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
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
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
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
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
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
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
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.
As a result, Carter says men should have their first
PSA test at age 40, when levels are usually lower and
prostate enlargement isn’t a confounding factor.
Establishing this early baseline, he argues, will help
clinicians more easily detect patients with small but
dangerous rises in PSA levels, even when the level itself
is still low. Equally important, PSA velocity could identify
men with slow-growing prostate cancer that may never
Mary Ann Ayd
Diet ends seizures for a 4-year-old
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.”
“It’s like we turned a page and got our child
back, Schwanke says.
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
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
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.
Also useful: Because the polymer can be shaped into tiny
pellets with even tinier reservoirs that contain and
then slowly release nerve growth factors, the potential’s
there to implant them anywhere you want nerves to grow,
or perhaps be protected, even in the spinal cord.
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.
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
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?
A. We use the most advanced molecular and cell biology
techniques, along with mouse genetics, to tackle clinical
problems. That’s not so common in psychiatry departments.