Activated Braf induces esophageal dilation and gastric epithelial hyperplasia in mice.

Germline mutations in BRAF are a major cause of cardio-facio-cutaneous (CFC) syndrome, which is characterized by heart defects, characteristic craniofacial dysmorphology and dermatologic abnormalities. Patients with CFC syndrome also commonly show gastrointestinal dysfunction, including feeding and swallowing difficulties and gastroesophageal reflux. We have previously found that knock-in mice expressing a Braf Q241R mutation exhibit CFC syndrome-related phenotypes, such as growth retardation, craniofacial dysmorphisms, congenital heart defects and learning deficits. However, it remains unclear whether BrafQ241R/+ mice exhibit gastrointestinal dysfunction. Here, we report that BrafQ241R/+ mice have neonatal feeding difficulties and esophageal dilation. The esophagus tissues from BrafQ241R/+ mice displayed incomplete replacement of smooth muscle with skeletal muscle and decreased contraction. Furthermore, the BrafQ241R/+ mice showed hyperkeratosis and a thickened muscle layer in the forestomach. Treatment with MEK inhibitors ameliorated the growth retardation, esophageal dilation, hyperkeratosis and thickened muscle layer in the forestomach in BrafQ241R/+ mice. The esophageal dilation with aberrant skeletal-smooth muscle boundary in BrafQ241R/+ mice were recovered after treatment with the histone H3K27 demethylase inhibitor GSK-J4. Our results provide clues to elucidate the pathogenesis and possible treatment of gastrointestinal dysfunction and failure to thrive in patients with CFC syndrome.

Enfermedades esofágicas: enfermedad por reflujo gastroesofágico, Barrett, acalasia y esofagitis eosinofílica / Esophageal diseases: GERD, Barrett, achalasia and eosinophilic esophagitis

En la Digestive Disease Week 2014 se han presentado importantes novedades en patología esofágica. A destacar, respecto de la enfermedad por reflujo gastroesofágico, la utilidad de la impedanciometría para el diagnóstico de la enfermedad por reflujo, o la eficacia de los inhibidores de la bomba de protones para el tratamiento del dolor torácico no coronario. Respecto del esófago de Barrett, que su prevalencia es idéntica en pacientes con y sin síntomas de reflujo, que el < 1 cm probablemente no precisa seguimiento y que en pacientes de edad y con Barrett largo, la endoscopia inicial pasa por alto hasta un 2% de lesiones significativas. Respecto de la acalasia, la miotomía quirúrgica no es superior a la dilatación endoscópica y podría ser menos efectiva que la miotomía endoscópica peroral (POEM). Respecto de la esofagitis eosinofílica, es importante tomar biopsias sistemáticamente en pacientes con disfagia, para no pasar por alto casos de esofagitis eosinofílica y que, en esta patología, la dilatación endoscópica rutinaria no solamente no parece útil para mejorar el curso de la enfermedad, sino que incluso podría empeorar la respuesta al tratamiento médico

At Digestive Disease Week (DDW) 2014, developments in esophageal disease were presented. Highlights include: the usefulness of impedancemetry to diagnose reflux disease, or the effectiveness of PPIs for treating non-cardiac chest pain. Concerning Barrett's esophagus, its prevalence is identical in patients with and without reflux symptoms, Barrett segments less than 1cm probably do not require follow-up, and in older patients with long-segment Barrett, initial endoscopies overlooked up to 2% of significant lesions. Regarding achalasia, surgical myotomy is no more effective than endoscopic dilation and may even be less effective than peroral endoscopic myotomy (POEM). In terms of eosinophilic esophagitis, it is important to systematically take biopsies in patients with dysphagia so that cases of eosinophilic esophagitis are not overlooked. In addition, for this condition, routine endoscopic dilations not only do not seem useful in improving the course of the disease, but could also worsen the response to medical treatment