The Pain and Paradox of Ulcers When I was in high school I sometimes worked in a local furniture store.

My boss at the store had an ulcer and blamed his gastric pains on stress, drinking, smoking, and the foods he ate. Certainly that was the conventional wisdom, and my agitated boss would occasional modify his behavior long enough to slurp down shots of milk or cream in the hope of extinguishing his fiery stomach. Twenty years later, I was working at the National Institutes of Health (NIH) studying the cause of my former boss’ pain. It was a bacterium called Helicobacter pylori. In the interval between the furniture store and the NIH, a revolution had occurred in the diagnosis and treatment of ulcers. Like many revolutions, this one began with a lone agitator trying to overthrow the dogma of a learned and powerful authority. The agitator was an Australian physician named Barry Marshall who thought peptic ulcers might be caused by the bacteria he occasional saw in biopsies of gastric tissue. Gastroenterologists and surgeons had other ideas; for decades they had been treating ulcers with prescriptions and surgery, and saw no reason to change those practices. In 1985, Marshall drank down a culture of H. pylori bacteria and promptly developed an ulcer. Then he cured his ulcer with antibiotics. If a picture is worth a thousand words, then sometimes a dramatic experiment is worth a Nobel Prize. Marshall received one in 2005. Today, many people—and some gastroenterologists—recognize the role of bacteria in causing ulcers. H. pylori is thought to cause 90% of duodenal (small intestine) ulcers and 80% of gastric (stomach) ulcers. It is a curious creature able to live comfortably in the churning,

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acid-rich environment of the stomach. It does this by breaking down a compound called urea to produce ammonia, which reduces the acidity around the bacteria. Interestingly, that’s also how doctors sometime diagnosis an ulcer. Patients drink a solution of mildly radioactive urea and their exhaled breath is checked for radioactive carbon dioxide. Examining the blood for antibodies to H. pylori, and biopsies collected during endoscopic examination also are good diagnostic tools. Today, ulcer patients can forgo the diary cream and the lectures about stress. Treatment regimens now consist of 10-14 days of antibiotics and an acid suppressant. The FDA has approved several such treatment regimens and their effectiveness varies from 61% to 94% depending on the type of antibiotics, patient compliance, and other factors. So who gets H. pylori infections and how are they infected in the first place? In developing countries, the bacteria are probably transmitted from person to person and directly from contaminated water supplies. According to the Centers for Disease Control and Prevention (CDC), about two thirds of the world’s population is infected. “Colonized” might be a better word than “infected” because most of those people will never have any symptoms from the H. pylori lurking in their stomachs. But many others can expect bouts of gastritis, and duodenal and gastric ulcers. Even worse, they may be at increased risk of gastric cancer. Gastric cancer is the second most common cancer in the world. It is more common in the developing world, and killed an estimated 700,000 people in 2002. In 1994, H. pylori was classified as a carcinogen or cancer-causing agent.

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Getting rid of H. pylori seems like a good idea. There is some evidence this is happening because of the widespread use of antibiotics here in the West. As antibiotics kill off H. pylori the rates of ulcer and gastric cancer appear to drop. Marty Blaser (New York University) found some evidence for his effect a few years ago. But he also found increasing rates of esophageal cancer. Cancer of the esophagus is usually preceded by acid reflux from the stomach, which damages cells in the esophagus. The presence of H. pylori in the upper stomach and lower esophagus may protect those cells by neutralizing the acid. In 2003, Blaser said, “Esophageal cancer is the fastest increasing cancer in the United States today.” So, you can take antibiotics to treat an ulcer and reduce your risk of gastric cancer by eliminating H. pylori, but then leave yourself more susceptible to esophageal cancer. To complicate the picture, there are essentially two different types of H. pylori: CagA+ and CagA-. H. pylori CagA+ seems to cause ulcers and gastric cancer, but protect against cancer of the esophagus. CagA- doesn’t seem to bother either organ. Perhaps someday the ideal treatment will involve antibiotic eradication of ulcercausing H. pylori bacteria and re-seeding of the stomach and esophagus with a strain of CagA- H. pylori. Until then, pass the Pepto-Bismol.

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