H. de Rooster

Canine Mammary Tumours, an Overview

Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Although the prevalence of these tumours decreases in regions where preventive ovari(ohyster)ectomy is performed, it remains an important disease entity in veterinary medicine. Moreover, treatment options are limited in comparison with human breast cancer. Nevertheless, recent human treatment protocols might have potential in bitches suffering from CMTs.

Immunopathological mechanisms in dogs with rupture of the cranial cruciate ligament

The majority of studies on cranial cruciate ligament (CrCL) disease to date have been carried out on dogs that already sustained a CrCL rupture, which is the end-stage of the disease. Investigations have recently been carried out to study humoral and cellular immunopathological mechanisms in predisposed dogs before clinical rupture of the contralateral CrCL. The cruciate ligaments are mainly composed of collagen type I, and immune responses to collagen have been suggested as a cause of CrCL degradation in dogs. None of these investigations showed evidence that anticollagen type I antibodies alone initiate CrCL damage. However, in predisposed dogs a distinct anticollagen type I antibody gradient was found towards the contralateral stifle joint that eventually sustained a CrCL rupture, suggesting that there was an inflammatory process present in these joints before detectable joint instability occurred. The importance of cellular reactivity to collagen type I in cruciate disease also remains unclear. Peripheral blood mononuclear cell proliferation to collagen type I was very diverse in dogs with cruciate disease whereas some sham operated dogs and healthy dogs tested positive as well. It is not yet determined whether cellular reactivity to collagen type I exists locally in the stifle joints nor whether this could initiate CrCL degradation. Inflammatory processes within the stifle joint can alter the composition of the cruciate ligaments. In animal models of immune-mediated synovitis, the mechanical strength of the CrCL is significantly reduced. Immunohistochemical studies on synovial tissues from dogs with rheumatoid arthritis and dogs with cruciate disease revealed that the pathologic features are similar in both joint pathologies and that the differences are mainly quantitative. Joint inflammation induced by biochemical factors such as cytokines has been implied in CrCL degeneration. In several studies, the levels of pro-inflammatory and T helper cytokines were measured in dogs that sustained a CrCL rupture, but the exact role of the various cytokines in the pathogenesis of CrCL disease remains inconclusive. More recently, the levels of the cytokines have been investigated over time in predisposed dogs before and after CrCL rupture. IL-8 expression tended to be higher in stifle joints that will rupture their CrCL during the next 6 months than in those that will not, indicating an inflammatory process in these joints before clinical rupture. This review provides a comprehensive overview of all possible implications of humoral and cell-mediated immune responses published in dogs with cruciate disease together with publications from human joint diseases. Furthermore, this review highlights recent findings on cytokines and proteinases in the accompanying joint inflammation.

Diagnosis of cranial cruciate ligament injury in dogs by tibial compression radiography

Stress radiographs were taken of 42 sound stifle joints, of five stifles with injuries other than cruciate disease, and of 72 stifles with surgically confirmed cranial cruciate damage. The stifles were also examined by the cranial drawer test. No false positive compression radiographs were obtained. In the 72 stifles with cranial cruciate damage, instability was diagnosed on the stressed view in all but two cases. The sensitivity of the radiographic tibial compression test was 97 per cent, compared with 86 per cent for the cranial drawer test; the specificities of the tests were 100 per cent and nearly 98 per cent, respectively.

Radiographic, computed tomographic and arthroscopic findings in 23 dogs with osteochondrosis of the tarsocrural joint

Twenty-three dogs with osteochondrosis of the tarsocrural joint were evaluated by radiography, computed tomography (Cr) and arthroscopy. The radiographic examination included an extended and flexed mediolateral, a plantarodorsal, a flexed dorsoplantar skyline view, and a plantaromedial-dorsolateral and a plantarolateral-dorsomedial view (two oblique views). The cT examination was carried out in ventral recumbency and 1 mm slices were taken with a bone window setting; 31 lesions were identified in the 46 joints examined. The arthroscopic exploration used either a plantar or a dorsal puncture, depending on the site of the lesion. In six cases the lateral, and in 17 cases the medial trochlear ridge was involved. Although the survey radiographs were sufficient to make a diagnosis, the cT examination helped to determine the exact site, and the number and size of the fragments of bone. A four-stage classification system comparable to the one used in man was established. Arthroscopy provided information about synovial inflammation and damage to the joint cartilage, and made it possible to remove fragments of bone from one-third of the cases.

A retrospective study of 109 dogs with mandibular fractures

OBJECTIVE To determine patient factors and fracture morphology of dogs presented with mandibular fractures to a small animal referral centre in South Africa. METHODS Patient data on age, sex, breed and aetiology of dogs with mandibular fractures were recorded. The fractures were classified according to the anatomical location, displacement, fracture type, fracture line direction, periodontal pathology, and whether there were teeth in the fracture line or not by evaluation of preoperative radiographs. Clinical observations indicated whether these fractures were open or closed. RESULTS In total, 109 dogs with 135 mandibular fractures were included in the study. Small breed dogs and dogs less than eight months of age predominated (102/109). Dog fights were the most common aetiology in this study (68/109). The molar region was the most commonly affected region (56/135). Evaluation of the radiographs revealed that transverse (73/135), relatively unstable (116/135), and displaced (112/135) fractures were the most common. The majority of fractures involved teeth in the fracture line (100/135), with the first molar frequently involved (54/135). The majority of fractures were open (104/135). CLINICAL SIGNIFICANCE The results obtained from this study may be used to guide patient and fracture morphology selection in biomechanical studies of mandibular fracture repair techniques. Screening of this patient population may inspire the search for new treatment options for mandibular fracture repair in South Africa.

The cat as a model for human obesity: insights into depot-specific inflammation associated with feline obesity

According to human research, the location of fat accumulation seems to play an important role in the induction of obesity-related inflammatory complications. To evaluate whether an inflammatory response to obesity depends on adipose tissue location, adipokine gene expression, presence of immune cells and adipocyte cell size of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were compared between lean and obese cats. Additionally, the present study proposes the cat as a model for human obesity and highlights the importance of animal models for human research. A total of ten chronically obese and ten lean control cats were included in the present study. Body weight, body condition score and body composition were determined. T-lymphocyte, B-lymphocyte, macrophage concentrations and adipocyte cell size were measured in adipose tissue at different locations. Serum leptin concentration and the mRNA expression of leptin and adiponectin, monocyte chemoattractant protein-1, chemoligand-5, IL-8, TNF-alpha, interferon-gamma, IL-6 and IL-10 were measured in blood and adipose tissues (abdominal and inguinal SAT, and omental, bladder and renal VAT). Feline obesity was characterised by increased adipocyte cell size and altered adipokine gene expression, in favour of pro-inflammatory cytokines and chemokines. Consequently, concentration of T-lymphocytes was increased in the adipose tissue of obese cats. Alteration of adipose tissue was location dependent in both lean and obese cats. Moreover, the observed changes were more prominent in SAT compared with VAT.

The accuracy of the Lactate Pro hand-held analyser to determine blood lactate in healthy dogs

OBJECTIVES The objective of this study was to determine the accuracy of the Lactate Pro hand-held analyser in measuring blood lactate levels. METHODS Blood was drawn from 15 healthy dogs into five tubes containing Na-EDTA. Lactate was measured immediately using the Lactate Pro analyser and a laboratory reference method. Further samples were analysed 120, 240, 480 and 1440 minutes later to artificially increase the lactate levels. Lactate was measured in blood samples of 60 healthy dogs using the Lactate Pro analyser to determine the reference interval of lactate concentration in normal dogs. RESULTS The correlation between the lactate concentration measured with the Lactate Pro analyser and the reference method was high. Lactate levels were lower when measured with the hand-held analyser than with the traditional laboratory determination. The reference interval for blood lactate concentrations in healthy dogs established by the Lactate Pro analyser was from the detection limit (0.8 mmol/l) up to 3.3 mmol/l. CLINICAL SIGNIFICANCE The Lactate Pro analyser provides quick and reliable measurements of blood lactate in dogs with blood lactate levels up to 10 mmol/l. Because of its small sample size, this analyser will be particularly appropriate for use in small animal intensive care.

Clinical, Pathologic, and Immunohistochemical Prognostic Factors in Dogs with Thyroid Carcinoma

Background Prognostic markers for dogs with thyroid tumors are limited. Hypothesis/Objectives To identify clinical, pathologic, and immunohistochemical prognostic factors for dogs with thyroid tumors. Animals Seventy dogs with thyroid neoplasia. Methods Retrospective study. Dogs with thyroid neoplasia were included when follow‐up information and formalin‐fixed paraffin‐embedded tumor samples were available. Immunohistochemistry (IHC) was performed for thyroglobulin, calcitonin, Ki‐67, and E‐cadherin. Correlation of tumor variables (diameter, volume, localization, scintigraphic uptake, thyroid function, IHC) with local invasiveness and metastatic disease was performed on all tumor samples. Forty‐four dogs treated by thyroidectomy were included in a survival analysis. Results Fifty dogs (71%) had differentiated follicular cell thyroid carcinoma (dFTC) and 20 (29%) had medullary thyroid carcinoma (MTC). At diagnosis, tumor diameter (P = .007; P = .038), tumor volume (P = .020), tumor fixation (P = .002), ectopic location (P = .002), follicular cell origin (P = .044), and Ki‐67 (P = .038) were positively associated with local invasiveness; tumor diameter (P = .002), tumor volume (P = .023), and bilateral location (P = .012) were positively associated with presence of distant metastases. Forty‐four dogs (28 dFTC, 16 MTC; stage I–III) underwent thyroidectomy. Outcome was comparable between dogs with dFTC and MTC. Macroscopic (P = .007) and histologic (P = .046) vascular invasion were independent negative predictors for disease‐free survival. Although time to presentation, histologic vascular invasion and Ki‐67 were negatively associated with time to metastases, and time to presentation was negatively associated with time to recurrence, no independent predictors were found. E‐cadherin expression was not associated with outcome. Conclusions and Clinical Importance Prognostic factors have been identified that provide relevant information for owners and clinicians.

Intratumoural interleukin 12 gene therapy stimulates the immune system and decreases angiogenesis in dogs with spontaneous cancer

Interleukin 12 (IL-12) is a powerful immunostimulatory cytokine with a strong antitumoural activity. In this work, the immunological, anti-angiogenic and clinical effects of three consecutive intratumoural IL-12 electrogene therapy (EGT) treatments were evaluated in nine dogs with spontaneous cancer. In all the dogs, tumour biopsies and blood samples were taken prior, during and after the intratumoural IL-12 EGT (on days 1, 8, 35 and 1, 3, 8, 15, 35, respectively). An initial decrease in immune cells was followed by an increase above baseline 1-3 weeks after treatment initiation. Interestingly, the decrease in peripheral leukocytes 2 days after the first intratumoural IL-12 EGT coincided with erythema and tumour swelling. Transient increases of IL-12 and interferon γ were measured in the serum and the tumour tissue, whereas IL-10 transiently increased only in the serum. The effect of intratumoural IL-12 EGT on the levels of IL-24 and vascular endothelial growth factor in the sera and tumour biopsies differed per dog. Via contrast-enhanced ultrasound (US) (on days 1, 8 and 35), we demonstrated that intratumoural IL-12 EGT resulted in a significant decrease of the relative blood volume and blood flow speed in the tumour compared with baseline. Metastases were present in two dogs. In one of these dogs, IL-12 EGT of the primary tumour caused a transient partial regression of the metastases, but not of the primary tumour. The second dog with metastases did not survive long enough to complete the entire treatment cycle. Despite encouraging immunostimulatory and anti-angiogenic effects after intratumoural IL-12 EGT, no clinically relevant outcomes were observed in this study, as persistent tumour regression could not be obtained. On the other hand, the laboratory and US results hold great promise for combinatorial strategies of intratumoural IL-12 EGT with conventional antitumour (immuno)therapies.

Combretastatin A4-phosphate and its potential in veterinary oncology: a review

For many years, research on anticancer therapy has focussed almost exclusively on targeting cancer cells directly, to selectively kill them or restrict their growth. But limited advances in this strategy have led researchers to shift their attention to other potential targets. Active research is now on-going on targeting tumour stroma. Vascular disrupting agents (VDAs) appear a promising class of anticancer drugs that are currently under investigation as a sole or combined therapy in human cancer patients. This article will briefly touch on the history and biology of combretastatin A4-phosphate (CA4P) as a typical example of VDAs and will concentrate on the side effects that can be expected when used in veterinary patients. Particularly, the pathogenesis of these side effects and how they may be prevented and/or treated will be discussed. The purpose of this article is to illustrate the potentials of CA4P as anticancer therapy in veterinary oncology patients.