ABSTRACT
Pheochromocytomas are rare neuroendocrine tumors that can affect people of all ages and are commonly diagnosed in the 4th and 5th decades of life. Familial pheochromocytomas are diagnosed mostly between the 2nd and 3rd decades of life. They can be benign or metastatic and often present as isolated tumors or along with other neuroendocrine syndromes. We present a case of an elderly man who underwent laparoscopic adrenalectomy for pheochromocytoma at the age of 60 years but developed recurrence of metastatic pheochromocytoma after ten years. We also conducted a literature review to understand the epidemiology and presentation of the tumor and to emphasize that there should be a low threshold of suspicion for timely diagnosis and management of recurrent pheochromocytoma.
Subject(s)
Pheochromocytoma/complications , Stroke/diagnosis , Aged , Humans , Intensive Care Units/organization & administration , Male , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Pheochromocytoma/diagnosis , Pheochromocytoma/genetics , Pheochromocytoma/physiopathology , Stroke/geneticsABSTRACT
Liver sinusoidal endothelial cells (LSECs) represent the permeable interface that segregates the blood compartment from the hepatic cells, regulating hepatic vascular tone and portal pressure amidst changes in the blood flow. In the presence of pathological conditions, phenotypic changes in LSECs contribute to the progression of chronic liver diseases, including the loss of endothelial permeability. Therefore, modulating LSECs offers a possible way to restore sinusoidal permeability and thereby improve hepatic recovery. Herein, we showed that titanium dioxide nanoparticles (TiO2 NPs) could induce transient leakiness in primary human hepatic sinusoidal endothelial cells (HHSECs). Interestingly, HHSECs exposed to these NPs exhibited reduced protein kinase B (Akt) phosphorylation, an important protein kinase which regulates cell attachment. Using a 3D co-culture system, we demonstrated that TiO2 NPs diminished the attachment of HHSECs onto normal human hepatic cell LO2. To further illustrate the significance of leakiness in liver sinusoids, we showed that NP-induced leakiness promoted Sunitinib transport across the HHSEC layer, resulting in increased drug uptake and efficacy. Hence, TiO2 NPs have the potential to modulate endothelial permeability within the specialized sinusoidal endothelium, especially during events of fibrosis and occlusion. This study highlighted the possible use of inorganic NPs as a novel strategy to promote drug delivery targeting the diseased liver.
