Never say never in medicine

MEDICAL MATTERS: The award of the 2005 Nobel Prize for Medicine to two Australian doctors for their discovery of a bacterium that causes stomach inflammation is a reminder of how far the treatment of peptic ulcer disease has progressed over the past couple of decades.

A peptic ulcer is a raw area or small hole in the lining of the stomach or the duodenum. Peptic ulceration occurs when gastric acid and a digestive enzyme called pepsin erode this lining.

It's not so long ago since the only treatment for ulcers in the stomach or the duodenum (the first part of the small intestine) - apart from imbibing large quantities of antacid - was an operation to cut the nerves controlling acid secretion in the stomach.

Working as a surgical intern, I remember almost every operating theatre list I drew up for the professor of surgery had a vagotomy listed on it.

This procedure involves opening the abdomen and identifying the main branches of the vagus nerve. Both these branches can be divided by the surgeon or he may attempt to perform a more selective vagotomy by cutting only those nerves that supply the acid producing portion of the stomach.

Either way, the peak acid output of the stomach is decreased by about 50 per cent. And while many patients were relieved by the procedure, up to one in five developed a recurrence of their ulcer.

The next big breakthrough, which initially heralded a less invasive "cure" for ulcers, was the development of a group of drugs that could block the secretion of acid.

Cimetidine (sold as Tagamet) and ranitidine (Zantac) will be familiar to a whole generation of readers. And while undoubtedly effective at reducing acid and symptoms of tummy pain and heartburn, both duodenal and gastric ulcers recurred despite initial healing rates of 70-80 per cent.

Next came a group of drugs called proton pump inhibitors. They, too, stopped gastric acid production, but at a later stage in its production and have been shown to have an ulcer healing rate of 96 per cent after six weeks treatment.

While both types of medication are good at both relieving symptoms and healing the ulcer, they are not as successful when it comes to preventing peptic ulcer recurrence.

Clearly, the overproduction of acid was not the only factor in the development of ulcers. Which is where Barry Marshall and Robin Warren, the Nobel Prize winners, enter the picture.

In the early 1980s Dr Warren found the bacterium Helicobacter pylori (H. pylori) in the lower part of the stomach in patients with gastritis (stomach inflammation). In a critical observation, he noted signs of inflammation in the lining of the stomach adjacent to the H. pylori.

Dr Marshall then got involved, using himself as a human "guinea pig".

First of all he volunteered to be "scoped", by a fellow gastroenterologist, who took several biopsies from Marshall's stomach to confirm that he did not have an ulcer or evidence of gastritis. Some 10 days later he swallowed a pure culture of H. pylori.

Within a week he had symptoms of gastritis and 10 days later, Marshall had a further series of internal examinations. This time the biopsies showed he had stomach inflammation. Following antibiotic treatment, his symptoms resolved.

Despite further research that proved their hypothesis that H. pylori caused peptic ulcers, Marshall and Warren had a hard time persuading the medical establishment that ulcers were linked with a bacteria.

Long accepted as a lifestyle disease, the establishment rubbished the Australian researchers' findings on the basis that no bacteria could survive in the highly acidic environment of the stomach.

Even when they showed that H. pylori grew under the protective coating of a naturally occurring mucus, medical opinion proved hard to shift. It stuck rigidly to stress and food as causative factors - often referred to as the "hurry, worry and curry" model of peptic ulcer disease.

This point was recognised by the Nobel Committee, which said the award went to Marshall and Warren "who with tenacity and a prepared mind challenged prevailing dogmas".

Now, of course, all peptic ulcers are initially treated with a short course of antibiotics and acid-blocking drugs.

Despite this significant breakthrough which radically reduced the recurrence rate of ulcers, the disease can cause dangerous complications in a small number of patients.

Ulcers can perforate through the thickness of the stomach wall, leading to the spillage of gastrointestinal contents into the abdominal cavity (peritonitis).

And, as demonstrated by the tragic death of Patrick Walsh in Monaghan hospital last week, bleeding can occur in up to 20 per cent of patients with a peptic ulcer.

But the real moral of the story of Dr Marshall and Dr Warren is the need for researchers to ignore conventional wisdom.

It is a classic illustration of the old medical maxim: "never say never in medicine".

Dr Muiris Houston is pleased to hear from readers at mhouston@irish-times.ie but regrets he cannot answer individual queries.