Page 75 - Effects of radiotherapy and hyperbaric oxygen therapy on oral microcirculation Renee Helmers

INTRODUCTION
Radiotherapy (RT) has an essential role in the treatment of head and neck (HN)
cancer patients. Irradiation (IR) of HN malignancies concomitantly elicits acute
and late injuries to healthy tissues resulting in clinical side effects such as oral
mucositis, dry mouth, ulceration and osteoradionecrosis.11,35 Acute side effects
of RT usually heal by the end of treatment, whereas possible late effects due to
reduced vascularity and fibrosis tend to occur after a period of several months
to years after treatment.4,31,33 RT induced hypovascularity could progress in a
hypocellular and hypoxic tissue state in which the distressed tissue is unable to
establish an adequate healing response to injury and eventually succumbs to
tissue breakdown and osteoradionecrosis (ORN).20 ORN in HN has a reported
incidence of 2-22%23,25,34 and is a potentially mutilating and complicated
pathology to manage. 4
Experimental research fulfills an essential role in providing standardization of a model and controlled environments for studying pathophysiology and interventional responses associated with HN IR injury. In clinical studies standardization in design is difficult to achieve as tumor location and radiation dose varies between patients. Late IR tissue histopathology involving human jawbone presents as a progressive state of hypovascularity and fibrosis.6,19 Experimental studies that aimed to create a late IR tissue injury model in the HN region were previously conducted. Distraction osteogenesis on rabbit irradiated mandibles showed general reduction in vascularity, osteoblastic activity and bone regeneration compared to non-IR controls.7,17,24,38 Increased fibrosis and decreased vascularity in the soft tissues surrounding the irradiated mandible was observed after 5 fractions of 15 Gy in a rat IR model.31 In another model using mini-pigs, an increased amount of fibrosis and decreased vascular lumens in the mandible was proportionally dependent with the dose administered (25-70 Gy) 14-24 weeks after RT.27 Studies directed at evaluating the effects of RT mainly investigated tissue quality at functional or subcellular level by measurements obtained using x-ray microtomography (micro-CT),16,38,39 microangiography,18 transmission electron microscopy31 and by looking at histopathology.6,7,16-18,24,27,29,31,38,39 A disadvantage associated with most of the techniques listed above is that they are invasive and often require tissue manipulation and/or injecting a contrast medium for data acquisition. To further advance knowledge on oral tissue microvascular integrity and
Onset of late irradiation effects
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