Do the words “medical research” conjure up a picture of university scientists hovering over test tubes? Maybe you envision clinical trials for new drugs happening in hospitals or doctors’ offices. You may be surprised to learn that at Keck Medicine of USC, doctors are using research to improve standards of care in a different setting: the operating room. USC surgeons are pushing the boundaries of their fields through groundbreaking procedures and scientific studies that could spur better treatments.
Some are pioneering techniques to remove cancer lodged in dangerous places. They’re also testing the use of new medical devices, including robots. Others are exploring the potential of gene therapy to spur the body to heal itself. At the same time, their colleagues are transforming the practice of organ transplantation.
Here’s a glimpse at some of the ways that Keck Medicine’s academic physicians are taking surgery where it has never gone before.
The patient needed help, and soon. A large cancerous tumor was growing from his right kidney upward into his heart. This tumor— what doctors call a stage IV tumor thrombus traveled from the man’s kidney through his blood vessels. It grew into the inferior vena cava—the largest vein that returns blood to the heart—and then expanded into one of the heart’s main chambers.
Without surgery, the kidney cancer would continue to grow rapidly, and risked breaking off in the man’s heart or lungs at any time, causing instantaneous death. To remove such tumors, surgeons typically have to open the entire chest and abdomen through a large incision. Patients usually need anywhere from 20 to 40 units of blood during the operation and, even as surgeons work to remove the tumor, tissue fragments might still enter the bloodstream and lodge in the heart or lungs.
Patients have a 1 in 20 chance of dying during the procedure.
Only a handful of medical centers nationwide can do this operation. Recently, a team of surgeons at Keck Medical Center of USC became the first in the world to remove a stage IV kidney cancer thrombus in a new, less invasive way—using robotic surgery, through small openings in the skin.
“Normally, this kind of surgery requires a large open cut from the neck all the way down to the pubic bone. We did it through six keyhole–sized cuts in the belly and one cut in the chest wall,” says Inderbir S. Gill, Distinguished Professor of Urology and executive director of the USC Institute of Urology. Gill led the multidisciplinary surgical team that performed the complex, 10-hour procedure.
The breakthrough surgery took extensive planning, including the creation of 3-D animated maps of the patient’s internal organs to reveal the exact position of the tumor thrombus. It also took precise choreography from surgical experts.
“Days before the surgery, we had two dry-run meetings to plan our strategy. Once in the operating room, everyone knew their role,” says Gill, associate dean for clinical innovation at the Keck School of Medicine of USC.
Namir Katkhouda, professor of surgery, controlled blood flow to the patient’s liver. Gill used the da Vinci Xi surgical robot to carefully remove the diseased kidney tissue through the keyhole-sized incisions. Next, cardiac surgeon Mark Cunningham placed the patient on a heart-bypass machine and stopped his heart.
Our success opens the door for robotic surgery to be used in more advanced interventions for the liver, pancreas, kidney and the chest.Inderbir Gill
From there, Cunningham and Gill worked simultaneously—Cunningham in the chest and Gill using the robot in the abdomen—to remove the rest of the tumor from the heart and the vena cava, the large vein it had used to travel into the heart. After ensuring that the entire tumor had been extracted, the two surgeons meticulously closed the incisions, took the patient off bypass and restarted his heart.
The team’s minimally invasive, robotic technique removed the tumor with far less trauma and blood loss (the doctors used only six units) and the patient recovered more quickly than he would have after the traditional open procedure. The man spent six days in the hospital instead of the two to three weeks typically required after open surgery.
With such advantages, Gill hopes other teams will follow USC’s lead in using robotic surgery to remove advanced tumors in other areas of the body. “Our success opens the door for robotic surgery to be used in more advanced interventions for the liver, pancreas, kidney and the chest,” he says. “It’s the kind of futuristic, surgical innovation we’re now doing at Keck Medicine of USC.”
If your liver is ever severely damaged by injury or disease, you’ll face a frightening reality: You need a new one, and few are available for transplant.
While waiting for a donor organ, you’ll discover that even if one becomes available, it might be diseased or too old to risk replacing your liver with it. Or, the donor could be located too far from your location for the organ to stay preserved during transport.
In 2016, surgeons performed about 7,500 transplants using livers from deceased donors in the U.S. alone. The same year, nearly 2,700 patients died waiting for one of these organs, according to Keck Medicine surgeon Linda Sher.
USC transplant surgeon Yuri Genyk explains that patients with end-stage kidney disease can be sustained on an artificial device with dialysis, but surgeons don’t have such devices for the liver. “So the shortage of donor livers results in patients dying if the operation is not performed in time,” Genyk says.
When an organ becomes available for a patient on the waiting list, a team is dispatched to evaluate it. If they consider the organ appropriate for transplantation, team members will transport it back to the recipient’s hospital. The liver is preserved in fluid, cooled and placed in an ice chest, where it remains until it’s readied for transplantation.
Unfortunately, organs can only be stored in the cold for so long. They may suffer injury, and doctors can’t predict how well they’ll work after storage.
To decide whether a liver should be transplanted, surgeons look at test results and the donor’s medical history. They also inspect the liver and, if needed, take a biopsy of the organ. Usually, surgeons determine the liver’s viability correctly. But because they don’t have completely reliable criteria, problems can arise: Sometimes a liver doesn’t work and needs to be exchanged urgently, or they use a liver that initially works but later develops problems. They also may reject a liver that might have worked, but they couldn’t be certain.
Now Keck Medicine surgeons are participating in an investigational clinical trial revolving around a different way to preserve livers. The trial is evaluating a device that uses what’s called normothermic machine perfusion—it circulates oxygenated blood and nutrients through the donor liver—and keeps it at a normal body temperature before transplantation. “The [donor] liver is kept in an environment analogous to the human body. We are hopeful that this investigational device may help reduce post-transplant complications,” says Genyk, director of abdominal organ transplantation at Keck Medical Center of USC.
Keck Medical Center became the first in the western United States to perform a liver transplant using the device as part of a U.S. Food and Drug Administration study. The clinical trial will evaluate how well the device preserves organs compared to the current practice of preserving them on ice.
Researchers hope that the device will not only better preserve donor organs, but also may help doctors evaluate their viability. “The ability to observe certain liver functions while the liver is on the device may in the future help in making the determination if the liver is suitable for transplant,” Sher says.
Using a marginal liver can risk a patient’s life, because if it fails to function properly after transplant, the patient may urgently need another transplant. Experts hope that the ability to assess donor livers may increase the number of organs available for transplantation and decrease the number that are discarded over concerns about their ability to function.
TO BRING BACK BONES
When fractures fail to heal, spinal bones need to be fused or a patient loses a great deal of bone in a traumatic injury, a surgeon’s go-to repair option is bone grafting. The procedure involves the transplant of bone, often harvested from the patient’s own pelvis or from a deceased donor. It can be painful and costly, and it doesn’t always work.
“We have cases that require multiple bone graft surgeries, because we are relying on the patient’s body to respond to the biological signals provided by the grafted bone,” says Keck Medicine orthopaedic surgeon Jay R. Lieberman. “If you have to operate on a limb two or three times, the chance of success goes down and the costs go up. Not to mention the discomfort for the patient.”
For Lieberman, chair of the Department of Orthopaedic Surgery in the Keck School of Medicine of USC, there had to be a better way. Now, with support from a five year, $2.2 million National Institutes of Health grant, he is exploring gene therapy as a possible alternative treatment in difficult bone repair cases.
His team will genetically modify human bone marrow cells—extracted from patients undergoing total hip replacement surgery—to overproduce a bone growth factor called bone morphogenetic protein, or BMP. The modified cells will be injected into rats in the lab to see whether they help heal large fractures.
With 3-D printing, you could take a CT scan of the bone and then produce a scaffold that can fit the bone defect as if doing a jigsaw puzzle.Jay Lieberman
The study will determine the therapy’s potential effectiveness and establish a dosing model that could be scaled up for use in humans and assessed for any problems.
If the cells produce too much BMP, it could lead to excessive bone growth, Lieberman says. He doubts that will be a significant risk, though, since the modified cells should die off quickly, resulting in “two to three months of protein production, not years.”
A critical step toward developing potential human therapies, the study also points to exciting future possibilities involving a combination of gene therapy and tissue engineering.
For example, a scaffold—made from critical elements found in bone like calcium phosphate—could be 3-D printed to match a missing section of bone. The scaffold would then be implanted into the bone defect and loaded with the genetically modified cells. The cells would spur bone growth over the scaffold, eventually filling in the missing bone.
“With 3-D printing, you could take a CT scan of the bone and then produce a scaffold that can fit the bone defect as if doing a jigsaw puzzle,” Lieberman says. “In two or three months you could have new bone—without any graft needed.”
If Lieberman’s study proves successful, his proposed gene therapy could move forward to a Phase I clinical safety trial in humans. But the information he’s gathering now is already informing patient care.
“It’s affected the way I review bone repair problems,” Lieberman says. “That’s the advantage of doing translational research. It makes you think about multiple treatment options, not just the ones in front of you. As long as you keep your eyes open, opportunities arise to benefit patients.”