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.

Yoon HY, et al. J Vet Sci. 2015 Mar;16(1):93-98. https://doi.org/10.4142/jvs.2015.16.1.93

A 7-month-old, 4.3-kg, spayed female bichon frise was referred for evaluation of chronic urinary incontinence. Abdominal radiographs revealed calculi within the right kidney and ureter. An ultrasound revealed a small right kidney. An abdominal computed tomography scan with contrast revealed that the left ureter was extramurally ectopic, inserting into the proximal urethra. A right intramural ectopic ureter was identified during cystotomy. Ureteronephrectomy was performed on the right, and ureteroneocystostomy was performed on the left. A telephone conversation with the owner 4 months after surgery revealed that the dog exhibited no evidence of urine dribbling, and urinary continence was maintained well on phenyl-propanolamine (1.75 mg/kg orally q 12 hours). This is the first report of successful surgical management of bilateral ureteral ectopia with concurrent, unilateral, renal dysplasia and urolithiasis

A castrated male Shih-Tzu dog was presented for evaluation of urine leakage after urethrotomy. A fistula with urine leakage was identified in the perineal region. On retrograde urethrography, the contrast extravasated from the penile urethra into the subcutaneous tissue of the perineum. Urine leakage with urethrocutaneous fistula was diagnosed. During surgery, the disrupted urethra wall and two urethral defects were identified. A fascia lata autograft was used, rather than primary repair of the urethra. Two pieces of fascia lata were harvested and sutured to the urethral defects. The fistula was treated with debridement and drainage. No evidence of urine leakage and dysuria was noted 6 months postoperatively. Thus, this case report describes successful urethral reconstruction using a fascia lata autograft.

Primary cranial mediastinal hemangiosarcomas are uncommon tumors. A 30-kg, 2-year-old, intact female German shepherd was presented for evaluation of cachexia and respiratory distress of a few days’ duration. Lateral radiographic projection of the thorax revealed significant pleural effusion. Computed tomography revealed a cranial mediastinal mass effect adjacent to the heart. On surgical exploration, a pedunculated mass attached to the esophagus, trachea, brachiocephalic trunk, left subclavian artery and cranial vena cava without attachment to the right atrium and auricular appendage was removed and debrided by use of blunt dissection and dry gauzes, respectively. Histopathology results described the cranial mediastinal mass as hemangiosarcoma. At 8 months and 5 days post-operatively, the patient died. Primary cranial mediastinal hemangiosarcomas, although a seemingly rare cause of thoracic pathology in young dogs, should be considered in the differential diagnosis for pleural effusion and soft tissue mass effect in the cranial mediastinum. This is the first case report in a dog to describe primary cranial mediastinal hemangiosarcoma.