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Abstract Background Traditional dosing of chemotherapy drugs based on body surface area may overdose small dogs, leading to an increased frequency of adverse events (AEs). Hypothesis/Objectives Evaluate the frequency of hematologic and gastrointestinal AEs in dogs with newly diagnosed lymphoma treated with vincristine weighing ≤15 kg in comparison to dogs weighing >15 kg. We hypothesized that dogs weighing ≤15 kg would experience a higher frequency of AEs. Animals One hundred and thirty-eight dogs with newly diagnosed lymphoma were treated with vincristine. Methods A multicenter retrospective study reviewing hematologic data and medical record information. Complete blood counts were performed no more than 24 hours before vincristine administration and then between 4 and 8 days post-administration. Data were evaluated using logistic regression or ordinal logistic regression. Results Thirty-eight dogs weighing ≤15 kg and 100 dogs weighing >15 kg were included. The median vincristine dose for both groups was 0.6 mg/m2. Seventeen (12.3%) instances of neutropenia occurred with no significant difference in overall frequency or grade between groups. Thirty initially asymptomatic substage A dogs (29.4%) experienced gastrointestinal AEs. Because of the widespread use of gastrointestinal supportive care medications, statistical comparison between groups could not be performed. Seven instances of hospitalization occurred (5.0%) and the risk of hospitalization did not differ significantly between groups (P = .37). Conclusions and Clinical Importance Vincristine dosed at ≤0.6 mg/m2 does not increase the risk of hematologic AEs in dogs weighing ≤15 kg.

Abstract Background Hypercalcemia of malignancy (HM) secondary to lymphoma in dogs has the potential to cause renal injury. Hypothesis/Objectives Characterize outcomes related to acute kidney injury (AKI) secondary to HM. We hypothesized that dogs do suffer AKI regardless of HM severity at the time of lymphoma diagnosis or relapse. Animals Retrospective study. Twenty-nine dogs with lymphoma, HM, and azotemia (International Renal Interest Society [IRIS] grade II or higher AKI) that underwent chemotherapy were identified at 2 veterinary institutions. Methods Logistic regression and descriptive statistical analysis were performed to evaluate data for potential prognostic factors. Results After initiating treatment, resolution of hypercalcemia and azotemia occurred in 100% (29/29) and 79.3% (23/29) of dogs, respectively. Resolution of azotemia was influenced by serum creatinine concentration (odds ratio [OR], 0.148; Confidence interval [CI], 0.03-0.734; P = .02) and total hypercalcemia (OR, 0.36; CI, 0.14-0.93; P = .04) at diagnosis, whereas blood urea nitrogen concentration, IRIS grade, sex, and whether or not dogs were hospitalized were not significant factors. At data analysis, 13.8% (4/29) of dogs were alive or lost to follow-up. Of those dead, 4 dogs (15%) had renal disease at the time of death, 2/4 having concurrent lymphoma progression. Conclusions and Clinical Importance Although AKI may be of clinical concern in dogs with HM secondary to lymphoma at diagnosis, death secondary to renal impairment appears to be infrequent.

Case summary An 11-year-old male castrated domestic shorthair cat presented with increased respiratory effort, pleural effusion, lymphadenopathy, lethargy and decreased appetite with weight loss. A diagnosis of T-zone lymphoma was made from histopathology of an extirpated popliteal lymph node that had a marked paracortical expansion of small lymphocytes and prominent high endothelial venule proliferation. T-cell receptor gamma (TRG) molecular clonality PCR yielded a clonal rearrangement and immunohistochemistry demonstrated that the neoplastic lymphocytes expressed CD3 and did not express CD20. The cat was initially treated with two doses of intravenous vincristine and oral prednisolone followed by oral chlorambucil. The pleural effusion, lymphadenopathy, lymphocytosis, abdominal organomegaly and lethargy resolved, and the cat’s appetite and body weight returned to normal. At the time of manuscript submission, the cat continued to do well, more than 24 months after presentation. Relevance and novel information T-zone lymphoma is a common indolent lymphoma in dogs, but it has only been histopathologically described in one cat before this report. This is the first report to describe the clinical presentation, clinicopathologic findings and outcome for a cat with T-zone lymphoma.

Abstract Background Total serum calcium (tCa) concentrations are poorly predictive of ionized calcium (iCa) status in dogs. Hypothesis There is an optimal threshold of tCa concentration that is highly predictive of ionized hypercalcemia and this threshold is higher in hyperphosphatemic dogs as compared to nonhyperphosphatemic dogs. Animals Nonhyperphosphatemic (n = 1593) and hyperphosphatemic (n = 250) adult dogs. Methods Retrospective medical record review of paired tCa and iCa concentration measurements in dogs presented to a university teaching hospital over a 5-year period. Positive and negative predictive values, sensitivity, and specificity were calculated for tCa concentration thresholds of 11.0-15.0 mg/dL (upper limit of laboratory reference interval = 11.5 mg/dL) in nonhyperphosphatemic and hyperphosphatemic groups. Results In nonhyperphosphatemic dogs, an optimal tCa concentration threshold of 12.0 mg/dL resulted in a positive predictive value of 93% (95% confidence interval [CI], 84%-98%) and sensitivity of 52% (95% CI, 43%-61%) for ionized hypercalcemia. An optimal tCa concentration threshold was not identified for hyperphosphatemic dogs. The nonhyperphosphatemic dogs had a higher prevalence of ionized hypercalcemia than the hyperphosphatemic dogs (7 versus 3%, P = .04) and a lower prevalence of ionized hypocalcemia (23 versus 62%, respectively; P < .001). Conclusions and Clinical Importance High tCa concentrations are strongly predictive of ionized hypercalcemia in nonhyperphosphatemic adult dogs and should prompt further diagnostic testing to determine the underlying cause of hypercalcemia. In this population, dogs without increased tCa concentrations rarely had ionized hypercalcemia, but iCa concentrations still should be evaluated in patients with tCa concentrations within the reference interval if there is clinical suspicion for calcium abnormalities.

Background Urothelial carcinoma (UC) accounts for > 90% of canine tumors occurring in the urinary bladder. Toceranib phosphate (TOC) is a multi-target receptor tyrosine kinase (RTK) inhibitor that exhibits activity against members of the split kinase family of RTKs. The purpose of this study was to evaluate primary UC tumors and UC cell lines for the expression and activation of VEGFR2, PDGFRα, PDGFRβ, and KIT to assess whether dysregulation of these RTKs may contribute to the observed biological activity of TOC. Results Transcript for VEGFR2, PDGFRα, PDGFRβ, and KIT was detected in all UC tissue samples and UC cell lines. The Proteome Profiler™ Human Phospho-RTK Array Kit (R & D Systems) provided a platform to assess phosphorylation of 42 different RTKs in primary UC tumors and UC cell lines. Evidence of PDGFRα and PDGFRβ phosphorylation was present in only 11% or 33% of UC tumors, respectively, and 25% of UC cell lines. Treatment of UC cell lines with TOC had no significant impact on cell proliferation, including UC cell lines with evidence of PDGFRβ phosphorylation. Conclusions Phosphorylation of several key RTKs targeted by TOC is present in a small subset of primary UC tumors and UC cell lines, suggesting that these RTKs do not exist in a state of continuous activation. These data suggest that activation of RTKs targeted by TOC is present in a small subset of UC tumors and UC cell lines and that treatment with TOC at physiologically relevant concentrations has no direct anti-proliferative effect on UC cells.

Case summary/ A 7-year-old male castrated domestic shorthair cat presented with a 5-day history of inappetence. A mid-abdominal mass was palpated and, on exploratory laparotomy, a cystic mass arising from the root of the mesentery was observed. The mass was drained, debulked and omentalized. Histopathologic examination and immunohistochemistry supported a diagnosis of hemangiosarcoma. Adjuvant doxorubicin was started and, prior to the third of five doses of doxorubicin, repeat abdominal ultrasound showed complete response of the primary tumor. Continued monitoring 240 days following histopathologic diagnosis revealed suspected metastasis to local lymph nodes, though the primary tumor remained absent on abdominal ultrasound. A second course of five doses of doxorubicin chemotherapy was completed. Serial abdominal ultrasounds demonstrated stable disease in the locoregional lymph nodes with no visible recurrence of the primary tumor. The cat presented 430 days following diagnosis with lethargy and inappetence. Abdominal ultrasound revealed suspected metastatic mesenteric and ileocolic lymphadenopathy, hepatic metastasis and peritoneal effusion, and the owner elected for humane euthanasia. Necropsy findings and negative immunohistochemical staining for lymphatic vessel endothelial receptor-1 were consistent with a metastatic mesenteric hemangiosarcoma. Relevance and novel information Hemangiosarcoma is an uncommon malignancy in cats, and few cases describing treatment have been reported. To our knowledge, this is the first report to describe the use of debulking surgery and adjuvant doxorubicin chemotherapy in the treatment of mesenteric hemangiosarcoma resulting in extended survival in a cat. Multimodal therapy can be considered for the management of cats with mesenteric hemangiosarcoma.

Background Insulinomas are the most common tumour of the endocrine pancreas in dogs. These malignant tumours have a high metastatic rate and limited chemotherapeutic options. The multi‐receptor tyrosine kinase inhibitor sunitinib malate has benefit in the treatment of metastatic insulinoma in people. Toceranib phosphate, an analogous veterinary agent, may provide benefit for dogs. Methods A retrospective study describing the extent and duration of clinical outcomes and adverse events (AEs) in dogs diagnosed with insulinoma and receiving toceranib. Results Records for 30 dogs diagnosed with insulinoma and having received toceranib were identified from a medical record search of five university and eight referral hospitals. The median progression‐free interval and overall survival time were 561 days (95% confidence interval (CI): [246, 727 days]) and 656 days (95% CI: [310, 1045 days]), respectively. Of the dogs for which the canine Response evaluation criteria for solid tumours tool could be applied, the majority (66.7%) showed either a complete response, partial response or stable disease. Time to clinical progression was associated with prior intervention and type of veterinary practice. Larger dogs were at increased risk for disease progression and death. No novel AEs were reported. Conclusions Most dogs diagnosed with insulinoma and receiving toceranib appeared to have a clinical benefit. Randomised, prospective studies are needed to better elucidate and objectively quantify the potential effect and survival benefit of toceranib therapy for management of insulinoma in dogs.

Background Canine hemangiosarcoma is a common and aggressive vascular malignancy predominantly affecting dogs over six years of age. Despite surgical resection followed by adjuvant chemotherapy, median survival remains around 4–6 months. Propranolol, a beta-adrenergic receptor (β-AR) antagonist, has shown efficacy in human angiosarcoma, a tumor with similar clinical and morphological characteristics, when combined with chemotherapy. Methods To determine if propranolol could be repurposed as an effective adjunct to chemotherapy, we conducted a phase I clinical study evaluating the safety and efficacy of propranolol combined with doxorubicin (PRO-DOX) in 20 dogs with stage 1 or stage 2 splenic hemangiosarcoma.Plasma from 19 dogs was analyzed for propranolol pharmacokinetics and RNA was extracted from tumors from 13 of the dogs for transcriptional profiling. Results Although propranolol did not appear to influence treatment outcomes, our results revealed long-term survival in young adult dogs (less than 6 years of age), suggesting the possibility of a better response to doxorubicin. Faster clearance of 4-OH propranolol also correlated with long-term survival in younger dogs, but this appeared to be associated with drug metabolism due to age rather than effects of the drug on survival outcomes. Gene expression analysis identified distinct age-associated tumor signatures, with young dogs exhibiting increased immune-related gene expression and older dogs showing elevated expression of genes associated with the cell cycle and the DNA damage response and repair. Conclusions These findings highlight several hallmarks of cellular aging in hemangiosarcoma that may influence treatment responses and long-term survival. Our findings suggest that young adult dogs with splenic hemangiosarcoma treated with doxorubicin have a better prognosis and underscore the need for further research into age-related molecular mechanisms of disease. These insights could refine therapeutic strategies and clinical decision-making in hemangiosarcoma management.

A 1-year-old, neutered male domestic shorthair cat with a several-day history of anorexia and lethargy presented to The Ohio State University Veterinary Medical Center. On physical examination, a mass-like lesion was palpated in the mid-abdomen. Abdominal radiographs, ultrasound and contrast-enhanced CT revealed a mass-like lesion associated with the right kidney. Unilateral nephrectomy with removal of the mass in its entirety was performed as the sole treatment modality, and histopathology revealed a renal nephroblastoma. Postoperatively, the cat was re-evaluated every 3-6 months. The cat continues to do well more than 3 years since diagnosis, which is longer than most published cases. This report aims to describe a case of feline nephroblastoma managed solely by surgical treatment, with an unexpectedly long survival time.