Natural History of Barrett's Esophagus Using Capsule Endomicroscopy

使用胶囊内镜检查巴雷特食管的自然史

• 批准号: 9277434
• 负责人: Guillermo J Tearney
• 金额: $ 67.83万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-04 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9277434
• 关键词: Ablation; Acids; Address; Architecture; Area; Barrett Esophagus; Biopsy; Biopsy Specimen; Cell Nucleus; Cellular Morphology; Chronic; Clinical Research; Clinical Trials; Columnar Metaplasia; Complex; Confocal Microscopy; Data; Data Set; Deglutition; Development; Devices; Diagnosis; Dimensions; Disease; Dysplasia; Effectiveness; Endoscopic Biopsy; Endoscopy; Engineering; Epithelial; Esophageal; Esophageal Adenocarcinoma; Esophageal mucous membrane; Esophagus; Evolution; Failure; Goblet Cells; Histologic; Image; Incidence; Inpatients; Knowledge; Laboratories; Left; Location; Longitudinal Studies; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of esophagus; Maps; Medicine; Metaplasia; Metaplastic; Methods; Microscopic; Mucous Membrane; Natural History; Nature; Optical Coherence Tomography; Oral cavity; Organ; Outpatients; Patients; Penetration; Peristalsis; Pharmacology; Positioning Attribute; Practice Guidelines; Procedures; Reflux; Research; Resolution; Sampling; Sampling Errors; Site; Societies; Spatial Distribution; Specimen; Speed; Squamous Epithelium; Structure; Surface; Techniques; Technology; Testing; Thick; Time; Tissues; Uncertainty; Validation; Withdrawal; base; cancer type; capsule; clinically significant; cost; design; disease natural history; imaging modality; improved; in vivo; microendoscopy; microscopic imaging; mortality; pill; prevent; prospective; prototype; public health relevance; radiofrequency; reflectance confocal microscopy; response; safety and feasibility; screening; sensor; standard of care

DESCRIPTION (provided by applicant): Barrett's esophagus (BE) is a condition where normal esophageal squamous mucosa changes to metaplastic columnar mucosa in response to chronic acid reflux. BE can progress to esophageal adenocarcinoma (EAC), a prevalent (~12,000 cases per year) and deadly cancer (~15% 5-year mortality rate). Current BE management strategies of anti-reflux therapy, endoscopic screening, and regular endoscopic biopsy surveillance and ablation therapy, has been largely ineffective for decreasing the mortality of EAC. One important reason for the failure of the standard of care is our lack of understanding of the microscopic natural history/evolution of BE which has led to controversies about its definition, uncertainty regarding its progression and clinical significance, and an inability to evaluate the effectiveness of pharmacologic and ablative therapies. These questions have arisen in part because the only method used to study BE is endoscopic biopsy, which is invasive, costly, and suffers from severe biopsy sampling limitations. Our laboratory has developed a new imaging concept termed tethered capsule endomicroscopy (TCE) that overcomes these limitations of endoscopic biopsy. TCE involves swallowing a tethered capsule that acquires three-dimensional microscopic images of the entire esophageal wall as it traverses the luminal organ via peristalsis or is pulled up towards the mouth using the tether. As opposed to endoscopy, TCE mitigates sampling error by evaluating the microscopic structure of the entire esophagus. The TCE procedure can be conducted in unsedated patients, making it simpler, faster, better tolerated, and less expensive than endoscopy. The first TCE prototype that we have demonstrated uses optical coherence tomography (OCT) to obtain cross-sectional images of the microscopic architecture of the esophagus at a resolution of 10 �m. In this proposal, we will advance TCE technology further by combining OCT with a high-speed reflectance confocal microscopy technique called spectrally encoded confocal microscopy (SECM) so that obtain both architectural and cellular morphologic information can be obtained from the same device. We will additionally incorporate a position sensor that will allow microscopic datasets acquired from the same patients at different time points to be registered to one another. Once this device is developed, we will utilize TCE in a multicenter (5-site) clinical trial to study the natural history of BE in 500 patients. Imaging will be conducted on a yearly basis in all patients for a duration of 3 years (1500 patient-years) and the TCE images will be evaluated to determine how BE changes over time. The results of this study will significantly contribute to the knowledge of BE, allowing us to answer longstanding questions about its microscopic definition, its progression and clinical significance, and the effectiveness of ablativ BE therapies. The knowledge gained from this study will be used to improve BE management strategies based on strong scientific evidence about the natural history of this disease.

描述(申请人提供)：巴雷特食道(BE)是一种正常的食道鳞状粘膜转化为化生柱状粘膜的情况，以回应慢性酸反流。BE可进展为食管腺癌(EAC)，这是一种常见的(每年约12,000例)和致命的癌症(约15%的5年死亡率)。目前的BE治疗策略包括抗反流治疗、内窥镜筛查、定期内窥镜活检监测和消融治疗，在很大程度上不能有效降低EAC的死亡率。护理标准失败的一个重要原因是我们对BE的微观自然历史/进化缺乏了解，这导致了对其定义的争议，对其进展和临床意义的不确定性，以及无法评估药物和消融治疗的有效性。出现这些问题的部分原因是用于研究BE的唯一方法是内窥镜活检，这是一种侵入性的、昂贵的方法，并且受到严格的活检样本限制。我们实验室开发了一种新的成像概念，称为栓系胶囊内窥镜检查(TCE)，它克服了内窥镜活检的这些局限性。TCE需要吞咽一个系留的胶囊，当它通过蠕动穿过管腔器官或使用系绳被拉向口腔时，该胶囊会获得整个食管壁的三维显微图像。与内窥镜检查不同，TCE通过评估整个食道的微观结构来减少采样误差。TCE程序可以在未服用镇静剂的患者中进行，使其比内窥镜检查更简单、更快、耐受性更好、成本更低。我们已经展示的第一台三氯乙烯样机使用光学相干断层成像(OCT)以10�m的分辨率获得食道微观结构的横断面图像。在这项提议中，我们将进一步推进TCE技术，将OCT与一种称为光谱编码共焦显微镜的高速反射共聚焦显微镜技术相结合，以便从同一设备上同时获得结构和细胞的形态信息。我们还将加入一个位置传感器，允许在不同时间点从同一患者那里获得的显微数据集相互注册。一旦该设备被开发出来，我们将在一项多中心(5个地点)的临床试验中使用TCE来研究500名患者的BE的自然病史。所有患者将每年进行一次成像，持续时间为3年(1500人年)，并对TCE图像进行评估，以确定随时间的变化情况。这项研究的结果将大大有助于我们对BE的认识，使我们能够回答长期存在的关于BE的微观定义、进展和临床意义以及消融治疗的有效性的问题。从这项研究中获得的知识将被用来改进基于关于这种疾病自然历史的强有力的科学证据的BE管理策略。