SAVING LIFE AND LIMB
Joel Mayerson, MD, leads a sarcoma team that tackles cases other hospitals turn away.
BY KENDALL POWELL
When orthopaedic oncologist Joel Mayerson, MD, and a team of surgeons resected the softballsized chondrosarcoma – a tumor of cartilage that does not respond to any known cancer treatment other than surgical removal "en bloc" – it left a gaping hole where the patient's lower spine and left leg connected to his pelvis.
The team now focused on repairing the damage with the nation's first live-bone pelvic reconstruction surgery. During the risky 36-hour, two-day operation, the patient, a 51-year-old mail carrier named Mike Prindle, lost 70 liters of blood –14 times the amount that normally circulates in the body.
"These are some of the largest surgeries you can do on the human body. They are life-threatening at any point in time in the OR," explains Mayerson, director of Musculoskeletal Oncology at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James.)
"We've spent a decade building a surgical and anesthesia team to care for these patients. If you are missing just one part of the surgical team, you cannot do these operations," says Mayerson.
Orthopaedic oncology presents significant challenges. It often requires removal of bone sections that are critical for walking, weight-bearing and limb function. Osteosarcomas in children require excision of bone from a stillgrowing skeleton. Removing a soft-tissue sarcoma can leave a void that must be filled through creative plastic surgery. Involvement of the spine and bowels can require additional specialist surgeons.
Mayerson's sarcoma team executes difficult, innovative surgeries to give patients the best chance for restoring mobility or even an active lifestyle. The team, which includes six surgical specialties, has a willingness to tackle first-of-their-kind and rare procedures, cases other hospitals would turn away.
Such operations need a high degree of coordination and communication among highpowered surgeons who normally would operate solo. The rare mix of personalities and skills on the
OSUCCC – James sarcoma team ensures patients get back to their lives and passions.
A 'SURGICAL DISEASE'
Mayerson's interest in orthopaedics began at age 15 when he injured his knee playing high school football in Lima, Ohio. Fascinated by his surgeon's ability to fix the injured joint, he thought he'd work in sports medicine. But on the first day of his senior medical school rotation in orthopaedic surgery at Johns Hopkins University in 1993, he watched orthopaedic oncologists perform limb-salvage surgery for a patient with an osteosarcoma of the femur.
"When I came home, I couldn't stop talking about it. My wife predicted that's what I would do," Mayerson recalls. Currently, he and his partner, Thomas Scharschmidt, MD, are two of only about 150 orthopaedic oncology surgeons in the United States. "Orthopaedic surgery normally deals with returning a patient to normal function. Orthopaedic oncology is about saving a life and returning the patient to as close to normal function as possible."
All sarcomas are different, as is the damage done by their removal, he says. "One thing I love about this field is that people can come in with a similar tumor, and you can solve the problem in different ways based on the tumor's location and the patient's needs and age," says Mayerson. About 2,500 cases of bone sarcoma are diagnosed annually in the United States, with about 800 of those being osteosarcoma in children. There are also just under 10,000 new softtissue sarcoma cases, which include about 50 subtypes that occur in muscle, fat, skin, cartilage and other tissues of mesenchymal origin. The team treats between 400 and 500 sarcoma patients yearly. Only a handful of those cases need megasurgery like Prindle's.
"A major challenge for us is the rarity of these tumors, which means there is little funding for research to improve their treatment," explains Scharschmidt, assistant professor of Orthopaedics at the OSUCCC – James.
James Boehmler, MD, a plastic and reconstructive microsurgeon on the team, notes that adult bone sarcomas and most soft-tissue sarcomas rarely respond to chemotherapy or radiation. "They also usually go unrecognized until they are very large tumors," he says. "And they tend to occur around major blood vessels and nerves in the inner thigh or pelvis, like the femoral artery and sciatic nerve and other areas of highvalue real estate."
That leaves surgery to remove these tumors, followed by reconstruction, with Mayerson, Scharschmidt, Boehmler and the other surgeons on the team often working in tandem. In a surgery as complex as the pelvic reconstruction, the surgeons include an orthopaedic oncologist, a general oncologist, a neurosurgeon, a urologist, a plastic surgeon and an anesthesiologist (see sidebar).
When Prindle arrived at The James in January 2009, he was limping from progressively worsening pain in his left hip and buttock. MRI and CT scans showed a tumor in his left pelvis. A needle biopsy confirmed chondrosarcoma, a cancer known to be immune to current therapies.
To save his life, the team would have to remove the tumor and a large section of surrounding tissue and bone. This would include the left half of his pelvis, the bottom of his spine, his left hip joint, and – with nothing left to connect it – his healthy left leg.
Fortunately, the tumor had not metastasized (nearly all metastatic and one-third to one-half of primary sarcomas are fatal).
Normally, loss of the left half of the pelvis would leave Prindle without an intact pelvic ring, which connects and stabilizes his remaining spine and leg. Without it, he would be unable to bear weight and walk, even with a prosthetic left leg. But, for a man who formerly walked eight-mile neighborhood routes and who was an avid golfer, the sarcoma team thought it could try something that had never been done before.
"We reasoned that we could reconstruct the pelvic ring using the healthy femur and the fibula that we had to remove," Mayerson recalls. The idea came up during the sarcoma tumor board meeting, a weekly discussion among surgeons, medical oncologists, radiation oncologists, pathologists and other team members about each case.
The team knew that pelvic reconstructions had been done using metal parts or donated cadaver bone, but neither of those options can support live bone in a weight-bearing area. They figured the living bones would heal into a more stable ring, suitable for supporting a prosthetic leg. The two-day surgery would require a dozen metal screws in Prindle's spine, a team of two dozen in the operating room, and close to 500 medical personnel for pre- and postoperative care. When the idea was presented to Prindle, remembers Mayerson, "He thought about it for a time, then said, 'If that's what it takes, that's what I'll do. I want to live, get better, and I want to walk.'" The innovative pelvic reconstruction won "Reconstructive Surgery of the Year" honors from the American Society of Reconstructive Microsurgeons in 2010 and was published in the Journal of Neurosurgery: Spine.
Frank conversations with patients are essential, says Boehmler. Although limb salvage has become standard whenever possible, the surgeons do not know exactly what structures are affected until they perform surgery. If a tumor encases nerves or critical blood vessels, the limb may not be functional.
Mayerson recalls the conversation with Dugan Smith's parents when he recommended that their 10-year-old son have a dramatic surgery called rotationplasty. The procedure is recommended for active, growing children who have an osteosarcoma around the knee. Surgeons remove the knee, then reattach the lower portion of the leg rotated 180 degrees so that the ankle joint replaces the knee. It creates a biological joint that grows with the child, who is able to run and jump on a prosthetic lower leg. Or in Smith's case, return to his passion: baseball.
Only about a dozen rotationplasties are done each year in the United States. Most patients in Smith's position get an above-knee amputation and are fitted with a prosthesis that requires expending about 70 percent more energy to walk. Some patients are candidates for a limb-salvage operation that uses an endoprosthesis – usually a metal replacement part for the bone that must be removed. These patients' limbs look normal except for a big scar and can function almost normally for walking and even swimming. But the activity required to play most sports will shred the metal and plastic parts of an endoprosthesis.
Rotationplasty seemed the best option for Smith, whose father coached him as pitcher of his Little League team. "Even for a welladjusted child like Dugan, it's a difficult emotional thing to do because your body looks very different from everyone else," Mayerson says. Three years later, an ESPN video shows Smith hitting a double and running the bases.
MIKE PRINDLE shortly after his innovative pelvic reconstruction.
Children like Smith represent an even rarer population of sarcoma patients, but they bring special challenges to the sarcoma team. Mayerson and the team have met those challenges by pioneering a new endoprosthesis technology that grows with children and lowers their risk of infection. In the past, children needed expansion surgeries every other year to lengthen their limb by about one centimeter until they finished growing. That could mean up to seven, fourhour surgeries and three- to four-day hospital stays. Worse yet, each expansion surgery carried a 10-percent risk of infection, with half of all infections resulting in amputation.
In 2002, in another "first," Mayerson performed a full femur replacement on a 10-year-old using a high-tech solution for lengthening limbs, the Repiphysis non-operative expandable prosthesis. By applying an external magnetic field, surgeons can heat and melt a plastic tube inside the device that releases the tension on a portion of a coiled spring. While there is some discomfort, the procedure requires no surgery or hospital stay, and it dramatically lowers the risk of infection.
BEYOND SURGERY FOR SARCOMAS
Even with advanced surgical techniques and prosthetic technologies that improve patients' functional outcomes, Mayerson notes that survival rates for sarcoma patients have plateaued in the last 25 years. "We've made people more functional – those who are living – but we haven't increased the percentage of survivors," he says.
Because they are both rare and diverse, sarcomas lack chemotherapy options. Pharmaceutical companies are unwilling to invest hundreds of millions of dollars to produce a drug for a few thousand patients each year. And research to learn which genetic mutations drive various types of sarcoma has been slow.
But the OSUCCC – James team aims to rectify that. "Our next biggest challenge is to classify these tumors based on their genomic expressions, and then to tailor treatment on an individual level," says Scharschmidt. "I absolutely think that will lead to improving our patient outcomes in the next five to ten years."
In collaboration with Peter Houghton, PhD, director of the Center for Childhood Cancer at Nationwide Children's Hospital, the team has been building a living-tissue bank of human sarcoma tumors. For every soft tissue sarcoma tumor resected, a sample is transplanted into an immunocompromised mouse, where it will grow and maintain its particular set of gene mutations.
The researchers will characterize the genetic profile of these tumors, which eventually will serve as a test bed for new therapies targeted to the specific mutations. Boehmler also sees potential for tissue engineering for orthopaedic oncology. He notes that when a tumor affects nerves and large blood vessels in a limb, it almost always leads to amputation. In contrast to bone, no replacement parts exist for nerves and vessels.
Instead, Boehmler says, regrowing a patient's own nerves and other tissues would preserve more functional limbs. And regenerating live bone to form, say, a 3-D half of a pelvis would be more advantageous than "spare parts surgery," he says. "The field of regenerative medicine will be a key contributor to the recovery and rehabilitation of these patients."
For now, Boehmler and his peers thrive on the surgical problem-solving of complicated cases like the pelvic reconstruction. "It's the ultimate teamwork to do surgery of this magnitude," notes Mayerson.
Considering the ordeal Prindle endured, his recovery was equally impressive. Mayerson recalls that Prindle left the hospital just 34 days after surgery with only a dose of Tylenol. He was eventually fitted with a state-of-the-art "smart" prosthesis with computerized hip and knee joints that learn his gait and automatically adjust to make walking easier.
"If you can give people a reasonable chance to be as functional as possible, a lot of people will take that chance," says Mayerson. "Mr. Prindle is an amazing person," he adds, with a hint of awe still in his voice. It's probably safe to assume that the feeling is mutual.
OHIO STATE'S SARCOMA TEAM
Procedures such as a radical pelvic reconstruction are truly team efforts. In addition to the lead surgeons Joel Mayerson, MD, Thomas Scharschmidt, MD, and James Boehmler, MD, it takes more than 500 people to care for these patients, including physicians from the blood bank and laboratory medicine; scrub technicians; operating-room, floor and clinic nurses; and a musculoskeletal oncology physician’s assistant. The OSUCCC – James sarcoma team also includes six medical specialties.
Carl Schmidt, MD
Pankaj Tiwari, MD
Peter muscarella II, MD
Michael Miller, MD
Ehud Mendel, MD
Albert Chao, MD
David Sharp, MD
Ergun Kocak, MD
Matharbootham Mani, MD