Veterinary Clinical Sciences - Research Publications
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ItemLow-grade gastrointestinal lymphoma in dogs: 20 cases (2010 to 2016)(WILEY, 2018-03)OBJECTIVES: To report the clinical presentation, treatment and prognosis of dogs with low-grade gastrointestinal lymphoma. MATERIALS AND METHODS: Cases were solicited from the American College of Veterinary Internal Medicine Oncology Diplomate listserv. Medical records of dogs with low-grade gastrointestinal lymphoma diagnosed via a combination of histology and immunohistochemistry with or without analysis of polymerase chain reaction for antigen receptor rearrangement were included. Signalment, clinical signs, diagnostic test results, chemotherapy protocol, response to treatment, date of first progression, rescue therapies and date and cause of death or last follow-up visit were collected. RESULTS: Twenty cases were included. Males and small breed dogs were over-represented. Frequent clinical signs included weight loss, vomiting and diarrhoea. Most lymphomas were T-cell phenotype (95%), and epitheliotropism was commonly described (60%). Immunohistochemistry, polymerase chain reaction for antigen receptor rearrangement or both were frequently required for definitive diagnosis. Two dogs had resection of an intestinal mass, and all dogs were treated with chemotherapy; chlorambucil and prednisone were most commonly prescribed. Overall response rate was 70%, and median survival time was 424 days (95% confidence interval: 105 to 1206 days). CLINICAL SIGNIFICANCE: Low-grade gastrointestinal lymphoma appears to be a rare condition in dogs, and treatment with chemotherapy results in a high response rate and favourable survival times. Further study is needed to determine its prevalence in dogs with chronic enteropathies.
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ItemInflammatory bowel disease versus chronic enteropathy in dogs: are they one and the same?(WILEY, 2016-11)The aim of this review is to discuss why "chronic enteropathy" might be a better term than "inflammatory bowel disease" in dogs, because the treatment and outcome of the disease is very different from that of inflammatory bowel disease in humans. The effect of food, antibiotics and immunosuppressant drugs on chronic enteropathy will be reviewed. New treatments under investigation will also be introduced. Although there are several studies evaluating treatment of chronic enteropathy in dogs, the quality and quantity of evidence supporting individual therapies remains scarce and more work is needed to improve management of this disease. Finally, new findings about dogs with chronic enteropathy complicated by protein-losing enteropathy will be discussed. Although prognosis for these dogs is poor, recent data might help improve their treatment.
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ItemThe utility of diagnostic tests for immune-mediated hemolytic anemia(WILEY, 2019-10)BACKGROUND: A definitive diagnosis of immune-mediated hemolytic anemia (IMHA) can be difficult to make. However, it is critical to differentiate IMHA from other causes of anemia due to the impact on prognosis and outcome for IMHA patients. Recently published American College of Veterinary Internal Medicine recommendations for the diagnosis of IMHA should be followed to concurrently confirm ongoing anemia, verify in vivo hemolysis, and detect anti-erythrocyte antibodies. The reliability of immunologic IMHA tests varies depending on which test is used and how it is performed. OBJECTIVES: Our aims were to determine which tests are currently used in veterinary medicine to diagnose IMHA and review the utility of assays that have historically been used to diagnose IMHA. METHODS: A short survey was designed to see which diagnostic tests for IMHA were currently being used by veterinary practices. The survey was distributed via list-serves to veterinarians and veterinary technologists. A literature review was performed to report the utility of diagnostic tests for the diagnosis of IMHA. RESULTS: Survey respondents indicated a variability in test protocols used to diagnose IMHA. Most respondents perform saline agglutination or Coombs' tests to detect anti-erythrocyte antibodies. Additional tests that can be used to support a diagnosis of IMHA are discussed in this review. CONCLUSIONS: A standardized diagnostic approach should be followed to differentiate IMHA from other causes of anemia. Test methodology can vary from one laboratory to another, and clinicians should be familiar with the procedures used by their laboratory.
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ItemTreatment response and long term follow up in nineteen dogs diagnosed with chronic enteropathy in Australia(WILEY, 2019-09)Chronic enteropathy (CE) in dogs is common worldwide, but little data is available from Australia. The aim of this study was to describe treatment response and long-term outcome in a cohort of dogs with CE. Dogs were prospectively enrolled at Murdoch University and the University of Melbourne. After diagnostic investigation to rule out diseases other than CE, dogs underwent sequential therapeutic trials until achieving a clinical response (diet then antibiotics, and finally immunosuppressants). Success was defined as 75% reduction of clinical severity for a minimum of five weeks. A total of 21 dogs were enrolled, and 19 completed the study. One dog was euthanised for lack of response to treatment and one excluded for lack of owner compliance. Most dogs responded to diet (n = 10), followed by antibiotics (n = 7) and immunosuppressants (n = 2). Long-term remission (median 21.1 months, [3.0-44.7]) was achieved in eight out of ten dietary responders without additional treatment. In contrast, only two dogs with antibiotic response remained in long-term remission, of which one needed on-going antibiotic treatment. Longer term remission was achieved in the two dogs treated with immunosuppressants with on-going low dose therapy. This study concludes that most dogs referred for CE in Australia respond to dietary treatment (even after previous dietary interventions), and remission is long-term compared to dogs treated with an antibiotic. Furthermore, the need for long-term antibiotics in some dogs to maintain response may lead to antibiotic resistance. This study supports adequate dietary trials for CE in dogs, and a need for alternative second-line treatments.
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ItemIntestinal Small Cell Lymphoma: Are Dogs Big Cats?(ACVIM, 2019-06-08)Previously T-cell lymphomas of the gastrointestinal tract in human were classified as enteropathy-associated T-cell lymphoma (EATL) type I and type II. Type I is associated with celiac disease and characterized by large lymphocytes, whereas type II is not associated to enteropathies and characterized by small lymphocytes. In view of these differences, the nomenclature has been changed and EATL currently refers only to type I and type II has been renamed monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).1 EATL has an aggressive clinical course and tumor cells most commonly have an αβ T-cell receptor phenotype. In comparison MEITL tumour cells express CD8, CD56, and megakaryocyte-associated tyrosine kinase. T-cell lymphoproliferative disorder (TLPD) is another type of small cell lymphoma described in the intestinal tract. This lymphoma has typically an indolent clinical course and commonly express CD8 and is negative for CD4 and CD56, Markers of T-cell lymphomas of the gastrointestinal tract have been much less extensively studied in cats and dogs and for this reason for the purpose of this lecture small cell lymphoma (SCL) will be used for neoplastic cells with nuclei smaller than 2 red blood cells in diameter and large cell lymphoma (LCL) for larger neoplastic cells. SCL characterized by infiltration of the intestinal mucosa by mature T-cells with variable epitheliotropism has been described for more than 10 years in cats. SCL has better outcome than other types of lymphoma in this species, with median survival times over 1.5 years.3 Although criteria have been described in cats to diagnose SCL, these are not as well defined in dogs. However, several recent studies support that SCL is also present in dogs and the clinical findings and outcome will be described in this presentation.
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ItemChronic Enteropathy In Canines: Prevalence, Impact And Management Strategies(Dove Press, 2019-12-06)In this article, the studies about the prevalence of chronic enteropathy are reviewed as well as the information regarding short- and long-term prognosis for dogs treated with the three most common therapies; these include dietary modification, antibiotics, and immunosuppressants. Although the data available are limited, most studies support a good to excellent long-term response in dogs that have a successful food trial, whereas the response is poor with antibiotics or on-going treatment is required to retain remission. There is a risk of antimicrobial resistance developing with inappropriate use of antimicrobials such as in these situations. The published information highlights the need for alternative strategies to antibiotic treatment to manipulate the GI microbiome, and in the final part of this article studies on the use of probiotic for the treatment of chronic enteropathy are reviewed.
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ItemACVIM consensus statement on the diagnosis of immune-mediated hemolytic anemia in dogs and cats(WILEY, 2019-03)Immune-mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune-mediated erythrocyte destruction, and adverse consequences of long-term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence-based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.
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ItemChanges in duodenal CD163-positive cells in dogs with chronic enteropathy after successful treatment(SAGE PUBLICATIONS LTD, 2018-10)Chronic enteropathy (CE) in dogs is characterized retrospectively per treatment response as food-responsive enteropathy (FRE), antibiotic-responsive enteropathy (ARE), and immunosuppressant-responsive enteropathy (IRE) - the latter most resembling inflammatory bowel disease in people. The aim of this study was to characterize duodenal macrophages (Mϕ) in CE using immunohistochemistry; with calprotectin (CAL) as a marker of early differentiated Mϕ and CD163 expression as a marker for resident Mϕ in the duodenum before and after treatment. Prior to treatment, dogs with FRE and IRE had a lower CD163+/CAL+ ratio than control dogs (CTRL) in crypts; this increased significantly and normalized compared with CTRL after treatment. Conversely, the CD163+/CAL+ ratio in dogs with ARE was comparable to that in healthy dogs before and after treatment. In summary, these results suggest that Mϕ play a role in the pathogenesis of CE in FRE and IRE, with a decrease in resident Mϕ and an increase in early differentiated Mϕ, but not in ARE dogs. Mϕ normalize after successful treatment.
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ItemEffect of immunosuppressive drugs on cytokine production in canine whole blood stimulated with lipopolysaccharide or a combination of ionomycin and phorbol 12-myristate 13-acetate(John Wiley & Sons, 2019-05)A pharmacodynamic assay has been previously developed to monitor ciclosporin treatment in dogs by assessing inhibition of cytokine transcription after whole blood stimulation with 12-myristate 13-1 acetate and ionomycin (PMA/I). In this study, whole blood stimulation with either PMA/I or lipopolysaccharide (LPS) was used to assess the effect of multiple drugs (azathioprine, ciclosporin, mycophenolate, leflunomide and prednisone) after a 7-day treatment course on production of cytokines measured with a multiplex assay in healthy dogs (n = 4 for each treatment). Interleukin-10 (IL-10), interferon gamma (IFN?) and tumour necrosis factor alpha (TNFa) were significantly activated by PMA/I stimulation and IL-6, IL-10 and TNFa by LPS stimulation, in the absence of immunosuppressive drugs. After ciclosporin treatment, IL-10, IFN? and TNFa production was significantly reduced after stimulation with PMA/I compared to pre-treatment. After prednisone treatment, TNFa production was significantly reduced after stimulation with PMA/I or LPS compared to pre-treatment. No significant change was observed after treatment with azathioprine, leflunomide or mycophenolate. This methodology may be useful to monitor dogs not only treated with ciclosporin, but also with prednisone or a combination of both. Further studies are needed to assess the use of this assay in a clinical setting.