A pilot study of toceranib/vinblastine therapy for canine transitional cell carcinoma.

BACKGROUND: Effective therapies for transitional cell carcinoma (TCC) are limited, with objective response rates to most chemotherapeutic regimens below 20%. The purpose of this study was to investigate the biologic activity of combined toceranib phosphate and vinblastine chemotherapy for treatment of TCC. A secondary objective was to compare the utility of Computed Tomography (CT) and abdominal ultrasound (AUS) in tumor response assessments. RESULTS: Dogs with TCC received vinblastine at 1.6 mg/m2 every 2 weeks and toceranib at 2.5-2.75 mg/kg on Monday/Wednesday/Friday. Tumor monitoring was achieved through CT and AUS. Five patients completed the 16-week study. Based on AUS assessments, 3 dogs experienced biologic response to therapy including partial responses (PR, n = 2) and stable disease (SD, n = 1). Based on CT, 5 dogs experienced a biologic response (n = 2 PR, n = 3 SD). Both imaging modalities (ultrasound and CT) were found to provide repeatable measurements between operators, however agreement between operator measurements was greater when CT images were used to assess tumor size. CONCLUSIONS: The combination of toceranib and vinblastine did not result in improved response rates. While agreement in tumor volume assessments between both AUS and CT were excellent between operators, this did not extend to assessment of tumor response. The higher rate of concordance between operators when assessing response to treatment with CT suggests that CT should be considered for future clinical trials involving canine bladder TCC to improve the accuracy and repeatability of tumor measurement. The data suggest that response to therapy as assessed by AUS or CT do not predict duration of clinical response.

Pulsed-wave Doppler ultrasonographic evaluation of hepatic veins during variable hemodynamic states in healthy anesthetized dogs.

OBJECTIVES: To quantify direction and velocity of blood flow in hepatic veins in dogs under different hemodynamic conditions by use of pulsed-wave Doppler ultrasonography. ANIMALS: 10 healthy dogs. PROCEDURE: Dogs were anesthetized, and venous flow velocities in the quadrate lobe were measured. Arterial blood pressure, right atrial pressure, pulmonary artery pressure, and cardiac output were measured simultaneously. The timing of each waveform during the cardiac cycle was used to identify velocity profiles. Peak waveform velocities were measured during conditions of light anesthesia with isoflurane (baseline; period 1), cardiovascular depression following administration of high-dose isoflurane and esmolol i.v. (period 2), cardiovascular depression with crystalloid volume expansion (period 3), and high cardiac output induced with dobutamine (period 4). Hemodynamic measurements and maximum waveform velocities were compared among the 4 periods by use of an ANOVA and univariate and multivariate linear regression. RESULTS: During each study period, 4 distinct, low-velocity waves were identified. Mean velocities recorded during period 1 were as follows: retrograde atrial contraction a-wave, 7.3 cm/s; antegrade systolic S-wave, 15.0 cm/s; retrograde venous return v-wave, 2.7 cm/s; and antegrade diastolic D-wave, 11.4 cm/s. Mean S:D ratio was 1.27. During periods 3 and 4, S-wave velocity increased; D-wave velocity was highest during period 4. CONCLUSIONS AND CLINICAL RELEVANCE: Consistent hepatic venous velocity profiles were observed in healthy dogs under different hemodynamic conditions. These findings provide baseline values that may be useful in evaluating clinical cases, but further study involving healthy, awake dogs and dogs with cardiac and hepatic diseases is required.

Determination of extrarenal plasma clearance and hepatic uptake of technetium-99m-mercaptoacetyltriglycine in cats.

OBJECTIVE: To determine maximum extrarenal plasma clearance of technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) and maximum extrarenal hepatic uptake of 99mTc-MAG3 in cats. ANIMALS: 6 clinically normal adult cats. PROCEDURES: Simultaneously, baseline plasma clearance and camera-based uptake of 99mTc-MAG3 were determined in anesthetized cats. Double exponential curves were fitted to plasma clearance data. Injected dose was divided by area under the curve and body weight to determine 99mTc-MAG3 clearance. Regions of interest were drawn around kidneys and liver, and percentage dose uptake was determined 1 to 3 minutes after injection. After bilateral nephrectomy, simultaneous extrarenal plasma clearance and camera-based hepatic uptake of 99mTc-MAG3 were evaluated in each cat. RESULTS: Mean +/- SD baseline plasma clearance and extrarenal clearance were 5.29 +/- 0.77 and 0.84 +/- 0.47 mL/min/kg, respectively. Mean extrarenal clearance (as a percentage of baseline plasma clearance) was 16.06 +/- 7.64%. For right, left, and both kidneys, mean percentage dose uptake was 9.42 +/- 2.58, 9.37 +/- 0.86, and 18.79 +/- 2.47%, respectively. Mean hepatic percentage dose uptake before and after nephrectomy was 12.95 +/- 0.93 and 21.47 +/- 2.00%, respectively. Mean percentage change of hepatic uptake after nephrectomy was 166.89 +/- 23.19%. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, extrarenal clearance of 99mTc-MAG3 is higher than that of other species; therefore, 99mTc-MAG3 is not useful for estimation of renal function in felids. Evaluation of renal function in cats may be more accurate via camera-based versus plasma clearance-based methods because camera-based studies can discriminate specific organs.

Ameloblastic odontoma in the mandible of a llama.

A 4-year-old llama had an aggressive, multiloculated, expansile bone lesion involving the rostral mandible. The mandibular lesion was imaged using radiography and computed tomography. Antemortem diagnosis of an ossifying fibroma was made histologically. Postmortem findings showed the lesion to be limited to the mandible. Final diagnosis was ameloblastic odontoma.

Effects of methimazole on thyroid gland uptake of 99mTC-pertechnetate in 19 hyperthyroid cats.

Nineteen cats with abnormally high serum T4 concentrations underwent thyroid scintigraphy using technetium-99m pertechnetate (99mTcO4) before and after 36 +/- 6 days of methimazole administration (approximately 2.5mg PO q 12 h). Thyroid-to-salivary gland ratios (T:S ratios) and percentage thyroidal uptake of injected radioactivity at 20 and 60min after injection of 99mTcO4 were compared before and after methimazole treatment. Serum thyroid stimulating hormone (TSH) concentration was measured before and after methimazole treatment. Quantitatively, there was a positive association between the thyroid uptake of 99mTcO4 and the serum T4 before treatment (r = 0.74-0.83). TSH suppression was present when cats were first evaluated for hyperthyroidism. Methimazole treatment did not relieve TSH suppression in 17 cats. Two cats with unilateral thyroid uptake developed bilateral, asymmetric thyroid uptake of 99mTcO4 after treatment and had the greatest increase in TSH concentration after treatment. Quantitatively, thyroid scintigraphy did not significantly change after methimazole treatment (P>0.1). Evaluation of serum TSH concentration may be helpful in identifying methimazole-induced changes in the scintigraphic features of hyperthyroidism in mildly hyperthyroid cats.