Veterinary and comparative oncology最新文献

In human medicine, serum lactate dehydrogenase (LDH) is a well-established prognostic marker in osteosarcoma, reflecting tumour burden. This study evaluates serum LDH as a prognostic biomarker in dogs with histologically confirmed appendicular osteosarcoma undergoing a complete staging work-up. Fifty-two dogs with osteosarcoma were prospectively enrolled, and LDH levels were assessed at diagnosis, prior to any treatment. Elevated LDH was observed in 34 (65.4%) dogs. All dogs with distant metastasis had increased LDH levels. A significant association was observed between elevated LDH and metastasis (p = 0.039). To assess the impact of LDH on survival, a subgroup analysis included 38 dogs without metastasis that underwent multimodal treatment and had a minimum follow-up of 180 days. Median time to progression (TTP) and overall survival (OS) were significantly shorter in dogs with elevated LDH (157 and 169 days, respectively) compared to those with LDH within reference limits (252 and 387 days, respectively; p = 0.035 and p = 0.017). On univariable analysis, elevated LDH was the only variable associated with an increased tumour progression risk (HR = 2.26, 95% CI = 1.09-4.69, p = 0.029). Additionally, elevated LDH, absence of immunotherapy administration, and increased serum alkaline phosphatase activity were significantly associated with a higher mortality risk. These findings suggest that elevated LDH at diagnosis indicates a more advanced disease stage and poorer prognosis in dogs with appendicular osteosarcoma. LDH may aid in treatment planning and prognosis assessment. Further studies should confirm these results and explore its combination with other biomarkers to refine prognostic evaluation.

Decreased kidney function is observed in some people receiving carboplatin, but limited literature explores this in dogs. The aim of this study was to evaluate the incidence and risk factors for decreased kidney function in dogs receiving carboplatin. A single-institute retrospective cohort study compared the incidence of decreased kidney function between non-azotaemic dogs receiving carboplatin and an age- and weight-matched cancer-bearing control group not receiving chemotherapy. Change in creatinine concentration and a linear mixed effects model were used to compare trends in creatinine between groups. Decreased kidney function was defined as a sustained increase in creatinine ≥ 26.5 μmol/L on ≥ 2 consecutive measurements compared to baseline; the VCOG-CTCAE v2 grading system for increased creatinine was also applied. Risk factors were explored. Ninety-eight dogs were included (n = 49/group). There was no difference in median change in creatinine concentration (+2.0 μmol/L; p = 0.311) or creatinine trends (p = 0.958) across the study period between groups. Incidence of decreased kidney function was low and did not significantly differ between groups (carboplatin group n = 4 [8.2%]; control group n = 2 [4.1%]; p = 0.678); no risk factors were identified. There was no difference in the frequency of VCOG grade one (p = 0.731), two (p = 0.641) or three (p = 0.429) creatinine adverse events between groups. Non-azotaemic dogs receiving carboplatin do not have a significantly increased short-term risk of decreased kidney function compared to those not receiving chemotherapy, although the numerical increase in incidence in dogs receiving carboplatin could be clinically relevant. Larger studies should aim to explore this further and investigate carboplatin's impact on subclinical and long-term renal function.

Histiocytic sarcoma (HS) is a highly metastatic cancer, and while response to several chemotherapy agents has been studied, the outcome remains poor. Vinorelbine (VNB) has been considered a possible treatment option, but data are limited. The aim of this study was to assess the efficacy and toxicity of VNB in canine HS. Medical records of dogs with HS, treated with VNB as first-line or rescue treatment, were reviewed. Overall response rate (ORR), progression-free survival (PFS), overall survival post-VNB (post.VNB.OST) and adverse events were evaluated. Associations between outcome measures and signalment, disease extent/location, diagnostic modality and response to previous chemotherapies were analysed. Eighteen dogs were included: 12 disseminated and six localised HS. VNB was a rescue treatment in all dogs. ORR was 38.9% [two complete responses (CR), five partial responses (PR)] including two dogs showing delayed best responses. Median PFS and post-VNB-OST for all dogs were 49 (95% CI: 33-166) and 75.5 days (95% CI: 55-174), respectively. Responders showed significantly longer median PFS (120 days) compared to non-responders (41 days). None of the other factors analysed were associated with ORR, PFS and post-VNB-OST, including pulmonary location. Neutropenia and gastrointestinal toxicity were common; however, the majority were low-grade with no hospitalisation required. Vinorelbine can be an effective and safe treatment for canine HS; disease location alone may not be a key predictive factor for VNB response and outcome. Further prospective studies on larger cohorts are required to confirm these findings.

The transferrin receptor-1 (TFR-1) is overexpressed in many types of human cancers and, in recent years, several studies have investigated its use as a preferential channel for drug cellular uptake in cancer therapy. In veterinary medicine, TFR-1 expression in cancer cells and tissues has been poorly described, as well as its therapeutic potential. In this study we investigated TFR-1 expression in different subtypes of canine mammary tumours (CMTs) and in two CMT cell lines, one primary (CIPp) and one metastatic (CIPm). Additionally, we also compared the in vitro efficacy of an engineered human apoferritin nanocage loaded with doxorubicin (HFn(DOX)) with the conventional doxorubicin treatment on CIPp and CIPm. In CMT tissues, TFR-1 was more expressed in the tumoral tissues compared to the hyperplastic counterparts, specifically with regards to carcinoma and malignant myoepithelioma and simple carcinoma subtypes (p < 0.05). CIPp and CIPm did not show any significant difference in TFR-1 protein expression, while TFR-1 gene expression was higher in CIPm (p < 0.05). The treatment with HFn(DOX) was more efficient than free doxorubicin only on CIPp at high concentrations (50 μM). In conclusion, we show for the first time the variability of TFR-1 expression in CMT tissues and cell lines. Although further investigations are necessary, HFn can be loaded with different chemotherapeutic compounds, becoming an innovative therapeutic tool for the treatment of cancers highly expressing TFR-1 in veterinary and human medicine.

Canine cardiac hemangiosarcoma (cHSA) represents a complex clinical challenge in that those afflicted have an acute risk of death due to cardiac tamponade and high morbidity and mortality given the frequency of metastasis. Previous studies show that radiation therapy (RT) can decrease the risk of tamponade; however, an optimal approach has yet to be determined. The objective of this study was to evaluate the outcomes of dogs with presumptive cHSA treated with varied RT protocols and modalities, and to contrast findings with previously published literature. Secondary objectives were to assess differences in outcomes between those that received chemotherapy post-RT or did not, single fraction versus multiple-fraction RT protocols, and CT-guided versus manually calculated treatment plans. Twenty-seven dogs with echocardiographic evidence of an atrial or auricular cardiac mass that received RT were included. The frequency of pericardiocentesis before and post-RT were compared. Overall survival time was determined, along with survival time specific to those that received chemotherapy, were treated with CT-based radiation plans, and were prescribed a single fraction versus multiple fractions. Pericardiocentesis was performed an average of 1.1 times per week before RT, and an average of 0.18 times per week after RT (p = 0.01). Median overall survival time was 137 days. Plans made without CT guidance were associated with more adverse radiation events, but all were minimally impactful on quality of life. Most dogs died or were euthanized due to metastatic disease. This study shows similar benefits to previously published data in a larger cohort of dogs using a less-conformal radiation modality. As well, it highlights future directions to identify optimal systemic therapies to delay the onset of metastasis.

The treatment of choice for canine alimentary tract neoplasms is surgical excision, but it can sometimes be difficult to achieve wide margins due to neoplasm location, size, or distribution. Optical coherence tomography (OCT) is a rapid, noninvasive imaging modality that uses light to characterise tissue microstructure to allow identification of different tissue types. Spectral domain (SD)-OCT allows for differentiation based on the total light intensity reflected from the tissue. Polarisation sensitive (PS)-OCT detects the polarisation state of light reflected by the tissues. The polarisation properties are phase retardation, degree of polarisation uniformity (DOPU), and optical axis. Our objective was to qualitatively characterise different tissues at the excision sites of alimentary tract neoplasms using OCT. Oral, liver, and other alimentary tumours including stomach, intestine, and pancreas were imaged. Samples were then fixed in formalin, paraffin embedded and stained with haematoxylin and eosin. OCT images and histology slides were compared, and the tissues were qualitatively described by a single investigator. We hypothesized that PS-OCT imaging would provide distinguishing characteristics of tissue appearances that could be used in the future to train observers or artificial intelligence to identify incomplete margins. Our results showed that alimentary tract tumours have disorganised microstructures on SD-OCT and PS-OCT DOPU, and PS-OCT phase retardation and optical axis values that differ from normal tissues. Thus, these characteristics can be used to differentiate neoplastic and normal tissues at surgical margins.

Lymphoscintigraphy is the gold standard among sentinel lymph node (SLN) mapping techniques. Unfortunately, lymphoscintigraphy is not readily accessible, leading to the need for validation of alternative techniques. The aim of this study is to compare near-infrared fluorescence lymphography (NIRF-L) with lymphoscintigraphy for SLN resection in MCT and assess the impact of intraoperative NIRF guidance. Forty-eight dogs with 60 MCT were included in this prospective, blinded, randomised controlled trial. Dogs underwent preoperative lymphoscintigraphy and were then randomised into two groups: in the treatment group (n = 30) intraoperative NIRF-L was performed; in the control group (n = 30) no intraoperative guidance was implemented. Detection rate, concordance, sensitivity, and negative predictive values were recorded for NIRF-L and lymphoscintigraphy. Surgical time and length of surgical incision were compared between treatment and control groups with the Wilcoxon test (5% significance). Detection rate was 100% for NIRF-L and 98% for lymphoscintigraphy. Discordance occurred in one case. Sensitivity of NIRF-L was 93.7% (95% C.I. 74.3%-99.3%) and negative predictive value ranged between 91.1% and 98.6% with a prevalence of nodal metastases of 61% and 18%. Based on the overlapping of the confidence intervals, NIRF-L was not statistically different to lymphoscintigraphy for sensitivity. Lymphadenectomy was unsuccessful in 4/30 (13%) cases in the control group. Surgical time and incision were significantly shorter in the treatment group (p < 0.001; p = 0.001). Based on our results, NIRF-L is a valid alternative to lymphoscintigraphy for SLN removal in MCT. Moreover, it improves the success of lymphadenectomy, reduces surgical time, and incision length compared to an unguided technique.

Adjuvant chemotherapy is a well-established treatment for large-breed dogs with appendicular osteosarcoma; however, it is unclear if it improves outcomes in small-breed dogs due to limited focused studies. This retrospective study aimed to investigate the oncologic outcomes of dogs weighting less than 15 kg with appendicular osteosarcoma that underwent curative resection with or without postoperative adjuvant chemotherapy. Endpoints were time to distant progression (TTDP) and overall survival (OS). Medical records from multiple institutions were reviewed, and 43 dogs were included in the analysis: 17 underwent surgery alone and 26 also received adjuvant chemotherapy. The median TTDP for all dogs was 265 days, with no significant difference between treatment groups. The median OS for all dogs was 270 days, and it was significantly different between amputated dogs (150 days) and those also receiving adjuvant chemotherapy (353 days, p = 0.002). In our cohort, osteosarcoma in small breeds behaved as aggressive as in large breeds. Adjuvant chemotherapy may prolong survival. Future randomised studies are needed to provide definitive evidence on the necessity of adjuvant chemotherapy to address metastatic spread in small-breed dogs with appendicular osteosarcoma.

Local treatment for dogs with regional lymph node metastasis secondary to apocrine gland anal sac adenocarcinoma (AGASACA) includes nodal extirpation or radiotherapy. Stereotactic body radiation therapy (SBRT) may provide a definitive intent treatment option for macroscopic nodal disease when surgery is declined or the disease is deemed inoperable. Twenty-five dogs receiving SBRT to the metastatic sacroiliac lymph nodes were retrospectively evaluated. Dogs were staged according to the previously published TNM staging system with 3 stage IIIa, 14 stage 3b, and 8 stage IV. The overall median survival time (MST) was 451 days and the stage did not significantly impact survival (p = 0.31). The overall median event-free survival time was 246 days. Significant positive prognostic factors included male sex, higher dose per fraction, and higher total dose (p = 0.034, 0.0035, 0.0047). Dogs receiving 6-7.5 Gy per fraction with a total dose of 30-37.5 Gy outperformed dogs receiving other protocols. Twelve dogs experienced gait changes in the hind limbs during the late radiation effects period. Resolution of hypercalcemia in 5 dogs was inconsistent and transient. The best response was complete in 21%, partial in 58%, and stable disease in 17% at a median of 100 days. Three dogs (12%) developed progression of treated lymph nodes at 157, 498, and 644 day. Eight dogs (32%) had recurrence of their primary (untreated by radiation) anal sac masses. SBRT was determined to be an effective alternative to surgical excision; however, more investigation is needed to determine the cause of gait changes in the late toxicity period.

Canine multicentric lymphoma (CML) is one of the most common malignancies in dogs. Although breed risk is important, environmental factors such as herbicides have also been implicated. The objective of this study was to determine whether genotoxic exposures to the herbicides 2,4-D and glyphosate are associated with CML, using dogs from the Golden Retriever Lifetime Study cohort. We measured urinary concentrations of glyphosate and 2,4-D in golden retrievers with CML and matched unaffected controls at two time points: at the time of diagnosis and 1 year prior to diagnosis. To assess the genotoxic potential of herbicide exposures, we used reverse dosimetry from urinary concentrations to estimate plasma concentrations. We then assessed the genotoxicity of these herbicide concentrations towards healthy canine peripheral blood mononuclear cells (PBMC's) in vitro using the CometChip assay, with and without canine liver microsomes. All dogs had detectable urinary exposures to 2,4-D (7.3-42.9 ng/mg creat) and glyphosate (0.4-80.7 ng/mg creat), with no differences between cases and controls at either time point. Both 2,4-D and glyphosate were genotoxic to canine PBMCs at concentrations of 0.10 μM and higher, with no consistent effects of canine liver microsomes on herbicide genotoxicity. No dogs reached estimated genotoxic plasma concentrations for glyphosate, but 4 of 30 golden retrievers with CML (13.3%) and 2 of 30 control dogs (6.7%) reached estimated genotoxic 2,4-D exposures (p = 0.67).