Outcome of 19 dogs with parathyroid carcinoma after surgical excision

Parathyroid carcinoma (PTC) is rare in dogs and there is little information documenting its treatment and prognosis. The objective of this study was to describe the outcome of dogs with PTC treated with surgical excision. Medical records of 19 dogs undergoing surgical excision of PTC between 1990 and 2010 were reviewed retrospectively. Dogs were presented for clinical hypercalcaemia or incidental hypercalcaemia noted by referring veterinarians on routine serum chemistry profiles. A parathyroid nodule was identified with cervical ultrasound in 17/17 dogs. Hypercalcaemia resolved in 18/19 dogs within 4 days postoperatively. Nine developed hypocalcaemia. None were confirmed to develop recurrent or metastatic PTC. The only death associated with PTC was a dog that was euthanized for intractable hypocalcaemia 9 days after surgery. Estimated 1-, 2- and 3-year survival rates were 72, 37 and 30%, respectively. Excision of PTC results in resolution of hypercalcaemia and excellent tumour control.     

Clinical outcome in 23 dogs with exocrine pancreatic carcinoma

Exocrine pancreatic carcinoma is uncommon in the dog and the veterinary literature surrounding the disease is minimal. Twenty‐three cases of canine exocrine pancreatic carcinoma were reviewed in a retrospective manner to obtain information on clinical presentation, behaviour and survival associated with the disease. Presenting clinical signs were nonspecific and included anorexia, lethargy, vomiting and abdominal pain. The overall median survival time was only 1 day but was confounded by the large number of dogs that were euthanized shortly after diagnosis. Metastatic disease was detected in 78% of cases at the time of diagnosis, attesting to the aggressive nature of the disease. Neither lymph node metastasis, tumour size nor tumour location had an impact on overall survival. Only one patient was a previous diabetic who is contrary to reports of the disease in people and felines. This retrospective study reaffirms the need for early detection measures to optimize disease control. However, the benefits of therapy with surgery or radiation and adjuvant chemotherapy remain to be elucidated in dogs with exocrine pancreatic carcinoma.     

Comparison of concurrent imaging modalities for staging of dogs with appendicular primary bone tumours

This study assessed the use of whole body computed tomography (CT) for the evaluation of metastasis in dogs with primary appendicular bone tumours compared to long bone survey radiography, bone scintigraphy and thoracic radiographs. Fifteen dogs were included in this pilot study. A construct reference standard was used for detection of bone metastasis, and negative thoracic radiographs were compared against CT. Definitive lesions were only identified on bone scintigraphy. Not all lesions agreed with the construct reference standard. No definitive lesions were identified on survey radiographs or CT. Lesions were identified on thoracic CT that were not visible radiographically. Equivocal ground glass pulmonary lesions progressed in three of four cases. Whole body CT was not a suitable alternative to bone scintigraphy; however, it was useful as an adjunctive diagnostic modality. Pulmonary lesions were visible on CT that were not seen radiographically and ground glass pulmonary lesions in dogs should be considered suspicious for metastasis.     

Prognostic factors in dogs with urinary bladder carcinoma

Medical records and biopsy specimens were retrospectively reviewed from 25 dogs diagnosed with unresectable urinary bladder carcinoma and treated with chemotherapy. Our intention was to identify clinical, histologic, and immunohistochemical indicators of prognosis. Immunohistochemical stains for P-glycoprotein, glutathione-S-transferase pi, and factor VIII-related antigen were applied to archived tissue. There were more spayed female dogs than castrated male dogs (76% versus 24%). Transitional cell carcinoma was the most common tumor (88%, n = 22), followed by undifferentiated carcinoma (8%, n = 2) and squamous cell carcinoma (4%, n = 1). Overall median survival was 251 days. Histologic diagnosis and immunohistochemical characteristics did not correlate with prognosis. Spayed females survived significantly longer than castrated males (358 days versus 145 days, P = .042). Dogs that received either doxorubicin or mitoxantrone in addition to a platinum-based chemotherapeutic (either cisplatin or carboplatin) lived significantly longer than those that received only a platinum compound (358 days versus 132 days, P = .042).     

Frameless stereotactic radiosurgery for the treatment of primary intracranial tumours in dogs

Stereotactic radiosurgery (SRS) is a procedure that delivers a single large radiation dose to a well‐defined target. Here, we describe a frameless SRS technique suitable for intracranial targets in canines. Medical records of dogs diagnosed with a primary intracranial tumour by imaging or histopathology that underwent SRS were retrospectively reviewed. Frameless SRS was used successfully to treat tumours in 51 dogs with a variety of head sizes and shapes. Tumours diagnosed included 38 meningiomas, 4 pituitary tumours, 4 trigeminal nerve tumours, 3 gliomas, 1 histiocytic sarcoma and 1 choroid plexus tumour. Median survival time was 399 days for all tumours and for dogs with meningiomas; cause‐specific survival was 493 days for both cohorts. Acute grade III central nervous system toxicity (altered mentation) occurred in two dogs. Frameless SRS resulted in survival times comparable to conventional radiation therapy, but with fewer acute adverse effects and only a single anaesthetic episode required for therapy.     

Drug dose and drug choice: Optimizing medical therapy for veterinary cancer

Although novel agents hold great promise for the treatment of animal neoplasia, there may be room for significant improvement in the use of currently available agents. These improvements include altered dosing schemes, novel combinations, and patient‐specific dosing or selection of agents. Previous studies have identified surrogates for “individualized dose intensity,”, for example, patient size, development of adverse effects, and pharmacokinetic parameters, as potential indicators of treatment efficacy in canine lymphoma, and strategies for patient‐specific dose escalation are discussed. Strategies for treatment selection in individual patients include conventional histopathology, protein‐based target assessment (eg, flow cytometry, immunohistochemistry, and mass spectrometry), and gene‐based target assessment (gene expression profiling and targeted or global sequencing strategies). Currently available data in animal cancer evaluating these strategies are reviewed, as well as ongoing studies and suggestions for future directions.     

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.     

Urogenital anomalies and urinary incontinence in an English Cocker Spaniel dog with XX sex reversal

A 3‐year‐old dog weighing 8 kg was referred with a disorder of sexual development and persistent urinary incontinence before and after gonadohysterectomy performed at a local animal hospital. Histopathological examination disclosed hypoplasia of the testes, epididymis, pampiniform plexus, and uterus. On ultrasonography, an anomalous structure containing anechoic fluid was identified in the region dorsal to the urinary bladder. An anomalous communication between the proximal urethra and the remnant uterus and vagina was found on retrograde urethrography under fluoroscopy. Reflux of contrast medium into the anomalous structure, suspected to be the uterus and cranial vagina, from the urethra was detected. Computed tomography identified the anomalous structure between the rectum and urethra. The anomalous structure was removed via laparotomy and the urinary incontinence resolved. The diagnosis of XX sex reversal with a developmental anomaly of the genitourinary tract was made on the basis of laparotomy findings and cytogenetic and SRY gene analyses.     

Outcome in dogs with advanced (stage 3b) anal sac gland carcinoma treated with surgery or hypofractionated radiation therapy

Stage 3b anal sac gland carcinoma (ASGC) can be life‐threatening. A surgical approach is not always possible or may be declined. Dogs with stage 3b ASGC treated with surgery or conformal radiation therapy (RT) with 8 × 3.8 Gy (total dose 30.4 Gy, over 2.5 weeks) were retrospectively evaluated. Patient characteristics, median progression‐free interval (PFI) and median survival time (MST) were compared. Twenty‐eight dogs were included; 15 underwent surgery, 13 underwent RT. At the time of presentation, 21% showed life‐threatening obstipation and 25% showed hypercalcaemia. PFI and MST for surgery cases were 159 days (95% CI: 135–184 days) and 182 days (95% CI: 146–218 days), both significantly lower than for RT cases with 347 days (95% CI: 240–454 days) and 447 days (95% CI: 222–672 days), (P = 0.01, P = 0.019). Surgery as well as RT led to a fast relief of symptoms. PFI and survival of surgical patients were significantly inferior to that of a comparable patient group treated with conformal hypofractionated RT.     

Use of adjuvant carboplatin for treatment of dogs with oral malignant melanoma following surgical excision

Melanoma is the most common oral malignancy in dogs. This retrospective study evaluated adjuvant carboplatin chemotherapy (with or without radiation therapy) in 17 dogs with malignant oral melanoma following surgical resection. The median dosage and number of doses of carboplatin administered to the 17 dogs was 300 mg m^?2 (range, 150–300 mg m^?2) and 4 (range, 2–11), respectively. The overall median progression‐free survival for all dogs was 259 days [95% confidence interval (CI₉₅), 119–399 days]. The first progression‐free survival event was local recurrence in seven dogs (41%) and metastases in seven dogs (41%). The median overall survival for all dogs was 440 days (CI₉₅, 247–633 days). The tumour was the cause of death in 10 dogs (59%). On the basis of this study, systemic therapy with carboplatin may be an appropriate adjunct to local treatment for canine malignant melanoma, although future prospective controlled studies are needed to compare treatment modalities for this aggressive neoplasia.     

Retrospective study evaluating the efficacy of stereotactic body radiation therapy for the treatment of confirmed or suspected primary pulmonary carcinomas in dogs

Canine primary pulmonary carcinomas (PCCs) are commonly treated with surgery with overall median survival times (MST) around a year; however, due to extent of disease, prognosis, or client preference, alternative treatments have been considered. Stereotactic body radiation therapy (SBRT) has been utilized in human cancer patients for local control of lung tumours as a surgical alternative. Twenty-one PCCs in 19 dogs that received SBRT for local control were retrospectively evaluated. Dogs were staged according to the canine lung carcinoma stage classification (CLCSC) system with three as Stage 1, five as Stage 2, three as Stage 3, and eight as Stage 4. Overall MST was 343 days with 38% of patients alive at 1 year. Stage did not significantly impact survival time (p = .72). Five (26%) dogs had lymphadenopathy and MST was not significantly different from dogs without lymphadenopathy (343 vs. 353 days; p = .54). Five out of 18 evaluable dogs (28%) experienced acute lung VRTOG effects and 2 of 12 dogs (17%) experienced late lung VRTOG effects. Median lung dose, V5, V20, and D30 to the lung did not correlate significantly with the development of adverse radiation events. Twelve dogs had follow-up imaging and the best response included a complete response (17%), partial response (42%), and stable disease (42%). Progressive disease was noted in seven dogs a median of 229 days after SBRT. SBRT was documented to be a safe and effective alternative to surgery and may have survival advantages for Stage 3 or 4 dogs according to the CLCSC.     

Plasma and urinary trypsinogen activation peptide in healthy dogs, dogs with pancreatitis and dogs with other systemic diseases

OBJECTIVE: To determine the specificity and sensitivity of plasma and urinary trypsinogen activation peptide (TAP) concentrations in diagnosing pancreatitis in dogs. DESIGN: Retrospective analysis of clinical cases. PROCEDURE: Dogs were classified into three groups: healthy animals, dogs with confirmed pancreatitis and dogs with nonpancreatic disease, which clinically or biochemically resembled pancreatitis. This last group was further subdivided into dogs with renal and those with nonrenal disease. The plasma and urinary TAP concentration was determined by a competitive enzyme immunoassay. Clinical cases additionally had serum trypsin-like immunoreactivity concentration measured, as well as radiography and ultrasound of the abdomen and further diagnostic procedures. Nonparametric analysis of variance (Kruskal-Wallis test) was performed using Statistix 4.0 program. RESULTS: There was a wide range of urinary TAP concentration in healthy dogs (mean 52.30 nmol/L, standard deviation 55.25) that made interpretation of urinary TAP concentrations difficult in the other groups. There was a narrow reference range for plasma TAP (mean 2.67 nmol/L, standard deviation 0.93). Plasma and urinary TAP concentrations, as well as urinary TAP to creatinine ratio, were all increased in dogs that died with necrotising pancreatitis. Values were not increased in mild, interstitial pancreatitis. Increased plasma TAP concentrations were also present in dogs with severe renal disease. CONCLUSION: Plasma TAP concentration is a good prognostic indicator in naturally occurring pancreatitis in dogs. The failure of TAP to increase in mild pancreatitis, and the increase present in severe renal disease, suggests its measurement has limited application as a sole diagnostic tool for canine pancreatitis. Further investigations are required in order to explain the large variability of urinary TAP concentration and the presence of circulating TAP in healthy dogs.     

Association between weight change during initial chemotherapy and clinical outcome in dogs with multicentric lymphoma

The majority of the known prognostic factors in dogs with lymphoma have been evaluated before treatment commences or at the time of diagnosis. Prognostic factors evaluated during the initial phase of treatment are less described but may provide important clinical information. In this retrospective study, 82 canine lymphoma patients were categorized according to the weight change between diagnosis and after 5 weeks of chemotherapy. Dogs that gained greater than 5% or lost greater than 5% of initial body weight were categorized as increased‐ or decreased‐weight groups, respectively. Those in which weight changed less than 5% were categorized as the maintained‐weight group. The median progression‐free survival (PFS) in the increased‐weight group, maintained‐weight group and decreased‐weight group was 226, 256 and 129 days, respectively. The decreased‐weight group had significantly shorter PFS than the increased and maintained groups (P = .023, P = .003, respectively). The median survival time (ST) in the increased‐weight group, maintained‐weight group and decreased‐weight group was 320, 339 and 222 days, respectively. There was no significant difference in ST among the three groups (P = .128). In Cox‐regression results, weight change group and initial body weight were significant risk factors associated to PFS (P = .007, P = .001, respectively) while only patient's initial body weight was a significant risk factor to ST (P = .013). In conclusion, evaluation of initial body weight and weight changes over time can provide valuable information regarding PFS and ST in dogs with multicentric lymphoma.     

Phase I clinical trial of oral rosiglitazone in combination with intravenous carboplatin in cancer‐bearing dogs

Rosiglitazone is an FDA‐approved peroxisome proliferator‐activated receptor gamma (PPARγ) agonist and antidiabetic agent in humans that has been investigated for its ability to reduce tumor cell growth. The purpose of this study was to determine the maximally tolerated dose, peak plasma concentrations and side effect profile of oral rosiglitazone when combined with carboplatin in dogs with cancer. Rosiglitazone was administered at 6 and 8 mg/m² to seven dogs. Carboplatin was administered at 240–300 mg/m² in combination with rosiglitazone. For toxicity evaluation, the toxicity data for the seven dogs in this study were combined with the toxicity data from three dogs previously reported in a methodology study. Peak plasma rosiglitazone concentrations varied with dose. The dose‐limiting toxicity was hepatic at a dose of 8 mg/m². Three dogs had mild to moderate alanine aminotransferase elevations but no changes in total bilirubin, alkaline phosphatase, blood glucose or γ‐glutamyltranspeptidase values were noted.