Novel Method of Surveillance in Barrett's Esophagus

描述（申请人提供）：Barrett食管被认为是食管腺癌的前体病变，而食管腺癌是男性中增长最快的癌症。关于这种情况的临床管理决策是基于巴雷特粘膜的活检，这些活检很难充分获得和解释，组织学检查成本高，并且经常错过重要的病变。使用刷细胞学方法收集Barrett食管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，以增加对恶性变化的敏感性。我们的假设是，对脱落细胞进行的数字图像分析（DIA）或荧光原位杂交（FISH）将能够预测Barrett食道的癌症发展。我们已经证明两者都与监测活检的组织学相关，FISH明显优于DIA。这是用一组12个探针完成的，这些探针针对巴雷特食道癌症进展的多个重要位点。根据这些信息，我们选择了四个非常有针对性的基因座，我们相信这些基因座可以让我们开发出一种高通量的检测方法，来确定巴雷特食管脱落细胞的癌症风险。我们的主要目的是利用监测活检的组织学结果，在细胞学标本中测试这种新的4探针FISH检测对DIA的影响，以供我们参考。这将通过对已知巴雷特食管患者的细胞学标本进行FISH和DIA来完成。第二个目的将是确定是否细胞学收集设备获得明显不同数量的脱落细胞将产生不同的结果使用FISH或DIA。市售的细胞学刷子收集脱落细胞的能力可相差6倍之多。我们开发了一种新的细胞学网络，它可以获得比刷子多五倍的细胞。我们建议随机化用于收集脱落细胞的类型细胞学收集设备，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巴雷特食道患者癌症风险的方法。希望通过FISH或DIA评估的细胞学，能够更好地掌握癌症风险信息，使患者能够及早发现癌症或进行防癌治疗，以减少食管癌相关死亡。这是一种创新的方法，医生可以通过这种方法诊断出食管癌高风险患者体内的癌症隐藏区域。

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.