Malignant melanomas are characterized by increased karyotypic complexity, extended aneuploidy and heteroploidy. We report a melanoma metastasis to the peritoneal cavity with an exceptionally stable, abnormal pseudodiploid karyotype as verified by G-Banding, subtelomeric, centromeric and quantitative Fluorescence in Situ Hybridization (FISH). Interestingly this tumor had no detectable telomerase activity as indicated by the Telomere Repeat Amplification Protocol. Telomeric Flow-FISH and quantitative telomeric FISH on mitotic preparations showed that malignant cells had relatively short telomeres. Microsatellite instability was ruled out by the allelic pattern of two major mononucleotide repeats. Our data suggest that a combination of melanoma specific genomic imbalances were sufficient and enough for this fatal tumor progression, that was not accompanied by genomic instability, telomerase activity, or the engagement of the alternative recombinatorial telomere lengthening pathway.
Growth deceleration has been acknowledged as a risk factor for perinatal complications and a criterion of late fetal growth restriction (FGR). The aim of this study was to assess the perinatal outcome of fetuses dropping by ≥50 estimated fetal weight (EFW) centiles while remaining > 10th centile between the second and third trimester. This is a non-concurrent cohort study of singleton pregnancies progressing after 32+0 weeks, who had their second- and third-trimester scans at our institutions were enrolled in the study. The perinatal outcome of AGA fetuses dropping more than 50 centiles was compared to that of fetuses with FGR, small for gestational age (SGA) and non-decelerating appropriate for gestational age (AGA-ND). The primary perinatal outcomes were perinatal death and neonatal intensive care (NICU) admission. Emergency Caesarean section rate was assessed as a secondary outcome. Our analysis included 4394 cases. Compared to non-decelerating SGA, fetuses crossing ≥50 centiles had higher rates of NICU admission[CC1] (2% and 3.5% respectively, odds ratio [OR] 1.8, 95% confidence interval [CI] CI 1.1-3.1) and perinatal death (1% and 0.3% respectively, OR 3.8, 95%CI 1.3-11.4). Regression analysis showed that significant predictors for perinatal death included maternal age, gestational age at birth, decelerating growth ≥50 centiles, conception through ART and third-trimester cerebroplacental ratio (CPR) centile (AUC 0.801). The significant independent predictors for NICU admission included maternal age, gestational age at birth and FGR (area under the curve [AUC] 0.851). AGA fetuses that cross > 50 EFW centiles between the second and third trimester are at increased risk of adverse perinatal outcome and it seems advisable that they are managed as typical FGR cases.
(Abstracted from N Engl J Med 2017;377:613–622) Since 1979, multiple studies have shown that low-dose aspirin in pregnancy can lower the occurrence of preeclampsia. Subsequent studies have shown that doses greater than 100 mg/d started before 16 weeks of gestation are most effective.
To report the incidence of preterm pre-eclampsia (PE) in women that fulfil the screening criteria of the NICE and ACOG and compare the incidence in those that are screen-positive and screen-negative by the FMF algorithm. This was a secondary analysis of data from the ASPRE study. The study population consisted of women with singleton pregnancies who had prospective screening for preterm-PE by the FMF algorithm that combines maternal factors and biomarkers at 11-13 weeks' gestation. We estimated the incidence of preterm-PE in those fulfilling the NICE and ACOG criteria; in these patients we then calculated the incidence of preterm-PE in those that were screen-negative relative to those that were screen-positive by the FMF algorithm. A total of 34,573 women with singleton pregnancies delivering at ≥24 weeks' gestation underwent prospective screening for preterm-PE, including 239 (0.7%) cases of preterm-PE. At least one of the ACOG criteria was fulfilled in 22,287 (64.5%) of pregnancies and the incidence of preterm-PE was 0.97%; in those that was FMF screen-positive the incidence was 4.80%, in those that were screen-negative it was 0.25% and the relative incidence (RI) in FMF-negative to FMF-positive was 0.051. In 1,392 (4.0%) pregnancies ≥1 NICE high-risk criteria was fulfilled and the incidence of preterm-PE was 5.17%; in those screen-positive and screen-negative by the FMF algorithm the incidence of preterm-PE was 8.71% and 0.65%, respectively and the RI was 0.075. In 2,360 (6.8%) pregnancies with ≥2 NICE moderate-risk criteria the incidence of preterm-PE was 1.74%; in those screen-positive and screen-negative by the FMF algorithm the incidence was 4.91% and 0.42%, respectively and the RI was 0.085. In ACOG or NICE screen-positive women that are screen-negative by the FMF algorithm the risk of preterm-PE is reduced to within or below background levels. The results provide further evidence to support risk based screening using biomarkers.
Giant ) is a rare placental tumor associated with complications including polyhydramnios, fetal anemia, cardiomegaly, hydrops and increased perinatal mortality1. Prenatal therapy may be performed when there are ultrasound features of fetal compromise and the gestation is not expected to survive. Therapeutic interventions include direct injection of various chemicals and laser coagulation of the tumor's feeding vessels2, 3. We report a case of a large chorioangioma located close to the placental cord insertion site, treated using interstitial laser coagulation. A 30-year-old patient presented at 24 weeks of gestation with polyhydramnios. On ultrasound, there was a large chorioangioma of 14 cm at its maximum diameter, arising from an anterior placenta within 1 cm of the placental cord insertion site (Figure 1). Three-dimensional Doppler ultrasound identified three deep feeding vessels and an additional large one running along the surface of the tumor connected directly to the umbilical cord confluence (Figure 2a). There was normal fetal growth, polyhydramnios with a deepest pool of 17 cm and mild fetal cardiomegaly. Peak systolic velocity (PSV) in the middle cerebral artery (MCA) was 51 cm/s (> 1.5 SD above the mean), indicating fetal anemia. Following counseling, the couple opted for vascular occlusion of the chorioangioma using interstitial laser photocoagulation. The procedure was performed under local anesthesia and continuous sonographic guidance. Routine prophylaxis with antibiotics (cephalexin, 2 g intravenously) was administered. A 17-gauge chorionic villus sampling needle (Chiba, Cook Inc., Bloomington, IN, USA) was inserted anteriorly, with the port of entry chosen to optimize visualization and operative access. A 1.07-mm non-contact laser fiber (Dornier MedTech GmbH, Wessling, Germany) was passed through the operative channel and coagulation was applied selectively to three feeding vessels, with 30–40-W intermittent beams depending on the diameter of the targeted vessel (Figure S1). The procedure was followed by amniodrainage of 3.5 L. One hour after the procedure, MCA-PSV was normal and the patient was discharged the next day. Five days later, there was significant sonographic evidence of degeneration within the tumor (Figure 2b). At 31 weeks of gestation, there was an acute drop in amniotic fluid followed by deterioration in fetal Dopplers. Cesarean section was performed for fetal distress after steroid administration to the mother. The neonate weighed 1760 g and was discharged healthy on day 40. Injection of toxic substances for the treatment of chorioangioma carries the risk of potential fetal exposure, to which at least one neonatal death has been attributed2. Laser photocoagulation can be performed either fetoscopically3 or using an ultrasound-guided interstitial approach4. Fetoscopy has a reported success rate of 60–80%; however, this technique may be difficult to perform in cases of anterior placenta3, 5. An interstitial approach is less invasive, using a device with a smaller diameter, and, in three of a series of cases in which it was used, was successful in all cases4. In the series of Zanardini4, the treated chorioangiomas were between 3.5 and 5.4 cm in diameter and close proximity to the cord was considered a contraindication for an interstitial approach in some cases because of a fear of possible excess thermal damage. The chorioangioma in the present case is, to the best of our knowledge, the largest reported one to be treated and the first treated by interstitial laser coagulation despite being located adjacent to the placental cord insertion site (Figure S2). This approach may be preferable in anterior placentas. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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