High Resolution Microendoscopy for the Detection of Esophageal Neoplasia

描述（由申请人提供）：尽管放化疗取得了进展，但由于诊断晚期，无法治愈，食管鳞状细胞癌（SCC）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Lugol's碘染色，并对异常（未染色）区域进行靶向活检。虽然Lugol's显著提高了标准白光内镜的敏感性，但特异性仍然较差，因为炎症和其他良性粘膜变化可模拟肿瘤。虽然高分辨率成像的共聚焦内窥镜已经被证明可以显著提高Lugol色内窥镜和其他宽视场技术的诊断准确性和产量，但现有的平台价格昂贵（约15万美元），并且仅在世界范围内的少数三级中心可用。我们的团队开发了一种低成本、便携式、电池供电的高分辨率显微内窥镜（HRME），可以提供食管上皮的亚细胞图像，并描绘与肿瘤相关的细胞和形态学变化。我们的中心假设是，这种低成本的成像设备将通过在临床不确定的区域提供实时的体内诊断（“光学活检”），提高当前内窥镜筛查实践的效率和产量。这将允许更多的选择性（即有针对性的）活组织检查，并将提供即时临床决策的潜力。为了确定这一点，我们将在美国和中国北部对高风险受试者进行内镜筛查，以检查疑似鳞状细胞瘤，并对该设备进行临床试验。具体而言，我们将确定(a) HRME在体内诊断食管鳞状瘤变的诊断准确性（敏感性和特异性），以及(b) HRME在该人群中的诊断率和潜在的临床影响。成功的结果可以很容易地转化为其他器官系统（皮肤，结肠，宫颈等）。

DESCRIPTION (provided by applicant): Despite advances in chemoradiation therapy, the 5-year survival rate from esophageal squamous cell cancer (SCC) 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 standard white-light endoscopy, specificity remains poor as inflammation and other benign mucosal changes can mimic neoplasia. While high-resolution imaging with confocal endomicroscopy has been shown to dramatically enhance the diagnostic accuracy and yield of Lugol's chromoendoscopy and other widefield techniques, existing platforms are costly (> $150,000) and only available in a handful of tertiary centers worldwide. Our group has developed a low-cost, portable, battery-operated high-resolution microendoscope (HRME) that can provide subcellular images of the esophageal epithelium and delineate the cellular and morphologic changes associated with neoplasia. Our central hypothesis is that this low-cost imaging device will increase the efficiency and yield of current endoscopic screening practices by offering a real-time, in vivo diagnosis ('optical biopsy') in clinically indeterminate areas. This will allow for more selective (i.e. targeted) biopsies and will offer the potential for immediate clinical decision- making. To determine this, we will conduct a clinical trial of the device in high-risk subjects undergoing endoscopic screening for suspected squamous cell neoplasia in both the United States and northern China. Specifically, we will determine (a) the diagnostic accuracy (sensitivity and specificity) of the HRME for the in vivo diagnosis of esophageal squamous neoplasia, and (b) the diagnostic yield and potential clinical impact of the HRME in this population. Successful results can easily be translated to other organ systems (skin, colon, cervix, etc.).