Fully percutaneous fetoscopic repair of myelomeningocele: 30-month follow-up data.

OBJECTIVE: This observational study reports on the postnatal mortality and 30-month outcome of children who underwent fully percutaneous fetoscopic repair of myelomeningocele (MMC) at a single center in Giessen, Germany. METHODS: Between October 2010 and August 2014, a total of 72 patients underwent fully percutaneous fetoscopic MMC closure at 21 + 0 to 29 + 1 (mean, 23 + 5) weeks' gestation. Of these, 52 (72%) participated in this study; however, 30-month mortality data are available for all 72 children. Children were examined at four timepoints: shortly after birth and at 3 months, 12 months and 30 months of corrected age. The patients underwent age-specific standardized neurological examinations and assessment of leg movements and ambulation at all timepoints. Cognitive and motor development were assessed using the Bayley Scales of Infant Development, second edition (BSID-II), at 30 months. RESULTS: All 72 children survived the intrauterine procedure, however, four (5.6%) infants died postnatally (including two of the 52 comprising the study cohort). Of the 52 patients included in the study, 11.5% were delivered before the 30th week of gestation (mean, 33 + 1 weeks) and, of the survivors, 48.1% had ventriculoperitoneal shunt placement. Of the 50 infants that were alive at 30 months, independent ambulation, without orthosis, was feasible for 46%. At 30 months of follow-up, 46% of children presented with a functional level that was at least two segments better than the anatomical level of the lesion. At 30 months, 70% of the children presented with BSID-II psychomotor development index score of ≥ 70 and 80% with BSID-II mental development index score of ≥ 70. CONCLUSION: Intrauterine repair of MMC by percutaneous fetoscopy shows largely similar outcomes to those reported for open repair, with respect to mortality, prematurity, shunt-placement rates, motor and mental development and free ambulation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of right ventricular function in fetal hypoplastic left heart syndrome by color tissue Doppler imaging.

OBJECTIVE: Postnatal outcome of fetuses with hypoplastic left heart syndrome (HLHS) is determined mainly by right ventricular function. Our study examines whether there are differences in right ventricular function during gestation of fetuses with HLHS compared with healthy fetuses. METHODS: A prospective study was conducted including 20 fetuses with HLHS and 20 gestational age-matched controls. Peak systolic and diastolic right ventricular free wall velocities were assessed using color tissue Doppler imaging (c-TDI). Subsequently, isovolumic time intervals, ejection time (ET'), E'/A' ratio and tissue Doppler-derived myocardial performance index (MPI') were calculated. Possible changes to c-TDI indices during the course of pregnancy in both the HLHS group and the control group were investigated. RESULTS: Examination of right ventricular function revealed significantly lower E' velocities (13.6 vs 21.0 cm/s; P = 0.017) and E'/A' ratios (0.55 vs 0.76; P = 0.012) and prolonged isovolumic contraction time (ICT') (57.0 vs 45.7 ms; P = 0.008) in the HLHS group compared with healthy fetuses. Furthermore, isovolumic relaxation time and MPI' increased significantly with gestational age in HLHS fetuses but not in controls. Values for systolic and diastolic peak velocities (E', A', S'), ET' and ICT' did not change significantly during gestation in either group. CONCLUSION: Right ventricular function in HLHS is altered as early as in fetal life, well before palliative surgery is performed. Future research should provide further insight into ventricular remodeling during gestation in cases of HLHS. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Pulmonary Vasoreactivity to Materno-Fetal Hyperoxygenation Testing in Fetuses with Hypoplastic Left Heart.

PURPOSE: The aim of the study was to describe the response of fetal lung vasculature to maternal hyperoxygenation (MH) in the case of prenatally diagnosed hypoplastic left heart (HLH) with intact or restrictive (IAS/RAS) and without restriction of the atrial septum. Furthermore, the ability of MH to differentiate between newborns with HLH who do not require immediate atrial septostomy and newborns who will undergo immediate left atrial septoplasty after birth was evaluated. MATERIALS AND METHODS: Cross-sectional prospective study of fetuses ≥ 26 weeks of gestation with prenatally diagnosed HLH. Lung perfusion (LP) was qualitatively assessed by color Doppler interrogation and LP was quantitatively measured using the pulsatility index for veins (PIV). Measurements were performed both with the mother breathing room air (LPRA) and after receiving 100% oxygen for 10 minutes (LPMH). The oxygen test was defined as positive if MH led to an increase in lung perfusion and as negative if MH did not lead to an increase. RESULTS: A total number of 22 pregnancies with hypoplasia of the left heart structures were included. 6/20 cases presented with an intact or restrictive atrial septum (IAS/RAS). All of these fetuses presented with a reduced LPRA. MH led to an increase in LP in 2/6 cases. The overall 30-day-survival rate was 83.3% (5/6). In 14/20 fetuses an open septum was detected. 11 cases had a normal LPRA, and the LPRA was reduced in 3/14 fetuses. The overall 30-day-survival rate was 92.9% (13/14). CONCLUSION: MH might be a useful adjunct in the assessment of pulmonary vasculopathy in fetuses with HLH.

Emission of herbivore elicitor-induced sesquiterpenes is regulated by stomatal aperture in maize (Zea mays) seedlings.

Maize seedlings emit sesquiterpenes during the day in response to insect herbivory. Parasitoids and predators use induced volatile blends to find their hosts or prey. To investigate the diurnal regulation of biosynthesis and emission of induced sesquiterpenes, we applied linolenoyl-L-glutamine (LG) to maize seedlings in the morning or evening using a cut-stem assay and tracked farnesene emission, in planta accumulation, as well as transcript levels of farnesyl pyrophosphate synthase 3 (ZmFPPS3) and terpene synthase10 (ZmTPS10) throughout the following day. Independent of time of day of LG treatment, maximum transcript levels of ZmFPPS3 and ZmTPS10 occurred within 3-4 h after elicitor application. The similarity between the patterns of farnesene emission and in planta accumulation in light-exposed seedlings in both time courses suggested unobstructed emission in the light. After evening induction, farnesene biosynthesis increased dramatically during early morning hours. Contrary to light-exposed seedlings dark-kept seedlings retained the majority of the synthesized farnesene. Two treatments to reduce stomatal aperture, dark exposure at midday, and abscisic acid treatment before daybreak, resulted in significantly reduced amounts of emitted and significantly increased amounts of in planta accumulating farnesene. Our results suggest that stomata not only play an important role in gas exchange for primary metabolism but also for indirect plant defences.

Evaluation of right ventricular function in fetuses with hypoplastic left heart syndrome using tissue Doppler techniques.

OBJECTIVE: The outcome of patients with hypoplastic left heart syndrome (HLHS) is influenced by right ventricular function. This study aimed to investigate whether differences in right ventricular function of fetuses with HLHS are present during gestation. METHODS: This was a prospective study comprising 14 fetuses with HLHS (28 measurements obtained in total) and 28 normal control fetuses (31 measurements obtained in total). The two groups were matched for gestational age. Ultrasound M-mode was used to assess displacement of the tricuspid annulus. Spectral Doppler and myocardial tissue Doppler-derived inflow and outflow velocities were assessed. Tricuspid valve peak early wave to peak active wave (E/A) ratio, the early wave to early diastolic annular relaxation velocity (E/E') ratio and the tissue Doppler-derived myocardial performance index (MPI') were calculated. RESULTS: E-wave velocity was significantly higher in fetuses with HLHS than in control fetuses (mean, 40.14 cm/s vs 35.47 cm/s; P < 0.05, respectively), and A-wave velocity in fetuses with HLHS showed a tendency for higher values in the right ventricle compared with normal control fetuses, but this did not reach statistical significance (61.16 cm/s vs 54.64 cm/s; P = 0.08). The E/A ratio increased during gestation in controls, but this increase was not seen in HLHS fetuses. Peak annular velocity during atrial contraction (A') and the E/E' ratio were significantly lower in controls than in HLHS fetuses: 9.50 cm/s vs 10.39 cm/s (P < 0.05) and 5.77 vs 7.37 (P < 0.05), respectively. There were no differences for right-ventricular MPI' or tricuspid annular plane systolic excursion between HLHS fetuses and controls. CONCLUSION: The results of this study show that altered right ventricular function in HLHS infants may develop antenatally. It is hoped that confirmation of these findings using Doppler-independent techniques will lead to further exploration of ventricular function in HLHS fetuses. Consequently, parental counseling and postnatal management strategies could be influenced.

Management of complicated monochorionic twin pregnancies.

Multiple gestation is associated with an increased risk for adverse pregnancy outcome. Monochorionic twins are at risk for complications specific to these pregnancies, such as twin-twin transfusion syndrome (TTTS) or twin reverse arterial perfusion (TRAP) sequence. In this article we give an overview on prenatal diagnosis, treatment and outcome of twin pregnancies complicated by TTTS and TRAP sequence.

Percutaneous minimal-access fetoscopic surgery for spina bifida aperta. Part II: maternal management and outcome.

OBJECTIVE: To assess maternal morbidity and outcome in women undergoing minimal-access fetoscopic surgery for spina bifida aperta. METHODS: This was a retrospective study of 51 women undergoing minimal-access fetoscopic surgery to improve postnatal neurological outcome of spina bifida aperta, at a mean gestational age of 24 weeks, at our center between July 2010 and June 2013. We analyzed various perioperative complications of surgery, namely: maternal and fetal death, need for maternal blood transfusion, placental abruption, pulmonary edema, spontaneous labor, oligohydramnios, chorioamnionitis, chorioamniotic membrane separation, duration of hospitalization, amniotic fluid leakage, gestational age at delivery and status of hysterotomy site. RESULTS: In none of the 51 women was there maternal demise, spontaneous labor, placental abruption or a need for maternal blood transfusion in the perioperative period. Chorioamniotic membrane separation occurred in one patient, mild pulmonary edema occurred in one and oligohydramnios occurred in seven. All fetuses survived surgery, but there was one very early preterm delivery 1 week after the procedure and this neonate died immediately, from early postoperative chorioamnionitis. Amniotic fluid leakage occurred in 43 patients, at a mean gestational age of 29.7 (range, 22.6-37.3) weeks; two of these patients developed chorioamnionitis. Duration of maternal hospitalization after surgery was 7.2 (range, 4-12) days. Mean gestational age at delivery was 33 (range, 24.6-38.1) weeks. All abdominal and uterine trocar insertion sites healed well. CONCLUSION: Minimal-access fetoscopic surgery for spina bifida aperta is apparently safe for most maternal patients. Despite the common occurrence of amniotic leakage, the majority of women deliver beyond 32 weeks of gestation.

First experience with three-dimensional speckle tracking (3D wall motion tracking) in fetal echocardiography.

OBJECTIVES: Fetal cardiac function can be quantified by different methods. This is the first approach of real three-dimensional(3 D)-based speckle tracking echocardiography in the fetus to assess different cardiac strain parameters. METHODS: We present preliminary results of fetal global myocardial strain analyses. For fetal echocardiography a Toshiba Artida system was used. Based on an apical or basal four-chamber view of the fetal heart, raw data volumes with a high temporal resolution were acquired and digitally stored. RESULTS: 8 individual healthy fetuses with an echocardiogram performed between 21 and 37 weeks of gestation were included. The mean temporal resolution was 31.2 ±â€Š4.3 volumes per second (vps). Basic parameters such as longitudinal and circumferential strain as well as advanced 3 D myocardial motion patterns such as area strain, rotation, twist and torsion were assessed. CONCLUSION: Currently the assessment of fetal myocardial deformation parameters by 3 D speckle tracking seems to be technically feasible only in individual cases. In the future further development of this technique is necessary to improve its application in fetal echocardiography.

Outcome after second-trimester amniocentesis and first-trimester chorionic villus sampling for prenatal diagnosis in multiple gestations.

PURPOSE: The purpose of this study was to classify pregnancy loss and fetal loss as well as the influence of maternal risk factors in multiple pregnancies. METHODS AND MATERIALS: Details of the procedure and pregnancy outcome of all patients were extracted from the clinical audit database of two tertiary centers. The files were collected in the time from January 1993 to May 2011.  The procedure-related pregnancy and fetal loss rate was classified as all unplanned abortions without important fetal abnormalities or obstetric complications within 14 days after AC and CVS. RESULTS: We had a total number of 288 multiple pregnancies with a total of 637 fetuses. After the exclusion of 112 pregnancies with abnormal karyotype or fetal abnormalities detected by ultrasound as well as cases of selective feticide, repeated invasive procedures and monochorionic-monoamniotic pregnancies, 176 pregnancies and 380 fetuses were left for final analysis. Overall 132 amniocenteses and 44 chorionic villous sampling procedures were performed. The total pregnancy loss rate was 8.0 % (14/176), 6.1 % (n = 8) for amniocentesis and 13.6 % (n = 6) for CVS.  The procedure-related pregnancy loss rate was 3.4 %, 2.3 % after amniocentesis (3 cases) and 6.8 % after CVS (3 cases). There was no statistical significance between the two procedures (p = 0.15). CONCLUSION: The procedure-related loss rate of 3.4 % can be compared to the rates in the literature. The higher loss rates in multiple pregnancies than in singleton pregnancies have to be discussed when counseling parents.

Prenatal assessment of ventriculocoronary connections and ventricular endocardial fibroelastosis in hypoplastic left heart.

OBJECTIVE: The outlook for newborns with hypoplastic left heart (HLH) has substantially improved over the last decade. However, differences in outcome among various anatomical subgroups have been described. We aimed to describe the incidence of ventriculocoronary communications and endocardial fibroelastosis in HLH and the possible implication on hospital survival (30 d). METHODS: We retrospectively reviewed our medical records, still frames and video loops of 72 fetuses with HLH and critical aortic valve stenosis and evolving HLH from 2008 - 2013. The presence of VCAC and EFE were systematically assessed. Outcome parameters were incidence of VCAC and EFE among different anatomical subgroups of HLH and hospital survival (30 d). RESULTS: 72 fetuses were included in this series. The incidence of VCAC was 11.1 % (8 cases) and EFE occurred in 33.3 % (24 cases). 5 fetuses with VCAC occurred in the subgroup of mitral valve stenosis/aortic valve atresia (MS/AA, 62.5 %) and 2 fetuses with VCAC occurred in the group of mitral atresia/aortic valve atresia (MA/AA, 25 %). Further classification was not possible in one case with VCAC (12.5 %). EFE predominantly occurred in the subgroup of MS/AA, MA/AA and in those cases with aortic valve stenosis and evolving HLH. The overall hospital survival on an intention-to-treat basis was 91.2 % (52/57 newborns). Hospital survival was 91 % for the subgroup of cases with MS/AA and for all other anatomical subgroups. CONCLUSION: The presence of VCAC in HLH can be diagnosed by fetal echocardiography predominantly occurring in cases with obstructed outflow and to some extent patent mitral valve. EFE is a frequent coexisting finding. Hospital survival was comparable among different anatomical subgroups and in cases with VCAC. The presence of VCAC in HLH did not limit the results of surgical palliation within the observation period of 30 days.

[Assessment of fetal cardiac function--established and novel methods]. / Beurteilung der fetalen kardialen Funktion--etablierte und neue Methoden.

Numerous maternal (diabetes, preeclampsia) and fetal pathologies (uteroplacental dysfunction, hydrops, infection, congenital heart disease) can lead to cardiac dysfunction in the fetus. This includes increase of pre- and afterload, compression of the heart, myocardial damage, hypoxia and hyperglycemia. Beside already established methods like m-mode and pulse-waved Doppler, new promising technologies like tissue Doppler and speckle tracking are available for monitoring fetal cardiac function. Some of these new techniques have not been part of clinical routine yet because no validation has been performed so far and/or the technique is too time-consuming. Other technologies are currently being tested and only part of research projects. Innovations like speckle tracking that have its seeds in adult cardiology, are still limited because of the smallness of the fetal heart, the higher heart rate, fetal and maternal moving artefacts and finally because of a missing fetal ECG signal. Therefore their application should be performed critically.

[Peri- and postoperative management for minimally invasive fetoscopic surgery of spina bifida]. / Peri- und postoperatives Management von Schwangeren nach minimal-invasiver fetoskopischer Patchabdeckung bei fetaler Spina bifida aperta.

Minimally invasive fetoscopic surgery for spina bifida has been developed to improve the postnatal neurological function of affected fetuses and to achieve a reduced maternal trauma compared to open fetal surgery. This article gives an overview on the peri- and postoperative management of such cases at our centre.

[Lower urinary tract obstruction (LUTO)--clinical picture, prenatal diagnostics and therapeutic options]. / Lower Urinary Tract Obstruction (LUTO)--Krankheitsbild, pränatale Diagnostik und Therapiemöglichkeiten.

The aetiology of urinary tract obstructions (LUTO) is heterogeneous. The most common entities are isolated posterior urethral valves or urethral atresia in male foetuses. In female foetuses LUTO is frequently a part of complex malformations. The natural history of LUTO is characterised by high morbidity and mortality due to the development of severe pulmonary hypoplasia caused by oligo- or anhydramnios affecting the cannalicular phase (16-24 weeks of gestation) of pulmonary development. The degree of renal damage is variable and ranges from mild renal impairment in infancy to end-stage renal insufficiency, necessitating dialysis and transplantation. Foetal interventions in order to bypass the obstruction are biologically plausible and technically feasible. Vesico-amniotic shunting as well as (currently less frequent) foetoscopic cystoscopy and laser ablation of posterior urethral valves are minimally invasive treatment options. Previous reports indicate that prenatal therapy is suitable to reduce perinatal mortality but does not improve postnatal renal function. Selection of foetuses who may profit from prenatal intervention is aggravated by the lack of reliable prognostic criteria for the prediction of postnatal renal function in both ultrasound and foetal urine analysis. Furthermore, there is no randomised trial available at the time of writing. Because of a relevant complication rate and still no clear evidence for foetal benefit, interventions should be performed in specialised centres. Further studies are necessary to improve case selection of affected foetuses and to evaluate the impact of interventions in earlier gestational weeks. The data from the PLUTO trial (percutaneous shunting in lower urinary tract obstruction) conducted by the University of Birmingham may help to answer these questions. In the meantime selection of foetuses for prenatal intervention puts high requirements on interdisciplinary counselling in every case. A general treatment algorithm for foetal therapy is not available at the moment.

Preferential streaming of the ductus venosus toward the right atrium is associated with a worse outcome despite a higher rate of invasive procedures in human fetuses with left diaphragmatic hernia.

PURPOSE: Preferential streaming of the ductus venosus (DV) toward the right atrium has been observed in fetuses with left diaphragmatic hernia (LDH). The purpose of this retrospective study was to compare survival rates to discharge between a group with preferential streaming of the DV toward the right heart and a group in which this abnormal flow pattern was not present. MATERIALS AND METHODS: We retrospectively searched our patient records for fetuses with LDH in whom liver position, DV streaming and postnatal outcome information was available. 55 cases were found and divided into two groups: Group I fetuses exhibited abnormal DV streaming toward the right side of the heart; group II fetuses did not. Various prognostic and outcome parameters were compared. RESULTS: 62 % of group I fetuses and 88 % of group II fetuses survived to discharge (p = 0.032). Fetoscopic tracheal balloon occlusion (FETO) was performed in 66 % of group I fetuses and 23 % of group II fetuses (p = 0.003). Postnatal ECMO therapy was performed in 55 % of group I fetuses and 23 % of group II infants (p = 0.025). Moderate to severe chronic lung disease in survivors was observed in 56 % of the survivors of group I and 9 % of the survivors of group II (p = 0.002). CONCLUSION: Preferential streaming of the DV toward the right heart in human fetuses with left-sided diaphragmatic hernia was associated with a poorer postnatal outcome despite a higher rate of invasive pre- and postnatal procedures compared to fetuses without this flow abnormality. Specifically, abnormal DV streaming was found to be an independent predictor for FETO.

Review on current management and outcome data of echogenic lung lesions and hydrothorax of the fetus.

This review focuses on the prenatal management and outcome of echogenic lung lesions and isolated hydrothorax of the fetus. We give an overview of the most common forms of echogenic lung lesions like cystic adenomatoid malformation of the lung and bronchopulmonary sequestration as well as of congenital high airway obstruction sequence. We review the occurrence, appearance, pathophysiology and natural history of these lesions. Furthermore we discuss selection criteria for intrauterine treatment and algorithms for prenatal surveillance of affected fetuses.

Fetal pulmonary venous flow and restrictive foramen ovale in hypoplastic left heart.

PURPOSE: Hypoplastic left heart (HLH) with intact or restrictive interatrial communication (HLH-IAS/RAS) is associated with high mortality rates. The object was to correlate pulmonary venous (PV) Doppler spectra and direct foramen ovale (FO) assessment with the neonatal need for early atrial septostomy (EAS) and neonatal outcome. MATERIALS AND METHODS: We reviewed all prenatal echocardiograms and outcomes of 51 fetuses with HLH and information about the interatrial communication between 1994 - 2011.  IAS/RAS was defined as a small/absent interatrial shunt on 2-dimensional imaging. Three PV Doppler spectra were observed: type A: continuous forward flow with a small a wave reversal; type B: continuous forward flow with increased a-wave reversal; type C: brief to-and-fro flow. RESULTS: Three of 51 neonates with type C pulmonary venous flow pattern and suspicion of IAS/RAS on 2-dimensional (2-DE) evaluation required EAS.  In one fetus pulmonary venous flow changed from type B to type C spectra throughout gestation. Fetuses with type C spectra showed a 71.4 % survival after 30 days compared to 92.3 % in fetuses with type A spectra. Short term survival after EAS was 33 %. CONCLUSION: Prenatal PV flow pattern and 2-DE of the FO size help in identifying the fetus at risk for neonatal EAS and patient selection for fetal cardiac intervention. Most late second trimester values will not change over time.

Fetal diagnosis of hypoplastic left heart, associations and outcomes in the current era.

PURPOSE: Hypoplastic left heart (HLH) is one of the most common forms of cardiac abnormality detectable during gestation by fetal echocardiography. Antenatal diagnosis allows for appropriate counseling and time to consider treatment options. We report the actual outcome data after fetal diagnosis of HLH. MATERIALS AND METHODS: Retrospective analysis of the outcome in all cases with HLH from 1994 - 2011 presenting in fetal life at two tertiary referral centers for prenatal diagnosis and pediatric cardiology. RESULTS: 105 cases were included and the overall survival is 40.9 % (43/105) after prenatal diagnosis. There was an 81.1 % survival rate in infants undergoing surgery and a 64.1 % survival rate from an intention-to-treat position. Two neonates died due to tamponade and cardiac arrest following balloon septostomy and one neonate from sepsis before surgery. Extracardiac anomalies occurred in three fetuses, and karyotype anomalies in seven fetuses (18.9 %). In 4 of 5 babies born with additional extracradiac or karyotype anomalies, parents opted for compassionate care. The first had trisomy 13, the second had trisomy 18, the third neonate presented with spina bifida, and the fourth presented with hydronephrosis and pulmonary atresia. Termination of pregnancy took place in 17 cases (16.1 %). CONCLUSION: Thorough antenatal evaluation should include karyotyping, detailed extracardiac and intracardiac assessment to accurately predict the risks of surgery. Prenatal counseling might be modified after the exclusion of additional anomalies. These data provide up-to-date information for parental counseling.

Fetal loss rate and associated risk factors after amniocentesis, chorionic villus sampling and fetal blood sampling.

PURPOSE: To assess the total and procedure-related fetal loss rate and associated risk factors following amniocentesis (AC), chorionic villus sampling (CVS) and fetal blood sampling (FBS). MATERIALS AND METHODS: We performed a retrospective analysis of patients with invasive diagnostics from 1993 to 2011 in two tertiary referral centers. We aimed to classify pregnancy loss after an invasive procedure and included the time after the invasive procedure and the result of targeted ultrasound/karyotype analysis in the analysis. Fetal losses occurring within two weeks after an invasive procedure were classified as procedure-related. RESULTS: After excluding 1553 pregnancies with abnormal karyotype, fetal malformations and multiple insertions, 6256 cases were retrieved for final analysis. The total fetal loss rate was 1.5 %. The procedure-related fetal loss rate was 0.4 % for AC, 1.1 % for CVS and 0.4 % for FBS. Maternal vaginal bleeding in the first trimester was significantly associated with an increased procedure-related fetal loss rate (p= 0.008). The number of invasive procedures declined during the study period with increasing numbers of CVS in the first trimester. CONCLUSION: In our population the procedure-related fetal loss rate was 0.4 % after AC and 1.1 % and 0.4 % after CVS and FBS, respectively. Different gestational ages at the time of invasive procedures might account in part for those differences. Vaginal bleeding during the first trimester is associated with increased procedure-related fetal loss. Overall, declining numbers of invasive procedures are the result of changing attitudes toward invasive procedures and more sophisticated noninvasive prenatal screening programs over the last 20 years.

Adamantinoma-like Ewing's sarcoma: genomic confirmation, phenotypic drift.

Ewing's sarcoma, a highly malignant neoplasm, is characterized by an 11;22 translocation [t(11;22) (q24;q12)], resulting in the fusion of genes FLII and EWS. Adamantinoma of extragnathic bones, a low-grade malignant neoplasm with epithelial features, is not typically considered in the differential diagnosis of Ewing's sarcoma. In this study, three osseous Ewing's sarcomas with histological, immunohistochemical, or ultrastructural epithelial features were subjected to reverse transcription-polymerase chain reaction and sequencing studies for the Ewing's sarcoma molecular rearrangement. (Two of the three cases were originally described as adamantinomas or nontypical Ewing's sarcoma before the availability of genetic characterization.) In addition, traditional cytogenetic analysis and a unique combined interphase molecular cytogenetic/ immunocytochemical approach with bicolor 11;22 translocation breakpoint flanking probes (cosmids) and pancytokeratin antibodies were performed on one neoplasm. At(11;22) (q24;q12) was found in one neoplasm and a type II EWS/FLI-1 fusion transcript was detected in all three neoplasms. The combined genetic/immunocytochemical approach revealed the presence of the 11 ;22 translocation in the nuclei of cytokeratin immunoreactive cells. These genotypic and phenotypic findings delineate a novel Ewing's sarcoma histologic variant, "adamantinoma-like Ewing's sarcoma."

Low-level chromosome 12 amplification in a primary lipoma of the lung: evidence for a pathogenetic relationship with common adipose tissue tumors.

Cytogenetic analysis of a primary lipoma of the lung removed from a 56-year-old woman revealed the presence of a supernumerary marker chromosome in all metaphase cells analyzed; namely, 47,XX,+mar. To the best of our knowledge, this is the first cytogenetic description of a primary lipoma of lung. Genetic analysis of intramuscular lipoma, atypical lipoma, and well-differentiated liposarcoma have revealed the presence of one to three supernumerary ring or giant marker chromosomes composed of chromosome 12 segments as the characteristic anomaly. The marker chromosome in the present case was shown to be composed entirely of chromosome 12 material by subsequent analysis with a chromosome 12-specific paint probe and fluorescence in situ hybridization. Thus, analogous to intramuscular lipoma, atypical lipoma, and well-differentiated liposarcoma, extra chromosome 12 material is present. These findings support a pathogenetic relationship between this lipoma of unusual anatomic location and common adipose tissue tumors.