High Resolution Microendoscopy for the Detection of Esophageal Neoplasia

描述（由申请人提供）：尽管放化疗治疗取得了进展，但由于诊断为晚期不可治愈阶段，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，对粘膜进行卢戈碘染色，对异常（未染色）区域进行靶向活检。虽然卢戈氏显着增加了标准白光内窥镜检查的灵敏度，但特异性仍然很差，因为炎症和其他良性粘膜变化可能与肿瘤相似。虽然使用共聚焦显微内镜的高分辨率成像已被证明可以显著提高卢戈染色内镜和其他宽视野技术的诊断准确性和产量，但现有平台价格昂贵（> 150，000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体内诊断（“光学活检”）来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（即靶向）活检，并将提供立即临床决策的可能性。为了确定这一点，我们将在美国和中国北方对接受内镜筛查疑似鳞状细胞瘤形成的高风险受试者进行该器械的临床试验。具体而言，我们将确定（a）HRME用于食管鳞状上皮瘤变体内诊断的诊断准确性（灵敏度和特异性），以及（B）HRME在该人群中的诊断率和潜在临床影响。成功的结果可以很容易地转移到其他器官系统（皮肤，结肠，子宫颈等）。 公共卫生相关性：食管癌是一个主要的全球性健康问题，在晚期诊断时预后不良。早期瘤形成的鉴别的改进为降低全世界的发病率和死亡率提供了最大的机会。

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.). PUBLIC HEALTH RELEVANCE: Esophageal cancer is a major global health problem and carries a poor prognosis when diagnosed at a late stage. The improved identification of early neoplasia offers the greatest opportunity to reduce morbidity and mortality worldwide.