High Resolution Microendoscopy for the Management of Esophageal Neoplasia

描述（由申请人提供）：尽管在放化疗治疗方面取得了进展，但由于在晚期无法治愈的阶段诊断，食管鳞状细胞瘤（ESCN）的5年生存率仍然只有15%。内镜筛查通常在高危人群中进行，对粘膜进行卢戈碘染色，对异常（未染色）区域进行靶向活检。虽然卢戈氏病显著增加了白色光内镜的敏感性（>95%），但特异性仍然很差（<65%），因为炎症和其他良性粘膜变化类似于肿瘤。虽然共聚焦显微内窥镜已被证明可以显著提高卢戈染色内窥镜的诊断准确性和产量，但现有平台价格昂贵（> 15万美元），仅在全球少数三级中心可用。我们的小组已经开发出一种便携式，电池供电，高分辨率显微内窥镜（mHRME），提供食管上皮的亚细胞图像，描绘与肿瘤相关的细胞和形态学变化。在最近的一项单臂试点试验（R21）中，HRME将Lugol筛查的灵敏度和特异性显著提高至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个低成本（<1600美元），基于平板电脑的系统，其软件界面可提供真实的实时图像解释帮助，从而促进经验不足的临床医生在低资源环境中的使用。我们的中心假设是，这种“光学”方法将提高效率，临床影响，和成本效益的现行标准的内镜筛查和监测。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镜筛查/监测标准进行比较。此外，我们还将构建、完善和分析ESCN疾病模型，以确定两国将HRME纳入内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其他器官（宫颈，结肠等）的全球癌症筛查。

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.).