What are the unresolved issues in GERD?

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 has no visible damage?
Why is it that some patients with more damage to the esophagus have less heartburn than patients with no damage?
Is heartburn not related to inflammation but rather to absorption of acid across the lining of the esophagus through widened spaces between the lining cells?
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.

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 endoscopic techniques that destroy the Barrett's cells (for example, 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. Another procedure endoscopically resects the lining of the esophagus affected by the changes of Barrett's.

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 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 impedance changes within the esophagus to identify reflux of liquid, be it acid or non-acid. By combining measurement of impedance 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.