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可用，结直肠癌(CRC)仍然是美国人癌症死亡的第二大原因。大约一半的人没有接受任何结直肠癌筛查，原因是费用、获取途径以及对程序和结肠清洗的不适的担忧。柔性乙状结肠镜检查(对远端结肠的内窥镜检查)是在社区进行的，与其他推荐的检查(如结肠镜检查、CT结肠造影术)相比具有许多优势，例如相对便宜、可获得更广泛的应用(由初级保健医生进行)，以及在降低结直肠癌死亡率和发病率方面被证明有效。然而，鉴于女性易患近端肿瘤，柔性乙状结肠镜检查对其不敏感。事实上，虽然flex sig在男性晚期腺瘤中发现了三分之二的病例，但在女性中只发现了三分之一，这突显了辅助手术的必要性。我们的多学科CRC预防小组专注于将新的光学技术应用于临床实践。利用四维弹性光散射指纹图谱(4D-ELF)，我们发现在结直肠癌模型中，隐窝周围毛细血管血液含量增加先于任何组织学异常(我们称之为EIBS(早期血液供应增加))。我们开发了一种与内窥镜兼容的光纤探头，并证明在距离肿瘤病变较远的地方可以检测到EIBS。在直肠中，在结肠其他部位有晚期肿瘤的患者中可以检测到EIBS。重要的是，直肠EIBS在女性(与无肿瘤对照组相比增加了~60%)比男性(~25%)在近端晚期肿瘤(这在柔性乙状结肠镜下看不到)中更健壮。因此，我们假设直肠EIBS测量将发现女性晚期近端肿瘤。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的参数，并确定人口统计因素(如年龄、种族、吸烟、用药)对这些标记物的影响。这些数据将被用来制定晚期近端腺瘤的预测规则。然后，我们将在一组单独的女性队列中前瞻性地验证这一预测规则，在完全结肠镜检查之前，模拟真实世界的灵活乙状结肠镜检查条件。这将为未来在女性中进行直肠EIBS作为FLEX SIG的辅助手段的多中心试验提供理论基础。如果成功，这种实用且相对便宜的方法可能对柔性乙状结肠镜作为一种准确、经济、患者友好的女性CRC筛查方法的复兴至关重要。公共卫生相关性：柔性乙状结肠镜作为结直肠癌筛查试验被广泛使用，但在检测女性癌前息肉方面并不准确，这主要是因为女性息肉往往位于柔性乙状结肠镜无法触及的地方。我们认为，评估视觉正常的直肠的浅表血液供应可能是唯一能够感觉到女性结肠上部分病变的方法。如果成功，这种相对便宜、易于使用的测试可能成为柔性乙状结肠镜检查的辅助手段，从而为女性进行准确且经济有效的结直肠癌筛查。

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.