Barrett's esophagus

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 or 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 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.

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 on alternate 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. Histamine ₂ 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.

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 the 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 what 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 <http://cancertrials.nci.nih.gov> or 1-800-4-CANCER.
• National Institutes of Health Clinical Trials <http://clinicaltrials.gov>.
• Center Watch: A Clinical Trials Listing <http://www.centerwatch.com>.

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.

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.

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 doctors, 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'sEsophagus." Archives of Internal Medicine. 159 (July 1999): 1411.

ORGANIZATIONS

American Cancer Society. (800) ACS-2345. <http://www.cancer.org>.

OTHER

Cancerlinksusa. <http:cancerlinksusa.com>.

OncoLink University of Pennsylvania Cancer Center. <http://cancer.med.upenn.edu/disease/esophageal>.

Tish Davidson, A.M.

KEY TERMS

Diaphragm

—The muscle that separates the abdominal cavity (stomach and intestines) from the thoracic cavity (heart and lungs).

Dysplasia

—The abnormal change in size, shape, or organization of adult cells.

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 clinical trials 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?