A pilot study investigating plasma pharmacokinetics and tolerance of oral capecitabine in carcinoma-bearing dogs.

BACKGROUND: Capecitabine is an oral prodrug of the active metabolite 5-fluorouracil, which has been used effectively in human colorectal, head and neck, and mammary carcinomas. Capecitabine has several properties that make it an attractive treatment option for dogs: (i) it is relatively inexpensive, (ii) it has a short half-life in humans, allowing for rapid plasma concentration changes to be achieved with dosage adjustments, (iii) it is effective for treating carcinomas in humans, for which there are no widely-effective oral chemotherapy options in dogs, and (iv) it is thought to preferentially target cancer cells due to different expression of thymidine phosphorylase, thereby decreasing the risk of off-target side effects. However, capecitabine has not been widely explored as a chemotherapy agent for dogs. The goal of this study was to determine the plasma disposition of capecitabine in dogs following a single oral dose and to document any adverse events associated with capecitabine administration over the course of 5 weeks. RESULTS: Capecitabine was well tolerated throughout the 5-week study period when administered to 5 dogs with naturally occurring carcinomas at 750 mg/m[Formula: see text] by mouth once daily for 14 consecutive days in a 3-week cycle. No dogs withdrew from the study due to adverse events or other causes. The median AUC[Formula: see text] was 890 h[Formula: see text]ng/ml (range 750-1100 h[Formula: see text]ng/ml); however, the maximum blood concentration and time to reach that concentration of capecitabine was highly variable after a single dose. CONCLUSIONS: Capecitabine appears well-tolerated as an oral chemotherapy agent for dogs with carcinomas, although individualized dosing may be necessary, and further studies are warranted.

Diagnostic benefits of platelet-to-lymphocyte, neutrophil-to-lymphocyte, and albumin-to-globulin ratios in dogs with nasal cavity diseases.

BACKGROUND: A multimodal approach for diagnostic tests under anesthesia is required to diagnose nasal cavity pathology (NP) reliably in dogs. Blood test results may provide clues to the suspected NP. METHODS: This prospective blinded study assessed 72 dogs with chronic nasal discharge due to NPs, and 10 healthy dogs as the control group (CG). NPs were diagnosed using whole-body computed tomography (CT), upper airway endoscopy, examination of nasal mucosal swabs by bacterial and fungal culture, and histopathological examination of nasal mucosa biopsies. The exclusion criteria were the presence of any additional diseases or corticosteroid pre-treatment. In consideration of these exclusion criteria, 55 dogs entered the study. Dogs were classified into benign (benign tumors, idiopathic rhinitis (IR), and others) and malignant (carcinomas and sarcomas) NP groups. Blood count and blood chemistry tests were performed. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and albumin-to-globulin ratio (AGR) were calculated and compared. RESULTS: 25 dogs with malignant NP (13 and 12 with carcinomas and sarcomas, respectively) and 30 dogs with benign NP (seven with benign tumors,13 with IR, and 10 others) were included. In general, in dogs with NP there were only slight abnormalities in complete blood count. However, PLR was significantly higher in dogs with malignant NP (carcinoma and sarcoma) than in those with benign NP and in the CG. Compared with the CG, the NLR was significantly increased in all dogs with NP, and the AGR was mild but significantly lower, except in dogs with sarcomas and benign tumors. CONCLUSIONS: In dogs with nasal disease alone, there are usually no marked abnormalities in blood count. However, while mildly increased NLR and decreased AGR can be observed in almost all NPs, an increased PLR may indicate a malignant NP and can be used as an additional screening tool in dogs with nasal discharge due to nasal cavity pathology.

Usability of serum hedgehog signalling proteins as biomarkers in canine mammary carcinomas.

BACKGROUND: The hedgehog signalling pathway has been implicated in tumourigenesis and progression of many tumour types. This pathway has recently emerged as a therapeutic target, and inhibitors of hedgehog signalling have gained considerable attention. In dogs, the roles of hedgehog signals in several types of tumours have been investigated, but their relationship with canine mammary gland tumours (MGTs) has not been established. This study aimed to evaluate the expression of sonic hedgehog (SHH) and glioma-associated oncogene 1 (GLI-1) in the serum and mammary tumour tissues of dogs. RESULTS: SHH and GLI-1 protein expression levels were significantly higher in MGT tissues than in normal mammary gland tissues, as well as in malignant MGT specimens than in benign MGT specimens. Serum levels of SHH and GLI-1 were higher in MGT patients than in healthy controls (p < .001 and .001, respectively). Serum SHH level showed a statistically significant relationship with metastatic status (p = .01), and serum GLI-1 level showed a statistically significant relationship with histologic grade (p = 0.048) and metastatic status (p = 0.007). Serum hedgehog signalling protein levels were not significantly associated with breed size, sex, tumour size, or histologic type. CONCLUSIONS: Hedgehog signalling protein expression in canine MGT tissue and serum differed according to the histological classification (benign and malignant) and metastatic status, indicating a relationship between the hedgehog signalling pathway and canine MGT. Thus, the hedgehog signalling pathway may serve as a new biomarker and therapeutic target in canine MGT patients.

A method for scoring 4-nitroquinoline 1-oxide-induced murine esophageal squamous neoplasia.

A mouse model for esophageal squamous cell carcinoma (ESCC) is induced by oral administration of the carcinogen 4-nitroquinoline 1-oxide (4-NQO). There is not an objective method for determining histopathologic severity of disease in this model. We aim to create a clearly defined and easily applied scoring system that can quantify the severity of 4-NQO-induced murine ESCC. Fifteen wild-type C57BL/6J mice were treated with 4-NQO for 8 (n = 8) or 16 (n = 7) weeks, while the rest (n = 9) were treated with vehicle, as 8 weeks of 4-NQO typically results in dysplasia and 16 weeks in carcinoma. We identified histologic abnormalities of the esophagus in this model and developed metrics to grade severity of dysplasia, papillomas, and invasion. Scores were then calculated using quantitative digitized image analysis for measuring depth and extent of each feature within the entire sample. Each feature was also assigned a weight based on its relation to cancer severity. Histology scores were significantly different in the three groups, suggesting that this method can discriminate dysplasia from carcinoma. This model can be applied to any mouse treated with 4-NQO.

Mammary carcinoma: Comparative oncology between small animals and humans-New therapeutic tools.

The poor outcomes associated with mammary carcinomas (MCs) in dogs and cats in terms of locoregional recurrence, distant metastasis and survival, highlight the need for better management of mammary cancers in small animals. By contrast, the outcomes of women with breast cancer (BC) have dramatically improved during the last 10 years, notably thanks to new therapeutic strategies. The aim of this article was to imagine what could be the future of therapy for dogs and cats with MCs if it became inspired from current practices in human BC. This article focuses on the importance of taking into account cancer stage and cancer subtypes in therapeutic plans, on locoregional treatments (surgery, radiation therapy), new developments in endocrine therapy, chemotherapy, PARP inhibitors and immunotherapy. Ideally, multimodal treatment regimens would be chosen according to cancer stage and cancer subtypes, and according to predictive factors that are still to be defined.

Outcomes and clinical features associated with surgically excised canine salivary gland carcinoma: A multi-institutional, retrospective, Veterinary Society of Surgical Oncology study.

OBJECTIVE: The objective of this study was to describe the clinical features, prognostic factors, and outcomes in dogs with surgically treated salivary gland carcinoma. STUDY DESIGN: Multi-institutional retrospective case series. ANIMALS: Seventy-two client-owned dogs from 16 institutions with surgically excised salivary gland carcinoma. METHODS: Medical records of dogs undergoing sialoadenectomy from January 1, 2000 to January 1, 2020 were reviewed for signalment, clinical signs, preoperative staging results, preoperative mass evaluation, complications, histopathologic diagnosis, local recurrence, metastatic disease, and survival times. Survival functions were estimated using the Kaplan-Meier estimator. Factors related to survival were individually tested using the log-rank test. RESULTS: The overall median survival time (MST) associated with salivary carcinoma was 1886 days. Local recurrence occurred in 29/69 (42%) dogs with an overall disease-free interval (DFI) of 191 days. Metastatic disease occurred in 22/69 (31.9%) dogs, with an overall DFI of 299 days. Lymph node metastasis was present at the time of surgery in 11/38 (28.9%) dogs in which lymphadenectomy was performed at the time of surgery; these dogs had a shorter DFI at 98 days (P = .03) and MST at 248 days (P < .001). CONCLUSION: The prognosis for dogs with salivary gland carcinoma treated surgically was more favorable than previously reported. Nodal metastasis was a negative prognostic factor for canine salivary gland carcinoma. CLINICAL SIGNIFICANCE: Surgical intervention should be considered for dogs with salivary carcinoma.

Metastatic carcinoma of unknown origin in a dog.

Although cancer of unknown primary origin (CUP) is well-described in the human literature, it is not as well-understood within veterinary medicine. This case report represents one of few focused on describing CUP in a dog. Key clinical message: Metastatic CUP should be considered as a differential diagnosis despite being a rare disease entity that is infrequently reported within the veterinary literature.

Carcinome métastatique d'origine inconnue chez un chien. Bien que le cancer d'origine primaire inconnue (CUP) soit bien décrit dans la littérature humaine, il n'est pas aussi bien compris en médecine vétérinaire. Ce rapport de cas représente l'un des rares à s'intéresser à la description du CUP chez un chien.Message clinique clé:Le CUP métastatique doit être considéré comme un diagnostic différentiel bien qu'il s'agisse d'une entité de maladie rare rarement rapportée dans la littérature vétérinaire.(Traduit par Dr Serge Messier).

Biphasic pleural mesothelioma in a goat.

An 8-year-old Saanen goat doe was seen for inappetence, tachycardia, and intermittent bluish-grey discoloration of the oral mucous membranes. On physical examination, the goat was mildly tachypneic and tachycardic, with reduced sounds auscultated on the left side of the thorax. Euthanasia was elected. Necropsy revealed an infiltrative, multinodular mass within the left thoracic cavity and innumerable small, tan nodules disseminated across the pleura of the lungs, thoracic walls, and diaphragm. Upon histologic examination, the mass was composed of highly pleomorphic, fusiform to polygonal cells. Neoplastic cells exhibited positive immunoreactivity for both cytokeratin and vimentin, consistent with a diagnosis of biphasic pleural mesothelioma. Key clinical message: Mesothelioma has rarely been described in the goat but should be considered as a differential diagnosis for thoracic masses in small ruminants, along with thymoma; metastatic neoplasia; carcinomatosis; and granulomatous lesions caused by parasites, bacteria, and fungi.

Mésothéliome pleural biphasique chez une chèvre. Une chèvre Saanen âgée de 8 ans a été vue pour de l'inappétence, une tachycardie et une décoloration gris bleuâtre intermittente des muqueuses buccales. À l'examen physique, la chèvre était légèrement tachypnéique et tachycardique, avec des sons réduits auscultés du côté gauche du thorax. Il a été décidé d'euthanasier l'animal. L'autopsie a révélé une masse multinodulaire infiltrante dans la cavité thoracique gauche et d'innombrables petits nodules brun clair disséminés à travers la plèvre pulmonaire, les parois thoraciques et le diaphragme. À l'examen histologique, la masse était composée de cellules hautement pléomorphes, fusiformes à polygonales. Les cellules néoplasiques ont présenté une immunoréactivité positive pour la cytokératine et la vimentine, compatible avec un diagnostic de mésothéliome pleural biphasique.Message clinique clé:Le mésothéliome a rarement été décrit chez la chèvre mais doit être considéré comme un diagnostic différentiel des masses thoraciques chez les petits ruminants, avec le thymome, la néoplasie métastatique, la carcinomatose et les lésions granulomateuses causées par des parasites, des bactéries et des champignons.(Traduit par Dr Serge Messier).

Vimentin and Ki-67 immunolabeling in canine gastric carcinomas and their prognostic value.

This study evaluated the expression of vimentin and Ki-67 proliferative index (PI) by immunohistochemistry in 30 canine gastric carcinomas (GCs) and a possible association with clinical and pathological features and patient's survival time. Vimentin immunoreactivity was assessed in neoplastic cells (in primary lesions, emboli, and metastases) and tumor-associated stroma (TAS) of canine GCs. Ki-67 PI was quantified in the neoplastic epithelial component. Vimentin immunolabeling in neoplastic cells was found in 30% of the primary lesions, in 82% of the neoplastic emboli, and in 50% of the metastases; in TAS, it was observed in all cases. A mean of 16% of the TAS was immunolabeled for vimentin. High vimentin immunolabeling in the TAS (>16%) was detected in 40% of cases. The average value of Ki-67 PI was 50%, and 80% of the lesions had Ki-67 PI above 20%. Vimentin immunolabeling in neoplastic cells was more frequent in less-differentiated carcinomas (diffuse [29%] and indeterminate types [75%]) than well-differentiated carcinomas (intestinal type [0%], P = .049). No significant differences were observed in vimentin immunolabeling in the TAS or Ki-67 PI according to histological diagnosis, depth of invasion, presence of neoplastic emboli or metastases. However, vimentin immunolabeling in the TAS was positively correlated with Ki-67 PI (r = .394, P = .031). Furthermore, a moderate negative correlation was observed between Ki-67 PI and survival time (r = -0.540). Our results suggest that vimentin and Ki-67 PI have potential for providing prognostic information in cases of canine GCs.

Morphological and immunohistochemical characterization and molecular classification of spontaneous mammary gland tumors in macropods.

Mammary gland neoplasms in macropods are uncommonly reported, and the morphological and immunohistochemical characteristics are incompletely described. The goal of this study was to describe the morphologic features of macropod mammary neoplasms and to determine the molecular subtypes of mammary carcinomas using a panel of antibodies against estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2), p63, smooth muscle actin (SMA), and epidermal growth factor receptor (EGFR). Biopsy and necropsy specimens were examined from 21 macropods with mammary tumors submitted to Northwest ZooPath from 1996 to 2019. In accordance with the histologic classification of canine mammary tumors proposed by Goldschmidt and colleagues, tubulopapillary (2), tubular (10), and comedo-carcinomas (2), adenoma (1), lobular hyperplasia (3), fibroadenomatous hyperplasia (1), and mastitis (2) were diagnosed. Red kangaroos (Osphranter rufus) were most commonly diagnosed with mammary carcinomas (79% of all carcinomas). Seven carcinomas had lymphovascular invasion and 2 also had pulmonary metastases. Six of these 7 carcinomas were classified as grade 3. Immunohistochemistry (IHC) for all antibodies was performed on 9/14 carcinomas, and partial IHC was performed for 3 cases. All 12 carcinomas were immunoreactive for PR, 5 for ER, 9 for EGFR, and none for Her-2. Five of the 9 mammary carcinomas with complete IHC data were classified as luminal A subtype, and 4 were normal-like subtype. Accurate classification of mammary tumors in macropods based on morphology, immunohistological characteristics, and molecular subtype may be helpful in guiding clinical management, prognosis, and potential therapeutic targets.

Bovine intracranial neoplasia: A retrospective case series.

This case series describes the clinical and pathological findings of intracranial neoplasms in cattle, a rare entity. Data and archived tissues from 24 intracranial tumors were reviewed and investigated by immunohistochemistry for S100, glial fibrillary acidic protein, synaptophysin, pancytokeratin, vimentin, neuron-specific enolase, oligodendrocyte transcription factor 2, and isocitrate dehydrogenase 1. Ages of affected cattle ranged from 6 months to 14 years (5.7 ± 3.6 years; mean ± SD). Predominant clinical signs were altered mental state, central vestibular dysfunction, and cerebellar incoordination. Twelve gliomas, all high grade, were the most common tumors observed: oligodendrogliomas (n = 6), astrocytomas (n = 4), and undefined gliomas (n = 2). The oligodendrogliomas were located in the brainstem and extended into the ventricles, whereas all astrocytomas were located in the forebrain. Isocitrate dehydrogenase 1 gene mutation as described in humans was not detected. The 5 meningiomas exhibited microcystic, chordoid, atypical, papillary, and anaplastic subtypes. Metastatic carcinomas (n = 4) were the only secondary tumor type present, and these were located at the level of the medulla with infiltration of cranial nerves and in one case leptomeningeal carcinomatosis. In addition, 2 medulloblastomas and 1 choroid plexus carcinoma were diagnosed. Immunohistochemistry for vimentin and pancytokeratin was particularly useful to distinguish meningiomas and choroid plexus carcinoma (positive for vimentin only) from mestastatic carcinomas (positive for cytokeratin only) as all showed a papillary growth pattern. Overall, the morphological features were comparable with other species and the human and canine classifications could be applied.

Clinical, advanced imaging data and outcome of inflammatory and neoplastic orbital disease in 81 dogs and 16 cats in Australia (2010-2019).

OBJECTIVE: To characterize the clinical presentation, advanced imaging features, and outcome of orbital disease in a referral population of dogs and cats that underwent computed tomography (CT) or magnetic resonance imaging (MRI). ANIMALS STUDIED: Client-owned animals. PROCEDURES: Animals referred for orbital disease undergoing ophthalmic examination and either head MRI or CT were included. Demographic and imaging features were compared between animals diagnosed with inflammatory disease and neoplastic disease using Mann-Whitney U and Fischer's exact tests. RESULTS: Ninety-seven animals (81 dogs and 16 cats) were included. Eighty-four and 13 patients underwent CT and MRI scanning, respectively. Inflammatory orbital disease was more frequently detected than neoplasia in dogs (59% vs. 41%) and cats (62% vs. 39%). Orbital cellulitis was the most common diagnosis in dogs (36/81, 44.4%) and cats (8/16, 80%). A foreign body was suspected in 36.1% of dogs with orbital cellulitis but only 3 were retrieved during orbitotomy. Multi-drug resistant bacteria were identified in 3 samples and influenced treatment plans. The most common neoplasms were sarcoma (10/30) and carcinoma (7/30) in dogs and lymphoma in cats (3/6). Imaging findings of osteolysis (p = 0.0002) and intracranial extension (p = 0.0001) were significantly associated with neoplasia in dogs. In contrast, osteolysis extension was present in cats with both inflammatory (7/10) and neoplastic (6/6) orbital disease. CONCLUSIONS: Inflammatory disease, particularly orbital cellulitis, was more common than neoplasia in dogs and cats with orbital disease in our population. We recommend including bacterial culture and susceptibility as part of the diagnostic work up when orbital cellulitis is suspected.

Submucosal resection via a transanal approach for treatment of epithelial rectal tumors - a multicenter study.

OBJECTIVE: To report complications and long-term outcomes after submucosal resections of benign and malignant epithelial rectal masses. STUDY DESIGN: Retrospective multicentric study. SAMPLE POPULATION: Medical records of 93 dogs at 7 referral hospitals. METHODS: Records were reviewed for surgical time, diagnosis, margins, complications, and recurrences. Survival of dogs was evaluated based on tumor types, categorized as benign, carcinoma in situ, and carcinoma. The Kaplan-Meier survival curve and Cox proportional hazards analysis were used to determine the association of a range of variables with recurrence and survival time. RESULTS: Duration of follow up was 708 days (range, 25-4383). Twenty-seven dogs (29%) developed complications. Recurrence was identified in 20/93 (21%), with 12/20 recurrent masses treated with repeat submucosal resection. Median survival was not reached in any group. The 1-,2-, 5-year survival rates for carcinomas were 95%, 89%, and 73% respectively. However, overall survival was longer for benign tumors than carcinomas (P = .001). Recurrence was more likely when complications (P = .032) or incomplete margins (P = .023) were present. Recurrence was associated with an increased risk of death (P = .046). CONCLUSION: Submucosal resection of both benign and malignant rectal masses was associated with a low rate of severe complications and prolonged survival in the 93 dogs described here. CLINICAL SIGNIFICANCE: Submucosal resection is a suitable technique for resection of selected rectal masses.

Outcome of Localized Bile Duct Carcinoma in Six Dogs Treated with Liver Lobectomy.

The prognosis for bile duct carcinoma in dogs is generally believed to be poor. However, only a few studies have evaluated the postoperative outcomes in such cases. The objective of this case series was to describe the postoperative outcomes of localized intrahepatic bile duct carcinoma in dogs. The electronic medical records of 16 dogs with bile duct carcinoma were reviewed, and 6 dogs were included in the study. All cases were diagnosed as bile duct carcinoma using postoperative pathology, and five of them had already been diagnosed using preoperative core biopsy. The tumors in all of the dogs were confirmed as completely resected on histopathological examination. Two dogs received toceranib following the surgery. The median follow-up time was 693 days (range, 420-1386 days), with a median survival time of 894 days (range, 420-1386 days). Local recurrence or distant metastases were detected in two of the six dogs (33%) on 354 and 398 days following surgery, respectively. The median progression-free survival was 492 days (range, 354-1386 days). In conclusion, dogs with localized intrahepatic bile duct carcinoma had a good prognosis following complete surgical resection.

Bronchial Stent Placement for Palliative Treatment of Pulmonary Carcinoma with Bronchial Obstruction in a Cat.

A feral, domestic shorthair was evaluated for palliative treatment of a pulmonary mass with secondary pneumonia. Because of the patient's temperament and extent of the mass, tracheobronchoscopy, bronchial stenting, and biopsy were elected, followed by adjuvant radiation therapy. Stent placement across the malignantly obstructed bronchus permitted drainage and recruitment of the infected lung lobe. Uncomplicated radiation therapy, stent extension, and debulking due to tissue ingrowth were subsequently performed. Successful palliation was achieved for 323 days with subsequent progressive pulmonary and liver metastases.

Canine mammary gland disease in New Zealand: a review of samples from 797 dogs.

AIMS: To evaluate the proportions of canine mammary gland lesions submitted to a New Zealand diagnostic laboratory, that were neoplastic vs. non-neoplastic and, among neoplasms, malignant vs. benign, and to determine whether age, reproductive status or breed of dog, or size of the mammary mass were associated with the histological diagnosis. METHODS: Canine mammary gland biopsies submitted between the start of 2012 and the end of 2016 were selected from the surgical biopsy database of IDEXX Laboratories, NZ. For each case, details on age, breed, and reproductive status of the patient were registered as reported by the submitting veterinarians, along with the size (classified as small, medium or large) of the lesion and the histological diagnosis reported by the pathologists. χ2 tests and independent sample t-tests were performed to evaluate associations. RESULTS: Samples (n = 895) were submitted from 797 dogs, of which 673 had mammary neoplasms while 124 had non-neoplastic lesions. Neoplasms composed of a single nodule were found in 591/673 (87.8%) dogs, while 82/673 (12.2%) dogs had multiple nodules. Of the total 771 neoplasms, 432 (56.0%) were histologically malignant, while 339 (44.0%) were benign. Among malignancies, the most common histological sub-types were simple carcinoma (160/771; 20.8%), complex carcinoma (54/771; 7%), and ductal carcinoma (32/771; 4.2%), while benign mixed mammary tumour (128/771, 16.6%) and complex adenoma (105/771; 13.6%) were the most frequently reported benign mammary neoplasms. There was no evidence of a difference in age (p = 0.09) or reproductive status (p = 0.79) of the dog or the size of the mass (p = 0.21) between neoplastic and non-neoplastic lesions. However, neoplastic mammary gland lesions were more frequent in purebred dogs (612/671; 91.2%) than crossbred dogs (61/126; 48.4%; p < 0.001). There was no evidence of a difference in age (p = 0.15) reproductive status (p = 0.36) or breed (p = 0.45) of dog between malignant and benign neoplasms. There was an association between size and histological benign or malignant status of a neoplasm (φ = 0.65, p < 0.001). CONCLUSIONS: Most canine mammary gland samples submitted for examination were neoplastic with slightly more malignant than benign lesions. Masses submitted from purebred dogs were more likely to be neoplastic, while large neoplasms were more likely to be malignant. CLINICAL RELEVANCE: The present findings provide the first description of the distribution of mammary gland lesions in a relatively large number of dogs in New Zealand, representing a preliminary investigation of canine mammary gland diseases in this country.

Pilot study evaluating the tolerability of a 3 Gy × 10 daily fraction 3D-conformal palliative radiation therapy protocol plus toceranib for the treatment of measurable carcinomas in the dog.

The use of radiation therapy in conjunction with small molecule inhibitors is an appealing treatment combination for non-resectable carcinomas, which tend to be locally invasive with variable risk of locoregional metastasis. This prospective, pilot study aimed to evaluate the tolerability and adverse event profile of concurrent toceranib and palliative-intent radiation therapy (PRT) in dogs with measurable carcinoma and to secondarily evaluate short-term measurable tumor response. Fifteen dogs with measurable carcinoma received toceranib and 3D-conformal PRT in 3 Gy/fraction for 10 daily fractions. Adverse events were graded using standard schemes and tolerability was followed via quality-of-life questionnaires during the 12-week treatment period. Thirteen dogs (87%) experienced acute radiation toxicity, graded as severe in three dogs. All dogs experienced toceranib toxicity, graded as severe in one dog. Seven dogs (47%) completed the 12-week study protocol; four were withdrawn due to toxicity and/or associated poor quality of life and four developed progressive disease. Based on these preliminary results, this 3D-conformal chemoradiation protocol should be considered with caution and only with proper owner education on potential toxicity. More conformal treatment planning techniques or alternative protocols should be investigated for improved tolerability.

RETROSPECTIVE REVIEW OF MORBIDITY AND MORTALITY IN A POPULATION OF CAPTIVE BUDGERIGARS (MELOPSITTACUS UNDULATES).

This retrospective study reviews the diseases associated with morbidity and mortality in 221 budgerigars (Melopsittacus undulates) from a captive population from 2013 to 2019. The study aimed to evaluate the health status of a flock of budgerigars typical of today's zoologic collections. Based on previous literature, it was hypothesized that age-related conditions such as neoplasia would be common, whereas metabolic and nutritional disorders would be less common. Neoplasia was widespread among the population, affecting 34% of birds (75/221). Carcinomas made up most neoplastic processes and most commonly affected the renal system (n = 22), followed by the proventriculus (n = 7). Pituitary, adrenal, and hepatocellular carcinomas were less commonly diagnosed. Sarcomas affected the population less often than carcinomas and were found within the coelom (undifferentiated four cases), within the spleen (three cases), within the kidney (two cases), and one subcutaneous soft tissue sarcoma. There were five cases of multicentric lymphoma found most commonly affecting the spleen and liver. Benign neoplasms affected the pituitary most commonly (nine cases), followed by the reproductive system, with seminomas (seven cases) being most common. Macrorhabdus ornithogaster (MO) was found in 56 cases. The majority (38 cases) were found in conjunction with a range of comorbidities, but several birds experienced MO infections alone, and it was thought to have been the cause of death in these birds (22 cases). In contrast to our hypothesis, disease associated with nutritional or metabolic disorders impacted a substantial portion of the population; hepatic lipidosis (26 cases) was the most common along with obesity (26 cases), followed by atherosclerosis, xanthomas, and gout (8, 7, and 4 cases, respectively). Traumatic lesions were noted in 41 cases and were most commonly characterized by head trauma and cerebral hemorrhage. Toxicity was rare; five total cases caused by a single carbon monoxide event were identified.

Intraluminal Uropygial Gland Epithelioma in an African Grey Parrot (Psittacus erithacus).

A 27-year-old female African grey parrot (Psittacus erithacus) presented as a referral for surgical removal of an enlarged uropygial gland that was first observed by the owner 6 months prior. Antibiotic therapy was attempted by the referring veterinarian with limited treatment response. No abnormalities were noted in the results of a complete blood count and plasma biochemistry panel. Computed tomographic imaging of the parrot showed a left-sided uropygial gland mass with no evidence of metastasis or invasion into the underlying soft tissue or bone. The uropygial gland was surgically excised in an attempt to obtain clean margins devoid of tumor cells. Histopathological evaluation of the submitted tissue was suggestive of an intraluminal uropygial gland epithelioma. Intraluminal epithelioma should be considered as a differential diagnosis in psittacine species that are presented with an asymmetrically enlarged uropygial gland.

Protease-Activated Receptor-2 Is Associated With Adverse Outcomes in Canine Mammary Carcinoma.

Protease-activated receptor-2 (PAR2) is a G protein-coupled receptor that is activated by serine proteases. In humans, PAR2 is highly expressed in various cancers, including breast cancer, and is associated with cancer progression and metastasis. However, the expression and roles of PAR2 in canine mammary carcinoma remain unclear. The purpose of this study was to examine the expression of PAR2 in canine mammary carcinoma, the association between PAR2 expression and clinical characteristics, and the role of PAR2 in the metastatic phenotypes of tumor cells. Mammary carcinoma from 31 dogs and 10 normal mammary glands were included in this study, and used for immunohistochemical analysis of PAR2 expression. Normal mammary glands did not express PAR2. In contrast, mammary carcinomas showed PAR2 immunoreactivity in the cytoplasm, and its expression level varied between specimens from negative to strongly positive. The overall survival of dogs with high PAR2 expression was shorter than that of dogs with low PAR2 expression. Moreover, PAR2 expression level was associated with the presence of lymph node involvement, advanced clinical stage, and high histopathological grade. In vitro analyses revealed that a PAR2 agonist accelerated cell migration and invasion in a canine mammary carcinoma cell line. In addition, the PAR2 agonist induced epithelial-mesenchymal transition and actin polymerization. These results suggest that PAR2 expression plays a role in tumor progression and clinical outcomes in canine mammary carcinoma.