[Congenital diaphragmatic hernia - mechanisms of pulmonary hypoplasia]. / Hernie congénitale du diaphragme : mécanismes de l'hypoplasie pulmonaire.

Congenital diaphragmatic hernia (CDH) is a common cause of severe neonatal respiratory distress. Mortality and morbidity are determined by the amount of pulmonary hypoplasia (PH) that occurs and by the development of therapy-resistant pulmonary hypertension. The pathogenesis and aetiology of CDH and its associated anomalies are still largely unknown despite all research efforts. The pathogenesis of CDH is based on an assumption linking herniation of abdominal viscera into the thorax with compression of the developing lung. PH, however, can also result from reduced distension of the developing lung secondary to impaired fetal breathing movements. Our understanding of CDH has also been aided by basic research with the use of dietary, teratogen-induced, and knockout models of CDH. These studies indicate that lung hypoplasia may involve disturbances of mitogenic signalling pathways fundamental to embryonic lung development. Recent data reveal the role of disruption of a retinoid-signalling pathway in the pathogenesis of CDH. Although multifactorial inheritance may best explain most cases of CDH in humans, much has been learned about the genetic factors that play a role in the development of CDH by studies of patients with CDH caused by specific genetic syndromes and chromosome anomalies. More research is warranted to improve our understanding of normal and abnormal lung development in relation to CDH. Such investigations will help in the design of new treatment strategies to improve the natural course or even to prevent this anomaly.

Prenatal diagnosis of lobar bronchial atresia.

We report three cases of fetal lobar bronchial atresia referred to our Fetal Medicine Center during the mid-trimester of pregnancy over the last 15 years. Lobar bronchial atresia can mimic a main stem bronchial atresia on mid-trimester ultrasound examination as it induces extensive lobar enlargement, major mediastinal shift and eversion of the diaphragm. It was associated with severe pulmonary hypoplasia in all three cases, even though polyhydramnios and ascites were absent in two. Termination of pregnancy was performed at parental request after extensive counseling in each of the cases and necropsy confirmed one or two enlarged lung lobes leading to major compression of the remaining lobe(s) of the ipsilateral lung, the contralateral lung and the heart. No other anomalies were observed and the karyotype was normal in all cases.

[Congenital lobar emphysema: a rare etiology of hyperechoic lung]. / Une étiologie rare de poumon hyperéchogène: l'emphysème lobaire géant congénital.

Lobar congenital emphysema is a rare pulmonary malformation corresponding to progressive overinflation of a pulmonary lobe secondary to partial bronchial obstruction. Prenatal diagnosis is mainly based on lung hyperechoic area. Sonographic features are not specific highlighting the interest of fetal MRI or postnatal tomodensitometry. This case report describes prenatal detection including pitfalls and postnatal management.

[Regression in primary cutaneous melanoma is not predictive for sentinel lymph node micrometastasis]. / Absence de valeur prédictive des signes de régression histologique sur l'envahissement du ganglion sentinelle.

BACKGROUND: The predictive value of regression in melanoma is debated. AIM OF THE STUDY: A retrospective single-centre study to evaluate the correlation between regression in primary skin tumor and the presence of micrometastases in sentinel lymph nodes. PATIENTS AND METHODS: Histological signs of regression in 84 melanomas (>1 mm) with corresponding sentinel lymph nodes were studied by two independent pathologists. RESULTS: Regression was seen in 40 skin melanoma tumors while micrometastasis was seen in 24. Of the tumors with micrometastasis, only 10 were regressive (RR: 0.47, p=0.49). Breslow value>2 mm and male sex were predictive for node micrometastasis (RR: 4.6, p=0.03 and RR: 7.6, p=0.006, respectively). On multivariate analysis, these two factors were independent. COMMENTS: These data suggest that regression in primary cutaneous melanoma is not predictive for lymph node metastasis.

Both GnRH agonist and continuous oral progestin treatments reduce the expression of the tyrosine kinase receptor B and mu-opioid receptor in deep infiltrating endometriosis.

BACKGROUND: Deep infiltrating endometriosis (DIE) is commonly associated with severe pain. The pain can be managed successfully with GnRH agonists or continuous progestins. The precise molecular mechanism by which DIE causes pain or why hormonal treatment is effective, however, remains unclear. We recently identified three potential candidate genes that might be involved in DIE pain pathways: tyrosine kinase receptor B (TrKB), mu-opioid receptor (MOR) and serotonin transporter (5HTT). We hypothesized that if these three genes were involved in DIE-associated pain, their expression levels would probably be modulated by GnRH agonist or progestin. In this study, we compared mRNA expression levels of TrKB, MOR and 5HTT in DIE among patients pre-operatively treated with GnRH agonist, progestin or without pre-operative medical treatments. METHODS: The expression levels of TrKB, MOR and 5HTT mRNA in DIE were determined using laser capture microdissection and real-time RT-PCR techniques. RESULTS: The expression levels of TrKB in epithelial cells and MOR in stromal cells from DIE were significantly decreased in patients with pre-operative GnRH agonist or progestin. There was no significant difference in 5HTT expression levels among untreated, GnRH agonist- and progestin-treated patients. CONCLUSION: The expression levels of TrKB and MOR genes in DIE appeared to be modulated by GnRH agonist or progestin. However, the functional roles of TrKB and MOR in DIE remain to be clarified.

Prenatal detection of mosaic isochromosome 20q: a fourth report with abnormal phenotype.

We described a new case of mosaic isochromosome 20q revealed by amniocentesis. The propositus presented with craniofacial dysmorphism, clubfeet, and vertebral abnormalities. A 46,XX,i(20)(q10)[14]/46,XX[1] karyotype was confirmed by FISH on cultured cells. The pregnancy was terminated. From review of literature, fetus with mosaic isochromosome 20q identified on amniocentesis are most likely to be phenotypically and cytogenetically normal after birth. So we performed CGH and array-CGH to exclude another possible imbalance. We discuss here the possible relation between this chromosomal abnormality and the abnormal phenotype.

Localization of human BRCA1 and BRCA2 in non-inherited colorectal carcinomas and matched normal mucosas.

We characterized the expression of BRCA1 and BRCA2 in 38 sporadic colorectal carcinomas and matched normal mucosas with 9 anti-BRCA1 antibodies and 4 anti-BRCA2 antibodies, raised against several different epitopes, using immunohistochemical technique. We demonstrated an increased BRCA1 and BRCA2 staining in the apical cell pole of epithelial malignant cells and we also revealed a significant increase in BRCA1 and BRCA2 nuclear foci in tumor colorectal specimens in comparison with corresponding normal tissues. These increases in BRCA1 and BRCA2 expression may be explained by the fact that colorectal tissue is subject to very active proliferation and differentiation.

Pseudo-meconium ileus due to cytomegalovirus infection: a report of three cases.

We observed three cases of antenatal ileus associated with cytomegalovirus (CMV) infection of the fetus and placenta. Two were detected antenatally because of increased echogenicity of the lower abdomen. In the first fetus, the ileus was associated with abnormalities of amniotic fluid enzymes but it was transient and not present at autopsy and the CMV infection was mild, without inflammatory infiltration or necrosis. In the two others, the ileus persisted and CMV-associated lesions were severe. In all three cases the virus was demonstrable in ganglion cells or within myenteric and submucosal plexuses all along the small and large intestine; ileus was imputed to CMV, which caused a paralytic ileus, and in one fetus meconium ileus was also present. A transient episode of ileus does not indicate that the fetus is free of disease and a wide range of causes must be considered, including CMV infection as well as the more usual causes such as cystic fibrosis (CF) and Hirschsprung's disease.