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.

在特定目标 3c 中，我们希望演示使用荧光标记的肽来引导组织活检 '广域内窥镜检查中巴雷特食管的扁平发育不良。虽然我们可以继续我们的 在结肠中的努力中，该器官的较大表面积使得在该演示中很难找到平坦的发育不良。 相反，在巴雷特食管的情况下，扁平发育不良更容易发生。这是一个 与胃食管癌相关的食管腺癌的重要癌前病变 90 这种癌症是白人男性中发病率增长最快的癌症。 91 不幸的是，巴雷特食管是一种常见疾病，7% 的患者被诊断出患有巴雷特食管。 接受结肠镜检查筛查结肠癌的患者，即使未接受结肠镜检查的患者，其患病率为 6% 有胃食管反流型症状。92 然而，只有一小部分巴雷特食管病例 进展为癌症。高达 25% 接受常规治疗的无症状患者中发现这种情况 93 有人建议，对这些患者最有效的方法应基于 发育异常的组织学证据，这是临床上唯一使用的进展为癌症的生物标志物。 所有临床指南都使用发育不良来确定患者的治疗和监测，但它是 认识到在 Barrett 节段内很难发现不典型增生，也很难对其进行标准化 解释。事实上，发育异常并不完全符合 NIH 的生物标志物标准，因为它确实无法客观地 一项研究表明，该研究评估了主要胃肠道疾病之间的一致性 美国病理学家发现，每个级别的不典型增生的 kappa 评分均为 0.42。72 内窥镜下可见正常鳞状上皮化生转化为柱状上皮 作为胃食管交界处的延伸。与结肠相似，巴雷特氏病患者的筛查 需要检测和定位不典型增生，该不典型增生是扁平的，内窥镜下与 Barrett 难以区分 食道在白光下。目前，广泛的活检在 1 至 2 cm 的 4 个象限中随机进行 建议间隔时间使用巨型活检钳（西雅图方案）。94 然而，由于该技术 该技术属于劳动密集型技术，需要使用治疗内窥镜，但美国只有不到 20% 的人使用它。 95 此外，这种筛查方法尚未被证明可以降低患病率 Barrett 食管进展为腺癌。96 因此，一种检测和定位的新方法 需要巴雷特食管的发育不良。