Most of them are about the diameter of a dime and the thickness of a penny, the product of a mysterious phenomenon in which the stomach or the first part of the small intestine literally digests itself.
They are at once the focus of some of the most successful advances in treatment of any field of modern medicine and stubbornly resistant to prediction or prevention. Ironically, when they are at their worst, they often give no pain warnings, manifesting themselves, instead, as potentially fatal hemorrhages in the early hours of the morning.
No Precise Identification
It's not even certain if they are the product of a disease or the result of a condition created in the body by an assortment of factors--both environmental and inherited--that have yet to be precisely identified. There is one thing that is fairly certain about them, though. They aren't stress-related and you cannot worry yourself into one. The most common drug that is used to treat them remains one of the most significant and successful breakthroughs of the era, yet it is incapable of producing a cure.
One of the most mundane, frequently uncomfortable and--occasionally--potentially dangerous, of common disorders, they lack the drama that surrounds such high-tech marvels as sewing the heart of a baboon into the chest of a baby or transplanting kidneys, lungs and livers. They are the subject of so many misconceptions that they have developed what might be called a folklore of their own.
They affect 4 million Americans by most counts--80,000 of whom may be chronically disabled. They are ulcers.
Tucked away in an unpretentious two-story building at the Veterans Administration Westside Hospital, a nationally known clinic is trying to solve some of the riddles that continue to surround ulcers. Yet at the same time the program, the Center for Ulcer Research and Education, is working hard to overcome a blow to the momentum of its research program suffered in 1981 when the renowned founder of the center, which is known by the acronym CURE, died of cancer.
Dr. Morton I. Grossman, who started CURE in 1974, had turned it into an internationally known center. Grossman, in the years before his death, had become something of a guru in the field of ulcer medicine and research. When Grossman died at age 62, local experts in ulcer medicine agreed the program he founded lost some of its direction--a period from which its current director, Dr. George Sachs, is determined it will recover. Sachs took over the CURE program two years ago.
As a result, according to Dr. Gary Van Deventer, director of CURE's clinic, the center is now actively seeking as many as two to four times the number of patients--about 450--as are currently enrolled in its research projects. CURE patients can refer themselves, but they must have been positively diagnosed as having ulcers before they turn to CURE. They are assigned to treatment programs in which a variety of possible advances are being tested in concert with existing therapies. The treatment CURE offers its patients--including both veterans and non-veterans--is free.
The patients become participants in an attempt to solve some of the mysteries of ulcers, a medical problem so common as to be considered mundane, but which remains mysterious enough that it isn't even certain how long ulcers have afflicted humans. It seems likely, however, said Van Deventer and Dr. John Walsh, CURE's associate director, that ulcers--at least the variety that infests the upper portion of the small intestine (called the duodenum)--may be a development of the 20th Century.
Ulcer death rates and hospitalizations have been on the decline since the early 1960s, according to a CURE survey published in 1983. Deaths have been cut by half and hospitalizations by nearly a quarter in the last 20 years. Deaths still occur, however--though they are fewer than three out of every 100,000 people in the United States. Still, researchers have found the economic costs--not to mention the toll of physical discomfort--remain high for ulcers. Direct costs for hospital and doctor care are estimated at $3.2 billion a year in this country.
An ulcer occurs when acid and gastric juice that normally aid in the routine digestion of food encounter a small spot in the lining (or the mucosa, as it is technically known) of the stomach or the intestine that has for some reason--doctors don't understand the cause--lost its ability to resist the acid's effects. As a result, the acid and gastric juices literally eat into the stomach or intestinal wall, creating the ulcer.
The lesions are normally about a centimeter--or somewhat less than the diameter of a dime--across, and about as deep as the thickness of a penny. However, in extreme cases, ulcers can become as large as a silver dollar.
"You can think of the stomach and the duodenum as a nicely balanced machine," Sachs said. "The balance is between making acid and digesting food on the one hand and preventing self-digestion on the other. If either factor (acid manufacture or resistance to acid) goes out of balance, you're likely to end up with an ulcer."
"We don't know if this is a condition or a disease or what," Walsh said. "It has been characterized by recurrent episodes with intervening periods of no activity. Chances are at least two out of three that if you have one ulcer, you're going to have another one."
If, by coincidence, the mucosa's natural resistance fails just above one of the many blood vessels that crisscross the intestinal tract, the resulting ulcer can permit the acid and juices to literally eat through the wall of the vessel. When that happens, the ulcer's most dangerous result can occur--sudden, catastrophic bleeding that often requires transfusions or emergency surgery. Ulcers that give no warning are called "silent" ulcers because patients who suffer from them may never experience symptoms normally associated with digestive disease before the heavy bleeding begins.
But such complications, Walsh said, occur in only between 10% and 25% of all cases--estimates vary--and Walsh said some higher-range measures of the complication rate may be artificially high. And, mysteriously, some ulcers never become symptomatic or troublesome and heal by themselves with the patient never knowing--at the time, anyway--he was affected.
The nagging uncertainty to all of this is why the mucosa's natural ability to resist self-digestion fails. The answer remains elusive and Sachs said microbiologists may not figure it out until sometime in the next century.
For most ulcer sufferers, pain is a first warning. Said Van Deventer and Walsh, ulcer sufferers often complain of pain that comes on at night or between meals. It's not terribly sharp, but seems sort of vague and gnawing. There may be a hunger or burning sensation. The nature of the symptoms, however, presents one of the major problems of ulcer treatment. Ulcer symptoms are identical to those of many other common and far less serious digestive disorders--most notably indigestion commonly brought on by stress.
The similarity has caused one of the major misunderstandings about ulcers, said Walsh and Van Deventer--that they are caused by emotional stress. They apparently aren't and the myth of the so-called "executive ulcer" is just that. In fact, CURE experts agreed, ulcer demographics are quite balanced, with blue-collar and white-collar workers equally at risk. In the United States, no single socioeconomic or ethnic group has a significantly greater or lesser risk of getting ulcers than the general population.
In fact, Walsh said, it is usually impossible to tell easily whether someone with the broad range of stomach symptoms has an ulcer or something else. Diagnosis is impossible, he said, without resorting to a machine called an endoscope--a fiber-optic tube doctors manipulate through the stomach and intestines looking for ulcers--or X-ray studies in which the stomach and duodenum are highlighted with radioactive dyes.
Impossible to Guess
It is simply not possible to guess who has an ulcer and who doesn't, Walsh said. "If you try, you'll be wrong in women two-thirds of the time and wrong in men half the time," he said. He said there is no explanation why women are even harder to diagnose.
One specific variety of the condition is, in fact, called the "stress ulcer," but CURE doctors said it is prompted by a different kind of stress--the shock sustained by the body in a major injury or burn.
In recent years, it has become clear that smoking tobacco apparently increases the risk of having ulcers--perhaps because the byproducts of smoke absorbed in the body effectively increase the amount of stomach acid, possibly disrupting the delicate balance of the intestinal tract.
Men used to suffer from ulcers far more commonly than women, but the gender gap has narrowed, just as it has in lung cancer--probably in large part for the same reason: Women are smoking more now and men less than in previous decades. "Men are dropping in their rates of stomach ulcer and women are catching up in duodenal ulcer," concluded Janet Alashoff, a statistical expert who serves as CURE's deputy director.
Since ulcers were first recognized, treating them has had the same goal: lowering the amount of acid in the digestive tract so symptoms are alleviated and the ulcer has a chance to heal. The CURE team emphasized, however, that though a new drug called cimetidine (marketed under the brand name Tagamet) was a major breakthrough in ulcer treatment when it was introduced in the late 1970s, no drug--including cimetidine--actually causes an ulcer to heal. Doctors have found that ulcer pain symptoms usually disappear long before the ulcer has actually healed.
Cimetidine marked a major advance in ulcer therapy because, while it has the same goal as earlier ulcer drugs--inhibiting acid production--cimetidine works better in a wider range of people than such preparations as Maalox, which once dominated ulcer therapy. Surgery to treat ulcer is less common now than it was before cimetidine came along, but Walsh and the rest of the CURE team noted that the surgery rates had begun to decline before cimetidine was introduced, implying that changes in philosophy among internists who specialize in ulcer treatment may be as responsible for the lessening of operations as the introduction of a better drug.
In recent years, other drugs have been introduced. One, called ranitidine and marketed under the brand name Zantac, is equally as effective as cimetidine. All of these preparations are members of a chemical family called H-2 receptors that impair acid production by affecting the natural manufacture of a substance called histamine, which can stimulate gastric secretion. There is a third member of the drug family in use, as well. Called sucralfate (marketed under the brand name Carafate), the drug has been plagued by questions whether it is as effective as its two chemical cousins.
There is some disagreement over whether the H-2 receptors are best when they are given on a continuous basis or simply reserved for use when a patient has specific symptoms. It is likely, Walsh said, to turn out that both approaches work--but not for the same patients.
Ulcer surgery is still resorted to when an ulcer bleeds severely or in some patients whose ulcers won't heal no matter what drug is used to control their acid secretion. Ulcer surgery does not involve cutting out the ulcerated area, necessarily. Instead, surgeons either cut nerves leading to the duodenum or remove a section of the stomach. The objective of both procedures is to inhibit acid production--the same goal of ulcer drugs.
Perhaps because treatment has never carried any certain guarantee of success, ulcer patients--and even their physicians--have perpetuated a series of what have turned out to be myths about coping with ulcers. Walsh said several of the most common survive. Among them:
--A bland, "ulcer diet" will help promote healing of ulcers. In fact, said Walsh and Van Deventer, researchers have never been able to link bland diets to ulcer progression in any way.
Bland diets may alleviate some symptoms of indigestion or stress-related upset stomach, but they will not have any effect on ulcers. "Diet is the one thing that has been studied that nobody can show a positive effect (for) on ulcer healing," Walsh said. In fact, in one eye-watering attempt to establish a dietary correlation, a group of stalwart research subjects (presumably with extremely strong constitutions) were fed pure jalapeno peppers. In later evaluation, it was discovered that the insides of their intestines had turned a shade of red, but no ulcers resulted.
--Milk will settle the stomach and alleviate ulcer symptoms. Totally false, Walsh said. In fact, there is some evidence that some chemicals in milk may actually stimulate stomach acid production and exacerbate ulcer symptoms.
--By drinking decaffeinated coffee or tea, an ulcer sufferer can cut the amount of acid generated from caffeine drinks. It isn't the caffeine in coffee and tea that stimulates acid, Walsh said, it is other chemicals. Decaffeinated versions of these beverages are no better for ulcer patients than the other forms.
New Classes of Drugs
On the frontier of ulcer therapy, said Sachs and Walsh, may be at least two new classes of drugs. One, called Omeprazole--which could be available for use in the United States within four years if tests on human patients scheduled to begin this year are successful--would be a more effective acid-stopper than the family of drugs that includes cimetidine and ranitidine.
That would still leave doctors with no effective way to promote healing of an ulcer--as opposed to minimizing acid so that, hopefully, it heals on its own. Within the next five to 20 years, however, said Sachs, there is a chance that a family of substances called prostaglandins may turn out to have the ability to actually cause ulcers to heal. The advance could largely eradicate the need for ulcer surgery and solve the problems of many patients with stubborn cases of repeated ulcer attacks.
Prostaglandins are fatty acid byproducts present in the body. There are more than a dozen different prostaglandins in the body and, starting in the early 1960s, scientists began to learn how they can be synthesized. Chemical manipulation of prostaglandins in general may make it possible to control a variety of body functions that cannot now be effectively influenced and ulcer therapy is generally viewed--at least for the moment--as one of the most promising potential fields for prostaglandin research.
But that is for the future. Today's ulcer patient may never benefit from prostaglandin therapy, or even from Omeprazole, which has yet to prove its worth conclusively in tests on humans.
Recalling his analogy about the nicely balanced machine gone mysteriously out of whack, Sachs pondered the challenge ulcers pose for researchers. "The trick will be to understand what went wrong . . . not how to inhibit acid secretion but why it went out of balance in the first place.
"That involves some fundamental aspects of cell biology we're still very ignorant of."