Barrett's esophagus

Key Terms: Diaphragm.

Definition

Barrett's esophagus is pre-cancerous condition in which normal cells lining the esophagus are replaced with abnormal cells that, in some people, develop into a type of cancer of the esophagus called adenocarcinoma.

Description

The esophagus is a tube 10–13 inches (25–33 cm) long and about 1 inch (2.5 cm) wide that carries food from the mouth to the stomach. Normally, the esophagus is lined with squamous epithelial cells. These cells are similar to skin cells, and look smooth and pinkish-white.

The stomach makes acid to help digest food. A different type of cell that is resistant to acid lines the stomach. These cells look red and velvety. At the place where the esophagus meets the stomach, there is a ring of muscle called the lower esophageal sphincter (LES) muscle that normally keeps acid stomach juices from backflowing into the esophagus. When this sphincter is not working correctly, due to a hiatal hernia, medications, or loss of muscle tone, acid material enters the bottom portion of the esophagus. This backflow is called reflux. When reflux occurs frequently over an extended period of time, it is called gastroesophageal reflux disease (GERD).

Acid and digestive enzymes from the stomach irritate the cells lining the esophagus. The result is inflammation of the esophagus called esophagitis, or heartburn. When the cells lining the lower esophagus are frequently exposed to stomach juices, they erode and are replaced with abnormal cells. These new cells are more resistant to stomach acids and, while they look similar to the cells lining the stomach, they are different. Under the microscope, they appear as a pre-cancerous type of cell not normally found in the body.

These new, pre-malignant cells are called specialized columnar cells. Once specialized columnar cells appear, even if the GERD is controlled and the esophagus heals, the abnormal cells remain and are not replaced with normal cells. The presence of patches of these abnormal red cells in the esophagus is known as Barrett's esophagus. The condition is named after British surgeon Norman Barrett (1903–1979).

Cancer that develops from Barrett's esophagus is called adenocarcinoma. It is one of two types of cancer of the esophagus. This type of cancer cannot occur unless the normal cells lining the esophagus have been damaged and replaced with abnormal cells.

Heartburn is an extremely common complaint. About 10% of people in the United States, or more than 20 million Americans, experience severe or frequent symptoms. Of those people who have frequent heartburn for five years or more, 10–20% develop Barrett's esophagus. From this group, approximately 5–10% go on to develop cancer. Overall, people with Barrett's esophagus have a 30- to 125-fold higher risk of developing adenocarcinoma than the general population.

Demographics

White men over age 45 who experience frequent heartburn for more than 10 years are at highest risk of developing adenocarcinoma arising from Barrett's esophagus. Adenocarcinoma is one of the most rapidly increasing types of cancer in the United States and Western Europe. Often, when the esophagus is damaged by stomach acid, the lining at the entrance to the stomach becomes thick and hard and the opening of the esophagus into the stomach narrows (stricture). People with strictures appear to be at higher risk of developing Barrett's esophagus than other people with GERD. Barrett's esophagus is rare in children.

Causes and Symptoms

Barrett's esophagus is caused by gastroesophageal reflux disease that allows the stomach's contents to damage the cells lining the lower esophagus. However, every person who has GERD does not develop Barrett's esophagus. Researchers have thus far been unable to predict which people who have heartburn 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 heart-burn and the development of Barrett's esophagus. Sometimes people with Barrett's esophagus will have no heartburn symptoms at all. In rare cases, damage to the esophagus may be caused by swallowing a corrosive substance such as lye.

The change from normal to pre-malignant cells that indicates Barrett's esophagus does not cause any particular symptoms. However, warning signs that should not be ignored include:

• frequent and long-standing heartburn
• trouble swallowing (dysphagia)
• vomiting blood
• pain under the breast bone where the esophagus meets the stomach
• unintentional weight loss because eating is painful

Diagnosis

Tissue biopsies and an endoscopy are used to diagnose Barrett's esophagus. An endoscopy is normally done in a clinic under sedation or light anesthesia. A flexible fiber-optic tube is inserted through the mouth and down into the esophagus, which allows a doctor to observe the lining of the esophagus.

Sometimes the line dividing the esophagus from the stomach is not clear. Many people who have trouble with heartburn have a condition called hiatal hernia. A hiatal hernia is a stretching, or dilation, of the hole of the diaphragm that allows a bit of the stomach to bulge up into the esophagus. Because the abnormal cells that develop with Barrett's esophagus look like the cells that normally line the stomach, simply looking at the esophagus during an endoscopy is often not enough to diagnose Barrett's esophagus.

Depending on what is observed, the doctor will use tiny clips at the end of the endoscope to collect samples of tissue. This is a painless procedure. The samples are sent to the laboratory where they are examined under the microscope. Microscopic findings that abnormal cells have replaced normal cells are the only definitive diagnosis of Barrett's esophagus.

Currently, trials are underway to find alternative ways to recognize abnormal esophageal cells. One trial involves the use of laser-induced spectroscopy to visually pinpoint abnormal cells during endoscopy. This has the advantage of requiring no tissue biopsies, and allows the doctor to make an immediate diagnosis rather than wait several days for laboratory results. The technique, however, is still in the experimental stage and is not part of normal clinical practice.

Treatment Team

A gastroenterologist (a specialist in diseases of the digestive system) will diagnose and monitor Barrett's esophagus. Should the pre-malignant cells of Barrett's esophagus develop into adenocarcinoma, an oncologist (cancer specialist) or a cancer surgeon will take over treatment of the cancer.

Clinical Staging, Treatments, and Prognosis

The American College of Gastroenterologists (ACG) recognizes five stages of cellular changes in biopsy samples obtained from the esophagus. These are (in increasing severity):

• Negative: No abnormal changes in the cells.
• Indefinite: A few cellular changes; often difficult to distinguish from low-grade dysplasia.
• Low-grade dysplasia: Some signs of cellular abnormality are present.
• High-grade dysplasia: Many signs of cellular abnormality are present.
• Carcinoma: Malignant cells are present.

Treatment and monitoring of Barrett's depends on the results of the biopsies. First-line treatment is aimed at stopping stomach acid from entering the esophagus and giving the lining of the esophagus a chance to heal. Two categories of drugs are used to prevent the stomach from producing acid. Histamine₂ blockers include cimetidine (Tagamet), ranitidine (Zantac), and nizatidine (Axid). Proton pump inhibitors include omeprazole (Prilosec)and lansoprazole (Prevacid). Lifetime therapy is usually necessary to control GERD, and higher than normal doses of these drugs may be necessary for people with Barrett's esophagus. Surgery to control GERD is recommended only when these drugs are ineffective or if the patient is unwilling or unable to continue taking them.

Monitoring by endoscopy with biopsies has been the standard approach to Barrett's esophagus. However, there is some debate about the effectiveness of the monitoring in detecting adenocarcinomas and about how cost-effective the monitoring is. Research in this area continues, but ACG guidelines (1999) suggest the following monitoring program:

• Negative or indefinite biopsies: At least two follow-up endoscopies and biopsies at two- to three-year intervals.
• Low-grade dysplasia: Endoscopies and biopsies every six months for a year, then every year if low-grade dysplasia continues.

Treatment of high-grade dysplasia is controversial. Diagnosis of high-grade dysplasia requires confirmation by at least one expert pathologist, with two experts' opinions recommended. One treatment choice is surgery to remove the esophagus (esophagectomy). About 40–45% of people who have high-grade dysplasia also have previously undetected adenocarcinoma. The advantage of surgically removing the esophagus is that the cancerous cells are also removed. However, in 2004 physicians emphasized that acid suppression is definitely favored over surgery, as is a new form of surgery called duodenal diversion.

The alternative to surgery is to continue to monitor cellular changes with endoscopies and biopsies every three months. The choice of treatment depends both on the health of the patient and on the patient's preference.

Surgical removal of the esophagus is the only effective way known to treat adenocarcinoma. The survival rate for people who progress from Barrett's esophagus to adenocarcinoma is poor, with fewer than 10% surviving five years. However, the earlier the cancer is detected and the esophagus removed, the greater the chances of survival.

Alternative and Complementary Therapies

Several non-medical ways to prevent GERD can be used effectively along with drug treatments that block the production of stomach acid. These include:

• raising the head of the bed a few inches on bricks to encourage gravity to keep the stomach contents from rising into the esophagus
• eliminating caffeine, acidic foods such as orange juice, and spicy foods from the diet
• eating smaller, more frequent meals, rather than large meals
• not eating within three hours of going to bed None of these methods have any reported adverse side effects.

Clinical Trials

Since adenocarcinoma arising from Barrett's esophagus is one of the fastest-growing cancers in the United States and Europe, it has sparked new research activity concerning more sensitive ways to identify high-grade dysplasia, the best methods of monitoring Barrett's esophagus, and the techniques to remove adenocarcinoma without removing the entire esophagus. One of these clinical trials involves using drugs to make cancer cells more sensitive to light, and then using a laser to kill these cells in the esophagus. Another clinical trial involves determining if genetic markers can be used to predict which people with Barrett's esophagus are at risk for developing cancer.

The selection of clinical trials underway changes frequently. Current information on clinical trials in process and where they are being held is available by entering the search term "Barrett's esophagus" at the following Web sites:

• National Cancer Institute or 1-800-4-CANCER.
• National Institutes of Health Clinical Trials .
• Center Watch: A Clinical Trials Listing .

Prevention

People cannot get esophageal adenocarcinoma unless the cells lining the esophagus are damaged. Prevention, therefore, involves prompt treatment of GERD. Some studies have found that factors that increase the risk of a person with the Barrett's esophagus condition developing into adenocarcinoma include heavy smoking, being overweight, and a family history of gastric cancer. People with chronic gastroesophageal reflux symptoms, particularly those over age 50, should have a screening upper endoscopy.

Special Concerns

People who are diagnosed with Barrett's esophagus should expect to eliminate caffeine from their diet as caffeine stimulates the production of stomach acid. Other foods that may need to be eliminated include citrus fruits and juices, tomatoes, and spicy foods.

Questions to Ask the Doctor

• How would you characterize the changes in the cells in my esophagus?
• What kind of drugs will you prescribe to control my reflux?
• What frequency of endoscopic monitoring do you propose?
• What are the chances of my Barrett's esophagus progressing to adenocarcinoma?
• If high-grade dysplasia is present, where can I get a second opinion?
• If high-grade dysplasia is present, what is involved in a esophagectomy?
• What is daily life like after an esophagectomy?
• Where can I find out more about clinicaltrials using drugs and light from a laser (called endoscopic laser photablation) to treat adenocarcinoma?
• What changes in my lifestyle can I make to help control my reflux?
• If my GERD cannot be controlled with medication, what is involved in surgery to control reflux?
• Are there any particular signs or symptoms that suggest that I should see a doctor immediately rather than waiting until my next scheduled endoscopy?

People with high-grade dysplasia are faced with the stressful decision of whether to undergo surgical removal of the esophagus and endure the lifestyle changes that loss of the esophagus involves, or whether to proceed with intensive monitoring, realizing that monitoring is not totally effective and that cancer may not always be detected early. People faced with this decision should discuss the matter with their physicians, their loved ones, and support group members to get a balanced picture of how their lives may be changed by their choices.

Resources

Books

Sharma, Prateek, Richard E. Sampliner, and Bradley Marino. Barrett's Esophagus and Esophageal Adenocarcinoma. 2nd ed. Boston: Blackwell Science, 2001.

Periodicals

D'Eprio, Nancy. "Barrett's Esophagus: Put Guidelines Into Practice." Patient Care 33 (September 1999): 73.

Jankowski, Janusz, et. al. "Barrett's Metaplasia." The Lancet 356 (December 2000): 2079.

McGarrity, Thomas. "Barrett's Oesophagus: The Continuing Conundrum." British Medical Journal 321 (November 2000): 1238.

Morales, Thomas G., and Richard E. Sampliner. "Barrett's Esophagus." Archives of Internal Medicine. 159 (July 1999): 1411.

"Researchers Describe Guidelines for Barrett Esophagus Screening." Biotech Week April 28, 2004: 606.

"Results of Surgical Treatment of Barrett Esophagus 1980—2003 Are Not Optimal." Biotech Week May 19, 2004: 582.

Organizations

American Cancer Society. (800) ACS-2345. .

Other

Cancerlinksusa. fc.

OncoLink University of Pennsylvania Cancer Center..

—Tish Davidson, A.M.; Teresa G. Odle

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Chronic peptic ulcer of the lower esophagus due to the presence of columnar epithelium resembling the mucosa of the gastric cardia. Also called Barrett's esophagus.

Barrett's esophagus
Classification and external resources
Endoscopic image of Barrett's esophagus, which is the area of red mucosa projecting like a tongue. Biopsies showed intestinal metaplasia.
ICD-10	K22.7
ICD-9	530.85
OMIM	109350
DiseasesDB	1246
MedlinePlus	001143
eMedicine	radio/73
MeSH	D001471

Barrett's esophagus (British English: Barrett's oesophagus), sometimes called Barrett's syndrome or columnar epithelium lined lower oesophagus (CELLO), refers to an abnormal change (metaplasia) in the cells of the inferior portion of the esophagus. A positive diagnosis generally requires observing specific macroscopic and microscopic changes. The normal squamous epithelium lining of the esophagus is replaced by metaplastic columnar epithelium. Columnar epithelium refers to a cell type that is typically found in more distal parts of the gastrointestinal system. The medical significance of Barrett’s esophagus is its strong association with esophageal adenocarcinoma, a particularly lethal cancer.

The main cause of Barrett's esophagus is thought to be an adaptation to chronic acid exposure from reflux esophagitis.^[1] In the last 40 years, the incidence of esophageal adenocarcinoma has been increasing in the Western world. Barrett's esophagus is found in 5–15% of patients who seek medical care for heartburn (gastroesophageal reflux disease, GERD), although a large subgroup of patients with Barrett's esophagus do not have symptoms.^[2] It is considered to be a premalignant condition because it is associated with an increased risk of esophageal cancer (more specifically, adenocarcinoma) of about 0.5% per patient-year.^[2][3] Diagnosis of Barrett's esophagus requires endoscopy (more specifically, esophagogastroduodenoscopy, a procedure in which a small camera is inserted through the mouth to examine the esophagus, stomach, and duodenum) and biopsy. The cells of Barrett's esophagus, after biopsy, are classified into four general categories: non-dysplastic, low-grade dysplasia, high-grade dysplasia, and frank carcinoma. High-grade dysplasia and frank carcinoma patients are generally advised to undergo surgical treatment. Non-dysplastic and low-grade patients are generally advised to undergo annual observation with endoscopy. In high-grade dysplasia, the risk of developing cancer might be at 10% per patient-year or greater.^[2]

The condition is named after Norman Barrett (1903–1979) who described the condition in 1950.^[4]

Contents 1 Symptoms 2 Mechanism 3 Diagnosis 4 Management 5 Prognosis 6 Epidemiology 7 History 8 Additional images 9 References 10 External links

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 the following symptoms:

• frequent and longstanding heartburn
• trouble swallowing (dysphagia)
• vomiting blood (hematemesis)
• pain under the breastbone where the esophagus meets the stomach
• unintentional weight loss because eating is painful

The risk of developing Barrett's esophagus is increased by central (vs. peripheral) obesity.^[5] 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.^[6]

Mechanism

Barrett's esophagus occurs due to chronic inflammation. The principal cause of the chronic inflammation is gastroesophageal reflux disease, GERD (UK: GORD). In this disease, acidic stomach, bile, small intestine and pancreatic contents cause damage to the cells of the lower esophagus. Recently, it was shown that bile acids are able to induce intestinal differentiation, in gastroesophageal junction cells, through inhibition of the Epidermal growth factor receptor (EGFR) receptor which results in inhibition of Akt, upregulation of the p50 subunit of NF-kB (NFKB1) and ultimately activation of the promotor of the homeobox gene CDX2. The latter mastergene is responsible for the expression of intestinal markers such as Guanylate cyclase 2C^[7] .^[8] This mechanism explains the selecion of HER2/neu (or ERBB2) 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 (GEJ). 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. In rare cases, damage to the esophagus may be caused by swallowing a corrosive substance such as lye.

Diagnosis

A new technique to detect and treat Barret's esophagus is being used in Portsmouth, Hampshire, United Kingdom with great success. Ordinary Vinegar highlights areas of concern: http://www.bbc.co.uk/news/uk-england-hampshire-15883589

Micrograph of Barrett's esophagus (left of image) and normal stratified squamous epithelium (right of image). Alcian blue stain.

High magnification micrograph of Barrett's esophagus showing the characteristic goblet cells. Alcian blue stain.

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—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.^[9]

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 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 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. It has been shown that the protein AGR2 is elevated in Barrett's esophagus,^[10] and can be used as a biomarker for distinguishing Barrett's epithelium from normal esophageal epithelium.^[11]

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.

Management

Many professional medical societies propose endoscopic screening of patients with GERD and endoscopic surveillance of patients with Barrett's esophagus, although little direct evidence supports this practice, which is common in many developed countries.^[2] Treatment options for high-grade dysplasia include surgical removal of the esophagus (esophagectomy) or endoscopic treatments such as endoscopic mucosal resection or ablation (destruction). Currently, there is no intervention that has been shown to prevent the development of Barrett's esophagus or its progression to esophageal cancer.^[2]

The risk of malignancy is highest in the U.S. in Caucasian men more than 50 years of age with more than 5 years of symptoms. Current recommendations include routine endoscopy and biopsy (looking for dysplastic changes). If two endoscopies and biopsy sessions performed within 12 months are negative for dysplasia then surveillance can be performed every 3 years while the underlying reflux is controlled with proton pump inhibitor drugs in combination with measures to prevent reflux. For patients found to have low grade or high grade dysplasia close observation and repeat endoscopy and biopsies are indicated and the patient should be followed closely by a gastroenterologist.

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. Additionally, a recent 5-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.^[12] 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.^[13]

Endoscopic mucosal resection (EMR) has also been evaluated as a management technique.^[14] Additionally an operation known as a Nissen fundoplication can reduce the reflux of acid from the stomach into the esophagus.^[15]

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.^[16][17] 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.

Prognosis

Barrett's esophagus is only a premalignant condition. Its malignant sequela, esophageal adenocarcinoma, has a mortality rate of over 85%.^[18] The risk of developing esophageal adenocarcinoma in people who have Barrett's esophagus has been estimated to be 6–7 per 1000 person-years,^[19][20] however 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).^[21] Most patients with esophageal carcinoma survive less than 1 year.^[22]

Epidemiology

The incidence in the United States among Caucasian men is 8 times the rate among Caucasian women and 5 times greater than African American men. Several studies have estimated the prevalence of Barrett's esophagus in the normal population to be 1.6%,^[23] 1.3%,^[24] and 3.6%.^[25]

History

Barrett first described the columnar metaplasia in 1950.^[4] An association with gastroesophageal reflux was made in 1953.^[26] An association with adenocarcinoma was made in 1975.^[27]

Additional images

• 

  Micrograph of Barrett's esophagus. Alcian blue stain.

References

1. ^ Stein H, Siewert J (1993). "Barrett's esophagus: pathogenesis, epidemiology, functional abnormalities, malignant degeneration, and surgical management". Dysphagia 8 (3): 276–88. doi:10.1007/BF01354551. PMID 8359051. 
2. ^ ^{a b c d e} Shaheen NJ, Richter JE (March 2009). "Barrett's oesophagus". Lancet 373 (9666): 850–61. doi:10.1016/S0140-6736(09)60487-6. PMID 19269522. 
3. ^ 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. doi:10.1002/jso.20359. PMID 16299787. 
4. ^ ^{a b} BARRETT NR (October 1950). "Chronic peptic ulcer of the oesophagus and 'oesophagitis'". Br J Surg 38 (150): 175–82. doi:10.1002/bjs.18003815005. PMID 14791960. 
5. ^ Edelstein ZR, Farrow DC, Bronner MP, Rosen SN, Vaughan TL (August 2007). "Central adiposity and risk of Barrett's esophagus". Gastroenterology 133 (2): 403–11. doi:10.1053/j.gastro.2007.05.026. PMID 17681161. 
6. ^ Reid BJ, Li X, Galipeau PC, Vaughan TL (February 2010). "Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis". Nat. Rev. Cancer 10 (2): 87–101. doi:10.1038/nrc2773. PMC 2879265. PMID 20094044. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2879265. 
7. ^ Debruyne PR, Witek M, Gong L, Birbe R, Chervoneva I, Jin T, Domon-Cell C, Palazzo JP, Freund JN, Li P, Pitari GM, Schulz S, Waldman SA (April 2006). "Bile acids induce ectopic expression of intestinal guanylyl cyclase C Through nuclear factor-kappaB and Cdx2 in human esophageal cells". Gastroenterology 130 (4): 1191–206. doi:10.1053/j.gastro.2005.12.032. PMID 16618413. 
8. ^ Gong L, Debruyne PR, Witek M, Nielsen K, Snook A, Lin JE, Bombonati A, Palazzo J, Schulz S, Waldman SA (2009). "Bile acids initiate lineage-addicted gastroesophageal tumorigenesis by suppressing the EGF receptor-AKT axis". Clin Transl Sci. 2 (4): 286–93. doi:10.1111/j.1752-8062.2009.00131.x. PMID 20443907. 
9. ^ Fléjou J (2005). "Barrett's oesophagus: from metaplasia to dysplasia and cancer". Gut 54 Suppl 1: i6–12. doi:10.1136/gut.2004.041525. PMC 1867794. PMID 15711008. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1867794. 
10. ^ Elizabeth Pohler, Ashley L. Craig, James Cotton, Laura Lawrie, John F. Dillon, Pete Ross, Neil Kernohan and Ted R. Hupp (2004). "The Barrett’s Antigen Anterior Gradient-2 Silences the p53 Transcriptional Response to DNA Damage". Molecular and Cellular Proteomics 3 (6): 534–547. doi:10.1074/mcp.M300089-MCP200. PMID 14967811. 
11. ^ Murray E, McKenna EO, Burch LR, Dillon J, Langridge-Smith P, Kolch W, Pitt A, Hupp TR (2007). "Microarray-formatted clinical biomarker assay development using peptide aptamers to anterior gradient-2". Biochemistry 46 (48): 13742–51. doi:10.1021/bi7008739. PMID 17994709. 
12. ^ Overholt BF, Wang KK, Burdick JS, et al. (2007). "Five-year efficacy and safety of photodynamic therapy with Photofrin in Barrett's high-grade dysplasia.". Gastrointestinal endoscopy 66 (3): 460–8. doi:10.1016/j.gie.2006.12.037. PMID 17643436. 
13. ^ 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". PLoS Medicine 4 (2): e67. doi:10.1371/journal.pmed.0040067. PMC 1808095. PMID 17326708. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1808095. 
14. ^ Reshamwala P, Darwin P (2006). "Endoscopic management of early gastric cancer". Curr Opin Gastroenterol 22 (5): 541–5. doi:10.1097/01.mog.0000239870.04457.80. PMID 16891887. 
15. ^ 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. doi:10.1016/S0003-4975(03)01352-3. PMID 14759403. 
16. ^ 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 (1): 47–56. doi:10.1053/gast.2003.50008. PMID 12512029. 
17. ^ 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 (12): 945–52. doi:10.1016/S1470-2045(05)70431-9. PMID 16321762. 
18. ^ Holmes RS, Vaughan TL (January 2007). "Epidemiology and pathogenesis of esophageal cancer". Semin Radiat Oncol 17 (1): 2–9. doi:10.1016/j.semradonc.2006.09.003. PMID 17185192. 
19. ^ Thomas T, Abrams KR, De Caestecker JS, Robinson RJ (December 2007). "Meta analysis: Cancer risk in Barrett's oesophagus". Aliment. Pharmacol. Ther. 26 (11–12): 1465–77. doi:10.1111/j.1365-2036.2007.03528.x. PMID 17900269. 
20. ^ Yousef F, Cardwell C, Cantwell MM, Galway K, Johnston BT, Murray L (August 2008). "The incidence of esophageal cancer and high-grade dysplasia in Barrett's esophagus: a systematic review and meta-analysis". Am. J. Epidemiol. 168 (3): 237––49. doi:10.1093/aje/kwn121. PMID 18550563. 
21. ^ Hvid-Jensen F, et al. (2011). "Incidence of adenocarcinoma among patients with Barrett's esophagus". N Engl J Med 365: 1375–383. doi:10.1056/NEJMoa1103042. http://www.nejm.org/doi/full/10.1056/NEJMoa1103042. 
22. ^ Polednak AP (May 2003). "Trends in survival for both histologic types of esophageal cancer in US surveillance, epidemiology and end results areas". Int. J. Cancer 105 (1): 98–100. doi:10.1002/ijc.11029. PMID 12672037. 
23. ^ Ronkainen J, Aro P, Storskrubb T, et al. (December 2005). "Prevalence of Barrett's esophagus in the general population: an endoscopic study". Gastroenterology 129 (6): 1825–31. doi:10.1053/j.gastro.2005.08.053. PMID 16344051. 
24. ^ Zagari RM, Fuccio L, Wallander MA, et al. (October 2008). "Gastro-oesophageal reflux symptoms, oesophagitis and Barrett's oesophagus in the general population: the Loiano-Monghidoro study". Gut 57 (10): 1354–9. doi:10.1136/gut.2007.145177. PMID 18424568. 
25. ^ Kim JY, Kim YS, Jung MK, et al. (April 2005). "Prevalence of Barrett's esophagus in Korea". J. Gastroenterol. Hepatol. 20 (4): 633–6. doi:10.1111/j.1440-1746.2005.03749.x. PMID 15836715. 
26. ^ ALLISON PR, JOHNSTONE AS (June 1953). "The oesophagus lined with gastric mucous membrane". Thorax 8 (2): 87–101. doi:10.1136/thx.8.2.87. PMC 1019247. PMID 13077502. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1019247. 
27. ^ Naef AP, Savary M, Ozzello L (November 1975). "Columnar-lined lower esophagus: an acquired lesion with malignant predisposition. Report on 140 cases of Barrett's esophagus with 12 adenocarcinomas". J. Thorac. Cardiovasc. Surg. 70 (5): 826–35. PMID 1186274. 

External links

• 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
• Barrett's Oesophagus Campaign Originally The Barrett's Oesophagus Foundation, the UK charity committed to research into prevention of adenocarcinoma of the esophagus
• Information on RadioFrequency Ablation for Barrett's Oesophagus

v d e Digestive system · Digestive disease · Gastroenterology (primarily K20–K93, 530–579) Upper GI tract Esophagus Esophagitis (Candidal, Herpetiform) · rupture (Boerhaave syndrome, Mallory-Weiss syndrome) · UES (Zenker's diverticulum) · LES (Barrett's esophagus) · Esophageal motility disorder (Nutcracker esophagus, Achalasia, Diffuse esophageal spasm, Gastroesophageal reflux disease (GERD)) · Laryngopharyngeal reflux (LPR) · Esophageal stricture · Megaesophagus Stomach Gastritis (Atrophic, Ménétrier's disease, Gastroenteritis) · Peptic (gastric) ulcer (Cushing ulcer, Dieulafoy's lesion) · Dyspepsia · Pyloric stenosis · Achlorhydria · Gastroparesis · Gastroptosis · Portal hypertensive gastropathy · Gastric antral vascular ectasia · Gastric dumping syndrome · Gastric volvulus Lower GI tract: Intestinal/ enteropathy Small intestine/ (duodenum/jejunum/ileum) Enteritis (Duodenitis, Jejunitis, Ileitis) — Peptic (duodenal) ulcer (Curling's ulcer) — Malabsorption: Coeliac · Tropical sprue · Blind loop syndrome · small bowel bacterial overgrowth syndrome  · Whipple's · Short bowel syndrome · Steatorrhea · Milroy disease · bile acid malabsorption Large intestine (appendix/colon) Appendicitis · Colitis (Pseudomembranous, Ulcerative, Ischemic, Microscopic, Collagenous, Lymphocytic) · Functional colonic disease (IBS, Intestinal pseudoobstruction/Ogilvie syndrome) — Megacolon/Toxic megacolon · Diverticulitis/Diverticulosis Large and/or small Enterocolitis (Necrotizing) · IBD (Crohn's disease) — vascular: Abdominal angina · Mesenteric ischemia · Angiodysplasia — Bowel obstruction: Ileus · Intussusception · Volvulus · Fecal impaction — Constipation · Diarrhea (Infectious) · Intestinal adhesions Rectum Proctitis (Radiation proctitis) · Proctalgia fugax · Rectal prolapse · Anismus Anal canal Anal fissure/Anal fistula · Anal abscess  · Anal dysplasia  · Pruritus ani GI bleeding/BIS Upper (Hematemesis, Melena) · Lower (Hematochezia) Accessory Liver Hepatitis (Viral hepatitis, Autoimmune hepatitis, Alcoholic hepatitis) · Cirrhosis (PBC) · Fatty liver (NASH) · vascular (Budd-Chiari syndrome, Hepatic veno-occlusive disease, Portal hypertension, Nutmeg liver) · Alcoholic liver disease · Liver failure (Hepatic encephalopathy, Acute liver failure) · Liver abscess (Pyogenic, Amoebic) · Hepatorenal syndrome · Peliosis hepatis Gallbladder Cholecystitis · Gallstones/Cholecystolithiasis · Cholesterolosis · Rokitansky-Aschoff sinuses · Postcholecystectomy syndrome · Porcelain gallbladder Bile duct/ other biliary tree Cholangitis (PSC, Secondary sclerosing cholangitis, Ascending) · Cholestasis/Mirizzi's syndrome · Biliary fistula · Haemobilia · Gallstones/Cholelithiasis common bile duct (Choledocholithiasis, Biliary dyskinesia) · Sphincter of Oddi dysfunction Pancreatic Pancreatitis (Acute, Chronic, Hereditary, Pancreatic abscess) · Pancreatic pseudocyst · Exocrine pancreatic insufficiency · Pancreatic fistula Abdominopelvic Hernia Diaphragmatic (Congenital) · Hiatus Inguinal (Indirect, Direct) · Umbilical · Femoral · Obturator · Spigelian lumbar (Petit's, Grynfeltt-Lesshaft) undefined location (Incisional · Internal hernia) Peritoneal Peritonitis (Spontaneous bacterial peritonitis) · Hemoperitoneum · Pneumoperitoneum M: DIG anat(t, g, p)/phys/devp/enzy noco/cong/tumr, sysi/epon proc, drug(A2A/2B/3/4/5/6/7/14/16), blte

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