Nanocytological Fecal Assessment to Personalize Colonoscopic Surveillance

纳米细胞粪便评估以个性化结肠镜监测

• 批准号: 8314770
• 负责人: Hemant K. Roy
• 金额: $ 30万
• 依托单位: NANOCYTOMICS, LLC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8314770
• 关键词: American; Area; Biomedical Engineering; Biophotonics; Businesses; Cancer Etiology; Cells; Cessation of life; Clinical; Clinical Trials; Collection; Colon; Colonoscopy; Colorectal; Colorectal Cancer; DNA; DNA Methylation; Data; Detection; Development; Epithelial; Feces; Future; Gastroenterologist; Genetic; Goals; Grant; Healthcare; Hemoglobin; Individual; Internal Medicine; Lead; Legal; Lesion; Maintenance; Malignant Neoplasms; Malignant neoplasm of lung; Marketing; Microsatellite Repeats; Microscopy; Modality; Modeling; Molecular; Mucous Membrane; Mucous body substance; Natural History; Neoplasms; Occult blood screen; Optics; Ovarian; Patient Schedules; Patients; Phase; Physicians; Polypectomy; Procedures; Recording of previous events; Recruitment Activity; Recurrence; Resources; Right colon; Risk; Schedule; Screening procedure; Small Business Technology Transfer Research; Source; Speed; Surgeon; Techniques; Technology; Technology Transfer; Testing; Time; Training; Translating; Universities; Validation; adenoma; base; cancer diagnosis; carcinogenesis; clinical application; clinical practice; colorectal cancer prevention; colorectal cancer screening; commercialization; cost; follow-up; high risk; improved; instrument; instrumentation; interest; light scattering; multidisciplinary; nanoscale; neoplastic; neoplastic cell; new technology; novel; prevent; product development; rectal; tumor

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). PUBLIC HEALTH RELEVANCE: CRCs remain the second leading cause of cancer deaths among Americans. Colonoscopy can prevent CRCs by identifying and removing precursor lesions but this often obligates serial examinations. However, follow up colonoscopies (surveillance) are vastly overused and still allow a significant number of cancers to occur. Our goal is to leverage the remarkable sensitivity of the powerful new technology, PWS to develop a highly accurate minimally intrusive fecal test that could enable personalization of the procedure intervals.

描述（由申请人提供）： 每年 500 万例结肠镜检查（对既往肿瘤的随访）的临床影响非常低（> 90% 无明显肿瘤）。与此同时，结肠镜检查（间隔癌）期间结直肠癌（CRC）的发生频率惊人地频繁，尤其是在近端结肠。间期结直肠癌的医学法律和临床后果导致过度使用监测结肠镜检查，从而产生不必要的费用、并发症等。粪便测试是一种有吸引力的潜在辅助手段，尽管典型的测试 （潜血、DNA、甲基化）对晚期腺瘤（CRC 预防工作的目标）的敏感性较差（约 10-40%）。我们的多学科结直肠癌预防小组开发了一种粘液层粪便结肠细胞生物光子学测试，可以检测现场致癌作用以及不太丰富的肿瘤产物。我们采用了超灵敏的新技术，即部分波谱显微镜 (PWS)。 PWS 首次提供了一种实用的方法来量化临床前模型中纳米级结构结肠上皮的变化（PNAS，2008）。我们已经证明，结肠细胞 PWS 分析在识别整个结肠中结肠晚期腺瘤个体方面的准确度约为 90% (n=141) (Gastro, 2011)。为了让 Nanocytomics 将粪便 PWS 商业化，以定制结肠镜筛查间隔，我们建议开发一种高通量仪器（第一阶段），其准确性和速度具有里程碑意义（每位患者 <10 分钟）。第 2 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推迟（n=200 例训练和 200 组测试集） 2. 调查患者是否需要进行加急结肠镜检查（n=250） ）。这些将与传统的粪便测试（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，从而代表一个巨大且明确的商业机会。此外，利用 PWS 识别现场致癌作用是一个明确应用于平均风险 CRC 筛查以及其他癌症（肺癌、卵巢癌等）的平台。 公共卫生相关性： 结直肠癌仍然是美国人癌症死亡的第二大原因。结肠镜检查可以通过识别和去除癌前病变来预防结直肠癌，但这通常需要进行系列检查。然而，后续结肠镜检查（监测）被严重过度使用，并且仍然导致大量癌症的发生。我们的目标是利用强大的新技术 PWS 的卓越灵敏度来开发高精度、微创粪便测试，从而实现手术间隔的个性化。