Advances in the therapy of Barrett’s Esophagus

The rising incidence of esophageal adenocarcinoma(EAC) in the world has led to continued interest in its precursor lesion,Barrett’s esophagus(BE). This review endeavors to summarize the recent advances in the therapy of BE with an emphasis on novel endoscopic therapies.     

Barrett's食管组织中环氧合酶-2的表达及食管动力学测定

目的:探讨Barrett's食管(BE)食管运动功能、环氧合酶-2(COX-2)的表达及其发病机制。方法:收集62例经内镜和病理确诊的BE患者的资料,对其中21例的食管动力学检查结果进行分析;采用免疫组化SP法检测其中37例食管黏膜组织中COX-2蛋白的表达。以20例同期健康体检者和23例反流性食管炎(RE)患者作对照。结果:BE组下食管括约肌(LES)压力低于RE组及健康对照组,BE组食管远端收缩波幅较RE组及对照组降低(P均<0.05),而食管近端收缩波幅3组间差异无统计学意义(P>0.05)。正常十二指肠上皮组织中COX-2无表达,而20/24无不典型增生BE肠化黏膜、12/13不典型增生BE肠化黏膜表达COX-2蛋白,且2者间表达差异无统计学意义(P<0.05)。结论:LES功能失调是BE主要发病机制,COX-2蛋白的表达是BE发生的早期事件。     

Barrett食管发生的腺癌

报告了16例Barrett食管癌的形态学特点并探讨了其组织发生来源。16例Barrett食管癌皆为腺癌,瘤体全部或大部位于食管内,9例见柱状上皮(Barrett上皮)并排除了肿瘤来自胃腺或食道粘液腺的可能,诊断是可靠的。16例中肿瘤体积最小者1cm,最大者10.5cm,7例呈膨胀性生长,9例呈浸润性生长,11例浸润食管壁全层,14例有淋巴结转移,关于组织发生来源,在有Barrett上皮的9例中8例有肠上皮化生,7例有非典型增生,6例有腺瘤,而15例对照组中除6例有轻度肠化生外,无腺瘤及非典型增生。作者认为Barrett食管癌来源于Barrett上皮。     

食管炎、食管溃疡和Barrett's食管的胃-食管反流与胃内pH值的关系

目的 探讨胃内pH值与胃食管反流的关系及胃-食管反流的病理生理机制.方法 采用便携式pH监测仪对18例食管炎、12例食管溃疡、10例Barrett's食管、15例健康人行24h食管和胃pH值同步监测,分别计算胃内各段pH值、胃-食管酸反流次数、长反流次数、最长反流时间以及pH值<4的时间占总时间的百分比.结果 ①食管炎组:上述各项指标在胃内pH值为1～4时明显高于对照组(P<0.05);当胃内pH值为1～2时,酸反流次数明显高于其他pH值段(P<0.05);②食管溃疡组:当胃内pH值为1～2时,酸反流次数、长反流时间明显高于其他pH值段(P<0.05);胃内pH值为1～3时,酸反流次数、长反流时间明显高于对照组(P<0.05);③Barrett's食管组:胃内pH值为2～3时的酸反流次数明显高于对照组;④当胃内pH值为1～2时,食管炎组、食管溃疡组酸反流次数明显高于Barrett's食管组.结论 当胃内pH值在1～2之间时,食管炎、食管溃疡的胃食管酸反流最为明显,食管黏膜损伤的严重程度与食管接触酸的次数及接触酸的时间长短有关;Barrett's食管的胃-食管酸反流与胃酸无明显关系.     

Gastroesophageal reflux, barrett esophagus, and esophageal cancer: scientific review

CONTEXT: Gastroesophageal reflux disease (GERD) is a risk factor for adenocarcinoma of the esophagus, a rare cancer whose incidence is increasing. Adenocarcinoma may develop from Barrett esophagus, a metaplastic change of the esophageal epithelium from squamous to intestinalized columnar mucosa, which is associated with chronic reflux. Some have recommended that patients with chronic reflux symptoms undergo upper endoscopy to assess for Barrett esophagus and to screen for cancer. OBJECTIVES: To review the evidence linking GERD and Barrett esophagus to esophageal adenocarcinoma and to examine the utility of upper endoscopy as a screening tool in adenocarcinoma of the esophagus among individuals with GERD. DATA SOURCES: A MEDLINE search was performed to identify all pertinent English-language reports about GERD, adenocarcinoma, and Barrett esophagus from 1968 through 2001. Reports were of randomized controlled clinical trials if available, case-control data if trials were unavailable, and cohort studies if case-control data were unavailable. Pertinent bibliographies were also reviewed to find reports not otherwise identified. STUDY SELECTION AND DATA EXTRACTION: Studies were selected by using the search terms gastroesophageal reflux, adenocarcinoma, and Barrett's esophagus, with subheadings for classification, complications, drug therapy, economics, epidemiology, mortality, surgery, and prevention and control. Clinical guidelines for the care of subjects with GERD and Barrett esophagus were retrieved and abstracted. DATA SYNTHESIS: Cohort studies demonstrate that symptoms of GERD occur monthly in almost 50% of US adults and weekly in almost 20%. Three large case-control studies demonstrate a positive association between reflux symptoms and risk of adenocarcinoma of the esophagus, with more prolonged and severe symptoms accentuating this risk. However, because of the low incidence of adenocarcinoma of the esophagus and the ubiquity of reflux symptoms, the risk of cancer in any given individual with reflux symptoms is low. No randomized trial data are available to demonstrate either decreased cancer incidence or increased life expectancy in subjects with GERD who undergo screening endoscopy. CONCLUSIONS: Strong evidence supports the association of GERD and adenocarcinoma of the esophagus; however, the risk of cancer in any given individual with GERD is low. Barrett esophagus appears to be a common precursor lesion to this cancer. Given the low absolute risk of cancer in those with GERD and the lack of demonstrated efficacy of endoscopic screening, insufficient evidence exists to endorse routine endoscopic screening of patients with chronic GERD symptoms.     

CyclinD1和GST-π在不同食管病变中的表达及意义

目的:探讨CyclinD1和GST-π在不同食管病变中表达的意义。方法:应用免疫组织化学SP法检测50例食管鳞癌及其周围正常食管粘膜、20例食管粘膜轻度不典型增生、20例食管粘膜重度不典型增生中Cy-clinD1和GST-π的表达。结果:在正常粘膜、轻度不典型增生、重度不典型增生及鳞状细胞癌中CyclinD1阳性率分别为30%,45%,65%,78%,癌组织及重度不典型增生中的表达明显高于正常粘膜及轻度不典型增生组织(P<0.01)。在正常粘膜、轻度不典型增生、重度不典型增生及鳞状细胞癌中GST-π阳性率分别为82%,75%,60%,52%,癌组织及重度不典型增生中GST-π的表达明显低于正常粘膜及轻度不典型增生组织(P<0.01)。结论:Cy-clinD1和GST-π与食管癌的发生密切相关。     

Adenocarcinoma of the gastro-esophagus junction associated to endobrachyesophagus. Two case reports. Review of the literature

Barrett esophagus (BE) is intestinal metaplasia (MI) within the distal tubular esophagus. The BE results in replacement of the normal squamous-lined epithelium with a columnar type epithelium. This metaplastic lesion is a clearly defined risk factor for the development of esophageal adenocarcinoma (ADC). In the western countries the incidence of adenocarcinoma of the lower esophagus and the gastro-esophagus junction have rapidly increased during the past twenty years. The 5-year survival is very poor. Although the relative risk of individuals in the United States with BE developing esophageal adenocarcinoma is very high, the absolute risk is extremely low due to the small number of cases. This lesion is caused by a persistent gastro-esophageal reflux. The nature of the reflux liquid is mixed acid and alkaline in the big majority of cases. A familial aggregation of BE and esophageal adenocarcinoma are present in 14% of patients with BE and esophageal adenocarcinoma. The diagnosis, the surveillance, the new tools of characterization of BE and the therapy remain an actual problem. We present 2 cases of endobrachyesophagus associated to an adenocarcinoma of the lower esophagus and a review of the main actual problem.     

骨形成蛋白4在Barrett食管与食管腺癌中的表达及意义

目的:探讨Barrett食管与食管腺癌组织中骨形成蛋白4(BMP4)的表达及临床意义。方法:应用免疫组化SP法检测Barrett食管无不典型增生组20例,低级别不典型增生组20例、高级别不典型增生组20例及食管腺癌组25例组织中BMP4的表达。结果:在Barrett食管无不典型增生组、低级别不典型增生组、高级别不典型增生组及食管腺癌组中BMP4阳性率分别为15.0%,30.0%,75.0%,76.0%。食管腺癌组及Barrett食管高级别不典型增生组中BMP4的表达阳性率明显高于无不典型增生组及低级别不典型增生组(P均<0.05)。结论:BMP4与食管腺癌的发生密切相关。     

Barrett食管的内镜治疗进展

Barrett食管是食管腺癌的癌前病变,其发展为食管腺癌的风险较普通人明显增高。目前主要的治疗方式有药物抑酸治疗、外科手术行食管切除和内镜下治疗。由于抑酸治疗的局限性、食管切除手术本身的高风险、术后诸多并发症、高费用等因素,以及随着近10余年来消化内镜的飞速发展和普及,内镜下治疗Barrett食管变得越来越普遍,也成为了研究的热点。该文就Barrett食管治疗方式的原理、疗效、安全性等方面进行综述。     

Proton-pump inhibitor therapy and the development of dysplasia in patients with Barrett's oesophagus

OBJECTIVE: To examine whether proton-pump inhibitor (PPI) therapy influences the incidence and progression of dysplasia in patients with Barrett's oesophagus. DESIGN AND SETTING: Review of prospective data on patients undergoing surveillance with regular endoscopy and biopsy at a private endoscopy centre in Canberra, ACT, between 1981 and 2001. PATIENTS: 350 patients diagnosed with Barrett's oesophagus. INTERVENTIONS: PPI therapy was progressively introduced into clinical practice from late 1989. Once begun, PPI therapy was ongoing, with no attempt to reduce the dose. MAIN OUTCOME MEASURES: Relationship between development of dysplasia or adenocarcinoma and delay between diagnosis with Barrett's oesophagus and starting PPI therapy was determined by Cox regression analyses, stratified by year of enrollment. Age, sex, presence of macroscopic markers (severe oesophagitis, nodularity, Barrett's ulcer, stricture) and use of aspirin or non-steroidal anti-inflammatory drugs were considered as confounding factors in the regression analyses. RESULTS: The 350 patients had 1422 surveillance endoscopies, with a median follow-up of 4.7 years. Patients who delayed using a PPI for 2 years or more after diagnosis with Barrett's oesophagus had 5.6 times (95% CI, 2.0-15.7) the risk of developing low-grade dysplasia at any given time as those who used a PPI in the first year. Similar results were found for the risk of developing high-grade dysplasia or adenocarcinoma (hazard ratio, 20.9; 95% CI, 2.8-158). CONCLUSIONS: Use of ongoing PPI therapy appeared beneficial in the prevention of dysplasia and adenocarcinoma in patients with Barrett's oesophagus. We suggest that all patients with this condition, even those with no oesophagitis or symptoms, should be encouraged to continue long term PPI therapy.     

食管鳞状细胞癌癌旁异型增生组织多种抑癌基因表达的研究

为了研究食管癌前病变组织中多种抑癌基因表达状况，我们应用Ｐ５３，Ｐ１６和ｎｍ２３蛋白对７４例食管癌旁异型增生组织进行了检测。结果：Ｐ５３和Ｐ１６蛋白均随异型增生病理级别的升高而标记的阳性率升高，Ｉ级异型增生Ｐ１６阳性率与Ⅱ～Ⅲ级比较有显著差异（Ｐ〈０．００５），ｎｍ２３蛋白随异型增生病理级别的升高而标记阳性率下降，Ⅰ～Ⅱ级阳性率与Ⅲ级比较差异有显著性（Ｐ〈０．００５）；Ｐ５３＋Ｐ１６＋ｎｍ２３阳性     

P~(53)andc-myc蛋白在食管癌及癌前病变中的表达意义

目的　探讨P53 及c -myc蛋白在食管癌及癌前病变中的表达及意义。方法　应用免疫组化SP法检测P53 及c -myc在 6 0例食管癌及 33例非典型增生中的表达。 结果　P53 及c -myc蛋白分别在食管癌与非典型增生I～II级中表达有显著差异 (P <0 .0 5 ) ;在食管癌与非典型增生III级表达中无显著差异 (P >0 .0 5 )。结论　P53 及c -myc蛋白异常表达 ,可为食管癌和癌前病变界限的划分提供参考依据。     

食管癌中癌基因产物c-fos,c-jun的表达及意义

目的探讨癌基因c-fos、c-jun表达产物与食管癌的发生、发展及预后的关系。方法用免疫组化SABC法,以兔抗c-fos、c-jun抗体标记90例食管癌和30例食管上皮不典型增生。观察其分化程度和组织学类型,食管癌的表达及阳性率比较。结果c-fos、c-jun阳性反应见于不典型增生上皮和食管癌组织,不典型增生上皮c-fos、c-jun阳性率分别为70.0%和50.0%,癌组织为58.8%和48.9%;食管癌表达的阳性率与癌组织分化程度和组织学类型有关（P〈0.05）。结论提示c-fos、c-jun过量表达可发生在不典型增生的食管上皮和食管癌组织。     

35例Barrett食管的临床病理分析

目的:探讨Barrett食管的临床、病理学特点,并通过免疫组织化学的表达结果,证实Barrett食管与食管腺癌之间的关系。方法:对胃镜及病理资料进行分类整理,重新阅片,确诊为Barrett食管的病例均进行免疫组化检查。结果:35例经胃镜及病理诊断为Barrett食管的患者,结合免疫组化检查,发现伴有上皮不典型增生的病例CerbB-2、P53、Ki-67均有不同程度的表达。结论:Barrett食管是一种癌前病变,由Barrett食管发展为食管腺癌的危险性在增加,因此,提高对Barrett食管的早期诊断,做到早发现、早治疗,降低食管腺癌的发生,提高生存率有重要的意义。     

食管跨粘膜电位的研究

许多食管疾患,如食管炎、癌和Barrett食管都累及食管粘膜,因此一种评价食管粘膜完整性的敏感正确的方法是很有意义的。现已建立了一种测定食管跨粘膜电位(以下简称PD)的方法。为了确定PD测定对诊断食管粘膜疾病是否有用,我们测量了家兔正常食管和急性实验性食管炎时的食管PD。家兔正常食管上、中及下段的PD平均值分别为-27mv,-28mv和-25mv,与Turner等人的结果相仿。食管炎症区的PD比正常食管的明显降低(P<0.001)。本研究的结果提示,食管PD测定是检出食管粘膜病变的一种安全、简单、快速而又敏感的方法。     

Barrett食管上皮的微细结构及意义

目的 通过透射电镜技术观察Barrett食管上皮的超微结构变化,并探讨其意义.方法 内镜下诊断Barrett食管,在食管下段行内镜下黏膜活检,标本分别经福尔马林、戊二醛固定,对经内镜及病理证实为Barrett食管伴肠上皮化生的黏膜行透射电镜观察.结果 Barrett食管上皮超微结构显示兼有鳞状上皮和腺上皮的结构特征,并多见一种形态特征介于黏液细胞和杯状细胞之间的"中间体"细胞.结论 Barrett食管上皮超微结构提示Barrett上皮可能起源于食管的多能干细胞,并具有多向分化潜能.     

食管癌和癌前期病变中GST-π的表达意义

用抗胎盘型谷胱甘肽S-转移酶(GST-π)抗体的ABC免疫组织化学技术检测了75例食管癌,82例食管上皮异型增生,59例正常食管上皮组织中GST-π活性.食管癌组织中GST-π阳性率为90.6％,食管上皮异型增生组织中73.2％呈GST-π阳性,正常食管上皮组织中3.4％呈GST-π阳性,其余96.6％呈阴性。值得注意是轻度异型增生时,GST-π阳性率为65.4％,而中度和重度异型增生时,其阳性率进一步升高,接近食管癌水平。GST-π在食管癌和癌前病变组织中的异常表达为肿瘤防治研究工作提供了有意义的酶学指标。     

食管癌的化学预防

目的 　为在扩大的人群中验证和推广河南林县河顺乡“七五”攻关成果 ,自1 992年在食管癌高发区河北省磁县 9个乡 ,进行食管癌前病变的药物阻断治疗研究。方法　 通过 40～ 6 5岁人群的食管细胞学普查 ,检出食管重增 3990例 ,轻增 5 34 6例 ,随机分为治疗组和对照组。重增和轻增治疗组分别服用中药增生平片和核黄素钙片 ,对照组均服用安慰剂。服药 3年后食管细胞学复查。结果　 重增治疗组癌变相对危险度( RR) =0 .5 0 ,95 % CI=0 .33～ 0 .75 ,抑癌率 49.9% ;同时根据细胞学五级六类分级标准计算整体疗效 ,以对照组为标准组 ,其 Ridit=0 .5 8,95 % CI=0 .5 6～ 0 .6 0。轻增组的结果分别为 Ridit=0 .5 9,95 % CI=0 .5 7～ 0 .6 1 ;RR=0 .80 ,95 % CI=0 .5 2～ 1 .2 2 ,抑癌率 2 0 .4%。结论　 本次结果与河南省林县大人群的阻断结果一致 ,表明增生平阻断食管癌前病变、预防食管癌的效果是肯定的。整体疗效显示 ,轻增人群服用核黄素钙片也有一定的潜在效果。     

Surveillance in Barrett's oesophagus: a personal view

Barrett's oesophagus is defined as columnar-lined oesophagus of any length containing specialised intestinal metaplasia. Diagnosis depends on close corroboration between the endoscopist and histopathologist. It occurs in 10% of patients presenting endoscopically with reflux symptoms and has an adenocarcinoma incidence of 0.4% to 2%. Surveillance is performed to detect precancerous change (dysplasia) and early stage disease has a good surgical prognosis. Computer models suggest cost efficacy comparable to other health measures. However most patients with Barrett's do not die of oesophageal cancer and elective oesophagectomy has an appreciable mortality. Endoscopic ablation techniques and improved definition of high risk subgroups will help shape future surveillance programmes.