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by Linda Lombardi
Elephants only rarely get cancer. When they do, it presents a unique set of challenges.
In 2016, keepers at the El Paso Zoo in Texas noticed something concerning about Juno, a female elephant: one of her mammary glands looked larger than the other. After several tries, each time with cautiously increased sedation, the veterinary staff got enough of a sample for a diagnosis of adenocarcinoma, a cancer of glandular cells.
This answer, of course, led to the next question - what to do? – and there were not a lot of precedents. Contacting other zoo vets and searching the literature turned up no previous cases. "This is the only case that we are aware of, of a mammary adenocarcinoma in an elephant," Chief Zoo Veterinarian Dr. Victoria Milne says. "That's not unexpected, because elephants don't get a lot of cancer for the size animal they are and how long they live."
Minimizing the Risks
So treatment was uncharted territory, but the most obvious possibility – surgical removal – was a no-go because the size of incision necessary would be problematic. "We can't keep them in a sterile environment - for their own welfare they need to be outside. And their trunk is like a little hand - they will pick at the incision sometimes, and you can't put a cone on an elephant," Milne says. "And their skin tends to open up with large incisions. It eventually heals, but healing can take months to a year."
It was also important to minimize the use of anesthesia as far as possible. One of the difficulties of working with wild animals is that very few procedures can be done while they're awake. At the same time, it's also much harder to minimize the risks of anesthesia. Some animals can be trained to offer a limb for an awake blood draw, as we can do with pets, but with most species and individuals that is not possible. "There are all kinds of diagnostics we want to do, including a physical exam and bloodwork, before we do anesthesia," says Milne,. "One of the complications we have in zoo medicine is that usually we can't even get those diagnostics until after the animal is anesthetized."
The good news was that the mass didn't seem to be growing very fast. Given her age – she was around 50 years old – they decided a less aggressive treatment was called for. "We wanted to slow it down," she says. "The goal was to be as noninvasive as possible and let her continue living her normal zoo elephant life."'
Breaking New Ground
The zoo reached out to specialists, which led them to veterinary oncologist Dr. Joseph Impellizeri. His expertise included use of a special instrument that uses an electrical pulse to drive chemotherapy agents into cancer cells. "The device we have allows for a very quick opening of the cell membrane so we have the opportunity to inject things around and in the tumor to be drawn into the tumor," he says. "The device provides an electrical impulse that opens the cell membrane." This treatment would be localized and would not require a large incision, so it seemed ideal.
Treating an elephant, however, was new territory for Impellizeri, whose usual patients are pets. "When I asked, can I get in there, can I touch it?... No, they said, she'll probably crush you," he recalls. Along with being hands-off till she was under anesthesia, he had to go to the patient rather than the other way around - as did the machine, so one of them was shipped to Texas, in a box about the size of a refrigerator.
Juno, on the other hand, had in a sense been preparing for this for years. So that she can be safely anesthetized, the zoo has a special chute that gradually squeezes closed to hold her upright as she falls asleep, then tilts so she's lying down for the procedure. She's rewarded with food for going into it every day, and they practice procedures like giving her an injection. "She's used to all of that, so that makes the whole process a lot less scary," says Milne.
Cutting Edge Treatment and Technology
Juno has had six treatments since the first in March 2017. After each one the tumor has shrunk, and once it's grown again, another treatment is performed. "In a perfect world, you would do this probably once every two or three weeks, maybe three or four times - that's what we would do in a dog or a cat," says Impellizeri. "In an 8000 pound Asian elephant, there's no way to justify that frequency of anesthesia. So we had to make some modifications, but has it been enough to keep this at bay and it has kept it from progressing."
After the first three chemotherapy treatments, another wrinkle was added: a type of immunotherapy, using a gene called IL12, that helps the body recognize the cancer as something it needs to fight. "It takes the body's immune system and says 'Hey, you think this looks like normal tissue but it's not, this is really foreign - let's go after it,'" he says.
For this, a slightly larger incision was needed (around four to six centimeters) so the question of how to close the wound arose, because working with elephant skin is nothing like working on a cat or dog. "The skin of an elephant has an outer layer - an epidermis - that is 2 to 2 1/2 centimeters thick, and it's amazingly tough – it's like armor," Impellizeri says. This is great in an elephant's normal life; for a vet, it's a bit of a problem: "What makes it so effective protecting against lion or hyena attacks makes it very difficult to cut and to bring tissue together to close."
Serendipitously, he connected with a Johnson and Johnson representative at a meeting. "I said, I have to treat this elephant, the epidermis is horribly thick, do you have anything? and she said, “We may have something for you that will work."
That "something" was a special suture with barbs running along its length that lock into the tissue, the STRATAFIX™ Knotless Tissue Control Device. For an elephant, it was just the thing Impellizeri was looking for. This was used successfully for her second three treatments, the last of which took place on February 15.
Looking to the Future
While Juno still has a tumor, the treatments have achieved the desired goal. "People ask, 'is it cured?'' says Impellizeri. "Sometimes 'cure' to an oncologist is to hold off on progression so the animal maintains her quality of life - which she certainly does."
And this experience may have repercussions beyond the life of this one elephant. Impellizeri is impressed that a smaller zoo like El Paso has enthusiastically pursued such a cutting edge treatment – which truly is unique. While other practices use similar devices, his is the only practice in the US using a generator made by the Italian company EvviVax. "It gives us more options for treating areas nobody else can treat," he says. "And at the same time, nobody else has the immunotherapy." He hopes that Juno's case will help other animals – and maybe even humans - by letting more people know what's possible. "Whether it's a zoo or a really dedicated owner, I think this will better educate exotic animal holdings about what can be done, and at the same time it brings to light what's emerging on the human side for newer ways to target the cancer cells and minimize negative side effects," he says.
Samples from Juno's case have also gone to cancer researchers. Milne says that researchers are very interested in understanding why elephants don't get as much cancer as we'd expect from their size and lifespan, and Juno is an interesting case because she is an elephant who did get it. Knowing what went wrong in a species that otherwise seems to have extra protection against cancer might help us figure out whether that's something that also goes wrong in other species, and whether and how it can be treated. "So hopefully," she says, "that will benefit other elephants and other animals and even people down the road."