Regardless of Age

A year after sharing his case results, “Surgeon to the Seniors” Steve Yang draws the national spotlight.

Thoracic surgeon Stephen Yang’s growing success with aging cancer patients is sending a ripple through medicine. The most recent evidence came in an October Wall Street Journal piece touting Yang as a boundary-pushing trendsetter. Since then, a rising tide of seniors previously deemed ineligible for surgery are finding their way into Yang’s office—and getting very different answers.

When he joined the faculty here, Yang took it as an article of faith that patients over 65 made poor candidates for surgery. But he also took note of the changing reality around him: More seniors were staying healthier longer, and many defied their biological age. Why not consider patients on their merits, regardless of age?

One by one, those cases added up into an entirely new success story. Of the 4,000 patients Yang has operated on during his 13 years here, 1,400 have been older than 65, 900 have been over 70, 500 over 75 and 175 over 80. His average mortality rate? About 1 percent.

 “A lot of people are still being denied an option for surgery, an option for cure,” Yang says. “My passion is that a lot of those people should be operated on, especially those with lung cancer. This is not because I’m cut-happy, but this is my specialty.”

The irony, Yang adds, is that his outcomes data for seniors are probably not unusual. He suspects that other thoracic surgeons have similar results but have not yet shared their data. He hopes to change that at an annual gathering of chest surgeons slated this November.

Yang’s next crusade, he says, will be for more objective standards for deciding when patients are operable. He envisions forming a “geriatric oncology team” within his division and says a new benefactor will likely make it possible for him to add another general thoracic surgeon.

And, in a development that gives his cause even greater traction, another of Yang’s high-profile patients has joined national gun-control advocate Sarah Brady in proclaiming his surgical skill. Pat Modell, wife of former Baltimore Ravens owner Art Modell, is now a lung cancer survivor after an operation in 2005 by Yang. Like other senior patients, she’s making no secret of her gratitude.

Ramsey Flynn

Briefer but Better

By overlapping chemo and radiation, Zellars aims to ease breast-cancer treatment

For 30 years, doctors have considered it dangerously toxic to treat breast cancer patients concurrently with chemotherapy and radiation. Patients who needed both therapies after surgery have therefore had to go through first one treatment and then the other in a regimen that could stretch to six months. Two years ago, Richard Zellars, a radiation oncologist here, decided that new understandings about therpay made it time to give the simultaneous approach another go. He proposed a clinical trial to demonstrate that concurrent chemo and radiation therapy, correctly administered, could work well.

In Zellars’ trial, the duration of each patient’s treatment would be trimmed, decreasing both the delays and the toxicity. Instead of receiving standard doses of chemo every three weeks for up to four and a half months, patients would receive the same doses at two-week intervals for a total of seven weeks. Radiation treatments, meanwhile, would overlap chemotherapy and be condensed to three weeks or less, instead of the usual six.

Among the evidence Zellars marshaled to support simultaneous therapy was literature showing that in patients who’ve had a lumpectomy, any major tumor recurrence tends to occur in the same breast quadrant as the original lesion. To prevent local recurrence, the radiation is therefore applied only to the area of the lumpectomy plus a small margin. Furthermore, studies of other cancers have also shown that there’s greater tumor cell “kill” when chemo is added to radiation.

Viola Collier Jones is among the 20 women who’ve now completed Zellars’ trial. A 55-year-old Washington, D.C., resident who underwent a lumpectomy at Hopkins in April 2005 for cancer that involved one lymph node, Jones signed on for the abbreviated chemo-radiation regimen that June and was finished by August. The only side effect that bothered her, she reports, was chemo-induced fatigue. That problem was managed with the same medications used during traditional chemo treatments. “If I had to do it all over again,” Jones says, “I would definitely choose that clinical trial.”

Zellars continues to enroll patients in his trial, “but we’ve already shown that the combination is safe,” he says. “The next goal is to establish long-term efficacy.”

Mary Ann Ayd

Get a PSA at 40?

An early baseline can give an early warning for prostate cancer

For years, 50 has been the recommended age for most men to have their first prostate-specific antigen level measurement. What’s been debated is the PSA level that should trigger a biopsy. Going below the long-accepted threshold of 4.0 ng/mL, as some urologists have urged, could increase detection of curable prostate cancers. It could also lead to overdiagnosis and overtreatment. Yet sticking with the higher level before ordering a biopsy could mean missing a biologically important cancer.

To get beyond the impasse, H. Ballentine Carter, director of Hopkins’ Division of Adult Urology, and investigators at the Baltimore Longitudinal Study of Aging (BLSA) looked at PSA velocity—how fast the blood serum level of the protein changes over time—as a marker for life-threatening cancers. Using BLSA samples, they determined PSA velocity in 980 study participants and found that not only could it predict death from prostate cancer, but that it could signal the risk 10 to 15 years ahead of diagnosis. Among their findings: In men with a PSA velocity above 0.35 ng/mL per year, there was significantly lower prostate cancer-specific survival at 25 years when compared to men with a PSA velocity of 0.35 ng/mL per year or lower.

Mary Ann Ayd

Atkins Scores

Diet ends seizures for a 4-year-old

When 4-year-old Genevieve Schwanke’s seizures became more frequent and intense in 2005, neurologist Eileen Vining told her mother, Bissett, about a new diet. Instead of the rigorous, high-fat, low-carbohydrate ketogenic diet, which has marvelous results in controlling epilepsy, but sometimes has side effects like kidney stones, Vining described a modified Atkins diet. It also produces ketones—a chemical by-product of fat that can inhibit seizures—but requires fewer restrictions on calories, fluids and proteins, and no fasting or hospitalization.

Schwanke enrolled her daughter in a six-month pilot study of the diet that pediatric neurologist Eric Kossoff was conducting. The results were astounding. “Within 36 hours, Genevieve didn’t have another seizure.”

In Kossoff’s study, 13 of 20 patients had a greater than 50 percent improvement in seizures, and seven had a greater than 90 percent improvement. Besides Genevieve, three other patients are now seizure free.. “Our study wasn’t large enough to say a modified Atkins diet should replace the ketogenic diet,” Kossoff says, but the results are encouraging.”

Mary Ann Ayd

It's Not Alzheimer's

The condition known as FTD is little known, but devastating.

>Psychiatrist Chiadi Onyike, FTD specialist.

Psychiatrist Chiadi Onyike remembers it vividly: A middle-aged woman sitting quietly at a dining table and repeatedly picking up her glass for a sip. Yet her plate was bare, her glass empty. “It’s the small scenerios,” he explains, “that give you a sense of frontotemporal dementia (FTD).”

Onyike, who heads the FTD clinic here, aims to increase awareness of this type dementia—often wrongly diagnosed as Alzheimer’s. “Up to 20 percent of middle-aged patients who seek memory or dementia help, ” he says, “have some form of FTD, but few physicians other than neuropsychiatrists or behavioral neurologists are aware of it.”

FTD covers up to seven fatal diseases all marked by dementia and atrophy of the brain’s frontal and/or anterior temporal lobes. The illnesses can affect behavior by causing what Onyike calls “a history of social miscues and misdemeanors:” (Uncle George’s wanting to wear sweatpants to work seems odd, but his rude remarks, his repeated hair-combing and overblown jolliness cross the line.) Patients’ speech also deteriorates: They may become mute, even lose their ability to comprehend language. In some cases, brain cells carry telltale tau or beta-amyloid proteins; others may display different signs or none at all. Some 40 percent of cases are familial, but even then, members of one family can have different types of the condition.

At the clinic, patients (with caregivers) initially spend two to three hours giving a detailed history and undergoing cognitive and neurological testing that may include brain imaging and EEGs. They receive a prognosis and also get help in knowing what to expect and how to handle care and other issues.

Families need calmness, because there’s no cure, Onyike says, “an ability to accept things as they are.” Growing up in Nigeria, he says, “I never knew the main role of medicine as providing a cure,”  I came to know it as providing clarity, comfort and guidance and—if you’re fortunate—a cure. In that case, you only walk a short way before you and patients shake hands. With FTD, you walk a longer distance, sometimes the whole way, with the family.”

Marjorie Centofanti

Nano-Spaghetti

Ahmet Höke uses masses of fine polymer fibers to encourage nerves to grow.

Ahmet Höke spends a lot of time thinking about nerves. Specifically, he ponders how to speed repair of injured peripheral nerves—those outside the central nervous system. Höke’s recent work tries to close the gap in severed peripheral nerves following accidents or other trauma. They won’t reconnect without help.

For years, neurosurgeons have tried grafting bits of patients’ more expendable nerves in the space. Or delicate, hollow tubes are sewn in to guide the way for nerve regrowth. Neither has a good track record. So when Höke learned that Kam Leong, a biomedical engineer also at Johns Hopkins, had created near-nano-scale fibers made of a nontoxic polymer, he persuaded him to stuff them into an existing nerve guide.

“I explained that I wanted spaghetti,” says Höke, “masses of the fibers fine enough for axons to attach to, wrap around and grow across.”

Now, Höke’s found that the nanofiber-containing tubes truly encourage nerve repair in rat models. But there’s more. Leong found a way to coat the fibers with specific natural growth factors, and Höke found that this step further speeds healing. He says the model could easily screen various growth factors to see which is the most growth-encouraging for nerves.

Marjorie Centofanti

The Hunt for Huntington's

Unlocking the black box to the fatal movement disorder

>Christopher Ross, leading the search.

Woody Guthrie had it . . . It gives you ceaseless, jerky movements . . . It’s fatal. That’s all most people usually know about Huntington’s disease. But for psychiatrist Christopher Ross, HD has becomes a defining work: Two decades ago, he set out to understand the biology of the condition—how it kills nerve cells.

Huntington’s is strongly genetic. Besides its terrible affect on movement, it brings on an asylum-full of psychiatric disturbances: apathy, depression, obsessions, psychosis, substance abuse, paranoia. All—so far—without a cure.
Ross, who’s head of the Huntington’s Disease Center—possibly the world’s largest HD clinic—has been in the thick of advancing understanding. Using the human HD gene (discovered in 1993), his team identified the novel genetic mutation—a mutant protein named huntingtin—and  showed that its“severity” matches the age of onset of the disease. They’ve also created a mouse model of HD to test therapies. Most interesting, they’ve found ways to slow the disease in lab animals.

Q. The HD gene surfaced 14 years ago, but there’s still no remedy.
A. We had no idea how difficult it’d be to find how huntingtin kills nerve cells. We know huntingtin’s cleaved into smaller molecules that aggregate inside cells. We know it triggers a host of toxic responses downstream and precisely what they are. We just need the intermediary steps. And we’re checking places to intervene—that first cleavage, for example. If an enzyme causes it, there’s a drug target.

Q. How could drug companies not be interested?
A. They are now! They used to think the market was too small. But that’s changing.

Q. Why?
A. Because Huntington’s resembles Parkinson’s and Alzheimer’s diseases in major ways. So if we find an HD treatment, something should be there for the other illnesses.

Q. Any possible therapies?
A. Two antidepressants, surprisingly, look interesting. Sertraline (Zoloft) slows brain shrinkage in our model mice. Paroxetine (Paxil) appears to do the same, partly by increasing the growth factor BDNF in the brain. We’re hoping clinical trials could be down the road.

Q. What’s your current treatment strategy?
A. We delay its onset as long as possible by combining approaches. That means we must catch patients before their symptoms develop—damage begins some 15 years before diagnosis is possible. So we’re actively seeking good predictors in people with the gene, things to tell us when to start treating.

Q. Is there anything about the Hopkins approach that sets us apart?

Marjorie Centofanti