Amanda's Operation: Not Bread and Butter

Ask Paul Colombani about the cases he operates on, and he'll tell you: “We don't do a lot of bread-and-butter surgery here. More and more, our patients come for a last-ditch operation.” Which could sound puzzling until this chief of pediatric surgery describes a case like 11-year-old Amanda Long's.

Born in Missouri with a rare congenital defect in which the esophagus fails to develop as a continuous passage from the mouth to the stomach, Amanda, had her esophagus reconnected during infancy and a second repair at age two. But after seven quiet years, “she would swallow and the food would get stuck at about the breastbone area,” her mother, Stephanie, describes. She stopped eating and started losing weight.

That marked the beginning of Amanda's year of five operations, and hovering on the brink of death. Physicians at Children's Mercy Hospital in Kansas City tried dilating the area so food might pass through, but the tissue became too thin. Then, surgeons found that her esophagus had fallen down to her spine. They closed her up after nine hours of exploration. Finally, a 21-hour procedure to remove her esophagus and replace it with a section of the small intestine failed. Hemorrhaging, vomiting blood and unable even to swallow her own saliva, Amanda was covered with massive infections from the various lines going into her body.

“But no one would touch her case,” her mother says. Hospitals all over the country said she would have to stay the way she was. Finally, Stephanie called Colombani and described Amanda's situation. His response was immediate: Staying the way she was wasn't an option.

And so, on Nov. 4, Colombani performed a procedure known as a gastric pull-up on Amanda that connected her stomach directly to what was left of her esophagus. It was a bloody 12-hour surgery during which Colombani struggled to remove the old, densely scarred graft. But after it was all over, Amanda spent a mere two weeks in the Hospital, and for the first time ever, she had no leaks in her follow-up swallow study.

Since then, Amanda's recovery has been slow but steady. This fall, she began middle school. And some days, she says dryly, “I can even eat double quarter pounders with cheese.”

Mary Ellen Miller

The Tiniest Transplant

> Brady Johnson, thriving two months after receiving a new liver.

Liver transplants—even on children—have been around awhile. But last year, when a two-week-old infant named Brady Johnson showed up at the Hospital weighing a little over five pounds and in liver failure, pediatric surgeon Henry Lau knew he was facing a different sort of challenge.

Brady, who had weighed in at five and a half pounds, had looked fine when he was born in Fairfax, Va. But just 18 hours later, he turned yellow. Doctors sent him home, fairly certain the jaundice would disappear. It didn't. Every time the baby's blood levels were checked, his bilirubin had gone up. He was suffering from a severe liver disturbance, but a test for the common culprit, a blockage in the ducts that drain bile from the liver, came out negative. For some unknown reason, Brady simply had a liver that wasn't working.

By the time the infant arrived at Hopkins on May 13, 2004, his white count had soared and his liver had completely shut down. “I've never seen anyone so yellow in my life,” his mother, Julie, remembers. Brady's only hope for survival would be a new liver. He went on the transplant list as status 1, meaning he was likely to die within days.

Nine days later, Julie and Eric Johnson learned that an infant's liver had become available, and pediatric surgeon Lau was about to begin putting it into their son. Brady would be the smallest liver transplant patient in Hopkins' history. “It doesn't get any bigger than this,” the anesthesiologist told the Johnsons.

Then, as Eric and Julie waited hour after gut-wrenching hour outside the OR, Lau removed their baby's failed liver and stitched the tiny donor organ into its cavity. Ten hours later, Lau came out to tell them Brady had pulled through, and “prayers wouldn't hurt.”

The baby's recovery from the huge surgery came inch by inch, but the transformation in his appearance, Julie says, was instantaneous. “Out came this beautiful child—pink. My husband called it the “oil change.”

Judy Minkove

Consultation with The Oracle of Preventative Cardiology

Amid a flood of new ideas for avoiding heart disease coming from the fall gathering of the American Heart Association, we've asked the Ciccarone Center's Roger Blumenthal for a summary.

Bill Clinton's surprise bypass got people talking about how someone with such top medical care could still require an emergency bypass. What happened?

Clinton's case exemplifies the weakness of relying solely on the traditional risk factors highlighted by the Framingham Study. Clinton appeared to be within acceptable ranges on blood lipids, but he had other risk factors that were not so apparent. We believe we can improve risk prediction with some emerging new factors, including genetics and protein analysis.

Are tests available for these new areas?

Not yet, but two other recently developed tests are. First is the coronary calcium scan, which can give us a pretty clear look at areas of atherosclerosis. We recently studied 2,000 patients with these scans. Their average age was 50, and many, like Bill Clinton, showed no evidence of markedly elevated traditional risk factors. We were surprised at how many had high levels of atherosclerosis.

The other test is for C-reactive protein, an agent that indicates inflammation anywhere in the body. A high CRP reading is now considered a good reason to treat patients previously deemed at intermediate risk for heart attack much more aggressively with aspirin and statin medication.

Is the treadmill stress test still considered valuable?

Yes, but we're learning more about how to interpret its results. We did a 20-year follow-up on people who had undergone cardiac stress tests and were impressed by two key factors. The first was that exercise capacity, or how long a person walks on the treadmill, is probably the best determinant of whether that person is going to have a heart attack or stroke over the next 20 years. The second stems from heart rate recovery—how much your heart rate drops in the two minutes after exercise. (In a healthy person, it should drop by about 50 beats per minute within two minutes.) It turns out that people with either below average capacity or below average recovery rates accounted for more than 90 percent of major cardiac events over the ensuing 20 years.

 Interviewed by Edith Nichols

A Ruptured Aneurysm in the Right Patient

> Surgeon Bruce Perler used a new technique to save Henrietta Bartecki

Early last summer, Henrietta Bartecki felt the worst pain she'd ever known—a terrible piercing on the right side of her abdomen. “I wouldn't wish it on a dog,” she says. The 84-year-old widow ended up at Hopkins, the hospital closest to her tiny row house. By the time she reached the emergency department, “Man, I was screamin' and hollerin',” she says.

Bartecki had suffered a ruptured abdominal aortic aneurysm, a condition so lethal that the massive internal bleeding kills half of victims before they even make it to the hospital. Only when the leaking blood happens to form a clot that seals the hole—thereby giving surgeons enough time to intervene—do patients make it through.

When Bruce Perler, director of vascular surgery, set eyes on Bartecki in the emergency department, he estimated her chances of surviving an open operation were less than 30 percent. Her age and underlying health problems—hypertension and heart disease—already put her behind the eight ball. Her body had also sustained a tremendous shock, and traditional surgery, releasing the clot to sew in a graft and repair the aneurysm, would cause her to lose more blood. “It's about as difficult a surgical procedure as we do,” Perler says.

Then it hit Perler that this woman might be a candidate for a new technology in which a graft is advanced up to the aneurysm through a small incision in the groin, then mesh-like stents are expanded to hold the graft in place. The technique had never been performed emergently here to fix a ruptured aneurysm. In the whole world, in fact, there had been only a few hundred such cases.

“You have to have the right patient with the right anatomy,” Perler explains, so Bartecki needed to remain stable long enough for him to get a CT scan, measure the size of her aneurysm, and make sure he had the right graft. “Turns out, we had one stent graft in house that was just the right size.”

Even after the minimally invasive surgery, Bartecki spent two weeks in the Hospital recovering, which convinced Perler that she probably would not have survived a traditional operation. Today, though, she's back home, going out for walks and playing bingo with her “lady friends.”

“Oh, no, I don't stay home!”

Mary Ellen Miller

Can This Drug Tame Hard-Core Depression?

To help John Helliwell with debilitating depression, physicians prescribed virtually every available antidepressant. Most of the drugs had no effect. Some worked briefly. Others launched him into his other nemesis, mania (even though he was also on a mood stabilizer). Helliwell, who was putting his wife and teenage son through what he describes as “holy hell,” finally rounded up the whole slew of meds and swallowed the lot.

Luckily, the 43-year-old Baltimorean was resuscitated. Then, shortly afterward, he happened on an ad for a Hopkins study led by psychiatrist Jennifer Payne testing a different kind of medication in people suffering from depression, who seemed impervious to known antidepressants. Payne was studying the drug riluzole, a neuroprotective agent that's typically used to slow the progression of ALS, or Lou Gehrig's disease. She had been reading data suggesting that excess glutamate—the brain's most widely distributed neurotransmitter—might play a role in triggering depression. One of riluzole's main effects is to inhibit the release of glutamate. Payne's double-blind trial would ask patients with bipolar disorder, like Helliwell, to continue taking a mood stabilizer while they also took either riluzole or a placebo.

Helliwell became one of Payne's first enrollees. At the end of his eight weeks in the study, he says he wasn't surprised to learn that he'd been taking riluzole, not placebo. The steady improvement in his mood and his sense of well-being was so obvious that he elected to continue the regimen. “It's the longest any drug has worked for me,” Helliwell says. “After years of curling up in a ball on the sofa, I get up every day and move forward.”

Mary Ann Ayd

Let's Meet... Luca Vricella

> Luca Vricella

“I love the anatomy, the attention to detail,” Luca Vricella says about his

job as a pediatric cardiac surgeon. “Technically, I think it's one of the most wonderful disciplines in surgery. All the instruments are small, the field is small, the patient is small.”

Vricella, who was born and raised in Rome, comes from a family of physicians, including his father, two uncles and his twin brother, who is a plastic surgeon. His own decision to become a pediatric cardiac surgeon occurred while he sat watching an open heart operation on a small black and white TV. “I thought, This is just absolutely fantastic.” He was 10 and never looked back.

During medical school, Vricella spent summers in the United States dabbling in American medicine. By the time he graduated, there was no doubt that he would leave Italy for the rest of his training. “I thought the hands-on experience was just fantastic, the way they gradually brought you up to very high-level, complex cases.”

Four years ago, as Vricella wound up his residency and fellowship, Hopkins' chief pediatric surgeon Duke Cameron recruited him for the faculty here. Describing why the thrill of his specialty remains as strong as ever, Vricella marveled recently, “Dr. Cameron and I just operated on a baby that was 2 days old, 2.8 kilos, and she's just about to go home doing well. I like the fact that it's the chance—how can you say?—to help a life that's developing. We establish a relationship with these families and patients, and it's a beautiful thing.”

Mary Ellen Miller

Ball and Socket Switch Makes an Arm Work

> Post-op, Mary Boody has no trouble raising her arm comfortably—finally.

With a single misstep on winter ice in 2003, Mary Boody crashed onto her shoulder and destroyed her right rotator cuff. Even after Boody underwent surgery to repair these vital muscles and tendons that stabilize the shoulder joint, followed by physical therapy, she remained in nonstop pain. Unable to lift her arm, she couldn't so much as comb her hair. Finally, her Eastern Shore physician referred her to orthopedic surgeon Edward McFarland at Hopkins.

Most minor rotator cuff tears can be treated nicely. But as recently as two years ago, patients with the major damage of an “end-stage tear arthropathy” like Boody's had to resign themselves to ongoing disability. The reason, McFarland says, is that even traditional joint replacement only works if a substantial portion of the rotator cuff is functioning. Otherwise, patients emerge much like a marionette with broken strings: sometimes in less pain yet missing the means to raise the affected arm much above their waist.

Now, however, McFarland has begun performing a novel three-hour operation that returns many of these patients to a freer life: He literally switches the positions of the shoulder's ball-and-socket assembly. By turning the scapula into the shoulder joint's ball and the upper end of the humerus into its socket, he taps the strength and mechanics of the large, triangular deltoid muscle covering the shoulder. The switch allows the arm to move forward, backward and sideways, while providing the joint with stability. Patients begin moving their arm in a day or two and need pain medication less than a week. Three months of physical therapy builds strength.

Mary Ann Ayd

The Brodsky Approach Saves a Life

> Rob Brodsky and Mark Strome, whose severe blood disorder is cured.

Mark Strome felt like one lucky guy as he drove his silver Maserati toward his mother's birthday party in June 1999. Every financial publication had recently touted his skill in creating one of the world's most successful hedge funds. But on that June morning, the Los Angeles financier got the first signal that his future may have hit a roadblock—a nosebleed that wouldn't stop.

Skipping the party, Strome drove straight to his physician, who cauterized his nose. When the bleeding kept on, the doctor ordered tests and found that Strome's platelet count was 1,000 out of a normal 200,000. “Go immediately to the hospital,” he directed. “And don't bump your head or you'll die.” A week later, Strome learned he had severe aplastic anemia (SAA), an amazingly rare disease in which the body's immune system renders the stem cells incapable of producing red and white blood cells and platelets. Death usually comes in one to two years.

Strome's LA hematologist suggested standard treatments—bone marrow transplant or the “gold-standard” drug, ATG (antithymocyte globulin). In Strome's case, no suitable donor appeared for him to have a bone marrow transplant, so he went on the drug. But ATG leaves patients wide open to side effects like infection, hormonal imbalance and osteoporosis. Up to half also have a relapse or develop some type of malignant blood disease. Strome followed the script. First, he improved and then the SAA came back. By August 2000, he'd run out of options. And at that crucial moment, a psychiatrist friend surfing the Web discovered Rob Brodsky.

Brodsky, a 44-year-old Johns Hopkins hematologist, has been achieving extraordinary results with SAA patients by treating them with a novel protocol. First, he gives them massive doses of the immunosuppressant cyclophosphamide, which stuns the bone marrow and sends already low blood counts plummeting to zero. Then, he waits as patients' decimated immune systems miraculously begin “rebooting” and return to what Brodsky describes as a “healthy, virgin state, like that of a newborn child.” Once that happens, the person's chance of developing SAA again becomes remote.

Two weeks later, Strome was in Brodsky's office hearing that the likelihood he could be cured was about 70 percent. But he would need to endure 12-hour days of drug infusions plus debilitating side effects. His treatments began the next week, followed by terrible nausea and a lung infection. But by Halloween of 2000, Mark Strome was back in LA, working out five times a week. Today, he is completely healthy.

The Schizophrenic Mind Becomes Clearer

> Akira Sawa in the lab.

Breathing heavily and carrying multiple bags, Akira Sawa raced into a classroom full of students last fall and apologized for being a “not so well organized person.” But Sawa, a neurobiology researcher who once practiced psychiatry in his native Japan, has impressed his fellow scientists as just the opposite. Over the last couple of years, using a highly systematic approach, he's made notable strides in determining the genetic basis for schizophrenia.

To get to the root of the disabling psychiatric condition, Sawa and his lab group have been zeroing in on a gene, named DISC1 (short for Disrupted In Schizophrenia 1). Researchers learned that DISC1 has something to do with schizophrenia several years ago when they studied a Scottish family with the disease peppered throughout and discovered that many members had a mutation in this gene. Sawa took this knowledge to the next step: Because scientists also knew from autopsies and MRIs that people with schizophrenia possess misshapen neurons and have abnormally large brain ventricles, he began looking for a link between these defects and mutant DISC1.

First, he created one set of neurons in which the DISC1 wasn't functioning and then he compared the behavior of these neurons with another set in which the gene was at work. What Sawa observed was amazing. The neurons with inactive DISC1 dawdled, while those where the gene was active moved in a swift and orderly fashion. The neurons with inactive DISC1 were also misshapen.

Once Sawa was certain of DISC1's role in schizophrenia, he went on to “knock down” the gene in laboratory mice. This, it turned out, actually induced the malformed neurons and large brain ventricles that appear in the human form of the disease. Now, Sawa is examining the “schizophrenic” mice more thoroughly to try to pinpoint other markers. Discovering these traits, he reasons, could help diagnose the condition and lead to drugs to treat it.

With such stunning successes in hand, Sawa is ready to start comparing living neurons from schizophrenia patients with neurons from healthy people. He extracts olfactory epithelium cells (a little tissue from the nose) from willing patients in a 10-minute outpatient procedure and starts analyzing. “What's so thrilling about all these experiments,” Sawa says, “is that they keep reminding us how precisely our brains are organized—which perpetually makes us appreciate the beauty of the human mind.”

Erika Gebel

A Newscaster Rejoins the World

>Newscaster Bob Turk on the air and hearing again.

For more than a decade, Baltimore newscaster Bob Turk battled increasing deafness. At first, he managed with hearing aids. But by late 2004, even the most expensive models were failing him: Hearing in his right ear had plummeted to less than 15 percent, and what speech he caught in his left ear kept breaking up. No longer able to understand the news anchors on the air, Turk's responses could sound confused. “After all those years at the station,” he says, “I didn't know if they'd keep me.”

Finally, Turk went public about his hearing loss in a broadcast last spring, and a coworker asked when he planned to do something about it. He decided right then to look into a cochlear implant.

Unlike hearing aids, which merely amplify sound, cochlear implants bypass impaired inner-ear structures and stimulate the auditory nerve directly via an electrode array surgically embedded in the cochlea. The devices have been well publicized in children, but adults with acquired deafness account for about half of Hopkins patients.

Most people don't seem aware, says John Niparko, director of Otology and Neurotology, that adults can do well with a cochlear implant. They benefit from their already-established ability to comprehend speech.

When the unit is activated a few weeks after surgery, Niparko explains, the patient's new perception of sound isn't automatically understandable as speech. The external components of the device, a sound processor, microphone and transmitter—must be individually mapped and fine-tuned. Further, patients must be highly motivated to relearn how to interpret incoming signals. “There's a big difference between having your sound sensitivity restored and being able to listen effectively,” Niparko says.

But Bob Turk surprised everyone. “The minute my implant was activated,” he reports, “it was like I was in a radio booth with a headset and mike. Right away, I heard and understood everything. And the next week, I was back on the air. If you ask me, John Niparko is a miracle worker.”

Mary Ann Ayd

Baiting the Hook

For Ivan Borello, a researcher at the Sidney Kimmel Cancer Center , who's been trying for awhile to teach the body to fight off cancer, the last few months have been heady. Working with two kinds of human T-cells—which come equipped with the power to identify cells foreign to the body and mark them for destruction—Borello and his team discovered that one group was “smarter.”

For the study, the researchers used only T-cells that had been primed to attack the bone cancer myeloma. They took some from the bone marrow, however, and the rest from the blood. When they tested the kill-rates of both T-cell groups, they found the bone marrow cells outperformed their blood counterparts by more than 90 percent.

“Now we have evidence that educating T-cells in the bone marrow may be the most effective way to get an anti-tumor response,” Borello says.

The next step will be to test the activated marrow T-cells in a few myeloma patients, both alone and in combination with a myeloma vaccine. What's especially exciting, though, is that the researchers believe that patients with other blood, bone marrow and solid tumors, such as breast cancer, may also benefit from this type of immunotherapy.

Vanessa Wasta