Running head: TRANSITIONAL CELL CARCINOMA IN A DOG Transitional Cell Carcinoma in a Dog Sarra Borne Lord Tarleton State University VETE 3313: Radiology and Clinical Imaging March 03, 2015 1 TRANSITIONAL CELL CARCINOMA IN A DOG 2 Transitional Cell Carcinoma in a Dog Slide 1. The use of retrograde cystography to assist in diagnosis of transitional cell carcinoma in a dog Slide 2: Harriet – History and Signalment. Harriet is a 10 year old, spayed female Scottish terrier. She is a generally healthy dog, with no previous history of significant illness or surgery. Her owners are concerned because she has had hematuria for the past few weeks. The referring vet has done urine cultures which have come back negative and has treated Harriet with three different antibiotics. Harriet showed improvement for a few days on the most recent course of antibiotics but has regressed and the owners feel that now she not only has hematuria, but is also straining to urinate, and is asking to go out more frequently. Harriet was referred for a urinary tract workup. Slide 3: Physical Exam. Harriet’s physical exam is essentially normal. She is a good weight for her size, her temperature, heart rate and respiratory rates are within normal limits. Her heart and lungs auscultate normally, and she shows no pain or guarding on abdominal palpation. A rectal palpation revealed formed stool in the colon. The owners agreed to a complete urinary tract workup including blood work and a urinalysis, a contrast study of the bladder and an abdominal ultrasound. The differential diagnosis includes resistant urinary tract infection (UTI), pyelonephritis, urinary tract polyps or neoplasia, urinary calculi, an anatomic defect or a foreign body (rare). Slide 4. Laboratory Findings. Harriet’s CBC was within reference interval limits on the analyzer, and there were no abnormalities on the blood smear review. Harriet’s biochemistry panel was unremarkable. The increase in ALKP was minimal and nonspecific. Harriet’s TRANSITIONAL CELL CARCINOMA IN A DOG 3 urinalysis was also nonspecific, other than a marked increase in RBC’s. No bacteria were appreciated on the sediment exam. Survey radiographs are taken of Harriet’s abdomen and chest. On her abdominal radiographs her kidneys appear to be of normal size and shape, and the other abdominal organs including the bladder appear to be within normal limits as well. The thoracic radiographs are also within normal limits, the heart is of a normal size and shape, and the lungs appear clear. The veterinarian requested a retrograde cystography series, including negative, positive and double contrast images. “Retrograde contrast cystography is a fast, simple and inexpensive technique that may provide valuable diagnostic and prognostic information about bladder disease” (Thrall, 2013, p. 729). Indications for cystography include patients with normal or abnormal survey radiographs of the bladder along with other clinical signs or urinary dysfunction such as dysuria, intermittent or chronic hematuria, and pollakiuria. An IV catheter was placed and Harriet was sedated with Dexdomitor and butorphanol. This provided adequate sedation for the catheterization and contrast studies; with the additional benefit of being reversible should complications arise. The hair around Harriet’s vulva was shaved and she was prepped with chlorhexidine scrub and a sterile saline rinse. Slide 5: Diagnostic Imaging, Negative Contrast. To perform a negative contrast study of the urinary bladder the patient needs to have a urinary catheter placed, urine is removed from the bladder, and the end of the catheter is attached to a three-way stopcock so that the operator can control air and fluid passage into and out of the bladder. While room air can be used, it is associated with the potentially fatal complication of an air embolism especially in patients with hematuria so it is much safer to use carbon dioxide or nitrous oxide if these are available. Other possible complications can include catheter induced trauma to the urethra or bladder, and over TRANSITIONAL CELL CARCINOMA IN A DOG 4 distension or rupture of the bladder. The amount of contrast media used should be carefully calculated based on the patient’s size, usually 3-5 ml/lb of body weight. In Harriet’s case between 50 and 80 ml will be sufficient. Right lateral and ventrodorsal radiographs are obtained. There appears to be a potential mass effect in the trigone area. To further define this mass effect the next step in the procedure is positive contrast cystography. Slide 6: Diagnostic Imaging, Positive Contrast. For the positive contrast study, the carbon dioxide is released from the bladder and it is refilled with a sterile, iodinated contrast media that has been diluted with sterile water to 150 mg/ml. Right lateral and ventrodorsal radiographs are obtained. If retrograde urethrogram images are desired to visualize defects in the urethra, images can be made with the catheter in the distal urethra while 5- 10 ml contrast media is introduced. This particular study was not done on Harriet. Positive contrast cystography allows better visualization of filling defects which are defined as objects occupying space in the lumen because they usually appear as areas of incomplete or no filling (black spaces) in the contrast media. Filling defects that are attached to the wall of the bladder (as in Harriet’s case) are usually tumors or polyps. Free floating filling defects can be uroliths, blood clots, bubbles or sloughing mucosa. Slide 7: Diagnostic Imaging, Double Contrast. Finally, a double contrast study was performed. The iodinated media was removed from Harriet’s bladder and air was reintroduced. Any remaining positive contrast material that is seen clinging to the walls of the bladder is because of the previously noted lesion. It allowed the veterinarian to have better visualization of the margins of the mass effect. Slide 8: Diagnostic Imaging, Ultrasound. To further increase visibility of the margins, and to assess the remaining abdominal organs an ultrasound was done. Harriet’s kidneys showed TRANSITIONAL CELL CARCINOMA IN A DOG 5 no signs of hydronephrosis, and there were no lesions visible in the liver or spleen that might suggest metatheses. The bladder had obviously irregular mucosa, with several thickened areas on the bladder wall that suggested diffuse disease. Some of the mesenteric lymph nodes adjacent to the bladder appear to be mildly to moderately enlarged. Slide 9: Diagnostic Imaging, Cystoscopy. While these findings were suggestive of bladder neoplasia, the only way to obtain a definitive diagnosis is to obtain samples of the lesions. Once there is reason to believe that there may be bladder neoplasia, aspirates of the bladder should be avoided as they may carry tumor cells on the needle that can seed into the mesentery and skin at the site or sites of the punctures. Cytologic evaluation can be done by rubbing the tip of the urinary catheter against the mass effect and aspirating to extract cells but this is not guaranteed. Surgical biopsy can be done but it is a very invasive procedure and unless the tumor appears to be of a type that can be excised surgically is not generally recommended. Cystoscopy allows the veterinarian to visualize the mass, and obtain samples using a specialized biopsy instrument. Harriet’s owners are contacted and give verbal consent for the procedure. Since Harriet is already heavily sedated a reduced dose of propofol is given to allow intubation and she is placed on gas anesthesia. A small rigid endoscope is passed through her urethra into her bladder, where the mass is visualized to be fimbriated (which is defined as fringed, or bordered by slender processes). Samples are collected for histopathology. Slide 10: Transitional Cell Carcinoma. The pathologist diagnoses Harriet’s tissue samples as being of a tumor type called transitional cell carcinoma. This is the most common cancer of the canine urinary bladder. It is a malignant tumor that develops from the epithelial TRANSITIONAL CELL CARCINOMA IN A DOG 6 cells that line the bladder. The exact cause of developing TCC are unknown, however, there may be a genetic predisposition as certain and specific breeds of dogs are more prone to developing TCC. These breeds include the Scottish Terrier, which has the highest incidence of all, almost 18% more likely to develop TCC than any other breed. West Highland White Terriers, Fox Terriers, Shetland Sheepdogs and Beagles also have a higher likelihood of developing TCC than other breeds. A 2004 study showed that shows that exposure to lawn chemicals and insecticides may produce a significantly increased risk of developing TCC especially in Scottish terriers, it is unknown if this factored into Harriet’s case (Glickman, Raghavan, Knapp, Bonney, & Dawson, 2004). Slide 11: Therapeutic Recommendations. There are several therapeutic options available for treatment of bladder tumors. Surgical resection can be done if the tumor is discrete and not located in the trigone area of the bladder. Tumors such as Harriet’s that are in the trigone region are not resectable because of the proximity to the ureters. This disease is progressive and most treatment is considered palliative. Median survival even with treatment is usually 18 months or less. Radiation therapy of the bladder is possible but when given in traditional doses can cause harmful complications such as a shrunken or scarred bladder and irritation to surrounding organs (Knapp, 2013). Most cases are treated with chemotherapy, with medical management. Piroxicam is the most common drug used in the treatment of dogs with TCC. Piroxicam is a non-steroidal antiinflammatory drug that has an unknown indirect antitumor activity. Piroxicam alone can produce a stable disease in some dogs that allows their cancer to be managed as a chronic disease (Knapp, 2013). Median survival of dogs treated with just piroxicam is 195 days. TRANSITIONAL CELL CARCINOMA IN A DOG 7 The addition of a chemotherapeutic agent such as mitoxantrone or vinblastine given as an infusion every 2 to 3 weeks can induce remission in approximately 35% of patients. Survival time with the combination therapy can be increased to 250 – 300 days. A study at Purdue University was done on metronomic therapy in the treatment of TCC. These dogs are given a low daily oral dose of chlorambucil. The study is promising in that approximately 70% of the 31 dogs enrolled achieved a stable disease state. Average survival time was 7 months, and this therapy was only started after other therapies had stopped working (Knapp, 2013). Harriet’s owners chose to treat her therapeutically with a combination of mitoxantrone every 2 weeks and piroxicam (0.3 mg/kg) daily. Her status will be reevaluated via ultrasonography every 2 weeks at her chemotherapy appointment. If her tumor is shrinking or remaining stable the treatment will be continued, if the cancer is not responding a different therapy will be started. Long term prognosis is guarded, but some patients can have good quality of life for extended periods. Metastatic disease is a common sequelae, regional lymph nodes and lungs are the most common sites for metastasis but other locations such as bone have been reported. Dogs with invasive tumors and/or nodal and distant metastasis have shorter survival times. In Harriet’s case the length of time between onset of signs and diagnosis, and start of chemotherapy before the tumor had a chance to metastasize may improve her long term prognosis. TRANSITIONAL CELL CARCINOMA IN A DOG References Caswell, M. (2011, June). Transitional cell carcinoma of the urinary bladder in a 14-year-old dog. The Canadian Veterinary Journal, 52, 673-675. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3095172/ Contrast studies of small animals. (2015). Retrieved from http://www.onlinevets.com/contrast_4.html Glickman, L. T., Raghavan, M., Knapp, D. W., Bonney, P. L., & Dawson, M. H. (2004). Herbicide exposure and the risk of transitional cell carcinoma of the urinary bladder in Scottish Terriers. Journal of the American Veterinary Medical Association, 224, 12901297. Knapp, D. W. (2013). Canine bladder cancer. Retrieved from https://www.vet.purdue.edu/pcop/files/docs/CanineUrinaryBladderCancer.pdf Scurell, E. (2012). Transitional cell carcinoma (TCC) in a dog. Retrieved from http://www.cytopath.co.uk/caseofmonthMarch2012.html The Finnish Veterinary Association. (n.d.). Kuvat figures. Retrieved from http://www.sell.fi/index.php?id=513 Thrall, D. E. (2013). Textbook of veterinary diagnostic radiology (6th ed.). : Saunders. 8