Everyone there is so positive and professional, and, although we came there for a sad reason, we are so grateful to have met all of you.
West Orange, NJ
Hope will be at the Penn Conference on March 11th and 12th. Stop by booth 202 in the exhibit hall to say hello!
Penn Annual Conference 2015 (CE)
Mar. 11&12, 2015 8:00am – 6:00pm
Sheraton Philadelphia Downtown Hotel
201 North 17th Street
Philadelphia, PA 19103
A 9 year old male castrated Labrador Retriever presented to the emergency service for vomiting, lethargy and discomfort. The day prior to presentation, he started vomiting and had been evaluated by his primary veterinarian. He was treated on an out-patient basis with supportive therapy (Maropitant, Metronidazole and a bland diet).
He continued to vomit overnight and was reevaluated by his primary veterinarian. He was depressed, had pale mucus membranes and bloodwork revealed hyperglycemia (129mg/dl, N:75-125), decreased sodium (139 mEq/l; N:141-152), mild anemia(Hct: 36.2%; :N:37-55), and thrombocytopenia (151 10^3/uL; N:200-500). Abdominal radiographs revealed a soft tissue mass effect cranial ventral to the stomach on the lateral view and decreased contrast. Thoracic radiographs had no significant findings.
He was referred to HopeVS’s emergency service for further treatment. A cursory emergency ultrasound documented mild peritoneal effusion and a mixed echogenic mass in the cranial abdomen. An abdominocentesis revealed nonclotting hemorrhagic effusion with a PCV of 49% and Total Solids of 5.8 g/dl. Extended data base noted increased lactate of 2.7 (0.6-2.5) and PCV: 37%/TS: 6.4g/dl. Coagulation profiles (PT/PTT) were within normal limits.
A complete abdominal ultrasound revealed a very large mass along the lesser curvature of the stomach measuring 6-8 cm in thickness and 12-16 cm in length. The mass was partially compartmentalized and occasionally cavitated but primarily consisted of a semi-solid disorganized clump of coalescing hyper and hypoechoic material that was closely associated with the gastric wall causing the lesser curvature to be concave and occasionally effacing the layers of the gastric wall. The was no direct evidence of a transmural lesion or of perforation. Portions of the mass close to the gastric wall were variably vascular though the majority of the mass was avascular. Several large pockets of faintly echogenic effusion throughout the ventral abdomen and the fat, omentum and mesentery were hyperechoic throughout the cranial abdomen surrounding the gastric mass. (Figure 1) After consultation with the owner, an abdominal exploratory with resection of the mass was recommended.
The patient was placed in dorsal recumbency and the ventral abdomen was clipped and prepped using standard aseptic technique. A ventral abdominal incision was made and approximately 500 mls of hemorrhagic effusion was removed from the abdomen. (Figure 2) Exploration of the abdomen revealed bleeding from a small break in the serosal surface on the ventral aspect of the stomach. Approximately 1/2 of the stomach palpated irregular (mildly thickened) and was bruised. The bruising extended around the majority of the pylorus and into the beginning of the duodenum on the dorsal aspect of the stomach. The remainder of the abdomen appeared normal. A pylorectomy was performed obtaining 1 cm margins around the bruised, thickened area followed by a gastroduodenostomy (Billroth I). Care was taken to assure that the biliary system was not disrupted. The major duodenal papilla was identified and was ~ 1 cm from the site of resection of the proximal duodenum. The gallbladder was easily expressed. A liver biopsy was obtained from the left lateral liver lobe using a guillotine method and the abdomen was closed routinely. All resected tissue, including the draining lymph node, was submitted for histopathology.
No significant lesions were noted in the liver or lymph node biopsies. Within the gastrointestinal tract an acute mural hematoma was noted with, mild lymphoplasmacytic gastritis and the presence of helicobacter. Further gross evaluation revealed a small white, firm nodule (1cm in diameter) at the periphery of the hematoma but within the gastric wall. Within this section, the wall was expanded by an unencapsulated neoplastic moderately to highly cellular proliferation of spindle cells arranged in interwoven bundles. The cells were described as elongated to cigar shaped nuclei with stippled chromatin and small to moderate amounts of eosinophilic cytoplasm with indistinct cell borders. Anisokaryosis was mild to moderate and mitotic activity was 44 per 10 high power fields. There was multifocal necrosis within the lesion containing accumulations of eosinophilic and karyorrhectic debris. There are dense infiltrates of small well differentiated lymphocytes and fibroplasia along the periphery of the tumor. The mass was greater than 5mms from a surgical margin. A diagnosis of a high grade sarcoma was made with the differentials of a leiomyosarcoma and gastrointestinal stromal tumor. Immunohistochemistry staining was negative for C-Kit, confirming a diagnosis of a high grade leiomyosarcoma.
The patient recovered uneventfully post-surgery and was discharged at 4 days post- surgery. A follow oncology consultation was performed and systemic therapy with Doxorubicin IV q 3 weeks for 4-5 cycles was recommended since the tumor was deemed high grade. A baseline abdominal ultrasound was performed prior to starting chemotherapy at 28 days postop and no overt evidence of recurrence was noted. The patient has received 2 cycles thus far with little issues noted.
Gastric tumors make up approximately 1-3% of malignant neoplasia in dogs and cats. In dogs, the most common gastric tumor is gastric adenocarcinoma, which accounts for 42-72% of malignant gastric neoplasia. Leiomyosarcoma, a tumor of smooth muscle, is the second most common type of gastrointestinal tumor in dogs but it occurs much less frequently than adenocarcinoma. It can occur anywhere in the gastrointestinal tract but occurs most commonly in the stomach and small intestine. Clinical signs are influenced by tumor location and can include vomiting, weight loss, inappetence, melena, lethargy, hematochezia and hematemesis. Perforation of the intestinal wall secondary to tumor infiltration has been reported but is more common with gastrointestinal stromal tumors than leiomyosarcomas. A hemoabdomen, as noted in this patient’s history, is not a common finding.
Imaging modalities most commonly used to evaluate a gastric mass include radiography (+/-contrast), ultrasonography and endoscopy. In addition, when working up a gastric mass, three view thoracic radiographs, abdominal ultrasound and full blood work are recommended to look for any evidence of spread, and evaluate for any concurrent disease. Paraneoplastic hypoglycemia has been reported in dogs with leiomyosarcoma. The exact mechanism is unclear ,but it is normally reversible following surgical treatment.
Surgical excision is the initial treatment of choice for gastric leimyosarcoma. Also, at the time of surgical exploration, biopsy of the draining lymph node is recommended. Histopathology with margin evaluate should be performed in all cases as adjuvant treatment recommendations will be made based on the margins and aggressiveness of the lesion.
On histopathologic evaluation, gastrointestinal stromal tumors and leiomyosarcoma have a similar appearance. Gastrointestinal stromal tumors arise from the interstitial cells of Cajal. They express the CD117 (c-KIT) transmembrane receptor and therefore stain positive on c-KIT immunohistochemistry staining. Leiomyosarcoma is negative for CD117. Therefore, c-KIT immunohistochemistry staining is often used to differentiate between the two types of neoplasia.
Currently there is not a published prognostically relevant grading scheme for gastric leiomyosarcoma specifically, but in cutaneous and subcutaneous soft tissue sarcomas, grade is based on differentiation, necrosis and mitotic activity. If considered low or moderate grade with clean margins, there is low chance for spread in general with sarcomas and surgery alone is recommended with no further adjuvant treatment postop. If sarcomas, including leiomyosarcoma, are considered high grade, even with complete excision, chemotherapy is recommended, however data regarding efficacy is lacking.
In one study, 10 dogs with gastrointestinal leiomyosarcoma, a median survival time of 7.8 months was noted with surgery alone was noted, however, only 3 of the 10 dogs had gastric leiomyosarcoma. Currently, no large scale studies exist comparing survival times in dogs treated with surgery alone vs. surgery and adjuvant chemotherapy.
Submitted by Dr. Lauren May VMD, DACVS
Bacon N. Soft Tissue Sarcomas. In: Dobson JM, Lascelles BDX, eds. BSAVA Manual of Canine and Feline Oncology. 3rd ed. Gloucester: BSAVA, 2011;178-190.
Culp WTN, Cavanaugh RP, et al. Alimentary tract. In: Kudnig ST, Sequin B, eds. Veterinary Surgical Oncology. UK: Wiley-Blackwell, 2012;179-271.
Dennis MM, McSporran KD, et al. Prognostic factors for cutaneous and subcutaneous soft tissue sarcomas in dogs. Vet Pathol 2011;48(1):73-84. http://vet.sagepub.com/content/48/1/73.short
Kuntz CA, Dernell WS, et al. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986–1996). J Am Vet Med Assoc 1997;211:1147–1151. http://europepmc.org/abstract/med/9364229
Liptak JM, Forrest LJ. Soft Tissue Sarcomas. In: Withrow ST, Vail DM, eds. Withrow & MacEwen’s Small Animal Clinical Oncology. 4th ed. St. Louis: Saunders Elsevier, 2007; 425-449.
Russell KN, Mehler SJ, et al. Clinical and immunohistochemical differentiation of gastrointestinal stromal tumors from leiomyosarcomas in dogs 42 cases (1990-2003) J Am Vet Med Assoc 2007;230:1329-33. http://avmajournals.avma.org/doi/abs/10.2460/javma.230.9.1329
Figure 1. Ultrasound image showing in cross section the proximity of the mass to the pylorus. The mass is indicated by the red arrow and the pylorus is labeled by the white arrow.
Intraoperative photo showing stomach wall with severe bruising. Region of stomach wall that had been bleeding is indicated by black arrow.
Traditionally, lymphoma was lymphoma as recipe protocols were commonplace that were considered a “one size fits all” for therapy. With the advent of newer immunologic, molecular and histologic diagnostics, the treatment of lymphoma is changing. Currently, decisions regarding which chemotherapeutic agents/protocols to be utilized is now based upon tumor grade, location, histologic subtype and phenotype.
On a very basic level, lymphoma is broken down into two main phenotypes, B and T cell. Traditionally 2/3 of dogs with lymphoma are classified as B cell and 1/3 are T cell. A minor percentage (<2%) are deemed “null cell.” Phenotyping of lymphoma patients can be achieved through a variety of tests including immunohistochemistry, immunocytochemistry, PARR and flow cytometry.
- Immunohistochemistry (IHC): IHC is still considered the “gold standard for determining phenotype utilizing a panel of markers that bind to surface proteins either on B cells (cd79a, cd21, Pax5) or T cells (cd5, cd3, cd,4, cd8). This requires tissue obtained either via a punch biopsy, tru-cut biopsy, or nodal extirpation.
- Immunocytochemistry (ICC): ICC utilizes the same antibodies as IHC but on cytology samples thus offering a more cost effective manner to obtain phenotype. The distinction is that nodal architecture is not evaluated thus specific subtypes of lymphoma cannot be determined.
- Polymerase Chain Reaction (PCR): This is a repetitive enzymatic reaction that generates ~109 copies of a particular DNA sequence from 1 original copy, thus a small sample can yield results. It utilizes heat-stable polymerases and sequence specific primers. This test is commonly used in the identification of infectious disease in human and veterinary medicine. PCR for antigen receptor rearrangement (PARR): Clonality is the hallmark of malignancy, and PARR amplifies the variable regions of immunoglobulin genes and T-cell receptor genes to detect the presence of a clonal population. PARR not only determines clonality (cancer) but will also determine the phenotype of lymphoma or lymphoid leukemias. Specific sites/samples that can be analyzed include: lymph node or mediastinal mass aspiration, body cavity fluids, cerebral spinal fluid, bone marrow or peripheral blood.
- Flow Cytometry (FCM): FCM is routinely used in human medicine early in the work-up of lymphoid malignancies and involves the use of monoclonal antibodies + fluorescent markers. This allows the evaluation of a large number of cells to determine differences in cell size (small vs large), phenotype of circulating atypical cells and presence of aberrant surface marker expression. FCM requires fresh samples of blood or tissue (lymph node, mediastinal mass) and is commercially available through major diagnostic laboratories.
T cell lymphoma is more commonly associated with certain breeds including the boxer, golden retriever, Australian shepherd, Asian lap dogs and Siberian husky. T cell LSA is also associated with certain anatomic forms including cutaneous (epitheliotropic, AKA ELSA), mediastinal, hepatic and gastrointestinal. Many studies have documented a worse prognosis for dogs with T-cell lymphoma and for this this reason, many oncologists have begun modifying protocols based upon phenotype. Further support of this was based upon a retrospective study in which the response of T cell LSA to a single dose of doxorubicin was ~50% vs ~100% for dogs with B cell LSA. The discussion was then raised to include more alkylating agents into T cell protocols based upon evidence of high responses in dogs with ELSA treated with lomustine (CCNU). Although, only 17% experienced a complete remission (CR), 61% experienced a partial remission (PR). The combination of L-asparagine, mechlorethamine, vincristine, procarbazine, and prednisone (L-MOPP) has been investigated in dogs T-cell lymphoma. Overall, L-MOPP protocol was associated with a complete remission rate of 78%, and overall survival 270 days, However, >20% were alive at >900 days. The challenge with this protocol is cost, difficulty of administration and toxicity. Currently protocols with substitutions of CCNU for doxorubicin and Elspar in each cycle are underway and are standard at this author’s practice.
Novel LSA Therapy:
Chemotherapy: Tanovea™ was discovered by Gilead Sciences, Inc., and licensed to VetDC (http://vet-dc.com/) for use in animal cancer, (previously known as VDC-1101) was designed to preferentially target and attack cancer cells implicated in lymphoma. In previous clinical studies, Tanovea™ has been shown to be highly effective with a 77% overall response rate. Tanovea™ was generally well-tolerated and demonstrated high rates of response in both dogs naïve to previous treatments as well as in dogs that relapsed or failed previous chemotherapy. Tanovea is administered IV on a 3 week schedule and large scale studies are underway. The goal of this study is to evaluate the effectiveness of TanoveaTM in naive or relapse lymphoma patients. The class of drug is unlike any in our current standard chemotherapy protocols thus offers the first new LSA drug in many years and preliminary results are promising. A clinical trial evaluating Tanovea has recently completed and a new trial evaluating Tanovea and Doxorubicin will be starting in the next month .
Monoclonal antibody therapy: A monoclonal antibody (mAb) can be used to specifically bind to target cells or proteins. This may then stimulate the patient’s immune system to attack those targeted cells and remove them from the body. In human oncology, monoclonal antibodies have been developed for T and B cell Lymphoma which allows the immune system to recognize, attack and remove them. Normal lymphocytes cell can be replenished, as stem cells within the bone marrow are not targeted and as such normal cells are replenished but the cancer lymphocytes are not. These have now become standard of care therapy in human oncology. Cancer cell killing is thought to be via three mechanisms:
- Antibody-dependent cellular cytotoxicity (ADCC)
- Complement-mediated cytotoxicity (CMC)
- Induction of apoptosis (natural cell death)
Two distinctly different veterinary monoclonal antibodies are available for dogs with T cell and B cell (conditional approval by USDA; Aratana: http://www.aratana.com/). To date they have been shown to safe and have a reasonable expectation of efficacy. Each are being evaluated in separate large scale trials (www.vetcancertrials.org) along with standard chemotherapy. If similar efficacy to their “human” counterparts is noted, they will become standard of care in veterinary medicine and further pointing toward the necessity to phenotype all LSA patients.
For a video displaying the mechanisms of action of a monoclonal antibody: http://aratana.com/therapeutics/pipeline/cancer
At HopeVS we currently have the T cell monoclonal antibody and thus the ability to add this to our arsenal of treatments options for dogs with T cell lymphoma. This includes naïve/relapse as well as gastrointestinal, mediastinal and cutaneous lymphoma. For more information regarding the schedule of treatments. Please contact us at (610) 296-2099 for more information regarding this novel and exciting therapy.
Submitted by Dr. Craig A Clifford DVM, MS, DACVIM (Oncology)
Hope Veterinary Specialists
1. Thalheim L; Williams LE, Borst LB, et al. J Vet Intern Med. 2013;27:1509-16. http://onlinelibrary.wiley.com/doi/10.1111/jvim.12185/full
2. Beaver LM, Strottner G, Klein MK. J Am Vet Med Assoc. 2010;237:1052-5. http://avmajournals.avma.org/doi/abs/10.2460/javma.237.9.1052
3. Brodsky EM, Mauldin GN, Lachowicz JL, et al. J Vet Intern Med. 2009;23:578-84. http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2009.0289.x/full
4. Vail D, Thamm DH, Reiser H, et al: Clin Cancer Res 2009;15:3503. http://www.ncbi.nlm.nih.gov/pubmed/19417014
5. Thamm DH, et al. BMC Vet Res. 2014 Jan 25;10:30. doi: 10.1186/1746-6148-10-30. http://www.ncbi.nlm.nih.gov/pubmed/24460928
6. Reiser H, Wang J, Chong L, et al. Clin Cancer Res. 2008;1;14:2824-32. http://www.ncbi.nlm.nih.gov/pubmed/18451250
Figure 1: a monoclonal antibody binding to its receptor on the surface of a lymphoma cell.
Bone tumors are relatively common tumors in dogs, specifically primary bone tumors such as osteosarcoma. However, secondary bone involvement with, multiple myeloma, histiocytic sarcoma, apocrine gland anal sac adenocarcinomas and transitional cell carcinomas, are also commonly observed in veterinary practice.1 Because of the intense and often chronic pain caused by focal bone destruction and the decrease in quality of life, amputation remains the treatment of choice for local control of appendicular bone tumors.2 However, amputation is not an option for every patient. Profound preexisting orthopedic or neurologic disease may prohibit a dog from functioning acceptably with only three limbs. In addition, some pet owners do not have the financial recourses to pursue aggressive surgery while others find the idea of amputation anathema. For all of these reasons, a palliative approach is often pursued.
Palliative treatment aims to alleviate the bone pain associated with the tumor. Bone pain from skeletal tumors develops by two mechanisms: first, as the malignant osteoblasts rapidly proliferate, normal stromal cells stimulate nociceptors, which are found at highest concentrations in the periosteum, leading to the sensation of pain. Second, continuous pain stimulation is maintained by the chronic dysregulation of bone resorption by osteoclasts.3,6
Because of the multimodal genesis of bone cancer pain, many patients remain refractory to traditional oral and transdermal analgesics. The use of bisphosphonate therapy is becoming increasingly more common in veterinary oncology. Bisphosphonates are synthetic analogues of pyrophosphates that have an affinity for bone mineral and decrease pain by inhibiting reabsorption of bone by osteoclasts. These molecules interfere with normal intracellular signaling mediated by GTP-binding proteins and cause disruption of cellular interactions with the extracellular matrix, thus leading to apoptosis of osteoclasts. 4
While many bisphosphonates are commercially available, two of the more commonly used bisphosphonates in veterinary medicine are pamidronate and zoledronate. Both are administered as an intravenous infusion up to every twenty-eight days and have been demonstrated to maintain analgesic effects for up to four months.5,6,7 While these infusions are largely well tolerated, mild gastrointestinal toxicity and, rarely, renal insufficiency have been reported. 2,6 Overall, bisphosphonates remain a relatively safe and effective treatment for alleviating pain and improving quality of life in dogs with bone tumors. Oral bisphosphonate therapy is not routinely indicated in dogs as esophageal irritation is a common sequelae. People are advised to remain vertical for 60 minutes after taking any oral bisphosphonate. The horizontal orientation of the esophagus in dogs and cats versus the vertical orientation of the esophagus in a standing person preclude this recommendation for veterinary patients.
Submitted by Dr. Ian Muldowney
- Fan, et al. Evaluation of Intravenous Pamidronate Administration in 33 Cancer-Bearing Dogs with Primary or Secondary Bone Involvement. J Vet Intern Med 2005;19:74–80.
- Kozicki AR, et al. Adjuvant therapy with carboplatin and pamidronate for canine appendicular osteosarcoma. Veterinary Comparative Oncology 2013.
- Goblirsch MJ, et al. Biology of bone cancer pain. Clinical Cancer Research, 12: 6231-6235, 2006.
- Gourion-Arsiquaud S, et al. Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone, 2010; 46: 666-672.
- Poirier VJ, et al. The bisphosphonates alendronate and zoledronate are inhibitors of canine and human osteosarcoma cell growth in vitro. Veterinary Comparative Oncology 2003; 1: 207–215.
- Fan, et al. Single-Agent Pamidronate for Palliative Therapy of Canine Appendicular Osteosarcoma Bone Pain. J Vet Intern Med, 2007;21:431-439. Fan, et al. Double-Blind Placebo-Controlled Trial of Adjuvant Pamidronate with Palliative Radiotherapy and Intravenous Doxorubicin for Canine Appendicular Osteosarcoma Bone Pain. J Vet Intern Med 2009;23:152–160.
Dr. Paul Orsini brings 20 years’ experience in Veterinary Dentistry & Oral Surgery to Hope VS
Hope Veterinary Specialists is delighted to announce the addition of Paul Orsini, DVM, DACVS, DAVDC to our specialist services, allowing Hope VS to serve dental and oral surgery patient referrals. Dr.Orsini has built an outstanding reputation for himself and his Dentistry and Oral Surgery Service over the last 20 years in our region. Hope VS welcomes his unparalleled level of experience in order to better serve your patients.
Dr. Paul Orsini is originally from New York and graduated from the New York State College of Veterinary Medicine (Cornell). After completing an internship and a three-year surgical residency at the University of Pennsylvania School Of Veterinary Medicine, he received his board certification by the American College of Veterinary Surgeons in 1994. Dr. Orsini then completed a second residency in dentistry from the University of Pennsylvania School Of Veterinary Medicine in 1995. He has been published in numerous journals, proceedings, and book chapters and has held lectureship and assistant professor positions in Veterinary Surgery, Dentistry and Anatomy at the University of Pennsylvania School Of Veterinary Medicine. He continues to be Director of Veterinary Anatomy at the veterinary school.
Hope VS values our partnership with you, our referring veterinarians, and when it comes to pet dental health we know that you are typically the pet owner’s first point of contact to learn about proper pet dental care. We hope to prove to be an invaluable resource to your clinic and the patients you may refer to us for the more complex cases involving dental disease and injury.
This new service offers advanced dental and oral disease therapies in dogs and cats. We treat a wide range of conditions which include the following:
- Periodontal disease
- Endodontic disease (ex. Root Canal Treatment)
- Restorative dentistry (ex. Crown Fabrication)
- Orthodontics (Interceptive and Active)
- General Oral Surgery (ex. Gingivectomy)
- Oral neoplasia treatment
- Advanced oral surgery (Including maxillectomy and mandibulectomy)
- Jaw & Skull fracture repair
- Temporomandibular joint disease: diagnosis and treatment
- Congenital defects of the head (ex. Cleft palate repair)
- Treatment of Feline Stomatitis and Feline Tooth Resorption
- Pet Dental Cleaning for higher anesthesia risk pets
The Dentistry and Oral Surgery Service offers advanced diagnostic techniques including detailed dental evaluation and charting in conjunction with intra-oral radiographic studies. We can provide advanced imaging studies prior to treating maxillofacial trauma and oral neoplasia. We work closely with our board-certified anesthesiologist and highly trained certified veterinary nurses to ensure the patient’s anesthesia and recovery is as safe as possible. After treatment, you can expect a full report for your records which details diagnosis, treatment, radiographs and any follow up care you will want to incorporate into the pet’s health plan.
Dr. Orsini is accepting new appointments & will offer procedures and recheck appointments Wednesday through Friday.
At Hope Veterinary Specialists we are committed to a pet’s whole health care needs and are excited to add the Dentistry and Oral Surgery Service to our specialty group and for the opportunity to care for your patients in this new capacity. Should you have any questions regarding this new service, please don’t hesitate to contact us!