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Cancer: An Overview
The types of cancer afflicting dogs, and some new methods in battling them.
By Moira Anderson Allen
Source: AKC Gazette, June 1990, pp 84-91.
In the waiting room of the clinic in Hermosa Beach, California, I noticed the usual assortment of patients. A sleek Doberman paced restlessly at the end of a short lead, ignoring the graying mixed-breed that trembled on the lap of her mistress. A black tomcat growled steadily from his cage on the floor. The coffee table was strewn with pet-care literature, magazines and styrofoam coffee cups.
But there was a subtle difference. The clients in this waiting room didn't have any of the "hurry-up-let's-get-it-over-with" attitude of owners waiting for routine vaccinations or checkups. They seemed lost in their own thoughts, or constantly touching their animals. Even the literature on the table was different; much of it discussed how to deal with bereavement. The woman with the mixed-breed quietly tucked one of the flyers into her purse.
The waiting room belonged to the AnimalCancerCenter, one of the few specialized cancer clinics in the country. The Doberman and the cat were waiting for their scheduled radiation treatments, while the elderly mixed-breed was there for a workup. She had just been diagnosed with breast cancer.
"He said I should put her to sleep right away," the woman said clearly close to tears. "He said there was nothing anyone could do," she added.
"My vet said the same thing," said the Doberman's owner. "But he's worked so hard - got his CDX, and then we did the therapy thing for a couple of years. It seemed like he deserved a decent retirement. My vet didn't think there was much hope, but he's doing fine!"
Hope - that was the word that had brought these clients to the AnimalCancerCenter, and as many as 2,000 like them every year. Hope that the dreaded word "cancer" was no longer synonymous with "euthanasia"; hope that a beloved companion could enjoy a few more months or even years of quality life.
Now, thanks to dramatic strides in the availability of expertise, equipment and treatment techniques over the last decade, that hope exists. Ten years ago, the life expectancy of a dog diagnosed with cancer was three weeks to six months. Now, with treatment, some dogs have lived five or six pain-free years, depending on the type of cancer.
Fifteen years ago, oncology - the study of cancer - was not even a veterinary specialty. Now clinics are able to hire specialists in the field. Equally importantly, they are able to obtain the vital equipment needed to treat various types of cancer - equipment that has been used in human hospitals for fifteen or twenty years and is now being discarded for modernized machinery and passed on to veterinary hospitals. Ironically, much of this equipment was originally tested on animals with cancer, and many of the treatments used on humans were pioneered on animals. At last, animals are reaping the benefits of the technology they helped create.
Cancer is a common disease in dogs as well as humans, with many parallels between the species - with the exception of lung cancer, according to Dr. Alice Villalobos, head of the AnimalCancerCenter, because "dogs don't smoke." Some breeds have been reported to develop particular types of cancer.
Dr. Villalobos speaks of cancer treatment in military terms, describing tumors as an aggressive enemy that wages a destructive battle at the cellular level. To win, or even conduct a successful holding action, it is necessary to know the nature of the enemy, get early "intelligence reports" on its presence and location, and apply the battery of modern weapons against it.
Arriving at a Diagnosis
Early discovery of any form of cancer is very important for treatment to be effective. It's not enough just to find a "lump"; it's necessary to determine what type of cancer is involved and how far it has spread through the animal's system. Once, this might have meant exploratory surgery or guesswork. Now, veterinarians have more sophisticated and less invasive tools at their disposal.
One of these is needle aspiration, which is used to "suck" samples of tumor cells or fluids for biopsy. I watched the monitor of an ultrasound machine as Dr. Villalobos handled a needle-aspiration biopsy of Suzy, a seven-year-old Poodle. A lump had been detected in the lymph nodes near the spine, a tricky place to probe. Thanks to the monitor, the veterinarian was able to watch the needle in motion, white against the dark fluid systems of the dog, and guide it precisely to the lump without risking damage to surrounding areas.
"The ultrasound machine has become one of our most important diagnostic tools," Dr. Villalobos told me. By bouncing sound waves off organs and tissue, ultrasound creates a moving, computer-enhanced image of what is going on inside the body, including organ function and blood flow. It can detect tumors where X rays can't, including in the liver, where they show up as black holes against the whitish mass of tissue.
"It's very important to determine whether tumors have spread to the liver," says Villalobos. "This means the cancer is well advanced, and surgery probably isn't going to do much good." Another benefit of ultrasound is that in most cases an animal does not have to be anesthetized or sedated. It does have to be shaved locally, as sound waves are absorbed by the hair.
Another useful tool is the use of fiberoptic instrumentation, including endoscopy, proctoscopy and bronchoscopy. This enables a veterinarian to look inside intestines, the esophagus, or the colon, to check for tumors or take tissue samples. This type of equipment is expensive but has become more readily available. CT (computerized tomography) scanners are also used to determine the location and size of tumors.
The dog owner is still the first line of detection, however. An alert owner performs a physical examination every time he washes, grooms or even pets his dog. The owner should also examine the dog's mouth periodically, looking under the tongue, inspecting the palate, and checking for any changes, swellings or ulcers. In dogs, one to two percent of all tumors occur in the mouth, and half of these are malignant. The owner is also familiar with the dog's routine and normal behavior, and can spot warning signs. (See the sidebar, ÍThe Twelve Warning Signs of CancerÎ) ÍBut the owner needs to be aware that dogs try to cover up problems, and will try to 'keep up with the group' as long as possible." Dr. Villalobos notes.
Many tumors are detected during a physical examination conducted by a veterinarian before routine vaccinations, and Dr. Villalobos points out that the cheaper route of vaccine clinics or home-administered vaccinations that bypass this regular physical can place dogs at a disadvantage. Obesity also makes cancer harder to detect and tumors harder to locate, and can mask other warning signs, such as shortness of breath.
"It's also extremely important to know all you can about the total health of the dog before going ahead with some form of treatment" says Dr. Villalobos, who recommends a full workup for any cancer patient. Such a workup studies the dog's entire system including blood and urine to determine not only the extent of the cancer but whether a dog has heartworm, kidney disease, or other problems that could interfere with treatment or make treatment especially risky. A workup may be expensive but can make a tremendous difference in the outcome and may also save the owner the cost of going ahead with costly but useless treatment.
Once the "enemy" has been detected, what then? A few years ago, surgical removal was about the only solution to cancer. Surgery removes the visible tumor. Unfortunately, a malignant tumor sends out cells microscopically beyond the primary tumor. These cells enter the circulation system either through the lymph system or the vascular system. In some types of tumors, the cells go to distant locations such as the lungs or the liver, others may remain concentrated in the local area. During aggressive surgery designed to be curative, a veterinarian will try to remove up to three centimeters of the surrounding tissue to catch these cells.
Radiation to the site of surgery can help destroy cells that have spread further . (See sidebar, ÍBNCT: Experimental Treatment for Brain TumorsÎ) Radiation treatment is prescribed in the number of "rads," usually between 4,000 to 6,000, to be administered to the patient. The prescription is "filled" by a radiation therapist, who administers a certain number of rads per treatment day.
The typical patient, according to Dr. Villalobos, will come in two to three times a week for a total of ten to twelve treatments. One side effect of radiation is a bad sunburn effect to the treated portion of the skin.
While I visited the AnimalCancerCenter, I met Dr. Villalobos' dog, Duncan, a Bernese Mountain Dog with a magnificent coat and a classic California laid-back personality. I would never have suspected that Duncan was there for his chemotherapy treatment.
Radiation is a localized treatment and is often combined with chemotherapy, which treats cancer at the systemic level. Chemotherapy is also used when cancer is too widespread to make surgery or radiation effective.
Chemotherapy involves the oral or intravenous administration of drugs to stop the reproduction of malignant cells anywhere in the body. Usually a combination of drugs is used to inhibit several different phases of growth. Anti-neoplastic drugs, for example, stop division of cancer cells by acting on different proteins in the DNA. An other drug stops the zonulas or strands the cells need to multiply; another inhibits certain molecular bondings; another will inhibit a certain reaction that is important in mitosis. "It's like sending in the Green Berets, the militia, the submarines and the air force," says Dr. Villalobos. "You're attacking the enemy from very different directions." Additional "clean-up" drugs are used to follow up.
Because intestinal and hair cells reproduce even faster than some tumor cells, chemotherapy interferes with them as well, which is why humans lose their hair and become nauseated when undergoing treatment. Dogs have an advantage here: except for a few breeds such as Poodle, Maltese and Lhasa Apsos, they don't have a continuous hair-growth cycle like humans. Poodles will lose their hair with some of the stronger drugs. Dogs also don't seem to become nauseated: after his treatment, Duncan was slobbering eagerly for his milk bone.
"It's not unusual for a dog to slow down during the day of treatment," says Dr. Villalobos. In addition, dogs don't have the emotional burden and mental feedback of fear and stress to aggravate the problem.
Before a dog is put on chemotherapy, the specialist will want to know as much as possible about the patient's organ functions and medical history. The condition of the dog's liver and kidneys, whether it has heart disease, whether it is diabetic or has pancreatic deficiency, and whether it is on other drugs, are all important variables in determining the impact of chemotherapy.
Another cancer treatment method is immunotherapy. In this form of therapy, agents are given that stimulate the patient's own immune system to fight the cancer. (See the sidebar, ÍAn Update on the Magic BulletÎ)
Hyperthermia involves bringing up the animal's body temperature to a point that is lethal to tumor cells. This can be done locally or involve the entire body. This treatment is still experimental (researchers are still determining the precise temperatures and exposure times), and requires anesthesia. It is difficult to perform on dogs, and is somewhat expensive and cumbersome. Another form of hyperthermia treatment, also known as thermomagnetic surgery, involves injecting a ferrosilicone fluid into the tumor and then heating the particles up to fifty-five to sixty degrees centigrade, temperatures cancer cells cannot survive. This is also a relatively uncommon treatment that is still being studied.
In cyrosurgery, liquid nitrogen in sprayed onto the tumor, and an instrument records the temperature. This is especially useful for skin and oral tumors, which turn black and drop off two weeks after being frozen. When a larger tumor is frozen, devices are used to monitor it at several different points, and surgeons also keep track of the animals's general body temperature. One must be careful not to freeze and damage normal tissues.
Many veterinarians still don't refer cancer patients to oncologist. Some feel that prolonged, expensive treatment that may buy no more than a year of additional life for an animal isn't worth the client's time and money.
Dr. Villalobos emphasizes that this is the owner's decision to make. Many owners, offered the choice of keeping a cherished companion for an additional year or more or saving money, adopt the "It's only money" attitude or find other ways to compensate for the costs. And cancer treatment isn't cheap: radiation treatments alone average around $75 per visit, for ten to twelve visits. A course of treatment combining radiation, chemotherapy, or other methods can cost $1,200 to $2,000, or more. Some pet insurance programs will cover a portion of the costs.
Nor is treatment foolproof. According to Dr. Villalobos, "Sometimes it's pure luck. You put all the right ingredients together, and sometimes it works, sometimes it doesn't." The basic health and age of the animal are also important factors. But dogs actually have an advantage over humans: They do not experience emotional trauma and stress and so their recovery rate is likely to be better.
There are only twenty-seven schools of veterinary medicine in the U.S., and only a handful of veterinary oncologists and specialty clinics, though more are opening every year. To locate a treatment center, ask your veterinarian, check with your nearest school of veterinary medicine or contact the local chapter of the Veterinary Medical Association.
The Most Common Cancers in Dogs
Cancer isn't an independent entity that invades the body, but a normal body cell gone berserk. Dr. Alice Villalobos of the AnimalCancerCenter in California describes it as war on a cellular level, and a malignant cell is very aggressive. Every cell has a special function. When a normal cell divides; it stops next to its neighbor. But when a cell becomes malignant, it begins to bread all the rules. It ceases to function as a kidney cell or blood cell; its only remaining function is to divide rapidly. It grows and laterally eats anything around it, killing other cells and even dissolving bone cells, to get them out of the way and take their place.
The type of cell that began the abnormal dividing will determine where the cancer will be located, how far it will spread and to what body systems, and what the chances of treatment are. Following are the more common types of cancer in dogs:
Skin is the most common site for tumors in the dog. However, not all skin tumors in the dog are malignant. Malignant melanomas start in the pigmented cells in the skin. In humans, this is the most common form of fatal skin cancer, usually appearing where pigmented cells cluster, such as in moles or freckles. Although malignant melanoma is the most common form of fatal skin cancer in humans, most dermal or skin melanomas in the dog are benign. On the other hand, melanoma in the mouth of dogs is a highly malignant disease. One to two percent of all dog tumors are in the mouth, of which fifty percent are malignant melanomas. Malignant melanomas spread through the circulation and lymph systems and will usually spread to the lungs if not caught early.
Another skin cancer, squamous cell carcinoma, is caused by excessive sun exposure. This type of skin cancer can appear as small or large ulcers that appear to be nonhealing, crusted sores. Squamous cell carcinomas also occur in the oral cavity and can metastasize as well.
Mast cell is a common skin tumor in dogs but rare in man. Mast cell tumors can appear anywhere on the body and are unpredictable; potentially, but not invariably, malignant. Therapy with corticosteroids and/or radiation therapy may be needed in addition to surgical removal. Mast cell tumors are generally not sensitive to chemotherapy, so newer methods of treatment are being explored.
Lymphoma or lymphosarcoma is a malignancy of lymphocytes involving the lymph nodes and any other organ. As this system extends throughout the body, the entire animal can become involved. These cancers generally stay in the lymph system in the early stages and don't attack bones or organs. In more advanced disease, they can enter the bone marrow, spleen and liver. Chemotherapy or chemoimmuotherapy is used to treat lymphomas.
Breast cancer is very common in dogs. Fifty percent of breast tumors become malignant, and may spread to other body systems, especially the lungs. though some veterinarians may feel comfortable leaving a small breast tumor in place for observation for a few months, Dr. Villalobos recommends that all such tumors be surgically removed immediately to be on the safe side.
Unspayed, unbred bitches are the most likely to develop breast cancer. Spaying before the first heat reduces the risk of breast cancer to almost zero, as well as the risk of uterine or ovarian cancer, because hormones sensitize breast tissues to malignant tumors. Spaying up until two and one-half years can still greatly reduce the risk.
Hemangiosarcomas occur in the spleen, especially in larger, older dogs. These often go undetected until rupture of the spleen causes the dog to bleed to death internally. Tumors such as this are often detected by abdominal palpation on routine vaccination physical. Hemangiosarcomas may spread through the bloodstream to the heart, lungs or liver. Ultrasound can help determine whether surgery for this tumor type will be effective. If the tumor has already spread, a splenectomy may not be that helpful. After surgery, chemotherapy is recommended to extend survival.
Osteosarcomas, or bone cancers, can spread throughout the entire body system. They are more common in large-breed males over five years old. Usually they appear first in one leg. The common treatment is amputation for pain control, followed by chemotherapy.
Testicular cancer, cancer of the prostate, and tumors (both benign and malignant) around the anus are common in intact male dogs, and tend to remain localized. Neutering greatly reduces the incidence of these malignancies in male dogs in their senior years.-MA
BNCT: Experimental Treatment For Brain Tumors
Brain tumors develop in dogs as frequently as in people. The most common types of canine brain tumor are gliomas and meningiomas. Gliomas are the result of uncontrolled division of the supportive cells within the brain tissue, while meningiomas stem from cells of the meningeal layers external to the brain.
Canine brain tumors occur more often in middle-aged or older animals. Certain breeds have predilections for different brain tumor types. Gliomas commonly occur in bracycephalic (broad-skulled) breeds of dogs, while meningiomas are found more frequently in dolicocephalic (long-snouted) breeds. Clinical signs exhibited by affected dogs depend on the region of brain affected by the abnormal growth. Common symptoms associated with canine brain tumors include onset of seizures late in life, behavior changes, difficulties in coordination or balance, visual defects, loss of function of nerves supplying the head or endocrine abnormalities.
Under ideal circumstances, diagnosis of and treatment for canine brain tumors is similar to that for people. Brain tumors in certain locations can be approached surgically. Success of surgery is limited due to difficulties in completely eradicating tumor tissue, and tumor recurrence is common. X-radiation therapy is available for the treatment of canine brain tumors at a limited number of veterinary medical centers. Radiation therapy for dogs with brain tumors can alleviate clinical signs for a variable time period, but it is difficult to draw conclusions on survival rates following treatment due to the small number of dogs that have been treated to date. When surgery or radiation therapy is not available, medical management using anti-inflammatory medications may alleviate symptoms for a limited time.
Boron Neutron Capture Therapy (BNCT) is an experimental form of radiation therapy that may offer advantages over conventional radiation techniques for people and animals with brain tumors and other forms of cancer. An initial series of companion dogs with brain tumors have been treated with BNCT through a Department of Energy-funded pilot study at Washington State University College of Veterinary Medicine and Surgery. Most of the treated dogs have been returned home and are being monitored for tumor recurrence and post-treatment effects.
BNCT involves the administration of a drug containing 10 Boron (10B). This is followed by radiation therapy using a specialized neutron beam. The neutrons interact with the 10 B atoms, causing a fission reaction which releases high-energy short-range particles that damage tissues only in the immediate vicinity (about the distance of an average cell width). Significant highly damaging radiation is produced only where the neutrons interact with the nonradioactive 10B atoms. BNCT, therefore, may represent a means to selectively treat a tumor with highly effective radiation while sparing normal surrounding tissues.
A treatment program for dogs with brain tumors will be continued if results in the initially treated group are favorable. In addition, studies evaluating the pharmacokinetic of 10B-containing compounds and studies on the radiation effects of BNCT continue. Owners with dogs having symptoms suggestive of the presence of a brain tumor are encouraged to have their referring veterinarian contact personnel of the WSU research program if they are interested in further information. In Washington, call (800) 345-3047; out-side Washington, (800) 537-3647.-Susan Kraft, D.V.M.; Patrick Gavin, D.V.M., Ph.D., Constance De Haan, D.V.M.
The authors are with WashingtonStateUniversity's College of Veterinary Medicine.
The Twelve Warning Signs of Cancer
1. Abnormal swellings that continue to grow, especially in the lymph glands
2. Sores that do not heal
3. Bleeding or discharge from the mouth, nose, urinary tract, vagina or rectum
4. Offensive odor
5. Difficulty eating and/or swallowing
6. Difficulty breathing
7. Difficulty urinating or defecating
8. Hesitation to exercise, or loss of energy
9. Loss of appetite, weight loss
10. Persistent lameness or stiffness of movement
11. Lump in the breast area
12. Abnormality or difference in size of testicles
(Courtesy of the AnimalCancerCenter)
An Update on The Magic Bullet
In February 1986, the GAZETTE published an article entitled "Speeding Towards the Magic Bullet" on the ongoing studies in cancer research at the University of Pennsylvania funded by the American Kennel Club. Canine lymphoma has remained one of our prime targets for new treatment approaches.
This form of lymph node cancer is one of the most common and yet treatable in the dog. The conventional treatment for lymphoma has been systemic chemotherapy since the malignant cell is a lymphocyte and can circulate throughout the body. However, with chemotherapy alone, the peak median survival times are six to ten months. The goal in our research has been to use immunotherapy with agents called biological response modifiers (BRMs) to improve the prognosis of canine lymphoma, that is, prolong remission durations off chemotherapy and improve overall survival times.
BRMs are aimed at stimulating the dog's own immune system to fight the cancer and are generally associated with fewer side effects than chemotherapy drugs.
We initially reported on the effectiveness of using tumor vaccines made from each dog's individual lymph nodes, but continued to look for improved methods of stimulating the immune system. In addition, there was always the limitation of needing a laboratory to prepare vaccines. Thus, we embarked on our studies of nomoclonal antibodies (Mabs) as a more sophisticated and easily producible BMR. To develop a monoclonal antibody, one takes a tumor from a patient, a dog in this case, and immunizes a mouse that has myeloma. Myeloma is a form of a cancer in animals and humans that affects the cells that make antibodies. If you give a tumor cell from a patient to a mouse with myeloma, the mouse will then make large quantities of antibody against the patient's tumor cell antigens. Through hybridoma technology, each mouse will make a specific antibody, or a monoclonal antibody, that can later be made in large quantities. Some of those monoclonal antibodies may be capable of killing tumor cells.
In the previous article, we had only produced and characterized the first Mabs against canine lymphoma. We have now completed our Phase I clinical studies which have investigated potential side effects and have preliminary clinical results in our Phase II studies aimed at looking at the effectiveness of Mabs in dogs with lymphoma. We observed no significant side effects in fifteen dogs treated with Mab.
Following those results, we initiated a study to compare the effectiveness of Mabs in the same treatment protocol we had used with our tumor vaccine following remission induction with chemotherapy. Following a complete diagnostic medical workup, dogs were started on eight weeks of low-dose chemotherapy followed by a three week rest from all therapy. This is to allow the immune system to recover from the effects of the chemotherapy. We then administer Mab therapy for five days via an intravenous injection. The dogs do not need to be hospitalized during this time.
We have recently compared the ongoing results of our Mab trail with our previously published results with tumor vaccine. With over forty dogs treated with Mab, they appear to have longer remission durations off all therapy and longer survival times than previously reported with chemotherapy alone. We are currently comparing the efficacy of Mab to that of tumor cell vaccine. The median survival time of dogs treated with chemotherapy and monoclonal antibody is currently 591 days. Eighteen percent of the 57 dogs on the Phase I study are Golden Retrievers.
The majority of owners who are referred with their dogs to Penn choose to treat their dogs and elect to use the chemoimmunotherapy. The reasons for owners' preference for the combined therapy are several. First, we stress the primary goal of therapy of cancer in dogs as being normal quality of life for the patient. Since the dogs are off chemotherapy much of the time, the dogs feel much better. Additionally, economics obviously play an important role in an owner's ability to treat his dog. The major expense in the lymphoma patient is the cost of the chemotherapy drugs and support care for resulting side effects. Naturally, if the dogs are off chemotherapy more of the time, the costs will be less. Even when the Mab becomes commercially available, we anticipate that the cost of the Mab will still be less than that of continuous chemotherapy.
An additional observation we have made in the dogs treated with chemoimmunotherapy is that they appear to remain sensitive to the chemotherapy drugs longer than dogs treated with the cytotoxic drugs alone. Treating tumor cells is similar to therapy of infections with antibiotics. The bacteria will become resistant to chronic use of the same antibiotics. The same phenomena occurs with chronic bombardment of tumor cells with the same chemotherapy drugs. Since control of lymphoma is dependent on responsiveness to chemotherapy drugs, drug resistance results in relapse, progressive disease and potentially death. Since dogs on immunotherapy are off chemotherapy for varying periods of time, chemotherapy remain effective if and when the dog relapses. Additionally, we suspect that the immune system itself may have a role in preventing drug resistance. Further studies will include using the magic bullet or Mab to target chemotherapy drugs or radionuclides to the tumor site.
Although our speeding bullet has been moving along at a rapid pace in canine lymphoma, we have been continuing to seek and pursue new methods of treatment for cancers in dogs that are not as responsive as lymphoma to chemotherapy. Those tumors include mast cell tumors, malignant melanoma, mammary adenocarcinoma and squamous cell carcinoma. Although progress has been made in humans with these cancers, the aggressive type of chemotherapy utilized would be very compromising to a dog's quality of life. Again we have turned to immunotherapy with BRMs for innovative therapy approaches, trying to treat the disease effectively with minimal compromise of quality of life.
In 1988, we started a clinical trail, funded in part by the Cetus Corporation, using interleukin-2 (IL-2) and tumor necrosis factor (TNF) as stimulants of the immune system. IL-2 and TNF are substances known as cytokines, meaning that they are naturally produced by the immune cells of our bodies. Through recombinant technology these cytokines can now be synthesized in the laboratory. The cytokines are biological factors that produce a variety of normal physiological responses including fever.
Fever has been shown to be an important response of the immune system in fighting cancer. Therefore, when we attempt to treat cancer with cytokines we expect to see some side effects including fever and a flu-like syndrome. This indicates that the immune system is able to respond to these factors. to date, we have seen encouraging responses in mast cell tumors and breast cancer, two of our most common and problem diseases.
Dogs are actively being sought for these trials. Through our continuing AKC support, we will be able to continue these very important explorations. -K. Ann Jeglum, V.M.D.
Dr. Jeglum is the staff oncologist at the University of Pennsylvania's School of Veterinary Medicine.
Any breed of dog can develop any type of cancer. The two most common malignant tumor types (excluding tumors of the skin) in the canine species are breast cancer and lymphatic cancer (lymphoma). However, there are certain breed-tumor relationships that are seen fairly consistently.
The following is a partial list of some of the more common malignant tumors seen in dogs. This information is from a variety of articles and texts, as well as from the case files of the AnimalMedicalCenter in New York.
Lymphoma - Boxer, Basset Hound, Scottish Terrier, Airedale Terrier, Bulldog, Golden Retriever, Labrador Retriever, Old English Sheepdog
Leukemia - Golden Retriever, Labrador Retriever
Oral Cancer - Cocker Spaniel, Boxer, Golden Retriever, Weimaraner, German Shorthaired Pointer
Bone Cancer - St. Bernard, Great Dane, Irish Wolfhound, Golden Retriever, Irish Setter, Doberman Pinscher
Pancreatic Cancer - Airedale Terrier
Hemangiosarcoma (tumor of the blood vessels of liver, spleen and heart) - German Shepherd Dog
Nasal sinus tumors - Airedale Terrier, Basset Hound, Old English Sheepdog, Scottish Terrier, West Highland White Terrier, Collie, Shetland Sheepdog
Dr. Mauldin is a staff oncologist with the Donaldson-Atwood Cancer Clinic of the AnimalMedicalCenter in New York.
Where To Go For Help
"It's a good idea to seek a second opinion when your dog is diagnosed with cancer," says Dr. Ralph Richardson, head of Veterinary Clinical Sciences at the VeterinaryMedicalSchool at PurdueUniversity. "Proceed very cautiously, as you would with any family member."
The following universities' schools and colleges of veterinary medicine offer a comprehensive program of radiation, chemotherapy, surgery and other forms of cancer treatment. All have board-certified oncologist on their staffs: AuburnUniversity; University of California, Davis; ColoradoStateUniversity; University of Florida; University of Illinois; University of Minnesota; North CarolinaStateUniversity; OhioStateUniversity; OhioStateUniversity; University of Pennsylvania; PurdueUniversity; University of Tennessee; TexasA&MUniversity; TuftsUniversity and the University of Wisconsin.
The AmericanCollege of Veterinary Internal Medicine has available a list of its twenty-eight Diplomates who are board-certified oncologist. It can be obtained by contacting the ACVIM at Suite C-1A, 620 North Main St., Blacksburg, VA 24060; (800) 245-9081.
The Veterinary Cancer Society can provide information on oncologist working in specific types of treatment (for example hyperthermia, chemotherapy or immunotherapy). The Society's address is P.O. Box 370450, San Diego, CA92137; (619) 295-6347.Several options exist for owners of dogs afflicted with cancer. Many more are being developed.-Dominique Davis.
The author is an assistant editor at the GAZETTE.
Moira Anderson Allen is a freelance writer and frequent contributor to the GAZETTE whose previous article, "Being of Sound Mind..." appeared in the February 1988 issue.
40% have weight loss, lethargy, anorexia, febrile episodes
splenomegaly usu in advanced stage
Other syndromes in lymphoma
spinal cord compression
any body location possible
ALL - Pathology and Natural Behavior
lasts always infiltrate marrow
variable degrees of anemia, thrombocytopenia, neutropenia
splenic and hepatic involvement common
extramedullary sites common
may develop lymphadenopathy
CLL - Pathology and Natural Behavior
marrow infiltration of small, well differentiated lymphs, amount less than ALL or MPD
mild anemia, other stem lines mildly affected
nodes minimally enlarged
cells appear normal, function abnormally
some accompanying gammopathy
immunoglobulin spike assoc with leukemic B cells
usu IgM (macrogammaglobulinemia)
Lymphoma - Histologic Classifications
most lymphomas are diffuse and intermediate/high grade
o reflects either aggressive behavior or late presentation
o does not take into account immunology
o majority of tumors are B cell but tumors are heterogeneous
History and Signs
multicentric form, with or without hepatosplenomegaly most common
assoc with weight loss, anorexia, lethargy
differentials of lymphadenopathy include bacterial or viral infection, parasites, neorickettsia,
fungal, metastatic tumor, immune-mediated disease
respiratory compromise by space occupying mass
thoracic mass differentials include mediastinal lymphoma, thymoma, metastatic thyroid
pulmonary infiltrate differentials include fungal infection, primary or metastatic tumor
weight loss, cachexia, malabsorption, vomiting and diarrhea
straining to defecate or hematochezia
Nonregenerative anemia of chronic disease
o indirect tumor osteolysis
o osteolysis by prostaglandins of the E series
o ectopic production of parathyroid-like hormone
o ectopic production of osteoclast-like activating factor (OAF)
o usu OAF-like in canine lymphoma
Resulting in hypercalemic nephropathy, anorexia, weight loss, PUPD, lethargy, muscular
weakness, lethargy, rare CNS
Diagnostics and Workup
CBC with differential
bone marrow aspiration cytology
serum electrophoresis if total protein elevated
monoclonal gammopathies in 6%
infiltration of marrow hallmark of ALL and CLL
Lymphoma - Fundamentals of Therapy
lymphoma is a whole body disease
o cures are rare, if not impossible
o single, extranodal sites (skin, oral cavity) may be treated with surgery or irradiation
the true goal of lymphoma therapy is provide the pet with a good quality of life
this is accomplished by inducing, maintaining, and reinducing remission
Key points about lymphoma therapy
combination therapy results in the longest responses
maintaining first remission easier than second remission
most protocols report a 75-80% CR rate
most protocols report a median survival of 8-14 mos
Response varies with
extent of disease
presence of concurrent medical problems
Relapse can occur if
dose or freq of drugs given is reduced too early
tumor cells resistant to the drug schedule or drugs used
Chemotherapy Protocols and Results
There are numerous protocols with variable results. Please consult with an Oncologist! In general, combination protocols work best (the more drugs that are used and the more often they are used, the better the prognosis).
Single Drug Therapy
Prednisone: 84% CR, med rem 53 days
Cytoxan: 44% CR, med rem 62 days
Vincristine: 67% CR, med rem 77 days
L-asparaginase: 90% CR, med rem 143 days
81% CR and PR
med rem 131 days
longer for Stage III
Adriamycin after Combination Therapy
4/12 second CR, range 35-210 days
45% CR and PR
CR = 93-127 days
PR = 40-42 days
76% CR and PR
CR = 143 days
66% CR and PR
CR = 123 days in cats
23% CR and PR
CR = 63 days
PR = 28 days
MAb 231 after c/t induction
med rem 142 days
med surv 491 days
longer than historical controls
40% response, 20% CR and 20% PR using vincristine and pred
8-241 day survival
doxorubicin and elspar may incr response
100% CR on bone marrow and peripheral blood exam
weekly chemo, with 2 week rest after doxorubicin
few dogs evaluated, should be better than vinc/pred
indolent disease, whether to treat controversial
observe and treat only during blast crisis
chlorambucil and pred, or use a platelet sparing drug, cytoxan
therapy usu considered palliative, CR rare
survival 2-3 yrs
may discontinue therapy if counts are stable
Tumor lysis syndrome
massive tumor destruction resulting in hyperuricemia, hyperkalemia, hyperphosphatemia,
renal failure and sudden death due to calcium and electrolyte imbalances
anatomic location: cutaneous, diffuse GI, CNS are poor
concurrent medical problems: hypercalcemia = poor
sex, poss males < females
best response - high grade
o usu cells in active cycle responsive to drugs
o low grade, insidious onset, slow growing
ALL - Prognosis
8/21 dogs CR or PR, median survival 120 days
CLL - Prognosis
slow, progressive, overall good, 18-30 mos
can present with hyperviscosity
Bottomline for Lymphoma Therapy
reinduce remission (rescue)
maintaining first remission easier than second remission
most protocols report a 75-80% CR rate
most protocols report a median survival of 8-14 mos
Original Doc: lymphomas_leukemia.doc
Diagnosis and Treatment of Some Common Malignancies in the Scottish Terrier
By E. Gregory MacEwen, V.M.D.
Associate Professor of Oncology
School of Veterinary Medicine
University of Wisconsin, Madison
As our understanding of the causes of cancer unfolds, it is becoming apparent that the majority of cancers are caused by environmental factors, and the minority of cancers are genetically fated to occur. Within the Scottish terrier breed; however, it would appear that genetics still plays a significant role in the development of cancer. Epidemiologic studies have shown that the Scottish terrier has a higher than expected incidence of lymphosarcoma, bladder carcinoma, oral melanoma, cancer of the skin (squamous cell carcinoma and mast cell sarcoma), and, to a lesser extent, nasal carcinoma and gastric carcinoma. Genetic susceptibility combined with environmental influences probably represent the major factors involved in cancer development in the Scottish terrier.
In this paper I will discuss how one might recognize or suspect a possible tumor and present the current approaches to treatment for that particular tumor. I think it is important to remember that cancer is frequently seen in the Scottie, and an early diagnosis can potentially lead to a successful course of treatment.
Lymphosarcoma is a common malignancy of the dog. It usually occurs in dogs between 5 and 7 years of age, although it has been seen in dogs less than I year of age. It is a cancer of the lymphatic system, usually originating in the lymph nodes located in the neck, shoulder, groin and back legs.
Lymphosarcoma can also originate in the chest cavity (thymus region), intestines, spleen, liver, skin, and bone marrow. The most common form involves the external lymph nodes; however, the disease can spread to the internal lymph nodes, spleen, and liver.
Among the earliest signs the owner might notice are "lumps" in the jaw or neck region. Some dogs show no signs of illness; others are lethargic, appear somewhat depressed, have a poor appetite, lose weight, run a fever, or drink a lot of water. If the chest cavity is involved, the dog might show signs of breathing difficulty or coughing. Gastrointestinal involvement is usually characterized by vomiting, diarrhea, abdominal enlargement, and weight loss. Involvement of the blood or bone marrow usually results in a progressive anemia, and the dog appears weak and lethargic.
Lymphosarcoma can be a very rapidly advancing disease, and early diagnosis is vital to successful therapy. Diagnosis is based on an evaluation of the hematological system, biochemical serum analysis, x-rays of the chest and abdomen, and a lymph node and/or bone marrow biopsy. Without treatment most dogs will die of this disease within I month after diagnosis.
This type of cancer can be effectively controlled with chemotherapy. Chemotherapy involves the use of drugs given both by injection and orally over a number of months or years. The drugs most commonly used are prednisone, cytoxan, vincristine, methotrexate, adriamycin, and L- asparaginase. The vast majority of dogs tolerate therapy very well with minimal serious side effects. Many dogs will develop some episodes of vomiting or diarrhea and loss of appetite within 24 to 48 hours after chemotherapy. This can usually be controlled with antivomiting medication and/or a subsequent reduction in the dose of that particular chemotherapeutic agent. There are no long-term debilitating effects of chemotherapy. Eighty percent of the dogs treated will undergo a complete remission (complete regression of the disease-not cure). The average dog will remain in remission for 10 to 12 months (with a range of 4 to 36-plus months), after which the disease becomes resistant to the drugs and reappears. Approximately 20 percent of treated dogs will survive 2 years or longer if multidrug combination chemotherapy is used. Recent studies have shown that females tend to have a better prognosis than males, surviving an average of 3 to 4 months longer. The reason for this is unknown (1).
In summary, canine lymphosarcoma is a fatal disease, and without treatment it will rapidly lead to death. The response to chemotherapy varies with each individual animal. Although chemotherapy is not curative, the life of many dogs can be prolonged with minimal side effects. The optimal chemotherapy protocol for lymphosarcoma has not been determined, but with appropriate chemotherapy one can expect an average survival time of 10 to 12 months after diagnosis.
Many studies in man and a few in the dog have revealed some known suspected causes of bladder cancer. Industrial chemicals, metabolites of foodstuffs, and polycyclic hydrocarbons have been associated with bladder cancer in man. Experimentally, beta-naphthylamine increases the incidence of bladder cancer in dogs. Other studies have shown that an increase in excretion of tryptophan metabolites may increase susceptibility to bladder cancer.
Most dogs with bladder cancer will present with signs of bleeding in the urine or straining to urinate. These signs may be identical to cystitis (bladder infection) or bladder stones (calculi). The major difference between an infection and cancer is that bladder cancer tends to be unresponsive to any type of antibiotic therapy. It can be extremely difficult to differentiate clinically between chronic bladder infection, stones, and cancer. Any dog (usually older than 8 years of age) with a chronic bloody urine and/or straining to urinate should be evaluated for possible bladder cancer.
Diagnosis is usually based on radiologic dye studies (cystogram and intravenous urogram) of the urinary tract. These studies will reveal a mass lesion in the bladder or urethra. Further studies that must be done to establish a diagnosis absolutely include cytologic examination of the urine for cancer cells and surgical exploration of the urinary bladder to obtain tissue for pathologic analysis. The most common tumor type seen is the transitional cell carcinoma.
Treatment of bladder cancer depends on the location and extent of the tumor (2). A partial cystectomy (bladder wall removal) is the treatment of choice. Unfortunately, the results of surgical treatment have not been very successful because at the time of diagnosis most dogs have a very advanced disease in which the tumors are too extensive for complete surgical excision. The use of chemotherapy (cytoxan, thio-tepa, and adriamycin) has been very disappointing, and only very minimal tumor control can be expected. Radiation therapy has not yielded very encouraging responses either. The best chance for control with this type of tumor is early diagnosis and aggressive surgical removal.
Oral melanomas are very malignant tumors that most often arise in the gum, lips, and tongue. They occur more frequently in darkly pigmented dogs (such as the Scottish terrier) and in older dogs (8 to 10 years of age). Melanomas can also occur on the digits, in the eye, and any place on the skin; however, melanomas of the oral cavity are most common and also the most malignant. Digital melanomas tend to be malignant also, but they have a better prognosis than those that occur in the oral cavity. Most skin melanomas are benign and have a very good prognosis.
Melanomas are usually observed as firm, pigmented masses in the oral cavity. Some of these tumors are amelanotic, that is they lack pigment. Dogs with these tumors may show no signs whatsoever. Sometimes the owner will notice an odor from the mouth, which he or she associates with the teeth, and will assume the dog needs dentistry. Melanomas can bleed easily, and small amounts of blood may be noted after the dog chews on a hard object. It is very important that a thorough physical examination be done once a year with special attention given to the oral cavity. Many of these oral tumors are diagnosed at the time of dentistry.
Oral melanomas can spread (metastasize) readily via the veins and lymphatics. It has been estimated that 25 percent to 30 percent of affected dogs will have lymph node metastasis at the time of diagnosis (3). Before any major surgical procedure is performed, chest radiographs should be taken to rule out possible lung metastasis. Surgical excision is the best treatment for oral melanomas. Cryosurgery (freezing) and electrosurgery can also be used. If the tumor is located on the lower jaw, and there is no evidence of metastasis, then radical removal of the section of the jaw (mandibulectomy) is advised. Dogs do very well and cosmetically look fine after a mandibulectomy.
The single most important prognostic factor for oral melanoma is tumor size. In dogs with an early diagnosis and a tumor of 2 cm (less than one inch) in diameter or less, the average survival time after surgery is around 16 months. In dogs with tumors greater than 2 cm in diameter or with evidence of lymph node metastasis, the average survival time is around 5 months. The results using radiation and chemotherapy have not been very rewarding. We have just completed a study using immunotherapy combined with surgery in dogs with oral melanoma (4). Using an agent called corynebacterium parvum (an immune stimulant with very minimal side effects), we found that in dogs with advanced disease (tumor size of 2 cm or with lymph node metastasis), we were able to improve survival from an average of 5 months to an average of 9 months. In dogs with small tumors (2 cm), C. parvum had minimal beneficial effects on survival time. C. parvum is given intravenously at frequent intervals after surgery.
Squamous Cell Carcinoma
Squamous cell carcinoma is a common cancer of the skin in Scotties, which occurs at an average age of 9 years. The most common sites are the digits, scrotum, lips, nose, and oral cavity. These tumors usually appear as solitary, proliferative, ulcerative or erosive lesions. The proliferative types may give the appearance of a cauliflower type of growth. The surface tends to ulcerate easily and bleed. The erosive tumors tend to appear as shallow, crusted ulcers that can become deep and crater-like. Squamous cell carcinomas tend to be invasive, and when metastasis occurs, it usually involves the lymph nodes and sometimes the lungs (5).
Surgical excision is the best treatment. The prognosis will depend on the location of the tumor, degree of invasiveness, and the histopathologic degree of malignancy. For those tumors that cannot be removed surgically, show evidence of invasion, or recur after surgery, radiation therapy should be performed.
MAST CELL SARCOMA
One of the most common types of skin cancer is the mast cell sarcoma. Despite the frequency of its occurrence; however, we lack a basic understanding of its cause and behavior. It is one of the most perplexing forms of cancer with which a veterinarian must deal.
Mast cell sarcomas usually arise from the skin or subcutaneous area. The most common tumor appears as a well circumscribed, raised, firm mass with a reddish appearance. Ulceration of the tumor with frequent bleeding is not uncommon. Another type usually appears as a soft, poorly cir- cumscribed mass, which rarely ulcerates. Mast cell tumors may vary from a very small solitary lesion (1 cm in diameter) to very large masses or multiple skin masses located either in one area or all over the body. These tumors frequently metastasize to the lymph nodes.
A complicating factor with mast cell tumors is that they can elaborate an excessive amount of histamine. The histamine can then stimulate the stomach to secrete an inordinate quantity of gastric acid. Thus, dogs with mast cell tumors are prone to gastric ulcers. The owner must be aware of this because dogs with long-standing tumors may start to vomit, lose weight, and pass blood into the intestinal tract. A bleeding ulcer leads to chronic anemia and dark tarry feces. If a dog has a mast cell tumor, a veterinarian should be consulted regarding the use of special antihistamines (cimetidine) to prevent this complication (6).
The best treatment for mast cell tumors is complete surgical excision (7, 8). The single most important prognostic factor associated with this type of tumor is the degree of malignancy. This is determined by a veterinary pathologist after the tumor is removed and submitted for analysis. Dogs with what is termed poorly differentiated cancers have an average survival of less than 4 months. Dogs with well differentiated cancers have a very good prognosis, and the vast majority will be cured with surgery alone. Dogs with intermediate differentiated cancers hdv-8@an average survival of 8 months after surgery.
Radiation therapy can be used very successfully to afford long-term control in at least 50 percent of the mast cell tumors treated. Radiation can be used as the primary treatment or in conjunction with surgery. The results of evaluating the response to radiation based on the histopathologic degree of malignancy has not been studied. Chemotherapy can be used, but this serves only for temporary control or to shrink the tumor prior to surgical excision. The drug most commonly used is the corticosteroid prednisone. Prednisone is given in very high doses, and some of the side effects include increased water intake, excessive urination, and a voracious appetite. Other chemotherapy drugs, such as vincristine and L-asparaginase, can also be used.
Nasal tumors occur more commonly in dogs of middle age (8 to 10 years old) and in medium to large breeds. The cause is unknown. Most dogs will have signs of chronic nasal discharge and sneezing. The discharge tends to be bloody and may have a mucoid component. The discharge is usually from one side, but, if both nostrils are affected, it may be bilateral. As the disease progresses, nasal and oral deformities may develop as a result of tumor invasion beyond the nasal cavity. Sometimes the tumor extends behind the eye, and the eye appears to deviate outwardly. When these deformities are noted, the prognosis is very poor.
It is very easy to confuse a nasal tumor with chronic bacterial and fungal infections or a possible foreign body in the nasal cavity (9). Most dogs with this disease are initially treated with antibiotics for a presumed infection or with antihistamines for sneezing. Any dog that does not respond to prolonged antibiotic therapy should have further diagnostic testing. The most informative diagnostic procedures include x-rays of the nasal cavity under anesthesia and a nasal flush procedure to obtain tissue samples for culture or pathologic analysis. Sometimes it is necessary to surgically explore the nasal cavity to obtain a diagnosis.
It is important to emphasize that for nasal cancer early diagnosis and aggressive treatment is paramount to long-term control and good quality of life. The best treatment for nasal cancer is the use of radiation therapy. At veterinary schools or institutions where orthovoltage radiation therapy is used, surgery should be done first to remove the tumor. At schools or institutions where cobalt therapy is available, surgery is not necessary. The average survival time for dogs with nasal tumors treated with radiation, with or without surgery, has ranged from 8 to 18 months (10). Most treatment failures result from local recurrence or the spread of tumor to the local lymph nodes. Dogs treated with surgery alone live only 3 to 5 months. There have been no studies to evaluate the effectiveness of chemotherapy in treating this type of cancer.
Gastric cancer occurs in dogs ranging in age from 3 to 13 years. The cause is unknown, but in humans gastric cancer has been associated with exposure to nitrates in the diet, use of highly salted and seasoned food, and low intakes of vitamins C and A.
The signs of gastric cancer are usually vomiting (sometimes with blood), loss of appetite, weight loss, and abdominal pain. An animal with gastric cancer typically shows chronic deterioration with a gradual onset of vomiting. Many dogs are treated with antivomiting medications and dietary changes. Usually at the time of diagnosis the disease has progressed to the point where effective treatment is hopeless.
Diagnosis is based on a barium series, which may show evidence of a mass lesion in the stomach wall; direct visualization of the stomach wall using a flexible fibroptic scope (gastroscopy); or exploratory surgery and direct visualization of the cancer. Confirmation of the diagnosis requires a biopsy and pathologic analysis. Most gastric tumors are carcinomas, and these are usually too extensive for surgery and have an extremely poor prognosis. Chemotherapy has not been helpful.
Some tumors that occur less commonly in the stomach include lymphosarcoma and benign leiomyoma. Lymphosarcoma can be treated with chemotherapy, with or without surgery; leiomyoma is treated with surgery alone (11).
In summary, the treatment of gastric tumors is difficult even for the most experienced surgeon. The potential complications are great, and recurrence is extremely common. In the vast majority of dogs, diagnosis is all that can be performed; very little can be done to treat these cancers.
1. MacEwen EG, Brown NO, Patnaik AK, et al.: Cyclic combination chemotherapy of canine lymphosarcoma. J Am Vet Med Assoc. 178:1178-1181,1981.
2. MacEwen EG, and Harvey HJ Urinary tract neoplasia in dogs and cats. In Pathophysiology in Small Animal Surgery (ed MJ Bojrab). Lea & Febiger, Philadelphia, 1981, pp 276-284.
3. Harvey HJ, MacEwen EG, Braun D, et al.: Prognosis after surgical excision of canine melanoma. J Am Vet Med Assoc 178: 580-582, 1981.
4. MacEwen EG, Patnaik AK, Harvey HJ, et al.: Canine oral melanoma: comparison of surgery versus surgery plus Corynebacterium parvum. Cancer Invest, 1986 (In Press).
5. Bevier DE, and Goldschmidt MH: Skin tumors in the dog. Part 1. Epithelial tumors and tumor-like lesions. Compend Contin Ed 3:389, 1981.
6. Macy DW: Canine mast cell tumors. Vet Clin NA 15:783-803, 1985.
7. Bostock DC: The prognosis following surgical removal of mastocytoma in dogs. J Small Anim Pract 14:27-40, 1973.
8. Patnaik AK, Ehler WN, and MacEwen EG: Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Vet Pathol 21:469-474, 1984.
9. MacEwen EG, Withrow SJ, and Patnaik AK: Nasal tumors in the dog: retrospective evaluation of diagnosis, prognosis and treatment. J Am Vet Med Assoc 170:45 -48, 1977.
10. Beck ER, and Withrow SJ: Tumors of the canine nasal cavity. Vet Clin NA 15:521-533,1985..
11. Crow SE: Tumors of the alimentary tract. Vet Clin NA 15:577-596, 1985.
Original Doc: cancers.doc
Source: Scottish Terrier Club of America’s 1986 Handbook, pages 152-158.
Caring for Pets with Cancer - Y2K Edition: Tumors of the Skin & Soft Tissues
Effect Of Fish Oil, Arginine And Doxorubicin Chemo-Therapy On Remission And Survival Time In Dogs With Lymphoma: A Double Blind, Randomized Placebo Controlled Study
By GK Ogilvie, MJ Fettman, CH Mallinckrodt, JAWalton, RA Hansen, DJ Davenport, KL Gross, KL Richardson.
Colorado State University, Ft. Collins, CO 80523, Hill's Science and TechnologyCenterTopeka, KS
Source: Emailed to ScottiePhile from Carole Owen, 19 December 2001.
Polyunsaturated n-3 fatty acids have been shown to inhibit the growth and metastasis of tumors. One previously reported study demonstrated that a diet supplemented with n-3 polyunsaturated fatty acids improved the disease free interval and survival time and lowered lactate and insulin levels in 32 dogs with lymphoma. The double blind, randomized study reported here was designed to evaluate the hypothesis that polyunsaturated n-3 fatty acids can improve metabolic parameters, decrease chemical indices of inflammation, enhance quality of life, and extend disease-free interval in dogs treted for lymphoblastic lymphoma with doxorubicin chemotherapy.
Seventy one dogs with lymphoma were randomized to receive one of two diets. The experimental diet was supplemented with menhaden fish oil and arginine while the otherwise identical control diet was supplemented with soybean oil. Diets were fed prior to and after remissions were attained with up to 5 dosages of doxcrubicin. Parameters examined included blood concentrations of glucose, lactic acid and insulin in response to glucose and diet tolerance tests, alpha-1 acid glycoprotein, tumor necrosis factor, interleukin-6, metalloproteinase levels, body weight, amino acid profiles, platelet aggregometry, resting energy expenditure, disease-free interval (DFI), survival time (ST), and clinical performance scores.
Dogs fed the experimental diet had significantly (P<0.05) higher mean serum levels of the n-3 fatty acids docosahexaenoic acid (C22:6) and eicosapentaenoic acid (C20:5) when compared to controls. Dogs fed the experimental diet had significantly higher levels of arginine than those in the control group. Higher serum levels of C22:6 and C20:5 were associated with lower (P<0.05) plasma lactic acid and insulin responses to intravenous glucose and diet tolerance testing. Interleukin 6 and TNF alpha levels were lower in dogs fed the experimental diet. Interleukin 6 levels were increased in dogs fed the control diet. Resting energy expenditure was lower in dogs fed the experimental diet compared to controls. The percentage of dogs with increased toxicity was significantly lower in the dogs fed the experimental diet compared to controls. Increasing C22:6 levels were significantly (P<0.05) associated with longer DFI and ST for dogs with lymphoma.
We conclude that fatty acids of the n-3 series normalize elevated blood lactic acid and insulin in a dose dependent manner, result in an increase in DFI, ST and improved quality of life in dogs with lymphoma.