Novel Method of Surveillance in Barrett's Esophagus

描述(申请人提供)：Barrett‘s食道被认为是食管腺癌的前驱病变，食管腺癌是男性增长最快的癌症。有关这种情况的临床处理决定是基于巴雷特粘膜的活检，这些活检很难获得和充分解释，组织学检查成本高昂，而且经常遗漏有意义的病变。使用刷检收集的Barrett‘s食道脱落细胞有可能快速评估其恶性潜能。我们建议研究两种新的方法来评估脱落细胞，以提高对恶变的敏感性。我们的假设是，对脱落细胞进行数字图像分析(DIA)或荧光原位杂交(FISH)将能够预测Barrett食道癌的发展。我们已经证明，两者都与组织学有很好的相关性，来自监视活检的FISH明显优于DIA。这是利用一组12个探针的研究完成的，这些探针针对Barrett‘s食道癌进展的多个重要位点。我们利用这些信息选择了四个非常有针对性的基因座，我们认为这些基因座应该允许我们开发一种高通量测试来确定Barrett‘s食道脱落细胞的癌症风险。我们的主要目标是在细胞学标本中测试这种新的4探针FISH检测DIA，并使用监视活检的组织学结果作为我们的参考。这将通过对已知的Barrett‘s食道患者的细胞学标本进行FISH和DIA来完成。第二个目标将是确定获取显著不同数量的脱落细胞的细胞学收集设备是否会使用FISH或DIA产生不同的结果。商业上可用的细胞学刷子在收集脱落细胞的能力方面可能会有多达6倍的差异。我们开发了一种新的细胞学网络，可以获得五倍于刷子的细胞。我们建议将用于收集脱落细胞的细胞学收集设备随机化，以确定这是否会影响DIA或FISH的结果。这项研究的结果可能会改变医生评估Barrett‘s食道患者癌症风险的方法。希望通过使用FISH或DIA进行细胞学评估，能够获得更好的癌症风险信息，以便患者能够更早地发现癌症或进行预防癌症的治疗，从而减少食道癌相关死亡。这是一种创新的方法，医生可以通过它来诊断食道癌高危患者体内隐藏的癌症区域。

DESCRIPTION (provided by applicant): Barrett's esophagus is felt to be the precursor lesion to esophageal adenocarcinoma which is the most rapidly increasing cancer in males. Clinical management decisions concerning this condition are based on biopsies of the Barrett's mucosa which are difficult to adequately obtain and interpret, costly to examine histologically, and often miss lesions of significance. The use of exfoliated cells from Barrett's esophagus collected with brush cytology has the potential to rapidly assess its malignant potential. We propose to investigate two novel methods to assess exfoliated cells to increase the sensitivity for malignant changes. It is our hypothesis that either digital image analysis (DIA) or fluorescent in situ hybridization (FISH) performed on exfoliated cells will be able to predict cancer development in Barrett's esophagus. We have demonstrated that both correlate well with histology from surveillance biopsies with FISH being significantly superior to DIA. This was done using an investigational set of twelve probes that targeted multiple important loci for cancer progression in Barrett's esophagus. We have taken this information to select four very targeted loci that we believe should allow us to develop a high-throughput test to determine cancer risk from exfoliated cells from Barrett's esophagus. Our primary aim will be to test this novel 4 probe FISH test against DIA in cytology specimens using the results of histology from surveillance biopsy for our reference. This will be accomplished by performing FISH and DIA on cytological specimens from patients with known Barrett's esophagus. A secondary aim will be to determine if cytological collection devices that acquire significantly different numbers of exfoliated cells will yield different results using FISH or DIA. Commercially available cytological brushes can vary as much as 6-fold in their ability to collect exfoliated cells. We have developed a novel cytology net that can acquire five times as many cells as the brushes. We propose to randomize the type cytology collection device used to collect the exfoliated cells to determine if this affects the results of DIA or FISH. The results of this study can potentially change the method by which physicians can evaluate the cancer risk of patients with Barrett's esophagus. It is hoped that by using cytology assessed with FISH or DIA, better information of cancer risk can be obtained so that patients can have cancers detected earlier or be treated to prevent cancer in order to decrease esophageal cancer related deaths. This is an innovative method by which a physician can diagnose hidden areas of cancer within patients who are at a high risk of developing esophageal cancer.