文章：

巴雷特食管和食管腺癌：新合成的时间

Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis

原文发布日期：2010-02-01

DOI: 10.1038/nrc2773

类型: Review Article

开放获取: 否

要点：

1. The paradigm that Barrett's oesophagus develops as a consequence of symptomatic gastroesophageal reflux disease and predisposes to oesophageal adenocarcinoma has dominated clinical thought for more than three decades. However, current approaches for controlling the incidence and mortality of oesophageal adenocarcinoma, which are largely based on endoscopic investigation of individuals with symptomatic gastroesophageal reflux disease, and histology-guided surveillance and treatment of individuals with Barrett's oesophagus, have considerable limitations.
2. Barrett's oesophagus rarely progresses to oesophageal adenocarcinoma, and a theory has recently been proposed that mucosal defences in most patients with Barrett's oesophagus represent successful adaptations to the harsh intra-oesophageal environment of chronic gastroesophageal reflux disease. Several mucosal defences that arise in Barrett's oesophagus have been identified, including the secretion of bicarbonate and mucous, expression of claudin 18 tight junctions, overexpression of defence and repair genes, and resistance to prolonged and repeated acid exposure.
3. The incidence of oesophageal adenocarcinoma has been rising at an alarming rate in the United States, Western Europe, Australia and in other developed countries over the past four decades, and there is disquieting evidence of increased incidence of oesophageal adenocarcinoma in some Asian populations.
4. Four risk factors — gastroesophageal reflux disease, obesity, cigarette smoking and poor diet — account for most oesophageal adenocarcinomas. The effects of obesity might influence both early and late stages of progression and interact biologically with gastroesophageal reflux disease, although a substantial proportion of the effect of obesity is likely to be through other pathways.
5. Neoplastic progression to oesophageal adenocarcinoma is characterized by genomic instability (including chromosomal instability in most cases), disruption of regulatory pathways and temporal evolution of clones that might be modulated by host and environmental risk and protective factors. Proper measurement and quantification of the complexity of these alterations creates opportunities and challenges for improved risk stratification, prevention and early detection.
6. Aspirin and other non-steroidal anti-inflammatory drugs have been consistently reported to have a protective association with oesophageal adenocarcinoma in case–control and cohort studies as well as meta-analyses; they might be useful in patients at both early and late stages of progression.
7. No intervention, whether based on lifestyle modification, chemoprevention or medical and surgical treatments, has yet been convincingly demonstrated in a randomized trial to reduce the incidence and/or mortality of oesophageal adenocarcinoma; this remains a particularly crucial area of unmet research need. New oesophageal adenocarcinoma prevention strategies are proposed to overcome these limitations.

要点翻译：

1. 巴雷特食管由症状性胃食管反流病发展而来并易诱发食管腺癌——这一范式主导临床思维已逾三十载。然而，当前控制食管腺癌发病率和死亡率的方法存在显著局限，这些方法主要基于对症状性胃食管反流病患者的内镜筛查，以及对巴雷特食管患者进行组织学指导的监测与治疗。
2. 巴雷特食管极少进展为食管腺癌，近期有理论提出：大多数巴雷特食管患者的黏膜防御机制是对慢性胃食管反流病恶劣的食管内环境的成功适应。已识别出巴雷特食管中产生的多种黏膜防御机制，包括碳酸氢盐与黏液分泌、claudin 18紧密连接蛋白表达、防御与修复基因的过表达，以及对长期反复酸暴露的耐受性。
3. 过去四十年间，美国、西欧、澳大利亚等发达国家的食管腺癌发病率以惊人速度持续攀升，且有令人不安的证据表明部分亚洲人群的食管腺癌发病率也在上升。
4. 胃食管反流病、肥胖、吸烟及不良饮食这四大危险因素构成了大多数食管腺癌的病因。肥胖的影响可能贯穿疾病进展的早晚期，并与胃食管反流病产生生物学交互作用，尽管其相当大部分效应可能通过其他途径实现。
5. 向食管腺癌的肿瘤性进展以基因组不稳定性（多数情况下包括染色体不稳定）、调控通路紊乱以及克隆的时间演化为特征，这些过程可能受宿主与环境风险及保护因素调控。准确衡量和量化这些改变的复杂性，为改善风险分层、预防及早期检测创造了机遇与挑战。
6. 病例对照研究、队列研究及荟萃分析均一致报道阿司匹林与非甾体抗炎药对食管腺癌具有保护作用，可能对疾病早晚期患者均有裨益。
7. 迄今为止，尚无任何干预措施——无论是基于生活方式调整、化学预防还是内科与外科治疗——能通过随机试验确证降低食管腺癌发病率和/或死亡率；这仍是未满足研究需求的关键领域。为突破这些局限，新的食管腺癌预防策略亟待探索。

英文摘要：

The public health importance of Barrett's oesophagus lies in its association with oesophageal adenocarcinoma. The incidence of oesophageal adenocarcinoma has risen at an alarming rate over the past four decades in many regions of the Western world, and there are indications that the incidence of this disease is on the rise in Asian populations in which it has been rare. Much has been learned of host and environmental risk factors that affect the incidence of oesophageal adenocarcinoma, and data indicate that patients with Barrett's oesophagus rarely develop oesophageal adenocarcinoma. Given that 95% of oesophageal adenocarcinomas arise in individuals without a prior diagnosis of Barrett's oesophagus, what strategies can be used to reduce late diagnosis of oesophageal adenocarcinoma?

摘要翻译： 

Barrett 食管的公共卫生重要性在于其与食管腺癌的关联。过去四十年间，食管腺癌的发病率在西方世界许多地区急剧上升，且有迹象表明，这一疾病在亚洲人群中的发病率也在上升，而此前该地区较为罕见。关于影响食管腺癌发病率的宿主和环境危险因素，已有大量研究，数据表明，Barrett 食管患者很少发展为食管腺癌。鉴于 95% 的食管腺癌发生于既往未被诊断为 Barrett 食管的个体，应采取何种策略以减少食管腺癌的晚期诊断？

原文链接：

Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis