Expression of cyclooxygenase-2 in transitional cell carcinoma of the urinary bladder in dogs

OBJECTIVE: To evaluate expression of cyclooxygenase (COX)-1 and COX-2 in the urinary bladder epithelium of clinically normal dogs and in transitional cell carcinoma cells of dogs. ANIMALS: 21 dogs with transitional cell carcinoma of the urinary bladder and 8 dogs with clinically normal urinary bladders. PROCEDURE: COX-1 and COX-2 were evaluated by use of isoform-specific antibodies with standard immunohistochemical methods. RESULT: COX-1, but not COX-2, was constitutively expressed in normal urinary bladder epithelium; however, COX-2 was expressed in neoplastic epithelium in primary tumors and in metastatic lesions of all 21 dogs and in new proliferating blood vessels in 3 dogs. Also, COX-1 was expressed in the neoplastic cells. CONCLUSIONS AND CLINICAL RELEVANCE: Lack of expression of COX-2 in normal bladder epithelium and its substantial expression in transitional cell carcinoma cells suggest that this isoform may be involved in tumor cell growth. Inhibition of COX-2 is a likely mechanism of the antineoplastic effects of non steroidal antiinflammatory drugs.     

Ureterocolonic anastomosis in a dog with transitional cell carcinoma of the urinary bladder

Ureterocolonic anastomosis and cystectomy were performed in a dog for treatment of transitional cell carcinoma of the urinary bladder. The dog remained an acceptable house pet for 10 months after surgery. However, the tumor recurred 10 months after surgery, and the dog was euthanatized. Our results indicated that the combination of ureterocolonic anastomosis and cystectomy can be an acceptable form of palliative treatment for transitional cell carcinoma of the urinary bladder in the dog.     

Carboplatin and piroxicam therapy in 31 dogs with transitional cell carcinoma of the urinary bladder

Invasive transitional cell carcinoma (TCC) of the urinary bladder responds poorly to medical therapy. Combining platinum chemotherapy with a cyclooxygenase (cox) inhibitor has shown promise against canine TCC, where the disease closely mimics the human condition. A phase II clinical trial of carboplatin combined with the cox inhibitor, piroxicam, was performed in 31 dogs with naturally occurring, histopathologically confirmed, measurable TCC. Complete tumour staging was performed before and at 6‐week intervals during therapy. Tumour responses in 29 dogs included 11 partial remissions, 13 stable disease and five progressive disease. Two of the 31 dogs were withdrawn prior to the re‐staging of the tumour. Gastrointestinal toxicity was observed in 23 dogs. Hematologic toxicity was noted in 11 dogs. The median survival was 161 days from first carboplatin treatment to death. In conclusion, carboplatin/piroxicam induced remission in 40% of dogs providing evidence that a cox inhibitor enhances the antitumour activity of carboplatin. The frequent toxicity and limited survival, however, do not support the use of this specific protocol against TCC.     

Evaluation of cisplatin administered with piroxicam in dogs with transitional cell carcinoma of the urinary bladder

OBJECTIVE: To evaluate the antitumor activity and toxic effects of a conservative dose of cisplatin administered in combination with piroxicam to dogs with transitional cell carcinoma (TCC) of the urinary bladder. DESIGN: Clinical trial (nonrandomized, noncontrolled). ANIMALS: 14 client-owned dogs with histologically confirmed TCC of the urinary bladder. PROCEDURES: Each dog was treated with cisplatin (50 mg/m(2), i.v., q 21 d [reduced to 40 mg/m(2), i.v., q 21 d because of toxic effects]) and piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h). A CBC, serum biochemical analyses, and urinalysis were performed prior to each cisplatin treatment. Tumor staging (determined from thoracic and abdominal radiographic and urinary bladder ultrasonographic findings) was performed before treatment and at 6-week intervals during treatment. RESULTS: 5 dogs received only 1 dose of cisplatin because of the rapid progression of disease (n = 2) or toxic effects (3). With regard to the neoplastic disease among the other 9 dogs, 1 had partial remission, 5 had stable disease, and 3 had progressive disease after 6 weeks of treatment. Median progression-free interval was 78 days (range, 20 to 112 days). Median survival time was 307 days (range, 29 to 929 days). Moderate to severe renal toxicosis and moderate to severe gastrointestinal toxicosis developed in 5 and 8 dogs, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Because of minimal efficacy and associated renal and gastrointestinal toxicosis, administration of cisplatin (40 to 50 mg/m(2)) with piroxicam cannot be recommended for treatment of dogs with TCC of the urinary bladder.     

Antitumor effects of deracoxib treatment in 26 dogs with transitional cell carcinoma of the urinary bladder

OBJECTIVE-To evaluate the antitumor activity and toxic effects of deracoxib, a selective cyclooxygenase-2 inhibitor, in dogs with transitional cell carcinoma (TCC) of the urinary bladder. DESIGN-Clinical trial. Animals-26 client-owned dogs with naturally occurring, histologically confirmed, measurableTCC of the urinary bladder. PROCEDURES-Dogs were treated PO with deracoxib at a dosage of 3 mg/kg/d (1.36 mg/lb/d) as a single-agent treatment for TCC. Tumor response was assessed via radiography, abdominal ultrasonography, and ultrasonographic mapping of urinary bladder masses. Toxic effects of deracoxib administration in dogs were assessed through clinical observations and hematologic and biochemical analyses. RESULTS-Of 24 dogs for which tumor response was assessed, 4 (17%) had partial remission, 17 (71%) had stable disease, and 3 (13%) had progressive disease; initial response could not be assessed in 2 of 26 dogs. The median survival time was 323 days. Median time to progressive disease was 133 days. Renal, hepatic, and gastrointestinal abnormalities attributed to deracoxib administration were noted in 4% (1/26), 4% (1/26), and 19% (5/26) of dogs, respectively. CONCLUSIONS AND CLINICAL RELEVANCE-Results indicated that deracoxib was generally well tolerated by dogs and had antitumor activity against TCC.     

Herbicide exposure and the risk of transitional cell carcinoma of the urinary bladder in Scottish Terriers

OBJECTIVE: To determine whether exposure to lawn or garden chemicals was associated with an increased risk of transitional cell carcinoma (TCC) of the urinary bladder in Scottish Terriers. DESIGN: Case-control study. ANIMALS: 83 Scottish Terriers with TCC (cases) and 83 Scottish Terriers with other health-related conditions (controls). PROCEDURE: Owners of study dogs completed a written questionnaire pertaining to exposure to lawn or garden chemicals during the year prior to diagnosis of TCC for case dogs and during a comparable period for control dogs. RESULTS: The risk of TCC was significantly increased among dogs exposed to lawns or gardens treated with both herbicides and insecticides (odds ratio [OR], 7.19) or with herbicides alone (OR, 3.62), but not among dogs exposed to lawns or gardens treated with insecticides alone (OR, 1.62), compared with dogs exposed to untreated lawns. Exposure to lawns or gardens treated with phenoxy herbicides (OR, 4.42) was associated with an increased risk of TCC, compared with exposure to untreated lawns or gardens, but exposure to lawns or gardens treated with nonphenoxy herbicides (OR, 3.49) was not significantly associated with risk of TCC. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that exposure to lawns or gardens treated with herbicides was associated with an increased risk of TCC in Scottish Terriers. Until additional studies are performed to prove or disprove a cause-and-effect relationship, owners of Scottish Terriers should minimize their dogs' access to lawns or gardens treated with phenoxy herbicides.     

Presumptive subcutaneous surgical transplantation of a urinary bladder transitional cell carcinoma in a dog

A urinary bladder mass in a 12-year-old spayed female West Highland White Terrier was diagnosed after exploratory surgery and biopsy as a transitional cell carcinoma. Four months later the dog presented with an ulcerated plaque-like cutaneous lesion at the previous surgical incision site; concurrent inguinal lymphadenopathy and recurrence of the urinary bladder mass were identified. Transitional cell carcinoma was diagnosed at all 3 sites. Although a definitive relationship cannot be established between the initial surgery for urinary bladder mass and the resultant subcutaneous lesion, surgical implantation should be considered as a source for the neoplastic cells.     

Cohort study of COX-1 and COX-2 expression in canine rectal and bladder tumours

OBJECTIVES: To determine the role that cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) play in malignant transformation in canine transitional cell carcinoma and rectal tumours. METHODS: Histological sections of 21 canine rectal adenocarcinomas and 18 canine transitional cell carcinomas were stained for COX-1 and COX-2. Mann-Whitney non-parametric tests were applied to determine if there was any relationship between the percentage of cells expressing COX-1 or COX-2, and between COX-1 and COX-2 staining intensity and age, breed or sex. RESULTS: For rectal adenocarcinomas, 19.0 per cent of the sections were negative for COX-1 and COX-2. A further 38.1 per cent of the sections were negative for COX-2 but positive for COX-1, and 38.1 per cent of the sections had rare or occasional single cells positive for COX-2. No significant differences were found in COX staining when compared with age, breed or sex. For transitional cell carcinomas, all of the sections were positive for COX-1 and COX-2. For COX-2 staining, 16.7 per cent had more than 30 per cent positive cells. For COX-1 staining, 38.9 per cent had more than 30 per cent positive cells. There was a significant increase in the percentage of COX-1 positive cells in small breed dogs (P = 0.0337). CLINICAL SIGNIFICANCE: The variations in COX expression reported in this study may explain the differences in the clinical response of transitional cell carcinomas and rectal adenocarcinomas following treatment with non-steroidal anti-inflammatory drugs.     

Clinical outcome of partial cystectomy for transitional cell carcinoma of the canine bladder

Canine transitional cell carcinoma (TCC) of the bladder has historically been treated with a combination of chemotherapy, cyclooxygenase inhibitors and radiation therapy. While surgery has been used to treat TCC of the bladder, its efficacy has yet to be established. Thirty‐seven client owned dogs that underwent partial cystectomy +/? various nonsurgical treatments for TCC were retrospectively evaluated. The overall median progression‐free interval (PFI) was 235 days and the median survival time (ST) was 348 days. Prognostic factors identified on univariate analysis significant for ST were age, tumor location, full thickness excision and frequency of piroxicam administration. Prognostic factors significant for PFI were full thickness excision and frequency of piroxicam administration. The median ST with partial cystectomy and daily piroxicam therapy, with or without chemotherapy, was 772 days. Dogs with non‐trigonal bladder TCC treated with full thickness partial cystectomy and daily piroxicam (+/? chemotherapy) may have improved outcome compared to dogs treated with medical therapy.     

Topical flea and tick pesticides and the risk of transitional cell carcinoma of the urinary bladder in Scottish Terriers

OBJECTIVE: To determine whether use of topical flea and tick products increases the risk of transitional cell carcinoma (TCC) of the urinary bladder in Scottish Terriers. DESIGN: Case-control study. ANIMALS: 87 adult Scottish Terriers with TCC (cases) and 83 adult Scottish Terriers with other health-related conditions (controls). PROCEDURE: Owners of study dogs were recruited through private veterinary practices and the Scottish Terrier Club of America. History of exposure to flea and tick products 1 year prior to diagnosis of TCC for case dogs and during a comparable period for control dogs was obtained through a questionnaire. Risk of TCC associated with exposure to flea and tick products was determined by means of univariate and multiple logistic regression analysis. RESULTS: After adjustment for host factors, Scottish Terriers treated with topical spot-on flea and tick products containing fipronil or imidacloprid did not have an increased risk of TCC, compared with Scottish Terriers that had never been exposed to any flea and tick products. The risk of TCC associated with use of older topical flea and tick products such as shampoos, dips, powders, sprays, and collars could not be evaluated because of the low number of owners in the study population that had used such products. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of topical spot-on flea and tick products does not increase the risk of TCC in Scottish Terriers.     

Immunohistochemical expression of p63, Ki67 and β‐catenin in canine transitional cell carcinoma and polypoid cystitis of the urinary bladder

Transitional cell carcinoma (TCC) is a urinary bladder tumour associated with high mortality in dogs. In this study, we investigated the feasibility of using p63, Ki67 or β‐catenin as a clinical marker for predicting biological behaviour and prognosis in canine TCC. Expression levels of these proteins in TCC (n = 25), polypoid cystitis (n = 5) and normal urinary bladder (n = 5) were scored after immunohistochemical staining. The staining scores for p63 (P < 0.01) and β‐catenin (P < 0.05) in TCC were significantly lower than those in normal urinary bladder and polypoid cystitis. In contrast, Ki67 (P < 0.01) staining scores in TCC were significantly higher than those in normal urinary bladder and polypoid cystitis. In TCC, low p63 expression was significantly related to the presence of vessel invasion (P < 0.05) and metastasis (P < 0.01) as well as short survival time (P < 0.05). These findings show that p63 could be a reliable marker for predicting prognosis in canine TCC.