Barrett's esophagus and its correlation with gastroesophageal reflux in Chinese

AIM:To study the prevalence of Barrett's esophagus inChinese and its correlation with gastroesophageal reflux.METHODS:This study was carried out in a large prospectiveseries of 391 patients who had undergone upper endoscopy.The patients were divided into 3 groups according to theposition of squamocolumnar junction(SCJ).Refluxesophagitis(RE)and its degree were recorded.Intestinalmetaplasia(IM)in biopsy specimen was typed according tohistochemistry and HE and alcian blue(pH2.5)stainingseparately.Results correlating with clinical,endoscopic,andpathological data were analysed.RESULTS:The prevalence of IM endoscopically appearingLong-segment Barrett's Esophagus(LSBE)was 26.53%,Short-segment Barrett's Esophagus(SSBE)was 33.85% andgastroesophageal junction(GEJ)was 34.00%.IM increasedwith age of above 40 years old and no difference was foundbetween male and female.Twelve were diagnosed asdysplasia(7 low -grade,5 high-grade),16 were diagnosedas cardiac adenocarcinoma and 1 as esophagealadenocarcinoma.The more far away the SCJ moved upwardabove GEJ,the higher the prevalence and the more severethe RE were.CONCLUSION:There was no difference of the prevalenceof IM in different places of SCJ,and IM increased with ageof above 40 years old.It is important to pay attention todysplasia in the distal esophagus and gastro-esophagealjunction,and adenocarcinoma is more common in cardiathan in esophagus.BE is a consequence of gastroesophagealreflux disease.     

Relationship of gastric Helicobacter pyloriinfection to Barrett＇s esophagus and gastro-esophageal reflux disease in Chinese

AIM:To evaluate the relationship of Helicobacter pylori infection to reflux esophagitis (RE), Barrett‘s esophagus (BE)and gastric intestinal metaplasia (IM).METHODS:RE,BE and gastric IM were determined by upper endoscopy. Patients were divided into 2 groups; those with squamocolumnar junction (SCJ) beyond gastroesophageal junction (GEJ)≥3cm (group A), and those with SCJ beyond GE.1 <3cm (group B). Biopsy specimens were obtainedend escopically from just below the SCJ, gastric antrum along the greater and lesser curvature. Pathological changes and Hpylorr infection were determined by HE staining, Alcian blue staining and Giemsa staining.RESULTS:The prevalence of Hpyloriinfection was 46.93%.There was no difference in the prevalence between males and females.The prevalence of Hpyloriinfection decreased stepwise significantly from RE grade I to Ⅲ.There was no difference in the prevalence between the two groups, and between long-segment and short-segment BE. In distal stomach, prevalence of Hpyloriinfection was significantly higher in patients with IM than those without IM.CONCLUSION: There is a protective role of Hpyloriinfectuion to GERD. There may be no relationship between Hpylori infection of stomach and BE. Hpyloriinfection is associated with the development of IN in the distal stomach.     

Barrett＇s esophagus： Prevalence and risk factors in patients with chronic GERD in Upper Egypt

AIM： To determine the prevalence and possible risk factors of Barrett＇s esophagus （BE） in patients with chronic gastroesophageal reflux disease （GERD） in EI Minya and Assuit, Upper Egypt. METHODS： One thousand consecutive patients with chronic GERD symptoms were included in the study over 2 years. They were subjected to history taking including a questionnaire for GERD symptoms, clinical examination and upper digestive tract endoscopy. Endoscopic signs suggestive of columnar-lined esophagus （CLE） were defined as mucosal tongues or an upward shift of the squamocolumnar junction. BF was diagnosed by pathological examination when specialized intestinal metaplasia was detected histologically in suspected CLE. pH was monitored in 40 patients. RESULTS： BE was present in 7.3% of patients with chronic GERD symptoms, with a mean age of 48.3 ± 8.2 years, which was significantly higher than patients with GERD without BE （37.4 ± 13.6 years）. Adenocarcinoma was detected in eight cases （0.8%）, six of them in BE patients. There was no significant difference between patients with BE and GERD regarding sex, smoking, alcohol consumption or symptoms of GERD. Patients with BE had significantly longer esophageal acid exposure time in the supine position, measured by pH monitoring. CONCLUSION： The prevalence of BE in patients with GERD who were referred for endoscopy was 7.3%. BE seems to be associated with older age and more in patients with nocturnal gastroesophageal reflux.     

Relationship of gastric Helicobacter pylori infection to Barrett's esophagus and gastro-esophageal reflux disease in Chinese

AIM:To evaluate the relationship of Helicobacter pyloriinfection to reflux esophagitis (RE),Barrett's esophagus (BE)and gastric intestinal metaplasia (IM).METHODS:RE,BE and gastric IM were determined by upperendoscopy.Patients were divided into 2 groups;those withsquamocolumnar junction (SCJ) beyond gastroesophagealjunction (GFJ)≥3cm (group A),and those with SCJ beyondGEJ<3 cm (group B).Biopsy specimens were obtainedendoscopically from just below the SCJ,gastric antrum alongthe greater and lesser curvature.Pathological changes andH pylori infection were determined by HE staining,Alcianblue staining and Giemsa staining.RESULTS:The prevalence of H pylori infection was 46.93%.There was no difference in the prevalence between malesand females.The prevalence of H pylori infection decreasedstepwise significantly from RE grade Ⅰ to Ⅲ.There was nodifference in the prevalence between the two groups,andbetween long-segment and short-segment BE.In distalstomach,prevalence of H pylori infection was significantlyhigher in patients with IM than those without IM.CONCLUSION:There is a protective role of H pylori infectionto GERD.There may be no relationship between H pyloriinfection of stomach and BE.H pylori infection is associatedwith the development of IM in the distal stomach.     

Gastroesophageal reflux disease:From heartburn to cancer

About 10%-15% of patients with gastroesophageal reflux disease develop Barrett’s esophagus. This is considered a premalignant condition because it can progress from metaplasia to high-grade dysplasia, and eventually to adenocarcinoma. Recently, major advances have been made in the endoscopic treatment of Barrett’s esophagus, therefore limiting the role of surgery in the treatment of this disease.     

Prevalence of bile reflux in gastroesophageal reflux disease patients not responsive to proton pump inhibitors

AIM： To determine the prevalence and characteristics of bile reflux in gastroesophageal reflux disease （GERD） patients with persistent symptoms who are nonresponsive to medical therapy. METHODS： Sixty-five patients （40 male, 25 female; mean age, 50±7.8 years） who continued to report symptoms after 8 wk of high-dose proton pump inhibitor （PPI） therapy, as well as 18 patients with Barrett＇s esophagus, were studied. All patients filled out symptom questionnaires and underwent endoscopy, manometry and combined pH-metry and bilimetry. RESULTS： There were 4 groups of patients： 22 （26.5%） without esophagitis, 24 （28.9%） grade A-B esophagitis, 19 （22.8%） grade C-D and 18 （21.6%） Barrett＇s esophagus. Heartburn was present in 71 patients （85.5%） and regurgitation in 55 （66.2%）, with 44 （53%） reporting simultaneous heartburn and regurgitation. The prevalence of pathologic acid reflux in the groups without esophagitis and with grades A-B and C-D esophagitis was 45.4%, 66.6% and 73.6%, respectively. The prevalence of pathologic bilirubin exposure in these 3 groups was 53.3%, 75% and 78.9%, respectively. The overall prevalence of bile reflux in non-responsive patients was 68.7%. Pathologic acid and bile reflux was observed in 22.7% and 58.1% of non-esophagitic patients and esophagitic patients, respectively.CONCLUSION： The high percentage of patients poorly responsive to PPI therapy may result from poor control of duodenogastroesophageal reflux. Many patients without esophagitis have simultaneous acid and bile reflux, which increases with increasing esophagitis grade.     

Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in esophageal carcinogenesis

AIM： To investigate the role of glutathione S-transferase （GST） and matrix metalloproteinase-9 （MMP-9） expressions in the development and progression of reflux esophagitis-Barrett＇s meta plasia-dysplasia-adenocarcinoma sequence in the esophagus. METHODS： GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohistochemistry including patients with reflux esophagitis （n = 7）, Barrett＇s metaplasia （n = 14）, Barrett and esophagitis （n = 8）, Barrett and dysplasia （n = 7）, esophageal adenocarcinoma （n = 8） and a control group without any histological changes （n = 7）. Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of 〈 0.05 was considered significant. RESULTS： GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett＇s metaplasia and the other groups. No major changes were observed between Barrett, esophagitis, and Barrett and concomitant esophagitis. Barrett and concomitant dysplasia, and adenocarcinoma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated （r = - 0.82）. CONCLUSION： Decreased GST and increased expression of MMP-9 in Barrett＇s metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett with dysplasia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett＇s esophagus might be useful to identify patients at higher risk for progression to cancer.     

Comparison of reflux esophagitis and its complications between African Americans and non-Hispanic whites

AIM： To determine the effect of ethnicity on the severity of reflux esophagitis （RE） and its complications.
METHODS： A retrospective search of the endoscopy database at the University of Florida Health Science Center/Jacksonville for all cases of reflux esophagitis and its complications from January 1 to March 31, 2001 was performed. Inclusion criteria were endoscopic evi- dence of esophagitis using the LA classification, reflux related complications and self-reported ethnicity. The data obtained included esophagitis grade, presence of a hiatal hernia, esophageal ulcer stricture and Barrett＇s esophagus, and endoscopy indication.
RESULTS： The search identified 259 patients with RE or its complications, of which 171 were non-Hispanic whites and 88 were African Americans. The mean ages and male/female ratios were similar in the two groups. RE grade, esophageal ulcer, stricture and hiatal hernia frequency were likewise similar in the groups. Barrett＇s esophagus was present more often in non-Hispanic whites than in African Americans （15.8% vs 4.5%; P 〈 0.01）. Heartburn was a more frequent indication for endoscopy in non-Hispanic whites with erosive esophagitis than in African Americans （28.1% vs 7.9%; P 〈 0.001）.
CONCLUSION： Distribution of RE grade and frequency of reflux-related esophageal ulcer, stricture and hiatal hernia are similar in non-Hispanic whites and African Americans. Heartburn was more frequently and nausea/vomiting less frequently reported as the primary endoscopic indication in non-Hispanic whites compared with African Americans with erosive esopha- gitis or its complications. African Americans have a decreased prevalence of Barrett＇s esophagus compared with non-Hispanic whites.     

Pathophysiology and treatment of Barrett’s esophagus

Gastroesophageal reflux disease (GERD) affects an estimated 20% of the population in the United States. About 10%-15% of patients with GERD develop Barrett’s esophagus, which can progress to adenocarcinoma, currently the most prevalent type of esophageal cancer. The esophagus is normally lined by squamous mucosa, therefore, it is clear that for adenocarcinoma to develop, there must be a sequence of events that result in transformation of the normal squamous mucosa into columnar epithelium. This sequence begins with gastroesophageal reflux, and with continued injury metaplastic columnar epithelium develops. This article reviews the pathophysiology of Barrett’s esophagus and implications for its treatment. The effect of medical and surgical therapy of Barrett’s esophagus is compared.     

Risk factors associated with Barrett’s epithelial dysplasia

AIM:To elucidate risk factors associated with dysplasia of short-segment Barrett’s esophagus(BE).METHODS:A total of 151 BE patients who underwent endoscopic examination from 2004 to 2008 in Aoyama Hospital,Tokyo Women’s Medical University,Japan and whose diagnosis was confirmed from biopsy specimens were enrolled in the study.BE was diagnosed based on endoscopic findings of gastric-appearing mucosa or apparent columnar-lined esophagus proximal to the esophagogastric junction.Dysplasia was classified into three grades-mild,moderate and severe-according to the guidelines of the Vienna Classification System for gastrointestinal epithelial neoplasia.Anthropometric and biochemical data were analyzed to identify risk factors for BE dysplasia.The prevalence of Helicobacter pylori(H.pylori)infection and the expression of p53 by immunohistological staining were also investigated.RESULTS:Histological examination classified patients into three types:specialized columnar epithelium(SCE)(n=65);junctional(n=38);and gastric fundic(n =48).The incidence of dysplasia or adenocarcinoma from BE of the SCE type was significantly higher than that of the other two types(P<0.01).The univariate analysis revealed that sex,H.pylori infection,body weight,p53 overexpression,and low diastolic blood pressure(BP)were associated with BE dysplasia.In contrast,body mass index,waist circumference,metabolic syndrome complications,and variables related to glucose or lipid metabolism were not associated with dysplasia.Multivariate logistic analysis showed that overexpression of p53[odds ratio(OR)=13.1,P=0.004],H.pylori infection(OR=0.19,P=0.066),and diastolic BP(OR=0.87,P=0.021)were independent risk factors for epithelial dysplasia in BE patients with the SCE type.CONCLUSION:Overexpression of p53 is a risk factor for dysplasia of BE,however,H.pylori infection and diastolic BP inversely associated with BE dysplasia might be protective.     

食管末端及胃食管连接处的肠化生、异型增生和肿瘤发病情况

目的 了解我国人食管末端和胃－食管连接处的肠化生（IM）及异型增生和肿瘤的发病状况，齿状线（SCJ）位置和反流性食管炎（RE）的关系。方法 调查记录391例患者的症状，胃镜下RE的表现，并根据SCJ的位置分为3组，其中，胃镜下见齿状线上移≥3cm为A组，＜3cm为B组，齿状线和GEJ同一水平的为C组。每例患者均于齿状线远端活检送病理检查。结果 A，B，C，3组IM发生率分别为26.53%,33.85%,34.00%;IM的发生在40岁以后随着年龄增长逐渐增加，男女之间无差异；361例患者中共诊断异型增生12例（轻度7例，中重度5例），贲门癌16例，食管腺癌1例；A，B，C3组RE的发病率分别为57．14％，22．83％，12．00％。结论 1．胃镜下提示为LSBE，SSBE和GEJ三组间的IM发生率无显著差异；2．应重视食管末端及胃－食管连接处异型增生的诊断；3．贲门癌发病远高于食管腺癌。     

Intestinal metaplasia at the gastroesophageal junction is associated with gastroesophageal reflux but not with Helicobacter pylori infection

Abstract

Objective: Studies of the etiology of intestinal metaplasia (IM) at a normal appearing gastroesophageal junction (GEJ) are conflicting as associations with both H. Pylori (HP) infection and gastroesophageal reflux has been reported. The aim of this study was to investigate whether IM at the GEJ is associated with gastroesophageal reflux or HP infection.

Material and methods: Fifty asymptomatic volunteers and 149 patients with reflux symptoms underwent endoscopy with biopsies obtained from the gastric antrum and the squamocolumnar junction (SCJ). All subjects underwent wireless 48?h pH monitoring with the electrode placed immediately above the SCJ and a fecal antigen test for HP infection. Clinical characteristics and the pattern of reflux were compared in subjects with and without IM.

Results: Three asymptomatic volunteers and 35 patients who had clearly irregular SCJs with short extensions of columnar mucosa were excluded from the study. In the remaining 47 asymptomatic volunteers and 114 patients, variables that reached a significance level of 0.1 or less on univariate analyses were used in a binomial regression analysis to assess their relative importance for the finding of IM. IM at the GEJ was significantly associated with abnormal distal esophageal acid exposure (5.5 (1.2–24.6), p?=?.026), the frequency of reflux episodes/hour (1.5 (1.1–2.2), p?=?.031), and an endoscopic appearance of the SCJ corresponding to ZAP grade I (4.6 (1.4–15.6), p?=?.013). There was no association with HP infection.

Conclusion: The finding of IM at an endoscopically normal-appearing GEJ is associated with gastroesophageal reflux but not with HP infection.     

Prevalence of Barrett's esophagus by endoscopy and histologic studies: a prospective evaluation of 306 control subjects and 376 patients with symptoms of gastroesophageal reflux

The classic endoscopic diagnosis of a Barrett's esophagus (BE) is based on the finding of > or =3 cm, of distal esophagus covered by specialized columnar epithelium. However, currently, it is based on the finding of intestinal metaplasia (IM) at the squamous-columnar mucosal junction, independent of its extent. The aim of this study was to determine the prevalence of Barrett's esophagus by endoscopic and histological findings in control subjects and in patients with symptoms of gastroesophageal reflux (GER). Three hundred and six control subjects and 376 patients with symptoms of gastroesophageal reflux were included in this prospective study. Patients with Barrett's esophagus were classified in three groups as follows. 1. Intestinal metaplasia at the cardia. When endoscopy showed non-Barrett's esophagus, but histological intestinal metaplasia was found. 2. Short-segment Barrett's esophagus. When <3 cm, was covered with tongues or finger-like or creeping substitution of distal esophagus. 3. Long-segment Barrett's esophagus. When > 3 cm, of distal esophagus was covered by specialized columnar epithelium. Two biopsies at the antrum, four biopsies at the squamous-columnar junction and one or two at the distal esophagus were taken. In control subjects, 1.6% showed histological IM at the esophagogastric junction. In patients with GER without esophagitis or with erosive esophagitis, IM was found in 18% and 10.7% respectively. 'Short-segment' Barrett's esophagus was three times more frequent than 'long-segment' Barrett's esophagus. Patients with Barrett's esophagus were significantly older than the other groups. The presence of complications or erosions, peptic ulcer or stricture were significantly more frequent among patients with 'long-segment' Barrett's esophagus (p < 0.0001). The prevalence of dysplasia was similar in all groups of patients with Barrett's esophagus. Complications such as ulcers, stricture and dysplasia were exclusively seen among patients with BE, whereas non-Barrett's patients did not exhibit these complications. In control subjects, IM can be found in a low percentage of cases. Among patients with symptoms of GER, the classic endoscopic diagnosis of a Barrett's esophagus can underestimate this condition in 80% of the cases. Patients with intestinal metaplasia at the cardia already present 17% of the cases with low-grade dysplasia. In all patients with symptoms of GER, systematic biopsies at the squamous-columnar junction should be taken.     

Colonization with cagA-positive Helicobacter pylori strains in intestinal metaplasia of the esophagus and the esophagogastric junction

OBJECTIVES: Recent studies indicate that colonization with cagA-positive Helicobacter pylori (H. pylori) strains may protect against gastroesophageal reflux disease (GERD) and its complications, but the role of cagA in the etiology of Barrett's esophagus has so far been poorly investigated. The pathogenesis of intestinal metaplasia (IM) at an endoscopically normal esophagogastric junction (EGJ) is still unclear, and the role of the H. pylori virulence factor cagA in it has not been investigated. The aim of our study was to assess the relationship between H. pylori and cagA-positive H. pylori in particular and IM at an endoscopically normal EGJ and Barrett's esophagus. METHODS: Serum samples were obtained from 62 patients without IM, 43 patients with IM at an endoscopically normal junction, and 51 patients with Barrett's esophagus. IM was defined as presence of goblet cells with positive staining with Alcian blue. The prevalence of H. pylori and cagA was investigated by assessment of IgG antibody levels as determined by ELISA. RESULTS: The overall H. pylori prevalence was 59% (92/156), and the cagA prevalence was 29% (46/156). Although 63% (39/62) of IM negative subjects and 74% (32/43) of those with IM at the junction were H. pylori positive, only 41% (21/51) of Barrett's patients tested positive. The differences between the IM negative and the Barrett's group (p = 0.02) and between IM at the junction and Barrett's were significant (p = 0.002). The relative cagA prevalence (percentage with cagA positivity and H. pylori positivity) was 56% (22/39) in patients who were IM negative, 59% (19/32) in those with IM at the junction, and 24% (5/21) in those with Barrett's. The prevalence of anti-CagA was significantly lower in patients with Barrett's esophagus compared with patients who were IM negative (p = 0.002) and those who had IM at the junction (p < 0.001). No difference in cagA prevalence was seen between the latter groups. CONCLUSIONS: These findings are in line with the concept that H. pylori and cagA-positive strains in particular protect against the development of Barrett's esophagus. In contrast, our findings do not support the theory that IM at an endoscopically normal esophagogastric junction is associated with H. pylori or cagA-positive strains. IM at the junction and Barrett's esophagus seem to have different etiologies.     

Prospective evaluation of the prevalence of gastric Helicobacter pylori infection in patients with GERD, Barrett's esophagus, Barrett's dysplasia, and Barrett's adenocarcinoma

OBJECTIVE: This study was undertaken to prospectively determine the prevalence of gastric H. pylori infection in Barrett's esophagus and Barrett's complicated by dysplasia or adenocarcinoma. METHODS: The prevalence of H. pylori was determined in Barrett's esophagus patients compared to a control population of patients with gastroesophageal reflux disease (GERD) only. All patients had a minimum of 10 gastric surveillance biopsies obtained. H. pylori colonization was determined upon the basis of hematoxylin and eosin and use of a modified Giemsa and or Steiner's silver stain of all gastric biopsy specimens. RESULTS: Two hundred and eighty-nine Barrett's patients and 217 GERD control patients were included in the study. H. pylori was found in 95/289 (32.9%) of the Barrett's patients, compared with 96/217 (44.2%) of the GERD controls (NS). Forty-seven of the Barrett's patients had low-grade dysplasia/indefinite dysplasia, 14 high-grade dysplasia, and 20 Barrett's adenocarcinoma. When Barrett's was subgrouped according to absence of dysplasia, and presence of low-grade dysplasia, high-grade dysplasia, or adenocarcinoma, H. pylori prevalence was found to be significantly less for patients with Barrett's high-grade dysplasia (14.3%) and adenocarcinoma (15.0%) versus patients with GERD alone (44.2%), Barrett's alone (35.1%), or Barrett's with low-grade dysplasia (36.2%) (p = 0.016). This difference could not be explained by differences between Barrett's esophagus patients infected with H. pylori and those who were not with respect to gender, smoking history, alcohol consumption, use of proton pump inhibitor, or length of Barrett's mucosa. CONCLUSIONS: Barrett's high-grade dysplasia and adenocarcinoma are significantly more prevalent in patients who are not infected with H. pylori. H. pylori appears to have a protective effect against the development of Barrett's adenocarcinoma.     

Barrett's esophagus and risk of esophageal adenocarcinoma

Barrett's esophagus is most often seen in white men with chronic heartburn who are generally older than 50 years of age. The prevalence of Barrett's esophagus is 10% to 15% in patients who are undergoing endosocopy for gastroesophageal reflux disease and 1% to 2% in asymptomatic American adults. Barrett's esophagus represents metaplastic columnar tissue with specialized intestinal metaplasia, and this condition carries an increased risk of esophageal adenocarcinoma. Patients with Barrett's esophagus have a risk of esophageal adenocarcinoma 30 to 60 times that of the general population with an incidence rate of over 100 times that of the general population. Esophageal adenocarcinoma has increased dramatically over the past few decades with specialized intestinal metaplasia being the most important risk factor for the development of dysplasia and cancer. Barrett's esophagus develops in the presence of persistent gastroesophageal reflux, which is an independent risk factor for adenocarcinoma. Other risk factors for adenocarcinoma in patients with Barrett's esophagus include length of Barrett's epithelium, low-grade dysplasia, and high-grade dysplasia. New data concerning the pathophysiology and biology of Barrett's epithelium may provide answers to prevent or treat esophageal cancer. This article briefly reviews Barrett's esophagus and focuses on the risk factors associated with its progression to adenocarcinoma.     

Hiatal hernia size,Barrett's length,and severity of acid reflux are all risk factors for esophageal adenocarcinoma

OBJECTIVE: The reasons for the development of dysplasia and adenocarcinoma in Barrett's mucosa are not well understood. The aims of this study were to characterize risk factors for the transition from Barrett's esophagus without dysplasia to Barrett's esophagus with high-grade dysplasia or esophageal adenocarcinoma. METHODS: A group of 131 patients with high-grade dysplasia or esophageal adenocarcinoma were selected as case subjects. A first population of 2170 patients without gastroesophageal reflux disease (GERD) and a second population of 1189 patients with Barrett's esophagus served as two control groups. Logistic regression analyses were used to compare the risk factors associated with the occurrence of high-grade dysplasia or esophageal adenocarcinoma. RESULTS: Patients with high-grade dysplasia or esophageal adenocarcinoma shared many characteristics with other forms of severe GERD, such as older age, male gender, and white ethnicity. The length of Barrett's esophagus and the size of hiatus hernia increased the risk for both conditions. Subjects with high-grade dysplasia and adenocarcinoma had more severe acid reflux than patients with other forms of GERD. Smoking and alcohol consumption did not affect the risk for developing high-grade dysplasia or adenocarcinoma in patients with Barrett's esophagus. CONCLUSIONS: High-grade dysplasia and esophageal adenocarcinoma seem to stem from an extreme and unfavorable constellation of all risk factors that are generally held responsible for the development of GERD and Barrett's esophagus.     

Role of nitric oxide in the pathogenesis of Barrett's-associated carcinogenesis

Barrett's esophagus(BE), a premalignant condition to Barrett's adenocarcinoma(BAC), is closely associated with chronic inflammation due to gastro-esophageal reflux. Caudal type homeobox 2(CDX2), a representative marker of BE, is increased during the metaplastic and neoplastic transformation of BE. Nitric oxide(NO) has been proposed to be a crucial mediator of Barrett's carcinogenesis. We previously demonstrated that CDX2 might be induced directly under stimulation of large amounts of NO generated around the gastroesophageal junction(GEJ) by activating epithelial growth factor receptor in a ligand-independent manner. Thus, we reviewed recent developments on the role of NO in Barrett's carcinogenesis. Notably, recent studies have reported that microbial communities in the distal esophagus are significantly different among groups with a normal esophagus, reflux esophagitis, BE or BAC, despite there being no difference in the bacterial quantity. Considering that microorganism components can be one of the major sources of large amounts of NO, these studies suggest that the bacterial composition in the distal esophagus might play an important role in regulating NO production during the carcinogenic process. Controlling an inflammatory reaction due to gastro-esophageal reflux or bacterial composition around the GEJ might help prevent the progression of Barrett's carcinogenesis by inhibiting NO production.     

Adenocarcinoma of the esophagogastric junction: could the characteristics of adjacent intestinal metaplasia help in the understanding of biopathogenesis?

We report a case of early adenocarcinoma arising in foci of intestinal metaplasia (IM) at a normal-appearing gastroesophageal junction (GEJ). The tumor infiltrated the submucosa without nodal involvement (T1N0). Non-neoplastic mucosa adjacent to neoplasia had foci of incomplete IM with a band-like CK20 positivity of the surface epithelium and a diffuse CK7 staining of both superficial and deep glands. There were histological features of reflux esophagitis as well as chronic non-atrophic, Helicobacter pylori-related pangastritis, without IM, at the extensively assessed gastric mucosa. In this case, the CK7/20 pattern of IM adjacent to neoplasia, the demonstration of reflux esophagitis, and the absence of IM in the stomach favor the theory that the pathogenesis of IM and associated adenocarcinoma of the GEJ is related to gastroesophageal reflux rather than H. pylori infection.