Conformity and controversies in the diagnosis, staging and follow-up evaluation of canine nodal lymphoma: a systematic review of the last 15 years of published literature

Diagnostic methods used in the initial and post-treatment evaluation of canine lymphoma are heterogeneous and can vary within countries and institutions. Accurate reporting of clinical stage and response assessment is crucial in determining the treatment efficacy and predicting prognosis. This study comprises a systematic review of all available canine multicentric lymphoma studies published over 15 years. Data concerning diagnosis, clinical stage evaluation and response assessment procedures were extracted and compared. Sixty-three studies met the eligibility criteria. Fifty-five (87.3%) studies were non-randomized prospective or retrospective studies. The survey results also expose variations in diagnostic criteria and treatment response assessment in canine multicentric lymphoma. Variations in staging procedures performed and recorded led to an unquantifiable heterogeneity among patients in and between studies, making it difficult to compare treatment efficacies. Awareness of this inconsistency of procedure and reporting may help in the design of future clinical trials

Concordance of c-kit mutational status in matched primary and metastatic cutaneous canine mast cell tumors at baseline

BackgroundMutation analysis of proto-oncogene c-kit (c-kit) is advisable before starting treatment with tyrosine kinase inhibitors in dogs with mast cell tumor (MCT), including those with metastatic disease. Testing is usually performed on primary tumors, assuming that c-kit mutation status does not change in metastasis.Hypothesis/ObjectivesTo give an insight into the mutational processes and to make a recommendation on the use of c-kit mutational analysis in the clinical setting.AnimalsTwenty-one client-owned dogs with metastatic MCT.MethodsDogs undergoing resection or biopsy for both primary and matched metastatic MCT were prospectively enrolled. Total RNA or DNA was extracted from primary MCT and corresponding metastases. Exons 8, 9, and 11 were amplified by PCR and sequenced. Genetic features between primary MCT and metastases were compared. Their correlation with clinicopathologic features was investigated.ResultsConcordance (mutated or wild-type) of mutational status, evaluable in 21 primary and matched metastatic (20 nodal and 1 splenic) MCTs, was 100%. Three new c-kit mutations were identified. No significant correlation was detected between c-kit mutation and clinicopathologic features.Conclusions and Clinical ImportanceProto-oncogene c-kit mutational status is conserved between any primary and its matched secondary tumor, suggesting that both can be used for c-kit mutational testing. Targeted therapies might be also used to treat metastatic disease

Complete compensation of criss-cross deflection in a negative ion accelerator by magnetic technique

During 2016, a joint experimental campaign was carried out by QST and Consorzio RFX on the Negative Ion Test Stand (NITS) at the QST Naka Fusion Institute, Japan, with the purpose of validating some design solutions adopted in MITICA, which is the full-scale prototype of the ITER NBI, presently under construction at Consorzio RFX, Padova, Italy. The main purpose of the campaign was to test a novel technique, for suppressing the beamlet criss-cross magnetic deflection. This new technique, involving a set of permanent magnets embedded in the Extraction Grid, named Asymmetric Deflection Compensation Magnets (ADCM), is potentially more performing and robust than the traditional electrostatic compensation methods. The results of this first campaign confirmed the effectiveness of the new magnetic configuration in reducing the criss-cross magnetic deflection. Nonetheless, contrary to expectations, a complete deflection correction was not achieved. By analyzing in detail the results, we found indications that a physical process, taking place just upstream of the plasma grid, was giving an important contribution to the final deflection of the negative ion beam. This process appears to be related to the drift of negative ions inside the plasma source, in the presence of a magnetic field transverse to the extraction direction, and results in a non-uniform ion current density extracted at the meniscus. Therefore, the numerical models adopted in the design were improved by including this previously disregarded effect, so as to obtain a much better matching with the experimental results. Based on the results of the first campaign, new permanent magnets were designed and installed on the Extraction Grid of NITS. A second QST-Consorzio RFX joint experimental campaign was then carried out in 2017, demonstrating the complete correction of the criss-cross deflection and confirming the validity of the novel magnetic configuration and of the hypothesis behind the new models. This contribution presents the results of the second joint experimental campaign on NITS along with the overall data analysis of both campaigns, and the description of the improved models. A general picture is given of the relation among magnetic field, beam energy, meniscus non-uniformity and beamlet deflection, constituting a useful database for the design of future machines

Lymphadenectomy improves outcome in dogs with resected Kiupel high-grade cutaneous mast cell tumours and overtly metastatic regional lymph nodes

Historically, the prognosis for dogs with stage II Kiupel high-grade cutaneous mast cell tumours has been considered poor

Prognostic value of pd-l1, pd-1 and cd8a in canine diffuse large b-cell lymphoma detected by rnascope

Immune checkpoints are a set of molecules dysregulated in several human and canine cancers and aberrations of the PD-1/PD-L1 axis are often correlated with a worse prognosis. To gain an insight into the role of immune checkpoints in canine diffuse large B-cell lymphoma (cDLBCL), we investigated PD-L1, PD-1 and CD8A expression by RNAscope. Results were correlated with several clinico-pathological features, including treatment, Ki67 index and outcome. A total of 33 dogs treated with chemotherapy (n = 12) or chemoimmunotherapy with APAVAC (n = 21) were included. PD-L1 signal was diffusely distributed among neoplastic cells, whereas PD-1 and CD8A were localized in tumor infiltrating lymphocytes. However, PD-1 mRNA was also retrieved in tumor cells. An association between PD-L1 and PD-1 scores was identified and a higher risk of relapse and lymphoma-related death was found in dogs treated with chemotherapy alone and dogs with higher PD-L1 and PD-1 scores. The correlation between PD-L1 and PD-1 is in line with the mechanism of immune checkpoints in cancers, where neoplastic cells overexpress PD-L1 that, in turn, binds PD-1 receptors in activated TIL. We also found that Ki67 index was significantly increased in dogs with the highest PD-L1 and PD-1 scores, indirectly suggesting a role in promoting tumor proliferation. Finally, even if the biological consequence of PD-1+ tumor cells is unknown, our findings suggest that PD-1 intrinsic expression in cDLBCL might contribute to tumor growth escaping adaptive immunity

Environmental risk factors for the development of oral squamous cell carcinoma in cats

Background: Risk factors for oral squamous cell carcinoma (OSCC) in cats are derived from a single study dated almost 20 years ago. The relationship between inflammation of oral tissues and OSCC is still unclear. Objectives: To investigate previously proposed and novel potential risk factors for OSCC development, including oral inflammatory diseases. Animals: Hundred cats with OSCC, 70 cats with chronic gingivostomatitis (CGS), 63 cats with periodontal disease (PD), and 500 controls. Methods: Prospective, observational case-control study. Cats with OSCC were compared with an age-matched control sample of client-owned cats and cats with CGS or PD. Owners of cats completed an anonymous questionnaire including demographic, environmental and lifestyle information. Results: On multivariable logistic regression, covariates significantly associated with an increased risk of OSCC were rural environment (OR: 1.77; 95% CI: 1.03-3.04; P =.04), outdoor access (OR: 1.68; 95% CI: 1.07-2.63; P =.02), environmental tobacco smoke (OR: 1.77; 95% CI: 1.05-3; P =.03), and petfood containing chemical additives (OR: 1.98; 95% CI: 1.04-3.76; P =.04). Risk factors shared with CGS and PD were outdoor access and petfood containing chemical additives, respectively. A history of oral inflammation was reported in 35% of cats with OSCC but did not emerge as a risk factor. Conclusions and Clinical Importance: The study proposes novel potential risk factors for OSCC in cats. Although a history of inflammatory oral disease was not significantly more frequent compared with random age-matched controls, OSCC shared several risk factors with CGS and PD

Sleeping Beauty: Anesthesia May Promote Relapse in Dogs With Diffuse Large B-Cell Lymphoma in Complete Remission After Chemo-Immunotherapy

Surgery-induced stress and anesthesia-related immunosuppression are believed to play a critical role in human oncology patients. Studies have hypothesized that anesthesia influences patients' outcome, promoting tumor recurrence and metastasis. Aim of the study was to investigate whether anesthesia promoted relapse in dogs with diffuse large B-cell lymphoma (DLBCL). Medical records were searched for dogs with DLBCL, that were in complete remission (CR) after the same chemo-immunotherapy protocol. Dogs receiving anesthesia were included if the procedure was performed while in CR. Time to relapse (TTR) was obtained via Kaplan–Meier method. Association between anesthesia and relapse was assessed using a nested case-control design and estimated using conditional logistic regression. Sixty-one dogs with DLBCL were included. Overall median TTR was 329 days (95% CI, 281–377). Forty-eight (79%) dogs relapsed during the study period, while 13 (21%) were still in CR at data analysis closure. Eighteen (30%) dogs received anesthesia with opioids, propofol, and isoflurane or sevoflurane. The relative risk of lymphoma relapse for dogs undergoing anesthesia was significantly higher compared with dogs not undergoing anesthesia, with an odds ratio of 3.09 (P = 0.019) on multivariable analysis. Anesthesia may promote relapse in dogs with DLBCL treated with chemo-immunotherapy, although a role of perioperative stress cannot be ultimately excluded. Considering the high frequency of anesthetic procedures required for diagnostic and therapeutic protocols among oncology patients, it is of utmost interest to characterize the effects of single anesthetic agents on the immune system. Further prospective studies are needed to better define the impact of anesthesia on patients' outcome