The Canadian Veterinary Journal La Revue Vétérinaire Canadienne The

April/Avril 2018 The Canadian Veterinary Journal

Vol. 59, No. 04 Vol. 59, La Revue vétérinaire canadienne

April/Avril 2018 Volume 59, No. 04

Successful management of lymphangiosarcoma in a puppy using a tyrosine kinase inhibitor

Primary colonic hemangiosarcoma in a dog

Retrobulbar malignant peripheral nerve sheath tumor in a golden retriever dog: A challenging diagnosis

Urethral intussusception following traumatic catheterization in a male cat

Sacrocaudal (sacrococcygeal) intervertebral disc protrusion in 2 cats

Surgical management of long bone fractures in cats using cortical bone allografts preserved in honey

Update on the use of trilostane in dogs

Evaluation of environmental sampling methods for detection of Salmonella enterica in a large animal veterinary hospital

Seroprevalence of Cache Valley virus and related viruses in sheep and other livestock from Saskatchewan, Canada

Effect of different analgesic techniques on hemodynamic variables recorded with an esophageal Doppler monitor during ovariohysterectomy in dogs

Estrogen-induced myelotoxicity in a 4-year-old golden retriever dog due to a Sertoli cell tumor FOR PERSONAL USE ONLY ID_96347_PC_Ads_DOG_CVJ_EN.pdf 1 3/6/18 6:26 PM

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APRIL/AVRIL 2018 Contents Table des matières

SCIENTIFIC RUBRIQUE SCIENTIFIQUE

CASE REPORTS REVIEW ARTICLE RAPPORTS DE CAS COMPTE RENDU 367 Successful management of 397 Update on the use of trilostane in dogs lymphangiosarcoma in a puppy using Julie Lemetayer, Shauna Blois a tyrosine kinase inhibitor Ji-Hyun Kim, Hakyoung Yoon, Hun-Young Yoon, ARTICLES Kidong Eom, Hyun-Jeong Sung, Jung-Hyun Kim 408 Evaluation of environmental sampling 373 Primary colonic hemangiosarcoma in a dog methods for detection of Salmonella Munetaka Iwata, Takeshi Aikawa, Yuta Miyazaki, enterica in a large animal veterinary hospital Shigeo Sadahiro Valerie R. Goeman, Stacy H. Tinkler, G. Kenitra Hammac, Audrey Ruple 379 Retrobulbar malignant peripheral nerve sheath tumor in a golden retriever dog: 413 Seroprevalence of Cache Valley virus and A challenging diagnosis related viruses in sheep and other livestock Cécile Briffod, Pierre Hélie, Julie De Lasalle, from Saskatchewan, Canada Louis-Philippe de Lorimier, Alicia R. Moreau, Fabienne D. Uehlinger, Wendy Wilkins, Derron A. Alves, Maria Vanore Dale L. Godson, Michael A. Drebot 385 Urethral intussusception following traumatic 419 Effect of different analgesic techniques catheterization in a male cat on hemodynamic variables recorded with Olivier Broux, Anne-Laure Etienne, an esophageal Doppler monitor during Annick Hamaide ovariohysterectomy in dogs 388 Sacrocaudal (sacrococcygeal) intervertebral Ignacio Sández, María Soto, Daniel Torralbo, Eva Rioja disc protrusion in 2 cats Gianluca Magi, Giunio Bruto Cherubini, STUDENT PAPER Olivier Taeymans COMMUNICATION ÉTUDIANTE 393 Surgical management of long bone fractures 425 Estrogen-induced myelotoxicity in a in cats using cortical bone allografts 4-year-old golden retriever dog due to preserved in honey a Sertoli cell tumor Márcio P. Ferreira, Marcelo M. Alievi, Isis S. Dal-Bó, Hayden Marshall Paula C.S. Gonzalez, Fernanda S. Nóbrega, Aline S. Gouvêa, Carlos A.C. Beck 349 QUIZ CORNER TEST ÉCLAIR

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APRIL/AVRIL 2018 Contents Table des matières

FEATURES RUBRIQUES SPÉCIALES

LETTER TO THE EDITOR BOOK REVIEW COURRIER DES LECTURES COMPTE RENDU DE LIVRE 337 Spore concentration and modified 407 Equine Laminitis host resistance as a cause of anthrax James L. Carmalt outbreaks — A comment Janice Crook NOTICES ANNONCES

EDITORIAL 392 New Products ÉDITORIAL Nouveaux produits 339 Challenges for the veterinary profession 396 Industry News Défis pour la profession vétérinaire Nouvelles de l’industrie Carlton Gyles 412 Index of Advertisers 345 VETERINARY MEDICAL ETHICS Index des annonceurs DÉONTOLOGIE VÉTÉRINAIRE 436 Classifieds Petites annonces CROSS-CANADA DISEASE REPORT RAPPORT DES MALADIES DIAGNOSTIQUÉES AU CANADA NEWS | NOUVELLES 429 First report of atypical porcine pestivirus in piglets with congenital tremor in Canada Fanny G. Dessureault, Martin Choinière, 351 NEWS Chantale Provost, Carl A. Gagnon NOUVELLES Heather Broughton, Isabelle Vallières THE ART OF PRIVATE VETERINARY PRACTICE L’ART DE LA PRATIQUE VÉTÉRINAIRE PRIVÉE 433 The bad news blues Myrna Milani

Contributors

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The Canadian Veterinary Journal Editorial policy: All published articles including editorials and letters reflect the La Revue vétérinaire canadienne opinions of the authors and do not necessarily reflect the opinion of the publisher. Publication of an advertisement does not necessarily imply that the publisher agrees 339 rue Booth Street with or supports the claims therein. Ottawa, Ontario K1R 7K1 Politique de la Rédaction : Tous les articles publiés, y compris les éditoriaux et les Telephone: (613) 236-1162 lettres, représentent l’opinion de l’auteur et non pas nécessairement la position de Fax: (613) 236-9681 l’éditeur. E-mail: [email protected] La publication d’une annonce ne signifie pas nécessairement que l’éditeur est d’accord Website/Site Web: www.canadianveterinarians.net avec son contenu ou qu’il l’appuie. www.veterinairesaucanada.net Editor-in-Chief/Rédacteur en chef © C anadian Veterinary Medical Association 2018 Carlton Gyles, Guelph, Ontario L’Association canadienne des médecins vétérinaires 2018 Associate Editors/Rédacteurs associés Bruce Grahn, Saskatoon, Saskatchewan The Canadian Veterinary Journal is indexed or abstracted in: Wayne McDonell, Guelph, Ontario La Revue vétérinaire canadienne est indexée ou ses articles sont Feature Editors/Rédacteurs des chroniques résumés dans : Jangi Bajwa, Burnaby, British Columbia AGRICOL, Biological Abstracts, Capsule Report, Current Contents — Agriculture, Bruce Grahn, Saskatoon, Saskatchewan Derwent Veterinary Drug File, EMBASE/Excerpta Medica, Myrna Milani, Charlestown, New Hampshire Index Veterinarius, Index Medicus, Quarterly Index, Science Citation Index, Small Debbie Stoewen, Ayr, Ontario Animal Practice, Veterinary Bulletin, Veterinary Reference Service, Veterinary Update. Tim Blackwell, Fergus, Ontario Assistant Editors/Rédacteurs adjoints Photo by/Photo de : Shutterstock Robert Friendship, Guelph, Ontario Greg Harasen, Regina, Saskatchewan Typesetting/Typographie Jacob Thundathil, Calgary, Alberta AN Design Communications Ron Johnson, Guelph, Ontario Richard Kennedy, Pincher Creek, Alberta Printed by/Imprimé par Shawn McKenna, Charlottetown, P.E.I. The Lowe-Martin Group Luis Gaitero, Guelph, Ontario Ottawa, Ontario Managing Editor/Directrice de la rédaction ISSN 0008-5286 Heather Broughton, Ottawa, Ontario Assistant Managing Editor/Directrice adjointe de la rédaction Return undeliverable Canadian addresses to: Stella Wheatley, Ottawa, Ontario 339 rue Booth Street Editorial Coordinator/Coordonnatrice de la rédaction Ottawa, Ontario K1R 7K1 Kelly Gray-Sabourin, Ottawa, Ontario e-mail: [email protected] Advertising Manager/Gérante de la publicité Laima Laffitte, Wendover, Ontario Subscriptions (2018). Annual: Canada $210 + applicable GST or HST; foreign $225 US; institutional $280. Express subscriptions available. Single issue/back issue: $25 each, institutional single issue = $50.00 + GST or HST, if applicable. (All prices Published monthly by/ subject to change.) Missing issues will be replaced if the Subscriptions Office is Publication mensuelle de notified within 6 months (for requests within Canada) and 1 year (for requests from Canadian Veterinary Medical Association abroad) of the issue date. The publisher expects to supply missing issues only when losses have been sustained in transit and when the reserve stock will permit. Telephone (613-236-1162) or (1-800-567-2862) and fax (613-236-9681) orders accepted with a valid Visa or MasterCard number. Please advise the publisher of address changes promptly. Abonnements (2018). Annuel : Canada 210 $ + TPS ou TVH en vigueur; pays étranger 225 $ É-U; prix d’une institution 280 $. Abonnement express disponible. Anciens numéros (chacun) : 25 $, ancien numéro d’institution 50 $ + TPS ou TVH en vigueur. Les prix sont sujets à changement sans préavis. Les numéros qui ne sont pas reçus seront remplacés si l’éditeur en est informée dans les 6 mois (pour les demandes venant du Canada) et 1 an (pour les demandes venant de l’étranger) suivant la date de parution. L’éditeur s’engage à remplacer les numéros manquants seulement lorsque les pertes ont été subies en transit et lorsque ses réserves le permettent. On peut payer son abonnement par téléphone (613-236-1162) ou (1-800-567-2862), par télécopieur (613-236-9681) ou par carte de crédit (Visa ou MasterCard). Veuillez aviser le bureau de l’éditeur de tout changement d’adresse.

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Spore concentration and modified host resistance as a cause of anthrax outbreaks — A comment Dear editor, to his volunteer experience around the globe to present an article I have been reading my CVJ monthly since I graduated. That’s that I think veterinarians in any scope of practice can learn 26 years. I generally put it in my list of chores. Not something from. It includes the concepts of global warming, geography, I enjoy. This has become a more common thought as I get older human culture, interspecies relationships, underlying disease, and perhaps more entrenched in my narrow niche of practice and immunity. It leaves me with hope for our profession. If you (affluent urban suburb, small animal). However, I was really glanced over his article because you thought it might not be excited by Dr. Robert Gainer’s article in the February CVJ relevant to you, I encourage you to re-read it. Congratulations entitled “Spore concentration and modified host resistance Dr. Gainer on a particularly impressive career and thank you as cause of anthrax outbreak’s: A practitioner’s perspective,” so much for sharing it. (Can Vet J 2018;59:185–187). Dr. Gainer has beautifully, elegantly, and creatively collected his life of practice and added it Janice Crook, DVM, North Vancouver, British Columbia.

Constructive and professional comments made in the spirit of intellectual debate are welcomed by the Editor. Writers are expected to be respectful of others and to ensure that letters are considerate and courteous. The Editor reserves the right to remove comments deemed to be inflammatory or disrespectful.

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Challenges for the veterinary profession Défis pour la profession vétérinaire

looked to several sources to identify perceived challenges for ai consulté plusieurs sources afin d’identifier les défis I the veterinary profession. There is evidence that our national J’ perçus au sein de la profession vétérinaire. J’ai trouvé and provincial professional organizations are doing an excellent des données signalant que nos organisations professionnelles job of assisting members in areas of animal health and the logical nationales et provinciales font de l’excellent travail pour aider extension to public health and One Health, and in working with les membres dans les domaines de la santé animale et dans le regulators to help us fulfill our mandate to society. For example, prolongement logique de la santé publique et d’Une seule santé a major initiative at present is helping veterinarians adapt to et en travaillant avec les organismes de réglementation afin new regulations related to the use of antimicrobial drugs. There de nous aider à exécuter notre mandat envers la société. Par are also other sources, such as private and public practitioners exemple, à l’heure actuelle, il y a une initiative majeure qui aide and educators, who have identified issues that they believe are les vétérinaires à s’adapter aux nouveaux règlements portant sur challenging for the profession. l’utilisation des antimicrobiens. Il y a aussi d’autres sources, One source I found very interesting was a column by comme des praticiens et des éducateurs privés et publics, qui Dr. Patty Khuly in Veterinary Practice News (1). Dr. Khuly is a ont identifié des enjeux qu’ils considèrent comme des défis pour veterinary practitioner and practice owner in Miami, Florida, la profession. and a frequent writer on various aspects of veterinary practice. Une source que j’ai trouvée très intéressante est un article She identified 7 challenges for the profession in 2017, 4 of de la Dre Patty Khuly dans Veterinary Practice News (1). La which apply to both the USA and Canada. The first of these Dre Khuly est praticienne vétérinaire et propriétaire de pratique 4 challenges, called The Corporate Squeeze, is the increasing à Miami, en Floride, et une chroniqueuse fréquente sur les consolidation of practice ownership by non-veterinarians, divers aspects de la pratique vétérinaire. Elle a identifié sept who are not likely to share the same priority as veterinarians défis pour la profession en 2017, dont quatre s’appliquent aux when it comes to the patient’s best interest. This is a topic on États-Unis et au Canada. Le premier de ces quatre défis, appelé which I have written previously. Recently, Mary Hope Kramer The Corporate Squeeze (La pression des grandes entreprises), also wrote on this subject — a concise and useful overview est la consolidation grandissante de la propriété des pratiques of the pros and cons of working in a clinic owned by a large par des non-vétérinaires qui ne partageront probablement pas corporation (2). In January of this year, Christopher Allen, a les mêmes priorités que les vétérinaires en ce qui concerne veterinarian and lawyer, gave us his perspective on reasons for l’intérêt supérieur des patients. C’est un sujet sur lequel j’ai the corporatization of the profession and “why veterinarians déjà écrit. Récemment, Mary Hope Kramer a aussi écrit à ce who hate corporate ownership end up selling out” (3). These are sujet en effectuant un survol concis et utile des avantages et des worth reading. inconvénients de travailler dans une clinique appartenant à une The 2nd issue, related to the first, is the decrease in opportu- grande société (2). En janvier de cette année, Christopher Allen, nities for 1- to 3-person practices. Dr. Khuly considers this to be médecin vétérinaire et avocat, nous a présenté son point de particularly worrying, given that “the veterinary temperament vue sur les raisons de la constitution en société de la profession is fundamentally independent.” I recall that years ago many et «pourquoi les vétérinaires qui détestent la propriété par student applicants seeking to enter the veterinary profession des grandes entreprises finissent par vendre» (3). Ces articles identified the opportunity to be an independent business méritent une lecture.

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person as one of the features that made the profession attractive. Le deuxième enjeu, qui est lié au premier, est la diminution However, this may be changing. A survey of US veterinarians de la présence des pratiques d’une à trois personnes. La in 2006 found that 53% aspired to practice ownership, in 2012 Dre Khuly considère que cette tendance est particulièrement that had fallen to 30%, and in 2015 it remained at 30% (4). inquiétante, vu que «le tempérament vétérinaire est In 2015, 38% of men, but only 24% of women, aspired to fondamentalement indépendant». Je me rappelle que, il y practice ownership. a plusieurs années, beaucoup de candidats étudiants qui The 3rd challenge is the divide between rich and poor pet cherchaient à entrer dans la profession vétérinaire jugeaient EDITORIAL owners. Dr. Khuly finds it heartbreaking when poor clients que la possibilité de gérer une entreprise indépendante était offer her $40 and inquire how much service that will buy. She l’un des avantages de profession. Cependant, cette tendance notes that “this glorious standard of care we’re so proud of is peut être en voie de changer. Un sondage réalisé en 2006 auprès leaving the majority of pet owners behind” and suggests that des vétérinaires américains a constaté que 53 % aspiraient à la the profession should be working with municipal governments possession d’une pratique tandis que, en 2012, ce chiffre avait to allocate more funds to enhancement of animal shelters and chuté à 30 % et que, en 2015, il demeurait toujours à 30 % (4). veterinary care within the shelters. I consider this to be a big En 2015, 38 % des hommes, mais seulement 24 % des femmes, challenge, the dimensions of which are likely to increase as the souhaitaient devenir propriétaires. gap between rich and poor increases and the requirements of Le troisième défi est l’écart entre les propriétaires d’animaux new standards of care become more expensive. A related matter de compagnie riches et pauvres. La Dre Khuly trouve qu’il is the provision of veterinary services to remote areas and areas est désolant lorsque des clients pauvres lui offrent 40 $ et with low-animal population density. demandent quels services ils peuvent se procurer à ce prix. Elle The 4th challenge is the lack of diversity in the veterinary signale que «cette glorieuse norme de soins dont nous sommes profession. Dr. Khuly states that “since ours is arguably the si fiers n’est pas à la mesure de la majorité des propriétaires whitest profession in America, and a conservative one at that, d’animaux de compagnie» et suggère que la profession devrait it only makes sense that we might have trouble attracting and travailler avec les gouvernements municipaux afin d’allouer maintaining veterinarians who hail from non-white backgrounds plus de fonds pour l’amélioration des refuges pour animaux and less traditional cultures.” I know that deans of veterinary et des soins vétérinaires dans les refuges. Je considère que schools in the US and Canada have been conscious of this cette situation représente un défi important, qui prendra challenge and have been seeking to encourage attendance at probablement de l’ampleur au fur et à mesure que l’écart entre veterinary schools by non-white students. It is likely that in the les riches et les pauvres augmentera et que les nouvelles normes past minorities did not see many people like themselves in the de soins deviendront plus dispendieuses. Une question connexe veterinary profession in Canada but I believe this is changing. est la prestation de services vétérinaires dans les régions éloignées In support of this belief, I have observed a noticeable increase et les régions ayant une faible densité de population animale. in non-white students in recent veterinary classes. It wasn’t so Le quatrième défi est l’absence de diversité au sein de la long ago that women didn’t see many people like themselves in profession vétérinaire. La Dre Khuly déclare que «vu que notre the veterinary profession; so change does occur. profession est sans doute la profession la plus blanche aux Another set of challenges (not on Dr. Khuly’s list) relate to États-Unis et qu’elle est de surcroît très conservatrice, il est veterinary education. Veterinary schools select the students, edu- entièrement logique que nous éprouvions de la difficulté à cate them on the basis of a curriculum that is typically developed attirer et à conserver des vétérinaires qui proviennent de milieux by academics with input from practitioners and which must non blancs et de cultures moins traditionnelles». Je sais que meet the demands of a comprehensive licensing examination. les doyens des écoles de médecine vétérinaire aux États-Unis The graduates then go out to work primarily with, and for, et au Canada sont conscients de ce défi et qu’ils cherchent à practitioners. The problem of trying to squeeze all the informa- encourager la fréquentation des écoles de médecine vétérinaire tion and technical skills associated with all species into a 4-year par des étudiants non blancs. Il est probable que, par le passé, curriculum, identified decades ago, is getting more severe with les minorités ne voyaient pas des personnes comme elles-mêmes every passing year as information expands and societal needs dans la profession vétérinaire au Canada, mais je crois que la evolve in both private and public practice. situation change. En effet, j’ai remarqué une hausse visible The Oxford dictionary defines a challenge as “a task or situ- des étudiants non blancs dans les plus récentes promotions ation that tests someone’s abilities.” These challenges will test vétérinaires. Il n’y a pas si longtemps que les femmes ne voyaient not only our abilities but also our resolve to tackle difficult and pas de personnes comme elles-mêmes dans la profession sometimes divisive issues that we encounter. vétérinaire. Il est donc permis de croire que des changements sont à l’œuvre. References Un autre groupe de défis (qui ne figuraient pas sur la liste 1. Khuly P. The 7 top challenges facing veterinary medicine in 2017. de la Dre Khuly) portent sur l’éducation vétérinaire. Les écoles February 27, 2017. Available from: https://www.veterinarypracticenews. com/the-7-top-challenges-facing-veterinary-medicine-in-2017/ Last de médecine vétérinaire choisissent les étudiants et elles leur accessed February 6, 2018. fournissent une éducation en se fondant sur un curriculum 2. Kramer MH. The Pros and Cons of Working at a Corporate Vet Clinic. qui est habituellement élaboré par des universitaires, avec October 23, 2017. Available from: https://www.thebalance.com/pros- and-cons-of-working-at-a-corporate-vet-clinic-125562 Last accessed la rétroaction des praticiens, et doit satisfaire aux exigences February 6, 2018. d’un examen d’agrément exhaustif. Les diplômés vont ensuite

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3. Allen CJ. Consolidation nation: Why veterinarians who hate corporate dvm360.com/state-profession-checking-veterinarians-practice-ownership- ownership end up selling out. January 31, 2018. Available from: http:// plans Last accessed February 1, 2018. ■ veterinarynews.dvm360.com/consolidation-nation-why-veterinarians- who-hate-corporate-ownership-end-selling-out Last accessed February 6, 2018. Carlton Gyles 4. DVM 360. State of the Profession: Checking in on veterinarians’ practice (Opinions expressed in this column are those of the Editor) ownership plans. February 6, 2016. Available from: http://veterinarynews.

2. KRAMER, M.H. The Pros and Cons of Working at a Corporate Vet Clinic.

ÉDITORIAL travailler principalement avec et pour des praticiens. L’inclusion des connaissances et des compétences techniques associées Le 23 octobre 2017. Disponible au : https://www.thebalance.com/ pros-and-cons-of-working-at-a-corporate-vet-clinic-125562 Dernière à toutes les espèces dans un curriculum de quatre ans qui a consultation le 6 février 2018. été identifié il y a plusieurs décennies devient de plus en plus 3. ALLEN, C.J. Consolidation nation: Why veterinarians who hate corporate difficile chaque année avec l’expansion de l’information et ownership end up selling out. Le 31 janvier 2018. Disponible au : http:// veterinarynews.dvm360.com/consolidation-nation-why-veterinarians- l’évolution des besoins sociétaux dans la pratique tant privée who-hate-corporate-ownership-end-selling-out Dernière consultation que publique. le 6 février 2018. Le dictionnaire Oxford définit un défi comme une tâche ou 4. DVM 360. State of the Profession: Checking in on veterinarians’ practice ownership plans. Le 6 février 2016. Disponible au : http://veterinarynews. une situation qui met à l’épreuve les aptitudes d’une personne. dvm360.com/state-profession-checking-veterinarians-practice-ownership- Ces défis mettront à l’épreuve non seulement nos aptitudes plans Dernière consultation le 1er février 2018. ■ mais aussi notre détermination à résoudre les enjeux difficiles et parfois conflictuels qui se présentent à nous. Carlton Gyles (Les opinions exprimées dans cette rubrique sont celles du Renvois rédacteur en chef.) 1. KHULY, P. The 7 top challenges facing veterinary medicine in 2017. Le 27 février 2017. Disponible au : https://www.veterinarypracticenews. com/the-7-top-challenges-facing-veterinary-medicine-in-2017/ Dernière consultation le 6 février 2018.

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Ethical question of the month — April 2018 A dairy client has purchased a new system for raising suckling calves with an automatic milk feeding machine. There are design components of this group housing system that are worrisome but the client assures you that the salesman knows all about how to raise calves in this set-up. You are taken aback when you are told the cost. Group housing is considered more welfare friendly than individual calf hutches, so you are pleased in this regard. It is not long, however, before calves are showing signs of severe respiratory disease. You suspect the design of the new housing/feeding system is at fault but the owner is reluctant to accept any suggestions about changes because of the large investment he has made. Despite your best efforts to have changes made, your client prefers to routinely use prophylactic antibiotics to control the respiratory disease. He says that not to use routine antibiotics on each calf is a welfare issue. With the increased emphasis on antimicrobial stewardship, you feel you are going backwards in terms of prudent use practices to use antibiotics to overcome poor management decisions. How do you balance your responsibility to decrease the development of antimicrobial resistance with your responsibility to protect the health and welfare of these calves? Question de déontologie du mois — Avril 2018 Un client laitier a acheté un nouveau système d’élevage des veaux au pis doté d’un nourrisseur-allaiteur. Il y a des éléments de conception du système de logement en groupe qui sont inquiétants mais le client vous assure que le vendeur est bien renseigné sur la façon d’élever des veaux dans cette installation. Vous êtes surpris lorsqu’il vous informe du prix. Le logement en groupe est considéré comme étant plus convivial pour le bien-être que les huches à veaux individuelles et vous êtes donc heureux à cet égard. Cependant, peu de temps après, les veaux manifestent des symptômes sérieux de maladie respiratoire. Vous soupçonnez que la conception de ce nouveau système de logement et d’allaitement est en cause mais le propriétaire manifeste de la réticence à accepter les modifications suggérées en raison des investissements importants. Malgré vos meilleurs efforts pour apporter des changements, votre client préfère l’utilisation régulière d’antibiotiques prophylactiques afin de contrôler les maladies respiratoires. Il dit que l’utilisation régulière des antibiotiques représente un enjeu de bien-être. Dans le contexte de l’importance grandissante de l’antibiogouvernance, vous estimez que vous effectuez un pas en arrière dans vos efforts de promotion de l’utilisation prudente des antibiotiques lorsque vous utilisez des antibiotiques pour compenser les mauvaises décisions de gestion. Comment pouvez-vous parvenir à un équilibre entre votre responsabilité de réduction du développement de la résistance aux antimicrobiens et votre responsabilité de protection de la santé et du bien-être de ces veaux?

Responses to the case presented are welcome. Please limit your Les réponses au cas présenté sont les bienvenues. Veuillez reply to approximately 50 words and forward along with your limiter votre réponse à environ 50 mots et nous la faire parvenir name and address to: Ethical Choices, c/o Dr. Tim Blackwell, par la poste avec vos nom et adresse à l’adresse suivante : 6486 E. Garafraxa, Townline, Belwood, Ontario N0B 1J0; Choix déontologiques, a/s du Dr Tim Blackwell, 6486, telephone: (519) 846-3413; fax: (519) 846-8178; e-mail: E. Garafraxa, Townline, Belwood (Ontario) N0B 1J0; [email protected] téléphone : (519) 846-3413; télécopieur : (519) 846-8178; Suggested ethical questions of the month are also welcome! All courriel : [email protected] ethical questions or scenarios in the ethics column are based Les propositions de questions déontologiques sont toujours on actual events, which are changed, including names, loca- bienvenues! Toutes les questions et situations présentées dans tions, species, etc., to protect the confidentiality of the parties cette chronique s’inspirent d=événements réels dont nous involved. modifions certains éléments, comme les noms, les endroits ou les espèces, pour protéger l=anonymat des personnes en cause.

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Ethical question of the month — January 2018 On dairy herd health visits you routinely bring your technician along to assist you with various procedures. This technician has worked with you for several years and you greatly respect their expertise, dedication, and animal care ethic. On your way back to the clinic after one such visit, the technician mentions to you that at the previous herd health visit he saw the owner’s son repeatedly use an electric prod on a cow that was down in the alleyway and could not get up. On this visit he witnessed the same young man kicking a cow in the head to get her to back out of a stall. You have had reservations about the son’s husbandry skills for some time but have never observed any abusive behavior yourself. The owner is an outstanding dairyman. He has had some problems with this boy but hopes to have his son keep the farm in the family after he retires. Your technician expects you to act on behalf of the welfare of the cows. You suspect the boy has some mental health issues but this, of course, is not your area of expertise. How should you respond?

DÉONTOLOGIEVÉTÉRINAIRE Question de déontologie du mois — Janvier 2018 Lors de vos rondes dans les troupeaux de vaches laitières, vous amenez habituellement votre technicien pour vous assister lors des diverses interventions. Ce technicien travaille pour vous depuis plusieurs années et vous avez un grand respect pour son expertise, son dévouement et son éthique des soins aux animaux. Pendant le trajet de retour à la clinique après l’une de ces visites, le technicien mentionne que lors de la visite précédente du troupeau, il avait vu le fils du propriétaire qui utilisait à répétition un bâton électronique sur une vache qui était couchée dans l’allée et ne pouvait pas se lever. Lors de cette visite, il avait vu le même jeune homme qui donnait des coups de pied sur la tête d’une vache pour la faire sortir d’une stalle. Vous éprouviez certaines réserves à propos des compétences d’élevage du fils, mais vous n’aviez jamais observé un comportement abusif de première main. Le propriétaire est un producteur laitier exceptionnel. Son fils lui a causé quelques problèmes mais il espère que le jeune homme gardera la ferme dans la famille après sa retraite. Votre technicien s’attend à ce que vous preniez des mesures afin de protéger le bien-être des vaches. Vous soupçonnez que le jeune homme souffre de problèmes de santé mentale, mais ce n’est pas, bien entendu, votre domaine d’expertise. Comment devriez-vous réagir?

An ethicist’s commentary animal-abusive son slated to succeed father in dairy Unlike numerous situations we have examined in this column, Beginning in the early 20th century, there has been a ten- this particular case seems quite straightforward, without moral dency among psychologists and psychiatrists to “medicalize” considerations pulling in opposite directions. The only thing evil. A therapist friend of mine pointed out that if one gets that may create some hesitation is the fact that the dairyman is into a fight with somebody else and kills them, that person will considering turning the dairy over to the son, and accusing the probably go to jail. On the other hand, if the same person were latter of cruelty would inevitably hurt the father, who is himself, to turn the victim into pâté and eat him, he will very likely be we are told, an exemplary and caring husbandry person. On the committed to a hospital on the grounds of insanity, and serve other hand, an intervention at this point by the veterinarian, much easier time. I for one, very strongly believe in the exis- however painful to the father it may be, is far better than allow- tence of evil that should not be explained away or excused as ing the ruination of the dairy and its reputation by turning man- “mental illness.” As Thomas Szasz famously pointed out in the agement over to what appears to be a psychopathic personality. 1960s, minds are not the sorts of things appropriately referred In 2002, a seminal paper by Gleyzer, Felthous and Holzer, to as sick, given that it is impossible to find pathological lesions entitled “Animal Cruelty and Psychiatric Disorders” appeared in minds. in the Journal of the American Academy of Psychiatry and the Paradigmatic examples of patent evil can be found in child Law, (J Am Acad Psychiatry Law 2002;30(2):257–65). The con- abuse or animal abuse, where beings that are totally innocent clusion articulated in this paper is highly relevant to our topic. are hurt, often in vicious and prolonged ways, to satisfy the The authors affirmed that “A history of animal cruelty during abuser’s sadistic desires. When ordinary people, possessed of childhood was significantly associated with APD [Antisocial common sense and common decency, respond to such a situa- Personality Disorder], antisocial personality traits, and poly- tion by affirming “that is sick,” they are simply trying to capture substance abuse. Mental retardation, psychotic disorders, and unfathomable badness in a simple, comprehensible rubric. alcohol abuse showed no such association.” Denuded of psychi- It is well-known that no psychiatric treatment can cure child atric jargon, this paper expresses a fact that has been known for abuse or animal abuse. When my son, a psychiatrist, went many centuries, ever since St. Thomas Aquinas forbade cruelty through his psychiatry residency, the residents were given the to animals on the grounds that those who are cruel to animals opportunity to interact with a person with a record of violent are very likely to “graduate” to abusing humans, a point that child sexual abuse. In the course of their discussion, the abuser has been repeatedly verified by looking at the backgrounds of repeatedly affirmed that he should not be released from custody, violent offenders in prisons. or he would do it again.

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Though details are scanty, there is every indication that the regularly observed, and never allowed to be in a situation where son described in this case is a sadistic animal abuser. I would he can hurt an animal. He certainly should never be placed in not be at all surprised if further investigation found that he charge, no matter how glibly and earnestly he promises to avoid ETHICS MEDICAL VETERINARY victimized children as well. In the current context, I am not such action in the future. It is well-known that psychopaths inclined to present an answer as to what should be done with are enormously capable of simulating empathy when it suits such people. But it is obvious that the animal abuser should them — witness the infamous case of Ted Bundy and numerous not be put in charge of the dairy, any more than a child abuser others lacking a conscience. It is far better morally to hurt the should be placed in charge of a day care center. father this one time than allow the son to trample and destroy Were I the veterinarian, I would handle this case as “preven- a life’s work of which he has every reason to be proud. tive medicine” aimed at forestalling animal pain and suffering. I would approach the father confidentially and forthrightly and explain why, at the very least, the son should be carefully and Bernard E. Rollin, PhD

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Quiz Corner Test éclair

1. In which of the following age groups of dogs are signs of 1. Chez le chien, les signes de dermatite atopique se atopic dermatitis typically first noted? manifestent en premier de façon caractéristique dans quel A. Younger than 6 months of age groupe d’âge suivant? B. 1 to 3 years of age A. moins de 6 mois; C. 5 to 7 years of age B. entre 1 et 3 ans; D. 7 to 10 years of age C. entre 5 et 7 ans; E. Older than 10 years of age D. entre 7 et 10 ans; E. plus de 10 ans. 2. Which of the following is the usual protocol for treatment of canine hyperadrenocorticism with mitotane (Lysodren)? 2. Lequel des protocoles suivants constitue le traitement A. Daily oral administration for the rest of the dog’s life habituel de l’hyperadrénocorticisme à l’aide de mitotane B. A daily oral administration induction phase, followed by a (Lysodren) chez le chien? once- or twice-weekly administration maintenance phase A. Administration orale quotidienne durant le reste de la vie C. A one-time course of 7 days of oral therapy du chien. D. Lower doses for the treatment of adrenal neoplasia than B. Administration orale quotidienne d’une phase d’induction, for pituitary origin hyperadrenocorticism suivie de l’administration d’une phase d’entretien, une à E. Intermittent dosing, only if the dog has polyuria deux fois par semaine. C. Un seul traitement de thérapie orale de 7 jours. 3. Which of the following is the most common arrhythmia D. Faibles doses pour le traitement du néoplasme surrénalien, resulting in poor athletic performance by horses? puis de l’hyperadrénocorticisme d’origine hypophysaire. A. Mitral regurgitation E. Dosage intermittent, seulement si le chien souffre de B. Aortic insufficiency polyurie. C. Tricuspid regurgitation D. Atrial fibrillation 3. Lequel des problèmes suivants représente l’arythmie la plus commune qui se traduit par de mauvaises performances 4. Regarding ferrets, which of the following is true? athlétiques chez le cheval? A. Collect three times the amount of blood as the volume A. régurgitation mitrale; of serum required. B. insuffisance aortique; B. Collect twice the amount of blood as the volume of serum C. régurgitation tricuspide; required. D. fibrillation auriculaire. C. Collect blood directly from the heart. D. Restrain a ferret by grasping the scruff of the neck and 4. À propos des furets, lequel des énoncés suivants est vrai? pulling the legs backward. A. Il faut prélever trois fois plus de sang que le volume de sérum nécessaire. B. Il faut prélever deux fois plus de sang que le volume de sérum nécessaire. C. Il faut prélever le sang directement du cœur. D. La contention d’un furet se fait en l’empoignant par la peau du cou et en tirant les membres vers l’arrière.

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CVJ / VOL 59 / APRIL 2018 349 FOR PERSONAL USE ONLY

5. A dairy producer’s bulk milk tank somatic cell count 5. La numération des cellules somatiques du réservoir à lait increases from 200 000 to 1 000 000 cells/mL over d’un producteur laitier augmente de 200 000 à 1 000 000 4 months. The producer milks 200 cows and recently pur- de cellules/ml depuis les 4 derniers mois. Le producteur trait chased 5 additional milking cows. No other management 200 vaches et a récemment acheté 5 autres vaches. Aucun changes have been made. The clinical mastitis rate concur- autre changement de gestion de troupeau n’a été fait. Le rently increased from 1% to 2% of milking cows. These taux de mammite clinique a augmenté parallèlement de 1 % changes could be attributable to increased incidence of à 2 % des vaches dont on fait la traite. Ces changements which of the following infections? peuvent être attribuables à l’augmentation de l’incidence de A. Escherichia coli laquelle des infections suivantes? B. Klebsiella pneumoniae A. Escherichia coli; TESTÉCLAIR C. Streptococcus agalactiae B. Klebsiella pneumoniae; D. Streptococcus uberis C. Streptococcus agalactiae; E. Staphylococcus chromogenes D. Streptococcus uberis; E. Staphylococcus chromogenes.

(See p. 435 for answers./Voir les réponses à la page 435.)

Questions and answers were derived from Review Questions and Answers Les questions et les réponses sont extraites de Review Questions and for Veterinary Boards 2nd ed., a 5-volume series including Basic Sciences, Answers for Veterinary Boards 2nd ed., une série de cinq volumes qui Clinical Sciences, Small Animal Medicine and Surgery, Large Animal comprend Basic Sciences, Clinical Sciences, Small Animal Medicine and Medicine and Surgery, and Ancillary Topics, by kind permission of the Surgery, Large Animal Medicine and Surgery, et Ancillary Topics, avec publisher, Mosby–Year Book, Inc., St. Louis, Missouri. l’aimable permission de l’éditeur, Mosby–Year Book, Inc. de St. Louis (Missouri).

Have Another Look at CJVR Avez-vous consulté la RCRV dernièrement? Members of the CVMA are entitled to receive the Canadian Journal Les membres de l’ACMV reçoivent un abonnement gratuit à la of Veterinary Research (CJVR) at no additional charge. The CJVR, Revue canadienne de recherche vétérinaire. On peut consulter la in the form of an interactive (portable document format) pdf, can RCRV, qui est présentée en format pdf interactif, sur le site Web be found on the CVMA member-only website (www.canadian de l’ACMV réservé aux membres (www.veterinairesaucanada.net/ veterinarians.net/publications-research-issue.aspx). publications-research-issue.aspx). Published by the CVMA, this quarterly, peer-reviewed journal is Publiée par l’ACMV, cette revue trimestrielle évaluée par les pairs Canada’s only national veterinary research publication. est la seule publication nationale de recherche vétérinaire au Canada.

Articles from the January 2018 issue of CJVR that Les articles suivants du numéro de janvier 2018 de might be of interest to practitioners include: la RCRV pourraient intéresser les praticiens : Comparison of antimicrobial resistance genes in feedlots Comparison of antimicrobial resistance genes in feedlots and urban wastewater on page 24 and urban wastewater à la page 24 Comparison of 3 vaccination strategies against Comparison of 3 vaccination strategies against porcine reproductive and respiratory syndrome virus, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, and porcine circovirus Mycoplasma hyopneumoniae, and porcine circovirus type 2 on 3 pathogen challenge model on page 39 type 2 on 3 pathogen challenge model à la page 39

The CJVR, along with the monthly Canadian La RCRV, avec La Revue vétérinaire canadienne qui est Veterinary Journal, is also archived on PubMed Central publiée mensuellement, est aussi archivée sur PubMed (www.pubmedcentral.com) 6 months after publication. Central (www.pubmedcentral.com) six mois après la An interactive pdf of The CVJ is also available on the publication. member-only section of the CVMA website. Un pdf interactif de La RVC est aussi disponible dans la section réservée aux membres du site Web de l’ACMV.

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NEWS | NOUVELLES

Celebrate the Value of Volunteering Célébrons la valeur du bénévolat National Volunteer Week — Semaine nationale de l’action bénévole — April 15 to 21, 2018 Du 15 au 21 avril 2018 ational Volunteer Week provides a wonderful opportunity to a Semaine nationale de l’action bénévole offre une merveilleuse Nhonor the veterinarians, veterinary technicians/technologists, Loccasion d’honorer les médecins vétérinaires, les techniciens students and other volunteers who donate their time and expertise et technologues vétérinaires, les étudiants en médecine ainsi to the various projects undertaken by the Canadian Veterinary que les autres bénévoles qui donnent de leur temps et de leur Medical Association (CVMA) in support of Canada’s veterinary expertise aux divers projets entrepris par l’Association canadienne profession. des médecins vétérinaires (ACMV) afin d’appuyer la profession This year’s National Volunteer Week theme is “Celebrate the vétérinaire au Canada. Value of Volunteering.” The time and effort CVMA volunteers Le thème de la Semaine nationale de l’action bénévole de dedicate to the Association is immeasurable and the individuals cette année est «Célébrons la valeur du bénévolat». Le temps et les are invaluable. The CVMA would have not reached the momen- efforts consacrés par les bénévoles de l’ACMV à l’Association sont tous milestone of 70 years of existence without the commit- incommensurables et les personnes sont inestimables. L’ACMV ment of the thousands of volunteers who have served with us n’aurait pas atteint le jalon considérable de 70 années d’existence over 7 decades. The CVMA depends on the contributions of sans l’engagement des milliers de bénévoles qui ont travaillé our devoted volunteers across Canada to help our Association pour nous depuis plus de sept décennies. L’ACMV compte sur les achieve a variety of goals and objectives, and ensure the voice of contributions de nos bénévoles dévoués au Canada afin d’aider the Canadian veterinary profession is heard across the country notre association à atteindre divers buts et objectifs et à veiller à ce and around the world. We are indebted to them for their service. que la voix de la profession vétérinaire se fasse entendre à l’échelle Over 600 volunteers support the work of the Association, du pays et partout dans le monde. Nous leur sommes redevables through their work on our Executive, Council, various standing de leur service. committees, advisory groups, and task forces, and by reviewing Plus de 600 bénévoles appuient l’Association, dans le cadre de articles for our journals. CVMA’s volunteers take time from their leur travail au sein de notre exécutif, du Conseil, des divers comités demanding schedules to act as ambassadors in media interviews permanents, des groupes consultatifs, des groupes de travail et en révisant des articles pour nos revues. Les bénévoles de l’ACMV consacrent du temps, malgré leur horaire chargé, pour agir à titre d’ambassadeurs lors d’entrevues avec les médias ainsi que pour représenter l’ACMV et la profession vétérinaire au sein de plus de 28 conseils externes, associations ainsi que groupes législatifs et stratégiques différents tant au Canada qu’à l’étranger. Voici un aperçu des nombreux exemples de la façon dont les bénévoles ont récemment contribué aux efforts de l’ACMV : Les bénévoles du Comité sur le bien-être des animaux (CBA) travaillent à la défense et à la promotion du bien-être animal au sein de l’industrie animale, du gouvernement et du public. Le Comité a mis à jour plusieurs énoncés de position, notamment : Responsabilité des professionnels vétérinaires à l’égard de la violence et de la négligence envers les animaux; Capture des animaux sauvages pour le commerce d’animaux de compagnie; Castration des bovins, des moutons et des chèvres; Castration des chevaux, des ânes et des mulets; Élevage des chiens; Stérilisation des chiens et des chats; et Piégeage des animaux à fourrure. Le CBA a élaboré de nouveaux énoncés de position sur les sujets suivants : Utilisation des animaux lors de sports compétitifs; Utilisation des animaux dans le cadre des spectacles et des loisirs; Bien-être des vaches

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N de réforme; et Systèmes de logement pour les poules pondeuses. Le CBA a aussi révisé plusieurs Codes de pratiques du Conseil national pour les soins aux animaux d’élevage (CNSAE), dont ceux pour les bisons, les veaux lourds et les lapins. Les membres du Comité sur les enjeux nationaux (CEN) assurent le leadership et la défense des intérêts pour les enjeux vétérinaires nationaux touchant la profession. En 2017, l’ACMV a tenu son deuxième Forum annuel sur les enjeux nationaux durant le congrès annuel afin de se pencher sur la médecine vétérinaire and represent the CVMA and the veterinary profession on complémentaire et parallèle. Le CEN se sert de la rétroaction reçue 28 different external boards, associations, legislative and policy- durant le forum afin de réviser son énoncé de position actuel sur making groups, both in Canada and abroad. le sujet. Un nouvel énoncé de position est en voie d’élaboration sur Some of the many examples of how volunteers have recently les animaux d’assistance. La révision de la position sur la dentisterie contributed to the CVMA’s efforts are listed below: vétérinaire est terminée et la révision des énoncés de position Volunteers on the Animal Welfare Committee (AWC) advo- suivants est actuellement en cours : Diètes à base d’aliments crus cate and promote animal welfare with the animal industry, gov- pour les animaux de compagnie; Télémédecine; Médecine vétérinaire ernment, and the public. The Committee has reviewed a number complémentaire et parallèle; et Vaccination des animaux. Les of position statements, including: Responsibility of Veterinary membres du CEN ont participé aux consultations de Santé Canada Professionals in Addressing Animal Abuse & Neglect; Capture of sur le projet de loi sur le cannabis, la modification des politiques et Wild Animals for the Pet Trade; Castration of Cattle, Sheep and règlements de Santé Canada pour l’utilisation des antimicrobiens Goats; Castration of Horses, Donkeys and Mules; Dog Breeding; vétérinaires, la Proposition de frais pour les médicaments et Neutering of Dogs and Cats (Spay/Castration); and Trapping les instruments médicaux de Santé Canada et la consultation of Fur-Bearing Animals. The AWC has developed new position de l’Agence de la réglementation de la lutte antiparasitaire sur statements on: The Use of Animals in Competitive Sport; The l’utilisation des produits destinés à un traitement localisé pour les Use of Animals in Entertainment and Recreation; The Welfare animaux de compagnie. of Cull Dairy Cows; and Housing Systems for Laying Hens. Le Groupe consultatif sur la gouvernance des produits The AWC has also reviewed several Codes of Practice under the pharmaceutiques vétérinaires a consacré beaucoup de temps National Farm Animal Care Council (NFACC) including for à la participation à des groupes consultatifs d’experts pour des Bison, Veal Cattle, and Rabbits. projets dirigés par l’ACMV sur la surveillance de l’utilisation des Members of the National Issues Committee (NIC) provide antimicrobiens et le renouvellement des lignes directrices pour leadership and advocacy on national veterinary issues affect- l’administration judicieuse des antimicrobiens vétérinaires en ing the profession. The CVMA held its 2nd National Issues collaboration avec des praticiens vétérinaires et des partenaires de Forum during its Annual Convention in 2017 highlighting l’industrie, des universités et du gouvernement. Complementary and Alternative Veterinary Medicine. The NIC Le Groupe consultatif environnemental continue de is using the feedback received during the forum to help revise travailler à l’Initiative de l’ACMV pour une pratique vétérinaire its current position statement on the subject. A new position écoresponsable afin de fournir une source d’information sur le Web statement is being developed on Service Animals. Revision of sur la façon d’atténuer l’impact environnemental des pratiques et the Veterinary Dentistry position statement is complete, and des infrastructures vétérinaires. Le groupe continue d’encourager revision on the following position statements is underway: Raw les pratiques à communiquer leurs histoires de réussites à l’ACMV et Meat-Based Diets for Pets; Telemedicine; Complementary and d’inciter les autres à suivre leur exemple sur le plan écologique. Le Alternative Veterinary Medicine; and Vaccination of Animals. groupe sert aussi de ressource au Comité sur les enjeux nationaux NIC members have participated on Health Canada consultations qui le consulte sur des enjeux environnementaux particuliers, y and engagements on the proposed Cannabis Act, changes to compris une consultation récente avec l’Agence de la réglementation Health Canada policies and regulations on the use of veterinary de la lutte antiparasitaire (ARLA) sur l’utilisation des produits antimicrobials, Health Canada’s Fee Proposal for Drugs and destinés à une utilisation localisée pour les animaux de compagnie. Medical Devices, and the Pest Management Regulatory Agency Le Groupe consultatif sur la gestion commerciale (GCGC) consultation on the use of spot-on products in pets. appuie l’ACMV afin d’atteindre l’un de ses trois objectifs stratégiques, The Veterinary Pharmaceutical Stewardship Advisory soit celui «d’aider les vétérinaires à obtenir une carrière prospère et Group has dedicated much time to participating on the expert à atteindre une vie équilibrée». Ces bénévoles offrent des conseils advisory groups for CVMA-led projects on Antimicrobial use et de la rétroaction afin d’atteindre les objectifs du Programme de Surveillance and Renewal of the Veterinary Antimicrobial gestion commerciale dans le but de favoriser le bien-être personnel Prudent Use Guidelines in collaboration with veterinary practi- et professionnel des membres de l’ACMV. En 2017, le GCGC a tioners and partners from industry, academia, and government. collaboré au lancement du partenariat de l’ACMV avec HRdownloads The Environmental Advisory Group continues to work on afin d’offrir aux membres de l’ACMV des services de gestion à des the CVMA Green Veterinary Practice Initiative, providing a web- tarifs réduits. based source of information on how to improve the environmen- Chaque année, les bénévoles du Groupe consultatif des tal impact of veterinary practices and infrastructure. The group communications aident à choisir le thème et le slogan de la

352 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY continues to encourage practices to share their success stories campagne annuelle de la Semaine de la vie animale et fournissent N with CVMA and entice others to follow in their environmental des conseils pendant la préparation et l’exécution de la campagne. footsteps. The Group also remains a resource for the National Le Groupe fournit de nouveau de l’expertise et des commentaires Issues Committee to consult on specific environmental issues, sur la vaste campagne de sensibilisation dans les médias sociaux. including a recent Pest Management Regulatory Agency (PMRA) Chaque mois, l’ACMV partage un message et un graphique dans consultation on the use of spot-on products in pets. les médias sociaux afin de rehausser la sensibilisation à l’égard des The Business Management Advisory Group (BMAG) enjeux liés à la santé et au bien-être des animaux et d’informer les helps the CVMA with one of its 3 strategic objectives; “helping propriétaires sur les mesures qu’ils peuvent prendre pour guérir ou veterinarians achieve a successful career and a balanced life.” prévenir des maladies. These volunteers provide guidance and input into the Business Le Comité du perfectionnement professionnel (CPP) Management Program’s objectives with the goal of fostering contribue à améliorer la formation continue et professionnelle CVMA members’ personal and professional well-being. In de ses membres et de tous les vétérinaires. Les programmes 2017, the BMAG helped launch CVMA’s partnership with scientifiques, les ateliers et les activités présentés lors du HRdownloads to offer CVMA members discounted manage- congrès annuel de l’ACMV permettent aux vétérinaires et aux ment resources. autres membres de l’équipe de la pratique d’améliorer la pratique Each year volunteers on the Communications Advisory professionnelle et d’entrer en contact avec leurs pairs des autres Group help choose the theme and slogan for the annual Animal régions du Canada. Le congrès 2017 s’est déroulé à Charlottetown, Health Week campaign and provide guidance throughout the à l’Île-du-Prince-Édouard, et a affiché la plus haute fréquentation campaign’s preparation and execution. The Group is once again à l’assemblée générale annuelle où l’on a recensé plus de providing expertise and insight into the extended social media 240 participants. L’introduction d’une nouvelle appli du congrès, awareness campaign. Each month the CVMA shares a social EventMobi, a permis une grande interaction sur place entre les media message and graphic intended to create more awareness délégués, les exposants et les commanditaires. L’Atlantic Veterinary of animal health and welfare issues and what their owners can College a organisé divers laboratoires de travaux pratiques sur do to help or prevent illness. des sujets allant de l’extraction des dents chez les chiens et les The Professional Development Committee (PDC) helps chats à l’hématologie des petits animaux. Le Programme des futurs advance the continuous, professional growth of its members and leaders a de nouveau remporté du succès avec un nombre record all veterinarians. The scientific program, workshops and activities de 37 participants. offered at the Annual CVMA Convention enable veterinarians Les bénévoles du Bureau national des examinateurs (BNE) and other members of the practice team to enhance professional facilitent l’administration des examens d’agrément vétérinaire du practice and connect with peers from across Canada. The 2017 Canada, ils participent au processus d’agrément des collèges Convention was held in Charlottetown, Prince Edward Island, de médecine vétérinaire et examinent et évaluent les titres de and boasted the highest Annual General Meeting turnout with compétence au nom de certains organismes de réglementation over 240 attendees. The introduction of a new Convention app, provinciaux. En 2017, le Bureau national des examinateurs a émis EventMobi, led to high onsite interaction between delegates, 551 Certificats de compétence aux diplômés des cinq facultés exhibitors, and sponsors. The Atlantic Veterinary College hosted de médecine vétérinaire du Canada ainsi qu’à des médecins various wet labs on topics ranging from tooth extraction in dogs vétérinaires formés à l’international qui avaient réussi les examens and cats to small animal hematology. The Emerging Leaders du BNE. Program was once again a success with a record high attendance Les bénévoles du Comité d’agrément des programmes de of 37 participants. technologie en santé animale et de techniques vétérinaires Volunteers of the National Examining Board (NEB) (CAPTSATV) travaillent afin d’identifier et de promouvoir des help with the administration of Canada’s veterinary licensing normes et l’agrément des programmes de technologie de la santé examinations, participate in the veterinary college accredita- animale et de techniques vétérinaires. Pour suivre l’évolution tion process, and review and evaluate credentials on behalf rapide des exigences et des besoins en pratique vétérinaire, le of some of the provincial licensing bodies. In 2017, the NEB CAPTSATV passe constamment en revue les normes d’agrément en issued 551 Certificates of Qualification to graduates from the collaboration avec les 19 programmes agréés au Canada et avec 5 Canadian veterinary colleges, as well as to internationally des partenaires comme l’American Veterinary Medical Association. trained veterinarians who completed the NEB exams. En 2017, des inspections ont été réalisées pour quatre programmes Volunteers of the Animal Health Technology/Veterinary de technologie de la santé animale au Canada. Technician Program Accreditation Committee (AHTVTPAC) La Réserve vétérinaire canadienne (RVC) de l’Association work to identify and promote standards and accreditation for canadienne des médecins vétérinaires est un groupe national de animal health technologist and veterinary technician programs. vétérinaires autorisés qui sont disposés à intervenir afin de porter The AHTVTPAC constantly reviews accreditation standards in assistance rapidement aux gouvernements lors d’interventions en collaboration with the 19 accredited programs in Canada and cas d’éclosions de maladies animales exotiques et d’autres urgences partners such as the American Veterinary Medical Association to et catastrophes à grande échelle qui touchent les animaux. keep up with rapidly changing requirements and evolving needs Les bénévoles du Comité de la rédaction supervisent le in veterinary practice. In 2017, 4 accreditation site visits were fonctionnement et le contenu éditorial de La Revue vétérinaire made at 4 AHT programs across Canada. canadienne et de la Revue canadienne de recherche vétérinaire. Ces

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N The Canadian Veterinary Medical Association’s Canadian deux publications ne pourraient pas exister sans la contribution Veterinary Reserve (CVR) is a national, volunteer membership bénévole des nombreux rédacteurs et lecteurs. of qualified Canadian veterinarians who make themselves avail- Le Comité des Étudiants de l’ACMV (ÉACMV) et le Groupe able to rapidly assist governments in responding to outbreaks consultatif de liaison avec les étudiants (GCLÉ) créent un of foreign animal disease and other large-scale emergencies and lien entre l’ACMV et les étudiants en médecine vétérinaire et les disasters affecting animals. professeurs des cinq facultés de médecine vétérinaire du Canada. The volunteers of the Editorial Committee oversee the En 2017, le Comité des ÉACMV a planifié le Symposium 2018 des operation and editorial content of The Canadian Veterinary ÉACMV, qui a été organisé par l’Atlantic Veterinary College qui a Journal and the Canadian Journal of Veterinary Research. These retenu les services de la Dre Michelle Oakley comme conférencière 2 publications could not exist without the volunteer contribution invitée de l’événement. Les ÉACMV ont aussi organisé la deuxième of the numerous editors and peer reviewers. édition annuelle de l’Atelier de leadership étudiant qui s’est tenu à The Students of the CVMA (SCVMA) Committee and the l’Ontario Veterinary College et a compté plus de 70 participants. Student Liaison Advisory Group (SLAG) link the CVMA with L’objectif du Groupe consultatif sur le bien-être vétérinaire student veterinarians and faculty members at Canada’s 5 veteri- consiste à élaborer et à promouvoir des initiatives et des nary colleges. In 2017, the SCVMA Committee planned the programmes de bien-être vétérinaire à l’échelle nationale afin de 2018 SCVMA Symposium, hosted by the Atlantic Veterinary servir de complément aux programmes provinciaux ainsi que d’aider College and secured Dr. Michelle Oakley as the event’s key- les groupes et les provinces à élargir leurs propres initiatives de note speaker. The SCVMA also held the 2nd annual Student bien-être. Le Groupe consultatif a créé une section sur le site Web Leadership Workshop at the Ontario Veterinary College with de l’ACMV et il continue d’ajouter des ressources pertinentes sous over 70 participants. les catégories de Santé mentale et bien-être psychologique, Santé The Veterinary Wellness Advisory Group’s objective is to physique et Bien-être des vétérinaires. Le Programme de mentorat develop and promote veterinary wellness initiatives and pro- de l’ACMV est un autre programme étroitement lié au bien-être des grams at a national level to complement provincial programs, membres. L’ACMV a aussi réalisé un sondage auprès de toutes and help groups and provinces in expanding their own wellness les associations provinciales de médecins vétérinaires et des initiatives. The Advisory Group developed a section on the organismes de réglementation afin d’obtenir des renseignements sur CVMA website and continues to add relevant resources under les programmes de bien-être et de counseling qu’ils offrent à leurs the categories of Emotional and Mental Health, Physical Health, membres, les services de counseling spécifiques qui sont fournis, and Veterinarian Wellness. The CVMA Mentoring Program is le coût de ces programmes et de compiler des statistiques sur another program that is closely linked to member wellness. The l’utilisation des services. Les résultats du sondage ont été compilés CVMA also undertook a survey of all the provincial veterinary et partagés avec toutes les associations provinciales de médecins associations and regulatory bodies to obtain information about vétérinaires à titre d’information. their respective wellness/counselling programs available to their C’est grâce au dévouement des nombreux bénévoles que les members; the specific counselling services being offered; the cost réalisations de l’ACMV sont mises en œuvre. Nous vous remercions to offer such programs; and some aggregate usage statistics. The sincèrement de faire don de votre temps et de votre expertise! survey results were compiled and shared with all the provincial veterinary medical associations for their information. The CVMA’s achievements are due to the devotion of our many volunteers. We sincerely thank you for donating your time and expertise.

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2018 CVMA Convention Congrès 2018 de l’ACMV N July 5 to 8, 2018 Du 5 au 8 juillet 2018 Ignite Your Passion! Éveillez votre passion! he CVMA Convention is less than 5 months away! Spring e congrès de l’ACMV aura lieu dans moins de cinq mois! Passez Tinto action if you have not already registered for the Laux actes dès maintenant si vous n’êtes pas déjà inscrit au Convention. congrès. On Thursday, July 5, Ms. Heather Romano from iVET360, Le jeudi 5 juillet, Mme Heather Romano de iVET360, présentera will present 6 sessions in Business Management: “New six ateliers en gestion commerciale : «Nouvelle génération de Generation of Culture.” Ms. Romano will review returning and culture». Mme Romano se penchera sur la réintroduction et la mise implementing innovative training solutions back to the practice; en œuvre de solutions de formation à la clinique, l’amélioration de improving employee engagement while creating more time for l’engagement des employés tout en créant plus de temps pour le the manager; and understanding the importance and imple- gestionnaire et la compréhension de l’importance et de la mise en mentation of routine progress communication. Dr. Romano œuvre d’une communication régulière des progrès. La Dre Romano brings over 20 years of veterinary hospital experience to her contribue plus de 20 années d’expérience en clinique vétérinaire à current position with iVET360, including 14 years in veterinary son poste actuel auprès de iVET360, dont 14 années en gestion management. vétérinaire. Looking for breakfast? In 2018, the Convention is pleased to Vous cherchez un endroit où déjeuner? En 2018, le congrès offer a number of sponsored interactive breakfasts. Start your offrira plusieurs petits déjeuners interactifs commandités. day with Curacore’s The Top 10 Areas of Research in Integrative Commencez la journée en assistant à la causerie de Curacore Medicine that are Transforming Practice; or join Elanco in review- intitulée «The Top 10 Areas of Research in Integrative Medicine that ing Emerging Issues with Echinococcus — Small Tapeworm, Big are Transforming Practice»; ou joignez-vous à Elanco pour examiner le Problem. Still hungry? Nucleus Regenerative Therapies, LLC will sujet suivant «Emerging Issues with Echinococcus — Small Tapeworm, be presenting Clinical and Histologic Data Pertaining to the use of Big Problem». Vous avez encore faim? La compagnie Nucleus a Polyacrylamide Hydrogel for Intra-articular Injection in Horses. Regenerative Therapies, LLC présentera la conférence «Clinical and In addition to the interactive breakfasts, the Convention Histologic Data Pertaining to the use of a Polyacrylamide Hydrogel for is also offering 2 interactive dinners. On Thursday, July 5, Intra-articular Injection in Horses». HealthyPets.io will be presenting Veterinary Telemedicine — How En plus des petits déjeuners interactifs, le congrès offrira aussi it Impacts Your Profession & Practice, followed by the Hill’s Pet deux dîners interactifs. Le jeudi 5 juillet, HealthyPets.io présentera Nutrition interactive dinner on Friday, July 6th. «Veterinary Telemedicine — How it Impacts Your Profession & For more information on the unique learning opportuni- Practice», suivi du dîner interactif de Hill’s Pet Nutrition le vendredi ties mentioned in this article, be sure to download the CVMA 6 juillet. Convention App. To download, simply enter eventmobi.com/ Pour en savoir davantage à propos des occasions d’apprentissage app/cvma18 into your smart phone and click “Get the App.” uniques mentionnées dans cet article, n’oubliez pas de télécharger Don’t have a smart phone? You can still view the app in your l’appli du congrès de l’ACMV. Pour la télécharger, il suffit d’entrer web browser (eventmobi.com/cvma18). eventmobi.com/app/cvma18 dans votre téléphone intelligent et de Visit the CVMA website to register before the early bird cliquer sur «Get the App». Vous n’avez pas de téléphone intelligent? May 31, 2018 deadline to receive the discounted registration Vous pouvez toujours visualiser l’appli dans votre navigateur Web fees. See you in Vancouver! (eventmobi.com/cvma18). (by Sarah Cunningham, Manager, Conventions, CVMA) Visitez le site Web de l’ACMV pour vous inscrire avant la date d’inscription hâtive du 31 mai 2018 et vous prévaloir des tarifs d’inscription réduits. Au plaisir de vous rencontrer à Vancouver! (par Sarah Cunningham, gestionnaire, Congrès, ACMV)

Ms./Mme Heather Romano

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N Canadian Veterinary Medical Association Leads Initiatives to Support Global and National Strategies to Reduce Antimicrobial Use L’Association canadienne des médecins vétérinaires dirige des initiatives afin d’appuyer les stratégies mondiales et nationales visant à réduire l’utilisation des antimicrobiens rom February 6 to 8, 2018, the Canadian Veterinary Medical u 6 au 8 février 2018, l’Association canadienne des médecins FAssociation (CVMA) led the 2nd phase of 2 initiatives that Dvétérinaires (ACMV) a dirigé la deuxième phase de deux supported the global and national strategy to reduce antimicro- initiatives qui ont appuyé la stratégie mondiale et nationale en bial resistance (AMR) and to improve antimicrobial stewardship vue de réduire la résistance aux antimicrobiens et d’améliorer and surveillance in animals. l’antibiogouvernance et la surveillance chez les animaux. “In light of upcoming federal government policy and regu- «À la lumière des modifications prochaines des politiques et latory changes affecting the use of antimicrobials in animals, de la réglementation du gouvernement touchant l’utilisation des the Canadian Veterinary Medical Association has been actively antimicrobiens chez les animaux, l’Association canadienne des engaged in activities intended to support a new approach toward médecins vétérinaires a participé activement à des activités visant veterinary oversight of antimicrobial use (AMU),” says 2017–18 à appuyer une nouvelle approche pour la surveillance vétérinaire de CVMA president, Dr. Troye McPherson. l’utilisation des antimicrobiens», dit la présidente 2017–2018 de Both initiatives have been underway since early 2017, with l’ACMV, la Dre Troye McPherson. financial support from the Canadian Food Inspection Agency, Les deux initiatives sont en cours depuis le début de 2017, avec and Agriculture and Agri-Food Canada. l’appui financier de l’Agence canadienne d’inspection des aliments Project activities were focused on developing ready-for- et d’Agriculture et Agroalimentaire Canada. delivery, practical tools to assist veterinarians in the prudent use Les activités des projets se sont concentrées sur la conception of antimicrobials for 6 defined species groups — swine, poultry, d’outils pratiques prêts à livrer afin d’aider les médecins vétérinaires beef, dairy, small ruminants, and companion animals, as well as dans l’utilisation prudente des antimicrobiens pour les six groupes conceptualizing, designing and implementing a pilot veterinary d’espèces définis — les porcs, la volaille, les bovins de boucherie, les AMU surveillance initiative that focuses initially on animal feed. bovins laitiers, les petits ruminants et les animaux de compagnie — “Linking the 2 activities into one workshop identified oppor- ainsi que sur la conceptualisation, la conception et la mise en tunities where AMU stewardship can help target surveillance œuvre d’une initiative pilote de surveillance de l’utilisation des activities and, vice versa, where surveillance data can support antimicrobiens qui se concentrera d’abord sur les aliments pour stewardship activities,” says Dr. McPherson. “The end goal was animaux.

Workshop participants included veterinary practitioners, veterinary regulatory bodies, federal and provincial government representatives, industry officials (producers, feed and animal health industries), and academics. Les participants à l’atelier comprenaient des praticiens vétérinaires, des organismes de réglementation de la médecine vétérinaire, des représentants des gouvernements fédéral et provinciaux, des représentants de l’industrie (producteurs, industries des aliments pour animaux et de la santé animale) et des universitaires.

356 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY to design a pilot initiative or initiatives in the form of a proto- «En combinant les deux activités dans un seul atelier, il a été N type that we can use in targeted regions and agricultural sectors possible d’identifier les occasions où l’antibiogouvernance peut to initiate veterinary based AMU surveillance in Canada.” cibler les activités de surveillance et, à l’opposé, où les données de The work by the Canadian Veterinary Medical Association surveillance peuvent appuyer les activités d’antibiogouvernance», will help Canada’s commitment to conserve the effectiveness dit la Dre McPherson. «Le but ultime consistait à concevoir une of antimicrobials now and into the future, in animals and ou plusieurs initiatives pilotes sous forme d’un prototype que humans, as described in Tackling Antimicrobial Resistance and nous pourrons utiliser dans des régions et des secteurs agricoles Antimicrobial Use: A Pan-Canadian Framework for Action. ciblés afin d’entamer la surveillance vétérinaire de l’utilisation des antimicrobiens au Canada.» Le travail de l’Association canadienne des médecins vétérinaires appuiera l’engagement du Canada à préserver l’efficacité des antimicrobiens aujourd’hui et dans l’avenir, tant chez les animaux que chez les humains, tel qu’il est décrit dans Lutter contre la résistance aux antimicrobiens et optimiser leur utilisation : un cadre d’action pancanadien.

Western College of Veterinary Cérémonie des sarraus du Western Medicine’s Lab Coat Ceremony College of Veterinary Medicine n the March issue of The CVJ there were erroneously 2 lab ans le numéro de mars de La RVC, nous avons publié par erreur Icoat photos of the University of Calgary Faculty of Veterinary Ddeux photos de la cérémonie des sarraus de la Faculté de Medicine used; one with the wrong caption and attributed to médecine vétérinaire de l’Université de Calgary dont une comportait WCVM. Here is the correct photo of the Western College of une légende mentionnant par erreur le WCVM. Voici la bonne photo Veterinary Medicine’s class of 2021 with their lab coats. We de la promotion 2021 du Western College of Veterinary Medicine apologize for the error. avec les sarraus. Nous nous excusons de cette erreur.

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N National Pet ID Week is April 15 to 21, 2018 La Semaine nationale de l’identification des animaux de compagnie se déroulera du 15 au 21 avril 2018 t is important to ensure your clients’ pets have reliable forms l est important de veiller à ce que les animaux de compagnie de Iof identification in the event they become lost. The Canadian Ivos clients possèdent des formes d’identification fiables pour qu’ils Veterinary Medical Association (CVMA) supports the per- puissent être retrouvés s’ils s’égarent. L’Association canadienne des manent identification of animals, and recommends the use of médecins vétérinaires (ACMV) appuie l’identification permanente des radio-frequency identification (RFID) products (microchips, animaux et elle recommande l’utilisation de produits d’identification transponders) that conform to the International Standards par radiofréquence (RFID) qui satisfont à la norme de technologie Organization (ISO) standard of technology. Read the CVMA’s de l’Organisation internationale de normalisation (ISO). On peut lire Microchip Animal Identification position statement under the la position de l’ACMV sur l’identification des animaux à l’aide d’une Policy & Advocacy tab of its website. micropuce sous l’onglet Politiques et défense des intérêts de son The CVMA recommends veterinarians use RFID products site Web. that have been successfully reviewed by the National Companion L’ACMV recommande que les vétérinaires utilisent des produits Animal Coalition (NCAC) and appear on the NCAC list of de RFID qui ont été testés avec succès par la Coalition nationale recognized products, which can be found under the Practice & pour les animaux de compagnie (CNAC) et qui figurent sur la liste Economics tab and Practice Tools section of the CVMA website. des produits reconnus par la CNAC qui se trouve sous l’onglet Pratique et finances, dans la section des Outils pour la pratique du site Web de l’ACMV.

World Veterinary Day Takes Place La Journée mondiale vétérinaire se on April 28, 2018 déroulera le 28 avril 2018 orld Veterinary Day will take place globally on April 28, a Journée mondiale vétérinaire se déroulera à l’échelle mondiale W2018. This event aims to highlight and promote the dif- Lle 28 avril 2018. Cet événement vise à souligner et à promouvoir ferent facets of the work performed by veterinarians all over the les différentes facettes du travail réalisé par les vétérinaires partout world, and to raise awareness of their contribution to improve dans le monde ainsi qu’à rehausser la sensibilisation à l’égard de animal health and welfare, as well as public health. Each year, a leur contribution au niveau de la santé et du bien-être des animaux different topic is selected by the World Veterinary Association ainsi que de la santé publique. Chaque année, un thème différent est (WVA) and the World Organisation for Animal Health (OIE); choisi par l’Association mondiale vétérinaire (AMV) et l’Organisation they initiate this event together. mondiale de la santé animale (OIE) qui organisent ensemble cet événement.

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SCVMA New Graduate Survey Report: Class of 2017 N Rapport sur le Sondage auprès des finissants des ÉACMV : Promotion 2017 ach year, the Students of the Canadian Veterinary Medical haque année, les Étudiants de l’Association canadienne des EAssociation (SCVMA) surveys recent Canadian veterinary Cmédecins vétérinaires (ÉACMV) effectuent un sondage auprès graduates and reports on current Canadian veterinary workplace des finissants des écoles de médecine vétérinaire et présentent un conditions. This year’s survey from the 2017 graduating class rapport sur les conditions de travail actuelles pour les médecins had a response rate of 25% (108 of 424 graduating students). vétérinaires au Canada. Le sondage de cette année auprès des Of these respondents, 83% identified as female and the ratio finissants de 2017 a récolté un taux de réponse de 25 % (108 between French and English respondents was 1:3. When inter- des 424 finissants). Parmi ces répondants, 83 % se sont identifiés preting the survey data, please note that not all respondents comme des femmes et le ratio entre les répondants francophones answered every question. et anglophones était de 1:3. Lors de l’interprétation des données, veuillez noter que ce ne sont pas tous les répondants qui ont Demographics répondu à toutes les questions. Figure 1. Graduating College (n = 105). Données démographiques 38 Figure 1. École d’obtention du diplôme (n = 105).

38 26

20 26 13 20 8 13

8 AVC FMV OVC WCVM UCVM

Figure 2. Where respondents primarily grew up (n = 106). AVC FMV OVC WCVM UCVM

Figure 2. Milieu dans lequel les répondants ont surtout grandi (n = 106).

15% On a Farm 13% Acreage 15 % Town/City 72% Ferme 13 % Terrain de plusieurs acres

Ville ou village 72 %

Employment data Employment data indicated that 96% of respondents have been employed since graduation, and the other 4% are not employed because they are continuing their education in pursuit of a Données sur l’emploi Masters or PhD. Les données sur l’emploi ont indiqué que 96 % des répondants occupaient un emploi depuis la fin du cours et 4 % des répondants ne travaillaient pas parce qu’ils poursuivaient leurs études pour l’obtention d’une maîtrise ou d’un doctorat.

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N Figure 3. If you are working in the veterinary field, did you Figure 3. Si vous travaillez dans le domaine vétérinaire, avez-vous secure this position before graduation? obtenu ce poste avant la fin du cours?

Yes No Oui Non

11% 11 % 16% 27% 24% 16 % 27 % 24 %

89% 84% 89 % 73% 76% 84 % 73 % 76 %

2017 2016 2015 2014 2017 2016 2015 2014

In 2017 (n = 102); 2016 (n = 140); 2015 (n = 107); 2014 En 2017 (n = 102); 2016 (n = 140); 2015 (n = 107); 2014 (n = 106). (n = 106) Figure 4. Search methods used by respondents in securing Figure 4. Méthodes de recherche utilisées par les répondants current employment (n = 112). pour trouver l’emploi actuel (n = 112).

Number of Nombre de Method Respondents % Méthode répondants % Internships 34 31% Internats 34 31 % J’ai travaillé à cet endroit pendant Worked there as an undergraduate 26 23% 26 23 % mes études Networking 16 14% Réseautage 16 14 % Provincial veterinary medical association 8 7% Petites annonces des associations classifieds 8 7 % provinciales de médecins vétérinaires Internet searches 6 5% Recherches Internet 6 5 % CVMA/The Canadian Veterinary Journal 2 2% ACMV/Petites annonces de classifieds 2 2 % La Revue vétérinaire canadienne Other 20 18% Autre 20 18 % *Note that respondents were allowed to indicate more than one method. *À noter que les répondants pouvaient indiquer plus d’une méthode. For the employed graduates (n = 101), 94% (95) are still cur- Pour les diplômés avec un emploi (n = 101), 94 % (95) rently working in the position they accepted after graduation. occupaient toujours le même poste qu’ils avaient accepté à la fin Among the 6 veterinarians no longer working in the position du cours. Parmi les 6 vétérinaires qui n’occupaient plus le poste they accepted after graduation, 2 attributed to a short-term qu’ils avaient accepté à la fin du cours, 2 ont dit qu’il s’agissait d’un contract, 3 did not like the employer and 1 did not like the job. contrat à court terme, 3 n’aimaient pas l’employeur et 1 n’aimait Graduates were asked if they are following the same career path pas le poste. On a demandé aux finissants s’ils avaient suivi le they intended upon graduating from veterinary college; 84% of même cheminement de carrière qu’ils avaient prévu au moment de graduates (n = 85) responded yes, with 13% (n = 13) responding l’obtention du diplôme : 84 % des finissants (n = 85) ont répondu no. The reasons 11 graduates gave for no longer following the oui et 13 % (n = 13) ont répondu non. Les raisons données pour le same career path were that their interests changed while they changement de cheminement de carrière étaient les suivantes : leurs were studying veterinary medicine (4), that there were not many intérêts avaient changé pendant le cours de médecine vétérinaire (4), jobs available in the area they originally intended to practice (1), il n’y avait pas beaucoup de postes dans le domaine d’exercice qu’ils changes in their personal life (4), and other (2). avaient d’abord choisi (1), des changements dans la vie personnelle Figure 5. Level of satisfaction with current employment (4) et autres raisons (2). position (n = 99). Figure 5. Niveau de satisfaction à l’égard du poste actuel (n = 99).

49% 49 %

34% 34 %

12% 12 % 5% 0% 5 % 0 % VERY SATISFIED NEUTRAL DISSATISFIED VERY SATISFIED DISSATISFIED TRÈS SATISFAIT(E) NEUTRE INSATISFAIT(E) TRÈS SATISFAIT(E) SATISFAIT(E)

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New graduate respondents work an average of 45 hours per Les finissants travaillent en moyenne 45 heures par semaine. N week. When asked about the make-up of veterinarian work Lorsqu’on les a interrogés à propos de la répartition des heures hours in the practice, respondents indicated they work with de travail pour les vétérinaires dans la pratique, les répondants 1 to 2 part-time veterinarians (, 35 hrs/wk) and 3 full-time ont indiqué qu’ils travaillaient avec 1 ou 2 vétérinaires à temps veterinarians (. 35 hrs/wk) on average. partiel (, 35 heures/semaine) et 3 vétérinaires à temps plein (. 35 heures/semaine) en moyenne. Figure 6. What is your current employment type? Figure 6. Quel est votre type d’emploi actuel? Government Industry/commercial Private clinical practice

Internship/residency Other Gouvernement Industrie/commerce Pratique clinique privée Internat/résidence Autre 3% 2% 2017 62% 3 % 30% 2% 3% 2017 62 % 30 % 3 % 2% 22% 2016 74% 2 % 1% 22 % 1% 2016 74 % 1 % 1 % 1% 11% 2015 87% 1 % 0% 11 % 1% 2015 87 % 0 % 1 % 0% 20% 2014 73% 0 % 3% 20 % 4% 2014 73 % 3 % 4 %

In 2017 (n = 99); 2016 (n = 139); 2015 (n = 106); 2014 (n = 106). En 2017 (n = 99); 2016 (n = 139); 2015 (n = 106); 2014 (n = 106) Figure 7. Average amount of time respondents indicated they spent treating the below species (n = 98). Figure 7. Pourcentage du temps que les répondants ont indiqué qu’ils consacraient aux espèces suivantes (n = 98). Species Time Spent Espèce % du temps Canine 45% Chiens 45 % Feline 34% Chats 34 % Equine 17% Équidés 17 % Bovine — Dairy 11% Bovins laitiers 11 % Bovine — Beef 6% Bovins de boucherie 6 % Poultry 6% Volaille 6 % Porcine 6% Porcs 6 % Caged pets and birds 3% Animaux et oiseaux en cage 3 % Small ruminants 1% Petits ruminants 1 % Farmed game 0% Gibier d’élevage 0 % Bovine — Veal 0% Bovins — Veaux 0 % Other 5% Autre 5 % No contact with species 7% Aucun contact avec les espèces 7 %

Income and Compensation Data Données sur le revenu et la rémunération New graduates were asked to share their average salary and debt On a demandé aux finissants de communiquer leur salaire moyen load as part of our survey. The average salary for new graduates et leur niveau d’endettement dans le cadre du sondage. Le salaire in residency or internship positions was $30 622, and the average moyen pour les finissants occupant des postes de résidence ou salary for all other employed new graduates was $74 418. The d’internat était de 30 622 $ et le salaire moyen pour tous les average debt load was calculated based on a student’s residency autres finissants avec un emploi s’élevait à 74 418 $. Le niveau status; the average debt of Canadian students was $56 928 and d’endettement moyen a été calculé en se basant sur le statut de the average debt of international students was $85 286. In order résidence de l’étudiant : la dette moyenne des étudiants canadiens

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N to better inform our readers, we have further separated the sum- était de 56 928 $ et le niveau moyen d’endettement des étudiants mary data as shown below. internationaux se situait à 85 286 $. Afin de mieux informer nos lecteurs, nous avons réparti les données sommaires dans la figure Figure 8. Province of employment for current graduates and ci-dessous. their mean annual salary ($CDN) by province (please note this summary data includes all types of employment). Figure 8. Province d’emploi des diplômés actuels et leur salaire annuel moyen ($ CA) par province (veuillez noter que Number ce sommaire des données comprend tous les types d’emploi). working in province Average Salary Nombre de Province/Territory (n = 98) salary respondents répondants Ontario 22 $67 045.95 (n = 22) travaillant dans la Quebec 23 $47 369.57 (n = 23) province Salaire Salaire des Alberta 18 $66 916.67 (n = 18) Province/Territoire (n = 98) moyen répondants British Columbia 7 $78 571.43 (n = 7) Ontario 22 67 045,95 $ (n = 22) Saskatchewan 6 $51 733.33 (n = 6) Québec 23 47 369,57 $ (n = 23) Manitoba 5 $74 400.00 (n = 5) Alberta 18 66 916,67 $ (n = 18) Prince Edward Island 4 $36 625.00 (n = 4) Colombie-Britannique 7 78 571,43 $ (n = 7) New Brunswick 2 $69 000.00 (n = 2) Saskatchewan 6 51 733,33 $ (n = 6) Nova Scotia 1 $66 500.00 (n = 1) Manitoba 5 74 400,00 $ (n = 5) Newfoundland and 0 N/A — Île-du-Prince-Édouard 4 36 625,00 $ (n = 4) Labrador Nouveau-Brunswick 2 69 000,00 $ Northwest Territories 0 N/A — (n = 2) Nunavut 0 N/A — Nouvelle-Écosse 1 66 500,00 $ (n = 1) Terre-Neuve-et- Yukon 0 N/A — 0 n.d. — Labrador International 11 $49 064.80 (n = 10) Territoires du Nord-Ouest 0 n.d. — N/A — Not available. Nunavut 0 n.d. — Figure 9. Method of compensation for new graduates (n = 97). Yukon 0 n.d. — International 11 49 064,80 $ (n = 10)

n.d. — non disponible.

2% Straight salary Figure 9. Mode de rémunération des finissants (n = 97). 15%

Base salary + percentage of gross earnings/billings

2 % Salaire fixe Income based on percentage 15 % 83% of gross earnings/billings Salaire de base plus un pourcentage des revenus bruts ou des montants facturés

Revenu basé sur un 83 % pourcentage des revenus bruts ou des montants facturés

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Figure 10. Average student debt upon graduation ($CDN) Figure 10. Dette étudiante moyenne ($ CA) selon la faculté de N according to the veterinary college and graduation year. médecine vétérinaire et la promotion.

Debt Dette 2017 2016 2015 2014 2017 2016 2015 2014 $100 625 $91 590 $101 454 $140 421 100 625 $ 91 590 $ 101 454 $ 140 421 $ AVC AVC (n = 8) (n = 18) (n = 11) (n = 19) (n = 8) (n = 18) (n = 11) (n = 19) $60 914 $50 190 $47 111 $50 500 60 914 $ 50 190 $ 47 111 $ 50 500 $ WCVM WCVM (n = 35) (n = 42) (n = 27) (n = 26) (n = 35) (n = 42) (n = 27) (n = 26) $59 077 $70 550 $74 083 $51 446 59 077 $ 70 550 $ 74 083 $ 51 446 $ UCVM UCVM (n = 13) (n = 8) (n = 12) (n = 13) (n = 13) (n = 8) (n = 12) (n = 13) $51 967 $54 950 $43 184 $55 133 51 967 $ 54 950 $ 43 184 $ 55 133 $ OVC OVC (n = 20) (n = 39) (n = 33) (n = 30) (n = 20) (n = 39) (n = 33) (n = 30) $36 568 $32 930 $19 687 $31 220 36 568 $ 32 930 $ 19 687 $ 31 220 $ FMV FMV (n = 22) (n = 28) (n = 24) (n = 25) (n = 22) (n = 28) (n = 24) (n = 25) Note: n = number of respondents by college each year. Nota : n = nombre de répondants par faculté chaque année.

Figure 11. Professional benefits offered in addition to base Figure 11. Avantages professionnels offerts en plus du salaire de salary (n = 95). base (n = 95).

Number of % of Nombre de % de Professional Benefits Respondents Respondents Avantages professionnels répondants répondants Payment of licensing fees 78 82% Paiement des frais de permis 78 82 % Frais de formation continue 74 78 % Continuing education fees 74 78% Assurance maladie 63 66 % Health insurance 63 66% Assurance pour faute 64 67 % Malpractice insurance 64 67% professionnelle Dental insurance 52 55% Assurance dentaire 52 55 % Payment of fees/Voluntary Paiement de la cotisation d’une professional association association professionnelle à 42 44% 42 44 % membership (e.g. AAHA, adhésion volontaire (p. ex., AAHA, CVMA, OVMA, AMVQ) ACMV, OVMA, AMVQ) Clothing allowances 41 43% Allocation vestimentaire 41 43 % Continuing education travel Dépenses pour les voyages liés à 37 40% 37 40 % expenses la formation continue After hours/On-call premiums 29 31% Primes pour le travail sur appel ou 29 31 % Sick leave/Compassionate leave 34 36% en dehors des heures normales Congé de maladie ou pour des Disability insurance 25 26% 34 36 % raisons personnelles Cellphone 27 28% Assurance invalidité 25 26 % Life insurance 23 24% Téléphone cellulaire 27 28 % Vehicle allowance/ 25 26% Assurance vie 23 24 % Transportation expenses Allocation pour un véhicule ou 25 26 % Pension 9 9% dépenses pour le transport Profit sharing 3 3% Fonds de retraite 9 9 % Retention 1 1% Partage des profits 3 3 % Other 6 6% Rétention 1 1 % *Note that respondents were allowed to indicate more than one benefit. Autre 6 6 % Other *À noter que les répondants pouvaient indiquer plus d’un avantage. Respondents indicated the top 3 challenges they face while work- Autres renseignements ing as a new graduate. The following challenges were among Les répondants ont indiqué les trois principaux défis qu’ils devaient the most frequently mentioned (listed in order of prevalence): relever dans leur emploi en tant que diplômé récent. Les défis • Client communication suivants figuraient parmi les plus fréquemment mentionnés (indiqués • Lack of confidence en ordre de fréquence) : • Development of clinical Sskills • Communication avec les clients • Mentorship • Manque de confiance

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N • Clinical decision-making and prioritizing diagnostics • Développement des compétences cliniques • Work-life balance • Mentorat • Prise de décisions cliniques et ordre de priorité des diagnostics Figure 12. Number of graduates who are currently members • Équilibre travail-vie of professional organizations other than their provincial regulatory body (n = 140). Figure 12. Nombre de finissants qui sont actuellement membres d’organisations professionnelles autres que leur organisme de Number of réglementation provincial (n = 140). Organization Respondents Canadian Veterinary Medical Association (CVMA) 73 Nombre de Organisation répondants Ontario Veterinary Medical Association (OVMA) 17 Association canadienne des médecins vétérinaires 73 American Animal Hospital Association (AAHA) 11 (ACMV) Association des Médecins Vétérinaires du Québec 11 Ontario Veterinary Medical Association (OVMA) 17 (AMVQ) American Animal Hospital Association (AAHA) 11 None 7 Association des médecins vétérinaires du Québec 11 Other (see below) 21 (AMVQ) Other organizations: Aucune 7 American Association Bovine Practitioners (AABP) Autre (voir ci-dessous) 21 American Association Equine Practitioners (AAEP) American Association for Laboratory Animal Science (AALAS) Autres organisations : American Association of Small Ruminant Practitioners (AASRP) American Association Bovine Practitioners (AABP) American Association of Swine Veterinarians (AASV) American Association Equine Practitioners (AAEP) American Veterinary Medical Association (AVMA) American Association for Laboratory Animal Science (AALAS) Canadian Bar Association (CBA) American Association of Small Ruminant Practitioners (AASRP) Canadian Embryo Transfer Association (CETA) American Association of Swine Veterinarians (AASV) California Veterinary Medical Association (CVMA) American Veterinary Medical Association (AVMA) Ontario Association of Bovine Practitioners (OABP) Association du Barreau canadien (ABC) Saskatchewan Association of Veterinary Technologists (SAVT) Association canadienne du transfert d’embryons (ACTE) Society of British Columbia Veterinarians (SBCV) California Veterinary Medical Association (CVMA) Western Canadian Association of Bovine Practitioners (WCABP) Ontario Association of Bovine Practitioners (OABP) Western Canadian Association of Swine Veterinarians (WCASV) Saskatchewan Association of Veterinary Technologists (SAVT) Society of British Columbia Veterinarians (SBCV) On behalf of the Students of the Canadian Veterinary Western Canadian Association of Bovine Practitioners (WCABP) Western Canadian Association of Swine Veterinarians (WCASV) Medical Association, I would like to thank the students of the graduating class of 2017 for taking the time to answer our Au nom des Étudiants de l’Association canadienne des médecins Annual Graduate Survey and providing insight to current and vétérinaires, j’aimerais remercier les étudiants de la promotion 2017 future veterinarians. qui ont pris le temps de répondre à notre Sondage annuel auprès (by Katelyn Elliott, SCVMA Representative, des finissants afin d’informer les médecins vétérinaires actuels et Ontario Veterinary College, Class of 2019) futurs. (par Katelyn Elliott, représentante des ÉACMV, Ontario Veterinary College, promotion 2019)

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The 2018 SCVMA Symposium Symposium 2018 des ÉACMV N “Mink, Mice, and Moose: «Visons, souris et originaux : The Diverse Field of Veterinary les divers domaines de la Medicine” médecine vétérinaire» n January 13 and 14, veterinary students from across es 13 et 14 janvier, les étudiants en médecine vétérinaire du OCanada participated in the 2018 Students of the CVMA LCanada ont participé au Symposium 2018 des Étudiants de (SCVMA) Symposium, held this year at the Atlantic Veterinary l’ACMV (ÉACMV) qui s’est tenu cette année à l’Atlantic Veterinary College (AVC), and it was simply an amazing weekend! The fun College (AVC) et la fin de semaine a tout simplement été filled days’ packed with lectures, wet labs, island tours, and an fantastique! Le voyage en a vraiment valu la peine, même malgré unforgettable keynote speaker made even all the flight delays le retard des vols au minuscule aéroport de Charlottetown, car les from the tiny Charlottetown airport well worth it. I would like participants ont fait l’expérience de journées amusantes remplies de to extend a huge thank you to all of the AVC students on the conférences, de laboratoires de travaux pratiques, d’excursions dans 2018 SCVMA Symposium Planning Executive, especially the l’île et d’une conférencière invitée inoubliable. J’aimerais sincèrement executive chair, Karie Bryenton, for their efforts in planning, remercier tous les étudiants de l’AVC membres du Comité exécutif coordinating and managing the various activities offered; your de planification du Symposium 2018 des ÉACMV, particulièrement work was appreciated by all. I would also like to thank the 2018 la présidente, Karie Bryenton, de leurs efforts en vue de planifier, SCVMA Symposium sponsors for their generosity and the de coordonner et de gérer les diverses activités offertes : votre Canadian Veterinary Medical Association for their unwavering travail a été grandement apprécié par tout un chacun. J’aimerais support and guidance; without your dedication to veterinary aussi remercier les commanditaires du Symposium 2018 des students and the profession as a whole, this annual event would ÉACMV de leur générosité et l’Association canadienne des médecins not be possible! vétérinaires pour son soutien indéfectible et ses conseils : sans The 2018 SCVMA Symposium commenced on Thursday votre dévouement envers les étudiants en médecine vétérinaire et with a simple meet and greet and trivia night, but it was really la profession dans son ensemble, cet événement annuel ne serait the Friday morning lectures that kicked-off the weekend event pas possible! with a bang! Students learned about a variety of topics, ranging Le Symposium 2018 des ÉACMV a commencé le jeudi par from poultry to equine medicine, from leaky gut syndrome to une simple soirée d’accueil et jeu-questionnaire, mais ce sont les epilepsy, and really everything in between. A few examples of conférences du vendredi matin qui ont vraiment donné un coup the lectures offered were: Cat Action PEI: A trap-neuter-release d’envoi spectaculaire à la fin de semaine! Les étudiants se sont renseignés sur divers sujets, allant de la médecine de la volaille à celle des équidés, du syndrome de l’intestin perméable à l’épilepsie, ainsi que sur une foule d’autres affections. Voici quelques exemples des conférences présentées : Cat Action PEI : un programme de capture-stérilisation-mise en liberté qui a un impact positif sur la population de chats féraux de l’île; la mortalité des baleines noires dans la région atlantique du Canada; et la vérité à propos de l’élevage des visons et du bien-être animal. Les laboratoires de travaux pratiques étaient ensuite au programme le vendredi après-midi. Les étudiants pouvaient notamment exercer leurs connaissances pratiques en échographie, participé à des rondes de cardiologie ou ils ont retroussé leurs manches pour des nécropsies d’oiseaux ou de mammifères marins! Le samedi matin, plusieurs excursions dans des fermes étaient organisées et les participants ont choisi entre les alpagas, les chèvres, les vaches laitières, les moutons laitiers ou même la fauconnerie Island Falconry Services. Le Symposium, qui se déroulait sous la bannière du thème «Visons, souris et orignaux : les divers domaines de la médecine vétérinaire», a représenté une excellente occasion pour les étudiants en médecine vétérinaire d’en apprendre davantage sur ce qui est considéré comme étant de la médecine vétérinaire «non conventionnelle». Tel qu’il a été mentionné précédemment, les étudiants ont eu le privilège de travailler auprès d’une foule d’espèces, allant des faucons aux chèvres, en passant par les Students practicing ultrasound-guided biopsies using Jello. dauphins! La conférencière invitée incarnait particulièrement ce Des étudiantes qui s’exercent à réaliser des biopsies guidées par échographie à l’aide de Jello. concept : la Dre Michelle Oakley est la seule vétérinaire pour

CVJ / VOL 59 / APRIL 2018 365 FOR PERSONAL USE ONLY

Dr. Jennifer MacLean leading an ultrasound demonstration. La Dre Jennifer MacLean lors de la démonstration d’une échographie.

Island Falconry Services provides a natural approach to pest bird control by introducing natural predators such as Saker Falcons, Gyr Falcons, Harris Hawkes, and Red Tail Hawkes to an area. During this presentation, an experienced Falconer taught the art of falconry and demonstrated their birds of prey in a field setting. Island Falconry Services offre une approche naturelle pour contrôler les oiseaux nuisibles en introduisant des prédateurs naturels comme le Faucon sacre, le Faucon gerfaut, la Buse de Harris et la Buse à queue rousse dans une région. Durant cette présentation, un fauconnier expérimenté a enseigné l’art de la fauconnerie et a donné une démonstration de ses oiseaux de proie sur le terrain.

program making positive changes in the island’s feral cat population; Right Whale toutes les espèces dans le vaste territoire Mortalities in Atlantic Canada; and The Truth About Mink Farming and Animal du Yukon, dans le nord du Canada, et elle Welfare. est aussi la vedette de l’émission Michelle Next on the schedule was Friday afternoon wet labs. Students had hands-on skills ou la vie sauvage au canal D. Le samedi practice with an ultrasound machine, participated in cardiology rounds, or rolled up après-midi, elle a présenté une merveilleuse their sleeves for avian and marine mammal necropsies, just to name a few! Saturday conférence sur sa vie d’étudiante à l’AVC, morning consisted of various farm tours; participants chose between alpacas, goats, son travail pour concilier les enfants et les dairy cows, cattle, dairy sheep, or even the Island Falconry Services. cours, son cheminement de praticienne With the overall theme “Mink, Mice, and Moose: The Diverse Field of Veterinary et elle nous a même impressionné avec Medicine,” it was a great occasion for Canadian veterinary students to learn more ses fusils à injection appelés Sassy et about what could be considered “unconventional” veterinary medicine. As previously Saucy. Pour conclure la fin de semaine, mentioned, students had the privilege of working with a whole range of species, les étudiants ont assisté à un banquet à from falcons to goats to dolphins! The keynote speaker was a great living example of la PEI Brewing Company où ils ont pu this concept: Dr. Michelle Oakley is the only all-species veterinarian for Northern savourer un excellent repas et participé à Canada’s vast Yukon territory and also the subject of National Geographic Wild’s series des conversations encore meilleures. Dr. Oakley: Yukon Vet. On Saturday afternoon, she gave a wonderful talk about her Le Symposium 2018 des ÉACMV previous student life at AVC, balancing children with classes, her path as a practitioner a été une merveilleuse expérience et and even impressed us with her dart guns named Sassy and Saucy. To close the weekend, j’encouragerais tous les étudiants à assister students attended a banquet at the PEI brewing company, involving great food and à l’événement de l’année prochaine, qui even greater conversations. sera organisé par mon école, la Faculté The 2018 SCVMA Symposium was a wonderful experience, and I encourage all stu- de médecine vétérinaire (FMV) à Saint- dents to attend next year’s event, hosted by my home school, the Faculty of Veterinary Hyacinthe, au Québec. Au plaisir de vous Medicine (FMV) in Saint-Hyacinthe, Quebec. Hope to see you there! y rencontrer! (by Marie-Anne Sirois, SCVMA representative at FMV, Montreal) (par Marie-Anne Sirois, représentante des ÉACMV à la FMV, Montréal)

366 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY Case Report Rapport de cas

Successful management of lymphangiosarcoma in a puppy using a tyrosine kinase inhibitor

Ji-Hyun Kim, Hakyoung Yoon, Hun-Young Yoon, Kidong Eom, Hyun-Jeong Sung, Jung-Hyun Kim

Abstract — A puppy was diagnosed with lymphangiosarcoma associated with lymphedema based on lymphography and histopathology. The lesions resolved after toceranib therapy, and the dog remains in remission 1 year later. This is the first report of a successful outcome following oral toceranib as first-line therapy for lymphangiosarcoma in a dog.

Résumé — Gestion réussie d’un lymphangiosarcome chez un chiot à l’aide d’un inhibiteur de la tyrosine- kinase. Un chiot a été diagnostiqué avec un lymphangiosarcome associé à un lymphœdème en se basant sur une lymphographie et l’histopathologie. Les lésions se sont résorbées après un traitement au tocéranib et le chien demeurait en rémission un an plus tard. Il s’agit du premier rapport d’un résultat favorable après le recours au tocéranib oral comme traitement de premier recours pour le lymphangiosarcome chez un chien. (Traduit par Isabelle Vallières) Can Vet J 2018;59:367–372

ymphangiosarcoma (LSA) is a rare malignant tumor arising macules (Figures 1A, 1E). Hematology and serum biochemistry L from lymphatic endothelial cells in humans and animals panels were within reference limits. Fluid aspirated from the (1). Generally, the treatment options recommended for adult lesions was serosanguinous, and concentrations of total protein, dogs with LSA are surgical excision, radiation, chemotherapy, creatinine, bilirubin, triglycerides, and cholesterol in the fluid and combination therapy (2). However, these treatments have were lower than those in serum. Cytologic evaluation of the not been well-studied in puppies. Furthermore, there have been fluid indicated that the cellularity of small lymphocytes was no reports of the clinical efficacy of a tyrosine kinase inhibi- higher than that of peripheral blood. There were no remark- tor (TKI) when used without concurrent chemotherapy for able findings on thoracic or abdominal radiographs, except the treatment of canine lymphangiosarcoma. This is the first for soft tissue swelling on the caudoventral abdominal wall. description of successful long-term management using a TKI as Enlargement of the medial iliac, hypogastric, popliteal, and a first-line therapy in a puppy with lymphangiosarcoma. inguinal lymph nodes was identified on ultrasonography; however, no vascular response was detected on color Doppler evalu- Case description ation. Leakage of urine was ruled out by retrograde fluoroscopic A 4-month-old castrated male mixed-breed dog weighing 6.8 kg urethrocystography. was presented with a 2-month history of recurrent subcutaneous Computed tomographic (CT) lymphography was performed edema after 2 surgeries for drainage of subcutaneous fluid. On using a 4-multidetector row system (LightSpeed; GE Medical presentation, physical examination revealed a body temperature Systems, Cleveland, Ohio, USA) to investigate the patient fur- of 39.9°C and severe pitting edema from the mid abdomen to ther (Figure 2). First, 60 mg of iodine/kg iohexol (Omnihexol the perineal region but no mass was detected. The edematous 300; Korea United Pharmaceutical, Seoul, Korea) (3) was region was warm and erythematous with dark purple-colored injected manually into the popliteal lymph nodes bilaterally

Department of Veterinary Surgery (Ji-Hyun Kim, H-Y Yoon), Department of Veterinary Medical Imaging (H Yoon, Eom), Department of Veterinary Internal Medicine (Sung, Jung-Hyun Kim), College of Veterinary Medicine, Konkuk University, #120 Neungdong-ro, Gwangjin-gu, Seoul, 143-701, Korea. Address all correspondence to Dr. Jung-Hyun Kim; e-mail: [email protected] Ji-Hyun Kim and Hakyoung Yoon contributed equally to this work. The authors have no affiliations or financial involvement with any organization or entity with a financial interest in, or in financial competition with, the subject matter or materials discussed in this article. Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ([email protected]) for additional copies or permission to use this material elsewhere.

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Figure 1. Gross lesions seen in a dog with lymphangiosarcoma at first presentation (A, E), 1 mo post-surgery (B, F), and at 7 d (C, G) and 1 y (D, H) after starting treatment with toceranib. Edema, erythema, and dark purple-colored macules were seen in the caudoventral abdomen and perineal region at initial presentation (A, E). The lesions recurred 1 mo after surgical ligation of the lymphatic duct and resection of the superficial inguinal subcutis and regional lymph nodes (B, F). Note that the macules have become vesicles. One week after starting treatment with toceranib (C, G), all lesions on the ventral abdomen and perineal area resolved. After 1 y of toceranib therapy (D, H), the patient remains in complete remission.

under ultrasound guidance. Computed tomographic scanning eral anesthesia. A lymphatic duct connecting to the superficial was performed in the ventrodorsal position 5 min after injection inguinal lymph nodes was seen in the left inguinal subcutaneous of the contrast medium. Ten minutes later, contrast medium region. Fluid was observed to be leaking from the lymphatic was injected into the left inguinal lymph nodes and a CT scan duct, so the duct was ligated with 3-0 polyglyconate (Maxon; was performed in the same manner. After a further 10 min, Covidien, Dublin, Republic of Ireland) and resected (Figure 3A). lymphography was carried out for the right inguinal lymph The subcutaneous tissue and enlarged medial iliac lymph nodes nodes. On lymphography, the popliteal lymph nodes showed were resected. All the tissues that were removed were submitted pooling of contrast medium bilaterally (Figures 2A, 2E, 2I). The for histopathology. Histopathologic analysis of the subcutane- right hypogastric lymph nodes and the afferent lymphatic ducts ous biopsy specimens showed poorly demarcated, infiltrative, from the right popliteal lymph nodes showed poor contrast and loosely cellular neoplasms composed of spindle cells form- enhancement. The right medial iliac lymph nodes (Figures 2D, ing multiple empty vascular-like spaces with no erythrocytes 2H, 2L) were not enhanced by contrast medium, except for (Figure 3B). The neoplastic cells had indistinct cell borders those in the focal and peripheral regions, including the afferent and contained fibrillary eosinophilic cytoplasm. Their nuclei lymphatic ducts. Gradual reduction of contrast enhancement were elongated and contained finely stippled chromatin and in the peripheral regions of the right hypogastric (Figures 2B, indistinct nucleoli. The resected lymphatic duct was composed 2F, 2J) and right medial iliac (Figures 2D, 2H, 2L) lymph nodes of adipose tissue with a small neoplastic focus that was identical was identified on lymphography. There was no relative contrast to the subcutaneous neoplasms. However, no neoplastic cells enhancement in the left hypogastric (Figures 2C, 2G, 2K) or were observed in the lymph nodes. left medial iliac (Figures 2D, 2H, 2L) lymph nodes or lymphatic A diagnosis of lymphedema with lymphatic obstruction ducts. Extensive leakage and accumulation of contrast medium and leakage caused by lymphangiosarcoma was made based was detected bilaterally in the inguinal region immediately on the history, clinical signs, histopathology results, and CT after injection (Figures 2F, 2G, and 2I to 2K). The lymphatic lymphography. The lymphedema improved markedly in the ducts connecting the sublumbar lymph nodes with the ingui- immediate postoperative period. The dog received empiric nal lymph nodes were not identified on either side. Computed antibiotic therapy consisting of amoxicillin-clavulanate (Amocla tomographic lymphography confirmed lymphatic obstruction Tab; Gunil Pharm, Seoul, Korea), 20 mg/kg body weight and leakage. (BW), PO, q12h, for 2 wk until negative aerobic and anaerobic Incisional biopsies of both inguinal regions and excisional bacterial cultures were obtained. The surgical wound healed biopsies of the enlarged lymph nodes were conducted under gen- well. An offer of adjunctive chemotherapy was declined by the

368 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY CASE REPORT CASE

Figure 2. Computed tomographic lymphography images at the level of the popliteal (PLN) (A), right (B) and left (C) hypogastric (HGLN), and medial iliac (MILN) lymph (D) nodes 5 min after injection of contrast medium into the popliteal lymph nodes bilaterally. (E–H) Images showing contrast enhancement of the lymph nodes 15 min after popliteal lymphography and immediately after injection of contrast medium into the left inguinal lymph nodes. (I–L) Demonstration of the effects 25 min after popliteal lymphography and immediately after injection of contrast medium into the right inguinal lymph nodes. Poor contrast enhancement of the sublumbar lymph nodes is seen on lymphography, with extensive leakage and accumulation (asterisks) of contrast medium immediately after lymphography of the inguinal lymph nodes bilaterally. The white and black arrowheads, respectively, indicate the urethral catheter and gravitation of contrast medium in the urinary bladder in the ventrodorsal position.

owner because of the dog’s young age and the risk of toxicity. after starting rutin indicated that there had been no adverse Oral TKI therapy with imatinib (Gleevec; Novartis, Basel, effects from these treatments except for mild leukopenia [white Switzerland), 10 mg/kg BW, q24h was started, along with a blood cell count (WBC) 4.3 3 109 cells/L; reference range: benzopyrone (Rutin 500 mg; Country Life, Yonkers, New York, 5.2 to 13.9 3 109 cells/L]. The WBC returned to normal USA), 500 mg/kg BW, PO, q12h. One month after surgery, (8.37 3 109 cells/L) 7 d after reducing the dose of toceranib the dog was re-presented to the hospital with acute recurrence to 2.2 mg/kg BW, PO, q48h. The patient remains in complete of inguinal edema, erythema, pain, and newly formed vesicles remission 1 y after starting toceranib therapy (Figures 1D (Figures 1B and 1F). At this time, the TKI was switched and 1H). The prescribed medications and doses over time are from imatinib to toceranib (Palladia; Pfizer Animal Health, shown in Figure 4. Parsippany-Troy Hills, New Jersey, USA), 2.75 mg/kg BW, PO, q48h. The erythema and edema disappeared 1 wk after Discussion administration of toceranib, and complete resolution of the To our knowledge, there has been 1 report of a dog treated with lesions was noted after 3 consecutive doses (Figures 1C and 1G). toceranib and metronomic chemotherapy as rescue therapy after Thereafter, the dose ranged from 2.75 mg to 3.25 mg/kg BW receiving doxorubicin (4), but there is no report of toceranib according to the growing patient’s increasing body weight and being used as a first-line therapy for canine lymphangiosarcoma. the various dose strengths of toceranib (10 mg and 15 mg) This is the first report to identify lymphatic obstruction and available in our hospital. Three months later, the dog developed leakage associated with lymphangiosarcoma on CT lymphog- intermittent mild swelling with pain in the inguinal region, raphy with multiple injection sites. which resolved within 1 wk of starting prednisolone (Solondo; Lymphangiosarcoma appears to be locally invasive and often Yahan, Taipei, Taiwan), 0.5 mg/kg BW, PO, tapered from twice has poorly defined borders, making adequate surgical excision daily to every other day. A hematology and serum chemistry difficult (2). Previously reported cases involved solitary masses panel performed 9 mo after starting toceranib and 10 mo that were surgically resected with a wide margin followed with

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Figure 3. Intraoperative photographs showing ligation of the inguinal lymphatic duct (A) and the histopathology of the inguinal subcutis (B) in a dog with lymphedema in the inguinal region. A — Leakage of fluid from the lymphatic duct connected to the superficial RAPPORTCAS DE inguinal lymph nodes is observed; the lymphatic duct is isolated and circumferentially double-ligated with 3-0 polyglyconate. B — Histopathology of a subcutaneous inguinal subcutis demonstrating a poorly demarcated, infiltrative, and loosely cellular neoplasm composed of spindle cells forming multiple empty vascular-like spaces with no erythrocytes. Their nuclei are elongated and have finely stippled chromatin and indistinct nucleoli. Hematoxylin and eosin staining, 4003.

Figure 4. Graph showing the medications administered and the changes in dose according to the patient’s clinical course. The patient was initially treated with imatinib 10 mg/kg BW per day PO for 1 mo. However, after relapse (asterisk) at 1 mo after surgery, imatinib was switched to toceranib 2.7 mg/kg BW on alternate days. The patient appeared to tolerate this dose, so toceranib was escalated to the maximum tolerated oral dose of 3.25 mg/kg BW on alternate days. Mild leukopenia was identified 9 mo after starting toceranib, so the dose was reduced to the minimum of 2.2 mg/kg BW orally on alternate days. Rutin, 500 mg/kg BW, orally twice daily was administered continuously after the initial presentation 12 mo earlier.

postoperative chemotherapy (2,5). In humans, the surgical Sagartz et al (1) reported that a 2-month-old puppy with lym- options for chronic lymphedema are lymphovenous anastomosis, phangiosarcoma, which was treated with chemotherapy using lymphatic grafting, and ligation and excision of retroperitoneal a morpholino-doxorubicin derivative for 6 cycles, developed lymphatic vessels with or without lymphovenous anastomoses parvoviral enteritis 1 mo after the final cycle was administered at (6). In the present case, the surgery was performed not only for the age of 6 mo; septic polyarthritis occurred a month later. The diagnostic purposes but also to relieve symptoms by removing dog was euthanized at that time. Such infections could develop subcutaneous tissue, ligating the lymphatics, and resecting the in response to immune suppression caused by chemotherapy in involved lymph nodes. The subcutaneous edema decreased after a growing dog. In the present case, targeted therapy was initi- the surgery, but the lymphedema recurred 4 wk later. ated after a postoperative relapse using a TKI without chemo- Because of the moderate to high metastatic potential of lym- therapy to reduce the risk of cytotoxic effects in normal cells. phangiosarcoma, adjunctive cytotoxic chemotherapy should be Of note, in canine oncology, toceranib phosphate has activity considered (2,7). However, our patient was diagnosed as having against both cancer cells and the tumor microenvironment via lymphangiosarcoma at the young age of 4 mo, and the owner inhibition of several cell surface and angiogenic receptors for refused the option of chemotherapy for this reason. Traditional vascular endothelial growth factor (VEGF), platelet-derived cytotoxic chemotherapy destroys not only cancer cells but also growth factor (PDGF), stem cell factor, cytokine Flt-3 ligand, normal cells and targets rapidly dividing cells, which can result and KIT (9). Toceranib is currently approved for the treatment in side effects, including bone marrow toxicity, gastrointestinal of canine cutaneous mast cell tumors, but also has potential toxicity, and hair loss (8). In young dogs that are still grow- therapeutic activity in other canine tumors expressing VEGF ing, normal cells are dividing more rapidly than in adult dogs; or having aberrant VEGF signaling (10). These tumors include therefore, chemotherapy could damage these cells and prevent various carcinomas, vascular tumors, meningiomas, and cutane- normal growth and development of the animal. For example, ous fibrosarcoma (10). Moreover, the findings of several clinical

370 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY investigations indicate a role for toceranib in the treatment of steroids, diuretics, anticoagulants, and fibrinolysin inhibitors. several canine neoplasms, including multiple myeloma, apo- When our patient developed intermittent mild swelling with crine gland adenocarcinoma in the anal sac, osteosarcoma, and pain during toceranib therapy, a steroid was administered inter- melanoma (9–12). However, the antitumoral effects of toceranib mittently because the dog had previously been diagnosed with when used without chemotherapy have not been investigated in lymphangiosarcoma that presented as diffuse swelling, which dogs with lymphangiosarcoma. In the present case, toceranib was considered to be the main cause of the dog’s discomfort and REPORT CASE showed significant clinical efficacy without chemotherapy. pain. In a retrospective study of canine lymphangiosarcoma, it Tyrosine kinase inhibitors also have cytotoxic effects in nor- was reported that anti-inflammatory doses of steroids reduced mal tissues, probably because of the effects of chronic inhibition the swelling adjacent to the mass but that non-steroidal anti- of the tyrosine kinase receptors expressed on normal cells (9). In inflammatory drugs did not have such an effect in dogs with adult dogs, toceranib can induce anorexia, vomiting, diarrhea, lymphangiosarcoma (2). Furthermore, a previous report on and gastrointestinal bleeding, which can be readily treated by human lymphedema demonstrated that intralymphatic steroid supportive therapy and a drug holiday (9,11). There are no therapy had beneficial effects and suggested that the lysosomal reports in the veterinary literature on the toxicity or safety of membrane-stabilizing effect of steroids potentially inhibits toceranib in dogs aged younger than 24 mo. However, long- the deposition of collagen (18). However, corticosteroids may term toceranib therapy was well-tolerated in our puppy, except inhibit growth when administered to immature animals (19), so for transient leukopenia noted 9 mo after starting treatment at we administered the drug intermittently at an anti-inflammatory the age of 5.5 mo. dose in our patient. Benzopyrones are also commonly used Imatinib is another TKI approved for clinical use and repre- to treat lymphedema, and have been reported to exert their sents a milestone in human cancer therapy (9). Initially imatinib effect via stimulation of proteolysis by tissue macrophages was administered herein because it was the only TKI available (17,20,21). In our puppy, rutin delayed the time to recurrence in our hospital at that time. When the lesions relapsed, the TKI of lymphedema by 2-fold (from 2 wk to 4 wk). Nevertheless, was switched from imatinib to toceranib; the lesions resolved the rapid clinical improvement suggests that toceranib can play after 3 consecutive doses of toceranib, possibly because of the a major role in the treatment of lymphangiosarcoma. Rutin was difference in the spectrum of activity between these 2 drugs. continued in addition to toceranib therapy in this case because The activities of the TKIs are similar but not the same. Imatinib rutin is inexpensive and generally considered to be free of side- is a small-molecule inhibitor of several tyrosine kinase recep- effects (17). It is impossible to judge whether toceranib alone or tors, including PDGF and KIT, but unlike toceranib has no in combination with rutin and intermittent prednisolone was activity against VEGF (12). The VEGF receptor has recently responsible for the tumor response. Although rutin appeared been shown to promote lymphangiogenesis in mice (2,13), to have little clinical efficacy alone and no cytotoxic effect, a and it is possible that toceranib inhibited lymphangiogenesis combination of rutin and a TKI may be more effective than in our canine patient with recurrent lymphedema caused by either agent alone. Intermittent prednisolone could also assist lymphangiosarcoma. in the management of the swelling associated with lymphangio- Toceranib was started at a dose of 2.7 mg/kg BW on alter- sarcoma. While some studies in humans have identified rutin to nate days. The patient appeared to tolerate this dose, so the be potentially hepatotoxic (22), no adverse effects were seen in drug dosage was increased to the maximum tolerated dose of the hematology and biochemistry profile in our patient during 3.25 mg/kg BW, PO, q48h. Nine months after starting tocera- 1 y of rutin therapy. nib, the patient developed transient mild leukopenia. Based on A diagnosis of lymphedema is initially made according to recent data suggesting that lower doses of toceranib have an findings on physical examination and patient history (15). improved safety profile while maintaining the biologic activity Further investigation of the competence of the lymphatic of the drug (10,14), the toceranib dosage was reduced to the system may include lymphography (15). There have been minimum of 2.2 mg/kg BW, PO, q48h and the leukopenia reports of CT lymphography with percutaneous injection of was improved 7 d later. The most common adverse effect of Iohexol into the popliteal lymph nodes in healthy dogs (3,23). toceranib is gastrointestinal toxicity (14) but mild neutropenia However, we were able to delineate the lymphatic obstruction can also occur. However, the WBC generally does not decrease and leakage inducing lymphedema more accurately in our case to below 1.5 3 109/L and the neutropenia often resolves over by lymphography with injection of Iohexol into multiple lymph time, as in our case (9). nodes. Lymphedema is characterized by accumulation of protein- To our knowledge, this case report is the first in which rich edema fluid in the interstitium in response to inadequate CT lymphography has been used to identify lymphatic obstruc- lymphatic drainage and is attributed to either congenital lym- tion and leakage associated with lymphadenopathy and lymphatic abnormalities or acquired lymphatic obstruction (15). phangiosarcoma using percutaneous injection of Iohexol into In previous reports on canine lymphangiosarcoma, edema multiple inguinal and popliteal lymph nodes bilaterally. In was sometimes observed at least 1 y before development of a our patient, the accumulation of contrast medium seen in the mass or diagnosis of the disease (7,15,16). In the early stages inguinal region on lymphography could have been caused by of lymphedema, before the development of fibrosis, medical occlusion of the lymphatic pathway by the lymphangiosarcoma therapy may decrease the swelling and allow the patient to be and leakage from the lymphatic vessels (16,24). The sublumbar more comfortable (17). The pharmacological options include lymph nodes (including the medial iliac, hypogastric, and sacral

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nodes) showed no or poor enhancement because of obstruc- 9. Bavcar S, Argyle DJ. Receptor tyrosine kinase inhibitors: Molecularly tion of lymphatic flow by sublumbar lymphadenopathy. In the targeted drugs for veterinary cancer therapy. Vet Comp Oncol 2012;10: 163–173. dog, the sublumbar lymph nodes receive lymph from the soft 10. Pan X, Tsimbas K, Kurzman ID, Vail DM. Safety evaluation of com- tissues, including the skin and muscles of the pelvis and hind bination CCNU and continuous toceranib phosphate (Palladia®) in limbs, as well as the genital organs (25). Therefore, obstruction tumour-bearing dogs: A phase I dose-finding study. Vet Comp Oncol 2016;14:202–209. of the sublumbar lymph nodes can induce stasis of lymph and 11. London CA, Hannah AL, Zadovoskaya R, et al. Phase I dose- edema of the hind limbs and pelvic and inguinal regions, as in escalating study of SU11654, a small molecule receptor tyrosine kinase our puppy. Finally, CT lymphography was useful for diagnos- inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res 2003;9:2755–2768. ing lymphedema and understanding the pathophysiology in 12. London CA. Kinase dysfunction and kinase inhibitors. Vet Dermatol this case. 2013;24:181–187. This is the first description of successful long-term man- 13. Dellinger MT, Meadows SM, Wynne K, Cleaver O, Brekken RA.

RAPPORTCAS DE Vascular endothelial growth factor receptor-2 promotes the development agement using TKI without concurrent chemotherapy in a of the lymphatic vasculature. PLoS One 2013;8:e74686. puppy with lymphangiosarcoma. Veterinarians could consider 14. Bernabe LF, Portela R, Nguyen S, et al. Evaluation of the adverse event toceranib as a first-line postoperative treatment option in a dog profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose. with lymphangiosarcoma and lymphedema. When extensive BMC Vet Res 2013;9:190. leakage of contrast medium is detected during lymphography, 15. Webb JA, Boston SE, Armstrong J, Moens NM. Lymphangiosarcoma lymphangiosarcoma-related lymphedema and lymphadenopathy associated with primary lymphedema in a Bouvier des Flandres. J Vet Med Sci 2004;18:122–124. should be included in the differential diagnosis. 16. Sicotte V, Benamou J, Fifle LC, et al. Use of surgery and mitoxantrone chemotherapy in a dog with disseminated lymphangiosarcoma. J Am Acknowledgment Vet Med Assoc 2012;241:1639–1644. 17. Fossum TW, King LA, Miller MW, Butler LM. Lymphedema. Clinical This study was supported by Konkuk University Veterinary signs, diagnosis, and treatment. J Vet Intern Med 1992;6:312–319. Medical Teaching Hospital, South Korea. CVJ 18. Fyfe NCM, Rutt DL, Edwards JM, Kinmonth JB. Intralymphatic steroid therapy for lymphoedema: Preliminary studies. Lymphology 1982; References 15:23–28. 19. Day MJ. Glucocorticosteroids and antihistamines. In: Maddison J, 1. Sagartz JE, Laimore MD, Haines D, Sheafor SE, Couto CG. Page S, Church D, eds. Small Animal Clinical Pharmacology. 1st ed. Lymphangiosarcoma in a young dog. Vet Pathol 1996;33:353–356. London, England: Saunders, 2002:223–232. 2. Curran KM, Halsey CH, Worley DR. Lymphangiosarcoma in 12 dogs: 20. Casley-Smith JR, Morgan RG, Piller NB. Treatment of lymphedema A case series (1998–2013). Vet Comp Oncol 2014;14:181–190. of the arms and legs with 5,6-benzo-[alpha]-pyrone. N Engl J Med 3. Chun H, Cho H, Cheon H, et al. Determination of optimal dosage and 1993;329:1158–1163. delay time for computed tomographic lymphography after percutaneous 21. Casley-Smith JR, Casley-Smith JR. The pathophysiology of lymph- injection of Iohexol into popliteal lymph nodes in dogs. J Vet Med Sci edema and the action of benzo-pyrones in reducing it. Lymphology 2009;71:873–878. 1988;21:190–194. 4. Marcinowska A, Warland J, Brearley M, Dobson J. A novel approach 22. Loprinzi CL, Kugler JW, Sloan JA, et al. Lack of effect of coumarin in to treatment of lymphangiosarcoma in a boxer dog. J Small Anim Pract women with lymphedema after treatment for breast cancer. N Engl J 2013;54:334–337. Med 1999;340:346–350. 5. Itoh T, Mikawa K, Mikawa M, Nibe K, Uchida K. Lymphangiosarcoma 23. Singh A, Brisson BA, Nykamp S, O’Sullivan ML. Comparison of com- in a dog treated with surgery and chemotherapy. J Vet Med Sci 2004;66: puted tomographic and radiographic popliteal lymphography in normal 197–199. dog. Vet Surg 2011;40:762–767. 6. Gloviczki P. Principles of surgical treatment of chronic lymphoedema. 24. Kang JH, Lee JY, Mo IP, et al. Secondary malignant lymphedema after Int Angiol 1999;18:42–46. mastectomy in two dogs. J Small Anim Pract 2007;48:579–583. 7. Barnes JC, Taylor SM, Clark EG, Haines DM, Broughton SJ. 25. Bezuidenhout AJ. The lymphatic system. In: Evans HE, de Lahunta A, Disseminated lymphangiosarcoma in a dog. Can Vet J 1997;38:42–44. eds. Miller’s Anatomy of the Dog. 4th ed. St. Louis, Missouri: Saunders, 8. Gustafson DL, Page RL. Cancer chemothrerapy. In: Withrow SJ, Vail 2013:550–552. DM, Page RL, eds. Small Animal Clinical Oncology. 5th ed. St. Louis, Missouri: Saunders, 2013:157–179.

372 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY Case Report Rapport de cas

Primary colonic hemangiosarcoma in a dog

Munetaka Iwata, Takeshi Aikawa, Yuta Miyazaki, Shigeo Sadahiro

Abstract — A 13-year-old spayed female miniature dachshund dog was presented with a history of hematochezia, melena, and weight loss. A colonic mass detected by exploratory celiotomy was resected and diagnosed as hemangiosarcoma (HSA). Liver lobectomy for hepatic HSA was performed 894 days after surgery. Adjuvant chemotherapy was declined. This is the first documentation of a canine colonic HSA.

Résumé — Hémangiosarcome primaire du côlon chez un chien. Une chienne Dachsund miniature stérilisée âgée de 13 ans a été présentée avec une anamnèse d’hématochézie, de méléna et de perte de poids. Une masse du côlon détectée par céliotomie exploratoire a été réséquée et diagnostiquée comme un hémangiosarcome (HSA). La lobectomie pour le HSA hépatique a été réalisée 894 jours après la chirurgie. La chimiothérapie adjuvante a été refusée. Il s’agit de la première documentation d’un HSA canin du côlon. (Traduit par Isabelle Vallières) Can Vet J 2018;59:373–378

Case description Japan), 0.7 mg/kg body weight (BW), PO, q24h, sucralfate (Ulcerlmin; Chugai Pharmaceutical, Tokyo, Japan), 500 mg, 13-year-old, 3.5-kg spayed female miniature dachshund PO, q12h, metronidazole (Flagyl; Shionogi & Co., Osaka, dog was referred to the Aikawa Veterinary Medical Center A Japan), 17.8 mg/kg BW, PO, q12h, and salazosulfapyridine with a 7-day history of hematochezia and melena. The patient (Salazopyrin tablet; Pfizer Japan, Aichi, Japan), 35.1 mg/kg was bright, alert, and responsive with a good appetite but had BW, PO, q12h, was started. Hematologic and serum biochem- lost weight (body condition score: 2/5). The remainder of this istry panels, conducted at the referring veterinarian’s office on patient’s physical examination findings including digital rectal the next day, were within normal limits [PCV: 39.8%, WBC: examination was unremarkable. 9900 cells/mL, total protein (TP): 54 g/L, albumin: 28 g/L]. A complete blood (cell) count (CBC) detected a mild regen- Fecal hemoglobin measured with a latex aggregation test was erative anemia [packed cell volume (PCV): 33.8%; reference 700 ng/mL (normal value: , 20 ng/mL). range (RR): 37% to 55%, Reticulocyte Production Index: . 2]. Since relapse of intestinal bleeding was subsequently noted, White blood cell (WBC) and platelet counts and the serum upper and lower gastrointestinal endoscopy was performed on biochemical profile were within normal limits. Red blood cells day 21 but detected no gastrointestinal tract inflammation, were detected in the feces. ulcers, or neoplastic lesions. Gastrointestinal biopsies were Three-view thoracic and 2-view abdominal radiography and taken from the gastric cardia, fundus, angular incisure, and echocardiography detected no abnormalities. Abdominal ultra- pylorus. Specimens were also obtained from the proximal and sonography detected 2 hypoechoic liver lesions (0.6 3 0.4 cm, distal duodenum, ileum, ileocecum, and proximal and distal 0.8 3 0.5 cm), 1 hyperechoic splenic lesion (0.2 3 0.2 cm) and colon. No abnormalities were noted on the gross morphology no lymphadenopathy. The remaining organs (gall bladder, kid- of gastrointestinal mucosal surface or on histopathology of the ney, urinary bladder, stomach, duodenum, pancreas, and small collected samples. Contrast gastrointestinal radiography using and large intestines) were unremarkable based on abdominal barium sulfate (Baritogen-sol; Fushimi Pharmaceutical, Kagawa, ultrasound examination. Japan), 5.7 mL/kg BW, PO, did not detect filling defects, intes- A gastrointestinal ulcer and colitis were suspected and medi- tinal obstruction, or any other abnormalities. cal treatment with famotidine (Gaster; Astellas Pharma, Tokyo, The dog was readmitted 5 d later because of decreased mobility, ataxia, and progressive worsening of hematochezia and Aikawa Veterinary Medical Center, Veterinary Surgical Service melena. Physical examination revealed pale mucous membranes, Japan, 4-3-1 Nishi-ochiai Shinjuku-ku, Tokyo 161-0031, Japan. weak femoral pulses, and no abnormalities on thoracic ausculta- Address all correspondence to Dr. Munetaka Iwata; e-mail: tion and abdominal palpation. Neurologic examination revealed [email protected] depressed but responsive mentation. Use of this article is limited to a single copy for personal study. Severe anemia (PCV: 15.0%, RR: 37% to 55%, Reticulocyte Anyone interested in obtaining reprints should contact the Production Index: . 2) with mild thrombocytopenia CVMA office ([email protected]) for additional (16.1 3 104/mL, RR: 20.0 to 50.0 3 104/mL), hypoalbumin- copies or permission to use this material elsewhere. emia (12 g/L, RR: 26 to 40 g/L), and hypokalemia (2.9 mEq/L,

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Figure 1. A — Full surgical abdominal exploration revealed a round dark red-violet mass located between the cecum and proximal colon. B, C — Histopathological diagnosis was consistent with an intestinal HSA with complete excision.

RR: 3.8 to 5.0 mEq/L) was observed. Since a definitive cause of mosis with 3-0 polydioxanone suture in a simple interrupted the intestinal bleeding was not identified, an exploratory lapa- pattern was performed. The abdominal cavity was lavaged rotomy was carried out the following day. The dog was admin- with 1.5 L of warm sterile saline (0.9% NaCl) solution prior istered atropine sulfate (Atropin sulfate injection; Mitsubishi to closure. Tanabe Pharma, Osaka, Japan), 0.05 mg/kg BW, SC, morphine The resected mass was fixed in neutral-buffered 10% forma- hydrochloride (Morphine hydrochloride; Shionogi, Osaka, lin, embedded in paraffin, sectioned in slices 5-mm thick, and Japan), 0.5 mg/kg BW, IM, and midazolam (Dormicam injec- stained with hematoxylin and eosin (H&E). The histopathologi- tion; Astellas Pharma, Tokyo, Japan), 0.3 mg/kg BW, IV, before cal diagnosis was consistent with an intestinal hemangiosarcoma induction with propofol (Propofol 1% injection; Mylan, Tokyo, (HSA) with complete excision (Figures 1B, C; 2A, B). Tumor Japan), 4 mg/kg BW, IV. Anesthesia was maintained with iso- cells located between the submucous and muscular layers did flurane (Isoflu; DS Pharma Animal Health, Osaka, Japan) in not destroy the mucosal membrane. oxygen. Pain management included epidural analgesia with mor- Hematochezia and melena subsided 2 d after surgery, and phine hydrochloride (0.1 mg/kg BW) and bupivacaine (Marcain anemia improved gradually. Antibiotics were administered for Injection 0.25%; Aspen pharma, Tokyo, Japan), 0.2 mg/kg BW, 7 d (Cefazolin injection; Fujita Pharmaceutical, Tokyo, Japan), after induction. 20 mg/kg BW, IV, q12h, and as the dog continued to eat and Full surgical abdominal exploration performed after whole drink without assistance, IV fluid therapy was discontinued. blood transfusion (22 mL/kg BW, IV) with continuous IV No complications were noted during hospitalization and the potassium supplementation (0.04 mmol/kg BW per hour, IV) patient was discharged 7 d after surgery. The owner declined revealed a round dark red-violet mass (2.0 3 2.0 3 2.0 cm) doxorubicin-based adjuvant chemotherapy. located at the proximal colon (Figure 1A). Bimonthly postoperative recheck abdominal ultrasonography The mass did not adhere to surrounding tissues, and the revealed increased numbers and enlargement of hypoechoic serosal surface of the colon was intact. The remainder of the liver lesions 612 d after resection of the colonic HSA. However, abdominal organs appeared normal; therefore, the colon was fine-needle aspiration was not performed due to concerns of considered to be the site of the primary lesion. The mass was bleeding risks. Contrast-enhanced computed tomography was resected with 3-cm margins and an end-to-end colonic anasto- declined by the owner.

374 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY CASE REPORT CASE

Figure 2. Histopathological examination of (A, B) colonic HSA and (C, D) hepatic HSA. A, C — Hematoxylin and eosin stain revealed marked nuclear atypia (arrowhead) and moderate mitotic activity of tumor cells (arrow). B, D — Immunohistochemical staining confirmed moderate membranous-cytoplasmic expression of factor VIII in tumor cells.

The patient was presented with mental dullness, anorexia, Contrast-computed tomography scanning performed after lethargy, and pale mucosal membranes 894 d after surgery. the liver lobectomy detected a hypodense, non-enhancing cystic A CBC revealed WBC: 9400 cells/mL, PCV: 45.2%, plate- lesion in the right middle liver lobe and no leakage of contrast lets: 18.6 3 104/mL with a normal serum biochemical profile. medium from the right liver lobe lesions. The gallbladder was Severe fluid accumulation in the abdominal cavity was suspected compressed and displaced caudally due to the mass (Figure 3). after abdominal radiography and ultrasonography. Abdominal There were no metastatic lesions noted in the brain, chest, or paracentesis revealed frank hemorrhage and the character of the abdominal cavity. effusion was as follows; WBC: 9900 cells/mL, PCV: 45.2%, Vitamin K injection (3 mg/kg BW, SC) and Ringer’s solution platelets: 6.3 3 104/mL, TP 54 g/L, specific gravity (SG) 1.038, with 5% D-glucose, gabexate mesilate (1 mg/kg BW per hour), glucose 5.6 mmol/L. Bleeding from the hypoechoic liver lesions glutathione (1 mg/kg BW per hour), glycyrrhizin (0.1 mg/kg was suspected. BW per hour), and vitamin B complex (B1, B2, B6, B12) infu- Since anemia and thrombocytopenia progressed over the sion therapy were administered after surgery. Based on the blood next day (WBC: 13 400 cells/mL, PCV: 22.0%, platelets: test results, disseminated intravascular coagulation (DIC) was 2.1 3 104/mL), an exploratory laparotomy was performed. suspected [thrombocytopenia, prolonged prothrombin time, Hemoabdomen due to ruptured left-sided liver lesions was increase of fibrin degradation products (FDP)] (Table 1). Despite diagnosed and a total left hepatic lobectomy was performed using continuous IV supplementation with potassium (0.04 mmol/kg a TA-30 stapling device with V3 cartridge (Tyco Healthcare, BW per hour) and dalteparin sodium injection (Fragmin, Kissei Princeton, New Jersey, USA) following a whole blood transfu- Pharmaceutical, Tokyo, Japan), 100 U/kg BW, SC, q24h, anemia sion (22 mL/kg BW, IV). Although grossly similar lesions were and thrombocytepenia progressed and the patient died 5 d after detected in the right medial liver lobe (2.8 3 3.1 3 2.7 cm), the emergency liver lobectomy. Necropsy was not performed due this lobe was not bleeding, and lobectomy was not performed. to the owner’s decision.

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Table 1. Results of blood tests after emergency liver lobectomy. Value Reference range WBC 13.2 3 109/L 6 to 12 3 109/L PCV 21.4% 37% to 55% Platelets 31 3 109/L 200 to 500 3 109/L Total protein 37 g/L 50 to 72 g/L Albumin 18 g/L 26 to 40 g/L ALT . 16.7 mkat/L 0.28 to 1.30 mkat/L AST 15.7 mkat/L 0.28 to 0.73 mkat/L ALP 7.97 mkat/L 0.78 to 4.24 mkat/L GGT 0.02 mkat/L 0.08 to 0.23 mkat/L Tbil 5.1 mmol/L 1.7 to 8.6 mmol/L m m NH3 15.7 mol/L 9.3 to 43.7 mol/L RAPPORTCAS DE Tchol 3.2 mmol/L 2.9 to 8.1 mmol/L BUN 5.5 mmol/L 3.3 to 10.4 mmol/L Glucose 8.3 mmol/L 4.2 to 7.1 mmol/L Partial thromboplastin time 14 s 10 to 16 s Prothrombin time 11 s 6 to 8 s Fibrinogen 3.44 mmol/L 2.53 to 11.03 mmol/L FDP 43.7 mg/L 0.0 to 5.0 mg/L Antithrombin 3 147% 102% to 156%

WBC — white blood cells; PCV — packed cell volume; ALT — alanine aminotransferase; AST — aspartate aminotransferase; ALP — alkaline phosphatase;

GGT — gamma-glutamyl aminotransferase; Tbil — total bilirubin; NH3 — ammonia; Tchol — total cholesterol; BUN — blood urea nitrogen; FDP — fibrin degradation Figure 3. Contrast enhanced computed tomography scanning products. performed after emergency liver lobectomy detected a 3-cm hypodense, non-enhancing cystic lesion in the right middle liver lobe (asterisk). The gallbladder was compressed and displaced HSA which had complete surgical resection was 780 d, stage 2 caudally due to mass effect (arrow). Transverse image of cranial (subcutaneous) and stage 3 (intramuscular) had MSTs of 172 to (A) and middle (B) part of liver. 307 d (2), suggesting the prognosis is different depending on the histopathological stage and status of surgical excision. The The histopathological diagnosis of left-sided liver mass was clinical course of canine intestinal HSA has not been well- consistent with HSA with incomplete excision (Figure 2C, D). documented (10,11). In human HSA, frequent primary sites are breast (35%), skin Discussion (20%), muscle or subcutaneous tissue (13%), heart (5%), bone Hemangiosarcoma (HSA) is a highly malignant neoplasm of (4%), spleen (4%), and liver (4%) (12–14). As with canine vascular endothelial origin that develops in any tissue with HSA, human HSA of the heart, spleen, and liver carry a poor blood vessels. The frequent primary sites of canine HSA are prognosis (5-year survival rate: 0%). But human HSA at other the spleen (50% to 65%), right atrium (3% to 25%), skin and sites have better 5-year survival rates (muscle and subcutaneous: subcutaneous tissues (13% to 17%), and liver (5% to 6%) (1). 74%, breast: 51%, skin: 43%, bone: 36%) (13). The histologi- Typical canine splenic HSA is characterized by early distant cal grade of human mammary HSA also determines the 5-year metastasis and poor survival rates, despite surgical resection and postoperative disease-free rate (low grade: 76%, intermediate adjuvant chemotherapy. The mean survival times (MSTs) for grade: 70%, and high grade: 15%) (15). dogs after splenectomy alone are 19 to 86 d, and the 12-month Intestinal HSA is also rare in humans and only 33 cases of survival percentage is 10% or less. Primary hepatic HSA carries small intestinal HSA have been reported in the English lit- an equally poor prognosis (1,2). erature over the past 42 y (12). Reported survival times after In contrast, several reports described long-term survival of being diagnosed varied (several days to 1 y: 21 reports, 1 to 2 y: digs with HSA of other sites of origin. A dog with primary lum- 6 reports, 2 to 5 y: 3 reports, unknown: 3 reports). Although bar extradural HSA survived over 15 mo after incomplete surgi- human small intestinal HSA was histologically classified into cal excision and chemotherapy (3). Three canine patients with well-differentiated, poorly differentiated, and epithelioid angio- penile HSA treated with complete resection with or without sarcoma, the prognosis was generally poor regardless of the his- chemotherapy survived 236 d, 206 d, and 20 mo, respectively tological grade (12). Two reports that described feline intestinal (4–6). A dog with intranasal HSA treated by incomplete surgical HSA (total of 20 cats) indicated a poor prognosis (MSTs was excision with radiation therapy survived more than 30 mo (7). not described) (16,17). Fourteen dogs with renal HSA treated with surgery with or The reason for the poor prognosis of human and feline intes- without adjuvant chemotherapy had improved 1-year survival tinal HSA may be partly due to late diagnosis. While cutaneous rates (29%) and longer MSTs (278 d) compared with previous and subcutaneous neoplasms are easy to identify because of reports of dogs with splenic and hepatic HSA (8). The MSTs their conspicuousness, the presenting symptoms associated with of 20 dogs with surgically treated lingual HSA combined with intestinal tumors are non-specific and often poorly defined (12). or without adjuvant chemotherapy was 553 d (9). The clinical manifestations of human patients with HSA of the Thus, prognosis of canine HSA varies, depending on the site small intestine included anorexia, weight loss, lethargy, vomit- of origin. Furthermore, the MSTs for dogs with stage 1 dermal ing, weakness, diarrhea, altered intestinal function, tenesmus,

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intestinal villi. This may be the reason bleeding was difficult to observe with non-invasive diagnostic techniques (Figure 4). Local recurrence was not observed by gastrointestinal palpation at the emergency liver lobectomy and postoperative contrast enhanced CT scanning. Histological diagnosis of the left-sided

liver mass was consistent with HSA and expression of factor REPORT CASE VIII in tumor cells was confirmed by immunohistochemical staining. The patient died due to rupture of the hepatic HSA and associated DIC 5 d after surgery. The authors cannot confirm whether the 2 hypo-echoic liver lesions identified at the first medical examination were the HSA that slowly enlarged. It is unclear whether the liver lesions were metastatic lesions of the colonic mass, or if they were synchro- nous lesions of HSA arising in many tissues simultaneously. It is possible that survival times of canine HSA are different depending on histological grading (21,22), as reported in human Figure 4. Histologically, several bleeding points were seen at the bottom of intestinal villi. There was no ulcer formation on the breast HSA. The relation between histological grading and prog- mucosal surface. nosis has not been well-described in canine HSA. Postoperative metastasis after long-term local control as reported in human intestinal HSA is another possibility. Liver nonspecific abdominal pain, melena, anemia, hypoglycemia, metastasis 33 mo after colonic HSA (primary lesion was breast) acute abdominal signs and/or symptoms of ileus, and even non- resection (23), lung metastasis 21 mo after duodenal HSA resec- specific chest pain (13,14). Clinical signs often relate to location (23), and abdominal wall metastasis 21 mo after duodenal tion of the tumor within the GI tract. Small intestinal lesions and ileal HSA resection (24) have been described in humans. commonly result in weight loss and large bowel lesions result in It is also possible that the hepatic HSA of the case herein was hematochezia and tenesmus. Since clinical symptoms may vary, a new primary lesion unrelated to the colonic HSA or a syn- a combination of multiple diagnostic tests is often required. chronous lesion. Radiography, contrast radiography, ultrasonography, and To our knowledge, this is the first documentation of a canine gastrointestinal endoscopy modalities that are commonly used HSA arising from the colon. This case suggests that canine HSA in the diagnosis and staging of animals with suspected intes- arising from the large intestine may have a better chance for tinal neoplasms (18). When these non-invasive or minimally long-term survival after complete surgical excision compared invasive diagnostics fail to confirm a diagnosis, an exploratory with splenic and hepatic HSA. laparotomy may be indicated for humans and dogs with persistent signs of intestinal disease (12,18). In the present case, the Acknowledgments tumor was not detected by non-invasive examinations. While The authors acknowledge Dr. Kyle G. Mathews at North Carolina computed tomography (CT) may reveal important information State University for editing and assistance with preparation of this about the gastrointestinal tract, it was not applied in this case article, Dr. Yumiko Kagawa, for histopathological diagnosis, and due to its emergent nature (19). Dr. Kiyotaka Arai, for assistance in preparing figures. CVJ Cutaneous, subcutaneous, and intramuscular HSA should be excised with 3-cm lateral margins and a minimum of 1 fascial References layer for deep margins. Wide surgical margins (i.e., 5 cm) are . 1 Smith AN. Hemangiosarcoma in dogs and cats. Vet Clin North Am generally recommended for intestinal tumors (2,20). In this case, Small Anim Pract 2003;33:533–552. to preserve the ileocolic valve, colonic resection, and anastomosis 2. Thamm DH. Miscellaneous tumors: Hemangiosarcoma. In: Withrow SJ, MacEwen EG, eds. Small Animal Clinical Oncology. 5th ed. was performed with 3-cm margins of normal intestine on either Philadelphia, Pennsylvania: WB Saunders, 2012:679–688. end of the mass. 3. Paek M, Glass E, Kent M, Clifford CA, De Lahunta A. Primary lumbar Histological examination of the mass confirmed complete extradural hemangiosarcoma in a dog. J Am Anim Hosp Assoc 2015; 51:191–196. resection and revealed typical anastomosing neoplastic vascular 4. Fry JK, Burney D, Hottinger H, Fabiani M, Feagin C. Pollakiuria and channels lined by spindle-shaped tumor cells with marked stranguria in a Labrador retriever with penile HSA. J Am Anim Hosp nuclear atypia and moderate mitotic activity, leading to the Assoc 2014;50:141–147. 5. Bolfer L, Schmit JM, McNeill AL, Ragetly CA, Bennett RA, McMichael diagnosis of HSA. There were multifocal areas of necrosis M. Penile amputation and scrotal urethrostomy followed by chemo- and tumor destroyed structures of the inner circular muscular therapy in a dog with penile hemangiosarcoma. J Am Anim Hosp Assoc layer, but tumor cells did not destroy mucosal membranes. In 2015;51:25–30. 6. Burchell RK, Kirberger RM, Janse van Rensberg DD. Haemangiosar addition, immunohistochemical staining confirmed moderate coma of the os penis in a dog: The most common neoplasm of the membranous-cytoplasmic expression of factor VIII in tumor canine penis. J S Afr Vet Assoc 2014;85:1092. cells (Figure 2A, B). 7. Fujita M, Takaishi Y, Yasuda D, et al. Intranasal hemangiosarcoma in a dog. J Vet Med Sci 2008;70:525–528. There was no ulcer formation on the mucosal surface; how- 8. Locke JE, Barber LG. Comparative aspects and clinical outcomes of ever, several small areas of bleeding were seen at the bottom of canine renal hemangiosarcoma. J Vet Intern Med 2006;20:962–967.

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. 9 Burton JH, Powers BE, Biller BJ. Clinical outcome in 20 cases of lin- 17. Culp WT, Drobatz KJ, Glassman MM, Baez JL, Aronson LR. Feline gual hemangiosarcoma in dogs: 1996–2011. Vet Comp Oncol 2014; visceral hemangiosarcoma. J Vet Intern Med 2008;22:148–152. 12:198–204. 18. Culp WT, Cavanaugh RP, Calfee EF, Buracco P, Banks TA. Alimentary 10. Crawshaw J, Berg J, Sardinas JC, et al. Prognosis for dogs with nonlym- tract. In: Simon TK, Bernard S, eds. Veterinary Surgical Oncology. phomatous, small intestinal tumors treated by surgical excision. J Am 1st ed. Ames, Iowa: Wiley-Blackwell, 2012:216–217. Anim Hosp Assoc 1998;34:451–456. 19. Vignoli M, Saunders J. Gastrointestinal tract. In: Schwarz T, Saunders 11. Dorn CR, Taylor DO, Schneider R, Hibbard HH, Klauber MR. Survey J, eds. Veterinary Computed Tomography. 1st ed. Ames, Iowa: Wiley- of animal neoplasms in Alameda and Contra Costa Counties, California. Blackwell, 2011:325–330. II. Cancer morbidity in dogs and cats from Alameda County. J Natl 20. Liptak JM, Dernell WS, Farese JP, Worley DR. Musculoskeletal system. Cancer Inst 1968;40:307–318. In: Simon TK, Bernard S, eds. Veterinary Surgical Oncology. 1st ed. 12. Zacarias Föhrding L, Macher A, Braunstein S, Knoefel WT, Topp SA. Ames, Iowa: Wiley-Blackwell, 2012:491–568. Small intestine bleeding due to multifocal hemangiosarcoma. World J 21. Bertazzolo W, Dell’Orco M, Bonfanti U, et al. Canine angiosarcoma: Gastroenterol 2012;18:6494–4500. Cytologic, histologic, and immunohistochemical correlations. Vet Clin 13. Fayette J, Martin E, Piperno-Neumann S, et al. Angiosarcomas, a hetero- Pathol 2005;34:28–34.

RAPPORTCAS DE geneous group of sarcomas with specific behavior depending on primary 22. Ogilvie GK, Powers BE, Mallinckrodt CH, Withrow SJ. Surgery and site: A retrospective study of 161 cases. Ann Oncol 2007;18:2030–2036. doxorubicin in dogs with hemangiosarcoma. J Vet Intern Med 1996; 14. Weiss S, Goldblum J. Malignant vascular tumors. In: Enzinger and 10:379–384. Weiss’s Soft Tissue Tumors. 4th ed. St. Louis, Missouri: Mosby, 2001: 23. Allison KH, Yoder BJ, Bronner MP, Goldblum JR, Rubin BP. 917–954. Angiosarcoma involving the gastrointestinal tract: A series of primary 15. Rosen PP, Kimmel M, Ernsberger D. Mammary angiosarcoma: The and metastatic cases. Am J Surg Pathol 2004;28:298–307. prognostic significance of tumor differentiation. Cancer 1988;62: 24. Aitola P, Poutiainen A, Nordback I. Small-bowel angiosarcoma after 2145–2151. pelvic irradiation: A report of two cases. Int J Colorectal Dis 1999; 16. Sharpe A, Cannon MJ, Lucke VM, Day MJ. Intestinal haemangiosar- 14:308–310. coma in the cat: Clinical and pathological features of four cases. J Small Anim Pract 2000;41:411–415.

378 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY Case Report Rapport de cas

Retrobulbar malignant peripheral nerve sheath tumor in a golden retriever dog: A challenging diagnosis

Cécile Briffod, Pierre Hélie, Julie De Lasalle, Louis-Philippe de Lorimier, Alicia R. Moreau, Derron A. Alves, Maria Vanore

Abstract — A 9-year-old golden retriever dog was diagnosed with a left retrobulbar mass. Fine-needle aspirations and incisional biopsies resulted in discordant diagnoses: myxosarcoma/myxoma or rhadomyosarcoma, respectively. Immunohistochemistry following exenteration allowed definitive diagnosis of malignant peripheral nerve sheath tumor with fibromyxomatous differentiation. Fifteen weeks after surgery, an aggressive recurrence resulted in euthanasia.

Résumé — Tumeur rétrobulbaire maligne des gaines nerveuses périphériques chez un Golden Retriever : un défi diagnostique. Une masse rétrobulbaire gauche a été diagnostiquée chez une Golden Retriever de 9 ans. Des aspirations à l’aiguille fine et des biopsies incisionnelles ont établi des diagnostics discordants : un myxosarcome/ myxome ou un rhabdomyosarcome, respectivement. Suite à l’exentération, l’immunohistochimie a permis un diagnostic définitif de tumeur maligne des gaines nerveuses périphériques avec différenciation fibro-myxomateuse. Quinze semaines après la chirurgie, une récidive agressive a conduit à l’euthanasie de la chienne. (Traduit par les auteurs) Can Vet J 2018;59:379–384 eoplasia is commonly observed as a cause of orbital pathol- well as in veterinary medicine. There is no one specific immuno- N ogy in older dogs. Numerous orbital neoplasms have been histochemical marker able to define a PNST, so a panel of mark- described in small animals, and can be primary, metastatic, ers is needed. Peripheral nerve sheath tumors are mesenchymal or from local extension of neoplasia of neighboring tissue. tumors positive for Vimentin. Immunoreactivity of S-100 is Approximately 75% to 95% of these tumors are malignant and restricted to a subpopulation of tumor cells, because this marker are associated with a poor prognosis (1,2). only labels neoplastic Schwann cells, not the remaining tumor Canine malignant peripheral nerve sheath tumors (MPNSTs) cells. Expression of glial fibrillary acidic protein (GFAP) is can occur in the peripheral nervous system (PNS) but also in variable (4). Documented cases of retrobulbar tumors of nerve soft tissues and various organs including the eye or orbit (3–6). sheath origin are scarce in the veterinary literature (5,7–9). These tumors occur in middle-aged to older dogs, particularly Among them, the most recent report was about a 1-year-old in medium- to large-breeds and are characterized by slow growth pug dog with a retrobulbar pigmented peripheral nerve sheath and rare metastasis (3,4). Lack of specific histological features tumor, whose prognosis was poor (5). of these tumors is a common diagnostic challenge in human as The aim of this work was to describe the clinical and imaging findings of a malignant retrobulbar peripheral nerve sheath tumor, underscoring its challenging histological and immunohistochemical diagnosis. A better characterization of retrobulbar Department of Clinical Sciences (Briffod, De Lasalle, Vanore), MPNST will allow veterinarians to understand its biological Department of Pathology and Microbiology (Hélie), Faculté de behavior and eventually improve patient management and Médecine Vétérinaire, Université de Montréal, 3200 rue Sicotte, prognosis. Saint-Hyacinthe, Quebec J2S 2M2; Department of Oncology, Centre Vétérinaire Rive-Sud, 7415 Taschereau, Brossard, Québec Case description J4Y 1A2 (de Lorimier); Veterinary Pathology Services, Joint A 9-year-old spayed female golden retriever dog was referred to Pathology Center, 606 Stephen Sitter Avenue, Silver Spring, the ophthalmology service of the Veterinary Teaching Hospital Maryland 20910, USA (Moreau, Alves). of Faculté de Médecine Vétérinaire, Université de Montréal, for Address all correspondence to Dr. Cécile Briffod; e-mail: evaluation of a left-sided periocular swelling of 2 months’ dura- [email protected] tion. The patient had been presented to a primary care veterinar- Use of this article is limited to a single copy for personal study. ian 2 mo before referral for serous discharge and discomfort of Anyone interested in obtaining reprints should contact the the left eye. An elevated nictitating membrane and mild swelling CVMA office ([email protected]) for additional of periocular soft tissues were noticed. A left eye uveitis was sus- copies or permission to use this material elsewhere. pected and topical treatment with dexamethasone/tobramycin

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eye drops (Tobradex, Alcon Canada, Mississauga, Ontario), 1 drop every 12 h for 2 wk, and a systemic nonsteroidal anti- inflammatory drug (Firocoxib, Previcox; Mérial, Baie D’Urfé, Quebec), 5 mg/kg body weight (BW), q24h for 5 to 7 d, were prescribed. Because of persistent clinical signs in spite of medical treatment, an ophthalmology consultation was requested. A complete ophthalmic examination was performed including slit-lamp biomicroscopy (SL-15 Portable Slit Lamp; Kowa Optimed, Torrance, California, USA) and indirect oph- thalmoscopy (HC50 L Headband Rheostat; Heine, Dover, New Hampshire, USA). A menace response was present in RAPPORTCAS DE both eyes. Palpebral, direct, and consensual pupillary light and dazzle reflexes were also present, normal, and symmetric for both eyes. Schirmer tear test I (Color bar Schirmer tear test; Eagle Vision, Denville, New Jersey, USA) values were 25 mm/min and 30 mm/min in the right and left eyes, respectively. Fluorescein staining (MINIMS FLN 2.0; Chauvin Pharmaceuticals, Chauvin Pharmaceuticals, Kingston upon Thames, England) was negative in both eyes. Intraocular pressure measurement was carried out with an applanation tonometer (Tonopen-Vet; Reichert, DePew, New York, USA) following application of a topical anesthetic (proparacaine hydrochloride 0.5%, Alcaïne; Figure 1. Dorsal (a) and sagittal (b) fast spin echo T2W (TR = 5650 ms and TE = 85 ms) MR images of the head. The Alcon Canada). Values were 7 mmHg in the right eye and left retrobulbar mass is well-defined and highly hyperintense 13 mmHg in the left eye. Some abnormalities were diagnosed to brain parenchyma. The mass infiltrates the left medial in both eyes: dark iris, multifocal posterior synechiae, resistance retrobulbar region and is associated with a mass effect creating a compression and a rostrolateral displacement to dilation, pigment deposit on the anterior lens capsule with of the globe. Transverse T1W-FLAIR (TR = 2403 ms and subcapsular lens opacities, and proteinaceous material in the TE = 26 ms) (c) pre- and (d) post-contrast MR images. The mass anterior chamber. These signs were consistent with pigmentary is hypointense and heterogeneous on pre-contrast T1W images (c) but shows strong heterogenous contrast enhancement (d). uveitis. Findings specific to the left eye included exophthalmos, Note the compression of the left globe on both images. The moderate resistance to retropulsion, an elevated third eyelid, zygomatic gland appeared normal and unaffected by the process and conjunctival follicular hyperplasia. No pain was elicited (c — white circle). upon opening the mouth and no mass was detected during oral examination. No additional abnormalities were noted on com- tion) and delayed dorsal and sagittal plane. A large conic mass plete physical examination. Results of a complete blood (cell) infiltrating the left medial retrobulbar region was visualized and count (CBC) and serum chemistry panel were unremarkable. associated with a mass effect creating a compression and a ros- The unilateral presentation combined with the absence of pain trolateral displacement of the globe (Figures 1a and 1b). Globe upon palpation and opening of the mouth, the slow progression sclera was distorted but remained well-defined and seemed of signs, the absence of leukocytosis upon blood analysis, and intact. The mass also involved the optic cone and it was unclear the age of the dog suggested that an infectious process or abscess if it was only severely compressing the extraocular muscles or if was unlikely. Main differential diagnoses included an orbital it was invading them. The zygomatic gland appeared normal and neoplasia or a salivary mucocele. An immune-mediated myositis unaffected by the process, and there was no evidence of bone could not be ruled out, but was considered unlikely. The patient lysis or invasion of the calvarium. The mass was well-defined, was placed under general anesthesia so that additional diagnostic highly hyperintense on T2w images, moderately hyperintense tests could be performed. on T2-FLAIR images, and hypointense and heterogeneous on Magnetic resonance images (MRI) of the head were acquired pre-contrast T1w images. Following administration of contrast using a 1.5 T magnet (GE Signa Echospeed HDx; General medium, the mass showed a strong and well-defined enhance- Electric Healthcare, Mississauga, Ontario). Pre-contrast images ment (Figures 1c and 1d). Based on magnetic resonance images, were acquired and included the following sequences: sagittal, a neoplastic process appeared most likely. The loculated nature transverse, and dorsal T2-weighted (T2-w) Fast Spin Echo of the mass, with cystic areas and the enhancement pattern on (FSE), transverse T2-w Fluid Attenuated Inversion Recovery MRI sequences were suggestive of myxosarcoma. Other differ- (FLAIR), transverse T1-w FLAIR, and transverse T2*-Gradient ential diagnoses included meningioma, malignant lymphoma, Recalled Echo (GRE), transverse T2-w SSFSE (Single Shot carcinoma, or sarcoma. Fast Spin Echo). Post-contrast images were acquired following Immediately following MRI, ultrasound-guided fine-needle intravenous administration of 0.1 mmol/kg BW of gadoben- aspirates (FNA) and trucut percutaneous incisional biopsies ate dimeglumine (Multihance; Bracco Diagnostics, Monroe of the retrobulbar mass were obtained with the dog still under Township, New Jersey, USA) and included transverse T1-w anesthesia. A cytology report identified numerous, scattered FSE (0, 5, and 15 min, respectively, after contrast administra- spindle or ovoid cells, with a high nucleocytoplasmic ratio

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50 mm 50 mm

Figure 2. a — Light microscopic image from echo-guided biopsy showing a mass with low cellularity with spindle cells in an abundant fibrovascular or myxoid stroma. Note the spindle cell with ill-defined margins, eosinophilic cytoplasm, and elongated nucleus consistent with muscle cells. b — Alcian blue stain showing abundant blue staining of mucin and pink to red staining of cells nuclei consistent with the myxoid feature of the mass.

and basophilic cytoplasm. Mild to moderate anisocytosis and and replaced extraocular muscles and orbital fat, and multifo- anisokaryosis were also observed. These cells were associated cally extended to some of the excision margins. with pink fibrillary material and some hemosiderophages, Histologically, the neoplasm consisted of interlacing streams and mucoid eosinophilic matrix that aligned red blood cells and bundles of loosely arranged to more tightly packed spindle (“windrowing” sign). The findings were consistent with a mes- cells with occasional nuclear palisading (i.e., “storiform pattern”) enchymal proliferation with mucin, suggesting a myxoma or supported by a fibromyxomatous matrix characterized by very a well-differentiated myxosarcoma with chronic hemorrhage. loose and myxomatous features in some areas to less cellular Histopathologic assessment revealed a poorly demarcated, and collagenous in others (Figure 3a). Additionally, neoplastic non-encapsulated mass with low cellularity (Figures 2a and 2b). spindle cells were associated with several small sections of nerves It was composed of spindle cells in an abundant fibrovascular in which Schwann cell proliferations were noticed. Anisocytosis to myxoid stroma (Figure 2b). Cells had a poorly defined cyto- and anisokaryosis were moderate; and up to 6 mitoses per plasm and a round to elongated nucleus. Rare cells with more 10 high power fields were counted. A preliminary diagnosis of abundant eosinophilic to amphophilic cytoplasm, consistent a malignant peripheral nerve sheath tumor was made based on with myoblasts, were seen. Anisocytosis and anisokaryosis were the histomorphologic features. In view of previous results on the moderate. There were up to 2 mitoses per high power field. A original biopsy and the possibility of a malignant PNST with presumptive diagnosis of embryonal rhabdomyosarcoma was rhabdomyoblastic differentiation (i.e., Triton tumor), immunohis- proposed. To try to corroborate this diagnosis, immunohisto- tochemistry for desmin (Biogenex; 1:40; no antigen retrieval) was chemistry for desmin (Biogenex. Fremont, California, USA; also performed on the neoplasm. There was strong immunoreac- 1:40; no antigen retrieval) was performed. The rare myoblast- tivity that was limited to extraocular muscle cells, either normal or like cells were strongly immuno-reactive, but the spindle cells interpreted as atrophic due to neoplastic infiltration; the spindle were not; thus, the diagnosis was still uncertain. cells were diffusely negative. A Triton tumor was thus excluded. Though a definitive diagnosis had not yet been obtained, a The case was referred to Veterinary Pathology Services, Joint high-grade sarcoma was suspected and an oncology consultation Pathology Center (606 Stephen Sitter Avenue, Silver Spring, obtained. On complete clinical staging, there was no detectable Maryland, USA) for second opinion consultation. The diag- evidence of metastasis or serious concurrent disease based on nosis of malignant PNST was supported and confirmed with abdominal ultrasonography, 3-view thoracic radiography, and immunohistochemistry. Immunohistochemical labeling for bilateral submandibular lymph node aspiration and cytology. S100 protein and glial fibrillary acidic protein (GFAP) were Various treatment options were discussed, including palliative performed and both were strongly positive (Figures 3b and 3c). or radiation therapy with curative intent and various systemic Seventeen days after surgery, the owner noticed an intermit- anticancer therapies, but orbital exenteration was recommended tent green discharge from the left nostril along with occasional as the treatment of choice in light of the localized disease and sneezing and stertor. Further investigations were declined and the opportunity to try to obtain a definitive diagnosis. a large-spectrum systemic antibiotic (Amoxicillin/clavulanic Sixteen days after the initial MRI, the patient was placed acid, 15 mg/kg BW, PO, q12 h for 2 wk) and a non-steroidal under general anesthesia and exenteration of the left eye and anti-inflammatory drug (Deracoxib, Deramaxx; Elanco Canada, orbit was performed. An irregular, solid, white neoplasm filled Guelph, Ontario), 1 mg/kg BW, PO, q24h for 5 to 7 d, were the retrobulbar space. The neoplasm measured approximately given to treat a possible orbital bacterial infection and/or inflam- 1.5 to 2 cm in diameter with ill-defined borders. It infiltrated matory reaction.

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50 mm

Figure 3. a — Light microscopic image demonstrating spindle neoplastic cells, arranged in a vaguely storiform pattern, separated by a loose fibromyxomatous matrix. Note the admixed hemosiderophages (arrows) that were also observed during cytologic examination. Inset. An infiltrative retrobulbar neoplasm that compresses the posterior segment (asterisk). Hematoxylin and eosin (H&E). b and c — Immunohistochemical characterization of neoplastic cells. Neoplastic cells show strong nuclear and cytoplasmic immunoreactivity for S100 protein (b) as well as cytoplasmic immunostaining for GFAP (c).

After a follow-up with an oncologist, an oral metronomic dose, PO. Fifteen weeks after the exenteration, given the per- chemotherapy protocol was chosen by the owner and consisted sistent and progressive upper respiratory signs associated with of the combined administration of an NSAID (Piroxicam; discomfort, a computed tomography (CT) scan of the head Nostrum Laboratories, Kansas City, Missouri, USA), 10 mg total (16-slice helical CT scanner, HiSpeed ZXi; General Electric, daily dose PO, a chemotherapeutic agent (Cyclophosphamide; Mississauga, Ontario) was obtained. Transverse, 1.25-mm thick Pharmacia & Upjohn, Mississauga, Ontario), 25 mg total daily images of the head were helically acquired and reconstructed dose PO on a 2 days on/1 day off schedule), and a diuretic using a soft tissue and bone algorithm. Post-contrast images were (Furosemide; Apotex, Toronto, Ontario), 40 mg total daily then acquired with soft tissue algorithm following intravenous

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decline in the quality of life and mild behavioral changes, the dog was euthanized 10 d later. No necropsy was performed to confirm the recurrence. Discussion

This case illustrates the marked morphologic variations of canine REPORT CASE malignant peripheral nerve sheath tumors and consequently the diagnostic challenge which they present. First, attempts to obtain a diagnosis were made via ultrasound-guided FNA and cytology, which provides a definitive diagnosis in approximately 45% of retrobulbar masses and is especially helpful with exfoliative neoplasia including lymphoma (2,10). Cytology results raised the suspicion of a myxoma or well differentiated myxosarcoma. The cytologic tentative diagnosis was supported by MRI features of the orbital mass consistent with a previous description (11). Myxoma or myxosarcoma are soft tissue tumors of fibroblastic origin that can be distinguished by the presence of an abundant myxoid stroma. They are most frequently located in skin or subcutaneous tissue and around joints, but may occur at any site in the body (12). Orbital myxomas and myxosarco- mas have been reported as rare tumors in humans and there are some reports of canine low-grade myxosarcoma localized in the retrobulbar space or involving the orbit (11,13). This presumptive diagnosis was challenged by the histologic results from ultrasound-guided incisional biopsies. Histologic diagnosis was difficult due to the small size of samples, the low cellularity, and the common myxomatous changes shared by many tumor types, including chondrosarcoma, liposarcoma, synovial sarcoma, smooth muscle tumors, embryonal rhabdomyosarcoma, PNST, neurofibroma, and mucinous adenocarcinoma. Based Figure 4. Transverse CT images (a) pre- (bone reconstruction on histomorphology and immunohistochemistry, a diagnosis algorithm) and (b) (detail reconstruction algorithm) post-contrast at the level of the caudal retro-orbital space. Note the bone lysis of rhabdomyosarcoma was considered for the initial biopsy, of the medial wall of the left orbit (a). This mass is characterised but was refuted based on results for the second biopsy. Canine by multiple fluid pockets with ring enhancement. Note the rhabdomyosarcomas are uncommon mesenchymal neoplasms extension of the mass into the cranial vault and the mass effect on olfactory bulb (b). Dorsal CT image (detail reconstruction of skeletal muscle origin with varying myogenic differentiation. algorithm) (c) post-contrast demonstrating invasion of the left Their common locations are in the larynx and urogenital tract nasal cavity. but they have been documented in the head, neck, and face (14,15). Orbital rhabdomyosarcoma seems rare in the dog and a retrospective study of 18 cases of orbital rhabdomyosarcoma administration of 68 mL of Iopamidol (300 mg/mL, Isovue 300; has been recently published (16). They are often metastatic and Bracco Diagnostics, Monroe Township, New Jersey, USA). The more aggressive in dogs less than 2-years of age, but may be ame- left orbit was completely occupied by an ill-defined, heteroge- nable to therapy in older dogs (16,17). Immunohistochemistry neous mass with irregular margins and multiple pockets of fluid for myogenic markers such as myogenin is useful in differen- (Figures 4a and 4b). This mass involved the orbital muscles, the tiating rhabdomyosarcomas from other mesenchymal tumors. medial pterygoid muscle, and invaded the left temporal muscle. Myoblast cells express desmin and positive labeling is common It was associated with bone lysis of the medial wall of the left to skeletal muscle, cardiac muscle, smooth muscle, and myo- orbit, and also infiltrated the left rostral frontal sinus, rostral fibroblast. In the retrospective study of Scott et al (16), all fossa of the cranial vault, and left sphenoid sinus. A mass effect 18 cases demonstrated positive immunolabeling for desmin and was also noticed in contact with the olfactory lobe (Figures 4a 9/18 cases showed cross-striations. In our case, for the second and 4c). The left nasal cavity and choanes were invaded but biopsy, the immunoreactivity was limited to extraocular muscle without lysis of the palatine bone. A mass effect on the soft palate cells but the spindle cells were negative and no cross-striation was described, caudally to left maxillary tooth M2. The left man- was observed. This pattern invalidated the first presumptive dibular, retropharyngeal, and parotid lymph nodes had a mild diagnosis of rhabdomyosarcoma. increase in size and irregular margins. With the aggressive nature Exenteration was performed as part of the therapeutic plan of the lesion and the animal’s history, a loco-regional recurrence with subsequent histologic assessment to provide a definitive of the PNST was strongly suspected. Given the poor prognosis, diagnosis. Again, due to overlapping features of their histologi- the owner elected to stop the chemotherapy. Because of a quick cal patterns, differentiation of soft tissue sarcomas presents a

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diagnostic challenge. In this case, a final diagnosis of peripheral 4. Sfacteria A, Perillo L, Macrì F, Lanteri G, Rifici C, Mazzullo G. nerve sheath tumor was reached. Immunohistochemically, PNST Peripheral nerve sheath tumor invading the nasal cavities of a 6-year-old female Pointer dog. Vet Q 2015;35:170–173. are variably positive for vimentin, S100 protein, and GFAP, 5. Curto E, Clode AB, Durrant J, Montgomery KW, Gilger BC. among other markers (18,19). In human malignant PNST, vari- Retrobulbar pigmented peripheral nerve sheath tumor in a dog. Vet able histologic patterns and heterogenous differentiation have Ophthalmol 2016;19:518–524. 6. Suzuki S, Uchida K, Nakayama H. The effects of tumor location on been reported (20). The patterns include epithelioid malignant diagnostic criteria for canine malignant peripheral nerve sheath tumors PNST or malignant PNST with divergent differentiation such as (MPNSTs) and the markers for distinction between canine MPNSTs rhabdomyoblastic (malignant Triton tumor), cartilaginous, osse- and canine perivascular wall tumors. Vet Pathol 2014;51:722–736. 7. Dennis R. Use of magnetic resonance imaging for the investigation of ous, angiomatous, and glandular or their complex (20). These orbital disease in small animals. J Small Anim Pract 2000;41:145–155. features have been found in dogs and other species (21–23). In 8. Lee AG, Johnson MC, Policeni BA, Smoker WRK. Imaging for neuro- this case, the mass presents variable histologic patterns consistent ophthalmic and orbital disease — A review. Clin Exp Ophthalmol 2009;

RAPPORTCAS DE 37:30–53. with what is described in the literature and cells were strongly 9. Armour MD, Broome M, Dell’Anna G, Blades NJ, Esson DW. A review positive for S100 protein and GFAP; this, combined with the of orbital and intracranial magnetic resonance imaging in 79 canine and 13 feline patients (2004–2010). Vet Ophthalmol 2011;14:215–226. histologic pattern, allowed for a diagnosis of malignant periph- 10. Betbeze C. Management of orbital diseases. Top Compan Anim Med eral nerve sheath tumor. 2015;30:107–117. With soft tissue sarcomas, a radical surgical resection with 11. Dennis R. Imaging features of orbital myxosarcoma in dogs. Vet Radiol Ultrasound 2008;49:256–263. wide tumor-free margins can be curative. For orbital neoplasia, 12. Parslow A, Taylor DP, Simpson DJ. Clinical, computed tomographic, wide tumor-free margins often require radical orbitectomy, an magnetic resonance imaging, and histologic findings associated with invasive and disfiguring procedure. Another approach is exen- myxomatous neoplasia of the temporomandibular joint in two dogs. J Am Vet Med Assoc 2016;11:1301–1307. teration with subsequent radiation therapy or chemotherapy, 13. Campos CB, Nunes FC, Gamba CO, et al. Canine low-grade intra- especially in cases of incomplete resection or with high-grade orbital myxosarcoma: Case report. Vet Ophthalmol 2015;18:251–253. tumors (24). In our case, histopathology assessment showed 14. Dunbar MD, Ginn P, Winter M, Miller KB, Craft W. Laryngeal rhab- domyoma in a dog. Vet Clin Pathol 2012;41:590–593. incomplete margins. Radiation therapy was proposed but 15. Boeloni JN, Reis AMS, Nascimento EF, Silva JF, Serakides R, Ocarino declined by the owner and an oral metronomic chemotherapy NM. Primary ovarian rhabdomyosarcoma in a dog. J Comp Pathol protocol was preferred (25–27). Malignant nerve sheath tumors 2012;147:455–459. 16. Scott EM, Teixeira LBC, Flanders DJ, Dubielzig RR, McLellan GJ. in dogs commonly recur following surgical excision but rarely Canine orbital rhabdomyosarcoma: A report of 18 cases. Vet Ophthalmol metastasize (3,5). In the case reported here, an aggressive loco- 2016;19:130–137. regional recurrence was diagnosed 15 wk following surgery 17. Kato Y, Notake H, Kimura J, et al. Orbital embryonal rhabdomyosarcoma with metastasis in a young dog. J Comp Pathol 2012;147: but upper respiratory signs had started 3 wk after surgery. 191–194. Occasionally, with aggressive sarcomas, such as rhabdomyosar- 18. Chijiwa K, Uchida K, Tateyama S. Immunohistochemical evaluation of coma in children and young dogs, surgery may not be associated canine peripheral nerve sheath tumors and other soft tissue sarcomas. Vet Pathol 2004;41:307–318. with a favorable outcome (16). Instead, a combination of neo- 19. Teixeira S, Amorim I, Rêma A, Faria F, Gartner F. Molecular heteroge- adjuvant radiation therapy and chemotherapy, with or without neity of canine cutaneous peripheral nerve sheath tumors: A drawback surgical intervention, may provide better outcome with longer in the diagnosis refinement. In Vivo 2016;30:819–827. 20. McMenamin ME, Fletcher CD. Expanding the spectrum of malignant survival and improved quality of life as documented for chil- change in schwannomas: Epithelioid malignant change, epithelioid dren (28). It is possible that the reported tumor behavior was malignant peripheral nerve sheath tumor, and epithelioid angiosarcoma: negatively impacted by surgical excision. Indeed, the surgical A study of 17 cases. Am J Surg Pathol 2001;25:13–25. 21. Sayama A, Okado K, Imaoka M, Yokouchi Y, Jindo T, Takasaki W. trauma associated with incomplete margins may have accelerated Subcutaneous soft tissue sarcoma with rhabdoid features in a dog. the local spread of the tumor. Because there was a delay (16 d) J Toxicol Pathol 2014;27:131–138. between the initial MRI and the surgery, it is also possible that 22. Volmer C, Caplier L, Reyes-Gomez E, Huet H, Owen RA, Fontaine JJ. An atypical peripheral nerve sheath tumour with pseudoglandular the sarcoma had already progressed in the periorbital tissues in architecture in a dog. J Vet Med Sci 2010;72:249–251. the days leading to surgery. 23. Kim DY, Cho DY, Kim DY, Lee J, Taylor HW. Malignant peripheral This case illustrates the importance of combining several nerve sheath tumor with divergent mesenchymal differentiations in a dog. J Vet Diag Investig 2003;15:174–178. diagnostic modalities to define the nature of certain types of ret- 24. Huang WT, Chen WJ, Hsu HC, Cheng YF, Eng HL. Retrobulbar cel- robulbar neoplasia in dogs and selected immunohistochemistry lular schwannoma. Two cases report and review of the literature. Pathol should be considered in addition to standard stains, especially Res Pract 2003;199:171–174. 25. Elmslie RE, Glawe P, Dow SW. Metronomic therapy with cyclophos- with soft tissue sarcomas. Exenteration benefits should be care- phamide and piroxicam effectively delays tumor recurrence in dogs fully assessed in cases of retrobulbar peripheral nerve sheath with incompletely resected soft tissue sarcomas. J Vet Intern Med 2008; 22:1373–1379. tumors. CVJ 26. Chan CM, Frimberger AE, Moore AS. Incidence of sterile hemor- rhagic cystitis in tumor-bearing dogs concurrently treated with oral References metronomic cyclophosphamide chemotherapy and furosemide: 55 cases . 1 Attali-Soussay K, Jegou JP, Clerc B. Retrobulbar tumors in dogs and (2009–2015). J Am Vet Med Assoc 2016;249:1408–1414. cats: 25 cases. Vet Ophthalmol 2001;4:19–27. 27. Setyo L, Ma M, Bunn T, Wyatt K, Wang P. Furosemide for prevention 2. Hendrix DV, Gelatt KN. Diagnosis, treatment and outcome of orbital of cyclophosphamide-associated sterile haemorrhagic cystitis in dogs neoplasia in dogs: A retrospective study of 44 cases. J Small Anim Pract receiving metronomic low-dose oral cyclophosphamide.Vet Comp Oncol 2000;41:105–108. Traumatol 2017; doi: 10.1111/vco.12292 3. Hagen FV, Romkes G, Kershaw O, Eule JC. Malignant peripheral nerve 28. Wexler LH. Rhabdomyosarcoma and other soft-tissue sarcomas. sheath tumor of the third eyelid in a 3-year-old Rhodesian Ridgeback. In: Lanzkowsky P, ed. Manual of Pediatric Hematology and Oncology. Clin Case Reports 2015;3:50–56. 5th ed. New York, New York: Academic Press, 2011:715–738.

384 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY Case Report Rapport de cas

Urethral intussusception following traumatic catheterization in a male cat

Olivier Broux, Anne-Laure Etienne, Annick Hamaide

Abstract — An 8-year-old, European male shorthair cat was presented with lower urinary tract obstruction. He was catheterized and referred. Retrograde cysto-urethrography suggested a urethral mass. Intussusception of the urethra with a partial rupture of the urethra was visualized. A perineal urethrostomy was performed. The cat was clinically normal at 15 months’ follow-up.

Résumé — Invagination urétrale secondaire à un cathétérisme traumatique chez un chat mâle. Un chat européen male de 8 ans présentant des signes d’obstruction du bas appareil urinaire a été cathéterisé et référé. L’urétrographie rétrograde suggérait une masse urétrale. Une intussusception de l’urètre avec une rupture partielle de l’urètre a été visualisée. Une urétrostomie périnéale a été réalisée. Le chat était cliniquement normal 15 mois après l’intervention. (Traduit par les auteurs) Can Vet J 2018;59:385–387

eline lower urinary tract diseases (FLUTD) are common relieved by catheterization to overcome resistance 3 cm cranial to F conditions in cats. Obstruction is reported in 28.6% to the external urethral opening of the penis. Contrast radiographs 58% of cases (1–2) and re-obstruction occurs in 22% to 45% showed no abnormalities. Urinalysis revealed struvite crystalluria within 6 mo (3–4). Almost exclusively male cats are reported, and the presence of Escherichia coli urinary tract infection. The due to their relatively long and narrow urethra (4). Differential cat received a single injection of cefovecin (Convenia; Pfizer diagnoses for urethral obstruction in cats include urolithiasis, Animal Health, Zaventem, Belgium), 8 mg/kg body weight urinary tract infection, idiopathic diseases, neoplasia, urethral (BW), SC, and prednisolone (Prednisolone 2.5%; V.M.D., stricture, anatomic malformations, and foreign bodies (4). Arendonk, Belgium), 0.5 mg/kg BW, SC. The urinary catheter Urethral injuries may result from pelvic fractures, vehicular was removed after 24 h. Three days later, urethral catheterization trauma, urethral calculi, gunshot trauma, bite wounds, or ure- was repeated because of a new episode of obstruction and the thral catheterization (5). In case of failure in medical treatment, catheter was left in situ. The cat was then referred for further perineal urethrostomy is the most commonly preferred surgical investigation. procedure to relieve the obstruction (6). At presentation, the cat was alert and physical examination revealed no abnormalities except a grade 3/6 left parasternal Case description heart murmur. Complete blood cell count and serum bio- An 8-year-old, European shorthair castrated male cat weigh- chemistry results were within normal limits. Urinalysis revealed ing 4.2 kg was referred for lower urinary tract obstruction. hematuria, proteinuria, specific gravity of 1.032, pH of 6, and Two years previously the cat had a first episode of stranguria and bacteriuria. Cytology revealed neutrophils, red blood cells, pollakiuria. At that time, the referring veterinarian performed and intracellular bacteria. Bacterial culture was positive for a cystotomy to remove cystic calculi diagnosed on abdominal Enterococcus faecalis which was susceptible to all tested antibiot- radiographs. No analysis of the calculi was done. During that ics. An echocardiography was performed revealing thickening period, the cat had 2 additional episodes of FLUTD, which were of the left ventricular wall with a left atrium within normal treated conservatively. Before referral, the cat was presented to limits. No contraindication for anesthesia was identified. Under the referring veterinarian for anuria. Urethral obstruction was sedation, a smooth urethral mass was identified by rectal palpation 3 cm cranial to the anus. On abdominal radiographs and Faculty of Veterinary Medicine, University of Liège, Av de ultrasonography (Figure 1), calculi/crystals were present in the Cureghem 3 (B44), 4000 Liège, Belgium. bladder and the urethra. A thickened bladder wall consistent Address all correspondence to Dr. Olivier Broux; e-mail: with cystitis and a bilateral moderate pyelectasia were present. [email protected] A hypoechoic, asymmetrical circumferential thickening of the Use of this article is limited to a single copy for personal study. urethral wall was visible using a perineal approach. A focal Anyone interested in obtaining reprints should contact the ampullar dilation of the pelvic urethra (Figure 2) on positive CVMA office ([email protected]) for additional retrograde cysto-urethrography was highly suggestive of an copies or permission to use this material elsewhere. asymmetric circumferential urethral intramural lesion. The

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Figure 1. Transverse ultrasonographic image of the caudal urethra (perineal approach). Hypoechoic circumferential thickening of the urethra is more severe dorsally within a poorly delineated hyperechoic image visible dorsally. Note the hyperechoic convex surface of the crystals in the urethra (white arrow) creating a strong acoustic shadow.

Figure 3. First catheter placed within the penile disrupted urethra (yellow arrow) and second within the remnant pelvic part of the urethra (green arrow).

toward the penile attachments at the ischial arch, the ventral penile ligament was severed, and the ischiocavernosus and ischiourethralis muscles were transected. Once the suspected urethral mass was reached, intussusception of the urethra with complete disruption between urethra and corpus cavernosum of the penile part of the urethra, and partial rupture of the urethra at the site of intussusception were visualized. A second urethral catheter was placed within the remnant pelvic portion Figure 2. Lateral radiographic view of the retrograde of the urethra (Figure 3). After removal of the caudal part of the urethrography. There is a focal, ampullar enlargement of the urethra and penis, the perineal urethrostomy was continued as urethra with 2 tubular filling defects (arrow) inside, 1 (larger) in previously described (7–8). Postoperative analgesia was provided continuity with the dorsal wall and 1 (thinner) with the ventral wall with secondary narrowing of the urethral lumen. An asymmetric with buprenorphine (Vetergesic; Alstoe Animal Health, Sheriff circumferential urethral intramural lesion is suspected. Hutton, York, UK), 0.015 mg/kg BW, IV, q6h. Several calculi were collected during the procedure and sent for analysis. The quantitative analysis of the uroliths (Minnesota Urolith Center, differential diagnosis was an intramural tumor, or less likely, Saint Paul, Minnesota, USA) determined that they were 100% another intramural lesion. Transrectal ultrasound-guided fine- calcium oxalate monohydrate. needle aspiration of the mass revealed polymorphonuclear cells Following recovery from anesthesia, the cat urinated nor- with intracellular bacteria and no signs of malignancy. Thoracic mally 4 h after surgery. The cat was discharged the day after radiographs revealed no sign of pulmonary metastasis. A surgical surgery and received amoxicillin-clavulanic acid (Synulox; approach via a perineal urethrostomy was planned in order to Pfizer Animal Health), 20 mg/kg BW, PO, q12h for 15 d and relieve the obstruction and resect the suspected mass. meloxicam (Metacam; Boehringer-Ingleheim), 0.1 mg/kg BW, The cat was anesthetized and placed in ventral recumbency. PO, q24h for 3 d. At recheck, 3 wk after surgery, the cat was The perineal region was clipped and prepared for surgery. doing well. The owners reported normal urination and no sign Urethral catheterization was easily performed but no urine of stranguria, hematuria, or dysuria. Three weeks after surgery, came through the catheter. An elliptical incision was made urinalysis was within normal limits, stitches were removed and around the scrotum and the prepuce, and the penis was freed the cat was released to normal activity. At 15 mo after surgery from the surrounding tissues. The dissection was extended the cat was clinically normal, without any urinary problems.

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Discussion This is the first report in veterinary medicine of urethral intussusception associated with a rupture following traumatic Although urethral catheterization has been reported to be a catheterization. When a cat is presented for FLUTD, care must potential cause of urethral rupture, to the authors’ knowl- be taken during urethral catheterization. More importantly, ure- edge, this is the first report in veterinary medicine of urethral thral intussusception can create an asymmetric circumferential intussusception following traumatic catheterization. Urethral intramural lesion on abdominal ultrasonography and retrograde REPORT CASE obstruction is a common disease in cats. Urethral plug, uroliths, urethrocystography. This should be taken into account in the and idiopathic causes are the most common etiologies. Medical differential diagnoses of a urethral mass in a cat following ure- management of urethral obstruction requires correction of elec- thral catheterization. CVJ trolyte abnormalities, restoration of tissue perfusion, analgesia for visceral pain, and release of the urethral obstruction (9). References The medical management may include urethral catheterization 1. Gerber B, Eichenberger S, Reusch CE. Guarded long-term prognosis in to relieve the obstruction. The urinary catheter is usually left in male cats with urethral obstruction. J Feline Med Surg 2008;10:16–23. place for 24 to 48 h (10). 2. Sævik B, Trangerud C, Ottesen N, Sørum H, Eggertsdóttir AV. Causes of lower urinary tract disease in Norwegian cats. J Feline Med Surg Urinary calculi as well as urethral catheterization to dislodge 2011;13:410–417. the calculi can cause damage to any portion of the urethra, but 3. Bovee KC, Reif JS, Maguire TG, Gaskell CJ, Batt RM. Recurrence of iatrogenic injuries are commonly in the penile portion and at the feline urethral obstruction. J Am Vet Med Assoc 1979;174:93–96. 4. Segev G, Liven H, Ranen E, Lavy E. Urethral obstruction in cats: level of the ischial arch (11). In a previous retrospective study on Predisposing factors, clinical, clinicopathological characteristics and 29 cats managed for urethral rupture, urethral obstruction and prognosis. J Feline Med Surg 2011;13:101–108. catheterization was found to be the cause of the injury in 23 cats 5. Meige F, Sarrau S, Autefage A. Management of traumatic urethral rupture in 11 cats using primary alignment with a urethral catheter. (11). Urethral trauma and bladder rupture following catheteriza- Vet Comp Orthop Traumatol 2008;21:76–84. tion can cause uroperitoneum in cats (12). In another study, all 6. Ruda L, Heiene R. Short- and long-term outcome after perineal ure- 15 cats undergoing perineal urethrostomy had urethral trauma throstomy in 86 cats with feline lower urinary tract disease. J Small Anim Pract 2012;53:693–698. attributed to prior catheterization (13). In order to avoid ure- 7. Fossum TW. Small Animal Surgery. 4th ed. Linn, Missouri: Elsevier, thral trauma by catheterization, it is recommended that sedation 2013:699–701. and analgesia be used. Some authors advocate decompression 8. Tobias KM, Johnston SA. Veterinary Surgery: Small Animal. 1st ed. St. Louis, Missouri: Elsevier, 2012:2000–2004. of the bladder by cystocentesis (9,14–16); there was no bladder 9. Hall J, Hall K, Powell LL, Lulich J. Outcome of male cats managed rupture associated with the procedure in 47 cats (9). The goal for urethral obstruction with decompressive cystocentesis and urinary is to relieve the pressure in the bladder, ureters, and kidneys, to catheterization: 47 cats (2009–2012). J Vet Emerg Crit Care 2015;25: 256–262. decrease pain, and provide time for stabilization of the patient 10. Balakrishnan A, Drobatz KJ. Management of urinary tract emergen- (15,16). Catheterization may facilitate retropulsion of urethral cies in small animals. Vet Clin North Am Small Anim Pract 2013;43: plugs or uroliths. It should be noted that the urinary catheter is 843–867. 11. Anderson RB, Aronson LR, Drobatz KJ, Atilla A. Prognostic factors for only used to perform hydropropulsion and not to mechanically successful outcome following urethral rupture in dogs and cats. J Am relieve the obstruction (13). However, successful treatment of 11 Anim Hosp Assoc 2006;42:136–146. 12. Aumann M, Worth LT, Drobatz KJ. Uroperitoneum in cats: 26 cases out of 15 male cats with urethral obstruction managed without 1986–1995. J Am Anim Hosp Assoc 1998;42:136–146. urethral catheterization has been reported (17). 13. Corgozinho KB, de Souza HJ, Pereira AN, et al. Catheter-induced Survey radiographs are useful to identify radiopaque urethral urethral trauma in cats with urethral obstruction. J Feline Med Surg 2007;9:481–486. calculi, abnormal urethral location, or concurrent pathology 14. Hostutler RA, Chew DJ, DiBartola SP. Recent concepts in feline lower causing urethral obstruction. Positive-contrast retrograde ure- urinary tract disease. Vet Clin North Am Small Anim Pract 2005; throcystography is the imaging modality of choice for evaluation 35:164–170. 15. Kruger JM, Osborne CA, Ulrich LK. Cystocentesis. Vet Clin North Am of urethral lesions (18). Ultrasonography is reported to be of Small Anim Pract 1996;26:353–361. value but is limited to the extrapelvic region (19). Computed 16. Osborne CA, Kruger JM, Lulich JP, Bartges JW, Polzin DJ. Medical tomographic and magnetic resonance imaging have yet to be management of feline urethral obstruction. Vet Clin North Am Small Anim Pract 1996;26:483–498. proven to be of any clinical use in animals with urethral disor- 17. Cooper ES, Owens TJ, Chew DJ, Buffington CAT. A protocol for man- ders (8). In our case, ultrasonography and retrograde cystoure- aging urethral obstruction in male cats without urethral catheterization. thrography lead to a suspicion of a urethral tumor. Moreover, J Am Vet Med Assoc 2010;237:1261–1266. 18. Thrall DE. Textbook of veterinary diagnostic radiology. 5th ed. cytology failed to establish a diagnosis and thoracic radiographs Philadelphia, Pennsylvania: Saunders, 2007:725–728. revealed no lung metastasis. However, the localization of the 19. Hanson JA, Tidwell AS. Ultrasonographic appearance of urethral tran- lesion allowed a perineal approach for resection of the mass. sitional cell carcinoma in ten dogs. Vet Radiol Ultrasound 1996;37: 293–299. The cat in our report was successfully treated with a perineal urethrostomy. The cat was discharged 24 h after surgery and was clinically normal 15 mo later.

CVJ / VOL 59 / APRIL 2018 387 FOR PERSONAL USE ONLY Case Report Rapport de cas

Sacrocaudal (sacrococcygeal) intervertebral disc protrusion in 2 cats

Gianluca Magi, Giunio Bruto Cherubini, Olivier Taeymans

Abstract — One cat was presented for investigation of urinary retention and constipation and a second cat was presented with decreased appetite, reluctance to jump, reduced level of activity, and constipation. Magnetic resonance imaging revealed dorsal bulging of the hypo-intense intervertebral disc at S3-Cd1 on fast spin echo T2. Dorsal laminectomy was performed and both cats recovered with resolution of neurological signs.

Résumé — Protrusion discale sacrocaudale (sacrococcygienne) chez 2 chats. Le chat 1 a été présenté en consultation pour exploration d’une rétention urinaire et constipation. Le chat 2 a été présenté en consultation pour baisse d’appétit, réticence à sauter, activité réduite et constipation. L’IRM a mis en évidence une protrusion dorsale du matériel discal hypointense au niveau de S3-Cd1 en fast spin echo T2. Une laminectomie dorsale a été réalisée chez ces deux chats chez qui une complète rémission clinique a été observée. (Traduit par les auteurs) Can Vet J 2018;59:388–392

ing and Smith (1) reported both Hansen type 1 (extrusion) Case descriptions K and type 2 (protrusion) intervertebral disc disease (IVDD) Case 1 in as many as 1 of every 4 cats in a cadaveric study performed in A 10-year-old, neutered male, Bengal-cross cat was presented for a population with no related neurological signs. The relevance neurological examination after 2 wk of urinary retention. The of this postmortem finding in live animals remains uncertain, cat had a 6-year history of intermittent constipation as a result however, as prevalence of clinically affecting IVDD in cats has of a pelvic fracture managed with conservative treatment. Before been estimated to be between 0.02% and 0.24% (2–4). In cats, referral, the cat had been hospitalized at the referring veterinary degenerative IVDD is considered a rare disease (4). practice for 2 wk with frequent draining through an indwell- In the veterinary literature, the most frequently reported ing urinary catheter. Adjunctive treatment with meloxicam, locations for IVDD among clinically affected cats are T13-L1, dantrolene, and prazosin at unknown dosages had not resulted L4-L5, and L7-S1. This is likely associated with stance configu- in clinical improvement and the referring veterinarian did not ration and range of motion of the spine in the cat (5). While observe any voluntary urination during this time. there are sporadic reports of sacrocaudal (sacrococcygeal) and Physical examination revealed a thickened, alopecic, and caudal (coccygeal) IVDD in dogs (6–8), to the authors’ knowl- ulcerated area at the ventral aspect of the base of the tail, edge disc disease in the caudal (coccygeal) spine has never been thought to be a self-induced traumatic lesion caused by pro- reported before in cats either in postmortem studies or in clini- longed licking of the area. The bladder was over-distended and cally affected animals. manual expression was not possible. On neurological examina- Signalment, neurological signs, magnetic resonance imaging tion, hypotonic anal sphincter, reduced perineal and bulbo- (MRI) findings, surgical treatment, and long-term post-operative cavernous reflexes, and pain at palpation of the lumbosacral area follow-up of 2 cats with a final diagnosis of sacrocaudal (sacro- of the spine were observed. Sensory and motor function of the coccygeal) intervertebral disc protrusion is described herein for tail were preserved, although the cat was reluctant to move the the first time. tail and slight pain was elicited on manipulation.

Case 2 A 2-year-old, neutered male, domestic shorthair cat was pre- Dick White Referrals, Six Mile Bottom, Cambridgeshire sented with a 1-month history of reduced appetite, reluctance CB8 0UH, United Kingdom. to jump, reduced level of activity, pain at extension of the pel- Address all correspondence to Dr. Gianluca Magi; e-mail: vic limbs, and transient constipation. The cat had no outdoor [email protected] access and no history of trauma was reported. The cat was Use of this article is limited to a single copy for personal study. initially seen at the referring veterinary practice where it was Anyone interested in obtaining reprints should contact the prescribed a 3-week course of meloxicam at an unknown dosage CVMA office ([email protected]) for additional with an unsatisfactory response and micro-enemas to promote copies or permission to use this material elsewhere. defecation.

388 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY CASE REPORT CASE

Figure 1. T2-weighted fast spin echo sagittal (left) and transverse (right) magnetic resonance images of sacrocaudal vertebral column at S3-Cd1 (asterisk). Kyphotic angulation of the spine is noted at this level with entire degeneration of the intervertebral disc and dorsal protrusion. Focal attenuation of the epidural fat is present in trans T2. Bladder (B) is markedly distended.

Physical examination was unremarkable. Neurological exami- were included. A kyphotic angulation of the spine at S3-Cd1 nation was unremarkable apart from reluctance to move and was noted with ventral deviation of the tail. The intervertebral pain being elicited at palpation of the lumbosacral area of the disc at S3-Cd1 was hypo-intense and severely protruded dor- spine and on tail manipulation. Sensory and motor function of sally. Almost complete focal attenuation of the epidural fat was the tail was preserved. present, presuming associated spinal nerve root compression. Other findings at MRI included a markedly fluid distended Diagnostic tests bladder reaching the caudal aspect of L2, the distal portion of For cat 1, a complete blood (cell) count (CBC) revealed a the descending colon distended with fecal material measuring mild nonregenerative anemia with reduced red blood cell count 1.5 3 L7 in diameter, and narrowing of the pelvic canal as a [4.70 3 1012/L; reference interval (RI): 7.00 to 11.60 3 1012/L], result of axial displacement of the right hemi-pelvis (Figure 1). hemoglobin 71 g/L (RI: 9.0 to 14.0 g/L), hematocrit 0.210 L/lL In cat 2, transverse T2-weighted FSE, sagittal T2-weighted (RI: 0.29 to 0.46 L/L); the serum biochemistry was unremark- FSE and STIR sequences were included. All intervertebral able. Urine analysis was conducted on a sample collected via discs maintained a hyperintense nucleus pulposus with the cystocentesis and showed evidence of urinary tract infection exception of S3-Cd1, which was hypointense and protruding with isolation of Enterococcus faecalis that was susceptible to dorsally. Mild spondylosis deformans was noted at this disc Amoxicillin/Clavulanate. space. A slight angulation of the vertebral column in this region In cat 2, a CBC and serum biochemistry were performed was noted, with reduction of the dorsoventral height of the before referral and were unremarkable. Survey spinal and pelvis canal, and presumed associated spinal nerve root compression. radiographs were taken at the referring practice. These were Furthermore, transitional vertebrae were noted at the lumbosa- reviewed at admission by a Board-certified radiologist (OT) and cral junction with sacralization of L7 (Figure 2). showed faint mineral opacity superimposed over the intervertebral disc space of S3-Cd1 extending dorsally over the ventral Treatment and clinical outcome aspect of the spinal canal. In light of the MRI findings, disc protrusion at the sacrocaudal Neuroanatomical localization for both cats was at the level (sacrococcygeal) disc space was considered a possible cause for of the lumbosacrocaudal (coccygeal) area. Thus, both cats had the presentation. Dorsal decompressive laminectomy with fen- MRI of the lumbosacral spine performed (Aperto, 0.4T; Hitachi estration in cat 1, and dorsal decompressive laminectomy alone Medical System, Wellingborough, UK). in cat 2 were elected as the treatments of choice. In cat 1, sagittal T2-weighted fast spin echo (FSE) and short Postoperative medications for cat 1 included diazepam TI inversion recovery (STIR), transverse T2-weighted FSE (Valium; Actavis, Whiddon Valley, Barnstaple, UK), 1 mg PO,

CVJ / VOL 59 / APRIL 2018 389 FOR PERSONAL USE ONLY RAPPORTCAS DE

Figure 2. T2-weighted sagittal (left) and transverse (right) magnetic resonance images of sacrocaudal and caudal vertebral column. Mild spondylosis deformans with degeneration of the nucleus pulposus is noted at S3-Cd1 (asterisk). Incomplete fusion of the second and third sacral segment with a vestigial intervertebral disc in-between is visible. In T2 trans there is reduction of dorsoventral height of the canal and associated spinal nerve root impingement. Transitional vertebra at LS with sacralization of L7.

q8h; prazosin (Hypovase; Pfizer, Tagworth, UK), 0.1 mg/kg body 3 d after the operation; it was pain-free and voluntarily urinated weight (BW), PO, q12h, bethanecol (Myotonine; Glenwood, and defecated. At 1-month follow-up, the cat showed mild para- Munchen, Germany), 0.5 mg/kg BW, PO, q12h, for 2 mo, paresis but there was no pain at palpation of the spine during meloxicam (Metacam; Boehringer Ingelheim, Bracknell, United neurological examination and the owner was pleased with the Kingdom), 0.05 mg/kg BW, PO for 5 d, gabapentin (Summit cat’s demeanor and quality of life. At a 20-month follow-up by Veterinary Pharmaceuticals, Kidlington, Oxfordshire, United telephone, the owner reported that the cat was leading an active Kingdom), 5 mg/kg BW, PO, q8h to 12h for 3 d, amoxicillin/ and playful life with no abnormalities in gait. clavunate (Noroclav; Norbrook), 20 mg/kg BW, PO, q12h for The final follow-up information for cats 1 and 2 (24 and 2 wk. An indwelling urinary catheter was left in place in cat 1 20 mo after surgery, respectively) was obtained via telephone for 10 d and was drained regularly every 3 h. Urinary culture and conversation with the owners and with the referring veterinar- sensitivity were repeated twice during hospitalization. ians. No clinical signs that could be related to caudal (coccygeal) Postoperative medications for cat 2 included gabapentin disc protrusion ever recurred during the period considered in (Summit Veterinary), 10 mg/kg BW, PO, q8h to 12h, diaz- both cats. epam (Valium; Pfizer), 1.5 mg q8h, and meloxicam (Metacam; Boehringer), 0.05 mg/kg BW, PO, all dispensed for 2 wk. Discussion Cat 1 showed a slow but progressive improvement in neu- Caudal (coccygeal) and sacrocaudal (sacrococcygeal) IVDD have rological status and was discharged 2 wk after surgery when it been reported sporadically in dogs (6–8), in which most of the regained the ability to urinate and defecate voluntarily. The last animals were affected by disc extrusion. Clinical presentation urine culture completed before removing the urinary catheter, for dogs with sacro/caudal (coccygeal) IVDD was mostly pain- did not show bacterial growth. At 1-month follow-up after related. Clinical signs in these dogs included pain associated discharge, neurological examination was unremarkable and with defecation, abnormal tail carriage, and pain elicited on the owner reported good mobility of the tail and regular and manipulation of the caudal lumbosacral area and tail during voluntary urination and defecation. At 24-month follow-up, neurological examination. the cat was still receiving lactulose daily (prescribed by the In the cats herein, neurological dysfunctions were also pres- referring veterinary surgeon as part of long-term conservative ent, such as urinary incontinence, hypotonic anal sphincter, management of chronic constipation), but no other episodes of reduction in perineal and bulbo-cavernous reflexes in cat 1, and constipation occurred after discharge. constipation with no signs of pain during defecation in cat 2. Cat 2 showed rapid and marked improvement on neurologi- In 1 study in cats (9), conus medullaris was found to reach at cal examination after decompressive surgery and was discharged least the level of the first sacral vertebra in almost 2/3 of the

390 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY cats examined, or even the junction between S1-S2 according deemed to be resolved. Other causes for mild paraparesis noted to others (10). Beyond this point the cauda equina, which at 1-month follow-up examination are possible but unknown. includes sacral and caudal (coccygeal) nerve roots, is encoun- The value of MRI in caudal (coccygeal) disc degeneration tered in the vertebral canal as far as the first caudal (coccygeal) has been reported in dogs (6,8). In the cats herein, a decreased vertebra (11). signal intensity of the nucleus pulposus of the affected disc,

In cat 1, urinary retention is thought to be a sequela of either compared to the other discs, was observed in the T2-weighted REPORT CASE pudendal, third sacral nerve and/or cauda equina compression sequences. Complete focal attenuation of the epidural fat in caused by the protruded disc at S3-Cd1. Lesions of the sacral cat 1 and reduction of the dorsoventral height of the vertebral cord, cauda equina, or pelvic and pudendal nerves abolish both canal in cat 2 suggested spinal nerve root compression. Magnetic voluntary and reflex micturition, producing what is referred to resonance imaging provided detailed images of the caudal spine, as lower motor neuron (LMN) bladder (12,13). The bladder allowing a diagnosis with a fair level of confidence, while radi- distends with urine, so if there is no resistance in the atonic ography in cat 2 showed only subtle changes difficult to relate urethralis muscle, urine continually overflows and dribbles from to the clinical presentation. the urethral orifice (12). The only resistance to this overflow is In dogs, caudal (coccygeal) discs have biochemical composi- the tone in the internal urethral sphincter that is controlled by tion and metabolic properties similar to lumbar discs, making it sympathetic nerves via the hypogastric nerve originating in the likely that they undergo the same degenerative processes as discs lumbar cord. Thus, although anatomically the lesion is affecting elsewhere (8,15). Studies on caudal (coccygeal) discs in cats are the LMN, sometimes the bladder may be difficult to express lacking to our knowledge, but a similar mechanism to explain due to increased sympathetic tone secondary either to pain or caudal (coccygeal) disc degeneration in cats may be plausible. suppression of normal sensory input from stretch receptors in In cat 1, on MRI, there was a kyphotic angulation of the the detrusor due to sacral nerves lesion, leaving the unbalanced spine at S3-Cd1 with ventral deviation of the tail. Although sympathetic nerve as the only functioning innervation (12). subluxation was not obvious during the surgical exploration, a Urinary infection, detected at presentation in cat 1, was likely chronic instability at the intervertebral space cannot be ruled secondary to the neurological dysfunction of the bladder, and out as a possible cause for disc degeneration and protrusion. this is a factor complicating prognosis (12). The reason why caudal (coccygeal) IVDD has never been Cat 1 was presented with a 6-year history of intermittent reported in cats before is unknown. Some subtle signs, such as fecal constipation resulting from a suspected pelvic trauma, a reluctance to jump or a reduced level of activity may be over- which was controlled with conservative treatment, until sudden looked as early indicators of IVDD, as proposed by Harris and deterioration occurred concomitantly with urinary retention Dhupa (16) for lumbosacral disc degeneration. As well, limited 2 wk before referral. On MRI, the pelvic canal was narrowed as access to or reluctance to seek referral for advanced diagnostic a result of axial displacement of the right hemipelvis and colon imaging may account for lack of any previous report of feline diameter was considered to be borderline with megacolon. At caudal (coccygeal) IVDD in the veterinary literature. 24-month follow-up the cat was still receiving lactulose daily, In conclusion, sacrocaudal (sacrococcygeal) intervertebral but no other episodes of constipation had occurred since dis- disc protrusion should be considered among other differential charge from our hospital. diagnoses in cats that are presented with urinary retention Constipation in cat 2, although resolved at the time of refer- and constipation, reluctance to move and jump, and pain on ral, was reported by the referring veterinary surgeon who man- manipulation of the sacrocaudal (sacrococcygeal) area. Advanced aged it with frequent enemas in the pre-referral period. Although diagnostic imaging of the caudal spine, such as MRI, should be never reported before, exacerbation of constipation in cat 1 and considered in these patients. Dorsal decompressive laminectomy constipation showed by cat 2 may be the consequence of com- in the sacrocaudal (sacrococcygeal) spine was very successful in pression or transient neurapraxia of the pelvic nerve caused by the long-term period for both cats, but larger numbers of cases disc protrusion at S3-Cd1. Nevertheless, it cannot be excluded are required to make any recommendations. Adequate commu- that constipation was caused instead by pain or inability to raise nication with owners regarding prognosis is important, especially the tail as occurs in dogs with sacrocaudal (sacrococcygeal) and if complicating factors, such as urinary infection, are present. caudal (coccygeal) IVDD (6–8). CVJ At 1-month follow-up, cat 2 showed mild paraparesis that References was unnoticed at the time of referral, probably due to the cat’s . 1 King AS, Smith RN. Degeneration of the intervertebral disc in the cat. reluctance to move. Walker et al (14) showed that the tail is Acta Orthop Scand 1964;34:139–158. used in cats for balance regulation during locomotion as well 2. Hoerlein BF. Intervertebral disc disease. In: Oliver JE, Hoerlein BF, eds. Veterinary Neurology. Philadelphia, Pennsylvania: WB Saunders, 1987: as for upward and downward jumping. Compression of caudal 321–340. (coccygeal) nerves caused by disc protrusion might have affected 3. Muñana KR, Olby NJ, Sharp NJ, Skeen TM. Intervertebral disk disease fine adjustments during locomotion, accounting for parapare- in 10 cats. J Am Anim Hosp Assoc 2001;37:384–389. 4. De Decker S, Warner AS, Volk HA. Prevalence and breed predisposition sis still noted during the follow-up examination. This theory for thoracolumbar intervertebral disc disease in cats. J Feline Med Surg might also explain the reluctance to jump noted by the owner 2017;19:419–423. before referral. Paraparesis might have improved with time as at 5. Marioni-Henry K. Feline spinal cord diseases. Vet Clin North Am Small Anim Pract 2010;40:1011–1028. 20-month follow-up the owner and the referring veterinarian did 6. Freeman P. Sacrococcygeal intervertebral disc extrusion in a dachshund. not report any abnormality in the cat’s gait and paraparesis was Vet Rec 2010;167:618–619.

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. 7 Akin EY, Narak J, Simpson ST. What is your diagnosis? J Am Vet Med 12. O’Brien D. Neurogenic disorders of micturition. Vet Clin North Am Assoc 2011;238:153–154. Small Anim Pract 1988;18:529–544. 8. Lawson CM, Reichle JK, Mcklveen T, Smith MO. Imaging findings in 13. DeLahunta A, Glass E. Veterinary Neuroanatomy and Clinical dogs with caudal intervertebral disc herniation. Vet Radiol Ultrasound Neurology. St. Louis, Missouri: Saunders Elsevier, 2015:184–190. 2011;52:487–489. 14. Walker C, Vierck CJ, Ritz LA. Balance in the cat: Role of the tail and 9. Maierl J, Reindl S, Knospe C. Observations on epidural anesthesia in effects of sacrocaudal transection. Behav Brain Res 1998;91:41–47. cats from the anatomical viewpoint. Tierärztl Prax 1997;25:267–270. 15. Oshima H, Ishihara H, Urban JP, Tsuji H. The use of coccygeal 10. Barone R, Simoens P. Anatomia comparata dei mammiferi domestici. discs to study intervertebral disc metabolism. J Orthopaedic Res Vol. 6: Neurologia, sistema nervoso centrale. [book in italian] Milan, 1993;11:332–338. Italy: Italy-Edagricole-New Business Media, 2006:150–157. 16. Harris JE, Dhupa S. Lumbosacral intervertebral disk disease in six cats. 11. Nickel R, Schummer A, Seiferle E. Midollo spinale. In: Trattato di J Am Anim Hosp Assoc 2008;44:109–115. anatomia degli animali domestici. Vol IV. Milan, Italy: Casa Editrice Ambrosiana, 1988:27–52. Italian translation of: Lehrbuch der anatomie der haustiere. Berlin: Verlag, 1975. RAPPORTCAS DE

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392 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY Case Report Rapport de cas

Surgical management of long bone fractures in cats using cortical bone allografts preserved in honey

Márcio P. Ferreira, Marcelo M. Alievi, Isis S. Dal-Bó, Paula C.S. Gonzalez, Fernanda S. Nóbrega, Aline S. Gouvêa, Carlos A.C. Beck

Abstract — This report describes comminuted fractures in 2 cats repaired by stabilization with cortical bone allografts that had been preserved in honey. Both cats exhibited appropriate post-operative weight-bearing. Preservation of bone in honey is a simple and widely available alternative for bone banking. This is the first report of a bone defect in cats repaired with bone preserved in honey.

Résumé — Gestion chirurgicale de fractures osseuses longues chez les chats à l’aide d’une allogreffe de la corticale préservée dans du miel. Ce rapport décrit deux fractures comminutives réparées par la stabilisation à l’aide de l’allogreffe de la corticale qui avait été préservée dans du miel. Les deux chats ont manifesté une mise en charge postopératoire appropriée. La préservation de l’os dans du miel est une méthode de remplacement simple et facilement disponible comme ostéothèque. Il s’agit du premier rapport d’un défaut osseux chez des chats qui a été réparé à l’aide d’un os préservé dans du miel. (Traduit par Isabelle Vallières) Can Vet J 2018;59:393–396

one fractures are one of the main afflictions of domestic osteoconduction and resistance of bone grafts (2) and it reduces B cats. Depending on the intensity of the trauma, the frac- the immunogenicity of the allograft. Furthermore, honey is ture may have such a high degree of comminution that anatomic inexpensive and easy to handle. As a preservation method for reduction of bone fragments is impaired (1). A cortical bone bone grafts, honey has already been experimentally used in birds allograft fixed with a plate and screws has been successfully (7), dogs (2), and domestic cats (8). Honey has also been used employed as one of the surgical treatments for this type of frac- as a preservative for human bone tissue (9). The successful use ture (2,3). This type of bone graft provides mechanical support of cortical bone allografts preserved in honey for the repair of and osteoconduction (4). Processing and storing methods that clinical comminuted fractures of long bones in domestic cats have been described for preservation of these grafts include is reported herein. lyophilization, freezing (5), immersion in glycerin, exposure to ethylene oxide (6), and gamma irradiation. Honey is being Case descriptions considered as an option for preservation of bone grafts. Besides Bone allografts its antimicrobial activity, honey has been shown to maintain Allografts were obtained from the hospital bone bank, mostly from animals euthanized due to severe trauma with no systemic Department of Animal Medicine, Veterinary Medicine, abnormalities. The bone grafts were harvested and processed University of Rio Grande do Sul, Porto Alegre, Brazil. aseptically and tested for microbiologic contamination at col- 9090 Bento Gonçalves Avenue, Porto Alegre, RS, Brazil lection and just before being grafted. No microorganisms grew 91540-000. in the samples from either graft. Before being grafted, the allografts were rehydrated in 0.9% sodium chloride solution Address all correspondence to Dr. Márcio P. Ferreira; e-mail: for at least 45 min. [email protected] The honey came from bees that pollinated mainly Yopo Dr. Dal-Bó’s current address is Department of Surgery, (Anadenanthera spp.) flowers. Harvesting of honey was approved Veterinary Medicine, University of São Paulo, São Paulo, by the Brazilian Federal Agricultural Inspection Service (SIF). Brazil. 87, Orlando de Marques Paiva avenue, São Paulo, SP, Analyses for bacterial and fungal growth in the honey were Brazil 05508-270. negative. The allografts were submerged in honey and individu- Dr. Nóbrega’s current address is 8000 Juca Batista Avenue, Porto ally kept in opaque plastic bottles, in the dark, and at room Alegre, RS, Brazil, 91781-200. temperature (20°C to 25°C). Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the Case 1 CVMA office ([email protected]) for additional A 2-year-old male domestic cat, weighing 4.5 kg, was admit- copies or permission to use this material elsewhere. ted to the Teaching Animal Hospital after being hit by a car.

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Figure 1. Tibial osteosynthesis in a domestic cat using a Figure 2. Femoral osteosynthesis in a domestic cat using a bone allograft that was preserved in honey. A — Pre-operative bone allograft that was preserved in honey. A — Preoperative radiograph showing comminuted fracture of the tibia. radiographic examination showing comminuted fracture of the B and C — Radiograph taken immediately after fracture repair. femur. B and C — Radiograph taken immediately after surgery. D — Radiograph (craniocaudal projection) 2 y after the surgical D — Radiograph (craniocaudal aspect) taken 15 mo after procedure, showing resorption of the bone allograft at the distal surgical repair showing fracture consolidation. E — Radiograph interface. E — Radiograph (mediolateral projection) taken 2 d (mediolateral aspect) taken 15 mo after surgical repair, showing after the surgical procedure. abundant callus formation.

On physical examination there were no abnormalities other Medley, Suzano, Brazil), 25 mg/kg BW, PO, q8h, for 7 d were than pain, abnormal mobility, and crepitation of the right administered. A Robert-Jones bandage was applied for 1 wk after tibia. Radiographic examination revealed a comminuted tibial surgery. The animal was submitted for radiographic examina- diaphyseal fracture (Figure 1A). The animal’s blood panel did tions every 30 d, for 6 mo. not identify any abnormalities. As soon as the bandage was removed, the animal exhibited adequate use of the repaired limb. There was radiographic evi- Surgical procedure dence of healing of the proximal host-allograft interface at 30 d After premedication with acepromazine maleate (Acepran; after surgery. However, bone resorption of the distal interface Vetnil, Louveira, Brazil), 0.05 mg/kg body weight (BW), IM was observed on the 60th day. Two years after the surgical pro- and meperidine (Cloridrato de petidina; União Química, Embu- cedure, radiographic examination showed complete remodeling Guaçu, Brazil) 3.0 mg/kg BW, IM, anesthesia was induced with of the proximal host-allograft interface and atrophic non-union propophol (Propovan; Cristália, São Paulo, Brazil), 5 mg/kg BW, of the distal interface (Figures 1D and 1E). The fibula had IV, and maintained with isofluorane in oxygen. An epidural abundant callus formation on its fractured site, near to the tibial block was given using morphine (Dimorf; Cristália), 0.1 mg/kg distal interface. The animal exhibited a grade 1 lameness of the BW and lidocaine (Xylestesin 2%; Cristália), 4 mg/kg BW. limb during walking (scale of 0 to 4 where: 0 = no lameness and Cephazolin (Ceflen; Agila, Campo dos Goytacazes, Brazil), 4 = non-weight-bearing lameness) both immediately and at the 22 mg/kg BW, IV was prophylactically administered at induc- 2-year period after surgery. tion and 90 min later. The animal was then positioned in dorsal recumbency for a craniomedial approach of the right tibia. Case 2 After debridement of the fracture site and removal of small A 4-year-old female domestic cat, weighing 3 kg, was admitted bone fragments, an osteotomy was completed with an oscillating after being involved in a car accident. At physical examination, saw to remove the ends of the bone fragments. A 3.5-cm long pain, abnormal mobility, and crepitation of the right femur were cortical bone allograft was used to fill the defect in the distal detected. Complete blood cell count and serum biochemical tibia. The bone graft had been preserved in honey for 36 d. The profile were unremarkable. Radiographic examination confirmed graft and host bone were stabilized with a 2.7-mm plate placed a comminuted diaphyseal fracture of the femur (Figure 2A). in the craniomedial surface of the tibia, and 2.7-mm cortical screws. Five screws were placed in the proximal host bone seg- Surgical procedure ment, 3 in the allograft, and 3 in the distal host bone segment The anesthesia protocol was the same as described for the cat (Figures 1B and 1C). in Case 1. Through a lateral approach to the femur, small bone fragments were removed and an osteotomy was performed to Postoperative care and outcome remove the bone fragments at the ends of the fracture for better After the surgery, enrofloxacin (Flotril; Schering-Plough, alignment of the bone allograft. The distal diaphyseal femur São Paulo, Brazil), 2.5 mg/kg BW, PO, q12h, for 10 d, meloxi- defect was replaced with a 3-cm long cortical bone allograft. The cam (Maxican; Ouro Fino, Cravinhos, Brazil), 0.1 mg/kg BW, allograft had been preserved in honey for 90 d. The allograft PO, q24h, for 5 d, tramadol (Tramadon; Cristália), 3 mg/kg was fixed with a 2.7-mm plate, placed on the lateral surface BW, PO, q8h, for 5 d, and metamizole (Dipirona sódica; of the femur and secured with eight 2.7-mm cortical screws.

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Three screws were inserted in the proximal femur fragment, Although there were only 2 animals in this study, the non-union 2 in the allograft, and 3 in the distal femur fragment (Figures 2B rate was similar to that reported in other studies that used honey and 2C). as bone tissue preservative (2,8), and in experiments with bone allografts in humans (21) in whom the rate was about 30%. Postoperative care and outcome In view of other fixation techniques used for comminuted

Postoperative therapy was the same as described for the cat in fractures in domestic cats, such as interlocking nail (26), exter- REPORT CASE Case 1. The animal was confined to a cage (1 m 3 0.5 m 3 nal skeletal fixator associated with intramedullary pins (27,28), 0.5 m) for the first 10 d. After that, it was taken for short walks, and bridge plating (29), the DCP (Dynamic Compression during which it had a satisfactory gait. Monthly radiographic Plate) used for the reported cases proved to be an efficient examinations were conducted and, on the 60th day after surgery, osteosynthesis method as it enabled an adequate and early use consolidation with abundant bridging callus was observed at of the limb in both animals. This is an important feature for the 2 host-allograft interfaces. Fifteen months after the fracture full recovery of orthopedic patients (30,31). Moreover, the repair, the animal displayed grade 1 lameness during walking close contact between bone graft and host bone provided by the (scale of 0 to 4, where: 0 = no lameness and 4 = non-weight- DCP promotes fast healing (2). Similar to what was observed bearing lameness) and, at radiographic examination, complete in femoral diaphysis of dogs after grafting of bones preserved bone healing and some callus remodeling into both interfaces in honey (2), a marked bone callus formation did not prevent were evident (Figures 2D and 2E). normal movement of the affected limb. The preservation period in honey, as used in this study, was Discussion also used with allogeneic bone engraftment in dogs (28 to Segmental cortical defects averaging 1.5 3 the bone diaphyseal 40 d) (2), domestic cats (30 to 35 d) (8), and domestic pigeons diameter impair bone healing in dogs and cats (10,11). Use of (30 to180 d) (7). The successful use of honey in an 8-month autologous grafts in cats is difficult due to the limited amount preservation period has been also reported. The maximum and of bone (12). Allografts can be effectively used for repairing minimum storage times for preservation of bone grafts in honey the defects caused by comminuted fractures and non-unions, still need further investigation. The antibacterial activity of for sparing animals with bone tumors, and for bone lengthen- honey varies considerably with the floral source (32); therefore, ing (13–15). Several allograft preservation methods have been it is important to use honey from a floral source associated with developed. high antibacterial activity. In our study we used honey from a Honey was chosen for the preservation of the bone allografts monoculture of Yopo (Anadenanthera spp.), but there are other used in these clinical cases because of its advantages over other floral sources known to result in honey with a high concentra- preservation methods. Besides the complexity and high cost tion of antibacterial activity. of most allograft processing and storing methods, some still This report is the first to describe the use of honey-preserved have adverse outcomes. Gamma radiation and ethylene oxide bone allografts to repair fractures in a clinical setting. Since can reduce incorporation of host bone at the graft site and, as rupture of nutrient-bearing blood vessels and lesions to adjacent well as lyophilization, freezing, and glycerin, can reduce the soft tissues caused by trauma during fracture of a bone do not mechanical strength of the bone graft (6). Honey, besides being happen to the same extent in experimental surgery, this report is readily available, allowing room temperature storage, reducing important for supporting the effectiveness of honey as a preser- allograft immunogenicity (8), and maintaining bone mechani- vation method for cortical bone allografts used to repair bones in cal strength, has been proven to have antimicrobial properties. adverse conditions. Honey-preserved cortical bone allografts can The antimicrobial activity of honey, in a bone graft preservation be used for repairing long bone defects caused by comminuted setting, is due to its hyperosmolarity (16), low pH (17), and fractures in domestic cats. Additional studies on the effects of the presence of phytochemical substances (16), determined to honey for preservation of animal tissues are necessary to ensure be non-peroxide antibacterial factors. Nevertheless, exposure grafting quality and to standardize the storage process. to light and high temperatures must be avoided to maintain such properties (18). Preservation in honey has also been suc- Acknowledgment cessfully applied to conservation of bone grafts in pigeons (7), The authors thank Dr. Cassio Ricardo Auada Ferrigno for his dogs (2), humans (9), and felines (8), and to human cornea help and advice on preparation and editing of this manuscript. (19) and skin (20). However, it is essential to monitor biologic CVJ growth since microorganisms have been detected in honey (2,8) and can jeopardize the success of its use and of the preserved References material. . 1 Scott HW, McLaughlin R. Introduction to feline orthopedic surgery. The main complications associated with cortical bone grafts In: Scott HW, McLaughlin R, eds. Feline Orthopedics. London, UK: are non-union, fracture, and infection (21–24). A non-union Manson Publishing, 2007:9–16. 2. Alievi MM, Schossler JEW, Guimarães LD, de Oliviera ANC, Traeslel occurred in 1 host-allograft interface of 1 cat in the present CK, Ferreiria PA. Implante ósseo cortical alógeno conservado em mel study; we consider that this occurred due to poor muscle cover- na reconstrução de falha óssea diafisária em fêmur de cães: avaliação age at the distal region of the tibia (25), rather than to a bone clínica e radiográfica. Cienc Rural 2007;37:450–457. 3. Harasen G. Repair of a comminuted femoral fracture in a cat using graft rejection, since there was no draining tract after 2 y and cortical and cancellous bone grafting techniques. Can Vet J 1997; honey has the ability to reduce antigenicity of such grafts (8). 38:574–575.

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. 4 Fitch R, Sinibaldi KR, Kerwin S, Newman-Gage H. Bone autografts 19. Abramov VG, Markicheva NA. Therapeutic lamellar keratoplasty with and allografts in dogs. Comp Vet Cont Ed 1997;19:558–575. honey preserved material. Oftalmol Zh 1983;38:81–83. 5. Nather A, Thambyah A, Goh JCH. Biomechanical strength of deep- 20. Subrahmanyan M. Storage of skin grafts in honey. Lancet 1993;341: frozen versus lyophilized large cortical allografts. Clin Biomech 2004;19: 63–64. 526–533. 21. Ortiz-cruz E, Gebhardt MC, Jennings LC, Springfield DS, Mankin HJ. 6. Coronado GS, Swenson CL, Martinez SA, Burkhardt KS, Arnoczky The results of transplantation of intercalary allografts after resection of SP. Effects of a 98% solution of glycerol or sterilization with ethylene tumors. J Bone Joint Surg Am 1997;79A:97–106. oxide on FeLV in bone allografts and effects on bone incorporation of 22. Thompson Jr, RC, Garg A, Clohisy DR, Cheng EY. Fractures in large allografts in cats. Am J Vet Res 2000;61:665–671. segment allografts. Clin Orthop Relat Res 2000;370:227–235. 7. Gaiga LH, Schossler JEW. Osteossíntese de úmero por xenoenxerto 23. Henry Jr, WB, Wadsworth PL. Retrospective analysis of failures in the ósseo preservado em mel em pombos domésticos (Columba livia). Cienc repair of severely comminuted long bone fractures using large diaphyseal Rural 2003;33:709–715. allografts. J Am Anim Hosp Assoc 1981;17:535–546. 8. Ferreira MP, Alievi MM, Beck CAC, et al. Comparison of lyophilization, 24. Tomford WW, Starkweather RJ, Goldman MH. A study of the clinical and freezing in honey as techniques to preserve cortical bone allografts incidence of infection in the use of banked allograft bone. J Bone Joint

RAPPORTCAS DE used to repair experimental femoral defects in domestic adult cats. Arq Surg Am 1981;63A:244–248. Bras Med Vet Zootec 2012;64:263–273. 25. Egger EL. Fractures of the radius and ulna. In: Slatter D, ed. Textbook 9. Mschvidobadse VM. Allotransplantation sterilisierter Knochen of Small Animal Surgery. 2nd ed. Vol. 2. Philadelphia, Pennsylvania: und Halbgelenke bei Knochendefekten. Zentralbl Chir 1978;103: Saunders, 1993:1736–1757. 1138–1148. 26. Díaz-Bertrana MC, Durall I, Puchol JL, Sanchez A, Franch J. 10. Key JA. The effects of a local calcium depot on osteogenesis and healing Interlocking nail treatment of long-bone fractures in cats: 33 cases of fractures. J Bone Joint Surg Am 1934;16A:176–184. (1995–2004). Vet Comp Orthop Traumatol 2005;18:119–126. 11. Toombs JP, Wallace LJ, Bjorling DE, Rowland GN. Evaluation of Key’s 27. Worth AJ. Management of fractures of the long bones of eight cats hypothesis in the feline tibia: An experimental model for augmented using external skeletal fixation and a tied-in intra-medullary pin with a bone healing studies. Am J Vet Res 1985;46:513–518. resin-acrylic bar. N Z Vet J 2007;55:191–197. 12. Dorea HC, McLaughlin RM, Cantwell HD, et al. Evaluation of heal- 28. Adamiak Z, Aleksiewicz R, Kostrzewski M, Mederski J. Comminuted ing in feline femoral defects filled with cancellous autograft, cancellous long bone fractures in cats caused by pneumatic gun shot and repaired allograft or bioglass. Vet Comp Orthop Traumatol 2005;18:157–168. using the external fixator “tie-in” technique. Pol J Vet Sci 2007; 13. Kerwin SC, Lewis DD, Elkins AD. Bone grafting and banking. 10:153–157. Compend Contin Educ Vet 1991;13:1558–1566. 29. Macias C, Gibbons SE, McKee WM. Y-T humeral fractures with supra- 14. Sinibaldi KR. Evaluation of full cortical allografts in 25 dogs. J Am Vet condylar comminution in five cats. J Small Anim Pract 2006;47:89–93. Med Assoc 1989;194:1570–1577. 30. O’Sullivan ME, Bronk JT, Chao EY, Kelly PJ. Experimental study of 15. Liptak JM, Dernell WS, Straw RC, et al. Intercalary bone grafts for joint the effect of weight bearing on fracture healing in the canine tibia. Clin and limb preservation in 17 dogs with high-grade malignant tumors of Orthop Relat Res 1994;302:273–283. the diaphysis. Vet Surg 2004;33:457–467. 31. Meadows TH, Bronk JT, Chao YS, Kelly PJ. Effect of weight-bearing 16. Cooper RA, Molan PC, Harding KG. Antibacterial activity of honey on healing of cortical defects in the canine tibia. J Bone Joint Surg Am against strains of Staphylococcus aureus from infected wounds. J R Soc 1990;71:1074–1080. Med 1999;92:283–285. 32. Allen KL, Molan PC, Reid GM. A survey of the antibacterial activity 17. Bergman A, Yanai J, Weiss J, Bell D, David MP. Acceleration of wound of some New Zealand honeys. J Pharm Pharmacol 1991;43:817–822. healing by topical application of honey. Am J Surg 1983;145:374–376. 18. Mathews KA, Binnington AG. Wound management using honey. Compend Contin Educ Vet 2002;24:53–60.

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396 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY Review Article Compte rendu

Update on the use of trilostane in dogs

Julie Lemetayer, Shauna Blois

Abstract — Many articles published in the past few years have contributed to a better understanding of the use of trilostane in dogs. Trilostane is a competitive inhibitor of 3b-hydroxysteroid dehydrogenase, the enzyme essential for synthesis of cortisol and all other steroids. Trilostane is reported to be safe and effective in the treatment of pituitary-dependent hyperadrenocorticism (HAC), adrenal-dependent HAC, and alopecia X. While trilostane controls most of the clinical signs associated with HAC, abnormalities such as hypertension, hypercoagulability, and proteinuria may persist despite therapy. Because the duration of cortisol suppression after a dose of trilostane is often less than 12 hours, many dogs with HAC could benefit from low dose trilostane treatment every 12 hours. Many controversies regarding trilostane still exist. This review provides a comprehensive commentary on trilostane’s indications, mode of action, dose, monitoring, efficacy, and adverse effects.

Résumé —Mise à jour sur l’utilisation du trilostane chez les chiens. De nombreux articles publiés au cours des dernières années ont contribué à une meilleure compréhension de l’utilisation du trilostane chez les chiens. Le trilostane est un inhibiteur compétitif de la 3b-hydroxystéroïde déshydrogénase, l’enzyme essentiel pour la synthèse du cortisol et de tous les autres stéroïdes. On signale que le trilostane est sûr et efficace pour le traitement de l’hyperadrénocorticisme pituitaire (HAC), le HAC adrénal et l’alopécie X. Bien que le trilostane maîtrise la plupart des signes cliniques associés au HAC, des anomalies comme l’hypertension, l’hypercoagulabilité et la protéinurie peuvent persister malgré la thérapie. Parce que la durée de la suppression du cortisol après une dose de trilostane est souvent de moins de 12 heures, plusieurs chiens atteints de HAC pourraient bénéficier d’un traitement à faible dose de trilostane toutes les 12 heures. Il subsiste encore beaucoup de controverse concernant le trilostane. Cet examen fournit un commentaire exhaustif sur les indications, le mode d’action, la dose, la surveillance, l’efficacité et les effets secondaires du trilostane. (Traduit par Isabelle Vallières) Can Vet J 2018;59:397–407

Introduction therapy. The optimal medical treatment should have minimal adverse effects while alleviating clinical signs associated with nce a diagnosis of hyperadrenocorticism (HAC) has been HAC, including polyuria-polydipsia (PUPD), polyphagia, made, treatment decisions are influenced by many factors O haircoat and skin changes, truncal obesity, muscle weakness, including etiology of HAC, client financial constraints, the level and alopecia (1). Ideally, it should also improve deleterious of commitment involved in treatment, and a consideration of physiological consequences of HAC including hypertension, the risk/benefit ratio of the treatment compared with the con- thromboembolism, and proteinuria. sequences associated with the disease. Trilostane is a synthetic steroid that selectively inhibits the Three main categories of options are available for the treat- enzyme 3b-hydroxysteroid dehydrogenase (3b-HSD) in the ment of pituitary-dependent and adrenal-dependent HAC adrenal cortex. This inhibition blocks the conversion of preg- (PDH and ADH) in dogs: medical, surgical, and radiation nenolone to progesterone (2), thereby inhibiting the production of glucocorticoids and, to a lesser extent, mineralocorticoids Department of Clinical Studies, Ontario Veterinary College, and sex hormones. University of Guelph, Guelph, Ontario N1C 1G9. Trilostane has been used in dogs with HAC for almost 20 y, Address all correspondence to Dr. Julie Lemetayer; e-mail: and a veterinary approved product was first marketed in Canada [email protected] in 2009. Control of clinical signs is gradual and variable among Use of this article is limited to a single copy for personal study. studies. Reports of good control ranged from , 50% to 100% Anyone interested in obtaining reprints should contact the of treated dogs after few weeks of treatment (3–13). However, CVMA office ([email protected]) for additional after several months of treatment, partial to complete control of copies or permission to use this material elsewhere. clinical signs occurred in . 75% of cases in published studies

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(3–13). Adverse effects are generally mild or moderate and are Dose reported to occur in 0% to 40% of cases (3–13). Trilostane is now supplied in 5-, 10-, 30-, 60-, and 120-mg A recent article reported that 26 dogs with untreated PDH capsules (Vetoryl). Currently, the manufacturer’s initial dose rec- had shorter mean survival times (506 d) than 17 dogs that were ommendation for trilostane is 2.2 to 6.6 mg/kg BW, PO, q24h treated with trilostane at 1 to 3 mg/kg body weight (BW) once based on body weight and capsule size. Previous label instruc- (q24h) or twice a day (q12h), whose median survival time was tions for trilostane recommended initial dosing by body weight not reached at the end of the study (14). This study suggests categories (, 5 kg, 30 mg; 5 to 20 kg; 60 mg; and . 20 kg; that withholding treatment for dogs with PDH could increase 120 mg; q24h). One study compared this dosing approach with the risk of death. Therefore, it suggests a positive effect of trilo- dosing at 2 to 5 mg/kg BW, q24h. The study found that there stane in dogs with PDH. However, the cause of death in many was comparable clinical improvement and decrease in cortisol

COMPTERENDU of the untreated dogs was either unknown or did not seem to in both dosing groups, but a lower risk of side effects was associ- be related to their HAC. In addition, the retrospective nature ated with mg/kg BW dosing (25). of that study makes it difficult to accurately compare untreated The use of compounded capsules, if necessary based on the dogs with dogs treated with trilostane. patient size, should be considered carefully. If compounded Similar efficacy, similar or even longer survival times, and doses are necessary, only the licensed trilostane product should similar or lower rates of adverse effects have been reported be used, and compounding should be performed by trained with trilostane compared to mitotane in both PDH and ADH pharmacists. A study evaluating trilostane products purchased (13,15–18). Longer survival was found when trilostane was from 8 compounding pharmacies found that actual concentra- compared to mitotane in a non-selective adrenolytic protocol tions in compounded capsules varied from 39% to 152.6% of (18). However, the veterinary literature is lacking large prospec- the label claim. Additionally, dissolution of the compounded tri- tive, randomized, controlled studies comparing trilostane and lostane was lower in 20% of tested products (26). The potential mitotane therapy to determine which is the superior treatment variation in strength and dissolution of compounded trilostane for dogs with HAC. could have negative impacts on management of patients with Many research articles detailing the use of trilostane in dogs HAC. With the advent of licensed 5 mg and 10 mg capsules, with HAC have been published. This article will summarize the use of compounded capsules is rarely necessary. the pharmacology of trilostane as well as the latest research on Studies in dogs with HAC treated with trilostane reported a trilostane treatment in canine HAC. wide variation in the dose necessary to control the disease, from 0.42 to 50 mg/kg BW per day (3–13,19,23) (Tables 1 and 2). Pharmacology However, these studies had very different study designs. While Trilostane is a competitive inhibitor of 3b-HSD. This block- most studies were prospective clinical trials, a few were retro- ade is reversible and appears to be dose-related (19). 3b-HSD spective studies (6,7,13) which carry more risk of selection bias, converts pregnenolone to progesterone, and dehydroepian- misclassification, and information bias than prospective studies. drosterone (DHEA) to androstendione. The enzymatic action The number of dogs included varied from 9 to 78 with differ- of 3b-HSD is thus essential for the synthesis of cortisol and all ences in dog breeds and body weight (3–13,19). The number of other steroids including mineralocorticoids, sex steroids, and dogs can affect statistical results with higher risk of type 2 errors other glucocorticoids. Inhibition of progesterone production in smaller populations (3,8,9,11,13). Dogs . 25 to 30 kg, and reduces the synthesis of cortisol in the zona fasciculata of the possibly also dogs . 15 kg, have been found to require a lower adrenal glands. It also decreases the production of aldosterone dose/kg BW of trilostane to control clinical signs compared in the zona glomerulosa and production of androstendione with dogs weighing # 15 kg (5,10,27). Studies which only in the zona reticularis. In contradiction with a previous study included dogs , 15 kg (3,9) or which segregated the smallest (20), a later study did not find an effect of trilostane on DHEA dogs (, 10 kg) to 1 group (7) had higher risk of bias. In addi- concentration. This suggests that there might be more than one tion, the diagnosis of HAC in dogs with supportive clinical form of the enzyme 3b-HSD present in dogs, with a variable and biochemical changes varied from a single confirmatory effect of trilostane on each isoenzyme (21). However, the first test (4–8,13) to at least 2 confirmatory tests (3,9–12). These study was in vivo while the second study was in vitro (21). This tests consisted of 1 to 2 urine cortisol to creatinine ratio(s) could account for the different results between the 2 studies. (UCCR), an adrenocorticotropic hormone (ACTH) stimula- Trilostane may also inhibit the enzymes 11b-hydroxylase tion test, and/or a low dose dexamethasone suppression test. and 11b-hydroxysteroid dehydrogenase (11b-HSD) in dogs Studies which used fewer tests to confirm the diagnosis of HAC (20,22). 11b-HSD catalyzes the conversion of physiologically were more likely to include dogs that were falsely diagnosed active cortisol to inactive cortisone. with HAC. Pharmacokinetic studies in healthy dogs showed that maximal The most notable differences among studies were the time plasma concentration of trilostane occurs 1.7 to 3.8 h following the ACTH stimulation test was performed after administra- administration and plasma concentration returns to baseline tion of trilostane and the definition of good disease control. by about 12 h [Vetoryl (trilostane) 2015 drug insert, Dechra Following administration of trilostane, the ACTH stimulation Veterinary Products, Pointe-Claire, Quebec]. Studies in dogs test was either performed variably within the day (4,5,9), 2 to with HAC have shown that trilostane’s activity can even be 6 h later (3,7), 3 to 4 h later (11), 3 h later (12), 2 to 4 h later considerably shorter than 12 h in some dogs (23,24). (6), 4 to 6 h later (8,10), or 8 to 12 h later (8,10,13). The

398 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY upper limit of the acceptable post-ACTH cortisol concentra- retrospective study, control of the clinical signs and cortisol tion range varied from 69 nmol/L (3) to 250 nmol/L (4) a few concentrations was seen sooner in the q12h treatment group. hours after administration of trilostane. In some studies, the The mean final dose was 7.6 mg/kg BW per day in the q24h trilostane dose was mostly changed based on the results of the group and 5.4 mg/kg BW per day in the q12h group (2.7 mg/kg ACTH stimulation test (3,5,7). In other studies, the trilostane BW, q12h). Reports of adverse effects, which were documented REVIEW ARTICLE REVIEW dose was left unchanged in dogs with high (and in some cases as mild to moderate in severity, were more common in the low) post-ACTH stimulation cortisol concentration as long as q12h versus the q24h treatment group. However, animals clinical signs were controlled (6,8,9,11,12). given trilostane q24h had a 15% increased chance of treatment Besides these differences in study design that could explain discontinuation although no clear explanation to explain the the wide differences in doses among the studies, some inter- difference was identified. individual variability could also be due to the low water solu- Cho et al (9) found fewer adverse effects with low dose (0.5 to bility of trilostane, and thus variable absorption of the drug 1 mg/kg BW) trilostane administered q12h compared with (15). In addition, it could be due to a variation in the 3b-HSD 30 mg/dog given q24h (6 to 12 mg/kg BW per day) in dogs activity in the dogs’ adrenal glands, or variable conversion into , 5 kg BW. While 100% success in controlling clinical signs active metabolites such as ketotrilostane (21). It is worth not- and cortisol concentrations was seen in both groups at 24 wk ing that to enhance absorption, trilostane should be given with after initiation of trilostane treatment, improvement occurred food, including on the days recheck ACTH stimulation tests more slowly in the q12h group. The mean final daily dose are being conducted. required for control of HAC was much lower in the q12h group In studies describing the use of trilostane q24h (Table 1) compared with the q24h treatment group (2.9 mg/kg BW per (3–9), the initial dose ranged from 1.0 to 20 mg/kg BW, q24h day in the q12h group and 7.1 mg/kg BW per day in the q24h with a mean dose of 2.9 to 6.4 mg/kg BW, q24h. The final trilo- group). Additionally, results suggested fewer adverse effects in stane dose varied from 0.8 to 50 mg/kg BW, q24h with a mean the q12h versus the q24h treatment group (9). dose of 2.8 to 19 mg/kg BW, q24h. However, as explained, the Arenas et al (8) compared dogs with PDH that were treated duration of cortisol suppression after a dose of trilostane is often with trilostane either q12h or q24h. The mean final dose was less than 12 h. Therefore, several studies have examined the use 4.6 mg/kg BW per day in the q24h group and 4.7 mg/kg BW and clinical efficacy of trilostane q12h for treatment of PDH per day in the q12h group (2.4 mg/kg BW). This study found and ADH (Table 2) (7–13). that more dogs in the q12h group had complete resolution of In studies describing the use of trilostane q12h, the initial clinical signs than in the q24h group (69% had complete clini- dose ranged from 0.5 to 7.5 mg/kg BW, q12h, with a mean cal recovery at 6 mo in the q12h group and 42% in the q24h dose of 0.78 to 3.1 mg/kg BW, q12h. The final trilostane dose group). While clinical response was more prevalent in the q12h varied from 0.21 to 9.05 mg/kg BW, q12h, with a mean dose of treatment group, there was no significant difference in the mean 1.43 to 3.75 mg/kg BW, q12h. Among the studies reported in post-ACTH cortisol concentration between groups. Both pro- Table 2, 10 out of 180 dogs (5.6%) required trilostane 3 times tocols were safe and generally well-tolerated. a day to successfully control their clinical signs (11,12). Based on these studies, it appears that use of trilostane q12h, In dogs treated with trilostane either q24h or q12h, frequent often given at total daily doses that are lower than the manu- dose adjustments were necessary to control the disease (3–13). facturer’s recommendations, results in a safe and effective treat- In these studies, clinical signs in dogs treated with trilostane ment for dogs with HAC. When using a twice-daily treatment q24h improved in . 75% of cases at 6 mo (3–9). However, the protocol, it is recommended to start at doses of 0.5 to 1 mg/kg rates of improvement were variable and 1 study reported only BW, q12h, with a maximum initial dose of 30 mg/dog for dogs 42% of the total cases (5/12 dogs) had complete resolution of . 30 kg. Indeed, complete control of clinical signs and cortisol clinical signs at 6 mo (8). Among studies reporting treatment concentrations can be achieved in some dogs using a very low with trilostane q12h, 67% to 100% of dogs were well-controlled dose of trilostane (12). at 6 mo (7–13). Between 2 to 4 mo, the cortisol was within the target range in 57% to 100% of the dogs treated with tri- Monitoring lostane q24h and in 69% to 100% of the dogs treated with Choosing the best monitoring protocol in HAC dogs undergo- trilostane q12h. ing treatment can be challenging. The ACTH stimulation test is Among the 11 studies listed in Tables 1 and 2, adverse effects currently the gold standard test used to monitor the response to were reported in 35/264 (13%) cases with q24h treatment and treatment of dogs with HAC. However, there are some limita- in 34/180 (19%) cases with q12h treatment. In both q12h tions to this test which will be discussed later. It is recommended and q24h treatment groups, most adverse effects were mild or that the ACTH stimulation test be conducted at 10 to 14 d moderate and included mild electrolyte abnormalities without after initiating trilostane or changing doses, then at 1, 3, and clinical signs, transient decrease in appetite, vomiting, diarrhea, subsequently every 3 to 6 mo after the trilostane dose becomes and lethargy. stable (15). It is generally accepted that clinical signs and cor- To date, 3 studies have directly compared the efficacy of tisol concentrations continue to improve in some dogs in the q24h versus q12h trilostane treatment in dogs with HAC. first month after starting trilostane therapy (12). Therefore, the Augusto et al (7) concluded that dogs treated either q24h or ACTH stimulation test performed after 10 to 14 d of onset of q12h showed similar improvement in clinical scores. In this therapy should be used only to ensure that there is no ex cessive

CVJ / VOL 59 / APRIL 2018 399 FOR PERSONAL USE ONLY

Table 1. Summary of clinical studies using once daily dosing of trilostane in dogs with hyperadrenocorticism. Reference numbers 3 4 5 6 7 8 9 Country Switzerland UK Australia Netherlands UK Spain South Korea Year of publication 2002 2002 2003 2008 2012 2013 2013 Number of dogs with PDH 11 78 30 63 47 16 7 Number of dogs with ADH 0 0 0 0 12 0 0 Starting dose, range in mg/kg BW, q24h 3.9 to 9.2 1.8 to 20.0 2.7 to 12.0 2.0 to 4.0 3.3 to 9.5 1.0 to 6.6 6 to 13.3 Starting dose, mean in mg/kg BW, q24h NS 5.9 NS NS 6.4 2.9 NS Monitoring 1, 3 to 4, 6 to 7, 12 to 16, 10 d, 1, 3, 6 mo, and then 10 d, 1, 3, then every 3 mo 3 wk then every 3 wk until 9 to 12 d, 1, 3, 6 mo 7d, 1, 3, 6 mo, 1 y 2 wk, 1, 2, 3, 4, 6 mo COMPTERENDU 24 to 28 wk every 3 to 6 mo thereafter stable, then every 3 mo Target cortisol in nmol/L 27 to 69 20 to 250 25–75 for tight control and 30–190 40 to 120 55 to 248 55 to 150 75–125 for acceptable control Time of sampling 2 to 6 h NS, most within a few hours NS 2–4 h 2 to 6 h 8 to 12 h NS ACTH stimulation test protocol 0.25 mg of tetracosactide IM, NS 5 mg/kg of tetracosactrin IV, 0.25 mg of tetracosactide IV, NS 0.25 mg of tetracosactide IM, 0.25 mg of tetracosactide IV, post-ACTH cortisol 60 min later post-ACTH cortisol 60 min later post-ACTH cortisol 90 min later post-ACTH cortisol 60 min later post-ACTH cortisol 60 min later Dose changes Increased in 5/11 (45%), Increased in 24/78 (31%), NS Increased in 22/63 and decreased NS In 12/16 dogs (75%). 9 increased, Dose increased 12 times from decreased in 3/11 (27%) decreased in 9/78 (11%) in 4/63 at 3 wk 2 decreased, 1 increased and 4th to 16th wk in total decreased Withdrawals None Discontinuation of trilostane None, but 2 dogs had trilostane None 29/59 (49%). No withdrawals due 2/16 (13%). Changed to None in 2 dogs for prolonged hypoAC discontinued for reasons to severe side effects of trilostane q12h treatment unrelated to the medication Final dose, range in mg/kg BW, q24h 4.1 to 15.6 NS 5.0 to 50.0 0.8–5.8 3.2 to 12 1.0–11.5 3.3 to 10.9 Final dose, mean in mg/kg BW, q24h NS 7.3 19 2.8 7.6 4.6 7.1 Number of dogs with clinical 9/11 (82%) at 6 mo 60/78 (77%) at 1 mo. Clinical improvement in all 60/63 (95%) Resolution of many clinical signs 5/13 complete (38%) and 2/7 (29%) at 1 mo, 5/7 (71%) 3 mo, improvement Improvement alopecia in dogs at 3 mo in all dogs at 3 mo. Improvement 3/13 (23%) partial response at 7/7 (100%) 4 and 6 mo 24/39 dogs (62%) at 3 mo of the skin only at 6 mo 1 mo, 5/12 (42%) complete or 5/12 (42%) partial response at 6 mo Number of dogs in target cortisol range NS 59/73 (81%) at 1 mo 9/30 (30%) at 1 mo, 60/63 (95%) NS 5/13 (38%) at 1 mo, 9/12 (75%) 5/7 (71%) at 4 wk, 7/7 (100%) at 17/30 (57%) at 3 mo, at 6 mo 2 mo, 5/7 (71%) between 2 and 23/29 (79%) at 6 mo 6 mo, 7/7 (100%) at 6 mo Number of dogs with adverse effects 2/11 (18%), mild 15/78 (19.2%). 2 dogs with No adverse effects for . 6 mo. 5/63 (7.9%). HypoAC including 1/59 (1.7%), mild 6/16 (37.5%), mild 2/7 (29%), transient hypoAC hypoAC (1 died). 13 dogs 4/30 (13.3%) dogs had signs 2 dogs with permanent hypoAC with minor adverse effects of hypoAC after . 12 mo of treatment Survival All alive at the end of the study 26 dogs dead at the end of the 5 dogs dead or euthanized for All alive at the end of the study All alive at the end of the study All alive at the end of the study All alive at the end of the study study, with 9 of unknown cause. causes unrelated to PDH 1 dog due to hypoAC. 2 deaths shortly after starting treatment Other comments Comparison q24h versus q12h Comparison q24h versus q12h Comparison q24h versus q12h treatment. Only dogs . 10 kg in treatment treatment q12h group. 8 centres. q24h and q12h groups studied over 2 separate time periods

BW — body weight; NS — not stated; PDH — pituitary-dependent hyperadrenocorticism; ADH — adrenal-dependent hyperadrenocorticism; HypoAC — hypoadrenocorticism; ACTH — adrenocorticotropic hormone.

suppression of cortisol concentrations. Complete control of products. Both IV and IM administration of cosyntropin cortisol concentrations and clinical signs is not expected at 10 to produce similar ACTH-stimulated cortisol concentrations in 14 d after starting therapy, and the dose should not be increased healthy dogs and in dogs with HAC (1,28). Doses of 1 mg/kg at this time or hypoadrenocorticism could result (15). BW and 5 mg/kg BW of cosyntropin were also recently found to Use of synthetic ACTH [Cortrosyn (cosyntropin) and produce similar results when reassessing dogs with HAC treated Synacthen (tetracosactrin or tetracosactide)] for ACTH stimu- with mitotane or trilostane. Therefore, the lower dose appears lation tests has been reported for diagnosing and monitoring to be a safe and more cost-effective way to use synthetic ACTH HAC in dogs. However, the potency of both drugs has not been for monitoring HAC in dogs undergoing treatment. However, compared. Samples for cortisol measurement are obtained at the same study found a significant difference between the 0 and 60 min after IV or IM injection of standard non-absorbed 2 doses in dogs suspected of having HAC. Therefore a dose of

400 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY

Table 1. Summary of clinical studies using once daily dosing of trilostane in dogs with hyperadrenocorticism. Reference numbers 3 4 5 6 7 8 9 Country Switzerland UK Australia Netherlands UK Spain South Korea Year of publication 2002 2002 2003 2008 2012 2013 2013 REVIEW ARTICLE REVIEW Number of dogs with PDH 11 78 30 63 47 16 7 Number of dogs with ADH 0 0 0 0 12 0 0 Starting dose, range in mg/kg BW, q24h 3.9 to 9.2 1.8 to 20.0 2.7 to 12.0 2.0 to 4.0 3.3 to 9.5 1.0 to 6.6 6 to 13.3 Starting dose, mean in mg/kg BW, q24h NS 5.9 NS NS 6.4 2.9 NS Monitoring 1, 3 to 4, 6 to 7, 12 to 16, 10 d, 1, 3, 6 mo, and then 10 d, 1, 3, then every 3 mo 3 wk then every 3 wk until 9 to 12 d, 1, 3, 6 mo 7d, 1, 3, 6 mo, 1 y 2 wk, 1, 2, 3, 4, 6 mo 24 to 28 wk every 3 to 6 mo thereafter stable, then every 3 mo Target cortisol in nmol/L 27 to 69 20 to 250 25–75 for tight control and 30–190 40 to 120 55 to 248 55 to 150 75–125 for acceptable control Time of sampling 2 to 6 h NS, most within a few hours NS 2–4 h 2 to 6 h 8 to 12 h NS ACTH stimulation test protocol 0.25 mg of tetracosactide IM, NS 5 mg/kg of tetracosactrin IV, 0.25 mg of tetracosactide IV, NS 0.25 mg of tetracosactide IM, 0.25 mg of tetracosactide IV, post-ACTH cortisol 60 min later post-ACTH cortisol 60 min later post-ACTH cortisol 90 min later post-ACTH cortisol 60 min later post-ACTH cortisol 60 min later Dose changes Increased in 5/11 (45%), Increased in 24/78 (31%), NS Increased in 22/63 and decreased NS In 12/16 dogs (75%). 9 increased, Dose increased 12 times from decreased in 3/11 (27%) decreased in 9/78 (11%) in 4/63 at 3 wk 2 decreased, 1 increased and 4th to 16th wk in total decreased Withdrawals None Discontinuation of trilostane None, but 2 dogs had trilostane None 29/59 (49%). No withdrawals due 2/16 (13%). Changed to None in 2 dogs for prolonged hypoAC discontinued for reasons to severe side effects of trilostane q12h treatment unrelated to the medication Final dose, range in mg/kg BW, q24h 4.1 to 15.6 NS 5.0 to 50.0 0.8–5.8 3.2 to 12 1.0–11.5 3.3 to 10.9 Final dose, mean in mg/kg BW, q24h NS 7.3 19 2.8 7.6 4.6 7.1 Number of dogs with clinical 9/11 (82%) at 6 mo 60/78 (77%) at 1 mo. Clinical improvement in all 60/63 (95%) Resolution of many clinical signs 5/13 complete (38%) and 2/7 (29%) at 1 mo, 5/7 (71%) 3 mo, improvement Improvement alopecia in dogs at 3 mo in all dogs at 3 mo. Improvement 3/13 (23%) partial response at 7/7 (100%) 4 and 6 mo 24/39 dogs (62%) at 3 mo of the skin only at 6 mo 1 mo, 5/12 (42%) complete or 5/12 (42%) partial response at 6 mo Number of dogs in target cortisol range NS 59/73 (81%) at 1 mo 9/30 (30%) at 1 mo, 60/63 (95%) NS 5/13 (38%) at 1 mo, 9/12 (75%) 5/7 (71%) at 4 wk, 7/7 (100%) at 17/30 (57%) at 3 mo, at 6 mo 2 mo, 5/7 (71%) between 2 and 23/29 (79%) at 6 mo 6 mo, 7/7 (100%) at 6 mo Number of dogs with adverse effects 2/11 (18%), mild 15/78 (19.2%). 2 dogs with No adverse effects for . 6 mo. 5/63 (7.9%). HypoAC including 1/59 (1.7%), mild 6/16 (37.5%), mild 2/7 (29%), transient hypoAC hypoAC (1 died). 13 dogs 4/30 (13.3%) dogs had signs 2 dogs with permanent hypoAC with minor adverse effects of hypoAC after . 12 mo of treatment Survival All alive at the end of the study 26 dogs dead at the end of the 5 dogs dead or euthanized for All alive at the end of the study All alive at the end of the study All alive at the end of the study All alive at the end of the study study, with 9 of unknown cause. causes unrelated to PDH 1 dog due to hypoAC. 2 deaths shortly after starting treatment Other comments Comparison q24h versus q12h Comparison q24h versus q12h Comparison q24h versus q12h treatment. Only dogs . 10 kg in treatment treatment q12h group. 8 centres. q24h and q12h groups studied over 2 separate time periods

5 mg/kg BW is still recommended when being used to diagnose compounded ACTH preparations may be less expensive, they HAC (29). are not recommended because their potency and the time that Use of depot tetracosactide (250 mg total dose or 5 mg/kg maximal concentration of cortisol occurs may vary significantly BW, IM) was evaluated in healthy dogs and in dogs with HAC among formulations, even potentially from bottle to bottle at a (30,31). However, since peak cortisol is only obtained 180 min specific compounding pharmacy (33). after IM injection, it is recommended to collect blood samples There is currently no standardization regarding the time at 0 and 180 min for cortisol measurement (30,31). when an ACTH stimulation test should be performed, nor the Only 1 small study evaluated the use of compounded ACTH optimal cortisol concentration target range. The manufacturer in 5 healthy dogs and found no difference in serum cortisol con- recommends that the ACTH stimulation test be performed centrations at 60 min for 4 compounded products (32). While 4 to 6 h after trilostane is administered. Studies report variable

CVJ / VOL 59 / APRIL 2018 401 FOR PERSONAL USE ONLY

Table 2. Summary of clinical studies using multiple-daily dosing of trilostane in dogs with hyperadrenocorticism. Reference numbers 10 11 12 7 8 9 13 Country Spain USA USA UK Spain South Korea Spain Year of publication 2006 2008 2011 2012 2013 2013 2014 Number of dogs with PDH 44 18 38 25 16 9 0 Number of dogs with ADH 0 4 9 5 0 0 12 Starting dose, range in mg/kg BW, q12h 1.2 to 7.5 0.5 to 2.5 0.21 to 1.1 1.5 to 2.9 1.25 to 2.75 0.5 to 1 NS Starting dose, mean in mg/kg BW, q12h 3.1 1.4 0.86 2.2 1.8 0.78 3 Monitoring 7 d, 1, 3, 6 mo, then every 1 to 2 wk, 1 to 2, 2 to 4 mo 1 to 2, 6 to 7, 15 to 17, 24 to 9 to 12 d, 1, 3, 6 mo 7 d, 1, 3, 6 mo, 1 y 2 wk, 1, 2, 3, 4, 6 mo 7 d, 1, 3, 6 mo, then every 3 mo COMPTERENDU 6 mo (up to 3.5 y) 28 wk Target cortisol in nmol/L 28 to 138 at 4 to 6 h and , 150 40 to 150 40 to 120 55 to 138 at 4 to 6 h and 55 to 150 , 248 27 to 248 at 8 to 12 h 55 to 248 at 8 to 12 h Time of sampling 4 to 6 h at 7 d, then 8 to 12 h 3 to 4 h 3 h 2 to 6 h 4 to 6 h at 7 d, then 8 to 12 h NS 8 to 12 h ACTH stimulation test protocol 5 mg/kg of tetracosactide IV, 0.25 mg of cosyntropin IM, 0.25 mg of cosyntropin IM, NS 0.25 mg of tetracosactide IM, 0.25 mg of tetracosactide IV, 0.25 mg of tetracosactide IM, post-ACTH cortisol 60 min later post-ACTH cortisol 60 min later post-ACTH cortisol 60 min later post-ACTH cortisol 60 min later post-ACTH cortisol 60 min later post-ACTH time NS Dose changes Increased in 19/44 (43%), both 10 increased at 4 to 8 wk, 18 increased at 1 to 2 wk, NS In 11/16 dogs (69%). 5 increased, Dose increased twice and 4 increased at 1 mo, 3 increased increased and decreased in 5 increased at 8 to 16 wk 17 increased at 6 to 7 wk, 6 increased and decreased decreased 5 times in total at 3, 6, and 12 mo 10/44 (23%), and decreased 1 increased 1 2 decreased at in 5/44 (11%) 15 to 17 wk, 1 progressively increased over 4 mo Withdrawals 5 for economic reasons. 4 dogs had surgery for ADH 2 no response, 2 dogs with signs 4/30 (13%). No withdrawn due None None None Discontinuation of trilostane in of hypoAC, 9 dogs had surgery for to severe side effects of trilostane 5 dogs for prolonged hypoAC ADH Final dose, range in mg/kg BW, q12h 1.3 to 9.05 at 6 mo 1.1 to 2.8 0.21 q12h to 10 q8h 1.4 to 4.4 1.4 to 4.45 0.9 to 1.9 NS Final dose, mean in mg/kg BW, q12h 3.75 at 6 mo 1.7 NS 2.7 2.35 1.43 NS Number of dogs receiving q8h treatment 0 3 7 0 0 0 0 Number of dogs with clinical efficacy 22/36 at 3 mo (61%), 20/30 at 15/22 (68%) improved at 9/9 ADH (100%) and Resolution of many clinical 8/11 complete (73%) and 2/9 (22%) at 1 mo, 4/9 (44%) 8/12 (67%) at 1 mo, then 6 mo (67%), 19/24 at 1 y (79%) 4 to 8 wk, 16/18 (89%) 15/38 PDH (39%) good at signs in all dogs at 9 to 12 d. 2/11 (18%) partial response at 3 mo, 8/9 (89%) 4 mo, 9/12 (75%) at 3, 6, and 12 mo at 8 to 16 wk 6 to 7 wk, 24/28 (86%) Improvement skin only at 3 mo 1 mo, 11/16 (69%) complete or 9/9 (100%) 6 mo PDH good at 6 mo 3/16 (19%) partial response at 6 mo Number of dogs in target cortisol range 25/36 (69%) at 3 mo 14/16 (88%) at 8 to 16 wk 7/9 (78%) and 15/38 (39%) at NS 7/11 (64%) at 1 mo, 9/16 (56%) 0/9 (0%) at 4 wk, 7/9 (78%) at 8/12 (67%) at 1 mo, then 6 to 7 wk at 6 mo 4 mo, 9/9 (100%) at 6 mo 9/12 (75%) at 3, 6 and 12 mo Number of dogs with adverse effects 11/44 (25%), mild in 3, mild to 2/22 (9%), severe 5/47 (10.6%), moderate in 4, 5/30 (17%), mild to moderate 7/16 (44%), mild None 4/12 (33%), mild in 3, severe in 1 moderate in 4, severe in 4 severe in 1 Survival 930 d, 29 dogs still alive at the All alive at the end of the study 1 dog euthanized for large All alive at the end of the study All alive at the end of the study All alive at the end of the study Mean survival of 17.7 1/2 4.2 mo end of the study pituitary mass (range: 3.3 to 55.0 mo; median, 14.0 mo) Other comments Comparison q24h versus q12h Comparison q24h versus Comparison q24h versus Comparison trilostane q12h versus treatment. Only dogs . 10 kg q12h treatment q12h treatment mitotane in q12h group. 8 centers. q24h and q12h groups studied over 2 separate time periods

timing for performance of ACTH stimulation for monitoring tions usually occur 2 to 4 h after trilostane administration (35), of trilostane treatment. Reported times include 2 to 6 h (3,7), so if the goal of the ACTH stimulation is to determine the 3 to 4 h (11), 3 h (12), 2 to 4 h (6), 4 to 6 h (8,10), or 8 to 12 h cortisol concentration when trilostane is maximally effective, an (8,10,13) after administration of trilostane. Post-ACTH cortisol ACTH stimulation test should be performed during this time concentrations vary with the time interval between dosing and interval. testing (11). One study demonstrated that a difference of only The literature reports various optimal target cortisol con- 2 h between the time the ACTH stimulation test was started centrations for dogs undergoing treatment of HAC. Neiger significantly changed the post-ACTH serum cortisol concentra- et al (4) found that good clinical control of PDH was usually tions (34). An ACTH stimulation test should therefore always associated with post-ACTH cortisol concentrations of 20 to be started at or about the same time after trilostane administra- 250 nmol/L, regardless of the time of the test. Others have tion in each individual patient. The lowest cortisol concentra- suggested target post-ACTH cortisol concentrations of , 70

402 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY

Table 2. Summary of clinical studies using multiple-daily dosing of trilostane in dogs with hyperadrenocorticism. Reference numbers 10 11 12 7 8 9 13 Country Spain USA USA UK Spain South Korea Spain Year of publication 2006 2008 2011 2012 2013 2013 2014 REVIEW ARTICLE REVIEW Number of dogs with PDH 44 18 38 25 16 9 0 Number of dogs with ADH 0 4 9 5 0 0 12 Starting dose, range in mg/kg BW, q12h 1.2 to 7.5 0.5 to 2.5 0.21 to 1.1 1.5 to 2.9 1.25 to 2.75 0.5 to 1 NS Starting dose, mean in mg/kg BW, q12h 3.1 1.4 0.86 2.2 1.8 0.78 3 Monitoring 7 d, 1, 3, 6 mo, then every 1 to 2 wk, 1 to 2, 2 to 4 mo 1 to 2, 6 to 7, 15 to 17, 24 to 9 to 12 d, 1, 3, 6 mo 7 d, 1, 3, 6 mo, 1 y 2 wk, 1, 2, 3, 4, 6 mo 7 d, 1, 3, 6 mo, then every 3 mo 6 mo (up to 3.5 y) 28 wk Target cortisol in nmol/L 28 to 138 at 4 to 6 h and , 150 40 to 150 40 to 120 55 to 138 at 4 to 6 h and 55 to 150 , 248 27 to 248 at 8 to 12 h 55 to 248 at 8 to 12 h Time of sampling 4 to 6 h at 7 d, then 8 to 12 h 3 to 4 h 3 h 2 to 6 h 4 to 6 h at 7 d, then 8 to 12 h NS 8 to 12 h ACTH stimulation test protocol 5 mg/kg of tetracosactide IV, 0.25 mg of cosyntropin IM, 0.25 mg of cosyntropin IM, NS 0.25 mg of tetracosactide IM, 0.25 mg of tetracosactide IV, 0.25 mg of tetracosactide IM, post-ACTH cortisol 60 min later post-ACTH cortisol 60 min later post-ACTH cortisol 60 min later post-ACTH cortisol 60 min later post-ACTH cortisol 60 min later post-ACTH time NS Dose changes Increased in 19/44 (43%), both 10 increased at 4 to 8 wk, 18 increased at 1 to 2 wk, NS In 11/16 dogs (69%). 5 increased, Dose increased twice and 4 increased at 1 mo, 3 increased increased and decreased in 5 increased at 8 to 16 wk 17 increased at 6 to 7 wk, 6 increased and decreased decreased 5 times in total at 3, 6, and 12 mo 10/44 (23%), and decreased 1 increased 1 2 decreased at in 5/44 (11%) 15 to 17 wk, 1 progressively increased over 4 mo Withdrawals 5 for economic reasons. 4 dogs had surgery for ADH 2 no response, 2 dogs with signs 4/30 (13%). No withdrawn due None None None Discontinuation of trilostane in of hypoAC, 9 dogs had surgery for to severe side effects of trilostane 5 dogs for prolonged hypoAC ADH Final dose, range in mg/kg BW, q12h 1.3 to 9.05 at 6 mo 1.1 to 2.8 0.21 q12h to 10 q8h 1.4 to 4.4 1.4 to 4.45 0.9 to 1.9 NS Final dose, mean in mg/kg BW, q12h 3.75 at 6 mo 1.7 NS 2.7 2.35 1.43 NS Number of dogs receiving q8h treatment 0 3 7 0 0 0 0 Number of dogs with clinical efficacy 22/36 at 3 mo (61%), 20/30 at 15/22 (68%) improved at 9/9 ADH (100%) and Resolution of many clinical 8/11 complete (73%) and 2/9 (22%) at 1 mo, 4/9 (44%) 8/12 (67%) at 1 mo, then 6 mo (67%), 19/24 at 1 y (79%) 4 to 8 wk, 16/18 (89%) 15/38 PDH (39%) good at signs in all dogs at 9 to 12 d. 2/11 (18%) partial response at 3 mo, 8/9 (89%) 4 mo, 9/12 (75%) at 3, 6, and 12 mo at 8 to 16 wk 6 to 7 wk, 24/28 (86%) Improvement skin only at 3 mo 1 mo, 11/16 (69%) complete or 9/9 (100%) 6 mo PDH good at 6 mo 3/16 (19%) partial response at 6 mo Number of dogs in target cortisol range 25/36 (69%) at 3 mo 14/16 (88%) at 8 to 16 wk 7/9 (78%) and 15/38 (39%) at NS 7/11 (64%) at 1 mo, 9/16 (56%) 0/9 (0%) at 4 wk, 7/9 (78%) at 8/12 (67%) at 1 mo, then 6 to 7 wk at 6 mo 4 mo, 9/9 (100%) at 6 mo 9/12 (75%) at 3, 6 and 12 mo Number of dogs with adverse effects 11/44 (25%), mild in 3, mild to 2/22 (9%), severe 5/47 (10.6%), moderate in 4, 5/30 (17%), mild to moderate 7/16 (44%), mild None 4/12 (33%), mild in 3, severe in 1 moderate in 4, severe in 4 severe in 1 Survival 930 d, 29 dogs still alive at the All alive at the end of the study 1 dog euthanized for large All alive at the end of the study All alive at the end of the study All alive at the end of the study Mean survival of 17.7 1/2 4.2 mo end of the study pituitary mass (range: 3.3 to 55.0 mo; median, 14.0 mo) Other comments Comparison q24h versus q12h Comparison q24h versus Comparison q24h versus Comparison trilostane q12h versus treatment. Only dogs . 10 kg q12h treatment q12h treatment mitotane in q12h group. 8 centers. q24h and q12h groups studied over 2 separate time periods

to 75 nmol/L (3,5), between 40 and 120 nmol/L (15), or There is a lack of clear recommendations of how to adjust , 150 nmol/L (9,11,12,36), for control of HAC. The authors the trilostane dose when dogs have well-regulated HAC, but of the present article recommend targeting a post-ACTH low cortisol concentrations before and after ACTH stimula- cortisol concentration , 150 nmol/L. However, if good clinical tion. One recent study examined a small group of dogs with control is achieved when post-ACTH cortisol concentrations well-regulated HAC and cortisol concentrations , 55 nmol/L are , 250 nmol/L, the dose can remain unchanged. It is worth before and after ACTH stimulation performed 3 to 6 h after mentioning that cortisol concentration can be affected by the trilostane was administered. A second ACTH stimulation test assay methodology and can vary among laboratories (37). revealed that the dogs had significantly increased cortisol con- Therefore, the cut-offs reported in the literature may be dif- centrations 9 to 12 h after the dose of trilostane was given (38). ficult to apply directly to data from another laboratory. Ideally, The authors suggested that a second ACTH stimulation test laboratory specific cut-offs should be used. performed later in the day could support continued treatment

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with the same trilostane dose, although further study is needed. Efficacy of trilostane In animals with low pre- and post-ACTH cortisol concentra- Clinical signs of HAC, such as PUPD, polyphagia, or lethargy, tions (, 40 to 55 nmol/L), the authors of the present article improve gradually over the first months of treatment in most recommend that the trilostane dose be decreased or discontinued dogs treated with trilostane q12h or q24h (Tables 1 and 2). (especially if cortisol concentration is , 30 nmol/L). If trilostane Resolution of dermatological abnormalities can take several is discontinued, it should be restarted at a lower dose only after more months after starting trilostane (7). an ACTH stimulation test shows that hypocortisolemia has Trilostane is effective for both PDH and ADH. In ADH resolved. cases, it can be used as a short-term treatment for the control Despite the study findings previously discussed, it remains of cortisol concentrations in preparation for adrenalectomy, or unclear whether the ACTH stimulation test is the best method as a long-term medical therapy (8,11,12). Similar survival times

COMPTERENDU for monitoring treatment with trilostane (23). In some dogs, but fewer side effects were reported with trilostane compared to the results of the ACTH stimulation test do not parallel the mitotane in the treatment of HAC due to ADH (8). control of clinical signs in dogs treated for HAC in both q12h The typical laboratory abnormalities associated with HAC, and q24h treatments (8,12). such as increase in liver enzymes, hypercholesterolemia, low Neiger et al (4) proposed that the administration of exog- urine specific gravity, secondary hyperparathyroidism and enous ACTH during stimulation testing may override the revers- increased phosphorus concentration have all improved with ible inhibition of cortisol synthesis by trilostane, particularly as trilostane treatment (3,7,9,44–46). the concentration of the drug decreases, such that the results of Along with the typical clinical signs associated with HAC, the ACTH stimulation test may be inaccurate. Another possible this disorder can also create severe physiological abnormalities. explanation would be that the action of trilostane is too short in Sequelae of HAC can include hypertension, proteinuria, hyper- these dogs to fully control their clinical signs. The frequency of coagulability, immunosuppression, insulin resistance, and soft administration may need to be increased in these dogs. Lastly, tissue calcification including calcinosis cutis, muscle wasting, undiagnosed concurrent diseases could mimic some of the and cranial cruciate rupture (1). Over half of HAC patients clinical signs associated with uncontrolled HAC. For instance, have hypertension at the time of diagnosis, and hypertension a persistence of PUPD in dogs with early chronic kidney disease does not resolve in many dogs treated with trilostane, even may be falsely interpreted as clinical signs of uncontrolled HAC. after a year of treatment (13,45,46). Persisting hypertension Measuring multiple cortisol concentrations over time, while could be explained by the fact that after trilostane treatment is expensive and time consuming, may be more accurate than a initiated, plasma renin activity increases (6), which may lead stimulation test. to activation of the renin-angiotensin-aldosterone system and Investigators have assessed other possible options for monitor- renal vasoconstriction. Proteinuria, as determined by the urinary ing treatment response in dogs with HAC. These have included protein-to-creatinine ratio, improves over time with trilostane the UCCR (5,11,12,39), the baseline cortisol (40,41) with or treatment, but some dogs remain proteinuric after a year of without combination with an endogenous ACTH and the corti- treatment (45,46). However, hypercoagulability, as measured sol/ACTH ratio (6,42), the pre-trilostane cortisol concentration by thromboelastographic variables, increased platelet count and alone or in combination with the 3 h post-trilostane cortisol fibrinogen concentration, did not improve following trilostane concentration (43). In many of these studies, results of these treatment in dogs with PDH over 6 mo (46). The persistence ancillary tests have been evaluated to determine whether they are of these physiologic abnormalities associated with HAC may be predictive of the ACTH stimulation test results, and therefore due to the serum cortisol concentration still exceeding physi- if they could be less expensive monitoring tools. The UCCR, ological concentrations during a certain period of the day, even baseline cortisol, endogenous ACTH, and cortisol/ACTH when trilostane is administered twice daily (45). ratio have not been found to be very reliable for this purpose. Hyperadrenocorticism is associated with calcium dysregula- However, as described, the ACTH stimulation test has its own tion that can lead to the development of calcium-oxalate uro- limitations making it challenging to assess utility of these other liths, soft tissue mineralization, such as calcification of the skin tests for the monitoring of HAC. (calcinosis cutis), or perihilar bronchial mineralization. Dogs Macfarlane et al (43) evaluated the utility of measuring a with HAC have higher parathyroid hormone and phosphate pre-trilostane cortisol concentration (considered peak cortisol concentrations than healthy dogs, and these abnormalities concentration) and a 3-hour post-trilostane cortisol concentra- improve in some dogs with HAC following treatment with tion (considered trough cortisol concentration). In this study, trilostane (44). Some patients had resolution of calcinosis cutis the pre-trilostane cortisol concentration as well as the 3-hour with trilostane treatment (4,47). post-trilostane cortisol concentration better reflected the level Little information is available on the use of trilostane in of clinical control in dogs with uncontrolled HAC than did dogs with concurrent HAC and diabetes mellitus. Excessive the post-ACTH cortisol concentration performed 3 h after cortisol concentration causes insulin resistance, making it more trilostane administration. Clinical control was determined difficult to regulate diabetes mellitus in dogs with concurrent by detailed questionnaires filled by the owners. However, uncontrolled HAC (1). Insulin resistance is expected to at least 94/110 tests (85%) were performed on dogs receiving q24h partially improve with trilostane treatment, and therefore, trilostane treatment; the results may be different with q12h tri- careful monitoring of blood glucose concentration is needed in lostane treatment. dogs treated for both disorders. In a small study of 8 dogs with

404 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY diabetes mellitus and HAC, insulin requirements and fructos- treated with trilostane is unknown. Usually trilostane inhibits amine concentrations were not consistently reduced during the production of glucocorticoids more than the production of trilostane treatment for HAC (48). However, the number of mineralocorticoids. However, it is possible that in some dogs, dogs included in the study was small and results may have been trilostane may more effectively block the synthesis of miner- different if a larger population had been used. Interestingly, and alocorticoids than glucocorticoids (11,12,55). If electrolyte REVIEW ARTICLE REVIEW likely only coincidentally, 10% of 103 dogs treated with trilo- changes are observed with trilostane treatment, a careful client stane developed diabetes mellitus after trilostane was initiated in interview to help detect clinical signs of hypoadrenocorticism 1 retrospective study (40% of them within the first 4 mo after and an ACTH stimulation test are recommended. It is possible starting trilostane) (49). that a short episode of hypocortisolemia (although not enough to induce clinical signs) may not be detected by the ACTH Safety of trilostane stimulation test (35). Trilostane has a relatively low incidence of adverse effects, especially when low doses are used. Adverse effects were reported Use in alopecia X in 35/264 (13%) dogs undergoing q24h treatment and in Alopecia X is a form of canine adult-onset alopecia that mainly 34/180 (19%) dogs receiving q12h treatment in a total of affects nordic breeds such as the Alaskan malamute, chow chow, 11 studies (3–13). Reported adverse effects include anorexia, keeshond, Pomeranian, Samoyed, and Siberian husky, and also lethargy, vomiting, diarrhea, and other events typical of a hypo- other breeds including the miniature poodle. This form of alo- adrenal state (hyperkalemia, hyponatremia, and hypovolemic pecia resembles the alopecia seen with HAC but other clinical shock) which may or may not be associated with adrenal necrosis signs of HAC, such as PUPD and polyphagia, are absent and and hemorrhage. Chronic trilostane use is also associated with traditional tests to diagnose HAC (low dose dexamethasone the development of diffuse and/or nodular hyperplasia (50), suppression test and ACTH stimulation) are normal. Despite enlargement (up to 60% of the original size) and change of these findings, trilostane has been shown to be effective in the echotexture of the adrenal glands on ultrasound (3). This may treatment of alopecia X. Currently, there are few data regard- be secondary to the increased endogenous ACTH concentration ing the treatment of alopecia X. The doses used in 3 published that is noted with trilostane treatment (51). studies were highly variable (56–58). Although more frequent with higher doses, adverse reactions The first effective reported doses for treatment of alopecia X to trilostane can occur with any dose and any frequency. These in Pomeranians and miniature poodles ranged from , 6 to include adverse reactions in dogs treated with trilostane doses . 23 mg/kg BW, q24h. Some dogs were treated with pulse , 1 mg/kg BW, q12h (12), suggesting that factors other than therapy (2 to 3 treatments per wk) after initial stabilization dose or frequency of administration may contribute to the (57). Three Alaskan malamutes were successfully treated in development of adverse effects. For instance, since trilostane is another study with doses of 3 to 3.6 mg/kg BW, q12h (58). metabolized by the liver and excreted in bile and urine, its use The frequency of administration was reduced to twice weekly is not recommended in dogs with liver or renal insufficiency after initial stabilization. More recently, successful treatment as dose accumulation may occur. Other factors could include has also been reported with a dose of 1 mg/kg BW, q12h in a particularly good absorption of the drug in some individuals, Pomeranians (56). Alopecia X has been postulated to be due to as well as individual or breed susceptibility to the effect of tri- increased concentration of 17-hydroxyprogesterone (17-OHP). lostane (21). Another possibility is that some dogs could have However, values of 17-OHP have been found to further increase been wrongly diagnosed with HAC. during successful treatment with trilostane (57). Although in theory the effects of trilostane as an enzyme In conclusion, there have been many studies published in the inhibitor should be rapidly reversible, prolonged adrenocortical past few years contributing to a better understanding of the use suppression can occur, and cases of permanent hypoadrenocorti- of trilostane in dogs. One of the most clinically relevant findings cism or adrenal necrosis following trilostane therapy have been that has been recently reported is the use of significantly lower described (5,6,10). In most of the described cases, prolonged doses, often given twice daily, which have effectively controlled iatrogenic hypoadrenocorticism occurred after several months HAC in dogs with fewer side effects. of treatment (5,10). However, 2 dogs developed prolonged Further study of the use of trilostane in dogs with HAC hypoadrenocorticism or isolated hypocortisolism following is needed to answer some ongoing clinical questions. First, short courses (3 and 13 d) of trilostane given at 2 to 5 mg/kg the results of an ACTH stimulation test, which is the current BW, q24h (52,53). Based on a study performed in rats, adrenal gold standard test for monitoring the effect of treatment with degeneration in this species is likely caused by the effect of trilostane, do not always correlate with clinical signs, making increased ACTH concentration on the adrenal glands rather it challenging to monitor dogs undergoing treatment. Second, than the direct effect of trilostane on the adrenal glands (54). there is no consensus on the optimal post-ACTH serum corti- Periodic monitoring of electrolyte concentrations during tri- sol concentration, the ideal timing of sampling after trilostane lostane treatment is also recommended since both hyperkalemia administration, or the appropriate starting dose and frequency. and hyponatremia are common (40). However, most dogs have Overall, trilostane is an effective and safe method of treating mild electrolyte derangements and ACTH stimulation testing PDH and ADH in many dogs, and is also reported to be effec- is typically not indicative of hypoadrenocorticism. The mecha- tive in the treatment of alopecia X. However, it is important nism of mild hyperkalemia or other electrolyte changes in dogs to note that trilostane might not correct physiological changes

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associated with HAC, including hypertension and proteinuria, 22. Teshima T, Matsumoto H, Kumagai T, Kurano M, Koyama H. Expression of 11beta-hydroxysteroid dehydrogenase isoforms in canine and these conditions may require specific therapy. CVJ adrenal glands treated with trilostane. Vet J 2014;200:452–455. 23. Bell R, Neiger R, McGrotty Y, Ramsey IK. Study of the effects of once References daily doses of trilostane on cortisol concentrations and responsiveness . 1 Behrend EN, Kooistra HS, Nelson R, Reusch CE, Scott-Moncrieff to adrenocorticotrophic hormone in hyperadrenocorticoid dogs. Vet JC. Diagnosis of spontaneous canine hyperadrenocorticism: 2012 Rec 2006;159:277–281. ACVIM consensus statement (small animal). J Vet Intern Med 2013; 24. Feldman E, Vaughn M, Nelson R. Duration of trilostane effectiveness in 27:1292–1304. dogs with naturally occurring hyper-adrenocorticism. Proc Annu Meet 2. Potts GO, Creange JE, Hardomg HR, Schane HP. Trilostane, an orally Am Coll Vet Intern Med 2007;21:597–597. active inhibitor of steroid biosynthesis. Steroids 1978;32:257–267. 25. Braun C, Boretti FS, Reusch CE, Sieber-Ruckstuhl NS. Comparison of 3. Ruckstuhl NS, Nett CS, Reusch CE. Results of clinical examinations, two treatment regimens with trilostane in dogs with pituitary-dependent laboratory tests, and ultrasonography in dogs with pituitary-dependent hyperadrenocorticism. Schweiz Arch Tierheilkd 2013;155:551–558. hyperadrenocorticism treated with trilostane. Am J Vet Res 2002; 26. Cook AK, Nieuwoudt CD, Longhofer SL. Pharmaceutical evaluation COMPTERENDU 63:506–512. of compounded trilostane products. J Am Anim Hosp Assoc 2012;48: 4. Neiger R, Ramsey I, O’Connor J, Hurley KJ, Mooney CT. Trilostane 228–233. treatment of 78 dogs with pituitary-dependent hyperadrenocorticism. 27. Feldman EC, Kass PH. 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Kemppainen RJ, Behrend EN, Busch KA. Use of compounded adreno- dependent hyperadrenocorticism. J Vet Intern Med 2013;27:91–98. corticotropic hormone (ACTH) for adrenal function testing in dogs. 10. Alenza DP, Arenas C, Lopez ML, Melian C. Long-term efficacy of J Am Anim Hosp Assoc 2005;41:368–372. trilostane administered twice daily in dogs with pituitary-dependent 33. Petersen M. What ACTH preparations should be used for stimulation hyperadrenocorticism. J Am Anim Hosp Assoc 2006;42:269–276. testing? Insights into Veterinary Endocrinology 2011. Available from: 11. Vaughan MA, Feldman EC, Hoar BR, Nelson RW. Evaluation of twice- http://endocrinevet.blogspot.com//2011/03/what-acth-preparations- daily, low-dose trilostane treatment administered orally in dogs with should-be-used.html Last accessed February 13, 2018. naturally occurring hyperadrenocorticism. J Am Vet Med Assoc 2008; 34. Bonadio CM, Feldman EC, Cohen TA, Kass PH. Comparison of 232:1321–1328. adrenocorticotropic hormone stimulation test results started 2 versus 12. Feldman EC. Evaluation of twice-daily lower-dose trilostane treatment 4 hours after trilostane administration in dogs with naturally occurring administered orally in dogs with naturally occurring hyperadrenocorti- hyperadrenocorticism. J Vet Intern Med 2014;28:1239–1243. cism. J Am Vet Med Assoc 2011;238:1441–1451. 35. Griebsch C, Lehnert C, Williams GJ, Failing K, Neiger R. Effect of 13. Arenas C, Melian C, Perez-Alenza MD. Long-term survival of dogs trilostane on hormone and serum electrolyte concentrations in dogs with adrenal-dependent hyperadrenocorticism: A comparison between with pituitary-dependent hyperadrenocorticism. J Vet Intern Med 2014; mitotane and twice daily trilostane treatment. J Vet Intern Med 2014; 28:160–165. 28:473–480. 36. McGrotty YL, Arteaga A, Knottenbelt CM, Ramsey IK, Eckersall PD. 14. Nagata N, Kojima K, Yuki M. 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47. Fialkovicova M, Mardzinova S, Karasova M, et al. Therapy of canine 54. Burkhardt WA, Guscetti F, Boretti FS, et al. Adrenocorticotropic hor- ARTICLE REVIEW hyperadrenocorticism (Cushing’s syndrome). Case report (abstract). mone, but not trilostane, causes severe adrenal hemorrhage, vacuoliza- Magy Allatorvosok 2012;134:271–279. tion, and apoptosis in rats. Domest Anim Endocrinol 2011;40:155–164. 48. McLauchlan G, Knottenbelt C, Augusto M, Helm J, McGrotty Y, 55. Reid LE, Behrend EN, Martin LG, et al. Effect of trilostane and mito- Ramsey I. Retrospective evaluation of the effect of trilostane on insulin tane on aldosterone secretory reserve in dogs with pituitary-dependent requirement and fructosamine concentration in eight diabetic dogs with hyperadrenocorticism. J Vet Intern Med 2014;28:443–450. hyperadrenocorticism. J Small Anim Pract 2010;51:642–648. 56. Sanches M, Jerico M, Januario E. Steroid hormone panel test and 49. Rochel D, Siliart B, Friol A, Jaillardon L. Trilostane drug safety surveil- trilostane and melatonin therapy in pomeranian dogs with alopecia X. lance: A retrospective study of 103 cases. Proc Ann Meet Eur Assoc Vet Proc Ann Meet Am Coll Vet Intern Med 2016;30:1451. Pharmacol Ther 2015;38:33–33. 57. Cerundolo R, Lloyd DH, Persechino A, Evans H, Cauvin A. Treatment 50. Reusch CE, Sieber-Ruckstuhl N, Wenger M, Lutz H, Perren A, of canine Alopecia X with trilostane. Vet Dermatol 2004;15:285–293. Pospischil A. Histological evaluation of the adrenal glands of seven 58. Leone F, Cerundolo R, Vercelli A, Lloyd DH. The use of trilostane for dogs with hyperadrenocorticism treated with trilostane. Vet Rec 2007; the treatment of alopecia X in Alaskan malamutes. J Am Anim Hosp 160:219–224. Assoc 2005;41:336–342. 51. Witt AL, Neiger R. Adrenocorticotropic hormone levels in dogs with pituitary-dependent hyperadrenocorticism following trilostane therapy. Vet Rec 2004;154:399–400.

Book Review Compte rendu de livre

Equine Laminitis treatment of the laminitic patient. There are additional sections on digital support and stabilization of the distal phalanx; treat- Belknap JK, ed. Wiley-Blackwell, Oxford, United Kingdom. ment — encompassing discussions on the use of casts, dorsal 2017. 455 pp. ISBN: 9781-1199-4471-3. hoof wall resections, and well-balanced chapters on contentious issues such as deep digital flexor tendon tenotomy and raising his book is a complete anthology of equine laminitis; tak- the heels of horses with chronic laminitis, as well as a good sec- T ing the reader from the historical reports of disease to the tion on the prevention of laminitis. modern understanding of the condition. It explores the normal This is not a handbook or a “how-to” text. It is a well-written anatomy of the foot, the underlying physiology and pathophysi- textbook which is beautifully balanced between research and ology of all three forms of laminitis (sepsis-associated, endocri- clinical applicability. As such, it should not be pulled out nopathic, and supporting limb); and the role of the lamellar when faced with a laminitic horse and expected to deliver a basal epithelial cell (LBEC). Crucially, this text manages to step-by-step guide to management. It is easy to read, and after integrate recent research findings with chapters describing the thoughtful consumption can be retrieved and re-examined when experimental models of laminitis, the hemodynamic and inflam- faced with a clinical case, or shown to an owner to illustrate a matory aspects of disease, and the role of endocrine and meta- difficult concept. Overall this is a textbook which has a place bolic dysregulation with practical, clinically applicable chapters on the shelf of all veterinary practices that do any amount of on the diagnosis and management of horses with this condition. equine clinical work. The flow between these seemingly diametrically opposed aspects of laminitis is seamless and easy to follow as a reader. Reviewed by James L. Carmalt, MA, VetMB, MVetSc, PhD, The clinical portion of the book is extensive and comprehen- FRCVS, DABVP(Eq), DAVDC(Eq), DACVSMR(Eq), DACVS, sive. Clearly identified sections written by multiple authors cover Professor — Equine Surgery, Western College of Veterinary the clinical presentation, diagnostic evaluation, and medical Medicine, University of Saskatchewan, Canada.

CVJ / VOL 59 / APRIL 2018 407 FOR PERSONAL USE ONLY Article

Evaluation of environmental sampling methods for detection of Salmonella enterica in a large animal veterinary hospital

Valerie R. Goeman, Stacy H. Tinkler, G. Kenitra Hammac, Audrey Ruple

Abstract — Environmental surveillance for Salmonella enterica can be used for early detection of contamination; thus routine sampling is an integral component of infection control programs in hospital environments. At the Purdue University Veterinary Teaching Hospital (PUVTH), the technique regularly employed in the large animal hospital for sample collection uses sterile gauze sponges for environmental sampling, which has proven labor- intensive and time-consuming. Alternative sampling methods use Swiffer brand electrostatic wipes for environmental sample collection, which are reportedly effective and efficient. It was hypothesized that use of Swiffer wipes for sample collection would be more efficient and less costly than the use of gauze sponges. A head-to-head comparison between the 2 sampling methods was conducted in the PUVTH large animal hospital and relative agreement, cost-effectiveness, and sampling efficiency were compared. There was fair agreement in culture results between the 2 sampling methods, but Swiffer wipes required less time and less physical effort to collect samples and were more cost-effective.

Résumé — Évaluation des méthodes de prélèvements d’échantillons environnementaux pour la détection de Salmonella enterica dans une clinique vétérinaire pour grands animaux. La surveillance environnementale pour Salmonella enterica peut être utilisée pour la détection précoce de la contamination. Des prélèvements réguliers font donc partie intégrante des programmes de contrôle des infections dans les milieux hospitaliers. À l’Hôpital d’enseignement vétérinaire de l’Université Purdue (Purdue University Veterinary Teaching Hospital ou PUVTH), on emploie régulièrement la technique d’utilisation des éponges de gaze stérilisée dans l’hôpital pour grands animaux pour prélever des échantillons environnementaux, une méthode qui s’est avérée laborieuse et longue. Des méthodes d’échantillonnage de remplacement utilisent des linges électrostatiques de marque Swiffer pour le prélèvement des échantillons environnementaux et ces méthodes seraient efficaces et efficientes. On a émis l’hypothèse que l’utilisation des linges Swiffer pour le prélèvement d’échantillons serait plus efficace et moins coûteuse que l’utilisation des éponges de gaze. Une comparaison directe entre les deux méthodes d’échantillonnage a été réalisée dans l’hôpital pour grands animaux du PUVTH et la concordance relative, l’économie et l’efficacité d’échantillonnage ont été comparées. Il y avait une concordance modérée entre les deux méthodes d’échantillonnage, mais les linges Swiffer exigeaient moins de temps et moins d’efforts physiques pour prélever les échantillons et ils étaient plus économiques. (Traduit par Isabelle Vallières) Can Vet J 2018;59:408–412

are obliged to minimize infectious disease hazards in veterinary Introduction hospitals (3,4). Animals in the community, such as on the isk of infection is increased in hospitalized animals because farm, and others which may have contact with patients after R of the stress of transportation and hospitalization and the discharge from hospital, are also at risk for disease transmission close proximity to other animals that are likely to be shedding and therefore represent a further ethical obligation for veteri- infectious agents (1,2). Creating a protective environment for narians in terms of preventing the spread of disease outside the hospitalized animals, clients, and hospital personnel is part of hospital environment (4). Thus, coordinated infection control the ethical and professional responsibility of veterinarians, who practices are necessary for optimization of patient care at

Department of Veterinary Clinical Sciences (Goeman, Tinkler), Department of Comparative Pathobiology (Hammac, Ruple), College of Veterinary Medicine, Purdue University, 625 Harrison Street, West Lafayette, Indiana 47907, USA; Indiana Animal Disease Diagnostic Laboratory, 406 South University, West Lafayette, Indiana 47907, USA (Hammac). Address all correspondence to Dr. Audrey Ruple; e-mail: [email protected] Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ([email protected]) for additional copies or permission to use this material elsewhere.

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veterinary hospitals and disease control within and outside the culture methods to the electrostatic wipe sampling and culture confines of the hospital environment. These control measures method in order to determine which surveillance system would should be used routinely and should be periodically evaluated be the most useful for detection of S. enterica in the large animal in order to ensure that occurrences of hospital-acquired disease hospital at PUVTH. are minimized (5,6). Salmonellosis has historically been the most prevalent hospital- Materials and methods

acquired infection (HAI) in veterinary teaching hospitals (1,7) Study overview ARTICLE and outbreaks of Salmonella spp. infections have resulted in Environmental samples were collected using 2 previously pub- hospital closures leading to significant financial losses as well lished environmental sampling methods (9,13) for detection as losses in client confidence, employee morale, and student of S. enterica in the large animal hospital at the PUVTH in educational opportunities (1). In one outbreak, financial losses June 2015. Relative agreement between culture results obtained resulting from hospital closure were estimated at $4.12 million using both methods, cost-effectiveness, and sampling efficiency (USD) and students were required to go out of state to complete of the 2 methods were compared. their large animal clinical training (8). Also, in addition to the impact HAIs have on patients, a survey of 38 veterinary hospitals Surveillance and infection control methods found that hospital personnel at 50% of hospitals had reported As part of the current surveillance methods employed by the significant health problems attributable to Salmonella enterica Infection Control Committee (ICC) at PUVTH, environmental infections in the 2 y before the interview (7), highlighting the samples are routinely collected from the large animal hospital risk of zoonotic disease transmission in veterinary hospitals. This biannually (once in May/June and once in September/October). is especially problematic given that data suggest HAIs can occur These samples are collected from floor drains, walls, hard for a number of months before patterns in clinical disease are rec- surfaces that are touched by hands and floors in areas that ognized (1); yet multiple veterinary hospitals have reported that have been cleaned using a standardized protocol including not surveillance activity is only initiated when there is a perceived more than 24 h before sample collection (14). Briefly, cleaning increase in HAIs rather than being conducted routinely (7). This protocols include removal of debris, application of 10% bleach highlights the critical need for the development and utilization and soap as needed, and weekly disinfection with a quaternary of sensitive sampling and culture systems (4) for early detection ammonia compound. Drains are flushed with water and approx- of infectious disease hazards. imately 7.6 L (2 gallons) of disinfectant once per week and stalls Environmental surveillance for Salmonella species can be are scrubbed with bleach and soap followed by disinfection after considered an integral part of a routine surveillance protocol discharge of hospitalized patients. (9,10) and has been shown to aid in the mitigation of at least 2 outbreaks in large animal veterinary teaching hospitals (8,11). Environmental sampling Current Salmonella sampling methods used in large animal Two sample collection devices were used for collection of envi- veterinary teaching hospitals in the US are not standardized (7) ronmental samples in this study: individually packaged gauze and there is no consensus regarding which detection method sponges and electrostatic (Swiffer) wipes. Established protocols is best (4,9,12). The absence of standardized surveillance tech- were used for both methods (9,13), which resulted in several niques has led to a corresponding lack of objective assessments differences between the 2 sampling procedures. In the method of specific infection control practices, especially in relation to established by the ICC in 2000, gauze sponges were moistened implementation within the veterinary hospital environment (4). with sterile saline and held with forceps, which were disinfected To date there has only been 1 hospital-based study directly with 70% ethanol between samples. Sterile gloves were also comparing 2 of these methods: gauze sponges and electrostatic worn, and a new set of gloves was used for each sample. Sponges (Swiffer) wipes (9). In that analysis, the use of electrostatic wipe were individually placed in non-sterile plastic bags and trans- sampling and culture method was found to be more sensitive ported to the laboratory immediately following sampling each than the sponge method and samples were considered easier day. For the electrostatic wipe method, wipes were attached to a to collect using the electrostatic wipes (9). The protocol for Swiffer sweeper mop using non-sterile gloved hands during sam- the environmental sampling method used in the large animal pling of walls and floors and were held in a non-sterile gloved hospital at the Purdue University Veterinary Teaching Hospital hand for collection of samples in small spaces. New non-sterile (PUVTH) was established in 2000 in response to an outbreak gloves were worn for each sample collected. After sampling, of salmonellosis (13). Under the current protocol, detection of wipes were placed into pre-labeled sterile Whirl-Pak bags and Salmonella spp. in the environment results in extensive cleaning immediately transported to the laboratory. In between samples, and disinfection in the areas of the hospital in which Salmonella the sweeper mop was disinfected with 70% ethanol and allowed spp. was detected (14). Upon contemporary evaluation of the to dry. An approximately equal surface area was sampled using environmental sampling protocol using guidelines established each of the collection methods. by the US Center for Disease Control and Prevention (CDC) Sampling by both methods was conducted in parallel within a (6), it was decided that the monitoring system lacked flexibil- period of 2 wk in June 2015. A total of 245 individual samples ity and timeliness, attributes considered necessary for optimal were collected using the gauze sponge method, the sampling surveillance systems. Therefore, the purpose of this study was protocol used by the PUVTH ICC. Electrostatic wipes were to directly compare the current environmental sampling and used to collect a total of 50 samples in the same areas of the

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hospital and at the same time as those sampled using the gauze Table 1. Culture results from environmental samples obtained using the gauze sponge and electrostatic wipe methods; sample sponge method. Though the same environments were sampled pairs based upon area of the hospital in which the sample with each method, fewer individual samples were taken using was collected. the Swiffer method as many of the samples were consolidated. Electrostatic wipe sampling For example, banks of stalls in each ward were combined as Gauze sponge a opposed to individually sampling each stall. This was done in an sampling Negative Positive Total effort to facilitate more routine sampling in the PUVTH large Negative 46 1 47 b animal hospital by reducing the total number of samples taken Positive 2 1 3 Total 48 2 50 during each sampling period. a

ARTICLE Positive samples were detected from 2 floor surfaces in the large animal hospital, 1 of which was in the same location from which a positive sample was collected Culture procedures from a floor drain using a gauze sponge. b Positive samples were detected from the inside of 2 floor drains in different All bacterial cultures were carried out at the Purdue Animal locations within the large animal hospital and from the exterior surface of a Disease Diagnostic Laboratory (ADDL). Samples collected using water hose. gauze sponges were placed in 100 mL of tetrathionate broth and incubated for 48 h at 37°C. They were then plated on xylose were positive samples detected using both collection methods. lysine tergitol-4 (XLT-4) agar and incubated for another 48 h at The k statistic (k = 0.37) indicated fair agreement between the 37°C, then plated on brilliant green agar and incubated for 24 h 2 methods in terms of ability to detect S. enterica from the envi- at 37°C. Samples collected using electrostatic wipes were placed ronment, though the low prevalence of positive culture results in 90 mL of buffered peptone water and incubated for 24 h at may have affected this value. 42°C. Following this, 1 mL of the buffered peptone water was Financial analysis showed that the total cost of supplies for transferred to 10 mL of tetrathionate broth with iodine and the gauze sponge method was $278.10, while the total cost for incubated for 24 h at 42°C, then 100 mL of the tetrathionate the electrostatic wipe method was $263.68 (Table 2); how- broth culture was added to 10 mL of Rappaport-Vassiliadis ever, most of the expenses for the electrostatic wipe method R10 broth and incubated for 24 h at 42°C. Each sample was were non-recurring fees, such as for the sweeper mops, etha- then plated on XLT-4 agar and incubated for 48 h at 35°C. nol, spray bottles, and caddy. Fees for bacterial culture were Colonies suspected to be S. enterica based upon appearance $3715 for the gauze sponge samples and $760 for the electro- were identified using the matrix-assisted laser desorption ioniza- static wipe samples. Time spent was estimated to be between tion — time of flight mass spectrometry [(MALDI-TOF MS) 16 to 40 person-hours for the gauze sponge method, and 1 to Biotyper; Bruker, Billerica, Massachusetts, USA], and isolates 2 person-hours for the electrostatic wipe method. It was also were submitted to the National Veterinary Services Laboratory noted that use of the Swiffer sweeper mops facilitated sample (NVSL) for serotyping. collection over large surfaces such as walls and floors.

Financial analysis Discussion Direct costs for each sampling method were calculated by add- This study suggests that culture results obtained from environ- ing the prices of all the equipment and sampling materials; they mental samples collected using either the gauze sponge or elec- were then compared. The number of person-hours needed to trostatic wipe technique are similar; however, use of electrostatic collect samples using each method were also compared on an wipes required less time and, subjectively, less physical effort to hour-per-hour basis. collect samples. Furthermore, the electrostatic wipe sampling protocol was more cost-effective than the gauze sponge protocol. Data analysis Because electrostatic wipes are less expensive and more efficient Culture results were described using descriptive statistics. in terms of time and physical effort, their use could facilitate Cohen’s k was used to evaluate agreement between the culture determination of the baseline rate of positive S. enterica cultures results collected with gauze sponge and electrostatic wipes using within a veterinary hospital setting. Records from PUVTH the following scale: 0 = no agreement; 0.01 to 0.20 = slight show that in the past, environmental samples were collected agreement; 0.21 to 0.40 = fair agreement; 0.41 to 0.60 = moder- using gauze sponges only biannually because of their high cost ate agreement; 0.61 to 0.80 = substantial agreement; and 0.81 to and the amount of physical effort required for their collection, 1.0 = near perfect agreement. All analyses were performed using resulting in insufficient data to determine the baseline rate of Stata SE13.1 (Stata, College Station, Texas, USA). contamination within the hospital or to allow for evaluation of trends. Therefore, in the PUVTH large animal hospital, use Results of electrostatic wipes for environmental sample collection is Salmonella enterica was cultured from 4% (2/50) of samples preferable to use of gauze sponges for routine environmental collected using electrostatic wipes and 1.2% (3/245) of samples surveillance. collected using gauze sponges (Table 1). Salmonella enterica This study was limited by the fact that not all samples taken was cultured from 2 floor drains and the exterior of 1 water with gauze sponges were directly matched with samples taken hose in different areas of the hospital using gauze sponges, and with electrostatic wipes. Since some areas of the hospital were from floor surfaces in 2 different areas of the hospital using only sampled with sponges the figures for total cost and physi- electrostatic wipes (Figure 1). In only 1 area of the hospital cal effort may be slightly underestimated for electrostatic wipes.

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G430

G440 G470 G520 G444 G460 G490 G502 G531

G441 G471 G442 G443 G533 G473 G504 G533 G460A G472 G490A GH15 G446 G445 G503A G535 G506 G522 ARTICLE G475 G507 G448 G447 G449A G460B G476 G539 G537 G508 G538 GH12 G477 G450 G478 G-04 G539 G513A G451 G513B G480 G481 G510 G542 G541 G513C G452 G453 G513D G543 G449 G482 GH13 G495 G512 G483 G513E G544 G455 G545 G484 G513F G514 G513G G485 G546 G547 G486 G513H

G456 G513J G488 G487 G516 G548 G513 G549

Gauze sponges Electrostatic wipes

Figure 1. Map of the large animal hospital at PUVTH. Locations of electrostatic wipe samples (Circles) and gauze sponge samples (Diamonds) which cultured positive are shown.

However, in areas that were sampled with both methods, each improved after switching from gauze sponges (8.8% positive) method was equally able to detect the presence of S. enterica. to electrostatic wipes (30% positive) during an active outbreak, Also, the sponges were used to sample inside floor drains, 2 of and that the electrostatic charge of the wipes combined with which cultured positive for S. enterica. In contrast, electrostatic the ability to sample larger areas led to more frequent recovery wipes were only used to sample the floor surfaces, including of bacteria (8). This change in protocol helped to reveal that the tops of each drain but not the inside the drain. The clini- Salmonella was present in areas of the hospital that had previ- cal significance of finding S. enterica at the bottom of a drain ously been culture-negative, but where animals were continuing is unknown, but in this case only 1 location corresponding to to acquire Salmonella infections. Use of gauze sponges resulted the drains that cultured positive using gauze was found to be in the false assumption that the hospital was not contaminated culture positive using the electrostatic wipes. In addition, the with Salmonella, but modifying the surveillance techniques to reliability of the Kappa statistic used may have been negatively include electrostatic wipes revealed that the sponges failed affected by the low prevalence of positive samples. Finally, it is to detect extensive environmental contamination. This shows important to note that the use of enrichment in the culturing that use of electrostatic wipes could potentially increase the effi- procedure makes the results solely qualitative; therefore, analysis ciency of environmental sampling used to detect Salmonella in of surveillance data over time will consider positive versus nega- large animal hospitals, which could create a more robust routine tive cultures only, and not level of contamination (9,10). surveillance system and optimize patient care. There has been only 1 study directly comparing the sensi- Electrostatic wipes were also shown to be useful as an aid tivity of pre-moistened sponges with electrostatic wipes in a to mitigation during a Salmonella outbreak at Colorado State veterinary hospital environment (9). In this study, the wipes University (CSU) in 2006 (11). Active environmental surveil- were found to be 3 times more sensitive in detecting the pres- lance using electrostatic wipes enabled early detection of the ence of Salmonella, which was recovered from 14% of the strain of Salmonella that was causing the outbreak within the electrostatic wipe samples but only 4% of the sponge samples hospital environment. Increased cleaning and disinfection of the (9). This difference in sensitivity could be due to either a dif- hospital environment was initiated after the environmental conference in ability to collect microorganisms and/or differences tamination was detected. This prevented further transmission of in laboratory culture techniques (9,14). Likewise, in the current Salmonella and hospital closure was avoided (11) and contrasts study, samples collected with electrostatic wipes appeared to with what occurred during a similar outbreak at CSU in 1996. be more likely to detect the presence of Salmonella compared During the 1996 outbreak, positive environmental cultures were with samples collected using gauze sponges. The reason for this detected at a rate of 2.5% using gauze sponges; in 2006, the rate apparent difference in sensitivity could be either the collection of positive cultures was 24.5% (days 1 to 35 of outbreak) using or culture techniques used. electrostatic wipes (11). In the wake of this most recent outbreak At the University of Pennsylvania, investigators found that the it was concluded that aggressive surveillance with electrostatic ability to detect environmental Salmonella appeared to be vastly wipes contributed to avoidance of hospital closure (11). In

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Table 2. Direct costs for the gauze sponge and electrostatic wipe References sampling methods used in the same areas of the large animal hospital at PUVTH. . 1 Morley PS. Biosecurity of veterinary practices. Vet Clin North Am Food Anim Pract 2002;18:133–155. Gauze sponge protocol Electrostatic wipe protocol 2. Smith BP, House JK, Magdesian KG, et al. Principles of an infectious (245 samples) ($) (50 samples) ($) disease control program for preventing nosocomial gastrointestinal and respiratory tract diseases in large animal veterinary hospitals. J Am Vet Sterile prep basins 20.00 Sweeper mops 55.96 Med Assoc 2004;225:1186–1195. Sterile gloves 200.00 Swiffer wipes 49.65 3. Morley PS. Evidence-based infection control. In: Clinical Practice: If 3 4 4 trays 12.00 Whirl-Pak bags 76.56 You Buy Clothes for the Emperor, Will He Wear Them? J Vet Intern Lactated Ringer’s 9.25 Examination gloves 37.00 Med 2013;27:430–438. Sponge forceps 12.00 Ethanol 38.03 4. Morley PS, Anderson MEC, Burgess BA, et al. Report of the third Sample bags 6.25 Spray bottle 1.76 ARTICLE a Havemeyer workshop on infection control in equine populations. Accel 18.60 Caddy 4.72 Equine Vet J 2013;45:131–136. Subtotal 278.10 Subtotal 263.68 5. Morley PS, Weese JS. Biosecurity and infection control for large animal Laboratory fees 3715.00 Laboratory fees 760.00 practices. In: Smith BP, ed. Large Animal Internal Medicine. 4th ed. Total $3993.10 Total $1023.68 New York, New York: Elsevier, 2008:1524–1550. a Hydrogen peroxide cleaner and disinfectant. 6. German RR, Lee LM, Horan J, Milstein R, Pertowski C, Waller M. Updated guidelines for evaluating public health surveillance systems. MMWR Recomm Rep 2001;50:1–35. 2000, PUVTH experienced an outbreak that resulted in hos- 7. Benedict KM, Morley PS, Van Metre DC. Characteristics of biosecurity and infection control programs at veterinary teaching hospitals. J Am pital closure, during which approximately 1100 environmental Vet Med Assoc 2008;233:767–773. samples were taken. Salmonella was isolated from only 1.1% of 8. Dallap Schaer BL, Aceto H, Rankin SC. Outbreak of Salmonellosis the samples; most of those positive isolates were detected from caused by Salmonella enterica Serovar Newport MDR-AmpC in a large animal veterinary teaching hospital. J Vet Intern Med 2010;24: drains located inside patient stalls (13). Use of electrostatic wipes 1138–1146. would aid in early detection, facilitating early intervention in 9. Ruple-Czerniak A, Bolte DS, Burgess BA, Morley PS. Comparison of order to curb future outbreaks and prevent hospital closure. two sampling and culture systems for detection of Salmonella enterica in the environment of a large animal hospital. Equine Vet J 2013; Though standardization of environmental surveillance tech- 46:499–502. niques across hospitals would facilitate research by providing 10. Burgess BA, Morley PS, Hyatt DR. Environmental surveillance for reliability and comparability of data (4), infection control Salmonella enterica in a veterinary teaching hospital. J Am Vet Med Assoc 2004;225:1344–1348. programs have to be customized to fit the needs of individual 11. Steneroden KK, Van Metre DC, Jackson C, Morley PS. Detection and hospitals (15). There is insufficient research to indicate whether control of a nosocomial outbreak caused by Salmonella Newport at a regularly conducted active surveillance as reported here is prefer- large animal hospital. J Vet Intern Med 2010;24:606–616. 12. Ekiri AB, Morton AJ, Long MT, Mackay RJ, Hernandez JA. Review of able to alternate strategies of infection control such as passive the epidemiology and infection control aspects of nosocomial Salmonella collection of diagnostic reports or test results. However, more infections in hospitalised horses. Equine Vet Educ 2010;22:631–641. visible efforts are inherently accompanied by increased awareness 13. Ward MP, Brady TH, Couëtil LL, Liljebjelke K, Maurer JJ, Wu CC. Investigation and control of an outbreak of salmonellosis caused by of infection control procedures (7) and detection of environ- multidrug-resistant Salmonella typhimurium in a population of hospital- mental contamination before an outbreak of disease occurs is ized horses. Vet Microbiol 2005;107:233–240. also a valuable outcome (7). In conclusion, with the significant 14. Burgess BA, Morley PS. Managing Salmonella in equine populations. Vet Clin North Am Equine Pract 2014;30:623–640. variability in Salmonella sampling and culture systems used in 15. Morley PS. Surveillance for nosocomial infections in veterinary hospi- large animal veterinary teaching hospitals, more studies of the tals. Vet Clin North Am Equine Pract 2004;20:561–576. kind reported here are needed to allow for direct comparison and evaluation of the efficacy of these methods (7,9) and to help facilitate customization of infection control programs. CVJ

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The participation of advertisers in the CVJ is an indication of their com- Le support des annonceurs démontre leur engagement pour mitment to the advancement of veterinary medicine in Canada. We l’avancement de la médecine vétérinaire au Canada. Nous vous encourage our readers to give their products and services appropriate encourageons à prendre connaissance de leurs services et produits. consideration. — Ed. — NDLR

412 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY Article

Seroprevalence of Cache Valley virus and related viruses in sheep and other livestock from Saskatchewan, Canada

Fabienne D. Uehlinger, Wendy Wilkins, Dale L. Godson, Michael A. Drebot

Abstract — Cache Valley virus, an orthobunyavirus, is an important cause of ovine neonatal malformations. Information on the seroprevalence of this virus in Saskatchewan livestock populations is lacking. The objectives of this study were to determine the seroprevalence of Cache Valley virus and closely related viruses in sheep, cattle, goats, horses, and mule deer in Saskatchewan by performing a plaque-reduction neutralization test using Cache Valley virus. In total, sera from 130 sheep from 50 flocks were tested. Seroprevalence in sheep was 64.6% (84/130) and 94.0% (47/50) of flocks had 1 or more seropositive sheep. Antibodies to Cache Valley virus or closely related viruses were also detected in serum samples collected from cattle, goats, horses, and mule deer with seroprevalences of 20.0% (5/25), 33.3% (8/24), 69.0% (40/58), and 50.8% (33/65), respectively. These results suggest widespread exposure to Cache Valley virus or closely related viruses in domestic animals and mule deer in Saskatchewan.

Résumé — Séroprevalence du virus de la Vallée Cache ou de virus connexes chez les moutons et d’autres animaux de cheptel en Saskatchewan, Canada. Le virus de la Vallée Cache, un orthobunyavirus, est une cause importante de malformations néonatales ovines. Il manque des renseignements sur la séroprévalence de ce virus dans les populations des cheptels de la Saskatchewan. Les objectifs de cette étude consistaient à déterminer la séroprévalence du virus de la Vallée Cache et des virus étroitement apparentés chez les moutons, les bovins, les chèvres, les chevaux et les cerfs mulets en Saskatchewan en réalisant un test de séro-neutralisation par réduction des plages en utilisant le virus de la Vallée Cache. Au total, le sérum provenant de 130 moutons dans 50 troupeaux a été testé. Chez les moutons, la séroprévalence était de 64,6 % (84/130) et 94,0 % (47/50) des troupeaux avaient un mouton ou plusieurs moutons séropositifs. Les anticorps pour le virus de la Vallée Cache ou les virus étroitement apparentés ont aussi été détectés dans les échantillons de sérum prélevés auprès des bovins, des chèvres, des chevaux et des cerfs mulets avec une séroprévalence de 20,0 % (5/25), de 33,3 % (8/24), de 69,0 % (40/58) et de 50,8 % (33/65), respectivement. Ces résultats suggèrent une vaste exposition au virus de la Vallée Cache ou à des virus étroitement apparentés chez les animaux domestiques et les cerfs mulets en Saskatchewan. (Traduit par Isabelle Vallières) Can Vet J 2018;59:413–418

Introduction occurs through mosquito bites but not through direct contact ache Valley virus (CVV), an arbovirus belonging to the with infected domestic or wild animals. Although other viruses C genus Orthobunyavirus (family Bunyaviridae, serogroup belonging to the Bunyamwera serogroup occur in the United Bunyamwera (BUN)), was first isolated from mosquitoes in States, such as the Potosi virus, Main Drain virus, Lokern virus, the Cache Valley, Utah, USA in 1956. This virus has since been Tensaw virus, and Northway virus, in terms of its impact on isolated from caribou, horses, sheep, cattle, and other domestic animal health, CVV is considered the most important in the and wild animals and is considered endemic in North America, USA (4). In humans, a diagnosis is rarely made, but limited the Caribbean, and Argentina (1–3). The virus is transmitted surveys indicate that the seroprevalence may be as high as 18% through Aedes and other non-Culex mosquitoes and is con- (5–8). To date, only 3 cases of severe CVV disease have been sidered an indirect zoonosis in humans, in whom infection reported in humans (5,9,10).

Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon S7N 5B4, Saskatchewan (Uehlinger); Government of Saskatchewan, Ministry of Agriculture Livestock Branch, 3085 Albert Street, Regina, Saskatchewan S4S 0B1 (Wilkins); Prairie Diagnostic Services, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4 (Godson); Zoonotic Diseases and Special Pathogens Division, National Disease Laboratory, Public Health Agency of Canada, 1050 Arlington Street, Winnipeg, Manitoba R3E 3R2 (Drebot) Address all correspondence to Dr. Wendy Wilkins; e-mail: [email protected] Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ([email protected]) for additional copies or permission to use this material elsewhere.

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Clinically, CVV is of most significance in the sheep industry All 980 flocks registered with the Saskatchewan Sheep in which infection of pregnant ewes can result in pregnancy Development Board as of December 2013 were eligible for failure or fetal malformations and, therefore, significant eco- inclusion in the study (23). Flock owners were contacted nomic losses (11). Infection in non-pregnant sheep tends to sequentially according to a list produced with a random number be subclinical, and there is 1 report of CVV in a clinically ill generator until the target of 75 participants was met. Producers ram (12). Overall, reproductive losses are amongst the most with at least 30 sheep were included. In each flock, 30 sheep significant economic burden to a sheep enterprise and there (rams and ewes; 2 y of age or older) were conveniently sampled are no vaccinations or treatments available for CVV in sheep. by jugular venipuncture using standard techniques. Flocks were Despite its importance to the sheep industry, systematic preva- visited once between May 1, 2013 and May 31, 2014.

ARTICLE lence investigations are few and some of the available data are In addition to the systematic sampling of sheep serum, in part limited due to non-random sampling or small sample convenience samples of bovine (n = 25), caprine (n = 24), and sizes. Recent investigations found a seroprevalence of 0.01% equine (n = 58) sera from Saskatchewan were tested for the in Montana (13) and 28.3% in 22 states in the USA (4), while presence of CVV antibody in samples submitted to Prairie older surveys from Texas and Maryland reported seroprevalences Diagnostic Services (PDS), Saskatoon, Saskatchewan, in 2012. of 19.1% (14) and 27.2% (6), respectively. Mule deer serum samples (n = 65) collected from southwestern In Canada, the first definitive report of Cache Valley virus Saskatchewan by the Canadian Cooperative Wildlife Health isolation from mosquitoes was made in Saskatchewan in 1973 Centre from 2007 to 2011 were also analyzed. These sam- (15). It has since been detected in mosquitoes from Alberta (16), ples had been collected for other studies or reasons unrelated Ontario (17), and Manitoba (18). Human disease due to CVV to CVV. has not been definitively reported in Canada, although seroprevalence in West Nile Virus-suspect persons tested in Manitoba Laboratory analysis and Saskatchewan ranged from 5% to 16% (8). Furthermore, in Sheep serum samples were submitted to PDS for testing as part a prioritization exercise conducted by provincial and territorial of the Maedi-visna surveillance program. Aliquots of serum public stakeholders, the virus was identified as having a high risk were stored at 220°C until they were forwarded to the National of emergence in Canada (19). Information is scarce with regard Microbiology Laboratory (NML), Winnipeg, Manitoba, for to the prevalence or incidence of CVV in Canadian livestock. tests for CVV and closely related viruses antibodies. Bovine, In 2012, Shapiro et al (20) for the first time reported CVV caprine, and equine serum samples submitted to the laboratory infections in malformed lambs from 2 flocks in Ontario and, for routine diagnostic testing were similarly stored and then in 2013, the virus was isolated from a flock in Quebec which forwarded. presented with fetal malformations (21). Most recently, ovine To identify serum samples with specific antibodies against fetal malformations appeared to have increased in Ontario dur- CVV or closely related viruses, a CVV-specific PRNT, which ing the 2015/16 lambing season, although the reasons for this may exhibit some cross-reactivity to antibodies against related emergence were unclear (22). BUN-serogroup viruses, was performed as previously described There is no information on the prevalence of orthobunyavi- (24). Briefly, for virus neutralization, several dilutions of test sera ruses such as CVV in livestock, particularly sheep, in western were placed in an incubator with a constant number of plaque

Canada. In light of this, the primary objective of this study was forming units (PFU) of CVV for 1 h at 37°C in 5% CO2. to assay sera from sheep in Saskatchewan by a plaque neutraliza- Six-well plates with Vero E6 cell monolayers were then used tion reduction test (PRNT) using CVV in order to detect anti- for further incubation of each aliquot, again for 1 h at 37°C. A bodies to CVV and closely related viruses. A secondary objective nutrient agar overlay was applied and the plates were incubated

was to report PRNT serology results for CVV and closely related at 37°C in 5% CO2 for approximately 3 d. To demonstrate viruses from other domestic (cattle, goats, horses) and wild plaque formation, a vital stain (neutral red) was spread over the (mule deer) animals conveniently sampled in Saskatchewan. plates. A serum sample was considered positive for viral antibodies if at least 90% of possible plaque formation relative to virus Materials and methods controls was inhibited. For sheep sera, the titration endpoint Sample population was the highest serum diluation with a plaque reduction of at A random number generator was used to select 130 serum least 90%. The PRNT results were considered positive if the samples for testing for antibodies against CVV and closely neutralizing antibody titre was $ 1:20. Further titrations were related viruses in sheep from an existing serum bank containing not performed for other livestock sera. 2041 sheep sera from 68 flocks across Saskatchewan. Sample size was a function of logistic and financial constraints. This Statistical analysis serum bank was established as part of a serosurveillance study The overall seroprevalence and 95% confidence interval (CI) for Maedi-visna in Saskatchewan sheep (23). Briefly, 75 meat for CVV or closely related viruses for the sheep samples were and dairy sheep flocks from Saskatchewan were selected through estimated taking into account the probability for random flock simple random sampling. In each flock, serum samples were col- selection within Saskatchewan and the probability for a sheep lected from 30 sheep. Private veterinarians collected the samples being sampled within each flock. Flock-level prevalence and after consulting with flock owners but all sampling costs were 95% CI were calculated. Summary statistics were generated paid for by the study. and descriptive statistics for number of animals tested per flock

414 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY ARTICLE

Figure 1. Map of Saskatchewan depicting the locations of sheep flocks seropositive for Cache Valley virus or closely related viruses (n = 47).

and flock sizes were depicted by median and interquartile range conducted using Stata IC 13.1 (StataCorp, College Station, (IQR) due to nonparametric distribution of these variables. Texas, USA). Percent positive and 95% CI were calculated for bovine, caprine, equine, and mule deer samples. The convenience sampling Results structure in these populations precluded calculations of sampling In total, 130 sheep sera were tested from 50 flocks across weights and simple proportions and 95% CI were calculated. A Saskatchewan; 84 sera tested positive for CVV or closely map was generated depicting the location of seropositive flocks related antibodies. The PRNT titers for the seropositive sheep in Saskatchewan. The information on location for the bovine, were as follows: . 80 (n = 55), 80 (n = 9), 40 (n = 13), caprine, and equine samples was insufficient to allow the genera- 20 (n = 7). Overall sheep-level seroprevalence was 64.6% (95% tion of a map. Deer samples all originated from within 1 rural CI: 51.3% to 72.2%). Of the flocks sampled, 94.0% (47/50; municipality in southwestern Saskatchewan. All analyses were 95% CI: 82.4% to 98.1%) had at least 1 seropositive sheep.

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Table 1. Number and proportion of serum samples from domestic animals from small (20 to 99) to medium-sized (100 to 499) and wild animals conveniently sampled in Saskatchewan that were positive for Cache Valley virus or closely related viruses. flocks were significantly more positive compared with large flocks (5001); herded/open-range sheep were less likely to be Number Number of positive compared to other management groups (fenced-range; Number of sampling positive samples Species of samples sites (%; 95% CI) pasture; feedlot), and lambing in an enclosed structure with door closed most of the time was associated with significantly higher Bovine 25 20 5 (20.0; 8.0 to 41.7) Caprine 24 1 8 (33.3; 16.7 to 55.5) seroprevalence compared with other management groups. The Equine 58 58 40 (69.0; 55.6 to 79.8) sampling strategy of the current study did not allow for more Mule deer 65 65 33 (50.8; 38.5 to 63.0) detailed analysis and, therefore, similar associations could not

ARTICLE be investigated. Based on the high flock-level seroprevalence of The number of randomly tested samples per flock ranged 94.0%, differences in herd-level risk factors might not have been from 1 to 7 (median: 3; IQR: 2 to 6) and flock size ranged detectable. However, the results by Meyers et al (4) highlight from 36 to 1004 (median: 92.5; IQR: 62 to 263) adult sheep important variables that must be considered when comparing (. 2 y old at the time of sampling). Flock size was not recorded CVV seroprevalence data between studies and among flocks. It is in 4 instances. Figure 1 shows the locations of seropositive flocks also interesting to note that Meyers et al (4) found a significantly in Saskatchewan and indicates widespread exposures to the virus higher seroprevalence in sheep from the eastern USA (96.4%) in the areas from which sheep sera were tested. compared to central (53.3%) and western (58.9%) USA. If a Table 1 shows the number of samples, number of sampling similar geographic difference in CVV is present in Canada and, sites, and percent positive samples from cattle, goats, horses and considering that the flock seroprevalence in the current study mule deer. All 24 goat samples were collected at 1 production was 94.0%, the flock seroprevalence in sheep in eastern Canada site, while the 25 cattle samples came from 20 farms (Table 1). could be as high as 100%. With regard to distribution within Each of the 58 horse samples originated from a different site Saskatchewan, Figure 1 demonstrates that CVV circulates widely (Table 1). The 65 mule deer serum samples were obtained from in southern Saskatchewan. 1 rural municipality in Saskatchewan (Table 1). Antibodies Antibodies to Cache Valley virus or closely related viruses against Cache Valley virus or closely related viruses were detected were also detected from all other domestic animal species in the sera of all species, with the highest seroprevalence found tested in this study. These results suggest a widespread high in the horse population (60.0%). exposure of domestic animals to CVV or closely related viruses Most of the seropositive goats (7/8), cattle (3/5), horses in Saskatchewan, although the convenient sampling structure (30/40), and mule deer (21/33) had CVV PRNT titers . 20. applied to these populations impedes extrapolation of the results to their respective animal populations. Discussion No comparative published literature was found on CVV sero- Documentation about CVV in sheep in Canada first became prevalence in livestock in other parts of Canada and few reports available in 2012 and 2013 when causes of malformed lambs from around the world have been published. However, limited were investigated in Ontario and Quebec (20,21); however, comparisons show that the high seroprevalence in horses and there has not previously been any information published on the the moderate seroprevalence in cattle in this study are similar seroprevalence of CVV (or closely related viruses) in sheep or to results from other investigations. In the USA, Buescher et al other animal species in Canada. Therefore, this is the first study (6) first reported on the presence of CVV antibodies in other to report results from a seroprevalence survey of CVV or closely animals and identified 84/88 horses, 61/118 cattle, 3/13 goats, related viruses in sheep and other domestic and wild animals 6/22 sheep, and 2/10 pigs as testing seropositive. More recently, in western Canada. the distribution of Bunyamwera serogroup viruses in cattle was Information on CVV seroprevalence in sheep worldwide is determined in a multi-state (n = 22) study in the USA (26). scarce. Compared to the limited available literature from North Cache Valley virus seroprevalence ranged from 4% to 56% and America, however, seroprevalence of CVV (or closely related was present in cattle from 21/22 states. In the Yucatan Peninsula viruses) was high (64.6%) in the sheep tested in this study. In of Mexico, 48/184 (26.1%) horses were seropositive for CVV, Montana, only 1 of 104 sheep was seropositive for CVV (13), while in Michigan, USA, 66.3% of 86 tested horses were CVV while 28.0% of 5150 sheep tested positive for CVV in a cross- seropositive (25,27). sectional, multi-state study in the USA (4). In Texas, 19.1% of Other orthobunyaviruses from the BUN serogroup, such 366 sheep and 34 of 50 flocks had CVV-specific antibodies (14), as Main Drain, Potosi, Lokern virus, Tensaw, and Northway while 12.9% of 31 sheep in the Yucatan Peninsula of Mexico viruses, occur in the USA (4). Of these, only Northway virus tested positive (25). Although differences in sampling strategies in mosquitoes from the Northwest Territories has been reported and analyses may hamper direct comparison of prevalence data in Canada (28) and, compared with other BUN viruses, CVV among studies, other factors must be considered such as flock has been predominantly isolated from mosquitoes in Canada management, environmental conditions, and regional differences (15–17,28,29). However, Bunyamwera serogroup viruses are influencing populations of transmitting mosquitoes and virus antigenically closely related and cross-reactions may occur. activity. Meyers et al (4) collected information on potential Therefore, some caution is warranted when interpreting the risk factors for CVV prevalence and found that older sheep results herein as they indicate exposure to all BUN serogroup and flocks with higher average age had a higher seroprevalence; viruses and not just CVV. Most of the sheep PRNT results using

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CVV, however, resulted in titers . 80 supporting exposure to factors such as geographic region, climate, and environmental CVV. Although not performed in this study, CVV-seropositive conditions. Although mule deer differ from white-tailed deer samples from sheep in Ontario and Quebec, which had given with regard to their social behaviors and habitats, and, therefore, birth to CVV-infected malformed lambs, were tested for cross- likely to the risk they may pose as reservoir hosts, this study reactivity to Potosi, Main Drain, Tensaw, Lokern, and Northway suggests that further investigation into the role of mule deer in viruses. There was very little evidence of exposure to these the epidemiology of CVV may be warranted.

BUN viruses based on a 4-fold or greater difference in PRNT A number of studies have addressed the presence and epi- ARTICLE titers to CVV (personal communication, M. Drebot, National demiology of CVV in mosquitoes. In the northeastern USA, Disease Laboratory, Winnipeg, Canada) and may further sup- CVV isolation varied greatly from year to year irrespective of the port that CVV exposure is more common than exposure to concentration of mosquitoes and virus activity was highest dur- other BUN-serogroup viruses in sheep in Canada. More caution ing August to September (34). Increased CVV presence in mos- may be warranted in the interpretation of the titers from cattle, quitoes during August to October was also found by Buescher goats, horses, and mule deer as titrations beyond 1:20 were et al (6). Additionally, the virus was found more often during not performed. In addition to BUN serogroup viruses, other years with above-average rainfall and resulting higher mosquito orthobunyaviruses, such as California serogroup viruses, circu- populations (34). These factors may translate into a higher CVV late widely throughout Canada and have been shown to infect seroprevalence in domestic and wild animals and increased sheep, cattle, and other livestock (30). Therefore, it is possible risk of infection in humans, but this has not been objectively that livestock may be exposed to different bunyaviruses during documented to date. However, it was recently hypothesized that their lifetime and antibodies to several different viruses may be similar influences, including warm autumn weather resulting documented upon further testing. However, as part of another in higher mosquito populations, may have contributed to the investigation, a subset of CVV positive sera from sheep and increased incidence of clinical CVV in sheep in Ontario (22). other livestock from the current study were also tested for the In Canada, the earliest documentation of CVV-positive mos- presence of antibodies to other bunyaviruses such as California quitoes (primarily Culiseta inornata) was reported in 1986 by serogroup viruses (e.g., Jamestown Canyon and snowshoe hare Calisher et al (28) from Alberta, Saskatchewan, Manitoba, and viruses) and no cross-reactive antibodies were detected using Ontario. The presence of CVV was suggested from Alberta in plaque reduction neutralization assays (personal communication, 1968 and was subsequently demonstrated in mosquitoes from M. Drebot, National Disease Laboratory, Winnipeg, Canada; Saskatchewan in 1973 and again in 1979 (15,29,35). Based data not shown). on their findings, Iversen et al (29) suggested that the prairie While significant economic impacts due to CVV in the sheep grasslands in Saskatchewan were enzootic for CVV and, similar industry are characterized by fetal malformations (e.g., arthro- to Calisher et al (28), the virus was also most commonly found gryposis, hydranencephaly), embryonic death, and mummifica- in C. inornata mosquito species. In eastern Canada (Ontario), tion, severe clinical disease in other livestock and horses appears the virus was again reported in 1980 (17) and most recently, to be rare (6,11). Calisher and Sever (31) reported the presence CVV was confirmed in mosquitoes in Alberta (16). Recent of CVV antibodies in cattle that gave birth to calves with comprehensive information on the presence of CVV in mosqui- arthrogryposis and hydranencephaly in Saskatchewan; however, toes in Canada was not available. However, changing climatic CVV prevalence in that cattle population was unknown and the and environmental conditions affecting mosquito populations association of CVV with those birth defects was unsubstantiated. and habitats, and increasing mobility of humans and animals In the apparent absence of considerable clinical and economic enhance the risk of virus introduction into naïve populations. consequences in CVV-exposed domestic animals (other than Given the changing environmental and climatic landscape and sheep), the importance in quantifying sero-prevalence in these the limited body of knowledge, a comprehensive, longitudinal species may lie primarily in gathering surveillance information study assessing flock-level risk factors and presence of CVV in to document the risk of exposure and potential illness in humans mosquitoes in Canada would contribute to improved surveil- and sheep. lance and risk assessments of this zoonotic pathogen. The primary amplifying vertebrate host for CVV is unknown A clinical diagnosis of Cache Valley virus is rarely made in but white-tailed deer are believed to play a role as a reservoir humans, likely in part due to the lack of specific CVV testing, and amplification host (32,33). Interestingly, there was no but limited surveys from the USA and Argentina indicate that significant association with number of CVV isolations from the seroprevalence may be as high as 18% (2,5–7). To date, only mosquitoes and estimated white-tailed deer densities in a recent 3 cases of severe CVV disease have been reported in humans study (34). In the current study, only mule deer samples were (5,9,10) and, while more information is necessary to determine analyzed, 50% of which contained antibodies against CVV or a potential association, CVV may be linked to macrocephaly closely related viruses. Compared with other serological surveys in infants (31). In Canada, clinical CVV infection in humans in deer populations, the seroprevalence in the mule deer tested has not been reported, but seroprevalence in West Nile virus- herein was markedly higher (32,33). It is unclear whether this suspect humans tested in Manitoba and Saskatchewan ranged is due to a true higher seroprevalence of CVV or closely related from 5% to 16% (8). Cache Valley virus is not a nationally viruses in mule deer in Saskatchewan compared with other deer notifiable disease, but CVV may increasingly become part of a populations or whether these findings reflect the variations in potential differential diagnosis in patients presenting with fever virus prevalence at the time of testing due to other influencing and neurologic signs during the mosquito season.

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In conclusion, the seroprevalence of CVV or closely 14. Chung SI, Livingston CW, Jr, Jones CW, Collisson EW. Cache Valley related viruses in selected domestic and wild animals from virus infection in Texas sheep flocks. J Am Vet Med Assoc 1991;199: 337–340. Saskatchewan, Canada, was high, and seropositive sheep flocks 15. Burton AN, McLintock J, Francy DB. Isolation of St. Louis encephalitis were distributed widely throughout southern Saskatchewan. Our and Cache Valley viruses from Saskatchewan mosquitoes. Can J Public observations indicate that there is the potential for economic Health 1973;64:368–373. 16. Pabbaraju K, Ho KC, Wong S, et al. Surveillance of mosquito-borne losses to the sheep industry due to CVV, in which clinical viruses in Alberta using reverse transcription polymerase chain reaction disease involving lambs can be significant. Although CVV- with generic primers. J Med Entomol 2009;46:640–648. associated fetal malformations have been reported recently in 17. Thorsen J, Artsob H, Spence L, Surgeoner G, Helson B, Wright R. Virus isolations from mosquitoes in southern Ontario, 1976 and 1977. Can Ontario and Quebec, the occurrence or the seasonal incidence J Microbiol 1980;26:436–440.

ARTICLE of deformed lambs due to this virus in western provinces has not 18. Makowski K, Dimitrova K, Andonova M, et al. The identification of been well-documented. Further investigation of suspected CVV probable cases of California serogroup virus infections in Manitoba in 2010. Can J Infect Dis Med Microbiol 2011;22:15A–16A. cases among sheep flocks in the prairies are justified to more 19. Kulkarni MA, Berrang-Ford L, Buck PA, Drebot MA, Lindsay LR, fully define the risks of viral infection. In addition, the high Ogden NH. Major emerging vector-borne zoonotic diseases of public seroprevalence for CVV or closely related viruses in mule deer, health importance in Canada. Emerg Microbes Infect 2015;4:e33. 20. Shapiro J, Brooks A, Menzies P, et al. Cache Valley virus identified as a which are abundant in western Canada, highlights the impor- cause of malformed lambs in Ontario. AHL Newsl 2012;16:15. tance of further investigating reservoir hosts for CVV in addi- 21. Côté G, Fournier D, Leboeuf A. Cas de malformations congénitales tion to white-tailed deer. Examination of infection rates among chez des ovins causées par le virus de la vallée cache (birth defect cases in sheep caused by Cache Valley virus) [monograph on the Internet], mosquito populations in Canada is also warranted to gain a 2013. MAPAQ, QC, Canada. Available from: http://www.cepoq.com/ better understanding of CVV epidemiology in this country. admin/useruploads/files/info_malformations_congenitales.pdf Last accessed February 20, 2018. 22. Jansen J, Spinato M, Menzies P. Cache Valley virus — A cause of birth Acknowledgments defects in Ontario lambs [monograph on the Internet], 2016. Available The study was supported by funding from the Saskatchewan from: http://oahn.ca/resources/small-ruminants/cache-valley-virus-a- cause-of-birth-defects-in-ontario-lambs/ Last accessed February 20, Agriculture Development Fund. The authors thank the 2018. Canadian Wildlife Health Cooperative Centre, Saskatoon, for 23. Heinrichs R, Wilkins W, Schroeder G, Campbell J. Prevalence of Maedi- the mule deer serum samples. The authors also acknowledge visna in Saskatchewan sheep. Can Vet J 2017;58:183–186. 24. Beaty BJ, Calisher CH, Shope RS. Diagnostic procedures for viral, the expert technical assistance provided by Kristina Dimitrova rickettsial and chlamydial infections. Washington, USA: Am Public and Maya Andonova during the testing of animal sera for CVV Health Assoc 1989:797–856. 25. Blitvich BJ, Saiyasombat R, Travassos da Rosa A, et al. Orthobunya antibody. CVJ viruses, a common cause of infection of livestock in the Yucatan peninsula of Mexico. Am J Trop Med Hyg 2012;87:1132–1139. References 26. Sahu SP, Pedersen DD, Ridpath HD, Ostlund EN, Schmitt BJ, Alstad . 1 Holden P, Hess AD. Cache Valley virus, a previously undescribed DA. Serologic survey of cattle in the northeastern and north central mosquito-borne agent. 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Am J Trop Med Hyg and other bunyamwera serogroup viruses in sheep in the United States. 1986;35:429–443. Vector Borne Zoonotic Dis 2015;15:683–693. 29. Iversen JO, Wagner RJ, Leung MK, Hayles LB, McLintock JR. Cache 5. Campbell GL, Mataczynski JD, Reisdorf ES, et al. Second human case Valley virus: Isolations from mosquitoes in Saskatchewan, 1972–1974. of Cache Valley virus disease. Emerg Infect Dis 2006;12:854–856. Can J Microbiol 1979;25:760–764. 6. Buescher EL, Byrne RJ, Clarke GC, et al. Cache Valley virus in the Del 30. Goff G, Whitney H, Drebot MA. Roles of host species, geographic Mar Va Peninsula. I. Virologic and serologic evidence of infection. Am separation, and isolation in the seroprevalence of Jamestown Canyon J Trop Med Hyg 1970;19:493–502. and snowshoe hare viruses in Newfoundland. Appl Environ Microbiol 7. Blitvich BJ, Saiyasombat R, Talavera-Aguilar LG, et al. Orthobunyavirus 2012;78:6734–6740. antibodies in humans, Yucatan Peninsula, Mexico. Emerg Infect Dis 31. 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418 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY Article

Effect of different analgesic techniques on hemodynamic variables recorded with an esophageal Doppler monitor during ovariohysterectomy in dogs

Ignacio Sández, María Soto, Daniel Torralbo, Eva Rioja

Abstract — This study compared the efficacy of intravenous (IV) fentanyl and ketamine with lumbosacral epidural lidocaine in dogs undergoing ovariohysterectomy. Dogs with esophageal Doppler monitoring (n = 112) were included in this retrospective study. All dogs were premedicated with dexmedetomidine and methadone, induced with IV propofol or alfaxalone and maintained using isoflurane and IV fentanyl, IV ketamine, or epidural lidocaine. Heart rate (HR), mean arterial pressure (MAP), expired fraction of isoflurane (ETIso), stroke distance (SD), minute distance (MD), peak velocity (PV) and mean acceleration (MA) were recorded before and after ligation of the ovarian pedicle (OvP). There were no differences for ETIso, HR, and MAP among fentanyl, ketamine, and control groups. Minute Distance, SD, MA and PV significantly decreased after OvP in fentanyl, ketamine, and control groups, but remained stable in the epidural group. Lumbosacral epidural lidocaine prevented hemodynamic depression changes caused by OvP ligation, whereas fentanyl and ketamine failed to do so.

Résumé — Effet de différentes techniques analgésiques sur les variables hémodynamiques enregistrées avec un moniteur Doppler œsophagien lors de l’ovariohystérectomie chez la chienne. Cette étude a comparé l’efficacité du fentanyl et de la kétamine administrés par voie intraveineuse (IV) à la lidocaïne épidurale lombosacrée chez des chiennes soumis à une ovariohystérectomie. Cent douze chiennes surveillées avec du Doppler œsophagien (n = 112) ont été inclus dans cette étude rétrospective. Tous les chiens ont été prémédiqués avec de la dexmédétomidine et de la méthadone, induits avec du propofol ou de l’alfaxalone IV et maintenus en utilisant de l’isoflurane et du fentanyl IV, de la kétamine IV ou de la lidocaïne épidurale. La fréquence cardiaque (FC), la pression artérielle moyenne (PAM), la fraction expirée d’isoflurane (ETIso), la distance d’éjection (DE), la distance minute (DM), la vitesse maximale (VMax) et l’accélération moyenne (AM) ont été enregistrées avant et après la ligature du pédicule ovairien (POv). Il n’y avait pas des différences pour ETIso, HR et MAP entre les groupes fentanyl, kétamine et témoin. La DM, DE, AM et Vmax avez diminué significativement après POv dans les groupes fentanyl, kétamine et témoins, mais ils restent stables dans le groupe épidural. La lidocaïne épidurale lombosacrée a évité des changements hémodynamiques provoqués par la POv, alors que le fentanyl et la kétamine ne l’ont pas fait. (Traduit par les auteurs) Can Vet J 2018;59:419–424

Introduction monly occur during surgery induced by nociceptive stimuli, variohysterectomy (OVH) is one of the most common mainly due to ligation of the ovarian pedicle (OvP) (1,2). These O surgical procedures in small animal practice. In most cases changes can be prevented or treated with analgesics, but their it is performed as a preventive measure and therefore the animals effectiveness varies (3–5). are usually young and healthy. Consequently, the procedure is Some studies have used parameters such as heart rate and typically considered to present low anesthetic risk. However, blood pressure to evaluate haemodynamic changes (2), while important neuro-hormonal and hemodynamic changes com- others have employed more specific hemodynamic parameters

Mobile Anaesthesia Service, Sinergia Veterinaria, Madrid, Spain (Sández, Soto, Torralbo); School of Veterinary Science, University of Liverpool, Liverpool, Merseyside, United Kingdom (Rioja). Address all correpondence to Dr. Ignacio Sández; e-mail: [email protected] Dr. Rioja’s current address is Anderson Moores Veterinary Specialists, Winchester, Hampshire, United Kingdom. The authors have no conflicts of interest to report. Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ([email protected]) for additional copies or permission to use this material elsewhere.

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such as cardiac index or cardiac contractility (6,7). However, to minutes after premedication, oxygen was administered via the best of our knowledge, no study has used a transesophageal face mask for 3 to 4 min, and either propofol (Propovet; Doppler monitor to assess the hemodynamic changes that occur Laboratorios Dr. Esteve), 1 to 2 mg/kg BW, IV, or alfaxalone during ligation of the OvP. (Alfaxan, Dechra Veterinary Products, Barcelona, Spain), 0.5 to The use of opioids to control perioperative pain is widely 1 mg/kg BW, IV, was administered to effect to allow orotracheal described for all types of surgery. Fentanyl, a potent synthetic intubation. Anesthesia was then maintained with isoflurane opioid with a short latency and duration, is widely used in (IsoFlo; Laboratorios Dr. Esteve) in 100% oxygen using a flow clinical practice to reduce high requirements of inhalational of approximately 20 mL/kg BW per minute in a semi-closed anesthetics that would be necessary to control the hemodynamic circle circuit.

ARTICLE response produced by nociceptive stimuli induced by a surgi- Isoflurane concentration was adjusted to achieve an appro- cal procedure. Ketamine is an N-methyl D-aspartate (NMDA) priate depth of anesthesia for surgery, seeking the absence receptor antagonist with analgesic effects, and has also been of palpebral reflexes, ventromedial position of the eye, and used for the management of perioperative pain in soft tissue relaxation of the jaw. If there was no hemodynamic response and orthopedic surgery, being more effective when administered during surgery, defined as . 20% increase in MAP or HR over preoperatively (8). Various studies have employed combinations 5 min, the vaporizer setting was reduced by 0.5%, which is of opioids and ketamine to reduce the need for inhalational routine in our anesthetic management. Ringer’s lactate (Lactato anesthetics and reduce postoperative pain (9,10). RingerVet, BBraun Vetcare, Barcelona, Spain) was administered Epidural administration of local anesthetics has proved very at 3 mL/kg BW per hour throughout anesthesia. effective in controlling perioperative pain. It has the added Dogs were allowed to breathe spontaneously unless end-tidal 9 . advantage of blocking sympathetic responses to surgical stimuli CO2 partial pressure (PE CO2) became 45 mmHg (6 kPa); if (11–13). that occurred, pressure-controled ventilation with a peak inspira- 9 The aims of this retrospective study were, firstly, to assess tory pressure of 10 cmH2O was initiated to maintain PE CO2 the efficacy of an esophageal Doppler monitor to evaluate the between 35 and 45 mmHg (4.6 to 6 kPa). hemodynamic changes that occur during OVH. Secondly, to In dogs that received a lumbosacral epidural injection, the compare the efficacy of the systemic administration of fentanyl injection site (L7-S1) was clipped and aseptically prepared. alone, or in combination with ketamine, with that of the lumbo- With the dog positioned in sternal recumbency and with the sacral epidural administration of lidocaine to block sympathetic pelvic limbs pulled cranially, the puncture site was located at responses to OvP ligation in dogs during OVH. Our hypotheses the lumbosacral space (L7-S1); an 18 G, 90-mm Tuohy needle were that a transesophageal Doppler monitor would be able to (Perican; BBraun Vetcare) was advanced through the skin and detect and track the hemodynamic changes during OVH in a supraspinous, interspinous, and interarcuate ligaments and sub- more predictable way than other hemodynamic parameters such sequently into the epidural space. Entering the epidural space as BP or HR, and that epidural lidocaine is better at prevent- was conﬁrmed using the hanging drop technique (14–16) and ing the hemodynamic response to OvP ligation than the use of lack of resistance to injection (16). When possible, the dorsal fentanyl with or without ketamine. metatarsal artery was cannulated with a 22 G, 25-mm cannula to allow continuous measurement of systolic, mean, and dia- Materials and methods stolic arterial blood pressure (SAP, MAP, and DAP, respectively). Animals In cases in which cannulation of the dorsal pedal artery was not A retrospective review was conducted of all anesthetic records possible, a high definition oscillometry monitor (HDO-Memo of dogs undergoing OVH performed at Sinergia Veterinaria Diagnostic S 1 B medVet, GMBH, Germany) was used. Anesthesia Service from January 2012 to March 2015. All Monitoring also included assessment of heart rate (HR), animal owners gave written consent for participation in this pulse oximetry, continuous electrocardiogram (ECG), end-tidal 9 retrospective study. CO2 partial pressure (PE CO2), end-tidal isoflurane concen- Anesthetic records from OVH (n = 245) that had a similar tration (ETIso), and esophageal temperature (DatexOmheda anesthetic protocol and use of a transoesophageal Doppler moni- AS3/Compact; Helsinki, Finland or DragerVitara 8060 PM, tor were studied. Exclusion criteria included an ASA status III Lübeck, Germany). The hemodynamic parameters stroke dis- or greater and lack of a complete record of all hemodynamic tance (SD), minute distance (MD), peak velocity (PV), and parameters before and during OvP ligation. Dogs were also median acceleration (MA) were monitored using a transesopha- excluded if an epidural was attempted but was considered unsuc- geal Doppler monitor (CardioQ; Deltex Medical, Chichester, cessful, based on the hanging drop technique. The age or weight West Sussex, United Kingdom) with a 50-cm long probe. The of the dogs was not reason for exclusion. tip of the probe was placed at the level where the descending aorta runs parallel to the esophagus, using the quality of the Anesthetic management Doppler signal and the Doppler sound on the monitor as a In all cases, premedication consisted of dexmedetomidine guide to locate the maximum flow rate. Once an appropriate sig- (Dexdomitor; Laboratorios Dr. Esteve, Barcelona, Spain), nal was obtained, the probe was maintained in this position by 3 to 4 mg/kg body weight (BW) and methadone (Metasedin; securing it to the animal’s mouth with tape. In addition to this, Laboratorios Dr. Esteve), 0.3 to 0.4 mg/kg BW adminis- the positioning of the transesophageal probe was checked before tered together in the same syringe via IM injection. Twenty each measurement. Stroke distance is a linear representation of

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Table 1. Median values (interquartile range) for ASA status, age, Table 2. Median values (interquartile range) of end tidal isoflurane weight, and times. concentration (%). CONT FEN FENKET EPI CONT FEN FENKET EPI ASA 1 (2) 1 (1) 1 (1) 1 (1) T0 1.28 (0.3) 1.33 (0.3) 1.28 (0.2) 1.18 (0.2) Age (y) 1 (6) 3 (5.3) 1.75 (5.3) 2 (5.5) T1 1.4 (0.3)a 1.41 (0.2)a 1.37 (0.2)a 1.15 (0.2) Weight (kg) 26 (20.5)a 10 (11.2) 18 (19)a 15 (15.4) a Tpre-ov (min) 30 (6) 35 (10) 35 (13) 37 (14) Statistically significant difference compared with the EPI group (P , 0.001). Tsx (min) 45 (20) 40 (10) 33.5 (14.4) 35 (15) CONT — control group; FEN — fentanyl group; FENKET — fentanyl and ARTICLE ketamine group; EPI — epidural group. a Statistically significant difference compared with FEN group (P , 0.05). Tpre-ov — time from premedication to ovarian pedicle ligation; Tsx — surgery time; CONT — control group; FEN — fentanyl group; FENKET — fentanyl in levels of ETIso at T0 and T1 between different groups, with and ketamine group; EPI — epidural group. post hoc pairwise comparisons when the overall difference was significant. The values at T0 and T1 were compared within each stroke volume, measured by the time/velocity integral, and MD group for each variable using the Wilcoxon signed-rank test. The is a linear representation of cardiac output (CO) and is calcu- level of significance was set at 95% (P , 0.05) and adjusted lated from SD 3 HR. Peak velocity is the maximum speed that P-values were used for post hoc comparisons. the blood reaches in the descending aorta and is closely related to contractility and afterload, while MA is the acceleration of Results blood as it leaves the aorta and is closely related to contractility No major complications such as severe hypotension (MAP and afterload (17). All values were calculated with an average , 50 mmHg), bradycardia (, 30 bpm), significant bleeding, of 20 cycles. or cardiac arrest were reported in the study. A total of 112 dogs were included in this study: 12 in group Study protocol CONT, 39 in group FEN, 35 in group FENKET, and 26 in Four groups could be identified depending on the analgesic group EPI. Two dogs were excluded from the study because they treatment employed prior to OvP ligation (based on anesthe- failed the hanging drop test and 1 because of excessive resistance siologists’ preferences): CONT (no extra analgesic, only those to injection of the anesthetic. There were no significant differ- used for premedication), FEN (fentanyl 3 to 5 mg/kg BW, IV, ences in age, ASA status, surgical time, and time from premedi- between 5 and 10 min before OvP ligation), FENKET (fentanyl cation to OvP ligation among the 4 groups; however, there was 3 to 5 mg/kg BW 1 ketamine 0.4 to 0.5 mg/kg BW, IV, between a significant difference in weight between FEN and FENKET 5 and 10 min before OvP ligation), EPI [lidocaine 2% adminis- (P = 0.013) and between FEN and CONT (P = 0.005) (Table 1). tered via lumbosacral epidural injection at a dose of 0.1 mL/cm End-tidal isoflurane concentration was not significantly dif- of occipito-coccygeal length (OCL), between 10 and 20 min ferent when the 4 groups were compared at T0 (P = 0.053), but before OvP ligation]. ETIso was significantly lower in the EPI group at T1 compared Recorded parameters were compared at 2 time points: T0 with the CONT group (P , 0.001), FEN group (P , 0.001), (5 to 10 min after induction of anesthesia, before surgical and FENKET group (P , 0.001) (Table 2). 9 stimulation and before the epidural injection) and T1 (during The DiffT1-T0 for HR, MAP, and PE CO2 was not sig- the first OvP ligation). No data were collected during the second nificantly different among groups (P = 0.843, P = 0.052, and OvP ligation to avoid the influence of the stimulus due to the P = 0.095, respectively). However, the DiffT1-T0 for MD, SD, previous OvP ligation. The variables recorded for subsequent MA, and PV were significantly different among groups, all with 9 # statistical analysis were: HR, MAP, ETIso, PE CO2, SD, MD, values of P 0.005, with the post-hoc comparisons showing PV, MA, and Temp. Surgical time and time from premedication that these differences were significant between the EPI group to OvP ligation were also recorded. All surgeries were performed and the other 3 groups (CONT, FEN, and FENKET). All these using a midline approach with the animal in dorsal recumbency. variables (MD, SD, MA, and PV) decreased significantly at T1 compared with their respective values at T0 in CONT, FEN, Statistical analysis and FENKET groups, unlike in the EPI group, in which the dif- A commercial statistical package (SPSS Version 21; IBM, ference between T1 and T0 was not significant for any variable. Armonk, New York, USA) was used for all statistical analyses. No significant differences were observed in MD, SD, MA, and Histograms and normality tests (Shapiro-Wilk) were performed PV when doing pairwise comparisons between CONT, FEN, for demographic and hemodynamic variables as well as for and FENKET groups (Table 3). The Temp was significantly ETIso levels in each group, revealing that they all had a non- lower in T1 than in T0 for all groups. normal distribution. The Kruskal-Wallis test was conducted to compare the differences between values during OvP ligation Discussion (T1) and baseline values (T0) (DiffT1-T0) for each hemo- The use of a transesophageal Doppler monitor allowed the dynamic variable among the 4 groups and also to compare detection of hemodynamic changes during OvP ligation that demographic variables between groups. When the test indicated were not detected with conventional cardiovascular moni- a statistically significant overall difference, post hoc comparisons toring, based on blood pressure and heart rate. In addition, were carried out between all pairs of groups. The Kruskal-Wallis according to the results of this retrospective study, the use of test was also used to determine whether there was any difference fentanyl and ketamine prior to OvP ligation did not offer any

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Table 3. Median values (interquartile range) for hemodynamic variables and mean values (6 standard

deviation) for temperature and end tidal CO2. CONT FEN FENKET EPI MAP (mmHg) T0 82 (6 27) 76.4 (6 20) 76.2 (6 19.5) 78.5 (6 31) T1 98.1 (6 32)a 82.3 (6 24)a 79 (6 23.7) 78.2 (6 19) DiffT1-T0 16 (6 36) 7.8 (6 19) 0.5 (6 15) 20.2 (6 6.3) HR (bpm) T0 71 (6 23.5) 76.2 (6 21) 67.6 (6 21.5) 81.8 (6 19.2) T1 66.6 (6 27) 70 (6 16)a 63.5 (6 25.5)a 75.7 (6 20.5)

ARTICLE DiffT1-T0 24.9 (6 22) 25.7 (6 26) 24 (6 10) 26 (6 17) PV (cm/s) T0 110.8 (6 59.5) 117.8 (6 44.5) 112.9 (6 36.7) 91.4 (6 36) T1 78.3 (6 36.5)a 83.8 (6 42)b 84.8 (6 31.8)b 88.7 (6 20.5) DiffT1-T0 232.4 (6 37)c 233.9 (6 43)c 228 (6 32)c 22.6 (6 22) MA (cm/s2) T0 13.1 (6 6.6) 13.1 (6 5.5) 12.2 (6 4.5) 9.7 (6 4.4) T1 9.3 (6 6.6)a 9.8 (6 4.7)b 9 (6 3.1)b 9.2 (6 2.7) DiffT1-T0 23.8 (6 4.2)c 23.2 (6 4.3)c 22.9 (6 3.9)c 20.5 (6 2.2) SD (cm) T0 18.5 (6 11.7) 17 (6 8.5) 18.2 (6 10.7) 13.6 (6 8.6) T1 11.2 (6 6.3)a 10.9 (6 7.8)b 12.4 (6 8)b 13.2 (6 5.6) DiffT1-T0 27.2 (6 8.8)c 26 (7.3)c 25.8 (6.1)c 20.3 (5) MD (cm) T0 1331 (6 724) 1323 (6 932) 1218 (6 745) 1109 (6 670) T1 722 (6 348)a 744 (6 450)b 760 (6 347)b 1009 (6 567) DiffT1-T0 2609.3 (6 730)c 2579.3 (6 894)c 2458 (6 546)c 299.8 (6 472) Temp (°C) T0 37.1 (6 0.6) 37.5 (6 0.7) 37.5 (6 0.8) 37.4 (6 0.5) T1 36.9 (6 0.7)a 37.3 (6 0.7)b 37.4 (6 0.7)a 37.2 (6 0.5)b DiffT1-T0 20.15 (6 0.19) 20.27 (6 0.3) 20.2 (6 0.2) 20.1 (6 0.07) 9 PE CO2 (mmHg) T0 41.5 (6 7) 41.5 (6 6) 40 (6 6) 40 (6 5) T1 37 (6 7) 41 (6 6) 42 (6 6) 39 (6 5) DiffT1-T0 21.4 (6 0.15) 20.5 (6 0.5) 1.8 (6 0.06) 20.7 (6 0.4)

MAP — median arterial pressure; HR — heart rate; PV — peak velocity; MA — median acceleration; SD — stroke distance; 9 MD — minute distance; Temp — Temperature; PE CO2 — end tidal CO2; CONT — control group; FEN — fentanyl group; FENKET — fentanyl and ketamine group; EPI — epidural group. a Statistically significant differences between values at T1 and at T0 within the same group (P , 0.05). b Statistically significant differences between values at T1 and at T0 within the same group (P , 0.001). c Statistically significant difference compared with the EPI group (P , 0.05).

hemodynamic advantage during anesthesia with isoflurane in stimulus (9,10). In those studies, fentanyl and ketamine reduced dogs premedicated with methadone and dexmedetomidine. the hemodynamic responses to surgery and also the requirements However, lumbosacral epidural administration of lidocaine, of inhalational agents, which contrasts with the results herein. using OCL to calculate the dose, prevented the hemodynamic However, those studies only measured HR and blood pressure, changes associated with OvP ligation. Furthermore, unlike whereas in the present study a transesophageal Doppler monitor fentanyl and ketamine, epidural administration of lidocaine in was used to detect changes in cardiac output using surrogate the present study reduced isoflurane requirements. parameters, and these were the ones that underwent most varia- In accordance with these findings it is apparent that standard tion during OvP ligation. Although some studies have analyzed monitoring is not sensitive enough to detect all of the hemo- cardiac output changes during OVH, measured using different dynamic effects of OvP ligation, even though they occur. An monitors (6,7), this study is the first to compare the changes important finding of this study is that with a more complete that occur during OVH with different common analgesic pro- monitoring (such as the transesophageal Doppler monitor, tocols in clinical cases using a transesophageal Doppler monitor. which allows the assessment of contractility, preload, and after- The transesophageal Doppler is a minimally invasive monitor load), an increase in afterload occurs despite the administration that yields values for what is happening in the patient, in real of traditional intravenous analgesics and that this hemodynamic time, without the need for regular re-calibration. The parameters effect is avoided with preemptive epidural blockade using 2% measured include SD and MD, which are a linear representa- lidocaine. tion of stroke volume and CO, respectively; and PV and MA, Various studies have used fentanyl and ketamine in an which are closely related to contractility and afterload. Although attempt to reduce requirements of inhalational anesthetics, and this monitor has shown a very good correlation with inva- to reduce or prevent the sympathetic response to a nociceptive sive monitors measuring CO in human medicine (18,19), it

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currently presents several limitations in veterinary medicine. to 0.4 mL/kg BW) as used in other studies (4,5), which in turn The most important limitation is that this monitor is designed may lead to better control of the sympathetic response to OvP for humans, and therefore the algorithm to calculate CO in ligation. Dosing local anesthetic according to OCL has been animals is not valid since it estimates the cross-sectional area of described in several studies (11,31,32) and has been shown to the descending aorta according to patient demographics (age, be a safe and effective technique. gender, and height). Hypothermia has important cardiovascular effects (33). In

A recent study compared CO measured by thermodilution this study all dogs showed slight hypothermia, with a reduction ARTICLE and CardioQ in healthy and normotensive dogs, and obtained in temperature throughout the anesthesia. This reduction was only a moderate correlation (17). However, other similar tech- statistically but not clinically significant in all groups. niques for measuring CO have been compared with thermodilu- There are several limitations that must be acknowledged, tion in dogs such as transesophageal Doppler echocardiography mainly related to the retrospective nature of the study. The (20) with a very good correlation and agreement, and transtho- first is that the lapse of time between premedication and OvP racic echocardiography (21) with a mild correlation and agree- ligation was similar in all cases, but could not be standardized. ment. Another study compared the CO obtained with CardioQ Also, although dogs receiving a similar anesthetic protocol were and other minimally invasive methods such as pulse contour used for the study and the doses administered were similar, they analysis in dogs, obtaining a very good correlation but showing were not exactly the same for all animals. The doses of fentanyl no consistent bias or degree of precision across all animals under and ketamine used are in a very small range of variation, and are any given cardiovascular state (22). Nonetheless, in the clinical doses commonly used in our practice. However, they may have patient with rapidly changing hemodynamics what is important been insufficient to fully control the hemodynamic response is to be able to detect changes in CO in real time, therefore the during OVH. It is possible that using higher doses would have trending ability of a monitor. In a study in dogs comparing allowed us to achieve the desired goal. CardioQ with thermodilution during massive hemorrhage and Another limitation is that no assessment of postoperative anal- subsequent resuscitation, CardioQ overestimated CO, but there gesia was made, which could have provided useful information was an excellent correlation in the magnitude and direction of on the effectiveness of the different analgesic protocols employed. the changes (23). Although the analgesic drugs used during the intraoperative The linear parameters (SD, MD) seem to adequately correlate period are of short duration, there might be differences in post- with those that can be measured by echocardiography in humans operative analgesia, as some studies have concluded that the use of (24). Mean distance has been used to monitor CO trends in drugs such as ketamine before OVH surgery improves postopera- human adults (25–28) and children (29,30). In a study in pigs, tive analgesia in dogs (8). Nonetheless, the present study focused MD was highly correlated with the CO values measured using on the assessment of hemodynamic changes during surgery. a fluorescent microsphere technique during cardiopulmonary Also, mechanical ventilation was initiated only in some cases resuscitation (30). to treat hypercapnia. The time when it was established was The reduction in SD, MD, PV, and MA observed during not recorded, and may have been during the entire surgery or OvP ligation in this study was probably caused by an increase only during a part of it. This is another limitation of the study in afterload due to peripheral vasoconstriction induced by the because mechanical ventilation may have some hemodynamic release of catecholamines when the nociceptive stimulus was impact, and therefore could affect the results obtained. triggered (1). Lastly, there was no homogeneous distribution of animals Loco-regional anesthesia has been used in many studies to in the 4 groups; the CONT group, for example, contained a reduce the hemodynamic response to OVH (3–5). In none of very small number of animals, which may have decreased the these studies was the use of loco-regional anesthesia sufficient statistical power to detect more differences between this and to completely prevent the hemodynamic changes during OVH, the EPI group. and the administration of rescue analgesics or hypnotics was Unfortunately, the total dose of epidural lidocaine given to necessary. In our study, the lumbosacral epidural administration these dogs was not recorded. It would have been interesting of lidocaine was an effective method to prevent the sympathetic to compare the doses using the OCL with those obtained using response to the nociceptive stimulation that occurs during OvP the weight. ligation, although all animals were under general anesthesia, and Although the hemodynamic changes observed in the dogs thus these responses may have already been attenuated. However, not administered epidural lidocaine were significant, the clini- the results obtained indicate that in the group of dogs receiving cal importance of these changes in healthy animals is unknown. epidural lidocaine, none of the parameters monitored with the Most likely, the observed reduction in cardiac output in these transoesophageal Doppler monitor underwent any significant cases does not have a significant effect on tissue perfusion, variation, while the percentage of isoflurane was lower than in as it was short-lived and the animals were healthy. However, the other groups. it could have an important impact on hypovolemic or septic In our study, the epidural lidocaine group had better results animals such as dogs with pyometra. Future studies assessing than those published in other studies, and this may have been the hemodynamic changes during abdominal surgery using the due to the method used to calculate the dose. It is possible that transesophageal monitor in sick animals are warranted. when lidocaine is dosed according to OCL, it reaches more In conclusion, the esophageal Doppler was able to detect the cranial spinal segments than when it is dosed by weight (at 0.25 changes produced by vasoconstriction that occur during OVH.

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Also, according to our results, lumbosacral epidural administra- 15. Albuquerque VB, Araújo MA, Ferreira GT, et al. Effects of ropivacaine 2 tion of lidocaine 2% dosed at 0.1 mL/cm of OCL was the most combined with morphine at 0.15 and 0.2 mg kg ( 1) in bitches undergoing epidural anesthesia. Acta Cir Bras 2015;30:222–238. effective treatment to prevent the increase in afterload associated 16. Iff I, Moens YP. Evaluation of extradural pressure waves and the ‘lack with OVH. It also decreased the use of inhalational anesthesia of resistance’ test to confirm extradural needle placement in dogs. Vet during surgery, whereas administration of fentanyl alone or with J 2010;185:328–331. 17. Canfrán S, Cediel R, Sández I, Caro-Vadillo A, Gómez de Segura IA. ketamine at the doses studied failed to significantly reduce the Evaluation of an oesophageal Doppler device for monitoring cardiac hemodynamic impact or anesthesia requirements during OVH. output in anaesthetised healthy normotensive dogs. J Small Anim Pract 2015;56:450–455. Acknowledgment 18. Klotz KF, Klingsiek S, Singer M, Wenk H, Eleftheriadis S, Kuppe H, Schmucker P. Continuous measurement of cardiac output during aortic

ARTICLE We thank Dr. Pablo Otero for his advice and suggestions for cross-clamping by the oesophageal Doppler monitor ODM 1. Br J Anaesth 1995;74:655–660. this study. CVJ 19. Lafanechère A, Albadalejo P, Raux M, et al. Cardiac output measurement during infrarenal aortic surgery: Echo-esophageal Doppler versus References thermodilution catheter. J Cardiothorac Vasc Anesth 2006;20:26–30. . 1 Väisänen M, Raekallio M, Kuusela E, et al. Evaluation of the periopera- 20. Yamashita K, Ueyama Y, Miyoshi K, et al. Minimally invasive determi- tive stress response in dogs administered medetomidine or acepromazine nation of cardiac output by transthoracic bioimpedance, partial carbon as part of the preanesthetic medication. Am J Vet Res 2002;63:969–975. dioxide rebreathing, and transesophageal Doppler echocardiography in Erratum in: Am J Vet Res 2002;63:1358. beagle dogs. J Vet Med Sci 2007;69:43–47. 2. Höglund OV, Olsson K, Hagman R, Öhlund M, Olsson U, Lagerstedt 21. Lopes PC, Sousa MG, Camacho AA, et al. Comparison between two AS. Comparison of haemodynamic changes during two surgical methods methods for cardiac output measurement in propofol-anesthetized dogs: for neutering female dogs. Res Vet Sci 2011;91:159–163. Thermodilution and Doppler. Vet Anaesth Analg 2010;37:401–408. 3. Bubalo V, Moens YP, Holzmann A, Coppens P. Anaesthetic sparing effect 22. Gunn SR, Kim HK, Harrigan PW, Pinsky MR. Ability of pulse contour of local anaesthesia of the ovarian pedicle during ovariohysterectomy in and oesophageal Doppler to estimate rapid changes in stroke volume. dogs. Vet Anaesth Analg 2008;35:537–542. Intensive Care Med 2006;32:1537–1546. 4. Pohl VH, Carregaro AB, Lopes C, Gehrcke MI, Muller DC, Garlet CD. 23. De Figueiredo LF, Cruz RJ, Silva E, Rocha E, Silva M. Cardiac output Epidural anesthesia and postoperatory analgesia with alpha-2 adrenergic determination during experimental hemorrhage and resuscitation using agonists and lidocaine for ovariohysterectomy in bitches. Can J Vet Res a transesophageal Doppler monitor. Artif Organs 2004;28:338–342. 2012;76:215–220. 24. Haites NE, McLennan FM, Mowat DH, Rawles JM. Assessment of 5. Diniz MS, Kanashiro GP, Bernardi CA, Nicácio GM, Cassu RN. cardiac output by the Doppler ultrasound technique alone. Br Heart J Extradural anaesthesia with lidocaine combined with fentanyl or metha- 1985;53:123–129. done to ovariohysterectomy in dogs. Acta Cir Bras 2013;28:531–536. 25. Mark JB, Steinbrook RA, Gugino LD, et al. Continuous noninvasive 6. Miyake Y, Wagner AE, Hellyer PW. Evaluation of hemodynamic mea- monitoring of cardiac output with esophageal Doppler ultrasound dur- surements, including lithium dilution cardiac output, in anesthetized ing cardiac surgery. Anesth Analg 1986;65:1013–1020. dogs undergoing ovariohysterectomy. J Am Vet Med Assoc 2005; 26. Singer M, Clarke J, Bennett ED. Continuous hemodynamic monitoring 227:1419–1423. by oesophageal Doppler. Crit Care Med 1989;17:447–452. 7. Rioja E, Gianotti G, Valverde A. Clinical use of a low-dose medetomi- 27. Haxby EJ, Gray MR, Rodriguez C, Nott D, Springall M, Mythen M. dine infusion in healthy dogs undergoing ovariohysterectomy. Can Vet Assessment of cardiovascular changes during laparoscopic hernia repair J 2013;54:864–868. using oesophageal Doppler. Br J Anaesth 1997;78:515–519. 8. Slingsby LS, Waterman-Pearson AE. The post-operative analgesic effects 28. Valtier B, Cholley BP, Belot JP, de la Coussaye JE, Mateo J, Payen DM. of ketamine after canine ovariohysterectomy — A comparison between Noninvasive monitoring of cardiac output in critically ill patients using pre- or post-operative administration. Res Vet Sci 2000;69:147–152. transoesophageal Doppler. Am J Respir Crit Care Med 1998;158:77–83. 9. Aguado D, Benito J, Gómez de Segura IA. Reduction of the minimum 29. Tibby SM, Hatherill M, Murdoch IA. Use of transoesophageal Doppler alveolar concentration of isoflurane in dogs using a constant rate of ultrasonography in ventilated pediatric patients: Derivation of cardiac infusion of lidocaine-ketamine in combination with either morphine output. Crit Care Med 2000;28:2045–2050. or fentanyl. Vet J 2011;189:63–66. 30. Lichtenberger M, DeBehnke D, Crowe DT, Rudloff E. Comparison 10. Gutierrez-Blanco E, Victoria-Mora JM, Ibancovichi-Camarillo JA, of esophageal Doppler monitor generated minute distance and cardiac et al. Evaluation of the isoflurane-sparing effects of fentanyl, lidocaine, output in a porcine model of ventricular fibrillation. Resuscitation ketamine, dexmedetomidine, or the combination lidocaine-ketamine- 1999;41:269–276. dexmedetomidine during ovariohysterectomy in dogs. Vet Anaesth Analg 30. Mohan UR, Britto J, Habibi P, de MC, Nadel S. Noninvasive measure- 2013;40:599–609. ment of cardiac output in critically ill children. Pediatr Cardiol 2002;23: 11. Hendrix PK, Raffe MR, Robinson EP, Felice LJ, Randall DA. Epidural 58–61. administration of bupivacaine, morphine or their combination for 31. Ganem EM, Vianna PT, Marques M, Castiglia YM, Vane LA. Effects postoperative analgesia in dogs. J Am Vet Med Assoc 1996;1; 209(3): of spinal administration of large volumes of 2% lidocaine and 1% 598–607. ropivacaine on spinal cord and meninges: Experimental study in dogs. 12. Pekcan Z, Koc B. The post-operative analgesic effects of epidurally Rev Bras Anestesiol 2003;53:351–360. administered morphine and transdermal fentanyl patch after ovario- 32. Otero P, Tarragona L, Ceballos M, et al. Epidural cephalic spread hysterectomy in dogs. Vet Anaesth Analg 2010;37:557–565. of a local anaesthetic in dogs: A mathematical model using the col- 13. O O, Smith LJ. A comparison of epidural analgesia provided by bupi- umn length. Proceedings of the 10th World Congress of Veterinary vacaine alone, bupivacaine 1 morphine, or bupivacaine 1 dexmedeto- Anaesthesia Glasgow (Scotland), August 31–September 4, 2009:125. midine for pelvic orthopedic surgery in dogs. Vet Anaesth Analg 2013; 33. Redondo JI, Suesta P, Serra I, et al. Retrospective study of the prevalence 40:527–536. of postanaesthetic hypothermia in dogs. Vet Rec 2012;171:374. 14. Naganobu K, Hagio M. The effect of body position on the ‘hanging drop’ method for identifying the extradural space in anaesthetized dogs. Vet Anaesth Analg 2007;34:59–62.

424 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY Student Paper Communication étudiante

Estrogen-induced myelotoxicity in a 4-year-old golden retriever dog due to a Sertoli cell tumor

Hayden Marshall

Abstract — A 4-year-old, unilateral cryptorchid golden retriever dog was presented to the Ontario Veterinary College Health Sciences Centre with gynecomastia, dribbling urine, lethargy, neutropenia, and thrombocytopenia. A Sertoli cell tumor was diagnosed in a cryptorchid testicle with estrogen-induced myelotoxicity. The tumor was removed and bone marrow regenerated within 4 months.

Résumé — Myélotoxicité induite par l’œstrogène chez un chien Golden retriever âgé de 4 ans causée par une tumeur à cellules de Sertoli. Un chien Golden retriever âgé de 4 ans avec cryptorchidie unilatérale a été présenté au Centre des sciences de la santé de l’Ontario Veterinary College atteint de gynécomastie, d’incontinence urinaire, de léthargie, de neutropénie et de thrombocytopénie. Une tumeur à cellules de Sertoli a été diagnostiquée dans un testicule cryptorchide avec de la myélotoxicité induite par l’œstrogène. La tumeur a été excisée et la moelle osseuse s’est régénérée dans un délai de 4 mois. (Traduit par Isabelle Vallières) Can Vet J 2018;59:425–427

4-year-old neutered male, unilateral cryptorchid golden lumbar lymphadenomegaly (Figure 1). A preputial swab revealed A retriever dog was first presented to the family veterinarian stratified squamous epithelium most consistent with high levels after a 6-week history of progressive gynecomastia and tenes- of estrogen. Given these results, a Sertoli cell tumor (SCT) from mus. Ten days before initial presentation the dog was noted the right cryptorchid testicle was suspected. The retained testicle to be lethargic and hyporexic. The dog had started to dribble and right medial iliac lymph node were removed by laparoscopic urine indoors and would wake the owners to go outside during surgery (Figure 2). The patient recovered well from the surgery the night. Blood analysis completed at the referring veterinary and went home the following day with amoxicillin/clavulanic clinic showed a leukopenia [WBC 1.67 3 109/L; reference acid (Clavaseptin; Vétoquinol, Princeville, Quebec), 14 mg/kg interval (RI): 5.05 to 16.76 3 109/L] characterized by a severe body weight (BW), PO, q12h, for 10 d and enrofloxacin neutropenia (0.02 3 109/L, RI: 2.95 to 11.64 3 109/L), (Baytril; Bayer, Mississauga, Ontario), 6.25 mg/kg BW, PO, thrombocytopenia (9 3 109/L; RI: 146 to 484 3 109/L), mild q24h, for 10 d to prevent infection, and tramadol (Tramadol anemia (0.323 L/L; RI: 0.373 to 0.617 L/L), and eosinopenia hydrochloride; Ontario Veterinary College Pharmacy, Guelph, (0.01 3 109/L; RI: 0.06 to 1.23 3 109/L). The patient was Ontario), 3 mg/kg BW, PO, q8h, for 4 d then 3 mg/kg BW, PO, referred to the Ontario Veterinary College Health Sciences q12h, for 3 d and gabapentin (Auro-Gabapentin; Auro Pharma, Centre where a physical examination detected a subtle mass Woodbridge, Ontario), 11 mg/kg BW, PO, q8h for 4 d, then effect in the cranial abdomen under the ribs and an easily pal- 11 mg/kg BW, PO q12h for 3 d for analgesia. pable prostate that was assessed to be painful on rectal exami- The patient’s first follow-up appointment was 1 wk post- nation. A complete blood (cell) count (CBC) demonstrated a operation. The gynecomastia and prostatomegaly had both pancytopenia that lacked evidence of regeneration, consistent significantly improved and the tenesmus had resolved. On with bone marrow suppression (Table 1). Abdominal ultrasound rectal palpation, the prostate was no longer painful. Progressive revealed a large 6 cm 3 7 cm mass consistent with a testicular improvement in the pancytopenia was noted over the following tumor, enlarged prostate with a large cystic feature, and mild 15 wk (Table 1).

Ontario Veterinary College, University of Guelph, Guelph, Discussion Ontario N1G 2W1. Testicular tumors are the second most common tumors to Address all correspondence to Hayden Marshall; e-mail: develop in intact male dogs, with the most common types being [email protected] interstitial cell tumors, seminomas, and SCTs (1,2). Sertoli cell Use of this article is limited to a single copy for personal study. tumors are the least common testicular tumors in dogs, but Anyone interested in obtaining reprints should contact the in cryptorchid testicles they are the most common tumor to CVMA office ([email protected]) for additional develop (3,4). Testicular tumors are approximately 13.6 times copies or permission to use this material elsewhere. more likely to develop in cryptorchid testicles than in scrotal

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Table 1. Summary of blood analyses from 2 days pre-surgery to 15 weeks post-surgery. 2 days 1 week 3 weeks 4 weeks 15 weeks Reference pre-surgery post-surgery post-surgery post-surgery post-surgery range White blood cells 1.7 3.5 3.9 4.0 6.3 4.9 to 15.4 (3 109/L) Hematocrit (L/L) 0.28 0.33 0.31 0.32 0.51 0.39 to 0.56 Platelets 16 29 16 44 215 117 to 418 (3 109/L) Segmented neutrophils 0.46 0.46 1.40 1.72 3.21 2.9 to 10.6 (3 109/L) Monocytes 0.09 0.07 0.16 0.12 0.38 0 to 1.1 (3 109/L) COMMUNICATIONÉTUDIANTE

testicles (2). Etiologies that have been suggested for tumor devel- istration of blood products and should have serial hemograms opment in cryptorchid testicles include increased temperature, performed to closely monitor bone marrow recovery (12). The dysgenesis of the testicles, and abnormal testicular development treatment protocol in 1 study of 8 dogs with SCT-induced (5). Sertoli cell tumors are rarely malignant and can therefore myelotoxicity included castration, antibiotics, fluid therapy, often be cured by resection due to their low metastatic rate (6). androgenic steroids, and transfusion with fresh whole blood or Many dogs with testicular tumors do not show clinical signs platelet-rich plasma (10). Of the 7 patients treated in this study, other than a palpable mass within scrotal testicles (7). When 2 dogs recovered and 5 died (10). In the patients that recovered, clinical signs are present, they often include feminization with hematologic parameters started to improve after 2 to 3 wk and associated gynecomastia, skin hyperpigmentation, and flank were normal after 5 mo (10). Of the 5 dogs that died, 3 died alopecia (7). from septicemia and 2 from severe anemia (10). Treatment Other factors that may increase the likelihood of developing is focused on maintaining the patient’s health until the bone a testicular tumor are age, breed, and exposure to environmental marrow begins to regenerate. Even with treatment, regenera- carcinogens. One study found that age was significantly associ- tion is uncommon and therefore the diagnosis of SCT-induced ated with the development of testicular tumors (8). The rate of myelotoxicity comes with a guarded prognosis (10). occurrence increased from 0.0% to 71.4% from the 0- to 3-year Bone marrow stimulation is one of the treatment options for age group to the 15- to 18-year age group (8). Interestingly, on myelotoxicity, but good evidence supporting the benefit of this average, dogs with Sertoli cell tumors were younger at diagnosis treatment is lacking. In humans, androgen therapy was shown than dogs with other types of testicular tumors (1). One report to lead to complete recovery in 50% of patients with aplastic (9) found that boxers are at an increased risk of developing anemia (13). In dogs, there are only a few reports of androgen testicular tumors, but a more recent study by Nodtvedt et al (1) therapy being effective in returning hematologic parameters to found that Shetland sheepdogs and collies were over-represented normal (14). Another bone marrow stimulant is lithium carbon- in the population of dogs with testicular tumors. Larger breeds ate, which has been shown to lead to full recovery in a few dogs may also be at a higher risk of developing testicular tumors, but (12). The way in which lithium stimulates the bone marrow is because of their shorter life span compared to smaller breeds, unclear. This treatment option is risky because lithium can cause they might not live long enough for the tumors to manifest (1). nephrotoxicosis, so serum concentrations should be monitored Sertoli cell tumors release estrogen which can lead to myelo- very closely to ensure safe dosing (12). In this case, bone marrow toxicity (10). Estrogen toxicity on the bone marrow has been stimulation was not required because the patient’s bone marrow well-studied. The initial stage is characterized by an increased responded on its own. production of neutrophils and a significant leukocytosis charac- As noted previously, SCTs often do not cause clinical signs terized by a neutrophilia (11). Subsequently, the bone marrow and can therefore be difficult to diagnose. Some new methods becomes congested with leukocytes and these congested regions may aid in their diagnosis. One recent study suggests that SCTs of bone marrow are replaced by edema (11). With normal bone may be detected by measuring blood concentration of anti- marrow tissue being replaced, all cell lines are affected and a Müllerian hormone (AMH) (7). Anti-Müllerian hormone is leukopenia, thrombocytopenia, and non-regenerative anemia expressed specifically by Sertoli cells and this study showed that develop (10). Increased endogenous estrogen also causes feminiz- dogs with SCTs had much higher concentrations of AMH than ing syndrome in males (10). Signs include symmetrical alopecia, dogs in the control group (7). Another method that may aid in cutaneous hyperpigmentation, pendulous prepuce, gynecomas- the diagnosis of SCTs is preputial cytology (15). This involves tia, and prostatic atrophy or enlargement (10). Treatment of exfoliating some cells by swabbing the prepuce with a cotton SCT and SCT-induced myelotoxicity involves primarily removal swab and then transferring the cells to a slide (15). The slide is of the affected testicle followed by correction of hematological then examined microscopically for cells called superficial cells abnormalities, treatment and prevention of infection, and bone (15). These cells are large, with a pyknotic, faint, or no obvious marrow stimulation (12). Patients may require ongoing admin- nucleus, as well as a highly folded cytoplasm. More than 20%

426 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY

A STUDENT PAPER STUDENT

Figure 2. Digital photograph of the excised retained testicle with a pen for size comparison.

References . 1 Nodtvedt A, Gamlem H, Gunnes G, Grotmol T, Indrebo A, Moe L. Breed differences in the proportional morbidity of testicular tumours and distribution of histopathologic types in a population-based canine cancer registry. Vet Comp Oncol 2010;9:45–54. 2. Hayes HM, Pendergrass TW. Canine testicular tumours: Epidemiological features of 410 dogs. Int J Cancer 1976;18:482–487. 3. Grieco V, Riccardi E, Greppi GF, Teruzzi F, Iermano V, Finazzi M. C Canine testicular tumours: A study on 232 dogs. J Comp Pathol 2008; 128:86–89. 4. Pendergrass TW, Hayes HM. Cryptorchidism and related defects in dogs: Epidemiologic comparison with man. Teratol 1975;12:51–55. 5. Hayes HM, Wilson GP, Pendergrass TW, Cox VS. Canine cryptorchidism and subsequent testicular neoplasia: Case-control study with epidemiologic update. Teratol 1985;32:51–56. 6. Dow C. Testicular tumours in the dog. J Comp Pathol 1962;72: 247–265. 7. Holst BS, Dreimanis U. Anti-Müllerian hormone: A potentially useful biomarker for the diagnosis of canine Sertoli cell tumours. BMC Vet Res 2015;11:166. 8. Santos RL, Silva CM, Ribeiro AFC, Serakides, R. Testicular tumors in dogs: Frequency and age distribution. Arq Bras Med Vet Zootec 2000; 1:25–26. 9. Priester WA, McKay FW. The occurrence of tumors in domestic animals. J Natl Cancer Inst Monogr 1980;54:1–210. Figure 1. A — Ultrasonographic appearance of the 6 cm 3 7 cm 10. Sherding RG, Wilson GP, Kociba GJ. Bone marrow hypoplasia in eight mass found in the right caudal abdomen. B — Ultrasonographic dogs with Sertoli cell tumor. J Am Vet Med Assoc 1981;178:497–501. appearance of the right lobe of the prostate with a large cystic 11. Crafts RC. The effects of estrogens on the bone marrow of adult female feature (3.3 cm 3 6.8 cm). C — Ultrasonographic appearance dogs. Blood 1948;3:276–285. of the left medial iliac lymph node which is mildly enlarged 12. Hall EJ. Use of lithium for treatment of estrogen-induced bone marrow (1.1 to 1.2 cm) and hypoechoic. hypoplasia in a dog. J Am Vet Med Assoc 1992;200:814–816. 13. Shabidi NT, Diamond LK. Testosterone-induced remission in aplastic anemia of both acquired and congenital types: Further observations in 24 cases. N Engl J Med 1961;264:953–967. 14. Legendre AM. Estrogen-induced bone marrow hypoplasia in a dog. superficial cells observed by cytology was significantly associated J Am Anim Hosp Assoc 1976;12:525–527. with increased serum estradiol concentrations. This method 15. Dreimanis U, Vargmar K, Falk T, Cigut M, Toresson L. Evaluation of had high specificity and sensitivity for diagnosing estrogen- preputial cytology in diagnosing oestrogen producing testicular tumours in dogs. J Small Anim Pract 2012;53:536–541. producing testicular tumors (15). Acknowledgment I thank Dr. Shauna Blois for her editorial assistance with this manuscript and for involving me in this case. CVJ

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First report of atypical porcine pestivirus in piglets with congenital tremor in Canada

Fanny G. Dessureault, Martin Choinière, Chantale Provost, Carl A. Gagnon

ongenital tremor, also referred to as dancing pigs (1), shiv- Type AII and a newly identified pestivirus tentatively named C ers (2), or myoclonia congenita (3,4), is a well-recognized, atypical porcine pestivirus (APPV) (11–14). usually sporadic phenomenon described in neonatal piglets There is no apparent breed predilection with Congenital (5,6). The condition, first described in the United States by tremor Type AII, but the sporadic disease is more frequent in Kinsley (1), is characterized by local or systemic muscle spasms litters of gilts (5). Also, the high prevalence of the disease, with appearing within hours of birth, ranging from mild tremors of increased mortality and morbidity in piglets, makes it of great the ears, flank, and hind leg, to severe systemic tremors resulting clinical interest. Moreover, the clinical resemblance between in difficulty standing and walking (5). The rhythmic tremors congenital tremor Type AI (caused by CSFV) and Type AII worsen with excitement but cease with sleep (6). Morbidity and (caused by APPV), makes it essential to differentiate between mortality may result from difficulties or an inability to nurse. the 2 conditions. Congenital tremor is not specific to any one cause and has Atypical porcine pestivirus has been identified in several been classified according to the presence (Type A) or absence countries around the world (11–18), but to the authors’ knowl- (Type B) of lesions, mainly hypomyelination, in the central edge, the infection has never been identified in Canada. Here nervous system (7). Congenital tremor Type A is subdivided we present the first report of APPV infection in piglets with into 5 subtypes, AI to AV, with distinctive causes (6). Type AI congenital tremor Type AII in Canada. is caused by transplacental infection with the pestivirus classical swine fever virus (CSFV) (7), while Types AIII and AIV Case description are inherited, and Type AV is of toxic origin (6–9). Congenital Two 2-day-old, F1 Yorkshire-Landrace piglets from a farrow-to- tremor Type AII was considered infectious in origin (5,7,10), finish multiplier farm with a high health status were submitted and recently a link was established between congenital tremor for postmortem examination. The clinical history was of congenital tremor. The farm, located in eastern Canada, housed 400 Landrace breeding sows in sanitized facilities equipped with Complexe de diagnostic et d’épidémiosurveillance vétérinaires air filtration system. A vaccination program for parvovirus, lep- du Québec (Dessureault), Centre de recherche en infectiologie tospirosis, and Erysipelothrix rhusiopathiae was in place and the porcine et avicole (Provost, Gagnon), and Service de diagnos- sows were in good health. The herd was negative for the infec- tic (Gagnon), Faculté de médecine vétérinaire, Université de tious agents porcine reproductive and respiratory syndrome virus Montréal, 3200 rue Sicotte, Saint-Hyacinthe, Québec J2S 2M2; (PRRSV), influenza, Mycoplasma hyopneumoniae, Actinobacillus Bureau vétérinaire Martin Choinière DMV Inc., 5 avenue Pie X, pleuropneumoniae, and transmissible gastroenteritis coronavirus. Victoriaville, Québec G6P 8S7 (Choinière). An outbreak of congenital tremor was observed at birth in Address all correspondence to Dr. Fanny Dessureault; e-mail: piglets of gilts, while piglets of multiparous sows showed no [email protected] clinical signs. Prior to this outbreak, congenital tremor had This work was funded by Ministère de l’Agriculture, des never been reported in the herd, which had produced 25 weaned Pêcheries et de l’Alimentation du Québec (MAPAQ) and piglets per sow over the previous 12 months. The clinician also Faculté de médecine vétérinaire, Université de Montréal. Carl reported normal mortality rates in piglets and sows before the A. Gagnon was financially supported by a Natural Sciences and outbreak, and the herd was in good health. Engineering Research Council of Canada (NSERC) discovery Replacement rate for this herd is around 40%, and groups of grant. approximately 20 gilts are introduced every 8 wk from a high Use of this article is limited to a single copy for personal study. health nucleus herd. Before or after farrowing, no clinical signs Anyone interested in obtaining reprints should contact the were reported from a group of 20 new gilts introduced to the CVMA office ([email protected]) for additional herd 6 mo earlier or from other sows within the herd. Five of copies or permission to use this material elsewhere. the new gilts produced litters affected by congential tremor, with

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100% of piglets within each litter displaying systemic tremors and difficulty standing or walking from birth (N = 61 piglets affected). Clinical signs were severe enough to impair nursing and cause mortality. During the same period, 14 other gilts had farrowed but none had piglets with congenital tremor. The average litter size was slightly smaller in congenital tremor-affected litters (12.2 piglets per litter) compared with other gilt litters (13.3 piglets per litter). There were no stillborns in the congenital tremor-affected litters. At 3 wk of age (time of weaning) the mortality rate in congenital tremor-affected litters had reached AU CANADA AU an average of 24.6% (15/61), varying from 13.3% (2/15) to 41.2% (7/17) between litters with congenital tremor, compared with an average mortality rate of 12.7% piglets per litter in Figure 1. Luxol Fast Blue staining of the thoracic spinal cord the other gilts. In surviving piglets, clinical signs of congenital of 2-day-old piglets. A — Unaffected piglet; there is regular myelination. B — Congenital tremor-affected piglets, there is tremor had completely vanished by 3 wk of age. an important loss of myelin from the periphery of the cord, RAPPORT DES MALADIES DIAGNOSTIQUÉES Body condition score was within normal limits at postmor- more severe in the lateral and ventral funiculi. Notice the normal tem examination of the 2 piglets with congenital tremor. The myelination in the nerve roots (internal control). Scale bars = 1 mm. stomach of 1 piglet, a 1.5-kg female, contained partly digested milk, while the stomach of the other, a 1.2-kg male, was empty. Meconium was still present in the colon of this piglet. No mac- spinal cord of the healthy subject (external control) appeared roscopic lesions were noted in the central nervous system (CNS). normal. No changes were noted in the cerebral cortex, cerebel- Most of the brain, the entire spinal cord, and sections of lum, and brainstem of affected piglets. No bacterial pathogens lungs, heart, liver, spleen, kidneys, skeletal muscles, small were isolated from culture. intestine, large intestine, tonsils, and thymus were fixed in 10% Molecular diagnostic results for PRRSV and PCV2 were buffered formalin for 24 h, processed routinely for histological negative. All frozen samples tested for APPV by RT-qPCR examination, and stained with hematoxylin phloxine saffron were positive, with Ct values of 26.09 for pool A, and 31.34 (HPS) stain. The same process was applied on the spinal cord of (subject 1) and 28.39 (subject 2) for pool B. Sections of for- a control subject, a healthy 2-day-old piglet from another farm malin-fixed and paraffin-embedded thoracic spinal cord from free of congenital tremor. Sections of thoracic spinal cord of the control piglet were negative for APPV by RT-qPCR, but the control and affected piglets were also stained with luxol fast sections from diseased piglets were positive, with Ct values of blue (LFB). Fresh specimens of lungs, ileum, and spiral colon 33.68 (subject 1) and 34.90 (subject 2). To confirm the APPV from piglets with congenital tremor were submitted for aerobic RT qPCR results, the PCR amplicon was sequenced and com- culture. Pools of tissues were frozen at 220°C and later tested pared to one recently reported in United States reference strain by reverse transcription quantitative real-time polymerase chain (GenBank accession numbers: KU194229). Interestingly, the reaction (RT-qPCR) for PRRSV (single pool of lungs, tonsils, nt identity of our sequence compared to that APPV reference thymus, and inguinal lymph nodes from both piglets), porcine strain was relatively low, with 87.9%. circovirus type 2 (PCV2; single pool of lungs, tonsils, thymus, and inguinal lymph nodes from both piglets) and APPV (pool Discussion A with lungs, tonsils, thymus, and inguinal lymph node from The clinical signs, postmortem and histopathology findings both subjects; pool B, 1 per piglet, with thymus, spleen, kidney, in the 2 pigs are consistent with CT type AII caused by APPV ileum, cortex, cerebellum, and brainstem). Sections of formalin- infection. Atypical porcine pestivirus is a recently discovered fixed and paraffin-embedded thoracic spinal cord from the porcine pestivirus, first described by Hause et al (11) following control piglet and the piglets with congenital tremor were also high throughput sequencing. Pestiviruses are enveloped, highly tested for APPV by RT-qPCR. The atypical porcine pestivirus variable RNA viruses belonging to the family Flaviviridae (19). RT-qPCR assay used was adapted from the report of Arruda et al Several pestiviruses are of great socioeconomic relevance, nota- (12). Briefly, this RT-qPCR assay targets the NS3 gene of the bly CSFV in pigs, bovine viral diarrhea virus type 1 (BVDV-1) virus and produces an amplicon of 123 nucleotides in length. and type 2 (BVDV-2) in cattle, and border disease virus (BDV) Microscopically, significant lesions were noted only in in sheep and goats (20). Fetal disease is a common feature of affected animals. In HPS-stained sections of cervical, thoracic, intrauterine pestivirus infections and in pigs, highly virulent and lumbar spinal cord, a few random vacuoles were seen in strains of CSFV cause severe clinical signs and high mortality both lateral and ventral funiculi (white matter), and oligoden- resulting in a significant decrease in productivity (19,20). It drocytes appeared more prominent compared with the control was believed that pestiviruses only affected ungulate species, piglet. Hypomyelination was evident as a lack of staining with but recently several novel pestiviruses were identified in various the LFB stain in the white matter of the spinal cord of piglets domestic and wild species including non-ungulate species such with congenital tremor, but not the healthy control (Figure 1). as the rat (21) and bat (22). In comparison, the amount of LFB-stained material (myelina- Atypical porcine pestivirus is one of the novel emerging pes- tion) in the adjacent nerve roots (internal control) and in the tiviruses identified in pigs. Others are Bungowannah virus (23)

430 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY and Linda virus (24). Bungowannah virus causes stillbirths or the white matter of the cerebellum and spinal cord (16). By heart disease and sudden death in piglets in Australia (25), while electron microscopy (16), hypomyelination and myelin disrup- Linda virus was identified in Austria from piglets with congeni- tion and myelin breakdown were described, while no detect- REPORT DISEASE CROSS-CANADA tal tremor and severe hypomyelination (24). The clinical signs able loss of oligodendrocytes was noted by immunoperoxidase and lesions observed in piglets infected with Linda virus are staining (16). Such findings suggest that APPV has deleterious quite similar to those of APPV infection, but phylogenic analysis functional effects on fetal oligodendrocytes, likely reducing revealed that Linda virus has closer identity with Bungowannah myelin development and function, or leading to degeneration virus than with APPV. of myelin. Phylogenic analysis revealed only a distant genetic relation- The presence of APPV detected by fluorescent in-situ hybrid- ship between APPV and ruminant pestiviruses and CSFV, with ization is reported in the inner granular layer of the cerebellum , 50% nucleotide identity with CSFV (11). A distant genetic and neurones of spinal ganglia, the epithelium of tonsils, and relationship was also noted between APPV and Bungowannah follicular centers of mandibular lymph nodes, but not in the virus and the rat pestivirus, while the bat pestivirus appears to thymus of piglets with congenital tremor type AII (13). be more closely related (11). Apart from the CNS (brain, cerebellum, brainstem, spinal Like other pestiviruses, APPV displays great genetic varia- cord, and trigeminal ganglia) and the lymphoid organs (thymus, tion, and a large number of strains (13–18,26). Reports of these tonsils, spleen, and mandibular, tracheal, inguinal, or mesenteric various strains in commercial pig populations in several coun- lymph nodes), the virus has also been identified by PCR from tries including Austria, China, Germany, Great Britain, Italy, peripheral nerves, heart, lungs, liver, kidney, bladder, pancreas, Netherlands, Serbia, Spain, Switzerland, and the USA, indicate small intestine, colon, salivary glands, skeletal muscle, umbili- it is widely distributed (12–18,26). The prevalence reported in cal blood, serum, cerebrospinal fluid, saliva, nasal swabs, rectal herds is variable but can be high (13,15,18). swabs, and even semen (12–14,16,18,32). The frequency of A strong association between CT type AII and APPV was identification and the genome load vary among samples and observed by several authors (12–14,16,17) and reproduction of among studies; however, lymphoid organs seem to be the most CT in piglets was achieved experimentally following inoculation frequently positive samples and usually with a higher viral of APPV into pregnant gilts at day 32 of gestation (14), and fol- genome load (13,14,17,18). The pathogenesis is still unclear lowing inoculation of APPV into pregnant gilts and fetal amni- and the presence of APPV in central nervous system may explain otic vesicle at day 45 or 62 of gestation (12). In both studies, the neurological symptoms. The presence of APPV in a wide variety inoculation times were established with the knowledge of fetal of other tissues suggests it replicates systemically. development of immunocompetence (around 70 d of gestation; No relationship has been established between the virus 5,27–29) and of the CNS (at 62 d of gestation; 30,31) in pigs. concentration in blood and severity of the disease (14), but the Congenital infection with APPV is typically associated with presence of APPV in samples such as rectal and nasal swabs, outbreaks of CT in litters of gilts (13,14,18), although piglets salivary glands, saliva, intestines, and semen represent potential born from higher parity sows can also be affected. While the sources for viral shedding into the environment. infection does not affect the number of piglets born per litter, One important observation in the literature is the high the prevalence of CT within a litter, which is highly variable, prevalence of APPV infection in herds or individuals with no can reach 100% (14). In the present case, the cause for a slightly obvious clinical disease (13–15,26) and studies suggest that lower number of piglets per litter within congenital tremor- congenital tremor type AII only occurs when naïve sows are affected litters compared with other litters remains unknown. infected at a specific time in gestation, before the development Morbidity is typically increased with congenital tremor, resulting of immunocompetence of the fetus (12,14, 6). Infection may frequently in growth retardation, but mortality can be normal not induce clinical signs in an immune herd. With clinical or increased (13,16,17). outbreaks of congenital tremor, asymptomatic viremic piglets The intensity of signs of congenital tremor can be variable are reported (17) and persistent shedding of the virus after (12,14,17), and mild tremor could be unnoticed or mistaken the resolution of clinical disease is observed (14,16,17). The for shivering from cold. While piglets will typically recover high prevalence of APPV in tonsils or serum from apparently completely within 2 to 3 wk (13), some authors (16) report the healthy pigs supports the presence of persistently infected ani- persistence of mild tremor of ear tips and flank for up to 14 wk, mals and may explain why congenital tremor can be recurrent after which it disappears completely. As with other types of con- (14). In such cases, congenital tremor will usually reappear genital tremor, no shaking is noted in these piglets during relax- after the introduction of new gilts, allowing clinically healthy ation or sleep, but tremors are increased or induced by stress. but chronically or persistently infected pigs to infect naïve Congenital tremor was the only clinical sign reported here. subjects (14,16). Other changes such as splay leg (12,14,16), which reflects Detection of the virus, sometimes with prolonged shedding muscle weakness, or an abnormal posture with xyphosis and ears (14,16), from feces, saliva, intestines, pancreas, salivary glands on the neck (14) are reported with APPV infection. (14,16,18) of pigs suggests that the transmission of the virus in The histological changes observed here are consistent with herd is fecal-oral, and its presence in semen (32) suggests it is lesions reported by previous authors (13,16). Congenital tremor also venereally transmitted. Higher viral load in lymphoid tissues due to APPV infection is typically caused by hypomyelination suggests an immunosuppressive capacity. In piglets, transpla- in the lateral white matter of the spinal cord only (13) or in cental transmission of the virus is the most likely transmission

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route. However, the sera of sows are usually negative for APPV 12. Arruda BL, Arruda PH, Magstadt DR, et al. Identification of a divergent at time of delivery (13,14). lineage porcine pestivirus in nursing piglets with congenital tremors and reproduction of disease following experimental inoculation. PLoS ONE Cell culture isolation was first achieved by Beer et al (15), but 2016; doi:10.1371/journal.pone.0150104. several authors have failed to replicate the virus (11–14,18), sug- 13. Postel A, Hansmann F, Baechlein C, et al. Presence of atypical porcine gesting that in vitro infectivity is limited. Isolation and passage pestivirus (APPV) genomes in newborn piglets correlated with congenital tremor. Sci Rep 2016; doi 10.1038/srep27735. on different porcine cells was recently achieved (16,33), but 14. de Groof A, Deij M, Guelen L, et al. Atypical porcine pestivirus: A pos- infection of subjects with isolated virus remains to be done. sible cause of congenital tremor type A-II in newborn piglets. Viruses The present case appears to be the first report of APPV in 2016;8:271; doi:10.3390/v8100271. 15. Beer M, Wernike K, Dräger C, et al. High prevalence of highly variable piglets with congenital tremor in Canada. The case history here atypical porcine pestiviruses found in Germany. Transbound Emerg Dis suggests the newly introduced gilts were infected after entry into 2016;64:e22–e26. AU CANADA AU this herd; the exact prevalence of the virus in Canadian herds, 16. Schwarz L, Riedel C, Högler S, et al. Congenital infection with atypical porcine pestivirus (APPV) is associated with disease and viral persis- the route of transmission of the infection, and its pathogenesis tence. Vet Res 2017;48:1; doi 10.1186/s13567-016-0406-1. in the Canadian context are unknown. A better understanding 17. Muñoz-González S, Canturri A, Pérez-Simó M, et al. First report of of APPV pathogenicity, epidemiology, and immunobiology is the novel atypical porcine pestivirus in Spain and a retrospective study. Transbound Emerg Dis 2017:1–5. required to detect affected herds and develop a vaccine and other 18. Yuan J, Han Z, Li J, et al. Atypical porcine pestivirus as a novel type RAPPORT DES MALADIES DIAGNOSTIQUÉES prevention strategies. of pestivirus in pigs in China. Front Microbiol 2017; doi 10.3389/ Finally, the diagnosis of APPV is particularly important fmicb.2017.00862. 19. Flaviviridae. In: Murphy FA, Gibbs EPJ, Horzinek MC, Studdert MJ, because CSFV, a federally reportable disease in Canada, is a eds. Veterinary Virology. 3rd ed. San Diego, California: Academic Press, clinical differential diagnosis for congenital tremor in piglets. 1999:555–569. Congenital tremor type AI and type AII cannot be clinically 20. Kirkland PD, Le Potier M-F, Vannier P, Finlaison D. Pestiviruses. In: Zimmerman JJ, Karriker LA, Ramirez A, Schwarts KJ, Stevenson GW, distinguished and adequate diagnostic tools are essential to eds. Diseases of Swine. 10th ed. Ames, Iowa: Wiley-Blackwell, 2012: distinguish between them. Fortunately, there is no evidence 538–553. of cross-reactivity with diagnostic tests routinely used for the 21. Firth C, Bhat M, Firth MA, et al. Detection of zoonotic pathogens and characterization of novel viruses carried by commensal Rattus norvegicus diagnosis of classical swine fever (32). It is unlikely that APPV in New York City. mBio 2014;5:e01933–14. could negatively impact the diagnosis and surveillance programs 22. Wu Z, Ren X, Yang L, et al. Virome analysis for identification of novel in place for CSFV. mammalian viruses in bat species from Chinese provinces. J Virol 2012; 86:10999–11012. 23. Kirkland PD, Frost MJ, Finlaison DS, King KR, Ridpath JF, Gu X. Acknowledgment Identification of a novel virus in pigs — Bungowannah virus: A possible We thank Dr. Lalitha Peddireddi for the confirmation of our new species of pestivirus. Virus Res 2007;129:26–34. 24. Lamp B, Schwarz L, Högler S, et al. Novel pestivirus species in pigs, atypical porcine pestivirus positive samples by her diagnostic Austria, 2015. Emerg Infect Dis 2017;23:1176–1179f. laboratory at Kansas State Veterinary Diagnostic Laboratory. 25. Kirkland PD, Read AJ, Frost J, Finlaison DS. Bungowannah virus — A probable new species of pestivirus — What have we found in the last References 10 years? Anim Health Res Rev 2015;16:60–63. 26. Postel A, Meyer D, Cagatay G, et al. High abundance and genetic . 1 Kinsley AT. Dancing pigs. Vet Med 1922;17:123. variability of atypical porcine pestivirus in pigs from Europe and Asia. 2. Nissley SM. Shivers in pigs. J Am Vet Med Assoc 1932;81:551. Emerg Infect Dis 2017;23:2104–2107. 3. Kernkamp HCH. Myoclonia congenita: A disease of newborn pigs. Vet 27. Salmon H. Immunité chez le fœtus et le nouveau-né : modèle porcin. Med 1950;45:189. Reprod Nutr Dévelop 1984;24:197–206. 4. Maplesden DC, Brown GCT. Myoclonia congenital in a litter of young 28. Nielsen J, Rønsholt L, Sørensen KJ. Experimental in utero infection pigs. Can J Vet Res 1957;21:170–172. of pig foetuses with porcine parvovirus (PPV). Vet Microbiol 1991; 5. Done S, Williamson SM, Strugnell BW. Nervous and locomotor 28:1–11. systems. In: Zimmerman JJ, Karriker LA, Ramirez A, Schwarts KJ, 29. Sinkora M, Butler JE. The ontogeny of the porcine immune system. Stevenson GW, eds. Diseases of Swine. 10th ed. Ames, Iowa: Wiley- Dev Comp Immunol 2009;33:273–283. Blackwell, 2012:303–305. 30. Pond WG, Boleman SL, Fiorotto ML, et al. Perinatal ontogeny of brain 6. Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy growth in the domestic pig. Proc Soc Exp Biol Med 2000;223:102–108. and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 1. London, 31. Sweasey D, Patterson DSP, Glancy EM. Biphasic myelination and the UK: Saunders Elsevier, 2016:336–338. fatty acid composition of cerebrosides and cholesterol esters in the devel- 7. Done JT. Congenital nervous diseases of pigs: A review. Lab Animal oping central nervous system of the domestic pig. J Neurochem 1976; 1968;2:207–217. 27:375–380. 8. Blakemore WF, Harding JD, Done JT. Ultrastructural observations on 32. Gatto IRH, Arruda PH, Visek CA, et al. Detection of atypical porcine the spinal cord of a Landrace pig with congenital tremor type AIII. Res pestivirus in semen from commercial boar studs in the United States. Vet Sci 1974;17:174–178. Transbound Emerg Dis 2017;1-5; doi 10.1111/tbed.12759 9. Blakemore WF, Harding JD. Ultrastructural observations on the spinal 33. Postel A, Meyer D, Petrov A, Becher P. Recent emergence of a novel cords piglets with congenital tremor type AIV. Res Vet Sci 1974;17: porcine pestivirus: Interference with classical swine fever diagnosis? 248–255. Emerg Microbes Infect 2017;6; doi 10.1038/emi.2017.5 10. Blomström A-L, Ley Cecilia, Jacobson M. Astrovirus as a possible cause of congenital tremor type AII in piglets? Acta Vet Scand 2014;56:82. 11. Hause BM, Collin EA, Peddireddi L, et al. Discovery of a novel putative atypical porcine pestivirus in pigs in the USA. J Gen Virol 2015;96:2994–2998.

432 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY The Art of Private Veterinary Practice L’art de la pratique vétérinaire privée

The bad news blues

Myrna Milani

hen Dr. Keats sees fellow veterinarian, Dr. Matera, waiting But although nothing had changed in the cat’s behavior since W anxiously for her at their favorite restaurant, she knows the clients got him — he was still the lovable hellion he had something serious bothers her good friend. Once Dr. Matera always been — everything about their relationship with him had convinces Dr. Keats that she and her family are fine, she describes changed dramatically. They brought him to the clinic because he the reason for requesting an emergency vent-session. was scratching his ears. When they left, they believed he could “You remember when I hired a new associate about 6 months drop dead at any minute. It took Dr. Matera an hour to get the ago?” begins Dr. Matera. Dr. Keats nods that she did, then adds couple calmed down. Even so, she knew that the damage had that she also recalls Dr. Matera telling her that the new associate been done. was very nice and had a brilliant academic record. But in her Whereas before that fateful veterinary visit, the cat’s incred- attempts to guess what so distressed her normally unflappable ible joie de vivre formed the keystone of the clients’ relationship friend, Dr. Keats also blurts out, “Oh, no! She didn’t falsify her with him, in the days afterward they felt obligated to abort those records or steal controlled drugs, did she?” same displays lest he overexert himself. Although making these Dr. Matera quickly assures Dr. Keats that her associate had changes made sense to the clients, it also hurt them to deny not committed any crime in the legal sense. But the associate Fireball the activities that played such an important role in his did contribute to a communications blunder serious enough and their lives. to cost Dr. Matera several nights’ sleep fearing the potential Further complicating matters, Fireball vigorously resisted loss of a good client. Superficially, the events described to Dr. their attempts to make him lead a quiet life at home. The more Matera by the shocked and disgruntled clients, the Caritas’, that the Caritas tried to prevent him from racing around his lovingly precipitated the crisis appeared straightforward. During a rou- enriched environment, the more effort he put into his attempts tine examination of their large, young, male, very high-energy to do exactly that. The positive human and feline emotions that cat, Fireball, the associate heard an “unusual” heart sound and once characterized his playful activities were replaced by human recommended a chest radiograph. Because the cat’s energy level and feline anxiety, frustration, and confusion. was such that the clients converted their entire apartment into “It gets worse,” Dr. Matera tells her friend after the latter a feline enrichment center to dissipate it, it came as no surprise expressed her regret over the unfortunate incident. “I discov- to them that he resisted this. After looking at the image, the ered that while I was calming Ms. Carita down, my associate associate gravely recommended that the doting clients make an was setting up an appointment with a cardiologist. But instead appointment with a veterinary cardiologist for further workup of referring them to the one the practice uses, because he has and prepare themselves for bad news. excellent client communication as well as diagnostic and treat- “I saw them leaving with the cat after that first appointment ment skills, she referred them to a friend of hers. I’d heard her and they looked so distressed, I immediately stopped and talked friend was competent, but didn’t have any firsthand experience to them,” Dr. Matera continues. “They’re great cat-lovers and with him. To my regret, I let it go. However, when I found out, excellent clients and I immediately thought that something I did ask the client to phone me as soon as they returned from horrible had happened to Fireball.” their appointment.” Like most clients, a certain amount of trepidation attended Dr. Milani is a behavior and bond practitioner, teacher, and the Caritas’ visit to a specialist. Because they had received no author of several books on the interaction of animal behavior, information on what to expect during their appointment, they health, and the human-animal relationship. spent the days prior to it running worst case scenarios. Nor Use of this article is limited to a single copy for personal study. was the trip to see the specialist a relaxing one. Like many cats, Anyone interested in obtaining reprints should contact the Fireball did not like being confined to a carrier and hated riding CVMA office ([email protected]) for additional in a car even more. Moreover, he made his displeasure known copies or permission to use this material elsewhere. in multiple ways. These displays, in turn, elicited owner images

CVJ / VOL 59 / APRIL 2018 433 FOR PERSONAL USE ONLY

of their distraught cat collapsing and dying before they arrived that she realized that her and her husband’s feelings about at their destination. quality-of-life were legitimate, she could handle this calmly and Following the appointment, a sobbing Ms. Carita called confidently herself.” Dr. Matera and confessed that she and her husband were so After the veterinarians’ traditional vent session dessert and worried about their cat that they could not concentrate on what coffee arrived, Dr. Matera informs her colleague how she then the cardiologist told them. met privately with her associate to discuss the handling of the “I think he called it CHM or maybe HCM. Something like Fireball/Carita case from that first diagnosis to the present. The that. But whatever it is, he said there was no hope for Fireball. practice had not lost a client. But now the client refused to see And that he wanted to see him again in 6 months,” she reported. the associate. Dr. Matera then told her client about feline hypertrophic car- “My associate looked crushed and I felt sorry for her,” contin- diomyopathy and promised to send her additional information. ues Dr. Matera. “But I didn’t apologize for her distress because Next, she asked the first question that saved at least her relation- she did something contrary to hospital policy that caused two ship with the clients: “How are you and your husband doing?” good clients and their animal unnecessary pain and suffering. The resulting outpouring of emotions and concerns did Fortunately, she understood my concerns and the rationale not surprise the experienced practitioner. Although it took behind them, and promised to work on her bad-news client

L’ART DE LA PRATIQUE VÉTÉRINAIREPRATIQUE LA DE PRIVÉE L’ART Ms. Carita a while to vent all the fear that now dominated her communication skills. I’m glad because I really didn’t want to and her husband’s relationship with their cat, Dr. Matera made let her go.” no attempt to interfere because she knew the client needed Dr. Keats nods in agreement because she shares her colleague’s this release. After Ms. Carita calmed down, Dr. Matera asked opinion that the human and animal pain caused by anxiety, another question that changed everything: “What can I do to frustration, and confusion is as real to those experiencing it as help?” any physical pain. Unless the new veterinarian learns to recog- After pondering this for a while, Ms. Carita revealed that the nize and address these negative emotional/bond components of thing that had upset them the most from the time the abnormal a medical problem, she would be a liability instead of an asset heart sound was detected through the visit with the veterinary to the practice. cardiologist was the emphasis on their cat dying. Sometimes the temptation can be great for practitioners to “We understand why they would want to prepare us for this,” focus on worst-case scenarios and dire prognoses in the belief she admitted. “And maybe from their perspective, doing this was that, should these come to pass, doing so will lessen the client’s the right thing to do. But they didn’t seem to realize that we sorrow. Within this group, some clinicians also may believe that didn’t want to prepare for Fireball to die. We weren’t in denial this poses the safest route for them personally. If the animal about this possibility. We wanted to focus on giving him a qual- dies, they rightfully can say they prepared the client for this ity life and enjoying him and our life together for however long possibility. If the animal does better than expected, they can we had. But nobody talked about how to do that.” take credit for that instead. But when clients maintain strong Dr. Matera then asked Ms. Carita if she and her husband emotional bonds with their animals, the unwillingness or inabil- would be willing to get a second opinion from a cardiologist ity of practitioners to offer practical quality-of-life support that whose quality-of-life orientation shared much in common with also supports the quality of the human-animal bond will be theirs. She also volunteered to arrange the appointment and noticed. At least some of these clients may believe the veterinar- ensure that copies of Fireball’s records were forwarded to the ian abandoned them and their animals when they needed the second specialist. practitioner’s help the most. Most practitioners would agree that “I even was willing to pay for the second consultation,” this is not the message they want their practice to communicate Dr. Matera tells Dr. Keats. “But the client was so touched and to the public. relieved by my offer, she wouldn’t accept it. She said that now

434 CVJ / VOL 59 / APRIL 2018 FOR PERSONAL USE ONLY

Answers to Quiz Corner Les réponses du test éclair

1. B) The immunologic reactions require prior sensitization (during 3. D) Atrial fibrillation is the most common arrhythmia to cause the first year of life) followed by re-exposure or a challenge poor athletic performance. in order for clinical signs to occur. Thus these dogs are usu - D) La fibrillation auriculaire est l’arythmie la plus commune ally between 1 and 3 years of age when symptoms are first causant de mauvaises performances athlétiques. noted. 4. A) Ferrets have a high packed cell volume (PCV), and three B) Les réactions immunologiques exigent une sensibilisation times the amount of serum required should be collected. antérieure (durant la première année de vie), suivie d’une Blood should not be collected from the heart. A ferret’s legs réexposition ou d’une provocation afin que les signes should not be pulled backward for restraint. cliniques puissent se manifester. Ainsi ces chiens sont âgés A) Les furets ont un hématocrite élevé et trois fois le volume habituellement de 1 à 3 ans lorsque les symptômes se de sérum doit être prélevé. Le sang ne doit pas être prélevé manifestent. du cœur. Lors des contentions, les membres des furets ne 2. B) Treatment is given daily during the induction phase and is doivent pas être tirés vers l’arrière. then followed by maintenance therapy given once- or twice- 5. C) Streptococcus agalactiae is the only contagious pathogen. weekly. The treatment of adrenal neoplasia with mitotane Escherichia coli, K. pneumoniae, and S. uberis are environ- typically requires higher doses than those used for pituitary- mental organisms and concurrent large increases in clinical based hyperadrenocorticism. Dogs can exhibit clinical signs case incidence rates would be expected. Staphylococcus of hyperadrenocorticism other than polyuria that warrant chromogenes is normal flora of cows’ teat skin; it is asso - therapy. ciated with subclinical mastitis but does not behave in a B) On administre le traitement quotidiennement durant la contagious manner. phase d’induction, puis il est suivi d’un traitement d’entretien C) Staphylococcus agalactiae est le seul agent pathogène administré d’une à deux fois par semaine. Le traitement contagieux. Escherichia coli, K. pneumoniae et S. uberis sont de la néoplasie surrénalienne à l’aide de mitotane exige des organismes environnementaux et on s’attendrait à de habituellement de plus fortes doses que celles utilisées pour fortes augmentations du taux d’incidence des cas cliniques. l’adrénocorticisme d’origine hypophysaire. Les chiens peuvent Staphylococcus chromogenes constitue la flore normale de manifester des signes cliniques d’hyperadrénocorticisme la peau des trayons des vaches. Cette bactérie est associée autres que ceux de la polyurie qui exige un traitement. à la mammite subclinique mais n’est pas contagieuse.

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