Coarse fractionated radiation therapy for pituitary tumours in cats: a retrospective study of 12 cases

This retrospective study describes the clinical progression of 12 cats with pituitary tumours treated with a coarse fractionated radiation protocol delivering a total dose of 37 Gy in five once weekly fractions. A pituitary macrotumour was identified in all 12 cats: 4 with neurological signs only and 8 with insulin‐resistant diabetes mellitus secondary to acromegaly. One of the cats with central neurological signs died before completing the radiotherapy course; the remaining three had partial or complete remissions of their central neurological signs. Of the cats with unstable diabetes mellitus, five no longer required insulin therapy, one required less insulin and two became stable. The overall median survival time was 72.6 weeks; four cats died from related causes, two from unrelated problems and six remain alive. Radiation therapy is confirmed as an effective treatment for feline pituitary tumours, giving prolonged survival and control of both paraneoplastic and mass effect signs.     

Linear-Accelerator-Based Modified Radiosurgical Treatment of Pituitary Tumors in Cats: 11 Cases (1997–2008)

Objective: Determine the efficacy and safety of a linear-accelerator-based single fraction radiosurgical approach to the treatment of pituitary tumors in cats.
Design: Retrospective study.
Animals: Eleven client-owned cats referred for treatment of pituitary tumors causing neurological signs, or poorly controlled diabetes mellitus (DM) secondary either to acromegaly or pituitary-dependent hyperadrenocortism.
Procedures: Cats underwent magnetic resonance imaging (MRI) of the brain to manually plan radiation therapy. After MRI, modified radiosurgery was performed by delivering a single large dose (15 or 20 Gy) of radiation while arcing a linear-accelerator-generated radiation beam around the cat's head with the pituitary mass at the center of the beam. Eight cats were treated once, 2 cats were treated twice, and 1 cat received 3 treatments. Treated cats were evaluated for improvement in endocrine function or resolution of neurological disease by review of medical records or contact with referring veterinarians and owners.
Results: Improvement in clinical signs occurred in 7/11 (63.6%) of treated cats. Five of 9 cats with poorly regulated DM had improved insulin responses, and 2/2 cats with neurological signs had clinical improvement. There were no confirmed acute or late adverse radiation effects. The overall median survival was 25 months (range, 1–60), and 3 cats were still alive.
Conclusions and Clinical Importance: Single fraction modified radiosurgery is a safe and effective approach to the treatment of pituitary tumors in cats.     

Feline Sinonasal Neoplasia: CT Staging and Prognosis with Mega Voltage Radiation Therapy

Introduction:  Megavoltage radiation is considered standard therapy for feline sinonasal neoplasia, but a paucity of published reports and the lack of a staging system based on advanced sectional imaging render accurate prognostication difficult. The aims of this retrospective study on feline sinonasal neoplasia were to adapt or develop a staging system based on advanced imaging, and to further define the prognosis with megavoltage radiation therapy.
Methods:  Medical records were reviewed, and CT images were evaluated by a single radiologist (JBG) and staged using a modified system previously reported for dogs. Further follow‐up information was obtained by telephone interviews with the referring veterinarians or owners.
Results:  Thirty‐six cats received megavoltage radiation for sinonasal neoplasia. Carcinomas (n = 17) and lymphomas (n = 16) were most common, followed by sarcomas (n = 3). A majority of immunophenotyped lymphomas were B‐cell (89%). Diagnostic CT images were available for review on 33 cats. The stage distribution was as follows: T1 (n = 3), T2 (n = 11), T3 (n = 5), T4 (n = 14). Lymphomas were more commonly T2 (n = 8) while a majority of carcinomas were T4 (n = 8). The median survival times have not yet been reached for any stage or disease subtype. The most common cause for euthanasia was local recurrence (15/19, 79%). Four cats that died of other causes lived between 1,124 and 2,322 days.
Conclusions:  Feline sinonasal neoplasia is uncommon, with carcinomas and lymphomas being most frequently encountered. Megavoltage radiation therapy appears to offer improved quality and duration of life for most patients, despite advanced staged at diagnosis in a majority.     

Exogenous Insulin Treatment after Hypofractionated Radiotherapy in Cats with Diabetes Mellitus and Acromegaly

Background: The optimal treatment for feline acromegaly has yet to be established. Surgical and medical therapies are minimally effective although radiotherapy might have greater efficacy. The purpose of this study was to review the response and outcome of cats with acromegaly and insulin-resistant diabetes mellitus (DM) to radiotherapy.
Hypotheses: That radiotherapy improves glycemic control in cats with acromegaly and that improved glycemic control is due to remission of clinical acromegaly; demonstrated by a fall in serum insulin-like growth factor-1 (IGF-1) concentrations.
Animals: Fourteen cats with naturally occurring acromegaly.
Methods: Retrospective case review; records of all cats treated for acromegaly with radiotherapy were reviewed from 1997 to 2008. Cats were selected on the basis of compatible clinical signs, laboratory features, and diagnostic imaging findings. Fourteen cats received radiotherapy, delivered in 10 fractions, 3 times a week to a total dose of 3,700 cGy.
Results: Thirteen of 14 cats had improved diabetic control after radiotherapy. These improvements were sustained for up to 60 months. DM progressed in 2 cats and 1 did not respond. Seven cats responded before the final treatment. Ten cats were euthanized, 1 as a consequence of radiotherapy. In 8 cats in which IGF-1 was measured after treatment, changes in its concentration did not reflect the clinical improvement in glycemic control.
Conclusions and Clinical Importance: Radiotherapy represents an effective treatment for cats with insulin-resistant DM resulting from acromegaly. IGF-1 concentration after treatment does not provide a suitable method by which remission from either acromegaly or insulin-resistant DM may be assessed.     

Efficacy and Toxicity of Intracavitary Administration of Pegylated Liposomal Encapsulated Doxorubicin (DOXIL) in Dogs with Hemangiosarcoma

Introduction:  Canine hemangiosarcoma (HSA) is a fatal malignancy and most dogs die within 6–8 months of diagnosis. The spleen is a common primary site, representing 50% of all cases. These dogs typically present with clinical signs due to tumor rupture and intra‐abdominal dissemination; the abdomen is also the main site of disease progression when these patients fail. Direct delivery of chemotherapy into the abdominal cavity may therefore be a rational approach in this malignancy.
Methods:  14 dogs with stage 2 or 3 splenic HSA were recruited. Doxil at a dose of 1 mg/kg was diluted in saline and administered via ultrasound‐guidance into the abdominal cavity. The dogs were scheduled to receive 4 treatments every 3 weeks. Samples of plasma and abdominal fluid were collected for pharmacokinetic analysis. All dogs were monitored for recurrence and complete necropsies were requested at death.
Results:  8 dogs with stage 3 and 6 dogs with stage 2 HSA were enrolled. All 14 dogs have died, 12/14 due to tumor and 2 from other causes. There was no difference in median survival days between stages (stage 2: 244, stage 3: 125, p = .22). All 12 dogs that died due to tumor‐related causes failed with intra‐abdominal recurrence. Necropsies showed that the dogs in this study had relatively fewer extra‐abdominal metastasis compared to dogs treated with systemic chemotherapy. Pk analysis showed detectable plasma doxorubicin 1 and 2 weeks after treatment.
Conclusion:  Direct abdominal administration of Doxil did not prevent intra‐abdominal recurrence; however, it appeared to provide effective systemic coverage.     

Outcomes of pituitary tumor irradiation in cats

BACKGROUND: Information on tumor control and normal tissue effects of radiotherapy to treat pituitary tumors in cats is limited. HYPOTHESIS: Radiation therapy is effective in controlling the clinical signs associated with pituitary tumors in cats, with a low incidence of adverse effects. ANIMALS: Eight cats were irradiated at Colorado State University between 1991 and 2002 for spontaneous pituitary tumors. METHODS: A retrospective review of records was made to assess tumor control and incidence of radiation-induced adverse effects. RESULTS: Pituitary carcinoma was diagnosed in 2 cats and pituitary adenoma in 6 cats. Total radiation dosage ranged from 4,500 to 5,400 cGy administered Monday through Friday in 270 or 300 cGy fractions. Acute effects were limited to epilation and mild otitis externa. Focal brain necrosis adjacent to regrowth of a pituitary carcinoma and a second tumor in the radiation field were reported as possible late effects. Median survival, regardless of cause of death of the 8 cats, was 17.4 months (range, 8.4 to 63.1 months). Median survival could not be determined if cats were censored for non-tumor-related causes of death. Six cats were alive at 1 year, and 3 cats were alive at 2 years after treatment. Tumor recurrence was seen in 1 cat with a pituitary carcinoma. Neurologic signs improved within 2 months in all 5 cats that presented with abnormal neurologic signs. Clinical signs caused by a concurrent endocrine disorder began to improve within 1-5 months in the 7 cats with hyperadrenocorticism or acromegaly. CONCLUSIONS AND CLINICAL RELEVANCE: Radiation therapy is an effective primary treatment modality for cats presenting with neurologic signs associated with a pituitary mass and can improve clinical signs associated with concurrent hyperadrenocorticism or acromegaly in cats with no neurologic abnormalities.     

Arytenoid Lateralization for Treatment of Laryngeal Paralysis in 10 Cats

Objective— To describe the signalment, history, clinical signs, surgical technique, and outcome for cats with laryngeal paralysis that had arytenoid lateralization.
Study Design— Case series.
Animals— Cats with laryngeal paralysis (n=10).
Methods— Medical records (1996–2002) for cats with laryngeal paralysis that had arytenoid lateralization were reviewed for signalment, history, clinical signs, degree of paralysis, cause, concurrent medical conditions, surgical technique, and outcome. Follow-up information was obtained from owners or referring veterinarians.
Results— Of 10 cats, 9 had bilateral and 1 had unilateral laryngeal paralysis. Arytenoid lateralization were unilateral (n=7), bilateral (1), and staged bilateral procedures (2), 10 days and 3 years apart, respectively. Postoperatively, 1 cat had persistent inspiratory noise because of minimal enlargement of the rima glottidis and 2 cats required a temporary tracheostomy for management of laryngeal swelling. Three cats developed aspiration pneumonia and died 4, 7, and 150 days after surgery; all 3 had bilateral (simultaneous or staged) procedures. Of the 7 remaining cats, 4 were alive at follow-up and 3 had died of causes unrelated to arytenoid lateralization. The calculated mean survival time for all 10 cats was 406 days (median, 150 days; range, 4–1825 days).
Conclusions— Arytenoid lateralization was effective at enlarging the rima glottidis and reducing signs of airway obstruction in most cats.
Clinical Relevance— Unilateral arytenoid lateralization is a feasible option for the surgical management of cats with marked clinical signs; however, bilateral procedures should be avoided or at least performed with considerable caution because of the apparent risk for aspiration pneumonia.     

Serum and Plasma Vascular Endothelial Growth Factor Levels in Various Cat Populations

Introduction:  Vascular endothelial growth factor (VEGF) is one of the most important mediators of angiogenesis. Elevated levels within tumors, and in serum, plasma, and tumor effusion have been correlated with the development of metastatic disease, recurrence, and poor prognosis in many tumors in humans. Canine VEGF has been sequenced as homologous with the human form, and elevated serum and plasma VEGF have been found in dogs with hemangiosarcoma. Feline VEGF has also been sequenced, and shares homology with the human and canine forms.
Materials and Methods:  Stored serum and plasma samples from normal cats, cats with various neoplasms, and cats with non‐neoplastic disease were evaluated with a commercial ELISA kit (R&D Systems, Minneapolis MN). Samples were run in duplicate, and a standard curve was performed for each plate. The data were analyzed for differences between populations, and between serum and plasma levels in the same patient to determine the optimal sample for evaluating VEGF in cats.
Results:  In seven apparently healthy cats mean plasma VEGF was 95.6 pg/mL. In non‐neoplastic disease (7 cases), mean plasma VEGF was 117.3 pg/mL and mean serum VEGF level was 219.7 pg/mL. In ten tumor‐bearing patients mean plasma VEGF was 247.1 pg/mL, and mean serum VEGF was 322.3 pg/mL. Statistical analysis showed no significant difference between mean serum and plasma VEGF concentrations within each group or between groups (p > 0.05).
Discussion:  Serum and plasma VEGF levels could not be used to distinguish between healthy cats and cats with neoplastic or non‐neoplastic disease.     

Long‐Term Totally Implantable Venous Access Ports in Dogs and Cats Receiving Chemotherapy

Introduction:  We evaluated the totally implantable subcutaneous vascular access port (VAP) in 16 cancer patients undergoing intermittent chemotherapy for more than 30 months.
Methods:  Ports were surgically placed (The CompanionPort, Norfolk Vet Products, Skokie, Illinois 60076) in the jugular vein of 12 dogs and 4 cats between 1/2002 and 7/2004. Body weight determined polyurethane catheter size (4, 5, 7 fr.). The polysulfone port, surrounded by titanium, was anchored to subcutaneous tissue in the dorsolateral neck and confirmed with C‐arm fluoroscopy. All blood samples were obtained via VAP. Nine anticancer agents, other medications, crystalloids/colloids, and whole blood were administered. Ports were flushed every 4–5 weeks with heparinized saline solution (100 IU/ml). Removed catheters were submitted for bacteriology.
Results:  Seven of 16 animals are still alive. VAP were used for 1.5 to more than 30 months with 4–60 injections/port. Catheter tips were visualized from the left atrium distally into the caudal vena cava. Adverse events included post‐operative subcutaneous bruising and/or hematoma (4/16), difficult aspiration (4/16), catheter malposition (1/16), positional flushing (1/16), and occlusion requiring replacement (1/16). No thrombus formation or extravasation was evident. Bacterial colonization without signs of septicemia was observed in 3/4 catheters.
Conclusions:  VAP are an effective way of achieving long‐term venous access in the dog and cat. Complications are typically minor and infrequent.     

Adverse Effects of Concurrent Carboplatin Chemotherapy and Radiation Therapy in Dogs

Background: Concurrent chemo- and radiotherapy improves outcome of certain human neoplasms but with increased signs of toxicity. Reports on adverse effects of concurrent chemo- and radiotherapy in the veterinary literature are scant.
Objective: To report adverse hematologic and gastrointestinal effects of combined carboplatin and radiation therapy in dogs.
Animals: Client-owned dogs with spontaneously occurring neoplasia.
Methods: Retrospective case study. Medical records of 65 dogs were reviewed. Criteria for inclusion were administration of radiation according to 1 of 3 fractionation schemes (19 × 3, 16 × 3, or 12 × 4 Gy) and administration of at least 1 concurrent carboplatin treatment at a dosage of 200–300 mg/m². Dog and treatment-related variables were analyzed for association with signs of intoxication.
Results: Median carboplatin dosage was 200 mg/m² (range, 200–250 mg/m²). Twelve of 58 dogs (21%) developed grade 3 or 4 neutropenia. Eleven of 56 dogs (20%) developed grade 3 or 4 thrombocytopenia. Six of 62 dogs (10%) developed grade 3, 4, or 5 gastrointestinal toxicosis. Analysis of association of dog and treatment-related variables with signs of intoxication was hampered by the small numbers of dogs in individual groups, and no statistically significant associations were found.
Conclusions and Clinical Importance: Combined modality therapy resulted in myelosuppression and gastrointestinal toxicosis. Future studies are needed to determine whether the potential benefit of combined modality therapy outweighs the risk of decreasing chemotherapy and radiation treatment intensity.     

Expression of E‐cadherin in Canine Anal Sac Apocrine Gland Adenocarcinoma and its Association with Survival

Introduction:  Inverse associations have been shown between E‐cadherin expression and degree of differentiation in canine mammary tumours and with the acquisition of malignancy in human epithelial cancers. The purpose of this study was to examine whether there was an association between prognosis, and the distribution or intensity of immunohistochemical staining for E‐cadherin in anal sac adenocarcinoma.
Methods:  Formalin‐fixed paraffin‐wax embedded canine anal sac adenocarcinoma specimens were obtained for 36 patients for whom clinical data, including survival statistics, were available. Canine mammary adenoma tissue was employed as the positive and negative controls with antibody diluent replacing the primary antibody in the latter. Samples were scored according to proportion of cells showing positive cytoplasmic membranous staining, intensity of cytoplasmic membranous staining and proportion of nuclei staining. As quality control, a sample of 10 slides was randomly selected for repeat evaluation; results exactly matched those obtained in the first assessment.
Results:  All anal sac adenocarcinoma cells expressed E‐cadherin to varying degrees. There was no evidence of an association between survival time and the intensity of staining or the proportion of nuclei staining. Patients whose tumours exhibited >75% positive cytoplasmic membranous staining survived significantly longer than those exhibiting <75% staining with median survival times of 1100 and 479 days respectively (log rank test: χ² = 3.89, 1 DF, p = 0.049).
Conclusion:  Immunohistochemical evaluation of the proportion of cells in anal sac adenocarcinoma samples exhibiting positive cytoplasmic membranous staining for E‐cadherin may allow improved determination of prognoses and could aid clinical decision making.     

Hyperadrenocorticism in cats: seven cases (1978-1987)

Hyperadrenocorticism was diagnosed in 7 cats with concurrent diabetes mellitus. Four cats had pituitary adenoma with bilateral adrenocortical hyperplasia, 1 cat had pituitary carcinoma with bilateral adrenocortical hyperplasia, 1 cat had adrenocortical carcinoma, and 1 cat had adrenocortical adenoma of the left adrenal gland. One year later, adrenocortical adenoma involving the right adrenal gland also was diagnosed in this cat. Clinical signs included polyuria and polydipsia (n = 7), development of pot-bellied appearance (n = 5), dermatologic alterations (n = 5), lethargy (n = 3), weight loss (n = 3), dyspnea/panting (n = 2), and recurrent bacterial infections (n = 2). In 6 cats, the diagnosis of hyperadrenocorticism was established before death on the basis of results of the ACTH stimulation test (n = 3) and the dexamethasone screening test (n = 5). Pituitary-dependent hyperadrenocorticism was differentiated from adrenocortical neoplasia on the basis of results of the dexamethasone suppression test (n = 4), endogenous ACTH concentration (n = 3), results of abdominal radiography and ultrasonography (n = 3), and exploratory celiotomy (n = 1). Four cats died or were euthanatized without treatment attempts. Treatment with mitotane followed by 60Co teletherapy was ineffective in one cat with pituitary adenoma. One cat with pituitary carcinoma died one week after bilateral adrenalectomy. Bilateral adrenocortical adenomas were removed surgically in the affected cat.     

COX‐2 Expression in Feline Oral Squamous Cell Carcinoma (FOSCC)– An Immunohistochemical Study and Analysis of Survival

Introduction:  Cyclooxygenase‐2 (COX‐2) catalyses the rate‐limiting step in the conversion of arachidonic acid to eicosanoids and has been found to be overexpressed in many human and some animal cancers. Overexpression of COX‐2 in head and neck SCC in humans is associated with shorter survival times. Non‐resectable, FOSCC is a devastating disease with no effective therapy. Overexpression of COX‐2 in FOSCC may support the anecdotal use of NSAID therapy. Identification of a prognostic marker in cats may permit more effective, targeted therapy.
Methods:  Immunohistochemistry was performed on formalin‐fixed, paraffin‐embedded tissue from 59 FOSCC cases using an indirect staining technique and feline foetal kidney as positive control. Polyclonal antiserum specific to COX‐1 and COX‐2 were used after antigen retrieval with pH6 citrate buffer. Retrospective, observational data were collected by practitioner questionnaires. A Kaplan‐Meier survival plot was derived.
Results:  55/59 questionnaires were returned (93% response rate). Median age at presentation was 10.9 years (range 7–15.5). Median survival time was 44 days (95% CL: 31, 79). Preliminary results show that COX‐1 staining was positive in all tumour tissues and in 86.7%(13/15 cases) of normal tissues. COX‐2 staining was positive in 67.3%(37/55) of tumour tissues and absent in normal tissue. Results of proportional hazards regression for survival and multiple logistic regression for COX expression including age, sex, breed, prior NSAID administration, other medication and COX expression as potential explanatory variables will be presented.
Conclusions:  These results indicated that COX‐1 and COX‐2 expression is seen in FOSCC but may not be predictive for survival.     

Efficacy of C/B‐OPP rescue for the treatment of relapsed canine lymphoma (1998–2004)

Introduction:  MOPP chemotherapy is useful for relapsed canine lymphoma. This study evaluates the efficacy of this protocol after substitution of CCNU (lomustine) or BiCNU (carmustine) for mechlorethamine (C/B‐OPP).
Methods:  Patient signalment, response to chemotherapy, toxicity and survival data were abstracted from medical records of dogs from receiving C/B‐OPP between 1998 and 2004.
Results:  Fifty‐eight dogs received C/B‐OPP rescue chemotherapy during the study period. The median remission duration after initial chemotherapy, consisting of CHOP‐based therapy in 91% of dogs, was 133 days (range, 10 to 932 days). Thirty‐eight of fifty‐eight dogs (66%) responded to C/B‐OPP rescue after relapse (22 CR, 16 PR), for a median of 48 days (range, 2 to 359 days). Overall, C/B‐OPP extended survival by a median of 90 days (range, 2 to 426 days). Twenty‐four dogs (41%) experienced one or more episodes of Grade II or higher gastrointestinal toxicity. Forty‐one dogs (71%) experienced one or more episodes of Grade II or higher hematologic toxicity. Twelve dogs (20%) developed regenerative anemia with diarrhea consistent with gastrointestinal hemorrhage. Treatment delays due to hematologic toxicity occurred in 37 dogs (63%). There were 16 nonfatal treatment‐related episodes of sepsis requiring hospitalization. 5 dogs died due to sepsis and/or chemotherapy‐related complications.
Conclusions:  C/B‐OPP chemotherapy has activity against relapsed canine lymphoma which is similar to that of traditional MOPP rescue therapy. Moderate to severe hematologic toxicity was observed. Further work is warranted to optimize drug doses and scheduling.     

Acromegaly in 14 Cats

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).     

A Single Sample Method for Evaluating 51Chromium-Ethylene Diaminic Tetraacetic Acid Clearance in Normal and Hyperthyroid Cats

Background: Chronic kidney failure is frequently seen in middle-aged and elderly cats. ⁵¹Chromium-ethylene diaminic tetraacetic acid (⁵¹Cr-EDTA) clearance and single blood sample (SBS) method are used in several species to estimate the glomerular filtration rate (GFR).
Hypothesis: The hypothesis of this study was that ⁵¹Cr-EDTA clearance could be determined using an SBS method in normal and hyperthyroid cats.
Animals: Forty-six cats were included in this study, with an average age of 9.5 years. Of these cats, 27 had hyperthyroidism; 19 were healthy.
Methods: After IV injection of ⁵¹Cr-EDTA (average dose: 4.25 MBq), 7 blood samples were obtained between 5 and 240 minutes. Reference clearance was calculated in mL/min and mL/min/kg body weight, using a 2-compartment model. Optimal time for clearance measurement with SBS was then determined by systematically comparing each individual plasma concentration to the reference multisample clearance.
Results: The average reference plasma clearance of ⁵¹Cr-EDTA for all cats was 14.9 mL/min (3.7 mL/min/kg). The clearance in hyperthyroid cats averaged 16.4 mL/min (4.3 mL/min/kg) and in normal cats averaged 10.3 mL/min (2.4 mL/min/kg).
The optimal time for the SBS was 48 minutes after injection of tracer ⁵¹Cr-EDTA ( R ²= 0.9414), giving the following converting equation: clearance = (0.0066 × DV_{48 minutes}) – 0.9277 (in mL/min).
Conclusions and Clinical Importance: In this study, the single sample ⁵¹Cr-EDTA clearance method was used to estimate the global GFR in cats. The method identified differences in clearance between normal and hyperthyroid cats. The optimal time for an SBS was 48 minutes.     

Transsphenoidal hypophysectomy for treatment of pituitary-dependent hyperadrenocorticism in 7 cats

OBJECTIVE: Evaluation of microsurgical transsphenoidal hypophysectomy for the treatment of pituitary-dependent hyperadrenocorticism (PDH) in cats. STUDY DESIGN: Prospective clinical study. ANIMALS OR SAMPLE POPULATION: Seven cats with PDH. METHODS: Urinary cortisol/creatinine ratios, pituitary-adrenocortical function tests, and computed tomography (CT) were performed on 7 cats that presented with a provisional diagnosis of hyperadrenocorticism. All cats underwent microsurgical transsphenoidal hypophysectomy with histologic examination of the excised specimen. Follow-up consisted of clinical evaluation, repeat adrenocortical function testing, and CT. RESULTS: Four cats had concurrent diabetes mellitus. In all cats, the urinary cortisol/creatinine (C/C) ratios were elevated. The dexamethasone screening test showed that 2 cats did not meet the criterion for hyperadrenocorticism. The response of the cats' plasma concentrations of cortisol and adrenocorticotrophic hormone to a high dose of dexamethasone varied from very sensitive to completely dexamethasone resistant. Basal plasma alpha-melanocyte-stimulating hormone concentrations were elevated in 2 cats with a pars intermedia adenoma and in 3 cats with an adenoma that originated from the anterior lobe. Preoperative CT enabled accurate assessment of pituitary size (5 nonenlarged pituitaries with a height <4 mm and 2 enlarged pituitaries with a height >5 mm) and localization relative to intraoperative anatomic landmarks. Two cats died within 4 weeks after surgery of a nonrelated disease. In the remaining 5 cats, the hyperadrenocorticism went into both clinical and biochemical remission. Hyperadrenocorticism recurred in 1 cat after 19 months, but no other therapy was given and the cat died at home 28 months after surgery. CT evaluation of this cat had identified pituitary remnants 6 weeks after surgery. The main postoperative complications were oronasal fistula (1 cat), complete dehiscence of the soft palate (1 cat), and transient reduction of tear production (1 cat). One cat died at 6 months (undefined anemia), and another cat at 8 months (recurrent nose and middle ear infection secondary to soft palate dehiscence) after surgery. In the surviving 2 cats, the remission periods at the time of writing were 46 and 15 months. In the 2 cats with sufficient follow-up time, the concurrent diabetes mellitus disappeared, ie, insulin treatment could be discontinued at 4 weeks and 5 months after hypophysectomy. In all 7 cats, the histologic diagnosis was pituitary adenoma. CONCLUSIONS: Microsurgical transsphenoidal hypophysectomy is an effective method of treatment for feline PDH in specialized veterinary institutions having access to advanced pituitary imaging techniques. Concurrent diabetes mellitus is usually reversible after hypophysectomy. Thorough presurgical screening for coexisting diseases is imperative. CLINICAL RELEVANCE: PDH in cats can be effectively treated by hypophysectomy. The neurosurgeon performing hypophysectomy must master a learning curve and must be familiar with the most frequent complications of the operation to treat them immediately and effectively. Urinary C/C ratios are sensitive indicators for the assessment of remission and recurrence of hyperadrenocorticism.     

Results of the Combined Treatment with Piroxicam and Carboplatin in Canine Oral Non‐Tonsillar Squamous Cell Carcinoma

Introduction:  Over‐expression of COX‐2 has been observed in several human and animal malignancies and is implicated in carcinogenesis through the conversion of arachidonic acid to PGE‐2. Use of platinum‐containing cytostatic agents and/or (non‐)specific COX‐2 inhibitors, has been reported as a treatment option for canine oral non‐tonsillar squamous cell carcinomas (ONT‐SCC). However, no study describes the effect of a combination of carboplatin and piroxicam on this tumor type.
Methods:  7 dogs with a T3 (WHO‐TNM) ONT‐SCC were treated with piroxicam and carboplatin. Five had bone involvement and no detectable metastasis. Two dogs without bone involvement had metastasis in the regional lymph nodes. Piroxicam was given orally 0.3 mg/kg s.i.d. Each dog was scheduled to receive between 6 and 12 carboplatin infusions (300 mg/m² i.v.) at 3 week intervals. Ondansetron and metoclopramide were used as anti‐emetic agents. The dogs are planned to receive piroxicam on a lifelong basis.
Results:  Complete response (CR) without adjuvant surgery was achieved in 4 of the 7 dogs. Two dogs needed adjuvant surgery to achieve CR. One dog had progressive disease and was euthanised 231 days after start of therapy. All the others were still alive and in CR at date of analysis. Median follow‐up was 335 days (107–689 days).
Conclusions:  Our study suggests that a combination of piroxicam and carboplatin is a useful treatment option for canine ONT‐SCC. All dogs tolerated therapy well and the 57% response rate for reaching a complete and durable remission without adjuvant surgery is promising.     

131‐I therapy for Advanced, Unresectable Thyroid Tumors in Dogs

Introduction:  Greater than 50% of dogs with thyroid tumors present with surgically unresectable disease for which external beam radiotherapy has been reported to prolong survival. The success of ¹³¹I for control of thyroid tumors in cats and in humans suggests such therapy may also play a role in the management of canine thyroid cancer.
Methods:  Thirty‐nine dogs with WHO stage II/III (invasive or ectopic; n = 32) or IV (metastatic; n = 7) thyroid tumors were treated with ¹³¹I alone. Changes in thyroid function, ^99MTc‐pertechnetate (^99MTc) scintigraphic changes, and tumor response were recorded. Dogs with ventral cervical tumors were evaluated for feasibility of surgical resection following ¹³¹I.
Results:  Median overall survival was 839 days and 366 days for dogs with stage II/III and stage IV tumors, respectively. Thyroid hormone status, site and surgical resection were not associated with outcome in dogs with stage II/III tumors. Three dogs developed severe bone marrow suppression.
Conclusions:  These findings suggest ¹³¹I should be investigated more thoroughly in dogs with thyroid tumors not considered surgical candidates to more clearly characterize the indications for therapy and followup recommendations. ¹³¹I dosimetry in dogs with thyroid tumors remains problematic. Administration of ¹³¹I is currently based on empiric recommendations and, in general, the treatment is well tolerated although additional studies are indicated to optimize response and minimize toxicity.     

Clinical evaluation of Alfaxan-CD® as an intravenous anaesthetic in young cats

Objective   To describe and evaluate the use of Alfaxan-CD ® as an intravenous anaesthetic in young cats.
Design   Thirty-five Domestic Short-hair cats aged from 3 to 12 months were admitted into the University Veterinary Teaching Hospital-Sydney for elective surgery. Anaesthesia was induced with Alfaxan-CD® and maintained with isoflurane: 22 cats received no premedication and 13 cats received acepromazine (0.03 mg/kg) and butorphanol (0.3 mg/kg) subcutaneously 30 min prior to induction.
Qualitative and quantitative data for induction and recovery were recorded. Physiological parameters were recorded at 0, 2 and 5 min post induction, and every 5 min thereafter until the end of the procedure.
Results   Intravenous injection of Alfaxan-CD® resulted in rapid induction of anaesthesia with a mean time to intubation of 122 s. The mean dose of Alfaxan-CD® used was 4.2 mg/kg in unpremedicated cats and 2.7 mg/kg in premedicated cats. All cats maintained a heart rate above 95 beats/min. No cat developed hypoxaemia. Hypercapnoea was detected in 4 cats and hypotension was observed in 18 cats. Time to extubation ranged from 1 to 9 min. The mean time to sternal recumbency for premedicated cats was 11 min; 77% of premedicated cats and 23% of unpremedicated cats had a recovery score of 1 or 2.
Conclusion   Alfaxan-CD® is an effective anaesthetic agent in young healthy cats, providing a smooth induction and rapid recovery. Cats that were premedicated with acepromazine and butorphanol prior to induction with Alfaxan-CD® had better recovery scores than those that were not premedicated.