Integrin α5 and Integrin α4 cooperate to promote endocardial differentiation and heart morphogenesis.

Endocardium is critically important for proper function of the cardiovascular system. Not only does endocardium connect the heart to blood vasculature, it also plays an important role in heart morphogenesis, valve formation, and ventricular trabeculation. The extracellular protein Fibronectin (Fn1) promotes endocardial differentiation, but the signaling pathways downstream of Fn1 that regulate endocardial development are not understood. Here, we analyzed the role of the Fibronectin receptors Integrin alpha5 (Itga5) and Integrin alpha4 (Itga4) in zebrafish heart development. We show that itga5 mRNA is expressed in both endocardium and myocardium during early stages of heart development. Through analysis of both itga5 single mutants and itga4;itga5 double mutants, we show that loss of both itga5 and itga4 results in enhanced defects in endocardial differentiation and morphogenesis compared to loss of itga5 alone. Loss of both itga5 and itga4 results in cardia bifida and severe myocardial morphology defects. Finally, we find that loss of itga5 and itga4 results in abnormally narrow anterior endodermal sheet morphology. Together, our results support a model in which Itga5 and Itga4 cooperate to promote endocardial differentiation, medial migration of endocardial and myocardial cells, and morphogenesis of anterior endoderm.

Minimally Invasive Surgery for Intrahepatic Cholangiocarcinoma: Patient Selection and Special Considerations.

Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary hepatic malignancy. Unfortunately, despite advancements in diagnosis, staging and management, mortality is high. Surgery remains the only curative treatment, but many patients present with advanced, unresectable disease. For patients able to undergo surgical resection, overall survival is improved, but remains low, with high rates of disease recurrence. Minimally invasive surgery (MIS), including laparoscopic and robotic approaches, are increasingly used in surgical resection for ICC. These approaches variably demonstrate faster recovery times, less blood loss, decreased postoperative pain and fewer postoperative complications, with adequate oncologic resections. This review examines patient selection and special considerations for MIS for ICC. Patient selection is critical and includes evaluation of a patient's anatomic and oncologic resectability, as well as comorbidities.