Duke University Alumni Magazine

SURGICAL ART AND ARTIFICE RECONSTRUCTIONS AND RESTORATIONS BY DENNIS MEREDITH While Duke plastic surgeons work in the operating room to reshape skin, fat, muscle, and bone to correct defects, their scientist colleagues experiment in the laboratory to speed wound healing and engineer living tissue transfers.

efore he begins the operation, the plastic surgeon surveys the gleaming surgical steel instruments arrayed neatly on the tray beside the operating table. He scrutinizes the razor-sharp scalpels, the clamps, the needles, and the scissors. He inspects the sturdy spirit-lifter, the gracefully curved confidence-builder, and the finely honed self-image-shaper.

Of course, the last three instruments are fanciful, but they might as well be real, given the outcome of plastic surgeons' labors. These physicians, with their meticulous reconstructions and restorations, are indeed surgeons of the spirit as well as the flesh--erasing the cleft lip of a child, repairing the face of the man disfigured in an auto accident, or returning a buoyant expression to the middle-aged woman whose face merciless gravity has tugged into a haggard mask.

Such skillful handiwork most visibly dramatizes the fact that surgery--and, indeed, all of medicine--is both high art and complex science. While Duke Medical Center's plastic surgeons work in the operating room to reshape skin, fat, muscle, and bone to correct defects, their scientist colleagues experiment in the laboratory to speed wound healing and engineer living tissue to improve artificial arteries and other implants. Such research has ambitious clinical aims, says L. Scott Levin '77, chief of the medical center's division of plastic, reconstructive, and maxillofacial surgery. "Within our lifetimes, we could likely see the construction of whole artificial body parts," he says. "We will be able to build a framework of bone, cartilage, muscle, and skin, and make a nose, an ear, a breast, or a hand."

Clearly, enormous scientific problems remain, cautions Levin, before the Six-Million-Dollar Man is more than science fiction. Scientists still need decades of research to learn how to cause blood vessels and functioning nerves to sprout within engineered body parts. And, like surgeons who transplant hearts, kidneys, and other organs, they must learn to overcome fully the body's immunity-system rejection of foreign tissue.

Hers: Time and gravity can drag the skin down to produce a scowling visage. Plastic surgeon Gregory Ruff restored a naturally pleasant expression to this young woman by using a face and neck lift, along with a "mask" lift of facial skin. Photo: Gregory Ruff	His: To Ruff, reshaping a face can be a fine, subtle art, as shown by his work with this young man. By slightly altering the shape of the nose, removing fat from the neck, and adding an implant to the chin, he achieved a more balanced look.

Levin and his colleagues are already up to the intricate surgical demands of installing tissue-engineered hands or other organs. The plastic surgeons, often working in multidisciplinary surgical teams, have long perfected the delicate microsurgical techniques for routinely reattaching limbs, and transplanting living tissue from one part of a patient's body to another. They frequently transplant toes to give hand-trauma patients a new thumb or finger. They also routinely restore the surface of severely wounded limbs by moving flaps of muscle and skin from other parts of the body. While such reconstructive surgery represents the Duke surgeons' major clinical effort, they are best known for their aesthetic surgery, blending artistic sense and surgical skill to create new images for their patients.

Working at Duke's new Center for Aesthetic Services, Levin and his colleagues perform facelifts, eyelid surgery, skin resurfacing and rejuvenation, brow and forehead lifts, nose surgery, chin augmentation, ear surgeries, liposuction, and breast enhancements. The demand for such surgeries is booming, says Gregory Georgiade M.D. '74, a trauma surgeon who specializes in breast restorations. "As our Baby Boomers start to age, they're probably far more body conscious and health conscious than the generation before them. They practice good health habits like not smoking and keeping their weight down, and they have new attitudes about aesthetic surgical procedures."

National statistics reflect the soaring popularity of cosmetic surgery. According to the American Society of Plastic and Reconstructive Surgeons (http://www.plasticsurgery.org/), between 1992 and 1997 alone, liposuction procedures increased 215 percent, eyelid surgery 86 percent, facelifts 52 percent, and breast augmentation 275 percent. In 1997 alone, patients in this country underwent more than half a million cosmetic procedures.

Ironically, plastic surgeons must involve themselves as much with the inside of a patient's head as the outside. Listening to the patients is paramount, says plastic surgeon Gregory Ruff, who works at the Aesthetics Center. "You can have ears like Dumbo, but when you first come in, I'm not going to say, 'Oh, are you here for your ears?' I want to hear from you. I don't want to be the person writing your list of problems for you. I want to know what you're not happy with."

Georgiade warns that some surgeons tend to ignore patients' wishes, because they see their patients as walking advertisements. "A patient might realistically be a good candidate for a number of procedures and the surgeon might feel that, if his name will be associated with that patient's results, he wants to have the best possible outcome. We have to make sure our perceptions take a back seat to what the patient wants." On the other hand, says Georgiade, other patients may be so unrealistic in their expectations that the surgeon must sometimes just say no.

"The physician needs to be comfortable that he can get in the range of the result the patient wants," Georgiade says. "If he can't get there, or if the patient will only accept the top 5 percent of outcomes for an operation to be satisfied, the surgeon probably shouldn't operate. For example, I sometimes see women who want me to give them the breasts they had when they were twenty, and without any scars. They may have significant droop, atrophy, stretch marks, and thinning skin, but expect those to be corrected. If I don't think I can get within the ballpark of what they expect, I shouldn't operate." Like his colleagues, Georgiade also must work within our culture's sometimes very different accepted norms for physical attractiveness. "When I go to international conferences, I see results of breast surgeries from other countries; if I got the same result here, the patient would probably shoot me."

North Americans tend to like larger projecting breasts, he says, while South Americans prefer smaller breasts, and Europeans most admire flatter, broader breasts. Ironically, many women in this country who seek larger breasts would be considered ideal in South America. He theorizes that American women prefer a larger post-surgery breast size because breast augmentation is more prevalent here, and women want more evident results. American women are also highly

averse to scarring, while South Americans are more interested in the shape and form of the breasts than the scars, says Georgiade. As exacting as his patients are in their requirements, he says, the best plastic surgeons are even greater perfectionists. "Ideally, the surgeon's going to be more critical of the result than the patient is--always looking for ways to make it better. In my operations, there are certain things I might not like about the outcome that just don't bother the patient."

The surgeon's continuing search for such perfection can be particularly frustrating because his artistic medium--flesh--can be such an unpredictable one. Gregory Ruff says surgeons must constantly judge how best to redrape skin in performing facelifts. "Skin will stretch in all directions, and you have to make that extension even, or the skin will give unevenly." Also, skin adjusts to stretching over time, as fluid shifts within the skin's supporting collagen fibers and the slippery fat beneath. In his many facelift operations, he has perfected the art of redraping with exquisite care, sometimes removing only small amounts of skin to achieve the ideal tightening. Working with fat is another artistic challenge entirely, says Ruff, who uses fat to fill

in facial creases or enlarge lips. "Fat that's been minced up and injected, probably three-fourths of it melts away on the average. Therefore, you've got a lot of potential difference between individuals, making a fat graft one of the trickiest things of all because so little of it is retained."

Rhinoplasties--popularly known as nose jobs--present their own set of surgical challenges, he says. "You've got the cartilage, which is deformable, and the nasal bones, which are very thin and delicate. And, you've got to work through an incision in one nostril where you're working with your head bent and a headlight on." Unlike many plastic surgeons, who work only in skin, Ruff is "good to the bone." His orthopedic surgical background allows him to sculpt a patient's underlying facial bones, reshaping cheekbones, for example. "Bone is a nice predictable substance in most circumstances. Whereas skin is always going to heal with scar tissue, bone will usually heal completely."

Ruff emphasizes that achieving perfection in plastic surgery often means making successive approximations toward an end, given the subtlety of the desired affect and the complexity of the medium. "In the general surgery training I had, when you removed a gall bladder, it didn't grow back, and you were done. But plastic surgery is something like golfing. You may not be able to predict exactly how a patient will heal the first time, you may hit a drive on the first operation, then a chip shot, and finally putt a couple of times before you get it just right, and both you and the patient are happy."

Facelifts are a good example, he says. "The underlying shape of the patient's face and the individual properties of the skin really determine how you shape the skin and pull the various muscles and connective tissue." Thus, Ruff tells his patients that the results of their cosmetic surgery will be like receiving a birthday present. "The present you may get may not be one that you've exactly specified, or you might as well have gone out and bought it yourself. But we're going to give you something nice, that you wanted, as close as we possibly can."

Duke Medical Center plastic surgeons all predict that future scientific and technological developments will profoundly benefit their clinical art. According to Georgiade, future breast reconstruction will be made using implants that are sturdier, and possess a biodegradable filler that more closely resembles the texture of natural breast tissue. For facelifts, Ruff foresees the possibility of porcupine-quill-like struts that can be inserted into facial and other tissues to support them and prevent the sagging of aging.

In his three years as chair of plastic surgery, Scott Levin has built clinical and basic laboratory research into a key element in the division's mission. He says the research involves not only faculty but also surgical residents, who constitute the future generation of clinician-researchers. He credits former surgery department chairman David Sabiston as a leading early champion of this philosophy. "Dr. Sabiston always emphasized the importance to medicine of the scholar-clinician-scientist combination, as has chief of experimental surgery Dani Bolognesi."

A serious problem in plastic surgery, says Levin, is that many new techniques spread out into surgical practice--along with great ballyhoo about their value--before scientists can do careful studies of their true effectiveness, especially scientists at university medical centers. "Such new technologies as laser skin resurfacing and the use of ultrasound to liquefy and remove fat spark a tremendous wave of over-enthusiasm. Everybody wants

Levin: as the chief of the plastic, reconstructive, and maxillofacial surgery division, he works with patients whose needs range from vanity to necessity Photo:Les Todd

to jump on the bandwagon, advertising the new technique to patients as the greatest thing since sliced bread. After this enthusiasm falls off, people begin to look at whether the technique is really practical and cost-beneficial."

Duke's plastic surgeons have done careful laboratory studies of ultrasound-assisted liposuction to separate hype from truth about its usefulness and inform surgeons about when to use the technique. Ruff cites the use of carbon dioxide lasers to resurface skin as another overhyped technique. Although introduced with great fanfare, the laser devices proved to cause more skin damage and required a longer healing time than the chemical peels that Ruff prefers for skin resurfacing.

In their clinical studies, Levin and his colleagues have made the pathway between clinic and laboratory a two-way street. In award-winning research, for example, they have applied endoscopic techniques--popularly known as "band-aid surgery"--to plastic surgery. Surgeons using endoscopic methods perform surgery by remote control by inserting video-carrying cables and instruments through a small slit into the body. Used primarily in abdominal surgery, the techniques have become enormously popular because they considerably reduce the time, scarring, bleeding, and pain of surgery--and allow faster healing. In their endoscopic approach to plastic surgery, Levin and his colleagues first insert a balloon expander through a slit that reaches between naturally occurring tissue layers. The surgeons inflate the balloon to separate the layers bloodlessly, opening space for surgical work or an implant. They first experimented with the new technique using cadavers in the division's Human Tissues Laboratory.

Once the technique was perfected, working in the Duke University/U.S. Surgical Corporation Endosurgical Center, they began applying it to patients, in muscle flap transfers, tissue expansion and harvest for reconstruction, breast augmentation, and face and neck lifts. They have also returned to the laboratory to use animal models to refine it further for clinical practice.

In their basic studies, scientists in the division explore the complex biology of wound-healing, biochemically "eavesdropping" on the healing wound itself. The snooping technique developed by researcher Spencer Brown--sponsored by the Plastic Surgery Educational Foundation--carries the impressive moniker "immuno-affinity capillary electrophoresis." The analytical method allows the researchers to make infinitesimally fine measurements of the chemicals in the fluid that bathes the cells rebuilding the wounded tissue. With their method, they can measure levels of key wound-healing chemicals called cytokines from as few as two cells. "Other researchers have tried to study wound-healing by taking overall blood samples, but those aren't detailed enough to tell you what's happening right at the wound site," says Brown. Their pilot studies have revealed ten to twenty times higher cytokine levels than in the bloodstream, telling them that they are zeroing in on the very heart of the healing process.

Says Levin, "A detailed molecular understanding of the wound environment will prove extremely valuable clinically. Medicine still does not understand such details of healing wounds. Even though we know about chemical growth factors that trigger wound-healing, we still have not been able to clinically deliver them to heal." Surgeons treat major wounds and non-healing pressure sores by importing skin and muscle to cover the wound, which somehow helps mobilize wound-healing cells to do their job. However, says Brown, "We don't know what the triggers are and the molecular mechanisms behind all this. And most important, we are desperately lacking information about what building blocks are missing in those wounds that are abnormal and don't heal."

The scientists' eavesdropping on the healing may also help them catch another culprit in the act: bacteria. "Many patients with wounds can have a smoldering infection that doesn't even show up in tests," says Brown. "They might be released from the hospital and months later come in with a raging infection that causes them to lose a limb, or worse. Our studies could result in a clinical test that allows a surgeon to sample wound fluid and detect biomarkers of bacterial infection to give a warning long before it becomes a problem."

The enormous clinical potential of such new research has led Levin and dermatologist Claude "Skip" Burton M.D. '79 to propose a wound center at Duke that will include a team of dermatologists, plastic surgeons, vascular surgeons, orthopedists, and other experts. Funded by Johnson & Johnson and other sources, the center will aim to move basic research advances in wound healing quickly into clinical practice to help patients.

The plastic surgery division's other major line of basic research, called "tissue engineering," aims to speed the time when surgeons can help their patients by transplanting body parts--including skin flaps, ears, breasts, and even hands--grown in a tissue bank. Maybe such a possibility seems like science fiction today, says Levin, but at one time so did now-routine surgical achievements. "Just twenty years ago, people would have been amazed that we could take a piece of vascularized fibula from the leg and make a jaw," says Levin. "But we do such surgeries routinely now."

When implants of engineered organs become possible, they will no doubt be done at Duke, says Levin, for the medical center is already among the country's leaders in "microvascular surgery." That involves completely removing living tissue from a patient and meticulously implanting it elsewhere on the body for reconstruction. Under Bruce Klitzman B.S.E. '74, director of the plastic surgery research laboratories, the division's scientists are exploring basic questions that will aid progress toward cultured body parts. The scientists are especially interested in the details of how body tissue grows blood vessels--a process called angiogenesis. "We can already grow two-dimensional sheets of tissue, where diffusion can supply nutrients and oxygen," says Klitzman. "But creating large blocks of tissue means that we also have to grow a blood supply."

In one set of experiments, the researchers are testing drugs and other techniques to persuade the body to grow a blood supply into the fibrous tissue that the body surrounds surgical implants with in order to "protect" itself. Such fibrous tissue currently fouls all implanted devices, such as the glucose sensors used in implantable insulin pumps for diabetics.

Another major tissue-engineering problem is producing the smaller artificial blood vessels necessary for finer reconstructive surgery and advanced transplants. Artificial vessels smaller than about one-quarter inch in diameter clog quickly with blood clots. The lack of smaller artificial vessel substitutes forces cardiac surgeons to use a patient's leg vein in coronary bypass surgery. Surgeons also need artificial vessels even smaller than coronary arteries to do many kinds of transplants and reconstructions, including those that bridge damaged sections of natural blood vessels.

To solve the clotting problem in artificial vessels, Klitzman and his colleagues are developing techniques to coat the inside of artificial vessels with the patient's own cells--called endothelial cells. The trick, says Klitzman, is to keep such cells "happy." "The endothelial cell is very dynamic, and if you 'anger' it as occurs during inflammation, it can cause clotting and other bad things that stop blood flow." Klitzman has found that simply gluing the cells to the inside of a blood vessel absolutely enrages them chemically. He and his co-workers are pinpointing the chemical changes in the inflamed cells that could lead to treatments that will prevent the cells from triggering clotting.

Among the challenges is attaching the cells to the inside of artificial vessels so that they will hold fast, yet grow and attach to one another to make a protective coating. Biomedical engineers Monte Reichert and George Truskey are working with Klitzman to perfect a superior biological glue, called biotin-avidin. "It's almost like tacking the cells in one spot to hold them firmly in place, yet allowing them to spread and attach to one another normally," Klitzman says.

Once he and other scientists perfect such natural cell adhesives, they hope to develop techniques to cover implants with such cells, to fool the body into accepting them more readily. Eventually, surgeons might first harvest a cell sample from a patient to "seed" the surface of such implants as heart-assist pumps, catheters, pacemakers, and artificial joints. After the cells have covered the implant, it will be essentially disguised from the immune system, which would ignore it, rather than attacking and causing potentially dangerous inflammation and rejection.

In all their clinical practice and basic research, the Duke plastic surgeons have found that living flesh is a wondrously complex and mysterious tissue. But they believe their advances mean that the next century will see incredible progress in both the art and the science of repairing and reshaping bodies.