Nicola Mason, an assistant professor of medicine at Penn Vet, sports a FitBit on her wrist. But to see her dashing around the corridors of Ryan Hospital, it’s hard to imagine she has trouble meeting her exercise goals.
On this day, Mason is in the thick of clinical trials designed to test a cancer vaccine. Four dogs await treatment, having traveled to Philadelphia from locales as near as Delaware and as distant as Seattle. All of their owners turned to Penn Vet with the hope that their pets, diagnosed with osteosarcoma, an aggressive form of bone cancer, might take advantage of Mason’s boundary-pushing scientific research to beat the odds and maximize their healthy lifespan.
Mason’s work exemplifies translational medicine—research that takes discoveries in the lab and applies them to treating real-world medical problems. The cancer vaccine, developed by Yvonne Paterson of Penn’s Perelman School of Medicine, uses a non-disease-causing form of the listeria bacteria, modified to express a protein found in cancer cells. The idea is to trigger an immune response specific to that protein, generating an army of white blood cells with the particular weapons they need to kill osteosarcoma. The potential benefits extend beyond the dogs in the trial; data from the canine experiments could help pave the way toward similar treatments being widely used in human cancer patients.
First up for the day is Ferdinand, a 100-plus pound Rottweiler who was originally diagnosed with osteosarcoma in his right front leg in June 2012. He is part of a trial that gives the vaccine after amputating the cancerous leg to prevent the disease from spreading. On average, dogs with osteosarcoma that undergo amputation live only a year after diagnosis. Ferdinand, two years out from his diagnosis and already a ripe 10 years of age, is tumor-free and doing extraordinarily well.
Next is a black Labrador retriever named Kasey, who flew in the night before all the way from Seattle. Only 2-and-a-half years old, she is young for an osteosarcoma patient, but Mason says her youth offers an example of how a cancer vaccine might one day help children with the disease.
“If you look at osteosarcoma cells from humans and from dogs, they appear very similar, even at the level of gene expression,” Mason says. “It is difficult to tell which cells came from a human and which ones came from a dog.”
When Mason re-enters the client waiting area, the owners of Shenan, an 8-year-old Bernese Mountain Dog, greet the researcher as an old friend, offering baked goods they’ve brought as a token of their gratefulness. Mason calls Shenan “our miracle dog.” Diagnosed with metastatic osteosarcoma more than a year ago, her right foreleg was amputated and she began receiving the experimental vaccinations in late 2013.
The final patient of the day is the imposing Queen Sheba, a 6-year-old Great Pyrenees who makes the trip up from her home in North Carolina every three weeks, often with decorative ribbons carefully tied in her ample fur. Sheba is a participant in a new trial Mason is conducting in which dogs keep their leg and receive radiation therapy before starting vaccinations.
“In these dogs, we’re trying to see if the vaccine can be effective against the primary tumors,” she says.
All the dogs undergo thorough workups before they receive the vaccine. Kasey’s goes smoothly, but Sheba’s and Ferdinand’s treatments will be delayed due to some underlying issues. And Shenan’s lucky road has hit a bump. A few new lumps noticed by her owners are diagnosed as cancerous tumors. She receives the vaccine, but Mason encourages her owners to keep pursuing Shenan’s “bucket list,” which includes romping around wineries, basking in attention. [Editor's Note: We're sad to report that Shenan passed away after we reported this story.]
In the end, every owner who enrolls their dog in a trial at Penn Vet is motivated by a desire to help their own pet, Mason says. But they’re also driven by a larger purpose.
“The information we’re getting from the dogs is really important,” she says. “It’s telling us that the vaccine can generate an immune response against the tumor cells; it’s telling us that this treatment appears to be working and preventing tumor-forming in the lungs. The owners really like that our work might help their dog, will definitely help other dogs, and at some stage will help human patients, too. It may start off as they’re just trying to help their dog. But through this process, they become part of our team, they become invested in the process, and they become strong advocates for what we’re doing.”
Yeager, a 7-year-old chocolate Labrador retriever, presented to the Minimally Invasive Surgery service at Penn Vet’s Ryan Hospital in September of 2014 for chronic pericardial effusion caused by a heart tumor.
A local veterinarian referred him to Ryan Hospital after the effusion—or excess fluid around the heart—was first diagnosed in March 2013. The school’s Cardiology Service evaluated Yeager to determine the underlying cause of the effusion before sending him to specialist Jeffrey J. Runge, an assistant professor of minimally invasive surgery.
Healthy animals have a very small, thin sac surrounding their heart that should contain little to no fluid. Runge says that when excess fluid accumulates in the sac, as is the case with pericardial effusion, the heart has difficulty beating and pumping blood through the body.
“In Yeager’s situation, due to the tumor, he had an abnormally large amount of this fluid being produced,” Runge says. “We had to go in, minimally invasively, and remove this sac so the fluid wouldn’t build up.”
Before surgery, Yeager underwent a CT scan of his chest to ensure that there was no evidence of metastasizing cancer, and to assess the thickness of his heart sac. Once the veterinary professionals concluded that Yeager did not have metastatic cancer, he proceeded to surgery in Ryan Hospital’s Buerger Family Foundation Minimally Invasive Surgery Suite.
The minimally invasive surgical team consists of Runge, two surgical residents, an intern, and a student.
Heart surgery in animals is usually performed by either sawing open the sternum, the bone in the middle of the chest, or by making an incision on one size of the chest and spreading apart the ribs. Both typically require large openings. Minimally invasive surgery—which is increasingly used in human medicine but rarely in animal medicine—permits veterinary surgeons to operate without the need to cut open a patient’s chest. This causes less trauma and post-operative pain, and allows for a faster recovery and return to function.
“Veterinary minimally invasive surgery is certainly unique,” Runge says. “There are very few practices in the world that can offer this type of care for animals, especially since it requires complex operative techniques, advanced training, and equipment that is not commonly available.”
For the operation, Yeager is positioned on his back and three small ports, each the width of a pencil, are placed into his chest and positioned around his sternum. This enables Runge and his team to put small cameras and miniaturized instruments into Yeager’s chest cavity—tools that provide an adequate view and access to the heart.
“These ports allow me not only to see his lungs and heart, but enable me to manipulate the tissue as well, like cutting into the pericardial sac and suctioning out the fluid,” Runge says.
The surgery takes approximately two hours and is completed without any difficulties. Yeager is up and walking a few hours after surgery, and is able to go home three days later.
“We were very happy with the outcome of the surgery,” says Runge. “There were no complications during anesthesia or during the operative procedure itself. We were able to visualize the heart, take adequate samples for a biopsy, and remove the sac that contained the pericardial effusion.”
“You’re so cute,” Maria Soltero-Rivera says calmly, the tip of her finger nestled between the front teeth of her patient’s mouth. “You’re so handsome.”
Soltero-Rivera stands in front of Johnny, a 5-year-old, black-and-white domestic short-haired cat, who sits in a tight crouch on the exam room table. She patiently waits for him to open wide and reveal his teeth and gums.
At first, Johnny won’t budge. Then, Soltero-Rivera, a lecturer in Penn Vet’s Dentistry & Oral Surgery Department, gives him a couple of gentle pets on his head. Johnny relents and Soltero-Rivera is able to peer inside.
She confirms that Johnny has a tooth resorption, in which a tooth is destroyed by cells called odontoclasts, usually starting at the gumline. The cause for this disease is unknown, and animals can’t regenerate a tooth once it’s gone. The recommended treatment for this disease, which is both common and painful in cats, is extraction of the tooth.
“They don’t seem to miss them,” Soltero-Rivera says to the owners, both vet techs themselves.
Properly functioning kidneys purify blood by cleaning out invaders like excess fluid, salts, and foreign toxins. They produce hormones that keep bones strong and blood healthy, and properly balance blood pressure by maintaining optimal levels of potassium and sodium. But when the kidneys aren’t working properly, waste accumulates in fatal amounts, causing both humans and animals to experience a lack of appetite, lethargy, vomiting, diarrhea, and overall misery.
When a person develops chronic kidney disease, or when a mischievous canine accidentally ingests a bottle’s worth of ibuprofen, doctors can perform hemodialysis, a process that allows blood to flow through a dialyzer—an artificial kidney—to extract excess wastes and fluids.
But unlike in human medicine, there are few hospitals in the country that perform hemodialysis on animals. And there’s only one that offers a Nephrology program complete with dialysis and minimally invasive renal transplantation for those with chronic kidney failure: Penn Vet’s Ryan Hospital. It’s expertise that has prompted patients to fly in from as far as Dubai in the Middle East.
“Normally, the kidneys get rid of the normal byproducts of metabolism we accumulate simply by being alive,” says JD Foster, a staff veterinarian and director of the hemodialysis and extracorporeal therapy program at Penn Vet. “This process simply helps to remove hundreds of those toxins for kidneys that aren’t working anymore. But dialysis is not like riding a bike. You’ll face new problems with each patient, and really with each treatment, so unless [a hospital] is doing it often like we are, it’s hard to be proficient.”
It’s a meticulous process from start to finish. The workspace is sanitized, the extracorporeal circuits—or bloodlines—are flushed with saline to clear air bubbles that could cause potential clotting, and the dialyzer is calibrated with a prescription unique to each patient’s case. Patients are fitted with a catheter at the neck, which is then connected to the dialyzer via the extracorporeal circuits. Over the course of several hours, blood flows through tiny straw-like tubes with pores that dissolve the toxins and flush out the patient’s system.
At Ryan Hospital, Foster says he sees more cats than dogs as dialysis patients, likely because of Penn Vet’s in-house transplant program, as well as the hospital’s urban setting. He explains the difficulties in performing hemodialysis on small patients.
“We’re about to process [the animal’s] entire blood volume over and over,” Foster says. “It’s challenging because animals like cats can be so small, but we need to flow their blood through this machine designed for humans at probably 50 miles a minute, which is pretty quick. With a catheter flowing at maximum capacity, if a cat wiggles, or turns their neck, or even blinks too hard, their catheter will kink, and there are various measures we have to take to fix that.”
Foster says most patients at Penn Vet are treated for acute kidney injury, which requires two to three treatments per week for as many as four weeks, and sometimes longer. It’s an expensive and involved process, but it’s one Foster says pet owners are increasingly willing to do—especially since it’s often a final lifeline for patients.
“When kidneys shut down, it’s a poor prognosis,” Foster says. “And if they’re bad enough that they need dialysis, it’s about a 50 percent survival rate, which sounds horrible. But when you think about it, every single patient that we treat has absolutely failed regular therapy and would have died. Yes, there are sad cases, but we take half of those patients, send them home, and they get to on and live really good lives. And that’s fantastic to be able to do.”