Gastric Intravascular Lymphoma in a Dog: Case Report and Literature Review.

Intravascular lymphoma (IVL) is a rare, high-grade, extranodal lymphoma characterized by selective proliferation of neoplastic lymphocytes within the lumen of small vessels. A 10 yr old female intact mixed-breed dog was presented with a 7 mo history of vomiting and anorexia. Physical examination revealed abdominal discomfort. Ultrasonography and endoscopy identified a submucosal gastric mass. Excision was performed by partial gastrectomy and histopathology and immunohistochemistry confirmed a T-cell IVL. The owner declined chemotherapy, and the dog was instead treated palliatively with prednisolone. Two months after surgery, vomiting recurred and abdominal ultrasonography revealed a large gastric ulcer with focal peritonitis. The dog was euthanized 4 mo after initial presentation and postmortem examination confirmed IVL recurrence in the stomach and an isolated nodule of neoplastic cells in the omentum. No involvement of other organs was found following histopathological examination. This is the first description of primary gastric intravascular lymphoma causing chronic vomiting in a dog.

RETROSPECTIVE COMPARISON OF THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY VS. PREDNISOLONE ALONE IN 30 CASES OF CANINE INFRATENTORIAL BRAIN TUMORS.

Infratentorial tumors are relatively infrequent in dogs and a lack of data makes it difficult to offer prognostic information. Untreated, dogs with these neoplasms have shorter survival times than those with supratentorial tumors. The role of radiation therapy (RT) in the management of infratentorial tumors is poorly defined and tumoral/peritumoral swelling in this site is a potential cause of serious acute side effects. The aim of this retrospective, cohort study was to describe cases of infratentorial tumors treated with fractionated three-dimensional conformal RT (3D CRT) and glucocorticoids (GC), and compare outcomes and survival with dogs affected by tumors in the same location that received GC alone. Thirty patients with a MRI diagnosis of infratentorial tumors were recruited (15 received RT and GC and 15 GC alone). None had mentation changes at presentation. For both groups, MRI and medical records were reviewed; and factors associated with survival were evaluated with Kaplan-Meier product limit survival and Cox regression analysis. Overall median survival time (MST) was 294 days (95% CI 42-545). The MST in the RT group was 756 days (95% CI 209-1302) vs. 89 days (95% CI 34.7-143.3 days) for those dogs treated palliatively with GC alone. This difference was statistically significant (P = 0.001). No other factors (including neurological signs, MRI features, tumor volume and total RT dose) were statistically associated with survival in the RT group. This study suggests that 3D CRT offers a survival advantage for dogs with infratentorial tumors compared to GC alone, and significant complications are uncommon.

Evaluation of the efficacy and safety of toceranib phosphate in cats with macroscopic mammary adenocarcinoma.

OBJECTIVES: Mammary tumours in cats are biologically aggressive. The standard of care relies upon wide surgical resection. Chemotherapy has been described in the macroscopic disease setting; however, limited efficacy has been shown. The aim of this study was to assess the efficacy of toceranib phosphate in macroscopic feline mammary tumours (FMTs). METHODS: A total of 17 cats with cytologically or histopathologically confirmed mammary adenocarcinoma (gross disease) were prospectively enrolled. Toceranib phosphate was administered at a median dose of 2.77 mg/kg (range 2.3-3.2) PO q48 h. No corticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs) were administered. Toxicity was graded according to Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE) v1.1 criteria. The response was assessed after 1 month, following Response Evaluation Criteria In Solid Tumours (RECIST) criteria. RESULTS: Toxicity was observed in eight cats, with most instances being grade 1 or 2, which were managed with supportive care. Only one cat experienced grade 3 toxicity (anorexia), which resolved after a dose reduction. Clinical benefit was seen in 12 (64.7%) cats and an objective response was seen in six (35.2%) cats. One cat experienced complete response, five had partial response, six had stable disease and five had progressive disease. One cat showed distant progression (malignant pleural effusion) despite continued partial remission of the primary tumour. The median progression-free survival and median overall survival time were 91 days (range 30-158) and 145 days (range 31-234), respectively. CONCLUSIONS AND RELEVANCE: Toceranib phosphate showed clinical benefit and a good safety profile in advanced or recurrent FMTs, offering a new alternative in the treatment of this disease; however, further prospective and randomised studies are required to further assess its efficacy. Interestingly, one cat developed distant metastases while the primary tumour showed partial response, suggesting that primary tumour and metastatic disease may not sustain the same sensitivity to toceranib.

Impact of 10% Dose Reductions and Duration of Treatment Delays in the Management of Chemotherapy-Induced Neutropenia in Dogs Treated With Common Chemotherapy Protocols: A Single-Centre Experience.

Neutropenia is a common chemotherapy-associated adverse event (AE) in dogs and a significant cause of decreased relative dose intensity. Dose reductions (DRs) and treatment delays (TDs) are frequently applied to decrease the risk of further neutropenic events (NEs) and AEs, but there is no standardised approach. The two main objectives of this retrospective study were to determine: (1) the failure rate of a 10% DR to prevent a subsequent inadequate absolute neutrophil count (ANC), defined as a nadir ANC <0.75 × 109/L or pretreatment ANC <1.5 × 109/L; and (2) if the duration of TDs due to pretreatment neutropenia affects the occurrence of subsequent NEs. A total of 1056 chemotherapy treatments were recorded for 128 dogs that developed at least one NE. In 75 of 124 (60.5%, 95% CI: 51.2%-69%) evaluable NEs, a nadir ANC of ≥0.75 × 109/L and pretreatment ANC of ≥1.5 × 109/L were achieved after a single 10% chemotherapy DR, while a 10% DR failed to prevent a subsequent inadequate ANC in the remaining 49/124 (39.5%, 95% CI: 30.1%-48.3%). The only variable associated with failure was the drug prescribed. DR failure occurred in 22/39 (56.4%, 95% CI: 40.9%-70.6%) lomustine DRs, 14/27 (51.9%, 95% CI: 33.9%-69.2%) cyclophosphamide DRs, but only 2/22 (9.1%, 95% CI: 2.5%-27.8%) doxorubicin DRs and 2/24 (8.3%, 95% CI: 2.3%-25.8%) vincristine DRs. Seventy-three evaluable TDs (mean: 5 days, SD ± 2.2 days) were prescribed. There was no association between TD duration and subsequent NEs (p = 0.11).

Dynamic contrast-enhanced computed tomography in dogs with nasal tumors.

BACKGROUND: Treatment of nasal tumors in dogs is associated with high morbidity and reliable prognostic factors are lacking. Dynamic contrast-enhanced computed tomography (DCECT) can be used to assess tumor perfusion. OBJECTIVES: To assess perfusion parameters of nasal tumors (correlating with tumor type) before and during radiotherapy (RT) and find potential correlation with survival. ANIMALS: Twenty-four client-owned dogs with nasal tumors, including 16 epithelial tumors and 8 sarcomas. METHODS: Prospective cross-sectional study. All dogs had baseline DCECT to assess fractional vascular volume (BV), blood flow (BF), and transit time (TT). Thirteen dogs had repeat DCECT after 12 Gy of megavoltage RT. Survival times were calculated. RESULTS: Median BV was 17.83 mL/100 g (range, 3.63-66.02), median BF was 122.63 mL/100 g/minute (range, 23.65-279.99), and median TT was 8.91 seconds (range, 4.57-14.23). Sarcomas had a significantly lower BF than adenocarcinomas (P = .002), carcinomas (P = .01), and other carcinomas (P = .001), and significantly lower BV than adenocarcinomas (P = .03) and other carcinomas (P = .004). Significant associations were found between epithelial tumors and sarcoma for change in tumor volume (P = .01), width (P = .004), and length (P = .02) in that epithelial tumors decreased in volume whereas sarcomas increased in volume. Perfusion parameters were not correlated with survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Nasal sarcomas have lower BV and BF than nasal carcinomas, and sarcomas have a lower size reduction than carcinomas early on during RT. Baseline results and changes in perfusion parameters may not be correlated with survival.

Dynamic contrast-enhanced computed tomography perfusion parameters of canine suspected brain tumors at baseline and during radiotherapy might be different depending on tumor location but not associated with survival.

Introduction: Treatment of brain tumors in dogs can be associated with significant morbidity and reliable prognostic factors are lacking. Dynamic contrast-enhanced computed tomography (DCECT) can be used to assess tumor perfusion. The objectives of this study were to assess perfusion parameters and change in size of suspected brain tumors before and during radiotherapy (RT) depending on their location and find a potential correlation with survival. Methods: Seventeen client-owned dogs with suspected brain tumors were prospectively recruited. All dogs had a baseline DCECT to assess mass size, blood volume (BV), blood flow (BF), and transit time (TT). Twelve dogs had a repeat DCECT after 12 Gy of megavoltage RT. Survival times were calculated. Results: Intra-axial masses had lower BF (p = 0.005) and BV (p < 0.001) than extra-axial masses but not than pituitary masses. Pituitary masses had lower BF (p = 0.001) and BV (p = 0.004) than extra-axial masses. The volume of the mass was positively associated with TT (p = 0.001) but not with BF and BV. Intra-axial masses showed a more marked decrease in size than extra-axial and pituitary masses during RT (p = 0.022 for length, p = 0.05 for height). Extra-axial masses showed a greater decrease in BF (p = 0.011) and BV (p = 0.012) during RT than pituitary masses and intra-axial masses. Heavier dogs had a shorter survival time (p = 0.011). Perfusion parameters were not correlated with survival. Conclusion: DCECT perfusion parameters and change in size of brain masses during RT might be different based on the location of the mass.

Dynamic contrast-enhanced computed tomography in 11 dogs with orofacial tumors.

OBJECTIVE: Treatment of orofacial tumors in dogs is associated with high morbidity and reliable prognostic factors are lacking. Dynamic contrast-enhanced computed tomography (DCECT) can be used to assess tumor perfusion. The objectives of this study were to describe the perfusion parameters of different types of orofacial tumors and to describe the changes in perfusion parameters during radiotherapy (RT) in a subset of them. ANIMALS: 11 dogs with orofacial tumors prospectively recruited. CLINICAL PRESENTATION AND PROCEDURES: All dogs had baseline DCECT to assess blood volume (BV), blood flow (BF), and transit time (TT). Five dogs had repeat DCECT during megavoltage RT. RESULTS: 5 squamous cell carcinomas, 3 sarcomas, 1 melanoma, 1 histiocytic sarcoma, and 1 acanthomatous ameloblastoma were included. Blood volume and BF were higher in squamous cell carcinomas than in sarcomas, although no statistical analysis was performed. At repeat DCECT, 4 dogs showed a reduction in the size of their tumor during RT. Among these dogs, 3 showed an increase in BV and BF and 1 a decrease in these parameters between the baseline and the follow-up DCECT. The only dog whose tumor increased in size between the first and the second DCECT showed a decrease in BV and BF. CLINICAL RELEVANCE: Perfusion parameters derived from DCECT were described in a series of dogs with various types of orofacial tumors. The results suggest that epithelial tumors could have higher BV and BF than mesenchymal tumors, although larger sample sizes are needed to support these preliminary findings.

Clinical presentation, treatment and outcome of canine malignant mesothelioma: A retrospective study of 34 cases.

Canine malignant mesothelioma (CMM) is a rare and aggressive tumour associated with a poor prognosis. Limited information is available regarding effective treatment options and prognostic factors. The purpose of this retrospective case series was to describe the clinical presentation, treatment and survival in a cohort of dogs with this disease and to investigate possible prognostic factors. Thirty-four dogs were included. Tachypnoea and dyspnoea due to pleural effusion were the most common presenting clinical signs. Twenty-two dogs had a subcutaneous access port placed and 25 dogs were treated with intracavitary and/or intravenous chemotherapy. The main protocols used were single-agent 5-FU (n = 14) and carboplatin single-agent or alternated with mitoxantrone (n = 10). The overall response rate (defined as more than 25% reduction in effusion volume) to chemotherapy treatment was 37% after 3-weeks and 24% after 15-weeks. The median survival time (MST) for all dogs was 195 days (95% CI 53-324). MST was 234 days for dogs receiving chemotherapy and 29 days for dogs not receiving chemotherapy. The 1-year survival rate was 22% for all dogs. Treatment with chemotherapy was the only significant prognostic factor associated with survival (p = .001). Further studies are needed to determine the optimal treatment approach for malignant mesothelioma in dogs. Nevertheless, effusion recurrence should be expected and the prognosis for these patients in the long-term is poor.

Lomustine, methotrexate and cytarabine chemotherapy as a rescue treatment for feline lymphoma.

OBJECTIVES: The aim of this study was to assess the efficacy and tolerability of lomustine, methotrexate and cytarabine chemotherapy as rescue treatment for feline lymphoma. METHODS: The medical records of 13 cats treated with lomustine, methotrexate and cytarabine for relapsed high-grade feline lymphoma, at a single institution between 2013 and 2018, were examined. All anatomical types were included. Data were analysed using descriptive statistics. RESULTS: Nine cats received all three drugs and four cats received only two drugs owing to progressive disease. In cats that received (or in which there was intention to treat with) all three drugs, 6/13 (46%) demonstrated a complete or partial response to chemotherapy. Treatment was generally well tolerated, although two cats experienced Veterinary Comparative Oncology Group (VCOG) grade 3 neutropenia and one cat experienced VCOG grade 3 thrombocytopenia. The median progression-free survival was 61 days (range 16-721 days). CONCLUSIONS AND RELEVANCE: CHOP-(cyclophosphamide, doxorubicin, vincristine, prednisolone) and COP-based protocols are established first-line chemotherapy for feline lymphoma, but standard rescue protocols are lacking. Lomustine has become a popular single-agent option, but prolonged or cumulative myelosuppression can result in treatment delays, risking relapse. Therefore, a multidrug lomustine-based protocol may be advantageous, and, from first principles, should also better overcome resistance. This study suggests that lomustine, methotrexate and cytarabine may represent an efficacious and well-tolerated protocol for feline lymphoma rescue.

Immunohistochemical expression and prognostic significance of MAGE-A in canine oral malignant melanoma.

Canine oral malignant melanoma (COMM) is considered a chemo-resistant cancer with a poor long-term prognosis. The melanoma-associated antigen A (MAGE-A) genes, which belong to the cancer-testis antigen family, are expressed in several different canine cancers but not in normal somatic tissue. This study evaluates the expression of MAGE-A proteins and their prognostic role in COMM. The study was conducted in 2 parts. During the first part, biopsies from oral malignant melanomas from 43 dogs were examined and immunohistochemically assessed for expression of MAGE-A proteins. For the second part, the association between MAGE-A expression and outcome was assessed using follow-up data which was available for 20 dogs whose primary tumour had been controlled with surgery +/- radiation therapy. MAGE-A proteins were expressed in 88.4% (38/43) of oral malignant melanomas and had a predominantly cytoplasmic expression pattern. Immunopositivity was observed in more than 50% of the cells in 21 dogs (48.8%). Immunostaining intensity was classified as weak, moderate and intense in 16 (37%), 16 (37%) and 6 (14%) cases, respectively. No staining for MAGE-A was seen in 5 dogs (11%). Dogs whose COMM had weak MAGE-A staining intensity had a median survival time (MST) of 320 days while this was 129 days for dogs with moderate and intense immunostaining (p = 0.161). Dogs whose COMM had >50% of positive staining neoplastic cells had an MST of 141 days and dogs with a staining <50% had an MST of 320 days (p = 0.164). MAGE-A expression did not influence survival in our cohort.

Investigation of thyroid function in dogs treated with the tyrosine kinase inhibitor toceranib.

Tyrosine kinase inhibitors are widely utilized in veterinary oncology for the treatment of mast cell and solid tumours. In man, these drugs are associated with thyroid dysfunction: however, to date only one study has investigated this in dogs. The aim of this study was to prospectively assess thyroid function in a group of dogs with cancer receiving toceranib. Thirty-four dogs were prospectively enrolled at two referral hospitals into two groups; those receiving toceranib with prednisolone and those receiving toceranib alone. Total thyroxine (TT4) and thyroid stimulating hormone (TSH) was monitored at regular time points during treatment. Follow-up data was available for 19 dogs. Overall, 12 incidences of elevated TSH occurred but none of these dogs had concurrent low TT4 concentrations. There was a significant difference in median TSH at week six compared with baseline. Hypothyroidism was not diagnosed in any patient during the study period. Patient drop-out was higher than anticipated which prevented the assessment of longer term toceranib administration on thyroid function. Toceranib therapy was not associated with hypothyroidism in this study but did result in elevations in TSH which confirms what has been previously reported. Toceranib should be considered to cause thyroid dysfunction in dogs and monitoring is advised.

Response and outcome following radiation therapy of macroscopic canine plasma cell tumours.

Thirty dogs with macroscopic plasma cell tumours (PCTs) were treated with radiation therapy (RT). Twelve patients were treated with palliative-intent prescriptions (range, 4-10 Gy/fraction (median, 7 Gy/fraction) for a total dose of 20 to 35 Gy (median total dose 30 Gy). Eighteen patients received definitive-intent prescriptions (range, 3.0-4.2 Gy/fraction (median, 3 Gy/fraction) for a total dose of 42 to 54 Gy (median total dose 48 Gy). Involved sites included the oral cavity, skin, multiple myeloma (MM)-associated lytic bone lesions, bone (solitary osseous plasmacytoma; SOP), nasal cavity, larynx, retrobulbar space, lymph node and rectum. Ninety-five percent of evaluable dogs had a complete (CR; 16/22) or partial response (PR; 5/22). Patients with MM experienced significant analgesia. The median progression-free survival (PFS) was 611 days (range: 36-2001 days). Events in the non-MM cases included in-field progression (5/26, 19%) and disseminated disease (5/26, 19%). The median survival time (MST) for all dogs was 697 days (range: 71-2075 days), and when only non-MM cases were considered, MST was 771 days (range: 71-2075 days). Fourteen patients were alive without disease progression or had died of unrelated causes. Achievement of a PR was associated with an inferior PFS and MST as compared with CR. Palliative-intent RT was associated with inferior MST as compared with definitive-intent RT. RT is a useful therapeutic modality for PCTs and tumour responses are often complete and durable, with protracted survivals. The optimal radiation dose and schedule are yet to be defined.

External beam radiotherapy for the treatment of feline salivary gland carcinoma: six new cases and a review of the literature.

CASE SERIES SUMMARY: Salivary gland carcinoma is uncommon in cats. We report the outcome of radiation therapy in six cases (four salivary gland adenocarcinomas, one tubulopapillary adenocarcinoma, one carcinoma). Five were treated after surgical excision of the primary tumour, but four had gross disease (primary or metastatic) at the time of starting radiotherapy. Exact progression-free interval from the start of radiotherapy in the two cats where this was known was 120 and 144 days, respectively. One cat was signed off at 766 days with no evidence of recurrence. Another cat was in remission at 202 days (when last seen by the referring practice) but subsequently developed recurrence (date uncertain). Survival time was known for three cats (55 days, 258 days and 570 days from initiation of radiotherapy, respectively). In two cases, locoregional progressive disease (PD) was confirmed, and the other presumed as the cause of death. Two cats, known to have developed PD, were alive at the time of writing (at 206 and 549 days, respectively). No cat died as a result of distant metastatic disease. RELEVANCE AND NOVEL INFORMATION: There is a paucity of information on the treatment of salivary gland tumours. In humans, as in cats, there is no optimised standard of care for malignant tumours. It is accepted that, for surgical candidates (even with large tumours), surgery and radiotherapy is superior to radiotherapy alone. However, the benefits of postoperative radiotherapy compared with surgery alone are only clear in patients with high-risk tumours (ie, those with large and invasive primary tumours, close or incomplete margins, high histopathological grade, histological evidence of neural or vascular invasion, or positive lymph nodes). This population is analogous to the population reported here, and likely to most cats presented in practice. Thus, radiation therapy may help improve locoregional control and survival in cats.

Non-islet-cell tumour hypoglycaemia in a cat with hepatocellular carcinoma.

CASE SUMMARY: An 11-year-old male neutered domestic shorthair cat presented with behavioural changes. Physical examination revealed bradycardia and a cranial abdominal mass. The cat was persistently hypoglycaemic (1.2 mmol/l; reference interval [RI] 3.5-5.5 mmol/l) with decreased fructosamine concentration suggesting chronic hypoglycaemia, and decreased insulin concentration excluding insulinoma. Alanine aminotransferase activity was markedly increased (1219.31 U/l; RI 15-60 U/l). On staging CT a large, multilobulated hepatic mass was identified, with no evidence of metastatic disease. After surgical removal serum glucose concentration and heart rate quickly returned to within the RIs. Histopathology was consistent with a solid-to-trabecular, well-differentiated, hepatocellular carcinoma. There was no recurrence of signs or mass during 8 months of follow-up, and the cat was still alive 20 months after surgery. RELEVANCE AND NOVEL INFORMATION: Non-islet-cell tumour hypoglycaemia (NICTH) is a rare but life-threatening paraneoplastic syndrome. In humans, hepatocellular carcinoma is the most common epithelial tumour causing NICTH, but these are uncommon in cats, and associated paraneoplastic hypoglycaemia has not been reported. Possible mechanisms include aberrant secretion of big insulin growth factor 2; however, this could not be confirmed. NICTH should be considered in the differential diagnosis of cats with persistent hypoglycaemia.

Evaluation of a multi-agent chemotherapy protocol combining dexamethasone, melphalan, actinomycin D, and cytarabine for the treatment of resistant canine non-Hodgkin high-grade lymphomas: a single centre's experience.

The DMAC protocol (dexamethasone, melphalan, actinomycin-D, cytarabine) has been evaluated in American studies for the treatment of relapsed canine lymphoma, comparing similarly to other rescue protocols. The aim of this study was to evaluate efficacy and toxicity of DMAC, in a larger UK cohort of resistant canine lymphomas. Medical records of dogs with resistant non-Hodgkin high-grade lymphomas that received DMAC as a rescue protocol were reviewed from 2007 to 2017. Response, time from initiation to discontinuation (TTD) and toxicity (Veterinary Cooperative Oncology Group criteria) were assessed. One hundred dogs were included; 86 received CEOP (modified CHOP including epirubicin) as first-line treatment. Thirty-five dogs (35%) responded: 21 complete responders (CRs) and 14 partial responders (PRs). Responders had significantly longer TTD (P < 0.001) compared with non-responders: 62 days (range 28-952) for CR vs 32 days (range 20-70) for PR. Six CR received more than six cycles of DMAC (range 7-36 cycles) and experienced a longer TTD (median 508, range 126-952 days). Thrombocytopenia occurred in 45% (24 grade 1-2, 21 grade 3-4) and neutropenia in 36% of cases (29 grade 1-2, 7 grade 3-4). Gastrointestinal toxicity occurred in 42% of dogs (40 grade 1-2, 2 grade 3-4). Owing to chemotherapy toxicity, treatment was discontinued in five, and hospitalization required in six cases. In this study, response to DMAC was lower and of generally shorter duration than previously reported. Toxicity was high, but infrequently led to hospitalization or discontinuation of treatment.

Owners 'perception of their cats' quality of life during COP chemotherapy for lymphoma.

Questionnaires regarding the perceptions of chemotherapy and its impact on the quality of life (QoL) of their cat were received from owners of 31 cats treated for lymphoma between 2002 and 2006 with COP (cyclophosphamide, vincristine, prednisolone) chemotherapy. The QoL scores prior to the onset of cancer (mean 9.5, range 6-10) were significantly higher than the ratings given after the onset of cancer but before commencement of chemotherapy (mean 3.9, range 1-9.4). The QoL scores during chemotherapy (mean 6.3, range 1-10) were also significantly lower than prior to the onset of cancer, but significantly higher during treatment than prior to starting treatment. Adverse effects were experienced by 27 (87%) cats during the course of chemotherapy. Twenty-five (83%) of clients were happy they treated their cat and 27 owners (87%) would treat another cat. The results suggest that COP chemotherapy is perceived by owners to be tolerated by cats.

Determination of serum fPLI concentrations in cats with diabetes mellitus.

Diabetes mellitus (DM) is one of the most common feline endocrinopathies. Pancreatitis is a reported cause for poor control of DM in cats; however, its prevalence in diabetic cats is unknown. Measurement of serum feline pancreatic lipase immunoreactivity (fPLI) has been proposed as a sensitive and specific test for the detection of pancreatitis in cats. The aim of this study was to assess fPLI concentrations in diabetic cats and compare these with non-diabetic cats of similar age. Samples from 29 cats with DM and 23 non-diabetic cats were analysed. Serum fPLI concentrations were significantly higher in samples from diabetic cats (P<0.01). A weak association was found between serum fructosamine and fPLI concentrations (R(2)=0.355, P=0.015), but there was no association between fPLI concentrations and the degree of diabetic control. There were no significant differences in reported clinical signs between cats with or without DM regardless of serum fPLI concentration. This is the first study to demonstrate elevated serum fPLI concentrations in cats with DM, suggesting that pancreatitis could be a significant comorbidity in these cats.

Use of recombinant human interferon alpha-2a in the management of a dog with epitheliotropic lymphoma.

An 8-year-old, mixed-breed dog with preputial epitheliotropic lymphoma was initially treated with cyclophosphamide, vincristine, and prednisolone. A short-term partial response was followed by disease progression after 4 weeks. Recombinant human interferon alpha-2a was administered starting at week 7. The interferon therapy resulted in rapid resolution of clinical signs and a 10-week disease-free interval. The lymphoma recurred at 17 weeks and did not respond to rescue chemotherapy. Additional oral lesions were treated with localized radiotherapy followed by increased dosages of interferon. This additional interferon treatment resulted in another 12 weeks of stable disease.

Identification of molecular genetic contributants to canine cutaneous mast cell tumour metastasis by global gene expression analysis.

Cutaneous mast cell tumours are one of the most common canine cancers. Approximately 25% of the tumours metastasise. Activating c-kit mutations are present in about 20% of tumours, but metastases occur in the absence of mutations. Tumour metastasis is associated with significantly diminished survival in spite of adjuvant chemotherapy. Available prognostic tests do not reliably predict whether a tumour will metastasise. In this study we compared the global expression profiles of 20 primary cutaneous mast cell tumours that metastasised with those of 20 primary tumours that did not metastasise. The objective was to identify genes associated with mast cell tumour metastatic progression that may represent targets for therapeutic intervention and biomarkers for prediction of tumour metastasis. Canine Gene 1.1 ST Arrays were employed for genome-wide expression analysis of formalin-fixed, paraffin-embedded biopsies of mast cell tumours borne by dogs that either died due to confirmed mast cell tumour metastasis, or were still alive more than 1000 days post-surgery. Decreased gene expression in the metastasising tumours appears to be associated with a loss of cell polarity, reduced cell-cell and cell-ECM adhesion, and increased cell deformability and motility. Dysregulated gene expression may also promote extracellular matrix and base membrane degradation, suppression of cell cycle arrest and apoptosis, and angiogenesis. Down-regulation of gene expression in the metastasising tumours may be achieved at least in part by small nucleolar RNA-derived RNA and microRNA-effected gene silencing. Employing cross-validation, a linear discriminant analysis-based classifier featuring 19 genes that displayed two-fold differences in expression between metastasising and non-metastasising tumours was estimated to classify metastasising and non-metastasising tumours with accuracies of 90-100% and 70-100%, respectively. The differential expression of 9 of the discriminator genes was confirmed by quantitative reverse transcription-PCR.