Task Specific Project 3

任务特定项目 3

• 批准号: 7728718
• 负责人: Alnawaz Rehemtulla
• 金额: $ 4.77万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-29 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7728718
• 关键词: Adenocarcinoma; Agreement; Area; Barrett Esophagus; Binding; Biological Markers; Biopsy; Caucasians; Caucasoid Race; Cells; Clinical; Colon; Colon Carcinoma; Colonoscopy; Columnar Epithelium; Condition; Detection; Diagnosis; Dysplasia; Endoscopes; Endoscopy; Esophageal; Esophageal Adenocarcinoma; Esophagogastric Junction; Fluorescein-5-isothiocyanate; Forcep; Gastroenterologist; Gastroesophageal reflux disease; Genus Cola; Guidelines; Incidence; Label; Ligands; Light; Localized; Malignant Neoplasms; Measures; Medical Surveillance; Metaplastic; Methods; Minority; Molecular Target; Organ; Pathologist; Patients; Peptides; Phage Display; Premalignant; Prevalence; Protocols documentation; Rate; Score; Screening procedure; Squamous Epithelium; Surface; Symptoms; Techniques; Therapeutic; Tissues; United States; United States National Institutes of Health; base; gastrointestinal; male

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.

在Specific Aim 3c中，我们希望展示荧光标记肽用于指导组织活检 在Barrett食管的大面积内镜检查中发现扁平型异型增生。虽然我们可以继续我们的 在结肠的努力，在这个器官的大表面积呈现平坦的异型增生很难找到这个演示。 相反，在Barrett食管的情况下，平坦型异型增生更容易接近。这是一 与胃食管癌相关食管腺癌的重要癌前状态 90这种癌症是高加索男性中发病率增长最快的癌症， 已标准化为发生率。91不幸的是，巴雷特食管是7%的人诊断出的常见疾病 接受结肠镜检查的结肠癌筛查患者，即使在未接受结肠镜检查的患者中， 92然而，只有少数巴雷特食管病例 发展到癌症。这种情况在高达25%的无症状患者中发现， 93有人建议，对这些患者最有效的方法应该是基于 发育异常的组织学证据，其是进展为癌症的唯一临床上使用的生物标志物。 所有临床指南都使用异型增生来确定患者的治疗和监测， 认识到发育不良在巴雷特节段内难以发现，并且难以将其标准化， 解释。事实上，异型增生并不完全符合NIH的生物标志物标准，因为它确实不能客观地 一项评估主要胃肠道疾病之间一致性的研究表明， 美国的病理学家发现，每一级发育不良的Kappa评分为0.42。 内镜下可见正常鳞状上皮化生为柱状上皮 作为胃食管连接处的延伸与结肠类似，筛查巴雷特氏病患者 需要检测和定位异型增生，异型增生是扁平的，内镜下与巴雷特氏病难以区分 食管在白色光下。目前，广泛的活组织检查随机在4个象限在1至2厘米 建议使用巨型活检钳（西雅图方案）进行间隔检查。 是劳动密集型的，需要治疗内窥镜，它被不到20%的美国人使用。 95此外，这种筛查方法并未显示出降低胃肠病的发生率。 Barrett食管发展为腺癌。96因此，一种新的检测和定位方法 在巴雷特食管的背景下发育不良是必要的。