Arterial flow focalization could increase tissue oxygen partial pressure, or trigger endothelial shear stress - a new concept to overcome cancer hypoxia-induced radiotherapy resistance, or stimulate liver regeneration during fulminant hepatitis.
Malignant tumor hypoxia, which occurs due to abnormal and poor circulation of the tumoral vasculature, is the major cause of tumor aggressivity and failure of oncology therapeutics, particularly radiotherapy. Indeed, radio-sensitivity is reduced up to 3-fold in tumoral tissues with a lower oxygen partial pressure (PtO2). As such, there is no efficient means for increasing tumor PtO2 during radiotherapy sessions. Through a concept called "arterial flow focalization", by controlled temporary endo or peri-vascular occlusion of the collateral arterial branch(es) upstream of the tumor (organ), it is possible to redirect blood flow through the principal artery of the downstream tumor (organ), thereby increasing tumor arterial flow, and hence oxygen supply, thus increasing tumor PtO2 at the desired intensity and timing, in synchrony with radiotherapy, and greatly improving radiosensitivity. Chemotherapy and photodynamic therapy efficacy could be also be increased, by increasing the PtO2 and by improvement of tumor blood perfusion and hence drug delivery to the tumor. Furthermore, controlled focalization of arterial flow could be used in all necrotic disease processes, particularly fulminant hepatitis, to stimulate hepatocyte regeneration, not only through hyper-oxygenation, but also through triggering of endothelial shear stress in the sinusoidal wall.
Reyal
Julien
J
Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Sakyoku, Kyoto, Japan. julien.reyal@orange.fr
D001158:Arteries / Q000503:physiopathology*; D001783:Blood Flow Velocity; D015687:Cell Hypoxia; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006505:Hepatitis / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D008115:Liver Regeneration; D008954:Models, Biological; D009369:Neoplasms / Q000503:physiopathology* / Q000532:radiotherapy; D010100:Oxygen / Q000378:metabolism*; D010477:Perfusion / Q000379:methods; D033081:Shear Strength; D017211:Treatment Failure
D010100:Oxygen