August 29, 2011
The Annals of Extreme Surgery
By BARRON H. LERNER
THE heat is on again in the world of cancer treatment, both literally and figuratively.
More and more doctors are now using an extremely aggressive procedure to treat certain colorectal and ovarian cancers called Hipec, in which patients first undergo surgery to remove any visible cancer, then have heated chemotherapy pumped into the abdominal cavity for 90 minutes to kill any remaining cells.
Although it has given some patients hope, there is almost no evidence that the treatment is more effective than traditional chemotherapy — besides one small trial in the Netherlands over a decade ago that did show a benefit, but in which 8 percent of the participants died from the procedure itself.
We shouldn’t be surprised by the sudden emergence of this therapy. Heated chemotherapy is the latest in a long list of very toxic treatments used by well-meaning cancer doctors who have confused doing more for patients with doing what is best for them.
History tells us that this “more is better” dictum is rarely true.
Aggressive cancer therapy started in the late 19th century with the radical mastectomy, which involved the removal of the breast, along with the chest muscle below it and nearby lymph nodes, and was championed by William S. Halsted, a surgeon at Johns Hopkins.
In the following decades, Dr. Halsted’s methods became more and more popular, particularly after World War II, when surgeons who had performed heroic operations on European battlefields returned to America optimistic about what could be achieved in cancer surgery. In an attempt to eradicate all potentially dangerous cells without the assistance of chemotherapy — which was not yet in wide use — surgeons began removing even parts of the sternum and rib cage of certain breast cancer patients in something called a super-radical mastectomy.
If the cancer had spread into the arms, surgeons at times removed entire shoulders (forequarter amputations). If the cancer was in the legs, part of the pelvis was removed with the leg (hindquarter amputations). The most aggressive operation of all was probably the pelvic exenteration, devised by the New York gynecologist Alexander Brunschwig. For cancers that had spread throughout a woman’s pelvis, he removed not only her gynecological organs but also her bladder and rectum.
The goal of these operations was straightforward: to remove as many cancer cells as possible, which would theoretically prolong the survival of patients and possibly even cure them. The problem was that none of these procedures had been formally tested in controlled clinical trials. By the 1960s, it had become clear that they were of little or no benefit, while causing dying cancer patients disfigurement and suffering.
Why such enthusiasm for aggressive surgery? The explanation can be gleaned from the language surgeons used to justify their operations. Military metaphors were ubiquitous. In 1946, Cushman Haagensen warned his colleagues against “surgical cowardice” in the face of the “formidable enemy” that was cancer. Jerome A. Urban, the father of the super-radical mastectomy, was fond of saying “lesser surgery is done by lesser surgeons.”
It was not only surgeons who made these assumptions. In the late 1980s, oncologists began treating metastatic breast cancer patients with a highly toxic and expensive regimen of so-called very-high-dose chemotherapy, followed by bone marrow transplants. Once again, early data proved misleading. Women who received this treatment turned out to live no longer than those getting standard chemotherapy, and many died from either the high doses or the side effects of the transplants.
Cancer patients and their families, desperate for anything that might work after exhausting all other treatment options, are also part of the problem. But the history of cancer treatment provides a crucial cautionary tale for both those seeking out and those providing heated chemotherapy today. Doing more for cancer patients has often served a cultural as opposed to a scientific purpose, reflecting more the desire to defeat the cancer enemy than to take care of sick patients. Hospitals should offer heated chemotherapy — and insurance companies should pay for it — only after controlled trials have proved its effectiveness.
In the meantime, we should remember not to conflate our efforts with our achievements.
Barron H. Lerner, a professor of medicine and public health at Columbia, is the author of “The Breast Cancer Wars: Hope, Fear and the Pursuit of a Cure in Twentieth-Century America” and the forthcoming “One for the Road: Drunk Driving Since 1900.”
September 26, 2011
Fighting Cervical Cancer With Vinegar and Ingenuity
By DONALD G. McNEIL Jr.
POYAI, Thailand — Maikaew Panomyai did a little dance coming out of the examination room, switching her hips, waving her fists in the air and crowing, in her limited English: “Everything’s O.K.! Everything’s O.K.!”
Translation: The nurse just told me I do not have cervical cancer, and even the little white spot I had treated three years ago is still gone.
What allowed the nurse to render that reassuring diagnosis was a remarkably simple, brief and inexpensive procedure, one with the potential to do for poor countries what the Pap smear did for rich ones: end cervical cancer’s reign as the No. 1 cancer killer of women. The magic ingredient? Household vinegar.
Every year, more than 250,000 women die of cervical cancer, nearly 85 percent of them in poor and middle-income countries. Decades ago, it killed more American women than any other cancer; now it lags far behind cancers of the lung, breast, colon and skin.
Nurses using the new procedure, developed by experts at the Johns Hopkins medical school in the 1990s and endorsed last year by the World Health Organization, brush vinegar on a woman’s cervix. It makes precancerous spots turn white. They can then be immediately frozen off with a metal probe cooled by a tank of carbon dioxide, available from any Coca-Cola bottling plant.
The procedure is one of a wide array of inexpensive but effective medical advances being tested in developing countries. New cheap diagnostic and surgical techniques, insecticides, drug regimens and prostheses are already beginning to save lives.
With a Pap smear, a doctor takes a scraping from the cervix, which is then sent to a laboratory to be scanned by a pathologist. Many poor countries lack high-quality labs, and the results can take weeks to arrive.
Women who return to distant areas where they live or work are often hard to reach, a problem if it turns out they have precancerous lesions.
Miss Maikaew, 37, could have been one of them. She is a restaurant cashier on faraway Ko Chang, a resort island. She was home in Poyai, a rice-farming village, for a brief visit and was screened at her mother’s urging.
The same thing had happened three years ago, and she did have a white spot then. (They resemble warts, and are caused by the human papillomavirus.) It was frozen off with cryotherapy, which had hurt a little, but was bearable, she said.
Since she has been screened twice in her 30s, her risk of developing cervical cancer has dropped by 65 percent, according to studies by the Alliance for Cervical Cancer Prevention, a coalition of international health organizations funded by the Bill & Melinda Gates Foundation.
The procedure, known as VIA/cryo for visualization of the cervix with acetic acid (vinegar) and treatment with cryotherapy, can be done by a nurse, and only one visit is needed to detect and kill an incipient cancer.
Thailand has gone further than any other nation in adopting it. More than 20 countries, including Ghana and Zimbabwe, have done pilot projects. But in Thailand, VIA/cryo is now routine in 29 of 75 provinces, and 500,000 of the 8 million women, ages 30 to 44, in the target population have been screened at least once.
Dr. Bandit Chumworathayi, a gynecologist at Khon Kaen University who helped run the first Thai study of VIA/cryo, explains that vinegar highlights the tumors because they have more DNA, and thus more protein and less water, than other tissue.
It reveals pre-tumors with more accuracy than a typical Pap smear. But it also has more false positives — spots that turn pale but are not malignant. As a result, some women get unnecessary cryotherapy.
But freezing is about 90 percent effective, and the main side effect is a burning sensation that fades in a day or two.
By contrast, biopsies, the old method, can cause bleeding.
“Some doctors resist” the cryotherapy approach, said Dr. Wachara Eamratsameekool, a gynecologist at rural Roi Et Hospital who helped pioneer the procedure. “They call it ‘poor care for poor people.’ This is a misunderstanding. It’s the most effective use of our resources.”
At a workshop, nurse trainees pored over flash cards showing cervixes with diagnosable problems. They did gynecological exams on lifelike mannequins with plastic cervixes. They performed cryotherapy on sliced frankfurters pinned deep inside plastic pipes. Then, after lunch, they broke into small groups and went by minibus to nearby rural clinics to practice on real women.
Because cervical cancer takes decades to develop, it is too early to prove that Thailand has lowered its cancer rate. In fact, Roi Et Province, where mass screening first began, has a rate higher than normal, but doctors attribute that to the extra testing. But of the 6,000 women recruited 11 years ago for the first trial, not a single one has developed full-blown cancer.
VIA/cryo was pioneered in the 1990s simultaneously by Dr. Paul D. Blumenthal, an American gynecologist working in Africa, and Dr. Rengaswamy Sankaranarayanan in India.
Dr. Blumenthal said he and colleagues at the Johns Hopkins medical school had debated ways to make cervical lesions easier to see, and concluded that whitening them with acetic acid would be effective. Freezing off lesions is routine in gynecology and dermatology; the challenge was making it cheap and easy. Liquid nitrogen is hard to get, but carbon dioxide is readily available.
Thailand seems made for the vinegar technique. It has more than 100,000 nurses and a network of rural clinics largely run by them.
Also, while poor rural villagers in many countries go to shamans or herbalists before they see doctors, poor Thais do not. Thailand has a 95 percent literacy rate, and doctors are trusted. The king is the son of a doctor and a nurse; his father trained at Harvard. One of the royal princesses has a doctorate in chemistry and an interest in cancer research.
But the real secret, Dr. Wachara said, is this: “Thailand has Lady Kobchitt.”
Dr. Kobchitt Limpaphayon to her colleagues at Bangkok’s Chulalongkorn University medical school and “Kobbie” to her classmates long ago at New York’s Albany Medical College, she is the gynecologist to the Thai royal family. “Kobbie is a force of nature,” said Dr. Blumenthal, who has taught with her. In 1971, as a young doctor, she moved from Albany to Baltimore to help start the Johns Hopkins Program for International Education in Gynecology and Obstetrics.
In 1999, she read one of Dr. Blumenthal’s papers and asked him to introduce VIA/cryo in Thailand. Without her connections and powers of persuasion, said Dr. Bandit, it would have been impossible to get the conservative Royal Thai College of Obstetricians and Gynecologists to give up Pap smears, or to persuade Parliament to allow nurses to do cryotherapy, a procedure previously reserved for doctors.
The free screenings at public clinics are crucial to people like Yupin Promasorn, 36, who was part of Miss Maikaew’s group.
She sells snacks in Bangkok, and her husband drives a tuk-tuk motorcycle taxi. With two children, she has no time to wait at Bangkok’s jammed public hospitals, and she is too poor to see a private doctor. So she and her husband drove the 12 hours here, to her native village, in his tuk-tuk. When she found out she was negative, she sat in a chair fanning herself.
“I feel like a heavy mountain is gone from my chest,” she said.
October 6, 2011
U.S. Panel Says No to Prostate Screening for Healthy Men
By GARDINER HARRIS
Healthy men should no longer receive a P.S.A. blood test to screen for prostate cancer because the test does not save lives over all and often leads to more tests and treatments that needlessly cause pain, impotence and incontinence in many, a key government health panel has decided.
The draft recommendation, by the United States Preventive Services Task Force and due for official release next week, is based on the results of five well-controlled clinical trials and could substantially change the care given to men 50 and older. There are 44 million such men in the United States, and 33 million of them have already had a P.S.A. test — sometimes without their knowledge — during routine physicals.
The task force’s recommendations are followed by most medical groups. Two years ago the task force recommended that women in their 40s should no longer get routine mammograms, setting off a firestorm of controversy. The recommendation to avoid the P.S.A. test is even more forceful and applies to healthy men of all ages.
“Unfortunately, the evidence now shows that this test does not save men’s lives,” said Dr. Virginia Moyer, a professor of pediatrics at Baylor College of Medicine and chairwoman of the task force. “This test cannot tell the difference between cancers that will and will not affect a man during his natural lifetime. We need to find one that does.”
"Cancer screening is a growing field; existing tests are becoming more sensitive, and new tests are constantly developed. We now have CT scanning for lung cancer, and there is also a blood test marketed by Johnson & Johnson known as a “liquid biopsy,” which searches for stray cancer cells in the bloodstream. More testing inevitably brings more treatment, because the urge to correct every cellular anomaly, no matter how small or potentially harmless, is practically irresistible. But if there is one lesson from the P.S.A. test, it is that more information and intervention do not always lead to less suffering."
Scientists are observing with increasing alarm that some very common hormone-mimicking chemicals can have grotesque effects.
A widely used herbicide acts as a female hormone and feminizes male animals in the wild. Thus male frogs can have female organs, and some male fish actually produce eggs. In a Florida lake contaminated by these chemicals, male alligators have tiny penises.
These days there is also growing evidence linking this class of chemicals to problems in humans. These include breast cancer, infertility, low sperm counts, genital deformities, early menstruation and even diabetes and obesity.
Philip Landrigan, a professor of pediatrics at Mount Sinai School of Medicine, says that a congenital defect called hypospadias — a misplacement of the urethra — is now twice as common among newborn boys as it used to be. He suspects endocrine disruptors, so called because they can wreak havoc with the endocrine system that governs hormones.
Endocrine disruptors are everywhere. They’re in thermal receipts that come out of gas pumps and A.T.M.’s. They’re in canned foods, cosmetics, plastics and food packaging. Test your blood or urine, and you’ll surely find them there, as well as in human breast milk and in cord blood of newborn babies.
In this campaign year, we are bound to hear endless complaints about excessive government regulation. But here’s an area where scientists are increasingly critical of our government for its failure to tackle Big Chem and regulate endocrine disruptors adequately.
Last month, the Endocrine Society, the leading association of hormone experts, scolded the Food and Drug Administration for its failure to ban bisphenol-A, a common endocrine disruptor known as BPA, from food packaging. Last year, eight medical organizations representing genetics, gynecology, urology and other fields made a joint call in Science magazine for tighter regulation of endocrine disruptors.
Shouldn’t our government be as vigilant about threats in our grocery stores as in the mountains of Afghanistan?
Researchers warn that endocrine disruptors can trigger hormonal changes in the body that may not show up for decades. One called DES, a synthetic form of estrogen, was once routinely given to pregnant women to prevent miscarriage or morning sickness, and it did little harm to the women themselves. But it turned out to cause vaginal cancer and breast cancer decades later in their daughters, so it is now banned.
Scientists have long known the tiniest variations in hormone levels influence fetal development. For example, a female twin is very slightly masculinized if the other twin is a male, because she is exposed to some of his hormones. Studies have found that these female twins, on average, end up slightly more aggressive and sensation-seeking as adults but have lower rates of eating disorders.
Now experts worry that endocrine disruptors have similar effects, acting as hormones and swamping the delicate balance for fetuses in particular. The latest initiative by scholars is a landmark 78-page analysis to be published next month in Endocrine Reviews, the leading publication in the field.
“Fundamental changes in chemical testing and safety determination are needed to protect human health,” the analysis declares. Linda S. Birnbaum, the nation’s chief environmental scientist and toxicologist, endorsed the findings.
The article was written by a 12-member panel that spent three years reviewing the evidence. It concluded that the nation’s safety system for endocrine disruptors is broken.
“For several well-studied endocrine disruptors, I think it is fair to say that we have enough data to conclude that these chemicals are not safe for human populations,” said Laura Vandenberg, a Tufts University developmental biologist who was the lead writer for the panel.
Worrying new research on the long-term effects of these chemicals is constantly being published. One study found that pregnant women who have higher levels of a common endocrine disruptor, PFOA, are three times as likely to have daughters who grow up to be overweight. Yet PFOA is unavoidable. It is in everything from microwave popcorn bags to carpet-cleaning solutions.
Big Chem says all this is sensationalist science. So far, it has blocked strict regulation in the United States, even as Europe and Canada have adopted tighter controls on endocrine disruptors.
Yes, there are uncertainties. But the scientists who know endocrine disruptors best overwhelmingly are already taking steps to protect their families. John Peterson Myers, chief scientist at Environmental Health Sciences and a co-author of the new analysis, said that his family had stopped buying canned food.
“We don’t microwave in plastic,” he added. “We don’t use pesticides in our house. I refuse receipts whenever I can. My default request at the A.T.M., known to my bank, is ‘no receipt.’ I never ask for a receipt from a gas station.”
I’m taking my cue from the experts, and I wish the Obama administration would as well.
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Typically, mention of our ever increasing sleeplessness is followed by calls for earlier bedtimes and a longer night’s sleep. But this directive may be part of the problem. Rather than helping us to get more rest, the tyranny of the eight-hour block reinforces a narrow conception of sleep and how we should approach it. Some of the time we spend tossing and turning may even result from misconceptions about sleep and our bodily needs: in fact neither our bodies nor our brains are built for the roughly one-third of our lives that we spend in bed.
The idea that we should sleep in eight-hour chunks is relatively recent. The world’s population sleeps in various and surprising ways. Millions of Chinese workers continue to put their heads on their desks for a nap of an hour or so after lunch, for example, and daytime napping is common from India to Spain.
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