Lymphatic Mapping and Sentinel Node ANALYSIS

描述(申请人提供)：结直肠癌(CRC)是第二位 是美国癌症死亡的主要原因。五年的生存 经过美国联合委员会的治疗，治愈率很高(90%) 癌症(AJCC)I期CRC，但随着疾病的进展而大幅下降 第二阶段(75%)和第三阶段(50%)。因此，淋巴的存在 淋巴结转移是影响预后的重要因素之一。 约三分之一的初诊为AJCC I或II期的患者 尽管有“阴性”的淋巴结，结直肠癌仍会发展成全身性疾病。这意味着 这些患者有隐匿性结节或全身疾病，目前尚无发现。 技巧。以往的研究表明，淋巴结微转移 超分期记录的病例与较差的存活率相关。因为平均水平 结直肠癌切除标本含有15个或以上淋巴结，利用 每个淋巴结的超分期技术将是劳动密集型和成本密集型的。 因此，一种将检查集中在最有可能发生淋巴结转移的方法 遏制转移将是有利的。 我们的假设是，不准确的病理分析(即 结直肠癌区域淋巴结的隐匿性转移)可能是I期或 会发展成系统性疾病的病人。为了解决这个问题， 改进的区域结节采样、病理分析和转移的方法 疾病检测是必要的。 JWCI开发了前哨淋巴结(SLN)技术，以改善分期和 减少黑色素瘤和乳房患者不必要的淋巴清扫 癌症。最近，新的分子技术和分子标记被 我们实验室开发的AD已被应用于提高对甲型肝炎的检测 微转移。我们已经成功地在试点中演示了SLN技术 对80例结直肠癌患者进行研究。此外，我们还鉴定了分子标记 在结肠癌细胞系、肿瘤组织和淋巴组织中 先导研究。更大规模的研究将提供统计意义 需要对结肠癌患者进行超分期并确定哪些患者 可能有复发的风险。 这项建议的具体目的是：1)确定准确性和 术中淋巴结标测和SLN活检的敏感性 2)评价分子和免疫组织化学检测方法。 以及，3)评估SLN的临床病理 超分期在预测疾病复发中的应用。这项建议 这种方法可能最终会改善患者对辅助治疗的选择 早期结肠癌切除后。

DESCRIPTION (Provided by applicant): Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. The five-year survival rate is high (90 percent) following treatment of American Joint Committee on Cancer (AJCC) stage I CRC but decreases substantially as disease progresses to stage II (75 percent) and stage III (50 percent). Hence, the presence of lymph node metastasis is one of the most important prognostic factors. Approximately one-third of patients initially diagnosed with AJCC stage I or II CRC develop systemic disease despite "negative" lymph nodes. This implies that these patients have occult nodal or systemic disease not detected by current techniques. Previous studies have demonstrated that lymph node micrometastases documented by ultrastaging correlate with poorer survival. Because the average CRC resection specimen contains 15 or more lymph nodes, the utilization of ultrastaging techniques on each lymph node would be labor and cost intensive. Therefore, a means of focusing an examination on the lymph nodes most likely to contain metastases would be advantageous. Our hypothesis is that inaccurate pathology analysis (i.e. the presence of occult metastasis in CRC regional lymph nodes) may account for the stage I or II patients that will develop systemic disease. To address this problem, improved methods for regional node sampling, pathology analysis, and metastatic disease detection are needed. JWCI developed the sentinel lymph node (SLN) technique to improve staging and reduce unnecessary lymph node dissections in patients with melanoma and breast cancer. More recently, novel molecular techniques and molecular markers were developed in our laboratory ad have been applied to increase the detection of micrometastases. We have successfully demonstrated the SLN technique in a pilot study with 80 CRC patients. Additionally, we have identified molecular markers in colon cancer cell lines, tumor tissue and lymph nodes from patients in the pilot study. A larger scale study will provide the statistical significance needed to ultrastage patients with colon cancer and determine which patients may be at risk for recurrence. The specific aims of this proposal are: 1) to determine the accuracy and sensitivity of intraoperative lymph node mapping and SLN biopsy in patients with CRC; 2) to evaluate molecular and immunohistochemical methods of detection of micrometastases in the SLN; and, 3) to evaluate the clinicopathological utility of ultrastaging in predicting disease recurrence. This proposed approach may ultimately improve the selection of patients for adjuvant therapy following resection of early-stage colon cancer.