Evaluation of clinical response and prognostic factors in canine multicentric lymphoma treated with first rescue therapy.

Despite an initial strong response in most dogs with multicentric lymphoma treated with chemotherapy, relapse remains common. There is no clearly superior first rescue protocol described either for resistant or relapsed canine multicentric lymphoma. The objectives of this study were to assess clinical response and outcomes for canine multicentric lymphoma treated with first rescue protocols. The secondary objective was to assess prognostic variables for dogs undergoing these protocols. This was a bi-institutional retrospective cohort study. Two hundred and sixty-five dogs were treated with first rescue chemotherapy, including anthracycline-based combination chemotherapy (CHOP-like, n = 50), nitrosourea alkylating agent-rich chemotherapy (n = 45), anthracycline-based or related compound chemotherapy (n = 34), or nitrosourea single-agent chemotherapy (n = 136). The overall median progression free survival time of first rescue protocol was 56.0 days (0-455 days). Important prognostic factors identified for first rescue protocol included the attainment of a complete response to the first rescue chemotherapy (p < .001), the use of a CHOP-like first rescue protocol (p = .009), duration of first remission (HR 0.997, p = .028), and if prednisolone was included in the first rescue protocol (HR 0.41, p = .003). Adverse events (AE) were common, with 81.1% of dogs experiencing at least one AE during first rescue chemotherapy. This study highlights the need for improved first rescue therapies to provide durable remission in canine resistant or relapsed lymphoma.

Genomic Analysis of Lymphoma Risk in Bullmastiff Dogs.

Lymphoma is the most common haematological malignancy affecting dogs and has a high incidence in the Bullmastiff breed. The aim of this study was to identify risk loci predisposing this breed to the disease. The average age of lymphoma diagnosis in 55 cases was less than 6 years, similar to the median age of 64 cases from our clinical and pathology databases. When fine-scale population structure was explored using NETVIEW, cases were distributed throughout an extended pedigree. When genotyped cases (n = 49) and dogs from the control group (n = 281) were compared in a genome-wide association analysis of lymphoma risk, the most prominent associated regions were detected on CFA13 and CFA33. The top SNPs in a 5.4 Mb region on CFA13 were significant at a chromosome-wide level, and the region was fine-mapped to ~1.2 Mb (CFA13: 25.2-26.4 Mb; CanFam3.1) with four potential functional candidates, including the MYC proto-oncogene bHLH transcription factor (MYC) and a region syntenic with the human and mouse lncRNA Pvt1 oncogene (PVT1). A 380 Kb associated region at CFA33: 7.7-8.1 Mb contained the coding sequence for SUMO specific peptidase7 (SENP7) and NFK inhibitor zeta (NFKBIZ) genes. These genes have annotations related to cancer, amongst others, and both have functional links to MYC regulation. Genomic signatures identified in lymphoma cases suggest that increased risk contributed by the regions identified by GWAS may complement a complex predisposing genetic background.

Long term survival of a dog with disseminated Aspergillus deflectus infection without definitive treatment.

Canine disseminated fungal infection by Aspergillus species carries a guarded to grave prognosis as they often rapidly progress and are refractory to treatment with many euthanased soon after diagnosis. This case report describes a 2.5 year old female spayed German Shepherd Dog diagnosed with disseminated Aspergillus deflectus infection for which definitive treatment was declined by the owners. With only palliative management the dog survived three years and two months before succumbing to chronic kidney disease.

Demographic risk factors for lymphoma in Australian dogs: 6201 cases.

BACKGROUND: Lymphoma is common in the dog. Studies of population risk factors primarily have been derived from referral institution or insurance data. OBJECTIVE: To identify and quantify the host risk factors for lymphoma in a broad population of Australian dogs. ANIMALS: Data on 6201 client owned dogs were retrieved from a commercial veterinary laboratory, a general practice group and 2 referral hospitals. METHODS: Data collected included breed, sex, and neuter status. A reference population of 640 105 dogs was generated from the referral hospitals and from council registration data. The risk of lymphoma by sex and neuter status was calculated as odds ratios (OR). RESULTS: The study identified 30 breeds at increased risk of lymphoma, 15 that have not been reported previously, and 26 breeds at decreased risk, 18 that have not been reported previously. Males were over represented compared to females with an OR of 1.1 (95% CI, 1.1-1.2; P < .001). Neutered animals were at higher risk compared to intact animals with an OR of 3.2 (95% CI, 2.9-3.5) which was found in both males (OR, 2.8; 95% CI; 2.5-3.2) and females (OR, 4.4; 95% CI, 3.5-5.1). CONCLUSIONS AND CLINICAL IMPORTANCE: Breed, sex, and neuter status alter the risk of lymphoma in dogs. These 3 factors must be considered when evaluating lymphoma risk as potential markers of underlying differences in disease etiology. Comparison of breeds at increased and decreased risk could be advantageous when evaluating specific etiological factors.

Effect of pimobendan on the clinical outcome and survival of cats with non-taurine responsive dilated cardiomyopathy.

This retrospective study was designed to assess the effect of pimobendan on the median survival time (MST) of cats with non-taurine responsive dilated cardiomyopathy (DCM). Thirty-two client-owned cats with a left ventricular internal dimension at end systole (LVIDs) >14 mm, a fractional shortening (FS) <28% and a lack of response to taurine therapy were included over a 9-year period (2001-2010). These cats were divided into pimobendan (n=16) and non-pimobendan (n=16) treatment groups. All cats received standard treatment with frusemide, taurine and benazepril or enalapril. Nine cats in the non-pimobendan group also received digoxin. The MST of the pimobendan group (49 days; range 1 to >502 days) was four times that of the non-pimobendan group (12 days; 1 to 244 days). The difference in survival between the two groups was statistically significant (P = 0.048). Hypothermia and FS <20% were associated with a poor prognosis. No adverse effects to pimobendan were noted.

Polyostotic lymphoma with multiple pathological fractures in a six-month-old cat.

A 6-month-old female neutered domestic shorthair cat was examined for pain and swelling of the distal limbs. Swelling and malalignment of both carpi, dorsiflexion of the distal metatarsals and a mild, multicentric lymphadenopathy were detected on examination. Screening blood tests revealed a biclonal gammopathy, hypercalcemia and atypical leukocytes. Survey radiographs revealed lysis and proliferative changes within the physes. Multiple pathological physeal fractures were present, including the distal radii, metacarpal and metatarsal bones. No treatment was attempted and the patient was euthanased. Histopathology revealed infiltration by monomorphic round cells within the liver, spleen, kidney and bone marrow. Immunohistochemistry revealed strong reactivity to CD20. Clonality assays revealed clonal results for the B-cell loci, consistent with B-cell lymphoma. To the authors' knowledge this is the first report of polyostotic lymphoma with multiple pathological fractures in a cat. The predominantly distal distribution of osseous lesions is rarely reported in dogs and humans.

Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of cisplatin administered with piroxicam, the antitumor activity and toxicity of cisplatin combined with piroxicam in dogs with oral malignant melanoma (OMM) and oral squamous cell carcinoma (SCC), and the effects of piroxicam on the pharmacokinetics of cisplatin in dogs with tumors. DESIGN: Prospective nonrandomized clinical trial. ANIMALS: 25 dogs. PROCEDURE: Dogs were treated with a combination of cisplatin (escalating dose with 6 hours of diuresis with saline [0.9% NaCI] solution) and piroxicam (0.3 mg/kg 10.14 mg/lb], PO, q 24 h). The initial cisplatin dose (50 mg/m2) was increased by 5 mg/m2 until the MTD was reached. Tumor stage and size were determined at 6-week intervals during treatment. The pharmacokinetics of cisplatin were determined in dogs receiving a combination of cisplatin and piroxicam during the clinical trial and dogs that were treated with cisplatin alone. RESULTS: 11 dogs with OMM and 9 dogs with SCC were included in the clinical trial. The MTD of cisplatin when administered in combination with piroxicam was 50 mg/m2. Tumor remission occurred in 5 of 9 dogs with SCC and 2 of 11 dogs with OMM. The most common abnormality observed was renal toxicosis. Clearance of cisplatin in dogs that were treated with cisplatin alone was not significantly different from that in dogs treated with a combination of cisplatin and piroxicam. CONCLUSIONS AND CLINICAL RELEVANCE: Cisplatin administered in combination with piroxicam had antitumor activity against OMM and SCC. The level of toxicity was acceptable, although renal function must be monitored carefully.

Canine anal sac adenocarcinomas: clinical presentation and response to therapy.

A retrospective study of 43 dogs with anal sac adenocarcinoma (ASAC) was performed to characterize the clinical presentation and response to treatment. Clinical signs at presentation varied considerably, with signs related either to sublumbar nodal metastasis (tenesmus or constipation) or hypercalcemia (polyuria-polydipsia and anorexia) being the most frequent findings. At the time of presentation, 23 (53%) dogs had hypercalcemia and 34 (79%) had metastases, with the regional lymph nodes (31 dogs, 72%) being the most common site of metastasis. A variety of chemotherapeutic agents were administered, with partial remission (PR) recorded in 4 of 13 (31%) dogs treated with cisplatin and in 1 of 3 (33%) dogs treated with carboplatin. The median survival for all dogs was 6 months (range, 2 days-41 months). There was no statistical association between the presence of hypercalcemia and survival, although the power of the study to detect an increase in survival of 3 months was low (.33). We conclude that platinum chemotherapy has antitumor activity in canine apocrine gland carcinoma and that further study of these agents is warranted.

Effects of the cyclooxygenase inhibitor, piroxicam, on tumor response, apoptosis, and angiogenesis in a canine model of human invasive urinary bladder cancer.

The mechanisms by which cyclooxygenase inhibitors exert antitumor effects are not completely defined but are postulated to involve antiangiogenic effects and induction of apoptosis. In this study, we determined the effects of the cox inhibitor, piroxicam, on tumor response, apoptotic index, proliferative index, cyclooxygenase-2 expression, prostaglandin E(2) concentration, tumor microvessel density, and urine basic fibroblast growth factor and vascular endothelial growth factor concentrations in pet dogs with naturally occurring invasive transitional cell carcinoma of the urinary bladder. Piroxicam caused reduction in tumor volume in 12 of 18 dogs, and this was strongly associated with induction of apoptosis (Fisher's exact test P < 0.015) and reduction in urine basic fibroblast growth factor concentration.