Retrospective analysis of carboplatin-induced cumulative neutropenia in cancer-bearing dogs.

OBJECTIVE: To determine the clinical significance of performing repeated postchemotherapy CBC for cancer-bearing dogs receiving ≥ 4 carboplatin treatments. The secondary aim was to identify risk factors associated with cumulative carboplatin-induced neutropenia in those dogs. ANIMALS: 40 client-owned dogs diagnosed with cancer. METHODS: A retrospective study using medical records from a single academic institution during 2012 to 2023. Dogs that received ≥ 4 doses of carboplatin with pre- and postchemotherapy CBCs available were included. Signalment and possible risk factors were recorded. Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events was used for neutropenia grading. RESULTS: 40 dogs met the inclusion criteria, with a total of 206 prechemotherapy and 188 postchemotherapy CBC results available. The median carboplatin dosage was 300 mg/m2 (range, 200 to 300 mg/m2). The median interval between carboplatin administration and the postchemotherapy CBC was 10 days (range, 6 to 38 days). Eleven dogs developed a grade 2 or higher neutropenia, with 5 dogs developing multiple neutropenic events, for a total of 18 separate events (18/394). Only 2 of 18 neutropenic events were recorded at the 10- to 14-day postchemotherapy CBC. The yield of detecting neutropenia at a postchemotherapy CBC at any carboplatin chemotherapy after the second dose was < 1% (1/149). Dogs that developed neutropenia at the pre-2nd chemotherapy CBC had a significantly higher risk of developing another neutropenic event at subsequent prechemotherapy CBC (P < .001). CLINICAL RELEVANCE: The incidence of cumulative neutropenia after 4 to 6 doses of carboplatin is low in cancer-bearing dogs. If a grade 2 or higher neutropenia is observed at or before the second prechemotherapy CBC, the dog is at a higher risk of developing neutropenia following future treatments.

Rapport de cas Surgical retrieval of a migrated vascular access port catheter in a dog.

A 4-year-old spayed female Boston terrier was diagnosed with a suspected meningioma involving the optic chiasm and resulting in vision loss. A vascular access port (VAP) was placed in the left medial saphenous vein to facilitate frequent anesthetic episodes for radiation therapy. Five days after placement, the VAP was nonfunctional with the silicone catheter still intact. During VAP removal surgery, it was discovered that the silicone catheter had migrated. Intraoperative focal ultrasound could not identify the migrated catheter within the pelvic limb. Thoracic computed tomography identified the migrated catheter retroflexed onto itself in the cranial vena cava and extending into the right pulmonary artery as it passed through the right side of the heart. The dog underwent a hybrid surgical approach consisting of an endovascular retrieval forceps technique with median sternotomy for intravenous non-radiopaque foreign body removal. Postoperative complications, including regurgitation and left atrial thrombus, were managed. The left atrial thrombus persisted for 10 mo after the hybrid surgery. Key clinical message: A hybrid approach consisting of an endovascular retrieval forceps technique with median sternotomy was effective in removing an intravenous non-radiopaque foreign body in a dog.

Récupération chirurgicale d'un cathéter de port d'accès vasculaire migré chez un chien. Une femelle terrier de Boston stérilisée âgée de 4 ans a reçu un diagnostic de méningiome présumé impliquant le chiasma optique et entraînant une perte de vision. Un port d'accès vasculaire (VAP) a été placé dans la veine saphène médiale gauche pour faciliter les épisodes fréquents d'anesthésie pour la radiothérapie. Cinq jours après la mise en place, le VAP était non fonctionnel avec le cathéter en silicone toujours intact. Au cours de la chirurgie de retrait du VAP, il a été découvert que le cathéter en silicone avait migré. L'échographie focale peropératoire n'a pas pu identifier le cathéter migré dans le membre pelvien. La tomodensitométrie thoracique a identifié le cathéter migré rétroflexé sur lui-même dans la veine cave crânienne et s'étendant dans l'artère pulmonaire droite lorsqu'il traversait le côté droit du coeur. Le chien a subi une approche chirurgicale hybride consistant en une technique de forceps de récupération endovasculaire avec sternotomie médiane pour l'extraction intraveineuse de corps étrangers nonradio-opaques. Les complications postopératoires, y compris la régurgitation et le thrombus auriculaire gauche, ont été prises en charge. Le thrombus auriculaire gauche a persisté pendant 10 mois après la chirurgie hybride.Message clinique clé :Une approche hybride consistant en une technique de forceps de récupération endovasculaire avec sternotomie médiane a été efficace pour retirer un corps étranger intraveineux non-radio-opaque chez un chien.(Traduit par Dr Serge Messier).

Use of MRI increases interobserver agreement on gross tumor volume for imaging-diagnosed canine intracranial meningioma.

There is a lack of information regarding interobserver agreement on canine meningioma gross tumor volume (GTV) delineation, and on the impact of MRI on this agreement. The objectives of this retrospective, secondary analysis, observer agreement study were to describe agreement between veterinary radiation oncologists on GTV for canine intracranial meningioma, and to compare interobserver agreement between delineation based on CT alone and delineation based on fused CT-MRI. Eighteen radiation oncologists delineated GTV for 13 dogs with an imaging diagnosis of meningioma on pre- and postcontrast CT, pre- and postcontrast T1-weighted magnetic resonance, and T2-weighted magnetic resonance images. Dice similarity coefficient (DSC), concordance index (CI), and center of volume (COV) were used to quantify interobserver agreement. Multilevel mixed models were used to examine the difference in volume, DSC, CI and COV 3D distance between CT and CT-MR imaging. The mean volume for GTV contours delineated using fused CT-MRI was larger than when CT alone was used for delineation (mean difference CT-MR - CT = 0.89 cm3, 95% CI 0.66 to 1.12, P < .001). Interobserver agreement on GTV was improved when MRI was used; the mean DSC and CI were higher, and the mean COV 3D distance was lower, when fused CT-MRI was used than when CT alone was used (P < .001 for all differences). Based on our results, fused CT-MRI is recommended for radiation therapy planning of canine intracranial meningioma.

Retrospective survey of owners' experiences with palliative radiation therapy for pets.

OBJECTIVE To describe animal owners' experiences with palliative radiation therapy (PRT) of pets and identify factors influencing satisfaction with their pets' treatment. DESIGN Retrospective, cross-sectional study. SAMPLE 118 owners of dogs, cats, or rabbits. PROCEDURES Medical records were searched to identify animals that underwent PRT between 2004 and 2013. Signalment, tumor-related data, and outcome information were recorded. Owners completed an electronic survey assessing satisfaction with treatment (ie, satisfaction with the decision for their pet to undergo PRT and indication that they would choose PRT for their pet again), expectations regarding PRT, and perceptions of their pets' quality of life (QOL) and signs of discomfort from acute adverse radiation effects. Additional data regarding practical aspects of treatment, pet death, communications with veterinarians, and owner demographics were collected. Variables were tested for association with measures of owner satisfaction. RESULTS 92 of 116 (79%) owners were satisfied with the decision to have their pets undergo PRT. Most (92/118 [78%]) owners reported their pet's QOL improved after PRT; these owners were significantly more likely to be satisfied than those who did not report improved QOL. Owners who perceived their pets had discomfort from adverse radiation effects (38/116 [33%]) were significantly less likely to be satisfied than owners who did not report this observation. Measures of satisfaction were not associated with patient survival time. Twenty-one of 118 (18%) owners indicated they expected PRT would cure their pet's tumor. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that short life expectancy should not deter recommendation of PRT for pets. Protocols that minimize risk of acute adverse effects may be advantageous. Veterinarians should attempt to ensure that owners understand the goals of PRT.

Tethered epidermal growth factor provides a survival advantage to mesenchymal stem cells.

MSC can act as a pluripotent source of reparative cells during injury and therefore have great potential in regenerative medicine and tissue engineering. However, the response of MSC to many growth factors and cytokines is unknown. Many envisioned applications of MSC, such as treating large defects in bone, involve in vivo implantation of MSC attached to a scaffold, a process that creates an acute inflammatory environment that may be hostile to MSC survival. Here, we investigated cellular responses of MSC on a biomaterial surface covalently modified with epidermal growth factor (EGF). We found that surface-tethered EGF promotes both cell spreading and survival more strongly than saturating concentrations of soluble EGF. By sustaining mitogen-activated protein kinase kinase-extracellular-regulated kinase signaling, tethered EGF increases the contact of MSC with an otherwise moderately adhesive synthetic polymer and confers resistance to cell death induced by the proinflammatory cytokine, Fas ligand. We concluded that tethered EGF may offer a protective advantage to MSC in vivo during acute inflammatory reactions to tissue engineering scaffolds. The tethered EGF-modified polymers described here could be used together with structural materials to construct MSC scaffolds for the treatment of hard-tissue lesions, such as large bony defects. Disclosure of potential conflicts of interest is found at the end of this article.

Epidermal growth factor as a candidate for ex vivo expansion of bone marrow-derived mesenchymal stem cells.

Bone marrow mesenchymal stem cells (BMMSCs) are pluripotent cells capable of differentiating into several cell types and are thus an attractive cell source for connective tissue engineering. A challenge in such a use is expansion and directed seeding in vitro, requiring proliferation and survival, and directed migration, respectively, prior to functional differentiation. The epidermal growth factor (EGF) receptor (EGFR) is the prototypal growth factor receptor and elicits these responses from a wide variety of stromal, epithelial, and endothelial cells. Ligands for this receptor are appealing for use in tissue engineering because they are relatively resistant to biological extremes and amenable to high-volume production. Therefore, we determined whether an EGFR ligand, EGF, could be used for ex vivo expansion of BMMSCs. EGF stimulated motility in rat and immortalized human BMMSCs. EGF-induced proliferation was observed in immortalized human BMMSCs but was not apparent in rat BMMSCs under our experimental conditions. EGF did not, however, rescue either type of BMMSC from apoptosis due to lack of serum. During our examination of key signaling intermediaries, EGF caused robust phosphorylation of extracellular signal-regulated protein kinase (ERK) and protein kinase B/akt (AKT) but only minimal phosphorylation of EGFR and phospholipase C-gamma in rat BMMSCs, whereas in the human BMMSCs these intermediaries were all strongly activated. EGF also induced robust ERK activation in primary porcine mesenchymal stem cells. EGF pretreatment or cotreatment did not interfere with secondarily induced differentiation of either type of BMMSC into adipogenic or osteogenic lineages. Platelet-derived growth factor (PDGF) effects were similar to but not additive with those elicited by EGF, with some quantitative differences; however, PDGF did interfere with the differentiation of these BMMSCs. These findings suggest that EGFR ligands could be used for ex vivo expansion and direction of BMMSCs.