Retrospective analysis of outcome and prognostic factors of subcutaneous mast cell tumours in dogs undergoing surgery with or without adjuvant treatment.

Subcutaneous mast cell tumours (SC MCTs) can display a different biological behaviour in dogs when compared to their cutaneous counterpart. There is a paucity of information with regards to the outcome of dogs with SC MCTs treated with surgery and/or receiving adjuvant chemotherapy. The aim of this study was to retrospectively review the outcome of dogs with surgically excised SC MCTs undergoing adjuvant treatment or not. A secondary aim was to assess prognostic factors in the same group. Fifty-two cases were included. Recurrence rate was 15% and 63% of evaluated lymph nodes were consistent with early or overt metastasis. Median survival time (range 83-1357 days) and median time to progression (range 14-1357 days) were not reached. Factors predictive of shorter overall survival time included increasing age (HR 1.29, 95% CI 1.06-1.55, p = .0092), presence of clinical signs at presentation (HR 10.44, 95% CI 2.69-40.52, p = .0007), mitotic count >4 (HR 8.69, 95% CI 2.55-29.55, p = 0.0005), presence of multinucleation (HR 4.21, 95% CI 1.35-13.18, p = .0135), use of neoadjuvant and adjuvant chemotherapy (HR 7.16, 95% CI 1.26-40.73, p = .0266). The same factors, together with increasing tumour dimensions, were predictive for shorter progression-free survival (PFS), including increasing age (p = .0012), presence of clinical signs at presentation (p = .0045), increasing tumour dimensions (p = .0004), MC > 4 (p = .0004), presence of multinucleation (p = .0282), use of neoadjuvant and adjuvant chemotherapy (p = .0485). No variables remained significant for overall survival using multivariate analysis. There was a longer survival in cases where chemotherapy was not required (HR 0.14, 95% CI 0.03-0.68, p = .0148), and this variable remained significant for PFS on multivariate analysis (HR 0.13, 95% CI 0.02-0.76, p = .02). In conclusion, our study suggests that dogs with SC MCTs, in the absence of negative prognostic factors, may have a prolonged survival when treated with surgery alone. Further studies are needed to clarify the role of adjuvant treatment for biologically aggressive SC MCTs in dogs.

Canine gastrointestinal stromal tumours treated with surgery and imatinib mesylate: three cases (2018-2020).

OBJECTIVES: Gastrointestinal stromal tumours (GISTs) are described in dogs and are histologically diagnosed with the aid of immunohistochemistry to allow differentiation from leiomyomas/leiomyosarcomas. These tumours express c-kit and in some cases could harbour mutations in KIT coding gene. MATERIALS AND METHODS: Dogs with a diagnosis of GIST previously confirmed with histopathology and immunohistochemistry were considered for inclusion. Medical records were reviewed for clinical signs at presentation, results of diagnostic tests, tumour location and treatment. To be included, patients had to undergo staging procedures and treatment with imatinib alone or in combination with surgery. Immunohistochemistry and KIT mutational analysis were performed assessing all included cases. RESULTS: Three cases were included. All cases underwent staging procedures and surgical excision. Tumours were located in the stomach (two cases) or caecum (one case). KIT mutational status was assessed and the presence of a 54-base pair deletion in exon 11 was identified in one case. Following surgery, imatinib was used to treat recurrent, metastatic or residual disease and resulted in complete response and stable disease in the macroscopic setting and no evidence of recurrence in the microscopic setting. Follow-up time was 890, 120 and 352 days, respectively. CLINICAL SIGNIFICANCE: Surgical and medical treatment resulted in a positive outcome in these cases of canine GIST. Imatinib treatment was well tolerated and resulted in a measurable response and a low spectrum of toxicities. Further studies on the tolerability and efficacy of imatinib in solid tumours and GIST are warranted to define its effectiveness and safety.

Percutaneous ultrasound-guided microwave ablation for treatment of hepatocellular carcinomas in dogs: four cases (2019-2020).

OBJECTIVES: To describe ultrasound-guided microwave ablation as a minimally invasive treatment option for primary or metastatic hepatocellular carcinomas. METHODS: Four client-owned dogs underwent percutaneous ultrasound-guided microwave ablation of three primary and one metastatic hepatocellular carcinoma, diagnosed on cytology/histopathology. In each case, multiple ultrasound-guided thermal lesions were created in a 10 to 40 minutes ablation at 30 to 35 W. Real-time monitoring was performed using 10 MHz diagnostic ultrasound transducers. The procedures were performed without complication and CT scans or abdominal ultrasounds were repeated immediately after. Patients were discharged on oral analgesia on the same day or 24 hours later. RESULTS: Hepatocellular carcinomas were successfully ablated, which in some cases resulted in an improvement in clinical signs and laboratory values. The patients were followed up for a time ranging between 39 and 649 days and no evidence of disease progression was found. Three out of four patients are still alive at the time of writing. CLINICAL SIGNIFICANCE: In these four patients, minimally invasive ultrasound-guided microwave ablation was feasible and resulted in no immediate complications. Regular imaging follow-up is recommended after the procedure and further studies on microwave ablation are warranted to establish its effectiveness in dogs with hepatocellular carcinomas.

Tolerability and outcome of palliative treatment for metastatic pulmonary carcinoma in cats.

OBJECTIVES: Pulmonary carcinoma is uncommon in cats and reporting of outcomes following medical treatment is limited, especially in presence of metastases. The aim of this study was to describe the outcome of cats affected by metastatic primary pulmonary carcinoma and to evaluate the tolerability of palliative treatment in this patient population. MATERIALS AND METHODS: Medical records were searched for cats with a cytological or histopathological diagnosis of primary pulmonary carcinoma and evidence of metastatic disease. Cats were treated with antineoplastic agents, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) or received no systemic treatment. Cases in which thoracic CT was not performed, and those lacking definitive diagnosis by cytology or histopathology or receiving curative-intent surgery were excluded. RESULTS: Thirty-four cats were identified: 18 were treated with antineoplastic agents and 16 received corticosteroids, NSAIDs or no treatment. Presenting clinical signs included coughing (53%), tachypnoea (26%), gastrointestinal signs (35%) and lethargy (18%). CT scan identified metastases to the lung parenchyma in all cases and additional metastatic lesions in 10 of 34 (59%) cases; pleural effusion was detected in 11 cases (32%). The overall median survival time for all cats was 64 days [range 1-1352 days; 95% confidence interval (CI) 48-164]. Presence of respiratory signs at presentation was the only factor influencing survival in the multivariable analysis. CLINICAL SIGNIFICANCE: Medical treatment was well tolerated and appeared to palliate clinical signs in cats with metastatic pulmonary carcinoma, albeit with a modest duration and short overall survival. The role and benefit of chemotherapy/antineoplastic agents versus conventional palliative drugs in this setting remains unclear.

Haematologic toxicity in dogs with mast cell tumours treated with vinblastine/prednisolone chemotherapy with/without radiotherapy.

OBJECTIVES: To determine whether dogs with surgically excised mast cell tumours receiving a vinblastine/prednisolone chemotherapy protocol in combination with radiation therapy are at greater risk of myelosuppression than patients receiving the chemotherapy protocol alone. MATERIALS AND METHODS: Retrospective study of clinical records of dogs with mast cell tumours that, subsequent to surgical excision, had received combination vinblasine/prednisolone chemotherapy. Dogs were assigned to two groups: those treated with adjunctive radiotherapy and vinblastine/prednisolone (RT group) and those treated with surgery followed by vinblastine/prednisolone alone (control group). Haematology results were compared between groups. RESULTS: Forty-three cases and 43 controls of similar breed, age and bodyweight were included. Concurrent radiation and vinblastine chemotherapy did not appear to increase the risk of neutropenia, which was observed in 18.6 and 23.2% of cases in the RT and control groups, respectively. CLINICAL SIGNIFICANCE: Radiation and vinblastine chemotherapy can be safely combined in dogs with mast cell tumours without increasing the risk of clinically important myelosuppression.

Outcome and prognostic factors in medically treated canine prostatic carcinomas: A multi-institutional study.

Literature describing medical treatment of canine prostatic carcinoma (PC) is sparse. The aims of this study were to assess outcomes, including time to progression (TTP) and median survival time (MST), of canine PC treated with non-steroidal anti-inflammatory drugs (NSAIDs) and/or chemotherapy, and to identify prognostic factors. Records from 8 institutions were searched for dogs with cytologically or histologically confirmed PC without bladder involvement: 67 dogs were included. Presenting signs were urinary (25), gastrointestinal ([GI], 11) and systemic (3); 16 dogs had GI and urinary signs, 7 dogs had systemic signs with concurrent GI or urinary signs and in 5 dogs the tumour was an incidental finding. Out of 27 dogs, 9 (33%) had positive urine culture. Metastases were identified in 26 dogs to lymph nodes (19), lungs (10), bone (2) and liver (1). Treatment included NSAIDs and chemotherapy (32), NSAIDs alone (31) and chemotherapy alone (4). The overall MST was 82 days (range 9-752) and median TTP was 63 days (range 9-752). Dogs receiving NSAIDs combined with chemotherapy experienced a significantly longer MST (106 vs 51 days; P = .035) and TTP (76 vs 44 days; P = .02) compared to dogs receiving NSAIDs alone. Intact dogs and those with metastatic disease had significantly shorter MST (31 vs 90 days, P = .018 and 49 vs 109 days, P = .037, respectively); intact dogs also had significantly shorter TTP (25 vs 63 days, P = .0003). This study suggests that a combination of NSAIDs and chemotherapy may improve outcomes in canine PC. Metastatic disease and being entire negatively influenced prognosis.

Temozolomide alone or in combination with doxorubicin as a rescue agent in 37 cases of canine multicentric lymphoma.

Temozolomide (TMZ) is an alkylating agent previously used in conjunction with doxorubicin (DOX) to treat dogs with relapsed lymphoma. However, there are very limited data for this drug when used as single agent. The aim of this retrospective study was to evaluate the efficacy and toxicity of TMZ in dogs with relapsed multicentric lymphoma that failed multi-agent chemotherapy protocols, and compare the outcome to a group of dogs receiving the same drug in combination with DOX. Twenty-six patients were included in the TMZ group and 11 in the TMZ/DOX group. Responses were evaluated via retrospective review of the medical records. The overall median survival time (MST) for both groups was 40 days (range 1-527 days). For the TMZ group, median time to progression (TTP) was 15 days (range 1-202 days) and MST 40 days (range 1-527 days), with an overall response rate (ORR) of 32% and 46% recorded toxicities. For the TMZ/DOX group, median TTP was 19 days (range 2-87 days) and MST 24 days (range 3-91 days), with an ORR of 60% and 63% recorded toxicities. However, a proportion of haematological toxicoses may have gone undetected due to the absence of associated clinical signs. The difference in MST and TTP between the 2 groups was not statistically significant. Similarly, no negative prognostic factors were identified. Although responses were generally short lived, this study suggests that TMZ may achieve similar efficacy to TMZ/DOX whilst being associated with a lower frequency of recorded toxicities.

A descriptive review of cardiac tumours in dogs and cats.

Cardiac tumours are uncommon in the canine and feline population and often an incidental finding. Common types include haemangiosarcoma (HSA), aortic body tumours (chemodectoma and paraganglioma) and lymphoma. These neoplasms can cause mild to severe, life-threatening clinical signs that are independent of the histological type and may be related to altered cardiovascular function or local haemorrhage/effusion into the pericardial space. Cardiac tumours may require symptomatic treatment aimed at controlling tumour bleeding and potential arrhythmias, and other signs caused by the mass effect. Additional treatment options include surgery, chemotherapy and radiotherapy. For all medical therapies, complete remission is unlikely and medical management, beyond adjunctive chemotherapy in HSA, requires further investigation but combination chemotherapy is recommended for lymphoma. The aim of this report is to summarize and critically appraise the current literature in a descriptive review. However, interpretation is limited by the lack of definitive diagnosis and retrospective nature of most studies.

Clinical outcome, PDGFRß and KIT expression in feline histiocytic disorders: a multicentre study.

Information about histiocytic disease in cats is limited. The aim of this study was to document clinical findings and outcome in feline histiocytic disorders, and characterize the expression of PDGFRß and KIT in order to identify potential treatment targets. Morphologically diagnosed feline histiocytic tumours were reviewed and characterized by immunohistochemistry (IHC). Five cases of feline progressive histiocytosis (FPH), eight histiocytic sarcomas (HS) and two haemophagocytic histiocytic sarcomas (HaeHS) were confirmed. PDGFRß was variably positive in most histiocytic cases, while KIT was negative in all. Clinical presentation, treatment and outcome were also evaluated. Partial responses were recorded in measurable disease with tyrosine kinase inhibitors and lomustine, and radiotherapy achieved long-term control in some cases. Survival times were shortest in HaeHS and disseminated disease. PDGFRß, but not KIT, may represent a therapeutic target in feline histiocytic disorders but more studies are needed to investigate other potential treatment targets.

Subclinical coeliac disease: an anthropometric assessment.

OBJECTIVES: To evaluate the prevalence of malnutrition in patients with untreated coeliac disease (CD) according to their pattern of presentation, and the effect of gluten-free diet (GFD) upon nutritional status. DESIGN: Cohort prospective study. SETTING: All subjects were seen at the outpatient 'malabsorption' clinic of the Department of Medical Pathology I, University of Bologna (referral centre), Bologna. SUBJECTS: Eighty consecutive patients with CD (48 with classical and 32 with subclinical presentation), 15 patients with dermatitis herpetiformis (DH) and 40 healthy volunteers (members of the hospital staff). MAIN OUTCOME MEASURES: The nutritional status was evaluated by anthropometric measurements (percentage of ideal body weight for height and sex, percentage of standard triceps skinfold thickness and percentage of ideal arm-muscle circumference). RESULTS: The overall prevalence of malnutrition in our series of CD patients was 53%. Prevalence of malnutrition (actual body weight less than 90% of the ideal) was significantly higher in classical coeliacs (67%) than in subclinical ones (31%, P < 0.002), in patients with DH (13%, P < 0.0003) and in healthy volunteers (13%, P < 0.0001). At diagnosis, percentage values of ideal body weight, triceps skinfold thickness and arm-muscle circumference were significantly lower (P < 0.0001, P < 0.0002 and P < 0.0003, respectively) in classical coeliacs (84.5 +/- 10.6, 71.2 +/- 28.1 and 87.1 +/- 10.8, respectively) than in subclinical coeliacs (95.5 +/- 9.1, 105.6 +/- 41.0 and 94.8 +/- 10.6, respectively). After GFD, 33% of classical and only 3% of subclinical coeliacs were still malnourished. CONCLUSIONS: Prevalence of malnutrition in CD is lower than was previously thought. CD patients with classical presentation may require a longer period of GFD to achieve a significant improvement of their nutritional status, with respect to those with subclinical presentation, probably because of a greater extent of intestinal damage. Finally, a careful evaluation of dietary habits is usually sufficient to identify incomplete adherence to GFD as the reason for nonimprovement of the nutritional status in patients with CD.

Subclinical celiac sprue. Increasing occurrence and clues to its diagnosis.

We have reviewed the clinical records of 226 consecutive adult patients with celiac sprue diagnosed in our department from 1972 to 1989. The study period has been divided into three subperiods of 6 years each (1972-1977, 1978-1983, 1984-1989). From the first to the third subperiod a significant increase in the number of new diagnoses and of the proportion of patients recognized by minor symptoms has been observed. These patients represent 50% of our series in the last 3 years of the study and 70% in 1989. Diagnosing subclinical forms of celiac sprue has significantly lowered the mean age at diagnosis and the female/male ratio. First-degree relatives of celiac patients; subjects who had a gluten-free diet for a period during childhood; patients with short stature, anemia, or amenorrhea of no obvious cause; or patients with unexplained immunological abnormalities are the groups in which most patients with subclinical celiac sprue have been found and in which potential patients should be sought. Helpful diagnostic tools include antigliadin antibody testing and the observation of absent or reduced Kerckring folds in the descending duodenum in the course of upper gastrointestinal endoscopy.

Non-absorbable antibiotics and small bowel bacterial overgrowth.

The normal gastrointestinal flora includes no more than 10(3) organisms/ml of gastric aspirate and no more than 10(5) organisms/ml of duodenal or jejunal juice. The organisms are primarily gram-positive and aerobic bacteria. In particular anatomical or functional predisposing conditions, an abnormal colonization takes place in the small bowel with microbial concentrations > or = 10(7)/ml of aspirate and with a predominance of anaerobes and coliforms. At times this small bowel bacterial overgrowth remains asymptomatic, but more often leads to a true malabsorption syndrome with symptoms, such as diarrhoea, weight loss and megaloblastic anemia. The most accurate procedure for confirming the presence of this condition is represented by the bacterological analysis of the jejunal aspirate. The routine use of this method is, however, notably hindered by the need for intubation of the patient and by the lack of laboratories suitably equipped for anaerobe culture. As an alternative to this complex procedure, numerous non-invasive tests have been perfected over the last few years, including the glucose- or lactulose- H2 breath test. The main aim of the treatment of the small bowel bacterial overgrowth is the suppression of the bacterial colonization using antimicrobial therapy. Among the local-action non-absorbable antibiotics, rifaximin, was shown to have bactericidal activity against aerobes and anaerobes bacteria, such as bacteroides, lactobacilli and clostrides. In controlled clinical trials the antibiotic has demonstrated therapeutic efficacy in bacterial origin diarrhoea, in porto-systemic encephalopathy, in diverticulosis and, finally, in small bowel bacterial overgrowth.

Endoscopic demonstration of loss of duodenal folds in the diagnosis of celiac disease.

Among 873 patients undergoing upper gastrointestinal endoscopy for various reasons over a two-year period, four had a loss of Kerckring's folds in the descending duodenum. Endoscopic duodenal biopsy in all four patients revealed subtotal villous atrophy due to celiac disease. We undertook a prospective study to evaluate the extent to which this finding predicted celiac disease in 65 consecutive patients referred for intestinal biopsy. Duodenal folds were absent or markedly decreased in 15 of 17 patients with subtotal villous atrophy and in 8 of 48 patients with partial villous atrophy or normal duodenal mucosa, giving a sensitivity of 88 percent and a specificity of 83 percent for this endoscopic finding with respect to celiac disease. We recommend that all patients undergoing upper gastrointestinal endoscopy be examined for the loss or reduction of duodenal folds and, should this be found, that the examination include duodenal biopsy. The value of this procedure as an aid in the diagnosis of celiac disease should be particularly great in patients with minimal, transient, or unrelated symptoms.