2016 SPRING: Pain Management for Cancer | Soft Tissue Sarcomas | An Italian Greyhound with a Swollen Chin | Diabetic Ketoacidosis | Elevated Liver Values in Normal Dog | Osteosarcoma | Feline Anemia Trial | Meet Oncologist Angela Kozicki | Meet Internist Kristopher Sharpe
Medical Director’s Notes
In this issue of Companion we focus on internal medicine and oncology, and I would just like to remind you of our strong commitment to these vital services as well as all of the services we provide. We have full-time internal medicine service at four of our five hospitals and full-time oncology services at three of our hospitals. We offer a wide range of diagnostics, including full-service ultrasound. You are always welcome to set up consultations.
We’re proud that our team includes experts such as Dr. Kristopher Sharpe, DVM, DACVIM, and Dr. Angela Kozicki, DVM, DACVIM-Oncology, whose bios you can read in this issue. But they are just a part of our lineup of accomplished veterinarians who are standing by to serve you, your clients and your patients. I’m delighted to be working with them.
I’m also honored to be working with you. Nothing is more important than our relationship with the primary care veterinary community. We greatly value the trust and confidence you have placed in us by referring your patients to BluePearl Veterinary Partners in Michigan.
Because of that, we would love to hear from you. Please call 248.354.6640 to share feedback or ask about a topic that we can discuss in an upcoming issue.
Jill Sackman, DVM, PhD, DACVS
Pain Management for Cancer Patients
The management of pain in cancer patients is among our highest priorities. Several options exist for pain management.
Non-steroidal anti-inflammatory drugs [NSAIDs]
NSAIDs are an essential part of most analgesic regimens. There are both non-selective (COX-1 and COX-2) and COX-2 selective families of NSAIDs. Not only do these drugs reduce mild to moderate pain, they are inexpensive and generally well tolerated. Some COX inhibitors may also have anti-tumor properties by promoting apoptosis or reducing angiogenesis. Potential adverse effects are mainly gastrointestinal related, and rarely, nephro- or hepatotoxicity. Periodic physical examination and monitoring of hematocrit, reticulocyte count (even if not anemic), chemistry profiles, and urinalysis is advised. As a general rule, NSAIDs should never be combined with glucocorticoids due to additive toxicities.
Short-acting steroids at anti-inflammatory doses may decrease mild inflammation and pain associated with certain tumors, such as mast cell tumors. Steroids may also be indicated in the treatment of lymphoid neoplasms (lymphoma, multiple myeloma, plasmacytoma, and leukemias) and myelomonocytic/histiocytic malignancies. For two reasons we recommend using steroids only after a definitive diagnosis has been made: premature use of steroids may complicate the establishment of a definitive diagnosis and accurate tumor staging; and, although controversial, they may negatively impact the prognosis if definitive therapy is employed. The potential adverse effects of short term and chronic steroid use include GI ulceration, PU/PD, polyphagia, panting and iatrogenic Cushing’s disease.
Opiates, indicated for patients with moderate to severe pain, are commonly used in hospitalized patients. Buprenorphine, a potent injectable opiate, is commonly used to treat cats and small dogs. The parenteral preparation, when given per os, is absorbed transgingivally. The volume required for this route of administration makes it impractical to use in medium or larger-breed dogs. Carefully selected patients may benefit from fentanyl patches, which provide approximately 4-5 days of pain relief. Tramadol, an inexpensive, orally administered synthetic morphine-like drug, is easily used on an outpatient basis. Tramadol may have synergistic effects when coupled with an NSAID. Potential adverse effects of opiates include respiratory depression, sedation and constipation.
Coarse fraction radiotherapy plays a crucial role in the management of tumor-related pain. Candidates for palliative radiation include those with non-resectable osteosarcoma, bone metastases, and non-resectable soft tissue sarcomas and carcinomas. Treatments are scheduled once weekly for three to six treatments. Palliative radiation can be used in conjunction with other pain management strategies.
In the management of moderate to severe pain, especially when seen with bone tumors, the combination of an NSAID, tramadol and gabapentin (a calcium channel blocker used for neuropathic pain control) is a great combination to keep our patients comfortable. Breaking the pain cycle and preventing a ramp up of the pain receptors can provided improved quality of life if additional treatment is not an option for our patients. Please call us if you have any questions about cancer pain management. We would be happy to discuss your case with you.
Soft Tissue Sarcomas
Tumors can arise from a number of different tissues within the submucosa. Many of these tumors exhibit similar biological behavior. Consequently, pathologists will frequently group them under the term soft tissue sarcoma. Examples of soft tissue sarcomas include hemangiopericytomas, neurofibromas, peripheral nerve sheath tumors, and fibrosarcomas.
Soft tissue sarcomas are typically classified as low-, intermediate-, or high-grade. These histopathologically defined categories are based on the appearance of the most aggressive-looking portion of the tumor. The goal of this classification system is to predict the local behavior and metastatic risk of the tumor. Most soft tissue sarcomas are classified as low-grade. High-grade tumors are uncommon.
All grades of soft tissue sarcomas are locally invasive sending microscopic tendrils from the main tumor out into the surrounding tissues. This can make it quite difficult for these tumors to be completely surgically excised. With the exception of high-grade tumors, most soft tissue sarcomas will not metastasize. The metastatic rate for soft tissue sarcomas as a group approximates 10%. By contrast, high grade soft tissue sarcomas have a 50% chance for metastasis.
Surgery is the preferred treatment for soft tissue sarcomas. However the opportunity to achieve a surgical cure is frequently limited by the ability of the surgeon to remove all the microscopic tendrils. The tendency for these tumors to develop on the limbs or over the thoracic wall and vertebral column makes wide surgical excision around these tumors difficult. If wide surgical margins are not obtained, regrowth of the tumor is almost certain. The median survival time for dogs treated with surgery alone in one report was less than 1.5 years.
When surgical excision of the soft tissue sarcoma is not complete, ancillary therapy should be pursued as soon as healing has occurred. Most tumors will show regrowth within months. Once the tumor starts to regrow, it becomes more difficult to treat. Therefore, radiation therapy is recommended as soon as possible after healing from surgical removal of the bulk of the tumor. Radiation therapy used in this setting typically consists of daily treatments for about 4 weeks. Some side effects to the surrounding tissues are to be expected but are also temporary. The oncologist will work with you to help decrease discomfort to your patient. Studies have demonstrated that radiation therapy, when administered after removing the bulk of visible disease, will prevent regrowth of soft tissue sarcomas in up to 85% of patients for at least 5 years. In most cases, this represents a cure.
For families that are not able or interested in pursuing radiation therapy, chemotherapy can be used in a “metronomic” small daily dosing fashion. The goal of this therapy is to slow the development of new blood vessels into the area and subsequently slow regrowth of the tumor.
The best time to treat a soft tissue sarcoma is when it is small or immediately after it has been removed. Don’t wait for it to regrow. Should you have a patient with a suspected soft tissue sarcoma, give us a call to discuss treatment options.
Critical Care Corner: The Italian Greyhound with a Swollen Chin
Adam Lancaster, DVM, DACVECC
Case snapshot: A 10-year-old spayed female Italian greyhound presented to the Auburn Hills critical care service for evaluation of acute onset of bruising and swelling under the chin.
History: The swelling under the chin had been previously identified as a mucocele and had been drained in the past, most recently the day before. Since being drained the day before, the swelling had doubled in size. A CBC was sent out to the lab the day before presentation from her primary care veterinarian and came back the day of presentation showing severe thrombocytopenia. Chest radiographs performed at that time showed pulmonary infiltrates. The patient was then referred to BluePearl.
Initial findings: On presentation to BluePearl the following day, there was a large swelling under the chin, multiple areas of petechia and ecchymosis, and the patient was tachypneic.
Diagnostics, treatment and outcome: An abdominal ultrasound showed a very nodular spleen (rule outs were neoplasia or severe extramedullary hematopoeisis). Given the very low platelet count (7k on the initial bloodwork) an immune-mediated process was suspected, and the pulmonary infiltrates were suspected to be pulmonary hemorrhage. The patient was started on immunosuppressive doses of steroids and eventually started on cyclosporine and mycophenolate when she did not respond to the steroids alone. Throughout this time her platelet count remained less than 5k.
Approximately 5 days after starting immunosuppressive therapy, it was elected to pursue splenectomy. A unit of frozen platelets was administered pre-operatively and splenectomy was performed without complication. By the following day her platelet count increased to 107k and was at almost 250k two days after surgery.
The patient was discharged home and weaned off of immunosuppressive therapy over the next 4 months. She has not had any reoccurrence of thrombocytopenia since surgery, and her long term prognosis is excellent.
Take-home points: Cases of immune-mediated thrombocytopenia that are not responsive to adequate immunosuppressive therapy may respond to adjunctive treatments such as splenectomy, human IVIG or plasmaphoresis. Once platelet counts recover, patients have a good long-term prognosis although some cases may relapse.
Diabetic Ketoacidosis in Dogs and Cats
Ketones are produced as an alternate energy source when glucose cannot meet demands. They are produced from acetyl-coenzyme A (acetyl-CoA), from the mitochondrial beta-oxidation of fatty acids in the liver. The three ketone bodies synthesized include beta-hydroxybutyrate, acetoacetate and acetone. Acetoacetate and beta-hydroxybutyrate are anions of moderately strong acids. Buildup of these ketone bodies results in ketotic acidosis.
Why do diabetic patients form ketone bodies? Diabetic patients, particularly those with concurrent disease, have low or relatively low insulin levels and increased glucagon levels. In normal patients insulin is needed for conversion of glucose to glycogen, storage of amino acids as protein, and storage of fatty acids as adipose tissue. Glucagon causes glycogenolysis, proteolysis and lipolysis. Therefore, in low insulin/high glucagon states there is increased synthesis of acteyl-CoA. In non-diabetic patients acetyl-CoA and pyruvate enter the citric acid cycle to form ATP. In diabetics glucose does not enter the cells in adequate amounts and decreased glycolysis results in decreased pyruvate production. An overall increase in production and decreased utilization of acetyl-CoA results.
- Median age is 8 years (8 months to 16 years)
- Concurrent disease in 70% of cases
- Most common concurrent diseases – pancreatitis, bacterial UTI, hyperadrenocorticism
- Median age is 9 years (2 to 16 years).
- Concurrent disease in 90% of cases
- Most common concurrent diseases – hepatic lipidosis, chronic renal failure, pancreatitis, bacterial/viral infections, neoplasia
Polyuria, polydipsia, lethargy, inappetance or anorexia, vomiting and weight loss. Other clinical signs may reflect concurrent diseases.
Dogs: non-regenerative anemia, left shift neutrophilia, thrombocytosis
Cats: non-regenerative anemia, left shift neutrophilia, increased Heinz body production
Dogs: persistent hyperglycemia, elevated ALKP, ALT, AST and cholesterol
Cats: persistent hyperglycemia, elevated ALT and cholesterol
Both dogs and cats will commonly have electrolyte abnormalities. Initially they may appear to have extracellular hyperkalemia. (This is due to dehydration, decreased renal excretion, decreased insulin, hyperglycemia and acidemia.) Hypokalemia can develop rapidly with IV fluid treatment. The same findings apply to phosphorus.
Dogs: decreased sodium, chloride and ionized calcium
Cats: decreased ionized magnesium
Less than 7.35 in all dogs and cats with DKA. The acidosis is due primarily to accumulation of ketone bodies, but may be made worse by vomiting, dehydration and renal hypoperfusion.
Ketonuria (not always, as the nitroprusside in reagent strip reacts with acetoacetate and not beta hydroxybutyrate (most common ketone))
Elevated WBCs or other signs of UTI (20% of dogs with DKA have bacterial growth on culture)
AUS, cPLI, fPLI, T4 in cats
Adrenal testing in dogs that have suspected Cushing’s disease should wait until the patient is recovered and not acutely ill.
Due to the critical status of these patients and rapid changes that can occur with glucose levels and electrolytes, referral to a 24-hour facility is strongly recommended.
Fluid therapy is the most important step in treatment. 0.9% NaCl can be used, but is an acidifying solution. Lactated ringers and Plasma-Lyte® contain buffers (lactate and acetate) that are converted to bicarbonate and may help with the acidosis. It is very important to correct and monitor electrolytes (especially K and phosphorus). Fluid therapy can be used to improve dehydration, hyperglycemia, acidosis and electrolyte abnormalities, and patients should be treated first for several hours (to correct dehydration) prior to insulin therapy.
Insulin therapy is necessary to correct the hyperglycemia. Regular insulin can be given as a CRI or intermittent IM injection.
Bicarbonate therapy should be used only if the pH remains low despite IV fluid therapy.
Treatment of concurrent diseases is important for resolution of ketosis.
Switching from regular insulin to long acting insulin takes place when the patient is eating and not vomiting. Once a long acting insulin is chosen, keeping the patient at least 24 hours is reasonable to monitor response.
Seventy percent of cats and dogs survive to discharge. Median time to discharge is 5 and 6 days respectively. Seven percent of dogs and 40% of cats have recurrent episodes of DKA. Dogs with Cushing’s disease are less likely to be discharged from hospital.
Given the expense of hospitalization for a patient with DKA, it is important to make sure that the owners are on board for long-term diabetes management and know what it means for them and their pet.
We would like to thank our colleague from our BluePearl hospitals in Georgia, Lisa Langs Rund, DVM, DACVIM, for allowing us to use this article in Companion.
Elevated Liver Values in a Normal Dog? Now What?
Have you ever found ALT and/or ALP values to be elevated on routine lab work in otherwise healthy dogs?
“Although there is always a cause for elevated liver enzymes, the cause may not be apparent on initial presentation. Based on how the liver functions in the body, many systemic abnormalities will cause varying degrees and patterns of liver enzyme elevations. For example, dogs and cats with GI disease can have mild to moderate elevations in ALT related to local inflammation or ascending infection,” said Dr. Kristopher Sharpe. Increased liver enzyme activity can be seen secondary to systemic or metabolic conditions such as Cushings disease, gastrointestinal conditions, allergies, heart disease, anemia or infections.
The presence of icterus warrants an immediate diagnostic workup.
If liver values are elevated two to three times above normal, a complete patient history, including medications being administered, and physical exam should be performed. Medications, which might be irritating to the liver, should be discontinued. Concurrent illnesses or conditions, including dental problems, should be treated. Switching to a novel meat diet might also be considered to exclude food allergies. Finally, a course of antibiotics followed by re-evaluation of the liver enzymes in 3 to 4 weeks is suggested.
Continued elevation of ALT and/or ALP values on re-evaluation would suggest ongoing liver irritation. Bile acid testing and ultrasound examination of the liver are recommended. Bile acid test results will provide information on the extent of liver involvement. Ultrasound will help assess the liver size, the presence of unusual liver parenchymal patterns, provide information about the biliary tree, pancreas, adrenal glands and GI tract, and allow for the collection of hepatic aspirates for initial cytologic evaluation.
If the bilirubin value is increased or the liver values are greater than four times elevated over normal values, further evaluation of the liver should not be delayed. A primary liver condition is more likely to be present.
Because osteosarcoma (OSA) arises from osteoblasts and activates osteoclasts, OSA lesions appear both proliferative and destructive. The majority, 75%, of OSAs occur in the appendicular skeleton, whereas 25% occur in the axial skeleton. OSA is aggressive systemically and has a high metastatic rate of >90% even though <10% of patients have evidence of macroscopic metastasis at the time of diagnosis. The most common areas of spread are the lungs and rarely other bones. Recommended staging tests include bloodwork, three-view thoracic radiographs and rarely fine needle aspirate of the regional lymph node.
There are two treatment pathways for OSA, aggressive therapy and palliative therapy. Aggressive therapy consists of surgery, amputation in most cases, to remove the primary tumor; however, a limb spare procedure can be considered in certain anatomic locations. Amputation is generally well tolerated in most patients. Forelimb amputations do require a longer adjustment period (usually around 2 weeks) because dogs put 60% of their weight on their forelimbs.
Amputation is followed by carboplatin chemotherapy, which is usually started 10-14 days after the amputation (at time of suture removal). Carboplatin, an IV chemotherapy agent given once every three weeks for a total of four treatments, is well-tolerated with a side effect rate of ~15-20%. The median survival time for dogs treated with a combination of surgery and carboplatin is ~10-18 months. The median survival time for dogs treated with amputation alone is 4-6 months.
Palliative therapy, which is meant to decrease the pain associated with OSA but not aggressively treat the disease itself, is also commonly performed. It is most commonly pursued in dogs that are poor candidates for aggressive therapy or when a client declines aggressive care. The two most common palliative therapies are palliative radiation therapy and pamidronate therapy.
Palliative radiation therapy consists of five treatments given on consecutive days, once daily for 5 days, or once weekly for four treatments. Palliative radiation therapy provides significant pain relief in ~75-85% of patients treated. It does require anesthesia for each treatment but is well tolerated. The median survival time for patients treated with palliative radiation therapy is ~4-6 months.
Pamidronate, an osteoclast inhibitor, can also be given in conjunction with radiation or by itself to help decrease the pain associated with OSA. Pamidronate is an IV drug that is given over 2 hours in the hospital once monthly. This medication is well tolerated but rarely can exacerbate underlying kidney issues, therefore kidney values are monitored when using this drug.
Should you have a patient with a suspected osteosarcoma please call a BluePearl oncologist to discuss treatment options.
Fully-Funded Feline Anemia Trial
BluePearl Veterinary Partners in Ann Arbor is currently recruiting patients for a fully-funded trial to evaluate the safety and efficacy of an oral medication to manage anemia associated with chronic kidney disease in cats. The study consists of two phases: the efficacy phase (28 days) and the maintenance phase (8 weeks).
- Cats, > 1 year old, male or female, > 2.0 kg
- Not pregnant, lactating or intended for breeding
- Diagnosis of chronic kidney disease
- Non-regenerative anemia with PCV < 27% at study days -7 and 0
- Stable concurrent medical conditions
- Cats may be receiving SQ fluids
- Fractious cats
- Positive urine culture on study day -7
- Systolic blood pressure > 165 mmHg on study days -7 or 0
- Previous treatment with erythrocyte stimulating agents (ESA), including erythropoietin (EPO)
- Previous blood transfusion since being diagnosed with CKD
- Severe clinical signs of inflammation not attributed to CKD
- Other significant uncontrolled medical issues
- FeLV+ or FIV+ (if not vaccinated, sponsor will cover the cost to test)
- Obvious signs of GI bleeding
The study medication, diagnostic lab work and examinations will be provided at no cost to owners. Owners will be expected to administer the study medication at home, keep an owner diary and comply with study protocols.
*Note that this study is not funded for diagnostic or treatment costs associated with the underlying renal disease. Those costs must still be assumed by the owner.
For more information, or if you have a patient who may meet the above requirements, please contact Dr. Jim Whitehead at 734.971.8774.
Meet our oncologist…
Angela Kozicki, DVM, DACVIM-Oncology
Angela Kozicki, DVM, DACVIM-Oncology
Dr. Angela Kozicki often tells clients that half of her job is to dispel myths about what cancer treatment actually looks like in veterinary medicine. Because of an experience either personally or with a family member, many clients have a negative image of cancer treatment, which understandably makes them hesitant to move forward with treatment for their pet. Dr. Kozicki and her team work hard to educate clients about cancer treatment, like chemotherapy, and how drastically reduced the side effects are for pets as compared to humans. Her team’s primary goal is to aggressively fight cancer; however, the quality of life of the patients has to be of utmost importance.
When asked if there a course that fascinated her to the extent that it changed her life, Dr. Kozicki responded, “Our pathology professors at Michigan State were amazing teachers, and I really found the subject fascinating. But once I entered the clinic, I realized that I loved the clinical environment and couldn’t possibly give up the opportunity to work with clients and patients every day. Therefore, being a pathologist was out of the question. Luckily, I had an externship in oncology which showed me that I could put my passion for pathology into practice as an oncologist.”
So what keeps Dr. Kozicki interested in cases day after day? The stories of her clients and their pets are what keep her going every day. Many of her patients are seen weekly or monthly, so she and her team get to know the patients and their families very well. She says she is truly honored to be able to play a small part in their lives.
Meet our internist…
Kristopher Sharpe, DVM, DACVIM
Medical Director, Grand Rapids
Kristopher Sharpe, DVM, DACVIM
Dr. Kristopher Sharpe has been with us in Grand Rapids since we opened the doors of the hospital. As the Medical Director in Grand Rapids, he takes great pride in what the hospital has been able to provide for the community and is humbled by the support that the local veterinarians show on a daily basis. He looks forward to continuing to bring state-of-the-art and compassionate advanced specialty care to the community for many years to come.
Patient care is a top priority, but interacting with the client on a personal level is a real passion of his. Dr. Sharpe tries to put himself in the client’s shoes treating them like he would treat his family and close friends. He considers communication key to his success as a clinician, communication with the client and communication with the primary care veterinarian so that he can provide the best collaborative care for his patients.
So, what keeps him interested day after day? Dr. Sharpe likes internal medicine because of the diverse and complex cases that he sees on a daily basis, and he likes putting all of the pieces together. A case may present one way, but the interesting part of an internal medicine case is that after evaluation and diagnostics, he might find that it is something completely different.