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Gallstones Dissolved by Gas Solvent

Times Medical Writer

Gallstones, a health problem believed to afflict up to 25 million Americans, can be dissolved in many cases quickly and safely with the help of a solvent widely used as an octane enhancer in gasoline, Mayo Clinic researchers reported today.

The experimental therapy, described in the New England Journal of Medicine, is one of several novel approaches to gallstones that experts hope will revolutionize gallstone treatment and eliminate the need for hundreds of thousands of surgeries.

“The report in the New England Journal is major and important,” said Dr. Leslie Schoenfield, director of gastroenterology at Cedars-Sinai Medical Center in Los Angeles. “It will provide another non-surgical approach for the treatment of gallstones.”

Gall-bladder removal is currently the preferred treatment for gallstones.

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The treatment reported by the Mayo researchers in Minnesota entails emptying the gall bladder of its liquid contents, then pumping a teaspoonful of an ether similar to anesthetic ether in and out of the gall bladder four to six times a minute.

The solvent, methyl tert-butyl ether, used in recent years to improve the quality of gasoline, is infused into the patient through a fine catheter with the circumference of a strand of spaghetti.

The catheter is threaded through the patient’s skin and into the gall bladder, a pear-shaped sac attached to the liver that serves as a reservoir for bile. Bile, secreted by the liver and released in the duodenum, plays a crucial role in digestion.

Within one to three days, the solvent dissolved the cholesterol gallstones in 72 of the 75 patients in the Mayo Clinic trial. The stones were at least 95% dissolved in 51 patients; 21 other patients were completely free of stones, according to the report.

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“I think it will be able to be used in a substantial proportion of patients who have gallstones who . . . would prefer not to have surgery or their physician would prefer for them not to have surgery,” said Dr. Johnson L. Thistle, who headed the study.

Some researchers, however, expressed concern about the use of the ether--a volatile, highly flammable organic solvent. If it were improperly administered and escaped from the gall bladder, the solvent might cause harm by triggering the breakdown of red blood cells.

The solvent did overflow in one patient, a 74-year-old woman, in the Mayo Clinic study. There was evidence of temporary blood cell damage, the researchers said. But the abnormalities disappeared, treatment was completed and the woman encountered no further problems, they said.

Thistle’s technique, which has also been tested on patients in Europe, is the latest in a string of non-surgical approaches to gallstones, a potentially dangerous and often painful condition believed to occur in 20% to 30% of all elderly people.

Gallstones are thought to be caused by metabolic abnormalities that lead to an excess of fatty cholesterol in the liver. The cholesterol, sometimes with calcium and bile pigments, forms stones ranging from the size of a pea to that of a large egg.

Stones can cause severe pain when they are passed in bile into the small intestine. They can also cause inflammation of the gall bladder and infections that can spread to liver tissue. They sometimes trigger jaundice and cirrhosis of the liver.

The most effective gallstone treatment is gall-bladder removal, an operation performed on about 500,000 Americans each year. Although the gall bladder is not essential to life, physicians say its removal can lead to digestive problems. They note that all surgery carries some risk.

Two additional new approaches also aim to dissolve the stones without surgery.

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One approach relies on drugs based on bile acids, substances that occur naturally in the body and are important in digesting fats. The drug ursodiol, made available in the United States late last year, has been found to dissolve stones with some success when taken orally.

A second alternative, being used only in supervised studies, relies on a device used more commonly to disintegrate kidney stones. The device, called a lithotripsy machine, generates shock waves that penetrate the patient’s body and can break up stones.

Both of those therapies, as well as the solvent treatment, have limitations. For example, gallstones recur in as many as half the patients treated. In addition, experts say each approach is suited only to specific groups of gallstone patients.

Ursodiol and an earlier drug called chenodiol can take as long as one or two years to work. The drug costs between $1,000 and $2,000 a year. Studies suggest that the treatment may be most effective on patients with multiple small stones and few acute symptoms.

Lithotripsy has been tested since late 1987 on people with larger but fewer stones. Researchers say it may eventually be used in combination with stone-dissolving drugs: Once the stones are shattered, drugs might be used to dissolve them fully before excretion.

As for the solvent treatment, experts speculate that it could prove most useful in patients in serious pain but who are unwilling or unable to undergo surgery. Its advantages include the speed with which it takes effect; drawbacks include the complexity of inserting the catheter and pumping the solvent in and out, researchers suggested.

“My feeling is that it probably is going to be most useful for the acutely ill patient who has some underlying disease that makes him a poor surgical risk,” said G. S. Tint, a researcher who co-authored an accompanying editorial on gallstone therapy in the journal.

“It seems to me it’s going to require a lot of skill to use,” said Tint, a professor at the New Jersey Medical School in Newark and the Veterans Administration Medical Center in East Orange, N.J., who works with ursodiol. “This is the problem.”

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The possible cost of the solvent treatment to a patient is not known because it is still being used only on an experimental, no-charge basis. Thistle, who said the principle expenses would be the labor of the physician and technician, estimated that the therapy would cost “substantially less than the cost of surgery.”

Gall-bladder removal is the most expensive of all the treatments: Researchers estimate that the cost of the surgery, related services and seven to 10 days’ hospitalization ranges from $7,000 to $12,000, depending on the region in which it is done.

What percentage of gall-bladder surgeries might eventually be avoided remains to be seen. Schoenfield of Cedars-Sinai, whose institution is working with all three new techniques, estimated that they might ultimately prove suitable for 60% of all patients.

Among the group still requiring surgery would be that minority of patients whose gallstones are calcified and cannot be dissolved, and those whose disease is so advanced and so painful that they require emergency surgery, Schoenfield said.


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