Barrett's esophagus
Encyclopedia
Barrett's esophagus (sometimes called Barrett's syndrome, CELLOcolumnar epithelium lined lower oesophagus) refers to an abnormal change (metaplasia
Metaplasia
Metaplasia is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or caused by some sort of abnormal stimulus...

) in the cells of the inferior portion of the esophagus
Esophagus
The esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...

. A positive diagnosis generally requires observing specific macroscopic and microscopic changes. The normal squamous epithelium
Squamous epithelium
In anatomy, squamous epithelium is an epithelium characterised by its most superficial layer consisting of flat, scale-like cells called squamous epithelial cells...

 lining of the esophagus is replaced by metaplastic columnar epithelium. Columnar epithelium refers to a cell type that is typically found in more distal parts of the gastrointestinal system. The medical significance of Barrett’s esophagus is its strong association with esophageal adenocarcinoma
Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...

, a particularly lethal cancer.

The main cause of Barrett's esophagus is thought to be an adaptation to chronic acid exposure from reflux esophagitis. In the last 40 years, the incidence of esophageal adenocarcinoma has been increasing in the Western world. Barrett's esophagus is found in 5–15% of patients who seek medical care for heartburn (gastroesophageal reflux disease
Gastroesophageal reflux disease
Gastroesophageal reflux disease , gastro-oesophageal reflux disease , gastric reflux disease, or acid reflux disease is chronic symptoms or mucosal damage caused by stomach acid coming up from the stomach into the esophagus...

, GERD), although a large subgroup of patients with Barrett's esophagus do not have symptoms. It is considered to be a premalignant condition
Premalignant condition
A precancerous condition is a disease, syndrome, or finding that, if left untreated, may lead to cancer. It is a generalized state associated with a significantly increased risk of cancer....

 because it is associated with an increased risk of esophageal cancer
Esophageal cancer
Esophageal cancer is malignancy of the esophagus. There are various subtypes, primarily squamous cell cancer and adenocarcinoma . Squamous cell cancer arises from the cells that line the upper part of the esophagus...

 (more specifically, adenocarcinoma) of about 0.5% per patient-year.
Diagnosis of Barrett's esophagus requires endoscopy
Endoscopy
Endoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...

 (more specifically, esophagogastroduodenoscopy
Esophagogastroduodenoscopy
For other expansions of the initialism "OGD", see the disambiguation page.In medicine , esophagogastroduodenoscopy is a diagnostic endoscopic procedure that visualizes the upper part of the gastrointestinal tract up to the duodenum...

, a procedure in which a small camera is inserted through the mouth to examine the esophagus, stomach, and duodenum
Duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...

) and biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

. The cells of Barrett's esophagus, after biopsy, are classified into four general categories: non-dysplastic, low-grade dysplasia
Dysplasia
Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...

, high-grade dysplasia, and frank carcinoma
Carcinoma
Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...

. High-grade dysplasia and frank carcinoma patients are generally advised to undergo surgical treatment. Non-dysplastic and low-grade patients are generally advised to undergo annual observation with endoscopy. In high-grade dysplasia, the risk of developing cancer might be at 10% per patient-year or greater.

The condition is named after Norman Barrett
Norman Barrett
Norman Rupert Barrett was an Australian-born British thoracic surgeon who is primarily remembered for describing Barrett’s oesophagus.-Early life:...

 (1903–1979) who described the condition in 1950.

Symptoms

The change from normal to premalignant cells that indicate Barrett's esophagus does not cause any particular symptoms. Barrett's esophagus, however, is associated with the following symptoms:
  • frequent and longstanding heartburn
    Heartburn
    Heartburn, also known as pyrosis or acid indigestion is a burning sensation in the chest, just behind the breastbone or in the epigastrium...

  • trouble swallowing (dysphagia
    Dysphagia
    Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....

    )
  • vomiting blood (hematemesis
    Hematemesis
    Hematemesis or haematemesis is the vomiting of blood. The source is generally the upper gastrointestinal tract. Patients can easily confuse it with hemoptysis , although the latter is more common.-Signs:...

    )
  • pain under the breastbone where the esophagus meets the stomach
  • unintentional weight loss because eating is painful


The risk of developing Barrett's esophagus is increased by central (vs. peripheral) obesity. The exact mechanism is unclear. The difference in distribution of fat among men (more central) and women (more peripheral) may explain the increased risk in males.

Mechanism

Barrett's esophagus occurs due to chronic inflammation. The principal cause of the chronic inflammation is gastroesophageal reflux disease
Gastroesophageal reflux disease
Gastroesophageal reflux disease , gastro-oesophageal reflux disease , gastric reflux disease, or acid reflux disease is chronic symptoms or mucosal damage caused by stomach acid coming up from the stomach into the esophagus...

, GERD (UK: GORD). In this disease, acidic stomach, bile, small intestine and pancreatic contents cause damage to the cells of the lower esophagus. Recently, it was shown that bile acids are able to induce intestinal differentiation, in gastroesophageal junction cells, through inhibition of the Epidermal growth factor receptor
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...

 (EGFR) receptor which results in inhibition of Akt
AKT
Akt, also known as Protein Kinase B , is a serine/threonine protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, cell proliferation, apoptosis, transcription and cell migration.-Family members:...

, upregulation of the p50 subunit of NF-kB
NF-kB
NF-κB is a protein complex that controls the transcription of DNA. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens...

 (NFKB1
NFKB1
Nuclear factor NF-kappa-B p105 subunit is a protein that in humans is encoded by the NFKB1 gene.This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and...

) and ultimately activation of the promotor of the homeobox gene CDX2
CDX2
Homeobox protein CDX-2 is a protein that in humans is encoded by the CDX2 gene. The protein encoded by this gene is a homeobox transcription factor.-Function:...

. The latter mastergene is responsible for the expression of intestinal markers such as Guanylate cyclase 2C
. This mechanism explains the selecion of HER2/neu
HER2/neu
HER-2 also known as proto-oncogene Neu, receptor tyrosine-protein kinase erbB-2, CD340 or p185 is an enzyme that in humans is encoded by the ERBB2 gene. Over expression of this gene is correlated with higher aggressiveness in breast cancers...

 (or ERBB2) overexpressing (lineage-addicted) cancer cells during the process of carcinogenesis and the efficacy of targeted therapy against the Her-2 receptor with trastuzumab
Trastuzumab
Trastuzumab is a monoclonal antibody that interferes with the HER2/neu receptor.The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell to inside the cell, and turn genes on and off...

 (Herceptin) in the treatment of adenocarcinomas at the gastroesophageal junction (GEJ).
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
Lye
Lye is a corrosive alkaline substance, commonly sodium hydroxide or historically potassium hydroxide . Previously, lye was among the many different alkalis leached from hardwood ashes...

.

Diagnosis

A new technique to detect and treat Barret's esophagus is being used in Portsmouth, Hampshire, United Kingdom with great success. Ordinary Vinegar highlights areas of concern: http://www.bbc.co.uk/news/uk-england-hampshire-15883589

Both macroscopic (from endoscopy) and microscopic positive findings are required to make a diagnosis. Barrett's esophagus is marked by the presence of columnar epithelia
Columnar epithelia
Columnar epithelia are epithelial cells whose heights are at least four times their width. Columnar epithelia are divided into simple , and stratified .* Simple columnar epithelia* Stratified columnar epithelia...

 in the lower esophagus, replacing the normal squamous cell epithelium—an example of metaplasia
Metaplasia
Metaplasia is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or caused by some sort of abnormal stimulus...

. 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
Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...

.

The metaplastic columnar cells may be of two types: gastric (similar to those in the stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...

, which is NOT technically Barrett's esophagus) or colonic (similar to cells in the intestine
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...

s). 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
Microscope
A microscope is an instrument used to see objects that are too small for the naked eye. The science of investigating small objects using such an instrument is called microscopy...

 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
AGR2
Anterior gradient homolog 2 is a human protein originally discovered in Xenopus laevis, encoded for by the gene of the same name. In Xenopus AGR2 plays a role in cement gland differentiation, however in human cancer cell lines high levels of AGR2 correlate with downregulation of the p53 response...

 is elevated in Barrett's esophagus, and can be used as a biomarker for distinguishing Barrett's epithelium from normal esophageal epithelium.

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.

Management

Many professional medical societies propose endoscopic screening
Screening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....

 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. Treatment options for high-grade dysplasia include surgical removal of the esophagus (esophagectomy
Esophagectomy
Esophagectomy or Oesophagectomy is the surgical removal of all or part of the esophagus .-Purpose:...

) 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.

The risk of malignancy is highest in the U.S. in Caucasian men more than 50 years of age with more than 5 years of symptoms. Current recommendations include routine endoscopy
Endoscopy
Endoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...

 and biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

 (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
Proton pump inhibitor
Proton-pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar...

 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
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

, radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...

, or systemic chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

. Additionally, a recent 5-year random-controlled trial has shown that photodynamic therapy
Photodynamic therapy
Photodynamic therapy is used clinically to treat a wide range of medical conditions, including malignant cancers, and is recognised as a treatment strategy which is both minimally invasive and minimally toxic...

 using photofrin is statistically more effective in eliminating dysplastic growth areas than sole use of a proton pump inhibitor. There is presently no reliable way to determine which patients with Barrett's esophagus will go on to develop esophageal cancer
Esophageal cancer
Esophageal cancer is malignancy of the esophagus. There are various subtypes, primarily squamous cell cancer and adenocarcinoma . Squamous cell cancer arises from the cells that line the upper part of the esophagus...

, 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.

Endoscopic mucosal resection (EMR) has also been evaluated as a management technique. Additionally an operation known as a Nissen fundoplication
Nissen fundoplication
Nissen fundoplication is a surgical procedure to treat gastroesophageal reflux disease and hiatus hernia. In GERD it is usually performed when medical therapy has failed, but with paraesophageal hiatus hernia, it is the first-line procedure...

 can reduce the reflux of acid from the stomach into the esophagus.

In a variety of studies, non-steroidal anti-inflammatory drugs (NSAIDS), like aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...

, have shown evidence of preventing esophageal cancer in Barrett's esophagus patients. 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.

Prognosis

Barrett's esophagus is only a premalignant condition. Its malignant sequela, esophageal adenocarcinoma, has a mortality rate of over 85%. The risk of developing esophageal adenocarcinoma in people who have Barrett's esophagus has been estimated to be 6–7 per 1000 person-years, however a cohort study of 11,028 patients from Denmark published in 2011 showed an incidence of only 1.2 per 1000 person-years (5.1 per 1000 person-years in patients with dysplasia, 1.0 per 1000 person-years in patients without dysplasia). Most patients with esophageal carcinoma survive less than 1 year.

Epidemiology

The incidence in the United States among Caucasian men is 8 times the rate among Caucasian women and 5 times greater than African American men. Several studies have estimated the prevalence of Barrett's esophagus in the normal population to be 1.6%, 1.3%, and 3.6%.

History

Barrett first described the columnar metaplasia in 1950. An association with gastroesophageal reflux was made in 1953. An association with adenocarcinoma was made in 1975.

External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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