Nanocytological Fecal Assessment to Personalize Colonoscopic Surveillance

描述(由申请人提供)： 每年监测的500万次结肠镜检查(对既往肿瘤的随访)对临床的影响非常低(90%没有明显的肿瘤)。与此相伴随的是结直肠癌(CRC)在两次结肠镜检查之间(间歇性癌症)的惊人频繁发生，尤其是在近端结肠。间歇性CRC的医疗法律和临床后果导致大量过度使用监视结肠镜检查，带来不必要的成本、并发症等。粪便检测是一个有吸引力的潜在辅助手段，尽管典型的检查 (隐血、DNA、甲基化)对晚期腺瘤的敏感性很差(~10-40%)，这是CRC预防工作的目标。我们的多学科结直肠癌预防小组已经开发出粘液层粪便结肠细胞生物光子学测试，该测试可以检测现场癌变以及数量较少的肿瘤产品。我们使用了我们的超灵敏新技术--部分波光谱显微镜(PWS)。PWS首次允许一种实用的方法来量化临床前模型中纳米尺度的结肠上皮结构改变(PNAS，2008)。我们已经证明，结肠细胞PWS分析对整个结肠(n=141)的晚期结肠腺瘤的个体识别准确率为~90%(Gastro，2011)。为了让纳米细胞公司将用于定制结肠镜筛查间隔的粪便PWS商业化，我们建议开发一种高通量仪器(第一阶段)，具有准确性和速度(每名患者10分钟)的里程碑。第二阶段将在两种常见情况下进行临床试验：1.确定原定接受结肠镜检查的患者是否可以安全地推迟(n=200个培训和200个测试组)2.调查患者是否需要进行快速结肠镜检查(n=250)。这些将与传统的粪便检测(免疫组织化学和DNA)进行比较。这些研究将有助于将PWS的力量与结肠镜筛查间隔个性化的临床应用联系起来，从而代表着一个巨大而明确的商业机会。此外，与其他癌症(肺癌、卵巢癌等)一样，用PWS鉴定现场癌变是一个明确的应用于平均风险CRC筛查的平台。

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).