Diagnosis: Skin Cancer
Destination: Michigan

When Athletic Director Bill Martin was diagnosed with melanoma a few years ago, it occurred to him that many of his staff members also spend a lot of time in the sun, which is one of the highest risk factors for the disease. And when, at Martin’s request, Timothy M. Johnson, M.D., head of the U-M skin cancer program, performed screenings for the Athletic Department, he found some form of skin cancer or pre-cancerous lesions in nearly two dozen staff members.

Head hockey coach Red Berenson and former head football coach Lloyd Carr, now associate athletic director, also revealed recently that they were diagnosed and treated for melanoma, the deadliest form of skin cancer.

The three Michigan sports leaders are doing well — as are members of the Athletic Department staff — and screenings have continued; the third was held this summer. The most common type of cancer in the U.S., skin cancer is highly curable when caught early and treated properly. For Berenson, Carr and Martin, it wasn’t just proximity that led them to the health system located in their own backyard for treatment; the U-M is a world leader in skin cancer diagnosis, treatment and research.

Carr has become an advocate after his diagnosis and treatment. “Do something about it,” he said during a recent television interview. “Don’t wait and hope that it goes away, because it’s not going away.”

Melanoma is the most frequent type of cancer diagnosed and treated at the U-M Comprehensive Cancer Center, which has the largest multidisciplinary melanoma program in the country and treats more skin cancer patients than nearly any other program. The U-M Health System also is leading the effort to find more effective treatments through an extensive, innovative and far-reaching program of skin cancer research.

Most skin cancers are non-melanoma of two primary types: basal cell carcinoma — slow-growing with a small likelihood of spreading to other parts of the body and accounting for 75 percent of all skin cancers; and squamous cell carcinoma — faster growing and potentially more invasive. A third type, Merkel cell carcinoma, is rare, but very deadly. The U-M program achieves a cure rate of approximately 90 percent to 99 percent for non-melanomas, even if other treatments have failed.

More than just high positive outcomes mark Michigan’s multidisciplinary skin cancer program as one of the best in the nation. One phone call results in coordination of all the collaborative care the patient will require, across several specialties with prompt access and efficient scheduling to eliminate wait times.

Bill Martin and his staff certainly appreciate the work of Tim Johnson and the skin cancer program. Nationwide, athletics organizations are doing more to help raise awareness about skin cancer and its prevention.

“I’m so thankful to Bill that he had this screening,” says Berenson, “because had he not had it, I probably would not have gone in. Had I not gone in, I would have been in serious trouble.”
—RICK KRUPINSKI

Gender and Depression

There’s good news and bad news about depression in women. The bad news is that women are twice as likely as men to develop depression. The good news is that women are 33 percent more likely to achieve complete remission of their symptoms when treated with a commonly used antidepressant.

The news about how men and women respond differently to antidepressants comes from a national, multi-year study of 2,876 men and women diagnosed with major depression and treated with citalopram, marketed as Celexa. Called STAR*D, the study is funded by the National Institute of Mental Health. Elizabeth Young, M.D., a professor of psychiatry, was the study’s lead author.

“Based on data from this large, well-controlled study, we are now confident there are true biological differences between how men and women respond to this antidepressant,” Young says. Although the reasons for the difference are unclear, Young notes that animal studies have suggested that hormonal differences between males and females may be a factor.

Young cautioned that the study’s results don’t mean that citalopram should be used only in women, since up to 24 percent of men in the study responded well to the drug. Instead, it illustrates the point that people with depression often need to try several treatments to find one that works best for them. —SP

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Keeping an Eye on Diabetes
Detecting signals from cells under stress

Nearly 24 million Americans with diabetes have a higher-than-normal risk of losing their vision, but many of them don’t know it.

According to the latest estimates from the U.S. Centers for Disease Control and Prevention, close to 8 percent of the U.S. population has diabetes. Early detection and treatment of diabetes is critical to preventing high levels of blood sugar from damaging cells in the retina — the thin layer of light-sensitive cells lining the back of the eye. This damage begins shortly after onset of the disease, but long before it can be detected during a routine eye exam.

Too often, patients aren’t tested for diabetes until they experience complications. By that time, cells in the eye, as well as other organs, may already have suffered irreparable harm. Diabetic retinopathy is the leading cause of blindness among working-age adults and affects 4.1 million people over age 40.

Now, Victor Elner, M.D., Ph.D., and Howard Petty, Ph.D. — researchers at the Kellogg Eye Center and professors of ophthalmology and visual sciences in the Medical School — have developed a noninvasive test that captures images of the eye and measures metabolic stress and tissue damage, two telltale signs of diabetes.

The computer imaging system Elner and Petty developed detects a glowing signal from flavoproteins in mitochondria, the energy factories in retinal cells. Flavoproteins are involved in many biological processes, including cell death. The glow, called flavoprotein autofluorescence or FA, occurs when retinal cells are in distress: The stronger the glow, the more severe the damage.

The new U-M imaging system can detect retinal dysfunction associated with disease several years before symptoms occur. Unlike glucose tolerance testing — the gold standard test for diabetes — patients don’t need to fast or undergo multiple blood draws. The new test takes less than 10 minutes.

“Essentially the patient just sits in front of the instrument, the device is focused on the eye, a specialized photograph is taken, and results are immediately available,” says Elner.

In a recent study, Elner and Petty measured and compared FA levels of 21 people with diabetes and 21 people who were the same age, but did not have diabetes. They found that FA activity was significantly higher in diabetic patients, regardless of disease severity, compared with healthy controls.

The U-M scientists say the screening test could be given routinely by an optometrist, ophthalmologist or trained office staff. Abnormal test results would be due to diabetes about 90 percent of the time. In 10 percent of cases, elevated FA would likely indicate other retinal diseases, such as glaucoma or age-related macular degeneration.

Elner and Petty hope their imaging technology will be used not only to screen people at risk of developing diabetes, but also on an ongoing basis to monitor disease severity in those who already have been diagnosed. “When retinal metabolic analysis is used routinely to help patients in the clinical setting,” says Petty, “we’ll know we’ve been successful.”

The University of Michigan has applied for a patent on the imaging technology, and Petty and Elner have formed a company called OcuSciences Inc. to develop and market it. —KIMBERLEE ROTH

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Gene Therapy to Fight Chronic Pain

What does the herpes simplex virus (HSV), the virus that causes cold sores, have to do with chronic pain? Plenty, if you ask David Fink, M.D., the Robert Brear Professor of Neurology, who has been studying the use of a modified herpes virus to deliver genes for pain-killing molecules to the nervous sytem. Now, years of animal research conducted by Fink and his research colleagues have culminated in the first human clinical trial of a gene therapy for chronic pain in patients with intractable pain from cancer.

Gene therapy is an attractive alternative to conventional pain medications because it allows the therapy to be delivered directly to the pain pathways, according to Fink. “We hope selective targeting will result in pain-relieving effects that cannot be achieved by systemic administration of opiate drugs,” he says.

In order to transform the virus into a gene delivery vehicle, or vector, Fink and his research colleagues removed genes that allow HSV to multiply and inserted the gene for enkephalin, one of the body’s natural painkillers. Injected into the skin, the vector is taken up by sensory nerve fibers that then produce enkephalin. Release of enkephalin from the nerve fibers into the spinal cord selectively blocks the transmission of pain signals, thus relieving pain.

The clinical trial is the first trial of gene therapy for pain, and the first gene transfer trial to use HSV-based vectors in patients. If it is successful, Fink hopes to follow with HSV vectors carrying other genes for the treatment of different types of chronic pain. —CLE

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Health Briefs

During the first six months of life, babies need to establish regular sleep-wake patterns, called circadian rhythms. But if Mom is depressed, it can interfere with this important milestone in a baby’s life. A recent U-M study found that babies with mothers who suffered from depression had much more trouble falling asleep, woke more often during the night and had weaker circadian rhythms than babies born to mothers who did not have depression.

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The U.S. Centers for Medicare and Medicaid Services have recognized the U-M Faculty Group Practice for providing high-quality care for older patients with heart disease and diabetes, while reducing the cost of treating all Medicare patients at the same time. The group includes 1,500 physicians working at U-M hospitals and health centers.

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Almost half of 1,132 breast cancer patients surveyed by U-M researchers didn’t know that their odds of surviving cancer, or having the cancer come back, were about the same whether they underwent a mastectomy or breast-conserving lumpectomy with radiation. African-American and Latina women were less likely to know than white women. U-M researchers say surgeons need to communicate more clearly and patients need to ask more questions. —SP

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