Can serum human epididymis protein 4 (HE4) support the decision to refer a patient with an ovarian mass to an oncology hospital?

INTRODUCTION: The value of serum human epididymis protein 4 (HE4) in guiding referral decisions in patients with an ovarian mass remains unclear, because the majority of studies investigating HE4 were performed in oncology hospitals. However, the decision to refer is made at general hospitals with a low ovarian cancer prevalence. We assessed accuracies of HE4 in differentiating benign or borderline from malignant tumors in patients presenting with an ovarian mass at general hospitals. METHOD: Patients with an ovarian mass were prospectively included between 2017 and 2021 in nine general hospitals. HE4 and CA125 were preoperatively measured and the risk of malignancy index (RMI) was calculated. Histological diagnosis was the reference standard. RESULTS: We included 316 patients, of whom 195 had a benign, 39 had a borderline and 82 had a malignant ovarian mass. HE4 had the highest AUC of 0.80 (95%CI 0.74-0.86), followed by RMI (0.71, 95%CI 0.64-0.78) and CA125 (0.69, 95%CI 0.62-0.75). Clinical setting significantly influenced biomarker performances. Applying age-dependent cut-off values for HE4 resulted in a better performance than one cut-off. Addition of HE4 to RMI resulted in a 32% decrease of unnecessary referred patients, while the number of correctly referred patients remained the same. CONCLUSION: HE4 is superior to RMI in predicting malignancy in patients with an ovarian mass from general hospitals. The addition of HE4 to the RMI improved HE4 alone. Although, there is still room for improvement, HE4 can guide referral decisions in patients with an ovarian mass to an oncology hospital.

Echogenicity changes in the fetal brain, a 6-year follow-up study.

OBJECTIVE: To asses the relation between echogenicity changes in the fetal brain and neurodevelopmental outcome until 6 years of age. METHODS: Fetuses (n = 124) from pregnancies affected by hypertensive disorders (n = 64) or preterm labor (n = 60) at risk for preterm birth (26-34 weeks gestation) were studied. Moderate echogenicity changes (periventricular grade IB, II; intraventricular grade II-III; local basal ganglia/thalami) in the fetal and neonatal brain were related to neurological outcome and Griffiths mental developmental scales quotients at 1, 2 and 6 years. Multiple regression analysis tested the influence of moderate echogenicity changes and perinatal clinical characteristics on composite outcome (death or abnormal neurodevelopment). RESULTS: Moderate echogenicity changes were present in 37/124 (30%) fetuses. Median gestational age and weight at birth were respectively 31 weeks (range 26-43), 1314 g (range 550-4330), mortality was 19%, follow-up loss 10%. Composite outcome was abnormal in 47/124 (38%). Fetal and neonatal moderate intraventricular echodensities were related to cerebral palsy at 6 years (p < 0.04). In the multiple regression analysis only gestational age was related to composite outcome (p = 0.005). CONCLUSIONS: Moderate intraventricular echodensities in the fetal brain related to cerebral palsy at 6 years of age. Gestational age at birth was the main predictor of abnormal composite outcome.

Placental histology related to fetal brain sonography.

BACKGROUND: Chronic hypoxia and inflammatory processes can induce placental disturbances that may indirectly lead to perinatal brain injury. OBJECTIVE: To study histological features of the placenta in relation to echogenicity changes in the periventricular white matter, ventricular system and basal ganglia/thalami of the fetal brain. DESIGN: Prospective study of 77 fetuses between 26 and 34 weeks gestational age with their placentas. The pregnancies were complicated by hypertensive disorders (n=42) or preterm labour (n=35). RESULTS: Of the placentas 79% showed uteroplacental hypoperfusion, inflammation or a combination. Transvaginal ultrasound examination of the brain revealed echogenicity changes in 73% of the fetuses (44 mild, 29 moderate). Moderate brain echogenicity changes (periventricular echodensity (PVE) grade IB: increased echogenicity brighter than choroid plexus, intraventricular echodensity (IVE) grade II and III: echodensity filling ventricle respectively <50% and ≥50%; basal ganglia/thalamic echodensity (BGTE): locally increased echogenicity within basal ganglia/thalami) were equally distributed over cases with uteroplacental hypoperfusion and inflammatory features in the placenta. PVE grade IB was always associated with placental pathology. The sensitivity and negative predictive value of placental pathology for moderate echogenicity changes were high (0.91 and 0.88, respectively), while the specificity and positive predictive value were low (0.27 and 0.34, respectively). CONCLUSIONS: Normal placental histology predicted no or mild echogenicity changes, supporting the view that the latter are physiological. Placental pathology was always present in cases with grade IB PVE, presumed to represent mild or early forms of white matter injury. Both uteroplacental hypoperfusion and inflammatory features were seen in placentas from pregnancies with hypertensive disorders.

Fetal general movements and brain sonography in a population at risk for preterm birth.

BACKGROUND: General movements (GMs) assessed three months post term are related to brain injury and neurological outcome. AIMS: To study GMs in fetuses and their predictive value for echogenicity changes in the fetal brain. STUDY DESIGN: Prospective study of fetal GMs (classified as normal or abnormal) and echogenicity changes in the periventricular, basal ganglia/thalami area, and ventricular system (classified as absent, mild or moderate). SUBJECTS: 121 fetuses from pregnancies affected by hypertensive disorders and/or preterm labour, at risk for preterm birth (26-34weeks gestational age). OUTCOME MEASURES: Prevalence of abnormal GMs, GM parameters (amplitude, speed and complexity), and moderate echogenicity changes in the fetal brain (periventricular >or=IB, intraventricular grade II/III, and basal ganglia/thalamus locally increased). Predictive values of GMs for clinical parameters and moderate echogenicity changes. RESULTS: GMs were abnormal in 58%, with amplitude affected in 96%, and speed and complexity in 59%. Abnormal GMs correlated with oligohydramnios (p=0.002) and hypertensive disorders (p=0.015). Echogenicity changes of the brain were absent, mild and moderate in 27%, 39% and 31%, respectively. The sensitivity of GMs for moderate echogenicity changes in the three areas combined was 0.65, and the periventricular area 0.85, specificity both 0.44, negative predictive values 0.73 and 0.96 respectively. CONCLUSIONS: Qualitative abnormal GMs are frequent in fetuses of compromised pregnancies, and correlate with hypertensive disorders and oligohydramnios. The amplitude of GMs was most frequently affected. Abnormal GMs relate to moderate echogenicity changes especially in the periventricular area of the fetal brain, while normal GMs predict absence of moderate echogenicity changes.

Changes in echogenicity in the fetal brain: a prevalence study in fetuses at risk for preterm delivery.

OBJECTIVES: To study the incidence of echodensities in the periventricular white matter, ventricular system, basal ganglia and thalamus of the brain in fetuses at risk for preterm delivery. METHODS: This was a prospective study of 124 fetuses with a gestational age between 26 and 34 weeks in pregnancies affected by either pregnancy-induced hypertensive disorders or preterm labor. Transvaginal ultrasound examination of the fetal brain in coronal and sagittal planes was performed weekly until delivery and the neonatal brain was examined within 24 h after delivery. RESULTS: In 66% of all fetuses, echodensities were found in one or more areas of the brain. They were present in the periventricular area in 52% of cases, the intraventricular area in 18% and in the basal ganglia and thalamus area in 28%. Changes in echogenicity were seen throughout the entire gestational-age period studied. Of the periventricular echodensities that exceeded in echodensity that of the choroid plexus, at least 50% persisted after delivery; at least 38% of the intraventricular echodensities and at least 32% of the basal ganglia and thalamus echodensities persisted after delivery. CONCLUSIONS: In high-risk fetuses, echodensities are a frequent finding in several areas in the brain. How far these echodensities are related to future outcome of the infant needs to be investigated.