Transitional cell carcinoma (TCC) is the most common malignant tumor of the canine urinary tract and tends to have a poor prognosis due to its invasive potential. Recent studies have reported that up to 80% of canine urothelial carcinoma has the BRAF V595E mutation, which is homologous to the human V600E mutation. Activating the BRAF mutation is an actionable target for developing effective therapeutic agents inhibiting the BRAF/mitogen-activated protein kinase (MAPK) pathway in canine cancer as well as human cancer. We established novel canine TCC cell lines from two tumor tissues and one metastatic lymph node of canine TCC patients harboring the BRAF V595E mutation. Tumor tissues highly expressed the BRAF mutant and phosphorylated extracellular signal-related kinases (ERK)1/2 proteins. The derived cell lines demonstrated activated MAPK pathways. We also evaluated the cell lines for sensitivity to BRAF inhibitors. Sorafenib, a multiple kinase inhibitor targeting RAF/vascular endothelial growth factor receptor (VEGFR), successfully inhibited the BRAF/MAPK pathway and induced apoptosis. The established canine TCC cell lines responded with greater sensitivity to sorafenib than to vemurafenib, which is known as a specific BRAF inhibitor in human cancer. Our results demonstrated that canine TCC cells showed different responses compared to human cancer with the BRAF V600E mutation. These cell lines would be valuable research materials to develop therapeutic strategies for canine TCC patients.

Pulmonary hypoplasia (PH) and congenital lobar emphysema (CLE) are very rare congenital pulmonary anomalies in veterinary medicine. PH refers to the incomplete pulmonary development due to embryologic imbalance of bronchial development between the lung buds, while CLE is defined as alveolar hyperinflation due to bronchial collapse during expiration caused by bronchial cartilage dysplasia, external bronchial compression, and idiopathic etiology. CLE may develop into pulmonary blebs or bullae that may rupture and induce a spontaneous pneumothorax. There are no reports on concurrent PH and CLE in animals. A 7-month-old castrated male Italian Greyhound weighing 5.5 kg presented with vomiting and acute onset of severe dyspnea without any previous history of disease. After emergency treatment including oxygen supplementation and thoracocentesis, plain radiology and computed tomography scanning were performed and lobar emphysema with multiple bullae in the left cranial lung lobe associated with tension pneumothorax was identified. Since the pneumothorax was not resolved despite continuous suction of intrathoracic air for 3 days, a complete lobectomy of the left cranial lung lobe was performed. The excised lobe was not grossly divided into cranial and caudal parts, but a tissue mass less than 1 cm in size was present at the hilum and cranial to the excised lobe. Postoperatively, the dog recovered rapidly without air retention in the thoracic cavity. Histopathologically, the mass was identified as a hypoplastic lung tissue with collapsed alveoli, bronchial dysplasia, and pulmonary arterial hypertrophy. Additionally, the excised lung lobe presented CLE with marked ectasia of alveoli, various blebs and bullae, and general bronchial cartilage dysplasia. According to gross and histopathologic findings, the dog was diagnosed with concurrent PH and CLE in the left cranial lung lobe. During 16 months of follow-up, the dog was well and without any respiratory problems. This case report confirmed the clinical and histologic features of two different types of rare congenital pulmonary anomalies, PH and CLE, which occurred concurrently in a single lung lobe of a young dog. The condition was successfully managed with lobectomy.

Transitional cell carcinoma (TCC) is the most common malignant tumor of the canine urinary tract. In this case study, a dog with metastatic urethral TCC was treated with sorafenib. The tumor expression levels of receptor tyrosine kinase genes, including VEGFR-1, VEGFR-2, PDGFR-α, PDGFR-β, ALK, EGFR, ErbB2, and B-RAF, were analyzed. VEGFR was overexpressed in tumor tissues compared to the normal tissues. Considering the high frequency of B-RAF mutation in canine urological tumors, the B-RAF gene was examined, and the B-RAF V595E mutation was detected in the tumor tissue. Therefore, the antitumor effect of sorafenib, a multi-tyrosine kinase inhibitor, on unresectable metastatic urethral TCC characterized by B-RAF V595E was evaluated and circulating cell-free tumor DNA (ctDNA) was assessed for monitoring the treatment response. After the initiation of oral sorafenib therapy (4 mg/kg/day escalated to 10 mg/kg/day), the dysuria was alleviated gradually, and the patient remained stable for 3 months. During that treatment period, the patient showed various levels of changes associated with B-RAF V595E mutation in ctDNA as evident from longitudinal plasma samples after initiation of sorafenib therapy. The findings of this study suggest that ctDNA may serve as a useful non-invasive tool for monitoring the treatment response to anticancer drugs.

A 7-month-old neutered male poodle dog presented with general deterioration and gastrointestinal symptoms after two separate operations: a jejunotomy for small-intestinal foreign body removal and an exploratory laparotomy for diagnosis and treatment of the gastrointestinal symptoms that occurred 1 month after the first surgery. The dog was diagnosed as having small-bowel obstruction (SBO) due to intra-abdominal adhesions and small-bowel fecal material (SBFM) by using abdominal radiography, ultrasonography, computed tomography, and laparotomy. We removed the obstructive adhesive lesion and SBFM through enterotomies and applied an autologous peritoneal graft to the released jejunum to prevent re-adhesion. After the surgical intervention, the dog recovered quickly and was healthy at 1 year after the surgery without gastrointestinal signs. To our knowledge, this study is the first report of a successful treatment of SBO induced by postoperative intra-abdominal adhesions and SBFM after laparotomies in a dog.

A four-year-old dachshund presented with a two-week history of pyrexia, depression, and cough. Four months earlier, the owner observed the dog swallow a whole popsicle stick, but the animal showed no clinical signs at that time. Radiography, ultrasonography, and computed tomography confirmed an intrathoracic linear foreign body and pleural effusion in the right thorax. The pleural fluid was bloody and purulent, and contained inflammatory cells and Escherichia coli. The dog was diagnosed with pyothorax induced by a foreign body, and was treated successfully by surgical removal of the foreign body, partial lung lobectomy, thoracic lavage, and antibiotics. The foreign body was identified as a popsicle stick that the dog had eaten.

Inter-individual variations in drug responses are major concerns in cancer treatment in human and veterinary oncology. Consequently, preclinical models have been proposed to predict drug responses and determine optimal individualized therapy. We aimed to evaluate the clinical utility of in vitro drug sensitivity testing using a patient-derived cell culture model to select appropriate adjuvant therapies for dogs with solid tumors. We screened medical records of 126 dogs with suspected tumors, including 33 dogs with solid tumors (guided group, 16; empirical group, 17). Anticancer drugs used for adjuvant therapy were determined based on in vitro drug sensitivity testing (guided group) or histopathological examination (empirical group) results. Time to tumor progression (TTP) was compared between groups. The guided group had significantly longer TTP than the empirical group (949 vs. 109 days). Median TTPs were significantly longer in the guided group than in the empirical group for dogs with incomplete surgical margin (949 vs. 109 days), dogs with mitotic count < 20 per 10 high power fields (949 vs. 105 days), dogs with no evidence of metastatic disease at initial diagnosis (455 vs. 196 days), and dogs receiving tyrosine kinase inhibitors (949 vs. 109 days). Our study suggests that in vitro drug sensitivity testing may be a useful tool for optimizing adjuvant therapy in dogs with solid tumors.