DRUG INDEX
Barrett's Esophagus Medical Author: Wilfred M. Weinstein, M.D.
Medical Editor: Leslie J. Schoenfield, M.D., Ph.D.
What is Barrett's esophagus?
Barrett's esophagus occurs as a complication of chronic gastroesophageal reflux disease (GERD), primarily in white males. GERD refers to the reflux of acidic fluid from the stomach into the esophagus (the swallowing tube), and is classically associated with heartburn.
There are two requirements for the diagnosis of Barrett's esophagus. To meet these requirements, an endoscopy of the esophagus must be done. In this procedure, a tube is inserted through the mouth and down the esophagus to view and biopsy the lining of the esophagus. The two requirements are: - During endoscopy of the lower esophagus, an abnormal pink lining is seen as replacing the normal whitish lining of the esophagus. This abnormal lining is seen to extend a short distance (usually less than 2.5 inches) up the esophagus from the gastroesophageal junction (the GE junction, which is where the esophagus joins the stomach).
- Biopsy (tissue sampling) of this abnormal lining shows (under the microscope) the presence of intestinal type cells that are called goblet cells, because of their shape. Other cells are also present, some of which resemble stomach cells. However, if intestinal goblet cells are not present, then the diagnosis of Barrett's esophagus should not be made.
Barrett's esophagus is officially coded by the Library of Congress for electronic searches of the literature as Barrett esophagus, but Barrett's esophagus (with the apostrophe "s") is the name used universally. The condition is named after a surgeon, Norman Barrett, who described the condition. However, it turns out that his interpretation of the findings was not correct. In 1953, Drs. Allison and Johnstone actually described this condition along the lines we now understand, namely that a metaplasia was occurring. (Metaplasia, which is discussed below, is the term used when one adult tissue replaces another.) Nevertheless, the condition has been immortalized with Barrett's name.
Initially, it was thought that the Barrett's esophagus consisted of stomach (gastric) tissue replacing the usual squamous lining of the esophagus. However, in the mid 70's, Dr. Paull and colleagues published a paper in which they described the mucosa (inner lining) of Barrett's esophagus in greater detail than had been done previously. They pointed out that Barrett's esophagus consisted of a metaplasia in which the normal lining of the esophagus was replaced with a mixture of gastric and intestinal lining cells. The intestinal-type lining cells are also called specialized columnar cells. For a number of years, some scientists thought that there were two types of Barrett's; one in which the normal lining was replaced with stomach (gastric) type cells only, and the second in which intestinal cells were present. However, the current belief is that only the presence of intestinal-type goblet cells establishes the diagnosis of Barrett's esophagus, regardless of what other cell types are present.
Why is there so much interest in Barrett's esophagus?
The reason for the great interest in Barrett's esophagus is that it is associated with an increased risk of cancer of the esophagus. In 1978, a paper was published showing a strong association between cancer of the esophagus and Barrett's esophagus in a small group of patients. The type of cancer that occurs in patients with Barrett's is adenocarcinoma, which arises from the intestinal metaplasia. The usual cancer of the esophagus is squamous-type carcinoma, which arises from the squamous lining that is normally present in the esophagus. The connection between adenocarcinoma of the esophagus and Barrett's esophagus is now clear. In fact, this type of tumor is increasing in frequency in most countries in the Western hemisphere.
The good news, however, is that the cancer occurs in relatively few patients with Barrett's esophagus. Still, the main challenge in this condition is to watch for early warning signs of cancer in these patients by taking biopsies at endoscopies at regular intervals. This practice is called surveillance and is similar, in principle, to the surveillance in women for cancer of the cervix, wherein PAP smears are taken at regular intervals.
What causes Barrett's esophagus?
Gastroesophageal reflux disease (GERD)
GERD causes Barrett's esophagus. The esophagus is a muscular tube that is located in the chest and is used to pass food from the mouth to the stomach. The lower esophageal sphincter (LES) is a valve that is located at the junction between the stomach and the esophagus. Its function is to prevent stomach acid and other contents of the stomach from coming back into the esophagus. GERD is a condition in which excessive acid-containing fluid refluxes (flows) back into the esophagus, in part because the lower esophageal sphincter is weak. The weakness of the LES may be related, in part, to the fact that virtually all GERD patients have a hiatal hernia . In a hiatal hernia, the upper few centimeters of the stomach slide back and forth between the abdomen and the chest. This sliding may interfere with how the sphincter works as a barrier to reflux from the stomach to the esophagus.
In former years, the term hernia was used instead of GERD in explaining to patients the basis of their symptoms (usually heartburn) because virtually all GERD patients have hiatal hernias. GERD, however, is the more accurate term. You see, hiatal hernias are extremely common in the population and yet only a small number of people with hernias develop GERD. In other words, the presence of a hiatal hernia does not mean you will develop GERD. On the flip side, however, if you have GERD, you will definitely have a hiatal hernia.
Thus, Barrett's esophagus is caused by chronic (many years duration) and usually severe acid reflux in people with GERD. So, in some patients with GERD, the esophagus reacts to the repeated injury from the acidic fluid by changing the type of cell in its lining from squamous (normal cells) to columnar (intestinal-type cells). This transformation is believed to be a protective response because the specialized columnar epithelium (epithelium means lining) in Barrett's esophagus is more resistant to injury from acid than is the squamous epithelium.
Is stomach acid the only trigger to the development of Barrett's esophagus?
The fluid in the stomach contains acid that is produced by the stomach. In addition, however, the fluid may contain bile acids (in bile produced by the liver) and enzymes (produced by the pancreas) that have refluxed back from the duodenum to the stomach. (The duodenum is the first part of the small intestine beyond the stomach.) The acid that refluxes from the stomach to the esophagus clearly is injurious to the esophagus. There is some evidence, however, that the bile and pancreatic enzymes combined with the acid may be more injurious than the acid alone.
A minority of scientists believes that the bile, independently of the acid, is injurious to the esophagus. Most scientists, however, disagree with this because it appears that the presence of bile in the esophagus is drastically reduced when the drugs that are commonly used for GERD inhibit acid production. In other words, the bile (and pancreatic juice) would first reflux from the duodenum into the stomach. Then, if the bile refluxes from the stomach into the esophagus, it will do so largely by riding along with the acid reflux. Thus, when the acid production (and acid reflux) is inhibited, then so is the bile reflux.
Who develops Barrett's esophagus?
Approximately 10 to 15% of individuals with chronic symptoms of GERD develop Barrett's esophagus. The estimates are, however, that Barrett's esophagus may affect as many as 1 in 100 to 1 in 500 in the general Caucasian population, especially white males. Therefore, many people with Barrett's esophagus do not know they have it, presumably because they have GERD without any symptoms at all, or with very mild and infrequent symptoms of GERD.
A great mystery of Barrett's esophagus is why the condition is so overwhelmingly more common in white males than in any other group. For example, although women and African-Americans do not seem to be protected from developing GERD, they are largely protected (especially African-Americans) from developing Barrett's esophagus and Barrett's cancer (adenocarcinoma). Furthermore, there is evidence that in the western hemisphere, esophageal cancer and cancer of the gastroesophageal junction (called cardia cancer) are increasing in frequency, perhaps more so than any other gastrointestinal tract cancer. (You should know, however, that colon cancer is still very much more common than esophageal cancer.)
Barrett's esophagus may run in some families. Studies are underway to determine if any genes or markers can be found in these families that would predict the development of Barrett's esophagus in the general population. In these Barrett's families, as well as with Barrett's in the general population, GERD is the common denominator. However, the question is why the Barrett's occurs more commonly in these families than in others with comparably severe GERD, but no family association.
What is the specific abnormality in the inner lining (epithelium) of Barrett's esophagus?
To repeat, the first criterion for the diagnosis of Barrett's esophagus is the finding at endoscopy of a pink lining (mucosa or epithelium) in the esophagus where it normally is not seen. This abnormal lining can have the appearance of circumferential involvement (like a band) or of tongues and/or islands of pink Barrett's-type mucosa. The second criterion is that biopsies from the pink mucosa in the esophagus reveal the characteristic intestinalized mucosa (the lining normally seen in the intestines) with the typical goblet cells.
The esophageal mucosal biopsies are done during an endoscopy. An upper gastrointestinal (UGI) endoscopy is a procedure in which the doctor inserts a long flexible tube (endoscope) through the mouth and down into the esophagus to directly visualize the lining (mucosa or epithelium) of the esophagus. During the same endoscopic examination, the stomach and duodenum also can be visualized with the UGI endoscope. Multiple small samples (biopsies) of the lining epithelial tissue can be obtained through the endoscope.
Intestinal metaplasia
As indicated previously, the process of the replacement of one tissue lining by another is called metaplasia. In the stomach and intestines, metaplasia is a common response to certain types of injury. As Henry Appelman, a pathologist, stated: "When the gut is under stress it wants to be something else." Other examples of metaplasia, in which one lining replaces another, are: (1) in the stomach, wherein chronic inflammation (gastritis) may result in an intestinal lining replacing parts of the normal stomach lining; and (2) in the duodenum (just beyond the stomach), where peptic ulcers occur, the intestinal tissue surrounding the ulcer often transforms into stomach-type tissue.
We believe that the process of metaplasia is a protective or adaptive response to injury of the lining (mucosa). However, the downside of metaplasia is that in Barrett's esophagus, it carries a small but definite increase in the risk of cancer of the esophagus of the adenocarcinoma type. Now, not all metaplasias have an increased risk of cancer. For example, of the two metaplasias referred to in the previous paragraph, intestinal metaplasia in the stomach can lead to cancer, but gastric metaplasia in the duodenal bulb, the first part of the small intestine, does not.
The process of developing Barrett's begins right at the junction of the stomach and esophageal linings. The esophagus normally is lined by squamous epithelium. This squamous epithelium (lining) has a pearly white appearance, whereas the lining in the stomach and intestines has a more salmon pink color. The squamous epithelium is made up of flat squamous cells, which are similar to skin cells. The stomach or gastric lining consists of taller columnar cells as seen under the microscope. The junction of the squamous epithelium of the esophagus and the gastric epithelium occurs right at the junction of the esophagus and stomach where, as you recall, the lower esophageal sphincter is located. The common border (interface) of these two linings is often referred to as the Z line, because when examined during an endoscopy, it has a zig zag appearance.
With progressive injury to the esophagus, the metaplasia moves up into the esophagus for a distance that differs from person to person, varying usually from about 0.5 to 2.5 inches (about 1 to 6 centimeters). It can move up the entire circumference of the esophagus, encircling the whole tube in the length it occupies, or it can move up as tongues and/or islands of Barrett's with normal (squamous) lining in between (appearing patchy). The stem (origin) cell type that turns into Barrett's esophagus is not known. Although intestinal type goblet cells are the characteristic feature (hallmark) for the diagnosis of Barrett's, other cells resembling those of the stomach are also present as part of this metaplasia.
Barrett's esophagus is often referred to as short or long-segment Barrett's, based on the length of the part of the esophagus that is affected. Short segment Barrett's generally refers to lengths of Barrett's that are 3 centimeters or less. Long segment Barrett's refers to Barrett's lengths of 4 centimeters or more. These designations are arbitrary, and they simply describe the length of the esophagus that is involved with Barrett's. They have little, if any, clinical significance.
Interestingly enough, once Barrett's esophagus is diagnosed in a patient, it does not seem to progress further up into the esophagus if the patient is being treated for GERD. Thus, it seems that whatever the length is of the involvement of Barrett's when the diagnosis is first made, it generally remains the same.
Intestinal metaplasia of the Z line (gastroesophageal junction) without visible Barrett's
If biopsies are taken from GERD patients with normal appearing Z lines (no visible evidence of Barrett's esophagus), up to 30% of these biopsies will show the same intestinal type goblet cells as those that are seen in Barrett's esophagus. However, we do not routinely biopsy normal appearing Z lines to look for this change (intestinal metaplasia), nor do we do surveillance when we find it there. The reason is that intestinal metaplasia of the gastroesophageal junction region (cardia) in GERD seems to occur with similar frequency in women and African Americans as in white males, yet their risk of overt Barrett's esophagus is much less than in white males.
Therefore, the results of a routine biopsy of a normal appearing Z line in GERD should not lead to any change in management. What's more, the finding of goblet cells in this context should not be labeled, as some have suggested, as ultrashort segment Barrett's. The main reason it should not be so-labeled is because the term Barrett's implies an increased risk of cancer, and we have no evidence that this finding is associated with an increased cancer risk.
What type of cancer may complicate Barrett's esophagus?
Adenocarcinoma of the esophagus
The type of cancer associated with Barrett's esophagus is adenocarcinoma of the esophagus. Cancer arising from the squamous lining of the esophagus is called squamous cancer. Among Caucasians, the rate (frequency over time) of squamous cancer is decreasing relative to Barrett's-associated adenocarcinoma. Other racial groups (e.g., African Americans) however, have not experienced the same rate of decline in squamous cancer relative to adenocarcinoma.
Smoking and excessive alcohol ingestion are clear-cut risk factors for squamous cancers. They are also risk factors for adenocarcinoma as a complication of Barrett's esophagus. In this situation, however, it is not clear if the smoking and alcohol increase the risk for adenocarcinoma by making the GERD more severe or if the smoking and alcohol have a more direct cancer-causing effect, as occurs in squamous cancer.
Forty years ago, when a patient was diagnosed with cancer of the lower esophagus, it was almost always of squamous type. Now, in white males, the chances are that 50% or more of the lower esophageal cancers are adenocarcinomas of the esophagus or cardia (gastroesophageal junction).
Throughout the remainder of this section, the term esophageal cancer will refer to adenocarcinoma arising from the Barrett's esophagus, that is, from the metaplastic epithelium.
What is the connection with cancer of the gastroesophageal junction (cardia)?
Cancer of the gastroesophageal junction is also called cardia cancer because the region where the esophagus meets the stomach is called the cardia. This cancer, like Barrett's-associated adenocarcinoma, is found predominantly in white males, is apparently increasing in frequency at the same rate as esophageal cancer, and is connected with chronic GERD. Therefore, it has been speculated that cardia cancer starts from short segments (e.g., 1-2 cm) of Barrett's. But then, by the time the diagnosis of cancer is made, the tumor may have overrun the short segment of Barrett's and may appear to be in the cardia. This speculation about the origin of cancer of the cardia, however, remains to be proven.
Why are cases of Barrett's-associated cancer and cancer of the cardia increasing?
The answer is not known. An increasing frequency of esophageal adenocarcinoma has been observed for at least 20 years, primarily in white males. One clue to the reason for this trend may be related to a decrease in the frequency of H. pylori infections of the stomach. In other words, people with Barrett's cancer, including cardia cancer, seem to have lower rates of H. pylori infection than others of the same age and sex in the same population.
H. pylori is the bacterium that is the major cause of ulcers. It is a very common infection worldwide and causes no symptoms in the vast majority of affected people. However, about 10% of persons with H. pylori develop peptic ulcers of the stomach and duodenum. These ulcers are treated by eliminating the bacteria, which eradication, in turn, prevents a relapse of the ulcers.
If H. pylori goes untreated and remains lifelong, it causes progressive inflammation of the stomach (gastritis). In middle age and beyond, this gastritis is associated with a reduced rate of acid secretion. In many areas of the world, however, this infection is decreasing in frequency, presumably because of better public health measures. Therefore, it is possible that the protective effect (i.e., decreased acid production) of chronic H. pylori infection on the stomach diminishes. In other words, with less H. pylori gastritis, the stomach produces more acid. At the same time, we are more predisposed to reflux well into our senior years. So, although this is not a settled issue, the decreasing frequency of H. pylori infection may be one reason for the increasing frequency of Barrett's-associated adenocarcinoma.
What is dysplasia in Barrett's esophagus?
Dysplasia is a change in the cells lining the esophagus in which the cells actually appear malignant (like cancer cells). However, these cells remain in place and don't invade outside of their normal lining (as does cancer). Dysplasia occurs as a series of cell changes as Barrett's esophagus progresses to Barrett's associated cancer. Patients with Barrett's are monitored with endoscopy and biopsies (surveillance) to detect these cellular changes (the dysplasia) or at worst, early cancer. Currently, there is no way to predict which of the minority of patients with Barrett's esophagus will develop dysplasia.
Dysplasia has also been identified adjacent to other tumors of the gastrointestinal tract as well. For example, dysplasia is found in half the cases of stomach cancer and in colon cancer, in which the dysplasia is visible as so-called adenomatous polyps. Additionally, dysplasia is the same early warning cell change that pathologists look for in PAP smears of the cervix.
What are the implications of dysplasia for cancer risk?
Dysplasia is considered premalignant. This means that if dysplasia has been demonstrated on several occasions, it is believed that the patient will develop cancer if he or she lives long enough. Dysplasia is categorized as being high, low, or indefinite grade. A designation of indefinite grade means that the pathologist is unsure as to whether low grade dysplasia is present or not. When high grade dysplasia is diagnosed, cancer may already be present, and if not, the risk of developing cancer sooner is greater than with the lesser grades of dysplasia.
In follow-up biopsies of patients with dysplasia, the condition cannot be found again in some patients, whereas in others, lesser grades of dysplasia are found. This absence or decrease of dysplasia may reflect sampling variation, the removal of tiny foci (groupings of cells) of dysplasia with the initial biopsy, or actual biological reversal. The exact reason(s) are unknown.
What are biomarkers?
Using molecular research techniques, some changes, referred to as biomarkers, can be detected in biopsy specimens before dysplasia develops. These changes are similar to those that are assessed in other cancers. Biomarkers include changes in DNA content of cells, in genes and chromosomes, and in growth factors. A number of these biomarkers can be shown to appear before and during the occurrence of dysplasia. The ultimate goal would be to find a magic marker that could tell us which patients, among those with no dysplasia or low grade dysplasia, are more likely to develop high grade dysplasia or cancer. These patients would then be followed by surveillance more closely than others.
At present, all patients with Barrett's esophagus, from a surveillance point of view, are treated the same. What doctors want to have are biomarkers in tissue biopsies or in the blood that would separate (stratify) the Barrett's patients based on their degrees of risk for cancer. Such stratification would allow doctors to do biopsies more frequently in the minority of patients who are at greater risk and less frequently in those predicted to have a lower risk of cancer.
Another use for proven biomarkers would be to help validate the pathologist's interpretation of dysplasia on biopsies.
What is the risk of adenocarcinoma of the esophagus in Barrett's?
When looking at Barrett's esophagus patients as a whole group, the risk of cancer has been found to be as low as 1 in 300 patient-years. This means that if we examined 300 patients yearly, one patient would be found to have cancer every year. What we really need to know, however, is something that's a bit different. That is, it would be even more helpful to know what the risk of cancer would be if someone with Barrett's is found to have NO DYSPLASIA after 1 or 2 years of surveillance. Our belief is that this risk would be much less than the above-quoted figures of 1 in 300 patient-years.
If a patient has high grade dysplasia and a biopsy is done within 3 months, up to about 50% of these patients may be found to have cancer. Also, we know that high grade dysplasia is associated with a greater immediate or short term risk of cancer, which ranges from 15% up to more than 50% in the published literature. Therefore, the first order of management when high grade dysplasia is found is to rule out the possibility that it points to the coexistence of an adenocarcinoma.
Low grade and indefinite dysplasia are much less threatening than high grade dysplasia, but we don't know just how much less. In fact, we don't have precise data to indicate just what the cancer risk is in Barrett's patients with low grade or indefinite dysplasia.
The diagnosis of dysplasia should be as certain and precise as possible because this diagnosis can prompt a change in the treatment or the intensity of follow-up of patients with Barrett's esophagus. Moreover, it takes a great deal of experience to be able to make a precise diagnosis of the presence or specific grade of dysplasia. Therefore, especially if a change in the routine management of Barrett's is contemplated, it is a common and useful practice to ask a second pathologist (or even a third, if necessary) to review the biopsies. The idea is to see if there is agreement between the pathologists and/or to get a more experienced opinion about the presence and grade of dysplasia.
If a person has a longer segment Barrett's, one would guess that the cancer risk is greater. The data, however, is controversial in this regard. For that reason, the current practice is to do endoscopic biopsy surveillance with similar frequency in patients with short and longer segment Barrett's esophagus.
What are the symptoms of Barrett's esophagus?
Barrett's esophagus has no unique symptoms. Patients with Barrett's have the symptoms of GERD (i.e., heartburn, regurgitation of fluid, nausea, etc.). The general trend is for Barrett's patients to have more severe GERD. However, not all Barrett's have marked symptoms of GERD, and some patients are detected almost accidentally with minimal symptoms of GERD.
Heartburn is a burning sensation behind the breastbone, usually in the lower half, but which may extend all the way up to the throat. Sometimes, it is accompanied by burning or pain in the pit of the stomach just below where the breastbone ends. The second most common symptom is regurgitation (backup) of bitter tasting fluid. GERD symptoms are often worse after meals and when lying flat.
The refluxed, regurgitated fluid may involve the lungs or voice box (larynx) and thereby produce what is called the extraesophageal (outside the esophagus) symptoms (manifestations) of GERD. These symptoms include new onset adult asthma , frequent bronchitis , chronic cough , sore throats, and hoarseness . For reasons we don't understand, some GERD patients have minimal heartburn but experience other GERD symptoms (e.g., regurgitation of bitter tasting fluid or even the extraesophageal symptoms) that are more dominant in either frequency and/or severity.
Other clinical features of GERD are due to strictures and ulceration of the esophagus. A stricture is a scarring (fibrosis) of the esophagus that may cause difficulty swallowing (dysphagia). The dysphagia is sensed as a sticking (stopping) in the chest (actually in the esophagus) of solid food, or even liquids when the dysphagia is severe. Strictures must be treated by stretching them at endoscopy with dilators. Untreated, strictures may promote more spillage of food and/or gastric fluids into the lungs. Not commonly seen in GERD is massive gastrointestinal (GI) bleeding that is caused by inflammation of the esophagus. Such massive GI bleeding would result in vomiting blood or passing black or maroon stools. More commonly, however, an inflamed esophagus can cause slow bleeding that is detected when anemia (low blood) is found and/or stools are tested chemically for blood.
How is GERD treated, with or without Barrett's esophagus?
Medical (non-surgical) therapy
The medical treatments for the symptoms of Barrett's esophagus are the same as those for GERD. For further information about the treatment of GERD, please read the article on Gastroesophageal Reflux Disease (GERD).
The suppression of acid is the backbone of treatment for GERD. For milder reflux symptoms, over the counter medications are commonly used, ranging from antacids to low doses of the class of drugs called H-2 receptor antagonists (or H2 blockers). Examples of H2 blockers are cimetidine (Tagamet) and famotidine (Pepcid). For more persistent symptoms, higher (prescription) doses of the H-2 receptor antagonist drugs may be used (e.g., ranitidine (Zantac), famotidine, nizatidine (Axid), and cimetidine).
However, for more persistent symptoms requiring maintenance (ongoing) therapy or for complicated GERD with strictures or bleeding, then proton pump inhibitors (PPIs) are used. Examples of PPIs are omeprazole (Prilosec), lansoprazole (Prevacid), pantoprazole (Protonix), rabeprazole (Aciphex), and esomeprazole (Nexium). Some patients need to take only one PPI pill daily, while others need two pills (a double dose) to control symptoms. The double dose can be taken as one pill twice daily or 2 pills once daily.
PPIs are potent inhibitors of the secretion of acid from the stomach. They are effective in relieving heartburn and healing esophageal inflammation (esophagitis) and esophageal ulcers that are induced by acid reflux. The PPIs are well tolerated with few side effects. After stopping these medications, however, the symptoms of acid reflux usually return soon, sometimes with increased intensity. This increase in symptoms occurs, in part, because of a rebound hypersecretion of acid, which is a response (secreting extra acid) that is prompted by the recovery from acid inhibition.
The long-term safety of the PPIs is an important consideration. Although stomach tumors (carcinoids) were reported in experiments with older female rats, similar tumors have not been observed in people after more than 15 years of PPI use. In some people on long term PPI therapy, small benign polyps (fundic gland polyps) may develop in the upper half of the stomach. However, these polyps do not require follow-up or biopsy because they remain benign (do not become malignant) and cause no problems.
A main point to remember about PPIs is that patients should never abruptly stop taking them. When PPIs are discontinued, the dose should gradually be decreased (tapered). You see, tapering the dose minimizes the rebound hypersecretion that can occur when PPIs are stopped. Thus, if a patient is hospitalized and cannot eat (or take pills), then intravenous acid-suppressing drugs at higher doses should be given to tide them over. Also, gradual lowering (tapering) of the dose of PPIs should be done when these drugs are to be discontinued after fundoplication (anti-reflux surgery) operations for GERD.
In addition to drug therapy, certain lifestyle maneuvers are very important. These include: - Lose weight, if overweight .
- Change diet , by reducing fat, chocolate, caffeine, and acid food and fluids (e.g., citrus).
- Stop smoking.
- Avoid excessive alcohol.
- Avoid food and fluids for 90 to 120 minutes before going to bed.
- Elevate your upper body when lying in bed by (e.g., putting blocks under the bed's feet at its head).
A number of drugs, including tricyclic antidepressants and calcium channel blockers, may promote gastroesophageal reflux. Therefore, if an alternative medication can be substituted for these drugs, this may help in the management of the reflux. Patients with GERD should consult their physicians regarding whether they are taking medications that can promote reflux and if alternatives are available.
Adjunctive (supplementary) drug therapy has been used in the past for patients whose symptoms are not easily controlled with, for example, a double daily dose of a PPI. The supplementary drugs have usually fallen into the class called prokinetics. These drugs work by accelerating gastric emptying so that there is less food and fluid available in the stomach for reflux. Cisapride was the most commonly used drug in this class, but it was taken off the market because of adverse cardiac effects. Metoclopramide (Reglan) is another prokinetic agent, but it is approved only for short term use and can cause drowsiness or restlessness. Although some other prokinetic drugs are available, none have had the kind of scrutiny in GERD as did cisapride. One drug that has similar actions to cisapride is domperidone (Motilium). It is available in many countries, but is not approved by the Food and Drug Administration (FDA) in the U.S.
Surgical treatment of GERD, with or without Barrett's esophagus
GERD, with or without the presence of Barrett's esophagus, sometimes is treated by anti-reflux surgery. This operation, called fundoplication , is done to stop the reflux of acid in GERD, with or without Barrett's esophagus. It is not done for the Barrett's esophagus itself. The operation involves wrapping the upper stomach (the fundus) around the lower end of the esophagus. The purpose of the wrap is to tighten up the lower esophageal sphincter (LES valve) that is intended to prevent the reflux of stomach contents into the esophagus.
There is no evidence that anti-reflux surgery, or for that matter, acid suppression therapy with drugs, decreases the risk of esophageal cancer. This doesn't mean that the possibility is excluded, but it would take long term studies to prove that either medical or surgical treatment decreases the risk of cancer.
Candidates for the fundoplication operation are patients with GERD who: - Have developed serious complications, such as persistent strictures; or
- Require high doses of acid suppressing medications on an ongoing basis, and want to come off these medications.
Today, this surgery is usually done laparoscopically without the need for a large incision. Therefore, patients can be discharged home within a few days with a much shorter recovery time. With laparoscopy , the operative field is visualized and the fundoplication accomplished through several small holes made in the abdomen. In some patients, for technical reasons, the laparoscopic type of surgery cannot be done, and the conventional open operation is necessary.
A number of new endoscopic approaches are being evaluated to possibly replace surgery (fundoplication) for the treatment of GERD. The idea is to endoscopically tighten up the junction between the stomach and esophagus to prevent reflux. The tightening is done during upper GI endoscopy by, for example, internally sewing (suturing) or clipping the region of the lower esophageal sphincter. Until five-year data are available showing that these techniques are as effective as fundoplication, they should be considered experimental.
Why is it important to screen patients with GERD to diagnose Barrett's esophagus?
Unfortunately, most of the cancers of the esophagus currently are detected too late to be treated effectively. By the time the cancer-related symptoms of chest pain, weight loss, and progressive difficulty in swallowing (dysphagia) lead to the diagnosis, the cancer may have already spread beyond the esophagus to other organs. Indeed, there is evidence that survival is markedly improved in cancers detected in the course of surveillance for dysplasia or cancer in Barrett's esophagus as compared with survival in cancers detected after cancer symptoms prompted the seeking of medical attention. Therefore, we want to make the diagnosis of Barrett's in GERD patients, and then begin surveillance for cancer in identified Barrett's patients.
The problem is, however, as mentioned previously, that only 5% of all patients with adenocarcinomas of the esophagus or cardia (gastroesophageal junction) have had an endoscopy to show that they had Barrett's esophagus. Thus, the challenge is to identify those GERD patients who have Barrett's by screening patients with chronic GERD. Yet, sufficient research has not been done to establish guidelines for selecting which patients with GERD should be screened by endoscopy.
For now, until data are available, it seems reasonable that if a patient with GERD cannot be taken off acid suppressing drugs after 2 to 3 years (because of persistent symptoms), then an endoscopy should be done to see if Barrett's esophagus is present. One endoscopy per lifetime in patients with GERD may turn out to be sufficient screening for Barrett's.
Why is it critical to be accurate in the diagnosis of Barrett's esophagus?
When a patient is referred for the diagnosis of Barrett's esophagus, it is important that any inflammation or ulcerations be healed first with acid-suppressing drugs for at least 6 weeks. I prefer a double daily dose of the proton pump inhibitor drugs for this purpose. There are two reasons to eliminate the inflammation first before diagnosing Barrett's. One is that Barrett's can be hidden beneath the inflamed, ulcerated lining, which functions as a form of camouflage. The second is that inflammatory changes can actually resemble dysplasia and, therefore, may lead to a false positive diagnosis of dysplasia.
In the initial diagnosis of Barrett's esophagus, the endoscopist (the doctor performing the endoscopy) needs to provide the pathologist with three landmarks so that a precise diagnosis of Barrett's can be made. - One is the location of the lower esophageal sphincter (LES) or gastroesophageal junction.
- The second is the upper end of the squamo-columnar junction (Z line), which now (with Barrett's) is into the esophagus (moved north).
- The third is the location of the biopsies.
The reason that such precise descriptions need to be made is because a false positive diagnosis of Barrett's may have serious implications. Thus, the diagnosis of Barrett's esophagus can lead to higher rates (costs) for obtaining life, health, or disability insurance, or sometimes even difficulty getting insurance at all. On the other hand, it's important to know when Barrett's is, in fact, present so that the patient can be enrolled in a proper surveillance program.
If the diagnosis of Barrett's esophagus is uncertain or equivocal, then it is worthwhile obtaining a second opinion with specialists in a center that has had extensive experience with Barrett's. There are at least three reasons for obtaining this additional consultation: - To avoid concern about a long term cancer risk if the diagnosis of Barrett's was incorrectly made.
- To avoid the insurance difficulties that may come with an incorrect diagnosis of Barrett's esophagus.
- To begin cancer surveillance if the diagnosis of Barrett's is confirmed.
What does endoscopic biopsy surveillance in Barrett's esophagus involve?
Periodic random biopsies
In established Barrett's esophagus, endoscopic surveillance is done at periodic intervals to look for dysplasia. At the time of the endoscopies, many random biopsies are taken of the Barrett's mucosa (lining) to diagnose the dysplasia. The recommended approach at each endoscopy is to do four mucosal biopsies (one in each quadrant of the circumference of the esophagus) at several levels of the Barrett's esophagus. The initial four biopsies should be done at the junction of the stomach and esophagus and four more biopsies (again, one in each quadrant) should be repeated every two centimeters (about ¾ inch) going up within the Barrett's zone. If available to the endoscopist, a larger forceps (the so-called jumbo forceps) is desirable to procure larger biopsy specimens.
The current trend is to spread out (increase) the surveillance intervals in Barrett's patients who do not have dysplasia. For example, the approach I use in these patients to look for dysplasia is to do the surveillance biopsies initially and a year later. Then, if no dysplasia is found, I do the surveillance every three years. Other doctors would do it every two years. The bottom line for endoscopists doing surveillance, however, is: "Do it right so we can do it less often."
There is some evidence to show that patients with cancers found in the course of surveillance have a better survival rate than those who come to the doctor (present), usually because of cancer symptoms, without any previous surveillance. The ultimate proof that surveillance works, however, can be obtained only when it is applied to the whole population at risk and not just to those who seek medical attention. The same issues pertain to any cancer screening tests (e.g., mammography and prostate cancer screening).
If cancers are found in Barrett's patients under surveillance, the 5-year survival rate should be at least 80%. This means that at least 80% of the cancer patients would be alive 5 years after treatment. The problem is that only 5% of patients undergoing surgery for esophageal adenocarcinoma have been diagnosed with Barrett's esophagus preoperatively. Thus, only the 5% with known Barrett's were eligible for surveillance before their surgery. In other words, the challenge is not to do more surveillance, but to conduct more screening to identify those who have Barrett's esophagus in the population with chronic GERD. Then, surveillance for cancer can be done in these patients with Barrett's.
Are there better ways to diagnose dysplasia than random biopsies?
There is great interest in developing techniques that would use targeted, rather than random biopsies in identifying areas of dysplasia or early cancer. Dysplasia is often endoscopically invisible, which means that it often can't be seen just by looking at the esophageal mucosa through the endoscope. So, different optical enhancing techniques are being evaluated. The idea is to highlight the areas of dysplasia to direct (target) the biopsies to these areas. These optical methods include the use of dye sprays (chromoendoscopy), spectrophotometry to measure light wave intensity, and a technique called optical coherence tomography. These procedures, however, remain experimental.
How is high grade dysplasia managed?
In treatments for cancer or related disorders, such as dysplasia, the most common standard by which treatments in studies are measured against each other is the 5-year outcome after treatment. For example, we just mentioned the 80% 5-year survival rate for esophageal cancers that were found by surveillance in Barrett's and then treated by esophagectomy (surgical removal of the esophagus).
The finding of high grade dysplasia in Barrett's may indicate that cancer is already present. For that reason, when high grade dysplasia is found, the first thing that should be done is to repeat the endoscopy and take more biopsies. For these rebiopsies, the recommendation is to take four biopsies (one in each quadrant) every one centimeter rather than every 2 centimeters. If the biopsy findings again reveal just high grade dysplasia, there are a number of management options, including esophagectomy, continued biopsy surveillance, and several experimental approaches.
Endoscopic ultrasound, when available, is invaluable in staging early cancers and dysplasia to determine the depth and amount of tissue involvement. It is a relatively new technique that uses endoscopes as dedicated ultrasound devices. In other words, these particular endoscopes are used only for doing endoscopic ultrasound. These instruments can literally see through the wall of the esophagus with much greater accuracy than, for example, CT scanning. Endoscopic ultrasound is available in many large centers that specialize in Barrett's esophagus and/or esophageal cancer.
Esophagectomy
The gold standard of management for high grade dysplasia has always been esophagectomy. Esophagectomy involves total removal of the esophagus except for a very short cuff of esophagus at its upper end. Then, the esophagus is replaced with a segment of colon, or the stomach is brought up under the breastbone and hooked up to the remaining cuff of the esophagus.
Patients with Barrett's who are going to undergo an esophagectomy should seek out an experienced surgeon with a good track record. They should interview the surgeon about his/her results. If necessary, for this surgery, a patient should consider traveling whatever distance is required to get to a center of excellence and concentrated experience. There is no validated or magic annual number of operations that provides enough surgical experience, but some surgeons believe it should be at least 20 per year. Moreover, what's important is not just the experience with the actual surgery, but also the experience of the team in doing the pre and post operative care.
The operative death rate (mortality) associated with esophagectomy for high grade dysplasia and early cancer is near 0% in modern series of cases. However, in the postoperative period, a host of complications (operative morbidity) may occur, most of which go away (are self limited). These complications may include delayed gastric emptying of food, temporary (transient) hoarseness, gastrointestinal strictures (narrowed areas caused by scarring), and others.
Follow-up biopsy surveillance, and esophagectomy ONLY if cancer is found
Some patients with high grade dysplasia opt to just have very close follow-up. In these individuals, endoscopic biopsy surveillance is done initially every 3 months for at least a year and then perhaps less often (e.g., every 4 to 6 months). The understanding is that surgery (esophagectomy) would be done if carcinoma were found in the course of the follow-up. This has not been a universally popular approach except at a few centers. It requires a commitment on the part of the endoscopist to do meticulous surveillance biopsies frequently. It also requires that the patient be content with the frequent follow-up and with the attendant uncertainty for what the future holds.
How are low grade dysplasia and indefinite dysplasia managed?
Low grade and indefinite dysplasias are managed simply by continuing endoscopic biopsy surveillance. For these patients, however, the follow-up interval is shortened from every 2 to 3 years (which is done for Barrett's with no dysplasia) to every six months for an indefinite period of time. Esophagectomy is not considered for low grade or indefinite dysplasia unless the patient develops high grade dysplasia or cancer during the surveillance.
What are the experimental approaches for treatment of high grade dysplasia?
Experimental options now exist for patients with high grade dysplasia. Patients entertaining these experimental treatments, however, should always seek out a research team that is doing studies with these techniques. For example, with these treatments, some patients need to be retreated, but long term studies are needed to define how often retreatment is needed. Nevertheless, because they avoid the need for esophagectomy, these techniques may eventually prove to be ideal for patients who are medically very frail.
Ablation therapy
Ablation therapy is the removal of the target tissue (e.g., Barrett's mucosa, high grade dysplasia, or cancer) by procedures (e.g., laser or electrocoagulation) that literally destroy that tissue. The results of ablation therapy in Barrett's with dysplasia (as well as without dysplasia, which is discussed in the next main section) have produced two conclusions. One is that ablation succeeds in more than half the cases. The second is that the recurrence rates at different centers differ widely.
The variations in both the initial success rates and in the rates of recurrence of the Barrett's lining (mucosa or epithelium) or Barrett's dysplasia reflect several factors. These factors include the early stage of knowledge in this field, differences in the several ablation techniques, and the varying degrees of acid suppression done after ablation. All ablation therapies require subsequent acid suppression therapy either with drugs or antireflux surgery to prevent the return (recurrence) of the Barrett's in the lining (epithelium) of the esophagus.
Photodynamic therapy (PDT)
PDT is a powerful method for ablation therapy. In fact, it is the most commonly used experimental treatment for high grade dysplasia in Barrett's esophagus. This technique involves the intravenous administration of a photosensitizing agent (e.g., sodium porfimer) that is taken up more selectively by dysplastic cells. Approximately 48 hours later, a laser light is used to illuminate the photosensitized cells and then burn them. The dysplasia that is treated in this way can be eliminated in more than 75% of patients. However, some Barrett's esophagus remains behind and needs biopsy follow-up or additional ablation. Long-term studies will be necessary to demonstrate whether this technique prevents esophageal adenocarcinoma on a long term basis (i.e., 5 years and longer after treatment).
One disadvantage of this commonly used photosensitizing agent is that skin sensitivity to light may persist for 6 weeks or more, which results in the easy development of sunburn. Patients, therefore, must remain out of the sunlight for this period. Other photosensitizing agents are being tested that have much less skin sensitivity, but studies are needed to determine if they are effective at eliminating the dysplasia. Esophageal narrowings (strictures) are common as a complication of PDT, but they can be managed by stretching (dilating) them until they no longer recur.
Other methods of ablation
Other experimental methods of ablation have been used to treat dysplasia, but they are less powerful than PDT and have, therefore, been applied more to low grade dysplasia and shorter segments of Barrett's with dysplasia (as well as to Barrett's without dysplasia, which is discussed in the next main section). These other experimental methods of ablation include argon (flame) plasma coagulation (APC) and multipolar electrocoagulation (MPEC). They work by burning off the dysplasia and the Barrett's through devices that are passed through a channel in an endoscope to the area to be treated.
Endoscopic mucosal resection (EMR)
Another experimental method to treat dysplasia, especially high grade dysplasia, is the removal of identified areas of the mucosa by cutting (resecting) them out. The resection is done using snares at endoscopy, similarly to the way that polyps of the colon are removed at colonoscopy . Again, we need 5-year follow-up data to prove that all of these experimental methods are effective.
Chemoprevention with drugs
The newer drugs used to treat arthritis , the COX-2 inhibitors , are beginning to be studied in Barrett's-associated dysplasia. The purpose of these studies is to see if these drugs can downgrade the severity of dysplasia or prevent dysplasia. This approach, which is called chemoprevention, is based upon the observation that adenomatous polyps of the colon in patients with familial polyposis (hereditary multiple colonic polyps) may decrease (regress) after treatment with these drugs or even with the older nonsteroidal antiinflammatory drugs (NSAIDs). The theoretical reason to try COX-2 inhibitors in Barrett's dysplasia is that the enzyme cyclooxygenase (COX), which these drugs inhibit, is present in large amounts in Barrett's dysplasia, as it is in adenomatous polyps of the colon.
It should be stressed that long term therapy with these drugs in Barrett's esophagus should remain in the experimental arena because they may be associated with certain complications or side effects (e.g., kidney or gastrointestinal problems).
What experimental options are there for Barrett's esophagus WITHOUT dysplasia?
In an ideal world, all Barrett's esophagus, with or without dysplasia, would be ablated and this reversal would last for life. Thereby, both Barrett's and its attendant risk of cancer would be eliminated. Experimental ablation (as described above for dysplasia) is underway and being evaluated in Barrett's without dysplasia. However, long term studies still are needed to prove the durability of the ablation and to show how to maintain it (e.g., with antireflux surgery or acid-suppressing drugs).
Barrett's mucosa without dysplasia can be destroyed by using the burning (flame or electrocoagulation) ablation techniques. (As already mentioned, the more powerful PDT has been used most commonly for high grade dysplasia or cancer.) To repress the Barrett's after ablation, however, requires the elimination of reflux for life, either with high dose acid suppressing drugs or anti-reflux surgery (fundoplication).
After an ablation procedure, and the injury it causes, the normal squamous lining in the esophagus grows back. Sometimes, however, after ablation in Barrett's with or without dysplasia, residual Barrett's mucosa remains under the new lining. The outcome and clinical significance of this subterranean Barrett's are not yet known.
We are in the dawn of research into these experimental approaches both to look for the best technique and then to have long term studies verify that the Barrett's esophagus remains suppressed. At present, most studies are still trying to determine the best techniques to achieve ablation. The necessary long term studies will take at least 5 years of follow-up. Finally, it should be stressed that ablation therapy is experimental and should be restricted to formal studies.
What does the future hold for Barrett's esophagus?
Most of the future developments in this field will depend on the results of research studies. The goals of such studies would be to: - Standardize the diagnosis of Barrett's, especially to avoid over diagnosis.
- Standardize how surveillance biopsies are done so that we can "do it right and do it less often," and devote more resources to the next step, which is screening.
- Develop strategies for determining whom to screen and when to screen for the presence of Barrett's esophagus among patients with chronic GERD. At present, most GERD patients who come to the doctor (presenting) with adenocarcinoma of the esophagus have never had an endoscopy to determine whether they had Barrett's esophagus.
- Look for biomarkers (molecular tests on tissues or in blood) that would be able to separate (stratify) the cancer risk in those with Barrett's who would need closer follow-up from the majority of Barrett's patients who do not.
- Evaluate the effectiveness and safety of the techniques for ablation and endoscopic mucosal resection (EMR) of Barrett's with and without dysplasia, and then to do long term follow-up studies to determine whether cancer is prevented.
- Evaluate better techniques for targeting biopsies to areas of dysplasia to avoid the currently used method of taking random biopsies.
- Evaluate better techniques for staging early cancer with refinements of endoscopic ultrasound and other imaging techniques.
- Barrett's esophagus is a complication of chronic (long lasting) and usually severe gastrointestinal reflux disease (GERD), but occurs in only a small percentage of people with GERD.
- Criteria are needed for screening patients with GERD for Barrett's esophagus. Until validated criteria are available, it seems reasonable to do screening endoscopies in GERD patients who cannot be taken off acid suppression therapy after 2 to 3 years.
- The diagnosis of Barrett's esophagus rests upon seeing (at an endoscopy) a pink esophageal lining (mucosa) that extends a short distance (usually less than 2.5 inches) up the esophagus from the gastroesophageal junction and finding intestinal type cells (goblet cells) on biopsy of the lining.
- There is a small but definite increased risk of cancer of the esophagus (adenocarcinoma) in people with Barrett's esophagus.
- If the diagnosis of Barrett's esophagus is uncertain, then a second opinion should be obtained because this diagnosis may generate greater costs than GERD alone, as well as difficulty in obtaining life, health, and disability insurance. It is critical to make an accurate diagnosis.
- The treatment for Barrett's esophagus is, in general, essentially the same as for GERD. Treatment of GERD either medically (acid-suppression drugs) or surgically (fundoplication), however, does not result in the disappearance of Barrett's esophagus or in a reduced cancer risk.
- Dysplasia is a cellular process that occurs in the Barrett's mucosal lining of the esophagus and indicates a heightened risk of cancer. Periodic endoscopic esophageal biopsies, therefore, are done in Barrett's to look for the dysplasia.
- The recommended frequency for endoscopic biopsy surveillance in Barrett's without dysplasia is annually twice, and then, if no dysplasia is found, every 3 years.
- Endoscopic biopsy surveillance for low grade or indefinite dysplasia should be done every 6 months indefinitely.
- The management of high grade dysplasia involves repeating the biopsies right after the high grade is discovered to rule out an accompanying cancer. Esophagectomy (surgical removal of the esophagus) is the gold standard of therapy for high grade dysplasia and cancer, but experimental procedures are available.
- Ablation (removal by destruction) and other experimental techniques look promising, but they need long term (5-year) data to prove their durability and impact on the natural history of Barrett's cells in the lining of the esophagus (epithelium), dysplasia, and early cancer.
|
DISCLAIMER:
Information on this site is provided for informational
purposes and is not meant to substitute for the advice
provided by your own physician or other medical professional.
You should not use the information contained herein
for diagnosing or treating a health problem or disease,
or prescribing any medication. You should read carefully
all product packaging. Not all Canadian drugs, Canada
prescription and Canadian prescription medicine is available
at discount Canadian on line pharmacies. If you have
or suspect that you have a medical problem, promptly
contact your health care provider. Information and statements
regarding diet supplements have not been evaluated by
Health Canada and are not intended to diagnose, treat,
cure, or prevent any disease. All trade and service
marks mentioned on this site are recognized as belonging
to their respective owners.
|
|
|
|
