Barrett's esophagus

Barrett's esophagus (British English: oesophagus) (sometimes called Barrett's syndrome, CELLO, columnar epithelium lined lower esophagus and colloquially referred to as Barrett's) refers to an abnormal change (metaplasia) in the cells of the lower end of the esophagus thought to be caused by damage from chronic acid exposure, or reflux esophagitis.[1] The normal lining of the esophagus (squamous epithelium) is replaced by an intestinal-type lining (columnar epithelium).

Barrett's esophagus is found in 5-15% of patients who seek medical care for heartburn (gastroesophageal reflux disease, GERD), although a large subgroup of patients with Barrett's esophagus do not have symptoms.[2] It is considered to be a premalignant condition because it is associated with an increased risk of esophageal cancer (more specifically, adenocarcinoma) of about 0.5% per patient-year.[3][2] Diagnosis of Barrett's esophagus requires endoscopy (more specifically, esophagogastroduodenoscopy, a procedure in which a small tube with a camera at the top is used to look at the esophagus, stomach and first part of the bowels) and biopsy (taking small tissue samples which are analysed using microscopy). The progression from Barrett's esophagus to esophageal cancer is divided into non-dysplastic changes, low-grade and high-grade dysplasia (abnormal cell maturation associated with a risk of progression to cancer) and frank carcinoma. In high-grade dysplasia, the risk of developing cancer might be at 10% per patient-year or greater.[2]

Many professional medical societies propose endoscopic screening of patients with GERD and endoscopic surveillance of patients with Barrett's esophagus, although little direct evidence supports this practice, which is common in many developed countries.[2] Treatment options for high-grade dysplasia include surgical removal of the esophagus (esophagectomy) or endoscopic treatments such as endoscopic mucosal resection or ablation (destruction). Currently, there is no intervention that has been shown to prevent the development of Barrett's esophagus or its progression to esophageal cancer.[2]

The condition is named after Norman Barrett (1903–1979) who described the condition in 1957.[4]

Contents [hide]
1 Causes and symptoms
2 Pathology
3 Treatment
4 Additional images
5 References
6 External links


[edit] Causes and symptoms
Barrett's esophagus is caused by gastroesophageal reflux disease, GERD (UK: GORD), which allows the stomach's contents to damage the cells lining the lower esophagus. Researchers are unable to predict which heartburn sufferers will develop Barrett's esophagus. While there is no relationship between the severity of heartburn and the development of Barrett's esophagus, there is a relationship between chronic heartburn and the development of Barrett's esophagus. Sometimes people with Barrett's esophagus will have no heartburn symptoms at all. In rare cases, damage to the esophagus may be caused by swallowing a corrosive substance such as lye.

The change from normal to premalignant cells that indicates Barrett's esophagus does not cause any particular symptoms. However, warning signs that should not be ignored include:

frequent and longstanding heartburn
trouble swallowing (dysphagia)
vomiting blood
pain under the breastbone where the esophagus meets the stomach
unintentional weight loss because eating is painful
[edit] Pathology

Micrograph of Barrett's esophagus (left of image) and normal stratified squamous epithelium (right of image). Alcian blue stain.
High magnification micrograph of Barrett's esophagus showing the characteristic goblet cells. Alcian blue stain.Barrett's esophagus is marked by the presence of columnar epithelia in the lower esophagus, replacing the normal squamous cell epithelium—an example of metaplasia. The secretory columnar epithelium may be more able to withstand the erosive action of the gastric secretions; however, this metaplasia confers an increased risk of adenocarcinoma.[5]

The metaplastic columnar cells may be of two types: gastric (similar to those in the stomach, which is NOT technically Barrett's esophagus) or colonic (similar to cells in the intestines). A biopsy of the affected area will often contain a mixture of the two. Colonic-type metaplasia is the type of metaplasia associated with risk of malignancy in genetically susceptible people.

The metaplasia of Barrett's esophagus is grossly visible through a gastroscope, but biopsy specimens must be examined under a microscope to determine whether cells are gastric or colonic in nature. Colonic metaplasia is usually identified by finding goblet cells in the epithelium and is necessary for the true diagnosis of Barrett's.

There are many histologic mimics of Barrett's esophagus (i.e. goblet cells occurring in the transitional epithelium of normal esophageal submucosal gland ducts, "pseudogoblet cells" in which abundant foveolar (gastric) type mucin simulates the acid mucin true goblet cells). Assessment of relationship to submucosal glands and transitional-type epithelium with examination of multiple levels through the tissue may allow the pathologist to reliably distinguish between goblet cells of submucosal gland ducts and true Barrett's esophagus (specialized columnar metaplasia). Use of the histochemical stain Alcian blue pH 2.5 is also frequently used to distinguish true intestinal-type mucins from their histologic mimics. Recently, immunohistochemical analysis with antibodies to CDX-2 (specific for mid and hindgut intestinal derivation) has also been utilized to identify true intestinal-type metaplastic cells. It has been shown that the protein AGR2 is elevated in Barrett's esophagus,[6] and can be used as a biomarker for distinguishing Barrett's epithelium from normal esophageal epithelium.[7]

After the initial diagnosis of Barrett's esophagus is rendered, affected persons undergo annual surveillance to detect changes that indicate higher risk to progression to cancer: development of dysplasia. There is considerable variability in assessment for dysplasia among pathologists. Recently, gastroenterology and GI pathology societies have recommended that any diagnosis of high grade dysplasia in Barrett's be confirmed by at least two fellowship trained GI pathologists prior to definitive treatment for patients.

[edit] Treatment
The risk of malignancy is highest in the U.S. in Caucasian men > 50 years of age with > 5 years of symptoms. It is unusual for African-American men to develop adenocarcinoma of the esophagus, the cancer associated with Barrett's. Current recommendations include routine endoscopy and biopsy (looking for dysplastic changes). If two endoscopies and biopsy sessions performed within 12 months are negative for dysplasia then surveillance can be performed every 3 years while the underlying reflux is controlled with proton pump inhibitor drugs in combination with measures to prevent reflux. For patients found to have low grade or high grade dysplasia close observation and repeat endoscopy and biopsies are indicated and the patient should be followed closely by a gastroenterologist.

Proton pump inhibitor drugs have not yet been proven to prevent esophageal cancer. Laser treatment is used in severe dysplasia, while overt malignancy may require surgery, radiation therapy, or systemic chemotherapy. Additionally, a recent 5-year random-controlled trial has shown that photodynamic therapy using photofrin is statistically more effective in eliminating dysplastic growth areas than sole use of a proton pump inhibitor.[8]There is presently no reliable way to determine which patients with Barrett's esophagus will go on to develop esophageal cancer, although a recent study found that the detection of three different genetic abnormalities were associated with as much as a 79% chance of developing cancer in 6 years.[9]

Endoscopic mucosal resection (EMR) has also been evaluated as a management technique.[10] Additionally an operation known as a Nissen fundoplication can reduce the reflux of acid from the stomach into the esophagus.[11]

In a variety of studies, non-steroidal anti-inflammatory drugs (NSAIDS), like aspirin, have shown evidence of preventing esophageal cancer in Barrett's esophagus patients.[12][13] However, none of these studies have been randomized, placebo controlled trials, which are considered the gold standard for evaluating a medical intervention. In addition, the best dose of NSAIDs for cancer prevention is not yet known.

[edit] Additional images
Micrograph of Barrett's esophagus. Alcian blue stain.


[edit] References
^ Stein H, Siewert J (1993). "Barrett's esophagus: pathogenesis, epidemiology, functional abnormalities, malignant degeneration, and surgical management". Dysphagia 8 (3): 276–88. doi:10.1007/BF01354551. PMID 8359051.
^ a b c d e Shaheen NJ, Richter JE (March 2009). "Barrett's oesophagus". Lancet 373 (9666): 850–61. doi:10.1016/S0140-6736(09)60487-6. PMID 19269522.
^ Koppert L, Wijnhoven B, van Dekken H, Tilanus H, Dinjens W (2005). "The molecular biology of esophageal adenocarcinoma". J Surg Oncol 92 (3): 169–90. doi:10.1002/jso.20359. PMID 16299787.
^ Barrett N (1957). "The lower esophagus lined by columnar epithelium". Surgery 41 (6): 881–94. PMID 13442856.
^ Fléjou J (2005). "Barrett's oesophagus: from metaplasia to dysplasia and cancer". Gut 54 Suppl 1: i6–12. doi:10.1136/gut.2004.041525. PMID 15711008.
^ Elizabeth Pohler, Ashley L. Craig, James Cotton, Laura Lawrie, John F. Dillon, Pete Ross, Neil Kernohan and Ted R. Hupp (2004). "The Barrett’s Antigen Anterior Gradient-2 Silences the p53 Transcriptional Response to DNA Damage". Molecular and Cellular Proteomics 3: 534–547. doi:10.1074/mcp.M300089-MCP200. PMID 14967811.
^ Murray E, McKenna EO, Burch LR, Dillon J, Langridge-Smith P, Kolch W, Pitt A, Hupp TR (2007). "Microarray-formatted clinical biomarker assay development using peptide aptamers to anterior gradient-2". Biochemistry 46: 13742–51. doi:10.1021/bi7008739. PMID 17994709.
^ Overholt BF, Wang KK, Burdick JS, et al. (2007). "Five-year efficacy and safety of photodynamic therapy with Photofrin in Barrett's high-grade dysplasia.". Gastrointestinal endoscopy 66 (3): 460–8. doi:10.1016/j.gie.2006.12.037. PMID 17643436.
^ Galipeau P, Li X, Blount PL, Maley CC, Sanchez CA Odze RD, Ayub K, Rabinovitch PS, Vaughan TV, Reid BJ (2007). "NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma". PLoS Medicine 4 (2): e67. doi:10.1371/journal.pmed.0040067. PMID 17326708.
^ Reshamwala P, Darwin P (2006). "Endoscopic management of early gastric cancer". Curr Opin Gastroenterol 22 (5): 541–5. doi:10.1097/01.mog.0000239870.04457.80. PMID 16891887.
^ Abbas A, Deschamps C, Cassivi SD, et al. (2004). "The role of laparoscopic fundoplication in Barrett’s esophagus". Annals of Thoracic Surgery 77 (2): 393–396. doi:10.1016/S0003-4975(03)01352-3. PMID 14759403.
^ Corley DA, Kerlikowske K, Verma R, Buffler P (2003). "Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis.". Gastroenterology 124: 47–56. doi:10.1053/gast.2003.50008. PMID 12512029.
^ Vaughan TL, Dong LM, Blount PL, Ayub K, Odze RD, Sanchez, CA, Rabinovitch PS, Reid BJ (2005). "Non-steroidal anti-inflammatory drugs and risk of neoplastic progression in Barrett's oesophagus: a prospective study". Lancet Oncol 6: 945–52. doi:10.1016/S1470-2045(05)70431-9. PMID 16321762.
[edit] External links
Barrett's Esophagus at National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD)
Barrett's Info a peer-reviewed web site of information on Barrett's esophagus and its clinical management.
Barrett's Esophagus at Johns Hopkins University
Barrett's Esophagus Video Overview and Barrett's Esophagus Health Information at Mayo Clinic
Barrett's Oesophagus Campaign Originally The Barrett's Oesophagus Foundation, the UK charity committed to research into prevention of adenocarcinoma of the esophagus