Task Specific Project 3

在特定的目标3c中，我们想要演示使用荧光标记的多肽来引导组织活检。 在广域内窥镜下观察Barrett‘s食道的扁平不典型增生。我们可以继续我们的 在结肠的努力下，这个器官的大表面积使得扁平的不典型增生很难在这个演示中找到。 相反，扁平型不典型增生更容易在Barrett‘s食道周围发生。这是一个 食管腺癌与胃食道相关的重要癌前状态 这种癌症是高加索男性中增长最快的癌症，其发病率 91不幸的是，Barrett‘s食道是一种常见的疾病，在7%的 接受结肠镜检查的患者结肠癌患病率为6%，即使在没有结肠癌的患者中也是如此 有胃食道反流型症状。92然而，只有一小部分Barrett‘s食道 癌症的进展。这种情况在接受常规治疗的无症状患者中高达25%。 93.有人建议，对这些患者最有效的治疗方法应该建立在 异型增生的组织学证据，这是唯一临床上使用的进展为癌症的生物标志物。 所有临床指南都使用异型增生来确定患者的治疗和监测，但它是 认识到异型增生在Barrett‘s节段内很难找到，也很难标准化 释义。事实上，异型增生并不能很好地符合NIH的生物标记物标准，因为它确实不能客观地 在一项评估领先的胃肠道疾病患者之间的一致性的研究中进行了测量 美国的病理学家发现，每一级不典型增生的卡帕评分为0.42。 内窥镜下可见正常鳞状上皮化生为柱状上皮 作为胃食道连接处的延伸。与结肠相似，Barrett‘s患者的筛查 需要检测和定位异型增生，它是平坦的，在内窥镜下与Barrett‘s不明显 白光下的食道。目前，在4个象限中随机进行1到2厘米的广泛活组织检查 建议间隔使用巨型活检钳(西雅图方案)。94然而，由于该技术 它是劳动密集型的，需要治疗性内窥镜，只有不到20%的美国人使用它。 此外，这种筛查方法还没有被证明可以降低 Barrett‘s食管腺癌的进展。96因此，一种新的检测和定位方法 需要在Barrett‘s食道周围发生异型增生。

In Specific Aim 3c, we would like to demonstrate the use of fluorescent-labeled peptides to guide tissue biopsy 'of flat dysplasia in the setting of Barrett's esophagus on wide area endoscopy. While we could continue our efforts in colon, the large surface area in this organ renders flat dysplasia difficult to find for this demonstration. Instead flat dysplasia is much more readily accessible in the setting of Barrett's esophagus. This is an important pre-malignant condition for esophageal adenocarcinoma that is associated with gastroesophageal reflux disease.90 This cancer is the most rapidly increasing cancer in Caucasian males when incidence rates are normalized to incidence.91 Unfortunately, Barrett's esophagus is a common condition diagnosed in 7% of patients undergoing screening colonoscopy for colon cancer with 6% prevalence even in those who have not had gastroesophageal reflux type symptoms.92 However, only a small minority of cases of Barrett's esophagus progress to cancer. This condition is found in as high as 25% of asymptomatic patients undergoing routine endoscopy.93 It has been suggested that the most effective approach to these patients should be based on the histological evidence of dysplasia which is the only clinically utilized biomarker for progression to cancer. Dysplasia is used by all of the clinical guidelines to determine therapy and surveillance in patients yet it is recognized that dysplasia is difficult to find within the Barrett's segment as well as difficult to standardize its interpretation. In fact, dysplasia does not well fit NIH criteria for a biomarker as it really cannot be objectively measured as demonstrated in a study that assessed agreement among the leading gastrointestinal pathologists in the United States and found a kappa score of 0.42 for each grade of dysplasia.72 This metaplastic conversion of normal squamous epithelium into columnar epithelium can be seen endoscopically as an extension of the gastroesophageal junction. Similar to the colon, screening of patients with Barrett's requires detection and localization of dysplasia, which is flat and endoscopically indistinct from Barrett's esophagus on white light. Currently, extensive biopsies performed randomly in 4 quadrants at 1 to 2 cm intervals using jumbo biopsy forceps (Seattle protocol) are recommended.94 However, because the technique is labor-intensive and requires a therapeutic endoscope, it is used by less than 20% of U.S. gastroenterologists.95 Furthermore, this method of screening has not been shown to reduce the rate of progression of Barrett's esophagus to adenocarcinoma.96 Thus, a new method for detecting and localizing dysplasia in the setting of Barrett's esophagus is needed.