Barrett's esophagus is a condition in which there is an abnormal (
metaplastic Metaplasticity is a term originally coined by W.C. Abraham and M.F. Bear to refer to the plasticity of synaptic plasticity. Until that time synaptic plasticity had referred to the plastic nature of ''individual'' synapses. However this new form re ...
) 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 ...
, from
stratified squamous epithelium to
simple columnar epithelium with interspersed
goblet cells that are normally present only in the
small intestine 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 bein ...
. This change is considered to be a
premalignant condition because it is associated with a high incidence of further transition to
esophageal adenocarcinoma
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 voi ...
, 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 b ...
.
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
An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are inse ...
: 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 dise ...
. The cells of Barrett's esophagus are classified into four categories: nondysplastic, low-grade
dysplasia
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 microscopi ...
, high-grade dysplasia, and frank
carcinoma. High-grade dysplasia and early stages of adenocarcinoma may be treated by endoscopic resection or
radiofrequency ablation
Radiofrequency ablation (RFA), also called fulguration, is a medical procedure in which part of the electrical conduction system of the heart, tumor or other dysfunctional tissue is ablated using the heat generated from medium frequency alternati ...
. Later stages of adenocarcinoma may be treated with
surgical resection or
palliation
Palliative care (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wit ...
. 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
Norman Rupert Barrett (16 May 1903 – 8 January 1979) was an Australian-born British thoracic surgeon who is widely yet mistakenly remembered for describing what became known as Barrett's oesophagus.
Early life
Norman Barrett was born on 16 M ...
(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
Heartburn, also known as pyrosis, cardialgia or acid indigestion, is a burning sensation in the central chest or upper central abdomen. Heartburn is usually due to regurgitation of gastric acid (gastric reflux) into the esophagus. It is the m ...
* 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 liq ...
)
* vomiting blood (
hematemesis
Hematemesis is the vomiting of blood. It is always an important sign. It can be confused with hemoptysis (coughing up blood) or epistaxis (nosebleed), which are more common. The source is generally the upper gastrointestinal tract, typically abo ...
)
* 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. Sha ...
where the esophagus meets the stomach
* pain when swallowing (
odynophagia
Odynophagia is pain when swallowing. The pain may be felt in the mouth or throat and can occur with or without difficulty swallowing. The pain may be described as an ache, burning sensation, or occasionally a stabbing pain that radiates to the b ...
), which can lead to unintentional weight loss
The risk of developing Barrett's esophagus is increased by
central obesity
Abdominal obesity, also known as central obesity and truncal obesity, is a condition when excessive visceral fat around the stomach and abdomen has built up to the extent that it is likely to have a negative impact on health. Abdominal obesity has ...
(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
![Histopathology of Barrett's esophagus, annotated](https://upload.wikimedia.org/wikipedia/commons/0/0c/Histopathology_of_Barrett%27s_esophagus%2C_annotated.jpg)
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
Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together wi ...
(
Herceptin
Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together wi ...
) 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 ...
, 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 abno ...
.
Individuals with
GERD Gerd or GERD may refer to:
* Gerd (given name), a list of people with the given name or nickname
* Gerd (moon), a moon of Saturn
* Gerd Island, South Orkney Islands, Antarctica
* Gastroesophageal reflux disease, a chronic symptom of mucosal damage ...
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 d ...
.
[
]
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
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 intercellula ...
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 intercellula ...
epithelium—an example of metaplasia
Metaplasia ( gr, "change in form") is the transformation of one differentiated cell type to another differentiated cell type. The change from one type of cell to another may be part of a normal maturation process, or caused by some sort of abno ...
. 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
An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are inse ...
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 local ]NHS
The National Health Service (NHS) is the umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...
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
Esophagogastroduodenoscopy (EGD) or oesophagogastroduodenoscopy (OGD), also called by various other names, is a diagnostic endoscopic procedure that visualizes the upper part of the gastrointestinal tract down to the duodenum. It is considere ...
, 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 invisi ...
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.
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
Epithelial dysplasia, a term becoming increasingly referred to as intraepithelial neoplasia, is the sum of various disturbances of epithelium, epithelial proliferation and differentiation as seen microscopically. Individual cellular features of d ...
(or " intraepithelial neoplasia").
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
Esophagectomy or oesophagectomy is the surgical removal of all or parts of the esophagus.
Medical uses
The principal objective is to remove the esophagus, a part of the gastrointestinal tract. This procedure is usually done for patients with esoph ...
) or endoscopic treatments such as endoscopic mucosal resection
Endoscopic mucosal resection is a technique used to remove cancerous or other abnormal lesions found in the digestive tract. It is one method of performing a mucosectomy.
For the esophagous
Endoscopic mucosal resection has been advocated for ...
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
An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are inse ...
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 dise ...
(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 microscopic ...
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
Radiofrequency ablation (RFA), also called fulguration, is a medical procedure in which part of the electrical conduction system of the heart, tumor or other dysfunctional tissue is ablated using the heat generated from medium frequency alternati ...
, 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 inhibitor
Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump.
They are the most potent inhibitor ...
s 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. Radi ...
, 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
Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance, used in conjunction with molecular oxygen to elicit cell death (phototoxicity).
PDT is popularly used in treating acne. It is used cl ...
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, 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
Endoscopic mucosal resection is a technique used to remove cancerous or other abnormal lesions found in the digestive tract. It is one method of performing a mucosectomy.
For the esophagous
Endoscopic mucosal resection has been advocated for ...
has also been evaluated as a management technique. Additionally an operation known as a Nissen fundoplication
A Nissen fundoplication, or laparoscopic Nissen fundoplication when performed via laparoscopic surgery, is a surgical procedure to treat gastroesophageal reflux disease (GERD) and hiatal hernia. In GERD, it is usually performed when medical thera ...
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 inc ...
(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, 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
The thorax or chest is a part of the anatomy of humans, mammals, and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main divisions of the crea ...
surgeon Norman Barrett
Norman Rupert Barrett (16 May 1903 – 8 January 1979) was an Australian-born British thoracic surgeon who is widely yet mistakenly remembered for describing what became known as Barrett's oesophagus.
Early life
Norman Barrett was born on 16 M ...
(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 conditionis 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 (NIDDK)
Barrett's esophagus Video Overview
an
Barrett's esophagus Health Information
at Mayo Clinic
The Mayo Clinic () is a nonprofit American academic medical center focused on integrated health care, education, and research. It employs over 4,500 physicians and scientists, along with another 58,400 administrative and allied health staff, ...
{{DEFAULTSORT:Barrett Esophagus
Esophagus disorders