Barrett's Esophagus Length Research Articles

Value of α‐methylacyl‐CoA racemase immunochemistry for predicting neoplastic progression in Barrett's oesophagus

To investigate the value of α-methylacyl-CoA racemase (AMACR) immunohistochemistry for predicting neoplastic progression in Barrett's oesophagus (BO). We conducted a case-control study within a prospective cohort of 720 BO patients. Patients who developed high-grade dysplasia or oesophageal adenocarcinoma were classified as cases, and patients without neoplastic progression as controls. AMACR expression was determined by immunohistochemistry in 12 127 biopsies from 635 patients, and was scored independently by two expert pathologists. Relative risks adjusted for age, gender, BO length and oesophagitis (RR(a)) were calculated in log-linear models. During a median follow-up of 6.6 years, 49 patients (8%) developed high-grade dysplasia or oesophageal adenocarcinoma. Although mild AMACR expression was associated with a trend towards an increased risk of neoplastic progression (RR(a) 1.6, 95% CI 0.9-3.1), the risk was especially elevated with strong AMACR expression (RR(a) 4.8, 95% CI 1.9-12.6). The positive predictive value of strong AMACR expression was slightly higher than that of low-grade dysplasia (22% versus 15%); the negative predictive value was slightly lower (91% versus 93%). Strong AMACR expression is associated with an increased risk of neoplastic progression in BO. However, AMACR expression appears to be a less powerful predictor for neoplastic progression than low-grade dysplasia.

Survival in esophageal high-grade dysplasia/adenocarcinoma post endoscopic resection

Endoscopic resection followed by ablative therapy is frequently used to treat esophageal high-grade dysplasia or early esophageal adenocarcinoma. To study outcomes in patients with high-grade dysplasia compared to those with esophageal adenocarcinoma after endoscopic resection. Retrospective, observational, descriptive, single-centre study from a prospective database. We extracted data from 116 endoscopic resections. Survival was plotted using Kaplan-Meier curves multivariable Cox-proportional hazard assess for possible predictors of survival post-endoscopic resection was performed. 116 patients (64 esophageal adenocarcinoma, 52 high-grade dysplasia) underwent endoscopic resection from May 2003 to June 2010. Mean age was 71 ± 11 years for high-grade dysplasia and 72 ± 10 years for esophageal adenocarcinoma. Median follow-up was 17 months. Eighty-five patients had negative margins on endoscopic resection. Five-year survivals for high-grade dysplasia and esophageal adenocarcinoma were 86% (range 68-100%) and 78% (59-96%), respectively. Survival was not significantly different between groups (p=0.20). Overall mortality rate was 10.6% (9/85). At multivariable Cox regression increased Barrett's oesophagus length was associated with worse survival (HR 1.18 [1.06-1.33], p=0.0039). Survival was not affected by the pathology before resection: HR 2.4 [95%CI, 0.70-8.4], p=0.16. Survival in patients with high-grade dysplasia of the oesophagus is similar to those with esophageal adenocarcinoma. Longer Barrett's oesophagus segments are associated with decreased survival.

PTH-053 High Definition (HD) Versus Standard Definition (SD) White Light Endoscopy for Detecting Early Neoplasia (EN) in Barrett’S Oesophagus (BO) During Surveillance Endoscopy. is It Time to Change the Standard of Care?

IntroductionHD endoscopy systems provide superior image resolution. However, the utility of this new and more expensive technology in lesion detection has not been evaluated so far.Our aim was to assess...

PTU-156 The Combination of Autofluorescence Imaging and Probe-Based Confocal Laser Endomicroscopy has an Excellent Diagnostic Accuracy for Dysplasia in Barrett’S Esophagus

IntroductionEndoscopic surveillance in Barrett’s oesophagus (BO) has major limitations including sampling error due to inconspicuous dysplasia, need for multiple biopsies and subjectivity of pathological assessment of dysplasia. Probe-based confocal laser...

Impact of Endoscopic Surveillance on Mortality From Barrett's Esophagus–Associated Esophageal Adenocarcinomas

Although patients with Barrett's esophagus commonly undergo endoscopic surveillance, its effectiveness in reducing mortality from esophageal/gastroesophageal junction adenocarcinomas has not been evaluated rigorously. We performed a case-control study in a community-based setting. Among 8272 members with Barrett's esophagus, we identified 351 esophageal adenocarcinoma: 70 in persons who had a prior diagnosis of Barrett's esophagus (who were eligible for surveillance); 51 of these patients died, 38 as a result of the cancers (cases). Surveillance histories were contrasted with a sample of 101 living persons with Barrett's esophagus (controls), matched for age, sex, and duration of follow-up evaluation. Surveillance within 3 years was not associated with a decreased risk of death from esophageal adenocarcinoma (adjusted odds ratio, 0.99; 95% confidence interval, 0.36-2.75). Fatal cases were nearly as likely to have received surveillance (55.3%) as were controls (60.4%). A Barrett's esophagus length longer than 3 cm and prior dysplasia each were associated with subsequent mortality, but adjustment for these did not change the main findings. Although all patients should be included in evaluations of effectiveness, excluding deaths related to cancer treatment and patients who failed to complete treatment, changed the magnitude, but not the significance, of the association (odds ratio, 0.46; 95% confidence interval, 0.13-1.64). Endoscopic surveillance of patients with Barrett's esophagus was not associated with a substantially decreased risk of death from esophageal adenocarcinoma. The results do not exclude a small to moderate benefit. However, if such a benefit exists, our findings indicate that it is substantially smaller than currently estimated. The effectiveness of surveillance was influenced partially by the acceptability of existing treatments and the occurrence of treatment-associated mortality.

Mo1894 Barrett's Esophagus Length Is Determined At the Time of Initial Development and Does Not Change Over Time: Results From a Large Multicenter Cohort

Mo1894 Barrett's Esophagus Length Is Determined At the Time of Initial Development and Does Not Change Over Time: Results From a Large Multicenter Cohort

Mo1897 GORD Symptoms and Demographic Factors As a Pre-Screening Tool for Barrett's Oesophagus

Introduction Barrett’s oesophagus (BO) occurs as consequence of reflux and is a risk factor for oesophageal adenocarcinoma (OAC). The current “gold-standard” for diagnosing BO is endoscopy which remains prohibitively expensive and impractical as a population screening tool. Therefore, we aimed to investigate the epidemiological factors and symptoms associated with BO in order to develop a pre-screening tool to aid decision making for diagnostic referrals. Methods A prospective (training) cohort of 1603 patients attending for gastroscopy was used for identification of risk factors to develop a risk prediction model. Factors significantly associated with BO in the univariate analysis were selected to develop a prediction model that was validated in an independent, external cohort of 504 patients in primary care. We used two definitions of BO in the current study: 1) columnar lined epithelium of oesophagus (CLE) of any length reported in the endoscopy report with columnar epithelium on biopsy 2) an intestinal metaplasia confirmed on histopathological assessment with endoscopic length of BO ≥2 cm (IM ≥ 2 cm). Results An eight-factor panel, including age, sex, smoking status, heartburn, acid reflux, chest pain, abdominal pain, anti-reflux medication, was identified from the training cohort with an area under the ROC curve (AUC) of 0.74 (95%CI: 0.70–0.77) for CLE, and 0.80 (95% CI: 0.75–0.84) for IM ≥ 2cm. This panel was significantly associated with BO in the external cohort, and the odds ratios for each factor increase were 1.43 (95%CI: 1.02–2.01) and 1.30 (95%CI: 1.04–1.62) for CLE and IM ≥ 2cm, respectively. The AUCs of the 8-factor panel for CLE and IM ≥ 2cm in the external cohorts were 0.85 (95%CI: 0.77–0.92) and 0.78 (95%CI: 0.71–0.84), respectively. After controlling for over-fitting, the AUCs dropped to 0.65 (95% CI: 0.54–0.77) and 0.67 (95%CI: 0.60–0.74), respectively. Conclusion An eight-factor panel can help predict the presence of BO and has the potential to be applied in the general population with GORD symptoms as a pre-screening tool to help select patients for further investigation. Disclosure of Interest None Declared.

Endotherapy for superficial adenocarcinoma of the esophagus: an American experience

EMR and ablation are increasingly being used alone or in combination for treatment of Barrett's neoplasia. Given a very low rate of lymph node metastasis, endotherapy has become an accepted treatment option for T1a esophageal adenocarcinoma (EAC) with low-risk features. To report our experience of endoscopic management of T1a EAC in a large, tertiary-care center. Retrospective review. Tertiary-care referral center. Patients treated endoscopically for low-risk T1a EAC at our center. EMR and endoscopic ablation. Death related to esophageal cancer, remission of adenocarcinoma, dysplasia, and intestinal metaplasia. A total of 54 patients underwent endotherapy for low-risk T1a EAC from 2006 to 2012. Mean (± SD) follow-up was 23 (± 16) months, mean (± SD) size of resected adenocarcinoma was 7.1 (± 4.3) mm, and mean (± SD) Barrett's esophagus length was 4.5 (± 3.9) cm. Band-assisted, cap-assisted, and lift and cut EMR were performed in 85%, 11%, and 4% of patients, respectively; 81% underwent additional ablative therapy (radiofrequency ablation 95%, cryotherapy 9%, photodynamic therapy 2%). Complete remission from cancer was achieved in 96%, complete remission from dysplasia in 87%, and complete remission from intestinal metaplasia in 59%. The overall survival was 89%; there were no deaths related to esophageal cancer. Retrospective study. Endotherapy for T1a EAC was safe and effective in our American cohort. Endotherapy should be considered primary therapy for appropriate patients with low-risk lesions. Complete Barrett's esophagus eradication after EMR is important to reduce the development of metachronous lesions.

PTU-172 Oesophageal cancer risk: results of a prospective cohort with Barrett's oesophagus

IntroductionWidely varying rates of oesophageal adenocarcinoma (OAC) in patients with Barrett's oesophagus (BO) have been reported, with recent studies and meta-analyses suggesting a lower incidence, affecting the cost effectiveness of...

Covering the Cover

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Relationship Between Barrett's Esophagus (BE) Length and the Risk of High Grade Dysplasia (HGD) and Esophageal Adenocarcinoma (EAC) in Patients With Non Dysplastic Barrett's Esophagus Results From a Large Multicenter Cohort

Relationship Between Barrett's Esophagus (BE) Length and the Risk of High Grade Dysplasia (HGD) and Esophageal Adenocarcinoma (EAC) in Patients With Non Dysplastic Barrett's Esophagus Results From a Large Multicenter Cohort

A randomised controlled trial of ALA versus photofrin PDT for high grade dysplasia in barrett's oesophagus

IntroductionSodium porfimer photodynamic therapy (sp-PDT) is a licensed minimally invasive treatment for Barrett's Oesophagus (BO) with high grade dysplasia (HGD). Complete reversal (CR)-HGD is 50% at 5 years. sp-PDT is...

The prague C & M criteria for grading barrett's oesophagus: a live endoscopy evaluation of observer agreement

IntroductionTo validate the Prague C and M criteria for the endoscopic diagnosis and grading of Barrett's oesophagus (BO) in a real-time clinical setting between two experienced endoscopists in a University...

MicroRNA-196a & microRNA-101 expression in Barrett's oesophagus in patients with medically and surgically treated gastro-oesophageal reflux

BackgroundProton pump inhibitor (PPI) medication and surgical fundoplication are used for the control of gastro-oesophageal reflux in patients with Barrett's oesophagus, but differ in their effectiveness for both acid and bile reflux. This might impact on the inflammatory processes that are associated with progression of Barrett's oesophagus to cancer, and this may be evident in the gene expression profile and microRNA expression pattern in Barrett's oesophagus mucosa. We hypothesised that two miRNAs with inflammatory and oncogenic roles, miR-101 and miR-196a, are differentially expressed in Barrett's oesophagus epithelium in patients with reflux treated medically vs. surgically.FindingsMucosal tissue was obtained at endoscopy from patients with Barrett's oesophagus whose reflux was controlled by proton pump inhibitor (PPI) therapy (n = 20) or by fundoplication (n = 19). RNA was extracted and the expression of miR-101 and miR-196a was measured using real-time reverse transcription - polymerase chain reaction. There were no significant differences in miR-101 and miR-196a expression in Barrett's oesophagus epithelium in patients treated by PPI vs. fundoplication (p = 0.768 and 0.211 respectively). Secondary analysis showed a correlation between miR-196a expression and Barrett's oesophagus segment length (p = 0.014).ConclusionThe method of reflux treatment did not influence the expression of miR-101 and miR-196a in Barrett's oesophagus. This data does not provide support to the hypothesis that surgical treatment of reflux better prevents cancer development in Barrett's oesophagus. The association between miR-196a expression and Barrett's oesophagus length is consistent with a tumour promoting role for miR-196a in Barrett's oesophagus.

The Effect of Long-term Control of Reflux by Fundoplication on Aberrant Deoxyribonucleic Acid Methylation in Patients With Barrett Esophagus

We investigated the relationship between reflux and aberrant deoxyribonucleic acid (DNA) methylation, comparing methylation in the columnar epithelium following successful fundoplication to that in subjects with a failed fundoplication. Gastroesophageal reflux is the main risk factor for Barrett esophagus and adenocarcinoma. In these diseases, there is a high level of DNA methylation. We enrolled 41 patients with Barrett esophagus and a fundoplication at least 5 years earlier for a 24-hour pH study, endoscopy, and collection of biopsies. Biopsies were obtained from 17 Barrett esophagus subjects who had not undergone esophageal surgery. At the time of the study, 31 subjects were pH normal, 10 abnormal. Columnar biopsies were collected from 21 of the pH normal and 9 pH abnormal subjects, and all no surgery subjects. Complete regression of columnar mucosa was seen in 7 subjects with pH normal and 1 with pH abnormal. The length of Barrett esophagus did not differ between groups preoperatively, but was significantly less at the time of the study in the pH normal compared with pH abnormal or no surgery groups. Significantly, fewer genes were methylated in the pH normal than the pH abnormal or no surgery groups, which did not differ from each other. The number of methylated genes correlated with increased reflux, intestinal metaplasia, and increased columnar-lined esophagus length, but not acid-suppression medication. Fundoplication that reduces reflux to normal levels can lead to regression of the columnar mucosa. Reflux is associated with aberrant DNA methylation, and control of reflux reduces deleterious genomic changes associated with cancer.

Long-term proton pump induced hypergastrinaemia does induce lineage-specific restitution but not clonal expansion in benign Barrett's oesophagus in vivo

BackgroundBarrett's oesophagus is a common premalignant lesion caused partly by acid reflux. Although the requisite therapy, proton pump inhibitors (PPIs), have been implicated in the progression of Barrett's oesophagus in...

Patient predictors of histopathologic response after photodynamic therapy of Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma

Photodynamic therapy (PDT) has been used extensively for endoscopic ablation of Barrett's esophagus with high-grade dysplasia (HGD) or intramucosal carcinoma. To identify patient variables that influence the likelihood of response to PDT. A retrospective cohort study. Tertiary-referral center. A total of 116 patients with Barrett's esophagus and with HGD, intramucosal carcinoma, or T1 cancer. PDT with porfimer sodium. (1) Ablation of HGD and/or intramucosal carcinoma and (2) eradication of all Barrett's epithelium. Of the patients, 51% underwent treatment for HGD and 49% of patients had intramucosal carcinoma or T1 cancer. At 12-month follow-up, ablation of HGD and/or cancer was observed in 70% of patients, and ablation of all Barrett's epithelium was observed in 39%. In multivariate analysis, the pretreatment length of Barrett's esophagus was inversely correlated with successful ablation of all Barrett's epithelium. Patients with Barrett's esophagus length more than 3 cm were less likely to experience complete ablation compared with patients with Barrett's esophagus length 3 cm or less (odds ratio [OR] 0.15 [95% CI, 0.04-0.50]). Patients with intramucosal carcinoma were not significantly less likely to experience elimination of HGD and/or cancer (OR 0.77 [95% CI, 0.30-2.00]) or ablation of all Barrett's epithelium (OR 0.82 [95% CI, 0.32-2.07]) compared with patients with HGD alone. Retrospective study, limited sample size without a control group for comparison. PDT of Barrett's esophagus with HGD, intramucosal carcinoma, or T1 cancer can result in ablation of dysplasia and/or eradication of all Barrett's epithelium. Factors associated with the likelihood of response include length of Barrett's esophagus. The presence of intramucosal carcinoma or T1 cancer was not associated with higher likelihood of treatment failure.

Barrett Esophagus

Obesity is a risk factor for esophageal adenocarcinoma, with a pathway through inflammation and metaplasia secondary to reflux the dominant hypothesis. The proinflammatory impact of adipocytokines associated with the metabolic syndrome of central adiposity may also be relevant. The objective of this study was to explore this profile in Barrett esophagus. Patients with specialized intestinal metaplasia were invited to attend the metabolic syndrome screening where they underwent anthropometry, segmental bioelectrical impedance analysis, and blood pressure measurement, and had blood taken for quantification of fasting lipids, insulin, glucose, C-reactive protein, and adipocytokines. One hundred two patients were studied. Forty-six percent of Barrett patients had metabolic syndrome and 78% were centrally obese. Patients with metabolic syndrome were significantly more obese by body mass index, had a 9.4 cm greater waistline, were more hypertensive, and were insulin resistant with 25% having fasting hyperinsulinemia compared with Barrett patients without metabolic syndrome. Metabolic syndrome was associated with elevated C-reactive protein, leptin, and a trend toward decreased adiponectin levels. Sixty percent of patients with long-segment Barrett had metabolic syndrome, and 92% were centrally obese compared with 23.8% and 62%, respectively (P = 0.007 and 0.005) in short-segment Barrett. Long-segment Barrett was associated with hyperinsulinemia and significantly increased levels of interleukin-6 compared with short-segment Barrett. The prevalence of metabolic syndrome in Barrett far exceeds population norms, and the syndrome was significantly associated with the length of specialized intestinal metaplasia. The data do suggest that the metabolic syndrome may be relevant to the continuum of metaplasia within the Barrett cohort.

Gene Expression Profiling Reveals Stromal Genes Expressed in Common Between Barrett’s Esophagus and Adenocarcinoma

Barrett's esophagus is a precursor of esophageal adenocarcinoma. DNA microarrays that enable a genome-wide assessment of gene expression enhance the identification of specific genes as well as gene expression patterns that are expressed by Barrett's esophagus and adenocarcinoma compared with normal tissues. Barrett's esophagus length has also been identified as a risk factor for progression to adenocarcinoma, but whether there are intrinsic biological differences between short-segment and long-segment Barrett's esophagus can be explored with microarrays. Gene expression profiles for endoscopically obtained biopsy specimens of Barrett's esophagus or esophageal adenocarcinoma and associated normal esophagus and duodenum were identified for 17 patients using DNA microarrays. Unsupervised and supervised approaches for data analysis defined similarities and differences between the tissues as well as correlations with clinical phenotypes. Each tissue displays a unique expression profile that distinguishes it from others. Barrett's esophagus and esophageal adenocarcinoma express a unique set of stromal genes that is distinct from normal tissues but similar to other cancers. Adenocarcinoma also showed lower and higher expression for many genes compared with Barrett's esophagus. No difference in gene expression was found between short-segment and long-segment Barrett's esophagus. The genome-wide assessment provided by current DNA microarrays reveals many candidate genes and patterns not previously identified. Stromal gene expression in Barrett's esophagus and adenocarcinoma is similar, indicating that these changes precede malignant transformation.

Short segment Barrett's esophagus and distal gastric intestinal metaplasia

Short segment Barrett's esophagus is defined by the presence of <3 cm of columnar-appearing mucosa in the distal esophagus with intestinal metaplasia on histophatological examination. Barrett's esophagus is a risk factor to develop adenocarcinoma of the esophagus. While Barrett's esophagus develops as a result of chronic gastroesophageal reflux disease, intestinal metaplasia in the gastric cardia is a consequence of chronic Helicobacter pylori infection and is associated with distal gastric intestinal metaplasia. It can be difficult to determine whether short-segment columnar epithelium with intestinal metaplasia are lining the esophagus (a condition called short segment Barrett's esophagus) or the proximal stomach (a condition called intestinal metaplasia of the gastric cardia). To study the association of short segment Barrett's esophagus (length <3 cm) with gastric intestinal metaplasia (antrum or body) and infection by H. pylori. Eight-nine patients with short segment columnar-appearing mucosa in the esophagus, length <3 cm, were studied. Symptoms of gastroesophageal reflux disease were recorded. Biopsies were obtained immediately below the squamous-columnar lining, from gastric antrum and gastric corpus for investigation of intestinal metaplasia and H. pylori. Forty-two from 89 (47.2%) patients were diagnosed with esophageal intestinal metaplasia by histopathology. The mean-age was significantly higher in the group with esophageal intestinal metaplasia. The two groups were similar in terms of gender (male: female), gastroesophageal reflux disease symptoms and H. pylori infection. Gastric intestinal metaplasia (antrum or body) was diagnosed in 21 from 42 (50.0%) patients in the group with esophageal intestinal metaplasia and 7 from 47 (14.9%) patients in the group with esophageal columnar appearing mucosa but without intestinal metaplasia. Intestinal metaplasia is a frequent finding in patients with <3 cm of columnar-appearing mucosa in the distal esophagus. In the present study, short segment intestinal metaplasia in the esophagus is associated with distal gastric intestinal metaplasia. Gastroesophageal reflux disease symptoms and H. pylori infection did not differ among the two groups studied.