Mast cell tumours in dogs less than 12 months of age: a multi-institutional retrospective study.

OBJECTIVES: To describe the clinicopathological and genetic characteristics of mast cell tumours in dogs less than 12 months old. MATERIALS AND METHODS: Retrospective review of dogs aged less than 12 months when diagnosed with mast cell tumours at three referral hospitals in the UK. RESULTS: Sixteen pure-bred dogs were included, of which 11 were female. The median age at first presentation and diagnosis were 7.6 and 9 months, respectively. In 13 dogs the mast cell tumours were cutaneous and in three they were subcutaneous. Four cutaneous mast cell tumours were described as high-grade (Patnaik or Kiupel) and nine were Patnaik grade II; three had mitotic index of >5 in 10 high-power fields. Of the three subcutaneous tumours, two had an infiltrative growth pattern and one had mitotic index of 10 per 10 high-power fields. Of 10 tested dogs, seven had c-kit mutations in exon 11 and Ki-67 score was above the cut-off value in nine. Four of 12 cases showed evidence of metastasis in the regional lymph nodes. After varying treatment protocols, all patients were alive and disease free at a median of 1115 days after diagnosis. CLINICAL SIGNIFICANCE: The prognosis of mast cell tumours in dogs less than a year old appears better than the adult counterparts, even without extensive treatment.

Genicular artery axial pattern flap for reconstruction of skin defects in 22 dogs.

OBJECTIVE: To report the use of the genicular artery axial pattern flap and the frequency and severity of complications in a consecutive series of clinical cases. MATERIALS AND METHODS: Medical records from one referral centre were retrospectively reviewed for cases requiring reconstruction using a genicular axial pattern flap between January 2012 and February 2018. RESULTS: Twenty-two dogs were included. Skin defects ranging from 12.6 to 81 cm2 (mean 32 cm2 ) on the lateral and cranial crus were successfully closed using the genicular artery axial pattern flap. Average flap survival was 99.1% with two dogs developing distal flap necrosis. Minor complications occurred in eight dogs (36%) including minor wound dehiscence, seroma formation and infection. Major complications requiring further surgery occurred in three dogs (13.6%). CLINICAL SIGNIFICANCE: The genicular artery axial pattern flap is useful in the reconstruction of small- to medium-sized skin defects of the lateral and cranial crus. The flap may be more robust and offer better viability than reported previously in experimental studies.

Survival analysis of dogs with advanced primary lung carcinoma treated by metronomic cyclophosphamide, piroxicam and thalidomide.

Unresectable or metastatic (advanced) primary pulmonary carcinoma (PPC) represents a therapeutic challenge where surgery may be contraindicated and the therapeutic role of maximum-tolerated dose (MTD) chemotherapy remains uncertain. This study was undertaken to explore the impact of metronomic chemotherapy (MC) in dogs with advanced PPC. Previously untreated dogs with advanced (T3 or N1 or M1) PPC, with complete staging work-up and follow-up data, receiving MC (comprising low-dose cyclophosphamide, piroxicam and thalidomide), surgery, MTD chemotherapy or no oncologic treatment were eligible for inclusion. For all patients, time to progression (TTP) and survival time (ST) were evaluated. Quality-of-life (QoL) was only evaluated in patients receiving MC. To assess QoL, owners of dogs receiving MC were asked to complete a questionnaire before and during treatment. Ninety-one dogs were included: 25 received MC, 36 were treated with surgery, 11 with MTD chemotherapy and 19 received no treatment. QoL was improved in dogs receiving MC. Median TTP was significantly longer in patients receiving MC (172 days) than patients undergoing surgery (87 days), receiving MTD chemotherapy (22 days), or no oncologic treatment (20 days). Median ST was similarly longer in patients receiving MC (139 days) than those undergoing surgery (92 days), MTD chemotherapy (61 days) and no oncologic treatment (60 days). In dogs with advanced PPC, MC achieved a measurable clinical benefit without significant risk or toxicity. This makes MC a potential alternative to other recognized management approaches.

Prognostic significance of clinical presentation, induction and rescue treatment in 42 cases of canine centroblastic diffuse large B-cell multicentric lymphoma in the United Kingdom.

Canine lymphoma is a heterogeneous group of diseases and many previous studies have evaluated the response of a mixed population of lymphoma cases to one specific treatment protocol. The aim of this retrospective study was to describe the outcome and prognostic factors in 42 cases of multicentric centroblastic diffuse large B-cell lymphoma treated with either a COP-type (35%) or CHOP-type (64%) induction chemotherapy. The objective response rate to induction therapy was 94%; entire dogs had a greater rate of complete vs partial remissions than neutered dogs (P = .017). Median progression-free survival for the first remission (PFS1) was 182 days; absence of anaemia at diagnosis (P = .002) and pretreatment neutrophil:lymphocyte ratio (NLR) below 9.44 (P = .015) were independently predictive of longer PFS1. Fifty-eight percent of dogs received rescue protocols with an objective response rate of 81%; 31% of dogs received further rescue protocols (up to a total of 5) and the median number of protocols administered were 2. Median overall survival (OS) was 322 days, the 1-year survival rate was 38% and the 2-year survival rate was 9%. Lymphocyte:monocyte ratio above 1.43 (P = .031), NLR below 11.44 (P = .009), the combination of induction and rescue therapy (P = .030) and the total number of doxorubicin doses used (P = .002) were independently predictive of longer OS. Use of a COP-type protocol induction compared with CHOP did not undermine OS providing doxorubicin was used as rescue therapy.

Use of Oncept melanoma vaccine in 69 canine oral malignant melanomas in the UK.

OBJECTIVES: Oral malignant melanomas carry a poor-to-guarded prognosis because of their local invasiveness and high metastatic propensity. The Oncept melanoma vaccine is licensed to treat dogs with stage II or III locally-controlled oral malignant melanoma and this retrospective study aimed to assess survival of affected dogs treated with the vaccine in the UK. MATERIAL AND METHODS: Medical records of dogs with histopathologically-confirmed oral malignant melanoma that received the vaccine as part of their treatment were evaluated. Survival analyses for potential prognostic factors were performed. RESULTS: Sixty-nine dogs were included; 56 dogs, staged I to III, and with previous locoregional therapy, had a median survival time of 455 days (95% CI: 324 to 586 days). Based on Kaplan-Meier survival analysis with associated log-rank testing, no significant prognostic factors were identified for this population. Of the 13 patients with macroscopic disease treated with vaccine alone or in combination therapy, eight showed clinical response. Three patients with stage IV oral malignant melanoma survived 171, 178 and 288 days from diagnosis. CLINICAL SIGNIFICANCE: Patients treated with the melanoma vaccine in our study had survival times similar to their counterparts receiving the vaccine in the USA. There were observed responses in patients with macroscopic disease and so the vaccine could be considered as palliative treatment in dogs with stage IV disease.

Outcome in dogs with advanced (stage 3b) anal sac gland carcinoma treated with surgery or hypofractionated radiation therapy.

Stage 3b anal sac gland carcinoma (ASGC) can be life-threatening. A surgical approach is not always possible or may be declined. Dogs with stage 3b ASGC treated with surgery or conformal radiation therapy (RT) with 8 × 3.8 Gy (total dose 30.4 Gy, over 2.5 weeks) were retrospectively evaluated. Patient characteristics, median progression-free interval (PFI) and median survival time (MST) were compared. Twenty-eight dogs were included; 15 underwent surgery, 13 underwent RT. At the time of presentation, 21% showed life-threatening obstipation and 25% showed hypercalcaemia. PFI and MST for surgery cases were 159 days (95% CI: 135-184 days) and 182 days (95% CI: 146-218 days), both significantly lower than for RT cases with 347 days (95% CI: 240-454 days) and 447 days (95% CI: 222-672 days), (P = 0.01, P = 0.019). Surgery as well as RT led to a fast relief of symptoms. PFI and survival of surgical patients were significantly inferior to that of a comparable patient group treated with conformal hypofractionated RT.

Clinical outcome, PDGFRß and KIT expression in feline histiocytic disorders: a multicentre study.

Information about histiocytic disease in cats is limited. The aim of this study was to document clinical findings and outcome in feline histiocytic disorders, and characterize the expression of PDGFRß and KIT in order to identify potential treatment targets. Morphologically diagnosed feline histiocytic tumours were reviewed and characterized by immunohistochemistry (IHC). Five cases of feline progressive histiocytosis (FPH), eight histiocytic sarcomas (HS) and two haemophagocytic histiocytic sarcomas (HaeHS) were confirmed. PDGFRß was variably positive in most histiocytic cases, while KIT was negative in all. Clinical presentation, treatment and outcome were also evaluated. Partial responses were recorded in measurable disease with tyrosine kinase inhibitors and lomustine, and radiotherapy achieved long-term control in some cases. Survival times were shortest in HaeHS and disseminated disease. PDGFRß, but not KIT, may represent a therapeutic target in feline histiocytic disorders but more studies are needed to investigate other potential treatment targets.

Conformity and controversies in the diagnosis, staging and follow-up evaluation of canine nodal lymphoma: a systematic review of the last 15 years of published literature.

Diagnostic methods used in the initial and post-treatment evaluation of canine lymphoma are heterogeneous and can vary within countries and institutions. Accurate reporting of clinical stage and response assessment is crucial in determining the treatment efficacy and predicting prognosis. This study comprises a systematic review of all available canine multicentric lymphoma studies published over 15 years. Data concerning diagnosis, clinical stage evaluation and response assessment procedures were extracted and compared. Sixty-three studies met the eligibility criteria. Fifty-five (87.3%) studies were non-randomized prospective or retrospective studies. The survey results also expose variations in diagnostic criteria and treatment response assessment in canine multicentric lymphoma. Variations in staging procedures performed and recorded led to an unquantifiable heterogeneity among patients in and between studies, making it difficult to compare treatment efficacies. Awareness of this inconsistency of procedure and reporting may help in the design of future clinical trials.

Immunohistochemical Labelling for Cyclo-oxygenase-2: Does the Positive Control Guarantee Standardized Results?

Since the identification of cyclo-oxygenase-2 as a potentially important therapeutic target in veterinary oncology, numerous studies on its expression have been conducted. Unfortunately, results have been heterogeneous and conclusions are difficult to draw. We tested the ability of a defined positive control to guarantee reproducibility of results among different laboratories. Valid positive controls were defined by positivity of the renal macula densa without background labelling. Fifteen colorectal tumours and 15 oral squamous cell carcinomas were labelled immunohistochemically by six European laboratories. Slides were evaluated in blinded fashion for percentage of positive cells and labelling intensity by three pathologists, and results were analyzed statistically for reproducibility and inter-reader variability. Macula densa positivity was an insufficiently sensitive control to guarantee reproducible results for percentage of positive cells and labelling intensity. Inter-reader variability was proven statistically, making the case for image analysis or other automated quantitative evaluation techniques.

Neoadjuvant and adjuvant chemotherapy combined with anatomical resection of feline injection-site sarcoma: results in 21 cats.

This study assesses the outcome of two combined treatment strategies for the treatment of feline injection-site sarcoma (FISS). Twenty-one cats with primary or recurrent FISS received 3 cycles of neoadjuvant chemotherapy with epirubicin (25 mg m(-2) ), then an anatomical resection of the entire muscle compartment containing the tumour was performed based on the findings of co-axial imaging. Cats then received a further 3 cycles of adjuvant chemotherapy. Follow-up was performed by telephone contact with a median follow-up time of 1072 days. Three cats (14%) developed local tumour recurrence at days 264, 664 and 1573 after surgery. A median survival time could not be calculated as over 80% of the study population remained alive or were censored due to death from other causes. When compared to historical controls, the results of this study demonstrate superior rates of tumour-free survival and disease-free interval.

Chest wall reconstruction with latissimus dorsi and an autologous thoracolumbar fascia graft in a dog.

A new technique for autogenous chest wall reconstruction using a latissimus dorsi muscle flap and a free graft of thoracolumbar fascia was utilised in a two-year-old Dobermann after resection of a high-grade osteosarcoma from the left thoracic wall. En bloc excision of the chest wall mass, including six ribs, was performed. The resulting chest wall defect was too large to be reconstructed with only a pedicled muscle flap and was reconstructed with a latissimus dorsi muscle flap cranially and a free graft of thoracolumbar fascia caudally. The graft was harvested easily, and there was no donor site morbidity or postoperative complications. A free graft of thoracolumbar fascia can be considered as an option to supplement autogenous reconstruction of the chest wall.

Temporally separated bilateral anal sac gland carcinomas in four dogs.

Anal sac gland carcinoma arising from the apocrine secretory epithelium in the anal sac wall, is locally invasive and highly metastatic. The majority of anal sac gland carcinomas are unilateral on presentation, but bilateral tumours have been identified. This case series presents the outcome of four unique cases of unilateral anal sac gland carcinoma which subsequently developed contralateral anal sac gland carcinoma 50 to 390 days after removal of the initial tumour. Median survival was 1035 days after initial diagnosis and 807 days after diagnosis of the second anal sac gland carcinoma.

Rectal lymphoma in 11 dogs: a retrospective study.

OBJECTIVES: To retrospectively evaluate the clinical behaviour and immunophenotype of lymphoma of the rectum in dogs. METHODS: Eleven dogs diagnosed with lymphoma of the rectum on histopathology were retrospectively reviewed. Immunohistochemistry with CD3 and CD79a antibodies was performed at diagnosis or retrospectively. RESULTS: Treatment protocol varied with six dogs undergoing surgery and adjuvant chemotherapy, two received chemotherapy after only incisional biopsy, one had surgical resection only, one was treated symptomatically and one dog was not treated. Chemotherapy treatment consisted of either a -low-dose COP (cyclophosphamide - prednisolone - vincristine) protocol (four dogs) or a six-week CHOP-based (cyclophosphamide - vincristine - -prednisolone - anthracycline) protocol (four dogs). Dogs that received chemotherapy lived significantly longer than dogs that did not receive chemotherapy (2352 versus 70 days). Median survival time was not reached, and there was an overall mean survival time of 1697 days. Immunohistochemistry was performed in 10 of 11 samples, and was consistent with B-cell -lymphoma in all cases. CLINICAL SIGNIFICANCE: Canine lymphoma of the rectum is associated with a favourable prognosis. Immunohistochemical evaluation of these lesions was consistent with B-cell lymphoma in all cases in which it was examined.

A randomized trial investigating the efficacy and safety of water soluble micellar paclitaxel (Paccal Vet) for treatment of nonresectable grade 2 or 3 mast cell tumors in dogs.

BACKGROUND: Effective treatments for dogs with advanced stage mast cell tumors (MCT) remain a pressing need. A micellar formulation of paclitaxel (paclitaxel [micellar]) has shown promise in early-phase studies. HYPOTHESIS/OBJECTIVES: The objective was to demonstrate greater activity for paclitaxel (micellar) compared with lomustine. The null hypothesis was µ(p) = µ(L) (ie, proportion of responders for the paclitaxel [micellar] and lomustine groups, respectively). ANIMALS: Two hundred and fifty-two dogs with advanced stage nonresectable grade 2 or 3 MCT. METHODS: Prospective multicenter randomized double-blind positive-controlled clinical trial. The primary endpoint was confirmed overall response rate (CORR) at 14 weeks. A secondary endpoint, biologic observed response rate (BORR), also was calculated. Safety was assessed by the characterization and grading of adverse events (AE). RESULTS: Overall CORR (7% versus 1%; P = .048) and BORR (23% versus 10%; P = .012) were greater for paclitaxel (micellar) compared with lomustine. Paclitaxel (micellar)-treated dogs were 6.5 times more likely to have a confirmed response and 3.1 times more likely to experience a biologic observed response. The majority of AE with paclitaxel (micellar) were transient and clinically manageable. Twenty-seven dogs (33%) receiving lomustine were discontinued because of hepatopathy compared with 3 dogs (2%) receiving paclitaxel (micellar) (P < .0001; odds ratio 26.7). CONCLUSIONS AND CLINICAL IMPORTANCE: Paclitaxel (micellar)'s activity and safety profile are superior to lomustine. The addition of an active and novel taxane to the veterinary armamentarium could fill a substantial need and, as its mechanism of action and AE profile do not overlap with currently available TKI, its availability could lead to effective combination protocols.

Canine tonsillar squamous cell carcinoma -- a multi-centre retrospective review of 44 clinical cases.

OBJECTIVES: To review the presenting clinical signs, treatment and survival of dogs with tonsillar squamous cell carcinoma and, if possible, to identify useful prognostic indicators. METHODS: Medical records of 44 dogs were reviewed retrospectively. Clinical signs, clinical stage, time of diagnosis, treatment and outcome were recorded. Data were analysed using the Kaplan-Meier, log-rank, Student's t test, Kruskal-Wallis test and Chi-square/Fisher Exact test as appropriate. RESULTS: The most frequent clinical signs were cough (12 dogs, 27%), enlarged lymph nodes (11 dogs, 25%) and dysphagia (11 dogs, 25%). Anorexia and lethargy were less common but were significantly associated with a poor outcome. No matter what treatment modalities were used, survival times were short and median survival time for all the dogs in the study was 179 days. However, there were a small number of long-term survivors. CLINICAL SIGNIFICANCE: Dogs with tonsillar squamous cell carcinoma that suffered anorexia and lethargy had shorter survival times than patients without these clinical signs. Although surgery, chemotherapy and radiotherapy seem to increase the median survival time of dogs diagnosed with tonsillar squamous cell carcinoma, there is no highly effective treatment for canine tonsillar squamous cell carcinoma.

Association between anal sac gland carcinoma and dog leukocyte antigen-DQB1 in the English Cocker Spaniel.

Anal sac gland carcinomas occur frequently in English Cocker Spaniels and, to a lesser extent, in other spaniel breeds. The disease typically presents in dogs aged 8 years or older and frequently metastasises to the local lymph nodes. The association between anal sac gland carcinoma in English Cocker Spaniels and the major histocompatibility complex class II loci (the dog leukocyte antigen loci DLA-DRB1, -DQA1, -DQB1) was investigated in 42 cases and 75 controls. Based on a corrected error rate of 0.017 for each test, the allele distribution in DLA-DRB1 showed no significant difference between cases and controls (P value = 0.019), while a significant difference was obtained for DLA-DQA1 and -DQB1 alleles (P values are 0.010 and 3.3 × 10⁻5). The DLA-DQB1*00701 allele was the most common in both cases and controls, but it had a higher frequency among the former (0.89) than in the latter (0.61), while the second most common allele had a higher frequency in the controls (0.23) than in the cases (0.07). Haplotype distributions were also significantly different between the two groups (P value = 1.61 × 10⁻4). This is the second disease in English Cocker Spaniels for which the most common DLA-DQB1 allele in the breed has been shown to have a higher frequency in cases than controls, while the second most common allele in the breed (*02001) has a significantly higher frequency in the controls, compared with the cases.

Outcome following removal of canine spindle cell tumours in first opinion practice: 104 cases.

OBJECTIVES: To define the outcome of a cohort of canine patients with a histological diagnosis of spindle cell tumour of soft tissue managed solely by surgery in first opinion practice. METHODS: Clinical details of 104 spindle cell sarcomas submitted to Finn Pathologists during the year 2000 were reviewed. Questionnaires were sent to the submitting veterinarians, requesting details about the tumour, surgery performed and ultimate outcome of the patient. RESULTS: The method of surgical resection was described as marginal in 45 dogs (44.2 per cent). Excision margins of 3 cm or more were described in less than 10 per cent of cases. Tumours recurred locally in 29 dogs (27.9 per cent). Eighteen dogs (21.7 per cent) died of tumour-related causes. Most deaths were unrelated to sarcoma (50 dogs, 60.2 per cent) or unknown (15 dogs, 18 per cent). The median survival time was 1013 days. Tumour size, location or degree of surgical resection were not significantly related to survival or tumour recurrence. A palpable assessment of tumour invasion into underlying tissues was significantly associated with decreased disease-free interval (P<0.0001) and survival time (P = 0.0070). CLINICAL SIGNIFICANCE: The results of this retrospective study indicate that many spindle cell tumours managed in first opinion practice exhibit a low-grade biological behaviour and may respond well to more conservative surgery than current recommendations advise.

Variation in position of the medial fabella in West Highland white terriers and other dogs.

OBJECTIVES: To investigate whether West Highland white terriers exhibit significant variation in the position of the medial fabella compared to both small and large breed dogs. METHODS: Criteria for the normal location of the medial fabella on a caudocranial radiograph were established. A retrospective analysis was undertaken of a consecutive series of bilateral caudocranial stifle joint radiographs from 70 West Highland white terriers, 100 small and 100 large control dogs by three reviewers. Medial fabellar location, cruciate ligament disease and medial patellar luxation were examined within and between groups. RESULTS: Abnormal medial fabellar location was identified in 70 per cent, 9 per cent and 0 per cent of West Highland white terriers, small dogs and large dogs, respectively. In the vast majority of the affected dogs, the fabella was found in a mediodistal location. Presence of concurrent cranial cruciate ligament disease or medial patellar luxation and body weight was excluded as confounding factors. CLINICAL SIGNIFICANCE: West Highland white terriers appear predisposed to, and have a high prevalence of, an abnormal mediodistal location of the medial fabella. The authors suggest this is an incidental finding and should not be confused with true pathological fabellar displacement.