Efficacy of verdinexor for the treatment of naïve canine epitheliotropic cutaneous T-cell lymphoma: An open-label pilot study.

BACKGROUND: Verdinexor (Laverdia-CA1; Dechra Veterinary Products), a selective inhibitor of nuclear export, has been utilised for treatment of non-Hodgkin T-cell lymphoma in dogs. However, the efficacy of verdinexor has not been evaluated for cutaneous epitheliotropic T-cell lymphoma (CETL). HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of verdinexor for the treatment of CETL. ANIMALS: Eight client-owned animals with CETL. MATERIALS AND METHODS: Patients received between 1.28 and 1.45 mg/kg verdinexor per os twice weekly with a minimum of 72 h between doses until disease progression or voluntary withdrawal. Adjunctive therapy with lokivetmab or prednisone was permitted after Day (D)14. Assessment of clinical lesions (canine Response Evaluation Criteria in Solid Tumors [cRECIST v1.0] and novel Canine Epitheliotropic Lymphoma Extent and Severity Index [CELESI]), pruritus (Visual Analog Scale) and treatment efficacy (owner global assessment of treatment efficacy [OGATE]) were evaluated every 14 days for 3 months, then monthly thereafter (mean 70 ± 43.4 days). RESULTS: Seventy-five percent of patients achieved complete response, partial response or stable disease. The mean time to disease progression was 56 ± 41 days. There was a significant reduction (p = 0.026) in total CELESI score when the lowest score for each dog was compared to their score at D0. Verdinexor did not significantly reduce pruritus at any time point (p = 0.45), including when given as a monotherapy or concurrently with lokivetmab ± glucocorticoids. On D28, 75% of owners rated response to treatment as 'fair' to 'excellent'. The most common adverse effects included weight loss, inappetence, vomiting and lethargy. CONCLUSIONS AND CLINICAL RELEVANCE: Verdinexor could be considered a safe, palliative treatment for canine CETL.

Feline Pituitary Adenomas: Correlation of Histologic and Immunohistochemical Characteristics With Clinical Findings and Case Outcome.

Pituitary glands from 141 feline autopsy cases were reviewed histologically. Adenoma and hyperplasia were the most common lesions at 13 cases each. Pituitary adenoma was more likely than hyperplasia to be associated with clinical evidence of endocrinopathy or an intracranial mass (P < .001). A histochemical and immunohistochemical panel was applied to 44 autopsy- or hypophysectomy-derived pituitary adenomas in 43 cats from 2 diagnostic laboratories. Adenomas were differentiated from hyperplasia by the presence of disrupted reticulin fibers. One cat had a double (somatotroph and melanotroph) adenoma. Twenty somatotroph adenomas consisted of periodic acid-Schiff (PAS)-negative acidophils that expressed growth hormone; 16/20 had hypersomatotropism; 17/20 had diabetes mellitus. Eleven melanotroph adenomas consisted of PAS-positive basophils or chromophobes that expressed melanocyte-stimulating and adrenocorticotrophic hormones; 5/11 had hypercortisolism; 6/11 had diabetes mellitus. Eleven gonadotroph adenomas consisted of PAS-negative chromophobes that expressed follicle-stimulating and/or luteinizing hormones. Two thyrotroph adenomas consisted of PAS-negative basophils or chromophobes that expressed thyroid-stimulating hormone. Pituitary-dependent disease was not recognized in cats with gonadotroph or thyrotroph adenomas. The Ki-67 proliferation index in hypophysectomy specimens was lower in somatotroph than in melanotroph adenomas. Fourteen cats with hypophysectomy-treated somatotroph or melanotroph adenoma had an 899-day median survival time versus 173 days in 17 nonsurgical cases. After adjusting for age, adenoma size and type, hypophysectomized cats had an overall better survival time than nonsurgical cases (P = .029). The study results underscore the value of hypophysectomy and trophic hormone immunohistochemistry in the treatment and classification of feline pituitary adenomas.

Immunohistochemical Evaluation of Canine Pituitary Adenomas Obtained by Transsphenoidal Hypophysectomy.

Hypophysectomy specimens from 16 dogs with pituitary adenoma were evaluated with periodic acid-Schiff (PAS), reticulin, and immunohistochemistry for adrenocorticotrophic hormone (ACTH), melanocyte stimulating hormone (MSH), growth hormone (GH), and Ki-67. The reticulin network was obliterated in all adenomas. One adenoma expressed ACTH and GH. Eight corticotroph adenomas were basophilic to chromophobic, and PAS- and ACTH-positive. Seven melanotroph adenomas were distinguished from corticotroph adenomas by expression of MSH. Pituitary-dependent hypercortisolism was diagnosed in 5 of 8 dogs with corticotroph and 4 of 7 with melanotroph adenoma. Pituitary height/brain area (P/B) ratio was elevated in all dogs. Previous canine hypophysectomy studies suggested that melanotroph adenomas were larger and carried a worse prognosis than corticotroph adenomas; however, in this study, corticotroph adenomas in comparison to melanotroph adenomas were larger (median P/B ratio: 1.06 versus 0.76), more proliferative (median Ki-67 index: 9.47% versus 1.99%), and associated with shorter survival (median: 300 versus 793 days). Recommended immunohistochemistry for PAS-positive pituitary adenomas includes ACTH and MSH to distinguish corticotrophs from melanotrophs and Ki-67 for proliferation index.

Histopathologic Findings in Canine Pituitary Glands.

To optimize the histologic evaluation of hypophysectomy specimens, sections of 207 canine pituitary glands (196 postmortem, 11 hypophysectomy specimens) were reviewed. Adenohypophyseal proliferation was the most common (n = 79) lesion. Proliferative lesions were sparsely to densely granulated; the granules were usually basophilic to chromophobic and periodic acid-Schiff-positive. Adenohypophyseal proliferation was classified as hyperplasia (n = 40) if ≤2 mm diameter with intact reticulin network, as microadenoma (n = 22) for 1-5 mm homogeneous nodules with lost reticulin network, or as macroadenoma (n = 17) for larger tumors. Craniopharyngeal duct cysts were common incidental lesions and the only lesion in 15 dogs. Uncommon diagnoses included lymphoma (n = 4), hemorrhagic necrosis (n = 4), metastatic carcinoma (n = 3), hypophysitis (n = 3), ependymoma (n = 2), craniopharyngioma (n = 2), and 1 case each of metastatic melanoma, pituicytoma, gliomatosis, germ cell tumor, meningioma, and atrophy. The pituitary histologic diagnosis was associated with hyperadrenocorticism (HAC; P < .001) and adrenocortical histologic diagnosis ( P = .025). Both HAC and adrenocortical hyperplasia showed a positive trend with the degree of adenohypophyseal proliferation. The association of adrenocortical hyperplasia with HAC was not significant ( P = .077). Dogs with adenohypophyseal proliferations were older than dogs with normal pituitary glands ( P < .05). Brachycephalic breeds were overrepresented among dogs with pituitary macroadenoma or craniopharyngeal duct cysts, but the association was not statistically significant ( P = .076). Adenohypophyseal hyperplasia was more common than adenoma among postmortem specimens, but was unexpected in >80% of cases. Pituitary macroadenoma was the most common diagnosis in hypophysectomy specimens.

Extraskeletal osteosarcoma of the heart presenting as infective endocarditis.

A 7 yr old castrated male Labrador retriever (35.6 kg) was evaluated for an acute onset of vomiting of 24 hr duration. On initial examination, the patient was febrile (103.8°F) and tachycardic (150 beats/min). Thoracic radiographs revealed left atrial enlargement with mild pulmonary infiltrates. The dog's condition worsened and repeat radiographs revealed worsening pulmonary infiltrates and pleural effusion. Treatment for heart failure was initiated. An echocardiogram showed a large 3 cm × 4 cm vegetation on the atrial surface of the posterior mitral valve. The patient was euthanized due to poor clinical appearance and infective endocarditis was suspected. Necropsy revealed an osteosarcoma of the posterior mitral valve, which cultured negative.

Prognostic value of serum total thyroxine concentration at admission to an intensive care unit for critically ill dogs.

OBJECTIVE: To determine whether serum total thyroxine (TT4) concentration at admission to an intensive care unit (ICU) was associated with mortality rate and duration of hospitalization for critically ill dogs. ANIMALS: 166 client-owned dogs that were hospitalized in the ICU of a private veterinary practice from January 2013 through December 2016 and for which serum TT4 concentration had been measured at admission. PROCEDURES: Medical records were reviewed to collect data regarding patient signalment, concurrent illnesses, medications, reason for hospitalization, outcome (death, euthanasia, or survival to hospital discharge), duration of hospitalization, and initial serum TT4 concentration. RESULTS: Mean age of the 166 dogs was 8.6 years (range, 1 to 16 years). Overall mortality rate was 15.7%, with 26 dogs failing to survive to hospital discharge. Of these 26 dogs, 7 died and 19 were euthanized. No significant association was identified between serum TT4 concentration at admission and survival to discharge (yes or no) or duration of hospitalization. Age was significantly associated with survival to discharge, with older dogs less likely to survive than younger dogs. Duration of hospitalization was also associated with survival to discharge, with longer hospital stays associated with a lower likelihood of survival to discharge. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that serum TT4 concentration at admission to an ICU had no prognostic value in this population of critically ill dogs.

Expected total thyroxine (TT4) concentrations and outlier values in 531,765 cats in the United States (2014-2015).

BACKGROUND: Levels exceeding the standard reference interval (RI) for total thyroxine (TT4) concentrations are diagnostic for hyperthyroidism, however some hyperthyroid cats have TT4 values within the RI. Determining outlier TT4 concentrations should aid practitioners in identification of hyperthyroidism. The objective of this study was to determine the expected distribution of TT4 concentration using a large population of cats (531,765) of unknown health status to identify unexpected TT4 concentrations (outlier), and determine whether this concentration changes with age. METHODOLOGY/PRINCIPLE FINDINGS: This study is a population-based, retrospective study evaluating an electronic database of laboratory results to identify unique TT4 measurement between January 2014 and July 2015. An expected distribution of TT4 concentrations was determined using a large population of cats (531,765) of unknown health status, and this in turn was used to identify unexpected TT4 concentrations (outlier) and determine whether this concentration changes with age. All cats between the age of 1 and 9 years (n = 141,294) had the same expected distribution of TT4 concentration (0.5-3.5ug/dL), and cats with a TT4 value >3.5ug/dL were determined to be unexpected outliers. There was a steep and progressive rise in both the total number and percentage of statistical outliers in the feline population as a function of age. The greatest acceleration in the percentage of outliers occurred between the age of 7 and 14 years, which was up to 4.6 times the rate seen between the age of 3 and 7 years. CONCLUSIONS: TT4 concentrations >3.5ug/dL represent outliers from the expected distribution of TT4 concentration. Furthermore, age has a strong influence on the proportion of cats. These findings suggest that patients with TT4 concentrations >3.5ug/dL should be more closely evaluated for hyperthyroidism, particularly between the ages of 7 and 14 years. This finding may aid clinicians in earlier identification of hyperthyroidism in at-risk patients.

Outcomes of the addition of pasireotide to traditional adrenal-directed treatment for dogs with pituitary-dependent hyperadrenocorticism secondary to macroadenoma: 9 cases (2013-2015).

OBJECTIVE To evaluate clinical signs, endocrine test results, and pituitary tumor size for dogs with medically managed pituitary-dependent hyperadrenocorticism (PDH) and macroadenoma following 6 months of concurrent treatment with pasireotide. DESIGN Prospective case series. ANIMALS 9 client-owned dogs with PDH and macroadenoma in which PDH had been successfully managed with adrenal-directed treatment (trilostane or mitotane). PROCEDURES Dogs were given pasireotide (0.03 mg/kg [0.014 mg/lb], SC, q 12 h) for 6 months, while adrenal-directed treatment was continued. Physical examination, basic clinicopathologic testing, ACTH stimulation testing, and plasma ACTH concentration measurement were performed before (baseline) and 3 and 6 months after treatment began. Measurements of pituitary gland volume and pituitary gland-to-brain ratio were performed via MRI at baseline and 6 months after treatment began. RESULTS No dog developed neurologic abnormalities or signs of adverse effects during the study period. No differences from baseline were identified in clinicopathologic values, ACTH stimulation test results, or plasma ACTH concentration at the 3- or 6-month assessment points. After 6 months of pasireotide treatment, 6 dogs had decreases in MRI-measured values, and 3 had increases. CONCLUSIONS AND CLINICAL RELEVANCE Pasireotide as administered in this study had no noted adverse effects on dogs with PDH and macroadenoma successfully managed with standard treatment. Placebo-controlled, randomized studies are needed to determine whether pasireotide protects from the development of neurologic signs or improves outcome in dogs with pituitary macroadenomas.

Intramuscular administration of a low dose of ACTH for ACTH stimulation testing in dogs.

OBJECTIVE: To compare adrenal gland stimulation achieved following administration of cosyntropin (5 microg/kg [2.3 microg/lb]) IM versus IV in healthy dogs and dogs with hyperadrenocorticism. DESIGN: Clinical trial. Animals-9 healthy dogs and 9 dogs with hyperadrenocorticism. PROCEDURES: In both groups, ACTH stimulation was performed twice. Healthy dogs were randomly assigned to receive cosyntropin IM or IV first, but all dogs with hyperadrenocorticism received cosyntropin IV first. In healthy dogs, serum cortisol concentration was measured before (baseline) and 30, 60, 90, and 120 minutes after cosyntropin administration. In dogs with hyperadrenocorticism, serum cortisol concentration was measured before and 60 minutes after cosyntropin administration. RESULTS: In the healthy dogs, serum cortisol concentration increased significantly after administration of cosyntropin, regardless of route of administration, and serum cortisol concentrations after IM administration were not significantly different from concentrations after IV administration. For both routes of administration, serum cortisol concentration peaked 60 or 90 minutes after cosyntropin administration. In dogs with hyperadrenocorticism, serum cortisol concentration was significantly increased 60 minutes after cosyntropin administration, compared with baseline concentration, and concentrations after IM administration were not significantly different from concentrations after IV administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in healthy dogs and dogs with hyperadrenocorticism, administration of cosyntropin at a dose of 5 microg/kg, IV or IM, resulted in equivalent adrenal gland stimulation.

Astrocytomas in young dogs.

Primary brain tumors are not commonly reported in young dogs; however, they are the second most common cancer in children. Astrocytomas are the majority of these tumors. This report presents three cases of astrocytomas in young dogs, indicating a possible higher incidence than what is currently held. When suspected, it is recommended that biopsy or surgical excision be performed to further characterize and grade the tumor and, if appropriate, guide treatment.