Nanocytological Fecal Assessment to Personalize Colonoscopic Surveillance

描述（由申请人提供）： 每年500万次监测结肠镜检查（对既往肿瘤进行随访）的临床影响非常低（>90%，无显著肿瘤）。与此并列的是结肠镜检查（间隔癌）之间结直肠癌（CRC）的惊人频繁发生，特别是在近端结肠。间隔CRC的医学法律和临床后果导致大量过度使用监测结肠镜检查，产生不必要的费用，并发症等。粪便检查代表了一种有吸引力的潜在辅助手段，尽管典型的检查 （潜血、DNA、甲基化）对于晚期腺瘤（CRC预防工作的目标）的敏感性较差（~10-40%）。我们的多学科CRC预防小组已经开发了一种粘液层粪便结肠细胞生物光子学测试，该测试允许检测现场致癌沿着不太丰富的肿瘤产物。我们采用了我们的超灵敏的新技术，分波光谱显微镜（PWS）。PWS首次允许在临床前模型中量化纳米级结构结肠上皮改变的实用模式（PNAS，2008）。我们已经证明，结肠细胞PWS分析在识别整个结肠的结肠晚期腺瘤个体方面具有约90%的准确性（n=141）（Gastro，2011）。为了使Nanocytomics将粪便PWS商业化以定制结肠镜筛查间隔，我们建议开发具有准确性和速度里程碑（每个患者<10分钟）的高通量仪器（第1阶段）。第二阶段将涉及两种常见情况下的临床试验：1.确定计划进行结肠镜检查的患者是否可以安全地推迟（n=200训练集和200测试集）2.调查患者是否需要接受快速结肠镜检查（n=250）。这些将与常规粪便试验（免疫组织化学和DNA）进行比较。这些研究将有助于将PWS的功能与结肠镜筛查间隔个性化的临床应用联系起来，因此代表了一个巨大且明确的商业机会。此外，用PWS鉴定现场致癌作用是一个平台，明确应用于平均风险CRC筛查沿着其他癌症（肺癌、卵巢癌等）。

DESCRIPTION (provided by applicant): The clinical impact of the 5 million annual surveillance colonoscopies (follow up of previous neoplasia) is remarkably low (>90% without significant neoplasia). Juxtaposed with this is the alarmingly frequent occurrence of colorectal cancers (CRCs) in between colonoscopies (interval cancers), especially in the proximal colon. The medico-legal and clinical consequences of interval CRCs lead to vast overuse of surveillance colonoscopy engendering unnecessary cost, complications etc. Fecal tests represent an attractive potential adjunct although the typical tests (occult blood, DNA, methylation) have a poor (~10-40%) sensitivity for advanced adenomas, the target of CRC prevention efforts. Our multidisciplinary CRC prevention group has developed a mucus layer fecal colonocyte biophotonics test that allows detection of both field carcinogenesis along with the less abundant tumor products. We have employed our ultrasensitive novel technology, partial wave spectroscopic microscopy (PWS). PWS allows, for the first time, a practical modality to quantify nanoscale architectural colonic epithelial alterations in preclinica models (PNAS, 2008). We have demonstrated that colonocyte PWS analysis has a ~90% accuracy of identifying individuals for colonic advanced adenomas throughout the colon (n=141) (Gastro, 2011). In order for Nanocytomics to commercialize fecal PWS for tailoring colonoscopic screening intervals, we propose to develop a high throughput instrument (phase 1) with milestones of accuracy and speed (<10 minutes per patient). Phase 2 will involve clinical trials in two common scenarios: 1. Determine whether a patient scheduled for colonoscopy can be safely postponed (n=200 training and 200 testing set) 2. Investigate whether a patient needs to have an expedited colonoscopy (n=250). These will be compared to conventional fecal tests (immunohistochemical and DNA). These studies will be instrumental to bridge the power of PWS to the clinical application off colonoscopic screening interval personalization thus representing a large and well defined commercial opportunity. Furthermore, identification of field carcinogenesis with PWS is a platform with clear applications for average risk CRC screening along with other cancers (lung, ovarian etc).