Symptoms and response to treatment (therapeutic trial)

The usual way that GERD is diagnosed-or at least suspected-is by its characteristic symptom, heartburn. Heartburn is most frequently described as a sub-sternal (under the middle of the chest) burning that occurs after meals and often worsens when lying down. To confirm the diagnosis, physicians often treat patients with medications to suppress the production of acid by the stomach. If the heartburn then is diminished to a large extent, the diagnosis of GERD is considered confirmed. This approach of making a diagnosis on the basis of a response of the symptoms to treatment is commonly called a therapeutic trial.

There are problems with this approach, however, primarily because it does not include diagnostic tests. For instance, patients who have conditions that can mimic GERD, specifically duodenal or gastric (stomach) ulcers, also can actually respond to such treatment. In this situation, if the physician assumes that the problem is GERD, he or she will not look for the cause of the ulcer disease. For example, a type of infection called Helicobacter pylori, or non-steroidal anti-inflammatory drugs (e.g., ibuprofen), can also cause ulcers and these conditions would be treated differently from GERD.

Moreover, as with any treatment, there is perhaps a 20% placebo effect, which means that 20% of patients will respond to a placebo (inactive) pill or, indeed, to any treatment. This means that 20% of patients who have causes of their symptoms other than GERD (or ulcers) will have a decrease in their symptoms after receiving the treatment for GERD. Thus, on the basis of their response to treatment (the therapeutic trial), these patients then will continue to be treated for GERD, even though they do not have GERD. What's more, the true cause of their symptoms will not be pursued further.

Importance of non-acidic reflux

Acid reflux clearly is injurious to the esophagus. What about non-acid reflux? As previously discussed, there are potentially injurious agents that can be refluxed other than acid, for example, bile. Esophageal acid testing accurately identifies acid reflux and has been extremely useful in studying the injurious effects of acid. Until recently, however, it has been impossible or difficult to accurately identify non-acid reflux and, therefore, to study whether or not non-acid reflux is injurious or can cause symptoms. A new technology allows the accurate determination of non-acid reflux. This technology uses the measurement of impedence changes within the esophagus to identify reflux of liquid, be it acid or non-acid. By combining measurement of impedence and ph it is possible to identify reflux and to tell if the reflux is acid or non-acid. It is too early to know how important non-acid reflux is in causing esophageal damage, symptoms, or complications, but there is little doubt that this new technology will be able to resolve the issues surrounding non-acid reflux.
GERD At A Glance

* GERD is a condition in which the acidified liquid contents of the stomach backs up into the esophagus.
* The causes of GERD include an abnormal lower esophageal sphincter, hiatal hernia, abnormal esophageal contractions, and slow emptying of the stomach.
* GERD may damage the lining of the esophagus, thereby causing inflammation (esophagitis), although usually it does not.
* The symptoms of uncomplicated GERD are heartburn, regurgitation, and nausea.
* Complications of GERD include ulcers and strictures of the esophagus, Barrett's esophagus, cough and asthma, throat and laryngeal inflammation, inflammation and infection of the lungs, and collection of fluid in the sinuses and middle ear.
* Barrett's esophagus is a pre-cancerous condition that requires periodic endoscopic surveillance for the development of cancer.
* GERD may be diagnosed or evaluated by a trial of treatment, endoscopy, biopsy, x-ray, examination of the throat and larynx, 24 hour esophageal acid testing, esophageal motility testing, emptying studies of the stomach, and esophageal acid perfusion.
* GERD is treated with life-style changes, antacids, histamine antagonists (H2 blockers), proton pump inhibitors (PPIs), pro-motility drugs, foam barriers, surgery, and endoscopy.

Management of Barrett's esophagus

Only 10% of patients with GERD have Barrett's esophagus. Some physicians have suggested that all patients with GERD should be screened with endoscopy for the presence of Barrett's. Then, if they have Barrett's, they can undergo regular endoscopic surveillance for the development of cancer. For most physicians, however, screening all patients with GERD seems unreasonable since it would require a tremendous increase in the cost of care for patients with GERD. One study suggested that cancer of the esophagus develops more often in patients who have had heartburn more frequently and/or for a longer period of time. Accordingly, perhaps screening for Barrett's esophagus is realistic only for those GERD patients with frequent and long-standing heartburn. However, studies have yet to demonstrate the value of this approach.

Periodic surveillance for cancer is recommended in patients with Barrett's esophagus. Yet, there also may be a role for other treatments. For example, since reflux is believed to be the cause of Barrett's esophagus, it is possible that early and aggressive treatment of GERD (elimination of virtually all reflux) will prevent the progression of Barrett's esophagus to cancer. Additionally, newer experimental techniques that destroy the Barrett's cells (e.g., laser or electrocautery) also may prevent the progression to cancer. Studies are needed in Barrett's to evaluate both the aggressive therapy of GERD and the destructive therapy of Barrett's for the prevention of esophageal cancer.

Although Barrett's esophagus clearly is a pre-cancerous condition, only a minority of patients with Barrett's esophagus will develop cancer. Moreover, periodic endoscopic surveillance for cancer is expensive and each endoscopy puts a patient at a slight risk for complications of endoscopy. Thus, investigators are seeking better ways of determining which patients with Barrett's are more likely to develop cancer and need more frequent endoscopic surveillance and which patients need infrequent surveillance or, perhaps, no surveillance. Accordingly, they are evaluating newer techniques (for example, analysis of the cells' DNA) to examine in more detail the altered cells in the esophagus of patients with Barrett's. In this way, the investigators are trying to identify cellular changes that can predict the later development of cancer.

The standard treatment for early cancers in Barrett's esophagus is surgical removal of a portion of the esophagus (esophagectomy). This is major surgery. However, several experimental procedures that do not require surgery are being evaluated for treating early cancers. For example, photodynamic therapy is a procedure in which the cancers are destroyed with light after they have been sensitized to the light by the intravenous injection of light-sensitizing chemicals.

Mechanism of heartburn and damage

One unresolved issue in GERD is the inconsistent relationships among acid reflux, heartburn, and damage to the lining of the esophagus (esophagitis and the complications). Why do only a few of the many episodes of acid reflux that occur in a patient with GERD cause heartburn? Why do some patients with mildly increased acid reflux develop heartburn, while other patients with the same amount of acid reflux do not? Why does heartburn usually occur in an esophagus that is not damaged? Why is it that some patients with more damage to the esophagus have less heartburn than patients with no damage? Clearly, we have much to learn about the relationship between acid reflux and esophageal damage, and about the processes (mechanisms) responsible for heartburn. This issue is of more than passing interest. Knowledge of the mechanisms that produce heartburn and esophageal damage raises the possibility of new treatments that would target processes other than acid reflux.

One of the more interesting theories that has been proposed to explain some of these questions involves the reason for pain when acid refluxes. It often is assumed that the pain is caused by irritating acid contacting an inflamed esophageal lining. But the esophageal lining usually is not inflamed. It is possible therefore, that the acid is stimulating the pain nerves within the esophageal wall just beneath the lining. Although this may be the case, a second explanation is supported by the work of one group of scientists. These scientists find that heartburn provoked by acid in the esophagus is associated with contraction of the muscle in the lower esophagus. Perhaps it is the contraction of the muscle that somehow leads to the pain. It also is possible, however, that the contraction is an epiphenomenon, that is, refluxed acid stimulates pain nerves and causes the muscle to contract, but it is not the contraction that causes the pain. More studies will be necessary before the exact mechanism(s) that causes heartburn is clear.

Understanding

In a normal digestive system

* The muscles that line your digestive system push food along in one direction.
* Special muscles called "sphincters" serve as valves that squeeze shut between one section of your digestive system and the next. Ordinarily, they allow food to pass only in one direction.
* Acid in the stomach helps digest food. The stomach lining resists the damaging effects of this acid.

When GERD strikes

* The sphincter between the stomach and the esophagus becomes loose or relaxes at the wrong time, allowing stomach acid to flow into the esophagus (acid reflux).
* Repeated acid reflux causes erosions or sores in the lining of the esophagus ("erosive esophagitis"), leading to pain or discomfort.
* GERD symptoms can be worse at night.

What are the symptoms of uncomplicated GERD?

The symptoms of uncomplicated GERD are primarily heartburn, regurgitation, and nausea. Other symptoms occur when there are complications of GERD and will be discussed with the complications.

Heartburn

When acid refluxes back into the esophagus in patients with GERD, nerve fibers in the esophagus are stimulated. This nerve stimulation results most commonly in heartburn, the pain that is characteristic of GERD. Heartburn usually is described as a burning pain in the middle of the chest. It may start high in the abdomen or may extend up into the neck. In some patients, however, the pain may be sharp or pressure-like, rather than burning. Such pain can mimic heart pain (angina). In other patients, the pain may extend to the back. Since acid reflux is more common after meals, heartburn is more common after meals. Heartburn is also more common when individuals lie down because without the effects of gravity, reflux occurs more easily, and acid is returned to the stomach more slowly.

Episodes of heartburn may occur infrequently or frequently, but episodes tend to happen periodically. This means that the episodes are more frequent or severe for a period of several weeks or months, and then they become less frequent or severe or even absent for several weeks or months. Nevertheless, heartburn is a life-long problem, and it almost always returns.

Regurgitation

Regurgitation is the appearance of refluxed liquid in the mouth. In GERD, usually only small quantities of liquid reach the esophagus, and the liquid remains in the lower esophagus. Occasionally, and particularly in some patients, larger quantities of liquid, sometimes containing food, are refluxed and reach the upper esophagus.

At the upper end of the esophagus is the upper esophageal sphincter (UES). The UES is a circular ring of muscle that is very similar in its actions to the LES. That is, the UES prevents esophageal contents from backing up into the throat. When small amounts of refluxed liquid and/or foods breach (get through) the UES and enter the throat, there may be an acid taste in the mouth. If larger quantities breach the UES, patients may suddenly find their mouths filled with the liquid or food. What's more, frequent or prolonged regurgitation can lead to acid-induced erosions of the teeth.

Nausea

Nausea is uncommon in GERD. In some patients, however, it may be frequent or severe and may result in vomiting. In fact, in patients with unexplained nausea and/or vomiting, GERD is one of the first conditions suspected. It is not clear why some patients with GERD develop mainly heartburn and others develop mainly nausea.

What is Acid Reflux

As is often the case, the body has ways (mechanisms) to protect itself from the harmful effects of reflux and acid. For example, most reflux occurs during the day when individuals are upright. In the upright position, the refluxed liquid is more likely to flow back down into the stomach due to the effect of gravity. In addition, while individuals are awake, they repeatedly swallow, whether or not there is reflux. Each swallow carries any refluxed liquid back into the stomach. Finally, the salivary glands in the mouth produce saliva, which contains bicarbonate. With each swallow, bicarbonate-containing saliva travels down the esophagus. The bicarbonate neutralizes the small amount of acid that remains in the esophagus after gravity and swallowing have removed most of the liquid.

Gravity, swallowing, and saliva are important protective mechanisms for the esophagus, but they are effective only when individuals are in the upright position. At night while sleeping, gravity is not in effect, swallowing stops, and the secretion of saliva is reduced. Therefore, reflux that occurs at night is more likely to result in acid remaining in the esophagus longer and causing greater damage to the esophagus.

Certain conditions make a person susceptible to GERD. For example, GERD can be a serious problem during pregnancy. The elevated hormone levels of pregnancy probably cause reflux by lowering the pressure in the lower esophageal sphincter (see below). At the same time, the growing fetus increases the pressure in the abdomen. Both of these effects would be expected to increase reflux. Also, patients with diseases that weaken the esophageal muscles (see below), such as scleroderma or mixed connective tissue diseases, are more prone to develop GERD.

What is Acid Reflux

GERD is a chronic condition. Once it begins, it usually is life-long. If there is injury to the lining of the esophagus (esophagitis), this also is a chronic condition. Moreover, after the esophagus has healed with treatment and treatment is stopped, the injury will return in most patients within a few months. Once treatment for GERD is begun, therefore, it usually will need to be continued indefinitely.

Actually, the reflux of the stomach's liquid contents into the esophagus occurs in most normal individuals. In fact, one study found that reflux occurs as frequently in normal individuals as in patients with GERD. In patients with GERD, however, the refluxed liquid contains acid more often, and the acid remains in the esophagus longer.