Evaluation of coated platelets, a subset of highly procoagulant platelets, in healthy dogs and dogs with neoplasia.

OBJECTIVE: To determine if dogs with neoplasia produce more coated platelets, a subpopulation of activated platelets generated by dual stimulation with thrombin and convulxin, a glycoprotein VI agonist, than healthy control dogs. ANIMALS: Client-owned dogs diagnosed with lymphoma (n = 19) or solid tumors (14) and healthy control dogs (14). PROCEDURES: Platelets were stimulated ex vivo with thrombin and convulxin. Flow cytometry was used to quantify the percentage of coated platelets based on high levels of surface fibrinogen. To compare the percentage of coated platelets between the three groups, an ANOVA was performed followed by pairwise 95% confidence intervals (CI) adjusted for multiple comparisons using Tukey's method. RESULTS: We observed a greater mean percentage of coated platelets in dogs with solid tumors, compared with healthy control dogs, by 10.9 percentage points (95% CI: -1.0, 22.8), and a mean percentage of coated platelets in dogs with lymphoma that was less than healthy control dogs by 0.3 percentage points (95% CI: -11.4, 10.8). CLINICAL RELEVANCE: This study provides the first data-based evidence that dogs with solid tumors may have a greater mean coated platelet percentage when compared with healthy control dogs, although there is overlap between groups. Further studies are needed investigating coated platelets in specific subsets of neoplasia and investigating additional mechanisms of hypercoagulability in dogs with neoplasia.

Comparison of complications and outcome following unilateral, staged bilateral, and single-stage bilateral ventral bulla osteotomy in cats.

OBJECTIVE: To compare complications and outcome following unilateral, staged bilateral, and single-stage bilateral ventral bulla osteotomy (VBO) in cats. ANIMALS: 282 client-owned cats treated by VBO at 25 veterinary referral and academic hospitals from 2005 through 2016. PROCEDURES: Medical records of cats were reviewed to collect information on signalment, clinical signs, diagnostic test results, surgical and postoperative management details, complications (anesthetic, surgical, and postoperative), and outcome. Associations were evaluated among selected variables. RESULTS: Unilateral, staged bilateral, and single-stage bilateral VBO was performed in 211, 7, and 64 cats, respectively, representing 289 separate procedures. Eighteen (9%), 2 (29%), and 30 (47%) of these cats, respectively, had postoperative respiratory complications. Cats treated with single-stage bilateral VBO were significantly more likely to have severe respiratory complications and surgery-related death than cats treated with other VBO procedures. Overall, 68.2% (n = 197) of the 289 procedures were associated with Horner syndrome (19.4% permanently), 30.1% (87) with head tilt (22.1% permanently), 13.5% (39) with facial nerve paralysis (8.0% permanently), and 6.2% (18) with local disease recurrence. Cats with (vs without) Horner syndrome, head tilt, and facial nerve paralysis before VBO had 2.6, 3.3, and 5.6 times the odds, respectively, of having these conditions permanently. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that staged bilateral VBO should be recommended over single-stage bilateral VBO for cats with bilateral middle ear disease. Cats with Horner syndrome, head tilt, and facial nerve paralysis before surgery were more likely to have these conditions permanently following surgery than were cats without these conditions.

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are uncommon intestinal neoplasms in the dog. Literature regarding adjunctive therapy for GISTs in dogs is sparse. High-risk GISTs in humans respond to tyrosine kinase inhibition in the adjuvant setting. OBJECTIVES: To review cases of toceranib phosphate use in dogs with GISTs and provide initial assessment of possible biological activity. A secondary aim was to evaluate patient and tumor characteristics for possible prognostic value. ANIMALS: Twenty-seven dogs with confirmed GISTs based on histopathology and immunohistochemistry treated with toceranib. METHODS: Retrospective study in which cases of toceranib use in dogs with GIST were solicited using the American College of Veterinary Internal Medicine Oncology and Small Animal Internal Medicine listservs. RESULTS: Five of 7 dogs with gross disease experienced clinical benefit (71%; 3 complete responses, 1 partial response, 1 stable disease). These included 2 dogs with durable responses after toceranib discontinuation. Median progression-free interval (PFI) in dogs with gross disease was 110 weeks (range, 36-155 weeks). Median PFI in dogs with microscopic disease was 67 weeks (range, 9-257 weeks). Metastasis at diagnosis (P = 0.04) and high mitotic index (P < 0.001) were associated with shorter PFI in toceranib-treated dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Biological activity of toceranib is evident in dogs with gross disease. Metastasis of GIST at diagnosis, as well as high tumor mitotic index, was associated with shorter PFI in toceranib-treated dogs. Larger studies are needed to define postsurgical risk and refine the use of toceranib in dogs with gross and microscopic GIST.

Primary appendicular hemangiosarcoma and telangiectatic osteosarcoma in 70 dogs: A Veterinary Society of Surgical Oncology retrospective study.

OBJECTIVE: To define and compare clinical characteristics of canine primary appendicular hemangiosarcoma (HSA) and telangiectatic osteosarcoma (tOSA), including signalment, presentation, response to treatment, and prognosis. STUDY DESIGN: Multi-institutional retrospective study. ANIMALS: Seventy dogs with primary appendicular HSA or tOSA. METHODS: Patient data were obtained from institutions' medical records. Immunohistochemistry was applied to archived tissues to establish tumor type. Patient characteristics, treatment responses, and outcomes were described and compared by tumor type. RESULTS: Forty-one HSA and 29 tOSA were identified. Dogs with HSA were more likely than dogs with tOSA to be male and have hind limb tumors; 78% of HSA occurred in hind limbs, particularly the tibia. Dogs with tOSA weighed a median of 9.9 kg (95% CI 4.6-15.3) more than dogs with HSA. Most dogs received antineoplastic treatment, predominantly amputation with or without adjuvant chemotherapy. Overall survival with local treatment and chemotherapy was 299 days (95% CI 123-750) for HSA and 213 days (95% CI 77-310) for tOSA. Younger age and more aggressive treatment were associated with longer survival in dogs with HSA but not tOSA. One-year survival rates did not differ between dogs with HSA (28%) and those with tOSA (7%). CONCLUSION: Distinct clinical features were identified between HSA and tOSA in this population. Both tumors were aggressive, with a high incidence of pulmonary metastases. However, local treatment combined with chemotherapy led to an average survival 7 months for tOSA and 10 months for HSA. CLINICAL SIGNIFICANCE: HSA should be considered as a differential in dogs with aggressive lytic bone lesions, particularly medium-sized dogs with tibial lesions. HSA has a unique clinical presentation but similar therapeutic response and outcome to OSA. Amputation and chemotherapy appear to prolong survival in some dogs with HSA and tOSA.

Retrospective evaluation of toceranib phosphate (Palladia) use in cats with mast cell neoplasia.

Objectives The purpose of this study was to solicit and compile data from practicing veterinary specialists regarding their use of toceranib in cats with mast cell neoplasia and to provide initial assessment of possible clinical benefit and adverse events. Methods The American College of Veterinary Internal Medicine and Oncology listservs were used to solicit data pertaining to cases in which toceranib was used in the treatment of feline mast cell neoplasia. Cases were included if the following data were received: signalment (age, sex, breed), diagnosis of mast cell neoplasia by either cytology or histopathology, anatomic classification of disease (cutaneous, splenic/hepatic, gastrointestinal, other), previous and concurrent treatment, toceranib dose (mg/kg) and schedule, duration of therapy, best response and documentation of adverse events. Results Case data from 50 cats with cutaneous (n = 22), splenic/hepatic (visceral) (n = 10), gastrointestinal (n = 17) or other (n = 1) mast cell neoplasia were received. Clinical benefit was seen in 80% (40/50), including 86% (19/22) with cutaneous, 80% (8/10) with visceral and 76% (13/17) with gastrointestinal involvement. A majority of cats (n = 35) received glucocorticoids during toceranib treatment. Median duration of treatment in cats experiencing clinical benefit was 36 weeks (range 4-106 weeks), 48 weeks (range 12-199 weeks) and 23 weeks (range 13-81 weeks) for cutaneous, visceral and gastrointestinal cases, respectively. Toceranib was administered at a median dose of 2.5 mg/kg (range 1.6-3.5 mg/kg); in 90% (45/50) the drug was given three times per week. Treatment was generally well tolerated with 60% (30/50) of cats experiencing adverse events. The majority of these events were low-grade (grade 1 or 2) gastrointestinal or hematologic events that resolved with treatment break and/or dose adjustment. Conclusions and relevance Toceranib appears to be well tolerated in feline patients with mast cell neoplasia. Biologic activity of this drug is evident in the studied cats; however, further prospective studies are needed to elucidate fully its role in treatment of this disease.

Response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol: 38 cases (1996-2003).

OBJECTIVE: To determine response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol. DESIGN: Retrospective study. ANIMALS: 38 cats with lymphoma. PROCEDURE: Medical records were reviewed, and information on age, sex, breed, FeLV and FIV infection status, anatomic form, clinical stage, and survival time was obtained. Immunophenotyping was not performed. RESULTS: Mean +/- SD age of the cats was 10.9 +/- 4.4 years. Overall median survival time was 210 days (interquartile range, 90 to 657 days), and overall duration of first remission was 156 days (interquartile range, 87 to 316 days). Age, sex, anatomic form, and clinical stage were not significantly associated with duration of first remission or survival time. Eighteen of the 38 (47%) cats had complete remission, 14 (37%) had partial remission, and 6 (16%) had no response. Duration of first remission was significantly longer for cats with complete remission (654 days) than for cats with partial remission (114 days). Median survival time for cats with complete remission (654 days) was significantly longer than median survival time for cats with partial remission (122 days) and for cats with no response (11 days). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a high percentage of cats with lymphoma will respond to treatment with the University of Wisconsin-Madison chemotherapy protocol. Age, sex, anatomic form, and clinical stage were not significantly associated with duration of first response or survival time, but initial response to treatment was.

Canine digital tumors: a veterinary cooperative oncology group retrospective study of 64 dogs.

We compared clinical characteristics and outcomes for dogs with various digital tumors. Medical records and histology specimens of affected dogs from 9 veterinary institutions were reviewed. Risk factors examined included age, weight, sex, tumor site (hindlimb or forelimb), local tumor (T) stage, metastases, tumor type, and treatment modality. The Kaplan-Meier product limit method was used to determine the effect of postulated risk factors on local disease-free interval (LDFI), metastasis-free interval (MFI), and survival time (ST). Outcomes were thought to differ significantly between groups when P < or = .003. Sixty-four dogs were included. Squamous cell carcinoma (SCC) accounted for 33 (51.6%) of the tumors. Three dogs presented with or developed multiple digital SCC. Other diagnoses included malignant melanoma (MM) (n = 10; 15.6%), osteosarcoma (OSA) (n = 4; 6.3%), hemangiopericytoma (n = 3; 4.7%), benign soft tissue tumors (n = 5; 7.8%), and malignant soft tissue tumors (n = 9; 14%). Fourteen dogs with malignancies had black hair coats, including 5 of the 10 dogs with MM. Surgery was the most common treatment and, regardless of the procedure, had a positive impact on survival. None of the patient variables assessed, including age, sex, tumor type, site, and stage, had a significant impact on ST. Both LDFI and MFI were negatively affected by higher T stage, but not by type of malignancy. Although metastasis at diagnosis correlated with a shorter LDFI, it did not have a significant impact on ST. On the basis of these findings, early surgical intervention is advised for the treatment of dogs with digital tumors, regardless of tumor type or the presence of metastatic disease.

Vancomycin for multi-drug resistant Enterococcus faecium cholangiohepatitis in a cat.

A 12-year-old, neutered male domestic shorthair cat was evaluated with a life-long history of intermittent, predominantly small bowel diarrhea and a 3 day history of hematochezia. At presentation, the cat had increased liver enzyme activities and an inflammatory leukogram. Histopathology demonstrated inflammatory bowel disease (IBD), cholangiohepatitis and pancreatitis. The cholangiohepatitis was associated with a multi-drug resistant Enterococcus faecium. Gallbladder agenesis was also documented. Treatment with vancomycin was safely instituted for 10 days. Clinical signs resolved, however, cure of the bacterial cholangiohepatitis was not achieved. The risk of vancomycin resistant enterococci (VRE) in human and veterinary medicine is discussed.

Effect of thalidomide on growth and metastasis of canine osteosarcoma cells after xenotransplantation in athymic mice.

OBJECTIVE: To determine whether thalidomide inhibits the growth of primary and pulmonary metastatic canine osteosarcoma in mice after xenotransplantation. ANIMALS: Athymic nude mice. PROCEDURE: Canine osteosarcoma cells were injected SC in 50 mice. Mice were randomly placed into the following groups: control group (n = 13; DMSO [drug vehicle] alone [0.1 mL/d, IP]); low-dose group (12; thalidomide [100 mg/kg, IP]), mid-dose group (13; thalidomide [200 mg/kg, IP]); and high-dose group (12; thalidomide [400 mg/kg, IP]). Starting on day 8, treatments were administered daily and tumor measurements were performed for 20 days. On day 28, mice were euthanatized and primary tumors were weighed. Lungs were examined histologically to determine the number of mice with metastasis and tumor emboli. Mean area of the pulmonary micrometastatic foci was determined for mice from each group. RESULTS: Primary tumor size and weight were not significantly different among groups. The number of mice in the mid-dose (200 mg/kg) and high-dose (400 mg/kg) groups with micrometastasis was significantly less than the number of control group mice; however, the number of mice with tumor emboli was not affected by thalidomide treatment. Size of micrometastasis lesions was not affected by thalidomide treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Mean area of micrometastases was not affected by treatment; however, growth of micrometastases had not yet reached an angiogenesis-dependent size. Although thalidomide did not affect growth of primary tumors in mice after xenotransplantation of canine osteosarcoma cells, our findings indicate that thalidomide may interfere with the ability of embolic tumor cells to complete the metastatic process within the lungs.

Aplastic anemia associated with prolonged high-dose trimethoprim-sulfadiazine administration in two dogs.

Trimethoprim-sulfadiazine (TMP-SDZ) (Tribressin tablets 120 - 100 mg sulfadiazine, 20-mg trimethoprim [Coopers Animal Health, Inc., A Pitman-Moore Company, Mundelein, Ill.]) is a broad spectrum antibiotic combination effective in the treatment of bacterial pneumonia, urinary tract infections, pyoderma, meningitis, and prostatitis.(1) In clinical trials in puppies and adult dogs, TMP-SDZ was considered safe at both the manufacturer's recommended dose (15 mg/kg, b.i.d., or 30 mg/kg, u.i.d., per os for < 14 days(2)) and at 10 times that dose for 20 dayS.(3) Many infections, however, require prolonged high-dose therapy for resolution. The following study describes two cases of aplastic anemia and sepsis associated with intermittent, chronic (17-25 days), high-dose (25-30 mg/kg, b.i.d., per os) TMP-SDZ therapy recommended for the treatment of pyoderma.(4-7)