Veterinary and comparative oncology最新文献

Intraoperative surgical margin evaluation is not routine in veterinary medicine. Polarisation-sensitive optical coherence tomography (PS-OCT) is a variant of spectral domain optical coherence tomography (SD-OCT) that can provide real-time cross-sectional imaging of surgical margins with additional information about the polarisation of light in tissues. The aims of this study were (1) to compare PS-OCT surgical margin images to histopathology of excised canine skin and subcutaneous tumour specimens, and (2) to determine if the addition of PS-OCT images improved the diagnostic accuracy of surgical margin assessment. The authors hypothesised that PS-OCT image features would resemble histopathologic tissue features and the addition of PS-OCT images would improve the accuracy of margin assessment. Sixty-one dogs with 79 skin and subcutaneous tumours were prospectively enrolled. Tumours were excised, the surgical margins were imaged with OCT and then submitted for histopathology. Six masked readers first received image interpretation training in SD-OCT only, followed by training in combined SD-OCT and PS-OCT 1 week later. The readers interpreted each image or video for the presence of cancer and the results were compared to histopathology. PS-OCT imaging features of surgical margin tissues were consistent with tissue histopathologic features at low power. The overall reader median sensitivity and specificity were 90.9% and 95.6% for SD-OCT only and 90.9% and 91.3% for combined SD-OCT and PS-OCT. The addition of PS-OCT images did not improve the diagnostic accuracy of the surgical margin assessment for skin and subcutaneous tumours but resulted in high accuracy of margin interpretation with readers of varying experience.

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.

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.

Cancer is a leading cause of mortality in older dogs. Despite the prevalence of chemotherapy in canine oncology, a good understanding of owners' observations of side effects and clinical signs in real time is still lacking. Owners' perceptions and reporting of clinical signs play an important role in monitoring a dog's condition during treatment and the use of digital owner-reported outcome measures could prove efficient in tracking chemotherapy side effects in the home environment. This could improve care and draws inspiration from the human use of patient-reported outcome measures in oncology. We aimed to develop and test a prototype digital measure for monitoring clinical signs and health-related quality of life in dogs undergoing chemotherapy, designed to facilitate owner participation in monitoring and support veterinary care. A rapid literature review was conducted to identify existing measures and their methodological limitations. Items were generated based on the Veterinary Comparative Oncology Group-Common Terminology Criteria for Adverse Events, existing client-reported outcome measures, and expert veterinary opinion. Proof-of-Concept testing was performed with 29 dog owners with pets undergoing chemotherapy. Participants completed daily assessments of their dog's clinical signs and weekly quality of life surveys over a 21-day period. A sub-sample participated in cognitive interviews to assess content validity and acceptability. Descriptive statistics were used to assess clinical signs and quality of life scores. Internal consistency and item discrimination were evaluated, and qualitative data were analyzed thematically. High adherence was reported, with a median of 21 daily and 3 weekly assessments completed. Participants found the assessments acceptable and beneficial. Fatigue, polydipsia, and anorexia were the most frequently reported clinical signs. Dogs experienced a median of 3 different clinical signs. The quality-of-life scale showed good internal consistency (Cronbach's α = 0.84). Participants appreciated the daily assessments, found them easy to complete, and believed the measure could help improve monitoring and decision-making during chemotherapy. The prototype tool, the Canine Cancer Outcome Measure (CAN-COM), demonstrated feasibility and acceptability for use by owners in the home environment for dogs undergoing chemotherapy. With further refinement and validation, such a tool could improve the monitoring of adverse events and support decision-making in veterinary oncology, enhancing the welfare of canine cancer patients.

Intra-operative staging of canine mast cell tumour (MCT) currently relies on routine cytology to determine nodal metastasis. While frozen section nodal histopathology is commonly used in humans, its applicability to veterinary settings is poorly characterised. The goal of this study was to determine the diagnostic performance of frozen section (FS) histopathology for diagnosing metastatic MCT, as compared to a formalin-fixed histopathologic gold standard. Performances of imprint cytology (IC) and fine needle aspirates (FNA) were also evaluated. Forty-one lymph nodes from 20 dogs with MCT were collected and stained with haematoxylin and eosin (HE) and Giemsa (formalin-fixed and frozen tissues), and Wright Giemsa and toluidine blue (IC and FNA). Nineteen out of 20 primary tumours were low grade. Frozen HE sections had poor agreement as compared to formalin-fixed HE histopathology (κ = 0.15); however, diagnostic performance increased to a good level of agreement when interpretation was combined with Giemsa (κ = 0.46). FNA and IC using Wright Giemsa had agreement comparable to combined frozen section histopathology (κ = 0.51 and 0.43, respectively). Combined frozen sections had a sensitivity of 65% and specificity of 93%, which was the same as FNA. Challenges encountered in morphologic interpretation of frozen sections included inadequate sectioning quality, architectural disruption, ruptured cells, and background metachromatic staining. These data provide support for FS histopathology as a feasible strategy for intra-operative detection of metastatic MCT, with diagnostic agreement similar to conventional cytology. Performance of FS histopathology is conditional upon a metachromatic stain evaluated in parallel with HE.

Canine cutaneous mast cell tumour (MCT) is the most common skin neoplasm in dogs, with histopathology serving as both the diagnostic and primary prognostic tool. However, identifying reliable biomarkers is essential for improving clinical decision-making. CD30, a member of the TNF receptor superfamily, is well-characterised in human haematopoietic malignancies. However, its role in canine MCTs remains unclear. This study aimed to evaluate CD30 expression in neoplastic mast cells and tumour-infiltrating lymphocytes (TILs), and to assess its prognostic significance in canine cutaneous MCTs. Immunohistochemical analysis of CD30, CD3, and PAX-5 was performed on 53 samples, and RNA sequencing was conducted to assess CD30 transcript levels in 17 cases. CD30 was detected in 94.6% of neoplastic mast cells, with strong staining observed in 35 cases and weak staining in 18. Strong CD30 expression (p = 0.0051), CD30+ TIL counts (p = 0.0105) and the diffuse infiltrate distribution pattern of CD3+ TILs (p = 0.0497) were associated with shorter post-surgical survival. RNA sequencing confirmed higher CD30 (TNFRSF8) gene expression levels in high-risk tumours (logFC = 2.3182; FDR = 0.0405). These findings suggest that CD30 is a promising biomarker with potential prognostic value in canine cutaneous MCTs.

Pet dogs with naturally occurring cancers provide valuable models for comparative oncology and pathology tumour registries offer a powerful resource for onco-epidemiological research. Here, we analysed the Small Animal Veterinary Surveillance Network (SAVSNET) pathology-based tumour registry (PTR), one of the largest veterinary tumour registries to date, focusing on four major canine tumours: mast cell tumour (MCT), osteosarcoma (OSA), haemangiosarcoma (HSA), and melanoma (MEL). A case-control study was conducted using a subset of 130 998 histologically confirmed tumours drawn from the pathology tumour registry containing over 1.1 million canine tumour records from 1.02 million dogs collected in the UK between 2010 and 2023. Case-control analyses were performed for melanoma, haemangiosarcoma, OSA and MCT using a denominator population of dogs attending first-opinion veterinary practices. Additionally for MCT, comparisons were made against dogs diagnosed with other tumour types ('tumour denominator' approach). Breed-specific risks were identified, including high odds ratios (OR) for Bulldog-related breeds and Retrievers with mast cell tumours (MCTs) (OR up to 6.8, 95% CI 6.0, 7.6), Rottweilers, Shar Pei and Giant-Schnauzer with melanoma (OR up to 50.3, 95% CI 24.7, 102.5), and German Shepherd Dogs, Mastiffs, and Bullmastiffs with haemangiosarcoma (OR up to 28.0, 95% CI 10.6, 40.9). Higher-grade MCT were diagnosed at older ages and certain breeds were more predisposed to higher-grade MCT (Shar Pei, Rottweiler) while others were more prone to low-grade MCTs (Boxer, Boston Terrier). Neutered dogs generally had higher tumour odds than entire dogs; for example, in MCTs, female-neutered vs. female-entire showed OR 1.81 (95% CI 1.6, 2.0) in ages 3-6, with similar patterns across older age bands. In general, the difference in OR values between entire and neutered dogs was consistently more pronounced in females than in males. These findings demonstrate the value of the SAVSNET PTR as a comprehensive resource for canine tumour surveillance, with potential to support health initiatives and cancer research by identifying breed-specific and demographic risk factors as well as a foundational tool for comparative cancer epidemiology.

Feline oral squamous cell carcinoma (FOSCC) and human head and neck squamous cell carcinoma (HNSCC) are the 4th most common malignant neoplasms in cats and humans. Most cats are not treated due to the poor prognosis and die of their disease within a few months of diagnosis. In humans, despite surgery, radiation therapy, and chemotherapy, 1/3 of patients develop loco-regional recurrence within 5 years. FOSCC has commonly been proposed as a model for HNSCC since FOSCC is a spontaneous model and exhibits similar biologic behaviour, treatment course, and outcome to the human disease. The objective of this study was to identify genetic similarities and differences with HNSCC, therapeutic targets, and possible causes of FOSCC through whole exome sequencing. Thirty-six matched normal FOSCC tumours and three matched normal chronic gingivostomatitis lesions were sequenced with a previously validated custom Roche Nimblegen exome reagent, based on the Felis_catus_9.0 genome assembly, covering 35.7 Mb. The exome libraries were pooled and sequenced on the Illumina Novaseq6000 as 2 × 150 bp reads. The data was analysed with the McDonnell Genome Institute's (MGI) cancer informatics pipelines, namely the Genome Modelling System (GMS), which was adapted to the feline genome. TP53 harboured consequential variants in 71% of the FOSCC tumours and was the most commonly mutated gene. Consequential variants in TTN were seen in 18% tumours and consequential variants in FSIP2, LRP1B, RYR2 were seen 9% of tumours. Genes with highly recurrent copy number variants (CNVs) included CKDN2A, PTEN, and MYC. TMB was very low, 0-1.6 (mean 0.66). Six cats had a history of chronic gingivostomatitis for years before the diagnosis of FOSCC. Despite the low TMB, the genomic landscape of FOSCC parallels HPV-negative HNSCC. Aside from TP53, recurrent small-scale mutations in FOSCC were uncommon, but recurrent CNVs were common. FOSCC is a genetically and clinically heterogenous cancer. A multifactorial cause is suspected. Chronic gingivostomatitis, immunosuppression, and/or viral infection may be associated with FOSCC in young cats.

Fixed dose rate (FDR) gemcitabine offers pharmacokinetic advantages over bolus dosing, and there is evidence in human medicine that FDR gemcitabine is more effective than intravenous (IV) bolus. To date, literature describing gemcitabine use in dogs is limited to bolus administration. The goal of this study was to describe the tolerability and adverse event profile of a novel FDR gemcitabine protocol in tumour-bearing dogs. Thirty-nine dogs who received at least one infusion of FDR gemcitabine at 400 mg/m² IV over 2 h (3.3 mg/m²/min) were retrospectively evaluated. An average of 4 FDR gemcitabine doses (range, 1-15) were administered per dog. Sixteen dogs (41%) developed neutropenia (12 Grade 1, 1 Grade 2, 2 Grade 3, 1 Grade 4) and 5 dogs (13%) developed thrombocytopenia (3 Grade 1, 1 Grade 2, 1 Grade 3). Gastrointestinal adverse events were reported in 23 dogs (59%), and all were classified as Grade 1 or 2. Of the 35 dogs who had gross disease and adequate information available to assess response to treatment, 8 dogs (23%) achieved a partial response (PR), 11 dogs (31%) maintained stable disease (SD) and 16 dogs (46%) experienced disease progression. PR was documented in 5 out of 8 dogs (63%) with squamous cell carcinoma. This FDR gemcitabine protocol demonstrated manageable toxicity and a promising response rate in dogs. Further investigation is warranted to explore its potential role in treating canine tumours.

Elective neck dissection (END) and sentinel lymph node biopsy (SLNB) are suggested for nodal staging of canine head and neck malignancies (HNM). This study aims to compare the morbidity of END to SLNB. Seventy-six client-owned dogs with HNM that underwent END (n = 28) or SLNB (n = 48) in two institutions were retrospectively enrolled. Retrieved variables included data on signalment, lymph centre and lymph nodes, intra- and post-surgical complications (PSC) of lymphadenectomy, and histopathology results. The cumulative incidence of PSC at 30 days was estimated for END and SLNB and compared with Gray's test. The influence of variables on the incidence of complications was evaluated using univariate and multivariate models. No intraoperative complication occurred. The PSC were mostly mild. Seroma was the most frequent. The cumulative incidence of PSC of lymphadenectomy at 30 days was 47.4%, and they were severe in 14% of cases. The incidence of PSC was 25% for SLNB and 85.7% for END, and the difference was statistically significant (p < 0.001). Clinically enlarged nodes (p = 0.03), institution (p = 0.03), increasing number of resected nodes (p < 0.001) and of lymph centres (p < 0.001) predicted a higher incidence of PSC in the univariate model. In the multivariate analysis, only the type of node management (END vs. SLNB) remained significant. Although lymphadenectomy is a well-tolerated procedure in dogs with HNM, END was correlated with a higher risk of PSC compared to SLNB. Stratification of dogs by the risk of multiple nodal metastases is warranted to identify those who may still benefit from END despite a higher PSC risk.