EXPERIMENTAL INTRAOPERATIVE RADIOTHERAPY

描述：(改编自调查人员摘要)长期 这项研究的目的是提供有关该类型和 术后对正常腹主动脉周围组织的预期损伤频率 术中放疗(IORT)。人们对IORT非常感兴趣，因为 改善对位于放射敏感结构附近或 涉及大血管或神经的。这项研究的一个具体目的是 确定正常组织受照射体积的影响。作为 IORT的主要优点是限制照射体积 可能的，关于剂量体积关系的信息最多 很重要。体积研究的另一个目标是确定 犬慢性期病变的进展及发病机制 IORT后不同间隔的腹主动脉周围组织。这件事会做到的 主要采用专门的组织学技术，包括超微结构 学习。特别令人感兴趣的是细胞反应 作为从非照射组织的迁移，照射野的外围 可以根据照射的体积来改变组织响应。 这项研究的第二个目的是估计修复的数量和速度 间隔可变的分割剂量技术应用于腹主动脉周围组织 在第一剂和第二剂之间。连续的功能检查将 包括主动脉造影术和主动脉压力测量，观察 周围神经损伤，电生理测量，静脉注射 尿路造影术，血液和尿液化验。其他功能检查 包括输尿管肌电图和压力测量。身体解剖 狗在接受治疗三年后将提供组织进行形态测量 大动脉，动脉，微血管，周围神经， 肌肉、输尿管和腰椎。特别值得关注的将是 实质、间质和微血管的体积变化百分比。 血管、神经病变、结构中血栓和动脉瘤的发展 输尿管的损伤和骨坏死将被评估。此信息将 为那些使用IORT的人提供指导，从而降低后期发展的风险 可以减少严重的正常组织并发症。 提出的问题对放射治疗更具普遍意义，而不是 只是为了进行术中放射治疗。评估的组织是 从大动脉到毛细血管，周围神经，肌肉， 骨头和输尿管。几乎没有专门针对这些人的研究 组织，即使它们包括最常见的危险组织 放射治疗在许多情况下是有剂量限制的。因为它的尺寸 对于狗，它们都可以在相同的动物和相同的领域进行研究 辐射的影响。到目前为止关于辐射修复的问题 反应的组织和体积效应尚未得到回答，并且是 放射治疗中的主要问题。 所提出的动物模型的另一个重要属性是功能性 组织学研究也可以在同一种动物身上进行。功能界别 研究与临床相关，瘫痪的终点，输尿管 结构、动脉瘤、血栓形成、骨坏死和肌肉萎缩 显然，辐射的临床后果很重要。仔细的组织学 通过评估，可以进行剂量反应比较和深入了解 导致晚期后果的机制和细胞相互作用 辐射。

DESCRIPTION: (Adapted from investigator's abstract) The long term objective of this research is to provide information on the type and expected frequency of injury to normal periaortic tissues following intraoperative irradiation (IORT). There is great interest in IORT for improving control of tumors located near radiosensitive structures or involving large vessels or nerves. A specific aim of this study is to determine the effect of the volume of normal tissue irradiated. As the major advantage of IORT is to restrict the irradiated volume as much as possible, information concerning dose volume relationships is most important. Another objective of the volume study is to determine the progression and pathogenesis of slowly developing lesions in canine periaortic tissues at variable intervals following IORT. This will be done primarily with specialized histologic techniques including ultrastructural studies. Of particular interest is the cellular response near the periphery of the irradiated field as migration from non-irradiated tissue may modify the tissue response depending on volume irradiated. A second aim of this is to estimate the amount and rate of repair of periaortic tissues using split dose techniques with variable intervals between the first and second dose. Sequential functional examinations will include aortagrams and aortic pressure measurements, observations for peripheral nerve injury, electrophysiologic measurements, intravenous urography, and blood and urine chemistries. Other functional examinations include ureteral electromyography and pressure measurements. Necropsies of dogs three years following treatment will provide tissues for morphometric analysis of the aorta, arteries, microvasculature, peripheral nerves, muscles, ureters, and lumbar vertebrae. Of special interest will be the percentage volume changes in parenchyma, stroma and microvasculature. Development of thrombi and aneurysms in vessels, neuropathies, structures of ureters and bone necrosis will be evaluated. This information will provide guidance to those using IORT so that the risk of late developing serious normal tissue complications can be reduced. The questions asked are of more general interest in radiation therapy than just for intraoperative radiation therapy. The tissues evaluated are the entire vascular tree from aorta to capillaries, peripheral nerves, muscle, bone and ureters. There is little research specifically directed at those tissues even though they include the most common tissues at risk in radiation therapy and in many cases are dose limiting. Because of the size of the dog, they can all be studied in the same animal and the same field of irradiation. Questions concerning radiation repair by these late responding tissues and volume effects have not been answered and are of major concern in radiation therapy. Another important attribute of the animal model proposed is that functional and histologic studies can be done on the same animal. The functional studies are clinically relevant, the end points of paralysis, ureteral structure, aneurysm, thrombosis, bone necrosis and muscle atrophy are obviously important clinical consequences of radiation. Careful histologic evaluations permit dose response comparisons and insight into the basic mechanisms and cellular interactions leading to late consequences of irradiation.