CAREER: Establishing the Efficacy of Cryomyolysis - Cryosurgery of Uterine Fibroids

9703326子宫肌瘤是妇科最常见的脏器疾病，也是女性进行大手术的最常见原因。目前的治疗方法包括子宫切除术(手术切除子宫)、肌瘤切除术(手术切除肌瘤)，以及最近的肌松解术(破坏体内的肌瘤)。这项拟议的工作将调查冷冻外科治疗肌瘤或冷冻肌松解术作为患有肌瘤但不希望接受手术切除肌瘤或其子宫的女性的保守替代方案的可能性。这些假设是：1.冷冻肌松解术的效果主要是由于血管损伤(对滋养肌瘤的血管网络的损伤)，而不是直接的细胞损伤(对肌瘤细胞本身的损伤)，以及2.细胞破坏的程度可以根据冷冻肌溶解术期间施加在组织上的热历史来预测。通过在提案的特定目标中检验这些假设，我们将能够回答以下问题：摧毁单个肌瘤细胞和组织需要将温度保持多低多长时间？冷冻外科在体内(体内)和体外(体外)摧毁细胞和组织的能力有区别吗？如果存在差异，是否可以归因于体内(体内)血管损伤机制？最后，在手术过程中形成的冰球的大小与由于这项技术而被破坏的组织的数量有什么关系？这些问题的答案对于彻底了解冷冻破坏的机制，从而谨慎有效地应用这一外科技术治疗子宫肌瘤至关重要。***

9703326 Bischof Uterine fibroids are the most common organ disease in gynecology and the most common reason for major surgery in women. Current treatments include hysterectomy (surgical removal of the uterus), myomectomy (surgical removal of the fibroid), and most recently myolysis (destruction of the fibroid in the body). The proposed work will investigate the potential of cryosurgery of the fibroid or cryomyolysis as a conservative alternative for women who suffer from fibroids but do not wish to undergo a surgical operation to remove either the fibroid or their uterus. The hypotheses are: 1. The effectiveness of cryomyolysis is due primarily to vascular injury (damage to the vascular network nourishing the fibroid) as opposed to direct cellular injury (damage to the fibroid cells themselves), and 2. The extent of cellular destruction can be predicted based on the thermal history imposed on the tissue during cryomyolysis. By testing these hypothesis in the specific aims of the proposal, we will be able to answer the following questions: How low a temperature held for what length of time is necessary to destroy single fibroid cells and tissues? Is there a difference in the ability of cryosurgery to destroy the cells and tissues when they are in the body (in vivo) vs. when they are outside of the body (in vitro)? If a difference exists, can it be attributed to a vascular in injury mechanism inside the body (in vivo)? And finally, how does the size of the ice ball that is formed during the surgery correlate to the amount of tissue destroyed as a result of the technique? The answers to these questions are critical to a thorough understanding of the mechanism of cryosurgical destruction and, consequently, to the prudent and effective application of this surgical technique in uterine fibroids. ***