Intracranial invasion of a mast cell tumour in a dog: A case report and review of the literature.

An 11-year-old, female-neutered beagle was presented with a growing soft tissue mass arising within the deep tissues of the left cranial cervical region. At presentation, facial asymmetry was evident along with palpable lymphadenomegaly. Magnetic resonance imaging demonstrated a locally invasive cervical mass with intracranial invasion through focal osteolysis of the occipital bone. After antihistamine administration, cytology confirmed mast cell tumour (MCT) with metastasis to local lymph nodes and liver. The owner chose to pursue lomustine and prednisolone, which were dispensed, but, before home administration, prolonged seizures/status epilepticus occurred prompting euthanasia. Postmortem examination confirmed a high-grade MCT associated with, and infiltrating through, muscle, calvarium, dura mata, leptomeninges and the underlying brain. We present the clinical, imaging, and pathological findings of an unprecedented case of extracranial MCT tumour causing osteolysis of an imperforate flat bone (occipital bone) and intracranial invasion.

Bicavitary effusion in cats: retrospective analysis of signalment, clinical investigations, diagnosis and outcome.

OBJECTIVES: The aim of this study was to describe the clinical and diagnostic findings and outcome of cats with bicavitary effusion presenting to a referral centre. METHODS: Medical records of cats presenting with bicavitary effusion were identified and their history, physical examination findings, clinicopathological data, diagnostic imaging findings, aetiology of bicavitary effusions (cardiac disease, neoplasia, infectious disease, sterile inflammatory disease, severe hypoalbuminaemia, trauma, coagulopathy or 'open' if no definitive diagnosis was reached) and outcome were recorded. Cox regression analysis was performed to identify independent predictors of death in cats with bicavitary effusion. Kaplan-Meier curves were generated for survival analysis. RESULTS: In total, 103 cats with bicavitary effusion were included. Neoplasia and cardiac disease were the most common aetiologies of bicavitary effusion, in 21 (20.4%) and 20 (19.4%) cats, respectively, followed by infectious disease (n = 11, 10.7%), trauma (n = 13, 12.6%), hypoalbuminaemia (n = 6, 5.8%), sterile inflammatory disease (n = 4, 3.9%) and coagulopathy (n = 1, 1.0%). The median survival time for all cats with bicavitary effusion was 3 days. Cats with a neoplastic aetiology had a 2.03 times greater risk of death compared with cats in which no diagnosis was achieved. Neoplasia (P = 0.030) and pedigree breed status (P = 0.016) were independent predictors of death in the multivariable Cox regression model. CONCLUSIONS AND RELEVANCE: This study highlights that bicavitary effusions in cats generally carry a guarded to poor prognosis, particularly if neoplasia is the underlying aetiology or if the cat is a pedigree breed. Cardiac disease appeared to be associated with a better prognosis, suggesting that assessment for congestive heart failure should be considered early when evaluating cats with bicavitary effusion. The prognosis for cats with feline infectious peritonitis is likely to be markedly improved by the advent of novel antiviral drugs, compared with the historical cohort of cats presented here.

OCCURRENCE OF GERM CELL NEOPLASIA IN MALE STRIPED BASS (MORONE SAXATILIS) UNDER HUMAN CARE IN A PUBLIC AQUARIUM: SURGICAL TREATMENT AND OUTCOME.

The striped bass (Morone saxatilis) has been a fish species of special concern in Canada since its marked decline in the early 21st century in the St. Lawrence River. Individuals kept in public aquaria contribute to public education and could support conservation efforts through research. Over a 3-yr period, 12 male striped bass housed in a multispecies exhibit developed coelomic distension. The testes were enlarged (12/12), cystic (2/12), and heterogeneous (3/12) on coelomic ultrasound. Upon coeliotomy, enlarged (12/12), partially (4/12) or totally white discolored (6/12) testes were noted. These were associated with coelomic hemorrhage (8/12), effusion (3/12) or adhesions to surrounding organs (9/12). Orchiectomies were performed in all fish. Among these, seven fish survived 2 mon postsurgery, and four fish were still alive 900 d postsurgery. Germ cell neoplasia was diagnosed on histopathological examination in 9 of 12 individuals, but no abnormalities were found in the three other cases. Preventive orchiectomies were performed on the remaining six male striped bass in this exhibit. Germ cell neoplasms were present in two of these six fish. No anesthetic or surgical complications were noted; all six cases were alive 2 mon postsurgery and four of the fish survived 900 d postsurgery. Survival times were not significantly different between fish that underwent preventive or curative orchiectomy (P = 0.19). Although risk factors associated with the development of these gonadal tumors remain unknown, a genetic or environmental origin is suspected. Orchiectomy should be considered in suspected cases of testicular tumors.

Challenges in diagnosing canine spindle cell tumours using immunohistochemistry, illustrated by three nonpigmented malignant cases from the nictitating membrane.

BACKGROUND: Nonpigmented malignant spindle cell tumours of the membrana nictitans are rare in dogs. In twenty-three years only three cases have been diagnosed in Scandinavia. This study describes the three cases of malignant tumours of the membrana nictitans recorded by the Eye Pathology Section, University of Copenhagen, Denmark, with reference to the clinical appearance and work-up, the treatment and prognosis, and the histopathological description including immunohistochemistry. The three cases are compared to previous publications on canine tumours of the nictitating membrane. We emphasize the importance of using protocols that are adapted to the specific species such as dogs. Opposite the human tissue responses, we even need more than one marker when diagnosing melanomas in dogs. RESULTS: The dogs presented were an 8-year-old Dachshund, a 12-year-old Akita and a 14-year-old Shetland Sheepdog. All three dogs were entire females. All three nictitating membrane tumours developed on the right nictitating membrane as firm or multilobulated hyperaemic masses. Two of the tumours were macroscopically nonpigmented, the third being partly pigmented on the surface and ulcerated. According to the histopathology and for two of the cases immunohistochemistry with dog-adapted protocols the diagnoses included one hemangiosarcoma and two amelanotic melanomas. Tumour regrowth developed in all three cases and repeated resections were completed 1, 2 and 3 times, respectively, with recurrence experienced within 1.5 months - 3 years. CONCLUSIONS: Nonpigmented malignant spindle cell tumours of the canine membrana nictitans are rare. Treatment of choice should be complete excision with a minimal histologic tumour-free distance and in case of a recurrence a full resection of the nictitating membrane. We strongly recommend a dog-adapted protocol for immunohistochemistry.

A novel model for predicting deep-seated candidiasis due to Candida glabrata among cancer patients: A 6-year study in a cancer center of China.

Followed by Candida albicans, Candida glabrata ranks as the second major species contributing to invasive candidiasis. Given the higher medical burden and lower susceptibility to azoles in C. glabrata infections, identifying these infections is critical. From 2016 to 2021, patients with deep-seated candidiasis due to C. glabrata and non-glabrata Candida met the criteria to be enrolled in the study. Clinical data were randomly divided into training and validation cohorts. A predictive model and nomogram were constructed using R software based on the stepwise algorithm and logistic regression. The performance of the model was assessed by the area under the receiver operating characteristic curve and decision curve analysis (DCA). A total of 197 patients were included in the study, 134 of them infected with non-glabrata Candida and 63 with C. glabrata. The predictive model for C. glabrata infection consisted of gastrointestinal cancer, co-infected with bacteria, diabetes mellitus, and kidney dysfunction. The specificity was 84.1% and the sensitivity was 61.5% in the validation cohort when the cutoff value was set to the same as the training cohort. Based on the model, treatment for patients with a high-risk threshold was better than 'treatment for all' in DCA, while opting low-risk patients out of treatment was also better than 'treatment for none' in opt-out DCA. The predictive model provides a rapid method for judging the probability of infections due to C. glabrata and will be of benefit to clinicians making decisions about therapy strategies.

The coinfection of ALVs causes severe pathogenicity in Three-Yellow chickens.

The coinfection of ALVs (ALV-J plus ALV-A or/and ALV-B) has played an important role in the incidence of tumors recently found in China in local breeds of yellow chickens. The study aims to obtain a better knowledge of the function and relevance of ALV coinfection in the clinical disease of avian leukosis, as well as its unique effect on the pathogenicity in Three-yellow chickens. One-day-old Three-yellow chicks (one day old) were infected with ALV-A, ALV-B, and ALV-J mono-infections, as well as ALV-A + J, ALV-B + J, and ALV-A + B + J coinfections, via intraperitoneal injection, and the chicks were then grown in isolators until they were 15 weeks old. The parameters, including the suppression of body weight gain, immune organ weight, viremia, histopathological changes and tumor incidence, were observed and compared with those of the uninfected control birds. The results demonstrated that coinfection with ALVs could induce more serious suppression of body weight gain (P < 0.05), damage to immune organs (P < 0.05) and higher tumor incidences than monoinfection, with triple infection producing the highest pathogenicity. The emergence of visible tumors and viremia occurred faster in the coinfected birds than in the monoinfected birds. These findings demonstrated that ALV coinfection resulted in considerably severe pathogenic and immunosuppressive consequences.

Tumor-like lymphoplasmacytic conjunctivitis in the third eyelid in a dog.

This report aims to describe a case of tumor-like lymphoplasmacytic conjunctivitis in a 7-year-old spayed-female Pomeranian. On complete ophthalmic examination, a mass with papillary projections was noted on the bulbar surface of the right third eyelid. Debulking of the mass was performed while preserving as much of the third eyelid as possible. On the histopathological examination, the mass was diagnosed as lymphoplasmacytic conjunctivitis with mild epithelial hyperplasia. Although a slight regrowth of the mass was noted 3 weeks after surgery, intralesional injection of triamcinolone acetonide led to its disappearance. There was no further recurrence after 5 months.

CT features of cutaneous and subcutaneous canine mast cell tumors and utility of conventional and indirect lymphography to detect clinically unknown mast cell tumors and to map the sentinel lymph nodes.

Computed tomography is frequently used to stage canine mast cell tumors (MCTs). The aims of this prospective, observational study were to describe the CT features of MCTs, to evaluate the performance of CT in detecting additional or incidental MCTs, to distinguish between cutaneous (cMCT) or subcutaneous (scMCT) MCTs, and to identify one or multiple sentinel lymph nodes (SLNs) by indirect CT lymphography (ICTL). Seventy-two dogs affected by 111 MCTs were included. The recorded parameters were: shape, size, attenuation (Hounsfield units [HU]), location (cutaneous or subcutaneous), and presence of fat stranding. The SLNs were compared with the regional lymph nodes and supplementary MCTs were registered. Mast cell tumors mostly appeared with well-defined margins (89%), round/oval shape (71%), homogeneous enhancement (90%) with a mean postcontrast density of 62.0 ± 23.4 HU and associated with fat stranding (43%). Cutaneous mast cell tumors were more frequently round (P = .003), whereas scMCTs were oval (P = .011) with a larger mean maximal diameter (2.91 ± 1.57 cm vs 1.46 ± 1.28 cm, P = .002) and more feeding vessels (77% vs 39% P = .044). Compared with histopathology, CT accuracy in differentiating cMCTs and sMCTs was 57%, with an interobserver agreement of 88% (three reviewers). Indirect CT lymphography showed the SLN in 82 of 85 (97%) cases, 32% of them not corresponding to the regional node. CT showed additional or incidental MCTs in 23 of 72 (32%) dogs. In conclusion, the common CT appearance of canine cMCTs and scMCTs is reported with some statistical differences between the two categories. CT is useful in identifying clinically undetected MCTs and SLNs, although it shows low accuracy in distinguishing between cMCT and scMCT.

Effects of maternal nutrient restriction during gestation on bovine serum microRNA abundance.

The objective was to determine the effects of maternal nutrient restriction during gestation on serum microRNA (miRNA) abundance in cattle. Primiparous Angus-cross cows (n=22) were fed either control (CON; to gain 1 Kg/week) or nutrient restricted (NR; 0.55% NEm) diets based on National Research Council requirements. On day 30 of gestation, cows were blocked by body condition and randomly assigned to one of three diets: CON (n=8) days 30-190; NR (n=7) days 30-110 followed by CON days 110-190 (NR/C); or CON (n=7) days 30-110 followed by NR days 110-190 (C/NR). At 190 days of gestation, maternal serum was collected for RNA isolation and analyzed using a miRNA microarray of known Bos taurus sequences. Data were normalized using LOWESS and analyzed via ANOVA. At 190 days of gestation, 16 miRNAs exhibited differential abundance (P<0.05) between treatments. Cows that underwent NR, irrespective of when the insult occurred, had downregulated bta-miR-126-3p compared to CON cows. Bta-miR-16b was downregulated and three miRNAs upregulated in NR/C compared to C/NR and CON cows. Additionally, seven miRNAs were downregulated and four miRNAs upregulated in C/NR compared to NR/C and CON cows. Comparison of NR/C and C/NR cows revealed three differentially abundant (P<0.04) miRNAs (bta-miR-2487_L-2R-3_1ss15CT, bta-miR-215, and bta-miR-760-5p). Top KEGG pathway enrichment of target genes included: pathways in cancer, PI3K-Akt signaling, focal adhesion, Ras signaling, proteoglycans in cancer, and MAPK signaling. In summary, maternal nutrient restriction altered serum miRNA abundance profiles irrespective of the time at which the nutritional insult was induced.

Veterinary Interventional Oncology.

Interventional oncology (IO) is a rapidly growing field in veterinary medicine and has been accepted as a fourth pillar of treatment of neoplastic disease with other modalities including surgery, chemotherapy, and radiation therapy. The major categories of IO therapies in companion animals are focused on the use of locoregional therapies and stenting of malignant obstructions. Although significant assessment of veterinary IO techniques is still necessary, early evaluation of these varying techniques is demonstrating promising results.

New Therapies in Veterinary Oncology.

The expanding number of specialized oncology therapeutics available in veterinary oncology can make staying updated on the most recent advances challenging. This article summarizes the mechanism of action, available supporting data, and clinical use of three key veterinary cancer/supportive care therapeutics: Laverdia-CA1, Canalevia-CA1, and Stelfonta. This information will help guide clinical use within your practice and can be incorporated into discussions with clients regarding the newest available options for their dogs with cancer.

Noninvasive Blood-Based Cancer Detection in Veterinary Medicine.

The past decade has seen incredible advances in blood-based cancer detection in people and in dogs - yet this represents only a glimpse of the benefits these tests can provide to patients. The clinical uses of this technology range from screening asymptomatic individuals for early detection to use as an aid in diagnosis when cancer is suspected, to cancer monitoring both during and after treatment. This article summarizes the benefits of early cancer detection and examines use cases and methods of blood-based cancer detection in dogs, including quantitative, qualitative, and alternative approaches.

Precision Medicine in Veterinary Science.

Precision medicine focuses on the clinical management of the individual patient, not on population-based findings. Successes from human precision medicine inform veterinary oncology. Early evidence of success for canines shows how precision medicine can be integrated into practice. Decreasing genomic profiling costs will allow increased utilization and subsequent improvement of knowledge base from which to make better informed decisions. Utility of precision medicine in canine oncology will only increase for improved cancer characterization, enhanced therapy selection, and overall more successful management of canine cancer. As such, practitioners are called to interpret and leverage precision medicine reports for their patients.

Septic Peritonitis Secondary to Neoplasia in Two Canine Cancer-Bearing Patients Lacking Gastrointestinal and Hepatic Organ Rupture.

In this case report, we describe the presentation, diagnosis, and outcome of septic peritonitis secondary to neoplasia in patients lacking evidence of gastrointestinal content leakage, liver abscessation, or other treatment-associated risk factors. Two dogs presented with a diagnosis of neoplasia and nonspecific clinical signs such as lethargy, hyporexia, vomiting, and discomfort that was localized to the abdomen. The diagnoses at presentation consisted of a perianal tumor consistent with apocrine gland anal sac adenocarcinoma and systemic mastocytosis. Neither of the dogs was considered systemically immunocompromised or had received recent cytotoxic chemotherapy treatment or surgical procedures. A common finding on blood work in the two dogs was the presence of band neutrophils. The diagnosis of septic peritonitis via fluid analysis and cytology was delayed in both cases. No treatment for the supposed underlying cause of septic peritonitis was pursued and euthanasia was pursued in both cases owing to poor prognosis. On necropsy, one dog was suspected to have developed septic peritonitis because of an abscessed lymph node, and in the other case, no definitive source was identified. Septic peritonitis can arise secondary to neoplasia that is not primarily involving the liver or gastrointestinal tract in canine patients that lack treatment-associated risk factors.

A RETROSPECTIVE STUDY OF DISEASE PROCESSES IN MANED WOLVES (CHRYSOCYON BRACHYURUS) IN NORTH AMERICAN ZOOLOGICAL INSTITUTIONS WITH EMPHASIS ON UROLITHIASIS, INFLAMMATORY BOWEL DISEASE, AND NEOPLASIA.

The objective of this retrospective study is to summarize causes of disease and mortality in maned wolves (Chrysocyon brachyurus) in the North American Species Survival Plan Program (SSP) population. This information will inform and enhance animal health, husbandry, and conservation efforts. Pathology reports were requested from all zoological institutions housing maned wolves between 1930 and 2021. Data were reviewed and cause of death (COD) and reported diseases were summarized and compared by age group, organ system and disease process. One hundred and seventy-one wolves, 82 females and 89 males, met the inclusion criteria. The majority were geriatric (>11 yr; n = 96) or adult (2-11 yr; n = 67). Noninfectious diseases were the most common COD by process (n = 94; 54.9%). For COD by organ system, diseases of the digestive (n = 41) and urinary (n = 34) systems were most common. Neoplasia was the most common noninfectious COD and was the primary COD in 37 wolves (21.6% overall; 39.4% of noninfectious diseases). A total of 145 benign (n = 72) and malignant (n = 73) neoplasms were diagnosed in 44 individuals. Dysgerminoma was the most commonly reported tumor (n = 18), and was the most common neoplastic COD (n = 8). Cystinuria or urolithiasis (n = 71) and gastritis, enteritis, enterocolitis, or colitis (n = 50) (overall and grouped in each system due to presumed common underlying cause) were also common but were more often reported as comorbidities than as COD (n = 16 and n = 11, respectively). Infectious COD were reported in 17 wolves and included babesiosis (n = 4), acanthocephalans (n = 2), and one viral infection. Infections with a variety of bacteria in different organ systems were a COD in eight wolves.

Direct comparison of canine and human immune responses using transcriptomic and functional analyses.

The canine spontaneous cancer model is increasingly utilized to evaluate new combined cancer immunotherapy approaches. While the major leukocyte subsets and phenotypes are closely related in dogs and humans, the functionality of T cells and antigen presenting cells in the two species has not been previously compared in detail. Such information would be important in interpreting immune response data and evaluating the potential toxicities of new cancer immunotherapies in dogs. To address this question, we used in vitro assays to compare the transcriptomic, cytokine, and proliferative responses of activated canine and human T cells, and also compared responses in activated macrophages. Transcriptomic analysis following T cell activation revealed shared expression of 515 significantly upregulated genes and 360 significantly downregulated immune genes. Pathway analysis identified 33 immune pathways shared between canine and human activated T cells, along with 34 immune pathways that were unique to each species. Activated human T cells exhibited a marked Th1 bias, whereas canine T cells were transcriptionally less active overall. Despite similar proliferative responses to activation, canine T cells produced significantly less IFN-γ than human T cells. Moreover, canine macrophages were significantly more responsive to activation by IFN-γ than human macrophages, as reflected by co-stimulatory molecule expression and TNF-α production. Thus, these studies revealed overall broad similarity in responses to immune activation between dogs and humans, but also uncovered important key quantitative and qualitative differences, particularly with respect to T cell responses, that should be considered in designing and evaluating cancer immunotherapy studies in dogs.

Genomic analysis across 53 canine cancer types reveals novel mutations and high clinical actionability potential.

A genomic understanding of the oncogenic processes and individual variability of human cancer has steadily fueled improvement in patient outcomes over the past 20 years. Mutations within tumour tissues are routinely assessed through clinical genomic diagnostic assays by academic and commercial laboratories to facilitate diagnosis, prognosis and effective treatment stratification. The application of genomics has unveiled a wealth of mutation-based biomarkers in canine cancers, suggesting that the transformative principles that have revolutionized human cancer medicine can be brought to bear in veterinary oncology. To advance clinical genomics and genomics-guided medicine in canine oncology, we have developed and validated a canine cancer next-generation sequencing gene panel for the identification of multiple mutation types in clinical specimens. With this panel, we examined the genomic landscapes of 828 tumours from 813 dogs, spanning 53 cancer types. We identified 7856 alterations, encompassing copy number variants, single nucleotide variants, indels and internal tandem duplications. Additionally, we evaluated the clinical utility of these alterations by incorporating a biomarker framework from comprehensive curation of primary canine literature and inferences from human cancer genomic biomarker literature and clinical diagnostics. Remarkably, nearly 90% of the cases exhibited mutations with diagnostic, prognostic or therapeutic implications. Our work represents a thorough assessment of genomic landscapes in a large cohort of canine cancers, the first of its kind for its comprehensive inclusion of multiple mutation types and structured annotation of biomarkers, demonstrating the clinical potential of leveraging mutation-based biomarkers in veterinary oncology.

Veterinary oncologists and pet owners differ in their perceptions of chemotherapy-related adverse events in cancer-bearing dogs.

OBJECTIVE: Chemotherapy is widely used in veterinary oncology but carries real and perceived risks of adverse events (AEs). Human cancer patients perceive AEs from chemotherapy as more severe than do their attending physicians. It is currently unknown whether this discrepancy exists in veterinary oncology. This survey study's aim was to assess differences in the ways that pet owners and veterinary oncologists perceive chemotherapy-related AEs. We hypothesized that veterinary oncologists would accept higher grade AEs and tolerate a greater risk of AEs of any grade than pet owners. SAMPLE: 152 pet owners and 111 veterinary oncologists. METHODS: Separate surveys were derived for pet owners and veterinary oncologists. Respondents were asked to define maximally acceptable AE scores and risks of AEs given 3 hypothetical outcomes of treatment: (1) cure, (2) extension of life, and (3) improved quality of life. Statistical tests were used to compare responses between groups. RESULTS: Veterinary oncologists accepted higher grade AEs if the hypothetical goal of chemotherapy was cancer cure (P = .003) or extension of life (P = .026), but owners accepted higher grade AEs if the goal of chemotherapy was to improve quality of life (P = .002). Owners accepted greater risk of moderate (P < .0001) or serious (P < .0001) AEs across the 3 treatment outcomes. CLINICAL RELEVANCE: This was the first study to assess how pet owners and veterinary oncologists differ in their perception of chemotherapy-related AEs. These initial results may help to frame discussions with pet owners on the expectations of chemotherapy.

Design of a randomized, placebo-controlled study evaluating efficacy and safety of a cancer preventative vaccine in dogs.

Preventative anti-cancer vaccination strategies have long been hampered by the challenge of targeting the diverse array of potential tumor antigens, with successes to date limited to cancers with viral etiologies. Identification and vaccination against frameshift neoantigens conserved across multiple species and tumor histologies is a potential cancer preventative strategy currently being investigated. Companion dogs spontaneously develop cancers at a similar incidence to those in people and are a complementary comparative patient population for the development of novel anti-cancer therapeutics. In addition to an intact immune system with tumors that arise in an autochthonous tumor microenvironment, dogs also have a shorter lifespan and temporally compressed tumor natural history as compared to humans, which allows for more rapid evaluation of safety, immunogenicity, and efficacy of cancer vaccination strategies. Here we describe the study protocol for the Vaccination Against Canine Cancer Study (VACCS), the largest interventional cancer clinical trial conducted in companion dogs to date. In addition to safety and immunogenicity, the primary endpoint of VACCS is the cumulative incidence (CI) of dogs developing malignant neoplasia of any type at the end of the study period. Secondary endpoints include changes in incidence of specific tumor types, survival times following neoplasia diagnosis, and all-cause mortality.