Minimally Invasive Molecular Approaches for the Detection of Barrett’s Esophagus and Esophageal Adenocarcinoma

用于检测 Barrett 食管和食管腺癌的微创分子方法

• 批准号: 10657632
• 负责人: Prasad G. Iyer
• 金额: $ 50万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-02 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657632
• 关键词: Address; Adenocarcinoma; Age; Algorithms; Barrett Esophagus; Biological Assay; Biopsy Specimen; Body mass index; Case/Control Studies; Chronic; Clinic; Clinical; Cytology; DNA; DNA Markers; DNA Methylation; Data; Deglutition; Demographic Factors; Dependence; Detection; Development; Devices; Diagnosis; Diagnostic; Dysplasia; Early Diagnosis; Effectiveness; Eligibility Determination; Endoscopy; Esophageal Adenocarcinoma; Esophageal Intraepithelial Neoplasia; Esophageal mucous membrane; Esophagus; Ethnic Origin; Evaluation; FDA approved; Gastroesophageal reflux disease; Health system; High grade dysplasia; Histology; Histopathology; Image; Individual; Intestinal Metaplasia; Lasers; Malignant Neoplasms; Measures; Medical center; Molecular; Oral cavity; Outcome; Participant; Patients; Polyurethanes; Population; Porifera; Precancerous Conditions; Predictive Value; Prevention; Prevention strategy; Recommendation; Recording of previous events; Reflex action; Research; Sampling; Sensitivity and Specificity; Smoking; Specimen; Stomach; Surveillance Program; Symptoms; Techniques; Testing; Tissue Sample; Uncertainty; VAV3 gene; Validation; Work; biomarker panel; bisulfite sequencing; candidate marker; capsule; cohort; cost; design; effective therapy; improved; innovation; meetings; microendoscopy; minimally invasive; molecular marker; novel; nursing administration; prediction algorithm; prevent; primary care clinic; screening; sex

PROJECT SUMMARY/ABSTRACT Esophageal adenocarcinoma (EAC) is a lethal cancer with poor outcomes (5 year survival <20%), when diagnosed after the onset of symptoms, but survival is excellent when diagnosed early. Intestinal metaplasia, or Barrett’s esophagus (BE), is the only known precursor of EAC, and progresses to EAC via development of dysplasia. EAC can be prevented by endoscopic therapy of dysplasia. Hence endoscopic screening for BE and endoscopic surveillance to detect dysplasia and EAC are recommended. However, > 60% of prevalent BE remains undiagnosed and 90% of all EAC cases are diagnosed outside a BE surveillance program. The major barrier to BE screening is the invasiveness and high cost of endoscopy. Further, screening is recommended only in those with chronic gastroesophageal reflux (GERD), despite 50% of BE/EAC patients not reporting GERD symptoms. Endoscopic surveillance misses 33% of prevalent EAC & dysplasia, due to the patchy distribution of dysplasia/EAC, and inadequate biopsy sampling. Hence the overall effectiveness of endoscopic surveillance is also severely compromised. We used reduced representation bisulfite sequencing (RRBS) to identify a panel of methylated DNA markers (MDMs) of BE and dysplasia/EAC followed by validation. MDM panels were highly discriminant (AUCs > 0.9) for BE and prevalent dysplasia/EAC. When assayed on esophageal cytology specimens obtained via a sponge on string (SOS) device, BE was detected with high accuracy (AUCs 0.97-1.0) in two case control studies done in referral populations. The FDA approved SOS device (Capnostics, Doylestown, PA) is a 25 mm polyurethane sponge compressed in a dissolvable capsule shell, which expands into a sphere in the stomach after being swallowed. When pulled out through the mouth via an attached string, sampling of the entire esophageal mucosa is achieved. The nurse-administered SOS test is safe and well tolerated with high participation rates (65%). Hence our central hypothesis is that novel discriminant MDMs assayed on esophageal cytology specimens obtained via the SOS device will enable accurate BE and dysplasia/EAC detection, in a screening population with and without chronic GERD. We will test this hypothesis by three specific aims. In specific Aim 1, we will measure the positive and negative predictive value of the SOS BE test in a screening eligible population from primary care clinics in the Mayo Health System and compare these values in those with and without GERD. In specific Aim 2 we will identify clinical and demographic factors, particularly GERD, influencing the accuracy a predetermined SOS BE test prediction algorithm. In Specific Aim 3, we will measure the accuracy of MDMs for the detection of dysplasia/EAC in BE, using the SOS device. Utilizing an innovative, minimally invasive (non-endoscopic) and molecular approach, this proposal will favorably impact BE detection and surveillance, enabling effective treatment, and improved EAC outcomes.

项目总结/文摘

项目成果

What is the optimal surveillance strategy for non-dysplastic Barrett's esophagus?

• DOI: 10.1007/s11938-020-00297-9
• 发表时间: 2020-09
• 期刊: Current treatment options in gastroenterology
• 作者: Gibbens Y;Iyer PG
• 通讯作者: Iyer PG

ACG Clinical Guideline: Diagnosis and Management of Barrett's Esophagus.

• DOI: 10.1038/ajg.2015.322
• 发表时间: 2016-01
• 期刊: AMERICAN JOURNAL OF GASTROENTEROLOGY
• 影响因子: 9.8
• 作者: Shaheen, Nicholas J.;Falk, Gary W.;Iyer, Prasad G.;Gerson, Lauren B.
• 通讯作者: Gerson, Lauren B.

Predicting Progression in Barrett's Esophagus: Is the Holy Grail Within Reach?

预测巴雷特食管的进展：圣杯触手可及吗？

• DOI: 10.14309/ajg.0000000000000635
• 发表时间: 2020
• 期刊: The American journal of gastroenterology
• 作者: Qin,Yi;Iyer,PrasadG
• 通讯作者: Iyer,PrasadG

Comparative Outcomes of Cap Assisted Endoscopic Resection and Endoscopic Submucosal Dissection in Dysplastic Barrett's Esophagus.

在发育异常的巴雷特食管中，帽辅助内窥镜切除和内窥镜粘膜下截面的比较结果。

• DOI: 10.1016/j.cgh.2020.11.017
• 发表时间: 2022-01
• 期刊: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
• 作者: Codipilly DC;Dhaliwal L;Oberoi M;Gandhi P;Johnson ML;Lansing RM;Harmsen WS;Wang KK;Iyer PG
• 通讯作者: Iyer PG

Population Based Time Trends in the Epidemiology and Mortality of Gastroesophageal Junction and Esophageal Adenocarcinoma.

基于人群的胃食管交界处和食管腺癌的流行病学和死亡率的时间趋势。

• DOI: 10.1007/s10620-023-08126-6
• 发表时间: 2024
• 期刊: Digestive diseases and sciences
• 影响因子: 3.1
• 作者: Agarwal,Siddharth;Bell,MatthewG;Dhaliwal,Lovekirat;Codipilly,DChamil;Dierkhising,RossA;Lansing,Ramona;Gibbons,ErinE;Leggett,CadmanL;Kisiel,JohnB;Iyer,PrasadG
• 通讯作者: Iyer,PrasadG