Maternal mutations of FOXF1 cause alveolar capillary dysplasia despite not being imprinted.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare cause of pulmonary hypertension in newborns. Maternally inherited point mutations in Forkhead Box F1 gene (FOXF1), deletions of the gene, or its long-range enhancers on the maternal allele are responsible for this neonatal lethal disorder. Here, we describe monozygotic twins and one full-term newborn with ACD and gastrointestinal malformations caused by de novo mutations of FOXF1 on the maternal-inherited alleles. Since this parental transmission is consistent with genomic imprinting, the parent-of-origin specific monoallelic expression of genes, we have undertaken a detailed analysis of both allelic expression and DNA methylation. FOXF1 and its neighboring gene FENDRR were both biallelically expressed in a wide range of fetal tissues, including lung and intestine. Furthermore, detailed methylation screening within the 16q24.1 regions failed to identify regions of allelic methylation, suggesting that disrupted imprinting is not responsible for ACDMPV.

Thoracoscopic segmentectomy of methylene blue dyed intralobar sequestrations.

Surgical resection of congenital lung lesions has evolved with minimally invasive and parenchyma-preserving techniques. Although these lesions are usually small and their limits can be suspected by direct vision or palpation, there are no clear anatomic landmarks to enable a precise resection. This report presents a new technique that helps to define the limits of intralobar sequestrations, leading to a safe and anatomic thoracoscopic segmentectomy.

Successful Fetoscopic Surgery to Release a Complete Obstruction of the Urethral Meatus in a Case of Congenital Megalourethra.

We report the successful use of fetoscopy to treat a case of severe low urinary tract obstruction (LUTO) secondary to a congenital megalourethra. A second trimester male fetus presented at 21 weeks of gestation with massive dilatation of the penile urethra. In addition, bilateral hydronephrosis, an enlarged and hypertrophic bladder, with progressive oligohydramnios were found, suggesting poor prognosis. Extensive counselling was performed and, after the approval from the local ethics committee and informed consent, patients accepted fetal therapy by fetoscopy. The procedure consisted in fetoscopic identification of the tip of the penis and confirmation of the complete absence of the urethral meatus. Thereafter, under combined endoscopic and ultrasound guidance a perforation of the tip of the penis was performed with contact diode laser, until an opening into the urethra was achieved. After the operation, resolution of the cystic penile dilation, with reduction of the penile size, and normalization of the amniotic fluid volume were observed. The pregnancy continued uneventfully and a normal male infant was born at term at the local hospital. The baby was developing normally with normal renal function at 6 months of age. Our report demonstrates that fetoscopic decompression of a distal urethra obstruction can achieve neonatal survival in the rare event of congenital megalourethra.

Airway and vascular maturation stimulated by tracheal occlusion do not correlate in the rabbit model of diaphragmatic hernia.

BACKGROUND: In animal models of congenital diaphragmatic hernia (CDH), tracheal occlusion (TO) has induced maturation of both airway spaces and vascular structures. Airway and vascular response to TO are assumed to occur in parallel. This study aims to describe and measure the relationship between airway and vascular maturation induced by TO. METHODS: A rabbit model of CDH on gestational day (GD) 23 and TO on GD 28 (term = GD 31) has been used. Two study groups have been defined: DH (diaphragmatic hernia) and TO (DH treated with TO). Animals were collected on GD 30 and blood flow data of the pulmonary artery (pulsatility index (PI) and fractional moving blood volume) were ultrasonographically measured. Lung morphometry consisted of measurements of radial alveolar count (RAC) and arterial muscular thickness. RESULTS: Animals in the DH group (n = 9) had the worst hemodynamic parameters; their lungs were hypoplastic and had the thickest arterial muscular layer. Animals in the TO group (n = 10) had all these effects reversed. There were no correlations among hemodynamic, airway, and vascular parameters, except for RAC and PI (r = -0.528, P = 0.043). CONCLUSION: Airway and vascular maturation after TO appear to be uncorrelated effects. TO could trigger several pathways that separately regulate airway and vascular responses.

Changes in lung tissue perfusion in the prediction of survival in fetuses with congenital diaphragmatic hernia treated with fetal endoscopic tracheal occlusion.

OBJECTIVE: To assess the impact of lung perfusion by fractional moving blood volume (FMBV) for the prediction of survival in fetuses with congenital diaphragmatic hernia (CDH) treated with fetal endoscopic tracheal occlusion (FETO). STUDY DESIGN: Lung perfusion by FMBV (%) and the observed/expected lung-to-head ratio (o/e LHR) were evaluated 1 day before and 7-14 days after FETO in a cohort of 62 CDH fetuses, and their isolated and combined values to predict survival was assessed. RESULTS: Preoperative lung perfusion did not show association with survival. However, after FETO, an increase in 30% of the preoperative lung FMBV and an increase in 50% of the LHR was significantly associated with the probability of survival. A model combining the changes in FMBV and o/e LHR after therapy allowed discrimination of cases with poor (10% survival), moderate (40-70% survival) and very good prognosis (100% survival). CONCLUSION: Changes in lung tissue perfusion, evaluated by FMBV after FETO, improved the prediction of survival in fetuses with CDH.

Lung tissue blood perfusion changes induced by in utero tracheal occlusion in a rabbit model of congenital diaphragmatic hernia.

OBJECTIVE: To analyze the impact of in utero tracheal occlusion (TO) on lung tissue blood perfusion, as measured by fractional moving blood volume (FMBV) and conventional spectral Doppler, in a rabbit model of congenital diaphragmatic hernia (CDH). METHODS: In 50 fetal rabbits, a left CDH was surgically created at 23 days of gestational age (GA). At 28 days of GA, the surviving CDH fetuses were randomly assigned to undergo either TO (CDH+TO group) or a sham operation (CDH group). Twenty littermates, which were not operated on, served as internal normal controls. At 30 days of GA, lung perfusion estimated by FMBV and spectral Doppler of the proximal intrapulmonary artery were evaluated in the right lung during cesarean section. Doppler waveform analysis included the pulsatility index (PI), peak early diastolic reverse flow and peak systolic velocity. RESULTS: Eleven CDH fetuses, 9 CDH+TO and 20 controls were suitable for the study. CDH fetuses showed a significantly higher PI [8.0 (SD 1.8) vs. 5.22 (SD 1.1), p < 0.001] and lower FMBV [13.5% (SD 4.6) vs. 23.0% (SD 2.1), p < 0.001] than the controls. In contrast, CDH+TO fetuses had a significantly lower PI [5.8 (SD 2.3) vs. 8.0 (SD 1.8), p = 0.015] and higher FMBV [27.6% (SD 7.1) vs. 13.5% (SD 4.6), p < 0.001] than CDH fetuses, with values similar to the controls. Peak early diastolic reverse flow and peak systolic velocity showed nonsignificant differences among the study groups. The lung to body weight ratio at necropsy correlated positively with lung FMBV (r = 0.60, p < 0.001) and negatively with the pulmonary artery PI (r = -0.48, p < 0.01). CONCLUSION: Tracheal occlusion is consistently associated with increased lung tissue perfusion and decreased intrapulmonary impedance in a rabbit model of CDH.

Myofibroblastic tumor causing severe neonatal distress. Successful surgical resection after embolization.

This report describes a case of a term male 3.1 kg, normal delivery, 38 weeks of gestation with a record of hydramnios by prenatal sonography. He had fetal acute suffering and respiratory distress. The first radiographic study showed a mass filling the whole left thorax cage causing erosion of the inferior edge of the third rib. The mediastinum was displaced to the right. Computed tomography scan confirmed a homogeneous tumor that filled the left thorax and displaced the mediastinum to the right without invasion. Surgical biopsy informed of a highly vascularized mesenchymal tumor. The tumor was embolized with Ivalon microparticles obtaining a nearly avascular mass. Complete surgical excision was made, including the whole mass and costal segments. Microscopically, it was an inflammatory myofibroblastic tumor. It was composed mainly of spindle-shaped cells without malignant features. On immunohistochemistry, the tumor showed positive staining for vimentin, whereas antidesmin antibodies and S-100 protein were negative. The aim of this article is to present an extremely uncommon case of neonatal distress caused by an intrathoracic, extrapulmonary myofibroblastic tumor. Complete surgical resection was possible after embolization.

Congenital epigastric evisceration: a case report.

A rare case of abdominal wall defect at the epigastric midline is presented. This newborn boy had only the greater omentum eviscerated, and no other abnormalities could be detected. This case does not seem to relate to the abdominal wall defects reported so far in the literature. This singular case contributes to enlarge the spectrum of congenital defects of the abdominal wall.

ECMO pediàtric. A propòsit de dos casos / ECMO pediátrico. A propósito de dos casos / Pediatric ECMO: report of two cases

Introducció. Les tècniques de suport vital extracorpori (ECMO) s’han demostrat altament eficaces per al tractament de la insuficiència respiratòria o cardiorespiratòria, del nadó, sense resposta al tractament convencional. Sense aquesta tècnica, la mortalitat supera el 80% dels casos. Des de l’any 1984, s’han registrat a l’ELSO (Extracorporeal Life Support Organization) un total de 14.700 casos neonatals, amb una supervivència del 80%. A l’edat pediàtrica, l’experiència és molt inferior, amb un total de 1.723 casos registrats i una supervivència global del 50%. Observació clínica. Al nostre hospital, hem tingut l’oportunitat de tractar dues malaltes en edat pediàtrica: 1r cas, nena de 3 anys, afecta de sèpsia per pneumococ, amb afectació pulmonar bilateral, i insuficiència cardiorespiratòria refractària al tractament convencional; 2n cas, nena d’1 any d’edat, afecta d’insuficiència respiratòria severa en el postoperatori immediat, de la reparació completa d’una Tetralogia de Fallot. En tots dos casos es van aplicar tècniques de suport venoarterial (ECMO V-A), durant 10 i 4 dies respectivament, i en un d’ells es van reconstruir els vasos, en el moment de la decanulació. Les dos malaltes van ser donades d’alta hospitalària, en bon estat i sense seqüeles. Es tracta dels primers casos en edat pediàtrica tractats amb èxit a Espanya. Comentaris. El tractament amb ECMO pot ser una tècnica de suport eficaç en el maneig de la insuficiència cardiorespiratòria refractària al tractament convencional, millorant la supervivència d’aquests malalts crítics (AU)

Introducción. Las técnicas de soporte vital extracorpóreo (ECMO), para el manejo del fallo respiratorio o cardiorrespiratorio del recién nacido, sin respuesta al tratamiento convencional, han demostrado su elevada eficacia. La mortalidad de estos pacientes sin ECMO es superior al 80% de los casos. Desde 1984, se han recogido un total de 14.700 casos registrados en la ELSO (Extracorporeal Life Support Organization), con una supervivencia global del 80%. La experiencia clínica en la edad pediátrica es mucho menor, con 1.723 casos registrados y una supervivencia global del 50%. Observación clínica. En nuestro hospital, hemos tratado dos pacientes en edad pediátrica: 1 caso, niña de 3 años, afecta de una sepsis por neumococo, con afectación pulmonar severa y fallo cardiorrespiratorio refractario; 2º caso niña de 1 año que presenta insuficiencia respiratoria grave en el postoperatorio inmediato de la reparación completa de una Tetralogía de Fallot. En ambos casos se aplicaron técnicas de soporte veno-arterial (ECMO V-A) y en uno de ellos se procedió a la reconstrucción vascular en el momento de la decanulación. Ambas pacientes fueron dadas de alta hospitalaria, en buen estado y sin secuelas. Se trata de los primeros pacientes, en edad pediátrica, tratados con éxito con esta técnica, en España. Comentarios. El tratamiento con ECMO puede ser un soporte eficaz pàra el fallo cardíaorrespiratorio refractario al tratamiento convencional, aumentando la supervivencia de estos pacientes críticos (AU)

Introduction. The techniques of extracorporeal life oxygenation (ECMO) have shown their efficacy in the acute management of neonatal respiratory or cardio-respiratory distress syndrome unresponsive to conventional therapy. Mortality in this group of patients without the use of ECMO is greater than 80%. Since 1984, 14,700 neonatal cases have been registered at the Extracorporeal Life Support Organization (ELSO), with an overall survival of 80%. The pediatric experience is much less extensive, with 1,723 recorded cases, and an overall survival of 50%. Clinical observation. We have treated two pediatric patients with ECMO. The first case was a 3 year-old girl with pneumococal sepsis and acute respiratory distress syndrome, which was unresponsive to conventional therapy; the second case was a 1 year-old girl who developed an acute and refractory respiratory failure in the immediate postoperative course of a complete repair of Tetralogy of Fallot. In both patients, the severity of the respiratory failure warranted veno-arterial ECMO, with good response. They were weaned at 10 and 4 days, respectively, with vascular repair at the time of decanulation in the second case. Both patients recovered completely and were eventually discharged without complications. Comments. ECMO therapy can be an effective support for the management of postoperative cardiac and respiratory failure refractory to medical management (AU)

¿Por qué son tan frecuentes las reintervenciones en los hipospadias? / Why are reoperation for hypospadias so frequent?

Objetivo. Averiguar el porqué de las frecuentes reintervenciones en el tratamiento del hipospadias. Método. Se revisaron los expedientes de 64 niños afectos de esta anomalía que fueron reoperados entre 1990 y 2000. La edad media de la reintervención fue 6.4 años. Todas las reoperaciones fueron hechas por una sola persona (JRS). El resultado fue evaluado en función de la erección correcta, de la ubicación del meato, del calibre de la uretra y del chorro miccional, y del aspecto del prepucio. La causa del problema, fue evaluada en función de la catalogación del tipo de hipospadias, del procedimiento quirúrgico inicial, de la presencia de complicaciones producidas por defectos de técnica y de la presencia de complicaciones ligadas a procedimientos de elevada complejidad. Resultado. Las reintervenciones se produjeron en hipospadias de todo tipo. Los motivos principales fueron: fístula, estenosis, megalouretra, y recidiva de la incurvación. El resultado final fue bueno en todos los casos. La causa del problema fue la mala catalogación del tipo de hipospadias en el 14 por ciento de los casos, el procedimiento quirúrgico inicial mal escogido en el 28 por ciento, la presencia de complicaciones producidas por defectos de técnica en el 56 por ciento, y la presencia de complicaciones ligadas a procedimientos de elevada complejidad en el 50 por ciento. Conclusiones. Es necesario reintervenir frecuentemente los hipospadias por cuatro motivos, que además, suelen estar imbricados. Para prevenir las complicaciones es necesario catalogar correctamente el tipo de hipospadias, escoger adecuadamente el procedimiento quirúrgico y realizar cuidadosamente la cirugía. (AU)