Improving Flexible Sigmoidoscopy in Women by Optical Analysis of Microvasculature

描述（由申请人提供）：尽管有无数的筛查测试，结直肠癌（CRC）仍然是美国人癌症死亡的第二大原因。大约一半的人口没有接受任何CRC筛查，因为成本，访问和担心不适的程序和结肠清洗。软式乙状结肠镜检查（远端结肠的内窥镜评价）在社区中进行，与其他推荐的检查（例如结肠镜检查、CT结肠造影）相比具有许多优势，例如相对便宜，更广泛可用（由初级保健医生进行），并且在降低CRC死亡率和发病率方面具有已证实的疗效。然而，乙状结肠软镜检查对女性患者不敏感，因为女性患者易发生近端肿瘤。事实上，尽管flex sig可以识别出三分之二的男性晚期腺瘤，但它只能检测到三分之一的女性晚期腺瘤，这凸显了采取预防性方法的必要性。我们的多学科CRC预防小组专注于将新型光学技术与临床实践相结合。使用4维弹性光散射指纹（4D-ELF），我们发表了在CRC模型中，在任何组织学异常之前，隐窝周围毛细血管血液含量增加（我们称之为EIBS（早期血液供应增加）的现象）。我们开发了一种内窥镜兼容的光纤探头，并证明了EIBS是可检测的肿瘤病变的距离。在直肠中，EIBS可在结肠其他部位存在晚期肿瘤的患者中检测到。重要的是，直肠EIBS在女性中（与无肿瘤对照组相比增加约60%）比男性（约25%）更强，用于近端晚期肿瘤（无法通过柔性乙状结肠镜可视化）。因此，我们假设直肠EIBS测量将发现妇女的晚期近端肿瘤。我们将对接受结肠镜检查的女性进行直肠EIBS分析。我们将确定诊断EIBS参数，并确定人口统计学因素（如年龄，种族，吸烟，药物使用）对这些标志物的影响。这些数据将用于制定晚期近端腺瘤的预测规则。然后，我们将前瞻性地验证这一预测规则的一个单独的队列的妇女模拟真实的世界的灵活乙状结肠镜检查筛查条件之前，全结肠镜检查。这将为将来进行直肠EIBS作为女性Flex sig辅助治疗的多中心试验提供理论依据。如果成功，这种实用且相对便宜的方法可能是软乙状结肠镜作为女性准确，具有成本效益和患者友好的CRC筛查选择的复兴的关键。公共卫生相关性：软性乙状结肠镜检查作为结直肠癌筛查试验是广泛可用的，但在检测女性癌前息肉时不准确，主要是因为女性息肉往往位于软性乙状结肠镜无法触及的地方。我们相信，评估视觉正常直肠的浅表血供可能是唯一能够感觉到这些病变进一步在结肠的妇女。如果成功的话，这种相对便宜，易于使用的测试可能是一种辅助手段，以灵活的乙状结肠镜检查，从而使准确和具有成本效益的结直肠癌筛查妇女。

DESCRIPTION (provided by applicant): Despite a myriad of screening tests available, colorectal cancer (CRC) remains the second leading cause of cancer deaths among Americans. Approximately half the population does not undergo any CRC screening because of cost, access and concerns about discomfort with both the procedure and colonic purge. Flexible sigmoidoscopy (endoscopic evaluation of the distal colon) is performed in the community and has many advantages over other recommended tests (e.g. colonoscopy, CT colography) such as being relatively inexpensive, more widely available (performed by primary care physicians) and proven efficacy at decreasing both CRC mortality and incidence. However, flexible sigmoidoscopy is insensitive in women given their predilection for proximal neoplasia. Indeed, while flex sig identifies two-thirds of advanced adenomas in men, it only detects one-third in women highlighting the need for adjunctive approaches. Our multi-disciplinary CRC prevention group has focused on bridging novel optical technologies to clinical practice. Using 4-dimensional elastic light scattering fingerprinting (4D-ELF), we published that in CRC models, the peri-cryptal capillary blood content was increased prior to any histological abnormalities (a phenomena we termed EIBS (early increase in blood supply). We developed an endoscopically- compatible fiber-optic probe and demonstrated that EIBS was detectable at a distance from neoplastic lesions. In the rectum, EIBS was detectable in patients harboring advanced neoplasia elsewhere in their colon. Importantly, rectal EIBS was more robust in women (~60% increase versus neoplasia-free controls) than men (~25%) for proximal advanced neoplasia (that was not visualizable by flexible sigmoidoscope). We, therefore, hypothesize that rectal EIBS measurement will detect advanced proximal neoplasia in women. We will obtain rectal EIBS analysis on women undergoing colonoscopy. We will identify diagnostic EIBS parameters and determine the impact of demographic factors (e.g. age, race, smoking, medication use) on these markers. This data will be used to formulate a prediction rule for advanced proximal adenomas. We will then prospectively validate this prediction rule on a separate cohort of women simulating real world flexible sigmoidoscopy screening conditions prior to full colonoscopy. This will provide the rationale to performing future multi-center trials of rectal EIBS as an adjunct to flex sig in women. If successful, this practical and relatively inexpensive approach may be pivotal for the resurgence of flexible sigmoidoscopy as an accurate, cost-effective and patient-friendly CRC screening option in women. PUBLIC HEALTH RELEVANCE: Flexible sigmoidoscopy as a colorectal cancer screening test is widely available but inaccurate at detecting premalignant polyps in women, largely because women's polyps tend to be located out of reach of the flexible sigmoidoscope. We believe that assessing the superficial blood supply in the visually normal rectum may be uniquely able to sense these lesions further up in the colon of women. If successful, this relatively inexpensive, easy-to-use test may be an adjunct to flexible sigmoidoscopy thereby allowing accurate and cost-effective colorectal cancer screening for women.