Barrett’s Esophagus

Barrett 食管
  • 文章类型: Journal Article
    背景:Barrett食管(BE)是一种与食管腺癌(EAC)风险增加相关的癌前病变。BE的准确诊断和发育不良的分级有助于优化BE患者的管理。然而,可能会错过BE,并且基于常规组织学对发育不良的准确分级具有相当大的观察者内部和观察者之间的差异。因此,明确定义的生物标志物测试仍然是不可或缺的。我们研究的目的是确定常规适用和相对特异性的生物标志物,以准确诊断BE。以及确定生物标志物来预测BE发育不良的进展风险。方法:回顾性,我们进行了免疫组织化学检测粘蛋白2(MUC2),三叶因子3(TFF3),p53,p16,细胞周期蛋白D1,Ki-67,β-catenin,和活检中的微小染色体维持(MCM2)。Prospective,为了识别染色体改变,我们对内镜监测时收集的新鲜毛刷样本进行了荧光原位杂交检测.结果:我们发现MUC2和TFF3是诊断BE的特异性标志物。异常表达,包括p53,Ki-67,p16,β-catenin的丢失和强烈过表达,细胞周期蛋白D1和MCM2与低度发育不良(LGD)显着相关,高度发育不良(HGD),和EAC组织学,肿瘤改变的风险相对较高。此外,BE不确定发育不良(IND)进展队列中p53和p16的异常表达预测了进展的风险.结论:评估生物标志物将是准确的BE组织学诊断的合适辅助手段,并提高BE发育不良分级的准确性。从而减少观察者间的可变性,特别是LGD和风险预测。
    Background: Barrett\'s esophagus (BE) is a pre-neoplastic condition associated with an increased risk of esophageal adenocarcinoma (EAC). The accurate diagnosis of BE and grading of dysplasia can help to optimize the management of patients with BE. However, BE may be missed and the accurate grading of dysplasia based on a routine histology has a considerable intra- and interobserver variability. Thus, well-defined biomarker testing remains indispensable. The aim of our study was to identify routinely applicable and relatively specific biomarkers for an accurate diagnosis of BE, as well as determining biomarkers to predict the risk of progression in BE-dysplasia. Methods: Retrospectively, we performed immunohistochemistry to test mucin 2(MUC2), trefoil factor 3 (TFF3), p53, p16, cyclin D1, Ki-67, beta-catenin, and minichromosome maintenance (MCM2) in biopsies. Prospectively, to identify chromosomal alterations, we conducted fluorescent in situ hybridization testing on fresh brush samples collected at the time of endoscopy surveillance. Results: We discovered that MUC2 and TFF3 are specific markers for the diagnosis of BE. Aberrant expression, including the loss and strong overexpression of p53, Ki-67, p16, beta-catenin, cyclin D1, and MCM2, was significantly associated with low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC histology, with a relatively high risk of neoplastic changes. Furthermore, the aberrant expressions of p53 and p16 in BE-indefinite dysplasia (IND) progressor cohorts predicted the risk of progression. Conclusions: Assessing the biomarkers would be a suitable adjunct to accurate BE histology diagnoses and improve the accuracy of BE-dysplasia grading, thus reducing interobserver variability, particularly of LGD and risk prediction.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    背景:与西方人群相比,中国的Barrett食管(BE)发病率较低。因此,在中国人群中进行的研究是有限的。目前可用于BE治疗的治疗方案包括氩等离子体凝固术(APC),射频消融和冷冻消融,都有不同程度的成功。
    目的:确定HybridAPC治疗BE的有效性和安全性。
    方法:研究队列包括接受HybridAPC消融治疗的BE患者。这些程序由来自不同三级医院的七名内窥镜医师进行。程序的持续时间,治愈率,记录1年随访时的并发症和复发率.
    结果:从2017年7月至2020年6月,80名受试者入选接受治疗,包括39名男性和41名女性,中位年龄为54岁(范围,30至83岁)。HybridAPC的技术成功率为100%,总治愈率为98.15%。术中无严重并发症发生。BE病例分为短段BE和长段BE。短节段BE患者均被认为治愈,无并发症。36例患者完成了为期一年的随访,无复发。24%的人患有轻度发育不良,通过一次术后治疗均已解决。该程序的平均持续时间为10.94±6.52分钟。
    结论:发现HybridAPC治疗BE是一种简单快速的方法,在短期随访期间是安全有效的,特别是在短段BE的情况下。该技术可以被认为是BE的可行替代消融治疗。
    BACKGROUND: The incidence of Barrett\'s esophagus (BE) in China is lower compared to the Western populations. Hence, studies conducted in the Chinese population has been limited. The current treatment options available for BE treatment includes argon plasma coagulation (APC), radiofrequency ablation and cryoablation, all with varying degrees of success.
    OBJECTIVE: To determine the efficacy and safety of HybridAPC in the treatment of BE.
    METHODS: The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment. These procedures were performed by seven endoscopists from different tertiary hospitals. The duration of the procedure, curative rate, complications and recurrent rate by 1-year follow-up were recorded.
    RESULTS: Eighty individuals were enrolled for treatment from July 2017 to June 2020, comprising of 39 males and 41 females with a median age of 54 years (range, 30 to 83 years). The technical success rate of HybridAPC was 100% and the overall curative rate was 98.15%. No severe complications occurred during the operation. BE cases were classified as short-segment BE and long-segment BE. Patients with short-segment BE were all considered cured without complications. Thirty-six patients completed the one-year follow-up without recurrence. Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment. The mean duration of the procedure was 10.94 ± 6.52 min.
    CONCLUSIONS: Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up, especially in cases of short-segment BE. This technique could be considered as a feasible alternative ablation therapy for BE.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:先前的观察性研究表明,胃食管反流病(GERD)和Barrett食管(BE)的患病率与社会经济状况有关。然而,由于传统观察性研究的方法局限性,确定因果关系是具有挑战性的。
    目的:使用孟德尔随机化(MR)探索这些疾病的患病率与社会经济状况之间的因果关系。
    方法:我们最初筛选了单核苷酸多态性(SNPs),作为8种社会经济状态表型的代表进行单变量MR分析。使用逆方差加权(IVW)方法作为主要分析方法来估计八种社会经济地位表型与GERD和BE风险之间的因果关系。然后,我们收集SNP的组合作为8种社会经济表型的复合代理,以基于IVWMVMR模型进行多变量MR(MVMR)分析。此外,使用两步MR调解分析来检查体重指数对关联的潜在调解,抑郁症(MDD),吸烟,酒精消费,和睡眠时间。
    结果:该研究确定了三种对GERD有显著影响的社会经济状况。其中包括家庭收入[优势比(OR):0.46;95%置信区间(95CI):0.31-0.70],教育程度(OR:0.23;95CI:0.18-0.29),以及招募时的汤森德剥夺指数(OR:1.57;95CI:1.04-2.37)。发现这些因素独立且主要影响GERD的遗传因果效应。此外,发现受教育程度对GERD的中介作用是由MDD介导的(介导比例:10.83%)。同样,受教育程度对BE的影响由MDD(介导比例:10.58%)和每日吸烟数量(介导比例:3.50%)介导.此外,观察到家庭收入对GERD的中介作用是由睡眠持续时间介导的(介导比例:9.75%)。
    结论:这项MR研究揭示了社会经济地位与GERD或BE之间的联系,为食管癌和癌前病变的预防提供见解。
    BACKGROUND: Previous observational studies have shown that the prevalence of gastroesophageal reflux disease (GERD) and Barrett\'s esophagus (BE) is associated with socioeconomic status. However, due to the methodological limitations of traditional observational studies, it is challenging to definitively establish causality.
    OBJECTIVE: To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization (MR).
    METHODS: We initially screened single nucleotide polymorphisms (SNPs) to serve as proxies for eight socioeconomic status phenotypes for univariate MR analysis. The inverse variance weighted (IVW) method was used as the primary analytical method to estimate the causal relationship between the eight socioeconomic status phenotypes and the risk of GERD and BE. We then collected combinations of SNPs as composite proxies for the eight socioeconomic phenotypes to perform multivariate MR (MVMR) analyses based on the IVW MVMR model. Furthermore, a two-step MR mediation analysis was used to examine the potential mediation of the associations by body mass index, major depressive disorder (MDD), smoking, alcohol consumption, and sleep duration.
    RESULTS: The study identified three socioeconomic statuses that had a significant impact on GERD. These included household income [odds ratio (OR): 0.46; 95% confidence interval (95%CI): 0.31-0.70], education attainment (OR: 0.23; 95%CI: 0.18-0.29), and the Townsend Deprivation Index at recruitment (OR: 1.57; 95%CI: 1.04-2.37). These factors were found to independently and predominantly influence the genetic causal effect of GERD. Furthermore, the mediating effect of educational attainment on GERD was found to be mediated by MDD (proportion mediated: 10.83%). Similarly, the effect of educational attainment on BE was mediated by MDD (proportion mediated: 10.58%) and the number of cigarettes smoked per day (proportion mediated: 3.50%). Additionally, the mediating effect of household income on GERD was observed to be mediated by sleep duration (proportion mediated: 9.75%).
    CONCLUSIONS: This MR study shed light on the link between socioeconomic status and GERD or BE, providing insights for the prevention of esophageal cancer and precancerous lesions.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    食管癌是全球癌症死亡的第六大原因。食管腺癌(EAC)的前兆是Barrett食管(BE)。早期诊断和治疗食管肿瘤(Barrett伴高度异型增生/粘膜内癌)可将5年生存率从10%提高到98%。是一个全球性的挑战;然而,目前用于早期BE检测的内窥镜成本很高,需要大量的基础设施来进行患者检查和镇静。我们描述了ScanCap的第一个原型的设计和评估,一个高分辨率的光学内窥镜系统,低成本系留胶囊,旨在提供高清晰度,蓝绿照明成像用于早期检测未镇静患者的BE。系留胶囊(直径12.8毫米,35.5毫米长)包含彩色相机和旋转镜,并设计为可吞咽;在胶囊通过系绳手动缩回时收集图像。系绳提供415nm和565nm波长的电力和照明,并将数据从相机传输到平板电脑。ScanCap原型胶囊用于对正常志愿者和离体食管切除的口腔粘膜进行成像;将图像与使用OlympusCV-180内窥镜获得的图像进行比较。在ScanCap图像中,完整口腔粘膜中的浅表毛细血管图像清晰可见。BE的诊断相关特征,包括不规则的Z线,粘膜扭曲,和扩张的脉管系统,在离体食管标本的ScanCap图像中清晰可见。
    Esophageal carcinoma is the sixth-leading cause of cancer death worldwide. A precursor to esophageal adenocarcinoma (EAC) is Barrett\'s Esophagus (BE). Early-stage diagnosis and treatment of esophageal neoplasia (Barrett\'s with high-grade dysplasia/intramucosal cancer) increase the five-year survival rate from 10% to 98%. BE is a global challenge; however, current endoscopes for early BE detection are costly and require extensive infrastructure for patient examination and sedation. We describe the design and evaluation of the first prototype of ScanCap, a high-resolution optical endoscopy system with a reusable, low-cost tethered capsule, designed to provide high-definition, blue-green illumination imaging for the early detection of BE in unsedated patients. The tethered capsule (12.8 mm diameter, 35.5 mm length) contains a color camera and rotating mirror and is designed to be swallowed; images are collected as the capsule is retracted manually via the tether. The tether provides electrical power and illumination at wavelengths of 415 nm and 565 nm and transmits data from the camera to a tablet. The ScanCap prototype capsule was used to image the oral mucosa in normal volunteers and ex vivo esophageal resections; images were compared to those obtained using an Olympus CV-180 endoscope. Images of superficial capillaries in intact oral mucosa were clearly visible in ScanCap images. Diagnostically relevant features of BE, including irregular Z-lines, distorted mucosa, and dilated vasculature, were clearly visible in ScanCap images of ex vivo esophageal specimens.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    我们检查了核梭杆菌(F.无癌患者(n=67;N组)的非肿瘤性Barrett食管(BE)中的核子)和完整的梭杆菌(泛梭菌),食管腺癌(EAC)(n=27)和EAC组织(n=22)。F.核仁仅在22.7%的EAC组织中检测到。泛梭菌在EAC组织中富集,并与侵袭性临床病理特征相关。非肿瘤性BE中泛梭菌的数量与疝和端粒缩短的存在有关。结果表明Fusobacterium物种在EAC和BE中的潜在关联,具有临床病理和分子特征。
    We examined Fusobacterium nucreatum (F. nucleatum) and whole Fusobacterium species (Pan-fusobacterium) in non-neoplastic Barrett\'s esophagus (BE) from patients without cancer (n = 67; N group), with esophageal adenocarcinoma (EAC) (n = 27) and EAC tissue (n = 22). F. nucleatum was only detectable in 22.7% of EAC tissue. Pan-fusobacterium was enriched in EAC tissue and associated with aggressive clinicopathological features. Amount of Pan-fusobacterium in non-neoplastic BE was correlated with presence of hital hernia and telomere shortening. The result suggested potential association of Fusobacterium species in EAC and BE, featuring clinicpathological and molecular features.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    食管癌(EC)是一个紧迫的全球健康问题,在全球癌症相关死亡中排名第八,也是癌症相关死亡的第六大原因。食管腺癌(EAC)和食管鳞状细胞癌(ESCC)是食管癌的两种主要组织学类型,具有不同的危险因素和地理分布。不幸的是,这两种类型的电子商务的结果仍然令人沮丧,在晚期诊断时,五年生存率不到20%。先进的内窥镜技术有可能大大提高患者的预后,并阻止癌前病变进展为癌症。然而,由于其侵入性和高成本,内窥镜检查的低筛查率阻碍了其有效性。尽管对风险预测因子进行了广泛的研究,大量病例仍未确诊,强调需要改进可以在人口层面实施的筛查技术。为了增加摄取,向微创的转变,良好的耐受性和成本效益的非内镜技术至关重要.在初级保健环境中实施此类设备,专门针对高危人群,可以是一个有前途的策略。随着早期发现和纳入监视计划,有希望通过现代微创内窥镜和外科技术大幅改善发病率和死亡率。
    Esophageal cancer (EC) is a pressing global health concern, ranking as the eighth most common cancer and the sixth leading cause for cancer-related deaths worldwide. Esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) are the two major histological types of esophageal cancer associated with distinct risk factors and geographical distributions. Unfortunately, the outcomes for both types of EC remain discouraging, with a five-year survival rate of less than 20% when diagnosed at advanced stages. Advanced endoscopic techniques have the potential to vastly enhance patient outcomes and impede the progression of pre-malignant lesions to cancer. However, low screening rates with endoscopy due to its invasive nature and high cost hinder its effectiveness. Despite extensive research on risk predictors, a significant number of cases still go undiagnosed, highlighting the need for improved screening techniques that can be implemented at the population level. To increase uptake, a shift towards minimally invasive, well-tolerated and cost-effective non-endoscopic technologies is crucial. The implementation of such devices in primary care settings, specifically targeting high-risk populations, can be a promising strategy. With early detection and enrollment in surveillance programs, there is hope for substantial improvement in morbidity and mortality rates through modern minimally invasive endoscopic and surgical techniques.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    背景:颗粒物暴露(PM)是全球呼吸消化疾病的原因。世界贸易中心(WTC)的破坏使纽约市的第一响应者和居民暴露于WTC-PM,并导致阻塞性气道疾病(OAD)。胃食管反流病(GERD)和Barrett食管(BE)。GERD不仅会降低与健康相关的生活质量,还会引起超出BE范围的并发症。GERD会引起或加剧过敏,鼻窦炎,支气管炎,和哮喘。呼吸消化轴的疾病特征可以重叠,通常需要更具侵入性的诊断测试和治疗方式。这表明需要开发新的GERD的非侵入性生物标志物,BE,气道高反应性(AHR),治疗功效,和症状的严重程度。
    方法:我们的观察性病例队列研究将利用纽约消防局(FDNY)-WTC暴露的纵向表型队列来识别AirwayDisease的Biomarker,B-arrett和U-侵入性诊断为R-EfluxN(BAD-BURN)。我们的研究人群由n=4,192个人组成,我们从中随机选择了一个子队列对照组(n=837)。然后,我们将招募i。AHR仅II的子组。只有GERDiii.BEiv.GERD/BE和AHR重叠或v.无GERD或AHR,来自亚队列对照组。然后我们将表型并检查这些亚组的非侵入性生物标志物,以鉴定诊断不足和/或治疗功效。这些发现可能进一步有助于未来生物合理疗法的发展,最终提高患者的护理和生活质量。
    结论:尽管许多研究表明气道和消化系统疾病之间存在相互依存关系,致病因素和具体机制尚不清楚.常规GERD诊断程序的侵入性和疾病特异性生物标志物的有限可用性使疾病的检测进一步复杂化。反流的管理很重要,因为它直接增加患癌症的风险,并对生活质量产生负面影响。因此,至关重要的是开发新的非侵入性疾病标记,可以有效的表型,促进癌前疾病的早期诊断,并确定潜在的治疗目标,以改善患者护理。
    背景:ClinicalTrials.gov标识符:NCT05216133;2022年1月18日。
    BACKGROUND: Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed fifirst responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal Refux disease (GERD) and Barrett\'s Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE. GERD can incite or exacerbate allergies, sinusitis, bronchitis, and asthma. Disease features of the aerodigestive axis can overlap, often necessitating more invasive diagnostic testing and treatment modalities. This presents a need to develop novel non-invasive biomarkers of GERD, BE, airway hyperreactivity (AHR), treatment efficacy, and severity of symptoms.
    METHODS: Our observational case-cohort study will leverage the longitudinally phenotyped Fire Department of New York (FDNY)-WTC exposed cohort to identify Biomarkers of Airway Disease, Barrett\'s and Underdiagnosed Refux Noninvasively (BAD-BURN). Our study population consists of n = 4,192 individuals from which we have randomly selected a sub-cohort control group (n = 837). We will then recruit subgroups of i. AHR only ii. GERD only iii. BE iv. GERD/BE and AHR overlap or v. No GERD or AHR, from the sub-cohort control group. We will then phenotype and examine non-invasive biomarkers of these subgroups to identify under-diagnosis and/or treatment efficacy. The findings may further contribute to the development of future biologically plausible therapies, ultimately enhance patient care and quality of life.
    CONCLUSIONS: Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. The detection of the disease is further complicated by the invasiveness of conventional GERD diagnosis procedures and the limited availability of disease-specific biomarkers. The management of Refux is important, as it directly increases risk of cancer and negatively impacts quality of life. Therefore, it is vital to develop novel noninvasive disease markers that can effectively phenotype, facilitate early diagnosis of premalignant disease and identify potential therapeutic targets to improve patient care.
    BACKGROUND: ClinicalTrials.gov Identifier: NCT05216133; January 18, 2022.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    目的:Barrett食管(BE)是食管腺癌(EAC)的前体。内镜根除治疗(EET)可以有效根除BE和相关瘤形成,并且比监测内镜检查具有更大的危害和资源使用风险。本临床实践指南旨在通过为在BE和相关瘤形成中使用EET提供循证实践建议来告知临床医生和患者。
    方法:建议评估的分级,开发和评估框架用于评估证据并提出建议。小组根据临床医生和患者的重要性,优先考虑临床问题和结果,进行了证据审查,并使用证据到决策框架来制定关于在以下情况下对BE患者使用EET的建议:存在(1)高度发育不良,(2)低度发育不良,(3)无发育不良,(4)选择逐步内镜黏膜切除术(EMR)或局灶性EMR加消融,(5)内镜黏膜下剥离术与EMR的比较。临床建议基于理想和不良效果之间的平衡,患者价值观,成本,和健康公平考虑。
    结果:专家组同意在BE和相关瘤形成中使用EET的5项建议。根据现有证据,专家组提出了在有BE高度发育不良的患者中支持EET的强烈推荐和在无发育不良的BE中反对EET的有条件推荐.专家组提出了有条件的建议,支持EET用于BE低度发育不良;BE低度发育不良患者在降低食管癌死亡率方面对潜在危害的重视程度较高,对益处的重视程度较低(不确定),可以合理选择监测内镜检查。在有可见病变的患者中,有条件的建议支持局灶性EMR加消融,而不是逐步EMR.在进行切除的可见肿瘤性病变的患者中,根据病变特点,建议使用内镜黏膜切除术或内镜黏膜下剥离术.
    结论:本文件全面概述了EET在BE和相关瘤形成治疗中的适应症。还提供了有关实施EET的注意事项的指导。提供者应根据患者的偏好进行共享决策。强调了证据的局限性和差距,以指导未来的研究机会。
    Barrett\'s esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Endoscopic eradication therapy (EET) can be effective in eradicating BE and related neoplasia and has greater risk of harms and resource use than surveillance endoscopy. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for the use of EET in BE and related neoplasia.
    The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the use of EET in patients with BE under the following scenarios: presence of (1) high-grade dysplasia, (2) low-grade dysplasia, (3) no dysplasia, and (4) choice of stepwise endoscopic mucosal resection (EMR) or focal EMR plus ablation, and (5) endoscopic submucosal dissection vs EMR. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations.
    The panel agreed on 5 recommendations for the use of EET in BE and related neoplasia. Based on the available evidence, the panel made a strong recommendation in favor of EET in patients with BE high-grade dysplasia and conditional recommendation against EET in BE without dysplasia. The panel made a conditional recommendation in favor of EET in BE low-grade dysplasia; patients with BE low-grade dysplasia who place a higher value on the potential harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality could reasonably select surveillance endoscopy. In patients with visible lesions, a conditional recommendation was made in favor of focal EMR plus ablation over stepwise EMR. In patients with visible neoplastic lesions undergoing resection, the use of either endoscopic mucosal resection or endoscopic submucosal dissection was suggested based on lesion characteristics.
    This document provides a comprehensive outline of the indications for EET in the management of BE and related neoplasia. Guidance is also provided regarding the considerations surrounding implementation of EET. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    背景:肠道菌群(GM)已被证明与许多胃肠道疾病有关,但其与胃食管反流病(GERD)和Barrett食管(BE)的因果关系尚未探讨。我们旨在通过孟德尔随机化(MR)分析揭示GM和GERD/BE与潜在介质之间的因果关系。
    方法:从MiBioGenConsortium(N=18,340)和荷兰微生物组项目(N=7,738)中提取了GM(包括301个细菌分类群和205个代谢途径)的摘要统计,GERD和BE来自多性状荟萃分析(NGERD=602,604,NBE=56,429)。采用双向双样本MR分析和连锁不平衡评分回归(LDSC)探讨GM与GERD/BE的遗传相关性。对GERD/BE的危险因素进行中介MR分析,包括体重指数(BMI),体重,2型糖尿病,抑郁症(MDD),开始吸烟,酒精消费,和饮食摄入(包括碳水化合物,糖,脂肪,蛋白质摄入量),检测GM和GERD/BE之间的潜在介质。
    结果:发现了11种细菌分类群和13种代谢途径与GERD相关,18个分类单元和5条途径与BE存在因果关系。中介MR分析表明,体重和BMI在这些关系中起着至关重要的作用。LDSC确定了1个分类单元和4个与GERD相关的代谢途径,和1个与BE相关的分类单元。prausnitzii物种对GERD(OR=1.087,95CI=1.01-1.17)和BE(OR=1.388,95CI=1.03-1.86)均具有暗示性影响,LDSC确定了它们的相关性。反向MR表明BE影响10个分类单元和4个途径。
    结论:这项研究建立了肠道菌群与GERD/BE之间的因果关系。并确定了可能的调解员。它为肠道微生物群在宿主GERD和BE的发展和进展中的作用提供了新的见解。
    BACKGROUND: Gut microbiota(GM) have been proven associated with lots of gastrointestinal diseases, but its causal relationship with Gastroesophageal reflux disease(GERD) and Barrett\'s esophagus(BE) hasn\'t been explored. We aimed to uncover the causal relation between GM and GERD/BE and potential mediators by utilizing Mendelian Randomization(MR) analysis.
    METHODS: Summary statistics of GM(comprising 301 bacteria taxa and 205 metabolism pathways) were extracted from MiBioGen Consortium(N = 18,340) and Dutch Microbiome Project(N = 7,738), GERD and BE from a multitrait meta-analysis(NGERD=602,604, NBE=56,429). Bidirectional two-sample MR analysis and linkage disequilibrium score regression(LDSC) were used to explore the genetic correlation between GM and GERD/BE. Mediation MR analysis was performed for the risk factors of GERD/BE, including Body mass index(BMI), weight, type 2 diabetes, major depressive disorder(MDD), smoking initiation, alcohol consumption, and dietary intake(including carbohydrate, sugar, fat, protein intake), to detect the potential mediators between GM and GERD/BE.
    RESULTS: 11 bacterial taxa and 13 metabolism pathways were found associated with GERD, and 18 taxa and 5 pathways exhibited causal relationship with BE. Mediation MR analysis suggested weight and BMI played a crucial role in these relationships. LDSC identified 1 taxon and 4 metabolism pathways related to GERD, and 1 taxon related to BE. Specie Faecalibacterium prausnitzii had a suggestive impact on both GERD(OR = 1.087, 95%CI = 1.01-1.17) and BE(OR = 1.388, 95%CI = 1.03-1.86) and LDSC had determined their correlation. Reverse MR indicated that BE impacted 10 taxa and 4 pathways.
    CONCLUSIONS: This study established a causal link between gut microbiota and GERD/BE, and identified the probable mediators. It offers new insights into the role of gut microbiota in the development and progression of GERD and BE in the host.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    目前,食管腺癌(EAC)的研究由于缺乏足够的模型来研究这种疾病而受到阻碍。传统的细胞系和基因工程小鼠模型缺乏生物学和生理学意义,而患者源性异种移植物的低效率限制了它们的潜在应用。这篇综述描述了使用患者来源的类器官(PDO)进行EAC研究的前景。这里,我们详细介绍了EACPDO培养的建立和优化方法,以及这些模型的当前和未来应用。我们进一步强调了EAC从其前体病变转化的机制中的关键知识空白,巴雷特食管(BE)。因此,我们还描述了BEPDO的培养要求,并尝试使用PDO模型对肿瘤发生进行建模。
    Currently, esophageal adenocarcinoma (EAC) research is hindered by a dearth of adequate models to study this disease. Traditional cell line and genetically engineered mouse models are lacking in biological and physiological significance, whilst the inefficiency of patient-derived xenografts limit their potential applications. This review describes the landscape of EAC research using patient-derived organoids (PDOs). Here, we detail the methods of establishment and optimization of EAC PDO cultures, as well as current and prospective applications of these models. We further highlight a crucial knowledge gap in the mechanisms of EAC transformation from its precursor lesion, Barrett\'s esophagus (BE). As such, we also describe the culture requirements of BE PDOs and attempts to model tumorigenesis using PDO models.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

公众号