Advanced Ultrasonic Evaluation of Sentinel Lymph Nodes

描述(由申请人提供)：河滨研究所、夏威夷大学和库阿基尼医学中心以及法国巴黎国家科学研究中心提议继续调查、改进和扩大新型定量超声方法的使用，以区分癌症患者的含癌和无癌淋巴结。淋巴结转移癌的检测对于准确的分期、预后和治疗计划是绝对关键的。我们的总体目标是显著减少现有组织病理学方法在25%到30%的解剖结节和50%有微转移的结节中检测转移的不可接受的失败。为了实现这一目标，我们建议在病理实验室开发使用高频超声的定量成像方法，以确定需要仔细组织学检查的解剖结节区域。我们已经朝着这个目标取得了令人振奋的进展，开发了一种灵敏和特异的超声方法，以高空间分辨率成像存在于淋巴结中的转移性疾病。我们的结果显示，对于广泛的癌症类型，我们具有在所解剖的淋巴结中检测癌症的非凡能力，并且它们有望提供一种革命性的方法来指导病理学家对所解剖的淋巴结中含有癌症的区域进行检测。我们提出的方法能够潜在地精确定位转移癌，当淋巴结包含微转移疾病时，可以极大地减少假阴性确定的发生，这一点很容易被当前的组织病理学方法忽视。我们目前的结果基本上证实了我们最初的假设，即所提出的方法可以同时识别解剖结节的含癌区域，灵敏度和特异度约为90%。这些发现鼓励我们的拟议研究完全达到我们的总体目标，它们表明同时达到95%的敏感度和特异度实际上是可能的。因此，我们建议获取更多数据来扩展我们现有的数据库，并彻底验证我们的发现。我们还建议研究在检查或手术室临床上应用相同频率的相同技术的可行性，以确定需要活检或剥离的结节。此外，我们建议改进使用甚高频超声显微镜的淋巴结超声散射模型，并制定能够在病理实验室常规执行结节评估的低成本超声仪器的工程规范。总之，该项目有助于对所有类型的癌症(如乳腺癌、结直肠癌、胃癌、胰腺癌、肺癌、甲状腺癌、前列腺癌等)的分期、预后和治疗计划的淋巴结评估，以及前哨淋巴结清扫术，例如乳腺癌。我们正在开发的方法可以对手术前或手术中检查的淋巴结节的原位评估、术中对区域淋巴结(包括前哨淋巴结)的评估以及术后对切除的淋巴结的评估产生重大的有益影响。

DESCRIPTION (provided by applicant): Riverside Research Institute, the University of Hawaii and Kuakini Medical Center, and the National Center for Scientific Research (Paris, France) propose to continue to investigate, refine, and expand the use of novel quantitative ultrasound methods for discriminating between cancer-containing and cancer-free lymph nodes of cancer patients. Detection of metastatic cancer in lymph nodes is absolutely crucial for accurate staging, prognosis, and treatment planning. Our overall objective is to reduce markedly the unacceptable failure of existing histopathological methods to detect metastases in 25% to 30% of dissected nodes and 50% in nodes with micrometastases. To achieve this objective, we proposed to develop quantitative imaging methods using high-frequency ultrasound in the pathology laboratory to identify regions of dissected nodes that warrant careful histologic examination. We have made exciting progress toward this objective by developing a sensitive and specific ultrasonic method of imaging metastatic disease present in lymph nodes with fine spatial resolution. Our results have shown a remarkable ability to detect cancer in dissected lymph nodes for a broad range of cancer types, and they promise a revolutionary means of guiding pathologists to cancer-containing regions of dissected lymph nodes. The demonstrated ability of our proposed methods to pinpoint metastatic cancer potentially can reduce the occurrence of false-negative determinations drastically when nodes contain micrometastatic disease, which easily can be overlooked using current histopathology methods. Our current results substantially have validated our original hypothesis that the proposed methods can identify cancer- containing regions of dissected nodes with a simultaneous sensitivity and specificity of approximately 90%. These findings provide encouragement that our proposed studies fully achieve our general objective, and they suggest that a simultaneous sensitivity and specificity exceeding 95% in fact may be possible. Therefore, we propose to acquire additional data to expand our existing database and thoroughly validate our findings. We also propose to investigate the feasibility of applying the same techniques at lower frequencies for clinical use in the examination or operating room to identify nodes that warrant biopsy or dissection. In addition, we propose to improve models for ultrasound scattering in lymph nodes using very-high-frequency ultrasonic microscopy and to formulate engineering specifications for a low-cost ultrasound instrument capable of performing node evaluations routinely in the pathology laboratory. In conclusion, this project can benefit lymph-node evaluations for staging, prognosis, and treatment planning of all types of cancers, e.g., breast, colorectal, gastric, pancreatic, lung, thyroid, prostate, etc., as well as sentinel-node dissection procedures, e.g., for breast cancer. The methods we are developing clearly can have a significant beneficial impact on in situ evaluations of lymph nodes examined prior to or during surgery, intra-operative evaluations of regional nodes including sentinel-nodes, and post-operative evaluations of dissected nodes.