Successful post-incomplete resection management of gastrointestinal stromal tumor using imatinib based on adenosine triphosphate-based tumor sensitivity assay in a dog.

Gastrointestinal stromal tumors arising from gastric cardia are uncommon in dogs. A few studies have shown the effectiveness of tyrosine kinase inhibitors in the treatment of canine gastrointestinal stromal tumors, but no standardized protocols are currently available. An 11-year-old spayed female Maltese dog was diagnosed with a gastrointestinal stromal tumor using histopathological and immunohistochemical analyses. An adenosine triphosphate-based tumor chemosensitivity assay revealed that imatinib at lower concentrations had a stronger inhibitory effect than toceranib. Based on the results of the assay, the dog was treated with imatinib after surgery. After 28 mo of therapy, there was no recurrence of the tumor. Key clinical message: Adenosine triphosphate-based tumor chemosensitivity assays may help clinicians to select appropriate postoperative chemotherapeutic drugs for incompletely resected gastrointestinal stromal tumors in dogs.

Gestion réussie à la suite d'une résection incomplète d'une tumeur stromale gastro-intestinale à l'aide de l'imatinib basée sur un test de sensibilité tumorale à base d'adénosine triphosphate chez un chien. Les tumeurs stromales gastro-intestinales résultant du cardia gastrique sont rares chez le chien. Quelques études ont montré l'efficacité des inhibiteurs de la tyrosine kinase dans le traitement des tumeurs stromales gastrointestinales canines, mais aucun protocole standardisé n'est actuellement disponible. Une chienne maltaise stérilisée de 11 ans a reçu un diagnostic de tumeur stromale gastro-intestinale à l'aide d'analyses histopathologiques et immunohistochimiques. Un test de chimiosensibilité tumorale à base d'adénosine triphosphate a révélé que l'imatinib à des concentrations plus faibles avait un effet inhibiteur plus fort que le tocéranib. Sur la base des résultats du test, le chien a été traité avec de l'imatinib après l'opération. Après 28 mois de traitement, il n'y a eu aucune récidive de la tumeur.Message clinique clé :Les tests de chimiosensibilité tumorale à base d'adénosine triphosphate peuvent aider les cliniciens à sélectionner les médicaments chimiothérapeutiques postopératoires appropriés pour les tumeurs stromales gastro-intestinales incomplètement réséquées chez le chien.(Traduit par Dr Serge Messier).

Establishment and characterization of six canine hepatocellular carcinoma cell lines.

Background: Hepatocellular carcinoma (HCC) is the most common malignant liver tumor in dogs. Although surgical resection is a major treatment option for canine HCC, there are no distinct strategies for unresectable tumor subtypes or adjuvant chemotherapy for tumors with positive margins. We aimed to establish and characterize novel HCC cell lines from canine patients. Methods: The cellular morphology, general growth features and tumorigenicity of the established cell lines were evaluated. We also examined the sensitivity of the cell lines to multi-target tyrosine kinase inhibitors (TKIs). Results: We established novel canine HCC cell lines from hepatic tumors and an additional kidney tumor of six canine patients. All cell lines showed colony forming and migratory ability. KU-cHCC-001 and KU-cHCC-001-Kidney, two cell lines exhibiting high epithelial-mesenchymal transition characteristics, showed tumorigenicity in xenografted mice. Toceranib, a veterinary TKI that targets vascular endothelial growth factor (VEGFR)/platelet-derived growth factor receptor (PDGFR)/c-kit, effectively inhibited the mitogen-activated protein kinase pathway and induced apoptosis. The established canine HCC cell lines showed greater sensitivity to toceranib than to sorafenib, a first-line treatment for human HCC targeting RAF/VEGFR/PDGFR. Sorafenib showed improved anti-tumor effects when co-treated with SCH772984, an extracellular signal-regulated kinase inhibitor. Conclusion: Our study suggests new therapeutic strategies for canine HCC, and these cell lines are valuable research materials for understanding HCC tumor biology in both humans and dogs.

Pulmonary passage of canine adipose tissue-derived mesenchymal stem cells through intravenous transplantation in mouse model.

IMPORTANCE: The intravenous administration of adipose tissue-derived mesenchymal stem cells (AdMSCs) in veterinary medicine is an attractive treatment option. On the other hand, it can result in severe complications, including pulmonary thromboembolism (PTE). OBJECTIVE: The present study assessed the occurrence of PTE after the intravenous infusion of canine AdMSCs (cAdMSCs) into experimental animals. METHODS: Five-week-old male BALB/c hairless mice were categorized into groups labeled A to G. In the control group (A), fluorescently stained 2 × 106 cAdMSCs were diluted in 200 µL of suspension and injected into the tail vein as a single bolus. The remaining groups included the following: group B with 5 × 106 cells, group C with 3 × 106 cells, group D with 1 × 106 cells, group E with 1 × 106 cells injected twice with a one-day interval, group F with 2 × 106 cells in 100 µL of suspension, and group G with 2 × 106 cells in 300 µL of suspension. RESULTS: Group D achieved a 100% survival rate, while none of the subjects in groups B and C survived (p = 0.002). Blood tests revealed a tendency for the D-dimer levels to increase as the cell dose increased (p = 0.006). The platelet count was higher in the low cell concentration groups and lower in the high cell concentration groups (p = 0.028). A histological examination revealed PTE in most deceased subjects (96.30%). CONCLUSIONS AND RELEVANCE: PTE was verified, and various variables were identified as potential contributing factors, including the cell dose, injection frequency, and suspension volume.

Clinical evaluation and surgical intervention for diaphragmatic eventration mimicking peritoneopericardial hernia in a cat.

A 2-year-old spayed female British Shorthair cat presented with an increased frequency and duration of cough since infant period. Based on radiographic, ultrasonographic, and computed tomography findings, peritoneopericardial diaphragmatic hernia was considered so that repair surgery was planned. During celiotomy, lax diaphragm was identified instead of defect. Transabdominal diaphragmatic plication was performed to resolve lax diaphragm and to prevent recurrence by overlapping relatively normal part of diaphragm. Diagnosed with diaphragmatic eventration postoperatively, the cat showed improvement in clinical signs and imaging results. Transabdominal diaphragmatic plication is a suitable treatment; the patient maintained normally during a 14-month follow-up period.

Double-wire woven nitinol stent for treating dogs with refractory tracheal collapse: A case series.

This retrospective case series describes the signalments, clinical signs, diagnostic test results, and postoperative complications obtained from the medical records of 10 client-owned dogs that underwent treatment for grade IV tracheal collapse using double-wire woven nitinol stents between October 2017 and September 2021. Respiratory signs resolved in all dogs immediately after tracheal stent placement. Mild to moderate stent fractures were identified in five dogs, of which two showed concurrent respiratory distress necessitating re-stenting after several months. Minor complications, such as stent migration, were absent. The double-wire woven nitinol stent optimised for the canine trachea showed favourable outcomes and minimal complications.

Reconstructive surgery with an autologous bone graft in a dog with presumptive chronic non-bacterial osteomyelitis.

A 15-year-old Cocker Spaniel was referred to for the evaluation of left forelimb lameness. Radiographic and computed tomography examinations revealed osteolysis of the proximal left third, fourth and fifth metacarpal bones and pathological fractures of the proximal left fourth metacarpal bone. Histopathological examination via bone biopsy did not provide a definitive diagnosis, and the owner elected limb-sparing surgery. The fourth metacarpal bone and digits were amputated. Subsequently, autologous bone grafts were performed on the lytic area of the third and fifth metacarpal bones. The dog showed improvement in gait 7 weeks after reconstructive surgery. Chronic non-bacterial osteomyelitis (CNO) was diagnosed by exclusion. To the best of our knowledge, CNO has not been previously reported in dogs.

Fatigue analysis of canine tracheal stents using the finite element method.

This study aimed to evaluate fatigue of three stent designs when various forces are applied and perform a comparative analyses. A computer simulation using the finite element method was performed. In particular, we constructed a three-dimensional finite element model of nitinol stents with three designs (S6: single-woven wire, wire diameter: 0.006 inch; D6: double-woven wire, wire diameter: 0.006 inch, and D7: double-woven wire, wire diameter: 0.007 inch) that are used to treat canine tracheal collapse (TC). The stents were subjected to a 200 mmHg compression force, a pure torsion force in a perpendicular direction, and a bending-torsion force combining perpendicular and axial forces. The von Mises stress was calculated to evaluate the extent of stent displacement, and Goodman diagrams were plotted to compare fatigue life cycles. D7 exhibited a longer fatigue life compared to S6 and D6. Under compression, pure torsion, and bending-torsion forces, displacement was the smallest for D7, followed by D6 and S6. Similarly, the fatigue life was the longest for D7, followed by D6 and S6. S6 showed the greatest displacement when subjected to external forces; among stents designed using the same wire, D6 displayed less displacement than S6, and D7 exhibited superior fatigue life when subjected to varying degrees of force. This study showed that the structural stability and fatigue life of stents could be effectively compared using finite element method D7 has the greatest stability and structural rigidity under cyclic load.

Adjuvant therapy with toceranib for hepatocellular carcinoma and cholangiocarcinoma in a Pomeranian.

A 10-year-old spayed female Pomeranian dog was referred for hepatic mass evaluation. Blood tests revealed mildly elevated alkaline phosphatase activities. Computed tomography revealed a mass with multiple nodules on the right hepatic medial lobe adjacent to the caudal vena cava; histopathology confirmed mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Because of incomplete resection, adjuvant therapy was recommended. As tumour cells showed PDGFR-α, c-Kit, and FGFR1 overexpression, the anticancer effect of tyrosine kinase inhibitors was evaluated on the cells; toceranib was the most effective and was administered starting with an extra-labelled dose. The dog remained stable for 2.3 years with mild adverse effects. To our knowledge, this is the first successful clinical application of toceranib in a dog with mixed HCC-CC.

Adjuvant therapy with imatinib for an incompletely resected multilobular tumour of bone in a dog.

A 5-year-old neutered male Shiba Inu dog presented with a history of oral bleeding, dysphagia, and depression for 3 weeks. The physical examination revealed a firm mass in the right caudal palatal region along the level of PM4-M2. On the computed tomography, the mass was round-to-oval in shape and 22 mm × 30 mm × 15 mm in size. The mass contained multiple bone attenuated materials with a palatal bone lysis of 4 mm × 6 mm. A complete resection of the mass was proposed; however, the owner declined due to the risk of complications associated with the radical surgery. Therefore, a palliative resection and biopsy of the mass were performed. On the histological examination, the mass was diagnosed as grade 2 multilobular tumour of bone (MTB). Since the mass was incompletely resected, adjuvant therapy was pursued along with targeted therapy using a tyrosine kinase inhibitor. The tumour cells showed overexpression of the receptor of tyrosine kinase for c-KIT, PDGFR-α, PDGFR-ß, and FGFR1 compared to normal tissue cells. Additionally, the cytotoxic effect of imatinib on the MTB cells was confirmed in vitro. Four weeks postoperatively, the administration of imatinib and carprofen was initiated and continued for 259 days. The patient maintained a good functional outcome for 306 days after the initial presentation.

Different outcomes of multiple sialadenitis involving the submandibular and zygomatic salivary glands in a Welsh Corgi dog.

A ten-year-old indoor, castrated male Cardigan Welsh Corgi (Canis familiaris) presented with the chief complaints of chronic vomiting, retching, hypersalivation, and bilateral submandibular masses for two months. The systemic examinations, including serum chemistry, radiography, ultrasonography, and fluoroscopy, were unremarkable. A fine-needle aspiration revealed bilateral submandibular sialadenitis. Broad-spectrum antibiotics with phenobarbital were prescribed to alleviate the ptyalism. Thereafter, the left submandibular glands were normalised, and the right submandibular glands decreased to half their size. Three weeks later, the animal had an emergency visit because of a sudden left exophthalmos. Computed tomography and magnetic resonance imaging revealed enlarged left zygomatic and right mandibular salivary glands. The affected glands were surgically removed; the histopathologic examination confirmed non-septic sialadenitis, and the patient was finally diagnosed with idiopathic sialadenitis. Vomiting continued after the gland removal and the dog required a gradual increase in the phenobarbital dosage and an additional antiepileptic drug (potassium bromide) to manage the symptoms. The patient died eight months later from an unknown cause. This case report of bilateral submandibular sialadenitis concurrent with unilateral zygomatic sialadenitis in a Welsh Corgi dog suggests that when multiple salivary glands are involved, the response to anti-epileptic drugs and the prognosis is poor compared to that involving a single salivary gland.