Efficacy of Vinblastine for Treatment of Canine Mast Cell Tumors

Background: The optimal dosage and clinical efficacy of vinblastine (VBL) for treatment of mast cell tumors (MCTs) in dogs has not been established. Hypothesis: Single‐agent VBL has antitumor activity against MCTs in dogs. Animals: Fifty‐one dogs with nonresectable grade II or III cutaneous MCTs. Methods: Prospective, open clinical trial. Dogs were systematically allocated (by hospital record number) to receive IV treatment with VBL at a dosage of 2.0 mg/m² (weekly for 4 treatments then biweekly for 4 treatments; VBL 2.0) or treatment with VBL at a dosage of 3.5 mg/m² (biweekly for 5 treatments; VBL 3.5). The primary outcome measure was reduction in tumor size. Results: Twenty‐five dogs were allocated to the VBL 2.0 group and 26 were allocated to the VBL 3.5 group. In the VBL 2.0 group, 3 (12%) had a partial response (PR) for a median of 77 days (range, 48–229 days). Overall response rate in the VBL 3.5 group was 27%. One dog (4%) had a complete response for 63 days and 6 dogs (23%) had a PR for a median of 28 days (range, 28–78 days). Toxicoses were uncommon in the VBL 2.0 group. Twelve (46%) dogs in the VBL 3.5 group had <500 neutrophils/μL 7 days after treatment; 2 dogs with neutropenia developed concurrent fevers. Conclusions and Clinical Importance: VBL, when used as a single‐agent, has activity against MCTs in dogs although the response rate is lower than those reported for VBL‐containing combination protocols. Further, findings suggest VBL at a dosage of 3.5 mg/m² should be considered for use in future phase II/III trials.     

c‐Kit Mutation and Localization Status as Response Predictors in Mast Cell Tumors in Dogs Treated with Prednisone and Toceranib or Vinblastine

Background

KIT inhibitors, such as toceranib (TOC), and vinblastine (VBL) have not been prospectively compared in the treatment of macroscopic mast cell tumors (MCTs). Also, it is unknown whether VBL or TOC is superior for treating MCT without c‐kit mutations.

Hypothesis/Objectives

To determine the value of KIT genotyping and localization in treatment decisions for dogs with macroscopic MCT. We hypothesized that c‐kit mutated MCT would have a better response to TOC than VBL.

Animals

Eighty‐eight client‐owned dogs with macroscopic MCT.

Methods

Prospective, randomized trial. Dogs were randomized to TOC (2.75 mg/kg EOD) or VBL (2.5 mg/m² weekly × 4 then EOW) by KIT localization and c‐kit mutation status using an adaptive randomization scheme.

Results

Sixty dogs were allocated to TOC and 28 to VBL. Of the dogs receiving TOC, 20% had c‐kit mutations, compared to 30% receiving VBL (P = 0.74). Overall response rates were 46% (TOC) and 30% (VBL) (odds ratio = 1.56 [0.62–3.92]; P = 0.28). Median progression‐free survival (PFS) for dogs receiving VBL was 78 days (7–1,521) and for TOC 95.5 (14–990); hazard ratio (HR) = 1.34 [0.72–2.50]; P = 0.36. Median overall survival (OS) was 241.5 days (10–1,521) for the VBL group and 159 (20–990) for the TOC group; HR = 0.80 ([0.45–1.41]; P = 0.44).

Conclusions and Clinical Importance

Neither PFS nor OS was significantly different between treatment groups. As the proportion of dogs with c‐kit mutations was not different between treatment groups in this population of dogs, c‐kit mutation status did not predict treatment response.     

Combination Chemotherapy with Continuous l-Asparaginase, Lomustine, and Prednisone for Relapsed Canine Lymphoma

Background: The combination of lomustine, l -asparaginase, and prednisone (LAP) is an effective rescue treatment for canine lymphoma (LSA). In a previous study, we reported that remission was typically lost around the time l -asparaginase was discontinued.
Hypothesis: Use of l -asparaginase with each lomustine treatment will be well tolerated and efficacious as a rescue therapy for canine LSA.
Animals: Forty-eight client-owned dogs with cytologically confirmed multicentric LSA whose disease had relapsed after a cyclophosphamide, doxorubicin, vincristine, and prednisone-based chemotherapy protocol were included.
Methods: Lomustine was administered orally at 3-week intervals, concurrently with subcutaneous or intramuscular l -asparaginase for a total of 5 doses or until disease progression. Prednisone was administered at a tapering dose for the duration of the protocol.
Results: The overall response rate (ORR) for dogs treated with this protocol was 77%, with 65% achieving a complete response (CR). The median time to progression (TTP) was 70 days. Based on loose comparison, these findings are not significantly different from our previously reported historical control. The actual CCNU dosage administered did not affect response rate or remission duration.
Conclusions/Clinical Importance: These findings support previous data concluding that the LAP protocol is a viable rescue treatment option for dogs with LSA. However, results from this study suggest that continued use of l -asparaginase with each lomustine treatment does not significantly increase remission duration and toxicity appears greater.     

Resection of Pulmonary Metastases in Canine Osteosarcoma: 36 Cases (1983–1992)

Thirty-six dogs underwent pulmonary metastatectomy for osteosarcoma. All patients had been treated for histologically confirmed osteosarcoma of the appendicular skeleton. Treatment for the primary tumor consisted of amputation or a limb sparing procedure in conjunction with adjuvant chemotherapy, local radiation therapy, or both.
Significant factors in determining prognosis included the disease-free interval (DFI) between treatment of the primary tumor and development of pulmonary metastases and the number of metastatic nodules present at surgery. Dogs that developed pulmonary metastases 300 days or more after diagnosis of the primary tumor had a median DFI of 128 days after metastatectomy. Dogs that developed pulmonary metastases fewer than 300 days after diagnosis had a median DFI of 58 days. Dogs with one or two metastatic nodules removed had a median DFI of 95 days, whereas dogs with three or more nodules removed had a median DFI of 53 days. The results of this study indicate that prognostic variables exist for dogs with metastatic pulmonary osteosarcoma and can help predict survival after metastatectomy. These variables are similar to the prognostic variables that have been determined for human patients undergoing pulmonary metastatectomy because of osteosarcoma. Though a controversial procedure, pulmonary metastatectomy seems to be a valid treatment option for selected dogs with metastatic pulmonary osteosarcoma.     

Idiopathic eosinophilic meningoencephalitis in Rottweiler dogs: three cases (1992–1997)

We report three cases of eosinophilic meningitis in young male Rottweiler type dogs in New Zealand. No cause for the disease was identified. There were variable clinical signs referable to central nervous system dysfunction, and a variable response to treatment.     

Congenital Cardiac Defects in Neonatal Foals: 18 Cases (1992–2007)

Background: Literature available regarding congenital cardiac defects in foals is limited to reports of individual cases or small case series.
Objective: To describe the clinical, echocardiographic, and necropsy findings and breed predilection of congenital cardiac defects in neonatal foals.
Animals: Eighteen foals <15 days of age with 1 or more congenital cardiac defects.
Methods: Medical records of foals diagnosed with congenital cardiac defects at the William R. Pritchard Veterinary Medical Teaching Hospital were reviewed. Data collected included history, signalment, clinical signs, laboratory data, diagnostic and necropsy results, and outcome.
Results: Arabian foals represented 39% of cases with congenital cardiac defects and were significantly ( P = .004) overrepresented (OR = 4.7 [CI: 1.8–12.4]) compared with the general hospital population. Ventricular septal defect (VSD) (14/18), tetralogy of Fallot (5/18), and tricuspid valve atresia (4/18) were the most common defects identified. A ≥3/6 heart murmur (14/14) accompanied by tachycardia (14/17), tachypnea (17/17), and cyanosis of mucous membranes (7/16) were the most common clinical signs. Concurrent congenital defects were common (9/18). Two foals, both with VSD, survived for ≥ 8 years after diagnosis and 1 was a successful performance horse.
Conclusions and Clinical Relevance: Arabian horses appear to have a predisposition for cardiac defects. The presence of a loud murmur (≥ 3/6), cyanotic membranes, and tachycardia or tachypnea in a neonatal foal should warrant thorough evaluation of the heart for congenital defects. Foals with cardiac defects should be closely evaluated for concurrent congenital defects in other body systems.     

Canine Bladder and Urethral Tumors: A Retrospective Study of 115 Cases (1980–1985)

One hundred and fifteen dogs with neoplasms of the lower urinary tract (bladder and/or urethra) were retrospectively evaluated at five referral institutions participating in ongoing studies by the Veterinary Cooperative Oncology Group. Most tumors were malignant (97%) and of epithelial origin (97%). Lower urinary tract tumors were more common in older dogs weighing greater than 10 kg. The following significant (P less than 0.05) statistical associations were found using the University of Guelph hospital population as control; there was no sex predisposition although the female:male ratio was 1.95:1. Neutered dogs were predisposed as were Airedale Terriers, Beagles, and Scottish Terriers, whereas German Shepherds were significantly under-represented among dogs with lower urinary tract tumors. These statistical associations should be interpreted cautiously because of possible demographic differences in hospital populations among the University of Guelph and other cooperating institutions. There were no significant correlations between age, gender, weight, breed, response to therapy, and survival time. Clinical signs were indicative of lower urinary tract disease and included hematuria, stranguria, and pollakiuria. The laboratory data were nonspecific except for urinalysis test results. Hematuria and inflammatory urinary sediments were most commonly reported; neoplastic cells were identified in the urine sediment of 30% of dogs with lower urinary tract tumors. Contrast cystography was a useful noninvasive diagnostic method since 96% of the dogs had a mass or filling defect in the lower urinary tract demonstrated by this technique.(ABSTRACT TRUNCATED AT 250 WORDS)     

Skin Lesions in Canine Leishmaniasis (Kala-Azar): A Clinical and Histopathological Study on 22 Spontaneous Cases in Greece

Abstract— Skin lesions occurring in 22 dogs with leishmaniasis (Kala-azar) were studied clinically and histopathologically, so as to better characterize the range of abnormalities encountered in this disease. The main clinical dermatological patterns observed were exfoliative dermatitis (90.9 per cent of dogs), ulcerations (63.6 per cent), onychogryposis (54.5 per cent), sterile pustular dermatitis (13.6 per cent), and paronychia (13.6 per cent). Most of the dogs (86.4 per cent) had more than one type of skin lesion. The most commonly seen histopathological patterns were granulomatous perifolliculitis and sebaceous adenitis (68.2 per cent), superficial and deep perivascular dermatitis (54.5 per cent), and interstitial dermatitis (50.0 per cent). Parasites, mostly within macrophages, were detected in the skin biopsies from 50.0 per cent of the dogs. Résumé— Les lesions cutanés de 22 chiens atteints de leishmaniose ont étéétudiées cliniquement et histopathologiquement, afin de mieux caractériser les anomalies observées lors de cette maladie. La principale manifestation dermatologique observée était une dermatitie exfoliative (90,9% des chiens), des ulcérations (63,6%), une onychogriphose (54,5%) une dermite pustuleuse stérile (13,6%) et une paronychie (13,6%). La plupart des chiens (84,6%) avaient plus d'un type de lésion cutanée. Les lesions histopathologiques les plus communes étaient des périfolliculites granulomateuses et des adénites sébacées (68,2%), une dermite superficielle et profonde périvasculire (54,5%), une dermite intersticielle (50%). Les parasites, généraiement dans les macrophages, ont été isolés dans une biopsie sur deux. Zusammenfassung— Hautveränderungen, die bei 22 Hunden mit Leishmaniose (Kala-azar) auftraten, wurden klinisch und histopathologisch untersucht, um die Spannweite der Veränderungen, die bei dieser Krankheit auftreten, besser charakterisieren zu können. Als hauptsächliche klinische dermatologische Symptome wurden exfoliative Dermatitis (90,9% der Hunde), Ulzerationen (63,6%), Onychogrypose (54,5%)), sterile pustulöse Dermatitis (13,6%) und Paronychie (13,6%) beobachtet. Die meisten Hunde (86,4%) wiesen mehr als einen Typ Hautveränderung auf. Die häufigsten histopathologischen Befunde bestanden in granulomatöser Perifollikulitis und Talgdrüsenadenitis (68,2%), oberflächlicher und tiefer perivaskulärer Dermatitis (54,5%) und interstitieller Dermatitis (50,0%). Die Parasiten, die meistens in den Makrophagen liegen, wurden in den Hautbiopsien bei 50,0% der Hunde entdeckt. Resumen Se estudiarion clínica e histopatológicamente las lesiones cutáneas padecidas por 22 perros con leismaniasis (Kala-azar), con el propósito de caracterizar el rango de abnormalidades producidas por la enfermedad. La sprincipales características patológicias observadas fueron: dermatitis exfoliativa (90.9% de los perros), ulceraciones (63.6%), onicogriposis (54.5%), dermatitis postular esteril (13.6%), y paronquia (13.6%). La mayoría de los perros, (86.4%), presentaban más de un tipo de lesion dérmica. Los modelos histopatológicos reconocidos más frequentemente fueron: perifoliculitis granulomatosa y adenitis sebácea (68.2%)), dermatitis perivascular superficial y profunda (54.5%), y dermatitis intersticial (50%). Las biopsias cutáneas detectaron parásitos, la mayoría en los macrófagos, en 50% de los perros.     

A Retrospective Study of Pemoline Toxicosis in Dogs: 101 Cases (1987–1997)

Pemoline is a central nervous system stimulant commonly used for Attension Deficit Disorder in humans. This study describes the clinical syndrome associated with pemoline ingestion as well as its treatment. Ten years worth (1987–1997) of records from the ASPCa National Animal Poison Control Center involving pemoline ingestion in dogs were reviewed. The data suggests that most dogs ingesting pemoline show signs of central nervous system and cardiovascular stimulation including hyperactivity, tremors, ataxia, seizure, tachycardia, hyperthermia, and mydriasis. Blood chemistry alterations included electrolyte imbalances in some dogs. The minimum dose reported to cause clinical signs was 2.8 mg/kg and the minimum dose reported to have caused death was 10 mg/kg. Dogs generally showed clinical signs within 30 minutes to 24 hours of ingestion. The duration of clinical signs ranged from 15 hours to four days. Ninety-four percent of the dogs recovered with supportive treatment. (Vet. Emerg. & Crit. Care, 9:203–207, 1999)     

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.     

Mares admitted to a referral hospital for postpartum emergencies: 163 cases (1992–2002)

Objective: To identify and describe the physical, historical, and clinicopathologic characteristics of diseases requiring emergency treatment in postpartum mares, and to evaluate the utility of these characteristics in making an accurate diagnosis in these mares. Design: Retrospective study. Setting: University large animal hospital. Animals: One hundred and sixty‐three mares admitted for emergency treatment within 30 days following parturition between the years 1992 and 2002. Interventions: None. Measurements and main results: Information obtained from the medical records included age, breed, date of admission, sex of the foal from this parturition, time from parturition to admission, duration of clinical signs prior to admission, and any report of dystocia or normal attended delivery, physical examination and clinicopathologic findings and diagnosis. Urogenital hemorrhage and large colon volvulus were the most common diagnoses, comprising 16.6% and 15.9% of total cases, respectively. Older mares were more likely to have a diagnosis of urogenital hemorrhage than younger mares. Mares with urogenital hemorrhage had a median age of 13 years and were admitted to the hospital significantly closer to parturition than mares with other diagnoses. Anemia, hypoproteinemia, and hypofibrinogenemia were significantly associated with a diagnosis of urogenital hemorrhage and occurred in 32%, 36%, and 26% of the mares with urogenital hemorrhage, respectively. Dystocia was more commonly reported (70%) in mares with metritis. Leukopenia was more common (88%) in mares with uterine tears. Conclusions: Careful evaluation of clinicopathologic data can aid the emergency clinician in making a correct diagnosis in postpartum mares with emergent problems.     

Steroid Responsive Meningitis-Arteritis: A Prospective Study of Potential Disease Markers, Prednisolone Treatment, and Long-Term Outcome in 20 Dogs (2006–2008)

Background: Previous multidrug studies have identified the value of prednisolone in treating steroid responsive meningitis-arteritis (SRMA) and the potential value of acute phase proteins (APPs) and immunoglobulin A (IgA) in diagnosis and monitoring.
Hypothesis: (1) Prednisolone monotherapy is a successful immunosuppressive modality in the treatment of SRMA; (2) protein markers are useful in identifying the potential for relapse.
Animals: Twenty client-owned dogs with SRMA presented to the University of Glasgow Small Animal Hospital between May 2006 and May 2008.
Methods: A prospective, observational study: CBC, biochemistry, and cerebrospinal fluid (CSF) analyses were performed. C-reactive protein (CRP), serum amyloid-A, α-1-acid glycoprotein, and haptoglobin (Hp) were assessed in the serum. IgA concentrations were determined in the serum and CSF.
Results: Clinical resolution of SRMA was achieved in all 20 dogs. Serum CRP concentration remained increased at remission in 16/20 dogs whereas CSF cytology was within normal limits in 20/20 dogs. Serum APPs decreased significantly on treatment ( P < .05) except Hp, which remained unaltered. Serum and CSF IgA concentrations remained increased for the duration of treatment.
Conclusions and Clinical Importance: The prednisolone regimen presented was successful in treating SRMA without the need for additional drugs. Serum APPs are of use in the diagnosis and management of SRMA, particularly in relation to identifying relapse. Serum and CSF IgA concentrations remain increased throughout disease, aiding in diagnosis but not contributing to the management of SRMA.     

Tracheobronchial Brush Cytology and Bronchoalveolar Lavage in Dogs and Cats with Chronic Cough: 45 Cases (2012–2014)

Background

Animals with chronic cough can have normal bronchoalveolar lavage fluid cytology when small airway disease is absent. Cytology of a tracheobronchial brushing can detect inflammation in larger airways; however, evaluation of this technique has been limited in veterinary medicine.

Objective

To compare airway brush cytology to bronchoalveolar lavage fluid analysis in dogs and cats with chronic cough.

Animals

Forty dogs and five cats undergoing bronchoscopic investigation of chronic cough.

Methods

Prospective study. Bronchoscopy and bronchoalveolar lavage were performed followed by tracheobronchial brushing of central airways. Results of cytologic assessment of BAL fluid and brush cytology were compared for the presence or absence of inflammation and concordance of inflammatory cell type.

Results

Brush cytology detected central airway inflammation in 34 of 40 (85%) dogs with inflammatory BAL fluid. However, the type of inflammation reported differed in 23 of 34 dogs. In five cats with inflammation in BAL fluid, brush cytology detected inflammation in four; the type of inflammation was discordant in all cats.

Conclusions and clinical relevance

Brush cytology has good agreement with BAL regarding the presence of inflammation, although the type of inflammation detected with the different sampling techniques commonly varies. Brush cytology can provide supplementary information to BAL, and additional studies will provide further information on the role of tracheobronchial brush cytology in the diagnosis and management of respiratory conditions.     

Treatment of canine mast cell tumours with vinblastine, cyclophosphamide and prednisone: 35 cases (1997–2004)

The purpose of this retrospective study was to determine the efficacy and toxicity of a combined protocol of vinblastine, cyclophosphamide and prednisone (VCP) in 35 dogs with mast cell tumours (MCTs). Eleven dogs had measurable disease (group 1) and 24 dogs had incompletely excised MCT or were at high risk for metastasis (group 2). Five patients in group 1 achieved complete response, two partial responses, two stable diseases and two progressive diseases. The median progression‐free survival time (PFST) for group 1 and 2 dogs was 74 and 865 days, respectively. The median overall survival time (OST) for group 1 and 2 dogs was 145 and >2092 days, respectively. Significant negative multivariate prognostic factors included macroscopic disease and reduced vinblastine (VBL) treatments for PFST, and presence of MCT in bone marrow analysis, Patnaik grade III MCT and reduced VBL treatments for OST. Toxicity was infrequent and self‐limiting. This study suggests that the VCP protocol should be considered as an option in the treatment of MCT in dogs.     

Cross-Sectional Imaging Characteristics of Pituitary Adenomas, Invasive Adenomas and Adenocarcinomas in Dogs: 33 Cases (1988–2006)

Background: Pituitary tumors in dogs can be adenomas, invasive adenomas, or adenocarcinomas. In people, invasive adenomas and pituitary adenocarcinomas carry a worse prognosis than adenomas.
Hypothesis/Objective: To identify differentiating features on cross-sectional imaging in dogs with pituitary adenomas, invasive adenomas, and adenocarcinomas.
Animals: Thirty-three dogs that had computed tomography (CT) or magnetic resonance imaging (MRI) performed and a necropsy diagnosis of pituitary adenoma ( n = 20), invasive adenoma ( n = 11), or adenocarcinoma ( n = 2).
Methods: Medical records were retrospectively reviewed for signalment, history, and diagnosis. CT and MR images were reviewed for characteristics of pituitary tumors.
Results: Mean (± standard deviation) age for dogs with pituitary adenomas (10.6 ± 2.9 years) was greater than that of those with invasive adenomas (8.3 ± 2.7 years, P = .04). Eighteen out of 20 (90%) dogs with adenomas had contrast-enhancing masses. Thirteen out of 20 (65%) had homogeneous enhancement. Mean adenoma height was 1.2 ± 0.7 cm. Eight out of 20 (40%) adenomas were round and 8/20 (40%) compressed surrounding brain. Eleven out of 11 dogs (100%) with invasive adenomas had contrast-enhancing masses. Seven out of 11 (64%) masses were homogeneous. Mean invasive adenoma height was 1.8 ± 0.7 cm, which was significantly greater than adenomas ( P = .03). Mass shape varied from round to oval to irregular. Six out of 11 (55%) masses compressed surrounding brain. Clinical and imaging features were variable for 2 dogs with adenocarcinomas.
Conclusions and Clinical Relevance: Invasive adenoma should be suspected if a dog with a pituitary tumor is <7.7 years of age and has a mass >1.9 cm in vertical height. Adenocarcinomas are uncommon and metastatic lesions were not seen with imaging.     

A Retrospective Study of Multi‐agent Chemotherapy including either Cyclophosphamide or Lomustine as Initial Therapy for Canine High‐grade T‐cell Lymphoma (2011‐2017)

Multi‐agent chemotherapy (vincristine, epirubicin and prednisolone) including either cyclophosphamide (CEOP) or lomustine (LEOP) was given as first‐line chemotherapy to treatment‐naïve canine lymphoma patients with measurable, high grade T‐cell lymphoma (HGTCL). All patients responded to either CEOP or LEOP. Toxicity was typical of multi‐agent chemotherapy protocols and 25% of dogs receiving lomustine exhibited mild‐to‐moderate ALT elevation and 29% grade 3 or 4 neutropenia. Median progression‐free survival (100 versus 269 days) and overall survival (155 versus 327 days) were significantly higher in patients receiving LEOP compared to CEOP. Overall survival was improved for patients receiving LEOP compared to those receiving CEOP followed by lomustine‐based rescue therapy. The results of this retrospective study support further evaluation of lomustine as part of first‐line, multi‐agent therapy for patients with HGTCL.