Angiofibroma of the nasal cavity in 13 dogs

This case series describes a rare entity, nasal angiofibroma, in 13 dogs that were presented to the University of Wisconsin, School of Veterinary Medicine from 1988 to 2000. All dogs in this case series presented with clinical signs and radiographic changes that were strongly suggestive of a locally invasive neoplasm. However, histopathology completed on transnostral core biopsy samples revealed benign appearing vascular proliferation with secondary lymphosuppurative inflammation was established despite cytologic criteria of malignancy present in five dogs. On the basis of the outcomes in this case series, nasal angiofibroma should be considered a differential for dogs presenting with clinical signs consistent with a malignant nasal tumour.     

Outcome following treatment of soft tissue and visceral extraskeletal osteosarcoma in 33 dogs: 2008–2013

Extraskeletal osteosarcoma (EOS) is a rare, highly malignant mesenchymal neoplasm arising from viscera or soft tissues characterised by the formation of osteoid in the absence of bone involvement. Owing to the rarity of these neoplasms very little information exists on treatment outcomes. The purpose of this study was to describe the outcome following surgical treatment of non‐mammary and non‐thyroidal soft tissue and visceral EOS in dogs. Thirty‐three dogs were identified; the most common primary tumour site was the spleen. Dogs that had wide or radical tumour excision had longer survival times compared with dogs that had only marginal tumour excision performed [median survival time of 90 days (range: 0–458 days) versus median survival time of 13 days (range: 0–20 days)]. The use of surgery should be considered in the management of dogs with non‐mammary and non‐thyroidal soft tissue and visceral EOS.     

Identification of occult micrometastases and isolated tumour cells within regional lymph nodes of previously diagnosed non‐metastatic (stage 0) canine carcinomas

Metastatic dissemination of carcinomas to lymph nodes impacts prognosis and treatment recommendations in human and veterinary medicine. Routine histopathologic evaluation of regional lymph nodes involves haematoxylin and eosin (H&E) staining to identify intra‐nodal neoplastic cells; however, identification of small volume metastases (micrometastases and individual tumour cells) may be missed without the aid of immunohistochemistry or additional step‐sections. The aim of this study was to identify occult carcinoma metastases in previously diagnosed non‐metastatic lymph nodes using step‐sections and pancytokeratin (panCK) immunohistochemistry. Samples from 20 regional lymph nodes diagnosed as non‐metastatic were serially sectioned and evaluated with panCK. Of these, 25% (n = 5) contained micrometastases (n = 1) or isolated tumour cells (n = 4). This study demonstrates the increased efficacy of serial step‐sections combined with panCK immunohistochemistry to identify small volume metastases in regional lymph nodes. The prognostic significance of micrometastases and isolated tumour cells in regional lymph nodes warrants further investigation in veterinary medicine.     

Ultrasound and computed tomography of the iliosacral lymphatic centre in dogs with anal sac gland carcinoma

In this prospective study, we hypothesized that computed tomography (CT) would identify more normal and abnormal iliosacral lymph nodes (LNs) than abdominal ultrasound in dogs with anal sac gland carcinoma (ASGC). Twelve client‐owned dogs with ASGC but without distant metastasis were enrolled. Abdominal ultrasound and contrast‐enhanced CT scans of the abdomen were obtained. Iliosacral LNs were counted and assessed for location, laterality and size. Significantly (P < 0.00001) more iliosacral LNs were identified with CT (61) than ultrasound (30), including significantly (P = 0.00012) more medial iliac LNs with CT (33) than ultrasound (19). There was no difference in number of internal iliac LNs identified with CT versus ultrasound. Significantly (P = 0.000061) more sacral LNs were identified with CT (15) than ultrasound (0). Ultrasound identified slightly more (7) abnormal iliosacral LNs than CT (5). Contrast CT was able to identify more normal but not more abnormal LNs than ultrasound.     

Retrospective study evaluating the efficacy of stereotactic body radiation therapy for the treatment of confirmed or suspected primary pulmonary carcinomas in dogs

Canine primary pulmonary carcinomas (PCCs) are commonly treated with surgery with overall median survival times (MST) around a year; however, due to extent of disease, prognosis, or client preference, alternative treatments have been considered. Stereotactic body radiation therapy (SBRT) has been utilized in human cancer patients for local control of lung tumours as a surgical alternative. Twenty-one PCCs in 19 dogs that received SBRT for local control were retrospectively evaluated. Dogs were staged according to the canine lung carcinoma stage classification (CLCSC) system with three as Stage 1, five as Stage 2, three as Stage 3, and eight as Stage 4. Overall MST was 343 days with 38% of patients alive at 1 year. Stage did not significantly impact survival time (p = .72). Five (26%) dogs had lymphadenopathy and MST was not significantly different from dogs without lymphadenopathy (343 vs. 353 days; p = .54). Five out of 18 evaluable dogs (28%) experienced acute lung VRTOG effects and 2 of 12 dogs (17%) experienced late lung VRTOG effects. Median lung dose, V5, V20, and D30 to the lung did not correlate significantly with the development of adverse radiation events. Twelve dogs had follow-up imaging and the best response included a complete response (17%), partial response (42%), and stable disease (42%). Progressive disease was noted in seven dogs a median of 229 days after SBRT. SBRT was documented to be a safe and effective alternative to surgery and may have survival advantages for Stage 3 or 4 dogs according to the CLCSC.     

Association of prognostic features and treatment on survival time of dogs with systemic mastocytosis: A retrospective analysis of 40 dogs

Systemic mastocytosis is a rare phenomenon, with limited information regarding prognostic features and effective treatment of canine patients with this disease. The objective of this study is to determine the impact of certain features and treatments on dogs with systemic mastocytosis. The medical records of 40 dogs from 4 northeastern US veterinary hospitals, with evidence of systemic mast cell disease, were evaluated retrospectively. Variables analysed with relation to overall survival and prognostic significance included treatment protocol used, substage, presence of a cutaneous or visceral tumour, presence of multiple cutaneous Mast cell tumours, grade of the primary tumour and metastatic site(s). Dogs with metastatic disease confined to distant lymph nodes lived longer than those with circulating mast cells in the blood (P = .001), and those with metastatic disease evident in more than 2 sites had a worse prognosis than those with disease in a single location (P = .005). Additionally, administration of chemotherapeutic agents led to increased survival over prednisone therapy alone (P = .008), with the combination of lomustine, vinblastine and prednisone prolonging survival over the tyrosine kinase inhibitor, toceranib phosphate (P = .002). Presence of mast cells in the blood and/or evidence of disease in more than 2 sites indicate widespread dissemination suggesting their use as negative prognostic features. Furthermore, a chemotherapy protocol including combination lomustine and vinblastine therapy may be more effective than toceranib phosphate for the treatment of dogs with disseminated mast cell disease. Overall, patients with systemic mastocytosis have a grave prognosis and more effective treatment options are needed.     

Cytological lymph node evaluation in dogs with mast cell tumours: association with grade and survival*

The purpose of this retrospective cohort study is to describe the association of cytological assessment of lymph node metastasis with survival and tumour grade in dogs with mast cell tumours. Regional lymph node aspirates of 152 dogs diagnosed with a mast cell tumour were reviewed and classified according to specific cytological criteria for staging. 97 dogs (63.8%) had stage I tumours, and 55 (36.2%) had stage II tumours. Stage II dogs had a significantly shorter survival time than dogs with stage I disease (0.8 and 6.2 years, respectively; P < 0.0001). Dogs with grade III mast cell tumours were more likely to have stage II disease (P = 0.004). These results suggest that cytological evaluation of lymph nodes in dogs with mast cell tumours provides useful and valuable clinical information, and the results correlate with tumour grade and outcome thus providing a practical and non‐invasive method for staging.     

Response evaluation criteria for solid tumours in dogs (v1.0): a Veterinary Cooperative Oncology Group (VCOG) consensus document

In veterinary medical oncology, there is currently no standardized protocol for assessing response to therapy in solid tumours. The lack of such a formalized guideline makes it challenging to critically compare outcome measures across various treatment protocols. The Veterinary Cooperative Oncology Group (VCOG) membership consensus document presented here is based on the recommendations of a subcommittee of American College of Veterinary Internal Medicine (ACVIM) board‐certified veterinary oncologists. This consensus paper has used the human response evaluation criteria in solid tumours (RECIST v1.1) as a framework to establish standard procedures for response assessment in canine solid tumours that is meant to be easy to use, repeatable and applicable across a variety of clinical trial structures in veterinary oncology. It is hoped that this new canine RECIST (cRECIST v1.0) will be adopted within the veterinary oncology community and thereby facilitate the comparison of current and future treatment protocols used for companion animals with cancer.     

Quality of life assessment in dogs and cats receiving chemotherapy – a review of current methods

This study aimed to review currently reported methods of assessing the effects of chemotherapy on the quality of life (QoL) of canine and feline patients and to explore novel ways to assess QoL in such patients in the light of the experience to date in human pediatric oncology. A qualitative comparative analysis of published papers on the effects of chemotherapy on QoL in dogs and cats were conducted. This was supplemented with a comparison of the parameters and domains used in veterinary QoL‐assessments with those used in the Pediatric Quality of Life Inventory (PedsQL^?) questionnaire designed to assess QoL in toddlers. Each of the identified publications including QoL‐assessment in dogs and cats receiving chemotherapy applied a different method of QoL‐assessment. In addition, the veterinary QoL‐assessments were mainly focused on physical clinical parameters, whereas the emotional (6/11), social (4/11) and role (4/11) domains were less represented. QoL‐assessment of cats and dogs receiving chemotherapy is in its infancy. The most commonly reported method to assess QoL was questionnaire based and mostly included physical and clinical parameters. Standardizing and including a complete range of potentially relevant parameters in future QoL assessments may benefit owner decision making.     

Gastric carcinoma in canines and humans,a review

Gastric carcinoma (GC) is the most common neoplasm in the stomach of dogs. Although incidence in the general population is reported to be low, breed‐specific GC has a high incidence. Median age at presentation ranges from 8 to approximately 10 years. The disease is mostly located in the lesser curvature and antropyloric region of the stomach. Unfortunately, diagnosis is usually made when the disease is at an advanced stage and, therefore, prognosis is poor. Due to similarities in clinical presentation, diagnosis, histology and prognosis, canine GC may serve as a valuable model for human GC. Extensive pedigrees of canine gastric carcinoma cases could reveal insights for human gastric carcinoma. Putative species differences include the role of Helicobacter in pathogenesis, the wide array of genetic data and screening available for humans, and treatment protocols that are available for human GC.     

Plasma biomarkers profile of female dogs with mammary carcinoma and its association with clinical and pathological features

The immunological biomarkers profiles were evaluated using Luminex as putative measures to monitor canine mammary carcinomas (MCs). Forty female dogs were categorized into benign mixed tumour (MC‐BMT = 28) and mammary carcinoma (MC=12). The ascendant biomarker signatures were used to compare the groups. For example, a higher frequency of MC‐BMT animals producing IL‐6, CXCL‐8 and CXCL‐10 was observed, whereas for the MC group IL‐2 and CXCL‐8 were detected. MC‐BMT animals without metastasis had an increase in the levels of IL‐2, CXCL‐8, CXCL‐10, IL‐6, TNF‐α, IL‐15 and a decrease in IL‐10 and CXCL‐8. MC‐BMT animals with metastasis showed only an increase in CXCL‐10 and a decrease in IL‐18. After comparing the ascendant signatures following the presence of metastasis in both groups, a higher frequency of dogs exhibiting IL‐10 production was observed. Pearson correlation (P = 0.0273) and receiver operating characteristic (ROC) curve analysis revealed that this pattern was associated with worse outcome and lower survival rates in MC animals.     

Inter‐ and intra‐rater reliability and agreement in determining subcutaneous tumour margins in dogs

The objective of this prospective study was to evaluate agreement and reliability of calliper‐based measurements of locally invasive subcutaneous malignant tumours in dogs. Four raters measured the longest diameter of 12 subcutaneous tumours (7 soft tissue sarcomas and 5 mast cell tumours) from 11 client‐owned dogs during 3 randomized, blinded measurement trials, both pre‐ and post‐sedation. Inter‐ and intra‐rater reliability was evaluated using intra‐class correlation coefficient (ICC) and agreement was evaluated using Bland‐Altman plots. Inter‐ and intra‐rater reliability was good (ICC range of 0.8694‐0.89520) and excellent (ICC range of 0.9720‐0.9966), respectively. For agreement calculations, an a priori clinically relevant limit of agreement of 10 mm was set. Inter‐ and intra‐rater agreement was unacceptable with inter‐rater limits of agreement ranging from 15.9 to 55.6 mm and intra‐rater limit of agreement ranging from 11.9 to 28.1 mm. Review of the measurement trial photographs revealed that calliper orientation changes were frequent, occurring in 9/12 (75%) and 8/12 (67%) pre‐ and post‐sedation cases. No significant correlation was found between inter‐rater measurement standard deviations and calliper orientation changes or dog body condition score. These findings suggest veterinarians may have poor agreement in determining the gross edge of tumours, which is expected to introduce bias and inconsistency in tumour staging, assessing response to therapy, and surgical margin planning. Due to the potential consequences for veterinary cancer patients, future studies are needed to validate the present findings.     

Prognostic impact of neoadjuvant aglepristone treatment in clinicopathological parameters of progesterone receptor‐positive canine mammary carcinomas

Neoadjuvant treatment of canine mammary carcinomas with the progesterone receptor (PR) antagonist aglepristone has a PR expression‐related inhibiting effect on proliferation index (PI). The aim of this study was to evaluate the effect of the treatment in the disease‐free period (DFP) and overall survival (OS) of canine mammary carcinomas. Fifty female dogs with mammary carcinomas were treated with aglepristone (n = 34) or oil vehicle (n = 16) before surgery (day 15). PR expression and PI were analysed by immunohistochemistry in samples taken at days 1 and 15. Epidemiological and clinicopathological data were assessed. DFP and OS data were retrieved every 4–6 months for at least 24 months after surgery. Aglepristone treatment increased DFP of animals bearing PR+ tumours with size smaller than 3 cm, complex and mixed tumours, with histologic grades I and II, and with PI ≤ 10%. Although further studies are necessary, current evidence points to treatment with aglepristone as useful for the management of canine mammary tumours.     

Comparison of two questionnaires to assess gastrointestinal toxicity in dogs and cats treated with chemotherapy*

Questionnaires completed by pet owners are widely used instruments to monitor adverse gastrointestinal (GI) effects in the owners' animals undergoing chemotherapy and for reporting toxicoses in clinical trials; however, no questionnaires have been formally evaluated. This study compares two questionnaire-based evaluations of adverse GI events: a basic, open-ended questionnaire and a detailed questionnaire modelled after the grading in the Veterinary Co-operative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE). Owners completed both questionnaires after their dog or cat received moderately emetogenic chemotherapy. Results were used to derive toxicity grades for anorexia, vomiting and diarrhoea. We evaluated 123 pairs of questionnaires. Disagreement in grade of anorexia, vomiting and diarrhoea was found in 24, 7 and 13% of paired questionnaires, respectively (κ = 0.63, 0.83 and 0.71, respectively). Although 'good' to 'very good' agreement was found, the potential for only 'fair' agreement between questionnaire methods is of concern and suggests a need to adopt a standardized form.     

The use of novel lymphatic endothelial cell‐specific immunohistochemical markers to differentiate cutaneous angiosarcomas in dogs

Lymphangiosarcomas are uncommon vascular neoplasms that arise from lymphatic endothelial cells (LECs). They efface and replace normal subcutaneous tissue and are characterised by arborising, vascular channels lined by a single layer of pleomorphic endothelial cells and a paucity of erythrocytes. Lymphangiosarcomas are architecturally similar to hemangiosarcomas, a common malignancy of vascular origin arising from blood vascular endothelial cells. Common immunohistochemical markers for vascular endothelium, such as Factor VIII‐related antigen (F8RA) and CD31, have traditionally been used to confirm the diagnosis of tumours of vascular origin. However, these markers fail to differentiate between lymphangiosarcoma and hemangiosarcoma, which often show overlapping morphologic features, disparate clinical behaviour and require different treatment modalities. Here we describe the use of two novel LEC‐specific markers, lymphatic vessel endothelial receptor‐1 (LYVE‐1) and prospero‐related homeobox gene‐1 (PROX‐1), to further differentiate between vascular tumours of lymphatic (lymphangiosarcoma) and blood (hemangiosarcoma) endothelial cell origin in the dog.     

Evaluation of optimal water fluoridation on the incidence and skeletal distribution of naturally arising osteosarcoma in pet dogs

Experimental toxicological studies in laboratory animals and epidemiological human studies have reported a possible association between water fluoridation and osteosarcoma (OSA). To further explore this possibility, a case‐control study of individual dogs evaluated by the UC Davis Veterinary Medical Teaching Hospital was conducted using ecologic data on water fluoridation based on the owner's residence. The case group included 161 dogs with OSA diagnosed between 2008–2012. Two cancer control groups included dogs diagnosed with lymphoma (LSA) or hemangiosarcoma (HSA) during the same period (n = 134 and n = 145, respectively). Dogs with OSA were not significantly more likely to live in an area with optimized fluoride in the water than dogs with LSA or HSA. Additional analyses within OSA patients also revealed no significant differences in age, or skeletal distribution of OSA cases relative to fluoride status. Taken together, these analyses do not support the hypothesis that optimal fluoridation of drinking water contributes to naturally occurring OSA in dogs.     

Use of CD9 and CD61 for the characterization of AML‐M7 by flow cytometry in a dog*

Acute megakaryoblastic leukaemia (AML‐M7) is a rare myeloproliferative disorder in domestic animals. Recently, thanks to the greater availability of immunophenotype techniques, precise diagnosis is more easily made. The morphological evaluation has its limitations, especially in the study of poorly differentiated cells. Few reports have described AML‐M7 in dogs using flow cytometry. This clinical case points out the utility of flow cytometry in the characterization of AML‐M7 in a 3‐year‐old German Shepherd dog. Flow cytometry investigation has established megakaryocytic lineage involvement by showing the presence of two megakaryocyte/platelet associated antigens (CD9 and CD61). In human medicine CD9 may be used as a platelet and megakaryocyte marker. There is an evidence of cross‐reactivity of human anti‐CD9 monoclonal antibody with canine samples. To our knowledge, the use of CD9 has never been described before, for this purpose in the dog.     

A retrospective analysis of the efficacy of Oncept vaccine for the adjunct treatment of canine oral malignant melanoma

Oral malignant melanoma (OMM) in the dog is often locally aggressive with a high metastatic potential and there are few treatment options that have been demonstrated to improve outcome of this disease. The purpose of this study was to determine whether adjunctive treatment with the Oncept melanoma vaccine affected the outcome of dogs with OMM that had achieved loco‐regional cancer control. Medical records from 45 dogs that presented to the Animal Cancer and Imaging Center were reviewed, including 30 dogs with stage II and III disease. Dogs that received the vaccine did not achieve a greater progression‐free survival, disease‐free interval or median survival time than dogs that did not receive the vaccine.     

A prospective evaluation of the impact of second‐opinion histopathology on diagnostic testing,cost and treatment in dogs and cats with cancer

Second‐opinion histopathology is a common practice in human medicine to avoid unnecessary procedures, costs and to optimize therapy. Histopathology review has been recommended in veterinary oncology as well. In this prospective evaluation of 52 tumours over a 1‐year period, there was diagnostic agreement between first and second opinions in 52% of cases. Twenty‐nine percent of cases had partial diagnostic disagreement, most often a change in grade, tumour subtype or margin status. Nineteen percent had complete diagnostic disagreement, including a change in cell of origin or a change from benign to malignant. Minor disagreements, which would not affect treatment or prognosis, were present in 21% of cases. Major disagreements, which would affect either treatment or prognosis, were present in 37% of cases. Costs of ideal staging and treatment recommendations were considerably different between first and second opinions.     

Pulmonary metastatectomy in the management of four dogs with hypertrophic osteopathy

The efficacy and outcome of pulmonary metastatectomy in the management of hypertrophic osteopathy (HO) secondary to metastatic osteosarcoma was retrospectively evaluated in four dogs. Metastatectomy was performed by subpleural enucleation, partial lung lobectomy or complete lung lobectomy through either a median sternotomy or thoracoscopically. Perioperative morbidity was minimal. Clinical signs associated with HO resolved within 24 h of pulmonary metastatectomy in all dogs. Durable remission of symptomatic HO was achieved in all dogs (range, 50–294 days), although recurrence of HO was noted in one dog, 246 days postmetastatectomy due to metastasis to the lungs and chest wall. Pulmonary metastatectomy resulted in a rapid and prolonged resolution of HO, and the clinical benefits of metastatectomy potentially exceed the morbidity associated with the surgical procedure.