crossover design, with a sample of 24 neonates, was used on three, routinely occurring events in the neonatal intensive care unit, where neonates were their own controls. The three events were baseline, non-pain and pain event. Neonates were independently assessed for their pain, using the Icelandic translation of the PIPP, at the bedside. RESULTS: Repeated measures analysis yielded a statistically significant main effect for the three events (pain, non-pain and baseline), thus differentiating pain from non-pain and baseline events (F = 57.11; P < 0.0001). Pair-wise comparisons were subsequently carried out and the results show that PIPP scores at the pain event (11.72) were significantly lower (P < 0.0001) than that at the non-pain event (6.04) and that at the baseline event (3.54; P < 0.0001). The PIPP scores at the non-pain event were also significantly higher than that at the baseline event (P < 0.0001). These results suggest that the PIPP measure is sensitive to a painful event and differentiates between stress and pain in a clinical context across linguistic barriers. The findings also revealed almost a complete correlation between the PIPP scores of the two independent nurse raters at all events (P < 0.0001). CONCLUSION: Therefore the authors conclude that the Icelandic translation of the PIPP qualifies as a satisfying measure of pain responses in Icelandic neonates and can be recommended for use by clinicians and researchers. More research is, however, needed to further the accuracy and validity of the PIPP measure in general to assess pain in neonates in comparison to other pain measures.     

High Plasma Erythropoietin Predicts Incident Fractures in Elderly Men with Normal Renal Function: The MrOS Sweden Cohort

Preclinical studies on the role of erythropoietin (EPO) in bone metabolism are contradictory. Regeneration models indicate an anabolic effect on bone healing, whereas models on physiologic bone remodeling indicate a catabolic effect on bone mass. No human studies on EPO and fracture risk are available. It is known that fibroblast growth factor 23 (FGF23) affects bone mineralization and that serum concentration of FGF23 is higher in men with decreased estimated glomerular filtration rate (eGFR). Recently, a direct association between EPO and FGF23 has been shown. We have explored the potential association between EPO and bone mineral density (BMD), fracture risk, and FGF23 in humans. Plasma levels of EPO were analyzed in 999 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) study, MrOS Sweden. The mean ± SD EPO was 11.5 ± 9.0 IU/L. Results were stratified by eGFR 60 mL/min. For men with eGFR ≥60 mL/min (n = 728), EPO was associated with age (r = 0.13, p < 0.001), total hip BMD (r = 0.14, p < 0.001), intact (i)FGF23 (r = 0.11, p = 0.004), and osteocalcin (r = −0.09, p = 0.022). The association between total hip BMD and EPO was independent of age, body mass index (BMI), iFGF23, and hemoglobin (beta = 0.019, p < 0.001). During the 10-year follow-up, 164 men had an X-ray–verified fracture, including 117 major osteoporotic fractures (MOF), 39 hip fractures, and 64 vertebral fractures. High EPO was associated with higher risk for incident fractures (hazard ratio [HR] = 1.43 per tertile EPO, 95% confidence interval [CI] 1.35–1.63), MOF (HR = 1.40 per tertile EPO, 95% CI 1.08–1.82), and vertebral fractures (HR = 1.42 per tertile EPO, 95% CI 1.00–2.01) in a fully adjusted Cox regression model. In men with eGFR<60 mL/min, no association was found between EPO and BMD or fracture risk. We here demonstrate that high levels of EPO are associated with increased fracture risk and increased BMD in elderly men with normal renal function. © 2019 American Society for Bone and Mineral Research.