胆汁酸在食管腺癌发病中作用的研究进展

Barrett食管(BE)是食管腺癌(EAC)的癌前病变。BE患者的胆汁反流往往较非BE胃食管反流病患者更常见且更为严重,反流的胆汁酸刺激食管上皮细胞产生活性氧簇、炎症因子,引起DNA损伤,进而影响细胞增殖与凋亡,参与BE的恶性转化。本文对胆汁酸在EAC发病中的作用以及相关EAC预防策略作一综述。     

Barrett食管与反流

目前大多数学认为Barrett食管（Barrett＇s esophagus，BE）的发生是胃食管反流造成食管下段黏膜的适应性变化，是反流性食管炎的常见并发症之一。正常人偶尔也可以出现反流，但时间甚短，主要于餐后发生，不足以造成食管黏膜的损伤，属于生理性反流；但当各种原因造成食管黏膜暴露于酸及胆汁的时间过长，就会导致食管黏膜的破损．出现糜烂、溃疡，久而久之就发生食管黏膜的移位。引起齿状线的上移。     

干细胞与Barrett食管的研究进展

<正>干细胞是一组自我更新、长期稳定分化的细胞群体。Barrett食管(Barrett esophagus,BE)是指食管远端黏膜上皮发生改变,正常的复层鳞状上皮被化生的肠型柱状上皮所替代的一种病理现象。BE是食管腺癌(esophageal adenocarcinoma,EAC)和部分胃-食管连接处腺癌的癌前病变。BE通常发生在慢性的胃食管反流病(gastroesophageal reflux     

胃酸在十二指肠液反流诱发食管腺癌中的作用

目的　探讨胃酸在十二指肠液反流诱发食管腺癌 (EAC)过程中的作用。方法　采用SD大鼠 ,通过手术产生三个实验组 :胃食管反流 (GER)组、十二指肠食管反流 (DER)组以及十二指肠胃食管反流 (DGER)组 ,并设无反流的假手术 (SO)对照组。术后 2 0周观察各组动物食管黏膜病变。结果　SO组未见明显病理学改变。各反流组均引发不同程度的食管炎。DER和DGER组基底细胞增生、鳞状上皮不典型增生和溃疡发生率显著高于GER组 (P <0 .0 1)。GER组没有出现Barrett’s食管 (BE)和食管腺癌 (EAC)。DER和DGER组BE发生率分别为 91.4 %和 84 .4 % ,EAC发生率分别为 2 5 .7%和5 3.1% ,均显著高于GER组 (P <0 .0 1)。DGER组EAC发生率显著高于DER组 (P <0 .0 5 )。结论　胃、十二指肠液反流均造成食管黏膜损伤 ,后者更为严重 ;十二指肠液反流在BE、EAC发展中发挥着尤为关键性的作用 ;胃酸在十二指肠液反流诱发EAC过程中起促进作用 ,显著增加十二指肠液反流诱发EAC的危险性     

Barrett食管黏膜中Ghrelin表达

目的探讨Barrett食管（Barrett’s esophagus,BE）患者食管黏膜中Ghrelin的表达变化;探讨BE与胆汁反流及幽门螺杆菌（Helicobacter pylori,H.pylori）感染的关系。方法应用免疫组化方法检测66例BE患者和30例对照者食管黏膜Ghrelin的表达。结果 Ghrelin在BE组黏膜表达高于对照组,差异有统计学意义（t=5.76,P〈0.05）。Ghrelin在特殊肠化生组黏膜表达高于对照组、贲门腺型组及胃底腺型组,胃底腺型组黏膜表达高于对照组及贲门腺型组;贲门腺型组表达高于对照组（F=22.64,P〈0.05）。不同化生组BE胆汁反流患者比例在特殊肠化生组高于其他两组,差异有统计学意义（χ2=12.61,P〈0.05）。BE组的H.pylori感染率低于对照组,差异有统计学意义（χ2=8.84,P〈0.05）。结论随着Barrett食管黏膜损伤程度加重,表现出不同类型的黏膜组织化生,从贲门型黏膜到特殊肠化生型黏膜中Ghrelin的表达逐渐增高;胆汁反流在BE黏膜组织肠化生过程中起重要作用;H.pylo-ri感染可能对食管有保护作用。     

我国Barrett食管相关性疾病的研究进展

在西方国家,食管腺癌(EAC)发病率逐年增加,且EAC与Barrett食管(BE)密切相关。近年来我国众多学者对BE和EAC发病情况进行了深入研究,但尚无文献对其进行总结分析。本文通过检索PubMed和中国医学文献数据库,分析了近年来有关我国BE和EAC研究的文章,探讨我国BE和EAC的发病情况和临床病理特点。检索词包括"Barrett食管"、"食管腺癌"、"中国人"和"中国"。通过分析发现,我国伴肠化生的BE检出率很低,一般人群为0.06%,有症状者检出率为1.8%。目前已确定我国BE的危险因素有老年和食管裂孔疝,其他可能的危险因素包括胃食管反流病、吸烟和酗酒。我国BE的发生与性别和肥胖无关。内镜下大多数柱状上皮食管和BE呈舌状或岛状,长度2 cm;我国长段BE非常罕见,尤其在女性人群中。近十年台湾和香港地区EAC的发病率很低,部分地区甚至有降低趋势。我国食管下段腺癌较少见,几乎所有胃食管连接(GEJ)处癌均以胃近端为中心生长。柱状上皮食管的临床意义及其是否存在恶变风险目前尚不清楚,需加大样本量进行更深入的研究。     

胃食管反流病与胃酸胆汁联合反流的关系

目的探讨胃食管反流病(gastroesophagealrefluxdisease,GERD)与胃酸胆汁联合反流的关系。方法2002-09～2004-09河南大学淮河医院及新乡医学院第二附属医院住院及门诊GERD患者82例,其中非糜烂性反流病(nonerosiverefluxdisease,NERD)22例,反流性食管炎(refluxesophagitis,RE)31例,Barrett食管(Barrett esophagus,BE)29例及健康对照组20例。应用便携式24hpH监测仪和胆汁反流监测仪对三组患者及对照组进行24h食管内pH和胆汁动态联合监测。结果RE、BE患者胃酸和胆汁联合反流比NERD患者和对照组更加频繁。结论胃酸和胆汁的联合反流在RE和BE的发病机制中起着更加重要的作用,同步监测食管pH值及胆汁变化对RE、BE的诊断和治疗具有重要的意义。     

反流性食管炎、Barrett食管和食管腺癌的研究

背景:胃食管反流病(GERD)是一种常见疾病,包括非糜烂性反流病(NERD)、反流性食管炎(RE)和Barrett食管(BE),近年其发病率逐渐增高。目的:探讨RE、BE与各种因素的关系。方法:应用反流性疾病问卷筛选具有胃食管反流症状的患者,行胃镜检查检测RE、BE和食管腺癌的检出率,分析吸烟、饮酒、饮食、年龄、性别和民族与RE、BE的关系。结果:共纳入1834例具有胃食管反流症状的患者,其中RE患者234例(12.8%);BE患者213例(11.6%),包括特殊肠化生型BE 47例;食管腺癌5例(0.3%)。蒙古族RE、BE的检出率显著高于汉族和其他民族。饮酒者中RE和BE的比例明显升高。BE患者中-重度异型增生和食管腺癌的检出率升高。结论:蒙古族人群RE和BE的检出率较高,饮酒与食管反流致损伤的关系密切,BE为食管腺癌的癌前病变。     

Barrett食管41例临床分析

[目的]探讨Barrett食管（BE）的临床特点及病因。[方法]对确诊的41例BE患者进行回顾性分析。[结果]41例BE患者表现为烧心、胸骨后疼痛、反酸等反流性食管炎症状及有反流性食管炎镜下表现者分别占75.61%、65.85%、58.54%和85.37%,伴胆汁反流者10例（24.40%）,伴食管裂孔疝6例（14.63%）,幽门螺杆菌（Hp）阳性者14例（34.15%）。[结论]BE多见于老年人,与胃食管反流密切相关,胆汁反流在BE的发病中可能占有重要地位,Hp感染与BE的确切关系有待进一步研究。     

Barrett食管化学预防机制研究进展

Barrett食管(BE)是胃食管反流病(GERD)的一种并发症,与食管腺癌密切相关。随着GERD发病率的增高,BE、食管腺癌的发病率也逐年增高。胃食管反流、酸暴露是重要的的发病因素,由于环氧合酶-2(COX-2)在BE、食管腺癌的早期高表达使得非甾体类消炎药(NSAID)及选择性COX-2抑制剂在BE的化学预防方面显得尤其重要。     

Clinical manifestations and esophageal complications of GERD

This report focuses on the manifestations of gastroesophageal reflux disease (GERD) that are caused directly by contact between refluxed gastric juice and the esophageal mucosa. These manifestations include heartburn, peptic esophageal erosion and ulceration, peptic esophageal stricture, and Barrett esophagus. Peptic esophageal erosions and ulcerations are excavated defects in the esophageal mucosa that result when epithelial cells succumb to the caustic effects of refluxed acid and pepsin. Uncommonly, esophageal ulcers are complicated by hemorrhage, perforation, and penetration into the airway. Esophageal ulcers can stimulate fibrous tissue production and collagen deposition that result in stricture formation, and the ulcers can heal through a metaplastic process in which an intestinal-type epithelium replaces the damaged squamous cells (Barrett esophagus). The management of these conditions is discussed below.     

Reflux injury of esophageal mucosa: experimental studies in animal models of esophagitis, Barrett''s esophagus and esophageal adenocarcinoma

Barrett's esophagus (BE), a gastroesophageal reflux associated complication, is defined as the replacement of normal esophageal squamous mucosa by specialized intestinal columnar mucosa with the appearance of goblet cells. The presence of BE is associated with an increased risk of developing esophageal adenocarcinoma (EAC). Although the exposure of gastroduodenal contents to the esophageal mucosa is considered to be an important risk factor for the development of esophagitis, BE and EAC, the mechanisms of reflux esophageal injury are not fully understood. Animal models are now being used extensively to identify the mechanisms of damage and to devise protective and mitigating strategies. Experimental studies on animal models by mimicking the processing of gastroesophageal reflux injury have bloomed during the past decades, however, there is controversy regarding which experimental model for reflux esophagitis, experimental BE and experimental EAC is best. In this review article we aim to clarify the basic understanding of gastroesophageal reflux injury and its complications of BE and EAC, as well as to present current understanding of the reflux experimental models. The animal models of experimental esophageal injury are summarized with focus on the surgical procedures to guide the investigator in choosing or developing a correct animal model in future studies. In addition, our own experimental studies of the animal models are also briefly discussed.     

反流性食管炎、Barrett食管的食管动力学研究

目的 探讨反流性食管炎(RE)、Barrett食管(BE)的动力学改变。方法 经内镜检查3 400例患者,分 RE、BE、对照组,进行症状调查、食管测压、食管24h pH检测,并行统计学分析。结果 RE与BE组间除吞咽不适外,烧心感、反酸及胸骨后疼痛的症状评分均为RE组大于BE组,且差异有显著性意义。部分RE、BE、对照组间食管运动功能比较,食管下括约肌静息压等差异均无显著性意义。食管24 h pH检测DeMeester评分、pH<4总时间、pH<4时间的百分比等 RE、BE组高于对照组,差异有显著性意义,但RE、BE组间差别无显著性意义。结论 食管反流症状与食管黏膜的内镜下表现不一致;食管组织化生与食管运动功能间无相关。     

Importance of bile reflux in Barrett's esophagus

Barrett's esophagus (BE) is an acquired condition in which the squamous epithelial lining of the lower esophagus is replaced by a columnar epithelium due to chronic gastroesophageal reflux. The role of acid and bile in the development of esophageal mucosal injury and the formation of BE is controversial. Acid and pepsin are unquestionably important in causing mucosal damage and BE formation in both animal models and humans. Animal studies suggest the potential for synergistic damage from conjugated bile acids and gastric acid, as well as from unconjugated bile acids and trypsin in more neutral pH settings. Evidence of the involvement of bile and its constituents in humans has been less conclusive; however, the advent of better technology to detect bile reflux is beginning to clarify the role of these constituents. Human studies show that the reflux of bile parallels acid reflux and increases with the severity of gastroesophageal reflux disease, being most marked in BE. However, recent ex vivo studies suggest that pulses of acid reflux may be more important than bile salts in the development of dysplasia or adenocarcinoma in Barrett's epithelium. Nevertheless, antireflux surgery and aggressive acid suppression with proton pump inhibitors will decrease both acid and bile refluxes, and eliminate the synergism between these two duodenogastric constituents.     

Esophageal strictures and lower esophagus lined with columnar epithelium

Radiographic, manometric, simultaneous radiographic-manometric, endoscopic, histologic and gastric secretory studies were performed on 12 consecutive patients with a benign peptic esophageal stricture. All patients had a segment of esophagus lined with columnar epithelium below the stricture and a small hiatal hernia. Four of them had a normotensive competent gastroesophageal sphincter and no evidence for reflux. Eight patients had free gastroesophageal reflux through a weak, incompetent sphincter. Esophagitis was not universally present. The type of heterotopic mucosa as well as the gastric secretory values showed no uniform pattern. Four patients with a fundic type of epithelium in the lower esophagus had discrete esophageal ulcers, but only 2 of them had evident gastroesophageal reflux. Local secretion of gastric juice seems to play a role in the genesis of these ulcers. There are strong arguments in favor of a congenital heterotopic mucosal lining in the lower esophagus in some patients, although a contributing role for reflux esophagitis cannot be excluded in others.     

How to Make a Barrett Esophagus: Pathophysiology of Columnar Metaplasia of the Esophagus

Barrett esophagus is defined as a specialized intestinal replacing the squamous epithelium of the esophageal mucosa in response to gastroesophageal reflux. Barrett metaplasia is a healing process that develops to protect the esophagus from further damage. Although mechanisms by which Barrett metaplasia evolves toward dysplasia and adenocarcinoma have been extensively studied, the process by which squamous epithelium is replaced by specialized intestinal metaplasia is poorly understood. Barrett esophagus develops when defense mechanisms in the esophageal mucosa (luminal secretion of mucus, bicarbonate, growth factors, etc.) are overwhelmed by an ongoing cycle of mucosal injury and repair. Hydrogen ion, pepsin, trypsin, and bile acids are considered harmful agents that synergistically invade the esophageal mucosa. Areas of destroyed squamous epithelium are then progressively reepithelized by a columnar epithelium that may originate from multipotent stem cells located within the basal layer of the normal esophageal mucosa or in the ducts of submucosal glands.     

Development of Barrett's esophagus six months after total gastrectomy

Barrett's esophagus (BE) is an acquired disease of the esophagus, in which esophageal squamous epithelium is changed by injury from reflux to metaplastic intestinal type columnar epithelium. BE is the premalignant lesion of adenocarcinoma of the esophagus. It is widely accepted that the long-standing reflux of gastric acid is a catalyst for the development of BE. More recent work points toward the reflux of duodenal secretions as a catalyst in this disease process as well. Moreover, the time course for the development of BE once a patient has reflux is not known. Our case challenges the currently defined time course of "long-standing" reflux symptoms for the development of BE, and supports the role of duodenal secretions alone in the development of BE. A 68-yr-old Caucasian man was admitted with weight loss, left upper quadrant pain, a hemoglobin of 6.8, and heme-positive stool. Esophagogastroduodenoscopy (EGD) revealed normal esophageal mucosa and a mass in the gastric cardia. Biopsies showed moderately differentiated gastric adenocarcinoma. The patient underwent a total gastrectomy, distal esophagectomy, and a Roux-en-Y esophagojejunostomy. Pathology confirmed gastric adenocarcinoma (T1 N0 Mx). The distal esophagus and gastroesophageal junction in the resected specimen were grossly and microscopically normal. Six months later an EGD, prompted by new complaints of regurgitation and dyspepsia, revealed distal esophageal mucosa lined by red-colored columnar tissue. Biopsies showed intestinal type epithelium. Thus, our case report's contribution to the current literature is twofold. It provides evidence of development of BE solely from duodenal reflux, and it documents a relatively short time span to development of BE.