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There are 5 to 6 levels of biomarker validation. Those for Barrett's esophagus are currently at level 3, despite small prospective studies. What is ideally required is a very large prospective assessment of biopsies in large cohorts, such as the ASPirin Esomeprazole Chemoprevention Trial (AspECT) and Barrett's Oesophagus Surveillance Study (BOSS) trials, so that unbiased and random selection of cases can be subjected to rigorous pathology and biomarker assessment (level 4). Only then can the predictive power of the data be exploited in a randomized intervention trial (level 5) whereby a series of biomarkers would trigger therapy. The real trouble is that this spot is currently occupied, satisfactorily according to some researchers, by conventional histological identification of high-grade dysplasia (HGD) as used in a recent randomized study of ablation in Barrett's esophagus (BE). [ABSTRACT FROM AUTHOR]

Gastric acid is believed to be an important etiological factor in the pathogenesis of Barrett's esophagus. Pulsatile acid exposure increases cell proliferation in ex vivo Barrrett's tissue and normalization of esophageal pH reverses this. Proton pump inhibitors (PPIs) are the mainstay of therapy in Barrett's esophagus, and have numerous beneficial effects including symptom control, reduction of inflammation, and promotion of the development of squamous islands. However, PPI therapy causes hypergastrinemia and has not prevented recent increase in the incidences of esophageal cancer. Additionally, evidence presented here by Feagins et al. suggests that acid exposure has a p53-mediated, antiproliferative effect on a nondysplastic Barrett's epithelial cell line, an effect that acid suppression might abrogate. These complex pH, inflammation, and growth factor biological interactions can be most reliably tested in large clinical trials with hard end points like cancer conversion or all causes of mortality. Combining the anti-inflammatory effects of acid suppression with aspirin, a nonsteroidal anti-inflammatory agent, is the subject of the AspECT clinical trial, and this may be the future of chemoprevention in Barrett's. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Barrett's esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD).METHODS:We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations.RESULTS:In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients.CONCLUSIONS:In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research. [ABSTRACT FROM AUTHOR]

The article offers information on several aspects of the periodical "American Journal of Gastroenterology" which includes previous publications, relation with the organization American College of Gastroenterology, and current and new members of the periodical. It mentions publication of immense data related to low-grade inflammation and immune response which causes gastrointestinal disorders. It highlights several new members including Peter Kahrilas, Peter Gibson and Phil Katz.

Barrett's esophagus (BE) is a common lesion that predisposes to a highly fatal esophageal adenocarcinoma (EA). There is evidence that BE or parts of its phenotype are genetically predisposed. Several single-nucleotide polymorphisms (SNPs) have been validated as predisposing to BE but the inherent flaws in the trial sizes, presence of controls and statistical power need circumspect analysis. The current paper links the interleukin 18 cytokine with BE and perhaps EA. Setting aside the issues above there are other issues such as the functional relevance of these SNPs for the association BE. There have been several case control series published indicating other genes. Furthermore, there are some sibling pairs study results with another set of genes identified. Invariably as useful as these studies are the size, scale to answer complex questions (complexity) and potential clinical significance are proportional in genomic studies. The new era of large-scale genome-wide studies in Barrett's and EA is needed. Shortly the first will be published showing two SNPs of significance in 7,838 Barrett's patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess the variation in practice of Barrett's esophagus (BE) management in comparison with accepted international guidelines before and after the introduction of a large BE randomized controlled trial (RCT) with protocols including those of tissue sampling. DESIGN: A validated anonymized questionnaire was sent to 401 senior attending gastroenterologists asking for details of their current management of BE, especially histological sampling. Of the 228 respondents, 57 individuals (each from a different center) were in the first group to enter the ASPirin Esomeprazole (BE) Chemoprevention Trial (AspECT), and we assessed change in practice in these centers. RESULTS: Ninety percent of specialists did not take adequate biopsies for histological diagnosis. Furthermore, 74% would consider aggressive surgical resection for prevalent cases of high-grade dysplasia in BE as their first-line choice despite the associated perioperative mortality. Ninety-two percent claim their lack of adherence to guidelines is because there is a need for stronger evidence for surveillance and medical interventions. Effect of the AspECT trial: Those clinicians in centers where the AspECT trial has started have improved adherence to ACG guidelines compared with their previous practice ( P < 0.05). BE patients now get 18.8% more biopsies compared with previous practice, and 37.7% if the patient is entered into the AspECT trial ( P < 0.01). CONCLUSIONS: This large study indicates both wide variation in practice and poor compliance with guidelines. Because optimal histology is arguably the most important facet of BE management, the improvement in practice in centers taking part in the AspECT trial indicates an additional value of large international RCTs. [ABSTRACT FROM AUTHOR]

Hereditary diffuse gastric cancer and tylosis are autosomal dominant cancer susceptibility syndromes. Accumulating evidence also suggests a genetic contribution to Barrett's esophagus and adenocarcinoma, traditionally considered acquired disorders. In this article we review the current knowledge on the genetic mechanisms underlying hereditary diffuse gastric cancer, tylosis, and Barrett's esophagus. Hereditary diffuse gastric cancer is a paradigm for hereditary cancer susceptibility syndromes with E-cadherin implicated as the dominant oncogene in up to one-third of cases. Tylosis in contrast remains the paradox as whilst the putative abnormality has been localized to the long arm of chromosome 17, sequencing of this region has failed to reveal a disease causing mutation. In the case of Barrett's esophagus and adenocarcinoma, although a validated specific disease-associated gene is yet to be identified, the increasing body of evidence of a possible genetic link is paving the way for subsequent prognostic studies such as AspECT (Aspirin Esomeprazole Chemoprevention Trial). For the clinician these advances in understanding are already having implications for practice in terms of improved screening and the stratification of management strategies. As the mechanisms continue to be defined, there is the real possibility that these mechanisms could be exploited or subverted in the design of new therapies. In the meantime, however, clinicians should undertake rigorous biopsy programs to ensure early invasive lesions are detected. [ABSTRACT FROM AUTHOR]

The article discusses the factors concerning the pathogenesis of pancreatic cancer. It is stated that genetic aspect is often associated to the invasion of pathogens. Here, it highlights the difficulties in recognizing pancreatic-cancer prone families such as deleterious mutation, phenotypic expression as well as environmental exposures to cancer-causing agents.

OBJECTIVES: A globally acceptable definition and classification of gastroesophageal reflux disease (GERD) is desirable for research and clinical practice. The aim of this initiative was to develop a consensus definition and classification that would be useful for patients, physicians, and regulatory agencies. METHODS: A modified Delphi process was employed to reach consensus using repeated iterative voting. A series of statements was developed by a working group of five experts after a systematic review of the literature in three databases (Embase, Cochrane trials register, Medline). Over a period of 2 yr, the statements were developed, modified, and approved through four rounds of voting. The voting group consisted of 44 experts from 18 countries. The final vote was conducted on a 6-point scale and consensus was defined a priori as agreement by two-thirds of the participants. RESULTS: The level of agreement strengthened throughout the process with two-thirds of the participants agreeing with 86%, 88%, 94%, and 100% of statements at each vote, respectively. At the final vote, 94% of the final 51 statements were approved by 90% of the Consensus Group, and 90% of statements were accepted with strong agreement or minor reservation. GERD was defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. The disease was subclassified into esophageal and extraesophageal syndromes. Novel aspects of the new definition include a patient-centered approach that is independent of endoscopic findings, subclassification of the disease into discrete syndromes, and the recognition of laryngitis, cough, asthma, and dental erosions as possible GERD syndromes. It also proposes a new definition for suspected and proven Barrett's esophagus. CONCLUSIONS: Evidence-based global consensus definitions are possible despite differences in terminology and language, prevalence, and manifestations of the disease in different countries. A global consensus definition for GERD may simplify disease management, allow collaborative research, and make studies more generalizable, assisting patients, physicians, and regulatory agencies. [ABSTRACT FROM AUTHOR]

Presents a list of authors who assisted the previous issue of the "American Journal of Gastroenterology."

A letter to the editor about gastic necrosis caused by growing pancreatic pseudocyst is presented.

A letter to the editor about sickle cell trait (SCT) is presented.

A letter to the editor is presented in response to an article about Barrett's esophagus in the May 2008 issue.

The incidence of esophageal adenocarcinoma continues to increase at a rate greater than that of any other cancer in the western world. Current strategies to deal with this situation are problematic, and the time has come for new approaches to this problem. Chemoprevention is one such approach. In this issue of the American Journal of Gastroenterology, Hur et al. examined Barrett's esophagus patient preferences for cancer chemoprevention with either aspirin or celecoxib. They found that 93% of their patients were willing to take one of these two drugs, but that nearly five times as many patients preferred aspirin to celecoxib (76% vs 15%). The most important reason for willingness to use celecoxib or aspirin was cancer prevention, while the most important reason for not using celecoxib was risk of myocardial infarction and for aspirin gastrointestinal adverse events. While this study indicates that there is a strong interest among Barrett's esophagus patients for chemoprevention, it is still premature for our patients to embark on such an approach. The role of chemoprevention in Barrett's esophagus still awaits the results of ongoing clinical trials in the United Kingdom and North America. [ABSTRACT FROM AUTHOR]

A response by Debasish Das and colleagues to a letter to the editor about their article on Barrett's esophagus is presented.

A letter to the editor about tobacco smoking in ulcerative colitis (UC) is presented.

A letter to the editor is presented in response to an article about gastrointestinal (GI) bleeding complications in patients with acute coronary syndromes (ACS).

A letter to the editor about infliximab in atypical pyoderma gangrenosum associated with ulcerative colitis is presented.

A letter to the editor about oral Crohn's disease is presented.

A letter to the editor is presented in response to an article about endoscopic diagnosis of adenocarcinoma.

A letter to the editor about impaired inactivation of digestive protease is presented.

A letter to the editor is presented in response to an article about endoscopic celiac plexus blockade.

A letter to the editor about bleeding colonic ulcer caused by invasive mold infection is presented.

A letter to the editor is presented in response to an article about the use of rectosigmoid biopsies for diagnosing graft-versus-host disease.

A response by Nicholas J. Talley to a letter to the editor about his article about rectal examination is presented.

A letter to the editor is presented in response to an article about gastroenterology research.

A response by Mitchell S. Cappell and Michael Davis to a letter to the editor about their article on gastroenterology research in the April 2008 issue is presented.

A response by Mitchell S. Cappell and Michael Davis to a letter to the editor about their article on gastroenterology in the April 2008 issue is presented.

A correction to the article "Oral Prolonged Release Beclomethasone Dipropionate and Prednisone in the Treatment of Active Ulcerative Colitis: Results From a Double-Blind, Randomized, Parallel Group Study" that was published in the journal in 2015 is presented.

A correction to the article "BOB CAT: A Large-Scale Review and Delphi Consensus for Management of Barrett's Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia" that was published in the journal in 2015 is presented.

A letter to the editor is presented in response to the article about rectal examination in gastroenterology.

A letter to the editor is presented in response to an article about farnesoid X receptors in Barrett's esophagus.

A response by Nicholas J. Talley to a letter to the editor about his article on the management of patients with early prostate cancer is presented.

A letter to the editor is presented in response to an article about rectal examination.

A letter to the editor is presented in response to an article about gastroenterology research.