| Barrett's esophagus|
|Endoscopic image of Barrett's esophagus, which is the area of red mucosa projecting like a tongue. Biopsies showed intestinal metaplasia.|
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Barrett's esophagus (sometimes called Barrett's syndrome, CELLO, columnar epithelium lined lower (o)esophagus or colloquially as Barrett's) refers to an abnormal change (metaplasia) in the cells of the lower end of the esophagus thought to be caused by damage from chronic acid exposure, or reflux esophagitis. Barrett's esophagus is found in about 10% of patients who seek medical care for heartburn (gastroesophageal reflux). It is considered to be a premalignant condition and is associated with an increased risk of esophageal cancer.
Barrett’s esophagus is a condition in which abnormal columnar epithelium replaces the normal squamous epithelium in the distal esophagus (metaplasia). The typical appearance is that of salmon pink segments of columnar epithelium extending above the GE (gastroenterology) junction, into the whitish squamous epithelium that is typically present in the distal esophagus. This can be seen on EGD (esophago-gastroduodenoscopy) in ~ 1 % of all patients, but in up to 20 % of those with symptoms of GERD (Gastroesophageal Reflux Disease). Although the diagnosis can be presumed during the EGD, it needs to be confirmed by biopsy.
- Unfortunately, there is a lot of debate as to where the esophagus ends. Anatomists, radiologists, physiologists and endoscopists can’t agree on the location of the GE junction, and this ‘line’ can vary by several centimeters depending on who defines it.
- Criteria differ from as little as 2 cm, to as much as 5 cm of abnormal epithelium needed to make the diagnosis.
- 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.
- This is the most common type of epithelial change that is associated with BE, and is also the type associated with the development of adenocarcinoma.
- Additionally, although the risk of developing adeno carcinoma with ‘extensive’ BE is clear, the risk is not defined for ‘short segment’ BE (< 2 – 3 cm of metaplasia).
- It appears that chronic GE reflux is causes the injury – repair cycle that stimulates squamous metaplasia. The columnar cells are more resistant to acid injury than the squamous cells.
- 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.
Norman Barrett, in 1950, defined the esophagus as, ‘that part of the foregut, distal to the cricopharyngeal sphincter, which is lined by squamous epithelium’. It is ironic, then, that columnar metaplasia of the esophagus is referred to as Barrett’s esophagus (BE). Tileston, however, was the first to describe columnar metaplasia of the esophagus in 1906, as ‘peptic ulcer of the esophagus’.
Causes and Symptoms
Barrett's esophagus is caused by gastroesophageal reflux disease, which allows the stomach's contents to damage the cells lining the lower esophagus. However, not every person who has GERD will develop Barrett's esophagus. 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. 25 % of patients are asymptomatic, and BE is picked up when EGD is performed for other, unrelated conditions. The radiographic appearance of BE is neither sensitive or specific, however certain findings are suggestive.
In rare cases, damage to the esophagus may be caused by swallowing a corrosive substance such as lye.
The change from normal to premalignant cells that indicates Barrett's esophagus does not cause any particular symptoms. However, warning signs that should not be ignored include:
- frequent and longstanding heartburn
- trouble swallowing (dysphagia)
- vomiting blood
- pain under the breastbone where the esophagus meets the stomach
- unintentional weight loss because eating is painful
Barrett's esophagus is marked by the presence of columnar epithelia 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.
The metaplastic columnar cells may be of two types: gastric (similar to those in the stomach, which is NOT technically Barrett's esophagus) or colonic (similar to cells in the intestines). 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 visible grossly 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 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.
In the United States, it is estimated that 8 - 12% of patients who are diagnosed with Barrett's esophagus have been mis-diagnosed. This significant diagnostic error may result in higher rates of medical and life insurance rates for those mis-diagnosed; as well as enrollment of patients in unnecessary surveillance programs (i.e. annual endoscopic evaluation and biopsy to monitor for the development of Barrett's esophagus). Second (consulting) opinions on pathologic materials are easily available as slides and tissue blocks are retained for 10 and 20 years, respectively. To request a consultation opinion, patients may contact their gastroenterologist for referral to a GI pathology specialty center.
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.
Recent evidence has pointed to a similar condition developing in the distal gut epithelium. Barrett's Anus is a metaplastic change in the distal rectum whose cellularity is similar to that of the gastric mucosa. While the condition is stable for many years, there has been recent evidence to show that it is the predisposing lesion to both anal teratoma and squamous cell carcinoma of the anus. Frequent bouts of steatorrhea are commonly cited as the most likely cause of Barrett's Anus, but much more research needs to be done in order to rule out causes such as HPV 8,13.
Current recommendations include routine endoscopy and biopsy (looking for dysplastic changes) every 12 months or so while the underlying reflux is controlled with proton pump inhibitor drugs in combination with measures to prevent reflux. 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, radiation therapy, or systemic chemotherapy. 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 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.
In a variety of studies, non-steroidal anti-inflammatory drugs (NSAIDS), like aspirin, 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.
Surgery and Device Based Therapy
- It seems that surgical therapy for BE / GERD may be superior to medical therapy (based on studies with 1 – 2 years of f/u in the medical arms).
- The next step is routine endoscopy to identify dysplasia. Patients with BE develop malignancy at a rate of 1 % / year. There are no studies, however, that correlate the presence of BE with a reduced survival. However, this may be due to the fact that the studies were carried out in an older population that died of disease other than esophageal CA, routine EGD is still recommended.
Epidemiology and Demographics
- BE can be seen in younger patients, but is most commonly diagnosed in patients ~ 55 years old.
- It is more common in whites, than blacks or Asians, and males are more frequently affected than females.
- Stein H, Siewert J (1993). "Barrett's esophagus: pathogenesis, epidemiology, functional abnormalities, malignant degeneration, and surgical management". Dysphagia 8 (3): 276-88. PMID 8359051.
- Koppert L, Wijnhoven B, van Dekken H, Tilanus H, Dinjens W (2005). "The molecular biology of esophageal adenocarcinoma". J Surg Oncol 92 (3): 169-90. PMID 16299787.
- Barrett N (1957). "The lower esophagus lined by columnar epithelium". Surgery 41 (6): 881-94. PMID 13442856.
- Fléjou J (2005). "Barrett's oesophagus: from metaplasia to dysplasia and cancer". Gut 54 Suppl 1: i6-12. PMID 15711008.
- Galipeau P, Li X, Blount PL, Maley CC, Sanchez CA Odze RD, Ayub K, Rabinovitch PS, Vaughan TV, Reid BJ (2007). "NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma" 4 (2): e67. PMID 17326708.
- Reshamwala P, Darwin P (2006). "Endoscopic management of early gastric cancer". Curr Opin Gastroenterol 22 (5): 541-5. PMID 16891887.
- Abbas A, Deschamps C, Cassivi SD, et al. (2004). "The role of laparoscopic fundoplication in Barrett’s esophagus". Annals of Thoracic Surgery 77 (2): 393-396. PMID 14759403.
- Corley DA, Kerlikowske K, Verma R, Buffler P (2003). "Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis.". Gastroenterology 124: 47-56. PMID 12512029.
- Vaughan TL, Dong LM, Blount PL, Ayub K, Odze RD, Sanchez, CA, Rabinovitch PS, Reid BJ (2005). "Non-steroidal anti-inflammatory drugs and risk of neoplastic progression in Barrett's oesophagus: a prospective study". Lancet Oncol 6: 945-52. PMID 16321762.
- Barrett's Esophagus at National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD)
- Barrett's Info a peer-reviewed web site of information on Barrett's esophagus and its clinical management.
- Barrett's Esophagus at Johns Hopkins University
- Barrett's Esophagus Video Overview and Barrett's Esophagus Health Information at Mayo Clinic
- The Barrett's Oesophagus Foundation The UK charity committed to research into prevention of adenocarcinoma of the oesophagus
| group5 = Clinical Trials Involving Barrett's esophagus | list5 = Ongoing Trials on Barrett's esophagus at Clinical Trials.gov • Trial results on Barrett's esophagus • Clinical Trials on Barrett's esophagus at Google
| group6 = Guidelines / Policies / Government Resources (FDA/CDC) Regarding Barrett's esophagus | list6 = US National Guidelines Clearinghouse on Barrett's esophagus • NICE Guidance on Barrett's esophagus • NHS PRODIGY Guidance • FDA on Barrett's esophagus • CDC on Barrett's esophagus
| group7 = Textbook Information on Barrett's esophagus | list7 = Books and Textbook Information on Barrett's esophagus
| group8 = Pharmacology Resources on Barrett's esophagus | list8 = AND (Dose)}} Dosing of Barrett's esophagus • AND (drug interactions)}} Drug interactions with Barrett's esophagus • AND (side effects)}} Side effects of Barrett's esophagus • AND (Allergy)}} Allergic reactions to Barrett's esophagus • AND (overdose)}} Overdose information on Barrett's esophagus • AND (carcinogenicity)}} Carcinogenicity information on Barrett's esophagus • AND (pregnancy)}} Barrett's esophagus in pregnancy • AND (pharmacokinetics)}} Pharmacokinetics of Barrett's esophagus •
| group9 = Genetics, Pharmacogenomics, and Proteinomics of Barrett's esophagus | list9 = AND (pharmacogenomics)}} Genetics of Barrett's esophagus • AND (pharmacogenomics)}} Pharmacogenomics of Barrett's esophagus • AND (proteomics)}} Proteomics of Barrett's esophagus
| group11 = Commentary on Barrett's esophagus | list11 = Blogs on Barrett's esophagus
| group12 = Patient Resources on Barrett's esophagus | list12 = Patient resources on Barrett's esophagus • Discussion groups on Barrett's esophagus • Patient Handouts on Barrett's esophagus • Directions to Hospitals Treating Barrett's esophagus • Risk calculators and risk factors for Barrett's esophagus
| group13 = Healthcare Provider Resources on Barrett's esophagus | list13 = Symptoms of Barrett's esophagus • Causes & Risk Factors for Barrett's esophagus • Diagnostic studies for Barrett's esophagus • Treatment of Barrett's esophagus
| group14 = Continuing Medical Education (CME) Programs on Barrett's esophagus | list14 = CME Programs on Barrett's esophagus
| group17 = Informatics Resources on Barrett's esophagus | list17 = List of terms related to Barrett's esophagus