Postoperative adjuvant treatment of invasive malignant mammary gland tumors in dogs with doxorubicin and docetaxel

BACKGROUND: Treatment outcome after surgery alone is unsatisfactory in dogs with invasive malignant mammary gland tumors. HYPOTHESIS: Adjuvant doxorubicin or docetaxel will improve the treatment outcome in dogs with high-risk malignant mammary gland tumors, and the use of docetaxel will be feasible in affected dogs. ANIMALS: Thirty-one dogs with malignant mammary gland tumors of histologic stages II and III (vascular or lymphatic invasion, regional lymph node metastasis, or distant metastasis) were used. METHODS: A prospective clinical trial in which dogs were treated with surgery alone (n = 19) or also received adjuvant chemotherapy (n = 12) with doxorubicin or docetaxel was conducted. Docetaxel was given as an IV infusion at a dose of 30 mg/m2 preceded by dexamethasone and diphenhydramine administration. RESULTS: The recurrence-free interval ranged from 13 to 2,585 days (median not reached); the median metastasis-free interval and overall survival were 294 days and 370 days, respectively. Dogs treated with chemotherapy had a tendency toward higher long-term local control and survival rates, but there was no significant difference in the recurrence-free interval (P = .17), time to metastasis (P = .71), and overall survival (P = .12). Factors found to influence the time to metastasis and overall survival included lymph node metastasis (P = .009) and tumor fixation to underlying structures (P = .043, time to metastasis), as well as age (P = .018) and histologic stage (P < .001, survival). Mild allergic skin reactions were the most frequently observed complications of docetaxel treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Chemotherapy did not lead to an improved outcome in this population. Docetaxel treatment was well tolerated. Additional investigations of adjuvant chemotherapy in dogs with high-risk mammary cancer are warranted.     

Correlation between the histopathological diagnosis by AgNOR count and AgNOR area in canine mammary tumors

Background: Mammary tumors are the most common type of tumor in female dogs. The histopathological diagnosis is usually made by a hematoxylin-eosin (HE) staining of the tumor, which then requires a pathologist's judgment for assessment of malignancy. The purpose of this study was to investigate an alternative silver staining of some argyrophilic nucleolar organizer regions (AgNOR) for improving the diagnostic accuracy with mammary tumors.
Hypothesis: There is a correlation between the histopathological diagnosis by AgNOR count and AgNOR area in canine mammary tumors.
Animals: Seventy-three canine mammary tumors from 33 female dogs.
Materials and Methods: The AgNOR staining was evaluated retrospectively in 73 canine mammary tumors with a parallel HE staining as a "Gold Standard." Both a quantitative manual counting method and a qualitative computerized morphometric method were tested.
Result: The result from both methods indicated a clinically relevant difference in the mean values of the AgNOR in the following 4 categories: malignant, benign, hyperplastic, and normal mammary tissue. The counting method was superior, with 89% of the cases given a correct diagnosis of a malignant or a nonmalignant canine mammary tumor. The 2 methods were then compared to test their ability to classify the tumors correctly. Again, the counting method was the most reliable method, with a sensitivity of 80% and a specificity of 76% when the upper 50% of the AgNOR counts were presumed malignant.
Conclusion and Clinical Importance: The results indicated that an AgNOR test could be an aid to pathologists as a prognostic indicator or to assist them in deciding between a benign or a malignant diagnosis in questionable cases.     

Effect of spaying and timing of spaying on survival of dogs with mammary carcinoma

The risk of developing mammary gland tumors in dogs is significantly decreased by ovariohysterectomy at an early age. However, previous studies have not found a benefit to ovariohysterectomy concurrent with tumor removal in dogs with established mammary gland tumors, suggesting that the progression of these tumors is independent of continued estrogen stimulation. The purpose of this study was to evaluate the effect of spaying and of the timing of spaying on survival in dogs with mammary gland carcinoma. Signalment, spay status and spay age, tumor characteristics, treatment. survival, and cause of death of 137 dogs with mammary gland carcinoma were analyzed. The dogs were classified into 3 groups according to spay status and spay time: intact dogs, dogs spayed less than 2 years before tumor surgery (SPAY 1), and dogs spayed more than 2 years before their tumor surgery (SPAY 2). Dogs in the SPAY 1 group lived significantly longer than dogs in SPAY 2 and intact dogs (median survival of 755 days, versus 301 and 286 days, respectively, P = .02 and .03). After adjusting for differences between the spay groups with regard to age, histologic differentiation, and vascular invasion, SPAY 1 dogs survived 45% longer compared to dogs that were either intact or in the SPAY 2 group (RR = .55; 95% CI .32-.93; P = .03). This study reveals ovariohysterectomy to be an effective adjunct to tumor removal in dogs with mammary gland carcinoma and that the timing of ovariohysterectomy is important in influencing survival.     

Serum alkaline phosphatase isoenzyme activities in canine malignant mammary neoplasms with and without osseous transformation

BACKGROUND: Increased serum activity of total alkaline phosphatase (TALP) has been found in dogs with mammary neoplasms, especially malignant mixed tumors. We hypothesized that the bone isoenzyme of alkaline phosphatase (BALP), a specific indicator of osteoblastic activity and bone formation, may contribute to increased TALP in dogs with mammary neoplasms with osseous transformation. OBJECTIVE: The purpose of this study was to compare serum TALP, BALP, and other ALP isoenzyme activities in dogs with mammary malignant neoplasms with and without osseous transformation. METHODS: Twenty-one female dogs with malignant mammary neoplasms were compared with 21 clinically healthy, age-matched female control dogs. Physical, clinicopathologic (including preprandial and postprandial serum bile acids, ACTH stimulation, and low-dose dexamethasone suppression tests), radiographic, and ultrasonographic examinations were performed on all dogs with tumors to assess coexisting conditions. On the basis of histologic examination of excised tumors, dogs were further classified as having epithelial (n = 11) or mesenchymal/mixed (epithelial-mesenchymal) (n = 10) neoplasms, the latter of which had histologic and radiologic evidence of bone formation. Serum TALP, BALP, liver alkaline phosphatase (LALP), and corticosteroid-induced alkaline phosphatase (CALP) activities were measured using biochemical methods. RESULTS: Dogs with malignant mammary tumors had significantly higher (P < .05) median serum TALP (170 U/L), BALP (59 U/L), LALP (49 U/L), and CALP (24 U/L) activities, compared with control dogs (81, 32, 37, and 5 U/L, respectively). Significantly higher activities of BALP and LALP were found in dogs with epithelial neoplasms; whereas, only CALP activity was higher in dogs with mesenchymal/mixed neoplasms. There was no significant difference in TALP or isoenzyme activitities between epithelial and mesenchymal/mixed groups. CONCLUSION: BALP activity is increased in some dogs with malignant mammary tumors but does not account for the increase in TALP in dogs with neoplasms that have osseous transformation.     

Immunocytochemical study of Ki-67 as a prognostic marker in canine mammary neoplasia

Background: Canine mammary tumors are challenging for clinicians and pathologists because of complex histologic classification, low specificity of cytologic diagnosis, and unpredictable biological behavior. In histologic specimens, expression of tumor proliferation marker Ki‐67, a nuclear nonhistone protein, has been shown to have prognostic value for canine mammary tumors and to correlate with malignancy and low survival rates. Objective: The objective of this study was to measure the proliferation index of canine mammary tumors by immunochemical detection of Ki‐67 in cytologic specimens and to determine its relationship to clinical and pathologic variables and patient outcome. Methods: Spontaneous mammary tumors from 31 female dogs were surgically excised. Imprint specimens for cytologic evaluation were wet‐fixed in ethanol; histologic specimens were prepared routinely. Immunostaining was performed with the PH 177 monoclonal antibody against Ki‐67; proliferation index was graded from negative to +++. Dogs were followed for 18 months. Multivariate logistic regression analysis was used to determine correlations between immunocytochemical results, tumor and clinical variables, and patient outcome. Results: Ki‐67 proliferation indices in cytologic specimens were significantly lower for nonmalignant tumors than for malignant tumors. High index values of Ki‐67 were positively correlated with metastasis, death from neoplasia, low disease‐free survival rates, and low overall survival rate. With the exception of 4 specimens for which cellularity was insufficient, positive expression of Ki‐67 in cytologic specimens correlated with that of histologic specimens. Conclusions: The prognostic value of the Ki‐67 index in canine mammary tumors by using wet‐fixed cytology imprint specimens was similar to that observed previously for histologic specimens. Immunocytochemical detection of Ki‐67 could improve the accuracy and value of cytology by providing safe and rapid information about malignancy and patient outcome.     

Investigation of serum survivin in dogs suffering from cancer: a multicenter study

BackgroundIn contrast to human medicine, only a small number of serum tumor markers are established in veterinary medicine even though they are a non-invasive diagnostic tool.ObjectivesThis study examined whether survivin could be suitable as a potential canine serum tumor marker.MethodsThis study measured the serum survivin concentrations of dogs with mammary tumors (n = 33), squamous cell carcinoma (n = 9), soft-tissue sarcoma (n = 18) and multicentric lymphoma (n = 22), using a commercially available, competitive immunoassay kit (BlueGene). The serum survivin concentrations were compared with those of a healthy control group (n = 20) and a control group of dogs with non-neoplastic diseases (n = 17).ResultsDogs with malignant tumors had serum survivin concentrations between 15 and 5,906 pg/mL (median, 72 pg/mL), those in the healthy group ranged from 7 to 99 pg/mL (median, 21 pg/mL) and those in the group of dogs suffering from non-neoplastic diseases from 15 to 93 pg/mL (median, 42 pg/mL). The differences in the survivin concentrations between the healthy dogs and dogs with malignant tumors and between the dogs with non-neoplastic diseases and those with malignant tumors were significant (p < 0.001 and p = 0.006, respectively).ConclusionsThe serum survivin concentrations in dogs with malignant tumors, with some exceptions, are higher than in dogs with benign tumors and dogs that do not suffer from a malignancy. Therefore, survivin can provide information on the presence of malignant tumors and be used as a tumor marker in dogs.     

Comparison of histology and clinical variables to DNA ploidy in canine mammary tumors

Flow cytometric DNA analysis was done on 132 canine mammary tumors from 99 dogs to evaluate the relation to histology and to clinical staging. Seventy-one tumors (54%) were histologically malignant; 38 (54%) of these were aneuploid and 33 (46%) were diploid. Fifty-two (39%) tumors were histologically benign, of which 45 (87%) were diploid and seven (13%) aneuploid. There were nine dysplastic mammae (7%); two were aneuploid and the rest diploid. DNA indices varied from 0.72 to 2.35. Of 58 mammary carcinomas, 25 (43%) were diploid and 33 (57%) were aneuploid (of the latter, 16 showed hypodiploidy and 17 hyperdiploidy with a predominance between DNA index 1.10 and 1.50). Three tumors (two carcinomas and one malignant mixed tumor) were multiploid with two aneuploid cell populations. The histological type varied within eight tumors, and in four of these the DNA index also varied. DNA indices varied within three tumors with uniform morphology. No correlation was found between DNA index and age of the dogs, nor between DNA index and tumor size. No significant differences were found between DNA index and histology, tumor growth pattern, or tumor location. Benign tumors were smaller than carcinomas, which were smaller than malignant mesenchymal tumors. Tumors growing adherent to the skin were larger than those not adherent to the skin. The regional lymph nodes were examined in 33 cases. No significant difference between the mean DNA index and presence of lymph node metastasis was found. These results show the possibility of using flow cytometry for DNA analysis in canine mammary tumors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic factors associated with survival two years after surgery in dogs with malignant mammary tumors: 79 cases (1998-2002)

OBJECTIVE: To identify prognostic factors for female dogs that have undergone surgical removal of malignant mammary tumors. DESIGN: Retrospective case series. ANIMALS: 79 female dogs with malignant mammary tumors. PROCEDURE: Information obtained from the medical records included breed, age, sex, tumor size (maximum diameter), number and location of affected mammary glands, time between tumor identification and surgical removal, radiographic evidence of distant metastasis, surgical procedure, ovariohysterectomy (OHE) status, histologic classification of the tumor, and survival time. RESULTS: Results of univariate analyses indicated that clinical stage, tumor size, OHE status, metastasis to adjacent lymph nodes or distant sites, and histologic classification of the tumor were significantly associated with survival 2 years after surgery. Tumors > or = 5 cm in diameter and tumors that had been identified > 6 months before surgery were more likely to metastasize to adjacent lymph nodes. Ovariohysterectomy was more beneficial in dogs with complex carcinomas than in dogs with simple carcinomas. In multivariate analyses, clinical stage, tumor size, and OHE status were significantly associated with survival 2 years after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that tumor stage, tumor size, and OHE status were significant prognostic factors associated with survival 2 years after surgery in dogs with malignant mammary tumors. Further, either dogs with tumors > or = 5 cm in diameter or dogs with tumors present for > 6 months prior to surgery had a higher risk of having lymph node metastases.     

Evaluation of outcome associated with subcutaneous and intramuscular hemangiosarcoma treated with adjuvant doxorubicin in dogs: 21 cases (2001-2006)

OBJECTIVE: To evaluate outcome associated with subcutaneous and intramuscular hemangiosarcomas treated with adjuvant doxorubicin in dogs. DESIGN: Retrospective case series. ANIMALS: 21 dogs. PROCEDURES: Records of dogs with histologically confirmed hemangiosarcoma, no detectable metastasis at initial evaluation, and adequate local tumor control were included. Age, sex, number of treatments, treatment interval, radiation therapy, and concurrent use of cyclophosphamide or deracoxib were evaluated for associations with disease-free interval (DFI) or survival time. Three to 6 cycles of doxorubicin were planned. Disease-free interval was defined as time of definitive surgery to time of local recurrence, metastasis, or both. Survival time was defined as the beginning of the DFI to time of death. RESULTS: 17 tumors were subcutaneous, and 4 were intramuscular. Median age was 9 years. Median weight was 31.1 kg (68.4 lb). Five dogs received adjuvant radiation therapy. Median DFI for subcutaneous tumors was 1,553 days (95% confidence interval [CI], 469 days to not estimable). Median DFI for intramuscular tumors was 265.5 days (95% CI, 123 to 301 days). Median survival time for subcutaneous tumors was 1,189 days (95% CI, 596 days to not estimable). Median survival time for intramuscular tumors was 272.5 days (95% CI, 123 to 355 days). For dogs with subcutaneous tumors, younger age (< 9 years) was associated with longer DFI and survival time. Dogs with subcutaneous tumors that did not receive radiation therapy had longer DFI. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with subcutaneous hemangiosarcoma had a more favorable outcome, compared with dogs with intramuscular hemangiosarcoma, when treated with adequate local control and adjuvant doxorubicin.     

Survival, neurologic response, and prognostic factors in dogs with pituitary masses treated with radiation therapy and untreated dogs

BACKGROUND: Pituitary masses in dogs are not uncommon tumors that can cause endocrine and neurologic signs and, if left untreated, can decrease life expectancy. HYPOTHESIS: Dogs with pituitary masses that received radiation therapy (RT) have more favorable neurologic outcomes and longer survival times compared with untreated dogs. ANIMALS: Nineteen dogs with a pituitary mass identified on CT or MR imaging were irradiated with 48 Gy given in 3 Gy daily-dose fractions. Twenty-seven untreated control dogs had pituitary masses. METHODS: Medical records of dogs with pituitary masses were retrospectively reviewed for clinical signs, mass size, and outcome. RESULTS: Median survival time was not reached in the treated group. Mean survival time in the treated group was 1,405 days (95% confidence interval [CI], 1,053-1,757 days) with 1-, 2-, and 3-year estimated survival of 93, 87, and 55%, respectively. Median survival in the nonirradiated group was 359 days (95% CI, 48-916 days), with a mean of 551 days (95% CI, 271-829 days). The 1-, 2-, and 3-year estimated survival was 45, 32, and 25%, respectively. Dogs that received RT for their pituitary tumors had significantly longer survival times than untreated dogs (P = .0039). Treated dogs with smaller tumors (based on maximal pituitary-to-brain height ratio or area of tumor to area of brain) lived longer than those with larger tumors (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: When compared with untreated dogs, RT increased survival and controlled neurologic signs in dogs with pituitary masses.     

The effect of cisterna chyli ablation combined with thoracic duct ligation on abdominal lymphatic drainage

OBJECTIVE: To evaluate the effect of cisterna chyli ablation (CCA) and thoracic duct ligation (TDL) on abdominal lymphatic drainage in normal dogs. STUDY DESIGN: Experimental study. ANIMALS: Nine female beagle dogs. METHODS: TDL was performed in 3 dogs and was combined with CCA (CCA-TDL) and local omentalization in 6 dogs. Contrast lymphangiography was attempted in all dogs immediately before and after TDL. Dogs were reanesthetized at 31-37 days for lymphatic studies by new methylene blue (NMB) injection into a mesenteric lymph node and by contrast lymphangiography. RESULTS: In 6 CCA-TDL dogs, 2 had direct shunting of contrast from the lymphatic system into major abdominal veins, 3 had contrast material that dissipated into abdominal vessels within the mesenteric root, and 1 had shunting into the azygous vein. NMB was not observed within the omental pedicle after CCA-TDL. Chylous drainage was by the azygous vein in all 3 TDL dogs. CONCLUSIONS: CCA-TDL disrupted chylous drainage to the thoracic duct and resulted in direct intraabdominal lymphaticovenous anastomoses identified by shunting of lymphatic flow directly into the abdominal vasculature in 5 of 6 CCA-TDL dogs. Omentalization of the cisternal ablation site was not beneficial in augmenting extrathoracic lymphatic drainage and is not recommended with CCA-TDL. CLINICAL RELEVANCE: CCA-TDL represents a novel approach to surgical redirection of chylous drainage to the venous circulation outside of the thorax and may be useful in the treatment of spontaneous chylothorax in the dog.     

The Prognostic Significance of Angiogenesis in Canine Mammary Tumors

The purpose of the study was to determine if neovascularization, a measure of angiogenesis, is correlated with metastasis of mammary tumors in dogs. Forty-six paraffin-embedded tissue blocks of benign and malignant canine mammary tumors obtained from 42 clinical cases at the Iowa State University Veterinary Teaching Hospital were retrieved from the archives of the Department of Veterinary Pathology. Of the dogs with malignant tumors, cases with and without lymph node metastasis were chosen. Neovascularization was quantified by light microscopy on formalin-fixed, paraffin-embedded sections of canine mammary tumors using an avidin biotin immunoperoxidase assay for factor VIII-related antigen. Mean microvessel counts for each group were statistically evaluated using analysis of variance. The mean number of microvessels was highest in the malignant tumors of dogs with lymph node metastasis (44). This number was significantly different from the mean number of microvessels in the benign tumors (28; P = .03) and a trend occurred toward higher microvessel counts in malignant tumors with lymph node metastasis versus malignant tumors of dogs without metastasis (32; P = .1). No significant difference was found between the number of microvessels found in malignant tumors without metastasis versus benign tumors. The trend toward higher microvessel counts in mammary tumors that have metastasized supports the premise that angiogenesis may be an independent and significant prognostic indicator in dogs with malignant mammary tumors, as it is in women with breast cancer.     

Analysis of Factors Affecting Survival in Dogs With Aortic Body Tumors

OBJECTIVE: To evaluate the effect of perioperative and operative variables on survival time in dogs with aortic body tumors. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Twenty-four client-owned dogs with histologically confirmed aortic body tumor. METHODS: Seventy-eight patient records of dogs seen at the University of Illinois Veterinary Teaching Hospital between 1989 and 1999 with a diagnosis of a heart-base mass were reviewed. Dogs without histologic conformation of an aortic body tumor were excluded. Age; sex; breed; the presence of pleural effusion, pericardial effusion, or abdominal effusion; evidence of cardiac arrhythmias; evidence of distant metastasis; treatment with pericardectomy; treatment with chemotherapy; and time from diagnosis until euthanasia or death were recorded on a spreadsheet. Cox proportional-hazard ratios were used to calculate the relationship of risk variables to survival time. Median survival time was determined using life-table analysis. RESULTS: Twenty-four dogs met the criteria for inclusion in the study. The median age of dogs with aortic body tumors was 9 years. All dogs had a surgical biopsy performed. Fourteen dogs had a pericardectomy at the time of the biopsy procedure. Of all factors analyzed, only treatment with pericardectomy had a significant influence on survival (P =.0029). Dogs that had pericardectomy survived longer (median survival, 730 days; range, 1-1,621 days) compared with dogs that did not have pericardectomy (median survival, 42 days; range, 1-180 days). This finding was independent of the presence or absence of pericardial effusion at the time of surgery. CLINICAL RELEVANCE: Dogs that are diagnosed with aortic body tumors may benefit from a pericardectomy at the time of surgical biopsy.     

Elective and emergency surgical management of adrenal gland tumors: 60 cases (1999-2006)

Sixty-one adrenal gland tumors were surgically removed from 60 dogs. Fifty-two dogs underwent elective adrenalectomy and 8 dogs underwent emergency adrenalectomy for acute adrenal hemorrhage. Size of adrenal tumors ranged from 10 mm to 80 mm. Histopathology confirmed a diagnosis of adrenocortical tumor in 47 dogs, 26 of which were malignant. Pheochromocytoma was diagnosed in 11 dogs. Six dogs had tumor invasion of the caudal vena cava. Of the seven dogs that did not survive the perioperative period, four underwent emergency adrenalectomy. No dogs with tumor invasion of the caudal vena cava died perioperatively. Perioperative morality rates were 5.7% for dogs that underwent elective adrenalectomy and 50% for dogs that underwent emergency adrenalectomy for acute adrenal hemorrhage. Median survival time was 492 days for the 53 dogs that survived the perioperative period. Of the factors analyzed, only adrenal tumor size and the presence of acute adrenal hemorrhage had predictive values for perioperative mortality. Those dogs that survived the perioperative period had extended survival times of up to 1,590 days. The mortality rate associated with elective adrenalectomy in dogs may be lower than previously reported. Dogs with very large tumors or acute adrenal hemorrhage may have a more guarded prognosis.     

Telomere length and telomerase activity in canine mammary gland tumors

OBJECTIVE: To measure telomere length and telomerase activity in naturally occurring canine mammary gland tumors. SAMPLE POPULATION: 27 mammary gland tumor specimens obtained during resection or necropsy and 12 mammary gland tissue specimens obtained from healthy (control) dogs. PROCEDURE: Telomere length in tissue specimens was measured by use of restriction endonuclease digestion and Southern blot analysis. Telomerase activity was measured by use of a telomeric repeat amplification protocol assay. RESULTS: Telomere length in mammary gland tumors ranged from 11.0 to 21.6 kilobase pairs (kbp; mean +/- SEM, 14.5+/-0.5 kbp) but did not differ among tumor types. Telomeres in mammary gland tumors were slightly shorter than in normal tissue specimens, but telomere length could not be directly compared between groups, because mean age of dogs was significantly different between groups. Age was negatively correlated with telomere length in control dogs but was not significantly correlated with length in affected dogs. Telomerase activity was detected in 26 of 27 mammary gland tumors and in 4 of 12 normal tissue specimens. However, telomerase activity and telomere length were not correlated in tumor specimens. CONCLUSIONS AND CLINICAL RELEVANCE: Telomere length is maintained in canine mammary gland tumors regardless of the age of the affected dog. Measurement of telomere length may be a useful tool for monitoring the in vivo effects of telomerase inhibitors in dogs with tumors.     

Complications associated with the use of indwelling epidural catheters in dogs: 81 cases (1996-1999)

OBJECTIVE: To evaluate complications associated with use of indwelling epidural catheters in dogs in a clinical setting. DESIGN: Retrospective clinical study. ANIMALS: 81 client-owned dogs. PROCEDURE: Medical records were reviewed for dogs in which a 19-gauge epidural catheter was placed percutaneously at L7-S1 and advanced to the point of maximum efficacy for pain control (between L7 and T4, depending on the procedure). Catheters were used to provide perioperative epidural analgesia during surgeries that included perineal (n = 6), hind limb (33), abdominal (43), thoracic (5), forelimb (2), and cervical (1) procedures. RESULTS: Catheters were maintained in situ from 1 to 7 days (mean, 2.3 days; median, 2.0 days). Sixty-four dogs did not have complications; 17 dogs had minor complications. Catheter dislodgement was the most common complication (13/80 [16%] dogs). Catheter site contamination without inflammation developed in 2 (2.4%) dogs; inflammation at the catheter site developed in 2 (2.4%) dogs but was not related to duration of time the catheter was in place. Complications were not serious and did not require treatment other than catheter removal. Dogs that dislodged their catheters were significantly younger (mean, 2.9 years; median, 2.0 years) than other dogs (mean, 6.2 years; median, 6.0 years). Dogs that received femoral fracture repair dislodged their catheters more often (62.5%) than dogs undergoing other procedures (10.9%). CONCLUSIONS AND CLINICAL RELEVANCE: The complication rate associated with temporary epidural catheterization of dogs appears to be low, and complications generally are not serious.     

Efficacy and toxicity of paclitaxel (Taxol) for the treatment of canine malignant tumors

Paclitaxel (Taxol) was administered to 25 dogs with histologically confirmed malignant tumors at a dosage of 165 mg/m2 i.v. over 3-6 hours every 3 weeks. Dogs received premedication with antihistimines and corticosteroids to reduce hypersensitivity reactions. However, 64% of the dogs still experienced allergic reactions. Six dogs (24%) had grade 3 or 4 neutropenia, 6 dogs (24%) required hospitalization and 3 dogs (12%) died of sepsis. Five dogs (20%) had a partial response (osteosarcoma [2 dogs] mammary carcinoma [2 dogs] and malignant histiocytosis [1 dog]) for a median duration of 53 days. The overall toxicity was unacceptable at the 165 mg/m2 dose. Therefore, subsequent evaluations of paclitaxel in tumor-bearing dogs should a starting dose of 132 mg/m2 i.v. every 3 weeks.     

Piroxicam Therapy in 34 Dogs With Transitional Cell Carcinoma of the Urinary Bladder

Thirty-four dogs with histopathologically confirmed, measurable, nonresectable transitional cell carcinoma of the urinary bladder were treated with piroxicam (0.3 mg/kg PO sid) and were evaluated for tumor response and drug toxicity. Dogs were evaluated at the Purdue University Veterinary Teaching Hospital by means of physical examination, thoracic and abdominal radiography, cystography, complete blood count, serum biochemistry profile, and urinalysis. In selected cases, prostaglandin E₂ (PGE₂) concentrations in plasma and in supernatants of stimulated monocytes, and natural killer cell activity were quantified, Dogs were evaluated before therapy and at 28 and 56 days after initiation of therapy. Dogs with stable disease or remission at 56 days remained on the study and were evaluated at 1 to 2 month intervals. Tumor responses were 2 complete remissions, 4 partial remissions, 18 stable diseases. and 10 progressive diseases. The median survival of all dogs was 181 days (range, 28 to 720+ days), with 2 dogs still alive. Piroxicam toxicity consisted of gastrointestinal irritation in 6 dogs and renal papillary necrosis (detected at necropsy) in 2 dogs. Monocyte production of PGE₂ appeared to decrease with therapy in dogs whose tumors were decreasing in size, and increased in dogs with tumor progression. A consistent pattern in natural killer cell activity was not observed. In vitro cytotoxicity assays against 4 canine tumor cell lines revealed no direct antitumor effects of piroxicam. In summary, antitumor activity, which was not likely the result of a direct cytotoxic effect, was observed in dogs with transitional cell carcinoma of the bladder treated with piroxicam.