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The z-line refers to the squamocolumnar junction which marks the transition between the normal stratified squamous epithelium of the distal esophagus and the columnar epithelium of the gastric cardia. An "irregular" z-line refers to an irregular appearing squamocolumnar junction characterized by the presence of columnar mucosa less than 1 cm in length that extends above the gastroesophageal junction. In contrast, Barrett's esophagus is diagnosed when columnar mucosa of at least 1 cm is seen in the distal esophagus extending above the gastroesophageal junction with biopsies demonstrating specialized intestinal metaplasia. Current guidelines recommend against taking routine biopsies from a normal or irregular z-line in the absence of visible abnormalities and advise against endoscopic surveillance in this patient population, in large part due to multiple studies demonstrating lack of progression to advanced neoplasia such as high-grade dysplasia or esophageal adenocarcinoma in patients with an irregular z-line. Despite these recommendations, a sizable number of patients without Barrett's esophagus undergo biopsies from the z-line and are subsequently recommended to have surveillance endoscopies. Furthermore, patients with an irregular z-line are often mislabelled as Barrett's esophagus resulting in significant downstream consequences including higher healthcare costs and reduced health-related quality of life. In this review, we highlight the importance of landmark identification of the distal esophagus and gastroesophageal junction at the time of endoscopy, share recommendations from current guidelines related to the z-line, examine rates of neoplastic progression in those with an irregular z-line, discuss consequences of routinely biopsying an irregular z-line, and highlight strategies on how to approach an irregular z-line if seen on endoscopy. A careful, high-quality endoscopic examination can help to identify visible abnormalities at the z-line, which, if present, should be targeted for biopsies to rule out dysplasia and neoplasia. [ABSTRACT FROM AUTHOR]

Background: Limited data are available on the epidemiology of gastroesophageal junction adenocarcinoma (GEJAC), particularly in comparison to esophageal adenocarcinoma (EAC). With the advent of molecular non-endoscopic Barrett's esophagus (BE) detection tests which sample the esophagus and gastroesophageal junction, early detection of EAC and GEJAC has become a possibility and their epidemiology has gained importance. Aims: We sought to evaluate time trends in the epidemiology and survival of patients with EAC and GEJAC in a population-based cohort. Methods: EAC and GEJAC patients from 1976 to 2019 were identified using ICD 9 and 10 diagnostic codes from the Rochester Epidemiology Project (REP). Clinical data and survival status were abstracted. Poisson regression was used to calculate incidence rate ratios (IRR). Survival analysis and Cox proportional models were used to assess predictors of survival. Results: We included 443 patients (287 EAC,156 GEJAC). The incidence of EAC and GEJAC during 1976–2019 was 1.40 (CI 1.1–1.74) and 0.83 (CI 0.61–1.11) per 100,000 people, respectively. There was an increase in the incidence of EAC (IRR = 2.45, p = 0.011) and GEJAC (IRR = 3.17, p = 0.08) from 2000 to 2004 compared to 1995–1999, plateauing in later time periods. Most patients had associated BE and presented at advanced stages, leading to high 5-year mortality rates (66% in EAC and 59% in GEJAC). Age and stage at diagnosis were predictors of mortality. Conclusion: The rising incidence of EAC/GEJAC appears to have plateaued somewhat in the last decade. However, both cancers present at advanced stages with persistently poor survival, underscoring the need for early detection. [ABSTRACT FROM AUTHOR]

Introduction: Endoscopic eradication therapy (EET) is the preferred treatment for Barrett's esophagus (BE)-related neoplasia patients. However, the impact of EET on critical outcomes, outside of clinical trials and registry data, remains scarcely studied. We aimed to assess real-world practice patterns and clinical outcomes among BE patients undergoing EET. Methods: TriNetX is a large research network comprising linked inpatient and outpatient electronic-health record-derived data from over 80,000,000 patients. Patients with a diagnosis of BE from 2015 to 2020 were identified and included if they underwent EET during the study period. The primary outcome was the progression to EAC after index EET. Secondary outcomes included rate of esophagectomy, and all-cause mortality. All outcomes were stratified by baseline histology. The incidence of EAC and all-cause mortality were reported in person-years and adjusted for age and sex. Results: A total of 4114 patients were analyzed. Distribution of baseline histology was as follows: NDBE (11.8%), LGD (21.4%), HGD (26.4%), EAC (20.8%), and unspecified (19.6%). The total incidence of EAC after index EET was 6.01 per 1000 person-years (PY) for the entire cohort with the highest rate in HGD patients (12.9/1000 PY). The incidence of all-cause mortality was 13.23 per 1000 PY with the highest rates in EAC patients (25.1 per 1000 PY). Rates of esophagectomy were < 1% for all grades of dysplasia. Conclusion: The results of this study provide "real-world" data on critical outcomes for BE patients undergoing EET, demonstrating a low risk of incident EAC, all-cause mortality, and need for esophagectomy. [ABSTRACT FROM AUTHOR]

Background: Endoscopic screening for Barrett's esophagus (BE) is common, costly, and underperformed in at-risk people. A non-endoscopic cell collection device can be used to collect esophageal cells, enabling BE screening. Aims: This study assessed the acceptability and adequacy of a commercial non-endoscopic cell collection device in a US population. Methods: Six sites enrolled patients with confirmed BE or heartburn/regurgitation for ≥ 6 months. Patients underwent administration of the device, consisting of a sponge encapsulated in a capsule. The capsule dwelled in the stomach for 7.5 min and was retracted via an attached suture. An adequate sample was ≥ 1 columnar cell by H&E staining. Sample quality was rated using a 0–5 scale, with 0 = no columnar cells and 5 = plentiful groups. Trefoil Factor 3 (TFF3) staining was performed. Accuracy was assessed using esophagogastroduodenoscopy (EGD)/biopsy as the gold standard. Results: Of 191 patients, 99.5% successfully swallowed the device. Overall sample adequacy was 91% (171/188), with 84% (158/188) high quality. The detachment rate was 2/190 (1%). Overall sensitivity, specificity, and accuracy of the assay with TFF3 staining were 76%, 77%, and 76%. Sensitivity, specificity, and accuracy for ≥ 3 cm BE were 86%, 77%, and 82%. Asked if willing to repeat the procedure, 93% would, and 65% indicated a preference for the device over EGD. Conclusions: This study demonstrated a high rate of sample adequacy and promising acceptability of this non-endoscopic sampling device in a US population. Diagnostic characteristics suggest that non-endoscopic assessment of BE deserves further development as an alternative to endoscopy. [ABSTRACT FROM AUTHOR]

Background/Aim: Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). Therefore, an accurate diagnosis of BE is important for the subsequent follow-up and early detection of EAC. However, the definitions of BE have not been standardized worldwide; columnar-lined epithelium (CLE) without intestinal metaplasia (IM) and/or < 1 cm is not diagnosed as BE in most countries. This study aimed to clarify the malignant potential of CLE without IM and/or < 1 cm genetically. Method: A total of 96 consecutive patients (including nine patients with EAC) who had CLE were examined. Biopsies for CLE were conducted, and patients were divided into those with IM and > 1 cm (Group A) and those without IM and/or < 1 cm (Group B). Malignant potential was assessed using immunochemical staining for p53. Moreover, causative genes were examined using next-generation sequencing (NGS) on ten patients without Helicobacter pylori infection and without atrophic gastritis. Result: Of the 96 patients, 66 were in Group B. The proportion of carcinoma/dysplasia in Group A was significantly higher than that in Group B (26.7% in Group A and 1.5% in Group B; p < 0.01). However, one EAC patient was found in Group B. In the immunostaining study for non-EAC patients, an abnormal expression of p53 was not observed in Group A, whereas p53 loss was observed in three patients (4.6%) in Group B. In the NGS study, a TP53 mutation was found in Group B. Conclusion: CLE without IM and/or < 1 cm has malignant potential. This result suggests that patients with CLE as well as BE need follow-up. [ABSTRACT FROM AUTHOR]

Background: There is a large Barrett's esophagus patient population undergoing endoscopic surveillance. Methods to stratify patients into higher and lower risk groups may enable more varied surveillance intervals for patients with non-dysplastic Barrett's esophagus that could optimize use of endoscopy resources. Objective: We aimed to assess whether risk of progression to esophageal adenocarcinoma differed in patients with multiple endoscopic biopsies negative for dysplasia. Methods: We conducted a retrospective cohort study among individuals from the population-based Northern Ireland Barrett's register with a histologically confirmed diagnosis of non-dysplastic Barrett's esophagus (with intestinal metaplasia) between 1993 and 2010, who had at least one endoscopic biopsy conducted at least 12 months after diagnosis. We used Poisson regression to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for the association between number of successive endoscopies showing non-dysplastic Barrett's esophagus and risk of esophageal adenocarcinoma alone, and combined with high-grade dysplasia, at the next endoscopy. Results: We identified 1761 individuals who met our eligibility criteria. Subsequent risk of progression to esophageal adenocarcinoma was lower at the next endoscopy following two endoscopies showing non-dysplastic Barrett's esophagus (IRR 0.26, 95% CI 0.10–0.66) than following one endoscopy showing non-dysplastic Barrett's esophagus. Similar findings were apparent for risk of progression to esophageal adenocarcinoma or high-grade dysplasia (IRR 0.41, 95% CI 0.22–0.79). Conclusion: The lower risk of malignant progression in individuals with persistent non-dysplastic Barrett's esophagus over two consecutive endoscopic biopsies but not for longer term persistence does not support hypotheses of persistence being an indicator of less biologically aggressive lesions. Instead, the initial difference may be attributable to post-endoscopy cancers and support the necessity of adhering to robust quality standards for endoscopic procedures. [ABSTRACT FROM AUTHOR]

Background and Aim: Although endoscopic recognition of dysplasia in Barrett's esophagus is difficult, experience in recognition of early neoplastic lesions is supposed to increase the detection of early neoplastic lesions. The aim of this study was to assess the significance of dysplasia in random biopsies in Barrett's esophagus, in the absence of reported visible lesions as well as the difference in final outcome of pathology. Methods: We retrospectively identified all patients with Barrett's esophagus with suspicion of dysplasia or early adenocarcinoma who were referred to our center between February 2008 and April 2016. We analyzed all endoscopy reports, pathology reports, and referral letters from 19 different hospitals. Patients were divided into two groups, based on the presence or absence of visible lesions reported upon referral. Results: In total, 170 patients diagnosed with dysplasia or adenocarcinoma were referred to our tertiary center. Ninety-one of these referred patients were referred with dysplasia or adenocarcinoma in random biopsies, without a reported lesion during endoscopy in the referral center. During endoscopic work-up at our center, a visible lesion was detected in 44 of these 91 patients (48.4%). After endoscopic work-up and treatment, adenocarcinoma was found in an additional 21 patients. Two of these patients were initially referred with low-grade dysplasia, and 19 patients were initially referred with high-grade dysplasia. The final pathology was upstaged in 35.8% of the patients. Conclusions: The presence of any grade of dysplasia in random biopsies during surveillance in referral centers is a marker for more severe final pathology. Training in recognition of early neoplastic lesions in Barrett's esophagus imaging is recommended for endoscopists performing Barrett's surveillance. [ABSTRACT FROM AUTHOR]

Background: Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans. Aims: To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia. Methods: Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett's mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. Results: Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1β, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1, and TWIST1), and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (-125b-5P, -132-3P, -548z, -551a, -504, -518, and -34a-5P). Of proteins analyzed by Western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2 and VEGF-R2 were noteworthy. Conclusions: When these mRNA, miRNA, and protein molecular data are considered collectively, a cancer chemopreventive action by zinc in Barrett's metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered, and inexpensive micronutrient, that could determine if a chemopreventive action truly exists. [ABSTRACT FROM AUTHOR]

Esophageal adenocarcinoma (EAC) continues to be a significant public health problem with survival rates that have remained stagnant. Although the population at the highest risk for EAC, i.e., patients with Barrett's esophagus (BE) has been clearly defined, patients with EAC continue to do poorly due to advanced stage at diagnosis. The field of extracellular vesicles (EV) could have huge application for the management of patients with BE and EAC by allowing timely diagnosis, serial monitoring, and improved understanding of disease biology. EV are actively packaged and actively secreted vesicles and contain microRNAs, proteins, lipids, and DNA. The contents of EV have been shown to provide useful insights into cellular transformation and pro-oncogenic processes. Early work shows promise but suffers from a high degree of technical and biological variation. The current review not only summarizes the current knowledge about EV as diagnostic biomarkers and their role in disease progression of BE and EAC but also provides the reader practical guidance to devise future experiments to perform well-designed studies. [ABSTRACT FROM AUTHOR]

Background: The incidence of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) continues to rise, and risk stratification of patients with BE is needed. Impaired esophageal motility is associated with gastroesophageal reflux disease; however, whether esophageal dysmotility is a risk factor for dysplasia progression in BE is incompletely understood. This study aimed to characterize esophageal motility patterns in patients with BE and identify physiologic factors associated with dysplasia progression in BE. Methods: This multicenter retrospective study assessed data from adult patients with histologically confirmed BE who underwent high-resolution esophageal manometry from 1/2014 to 1/2018 at four tertiary care centers. Longitudinal data were collected when available among patients with non-dysplastic BE (NDBE) and separated as: no dysplastic progression or positive dysplastic progression. Multivariable logistic regression assessed for independent predictors of dysplasia progression. Results: Among 193 patients, histology at index endoscopy identified 152 (79%) NDBE, 23 (12%) low-grade dysplasia, 14 (7%) high-grade dysplasia, and 4 (2%) EAC. Ninety-eight (51%) had abnormal esophageal motor function on manometry. Longitudinal data were available for 84 of 152 patients with initial NDBE. Twelve (14%) exhibited dysplastic progression to low-grade (6) or high-grade (6) dysplasia. Mean esophageal distal contractile integral was lower for patients that progressed [455 mmHg s cm (SD 515)] compared with patients who did not progress [987 mmHg s cm (SD 953); aOR 1.21 (95% CI 1.01, 1.44)]. Conclusion: In this retrospective study of 193 BE patients, the majority exhibited abnormal esophageal motor function. Reduced esophageal contractility was independently associated with dysplastic progression in BE. Characterizing esophageal physiology in BE may help to risk stratify patients. [ABSTRACT FROM AUTHOR]

Background: Clinical prediction models targeting patients for Barrett's esophagus (BE) screening include data obtained by interview, questionnaire, and body measurements. A tool based on electronic health records (EHR) data could reduce cost and enhance usability, particularly if combined with non-endoscopic BE screening methods.Aims: To determine whether EHR-based data can identify BE patients.Methods: We performed a retrospective review of patients ages 50-75 who underwent a first-time esophagogastroduodenoscopy. Data extracted from the EHR included demographics and BE risk factors. Endoscopy and pathology reports were reviewed for histologically confirmed BE. Screening criteria modified from clinical guidelines were assessed for association with BE. Subsequently, a score based on multivariate logistic regression was developed and assessed for its ability to identify BE subjects.Results: A total of 2931 patients were assessed, and BE was found in 1.9%. Subjects who met screening criteria were more likely to have BE (3.3% vs. 1.1%, p = 0.001), and the criteria predicted BE with an AUROC of 0.65 (95% CI 0.59-0.71). A score based on logistic regression modeling included gastroesophageal reflux disease, sex, body mass index, and ever-smoker status and identified BE subjects with an AUROC of 0.71 (95% CI 0.64-0.77). Both prediction tools produced higher AUROCs in women than in men.Conclusions: EHR-based BE risk prediction tools identify BE patients with fair accuracy. While these tools may improve the efficiency of patient targeting for BE screening in the primary care setting, challenges remain to identify high-risk patients for non-invasive BE screening in clinical practice. [ABSTRACT FROM AUTHOR]

Traditionally, early esophageal cancer (i.e., cancer limited to the mucosa or superficial submucosa) was managed surgically; the gastroenterologist's role was primarily to diagnose the tumor. Over the last decade, advances in endoscopic imaging, ablation, and resection techniques have resulted in a paradigm shift-diagnosis, staging, treatment, and surveillance are within the endoscopist's domain. Yet, there are few reviews that provide a focused, evidence-based approach to early esophageal cancer, and highlight areas of controversy for practicing gastroenterologists. In this manuscript, we will discuss the following: (1) utility of novel endoscopic technologies to identify high-grade dysplasia and early esophageal cancer, (2) role of endoscopic resection and imaging to stage early esophageal cancer, (3) endoscopic therapies for early esophageal cancer, and (4) indications for surgical and multidisciplinary management. [ABSTRACT FROM AUTHOR]

Risk stratification of patients with Barrett's esophagus (BE) presently relies on the histopathologic grade of dysplasia found in esophageal biopsies, which is limited by sampling error and inter-pathologist variability. p53 immunostaining of BE biopsies has shown promise as an adjunct tool but is not recommended by American gastroenterology societies, who cite insufficient evidence of its prognostic value. We have conducted a systematic review and meta-analyses to clarify this value. We searched for studies that: (1) used immunohistochemistry to assess p53 expression in esophageal biopsies of BE patients and (2) reported subsequent neoplastic progression. We performed separate meta-analyses of case-control studies and cohort studies. We identified 14 relevant reports describing 8 case-control studies comprising 1435 patients and 7 cohort studies comprising 582 patients. In the case-control study meta-analysis of the risk of neoplasia with aberrant p53 expression, the fixed- and random-effect estimates of average effect size with aberrant p53 expression were OR 3.84, p < .001 (95% CI 2.79-5.27) and OR 5.95, p < .001 (95% CI 2.68-13.22), respectively. In the cohort study meta-analysis, the fixed- and random-effect estimates of average effect size were RR = 17.31, p < .001 (95% CI 9.35-32.08) and RR = 14.25, p < .001 (95% CI 6.76-30.02), respectively. Separate meta-analyses of case-control and cohort studies of BE patients who had baseline biopsies with p53 immunostaining revealed consistent, strong, and significant associations between aberrant p53 immunostaining and progression to high-grade dysplasia or esophageal adenocarcinoma. These findings support the use of p53 immunostaining as an adjunct to routine clinical diagnosis for dysplasia in BE patients. [ABSTRACT FROM AUTHOR]

Background: Barrett's esophagus (BE) is the premalignant lesion of esophageal adenocarcinoma (EAC) and is the target of early detection and prevention efforts for EAC.Aims: We sought to evaluate what proportion and temporal trends of EAC patients had missed opportunities for screening and surveillance of BE.Methods: Our study included 182 patients with EAC at the Michael E. DeBakey VA Medical Center in Houston, Texas, between 02/2005 and 09/2017. We conducted a retrospective audit of patients' medical records for any previous upper endoscopies (EGDs) for screening or surveillance of BE prior to their EAC diagnosis.Results: The mean age of the cohort was 67.3 years (SD = 9.5); 99.5% of patients were male, and 85.2% were white. Only 45 patients (24.7%) had EGD at any time prior to the cancer diagnosing EGD, of whom 29 (15.9% of all EAC cases) had an established BE diagnosis. In the 137 patients with no prior EGD, most (63.5%) had GERD or were obese or ever smokers. There were no changes in patterns over time. For the 29 patients with prior established BE, 22 (75.8%) were diagnosed with EAC as a result of surveillance EGD. Patients with prior established BE were more likely to be diagnosed at 0 or I stage (p < 0.001) and managed with endoscopic or surgical modalities (p < 0.001) than patients without prior BE.Conclusions: Despite having established risk factors for BE, the majority of EAC patients had no prior EGD to screen for BE. BE screening may represent the largest missed opportunity to reduce EAC mortality. [ABSTRACT FROM AUTHOR]

Barrett's esophagus (BE) is a very common condition. We have obtained fairly profound knowledge of the natural history of this condition. This results from many cross-sectional and cohort studies, many describing patients undergoing long-term surveillance. Their consent to use their clinical data has improved our knowledge to the benefit of these same and other patients. The prevalence of BE increases with age both in men and in women. This increase starts at a younger age in men than in women. The incidence of high-grade dysplasia and cancer in BE depends on segment length, gender, and age. The latter two likely indicate the duration of the presence of BE in an individual patient. Other factors that influence the incidence of dysplasia and cancer are smoking behavior and use of certain medications such as PPIs, statins, and NSAIDs. Surveillance of BE and treatment of dysplasia can impact the incidence of and mortality due to esophageal adenocarcinoma. This is of major benefit to a subgroup of BE patients. The epidemiology and burden of disease ask for further efforts to develop targeted screening, surveillance, and intervention techniques in coming years. [ABSTRACT FROM AUTHOR]

The cost-effectiveness of screening and surveillance for Barrett's esophagus continues to evolve as the incidence of esophageal adenocarcinoma increases, biomarkers enhance the identification of individuals at highest risk for developing cancer, and endoscopic eradication of Barrett's esophagus improves. Screening to detect Barrett's esophagus may be cost-effective in selected high-risk groups based on age, race, sex and other factors such as symptoms of heartburn. Currently, endoscopic eradication therapy for Barrett's esophagus and high-grade dysplasia is a cost-effective intervention, while endoscopic therapy for non-dysplastic Barrett's esophagus is not a cost-effective strategy. As diagnosis of low-grade dysplasia improves, endoscopic eradication therapy may also prove to be a cost-effective intervention. [ABSTRACT FROM AUTHOR]

Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), a condition where the normal squamous epithelia is replaced by specialized intestinal metaplasia in response to chronic gastroesophageal acid reflux. In a minority of individuals, BE can progress to low- and high-grade dysplasia and eventually to intra-mucosal and then invasive carcinoma. BE provides researchers with a unique model to characterize the process by which a carcinoma arises from its precursor lesion. Molecular studies of BE have demonstrated that it is not simply a metaplastic tissue, but rather it harbors frequent alterations that are also present in dysplastic BE and in EAC. Both BE and EAC are characterized by loss of heterozygosity, aneuploidy, specific genetic mutations, and clonal diversity. Epigenetic abnormalities, primary alterations in DNA methylation, are also frequently seen in BE and EAC. Candidate gene and array-based approaches have demonstrated that numerous tumor suppressor genes exhibit aberrant promoter methylation, and some of these altered genes are associated with the neoplastic progression of BE. It has also been shown that the BE and EAC epigenomes are characterized by hypomethylation of intragenic and non-coding regions Recent studies have also provided new insight into the evolutionary forces underlying the molecular alterations seen in BE and EAC and into the molecular pathogenesis of EAC. [ABSTRACT FROM AUTHOR]

Since the early 1970s, the incidence of esophageal adenocarcinoma (EA) has increased dramatically in most Western populations while the incidence of esophageal squamous cell carcinoma has decreased. As a result, EA has become the predominant subtype of esophageal cancer in North America and Europe and is an important contributor to overall cancer mortality. Barrett's esophagus (BE), a metaplastic columnar epithelium of the distal esophagus, is the known precursor lesion for EA. EA and BE occur more frequently in white men over 50 years old, as well as in people with frequent symptoms of gastroesophageal reflux, in smokers, and in people who are obese. Conversely, EA and BE are less common in persons using nonsteroidal anti-inflammatory drugs and in person with Helicobacter pylori infection. The 5-year survival rate for patients with EA, although generally poor, has improved during the past decade, and long-term survival is increasingly possible for patients with early or locally advanced disease. This review combines a synthesis of published studies with an analysis of data from the United States National Cancer Institute's Surveillance, Epidemiology, and End Results program to discuss the change in incidence of EA and summarize current knowledge of risk factors. [ABSTRACT FROM AUTHOR]

Background: An association between inlet patches and proximal esophageal adenocarcinomas is currently suspected because of numerous case reports of simultaneous occurrence of both diseases.Aims: To analyze whether inlet patches are significantly associated with proximal esophageal adenocarcinomas in a large population.Methods: Computerized search of pathology and EGD reports revealed 398 cases of esophageal adenocarcinomas among 156,236 EGDs (performed on 106,510 patients) diagnosed by histopathology performed at Royal Oak/Troy, William Beaumont Hospitals, 2003-2016. Adenocarcinomas localized as distal, middle, or proximal; and characterized as associated versus unassociated with inlet patches. Medical records were reviewed. Endoscopic photographs, radiologic images, and pathologic slides were re-reviewed. Two researchers independently performed systematic computerized literature searches; cases of simultaneous diseases identified by consensus.Results: Adenocarcinoma locations included: distal-381, middle-14, and proximal esophagus-3. Five patients had inlet patches with esophageal adenocarcinomas located at: distal-2, middle-0, and proximal esophagus-3 (relative frequency of inlet patches with cancers of distal/middle esophagus = 2/395 [.5%] vs. proximal esophagus = 3/3 [100%], p < .000001, 95% OR CI > 50.1, Fisher's exact test). Cases of proximal esophageal adenocarcinomas within inlet patches included: (1) Seventy-eight-year-old man presented with dysphagia. Neck CT showed proximal esophageal mass. EGD revealed semi-circumferential, multinodular, 3.0 × 1.5 cm mass within inlet patch. Histopathology of biopsies revealed moderately-to-poorly differentiated adenocarcinoma. Patient received chemoradiotherapy and expired 2 years later. (2) Seventy-nine-year-old man presented with anorexia and weight loss. EGD demonstrated proximal esophageal mass within inlet patch. Histopathology of biopsies revealed poorly differentiated, signet ring cell adenocarcinoma. Chest CT revealed 3.4 × 2.1-cm-proximal esophageal mass. Patient expired 4 months later. (3) Sixty-year-old man presented with dysphagia. EGD revealed 4-cm-long, semi-circumferential, proximal esophageal mass within inlet patch. Histopathology of biopsies revealed poorly differentiated adenocarcinoma. Patient underwent emergency esophagectomy for esophageal perforation 2 weeks after initiating chemoradiotherapy, and died shortly thereafter. Literature review revealed 39 cases of simultaneous disease.Study Limitations: Potential underreporting by endoscopists of inlet patches at EGD.Conclusions: Study supplements 39 previously reported cases of simultaneous disease, by adding three new cases, and by novel report of statistically significant association between these two entities, which has important implications in the pathophysiology of proximal esophageal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: We showed previously that nuclear localization of the androgen receptor (AR) and expression of the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma (EAC) tissues were associated with decreased patient survival, suggesting a role for androgens in this cancer.Aim: To investigate the effect of the AR ligand 5α-dihydrotestosterone (DHT) on AR-expressing EAC cell lines in vitro.Methods and Results: In tissue resection specimens from EAC patients, FKBP5 expression was positively associated with proliferation as measured by Ki-67 expression. We stably transduced AR into three AR-negative EAC cell lines, OE33, JH-EsoAd1, and OE19, to investigate androgen signaling in vitro. In the AR-expressing cell lines, 10 nM DHT, the concentration typically used to study AR signaling, induced changes in the expression of androgen-responsive genes and inhibited proliferation by inducing cell cycle arrest and senescence. At lower DHT concentrations near the half maximal inhibitory concentration (IC50), the AR-expressing cell lines proliferated and there were changes in the expression of androgen-responsive genes. In direct co-culture with cancer-associated fibroblast-like PShTert myofibroblasts, 10 nM DHT induced changes in the expression of androgen-responsive genes but did not inhibit proliferation.Conclusions: This is the first study to show that EAC cell lines respond to androgen in vitro. Proliferation together with the expression of androgen-responsive genes was dependent on the concentration of DHT, or the presence of a permissive microenvironment, consistent with observations in the tissues. These findings are consistent with a role for androgen signaling in EAC. [ABSTRACT FROM AUTHOR]

Background and Aims: Barrett's esophagus, a metaplasia resulting from a long-standing reflux disease, and its progression to esophageal adenocarcinoma (EAC) are characterized by activation of pro-inflammatory pathways, induced by cytokines.Methods: An in vitro cell culture system representing the sequence of squamous epithelium (EPC1 and EPC2), Barrett's metaplasia (CP-A), dysplasia (CP-B) to EAC (OE33 and OE19) was used to investigate TNF-α-mediated induction of interleukin-8 (IL-8).Results: IL-6 and IL-8 expressions are increasing with the progression of Barrett's esophagus, with the highest expression of both cytokines in the dysplastic cell line CP-B. IL-8 expression in EAC cells was approx. 4.4-fold (OE33) and eightfold (OE19) higher in EAC cells than in squamous epithelium cells (EPC1 and EPC2). The pro-inflammatory cytokine TNF-α increased IL-8 expression in a time-, concentration-, and stage-specific manner. Furthermore, TNF-α changed the EMT marker profile in OE33 cells by decreasing the epithelial marker E-cadherin and increasing the mesenchymal marker vimentin. The anti-inflammatory compound curcumin was able to repress proliferation and to activate apoptosis in both EAC cell lines.Conclusion: The increased basal expression levels of IL-8 with the progression of Barrett's esophagus constrain NFκB activation and its contribution in the manifestation of Barrett's esophagus. An anti-inflammatory compound, such as curcumin, could create an anti-inflammatory microenvironment and thus potentially support an increase chemosensitivity in EAC cells. [ABSTRACT FROM AUTHOR]

Background: Narrow band imaging (NBI) allows identification of abnormal areas of Barrett's esophagus (BE) and could facilitate targeted biopsies.Aims: We evaluated the diagnostic accuracy for dysplasia prediction using non-magnifying NBI in Evis Exera III processors and high-definition endoscopes using the Barrett International NBI Group (BING) classification, as well as inter/intraobserver agreement for dysplasia prediction and mucosal/vascular patterns.Methods: Eight observers (4 staff endoscopists and 4 trainee endoscopists) evaluated 100 images selected from an anonymized bank of 470 photographs using the BING classification. Observers were to assign their individual assessment of the mucosal and vascular pattern, and prediction for dysplasia. Accuracy for dysplasia prediction and intra/interobserver agreement was calculated.Results: Dysplasia prediction had an accuracy of 81.1%, sensitivity of 48.4%, and a specificity of 91%. Positive predictive value and negative predictive value (NPV) were 61.4 and 85.5%, respectively. Dysplasia prediction done with a high degree of confidence (vs. low degree of confidence) had better diagnostic accuracy (85.8 vs. 70.7%). Interobserver concordance for dysplasia was weak: Κ = 0.40. Agreement for mucosal and vascular patterns was 0.39 and 0.30, respectively. Intraobserver concordance (assessed 6 months after initial test) for mucosal pattern, vascular pattern, and dysplasia prediction was moderate: Κ = 0.56, Κ = 0.47 and Κ = 0.60, respectively.Conclusions: Our results showed that NBI had a significant accuracy in BE assessment for dysplasia prediction, high specificity (>90%), and NPV (>85%), with suboptimal sensitivity. NBI could be a useful additional tool for BE inspection and targeted biopsies, but cannot avoid the need for biopsies following the Seattle protocol. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that chronic inflammation-associated cancer is relevant to microbiome. Esophageal adenocarcinoma arises from an inflammatory condition called Barrett's esophagus, which is caused by gastroesophageal reflux. We hypothesized that esophageal microbiome plays a role in carcinogenesis of esophageal adenocarcinoma.Aim: We investigated whether alteration of microbiome using antibiotics affects the development of esophageal adenocarcinoma in a rat model.Methods: Seven-week-old male Wistar rats which had undergone esophagojejunostomy were divided into control (n = 21) and antibiotic groups (n = 22) at 21 weeks after surgery. Control animals were given drinking water, while the other group was given penicillin G and streptomycin in drinking water until rats were killed at 40 weeks after operation. Incidence rates of Barrett's esophagus and adenocarcinoma in each group were evaluated by histological analysis. DNA was extracted from a portion of the distal esophagus, and the microbiome was investigated using terminal restriction fragment length polymorphism (T-RFLP) analysis.Results: All rats in both groups developed Barrett's esophagus. Incidence of esophageal adenocarcinoma was similar between both groups with a trend to reduced incidence in the antibiotics group (89 % in the control group, 71 % in the antibiotics group, P = 0.365). T-RFLP analysis showed that esophageal microbiome was different between two groups such as the proportion of Lactobacillales was lower in the antibiotics group and Clostridium cluster XIVa and XVIII was higher in the antibiotics group.Conclusions: Alteration of microbiome does not affect the incidence of esophageal adenocarcinoma. Microbiome may not contribute to the development of esophageal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Predictors of erosive esophagitis (EE) and Barrett's esophagus (BE) and the influence of number of risk factors in the community are not well defined.Methods: Rates of BE and EE among community residents identified in a randomized screening trial were defined. The risk of EE and BE associated with single and multiple risk factors (gender, age, GERD, Caucasian ethnicity, ever tobacco use, excess alcohol use, family history of BE or EAC, and central obesity) was analyzed.Results: Sixty-eight (33 %) of 205 subjects had EE and/or BE. BE prevalence was 7.8 % with dysplasia present in 1.5 %. Rates were comparable between subjects with and without GERD. Male sex and central obesity were independent risk factors. The odds of EE or BE were 3.7 times higher in subjects with three or four risk factors and 5.7 times higher in subjects with five or more risk factors compared with those with two or less factors.Conclusions: EE and BE are prevalent in the community regardless of the presence of GERD. Risk appeared to be additive, increasing substantially with three or more risk factors. [ABSTRACT FROM AUTHOR]

Background and Aim: Recent observational studies have shown therapeutic benefits of acetylsalicylic acid (ASA) in several types of cancer. We examined whether ASA exerts antitumor activity in esophageal adenocarcinoma (EAC).Methods: Human EAC cells (OE33) were treated with ASA (0-5 mM) to evaluate proliferation, apoptosis, and migration. In vivo model: OE33-derived tumors were subcutaneously implanted into athymic mice which were allocated to ASA (5 or 50 mg/kg/day)/vehicle (5-6 animals/group). Tumor growth was assessed every 2-3 days, and after 40 days, mice were euthanized. Plasma drug levels were determined by high-performance liquid chromatography. Histological and immunohistochemical (Ki67, activated caspase-3) analysis of tumors were performed. The effect of ASA on tumor prostaglandin E2 (PGE2) levels was also evaluated.Results: In vitro cell proliferation and migration were significantly inhibited while apoptosis increased (p < 0.05) by ASA. Although ASA did not induce tumor remission, tumor progression was significantly lower in ASA-treated mice when compared to non-treated animals (478 % in mice treated with 5 mg/kg/day ASA vs. 2696 % control; 748 % in mice treated with 50 mg/kg/day ASA vs. 2670 % control). Maximum tumor inhibition was 92 and 85 %, respectively. This effect was associated with a significant decrease of proliferation index in tumors. ASA 5 mg/kg/day did not modify tumor PGE2 levels. Whereas tumor PGE2 content in mice treated with ASA 50 mg/kg was lower than in control mice, the difference was not significant.Conclusion: Although these results need to be confirmed in other EAC cells, our data suggest a role for ASA in the treatment of this tumor. [ABSTRACT FROM AUTHOR]

Esophageal adenocarcinoma and its precursor Barrett's esophagus have been rapidly increasing in incidence for half a century, for reasons not adequately explained by currently identified risk factors such as gastroesophageal reflux disease and obesity. The upper gastrointestinal microbiome may represent another potential cofactor. The distal esophagus has a distinct microbiome of predominantly oral-derived flora, which is altered in Barrett's esophagus and reflux esophagitis. Chronic low-grade inflammation or direct carcinogenesis from this altered microbiome may combine with known risk factors to promote Barrett's metaplasia and progression to adenocarcinoma. [ABSTRACT FROM AUTHOR]

Barrett's esophagus (BE) is intestinal metaplasia of the lower esophagus and a precursor lesion for esophageal adenocarcinoma (EAC). Both are important health issues as they have rising incidences in the Western world. Improving the management of BE relies on understanding the underlying biology of this disease, but the exact biological mechanisms have been difficult to determine. BE is generally thought to be an acquired condition that develops secondarily to chronic gastroesophageal reflux. However, multiple reports of familial clustering of patients with BE and/or EAC suggest a possible inherited predisposition to BE may be driving this condition, at least in a subset of patients. Identifying the genetic variants that predispose to BE in these families would open up the possibility for blood-based screening tests that could inform decision-making in regard to surveillance strategies, particularly for relatives of patients with BE and/or EAC. Perhaps more importantly, understanding the genetic mechanisms that predispose to BE may provide valuable insights into the biology of this condition and potentially identify novel targets for therapeutic intervention. Here we review the current evidence for a genetic predisposition to BE and discuss the potential implications of these findings. [ABSTRACT FROM AUTHOR]

Background: Esophageal epithelial microRNAs may be used to diagnose Barrett's esophagus (BE) and possibly monitor its progression to esophageal adenocarcinoma (EAC).Aims: We reviewed studies that have investigated this to identify microRNAs with high biomarker potential for screening and disease monitoring in BE.Methods: PubMed and EMBASE databases were searched for studies that quantified esophageal epithelial microRNAs. Publications reporting microRNA comparisons of normal, non-dysplastic BE, BE with high-grade dysplasia (HGD), and EAC tissues using both unbiased discovery and independent validation phases were reviewed.Results: Eleven studies on microRNA expression differences between normal epithelium and non-dysplastic BE (seven studies), HGD (4) or EAC (7), or between non-dysplastic BE and HGD (3) or EAC (6) were identified, and the findings of their validation phase were analyzed. Increased miR-192, -194, and -215, and reduced miR-203 and -205 expression in BE compared to normal was noticed by all 4-6 of the seven studies that examined these microRNAs. In heterogeneity tests of the reported fold-change values, the I (2) statistics were 7.9-17.1 % (all P < 0.05). Elevated miR-192, -194, and -215, and diminished miR-203 and -205 levels were also noted for comparisons of HGD or EAC against normal. In contrast, a consistent microRNA expression difference was absent for the comparisons of HGD or EAC against BE.Conclusions: MicroRNAs miR-192, -194, -203, -205, and -215 are promising tissue biomarkers for diagnosing BE. Cross-sectional data suggest that microRNAs may have a limited role in separating BE from HGD/EAC epithelia but need further testing in longitudinal follow-up studies. [ABSTRACT FROM AUTHOR]

Background: Doublecortin-like kinase 1 (DCLK1), a putative tumor stem cell marker has been shown to be highly expressed in the stromal and epithelial compartments in colon and pancreatic cancer as well as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Aim: To prospectively investigate whether the immunohistochemical expression of DCLK1 was associated with detectable DCLK1 plasma expression in patients with existing BE and EAC. Methods: Immunohistochemistry was performed on paraffin-embedded sections using DCLK1 antibody and scored based on staining intensity and tissue involvement. Purified human plasma samples were subjected to Western blot and ELISA analysis. Results: Forty (40) patients were enrolled: 10 controls (normal endoscopy) and 30 with BE/EAC (13 nondysplastic BE [NDBE], 9 dysplastic BE [DBE] and 8 EAC). Mean epithelial DCLK1 staining was as follows: controls = 0.11, NDBE = 3.83, DBE = 6.0, EAC = 7.17. Mean stromal DCLK1 staining was as follows: NDBE = 5.83, DBE = 5.375, EAC = 10.83. DCLK1 was detected by plasma Western blot in 1 control and in all patients with BE/EAC p < 0.0005. Plasma DCLK1 was elevated by ELISA in EAC compared to other groups, p < 0.05. Conclusions: Increased expression of DCLK1 was observed in the epithelium, stroma and plasma of patients with BE/EAC. Furthermore, the presence of detectable DCLK1 in plasma of BE/EAC patients may provide a less invasive, detection tool in those patients as well as represent a novel molecular marker distinguishing between normal esophageal mucosa and BE or EAC. [ABSTRACT FROM AUTHOR]

Background: Screening for Barrett's esophagus (BE) and adenocarcinoma (EAC) is controversial, but interest remains in finding the optimal method. Attitudes on screening within the community are unknown. We aimed to assess these attitudes via a survey. Study: A mixed-mode survey was conducted in adults >50 years to assess awareness regarding BE, willingness to participate in screening, and preferences regarding method of screening. Methods evaluated were sedated endoscopy (sEGD), unsedated transnasal endoscopy (uTNE) and video capsule (VCE). Results: A total of 136 from 413 (33 %) adults responded [47 % males, mean (SD) age 63 (10.2) years], and 26 % of responders knew of BE at baseline. After reading the information on BE, 72 % were interested in screening. A history of undergoing screening tests and GI symptoms were predictive of interest. Unsedated techniques were preferred by 64 % (VCE: 56 % and uTNE: 8 %) versus sEGD (36 %). Conclusions: The majority of adults were willing to undergo screening for BE/EAC, with a preference for unsedated techniques. [ABSTRACT FROM AUTHOR]

Background: Proton pump inhibitors (PPIs) may reduce the risk of esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. PPIs are prescribed for virtually all patients with Barrett's esophagus, irrespective of the presence of reflux symptoms, and represent a de facto chemopreventive agent in this population. However, long-term PPI use has been associated with several adverse effects, and the cost-effectiveness of chemoprevention with PPIs has not been evaluated. Aim: The purpose of this study was to assess the cost-effectiveness of PPIs for the prevention of EAC in Barrett's esophagus without reflux. Methods: We designed a state-transition Markov microsimulation model of a hypothetical cohort of 50-year-old white men with Barrett's esophagus. We modeled chemoprevention with PPIs or no chemoprevention, with endoscopic surveillance for all treatment arms. Outcome measures were life-years, quality-adjusted life years (QALYs), incident EAC cases and deaths, costs, and incremental cost-effectiveness ratios. Results: Assuming 50 % reduction in EAC, chemoprevention with PPIs was a cost-effective strategy compared to no chemoprevention. In our model, administration of PPIs cost $23,000 per patient and resulted in a gain of 0.32 QALYs for an incremental cost-effectiveness ratio of $12,000/QALY. In sensitivity analyses, PPIs would be cost-effective at $50,000/QALY if they reduce EAC risk by at least 19 %. Conclusions: Chemoprevention with PPIs in patients with Barrett's esophagus without reflux is cost-effective if PPIs reduce EAC by a minimum of 19 %. The identification of subgroups of Barrett's esophagus patients at increased risk for progression would lead to more cost-effective strategies for the prevention of esophageal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: We conducted a systematic review and meta-analysis of meat intake and esophageal cancer risk, with subgroup analyses based on meat type and histological type of cancer. Aims: The purpose of this study was to investigate the association between meat intake and risk of esophageal cancer. Methods: We searched MEDLINE, EMBASE and Cochrane Library (April 2013) for cohort and case-control studies that assessed meat intake and esophageal cancer risk. Random-effect or fixed-effect models were used to pool relative risks (RRs) from individual studies with heterogeneity and publication bias analyses carried out. Seven cohort and 28 case-control studies were included. Results: The summary RRs for esophageal cancer for the highest versus lowest consumption categories were 1.19 (95 % confidence interval [CI] 0.98-1.46) for total meat, 1.55 (95 % CI 1.22-1.96) for red meat, 1.33 (95 % CI 1.04-1.69) for processed meat, 0.72 (95 % CI 0.60-0.86) for white meat, 0.83 (95 % CI 0.72-0.96) for poultry, and 0.95 (95 % CI 0.76-1.19) for fish. When striated by histological subtype, positive associations were seen among esophageal squamous cell carcinoma and red meat, white meat and poultry, and esophageal adenocarcinoma with total meat and processed meat. Conclusions: Meat consumption is associated with esophageal cancer risk, which depends on meat type and histological type of esophageal cancer. High intake of red meat and low intake of poultry are associated with an increased risk of esophageal squamous cell carcinoma. High meat intake, especially processed meat, is likely to increase esophageal adenocarcinoma risk. And fish consumption may not be associated with incidence of esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Esophageal adenocarcinoma (EAC) has a very high case fatality rate and is one of the fastest rising cancers worldwide. At the same time, research into EAC has been hampered by a relative lack of pre-clinical models, including representative cell lines. Aim: The purpose of this study was to establish and characterize a new EAC cell line. Methods: Tumor cells were isolated from EAC tissue by enzymatic digestion. Origin of the cell line was confirmed by microsatellite-based genotyping. A panel of cancer-related genes was screened for mutations by targeted deep sequencing, Sanger sequencing and high resolution melting. CDKN2A promoter methylation was assessed by methylation specific high resolution melting. HER2 amplification was assessed by fluorescent in situ hybridization. Immunohistochemistry was used to assess expression of markers in xenografts grown in SCID mice. Results: A novel EAC cell line, OANC1, was derived from a Barrett's-associated EAC. Microsatellite-based genotyping of OANC1 and patient DNA confirmed the origin of the cell line. Sequencing of OANC1 DNA identified homozygous TP53 missense (c.856G>A, p.E286K) and SMAD4 nonsense (c.1333C>T, p.R445X) mutations. OANC1 are tumorigenic when injected sub-cutaneously into SCID mice and xenografts were positive for columnar, glandular and intestinal epithelial markers commonly expressed in EAC. Xenografts exhibited strong p53 expression, consistent with a TP53 mutation. Some proteins, including p16, EGFR and β-catenin, had heterogeneous expression patterns across xenograft cross-sections, indicative of tumor heterogeneity. Conclusions: OANC1 represents a valuable addition to the limited range of pre-clinical models for EAC. This new cell line will be a useful model system for researchers studying both basic and translational aspects of this disease. [ABSTRACT FROM AUTHOR]

Background: Deoxycholic acid (DCA) promotes the development and progression of esophageal adenocarcinoma (EAC) by inducing inflammation. Adiponectin is reported to have anti-inflammatory and anti-tumor effects. Purpose: This study investigated the effects of two types of adiponectin, full-length adiponectin (f-Ad) and globular adiponectin (g-Ad), on DCA-induced inflammation, and investigated the involvement of the reactive oxygen species (ROS)/NF-κB signaling pathway in inflammation in EAC. Methods: OE19 cells were treated with DCA (50-300 μ M) and/or f-Ad/g-Ad (10.0 μg/ml) or N-acetylcysteine (NAC). The viability of cells exposed to DCA was measured by use of the MTT assay. mRNA and protein levels of the inflammatory factors were examined by real-time PCR and ELISA. Intra-cellular ROS levels were determined by use of flow cytometry. Protein levels of total and p-NF-κB p65 were measured by western blot. Results: DCA induced dose and time-dependent cytotoxicity. mRNA and protein expression of TNF-α, IL-8, and IL-6 in cells treated with DCA alone were up-regulated, and intra-cellular ROS and p-NF-κB p65 protein levels were also increased. g-Ad promoted inflammatory factor production, ROS levels, and p-NF-κB p65 protein expression whereas f-Ad had a suppressive effect. When combined with DCA, g-Ad enhanced the pro-inflammatory effect of DCA whereas f-Ad, similar to NAC, suppressed the effect. Conclusion: DCA has a pro-inflammatory effect in EAC. f-Ad has an anti-inflammatory effect whereas g-Ad seems to have a pro-inflammatory effect in an ROS/NF-κB p65-dependent manner. This indicates that f-Ad could be a potential anti-inflammatory reagent for cancer therapy. [ABSTRACT FROM AUTHOR]

Background: There are limited data on the effect of endoscopic mucosal resection (EMR) on changes of histopathologic diagnosis for Barrett's esophagus (BE) patients undergoing endoscopic eradication therapy (EET); especially those without visible lesions. Aim: To compare the frequency of changes of diagnosis by EMR compared with pre-EMR biopsy diagnosis for patients with and without visible lesions. Methods: In this multicenter outcomes project, patients with Barrett's-related neoplasia undergoing EET at three tertiary-care centers were included. Patients undergoing biopsies followed by EMR within six months were included. The main outcome measures were frequency of overall change of histopathologic diagnosis, change based on pre-EMR biopsy diagnosis, and change based on the presence of visible lesions. Results: One-hundred and thirty-eight BE patients (low-grade dysplasia (LGD) 15 (10.9 %), high-grade dysplasia (HGD) 87 (63 %), esophageal adenocarcinoma (EAC) 36 (26.1 %)) were included; 114 (82.6 %) patients had visible lesions. EMR resulted in a change of diagnosis for 43 (31.1 %) patients (upgrade 14 (10.1 %); downgrade 29 (21 %)). For HGD patients, EMR downstaged dysplasia grade for 17 (19.5 %) cases and upstaged it to EAC for nine (10.3 %) cases. There was a change of diagnosis for 26 (29.9 %) HGD patients, irrespective of the presence or absence of visible lesions ( p = 0.76). For EAC patients, EMR downstaged dysplasia grade in 10 (27.8 %) cases. There was a change of diagnosis for 10 (27.8 %) EAC patients, irrespective of the presence or absence of endoscopically visible lesions ( p = 0.48). Conclusions: EMR results in a change of diagnosis for approximately 30 % of BE patients with early neoplasia (with and without visible lesions) referred for EET. [ABSTRACT FROM AUTHOR]

Background: Histopathologic differentiation between the stages of Barrett's carcinogenesis is often challenging. Liver-intestine (LI)-cadherin, an intestine-specific marker, is involved in intestinal metaplasia development in gastric and colon cancers and could be of value in diagnosis and differentiation. Aims: To examine the expression of LI-cadherin in the sequence of Barrett's carcinogenesis and to evaluate its association with clinicopathological data. Methods: LI-cadherin expression was immunohistologically investigated, by use of anti-CDH17 antibody, in gastric mucosa (GM) biopsies taken from the cardia ( n = 9), in Barrett's esophagus (BE) without intraepithelial neoplasia (without IEN) ( n = 9) and BE with low-grade IEN ( n = 11), and in esophageal adenocarcinoma (ADC) ( n = 13). Results: The immunoreactivity score was highest in adenocarcinoma (mean IRS = 4.0), and dropped gradually from BE with IEN and BE without IEN (mean IRS = 2.0) to cardia mucosa (IRS = 0). Similarly, the intensity of staining and the percentage of positive cells increased during the sequential stages of BE carcinogenesis. Comparative analysis showed that LI-cadherin expression was significantly different between cardiac epithelium and ADC. Also, percentage of positive cells in GM was significantly different from that in BE with IEN. LI-cadherin IRS was lower for tumors with poor differentiation than for moderately differentiated tumors, but the difference was not statistically significant. Conclusions: LI-cadherin is a sensitive marker of intestinal metaplasia and can be helpful for early histologic diagnosis of Barrett's esophagus; it is, however, not significantly different between BE with and without IEN, and cannot be used to distinguish between these. [ABSTRACT FROM AUTHOR]

Background: Achalasia is characterized by esophageal aperistalsis and impaired relaxation of the lower esophageal sphincter (LES). This contrasts with an insufficient LES, predisposing to gastro-esophageal reflux and Barrett's esophagus. The co-incidence of achalasia and BE is rare. Pneumatic dilatation (PD) may lead to gastro-esophageal reflux, Barrett's esophagus development, and esophageal adenocarcinoma. Aims: To determine the incidence of Barrett's esophagus and esophageal adenocarcinoma in achalasia patients treated with PD. Methods: We performed a single-center cohort follow-up study of 331 achalasia patients treated with PD. Mean follow-up was 8.9 years, consisting of regular esophageal manometry, timed barium esophagram, and endoscopy. Results: Twenty-eight (8.4 %) patients were diagnosed with Barrett's esophagus, one at baseline endoscopy. This corresponds with an annual incidence of Barrett's esophagus of 1.00 % (95 % CI 0.62-1.37). Hiatal herniation was present in 74 patients and 21 developed Barrett's esophagus compared to seven of 257 patients without a hiatal hernia. Statistical analysis revealed a hazard ratio of 8.04 to develop Barrett's esophagus if a hiatal hernia was present. Post-treatment LES pressures were lower in patients with Barrett's esophagus than in those without (13.9 vs. 17.4 mmHg; p = 0.03). Two (0.6 %) patients developed esophageal adenocarcinoma during follow-up. Conclusions: Barrett's esophagus is incidentally diagnosed in untreated achalasia patients despite high LES pressures, but is more common after successful treatment, especially in the presence of hiatal herniation. Patients treated for achalasia should be considered for GERD treatment and surveillance of development of Barrett's esophagus, in particular, when they have low LES pressures and a hiatal herniation. [ABSTRACT FROM AUTHOR]

Background: Probe-based confocal laser endomicroscopy (pCLE) is a new technique allowing in vivo detection of neoplastic tissue using a standard endoscope. Aims: Our aim was to compare the incident dysplasia detection rate of biopsies obtained by high-definition white light endoscopy (HD-WLE) or by pCLE in a cohort of patients with Barrett's esophagus (BE) participating in a surveillance program. Methods: Fifty of 100 patients underwent pCLE in addition to HD-WLE. Four-quadrant biopsy specimens according to the Seattle biopsy protocol were obtained in all patients to ensure standard-of-care. Diagnosis of dysplasia/neoplasia was made by a blinded gastrointestinal pathologist. Results: Incident high-grade dysplasia (HGD) and low-grade dysplasia (LGD) were diagnosed in 3/100 and in 16/100 cases. In the HD-WLE group, areas suspicious for neoplasia were not observed and dysplasia was diagnosed in 5/50 (10 %) patients (one with HGD). In the pCLE group, areas suspicious for neoplasia were observed by pCLE in 21/50 (42 %) patients; dysplasia was confirmed in 14 cases (28 %) (two with HGD). The dysplasia detection rate was significantly higher in the pCLE group than in the HD-WLE group ( P = 0.04). The sensitivity, specificity, positive and negative predictive values of pCLE for dysplasia were 100, 83, 67, and 100 %, respectively. Conclusions: Incident dysplasia can be more frequently detected by pCLE than by HD-WLE in BE. The higher dysplasia detection rate provided by pCLE could improve the efficacy of BE surveillance programs. [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer accounts for a considerable proportion of carcinomas of the upper gastrointestinal tract in African Americans. Our aim was to describe the epidemiology of esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EA) among African Americans in the last five decades.Methods: A total of 601 records of patients with documented esophageal cancer between 1959 and 2007 at Howard University Hospital were reviewed. Demographic characteristics, risk factors, clinical stage and histological findings were reviewed. The change in prevalence of the disease and the interaction between main risk factors with tumor stage of the patients were assessed over the years of this study.Result: A total of 552 patients (91.8%) had ESCC while 49 patients (8.2%) had EA. The mean age at diagnosis was 60.1 and 60.6 years for ESCC and EA, respectively (P = 0.8). The peak incidence was in the 1980-1989 decade. Out of 136 ESCC patients with TNM staging information, 130 (95.6%) were diagnosed in stage 2 and above. The majority (73%) of the ESCC were in the mid- and upper third of the esophagus and associated with smoking and alcohol exposure. The majority (81%) of the EA were in the mid- and lower third. The most common presenting symptoms were dysphagia (77.7%), and weight loss (31.9%).Conclusion: ESCC is the predominant esophageal cancer in African Americans and diagnosed in late stages, and its diagnosis in our institution has decreased since 1990. A combination of genetic factors, environmental influences (e.g., those related to diet), and the deleterious changes associated with smoking and alcohol consumption, and differences in tumor histology, are the obvious parameters that should be the focus of future studies, and early diagnosis at an earlier stage should be considered among blacks. [ABSTRACT FROM AUTHOR]

Background: Recent case reports suggested a link between oral bisphosphonate use and esophageal cancer. We therefore examined the association between these medications and the risk of esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE).Design: This was a nested, matched case-control study. Cases with incident EAC at least 6 months following BE index date were matched by incidence density sampling to controls with BE without EAC. Patients with BE were found in the national Department of Veterans Affairs computerized databases, and each filled prescriptions for oral bisphosphonates between BE diagnosis and EAC diagnosis (or corresponding dates in controls). Incidence density ratios were calculated using conditional logistic regression models.Results: In a cohort of 11,823 patients with BE, we compared 116 cases and 696 controls. Most were men (97%). Most cases and controls had at least one filled proton pump inhibitor (PPI) prescription (95 vs. 94%, P = 0.5). Filled bisphosphonate prescriptions were very uncommon (1.7 vs. 1.9%) and were not associated with EAC; the incidence density ratio was 0.92 (95% CI, 0.21-4.15).Conclusion: In patients with BE, oral bisphosphonates were not associated with an increased risk of EAC. [ABSTRACT FROM AUTHOR]

Background: It is not known whether there have been recent changes in demographic or clinical characteristics among patients newly diagnosed with Barrett's esophagus (BE), which could be a result of changes in disease epidemiology or of screening or surveillance effects, and could have clinical implications.Aims: The aim of this study was to determine whether there has been a shift in age at diagnosis of BE over the past decade. Secondary aims were to determine whether there has been a shift in patient body mass index (BMI) or BE segment length.Methods: An endoscopic database at a tertiary medical center was used to identify all esophagogastroduodenoscopies (EGDs) performed between 1997 and 2007. The cohort was restricted to patients newly diagnosed with BE. Pathology records were reviewed to confirm biopsy findings of intestinal metaplasia (IM).Results: BE was diagnosed in 378 subjects between 1997 and 2007. Mean age at diagnosis of BE was 60.7 +/- 14.1 years, with mean BMI of 27.4 +/- 5.2 kg/m(2) and mean BE segment length of 4.7 +/- 3.7 cm. Between 1997 and 2007 there was no significant change in mean age at diagnosis, BMI, BE segment length or in proportion of men versus women newly diagnosed.Conclusions: Despite an increase in volume of EGDs performed in an open-access endoscopy unit between 1997 and 2007, there was no appreciable shift in age at diagnosis of BE. BMI and BE segment length among newly diagnosed patients also remained stable over this time period. [ABSTRACT FROM AUTHOR]

Esophageal adenocarcinoma (EAC), one of the fastest growing cancers in the United States, is increasingly recognized in younger patients in whom the clinicopathologic features have been poorly described. We aim to compare clinical presentation between early (i.e.,

The epidemiology of esophageal squamous cell cancer has remained poorly understood. The occupational distribution of this cancer may provide clues about its yet unknown etiology. Data files from the National Center for Health Statistics (NCHS) of the United States offer a unique source to study causes of death, broken down by occupation and industry. The number of deaths from esophageal cancer was retrieved from the computerized US vital statistics. Mortality by occupation or industry was expressed as standardized proportional mortality ratio (PMR), adjusted by age, gender, and ethnicity. Between 1991 and 1996, 63,717 subjects died from esophageal squamous cell carcinoma. Mortality was particularly high among nonwhites and men. The industrial and the occupational distributions shared a similar pattern. Mortality from esophageal squamous cell carcinoma occurred more frequently among subjects exposed to silica dust, such as brickmasons and stonemasons, concrete and terrazzo finishers, roofers, and construction laborers. It was also high in such industries as unspecified machinery or manufacturing and such occupations as unspecified material handlers, janitors, or cleaners. It was low in industries and occupations associated with agriculture, clergy, work in religious organizations, and textiles. In conclusion, mortality from esophageal squamous cell carcinoma appeared to be low in occupations associated with less consumption of alcohol and tobacco. It was high among occupations potentially associated with exposure to silica dust and chemical solvents or detergents. [ABSTRACT FROM AUTHOR]

Esophageal adenocarcinoma is increasing in incidence and has a high mortality unless detected early. Barrett's esophagus is the only known risk factor for this cancer; however, whether endoscopic surveillance reduces morbidity and mortality is controversial. Endoscopic cancer surveillance programes for Barrett's esophagus are not routinely practiced in the UK, and this is the first study to examine whether a rigorous surveillance protocol increases the detection rate of early oesophageal cancer. All patients with a diagnosis of Barrett's esophagus or associated adenocarcinoma attending Havering Hospitals NHS Trust between 1992 and 1998 were included. A retrospective analysis was made of patients undergoing informal surveillance (96 patients, 1992-1997) and a prospective analysis was conducted following the implementation of a rigorous protocol (108 patients, 1997-1998). Over the same time periods Barrett's associated cancers diagnosed in patients not undergoing surveillance were analyzed (262 patients 1992-1997, 98 patients 1997-1998). From 1992 to 1997, one case of high-grade dysplasia was detected (N = 96, 1%). From 1997 to 1998, two cancers and three high-grade dysplasias were detected during rigorous surveillance (N = 108, 4.6%). Three of these patients have had curative esophagectomies (one high-grade dysplasia and two T1,N0,M0 tumors). In 1992-1997, 10 patients were found to have cancer in previously undiagnosed Barrett's esophagus (N = 262, 3.8%). Of 3/10 cancers treated surgically, one patient had a curative procedure (T1,N0,M0). In 1997-1998, nine patients were found to have de novo Barrett's esophagus cancer (N = 88, 10.2%) and three had curative resections (T1,N0,M0). Two of the patients with T1 lesions had no endoscopic evidence of cancer but were detected as a result of the multiple biopsy protocol. In conclusion, a rigorous biopsy protocol increases the detection of early cancer in Barrett's esophagus. [ABSTRACT FROM AUTHOR]

Our purpose was to evaluate the relationship between the clinical and histological features in a cohort of patients who had gastroesophageal reflux-related lesions diagnosed after upper digestive endoscopy. In all, 589 patients scheduled for elective endoscopy in a multicentric prospective study were evaluated. Multiple biopsies from the distal esophagus showing aspects of esophagitis or metaplastic epithelium were taken. Esophagitis was histologically detected in 25.6%, gastric-type Barrett's esophagus in 36.2%, and specialized columnar epithelium in 33.1%. The frequency of esophagitis was constant across age decades. Patients with specialized columnar epithelium were significantly older (P = 0.01) and had a greater extent of metaplastic epithelium (P<0.0001). Specialized columnar epithelium was observed in 15% of patients with only distal esophagitis. In conclusion, endoscopic esophagitis was constant across age strata. The presence of specialized columnar epithelium was associated with older age and with longer segments of Barrett's esophagus. Short areas of esophagitis should be biopsied in view of their potential for holding areas of specialized columnar epithelium. [ABSTRACT FROM AUTHOR]