Spectroscopic Markers to Risk-Stratify Colonic Neoplasia

描述(申请人提供)：为了优化结肠镜检查结直肠癌(CRC)的风险效益和成本效益，风险分层是至关重要的。利用“场效应”，即容易接近的结肠粘膜(即直肠)应该反映整个结肠的肿瘤风险，这是一个有吸引力的命题。然而，目前的标记物如远端/直肠腺瘤和迷走性隐窝病灶(ACF)缺乏对临床实用的敏感性和预测价值。我们最近开发了四维弹性光散射指纹技术(4D-ELF)，这是一种生物医学光学技术，使我们能够在原位收集迄今为止无法获得的关于活上皮纳米/微结构的定量信息。使用4D-ELF，我们在组织学上正常的粘膜中发现了几个光谱特征，这些特征早于所有传统的结直肠癌生物标记物，并且是结肠癌发生实验模型中最早的“场效应”标记物之一。事实上，直肠光谱标记物对肿瘤风险具有前所未有的敏感性、特异性、阳性预测值和阴性预测值。初步研究证实了这些光谱标记与人类的相关性。这项拟议的项目将检验直肠光谱标记物可以预测并发和未来结肠肿瘤发生的假设。在这一应用中，我们建议构建一种内窥镜兼容的4D-ELF探头，以评估在中等风险患者的结肠镜检查中发现肿瘤的直肠光谱标记物(已建立的和新的)预测规则的性能特征。我们还将通过评估直肠ACF数量和接受结直肠癌切除患者的监测内窥镜中腺瘤的发生，来确定光谱标记物预测未来肿瘤形成的能力。最后，我们将进行初步研究，以了解光谱标记的生物学基础。将来，光谱标志物可以在常规直肠检查中用4D-ELF探头进行分析(不需要肠道准备或结肠镜检查)，从而提供一种实用而准确的手段来确定最佳的CRC筛查方案，例如需要结肠镜检查。

DESCRIPTION (provided by applicant): In order to optimize the risk-benefit and cost-effectiveness of colonoscopy for colorectal cancer (CRC) screening, risk-stratification is of paramount importance. Exploitation of the "field effect" in which readily accessible colonic mucosa (i.e. rectum) should reflect the neoplastic risk throughout the colon, is an attractive proposition. However, current markers such as distal/rectal adenomas and aberrant crypt foci (ACF) lack the sensitivity and predictive value for clinical utility. We have recently developed four-dimensional elastic light scattering "fingerprinting" (4D-ELF), a biomedical optics technology that allows us to gather heretofore unattainable quantitative information about nano/micro-architecture of living epithelia in situ. Using 4D-ELF, we discovered several spectral signatures in histologically normal mucosa that preceded all conventional biomarkers of CRC and served as one of the earliest markers of the "field effect" in experimental models of colon carcinogenesis. Indeed, rectal spectral markers had unprecedented sensitivity, specificity, positive and negative predictive values for neoplastic risk. Pilot studies confirmed the relevance of these spectral markers to humans. The proposed project will test the hypothesis that rectal spectral markers can predict the occurrence of concurrent and future colonic neoplasia. In this application, we propose to construct an endoscopically compatible 4D-ELF probe in order to assess performance characteristic of prediction rules of rectal spectral markers (established and novel) for neoplasia detected on colonoscopy in average risk patients. We will also ascertain the ability of spectral markers to predict future neoplasia by evaluating rectal ACF number and adenoma occurrence in surveillance endoscopies of patients undergoing CRC resection. Finally, we will perform initial studies to understand the biological basis of spectral markers. In the future, spectral markers may be assayed with a 4D-ELF probe during a routine rectal examination (without the need for bowel preparation or colonoscopy) thus providing a practical and accurate means of determining the optimal CRC screening regimen, such as the need for colonoscopy.