Metaplastic Columnar Epithelium Research Articles

On-chip Raman spectroscopy of live single cells for the staging of oesophageal adenocarcinoma progression.

The absence of early diagnosis contributes to oesophageal cancer being the sixth most common cause of global cancer-associated deaths, with a 5-year survival rate of < 20%. Barrett's oesophagus is the main pre-cancerous condition to adenocarcinoma development, characterised by the morphological transition of oesophageal squamous epithelium to metaplastic columnar epithelium. Early tracking and treatment of oesophageal adenocarcinoma could dramatically improve with diagnosis and monitoring of patients with Barrett's Oesophagus. Current diagnostic methods involve invasive techniques such as endoscopies and, with only a few identified biomarkers of disease progression, the detection of oesophageal adenocarcinoma is costly and challenging. In this work, single-cell Raman spectroscopy was combined with microfluidic techniques to characterise the development of oesophageal adenocarcinoma through the progression of healthy epithelial, Barrett's oesophagus and oesophageal adenocarcinoma cell lines. Principal component analysis and linear discriminant analysis were used to classify the different stages of cancer progression. with the ability to differentiate between healthy and cancerous cells with an accuracy of 97%. Whilst the approach could also separate the dysplastic stages from healthy or cancer with high accuracy-the intra-class separation was approximately 68%. Overall, these results highlight the potential for rapid and reliable diagnostic/prognostic screening of Barrett's Oesophagus patients.

Letter to Editor "Barret’s Esophagus Screening: An Inevitable Urge For Gastroenterologists"

The presence of benign esophageal diseases including gastroesophageal reflux disease, barrets esophagus,hiatal hernia and achalasia have been arousing the curiosity of young clinicians , scientists and researchers for decades and years to follow.1 Dyspepsia is one of the most common symptoms experienced by the patients and witnessed by the doctors during routine clinical consultations. This does accompany regurgitation of food, bad taste in mouth early morning, chest pain and sometimes alarm symptoms including hematemesis, malena, unintentional weight loss and dysphagia.That is the point where one has to rethink and diagnosis treatment strategies and review patients accordingly.2&#x0D; Barrett’s oesophagus is defined as ‘an oesophagus in which any portion of the normal squamous lining has been replaced by metaplastic columnar epithelium. Barrets esophagus is a benign condition with a potential to transform to oesophageal carcinoma.3 There is a long history gastroesopheal reflux disease symptoms. In our country there is a trend of self medicating oneself before coming to any physician in the general practice who also treats the patients for years before referral to gastroenterologist who can think out of the box and do invasive investigations like endoscopy, CT chest and non invasive one like barium swallow. Most of the people ponder over when is right moment for screening the patients for Barrets esophagus and Esophageal Cancer Screening. A lot depends on the biopsy report and its findings in terms of having low grade, indefinite for dysplasia and high grade dysplasia.4&#x0D; Low grade dysplasia in terms of surveillance carries less significance in which the guidelines suggest the time interval can be enhanced to 2-3 years in case of permanent regression with proton pump inhibitors given for 8 weeks The high grade dysplasia is an alarm finding for any gastroenterologist requirement more aggressive screening and management as there is a 30-40% risk of oesophageal carcinoma.5 This will need discussion by multidisciplinary teams including gastroenterologists, oncologists and pathologists as well.5&#x0D; There is usage of proton pump inhibitors for years by the patients that is itself a risk factor for complications such as atrophic gastritis, pernicious anaemia, osteoporosis and even cancer.6 The resistance of symptoms to standard and even high doses of proton pump inhibitors is an indication for endoscopy as well. The role of PPI in asymptomatic patients is not substantiated by enough evidence in the literature However, in clinical practice, most patients are advised long term PPI based on the premise that chronic acid exposure may contribute towards Barrett’s Esophagus.6 So the bottom line is that there should be no hesitation in expediting the referral of such patients for urgent gastroenterology consultation who may do subsequent endoscopy after thorough examination of the patients.&#x0D; American Gastroenterological Association has strong recommendations for screening for Barrett oesophagus in patients older than 50 years with symptomatic GERD and at least one additional risk factor for oesophageal adenocarcinoma.7 Almost similar guidelines have been formulated by other reputed societies as well including British Society Of Gastroenterology. There is a phobia of endoscopies in general public and they are reluctant to do them. But once the indication is clear then the patient should be counselled thorough as in case of oesophageal cancer for which a Barrets Oesophagus is a risk factor, early diagnosis is the key as surgery is curative. Indeed it is and should be irresistible urge for gastroenterologists to screen such patients.7

Barrett's Esophagus: An Updated Review.

Barrett's esophagus (BE) is a change in the distal esophageal mucosal lining, whereby metaplastic columnar epithelium replaces squamous epithelium of the esophagus. This change represents a pre-malignant mucosal transformation which has a known association with the development of esophageal adenocarcinoma. Gastroesophageal reflux disease is a risk factor for BE, other risk factors include patients who are Caucasian, age &gt; 50 years, central obesity, tobacco use, history of peptic stricture and erosive gastritis. Screening for BE remains selective based on risk factors, a screening program in the general population is not routinely recommended. Diagnosis of BE is established with a combination of endoscopic recognition, targeted biopsies, and histologic confirmation of columnar metaplasia. We aim to provide a comprehensive review of the epidemiology, pathogenesis, screening and advanced techniques of detecting and eradicating Barrett's esophagus.

Trefoil factor 1 inhibits the development of esophageal adenocarcinoma from Barrett's epithelium

AbstractTrefoil factor family 1 (TFF1) is one of three members of the trefoil factor family that are abundantly expressed in the gastrointestinal mucosal epithelium. Recent studies have shown that TFF1 acts as a tumor suppressor in gastric, pancreatic and hepatocellular carcinogenesis; however, little is known about its function in esophageal carcinogenesis, especially in esophageal adenocarcinoma (EAC). Barrett's epithelium is the metaplastic columnar epithelium of the esophagus and a known premalignant lesion of EAC. To investigate the role of TFF1 in EAC development, a mouse model of Barrett's epithelium was employed, and human specimens of EAC were assessed by immunohistochemistry (IHC) and methylation-specific PCR. Wild-type (WT) mice underwent gastrojejunostomy on the forestomach, resulting in the development of Barrett's epithelium-like (BE-like) epithelium adjacent to the anastomotic site. BE-like epithelium in these mice expressed TFF1, indicating the association of TFF1 with esophageal adenocarcinoma. TFF1-knockout (TFF1KO) mice underwent the same procedure as well, revealing that a deficiency in TFF1 resulted in the development of adenocarcinoma in the anastomotic site, presumably from BE-like epithelium. IHC of human samples revealed strong TFF1 expression in Barrett's epithelium, which was lost in some EACs, confirming the association between TFF1 and EAC development. Aberrant DNA hypermethylation in TFF1 promoter lesions was detected in TFF1-negative human EAC samples, further confirming not only the role of TFF1 in EAC but also the underlying mechanisms of TFF1 regulation. In addition, IHC revealed the nuclear translocation of β-catenin in human and mouse EAC, suggesting that activation of the Wnt/β-catenin pathway was induced by the loss of TFF1. In conclusion, these results indicate that TFF1 functions as a tumor suppressor to inhibit the development of esophageal carcinogenesis from Barrett's epithelium.

MO43-1 Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) and associated risk of Barrett's esophagus: A systematic review

Barrett's esophagus (BE) is a condition characterized by conversion of normal squamous epithelium into metaplastic columnar epithelium. Individuals with BE are predisposed to esophageal adenocarcinoma, a cancer with high morbidity and mortality. Aspirin and other NSAIDs have been suggested to protect against esophageal adenocarcinoma. The aim of this study is to evaluate the risk of developing Barrett's esophagus with aspirin or other NSAIDs intake.

Identification of miRNAs and genes for predicting Barrett's esophagus progressing to esophageal adenocarcinoma using miRNA-mRNA integrated analysis.

Barrett’s esophagus (BE) is defined as any metaplastic columnar epithelium in the distal esophagus, which predisposes to esophageal adenocarcinoma (EAC). Yet, the mechanism through which BE develops to EAC still remain unclear. Moreover, the miRNA-mRNA regulatory network in distinguishing BE from EAC still remains poorly understood. To identify differentially expressed miRNAs (DEMs) and genes (DEGs) between EAC and BE from tissue samples, gene expression microarray datasets GSE13898, GSE26886, GSE1420 and miRNA microarray datasets GSE16456, GSE20099 were downloaded from Gene Expression Omnibus (GEO) database. GEO2R was used to screen the DEMs and DEGs. Pathway and functional enrichment analysis were performed by DAVID database. The protein–protein interaction (PPI) network was constructed by STRING and been visualized by Cytoscape software. Finnal, survival analysis was performed basing TCGA database. A total of 21 DEMs were identified. The enriched functions and pathways analysis inclued Epstein-Barr virus infection, herpesvirus infection and TRP channels. GART, TNFSF11, GTSE1, NEK2, ICAM1, PSMD12, CTNNB1, CDH1, PSEN1, IL1B, CTNND1, JAG1, CDH17, ITCH, CALM1 and ITGA6 were considered as the hub-genes. Hsa-miR-143 and hsa-miR-133b were the highest connectivity target gene. JAG1 was predicted as the largest number of target miRNAs. The expression of hsa-miR-181d, hsa-miR-185, hsa-miR-15b, hsa-miR-214 and hsa-miR-496 was significantly different between normal tissue and EAC. CDH1, GART, GTSE1, NEK2 and hsa-miR-496, hsa-miR-214, hsa-miR-15b were found to be correlated with survival.

Nitric oxide could promote development of Barrett's esophagus by S-nitrosylation-induced inhibition of Rho-ROCK signaling in esophageal fibroblasts.

Barrett's esophagus arises in the process of wound healing in distal esophageal epithelium damaged by gastroesophageal reflux disease. Differentiation of fibroblast into myofibroblasts, a smooth muscle cell-like phenotype and tissue contraction are crucial processes in wound healing. No study has evaluated mechanism by which luminal esophageal nitric oxide (NO) affect Rho-associated coiled coil-forming protein kinase (Rho-ROCK) signaling pathway, a key factor of tissue contraction, in stromal fibroblasts to develop Barrett's esophagus. Using esophageal fibroblasts, we performed collagen-based cell contraction assays and evaluated influence of Rho-ROCK signaling in the exposure to acidic bile salts and NOC-9, which is an NO donor. We found that enhanced cell contraction induced by acidic bile salts was inhibited by NO, accompanied by decrease in phosphorylated myosin light chain expression and stress fiber formation. NO directly S-nitrosylated GTP-RhoA and consequently blocked Rho-ROCK signaling. Moreover, exposure to NO and Y27632, a Rho-ROCK signaling inhibitor, decreased α-SMA expression and increased bone morphogenetic protein-4 (BMP4) expression and secretion. These findings could account for the increased expression of BMP4 in the columnar epithelial cells and stromal fibroblasts in human Barrett's esophagus. NO could impair wound contraction by blocking the Rho-ROCK signaling pathway and promote the development of Barrett's esophagus.NEW & NOTEWORTHY Barrett's esophagus is the condition where esophageal epithelium damaged by gastroesophageal reflux disease (GERD) is abnormally healed via replacing of metaplastic columnar epithelium, but very few studies have conducted focusing wound healing in the development of Barrett's esophagus. Esophageal luminal nitric oxide inhibits Rho-ROCK signaling pathway in esophageal fibroblasts, which leads to delay tissue contraction, a pivotal step in proper wound healing. Moreover, this inhibition increases tissue BMP4 expression. Impaired wound healing could be related to Barrett's esophagus.

Evaluation of autologus platelet-rich plasma versus silver nitrate in the treatment of cervical erosion

Background Cervical erosion is identified by the existence of columnar cells on the ectocervix rather than on the squamous epithelium. Adolescent age, pregnancy, and hormonal contraception are all causes of erosion. Some doctors think erosion is a typical asymptomatic variation, while others believe it is caused by persistent cervicitis. Metaplastic columnar epithelium may cause a variety of symptoms such as vaginal discharge, leukorrhea, postcoital bleeding, pelvic discomfort, and dyspareunia. Laser ablation, microwave ablation, platelet-rich plasma (PRP) injections, herbal treatments, and cryosurgery have all been reported as therapeutic options. Aim Evaluating the therapeutic effect of applying an autologous PRP in cervical erosion versus chemical cautery with silver nitrate. Patients and methods Randomized controlled clinical study on 100 patients at the outpatient clinic of the Obstetrics and Gynecology Department, Faculty of Medicine, Tanta University Hospitals. A total of 50 patients was assigned as the PRP group), the study group, while the other was the silver nitrate group. Follow-up visits occurred on the 1st, 2nd, 4th, 6th, 8th, 10tht, and 12th week posttreatment for the lesion size changes, symptom relief, postprocedure discomfort, pain, and long-term complications. Results PRP and silver nitrate are now being used to treat symptomatic patients with cervical erosion. Because it resulted in a faster tissue healing time and fewer complications, autologous PRP has the potential to replace alternative unpleasant treatment options such as cautery, with promising results for inflamed and injured cervical tissue with erosion repair. Conclusion PRP shows no immunogenic difficulty or ethical matters as autologous. It stops damage to the cervix and hence prevention from cervical cancer.

Evaluation of Barrett's Esophagus

AbstractBarrett's esophagus (BE) is the condition in which a metaplastic columnar epithelium that is predisposed to malignancy replaces the stratified squamous epithelium that normally lines the distal esophagus. BE develops as a consequence of chronic gastroesophageal reflux disease and predisposes to esophageal adenocarcinoma (EAC). Several societal guidelines recommend screening and surveillance for BE to reduce the risk of EAC and its related morbidity and mortality. Even among persons undergoing screening and surveillance, a substantial proportion of cases of EAC can be missed. Consequently, the armamentarium for the evaluation of BE has expanded rapidly over the past decade. In this article, we summarize the pathophysiology and diagnosis of BE. We also discuss the latest advancements in the evaluation of BE.

The evolution of endoscopic therapy for Barrett's esophagus.

Barrett’s esophagus is the condition in which a metaplastic columnar epithelium replaces the stratified squamous epithelium that normally lines the distal esophagus. The condition develops as a consequence of chronic gastroesophageal reflux disease and predisposes the patient to the development of esophageal adenocarcinoma. The diagnosis and management of Barrett’s esophagus have undergone dramatic changes over the years and continue to evolve today. Endoscopic eradication therapy has revolutionized the management of dysplastic Barrett’s esophagus and early esophageal adenocarcinoma by significantly reducing the morbidity and mortality associated with the prior gold standard of therapy, esophagectomy. The purpose of this review is to highlight current principles in the management and endoscopic treatment of this disease.

Biological markers of Barrett’s esophagus progression to adenocarcinoma

Barrett’s esophagus (BE) is a condition in which a stratifi ed squamous epithelium of the distal esophagus is replaced with a metaplastic intestinal-type columnar epithelium. BE is a precancerous condition associated with an increased risk of esophageal adenocarcinoma (EA). Current clinical practice guidelines recommend endoscopic surveillance with histological examination of esophageal biopsies for early detection of the EA. Epithelial dysplasia is the only clinically meaningful indicator of the risk for development carcinoma in BE, which is now used in practice. The existing limitations of this approach require new tools for the detection of early neoplastic disorders in BE and additional criteria to assess a risk for their progression. Within the framework of this review, the most signifi cant genetic and molecular indicators that can claim the role of diagnostic or predictive biological markers in BE are considered.

In reply: Barrett esophagus: Definition, treatment

Dr. Lai points out that the broader definition of Barrett esophagus can include the presence of metaplastic columnar epithelium that replaces the normal stratified squamous epithelium in the distal esophagus. Guidelines of both the American College of Gastroenterology[1][1] and the American

2867 Barrett's Esophagus Screening: A Survey of Primary Care Physicians to Assess Knowledge Gaps

INTRODUCTION: Barrett’s esophagus (BE) is a condition in which metaplastic columnar epithelium with goblet cells replaces the stratified squamous epithelium normally found in the distal esophagus. It is a precursor for esophageal adenocarcinoma (EAC), however screening for BE remains a controversial topic and any guidelines that exist may not be well known among primary care physicians (PCPs). The transformation from nondysplastic BE to EAC has a slow rate of progression, giving screening for BE the potential to identify patients earlier via endoscopic visualization and confirmatory biopsy. A prior study found that less than 5% of patients undergoing resection for EAC had a prior diagnosis of BE, 1 indicating potential missed opportunities for screening of appropriate patients. Newer data recommends selective screening via stratification of patients based on risk factors. PCPs are often a patients first line of contact within the healthcare system; therefore, they should have an thorough understanding of the risk factors for BE and be comfortable in identifying appropriate patients to refer for screening. METHODS: We conducted a survey of PCPs (n = 63) at a large urban university hospital. The survey consisted of eight questions regarding risk factors, screening recommendations and physician comfort in identifying appropriate patients for BE screening. RESULTS: Collectively, PCPs scored 60%, suggesting a significant lack of knowledge regarding BE, with only 13% of participants answering all questions correctly. In regards to identifying risk factors, only 25% answered correctly. 41% of respondents indicated they are comfortable identifying appropriate patients for screening. Comfortability was assessed on a scale of 1-5, with 1 being not comfortable at all. The average response was 3.02, reflecting neutrality in physician comfort. CONCLUSION: Our survey found that knowledge of risk factors among PCPs may be inadequate. Additionally, PCPs acknowledge they are not comfortable identifying appropriate patients for screening. This may stem from not being familiar with known risk factors or not being up to date with screening guidelines. Those in practice longer said they are more comfortable, however were not more knowledgeable in risk factors and screening guidelines, indicating that increased education is necessary throughout a physician's career. 1. Dulai, Gareth S., et al. "Preoperative prevalence of Barrett's esophagus in esophageal adenocarcinoma: a systematic review." Gastroenterology (2002): 26-33.

Z-line alterations and gastroesophageal reflux: an endoscopic population-based prospective cohort study

Background and study aims: Barrett's esophagus is a premalignant condition in the distal esophagus associated with esophageal adenocarcinoma. Since gastroesophageal reflux is known to be of etiological importance in both Barrett's esophagus and esophageal adenocarcinoma, we aimed to study which endoscopic alterations at the Z-line can be attributed to a previous history of reflux symptoms.Patients and methods: From 1988, a population cohort in Sweden has been prospectively studied regarding gastrointestinal symptoms, using a validated questionnaire. In 2012, the population was invited to undergo a gastroscopy and participate in the present study. In order to determine which endoscopic alterations that can be attributed to a previous history of gastroesophageal reflux, three different endoscopic definitions of columnar-lined esophagus (CLE) were used: (1) ZAP I, An irregular Z-line with a suspicion of tongue-like protrusions; (2) ZAP II/III, Distinct, obvious tongues of metaplastic columnar epithelium; (3) CLE ≥1 cm, The Prague C/M-classification with a minimum length of 1 cm.Results: A total of 165 community subjects were included in the study. Of these, 40 had CLE ≥ 1 cm, 99 had ZAP I, and 26 had ZAP II/III. ZAP II/III was associated with an over threefold risk of previous GER symptoms (OR: 3.60, CI: 1.49–8.70). No association was found between gastroesophageal reflux and ZAP I (OR: 2.06, CI: 0.85–5.00), or CLE ≥1 cm (OR: 1.64, CI: 0.77–3.49).Conclusions: In a general community, the only endoscopic alteration to the Z-line definitely linked to longstanding GER symptoms was the presence of obvious tongues of metaplastic columnar epithelium (ZAP II/III).

Role of Kruppel-Like Factor 5 in Deoxycholic Acid-Mediated Intestinal Transdifferentiation of Esophageal Squamous Epithelium.

Barrett's esophagus (BE) is an acquired condition in which normal squamous epithelium is replaced with metaplastic columnar epithelium as a consequence of gastroesophageal reflux disease. BE is known as a precursor of esophageal adenocarcinoma. Currently, the molecular mechanism underlying epithelial metaplasia in BE patients remains unknown. Therefore, we investigated the role of Krüppel-like factor 5 (KLF5) signaling in the initiation of BE-associated metaplasia. Sprague-Dawley (SD) rats were used to create a surgical model of bile reflux injury. Immunohistochemistry was performed to analyze human and mouse esophageal specimens. Human esophageal squamous epithelial (HET-1A) cells were treated with bile acid and used in transfection experiments. Quantitative real-time PCR and western blot analysis were performed to detect the expression of KLF5, CDX2, MUC2 and villin.Epithelial tissue from both the rat BE model and human BE patients strongly expressed KLF5, CDX2, MUC2, and villin. Bile acid treatment also increased the expression of KLF5, CDX2, MUC2 and villin in esophageal epithelial cells in a time-dependent manner. Moreover, siRNA-mediated knockdown of KLF5 blocked the expression of CDX2, MUC2 and villin, but transfection of a KLF5 expression vector into esophageal epithelial cells promoted their transdifferentiation into columnar-like cells, as demonstrated by increased expression of the intestinal markers CDX2, MUC2 and villin. Thus, in addition to its function as a transcription factor, KLF5 may be linked to an increased risk of BE development.

Barrett's Esophagus: A Molecular Overview.

Barrett’s esophagus (BE) is an asymptomatic condition of the distal esophagus that can progress to aggressive adenocarcinoma of the esophagus. Although BE is not malignant, the amount of deoxyribonucleic acid (DNA) damage is comparable to some malignancies such as melanoma and breast carcinoma. The purpose of this literature review is to evaluate the anomalies that underlie the transformation of the normal stratified squamous epithelium of the esophagus into metaplastic columnar epithelium with a potential of progressing into esophageal adenocarcinoma based on an appraisal and scrutiny of the literature published since 2000. A systematic search of freely available journal articles pertinent to the pathoetiology (molecular and clinical risk factors) of BE was performed within PubMed and Google Scholar. All articles published in English reporting on the risks and molecular transformation of normal esophageal mucosa into metaplastic mucosa were considered; the research did not look further to the pathoetiology of esophageal adenocarcinoma. Each journal article was assessed based on the content, relevance, and applicability to this literature review. An assessment of 118 full-length articles produced 18 articles for the qualitative analysis. We noted risk factors, such as gastroesophageal reflux of acid and bile, cause aberrations at a molecular level to alter cell cycle control to culminate in morphological changes in esophageal mucosa, producing metaplastic cells with a potential of malignant transformation. There is a need for translational research to bridge the gap between genetics and molecular knowledge to achieve clinical preventive, diagnostic, and therapeutic approaches to addressing BE.

Clinical Guidelines Update on the Diagnosis and Management of Barrett's Esophagus.

Barrett's esophagus is a condition in which metaplastic columnar epithelium replaces stratified squamous epithelium in the distal esophagus. This condition occurs due to chronic gastroesophageal reflux disease and is a risk factor for the development of esophageal adenocarcinoma. Multiple clinical guidelines have been published around the world in recent years to assist gastroenterologists in the management of these patients and have evolved as new data have become available. While some information such as surveillance technique has not drastically changed, there has been an evolution over the years in diagnostic criteria, screening and endoscopic therapy with a variety of subtle differences among the different guidelines. Herein, we highlight areas of agreement and disagreement on definitions, screening, surveillance, and treatment techniques among these guidelines for the optimal management of Barrett's esophagus patients.

Barrett's Esophagus and Esophageal Adenocarcinoma: How Common Are They Really?

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 50years 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.

Barrett's oesophagus: epidemiology, diagnosis and clinical management

Barrett's oesophagus is a condition characterised by partial replacement of the normal squamous epithelium of the lower oesophagus by a metaplastic columnar epithelium containing goblet cells (intestinal metaplasia). Barrett's oesophagus is important clinically because those afflicted are predisposed to oesophageal adenocarcinoma. Prevalence surveys suggest that up to 2% of the population may be affected; most will be unaware of their diagnosis. Risk factors include age, male sex, gastro-oesophageal acid reflux, central obesity and smoking. Helicobacter pylori infection confers a reduced risk of Barrett's oesophagus. Risks of cancer progression are lower than originally reported and are now estimated at 1-3 per 1000 patient-years for patients with non-dysplastic Barrett's oesophagus. Progression rates are higher for patients with long segment (≥ 3 cm) and dysplastic Barrett's oesophagus. Australian guidelines have been developed to aid practitioners in managing patients with Barrett's oesophagus and early oesophageal adenocarcinoma. While generalised population screening for Barrett's oesophagus is not recommended, endoscopic surveillance of patients with confirmed Barrett's oesophagus is recommended, with surveillance intervals dependent on segment length and presence of dysplasia. New techniques such as endoscopic mucosal resection and endoscopic radiofrequency ablation are now available to treat patients with dysplasia and early oesophageal adenocarcinoma. New screening and surveillance technologies are currently under investigation; these may prove cost-effective in identifying and managing patients in the community.

Transcommitment: Paving the Way to Barrett's Metaplasia.

Barrett's esophagus is the condition in which metaplastic columnar epithelium that predisposes to cancer development replaces stratified squamous epithelium in the distal esophagus. Potential sources for the cell or tissue of origin for metaplastic Barrett's epithelium are reviewed including native esophageal differentiated squamous cells, progenitor cells native to the esophagus located within the squamous epithelium or in the submucosal glands or ducts, circulating bone marrow-derived stem cells, and columnar progenitor cells from the squamocolumnar junction or the gastric cardia that proximally shift into the esophagus to fill voids left by damaged squamous epithelium. Wherever its source the original cell must undergo molecular reprogramming (i.e., either transdifferentiation or transcommitment) to give rise to specialized intestinal metaplasia. Transcription factors that specify squamous, columnar, intestinal, and mucus-secreting epithelial differentiation are discussed. An improved understanding of how esophageal columnar metaplasia forms could lead to development of effective treatment or prevention strategies for Barrett's esophagus. It could also more broadly inform upon normal tissue development and differentiation, wound healing, and stem cell biology.