Veterinary and comparative oncology最新文献

Surgery is a common treatment for intracranial meningiomas in dogs, although the prognostic impact of the extent of resection (EOR) has not been systematically evaluated. This retrospective study identified prognostic factors associated with clinical outcomes in dogs that underwent surgery and early post-operative magnetic resonance imaging (epoMRI) to evaluate meningioma EOR. We hypothesised that gross total tumour resection (GTR) would result in longer progression free (PFS) and overall survival (OS), and superior post-operative seizure control and resolution of neurological dysfunction than subtotal resection (STR). Multivariable logistic regression was used to identify prognostic factors, and Kaplan-Meier analyses to compare survival outcomes. Forty-one dogs were included of which 24 (59%) had GTR and 17 (41%) had STR. GTR was associated with decreased rates of tumour progression (HR = 0.21; 95% CI, 0.09-0.42; p < 0.0001) and death (HR = 0.49; 95% CI, 0.14-0.69; p < 0.0001), and longer PFS (618 vs. 189 days, p < 0.0001) and OS (694 vs. 349 days, p < 0.0001) compared to STR. Higher tumour grade and increasing age negatively impacted PFS and OS, respectively. Seizure freedom was attained in a larger proportion of dogs with GTR (18/20 [90%]) than STR (4/13 [31%]; p < 0.001), but rates of improvement of neurological deficits were not different between groups. GTR resulted in durable clinical improvements and survivals in the absence of adjuvant treatments. EpoMRI to assess EOR should be routinely incorporated into management of canine meningiomas to inform outcome expectations, and to identify STR cases in which adjuvant therapies should be considered.

Radiation therapy (RT) has emerged as a promising non-surgical approach for treating canine adrenal tumours. This multi-institutional, retrospective study describes clinical outcomes for 21 dogs having been prescribed a course of hypofractionated image-guided intensity-modulated RT (IMRT) entailing delivery of 25-35 Gy total in 5 fractions given over 5-15 days for an adrenal tumour. Diagnoses were based on imaging (abdominal ultrasound or computed tomography) and biochemical testing. All dogs had unilateral or bilateral irregular adrenal masses with evidence of vessel compression or invasion. Adrenal masses were incidentally identified in 11 dogs. The clinical diagnoses included pheochromocytoma (n = 13, 61.9%), adrenocortical adenocarcinoma (n = 2, 9.5%) and unspecified (n = 6, 28.6%). Among the 16 dogs with available follow-up imaging, the rates of partial response and stable disease were 37.5% (6/16) and 62.5% (10/16), respectively. Mild gastrointestinal side effects related to RT were reported in four dogs (19%). Early death that could have been attributable to tumour or complications of treatment occurred in two dogs (9.5%) at 21 and 52 days post-RT; one presenting with acute vomiting, and the other presenting with vomiting, tremors, and shock before death. Of the 15 deceased dogs, 4 (26.7%) died due to tumour-related causes and 11 died due to unknown (n = 2) or unrelated (n = 9) causes. The median overall survival time was 377 days, with a median follow-up time of 458 days for censored patients (n = 6). The one- and two-year survival rates were 59.4% and 34.7%, respectively. These data build upon prior published reports, demonstrating that RT can be associated with prolonged survival in dogs with adrenal tumours. Hypofractionated IMRT appears to offer a potential survival benefit even in dogs with major vessel invasion or comorbidities. Future research should focus on identifying risk factors for early death and determining which patient populations are most likely to benefit from RT.

The cardiac-gated computed tomography (CT) scan reports of 12 dogs with right auricular appendage masses between 2018 and 2023 were reviewed to describe the use of cardiac-gated CT for assessment of right auricular appendage tumour location and extent and for staging. Imaging reports from thoracic radiographs, CT scans, abdominal ultrasound, and echocardiogram were evaluated for detection of a cardiac mass, mass location on the heart, and detection and location of suspected metastases. Surgery and necropsy reports were evaluated for definitive location of the cardiac mass. Descriptive statistics were performed. Cardiac-gated CT identified a mass that was confined to the right auricular appendage in seven dogs and involved additional cardiac structures in five dogs. Metastases were suspected on CT in 10 dogs. Surgery with the intent to remove the mass for cytoreduction was pursued in five dogs. Right auriculectomy was performed in four dogs. One dog whose mass was suspected to extend beyond the right auricular appendage on CT died during attempted surgical resection. Cardiac-gated CT helped guide clinical decision making by providing information about the location and extent of the mass to assess feasibility of surgical resection and also functioned as a sensitive staging test.

A clear understanding of human and canine osteosarcoma (hOS and cOS) immunobiology is needed to develop effective immunotherapeutic strategies, a promising option to improve outcomes. Previous studies in humans and dogs have underscored the importance of the macrophagic infiltrate. Notably, high M2-like macrophage infiltration has been associated with increased metastatic progression-free survival in hOS treated with surgery and chemotherapy. Given the strong similarities between hOS and cOS, we hypothesized that tumour infiltration by M2-like macrophages would also be associated with an improved prognosis in dogs. Eighty-four dogs with a histological diagnosis of cOS were retrospectively selected from the database of five veterinary institutions and one pathology laboratory. Medical data and associated cOS samples were retrieved from electronic records and original pathology laboratories. Macrophage populations were identified by immunohistochemistry using anti-CD204 and anti-CD206 antibodies. Univariate and multivariate Cox proportional hazard models were performed to identify factors associated with overall survival time (OST) in dogs treated with surgery with (SOC) or without (SxOnly) adjuvant chemotherapy. In dogs treated surgically (SOC + SxOnly), only high CD206+ infiltrate was associated with longer OST in both univariate (p = 0.019) and multivariate analysis (p = 0.014). Within the SOC group, high CD206+ infiltrate (p = 0.006) and lower body weight (p = 0.029) were associated with better outcome in the univariate analysis while high CD206+ infiltrate (p = 0.003) and female sex (p = 0.044) were associated with a longer survival in the multivariate analysis. This observation underscores the role of M2-like macrophages in OS and strengthens the relevance of cOS as a model for hOS in the immunological field.

Canine oral malignant melanoma (OMM) has a high potential for lymph node (LN) metastasis. Standard care involves surgical excision of the OMM with sentinel and draining LNs regardless of metastatic status but carries the risk of complications. Optical coherence tomography (OCT) is a rapid, noninvasive imaging modality that has been evaluated for LN metastasis detection in human breast cancer but not yet translated to canines. The purpose of this study was to (1) compare OCT imaging features from nonmetastatic and metastatic LNs with corresponding histopathology and (2) evaluate the diagnostic accuracy of OCT imaging in identifying metastatic LNs. Thirteen dogs with OMM were prospectively enrolled and sentinel LNs were identified by indirect computed tomography lymphography. OMM and draining LNs were surgically removed. Excised LNs (n = 50) from thirteen dogs were imaged with OCT and submitted for histopathology. OCT images of 18 LNs from the first five enrolled dogs were compared to histopathology to identify image features of metastatic and nonmetastatic LNs and identify images for observer training. The subsequent OCT images of 32 LNs of eight dogs were used to generate a test set for six observers with varying OCT experience for assessment of diagnostic accuracy. The sensitivity, specificity, and correct classification rate of OCT imaging for OMM LN metastasis in dogs was 75% (95% CI: 61.2%-85.1%), 76.6% (95% CI: 70.1%-82.0%), and 76.3% (95% CI: 70.5%-81.2%), respectively. OCT image features of nonmetastatic and metastatic LNs show diagnostic potential for intraoperative detection of OMM LN metastasis.

Lymph node (LN) metastasis has been associated with shorter survival times in dogs with mast cell tumour (MCT), and treatment of metastatic LN with lymphadenectomy or irradiation has been demonstrated to improve outcomes. Identification of metastatic LN in dogs with MCT is therefore of both prognostic and therapeutic significance. The aim of this prospective, exploratory study was to investigate whether fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) is a useful staging tool for the detection of metastatic LN in dogs with cutaneous or subcutaneous MCT, using histopathology as the gold standard. Sixteen client-owned dogs with cytologically or histologically confirmed cutaneous or subcutaneous MCTs underwent full-body ¹⁸F-FDG-PET/CT followed by surgical removal and histopathology of the primary tumour and regional LN(s). The maximum standard uptake value (SUV_max) of the tumour and LN(s) was measured. Primary tumours were graded using both the Patnaik and Kiupel grading systems, and mitotic count was tabulated. LNs were categorised based on Weishaar's histologic criteria for nodal metastasis. Eighteen primary tumours were excised: six subcutaneous and 12 cutaneous MCTs. Of 33 excised regional LNs, 18 (55%) were categorised as metastatic (≥ HN2). There was no difference between the median SUV_max of metastatic (3.88) and nonmetastatic LNs (3.16) (p = 0.41). SUV_max was positively correlated with the mitotic count of the primary tumour (p = 0.02). The results of this exploratory study suggest that ¹⁸F-FDG-PET/CT may not be useful for identifying metastatic LNs in canine MCT.

Canine lymphoma is a common haematopoietic neoplasm. Immunophenotype is a major prognostic factor and may influence treatment recommendations. This study assessed the diagnostic performance of the Sysmex XN-1000V white blood cell differential (WDF) scattergram to differentiate canine nodal large B-cell and T-cell lymphoma, using the percentage of highly fluorescent cells (%HFC) and visual WDF scattergram evaluation. A retrospective study was conducted on data from cases of cytologically diagnosed canine large cell lymphoma. Cases had concurrent lymph node aspirate cell suspensions in saline that were analysed using the Sysmex XN-1000V and multiparametric flow cytometry (FC) for lymphoma classification as B or T-cell. Large B-cell lymphomas (n = 86) showed significantly higher %HFC compared to large T-cell lymphomas (n = 17), with a median (IQR) of 50% (36-84) and 9.7% (3.9-19), respectively. The ROC analysis showed an AUC of 0.93, with an optimal cutoff of < 24.15 %HFC for identifying T-cell lymphoma, achieving 88.24% sensitivity, 87.21% specificity, 57.69% PPV and 97.40% NPV. The following data is expressed as 'overall-percentage-agreement (kappa value)'. Using the previous cutoff, the agreement between the %HFC classification and FC was 88.24% (κ = 0.76). Regarding the WDF scattergram evaluation, the intra- and inter-observer agreement were 86.27% (κ = 0.71) and 67.65% (κ = 0.55), respectively. Agreement between the WDF scattergram evaluation and FC was 77.45% (κ = 0.55), and improved to 90.63% (κ = 0.74) when just the confident cases were used. In conclusion, a preliminary assessment of the phenotype of canine nodal large cell lymphoma can be made using either the visual inspection of the WDF scattergram or the %HFC. This could serve as a cost-effective, fast screening tool while awaiting definitive flow cytometry results.

Glomerular filtration rate (GFR) predicts carboplatin clearance and myelotoxicity in humans and cats. This relationship is unknown in dogs. In canines, elevated serum symmetric dimethylarginine (SDMA) correlates with reduced GFR. This study prospectively evaluated whether dogs with elevated SDMA (> 14 μg/dL) are at increased risk of hematologic and gastrointestinal toxicity following carboplatin chemotherapy. Plasma samples were collected to determine if SDMA or other factors are significant determinants of carboplatin pharmacokinetics. Thirty client-owned dogs weighing > 15 kg with confirmed neoplasia were enrolled. Dogs received carboplatin intravenously (300 mg/m²). SDMA was measured on the day of treatment. Nonlinear mixed effects modelling was done to identify possible covariates affecting pharmacokinetic parameters. Adverse effects were monitored with weekly complete blood counts and owner assessment forms. Five dogs had elevated SDMA; four had significantly reduced carboplatin clearance (mean 93.9, range 76.1-116.8 mL/h/kg) compared with dogs with SDMA ≤ 14 μg/dL (mean 185.4, range 114.3-268.3 mL/h/kg, p < 0.001). Three dogs with elevated SDMA experienced grade 4 neutropenia; one was euthanized due to sepsis. Two additional dogs with elevated SDMA were euthanized 5- and 13-days post treatment due to severe gastrointestinal signs. Twenty-five dogs had SDMA ≤ 14 μg/dL: 10 had asymptomatic grade 3 or 4 neutropenia, 3 had grade 3 or 4 GI toxicity, and none died. Elevated SDMA was associated with decreased carboplatin clearance in dogs and predicted risk for treatment-related toxicity and death in our study population.

Dogs with intracranial tumours routinely receive radiotherapy, yet species-specific dose-volume constraints for normal brain tissue remain undefined. In human radiation oncology, exceeding certain brain dose-volume thresholds markedly increases the risk of radiation-induced injury (e.g., radionecrosis). Current veterinary practice often extrapolates human guidelines without validation in discrete species, creating a gap in evidence-based planning. This study aimed to identify brain dose-volume thresholds associated with overall survival (OS) in canine brain-tumour patients. We pooled data from two prospective randomised trials (n = 105 dogs) treated with 10 daily fractions of 4 Gy (total 40 Gy) for intracranial tumours at a single institution. Semi-automated scripting extracted multiple dose-volume metrics, including generalised equivalent uniform dose (gEUD), for the whole brain and brain minus gross tumour volume (Brain-GTV). An iterative Kaplan-Meier and Cox proportional hazards approach identified optimal dosimetric cutoffs, which were then adjusted for tumour volume and body weight via a regression residual method. A brain-volume-adjusted gEUD threshold was also derived to account for variation in brain size. Exposure to normal brain to doses around 30-40 Gy emerged as the strongest predictor of OS. Brain-GTV V32 Gy ≤ 13 cm³ was associated with longer OS (covariate-adjusted cutoff 13.4 cm³, HR = 1.74; p = 0.022, unadjusted optimal split 11.5 cm³, HR = 2.08; p = 0.001). Whole-brain gEUD > 30 Gy similarly predicted poorer survival (HR = 1.72; p = 0.034). Implementing a personalised gEUD ceiling increased 2-year sensitivity from 31% to 38% with only a three-point drop in specificity. In a 10 × 4 Gy canine intracranial radiotherapy model, limiting Brain-GTV V32 Gy to ≤ 13 cm³ and whole-brain gEUD to ≤ 30 Gy was associated with longer overall survival. A brain-volume-adjusted gEUD ceiling further refined risk prediction. These evidence-based thresholds provide actionable guidance for veterinary treatment planning, with the potential to improve outcomes in canine brain tumour therapy.

Mammary carcinomas are aggressive neoplasms and a significant cause of mortality in female cats. Despite surgical removal, feline mammary carcinoma (FMC) often recurs or metastasizes. Specific tumour biomarkers are necessary for early detection, prognosis and therapy selection. This study aims to identify candidate biomarkers for FMC by comparing tissue proteomic profiles among grades of 31 FMC cats and six normal mammary tissues (control) using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Candidate proteins identified by LC-MS/MS were validated by Western blotting and LC-MS/MS. Prognostic values of candidate proteins were evaluated using immunohistochemistry and survival analysis. Protein-chemotherapy drug interaction networks were also evaluated. Among the 268 differential proteins observed, dermatopontin (DPT) expression was significantly downregulated, while sorting nexin 5 (SNX5) expression was elevated in cancerous tissues compared to controls (p < 0.05). Immunohistochemistry results revealed a significant association of DPT and SNX5 with stages (DPT, p < 0.0001; SNX5, p = 0.046) and grades of FMC (DPT, p < 0.0001; SNX5, p = 0.04). Low DPT expression was associated with poor overall survival (p = 0.02), along with Stage 4 FMC (p = 0.0001), high mitotic count (p = 0.003) and the presence of lymphovascular invasion (p = 0.003). Moreover, protein-chemotherapy drug interaction showed a relationship of DPT with doxorubicin, lapatinib and neratinib. This study identified DPT and SNX5 as potential diagnostic and therapeutic targets for FMC, with DPT emerging as a promising prognostic biomarker.