Veterinary and comparative oncology最新文献

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.

Mechlorethamine is commonly prescribed to dogs at 3 mg/m². The minimal toxicity observed indicates that higher doses of mechlorethamine are likely tolerable. The primary objective of this study was to determine the maximally tolerated dose (MTD) of mechlorethamine in dogs with lymphoma. The secondary objectives were to describe the toxicity associated with increased mechlorethamine dose and to evaluate the response in treatment-naive dogs treated at the MTD. Dogs with histologically or cytologically confirmed intermediate to large cell lymphoma were enrolled using a 3 + 3 dose escalation model, starting at 3.5 mg/m² mechlorethamine IV, with planned dose increments of 10%-15% between cohorts. Adverse events were monitored per VCOG-CTCAE guidelines. Dose-limiting toxicity was defined as any grade 3 or 4 adverse event. Thirty dogs were enrolled across nine cohorts. Two dogs treated at 12.3 mg/m² developed asymptomatic grade 4 neutropenia 7 days after mechlorethamine administration, leading to a MTD of 10.7 mg/m². Low-grade vomiting, diarrhoea, and inappetence were recorded amongst dogs at several dose levels and were managed with supportive medications. Six of 10 chemotherapy-naïve dogs treated at the MTD, representing a separate cohort, showed partial responses (PR) 7 days post-administration; however, PR was also observed at dosages ranging from 3.5 to 12.3 mg/m² in pre-treated patients. A higher dose of mechlorethamine than previously reported can be safely administered as a single agent to dogs. Increasing the dose of mechlorethamine in combination therapies might offer greater therapeutic benefits.

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.

Alkaline phosphatase (ALP) enzymatic activity has been proposed as a marker for distinguishing canine acute leukaemia (AL) subtypes (i.e., myeloid vs. lymphoid). However, ALP enzymatic activity has not been fully evaluated in CD34+ AL. Determine whether ALP enzymatic activity can differentiate CD34+ AL subtypes in dogs and distinguish CD34+ AL from CD34- haematopoietic tumours in tissue/effusion samples. Peripheral blood from 64 dogs with CD34+ AL, 10 with B cell chronic lymphocytic leukaemia (CLL), and 10 healthy controls were prospectively evaluated for ALP enzymatic activity via cytochemical staining; a subset also underwent ALP detection by flow cytometry (FC). Archived cytology slides from 67 tissue/effusion specimens, including 27 CD34+ AL, 22 T cell lymphomas, and 18 B cell lymphomas, were retrospectively assessed. CD34+ AL cases were categorised as acute myeloid leukaemia (AML), acute lymphoid leukaemia (ALL) or acute unclassifiable leukaemia (AUL) by established FC criteria. ALP positivity was defined as > 3% ALP+ neoplastic cells, which was selected based on receiver operating characteristic (ROC) curve analysis. Cytochemical ALP activity was detected in 61/64 (95.3%) CD34+ AL cases, with no significant differences between AML, ALL, and AUL subtypes (p > 0.05). All lymphoma and B cell CLL cases were ALP-negative. FC-based ALP analysis showed poor concordance with cytochemistry, and the correlation between %CD34 + ALP+ cells and %ALP+ neoplastic cells was weak (Spearman's ρ = 0.25). While ALP enzymatic activity is present in most CD34+ AL cases, it does not reliably differentiate CD34+ AL subtypes via cytochemistry. However, ALP may help distinguish CD34+ AL from B and T cell lymphomas. FC-based ALP analysis is not a reliable marker for CD34+ AL classification.

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.

Mast cell tumours (MCTs) are common in dogs. Treatment options include surgery, radiation therapy, and cytotoxic chemotherapy; however, in cases of inoperable or metastatic tumours, tyrosine kinase inhibitors (TKIs) can be used. Imatinib mesylate has been used in the treatment of solid tumours in both human and veterinary medicine. Previous studies have shown some efficacy in dogs with MCTs; however, additional data are needed to better define the optimal dosage, toxicity profile, and clinical outcomes associated with its use. Dogs with a cytological or histopathological diagnosis of mucosal, cutaneous or subcutaneous MCTs were included. Medical records from 2017 to 2024 were reviewed for clinical presentation, results of staging procedures, diagnostic tests, and treatment. Inclusion required the presence of macroscopic disease and administration of imatinib, either as a sole treatment or in combination with surgery. Thirty-five cases were included, all receiving medical treatment with or without surgical excision. Imatinib was administered as first-line treatment in 8 dogs (22.8%) and as a rescue treatment in 27 dogs (77.1%), achieving an overall clinical benefit, including complete response, partial response, and stable disease of 77%. Median progression-free survival was 37 days (range 13-770 days), while the overall median survival time (MST) was 270 days (range 83-1396 days). Following imatinib treatment, the MST was 105 days (range 22-1145 days). Gastrointestinal and haematological adverse events were recorded in 2 (5.7%) and 3 (8.6%) dogs, respectively, and were self-limiting. Imatinib treatment was generally well tolerated, with measurable clinical responses observed and only a limited spectrum of toxicities. Further studies are warranted to better characterise its safety and efficacy in dogs with MCTs.

Human epidermal growth factor receptor 2 (HER2) gene mutations have been reported in 5% to 38% of canine pulmonary adenocarcinomas (cPACs), most commonly as V659E mutations in exon 20. However, their prognostic and predictive significance remains unclear. This retrospective, single-centre cohort study investigated the frequency of HER2 mutations in surgically resected cPACs and their association with clinical outcomes. Between 2005 and 2021, lung masses histologically diagnosed as cPACs were collected and subjected to direct sequencing of HER2 exons 20 and 21. A total of 72 dogs were enrolled, with successful HER2 gene analysis in 69 cases. HER2 exon 20 missense mutations were identified in 20 dogs (29.0%), including 18 harbouring the previously reported V659E hotspot mutation within the transmembrane domain. Homozygous mutations were detected in 13 dogs. Univariable analysis revealed associations between progression-free interval (PFI) and clinical signs, tumour size classification, lymph node metastasis, surgical margin status, and histologic grade. Overall survival time (OST) was associated with age, clinical signs, tumour size > 7 cm, histologic subtype, lymph node metastasis, and margin status. In multivariable analysis, tumour size classification and margin status remained significantly associated with PFI, while age, tumour size > 7 cm, and histologic subtype were independently associated with OST. Notably, the presence of HER2 mutations was significantly associated with prolonged PFI in both univariable and multivariable analyses, although no significant association with OST was observed. These findings suggest that HER2 mutation status may serve as a favourable prognostic marker for disease progression in surgically resected cPACs.

Canine phaeochromocytomas (PCCs) are neuroendocrine tumours with malignant potential. Metastatic disease remains the sole definitive evidence of malignancy. Histopathological criteria to predict long-term survival have not been established in dogs. This study evaluated the reproducibility and prognostic value of histopathological parameters derived from human scoring systems, along with the Ki67 proliferation index (PI), in dogs after adrenalectomy for PCC. Tumour samples from 41 dogs were assessed by a veterinary pathologist and pathology resident. Of 10 histopathological parameters examined, only necrosis, tumour cell spindling, and extension into adipose tissue achieved sufficient inter- and intra-observer agreement (≥ 0.40) for inclusion in survival analyses, while Ki67 PI demonstrated excellent reproducibility (≥ 0.95). A composite histopathological score was generated by summing these three parameters and a dichotomised Ki67 PI (optimal cutoff 18%), as determined by ROC analysis. Among the 41 dogs, eight died within 2 weeks postoperatively, leaving 33 long-term survivors with four tumour-related events. Kaplan-Meier analysis showed significantly poorer survival (p < 0.001) in dogs with a high Ki67 PI (≥ 18%), whereas the composite score showed a borderline significant association with outcome in Cox regression (p = 0.056; hazard ratio 2.80). Overall, dogs surviving the immediate postoperative period demonstrated a favourable prognosis (mean overall survival of 2456 days). These findings suggest that, in this cohort with few tumour-related events, the dichotomised Ki67 PI alone may serve as a clinically applicable prognosticator for canine PCC. However, further research in larger populations is needed to determine whether a composite score adds prognostic value and guides postoperative management.

Diffuse large B-cell lymphoma (DLBCL) is one of the most prevalent haematological malignancies in both humans and dogs, characterised in both species by significant clinical heterogeneity and limited prognostic predictability. With the introduction of next-generation sequencing (NGS) technologies in veterinary medicine over the past decade, researchers have begun to elucidate the molecular basis of canine DLBCL (cDLBCL); however, much of the clinical heterogeneity associated with this tumour remains unexplained. In this study, we performed whole genome sequencing on 10 cDLBCL cases, all treated with chemo-immunotherapy, which exhibited similar clinico-pathological features but markedly different outcomes. Cases were classified as "poor" or "good" responders based on whether their lymphoma-specific survival fell below or above the cohort's median. Protein-coding variants and copy number aberrations unique to poor or good responders revealed novel candidate genes not previously identified in cDLBCL studies, while splicing, untranslated regions, and intronic variants were detected in genes already known to be recurrently mutated. In conclusion, our investigation has broadened the spectrum of potentially pathogenic variants implicated in cDLBCL, though further studies with larger cohorts are necessary to validate these findings.