SCINTIGRAPHIC TRACKING OF MESENCHYMAL STEM CELLS AFTER PORTAL,SYSTEMIC INTRAVENOUS AND SPLENIC ADMINISTRATION IN HEALTHY BEAGLE DOGS

Mesenchymal stem cells have been proposed to treat liver disease in the dog. The objective of this study was to compare portal, systemic intravenous and splenic injections for administration of mesenchymal stem cells to target the liver in healthy beagle dogs. Four healthy beagle dogs were included in the study. Each dog received mesenchymal stem cells via all three delivery methods in randomized order, 1 week apart. Ten million fat‐derived allogeneic mesenchymal stem cells labeled with Technetium‐99m (99mTc)‐hexamethyl‐propylene amine oxime(HMPAO) were used for each injection. Right lateral, left lateral, ventral, and dorsal scintigraphic images were obtained with a gamma camera equipped with a low‐energy all‐purpose collimator immediately after injection and 1, 6, and 24 h later. Mesenchymal stem cells distribution was assessed subjectively using all four views. Pulmonary, hepatic, and splenic uptake was quantified from the right lateral view, at each time point. Portal injection resulted in diffuse homogeneous high uptake through the liver, whereas the systemic intravenous injection led to mesenchymal stem cell trapping in the lungs. After splenic injection, mild splenic retention and high homogeneous diffuse hepatic uptake were observed. Systemic injection of mesenchymal stem cells may not be a desirable technique for liver therapy due to pulmonary trapping. Splenic injection represents a good alternative to portal injection. Scintigraphic tracking with 99mTc‐HMPAO is a valuable technique for assessing mesenchymal stem cells distribution and quantification shortly after administration. Data obtained at 24 h should be interpreted cautiously due to suboptimal labeling persistence.     

SUSCEPTIBILITY ARTIFACTS ON T2*‐WEIGHTED MAGNETIC RESONANCE IMAGING OF THE CANINE AND FELINE SPINE

The T2*‐weighted gradient recalled echo sequence is a sensitive means to detect blood degradation products. While not a routine sequence in magnetic resonance imaging of the spine in small animals, it can provide additional valuable information in select cases. The goal of this retrospective, cross‐sectional study was to describe findings when acquiring this sequence during magnetic resonance imaging examination of the spine in small animals. The University of Tennessee's veterinary radiology database was searched for dogs and cats that underwent magnetic resonance imaging for suspect spinal disease in which a T2*‐weighted gradient recalled echo sequence was acquired and susceptibility artifact was identified. The following information was recorded: signalment, clinical signs, location and appearance of susceptibility artifact, and final diagnosis. Thirty‐nine cases were included in the study. Extradural susceptibility artifacts were observed in cases of intervertebral disc herniation with or without associated hemorrhage (n = 28), extradural hemorrhage associated with spinal trauma (n = 2), hemophilia (n = 1), and in a cystic extradural mass (n = 1). Remaining lesions displaying susceptibility artifact were intramedullary and included presumptive acute noncompressive nucleus pulposus extrusion (n = 2), hematoma (n = 1), hemangiosarcoma metastasis (n = 1), intramedullary disc extrusion (n = 1), presumptive meningomyelitis (n = 1), and a mass of undetermined etiology (n = 1). Inclusion of a T2*‐weighted gradient recalled echo sequence may be helpful in spinal magnetic resonance imaging when standard imaging sequences are ambiguous or intramedullary lesions are observed.     

COMBINATION OF RADIATION THERAPY AND FIROCOXIB FOR THE TREATMENT OF CANINE NASAL CARCINOMA

Carcinomas represent two‐thirds of canine nasosinal neoplasms. Although radiation therapy (RT) is the standard of care, the incidence of local recurrence following treatment is high. Cyclooxygenase‐isoform‐2 (COX‐2) is expressed in 71–95% of canine nasal carcinomas and has been implicated in tumor growth and angiogenesis. Accordingly, COX‐2 inhibition seems rational to improve outcome. Dogs with histologically confirmed, previously untreated nasal carcinomas were randomized to receive the combination of a selective COX‐2 inhibitor (firocoxib) and palliative RT (Group 1) or RT and placebo (Group 2). Patients were regularly monitored with blood tests, urinalysis, and computed tomography. Pet owners were asked to complete monthly a quality‐of‐life questionnaire. Twenty‐four dogs were prospectively enrolled. According to Adams modified system, there were five stage 1, five stage 2, three stage 3, and 11 stage 4 tumors. Two dogs had metastases to regional lymph nodes. Median progression‐free interval and overall survival were 228 and 335 days in Group 1 (n = 12) and 234 and 244 days in Group 2 (n = 12). These differences were not statistically significant. The involvement of regional lymph nodes was significantly associated with progression‐free interval and overall survival (P = 0.004). Quality of life was significantly improved in Group 1 (P = 0.008). In particular, a significant difference was observed for activity and appetite. Although not providing a significant enhancement of progression‐free interval and overall survival, firocoxib in combination with RT is safe and improved life quality in dogs with nasal carcinomas.     

Flow cytometric evaluation of ki67 for the determination of malignancy grade in canine lymphoma

Ki67 is a nuclear antigen significantly correlated with degree of malignancy in human non‐Hodgkin lymphomas. We wanted to assess the ability of flow cytometric evaluation of Ki67 index (Ki67I) in differentiating the grade of malignancy in canine lymphomas. Ki67I was determined on lymph node aspirates of 90 immunophenotyped lymphomas classified according to the updated Kiel classification: 80 high grade (HG, 62 B cell and 18 T cell) and 10 low grade (LG, 3 B cell and 7 T cell) lymphomas. HG lymphomas showed significantly higher Ki67I compared with LG lymphomas (P < 0.0001). A significant difference in HG lymphomas was detected between B‐ and T‐immunophenotypes. Receiver operating characteristic (ROC) curve highlighted a high accuracy of Ki67I in recognizing HG lymphomas [area under the curve (AUC) = 99.4] and a cut‐off value of 12.2% was established (sensitivity = 96.3% and specificity = 100%). Thus, we suggest the combination of Ki67I flow cytometric determination and immunophenotype as a reliable tool to classify canine lymphomas.     

Quantitative morphology in canine cutaneous soft tissue sarcomas

Stained cytological specimens from 24 dogs with spontaneous soft tissue sarcomas [fibrosarcoma (n = 8), liposarcoma (n = 8) and haemangiopericytoma (n = 8)], and 24 dogs with reactive connective tissue lesions [granulation tissue (n = 12) and dermal fibrosis (n = 12)] were analysed by computer‐assisted nuclear morphometry. The studied morphometric parameters were: mean nuclear area (MNA; µm²), mean nuclear perimeter (MNP; µm), mean nuclear diameter (MND mean; µm), minimum nuclear diameter (D_min; µm) and maximum nuclear diameter (D_max; µm). The study aimed to evaluate (1) possibility for quantitative differentiation of soft tissue sarcomas from reactive connective tissue lesions and (2) by using cytomorphometry, to differentiate the various histopathological soft tissue sarcomas subtypes in dogs. The mean values of all nuclear cytomorphometric parameters (except for D_max) were statistically significantly higher in reactive connective tissue processes than in soft tissue sarcomas. At the same time, however, there were no considerable differences among the different sarcoma subtypes. The results demonstrated that the quantitative differentiation of reactive connective tissue processes from soft tissue sarcomas in dogs is possible, but the same was not true for the different canine soft tissue sarcoma subtypes. Further investigations on this topic are necessary for thorough explication of the role of quantitative morphology in the diagnostics of mesenchymal neoplasms and tumour‐like fibrous lesions in dogs