Canine brain tumours: a model for the human disease?

Canine brain tumours are becoming established as naturally occurring models of disease to advance diagnostic and therapeutic understanding successfully. The size and structure of the dog's brain, histopathology and molecular characteristics of canine brain tumours, as well as the presence of an intact immune system, all support the potential success of this model. The limited success of current therapeutic regimens such as surgery and radiation for dogs with intracranial tumours means that there can be tremendous mutual benefit from collaboration with our human counterparts resulting in the development of new treatments. The similarities and differences between the canine and human diseases are described in this article, emphasizing both the importance and limitations of canines in brain tumour research. Recent clinical veterinary therapeutic trials are also described to demonstrate the areas of research in which canines have already been utilized and to highlight the important potential benefits of translational research to companion dogs.     

Photodynamic detection of a canine glioblastoma using 5-aminolevulinic acid

Photodynamic detection using 5-aminolevulinic acid has been used to identify the surgical margins during resection of human primary brain tumours. Although there are some reports on its use in malignant tumours in veterinary medicine, it has never been used for primary brain tumours. Here we describe a canine glioblastoma that was detected at autopsy with protoporphyrin IX fluorescence induced by orally administered 5-aminolevulinic acid. The fluorescence was strongest towards the centre of the lesion and was absent in normal brain tissue. Moreover, the fluorescence findings were consistent with MRI and histopathological findings. Our findings suggest that photodynamic detection using 5-aminolevulinic acid might be useful for intraoperative fluorescence-guided resection of malignant gliomas in dogs.     

Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature

Cutaneous paraneoplastic syndromes are a group of noncancerous dermatoses associated with internal malignancy. Their recognition can facilitate detection and timely treatment of underlying cancer. More than 30 such disorders have been identified in the human scientific literature, whereas only a few are described in veterinary medicine. This may reflect a lower incidence in animals than in people or may be the result of failure to recognize an association between certain skin lesions and neoplasia. Establishing a relationship between a cutaneous disorder and neoplasia can be difficult unless the skin lesions are rare and almost always associated with a particular tumour type, as is the case for most recognized veterinary paraneoplastic dermatoses. Among these are feline paraneoplastic alopecia, feline thymoma-associated exfoliative dermatitis, nodular dermatofibrosis, feminization syndrome associated with testicular tumours, superficial necrolytic dermatitis and paraneoplastic pemphigus. The aetiology of most cutaneous paraneoplastic syndromes has remained elusive in both people and animals.     

Histologic and immunohistochemical characterization of thymic epithelial tumours in the dog

Thymic epithelial tumour (TET) histologic subclassification has not been well described in the veterinary literature as it has in humans. The objective of this study was to identify and describe TET subtypes in dogs and to determine the utility of immunohistochemistry (IHC) in differentiating these subtypes. Samples were reviewed and classified according to a modified World Health Organization (WHO) criteria for human tumours of thymic origin. Signallment, presenting signs, treatment and survival data was collected from medical records. Histologic review confirmed the same subtypes as described in humans. Presence of high stage disease, pleomorphism, mitotic figures and capsular invasion was more common in atypical thymomas and thymic carcinomas than in thymomas. IHC was performed for GLUT‐1, CD5, CD117 and CK8/18; however, this was not useful in classifying the tumours.     

Veterinary Randomized Clinical Trial Reporting: A Review of the Small Animal Literature

The randomized clinical trial (RCT) is a valuable research method for the evaluation of new treatment and prevention regimens in veterinary medicine. Reporting of clinical trials in other disciplines has not been complete. Without complete information on the conduct and results of a clinical trial, readers cannot optimize their use of the information presented. This report represents an objective review of randomized clinical trials in the veterinary small animal literature from 1986 to 1990. Results indicate that RCT reports in the small animal veterinary literature are incomplete. The importance of reporting on particular aspects of RCT research is described.     

The role of hypoxia in canine cancer

Human oncology has clearly demonstrated the existence of hypoxic tumours and the problematic nature of those tumours. Hypoxia is a significant problem in the treatment of all types of solid tumours and a common reason for treatment failure. Hypoxia is a negative prognostic indicator of survival and is correlated with the development of metastatic disease. Resistance to radiation therapy and chemotherapy can be because of hypoxia. There are two dominant types of hypoxia recognized in tumours, static and intermittent. Both types of hypoxia are important in terms of resistance. A variety of physiological factors cause hypoxia, and in turn, hypoxia can induce genetic and physiological changes. A limited number of studies have documented that hypoxia exists in spontaneous canine tumours. The knowledge from the human literature of problematic nature of hypoxic tumours combined with the rapid growth of veterinary oncology has necessitated a better understanding of hypoxia in canine tumours.     

Clinical approach to renal neoplasia in budgerigars (Melopsittacus undulatus)

Renal neoplasia in budgerigars (Melopsittacus undulatus) is seen regularly in general practice and is of interest to many practicing veterinary surgeons. This review article provides an overview of the current knowledge and the most recent reports in avian literature regarding renal tumours in budgerigars, with the emphasis on clinical diagnosis and treatment. The high prevalence of renal neoplasia in budgerigar is discussed, with notes on the most commonly diagnosed tumours, possibility of metastases, sex and age predisposition. The possibility of ultrasonography and radiography in the diagnosis of this pathological condition are compared as well as the possible role of blood and urine analyses. Two studies are described, both of which investigate the possible involvement of a retrovirus as the aetiological agent.     

Congenital lipoblastoma in a neonate calf: first report in veterinary literature

Lipoblastoma is a rare benign tumour of adipose tissue that usually occurs in young children. Although around 100 cases of lipoblastoma have been reported in humans, no report has been previously described in animals. This case report describes the clinical and histopathological findings of a congenital lipoblastoma located at the tail base of a 2-day-old male calf. Grossly, the mass was pink with a partly ulcerated and haemorrhagic surface. The calf showed no neurological deficits. Radiographs of the vertebral column revealed no abnormalities, and surgical excision was performed. Histopathology of the mass was consistent with lipoblastoma. The calf was followed up for 13 months and found to be healthy with no signs of recurrence. To the best of the authors' knowledge, this is the first case of lipoblastoma in the veterinary literature. Lipoblastoma should thus be considered in the differential diagnosis list for congenital adipose tissue tumours in animals.     

Multiple progressive piloleiomyomas in a ferret (Mustela putorius furo): a case report

A 2.5‐year‐old ovariectomized female ferret developed multiple progressive linear and raised nodules on the skin. The first lesions occurred on the tail, which was then amputated. Over the following 3 years, additional lesions appeared in the vicinity of the scar and then further rostrally on the flanks and thorax. Histological and immunohistochemical investigation led to a diagnosis of multiple piloleiomyomas. The unique characteristics of this ferret disease are described and compared with those of multiple piloleiomyomas in humans and with those of other cutaneous smooth muscle cell tumours reported in the veterinary literature.     

Does the taking of biopsies affect the metastatic potential of tumours? A systematic review of reports on veterinary and human cases and animal models

Clinicians and pathologists are sporadically asked by owners whether the taking of tumour biopsies may affect the behaviour of the tumour, including its potential to metastasise. Unfortunately, systematic studies on this subject are unavailable in veterinary medicine, and the aim of this study was to estimate the risk of adverse effects of biopsy taking on tumour progression in animals. A systematic review of veterinary and human case reports and clinical studies as well as experimental animal models of biopsy-induced tumour metastasis was undertaken. There were only two veterinary case reports of needle tract metastases (NTM) following the taking of needle biopsies from urogenital and pulmonary tumours. Seventeen experimental studies found a high incidence of NTM but only a rat osteosarcoma and a hamster squamous carcinoma model showed an increased incidence of distant or regional metastases after incision or excision biopsy. In human medicine, the occurrence of NTM has been reported after the taking of biopsies from mesotheliomas (15%), melanomas (11%) and gall bladder tumours (11%), liver metastases of colon carcinomas (4%) and mammary carcinomas (4%) but an incidence of only <1% for all other tumours. Circulating tumour cells increased immediately after the taking of biopsies from human squamous cell, prostate, breast and hepatocellular carcinomas. Although no increased risk of biopsy-induced distant metastasis has been reported for any type of tumour, this is inconclusive due to a lack of non-biopsied control groups in human studies. Reports of biopsy-induced metastasis in animal tumours indicate that the taking of transcutaneous biopsies from urogenital tumours may be associated with a risk of NTM. However, there is no evidence of a general increase in risk of distant metastases in any tumour type in people or animals. The overall risk therefore appears to be negligible when compared to the valuable information obtained from biopsies in veterinary practice.     

A general survey of tumours in the horse.

Published figures from veterinary schools indicate that tumours may account for about 1 to 3 per cent of surgical cases. In this paper an account is given of clinical and pathological aspects of the tumours that are most likely to be encountered in practice, either as visibly or palpably detectable masses of tissue, or as internal tumours responsible for clinical signs. Amongst the common and important tumours dealt with, the most prominent are "equine sarcoid", squamous-cell carcinoma (of eye region and of glans penis), granulosa-cell tumours and melanomas. Well over a hundred references provide entry to the relevant literature. The need for further pathological and clinical studies of equine tumours is stressed.     

The animal's microbiome and cancer: A translational perspective

Cancer is a substantial global health problem both in humans and animals with a consistent increase in mortality and incidence rate. The commensal microbiota has been involved in the regulation of several physiological and pathological processes, both within the gastrointestinal system and at distant tissue locations. Cancer is not an exception, and different aspects of the microbiome have been described to have anti- or pro-tumour effects. Using new techniques, for example high-throughput DNA sequencing, microbial populations of the human body have been largely described and, in the last years, studies more focused on companions' animals have emerged. In general, the recent investigations of faecal microbial phylogeny and functional capacity of the canine and feline gut have shown similarities with human gut. In this translational study we will review and summarize the relation between the microbiota and cancer, in humans and companion animals, and compare their resemblance in the type of neoplasms already studied in veterinary medicine: multicentric and intestinal lymphoma, colorectal tumours, nasal neoplasia and mast cell tumours. In the context of One Health, microbiota and microbiome integrative studies may contribute to the understanding of the tumourigenesis process, besides offering an opportunity to develop new diagnostics and therapeutic biomarkers both for veterinary and human oncology.     

INVITED REVIEW—NEUROIMAGING RESPONSE ASSESSMENT CRITERIA FOR BRAIN TUMORS IN VETERINARY PATIENTS

The evaluation of therapeutic response using cross‐sectional imaging techniques, particularly gadolinium‐enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the response evaluation criteria in solid tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging‐based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and response assessment in neuro‐oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment‐induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy‐induced changes. Finally, although objective endpoints such as MR imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria.     

Contrast ultrasound: general principles and veterinary clinical applications

The concept of contrast enhancement has significantly extended the usefulness of ultrasound imaging in human medicine and medical research over the past decade. The persistence and efficacy of ultrasound contrast agents has been improved and specific imaging sequences have been developed. Contrast ultrasound provides Doppler and grey-scale enhancement. Doppler examinations are improved when studying deep or small vessels and vessels with low flow velocities. Specific contrast imaging sequences allow detection of tissue enhancement with grey-scale ultrasound which enables assessment of tissue perfusion. Major clinical applications of contrast ultrasound in the human medicine field are the heart, the parenchymal organs such as the liver, spleen and kidneys, and vascular applications. Many other interesting applications have been identified and beside their diagnostic value, intensive research is currently investigating the use of ultrasound contrast agents for therapeutic applications such as targeted delivery of drug- or gene-loaded microbubbles. In the last few years, contrast ultrasound has also been introduced in veterinary medicine. Its usefulness has been shown in diseases of the liver, spleen, kidney, pancreas, lymph nodes and superficial tumours. In the present article, an overview of the physical principles, imaging techniques and image analyses is presented. In addition, a literature review details the current use in veterinary medicine and areas of potential utilization are discussed.     

Myelopathy caused by a histiocytic sarcoma in a cat

An eight-year-old, female spayed, domestic shorthair cat presented with a three-week history of progressive general proprioceptive ataxia and upper motor neuron paresis of the hindlimbs. Computed tomography revealed a mediastinal mass invading the vertebral canal with the T1 spinal nerve and roots, causing extramedullary compression of the cranial thoracic spinal cord. Histopathological and immunohistochemical studies of the mass during postmortem examination disclosed a neoplasm, later determined to be a poorly differentiated histiocytic sarcoma. Feline histiocytic tumours are rare, with only two prior reports existing in the veterinary literature. This report details a case work-up and reviews the literature on feline histiocytic diseases and tumours affecting the feline spinal     

Ciliary body epithelial tumours in the dog and cat; a report of thirteen cases

The veterinary literature regarding ciliary body epithelial tumours is reviewed with a comparative perspective to serve as a background for a discussion of the epidemiological, clinical, morphological, and biological behavioural features of eleven canine and two feline cases. Six of the canine cases were adenomas and five were adenocarcinomas; both feline cases were adenocarcinomas. It would appear that these lesions are relatively common intraocular tumours that may present with a variety of clinical signs and relatively consistent morphological characteristics. The potential for metastasis of malignant tumours exists but metastasis occurs infrequently in the advanced stages of the disease. Differential diagnosis and clinical management are discussed.     

Clinical utility of pneumogastrography in dogs

Pneumogastrography utilizes negative contrast media such as air or carbonated beverages to improve visualization of luminal contents and mucosal surfaces within the stomach. Pneumogastrography as a diagnostic technique in cases of gastric disease has not been widely described in the veterinary literature and is a procedure that may yield additional information not obtained from survey radiographs. This technique is useful in the diagnosis of luminal and mucosal gastric diseases. In this article, the pneumogastrography technique and relevant literature are reviewed. Six case examples are included that demonstrate the utility of pneumogastrography in dogs with gastric disease.     

Fibromatous epulis and peripheral odontogenic fibroma in horses

Fibromatous epulis is a rare tumour in horses which is analogous to the same condition in dogs and peripheral odontogenic fibromas in man. The nomenclature is varied throughout the veterinary literature, but these tumours are most correctly known as peripheral odontogenic fibromas. Although these lesions are benign, they have a high recurrence rate in other species, so wide local excision is important to give the best possible prognosis.     

Successful treatment of hepatic failure secondary to diazepam administration in a cat

A 2-year-old castrated male domestic shorthair cat developed acute hepatic failure following oral diazepam administration for behavioral problems. The patient survived with intensive supportive care and was discharged after 5 days in hospital. Successful treatment of diazepam-associated fulminant hepatic failure in cats has rarely been described in the veterinary literature.