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Slow burn: Years of chronic acid reflux can lead to serious consequences, including a deadly form of cancer

The burning feeling behind the breastbone starts shortly after eating. A sour, bitter taste creeps into the mouth, accompanied by a burning sensation in the back of the throat. The burn may last a few minutes, or even several hours.

The problem is heartburn, and nearly every person will experience it at some point in time. According to the American College of Gastroenterology, more than 60 million Americans have acid reflux at least once a month. But just because acid reflux is common does not mean it is harmless. In fact, for some people, it can become deadly.

Years of chronic, severe heartburn can lead to the development of esophageal cancer, a little-talked-about but highly fatal cancer. Statistics show that one-third of patients die within a few months after diagnosis. The five-year survival rate is a dismal 15 percent, especially when compared to a five-year survival rate of 88 percent for breast cancer and 564 percent for colon cancer.

"Of all the human cancers, esophageal cancer is probably the most devastating and the most deadly," says Tom R. DeMeester, MD, the Jeffrey P. Smith Chair in Surgery, and chair of the Department of Surgery at the Keck School of Medicine of USC.

Even more alarming, esophageal cancer is the fastest rising cancer in the country. While still relatively rare, with 14,550 new cases a year, it is approximately five times as common as it was in the 1970s.

No one is quite sure what is fueling this rapid rise, but DeMeester and his colleagues suspect that it is not just chronic heartburn, but the way chronic heartburn is being treated.

Valve trouble

For many people, occasional heartburn is the price they pay for a spicy, greasy or too-heavy meal. But for those with frequent heartburn, it may be a symptom of a more serious problem called gastroesophageal reflux disease or GERD.

GERD is a condition in which the acidic gastric juices in the stomach "reflux" or flow backward into the esophagus because of a malfunction of the valve that separates the esophagus and the stomach. The resulting sting is heartburn, which may be accompanied by a chronic cough, hoarseness and chest and stomach pains.

The esophagus is a soft, muscular tube that carries food and liquids from the mouth to the stomach. Normally, the muscular valve at the bottom of the esophagus, called the lower esophageal sphincter, opens to let food enter the stomach--and then closes to keep the stomach's contents from coming back in.

In people with GERD, the valve relaxes too often, allowing stomach acid to slosh back into the esophagus. Over time, the acid begins to corrode the lining of the esophagus, and abnormal tissue begins to develop. This new tissue no longer resembles the smooth, skin-like appearance of the esophagus and instead begins to look more like the roughridged lining of the stomach.

The esophageal lining may also change to resemble the intestines. This change is called Barrett's esophagus and is a red flag warning for people with GERD. Although people with Barrett's may never develop esophageal cancer, nearly everyone who develops esophageal cancer has Barrett's first.

According to a study published last year in the journal Gastroenterology, about three million Americans are estimated to have Barrett's, giving them about a one percent risk per year of developing cancer. That may not sound high, but DeMeester points out that it is a cumulative risk. So, for example, if you live with Barrett's for 10 years, you have a 10 percent chance of developing cancer.

"People tend to put it underneath the carpet and say, "It's only one in a hundred, it's not that big a risk,'" he explains. "But the risk keeps adding up."

Acid suppression

Adenocarcinoma of the esophagus, the form of esophageal cancer that is linked to heartburn, was practically non-existent 30 years ago, says Leslie Bernstein, Ph.D., the AFLAC Chair in Cancer Research and professor of preventive medicine at the Keck School.
Back then, the most common form of esophageal cancer was squamous cell carcinoma, a disease linked to smoking and heavy alcohol use. As smoking rates have declined in the United States, rates of squamous cell carcinoma have also declined.

But adenocarcinoma of the esophagus has been rising since the late 1970s and is now the most common esophageal cancer. In Los Angeles County, there were less than 10 annual cases of the disease in the 1970s, compared with 118 today, Bernstein says, with non-Hispanic white men and Hispanic men being affected more often than women and other ethnic groups.

Speculation about why this cancer has risen at such an alarming rate includes unhealthy diets and obesity, itself a growing epidemic. There also is a theory that a change in the way heartburn is treated may inadvertently be setting the stage for more of these cancers to develop.

People with GERD have long used antacids to battle heartburn. In the late 1970s, a new class of medications called H-2 blockers--which includes brand names such as Tagamet, Pepcid and Zantac--came on the scene. Instead of neutralizing acid, these drugs worked by limiting the production of stomach acid.

Ten years later, another class of drugs called proton-pump inhibitors was introduced. These drugs, which include Prilosec, Prevacid, Nexium and Protonix, were even more effective at suppressing acid production.

The drugs have worked wonders in stopping heartburn symptoms in people with reflux disease. Another benefit is that people with GERD no longer suffer from severe scarring and ulcers in their esophagus--all serious long-term effects of acid reflux. (Also see our Q&A: Medications for Acid Reflux)

But there is some preliminary research that proton-pump inhibitors may cause unintended consequences in some people. The drugs work not by stopping the reflux itself, but by reducing the amount of acid in the stomach's gastric juices.

The problem is that acid is not the only substance in the stomach.

Bile is a part of the blend, too. A greenish-yellow fluid from the liver, bile aids in the digestion of fats and in the removal of toxins from the body. If bile is in the stomach, and acid is suppressed, a patient with GERD will reflux mostly bile back into the esophagus instead of mostly acid.

While bile does not burn, it is an alkaline substance and can be dangerous under certain circumstances, explains Jeffrey Hagen, M.D., associate professor of surgery at the Keck School
.
"There is experimental evidence to suggest that the altering of the pH of the stomach may be quite injurious from the standpoint of developing Barrett's esophagus and ultimately, cancer," Hagen says.

Here's why: under normal conditions, the stomach is a highly acidic place, causing bile to harmlessly precipitate, like snow. In fact, this is one of the important roles acid plays in the stomach, besides warding off bacteria and foreign compounds.

But the use of proton-pump inhibitors creates a stomach environment that is less acidic. Without enough acid to break down the bile, it can stay intact and become capable of penetrating cell walls and wreaking havoc. The theory is that this may lead to Barrett's and cancer.

"Bile is at the scene of the crime in adenocarcinoma of the esophagus all the time," DeMeester says. "It's a very noxious substance."

In addition, a large Swedish epidemiological study on esophageal cancer found that patients with GERD who used protonpump inhibitors to relieve their symptoms were three times more likely to develop cancer than those people who did not use the medication.
Makers of proton-pump inhibitors have stated there is no real evidence that these medications play any role in esophageal cancer. In an article last year in The Wall Street Journal, a spokesperson for pharmaceutical manufacturer AstraZeneca argued that the first spike in cancer cases occurred before proton-pump inhibitors were introduced, and they may even have a protective effect against cancer.

Stopping reflux

DeMeester and Hagen stress that taking acid-suppressing drugs for occasional heartburn does not pose a problem. But for people with chronic GERD, another option is anti-reflux surgery. This laparoscopic surgery involves reinforcing the malfunctioning valve between the esophagus and the stomach to stop reflux. Surgeons do this by wrapping the upper portion of the stomach around the lowest portion of the esophagus, in much the same way that a bun wraps around a hot dog.

The surgery usually involves a one- or two-day hospital stay. Post-surgery, patients need to refrain from strenuous activities for about eight to 12 weeks. Long-term side effects are generally uncommon, although some patients report stomach bloating.

Anti-reflux surgery is effective at stopping reflux in about 93 percent of patients, DeMeester says. He highly recommends the surgery to his patients who have inflammation in their esophageal lining. For those patients with Barrett's, he urges them to have the surgery to stop more reflux from occurring--and possibly heal the damage.

"If there is only a small amount of Barrett's in the lining, there is a 75 percent chance it will reverse after the surgery," he says. ( See our Q&A: Acid Reflux Surgery)

Caught early

Hagen stresses that better monitoring is needed for all patients with GERD. Currently, many people feel better simply by taking prescription medications, leading them--and sometimes their doctors--to assume they are fine. In addition, the availability of over-the-counter medications allows many patients with GERD to treat themselves.

"Control of the symptoms is not good enough," Hagen argues. "Control of the reflux is the key."

DeMeester recommends an endoscopy for people who have had frequent, severe reflux for five years or more, or for those who are dependent on medications to control heartburn. An endoscopy involves inserting a lighted scope into the patient's throat to check for cancer, Barrett's esophagus or any inflammation in the lining.

If there is no damage, patients can continue taking acid-suppressing medications if they choose, DeMeester says, although they should be re-checked in five years if their reflux continues. Patients with Barrett's, he says, need to be examined every year to check for any cancerous changes.

Esophageal cancer typically does not cause symptoms until it is farther advanced; so early screening for those at risk is critical. If esophageal cancer is caught early, survival rates go way up. At a very early stage, the cancer can be removed with almost 100 percent success. If it has penetrated more deeply into the esophageal wall, part or the entire esophagus may have to be removed and reconstructed.

If left unchecked, though, the unique anatomy and location of the esophagus makes it easy for this cancer to spread to nearby lymph nodes. Once it has metastasized, survival rates plummet.

The best advice for patients, says Hagen, is to see a physician--preferably a gastroenterologist or surgeon who specializes in GERD and is current with new developments.

"People with frequent, severe reflux need to realize that they should not treat themselves," he says. "They are slowly burning themselves up inside.

By Mortin - Copyright 2009
Last modification 23/04/2010

Source: from the Fall 2006 issue of USC Health magazine, University of Southern California