Barrett's esophagus

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amresh Kumar MD [2], Hamid Qazi, MD, BSc [3]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amresh Kumar MD [2]

Barrett’s esophagus was first discovered by Dr. Norman Barrett, a Australian-born British surgeon at St Thomas’ Hospital, in 1957. Tileston, in 1906, was the first to describe columnar metaplasia of the esophagus, as ‘peptic ulcer of the esophagus’.

The following are a few aspects about the historical perspective of Barrett’s esophagus :^[1][2]

• Norman Barrett, in 1957, defined the esophagus as, ‘that part of the fore-gut, distal to the cricopharyngeal sphincter, which is lined by squamous epithelium’.
• The columnar metaplasia of the esophagus is referred to as Barrett’s esophagus (BE).
• Tileston, in 1906, was the first to describe columnar metaplasia of the esophagus, as ‘peptic ulcer of the esophagus’.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amresh Kumar MD [2]

Barrett’s esophagus may be classified according to the distance between Z line and gastroesophgeal junction (GEJ) into two subtypes which are long segment barrett’s esophagus and short segment barrett’s esophagus.

• Barrett’s esophagus may be classified according to the distance between Z line and gastroesophgeal junction (GEJ) into 2 subtypes: Long segment Barrett’s esophagus and short segment Barrett’s esophagus.^[1][2]
• Long segment Barrett’s esophagus: If the distance between the Z-line and the GEJ is ≥3 cm, it is called long segment barrett’s esophagus
• Short segment Barrett’s esophagus: If the distance between the Z-line and GEJ is <3 cm, it is called short segment barrett’s esophagus

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amresh Kumar MD [2]

Barrett’s esophagus is marked by the presence of columnar epithelium in the lower esophagus, replacing the normal squamous cell epithelium; an example of metaplasia. The columnar epithelium is better able to withstand the erosive action of the gastric secretions; however, this metaplasia confers an increased cancer risk of the adenocarcinoma type.

• Barrett’s esophagus (BE) is the metaplasia which occurs due to change in epithelium from normal squamous cell epithelium to columnar cell epithelium in the lower end of esophagus due to the corrosive action of gastric secretions in the lower end of the esophagus.^[1][2] Barrett’s esophagus has increased risk of developing into esophageal adenocarcinoma.^[3][4][5]

• There are two types of cells occur in the metaplastic columnar epithelium of Barrett’s esophagus: one is gastric type and other is colonic type. Gastric type resemble the same cells which line the gastric epithelium and colonic type resembles the same cells lining the intestinal epithelium. There will be combination of both type of cells seen on the biopsies taken from these patients during the endoscopy. The type of metaplasia in which there is increased chance of developing into Barrett’s esophagus is colonic type metaplasia in patients with increased genetic risk.^{[6][7][8][9][10][11][12]}

• Barrett’s esophagus can be seen grossly by its red/light brown color of its mucosa as compared to the light pink color of normal mucosa of esophagus under endoscopic examination, but it is very important to take biopsy specimens during endoscopic examination and should be microscopically examined to see what type of cells are present among both the types of gastric and colonic type of cells. To make the final diagnosis of Barrett’s, it is very necessary to find the colonic metaplasia and which can be identified by finding of the goblet cells in the epithelium of the biopsy specimens.^[10][11][12]

• One of the main causes of the Barrett’s esophagus is gastroesophageal reflux disease (GERD). It has been seen in many studies that chronic reflux caused by GERD induces a vicious circle of injuries and repair cycle in the squamous epithelium of esophagus. By this process, it leads to change of epithelium from normal squamous epithelium to the columnar epithelium as columnar epithelium is less susceptible to the injury caused by the acid injury as compared to the squamous epithelium.^{[13][14][15][16][17]}

• Patients with BE tend to have more severe GERD.

• Although one would think that BE develops over years, with slow replacement of squamous cells by columnar cells, it appears that this is not the case. BE tends to develop all at once with little or no progression. The reason for this is unknown.

• The development of Barrett’s esophagus is the result of multiple genetic mutations including mutations on chromosome 11p in European ancestry, genetic mutation of MGST1, mutations of genes GDF7 and TBX5, polymorphisms in genes in the androgen pathway and genetic mutations in p53 tumor suppressor.^{[6][7][8][9][10][11][12]}

Barrett’s esophagus is associated with following associated conditions:

• Gastroesophageal reflux disease^[16][17][14]
• Systemic Sclerosis^[18]
• Metabolic Syndrome^[19][20][21]

• Normally the mucosa of normal esophagus is light pink color as seen from underlying picture.
• On gross pathology, Barrett’s esophagus looks like Red/light brown esophageal mucosa.

• On microscopic histopathological analysis, gastric junctional type epithelium, gastric fundus type epithelium and specialized intestinal columnar metaplasia are characteristic findings of Barrett’s esophagus.^[22][23]

• Paull et.al. described three types of columnar epithelium that can be seen in BE:

  • Gastric junctional-type epithelium which has a pitted (foveolar) surface and mucus-secreting cells.
  • Gastric fundus-type epithelium that also has a pitted surface lined by mucus-secreting cells, in addition to having a deeper glandular layer that contains chief and parietal cells.
  • Specialized intestinal (columnar) metaplasia that has a villiform surface with mucus secreting columnar cells and goblet cells.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amresh Kumar MD [2]

Barrett’s Oesophagus is commonly caused by Gastroesophageal reflux disease.

Barrett’s esophagus is caused by Gastroesophageal reflux disease (GERD). There are several anatomic-pathophysiologic abnormalities that may contribute to GERD:^{[1][2][3][4][5]}

• Hypersecretion of gastric acid
• Decreased concentration of epidermal growth factor in salivary secretions
• Diminished esophageal pain sensitivity
• Poor contraction of the esophagus
• Decreased muscle tone of the lower esophageal sphincter

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amresh Kumar MD [2]

Barrett’s esophagus must be differentiated from esophagitis, peptic ulcer disease, GERD, esophageal carcinoma and esophageal motor disorders.

Barrett’s esophagus should be differentiated from the following diseases;

• Esophagitis^[1]
  • Pill esophagitis
  • Eosinophilic esophagitis
  • Infectious esophagitis

• GERD^[2][3]
• Esophageal carcinoma ^[4]
• Peptic ulcer disease
• Esophageal motor disorders

Disease	Signs and Symptoms								Barium esophagogram	Endoscopy	Other imaging and laboratory findings	Gold Standard
	Onset	Dysphagia			Weight loss	Heartburn	Other findings	Mental status
		Solids	Liquids	Type
Barrett’s esophagus	Gradual	+	–	Progressive	+/-	+	GERD Symptoms Chest pain Chronic cough Laryngitis Regurgitation Heartburn	Normal	Mid or high esophageal ulcer Mid or high esophageal web-like stricture Reticular mucosal pattern	The esophageal lining appears pink or red and velvety.	No any other test is done to diagnose Barrett’s esophagus	Esophageal Biopsy
Eosinophilic esophagitis	Gradual	+		Progressive	+/-	+/-	Chest pain Food impaction Cough	Normal	Multiple rings in the esophagus	Concentric rings of the esophagus– Trachealization of the esophagus	Increased serum IgE levels	Esophageal biopsy
Esophageal carcinoma	Gradual	+	+	Progressive	+	+/-	Lymphadenopathy Cachexia	Normal	Irregular stricture Pre-stricture dilatation	Esophageal obstruction Staging of disease	CT and PET scan is an optional test for staging of the disease	Biopsy
Motor disorders (Myasthenia gravis)	Gradual	+	+	Progressive	+/-	–	Ptosis Diplopia Fatigue	Normal	Stasis in pharynx and pooling in pharyngeal recesses	Velopharyngeal insufficiency Delayed swallowing function	CT may show anterior mediastinal mass (thymoma) Positive tensilon test	Anti–acetylcholine receptor antibody test
GERD	Gradual Sudden onset	+	–	Progressive	+/-	+	Cough Hoarseness	Normal	Free acid reflux Esophagitis with scarring Strictures Barrett’s oesophagus	Erythema, erosions and ulceration Barrett’s esophagus	Esophageal manometry may show decreased tone of LES	24 hour esophageal pH monitoring

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amresh Kumar MD [2]

Barrett’s esophagus can be seen in younger patients, but is most commonly diagnosed in patients ~ 55 years old.

• The incidence of Barrett’s esophagus is approximately 400 per 100,000 individuals worldwide.^[1]

• The prevalence of barrett’s esophagus is approximately 2000 per 100,000 individuals worldwide.^[2]

• The incidence of Barrett’s esophagus increases with age; the median age at diagnosis is 55 years.^[3]
• Barrett’s esophagus hardly affects individuals younger than 5 years of age.^[4]
• Barrett’s esophagus can be seen in younger patients, but is most commonly diagnosed in patients ~ 55 years old.^[3][4]
• It is an acquired condition, seen in children but rarely in younger than age of five.^[4]

• Barrett’s esophagus usually affects individuals of the Caucasians race. Blacks and Asians individuals are less likely to develop Barrett’s esophagus.^[5][6]
• The prevalence in hispanic population is unclear, some studies compare it to caucasian prevalence and other studies show a lower prevalence.^[6][5]

• Males are more commonly affected by Barrett’s esophagus than females.^[7][8] The male to female ratio is approximately 1.96 to 1.^[9]

• Barrett’s esophagus is a common disease that tends to affect equally to people in both Asian countries as well as Western countries.^[10]

• In one of the study in Sweden, it is published that the estimated rate of Barrett’s esophagus in the general population was around 1.6 percent.^[11]
• Based on these data, the estimated prevalence rate of Barrett’s esophagus in the United States population, it would be around 3.3 million individuals.^[12]

• Barrett’s esophagus is very common in developing countries and it shares the same kind of risk factors and potential towards neoplastic process as compared to those seen in developed countries.^[10]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amresh Kumar MD [2]

The most potent risk factor in the development of Barrett’s Oesophagus is chronic GERD. Other risk factors include age (>older than 50 years), sex (male), race (caucasian), hiatal hernia, elevated body mass index and intra-abdominal distribution of body fat.

The followings are the risk factors for the Barrett’s esophagus;

• Age: Older than 50 years
• Sex: Male>female^[1][2]
• Race: Caucasian
• Other:^{[3][4][5][6][7][8][9]}
  • Chronic GERD
  • Hiatal hernia
  • Elevated body mass index
  • Intra-abdominal distribution of body fat

• Barrett’s esophagus is less common in patients having Helicobacter pylori infection.^[10][11][12]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amresh Kumar MD [2]

Barrett’s esophagus is a major risk factor for development of esophageal adenocarcinoma. After diagnosis, regular surveillance is needed based on the grade of dysplasia. Screening for barrett’s esophagus is strongly recommended with multiple risk factors for esophageal adenocarcinoma include: Age > 50 years old, male, white, chronic GERD, hiatal hernia, elevated BMI (body mass index), and intra-abdominal distribution of body fat. Screening is weakly recommended in general population with GERD and no risk factors.

Barrett’s esophagus is a major risk factor for development of esophageal adenocarcinoma.^{[1][2][3][4][5]} After diagnosis, regular surveillance is needed based on the grade of dysplasia.

Screening for barrett’s esophagus is strongly recommended in:

• Age > 50 years old
• male
• White
• Chronic GERD
• hiatal hernia
• Elevated BMI (body mass index)
• Intra-abdominal distribution of body fat^[6]

Screening is weakly recommended due to moderate-quality evidence:^[6]

• Endoscopic surveillance in patients with Barrett’s esophagus is recommended within the following intervals:
  • No dysplasia: 3–5 years
  • Low-grade dysplasia: 6–12 months
  • High-grade dysplasia in the absence of eradication therapy: 3 months

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amresh Kumar MD [2]

Common complications of Barrett’s esophagus include esophageal carcinoma, esophageal stricture and esophageal ulcers.

Barrett’s esophagus is associated with increased risk of esophageal cancer. Follow-up endoscopy is recommended for dysplasia or cancer evaluation.

• The symptoms of Barrett’s esophagus usually develop in the fifth/sixth decade of life, and start with symptoms of GERD such as heartburn, regurgitation and dysphagia.
• If left untreated, 100 to 400 out of 100,000 patients with Barrett’s esophagus may progress to develop esophageal adenocarcinoma. ^{[1][2][3][4][5]}

• Common complications of Barrett’s esophagus include:
  • Esophageal carcinoma^[6]
  • Esophageal stricture^[7]
  • Esophageal ulcers^[7]

• From low-grade dysplasia to high-grade dysplasia or esophageal adenocarcinoma: 0.5 to 13.4% per year
• From high-grade dysplasia to cancer: 6% per year^[8]

• Prognosis is generally good for Barrett’s esophagus, but if it is associated with esophageal adenocarcinoma then 5 year survival rate of patients with Barrett’s esophagus is approximately 20%.^[9]

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