High Resolution Microendoscopy for the Management of Esophageal Neoplasia

描述(由申请人提供)：尽管放化疗取得了进展，但由于诊断处于晚期，无法治愈，食道鳞状细胞瘤(ESCN)的五年存活率仍然很低，仅为15%。内窥镜筛查通常在高危人群中进行，对粘膜进行卢戈氏碘染色，并对异常(未染色)区域进行有针对性的活检。虽然Lugol氏显著提高了白光内窥镜检查的敏感性(&gt；95%)，但特异性仍然很低(&lt；65%)，因为炎症和其他良性粘膜病变类似于肿瘤。虽然共焦显微内窥镜已被证明可以显著提高Lugol的染色内窥镜的诊断准确性和产量，但现有的平台价格昂贵(15万美元)，而且仅在全球少数几个三级中心提供。我们团队开发了一种便携式、电池供电的高分辨率显微内窥镜(MHRME)，它提供了食道上皮的亚细胞图像，描绘了与肿瘤相关的细胞和形态变化。在最近的一项单臂试验(R21)中，HRME显著提高了卢戈尔筛查的敏感性和特异性，分别达到100%和89%。基于我们广泛的初步数据，我们现在建议优化和验证一种低成本(1600美元)的基于平板电脑的系统，该系统具有提供实时图像解释辅助的软件界面，从而促进经验较少的临床医生在低资源环境下的使用。我们的中心假设是，这种“最佳”方法将提高当前标准的内窥镜筛查和监测的效率、临床影响和成本效益。为了验证这一点，我们将对我们的‘光学活检’方法进行一项随机、多中心试验，将其与美国和中国目前的内窥镜筛查/监测标准进行比较。此外，我们将构建、改进和分析ESCN的疾病模型，以确定将HRME纳入两国内窥镜筛查和监测的有效性和成本效益。成功的结果可以很容易地转化为全球其他器官(宫颈、结肠等)的癌症筛查。

DESCRIPTION (provided by applicant): Despite advances in chemoradiation therapy, the five-year survival rate for esophageal squamous cell neoplasia (ESCN) remains a dismal 15% due to diagnosis at a late, incurable stage. Endoscopic screening is typically performed in high-risk populations with Lugol's iodine staining of the mucosa and targeted biopsy of abnormal (unstained) areas. While Lugol's significantly increases the sensitivity of white light endoscopy (>95%), specificity remains poor (<65%) as inflammation and other benign mucosal changes mimic neoplasia. While confocal microendoscopy has been shown to dramatically enhance the diagnostic accuracy and yield of Lugol's chromoendoscopy, existing platforms are costly (>$150,000) and only available in a handful of tertiary centers worldwide. Our group has developed a portable, battery-operated, high-resolution microendoscope (mHRME) that provides subcellular images of the esophageal epithelium, delineating the cellular and morphologic changes associated with neoplasia. In a recent, single-arm pilot trial (R21), the HRME significantly increased the sensitivity and specificity of Lugol's screening to 100% and 89%. Based on our extensive preliminary data, we now propose to optimize and validate a lower-cost (<$1600), tablet-based system with a software interface that provides real- time image interpretation assistance, thus facilitating usage by less-experienced clinicians in low-resource settings. Our central hypothesis is that this 'optical' approach will increase the efficiency, clinical impact, and cost-effectiveness of the current standard of endoscopic screening and surveillance. To validate this, we will conduct a randomized, multicenter trial of our 'optical biopsy' approach comparing it to the current standard of endoscopic screening/surveillance in the U.S. and China. In addition, we will construct, refine and analyze a disease model of ESCN to determine the effectiveness and cost-effectiveness of incorporating HRME into endoscopic screening and surveillance in both countries. Successful results can easily be translated to global cancer screening in other organs (cervix, colon, etc.).