This month, Dr. Sydney Spiesel discusses wireless capsule endoscopy, the latest breast cancer research, the potential benefits of nasal sprays for treating sinus problems, and music as pain relief. (Click here and here for the last two monthly columns.)
Wireless capsule endoscopy: a worthwhile new toy.
The invention: Wireless capsule endoscopy is an advance that allows a patient to swallow a disposable capsule (about the size of a large vitamin pill) which contains a video camera, four teeny but bright sources of light, a TV transmitter, and a battery. For about eight hours, the capsule transmits two images per second of the inside of the intestines to a receiver-recorder that a patient wears on his or her belt. Licensed for medical use in the United States in 2001, the device has been used in more than 100,000 patients so far. It's expensive—each capsule costs about $450—but it makes it possible to examine visually large parts of the small intestine that were previously inaccessible to even the fanciest flexible endoscopes snaked in from above or below.
Its uses: Is the wireless endoscope an overpriced medical toy or a genuinely useful instrument? I am surprised and delighted to tell you that it is genuinely useful. It can be daunting to find the cause of chronic intestinal bleeding or diarrhea, or to diagnose conditions like Crohn's disease or tuberculosis of the bowel (the latter fortunately quite rare these days). Much of the bowel is inaccessible to the gastroenterologist's periscope. X-rays and CT scans don't reveal as much as they ought to and, anyway, often require exposure to doses of radiation that are larger than desirable.
The new research: In a study of more than 50 patients, a research group headed by Dr. W.A. Voderholzer of Humboldt University in Berlin compared the video capsule and the CT scan, the previous gold standard, in diagnosing Crohn's disease. The team found that the capsule method of diagnosis was far superior—it identified signs of the disease 35 percent more frequently than the best results attained by CT scan. (In another study, radiologists using CT scans to look for signs of Crohn's often couldn't find them even when they were shown the location of abnormal bowel as identified by the wireless capsule.) Unexpectedly, Voderholzer's group found that the diseased tissue in some of their Crohn's patients was located higher in the bowel than previously thought. This information led to more closely focused treatment.
Conclusion: One characteristic of Crohn's disease is scarring of the intestinal wall, which can lead to a narrowing of the passage. There has been concern that as a result the endoscopy capsule could get stuck. That indeed happened twice in the course of Voderholzer's study. But in both cases, the capsule eventually passed, with a little help but without surgery. Usually, I am fascinated by cunning new medical devices but also suspicious of them—they often turn out to be too much buck for not enough bang. However, the capsule endoscope seems to be the exception to that rule.
Breast cancer: the good news, and the inconclusive.
State of the science: Every day, it seems, brings reports of new and usually confusing research about breast cancer. Distressingly, it is not unusual for a study to apparently settle one question but raise a whole set of new ones. The Women's Health Initiative study, which included more than 100,000 postmenopausal women, was so big and so carefully planned and executed that doctors could hardly wait the 20-plus years it took to see the results, especially regarding the effects of hormone-replacement therapy and diet. Well, the results are now coming in and they are little short of maddening.
Hormone-replacement therapy 1: One of the first of the WHI studies to be reported found that giving both estrogen and progestin to women after menopause produced more health risks than benefits. Women on this therapy had a small but real increased risk of heart disease, breast cancer, stroke, and blood clots in the lungs. Since the study's main purpose was to determine whether the hormone treatment would prevent heart disease, it was stopped as soon as it became clear that the treatment did the opposite. After publication, many women quit taking hormone replacement therapy.
Hormone-replacement therapy 2: But another WHI study looked at estrogen alone, and the results of a re-examination of that study have just been published by a group headed by Dr. Marcia Stefanick, an epidemiologist at Stanford University. Like the two-hormone study, the estrogen-alone study was stopped early because experimental subjects were found to be at increased risk of stroke and at no less risk of coronary heart disease—and again, the primary goal of the study was to track heart disease. But re-examining the data turned up a finding that makes the study's early termination a little frustrating. The women receiving estrogen treatment had no increased risk of invasive breast cancer compared to the women given a placebo, which hints that the problem ingredient in the double-hormone trial was the progestin. And the data suggest that the estrogen-treated women may have had a decreased risk of breast cancer compared to women who had no hormone treatment. If the study had gone on just a little longer, a clear answer might have emerged.
Tamoxifen and raloxifene: There is good news in another large study that's soon to be formally reported. The National Cancer Institute's "Study of Tamoxifen and Raloxifene," in which almost 20,000 women participated, compared the value of two medications in preventing the development of breast cancer in high-risk postmenopausal women. Some were treated with a placebo, others took tamoxifen, a medication used to treat some breast cancers, and a third group took raloxifene, a drug used to help prevent elderly women from developing osteoporosis (the weakening and loss of calcium from bones that often comes with aging). Previous research had shown that tamoxifen decreases the risk for developing breast cancer. But many doctors were reluctant to prescribe it because of side effects: an increased likelihood of uterine cancer and increased probability of developing serious blood clots in the lungs or the deep veins.
Key finding: The STAR study showed that the two drugs were equally good at preventing the development of breast cancer. But raloxifine carried less risk: In the study, women who took it had a markedly lower rate of blood clot formation and a lower rate of developing uterine cancer. Other studies, too, suggest that raloxifene doesn't increase the risk of uterine cancer. And—perhaps most remarkably—raloxifene is less expensive than tamoxifen.
Conclusion: What to make of all this? It's tremendously exciting to have a new, safer drug that can help prevent breast cancer and strengthen women's bones at the same time. The first wave of the fight against cancer involved learning from epidemiological studies how to help prevent the disease—by avoiding cigarette smoke and diesel emissions, for instance. We can all hope that medications like raloxifene represent the second wave of assault. And the third wave is following close behind: the imminent arrival of the vaccines that prevent cervical cancer. Finally, progress.
Sinus sufferers: Quit begging for antibiotics.
The pitch: For doctors, a curse of the otherwise delightful season of spring is the piteous cry of sinus sufferers. Everybody who watches TV commercials knows that his runny nose comes from a sinus infection that he wants fixed, fixed right away, and fixed with antibiotics. All too often, doctors accede to this demand—studies have shown that 85 percent to 98 percent of primary-care patients with rhinosinusitis (the inflammation of the nose and sinuses called "sinus congestion" or "sinus infection" on television) will leave their practitioner's office with an antibiotic prescription in hand. Why?
The consequences: In this era of medicine driven by time pressure, it may seem easier—and it's certainly faster—for a doctor to whip out the prescription pad than to take the time to explain the relative risks and benefits of using antibiotics. Also, doctors know that a badly infected sinus, if left untreated, can have disastrous consequences. Finally, though most cases of rhinosinusitis go away on their own, it's long been understood that some patients do benefit from antibiotic treatment.
So, are all those antibiotics prescriptions a bad thing? Actually, yes. They increase the allergy risk for patients, which causes immediate problems and limits future access to antibiotics that are really needed. And they generate dangerously antibiotic-resistant bacteria.
The ailment: Sinuses are air spaces. They form in the bones of the skull as dimples in very young children, and gradually expand with age to form deep hollows lined with mucus-producing cells. When allergy or infection causes the linings to swell, the entrances to the hollow spaces can become blocked, trapping the mucus secretions in pools that are a bacterial breeding ground. And when the entrances to the sinuses become blocked, whether or not the trapped mucus becomes infected, the increased pressure inside can be extremely painful.
When the trapped mucus does become infected (the patient may have a high fever or a smelly nasal discharge), antibiotics are likely to be very helpful. But when simple rhinosinusitis that doesn't involve such a significant infection is treated with antibiotics in both children and adults, there is, on average, only a modest benefit. For example, antibiotics slightly shorten the length of time some children have a runny nose. Given the risk of adverse effects when antibiotics are used, other treatments would be preferred, if we could find ones that work.
The new research: A recent paper by Dr. Eli Meltzer of the Allergy and Asthma Medical Group of San Diego and two collaborators studied almost 1,000 children to compare the effects of treating rhinosinusitis with amoxicillin, a nasal steroid spray, or dummy capsules or a placebo spray. As expected from previous studies, on average amoxicillin improved the children's symptoms more than treatment with placebo. However, the nasal steroid alone, used once a day, was as effective as amoxicillin. And when the spray was used twice a day, it worked rather better than the antibiotic. The particular nasal spray chosen for this study was the steroid mometasone. Its manufacturer was a study sponsor, and probably any of the nasal steroid sprays on the market would have worked as well. The only downside to steroid nasal spray use (as opposed to other forms of steroids) is that most children hate to blow the stuff up their noses. So, it seems like the more attractive option, for children at least. Time and further studies will be needed to see if it's equally effective for adults.
Musical pain relief?
The need: A central task of medicine is pain relief. Sometimes, however, the treatments are as painful or risky as the conditions they are intended to help. Before the introduction of anesthesia with ether in 1846, surgery was so agonizing that patients would often prefer death. And anesthesia is not useful for the relief of longer or more generalized pain. For that, we need analgesia, a treatment or medication that alleviates pain without extinguishing wakefulness or sensation.
The competition: Almost all of us make use of analgesic agents regularly—perhaps too regularly. The trouble is that these beneficial products exact a price that sometimes seems proportional to their effectiveness. Opiates, for example, are great analgesics. But these derivatives of morphine or similar drugs carry a serious risk of addiction (don't worry, a few doses won't do it) and of tolerance, requiring ever-increasing doses for the same degree of pain relief. Opiates also can shut down the bodily machinery that tells us to breathe. Other analgesic drugs have their own side effects, ranging from a tendency to damage the lining of the stomach to increasing the risk of heart attack.
The new research: The ideal analgesic would diminish pain perception without increasing the risk of harm to patients. How about … music? A recent study, led by Dr. M.S. Cepeda of Javieriana University in Bogota, Colombia, and Tufts-New England Medical Center, put together the results of 51 different papers (involving more than 3,500 patients) that evaluated the value of music for pain relief. The studies examined the effect of music on chronic or cancer pain, acute pain following surgery, labor pain, and the pain produced by medical or experimental procedures. The amelioration of pain was measured in two ways, one subjective and the other objective. Did patients hearing music report a substantial decrease in the pain they felt? And did they require less opiate medication than similar patients who didn't hear music?
The findings: The results Cepeda found were positive but not powerful. In most of the studies, listening to music modestly decreased patients' reported perception of pain (no matter what its cause) or was associated with somewhat less need for opiate medication. But the differences weren't strong enough to make clear whether music is clinically useful. Perhaps the most interesting results came from the studies in which patients were allowed pick the music they wanted to listen to. Contrary to what one might expect, freedom to choose pretty much killed the benefit for pain relief. Which leaves another question crying out to be answered: Would people feel more relief if they were made to listen to music they hate? We could try this out by playing, say, Metallica for a classicist in a dental chair, or a late Beethoven quartet for a biker about to get a tattoo.