Canine oral mucosal mast cell tumours.

Mast cell tumours (MCTs) are the most common cutaneous tumours of dogs, however rarely they can arise from the oral mucosa. This subset of MCT is reported to demonstrate a more aggressive clinical course than those tumours on the haired skin and the authors hypothesised that dogs with oral, mucosal MCT would have a high incidence of local lymph node metastasis at presentation and that this would be a negative prognostic factor. An additional hypothesis was that mitotic index (MI) would be prognostic. This retrospective study examines 33 dogs with MCTs arising from the oral mucosa. The results suggest that oral mucosal MCTs in the dog have a high incidence of lymph node metastasis at diagnosis (55%) which results in a poor prognosis. MI and nodal metastasis is highly prognostic. Loco-regional progression is common in these patients and dogs with adequate local control of their tumour had an improved outcome. Despite a more aggressive clinical course, treatment can result in protracted survivals, even when metastasis is present.

Gastrointestinal toxicity after vincristine or cyclophosphamide administered with or without maropitant in dogs: a prospective randomised controlled study.

OBJECTIVES: To assess the prevalence of gastrointestinal toxicity in dogs receiving chemotherapy with vincristine and cyclophosphamide and the efficacy of maropitant citrate (Cerenia™, Zoetis) in reducing these events. METHODS: Dogs receiving chemotherapy with cyclophosphamide or vincristine were randomised to either receive maropitant or not in the period immediately after treatment and for 4 days afterwards. Owners completed a diary of adverse events following treatment. RESULTS: Adverse events occurred in 40/58 (69%) dogs in the vincristine group. Most of these adverse events were mild and included: lethargy (62%), appetite loss (43%), diarrhoea (34%) and vomiting (24%). Adverse events occurred in 34/42 (81%) dogs treated with cyclophosphamide. Most of these adverse events were mild and included: lethargy (62%), diarrhoea (36%), appetite loss (36%) and vomiting (21%). There was no difference in total clinical score, vomiting, diarrhoea, appetite loss or lethargy score between dogs treated with maropitant and non-treated dogs in either the vincristine or cyclophosphamide groups. CLINICAL SIGNIFICANCE: Chemotherapy-related side effects are frequent but usually mild in dogs receiving vincristine or cyclophosphamide. Prophylactic administration of maropitant does not reduce the frequency of adverse events and maropitant should be administered only as required for individual cases.

Epirubicin as part of a multi-agent chemotherapy protocol for canine lymphoma.

The aim of the study was to report the outcome of treatment of 97 dogs with lymphoma that received a multi-agent chemotherapy protocol containing epirubicin as the primary anthracycline. Seventy-five dogs received a 25-week protocol with no maintenance phase whilst 22 dogs received a maintenance phase. Complete response rate was 96% and time to first relapse (TTR) and overall survival (OS) time for all dogs were 216 and 342 days, respectively. Dogs with T-cell lymphoma and those classified as WHO substage b had significantly poorer OS times and TTR. The protocol was well tolerated with toxicity similar to doxorubicin-containing protocols. Epirubicin as part of a multi-agent protocol is safe and effective in the treatment of canine multicentric lymphoma. There is a high initial response rate and an overall median survival time that is similar to other published doxorubicin-containing protocols.

Toxicity associated with epirubicin treatments in a large case series of dogs.

Epirubicin is a stereoisomer of doxorubicin that is widely used in human oncology. The purpose of this study was to evaluate the toxicity associated with epirubicin administration in dogs. Three hundred and fifteen treatments were administered to 139 dogs. Patients received between one and seven doses. One hundred and sixteen treatments were associated with toxicity in 81 patients (50 episodes of lethargy, 49 of diarrhoea, 42 of vomiting, 40 of anorexia, 2 hypersensitivity reactions and 2 suspected extravasations). Thirty-six (11%) adverse events resulted in hospitalization in 33 (24%) patients, of which 15 were neutropenic and 9 pyrexic. Mean duration of hospitalization was 3.4 days and 33 patients recovered uneventfully. Owners of 11 patients declined further treatment after toxicity occurred. After 25 treatments associated with toxicity, dose reductions reduced toxicity. The use of prophylactic anti-emetics, gastroprotectants and antibiotics did not reduce the frequency of gastrointestinal toxicity.

Toxicities and salvage therapy following overdose of vinblastine in a cat.

A cat receiving chemotherapy for lymphoma was administered a four times overdose of vinblastine in error. Severe, acute life-threatening toxicities occurred. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was suspected based on electrolyte disturbances. A favourable outcome was achieved with aggressive supportive care. Personnel involved in administering chemotherapy to small animal patients must check that the patient is receiving the correct drug, at the appropriate dose, prior to every treatment.

A phase II clinical trial of vinorelbine in dogs with cutaneous mast cell tumors.

BACKGROUND: Few effective drugs are available to treat dogs with locally aggressive or metastatic mast cell disease. HYPOTHESIS: Vinorelbine, a semisynthetic derivative of vinblastine, is an effective drug for the treatment of canine mast cell tumors (MCT). ANIMALS: Twenty-four dogs with cutaneous MCT. METHODS: Dogs with at least 1 measurable, cytologically confirmed, and previously untreated cutaneous MCT received a single treatment with vinorelbine at the previously established dosage of 15 mg/m2 IV. Tumor measurements and CBC were evaluated before and 7 days after treatment. Adverse events were graded according to Veterinary Cooperative Oncology Group (VCOG) guidelines. STATISTICS: Data were accrued in accordance with a Simon's 2-stage design with a noninteresting response rate of .05, a target response of .25, and alpha and beta values of .10. RESULTS: Three of 24 dogs (13%) had a response to treatment, including 1 measurable complete response and 1 measurable partial response. The 3rd dog had microscopic complete response to treatment with stable measurable disease. Twenty other dogs (83%) had stable disease and 1 dog (4%) had progressive disease. Neutropenia occurred in 13 dogs (54%) (grade 1, n = 4; grade 3, n = 6; grade 4, n = 3). Gastrointestinal toxicity occurred in 11 dogs (46%) (anorexia: grade 1, n = 3; grade 2, n = 1; grade 3, n = 1; diarrhea: grade 1, n = 2; grade 3, n = 1; vomiting: grade 1, n = 5; grade 3, n = 1). CONCLUSIONS AND CLINICAL IMPORTANCE: Vinorelbine was associated with an overall response rate of 13% and a high prevalence of neutropenia. Additional studies are indicated to determine if repeated dosing of vinorelbine or combination of vinorelbine with other drugs increases the observed biologic activity against canine MCT.

ALS incidence in Nova Scotia over a 20-year-period: a prospective study.

OBJECTIVE: Previous studies have suggested that the incidence of amyotrophic lateral sclerosis (ALS) in Nova Scotia is relatively high and increasing over time. This study was performed to determine the current incidence of ALS in Nova Scotia and to compare this to data collected in 1984 and 1995. METHODS: All physiatrists and neurologists were surveyed on a monthly basis over one year to record all new cases of ALS diagnosed in Nova Scotia. Data was compared to that collected using similar methods in 1984 and 1995. To validate our methods, we also performed a retrospective study using a provincial health care database. RESULTS: There were 21 new ALS cases in Nova Scotia during the 2003 study period, yielding a crude incidence of 2.24/100,000. The age-adjusted incident rate for 2003 was 2.13 (95% CI = 0.11-4.15). The age-adjusted rate for 1995 was 2.3 (95% CI = 0.08-4.53) while the age-adjusted rate for 1984 was 2.22 (95% CI = 0.13-4.32). Analysis of provincial health records identified 24 cases of ALS and an age-adjusted incidence of 2.44/100,000. CONCLUSIONS: The age-adjusted incidence of ALS in Nova Scotia has remained stable over the period 1984-2003. The incidence is similar to that reported in several other parts of the world.

Progress in clinical neurosciences: Charcot-Marie-Tooth disease and related inherited peripheral neuropathies.

The classification of Charcot-Marie-Tooth disease and related hereditary motor and sensory neuropathies has evolved to incorporate clinical, electrophysiological and burgeoning molecular genetic information that characterize the many disorders. For several inherited neuropathies, the gene product abnormality is known and for others, candidate genes have been identified. Genetic testing can pinpoint a specific inherited neuropathy for many patients. However, clinical and electrophysiological assessments continue to be essential tools for diagnosis and management of this disease group. This article reviews clinical, electrophysiological, pathological and molecular aspects of hereditary motor and sensory neuropathies.

Autonomic neuropathy associated with sicca complex.

We retrospectively studied 52 patients with sicca complex who presented primarily with peripheral neuropathic symptoms to assess the degree of autonomic involvement and its relationship to somatic neuropathy, serological tests and extraglandular disease. One patient presented with severe panautonomic dysfunction, with another six patients reporting prominent autonomic symptoms, and a further 40 patients having mild or asymptomatic disease. Eighty-seven percent of patients showed abnormalities on an autonomic reflex screen (ARS). Fifty-eight percent of patients showed a mixed pattern of autonomic dysfunction with abnormalities in two or more ARS subgroups of sudomotor, cardiovagal and adrenergic function. Three patients had a cholinergic autonomic neuropathy with sparing of adrenergic function. Tonic pupils were present in 13 patients. Autonomic neuropathy occurred in patients with a variety of somatic neuropathy subtypes, without a clear relationship between the type of autonomic neuropathy and the type of somatic peripheral neuropathy. Extraglandular disease was uncommon, occurring in only four patients. Serological abnormalities (extractable nuclear antigen [ENA], SS-A, SS-B) occurred in 20% of patients. We conclude that: (1) A wide spectrum of autonomic dysfunction is seen in sicca complex. (2) Severe autonomic involvement is uncommon, with most patients showing mildly symptomatic or asymptomatic disease. (3) Overall, characteristic patterns of autonomic dysfunction did not predominate, and there were no clear relationships with the different types of somatic peripheral neuropathy. (4) Clinical and serological evidence of non-neurological extraglandular disease is uncommon in this group of patients.

Peripheral neuropathy associated with sicca complex.

Peripheral neuropathy occurs in Sjögren's syndrome, a disorder in which systemic immunologic phenomena, including vasculitis, are common. Neuropathy also occurs with isolated sicca complex (keratoconjunctivits sicca and xerostomia); whether this represents a distinct syndrome is unclear. We retrospectively studied 54 patients with sicca complex and peripheral neuropathy to determine mode of presentation, neuropathic patterns, frequency and pattern of serologic abnormalities, and frequency of systemic disease, including necrotizing vasculitis. Peripheral neuropathy was the presenting problem in 87%. Although sicca symptoms occurred in 93%, they were a presenting complaint in only 11% and were usually mild, reported only after specific inquiry. Minor salivary gland biopsy was positive in 73%. Sensory neuropathies strongly predominated; 61% of patients manifested either sensory polyneuropathy or polyganglionopathy. Less common patterns included sensorimotor polyneuropathy (17%) and polyradiculoneuropathy (11%). Vasculitic neuropathy was demonstrated in only two patients, but nonspecific epineurial inflammation was present in 70% of nerve biopsies. Clinical evidence of systemic disease was uncommon, particularly in the sensory polyganglionopathy group, in whom extraglandular features other than weight loss occurred in only 1 of 12 patients. Antibodies to extractable nuclear antigens, the most specific serologic marker of Sjögren's syndrome, were present in 10.4%. We conclude that peripheral neuropathy and isolated sicca complex form a distinctive syndrome in which neuropathy is the presenting feature and sicca is easily overlooked; sensory polyneuropathy and polyganglionopathy predominate; serology is confirmatory but very insensitive; and extraglandular disease, including vasculitis, is uncommon compared with typical Sjögren's syndrome. Tests of ocular or salivary involvement are needed for diagnosis, and demonstration of inflammation in biopsied nerve is supportive. Improved definition of this disorder should permit further studies of natural history and efficacy of immunotherapy.

Ten steps in characterizing and diagnosing patients with peripheral neuropathy.

Cost-effective approaches for arriving at correct diagnoses should be used. Herein, we compare three approaches for the differential diagnosis of a common neurologic syndrome, peripheral neuropathy. In the "shotgun" approach, a standard battery of hematologic, biochemical, serologic, antibody, enzyme, molecular genetic, and other tests are ordered after the presence of a neuropathy is established, without a detailed characterization of the neuropathy. In the "gestalt" approach, the specific variety of neuropathy is identified by recognition of a clinical pattern of symptoms, course, or disease associations. The "10-step" approach, encompassing components of the two other methods and adding others, evolved from our assessment of many patients with peripheral neuropathy. In the 10-step approach, the history and neurologic examination place the patient's disorder into one of perhaps 21 anatomic-pathologic patterns. Next, electrophysiologic and other tests confirm the correctness of this anatomic-pathologic patterns. Finally, a series of evaluations exclude or include an increasingly shorter list of diagnoses until only one likely one remains or the disorder remains undiagnosed. We advocate the 10-step over the shotgun or gestalt approach, because it emphasizes careful initial characterization of neuropathy and emphasizes use of a logical step-by-step inclusion or exclusion to arrive at a short list of diagnostic possibilities. The approach depends ultimately on the judgement of adequately trained and experienced physicians, not on the results of single tests. The 10-step approach is not a mindless algorithm, leading inevitably to the correct diagnosis, but depends on judgment based on extensive background and neurobiologic and clinical knowledge and training.