Barrett's esophagus is a condition in which there is an abnormal (
metaplastic) change in the
mucosal cells lining the lower portion of the
esophagus
The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the ...
, from
stratified squamous epithelium
A stratified squamous epithelium consists of squamous (flattened) epithelial cells arranged in layers upon a basal membrane. Only one layer is in contact with the basement membrane; the other layers adhere to one another to maintain structural i ...
to
simple columnar epithelium with interspersed
goblet cell
Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 5AC. The goblet cells mainly use the merocrine method of secretion, secreting vesicles into a duct, but may use apocrine methods, budding off their se ...
s that are normally present only in the
small intestine
The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through t ...
and
large intestine
The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being r ...
. This change is considered to be a
premalignant condition
A precancerous condition is a condition, tumor or lesion involving abnormal cells which are associated with an increased risk of developing into cancer. Clinically, precancerous conditions encompass a variety of abnormal tissues with an increased ...
because it is associated with a high incidence of further transition to
esophageal adenocarcinoma, an often-deadly
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
.
The main cause of Barrett's esophagus is thought to be an adaptation to chronic acid exposure from reflux esophagitis.
Barrett's esophagus is diagnosed by
endoscopy: observing the characteristic appearance of this condition by direct inspection of the lower esophagus; followed by microscopic examination of tissue from the affected area obtained from
biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a d ...
. The cells of Barrett's esophagus are classified into four categories: nondysplastic, low-grade
dysplasia, high-grade dysplasia, and frank
carcinoma. High-grade dysplasia and early stages of adenocarcinoma may be treated by endoscopic resection or
radiofrequency ablation. Later stages of adenocarcinoma may be treated with
surgical resection or
palliation. Those with nondysplastic or low-grade dysplasia are managed by annual observation with endoscopy, or treatment with radiofrequency ablation. In high-grade dysplasia, the risk of developing cancer might be at 10% per patient-year or greater.
The incidence of esophageal adenocarcinoma has increased substantially in the Western world in recent years.
The condition is found in 5–15% of patients who seek medical care for heartburn (
gastroesophageal reflux disease
Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...
, or GERD), although a large subgroup of patients with Barrett's esophagus are asymptomatic. The condition is named after
surgeon Norman Barrett (1903–1979) even though the condition was originally described by Philip Rowland Allison in 1946.
Signs and symptoms
The change from normal to premalignant cells indicate Barrett's esophagus does not cause any particular symptoms. Barrett's esophagus, however, is associated with these symptoms:
* frequent and longstanding
heartburn
* trouble swallowing (
dysphagia
Dysphagia is difficulty in swallowing. Although classified under " symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right.
It may be a sensation that suggests difficulty in the passage of solids or liqu ...
)
* vomiting blood (
hematemesis)
* pain under the
sternum
The sternum or breastbone is a long flat bone located in the central part of the chest. It connects to the ribs via cartilage and forms the front of the rib cage, thus helping to protect the heart, lungs, and major blood vessels from injury. ...
where the esophagus meets the stomach
* pain when swallowing (
odynophagia), which can lead to unintentional weight loss
The risk of developing Barrett's esophagus is increased by
central obesity (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.
Pathophysiology
Barrett's esophagus occurs due to chronic inflammation. The principal cause of chronic inflammation is
gastroesophageal reflux disease
Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...
, GERD (UK: GORD). In this disease, acidic stomach, bile, and small intestine and pancreatic contents cause damage to the cells of the lower esophagus. In turn, this provokes an advantage for cells more resistant to these noxious stimuli in particular
HOXA13-expressing stem cells that are characterised by distal (intestinal) characteristics and outcompete the normal squamous cells.
This mechanism also explains the selection of
HER2/neu
Receptor tyrosine-protein kinase erbB-2 is a protein that in humans is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently refer ...
(also called ERBB2) and the overexpressing (lineage-addicted) cancer cells during the process of carcinogenesis, and the efficacy of targeted therapy against the Her-2 receptor with
trastuzumab (
Herceptin) in the treatment of adenocarcinomas at the gastroesophageal junction.
Researchers are unable to predict who with heartburn will develop Barrett's esophagus. While no relationship exists between the severity of heartburn and the development of Barrett's esophagus, a relationship does exist between chronic heartburn and the development of Barrett's esophagus. Sometimes, people with Barrett's esophagus have no heartburn symptoms at all.
Some anecdotal evidence indicates those with the eating disorder
bulimia
Bulimia nervosa, also known as simply bulimia, is an eating disorder characterized by binge eating followed by purging or fasting, and excessive concern with body shape and weight. The aim of this activity is to expel the body of calories eaten ...
are more likely to develop Barrett's esophagus because bulimia can cause severe acid reflux, and because purging also floods the esophagus with acid. However, a link between bulimia and Barrett's esophagus remains unproven.
During episodes of reflux,
bile acids enter the
esophagus
The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the ...
, and this may be an important factor in
carcinogenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...
.
Individuals with
GERD and BE are exposed to high concentrations of
deoxycholic acid
Deoxycholic acid is a bile acid. Deoxycholic acid is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria. The two primary bile acids secreted by the liver are cholic acid and chenodeoxycholic acid. Bacteria ...
that has cytotoxic effects and can cause
DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
.
[
]
Diagnosis
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 in the lower esophagus, replacing the normal squamous cell
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...
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.
Screening
Screening endoscopy is recommended among males over the age of 60 who have reflux symptoms that are of long duration and not controllable with treatment. Among those not expected to live more than five years screening is not recommended.[
The Seattle protocol is used commonly in endoscopy to obtain endoscopic biopsies for screening, taken every 1 to 2 cm from the gastroesophageal junction.
Since the ]COVID-19 pandemic In Scotland
The COVID-19 pandemic in Scotland is part of the COVID-19 pandemic of coronavirus disease-2019, caused by the virus SARS-CoV-2. The first case of COVID-19 was confirmed in Scotland on 1 March 2020. Community transmission was first reported on ...
, the local NHS started using a swallowable sponge (Cytosponge) in hospitals to collect cell samples for diagnosis. Preliminary studies have shown this diagnostic test to be a useful tool for screening people with heartburn symptoms and improved diagnosis.
Intestinal metaplasia
The presence of goblet cells, called intestinal metaplasia, is necessary to make a diagnosis of Barrett's esophagus. This frequently occurs in the presence of other metaplastic columnar cells, but only the presence of goblet cells is diagnostic. The metaplasia is grossly visible through a gastroscope, but biopsy specimens must be examined under a microscope
A microscope () is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisibl ...
to determine whether cells are gastric or colonic in nature. Colonic metaplasia is usually identified by finding goblet cell
Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 5AC. The goblet cells mainly use the merocrine method of secretion, secreting vesicles into a duct, but may use apocrine methods, budding off their se ...
s in the epithelium and is necessary for the true diagnosis.
Many histologic mimics of Barrett's esophagus are known (i.e. goblet cells occurring in the transitional epithelium of normal esophageal submucosal gland ducts, "pseudogoblet cells" in which abundant foveolar astrictype 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). 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 used to identify true intestinal-type metaplastic cells. The protein AGR2 is elevated in Barrett's esophagus and can be used as a biomarker for distinguishing Barrett epithelium from normal esophageal epithelium.
The presence of intestinal metaplasia in Barrett's esophagus represents a marker for the progression of metaplasia towards dysplasia and eventually adenocarcinoma. This factor combined with two different immunohistochemical expression of p53, Her2 and p16 leads to two different genetic pathways that likely progress to dysplasia in Barrett's esophagus. Also intestinal metaplastic cells can be positive for CK 7+/CK20-.
Epithelial dysplasia
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 epithelial dysplasia (or "intraepithelial neoplasia
Intraepithelial neoplasia (IEN) is the development of a benign neoplasia or high-grade dysplasia in an epithelium. The exact dividing line between dysplasia and neoplasia has been very difficult to draw throughout the era of medical science. It ...
").
Among all metaplastic lesions, around 8% were associated with dysplasia. particularly a recent study demonstrated that dysplastic lesions were located mainly in the posterior wall of the esophagus.
Considerable variability is seen in assessment for dysplasia among pathologists. Recently, gastroenterology and GI pathology societies have recommended that any diagnosis of high-grade dysplasia in Barrett be confirmed by at least two fellowship-trained GI pathologists prior to definitive treatment for patients. For more accuracy and reproducibility, it is also recommended to follow international classification systems, such as the "Vienna classification" of gastrointestinal epithelial neoplasia (2000).
Management
Many people with Barrett's esophagus do not have dysplasia. Medical societies recommend that if a patient has Barrett's esophagus, and if the past two endoscopy and biopsy examinations have confirmed the absence of dysplasia, then the patient should not have another endoscopy within three years.
Endoscopic surveillance of people with Barrett's esophagus is often recommended, although little direct evidence supports this practice. Treatment options for high-grade dysplasia include surgical removal of the esophagus ( esophagectomy) or endoscopic treatments such as endoscopic mucosal resection or ablation (destruction).
The risk of malignancy is highest in the United States in Caucasian men over fifty years of age with more than five years of symptoms. Current recommendations include routine endoscopy and biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a d ...
(looking for dysplastic change
Dysplasia is any of various types of abnormal growth or development of cells ( microscopic scale) or organs ( macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscop ...
s). Although in the past physicians have taken a watchful waiting approach, newly published research supports consideration of intervention for Barrett's esophagus. Balloon-based radiofrequency ablation, invented by Ganz, Stern, and Zelickson in 1999, is a new treatment modality for the treatment of Barrett's esophagus and dysplasia and has been the subject of numerous published clinical trials. The findings demonstrate radiofrequency ablation is at least 90% effective to completely clear Barrett's esophagus and dysplasia, with durability of up to five years and a favorable safety profile.[
Anti-reflux surgery has not been proven to prevent esophageal cancer. However, the indication is that proton pump inhibitors are effective in limiting the progression of esophageal cancer. Laser treatment is used in severe dysplasia, while overt malignancy may require surgery, ]radiation therapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...
, or systemic chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
. A recent five-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.
There is presently no reliable way to determine which patients with Barrett's esophagus will go on to develop esophageal cancer
Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Other symptoms may include pain when swallowing, a hoarse vo ...
, although a recent study found the detection of three different genetic abnormalities was associated with as much as a 79% chance of developing cancer in six years.
Endoscopic mucosal resection has also been evaluated as a management technique. Additionally an operation known as a Nissen fundoplication can reduce the reflux of acid from the stomach into the esophagus.
In a variety of studies, nonsteroidal anti-inflammatory drugs ( NSAIDS) such as low-dose aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat in ...
(75–300 mg/day) have shown evidence of preventing esophageal cancer in people with Barrett's esophagus.
Prognosis
Barrett's esophagus is a ''pre''malignant condition, not a malignant one. Its malignant sequela, esophagogastric junctional adenocarcinoma Oesophagogastric junctional adenocarcinoma (OGJ adenocarcinoma) is a cancer of the lower part of the oesophagus with a rising incidence in Western countries. This disease is often linked to Barrett's oesophagus.
The incidence of OGJ 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, but 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).
The relative risk of esophageal adenocarcinoma is about ten times higher in those with Barrett's esophagus than the general population. Most patients with esophageal carcinoma survive less than one year.
Epidemiology
The incidence in the United States among Caucasian men is eight times the rate among Caucasian women and five times greater than African American men. Overall, the male to female ratio of Barrett's esophagus is 10:1. Several studies have estimated the prevalence of Barrett's esophagus in the general population to be 1.3% to 1.6% in two European populations (Italian and Swedish), and 3.6% in a Korean population.
History
The condition is named after Australian thoracic surgeon Norman Barrett (1903–1979), who in 1950 argued that "ulcers are found below the squamocolumnar junction ... represent gastric ulcers within 'a pouch of stomach ... drawn up by scar tissue into the mediastinum' ... representing an example of a 'congenital short esophagus. In contrast, Philip Rowland Allison and Alan Johnstone argued that the condition related to the "esophagus lined with gastric mucous membrane and not intra-thoracic stomach as Barrett mistakenly believed." Philip Allison, cardiothoracic surgeon and Chair of Surgery at the University of Oxford, suggested "calling the chronic peptic ulcer crater of the esophagus a 'Barrett's ulcer, but added this name did not imply agreement with "Barrett's description of an esophagus lined with gastric mucous membrane as stomach." Bani-Hani KE and Bani-Hani KR argue that the terminology and definition of Barrett's esophagus is surrounded by extraordinary confusion unlike most other medical conditions and that " e use of the eponym 'Barrett's' to describe he condition
He or HE may refer to:
Language
* He (pronoun), an English pronoun
* He (kana), the romanization of the Japanese kana へ
* He (letter), the fifth letter of many Semitic alphabets
* He (Cyrillic), a letter of the Cyrillic script called ''He'' in ...
is not justified from a historical point of view". Bani-Hani KE and Bani-Hani KR investigated the historical aspects of the condition and found they could establish "how little Norman Barrett had contributed to the core concept of this condition in comparison to the contributions of other investigators, particularly the contribution of Philip Allison".
A further association was made with adenocarcinoma in 1975.
References
External links
Barrett's esophagus
at National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Barrett's esophagus Video Overview
an
Barrett's esophagus Health Information
at Mayo Clinic
{{DEFAULTSORT:Barrett Esophagus
Esophagus disorders