Vincristine-induced adverse events related to body weight in dogs treated for lymphoma.

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.

Clinical outcomes in cats with renal carcinoma undergoing nephrectomy: A retrospective study.

Renal carcinomas (RC) are uncommonly encountered in feline medicine. Limited information regarding clinical presentation and postoperative outcomes is available. The purpose of this multi-institutional, retrospective study was to describe the presenting features and clinical outcomes of cats with RC undergoing nephrectomy. Thirty-six client-owned cats were included. Medical records from participating institutions were searched to identify cats that had a histopathologic diagnosis of RC and underwent nephrectomy from January 2001 to October 2021. The most common presenting complaints were weight loss (36.1%) and hyporexia (30.6%). Based on preoperative imaging and intraoperative findings, eight cats had suspected metastasis at the time of surgery (22.2%). Twenty-eight cats survived to discharge (77.8%). Median progression free interval (PFI) could not be determined, as only six cats developed suspected recurrence (16.7%) and seven cats developed suspected metastasis (19.4%). The all-cause median survival time (MST) was 203 days (95% confidence interval [CI]: 84, 1379 days). When cases that died prior to discharge were excluded, MST increased to 1217 days (95% CI: 127, 1641 days). One-year, two-year, and three-year survival rates were all 40.4%. Neither renal tumour histologic subtype nor the presence of preoperative azotemia, anaemia, erythrocytosis, haematuria, or suspected metastasis at diagnosis were found to influence survival. For cats surviving to discharge, prolonged survival times were possible. Further studies are necessary to elucidate other potential prognostic factors, the utility of postoperative adjuvant treatment, and to identify cats at-risk of mortality in the perioperative period.

Imaging features of benign synovial inflammation affecting the long digital extensor tendon sheath in a dog.

A dog was evaluated for right pelvic limb lameness. Computed tomography and magnetic resonance imaging revealed an irregular, contrast-enhancing mass extending along the proximolateral right tibia, involving the long digital extensor tendon (LDET) ± cranial tibialis muscle. Pulmonary nodules, nonspecific hepatomegaly, and splenic nodules were also present. The primary differential diagnosis was soft tissue neoplasia. Surgical biopsy with histopathology revealed benign, chronic inflammation, and fibrosis. Idiopathic synovial inflammation should be included as a differential diagnosis for dogs with this combination of clinical and imaging characteristics.

Clinical Utility of Cytology from Preoperative Percutaneous Fine Needle Aspirates of Solitary Liver Masses in 220 Dogs: A Retrospective Study (2009-2019).

When a solitary liver mass is identified in a dog, a fine-needle aspirate (FNA) is commonly employed to attempt to obtain a diagnosis. Little information is provided in the literature evaluating the sensitivity/specificity of FNA cytology for solitary liver masses. We hypothesized that liver lesion size nor the presence of cavitation would impact the success of cytological diagnosis. Medical records were obtained for 220 client-owned dogs. Inclusion criteria included preoperative abdominal imaging, percutaneous FNA of a solitary hepatic mass with cytologic interpretation by a board-certified pathologist, and a surgical biopsy or mass excision yielding a histopathological diagnosis. Six dogs (2.7%) experienced a complication after FNA, none considered severe. The agreement rate for correct cytologic diagnosis was 22.9% (49/220). Of the neoplastic masses 18.9% (35/185) were correctly diagnosed via cytology. The overall sensitivity was 60%, and the specificity was 68.6%. Neither institution (P = 0.16), lesion size (P = 0.88), cavitation (P = 0.34), or needle gauge (P = 0.20) had an association with correct diagnosis. This study demonstrates that, although there is a low risk of complications following FNA of a hepatic mass, overall success rate for correct cytologic diagnosis based on FNA was low compared to histopathologic diagnosis.

Retrospective study of 20 cats surgically treated for insulinoma.

OBJECTIVE: To report the clinical signs, histopathology results, and prognostic factors for outcomes following excision for feline insulinoma (INS). STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Twenty client-owned cats. METHODS: Medical records from 2006 to 2020 were reviewed by Veterinary Society of Surgical Oncology members for cats with hypoglycemia resulting from INS, with surgical excision and follow up. Clinical signs and histopathology results were summarized. Factors potentially related to disease-free interval (DFI), disease-related death (DRD), and overall survival time (OST) were analyzed with a Cox proportional hazards regression analysis. RESULTS: All cats were hypoglycemic on presentation with neurologic signs in 18 out of 20 and inappropriate insulin levels in 12/13. Excision of insulinomas resulted in immediate euglycemia or hyperglycemia in 18 cats. Eighteen cats survived to hospital discharge. The median time to death or last postoperative follow up was 664 days (range: 2-1205 days). Prognostic factors included age at presentation (for DFI); time to postoperative euglycemia (for DRD); preoperative and postoperative serum blood glucose concentrations; metastasis at the time of surgery (DFI and DRD), and histopathologic tumor invasion (for OST). The median OST for all cats was 863 days. The 1-, 2- and 3-year survival rates were 75%, 51%, and 10%, respectively. CONCLUSION: Excision of insulinoma resulted in euglycemia or hyperglycemia in most cats. Negative prognostic factors included young age, low serum glucose concentrations, metastasis at time of surgery, tumor invasion, and shorter time to euglycemia. CLINICAL SIGNIFICANCE: Surgical excision resulted in survival times comparable to those of canine INS.

Use of doxorubicin chemotherapy following debulking surgery in the treatment of a cat with mesenteric hemangiosarcoma.

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.

Evaluation of coated platelets, a subset of highly procoagulant platelets, in healthy dogs and dogs with neoplasia.

OBJECTIVE: To determine if dogs with neoplasia produce more coated platelets, a subpopulation of activated platelets generated by dual stimulation with thrombin and convulxin, a glycoprotein VI agonist, than healthy control dogs. ANIMALS: Client-owned dogs diagnosed with lymphoma (n = 19) or solid tumors (14) and healthy control dogs (14). PROCEDURES: Platelets were stimulated ex vivo with thrombin and convulxin. Flow cytometry was used to quantify the percentage of coated platelets based on high levels of surface fibrinogen. To compare the percentage of coated platelets between the three groups, an ANOVA was performed followed by pairwise 95% confidence intervals (CI) adjusted for multiple comparisons using Tukey's method. RESULTS: We observed a greater mean percentage of coated platelets in dogs with solid tumors, compared with healthy control dogs, by 10.9 percentage points (95% CI: -1.0, 22.8), and a mean percentage of coated platelets in dogs with lymphoma that was less than healthy control dogs by 0.3 percentage points (95% CI: -11.4, 10.8). CLINICAL RELEVANCE: This study provides the first data-based evidence that dogs with solid tumors may have a greater mean coated platelet percentage when compared with healthy control dogs, although there is overlap between groups. Further studies are needed investigating coated platelets in specific subsets of neoplasia and investigating additional mechanisms of hypercoagulability in dogs with neoplasia.

A retrospective analysis of 11 dogs with surface osteosarcoma.

While the majority of canine osteosarcomas (OSA) arise from the medullary cavity, a subset arises from the surface of bone. In humans, surface OSA often has a more indolent disease course with better outcomes than medullary OSA. The aim of this retrospective case series was to evaluate the clinical outcome and potential prognostic factors of dogs with surface OSA. Medical records from 11 dogs previously diagnosed with surface OSA were included. Histopathology of cases was evaluated during case review by two veterinary anatomic pathologists. Median progression free interval (PFI) and overall median survival time (OST) were estimated using Kaplan-Meier methods. Intergroup comparisons were performed using log-rank tests. Six dogs were diagnosed with periosteal OSA, 4 dogs with parosteal OSA, and one dog with an unclassified surface OSA. Two dogs were found to have metastatic disease at the time of diagnosis and four developed metastatic lesions after treatment. The median PFI and median OST for all dogs with surface OSA was 425 and 555 days, respectively. The 6 dogs diagnosed with periosteal OSA had a median PFI of 461 days and median OST of 555 days, while the 4 dogs with parosteal OSA had a PFI of 350 days and the OST could not be calculated. Multiple prognostic factors (surgery, systemic adjunctive therapy, elevated alkaline phosphatase at diagnosis, appendicular vs axial location, mitotic count, and tumour grade) were evaluated and none were prognostic for PFI or OST. Dogs with surface OSA appear to have prolonged PFI and OST, consistent with humans with surface OSA.

Feline cutaneous lymphoma: an evaluation of disease presentation and factors affecting response to treatment.

OBJECTIVES: The primary goal of this study was to characterize the clinical presentation of feline cutaneous lymphoma. The secondary aims included determining if treatment or initial response to treatment affected the overall survival of patients, and understanding if disease characteristics such as immunophenotype, cell size or the presence of epitheliotropism influenced response to treatment. METHODS: Veterinary medical oncologists at four academic veterinary teaching hospitals submitted cases of feline patients with cutaneous lymphoma diagnosed by histopathology or cytology. Signalment, feline leukemia virus (FeLV)/feline immunodeficiency virus (FIV) status, physical examination findings, clinical signs, diagnostic tests, therapy, response and outcome, and necropsy findings, when available, were recorded. RESULTS: Forty-one patients were identified and described. The majority of patients were domestic shorthair cats (n = 29). The median age at diagnosis was 12.3 years. Males were over-represented in the population (n = 30). In the majority of patients (n = 33), the FIV/FeLV status was unknown. Twenty patients were fully staged. Thirty-four patients were treated with a variety of modalities, including surgery, radiation, single-agent or combination chemotherapy, or prednisolone only. In multiple patients, surgery or radiation was combined with a systemic therapy. Of 34 patients treated with some form of therapy, 20 responded (achieving either a partial response or complete remission). CONCLUSIONS AND RELEVANCE: Clinical signs and physical examination findings varied among patients. Response to therapy appeared to be associated with survival (P = 0.0025); however, this population was highly censored. Immunophenotype, cell size and the presence of epitheliotropism did not influence treatment response. Results were limited by small numbers of patients, heterogeneous disease manifestations and treatment protocols. Further studies are necessary to evaluate the effect of specific treatment modalities and disease subtype on prognosis.

Characterization of receptor tyrosine kinase activation and biological activity of toceranib phosphate in canine urothelial carcinoma cell lines.

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, PDGFRß, and KIT to assess whether dysregulation of these RTKs may contribute to the observed biological activity of TOC. RESULTS: Transcript for VEGFR2, PDGFRα, PDGFRß, 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 PDGFRß 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 PDGFRß 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.

Outcomes of cats treated with maxillectomy: 60 cases. A Veterinary Society of Surgical Oncology retrospective study.

Maxillectomy is poorly described for the management of oral tumours in cats and is occasionally not recommended because of the high complication rate and sub-optimal outcome reported in cats treated with mandibulectomy. The purpose of this study was to retrospectively evaluate the complications and oncologic outcome in cats treated with maxillectomy. Sixty cats were included in the study. Maxillectomy procedures included unilateral rostral (20.0%), bilateral rostral (23.3%), segmental (10.0%), caudal (20.0%) and total unilateral maxillectomy (26.7%). Intra-operative and post-operative complications were reported in 10 (16.7%) and 34 (56.7%) cats, respectively. The most common post-operative complications were hyporexia (20.0%) and incisional dehiscence (20.0%). The median duration of hyporexia was 7 days. Benign tumours were diagnosed in 19 cats (31.7%) and malignant tumours in 41 cats (68.3%). Local recurrence and metastatic rates were 18.3% and 4.9%, respectively; the median progression-free interval (PFI) was not reached. The disease-related median survival time was not reached overall or for either benign or malignant tumours. The 1- and 2-year survival rates were, respectively, 100% and 79% for cats with benign tumours, 89% and 89% for cats with malignant tumours, 94% and 94% for cats with fibrosarcomas, 83% and 83% for cats with squamous cell carcinomas, and 80% and 80% for cats with osteosarcomas. Poor prognostic factors included mitotic index for PFI, adjuvant chemotherapy for both PFI and survival time, and local recurrence for survival time. Maxillectomy is a viable treatment option for cats resulting in good local tumour control and long survival times.

Determination of a serum total calcium concentration threshold for accurate prediction of ionized hypercalcemia in dogs with and without hyperphosphatemia.

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.

Perioperative complications and outcome after surgery for treatment of gastric carcinoma in dogs: A Veterinary Society of Surgical Oncology retrospective study of 40 cases (2004-2018).

OBJECTIVE: To describe the clinical characteristics, perioperative complications, and outcomes in dogs surgically treated for gastric carcinoma. STUDY DESIGN: Multi-institutional retrospective case series. ANIMALS: Forty client-owned dogs with histologically confirmed gastric carcinoma. METHODS: Medical records were reviewed for preoperative diagnostics, surgery, histopathology, postoperative complications, adjuvant chemotherapy, disease progression, and survival. Variables were assessed for associations with outcome by using Cox proportional hazards regression analysis. RESULTS: Surgical treatment included partial gastrectomy (28 dogs), Billroth I (9 dogs), subtotal gastrectomy (2 dogs), and submucosal resection (1 dog). Major postoperative complications occurred in 8 of 40 dogs, including septic peritonitis secondary to dehiscence in 4 dogs. The median progression free interval was 54 days, and the median survival time (MST) was 178 days (range, 1-1902). According to multivariable analysis results, experiencing an intraoperative complication was associated with an increased risk of death (hazard ratio [HR] 3.5, 95% CI 1.1-9.8, P = .005), and administration of adjuvant chemotherapy correlated with an improved survival (HR 0.4, 95% CI 0.2-0.9, P = .03). CONCLUSION: In this population of dogs, MST exceeded historically reported data, major postoperative complication rates were comparable to established literature, and administration of adjuvant chemotherapy was associated with improved survival. CLINICAL SIGNIFICANCE: Results from this study may be used to counsel owners more accurately regarding prognosis for dogs undergoing surgical excision for gastric carcinoma.

Primary pulmonary histiocytic sarcoma in dogs: A retrospective analysis of 37 cases (2000-2015).

Primary pulmonary histiocytic sarcoma (PHS) has been reported, but is not well characterized. The aim of this retrospective study was to describe clinical characteristics, characterize prognostic factors and report the outcome of a larger group of dogs with primary PHS. Medical records of dogs diagnosed with primary PHS at 11 institutions were retrospectively reviewed. Thirty-seven dogs were included; 13 received CCNU-based chemotherapy alone, 18 received surgery and adjuvant CCNU-based chemotherapy, 3 received medical management alone and 3 dogs received surgery alone. The overall median progression free survival (PFS) and the median survival (overall survival [OS]) were 197 and 237 days, respectively. Measurable responses were noted in dogs receiving only chemotherapy; however, responses were not durable with PFS (91 days) and OS times (131 days) shorter than overall medians. Dogs that received surgery and chemotherapy had significantly prolonged PFS (276 days, P = 0.001) and OS (374 days, P = 0.001), compared with dogs not receiving surgery. As only three dogs undergoing surgery did not receive chemotherapy, it is not possible to determine the contribution of chemotherapy as an adjuvant to surgery. Dogs without evidence of intra-thoracic metastatic disease were much more likely to undergo surgery (odds ratio = 7.04; P = 0.018). While the presence of metastasis or clinical signs at diagnosis negatively impacted PFS, only the former negatively impacted OS. These data imply that dogs presenting with PHS amenable to surgery (ie, no clinical evidence of metastasis) benefit from surgical intervention; however, the lack of a comparable surgery alone group precludes assessment of the efficacy of post-surgical adjuvant chemotherapy.

Parenchymal signal intensity in 3-T body MRI of dogs with hematopoietic neoplasia.

We performed a preliminary study involving 10 dogs to assess the applicability of body MRI for staging of canine diffuse hematopoietic neoplasia. T1-weighted (before and after intravenous gadolinium), T2-weighted, in-phase, out-of-phase, and short tau inversion recovery pulse sequences were used. By using digital region of interest (ROI) and visual comparison techniques, relative parenchymal organ (medial iliac lymph nodes, liver, spleen, kidney cortex, and kidney medulla) signal intensity was quantified as less than, equal to, or greater than that of skeletal muscle in 2 clinically normal young adult dogs and 10 dogs affected with either B-cell lymphoma (n = 7) or myelodysplastic syndrome (n = 3). Falciform fat and urinary bladder were evaluated to provide additional perspective regarding signal intensity from the pulse sequences. Dogs with nonfocal disease could be distinguished from normal dogs according to both the visual and ROI signal-intensity relationships. In normal dogs, liver signal intensity on the T2-weighted sequence was greater than that of skeletal muscle by using either the visual or ROI approach. However in affected dogs, T2-weighted liver signal intensity was less than that of skeletal muscle by using either the ROI approach (10 of 10 dogs) or the visual approach (9 of 10 dogs). These findings suggest that the comparison of relative signal intensity among organs may have merit as a research model for infiltrative parenchymal disease (ROI approach) or metabolic effects of disease; this comparison may have practical clinical applicability (visual comparison approach) as well.

Initial evaluation of safety of wide-field irradiation in the treatment of hematopoietic neoplasia in the cat.

Localized radiation therapy is well tolerated in cats with confined tumors; however, the use of wide-field radiation therapy to treat disseminated neoplasia has not been evaluated systematically in this species. Wide-field external beam radiation therapy, which we define as irradiation of cranial or caudal halves of the body either individually or sequentially, was undertaken as an experimental option to treat cats with either chemotherapy-refractory or naive hematopoietic neoplasia considered to have a poor prognosis. Fifteen cats with hematopoietic malignancies received wide-field external beam radiation therapy between 2003 and 2006. Cats received 8 Gy delivered in 4 Gy fractions with 60Co photons. Treatment-related toxicity was scored according to criteria established by the Veterinary Cooperative Oncology Group. Animals without preexisting abnormalities on hemograms exhibited no or mild (Grade 1 or 2) hematopoietic toxicity. Although most cats (14 of 15) had preexisting gastrointestinal (GI) signs, these signs were stable (29%) or improved (42%) following irradiation. Worsening GI signs following irradiation occurred transiently in two cats and in association with progressive disease in two others. No pulmonary, renal, hepatic, or dermatologic toxicities were detected. In summary, wide-field external beam radiation therapy can be administered safely to, and may provide therapeutic benefit for, cats with disseminated hematopoietic neoplasia.