Obesity and lifestyle risk factors for gastroesophageal reflux disease, Barrett esophagus and esophageal adenocarcinoma

The aim of this study was to examine the association of obesity with esophageal adenocarcinoma, and with the precursor lesions Barrett esophagus and gastroesophageal reflux disease (GERD). This case-control study included cases with GERD (n = 142), Barrett esophagus (n = 130), and esophageal adenocarcinoma (n = 57). Controls comprised 102 asymptomatic individuals. Using logistic regression methods, we compared obesity rates between cases and controls adjusting for differences in age, gender, and lifestyle risk factors. Relative to normal weight, obese individuals were at increased risk for esophageal adenocarcinoma (Odds Ratio [OR] 4.67, 95% Confidence Interval [CI] 1.27-17.9). Diets high in vitamin C were associated with a lower risk for GERD (OR 0.40, 95% CI 0.19-0.87), Barrett esophagus (OR 0.44, 95% CI 0.20-0.98), and esophageal adenocarcinoma (OR 0.21, 95% CI 0.06-0.77). For the more established risk factors, we confirmed that smoking was a significant risk factor for esophageal adenocarcinoma, and that increased liquor consumption was associated with GERD and Barrett esophagus. In light of the current obesity epidemic, esophageal adenocarcinoma incidence rates are expected to continue to increase. Successful promotion of healthy body weight and diets high in vitamin C may substantially reduce the incidence of this disease.     

胆汁返流与Barrett食管及食管肿瘤

Barrett食管是一类公认的食管腺癌癌前病变, 在西方国家常见．近年来在中国也有上升的趋势．目前有研究显示胆汁返流与Barrett食管及食管腺癌有关联．有研究显示胆汁返流可能导致Barrett食管发病率上升,从而食管腺癌发生率亦上升．其可能的机制涉及到返流时胆盐在 Barrett食管过程中对有关癌基因的影响、慢性炎症在其中的作用、胆囊切除术后相应的解剖学改变等．本文就此作一综述．     

Gastroesophageal reflux and Barrett's esophagus in adults born with esophageal atresia

OBJECTIVE: Postoperative morbidity after correction of esophageal atresia is partly determined by gastroesophageal reflux disease, which has been proven to affect from one-half to two-thirds of patients during childhood. We conducted a follow-up study to test our hypothesis that, if former patients still show gastroesophageal reflux at adult age, they are at high risk for developing Barrett's esophagus, which is considered to be premalignant. METHODS: Of 69 patients born between 1971 and 1978, all having undergone a primary anastomosis, 24 had died, five of them because of aspiration. Of the 45 survivors, 39 could be traced; they all completed a questionnaire inquiring after symptoms related to the esophagus. Of these patients, 34 underwent an additional esophagogastrocopy. RESULTS: Only nine of the 39 patients had no symptoms at all; 30 had mild to severe dysphagia symptoms, and 13 had mild to severe reflux symptoms. Esophagogastrocopy in 34 patients revealed that the anastomosis was still recognizable in all cases, but stenoses were not found. Six patients showed a small hiatal hernia, and one a large one. The incidences of reflux symptoms (13/39, p < 0.01), reflux esophagitis (9/34, p < 0.01) and Barrett's esophagus (2/34, p < 0.001) were significantly higher than in the normal population. CONCLUSIONS: This group seems to be at risk for developing Barrett's esophagus. As this is the first follow-up study of a consecutive group of adult esophageal atresia patients, we think it is advisable to perform an esophagogastroscopy in all patients at adulthood until more long term follow-up data are available.     

From reflux esophagitis to Barrett's esophagus and esophageal adenocarcinoma

The occurrence of gastroesophageal reflux disease is common in the human population.Almost all cases of esophageal adenocarcinoma are derived from Barrett's esophagus,which is a complication of esophageal adenocarcinoma precancerous lesions.Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett's esophagus.The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia,which is closely associated with the development of esophageal adenocarcinoma.However,the exact mechanism of injury is not completely understood.Various animal models of the developmental mechanisms of disease,and theoretical and clinical effects of drug treatment have been widely used in research.Recently,animal models employed in studies on gastroesophageal reflux injury have allowed significant progress.The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results.In this article,various modeling methods are reviewed,with discussion of the major findings on the developmental mechanism of Barrett's esophagus,which should help to develop better prevention and treatment strategies for Barrett's esophagus.     

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。     

Familial trends of inheritance in gastro esophageal reflux disease, Barrett''s esophagus and Barrett''s adenocarcinoma: 20 families

We reported four families with familial Barrett's esophagus (FBE) in 1993. This follow-up study includes an additional 16 families with FBE, gastroesophageal reflux disease (GERD) and BE-related adenocarcinoma (BEAC) highlighting the familial trends of inheritance. A retrospective survey of endoscopic and histopathological reports on 95 confirmed cases of BE from 1975 to 2005 was performed and a detailed family history was obtained. Five representative pedigrees from a total of 20 are discussed here. These 20 families represent one of the largest cohorts studied over three decades from a single institution. Familial BE is more common than previously thought and the prevalence of GERD, BE and BEAC in these families is distinctly higher than with sporadic cases. The conditions appear to be inherited in an autosomal dominant fashion with incomplete penetrance. Hence diligence in taking family history with BE patients is critical since the endoscopic screening of relatives is warranted in FBE. Earlier diagnosis and surveillance of FBE should hopefully improve outcomes.     

反流性咽喉炎的研究进展

随着对胃食管反流病认识的深入,其对咽喉部的影响越来越受到临床的关注,研究证明它是导致咽喉部疾病的重要致病因素之一。胃食管反流对消化系统影响的研究很多,但其与咽喉反流性疾病的相关研究甚少,很多基层医生对该病还不甚了解。本文主要对反流性咽喉炎的发病机制、临床表现、诊断方法和治疗作一综述。     

Gastroesophageal reflux disease

GERD is a common chronic gastrointestinal disorder, and its prevalence in Asia is increasing. Classical symptoms of heartburn and regurgitation are common presentations. There is no standard criterion for the diagnosis of GERD, and 24-h pH monitoring lacks sensitivity in NERD. Furthermore, diagnostic studies for gastroesophageal reflux disease have several limitations. A short course of PPI is often used in clinical practice as a diagnostic test for gastroesophageal reflux disease. Elderly patients with GERD usually present with atypical manifestations, and they tend to develop more severe disease. PPI remains the mainstay of treatment for GERD. In a subset of patients who wish to discontinue maintenance treatment, anti-reflux surgery is a therapeutic option.     

Gastroesophageal reflux disease

Opinion Statement Prior to the advent of proton pump inhibitors, internists recommended antireflux surgery primarily for patients whose gastroesophageal reflux disease (GERD) failed to respond to medical therapy. Although many physicians still cling to the notion that antireflux surgery is a procedure best reserved for “medical failures,” today this position is inappropriate. Modern medical treatments for GERD are extraordinarily effective in healing reflux esophagitis. It is uncommon to encounter patients with heartburn or esophagitis due to GERD who do not respond to aggressive antisecretory therapy. Indeed, the very diagnosis of GERD must be questioned for patients whose esophageal signs and symptoms are unaffected by the administration of proton pump inhibitors in high dosages. In the large majority of these so-called refractory patients, protracted esophageal pH monitoring reveals good control of acid reflux by the proton pump inhibitors. This finding indicates that the persistent symptoms usually are not due to acid reflux, but to other problems such as functional bowel disorders. Medical treatment fails in such patients because the diagnosis is mistaken, not because the drugs fail to control acid reflux. Modern antireflux surgery also is highly effective for controlling acid reflux, but fundoplication will not be effective for relieving symptoms in patients whose symptoms are not reflux-induced. Therefore, many patients deemed failures of modern medical therapy would be surgical failures as well. Antireflux surgery is an excellent treatment option for patients with documented GERD who respond well to medical therapy, but who wish to avoid the expense, inconvenience, and theoretical risks associated with lifelong medical treatment. Ironically, surgical therapy for GERD today is best reserved for patients who are medical successes.     

Gastroesophageal reflux disease

Opinion statement Lifestyle modifications should be discussed with every patient with symptoms of chronic gastroesophageal reflux disease (GERD). Proton pump inhibitors are the most efficacious medical therapy for GERD. H₂ receptor antagonists are likely to be effective in patients with mild to moderate GERD and for occasional symptoms. Promotility drugs have limited efficacy and produce frequent side effects. Surgery is a reasonable option for chronic management. Endoscopic therapy remains experimental until more long-term results are available.     

Gastroesophageal reflux disease: clinical, endoscopic, and intraluminal esophageal pH monitoring evaluation

One hundred and twenty-two patients with gastroesophageal reflux disease were studied (90 with and 32 without esophagitis) with the objective of analyzing possible differences between those with and without esophagitis. Evaluation consisted of clinical interview, endoscopy of the high digestive tract, esophageal manometry, and pH monitoring. There was no significant difference between the groups in age, sex, or symptoms. The incidence of hiatal hernia was greater in the group with esophagitis. Although the frequency of motor changes was similar, the type of anomaly was different. The reflux pattern was very similar in both groups. Therefore, the concept of reflux disease, esophagitis, and pathological reflux still needs a broader definition for greater diagnostic precision and for comparing the results of different studies on the subject. Normal reflux (confirmed using pH esophageal monitoring) in 12.2% of patients with esophagitis suggests that other factors are implicated in the etiology of the disease besides those measured using this examination.     

Barrett食管和食管腺癌的基因表达谱研究

目的:研究Barrett食管(BE)和食管腺癌的基因表达谱,筛查与食管腺癌相关的基因.方法:使用Dchip软件对已经在GEO数据库中公开的BE和食管腺癌Affymetrix芯片表达谱数据进行分析.还原扫描图像进行独立核验,并对基因和组织进行双向聚类,最后用配对t检验筛查出在BE和食管腺癌中表达水平都发生变化的基因,并进一步分析其功能.结果:24张Affymetrix芯片的杂交质量稳定,被污染和发生交叉杂交的探针簇都少于5%.对基因和样本的双向聚类表明,大部分组织分类正确.只有N8和A5位于错误的组织类型中.对其余22张芯片再次分别进行配对t检验,得到24个基因.其中表达水平呈进行性上升的5个,呈进行性下降的19个.新检出的PITX1已在稍前不久的另一项研究中得到证实.结论:用新的分析方法研究已公开的表达谱芯片资料为研究肿瘤的发病机制提供了新的手段.     

趋化因子受体4在Barrett食管、食管腺癌和食管鳞状细胞癌中的表达及其意义

目的 了解趋化因子受体（CXCR4）在Barrett食管（BE）、食管腺癌和食管鳞状细胞癌中的表达,及其与病理分化程度、临床分期及淋巴结转移之间的关系.方法 应用免疫组织化学SP法对正常食管黏膜56例、BE 80例（其中伴多灶性异型增生22例）、食管腺癌25例和食管鳞状细胞癌组织48例标本中CXCR4的表达进行检测,并用仪器对表达结果进行图像分析,然后进行统计学分析.结果 （1）CXCR4在大部分BE、食管腺癌和食管鳞状细胞癌中呈阳性表达（其阳性率分别为78.8%、68.0%、83.3%）,3组间差异无统计学意义（P＞0.05）,而在正常食管黏膜组中呈阴性或弱阳性表达（阳性率为39.3%）,差异有统计学意义（P＜0.01）;（2）CXCR4在BE、食管腺癌和食管鳞状细胞癌的表达与性别、年龄、病变发生位置均无关（P＞0.05）;（3）CXCR4在BE无异型增生和BE伴多灶性异型增生组织标本中的表达差异无统计学意义（P＞0.05）;（4）CXCR4在食管腺癌高分化较中-低分化者、有淋巴结转移较无淋巴结转移者中的表达均高（P＜0.05）;（5）CXCR4在食管鳞状细胞癌表达水平在肿瘤TNM分期的Ⅲ-Ⅳ级较Ⅰ-Ⅱ级者、有淋巴结转移较无淋巴结转移者中的表达均高（P＜0.05）,高分化较中-低分化则明显更高（P＜0.01）.结论 CXCR4的表达上调可能是食管腺癌和鳞癌的一个普遍特征,与食管病理组织学类型无关,其表达在BE阶段就已上调,并与食管腺癌和鳞癌的分化程度,有无淋巴结转移和TNM分期有一定相关性.CXCR4的表达对BE、食管腺癌和鳞癌的诊断具有指导价值,有可能成为肿瘤治疗的一个新靶点.