胃酸和十二指肠胃食管反流在Barrett‘s食管中的作用

目的 研究胃食管反流（GER）和十二指肠胃食管反流（DGER）在Barrett's食管发生中的作用。方法 20例经内镜和组织学诊断的Barrett's食管患者及10例内镜检查正常的无症状健康自愿者,经一整夜空腹后,以Bilitec2000胆反流和pH监测仪24h同步监测食管pH值和胆红素浓度。结果 Barrett's食管酸暴露总时间百分及经胆红素吸收值≥0.14为胆反流的时间百分较对照组显著增高,酸反流和DGER同时存在占Barrett's食管食管中的绝大部分（65％）,而其中4例有并发症的Barrett's食管则全部存在混合反流,大部分DGER事件发生pH＜4的环境中。结论 酸反流和DGER在Barrett's食管中发生率高且大部分反流同时发生,酸和DEGR在Barrett's食管发生中可能起协同作用。     

胃酸和十二指肠胃食管反流在非糜烂性反流病中的作用

背景:胃酸和十二指肠胃食管反流(DGER)在我国非糜烂性反流病(NERD)患者发病中的作用尚不清楚。目的:探讨胃酸和DGER在NERD发病中的作用。方法:选取在消化专科门诊连续就诊的具有烧心和(或)反酸等反流症状的所有患者为研究对象,所有入选者填写一份问卷后,依顺序行胃镜检查、24h食管pH监测和24h食管胆汁联合监测。结果:共有82例NERD患者入选,平均年龄为42.7岁±11.7岁。其中,24例(29.3%)24h食管pH监测阳性[NERDpH(+)],58例(70.7%)24h食管pH监测阴性[NERDpH(-)];43例(52.4%)为DGER阳性,39例(47.6%)为DGER阴性。联合监测结果为,82例患者中15例(18.3%)病理性酸反流与DGER并存,9例(11.0%)存在单一的病理性酸反流,28例(34.1%)存在单一的DGER,30例(36.6%)则无病理性酸反流,且DGER阴性。采用24h食管pH监测组对NERD的诊断率为29.3%,而联合24h食管胆汁监测,则NERD的诊断率升高到63.4%。24例NERDpH(+)者中,15例(62.5%)存在DGER;58例NERDpH(-)者中,28例(48.3%)存在DGER;NERDpH(+)组与NERDpH(-)组DGER发生率无显著性差异(χ2=1.377,P=0.241)。结论:NERD的病理性酸反流比例相对较低,联合24h食管pH和胆汁监测可明显提高NERD的诊断率,DGER在NERD中的作用地位不容忽视。     

十二指肠胃食管反流在胃食管反流病中的作用

目的　研究十二指肠胃食管反流 (DGER)在胃食管反流病发病机制中的作用及其对非糜烂性反流病 (NERD)的诊断价值。方法　 95例患者根据内镜检查的结果分为反流性食管炎和NERD组 ,对其均进行 2 4h食管 pH和胆汁联合监测。 结果　反流性食管炎患者DGER的各项指标 :吸光度值 >0 14时间百分比 (% )、总反流次数和反流 >5min的次数分别为 19 0 5± 2 3 4 4、30 5 6±34 0 4和 5 90± 6 37,均显著高于NERD组相应的 7 2 6± 11 0 8、15 6 8± 2 0 92和 2 5 9± 3 5 7(P <0 0 5 ) ,而酸反流差异无显著性 ,随着反流性食管炎的程度加重DGER发生率增高 ;18 2 %的NERD患者存在单纯DGER ,联合胆汁监测可使NERD诊断阳性率由 6 5 9%升高到 84 1%。结论　DGER可以单独发生 ,在引起反流性食管黏膜损伤或症状方面都有作用 ,2 4h食管 pH和胆汁联合监测有助于NERD的诊断。     

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。     

胆汁反流对Barrett食管及食管腺癌的作用及其机制

近30年来,食管腺癌(EA)的发病率显著上升,可能与胃食管反流病(GERD)发病率上升有关.GERD是常见的消化道动力障碍性疾病,包括非糜烂性胃食管反流病(NERD)、反流性食管炎(RE)、Barrett食管(BE),并发症包括食管狭窄、EA等.     

胃食管反流病

随着胃食管反流病(GERD)患病率的增加，GERD相关并发症亦有所增加，包括Barrett食管和食管腺癌。过去1年提出的有关GERD病理生理学的新观点有助于我们更好地理解反流性疾病发病和黏膜损伤症状之间的关系，并提供针对病人个体化病理生理缺陷的治疗。     

十二指肠胃食管反流研究进展

胃和 (或 )十二指肠内容物反流入食管产生症状或并发症时 ,称为胃食管反流病 (ＧＥＲＤ)。十二指肠内容物经幽门反流入胃内称为十二指肠胃反流 (ＤＧＲ) ,如进一步反流入食管则形成十二指肠胃食管反流(ＤＧＥＲ) ,若反流量大、频率高、持续时间长 ,则可能引起病理性损害。现就十二指肠胃食管反流的病因和致病机制、临床意义、检测方法及防治措施作以下综述。　　十二指肠胃食管反流的病因和致病机制若发生十二指肠胃食管反流则首先要有十二指肠胃反流 ,许多结构或功能紊乱均可引起十二指肠胃反流 ,如胃部分切除术后、胃十二指肠运动异常、胆…     

十二指肠球部溃疡伴胃食管反流患者食管动力及胃内pH值监测

目的：探讨胃食管反流(GER)常见于十二指肠球部溃疡的原因。方法：选择近5年我院接受胃食管动力检查并行胃镜检查明确诊断为十二指肠球部溃疡的患者46例。食管pH监测胃食管酸反流阳性或胃镜检查存在反流性食管炎(RE)者为反流组，食管pH值监测胃食管酸反流阴性者为非反流组。比较两组食管下括约肌(IES)、食管体部及食管上括约肌(UES)等功能差别，同时对两组胃pH值监测进行比较。结果：十二指肠球部溃疡患者为GER／RE的高发人群，反流组与非反流组LES长度、功能压、食管体部清除功能、UES静息压比较差异无显著性。反流组每日不同时限胃酸分泌高于非反流组。结论：十二指肠球部溃疡易合并GER／RE与胃酸增高有关，与食管动力变化关系不大。     

反流性食管炎与食管腺癌

食管腺癌（EAC）的发病率在西方国家以年均10％的速度递增,其恶性程度较高,较早出现淋巴结转移,预后很差。在我国,随着生活水平的提高和生活方式的改变,食管腺癌的发病率亦呈现出升高的趋势。胃食管反流导致的食管黏膜慢性炎症是食管腺癌发生的重要危险因素。伴随食管反流的患者发展为腺癌的风险提高了2～7倍,且患癌风险与反流症状的严重程度和持续时间密切相关。     

Ki-67在Barrett食管、重度反流性食管炎和食管腺癌中的表达和意义

背景：Barrett食管是一种食管腺癌癌前病变。Ki-67是一种能较准确地评估细胞增殖状态的抗原，在肿瘤进程中可能起重要作用。目的：研究Ki-67在Barrett食管、重度反流性食管炎和食管腺癌中的表达和意义。方法：应用免疫组化SP法测定59例Barrett食管、5例重度反流性食管炎、5例食管腺癌和10例正常食管黏膜组织中Ki-67的表达。结果：Ki-67在重度反流性食管炎中的阳性率为80．0％，Barrett食管阳性率为76．3％，与正常食管黏膜组织（20．0％）相比有显著差异（P〈0．05）：食管腺癌阳性率为100％。Ki-67的表达随Barrett食管肠化生程度的加重而增高（P〈0．05）；而不同长度（短段、长段）、肠化生黏膜形态（全周型、舌型和岛型）以及不同程度（轻度、中度）异型增生的Barrett食管，Ki-67的表达均无显著差异（P〉0．05）。结论：Ki-67在重度反流性食管炎和Barrett食管中表达增强，提示其在食管腺癌进程中起重要作用。     

Gene expression in rats with Barrett＇s esophagus and esophageal adenocarcinoma induced by gastroduodenoesophageal reflux

AIM: To study the different gene expression profiles in rats with Barrett's esophagus (BE) and esophageal adenocarcinoma (EA) induced by gastro-duodeno-esophageal reflux. METHODS: Esophagoduodenostomy was performed in 8-wk old Sprague-Dawley rats to induce gastro-duodeno-esophageal reflux, and a group of rats that received sham operation served as control. Esophageal epithelial pathological tissues were dissected and frozen in liquid nitrogen immediately. The expression profiles of 4 096 genes in EA and BE tissues were compared to normal esophagus epithelium in normal control (NC) by cDNA microarray. RESULTS: Four hundred and forty-eight genes in BE were more than three times different from those in NC, including 312 upregulated and 136 downregulated genes. Three hundred and seventy-seven genes in EA were more than three times different from those in NC, including 255 upregulated and 142 downregulated genes. Compared to BE, there were 122 upregulated and 156 downregulated genes in EA. In the present study, the interested genes were those involved in carcinogenesis. Among them, the upregulated genes included cathepsin C, aminopeptidase M, arachidonic acid epoxygenase, tryptophan-2,3-dioxygenase, ubiquitin-conjugating enzyme, cyclic GMP-stimulated phosphodiesterase, tissue inhibitor of metalloproteinase-1, betaine-homocysteine methyltra nsferase, lysozyme, complement 4b binding protein, complement 9 protein, insulin-like growth factor binding protein, UDP-glucuronosyltransferase, tissue inhibitor of metalloproteinase-3, aldolase B, retinoid X receptor gamma, carboxylesterase and testicular cell adhesion molecule 1. The downregulated genes included glutathione synthetase, lecithin-cholesterol acyltransferase, p55CDC, heart fatty acid binding protein, cell adhesion regulator and endothelial cell selectin ligand. CONCLUSION: Esophageal epithelium exposed excessively to harmful ingredients of duodenal and gastric reflux may develop into BE and even EA gradually. The gene expression level is different between EA and BE, and may be related to the occurrence and progression of EA.     

Exposure to gastric juice may not cause adenocarcinogenesis of the esophagus

AIM: To determine the effects of gastric juice on the development of esophageal adenocarcinoma (EAC). METHODS: A animal model of duodenogastroesophageal reflux was established in Sprague-Dawley rats undergoing esophagoduodenostomy. The development of EAC and forestomach adenocarcinoma was investigated 40 wk after the treatment. Intraluminal pH and bile of the forestomach were measured. RESULTS: There were no significant differences in pH (t=0.117, P=0.925) or bile (χ2=0.036, P=0.85) in the forestomach before and 40 wk after esophagoduodenostomy. There were also no significant differences between the model and controls during esophagoduodenostomy or 40 wk after esophagoduodenostomy. The incidence of intestinal metaplasia (88%) and intestinal metaplasia with dysplasia and adenocarcinoma (28%) in the esophagus in the model was higher than in the controls 40 wk after surgery (χ2=43.06, P < 0.001 and χ2=9.33, P=0.002, respectively) and in the forestomach in the model (χ2=32.05, P < 0.001 and χ2=8.14, P=0.004, respectively). The incidence rates of inflammation in the esophagus and forestomach were 100% and 96%, respectively (χ2=1.02, P=0.31) in the model, which was higher than in the esophageal control (6.8%) (χ2=42.70, P < 0.001). CONCLUSION: Gastric juice exposure may not cause intestinal metaplasia with dysplasia or adenocarcinoma of the forestomach and may not be related to EAC.     

Barrett食管的酸反流类型

目的：了解Barrett食管的发生与胃食管酸反流类型之间的关系。方法：对23例Barrett食管及37例反流性食管炎（Ⅱ级16例，Ⅱ、Ⅲ级21例）病人行24小时食管内pH监测。分别将直立位和卧位pH＜4的百分时间；反流次数；反流持续5分钟以上的反流次数；最长反流持续时间之间进行比较。结果：两组直立位时Ⅰ级食管炎组与Barrett食管比较，差异有显著性（P＜0．01，P＜0．01，P＜0．05，P＜0．01），Ⅱ、Ⅲ级食管炎组与Barrett食管比较差异无显著性（P＞0．05）。卧位时，无论是Ⅰ级食管炎还是Ⅱ、Ⅲ级食管炎组各指标与Barrett食管比较，差异均有显著性（P＜0．05，P＜0．001）．结论：卧位酸反流在Barrett食管的发病中可能起重要作用。     

Gene expression in Barrett＇s esophagus and reflux esophagitis induced by gastroduodenoesophageal reflux in rats

AIM: To investigate the difference of gene expression profiles between Barrett's esophagus and reflux esophagitis induced by gastroduodenoesophageal reflux in rats. METHODS: Eight-week-old Sprague-Dawley rats were treated esophagoduodenostomy to produce gastroduodenoesophageal reflux, and another group received sham operation as control. Esophageal epithelial tissues were dissected and frozen in liquid nitrogen immediately for pathology 40 wk after surgery. The expression profiles of 4 096 genes in reflux esophagitis and Barrett's esophagus tissues were compared with normal esophageal epithelium by cDNA microarray. RESULTS: Four hundred and forty-eight genes in Barrett's esophagus were more than three times different from those in normal esophageal epithelium, including 312 up-regulated and 136 down-regulated genes. Two hundred and thirty-two genes in RE were more than three times different from those in normal esophageal epithelium, 90 up-regulated and 142 down-regulated genes. Compared to reflux esophagitis, there were 214 up-regulated and 142 down-regulated genes in Barrett's esophagus. CONCLUSION: Esophageal epithelium exposed excessively to harmful ingredients of duodenal and gastric reflux can develop esophagitis and Barrett's esophagus gradually. The gene expression level is different between reflux esophagitis and Barrett's esophagus and the differentially expressed genes might be related to the occurrence and development of Barrett's esophagus and the promotion or progression in adenocarcinoma.     

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.     

COX-2在Barrett食管和食管腺癌中的表达及意义

目的:探讨环氧合酶-2(COX-2)及其催化产生的前列腺素E2(PGE2)与Barrett食管及食管腺癌的关系．方法:采用RT-PCR、免疫组化和RIA等方法,分别测定Barrett食管组(n=16),食管腺癌组(n=17)和正常对照组(n=20)食管黏膜中COX-2 mRNA的表达率、 COX-2蛋白在组织中的表达率和在细胞中的分布情况,以及PGE2在组织中的含量．结果:87．50％(14／16)的Barrett食管和88．24％(15／17) 的食管腺癌中COX-2 mRNA呈阳性表达,与对照组 25．00％(5／20)比较均有显著差异(P<0．01)．免疫组织化学研究显示:COX-2蛋白在Barrett食管上皮细胞和食管腺癌的癌细胞细胞质中呈阳性表达,81．25％(13／16) 的Barrett食管和76．47％(13／17)的食管腺癌中COX-2 蛋白呈阳性表达,与对照组20．00％(4／20)比较均有显著差异(P<0．01),但Barrett食管组和食管腺癌组 COX-2蛋白表达率之间无显著差异(P>0．05)．放射免疫分析测定显示:Barrett食管组(541．41±34．30 ng／g)和食管腺癌组(559．224±37．77 ng／g)中PGE2的含量与对照组(357．10±37．58 ng／g)相比均有显著差异 (P<0．05),Barrett食管组和食管腺癌组之间PGE2的含量无显著差异(P>0．05)．结论:COX-2及其mRNA蛋白在Barrett食管和食管腺癌中均呈高表达．PGE2的含量在Barrett食管和食管腺癌中均增高．COX-2及其催化产生的PGE2可能与 Barrett食管及食管腺癌的形成有关．     

胆汁酸在Barrett食管和食管腺癌发病中的作用

目的探讨胆汁酸在Barrett食管(BE)及食管腺癌(EAC)发病中的作用,为预防、治疗BE、EAC的发生提供参考依据。 方法选取2017年8月10日至2020年10月30日于茌平区人民医院就诊,反流性疾病问卷评分>12分的患者,对其行无痛胃镜检查,镜下胃液留取及食管下段(胃食管结合部上1 cm处)黏膜组织活检,进行胃液、食管下段黏膜胆汁酸浓度检测。 结果所检患者胃液中均检测到不同浓度的胆汁酸,且BE、EAC患者胃液及食管下段黏膜组织总胆汁酸浓度较非糜烂性反流病(NERD)、反流性食管炎(RE)患者胃液及食管下段黏膜组织总胆汁酸浓度明显升高(P值均<0.05)。 结论胆汁酸在BE、EAC患者胃液及食管下段黏膜组织中的浓度较无Barrett食管的胃食管反流病患者的浓度明显升高,提示胆汁反流可能与胃食管结合部黏膜细胞恶性转化相关,抑制胆汁反流可能成为预防BE、EAC发生的必要干预措施。     

Characteristics of patients with columnar-lined Barrett＇s esophagus and risk factors for progression to esophageal adenocarcinoma

AIM: To determine the risk factors for the development of esophageal adenocarcinoma in these patients with columnar-lined esophagus (CLE). METHODS: Data collected retrospectively on 597 consecutive patients diagnosed at endoscopy and histology to have CLE at Leeds General Infirmary between 1984 and 1995 were analyzed. Factors evaluated included age, sex, length of columnar segment, smoking, and drinking habits, history of non-steroidal ingestion, presence of endoscopic esophagitis, ulceration or benign strictures and presence of Helicobacter pylori in esophageal biopsies. Univariate and multivariate analyses were performed to identify risk factors for the development of adenocarcinoma. RESULTS: Forty-four patients presented or developed esophageal adenocarcinoma during follow-up. Independent risk factors for the development of adenocarcinoma in patients with CLE were males (OR 5.12, 95%CI 2.04-12.84, P = 0.0005), and benign esophageal stricture (OR 4.37, 95%CI 2.02-9.45, P = 0.0002). Male subjects and patients who developed benign esophageal stricture constituted 86% (n = 38) of all patients who presented or developed esophageal adenocarcinoma. The presence of esophagitis was associated with a significant reduction in the development of esophageal carcinoma (OR 0.28, 95%CI 0.13-0.57, P = 0.0006). No other clinical characteristics differentiate between the non-malignant and malignant group. CONCLUSION: In patients with CLE, endoscopic surveillance for the early detection of adenocarcinoma may be restricted to male subjects, as well as patients who develop benign esophageal strictures.     

Indomethacin but not a selective cyclooxygenase-2 inhibitor inhibits esophageal adenocarcinogenesis in rats

AIM:To evaluate the effects of indomethacin [dual cyclooxygenase(COX)-1/COX-2 inhibitor] and 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl) phenyl)2-(5H)-furanone(MF-tricyclic)(COX-2 selective inhibitor) in a rat experimental model of Barrett's esophagus and esophageal adenocarcinoma.METHODS:A total of 112 surviving post-surgery rats were randomly divided into three groups:the control group(n = 48),which did not receive any treatment;the indomethacin group(n = 32),which were given 2 mg/kg per day of the COX-1/COX-2 inhibitor;and the MF-tricyclic group(n = 32),which received 10 mg/kg per day of the selective COX-2 inhibitor.Randomly selected rats were killed either 8 wk or 16 wk after surgery.The timing of the deaths was in accordance with a previous study performed in our group.Only rats that were killed at the times designated by the protocol were included in the study.We then assessed the histology and prostaglandin E2(PGE2) expression levels in the rat esophagi.An additional group of eight animals that did not undergo esophagojejunostomy were included in order to obtain normal esophageal tissue as a control.RESULTS:Compared to a control group with no treatment(vehicle-treated rats),indomethacin treatment was associated with decreases in ulcerated esophageal mucosa(16% vs 35% and 14% vs 17%,2 mo and 4 mo after surgery,respectively;P = 0.021),length of intestinal metaplasia in continuity with anastomosis(2 ± 1.17 mm vs 2.29 ± 0.75 mm and 1.25 ± 0.42 mm vs 3.5 ± 1.54 mm,2 mo and 4 mo after surgery,respectively;P = 0.007),presence of intestinal metaplasia beyond anastomosis(20% vs 71.4% and 0% vs 60%,2 mo and 4 mo after surgery,respectively;P = 0.009),severity of dysplasia(0% vs 71.4% and 20% vs 85.7% high-grade dysplasia,2 mo and 4 mo after surgery,respectively;P = 0.002),and adenocarcinoma incidence(0% vs 57.1% and 0% vs 60%,2 mo and 4 mo after surgery,respectively;P 0.0001).Treatment with the selective COX-2 inhibitor,MF-tricyclic,did not prevent development of intestinal metaplasia or adenocarcinoma.In parallel,we observed a significant decrease in PGE2 levels in indomethacin-treated rats,but not in those treated with MF-tricyclic,at both 2 mo and 4 mo.Compared to control rats that did not undergo surgery(68 ± 8 ng/g,P = 0.0022 Kruskal-Wallis test) there was a significant increase in PGE2 levels in the esophageal tissue of the rats that underwent surgery either 2 mo(1332 ± 656 ng/g) or 4 mo(1121 ± 1015 ng/g) after esophagojejunostomy.However,no differences were found when esophageal PGE2 levels were compared 2 mo vs 4 mo post-esophagojejunostomy.At both the 2-and 4-mo timepoints,we observed a significant decrease in PGE2 levels in indomethacin-treated rat esophagi compared to those in either the control or MF-tricyclic groups(P = 0.049 and P = 0.017,respectively).No differences in PGE2 levels were found when we compared levels in rats treated with MF-tricyclic to not-treated rats.CONCLUSION:In this rat model of gastrointestinal reflux,indomethacin was associated with a decrease in the severity of esophagitis and reduced development of esophageal intestinal metaplasia and adenocarcinoma.     

MicroRNAs, development of Barrett’s esophagus, and progression to esophageal adenocarcinoma

Barrett's esophagus is a premalignant condition caused by gastroesophageal reflux. Once developed, it can progress through varying grades of dysplasia to esoph-ageal adenocarcinoma. Whilst it is well accepted that Barrett's esophagus is caused by gastroesophageal reflux, the molecular mechanisms of its pathogenesis and progression to cancer remain unclear. MicroRNAs (miRNAs) are short segments of RNA that have been shown to control the expression of many human genes. They have been implicated in most cellul...