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Journal Rounds

brum-webBy Doug Brum, DVM
www.angell.org/internalmedicine
internalmedicine@angell.org
617-541-5186

I wanted to share a few articles that have been recently published that I found interesting and pertinent to practice.

Clinical features of progressive vacuolar hepatopathy in Scottish Terriers with and without hepatocellular carcinoma: 114 cases (1980-2013)
Cortright, Center, Randolph, et al.  JVMA, Vol 245, No 7, Oct 1 2014

In this retrospective study, the authors describe 114 Scottish Terriers diagnosed with vacuolar hepatopathy (VH). VH may occur in any breed, but Scottish Terriers are predisposed. Many clinicians have historically thought that VH was mostly a benign change in the liver; this large study showed otherwise. VH can potentially be a progressive hepatopathy, with the ALP increasing over time, which correlates with progressive liver pathology and clinical illness. Clinical illness includes signs of adrenal hormone excess, gall bladder mucocele formation, abnormal copper accumulation, and development of hepatic adenocarcinoma.

Forty percent of dogs with liver biopsies suggestive of vacuolar hepatopathy had clinical signs and diagnostic tests supporting adrenal hyperactivity. ACTH stimulation tests, LDD suppression tests and an ACTH stimulated sex hormone profile were used for adrenal evaluation.  The majority of these dogs had increases in sex hormones (mostly progesterone and androstenedione). Interestingly, all the dogs (13) with clinical signs and diagnostic tests supporting adrenal hyperactivity that were medical treated did poorly. Dogs treated with Mitotane or ketoconazole either became ill, or died. Trilostane was better tolerated, but did not change clinical or pathological signs. Given that the majority of the adrenal hyperactivity was related to sex hormone excess, treatment with Trilostane may also be contraindicated.

Dogs with VH were also at increased risk of having a gall bladder mucocele (16%). This agrees with previous studies that have shown a connection between adrenal hyperactivity and mucocele development.1

Hepatic copper was only measured in about 1/3 of the cases, but in those animals copper was elevated in 72% of the liver samples. The authors stressed the value of quantitative copper analysis on biopsies; as chelation, antioxidant and dietary therapy significantly improve longevity.

Perhaps the most compelling finding in this study was the association of hepatocellular carcinoma (HC) in 34% of dogs with VH. Based on histopathology the authors suggest that VH may start as a more benign condition, but the lesions may change to a more degenerative VH with formation of regenerative foci that may have dysplastic foci. This may precede neoplastic transformation.

This article shows a correlation to potential progressive liver disease in Scottish Terriers with increases in ALP and VH.  Based on this, they recommend that all Scottish Terriers with increased ALP (with or without a diagnosis of VH) have biannual liver panels and yearly abdominal ultrasounds. Early detection of hepatic neoplasia or early detection of gall bladder mucoceles will lead to better surgical outcomes and overall better outcomes in affected dogs. It is unknown whether other dog breeds have a similar predisposition, but careful monitoring in all breeds should be considered.

Signalment Changes in Canine Leptospirosis between 1970 and 2009
Lee, Guptill, Johnson, Moore  JVIM 2014; 28:294-299

In a previous large-scale study2, Leptospirosis was found to be more associated with large breed, working or outdoor dogs. Smaller or “companion” dogs were thought to be at decreased risk. This current study was a continuation of the older study, and evaluated the prevalence and patient sigalment by decade in cases diagnosed at veterinary teaching hospitals up to 2009.

A total of 1,091 cases of Leptospirosis were diagnosed from 1,659,146 dogs evaluated over the 40-year period (approximately 1 dog out of 1,600 cases). The most cases of Leptospirosis were diagnosed in 1971, and then the prevalence decreased through the 1980’s. The prevalence began increasing in the 1990’s, with the most significant increase in the 2000s.

Probably the most interesting finding of this study was the signalment change in dogs. There was a significant increase in incidence among dogs under 15 pounds and in the terrier group from 2000-2009. The authors speculate that the increased numbers of small dogs affected could have occurred from several factors. Urbanization would provide more contact with wild life reservoir hosts, thus leading to more potential small urban dog exposure.  Additionally, many veterinarians and owners are hesitant to vaccinate smaller dogs for Leptospirosis because vaccine-associated adverse effects are more common in smaller breed dogs. Smaller breed urban dogs were also commonly thought to have less risk factors for Leptospirosis exposure, making veterinarians less likely to vaccinate. Based on the findings of this study, when a practitioner is faced with a small urban dog with clinical signs of Leptospirosis, the diagnosis should not be excluded based on signalment.  In fact, it might be more likely that this dog has the disease, as opposed to the previously thought “classic” large breed outdoor dog.  Vaccine protocols to include “dogs at risk” might need to be re-evaluated.

Effect of dosing interval on efficacy of maropitant for prevention of hydromorphone-induced vomiting and signs of nausea in dogs
Kraus, JAVMA, Vol 245, No 9 November 1, 2014

Hydromorphone and other opioids are common pre-operative analgesic agents. Unfortunately, these classes of drugs often carry the unwanted side effects of nausea and vomiting. Results of a recent study3 showed that Maropitant administered orally to dogs 2 hours prior to administration of hydromorphone prevented vomiting, but 60% of dogs still showed signs of significant nausea. This paper attempted to evaluate the most effective dosing interval of Maropitant in order to prevent vomiting as well as nausea. Maropitant was given SQ (1mg/kg), as opposed to orally in the previous study. Dogs were divided into groups of 10 and given Maropitant prior to administration of hydromorphone (times 0, 15, 30, 45, and 60 minutes).

The results showed that Maropitant effectively reduced or prevented vomiting when given at least 15 minutes prior to hydromorphone (2/10 dogs vomited at 15 minutes where none of the 30 dogs vomited when given at 30-60 minutes); however, Maripotant needed to be given 60 minutes before hydromorphone to significantly decrease signs of nausea. These findings suggest that injectable Maropitant should be given 60 minutes prior to opioid analgesia.

For more information about Angell’s Internal Medicine service, please call 617-541-5186 or e-mail internalmedicine@angell.org.

1 Mesich MLL, Mayhew PD, Paek M, er al. Gallbladder mucoceles and their association with endocrinopathies in dogs: a retrospective case-control study. J Small Anim Pract 2009;50: 63—635.
2 Ward et al. Prevalence of and risk factors for leptospirosis among dogs in the United States and Canada: 677 cases (1970-1998).  JAAHA 2002;220:53-58.
3 Hay Kraus BL. Efficacy of orally administered maropitant citrate in preventing vomiting associated with hydromorphone administration in dogs. JMVMA 2014;244: 1164-1169.

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