BARRETT’S ESOPHAGUS

SUBMITTED BY SUBMITTED TO
SAFEER MOHAMMED S DR. MARIETTA DAVIDIAN
302-B GENERAL MEDICINE
 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, from normal stratified squamous epithelium to
simple columnar epithelium with interspersed goblet cells(normally
present only in the small intestine, and large intestine).
 This change is considered to be a premalignant condition because it
is associated with a high incidence of further transition to
esophageal adenocarcinoma, an often-deadly cancer.
 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.
 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.

The difference in
distribution of fat among
men (more central) and
women (more peripheral)
may explain the increased
risk in males.
PROGNOSIS

 Barrett's esophagus is a premalignant condition, not a malignant one. It’s

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 persons/year (5 per 1000
person/year in patients with dysplasia, 1.0 per 1000 person-years in patients
without dysplasia).
 The relative risk of esophageal adenocarcinoma is approximately 10 in those with
Barrett's esophagus, compared to the general population. Most patients with
esophageal carcinoma survive less than one year.
SIGNS & 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 these
symptoms:
 frequent and longstanding heartburn
 trouble swallowing (dysphagia)
 vomiting blood (hematemesis)
 pain under the sternum where the esophagus meets the stomach
 unintentional weight loss because eating is painful (odynophagia)
 The risk of developing Barrett's esophagus is increased by central obesity (vs. peripheral
obesity). The exact mechanism is unclear.
PATHOPHYSIOLOGY
 Barrett's esophagus occurs due to chronic inflammation.
 The principal cause of the chronic inflammation is gastroesophageal reflux
disease, GERD.
 In this disease, acidic stomach, bile, and small intestine and pancreatic contents
cause damage to the cells of the lower esophagus.
 Recently, bile acids were shown to be able to induce intestinal differentiation, in
gastroesophageal junction cells, through inhibition of the epidermal growth factor
receptor (EGFR) and the protein kinase enzyme.
 This results in the eventual up-regulation of the p50 subunit of protein complex NF-
κB (NFKB1), and ultimately activation of the homeobox gene CDX2, which is
responsible for the expression of intestinal enzymes such as guanylate cyclase 2C.
 This mechanism also explains the selection of HER2/neu (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
Herceptin in the treatment of adenocarcinomas at the gastroesophageal junction.
 Is over eating a reason for Barrett’s esophagus?

 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. In
rare cases, damage to the esophagus may be caused by swallowing a corrosive
substance such as lye.
 Some evidence indicates those with the eating disorder bulimia 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.
DIAGNOSIS
 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 5 years screening is not
recommended.
 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 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 [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).
 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"). 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 Oesophagus.
 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 following international
classification system 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
esophaguses (esophagectomy) or endoscopic treatments such as endoscopic
mucosal resection or ablation (destruction).
 The risk of malignancy is highest in the U.S. in Caucasian men over fifty years of
age with more than five years of symptoms. Current recommendations include
routine endoscopy and biopsy (looking for dysplastic changes).
 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 has an efficacy of 90% or greater
with respect to complete clearance of Barrett's esophagus and dysplasia with
durability 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, or systemic
chemotherapy. 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, 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), like
aspirin, have shown evidence of preventing esophageal cancer in people with
Barrett's esophagus.
 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.
 REFERENCES

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Koppert LB, Wijnhoven BP, van Dekken H, Tilanus HW, Dinjens WN (December 2005). "The
molecular biology of esophageal adenocarcinoma". Journal of Surgical Oncology. 92 (3): 169–90.
Stein HJ, Siewert JR (1993). "Barrett's esophagus: pathogenesis, epidemiology, functional
abnormalities, malignant degeneration, and surgical management". Dysphagia. 8 (3): 276–88.
Shaheen, Nicholas J.; Falk, Gary W.; Iyer, Prasad G.; Gerson, Lauren B.; American College of
Gastroenterology (January 2016). "ACG Clinical Guideline: Diagnosis and Management of
Barrett's Esophagus". The American Journal of Gastroenterology. 111 (1): 30–50, quiz 51.