• Galbladder mucoceles
DeMonaco SM, Grant DC, Larson MM, et al. Spontaneous Course of Biliary Sludge Over 12 Months in Dogs with Ultrasonographically Identified Biliary Sludge. Journal of Veterinary Internal Medicine, 2016; 30:771-778. http://onlinelibrary.wiley.com/doi/10.1111/jvim.13929/abstract?campaign=wolearlyview
This study was performed at the Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA.
Background: Biliary sludge is associated with gallbladder (GB) dysmotility and mucus hypersecretion suggesting a link between biliary sludge and the formation of GB mucoceles (GBM). If biliary sludge progresses to GBM, treatment to reduce the production and progression of sludge is warranted.
Hypothesis/Objectives: The objective of this study was to determine the course of biliary sludge in dogs.
Animals: Seventy-seven healthy, client-owned dogs ≥4 years of age screened for biliary sludge; 45 affected dogs identified.
Methods: Prospective, observational design. Serial ultrasound examinations were evaluated at 3, 6, 9, and 12 months to monitor degree of sludge based on proportion of GB filled with sludge (mild [0.01–24.4%], moderate [24.5–49.4%], moderate to severe [49.5–74.4%], severe [74.5–100%]), gravity dependency of sludge, and GB dimensions.
Results: After 1 year of follow-up, the degree of sludge was mild (34%), moderate (47%), moderate to severe (13%), severe (3%), or absent (3%). There was no significant difference in median degree of sludge over 1 year (P = .36). There were no significant changes in the gravity dependency of sludge over 1 year. A subset of dogs, 24%, with initial gravity-dependent sludge developed a combination of nondependent and dependent sludge. Dogs had resolved (2%), decreased (19%), static (40%), increased (29%), or recurrent (10%) sludge at the conclusion of the study.
Conclusions and Clinical Importance: Biliary sludge was prevalent, affected dogs remained asymptomatic, and it rarely resolves in healthy dogs over a period of 1 year. Some dogs developed nongravity-dependent sludge within 1 year, which might indicate changes in consistency of sludge.
Gookin JL, Correa MT, Peters A, et al. Association of Gallbladder Mucocele Histologic Diagnosis with Selected Drug Use in Dogs: A Matched Case-Control Study. Journal of Veterinary Internal Medicine, 2015; 29: 1464–1472. doi: 10.1111/jvim.13649. http://onlinelibrary.wiley.com/doi/10.1111/jvim.13649/abstract
The study was conducted at the College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 20607.
Keywords: Bile; Canine; Mucus; Xenobiotic
Background: The cause of gallbladder mucocele (GBM) formation in dogs currently is unknown. Many available drugs represent a newer generation of xenobiotics that may predispose dogs to GBM formation.
Objective: To determine if there is an association between the histologic diagnosis of GBM in dogs and administration of selected drugs.
Animals: Eighty-one dogs with a histologic diagnosis of GBM and 162 breed, age, and admission date-matched control dogs from a single referral institution.
Methods: Medical records of dogs with GBM and control dogs from 2001 to 2011 were reviewed. Owner verification of drug history was sought by a standard questionnaire. Reported use of heartworm, flea, and tick preventatives as well as nonsteroidal anti-inflammatory drugs, analgesics, corticosteroids, or medications for treatment of osteoarthritis was recorded.
Results: Dogs with GBM were 2.2 times as likely to have had reported use of thyroxine (as a proxy for the diagnosis of hypothyroidism) as control dogs (95% confidence interval [CI], 0.949–5.051), 3.6 times as likely to have had reported treatment for Cushing's disease (95% CI, 1.228–10.612), and 2.3 times as likely to have had reported use of products containing imidacloprid (95% CI, 1.094–4.723). Analysis of a data subset containing only Shetland sheepdogs (23 GBM and 46 control) indicated that Shetland sheepdogs with GBM formation were 9.3 times as likely to have had reported use of imidacloprid as were control Shetland sheepdogs (95% CI, 1.103–78.239).
Conclusions and Clinical Importance: This study provides evidence for an association between selected drug use and GBM formation in dogs. A larger epidemiologic study of Shetland sheepdogs with GBM formation and exposure to imidacloprid is warranted.
Guess SC, Harkin KR, Biller DS: Anicteric gallbladder rupture in dogs: 5 cases (2007–2013). J Am Vet Med Assoc. 2015; 247:1412–1414. doi: 10.2460/javma.247.12.1412
Take home points:
• 5 dogs were affected, only one was a Shetland Sheepdog.
• Gallbladder rupture was thought to be secondary to gallbladder mucoceles.
• Bloodwork did not identify a gallbladder problem.
• Free abdominal fluid was identified via ultrasound evaluation in all dogs.
• Evaluation of free abdominal fluid for bile acids may be needed to confirm gallbladder rupture.
• Gallbladder rupture is a surgical emergency.
Excerpts from the article are presented below.
…….Five dogs met the criteria for study inclusion (2 spayed females and 3 castrated males). The breeds included mixed (n = 2), Pomeranian (1), Shetland Sheepdog (1), and Bichon Frise (1). Mean age at the time of diagnosis was 10 years (median, 10 years; range, 8 to 12 years). Mean and median body weights were 15.3 and 14 kg (33.7 and 30.8 lb.), respectively…..
This retrospective case series included 5 dogs with gallbladder rupture, mild to moderate abdominal effusion, and serum total bilirubin concentrations within reference limits. All dogs described in this report had free abdominal fluid detected during an ultrasonographic examination and surgically confirmed gallbladder rupture. Although hyperbilirubinemia is typically considered a key part of the diagnosis in patients with biliary disease,5 results of this case series show that patients can have a ruptured gallbladder without evidence of icterus, with serum total bilirubin concentrations within reference limits, and with unremarkable peritoneal fluid bilirubin concentration (< 2 times the concentration in serum)………
The findings of this case series suggested that hyperbilirubinemia and high concentrations of bilirubin in abdominal fluid contents are not necessarily present in dogs with gallbladder rupture. Furthermore, our results suggested that testing of abdominal fluid for bile acids may be indicated in some cases in which a diagnosis remains challenging or elusive. Additional studies are needed to further evaluate the diagnostic value of abdominal fluid bile acids measurement prospectively in a larger number of patients….
Four of the 5 dogs described in the present report had evidence of gallbladder necrosis, and 1 dog had evidence of fibrinolytic, suppurative cholecystitis on histologic evaluation. Although the number of dogs in this study was extremely small, on the basis of histopathologic findings in these cases, pressure necrosis secondary to gallbladder mucocele presence is considered a possible mechanism for gallbladder rupture, and this hypothesis has been described previously.4,7,8 Because the prevalence of gallbladder mucocele is reportedly increasing in canine patients, further exploration into the pathogenesis of mucoceles and gallbladder rupture without bile duct obstruction is needed in veterinary medicine.2,4,8,12 …”
Kesimer M, Cullen J, Cao R, Radicioni G, et al. Excess Secretion of Gel-Forming Mucins and Associated Innate Defense Proteins with Defective Mucin Un-Packaging Underpin Gallbladder Mucocele Formation in Dogs. PLoS ONE; 2015; 10(9): e0138988. doi:10.1371/journal.pone.0138988, http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138988
Mucosal protection of the gallbladder is vital yet we know very little about the mechanisms involved. In domestic dogs, an emergent syndrome referred to as gallbladder mucocele formation is characterized by excessive secretion of abnormal mucus that results in obstruction and rupture of the gallbladder. The cause of gallbladder mucocele formation is unknown. In these first mechanistic studies of this disease, we investigated normal and mucocele-forming dog gallbladders to determine the source, identity, biophysical properties, and protein associates of the culprit mucins with aim to identify causes for abnormal mucus behavior. We established that mucocele formation involves an adoptive excess secretion of gel forming mucins with abnormal properties by the gallbladder epithelium. The mucus is characterized by a disproportionally significant increase in Muc5ac relative to Muc5b, defective mucin un-packaging, and mucin-interacting innate defense proteins that are capable of dramatically altering the physical and functional properties of mucus. These findings provide an explanation for abnormal mucus behavior and based on similarity to mucus observed in the airways of people with cystic fibrosis, suggest that abnormal mechanisms for maintenance of gallbladder epithelial hydration may be an instigating factor for mucocele formation in dogs.
The underlying cause of gallbladder mucocele formation in the dog is currently somewhat of a mystery. Several predisposing factors such as breed predisposition [11, 15], concurrent endocrinopathies , and hyperlipidemia [11, 15] suggest both a genetic and hormonal/metabolic contribution to disease pathogenesis. However, the breeds of dog affected and endocrinopathies commonly associated with gallbladder mucocele formation have existed long before emergence of the disease as a clinical entity and are not found in all dogs diagnosed with the disease. Accordingly, these are unlikely to be a direct cause, but rather an exacerbating factor to disease pathogenesis. Efforts to link a genetic defect in ABCB4, a hepatocyte canicular membrane phosphatidylcholine flippase, in the Shetland sheepdog was initially promising but later disproven . A theory that poor gallbladder motility  causes gallbladder mucocele formation is difficult to prove once the gallbladder is filled with mucus and gallbladder paresis does not result in mucocele formation in people. The disease is not a consequence of common bile duct obstruction , however mucus can eventually extend into and obstruct hepatic bile drainage. Increased mucin secretion can be caused by bacterial cholecystitis; however infection of the gallbladder is an inconsistent finding in dogs with gallbladder mucocele formation [9–12, 14]. Despite many descriptions of proliferative changes in the gallbladder epithelium , there exist no diseases of the gallbladder in people that closely mirror the histological appearance of gallbladder mucocele formation in dogs. The only descriptions of gallbladder mucosa that are similar to gallbladder mucocele formation are in animals experimentally treated with progestins [27–29] or lacking functional cystic fibrosis transmembrane regulatory (CFTR) protein expression[30,31]. Alas, the specific mechanisms underpinning the initiating event of the disease pathogenesis in dogs has remained elusive. …… MORE…….
Cullen JM, Willson CJ, Minch, JD, Kimbrough CL, Mealey KL. Lack of association of ABCB4 insertion mutation with gallbladder mucoceles in dogs. Journal of Veterinary Diagnostic Investigation, 2014; 26:434-436.
The etiology of canine gallbladder mucocele (GBM) has not yet been identified. However, several studies have linked GBM in dogs to particular breeds (Shetland Sheepdogs are commonly implicated), concurrent endocrine disease (hyperadrenocorticism and/or hypothyroidism), and a mutation in the canine ABCB4 gene (ABCB4 1583_1584G), particularly in Shetland Sheepdogs. The current study assessed ABCB4 1583_1584G, in a wider sample of dogs with GBM compared with age and breed-matched controls. ABCB4 1583_1584G was identified in 4 of 8 Shetland Sheepdogs and 13 of 28 other breeds with GBM. ABCB4 1583_1584G was also detected in 9 of 12 Shetland Sheepdogs and 23 of 37 other breeds that did not have GBM. No statistically significant association existed between ABCB4 1583_1584G and the presence of GBM for all dogs combined or for Shetland Sheepdogs alone. In contrast to previously reported findings, the current study did not identify a strong association between ABCB4 1583_1584G and GBM in Shetland Sheepdogs or other breeds.
Malek S, Sinclair E, Hosgood, G, Moens, et al. Clinical Findings and Prognostic Factors for Dogs Undergoing Cholecystectomy for Gall Bladder Mucocele. Veterinary Surgery, 2013; 42: 418–426. doi: 10.1111/j.1532-950X.2012.01072.x http://onlinelibrary.wiley.com/doi/10.1111/j.1532-950X.2012.01072.x/abstract
Diagnosis of gallbladder mucoceles was confirmed by histopathology and 74% were diagnosed based on preoperative abdominal ultrasonography. Intraoperative evidence of gall bladder rupture was noted in 10 dogs (23%), and 16 (37%) had evidence of previous leakage in the abdominal cavity. One dog had positive bacterial growth from the gall bladder content. The most common histopathologic findings in liver biopsies obtained at surgery were cholangiohepatitis, biliary hyperplasia, or cholestasis. Univariate analysis showed evidence of postoperative hypotension (P = .05) to be significantly negatively associated with survival. Significant difference in mean postoperative serum lactate (P = .034) and postoperative packed cell volume (P = .063) between dogs that survived and died was also noted.
Elevations in postoperative serum lactate concentrations and immediate postoperative hypotension in dogs undergoing cholecystectomy for gall bladder mucoceles are associated with poor clinical outcome.
5 of the dogs in the above study were Shetland Sheepdogs.
Tsukagoshi T, Ohno K, Tsukamoto A, et.al. Decreased gallbladder emptying in dogs with biliary sludge or gallbladder mucocele. Vet Radiol & Ultrasound. 2012; 53:84-91.
Biliary sludge in dogs is dismissed commonly as an incidental finding. On the other hand, gallbladder mucocele is reported increasingly in dogs and can lead to biliary obstruction or gallbladder rupture. Cholestasis is suspected to play a role in development of sludge and mucoceles, though there are no data in dogs to support this. We investigated gallbladder emptying, a key factor in biliary flow, in dogs with mobile sludge, immobile sludge, or gallbladder mucocele and in healthy controls. Gallbladder ejection fraction estimated by ultrasonography was used as the index of gallbladder emptying. The ejection fraction at 60 min after eating was significantly decreased in all three abnormal groups. Moreover, all dogs with sludge or a mucocele had gallbladder distension. These changes were the greatest in the mucocele group. Thus, biliary stasis occurs not only in dogs with gallbladder mucocele but also in dogs with biliary sludge. Cholestasis may play a role in the pathogenesis or progression of these diseases in dogs.
Comment: Two of 7 dogs with mucoceles were Shetland Sheepdogs.
University of Tokyo, Tokyo, Japan.
Mealey KL, Minch JD, White SN, et al: An insertion mutation in ABCB4 is associated with gallbladder mucocele formation in dogs. Comp Hepatol, 2010; 9:6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904718/?tool=pubmed
ABCB4 functions as a phosphatidylcholine translocater, flipping phosphatidylcholine across hepatocyte canalicular membranes into biliary canaliculi. In people, ABCB4 gene mutations are associated with several disease syndromes including intrahepatic cholestasis of pregnancy, progressive familial intrahepatic cholestasis (type 3), primary biliary cirrhosis, and cholelithiasis. Hepatobiliary disease, specifically gallbladder mucocele formation, has been recognized with increased frequency in dogs during the past decade. Because Shetland Sheepdogs are considered to be predisposed to gallbladder mucoceles, we initially investigated ABCB4 as a candidate gene for gallbladder mucocele formation in that breed, but included affected dogs of other breeds as well.
An insertion (G) mutation in exon 12 of canine ABCB4 (ABCB4 1583_1584G) was found to be significantly associated with hepatobiliary disease in Shetland Sheepdogs specifically (P < 0.0001) as well as other breeds (P < 0.0006). ABCB4 1583_1584G results in a frame shift generating four stop codons that prematurely terminate ABCB4 protein synthesis within exon 12, abolishing over half of the protein including critical ATP and a putative substrate binding site.
The finding of a significant association of ABCB4 1583_1584G with gallbladder mucoceles in dogs suggests that this phospholipid flippase may play a role in the pathophysiology of this disorder. Affected dogs may provide a useful model for identifying novel treatment strategies for ABCB4-associated hepatobiliary disease in people.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA
Mayhew PD, Mehler SJ, Radhakrishnan A. Laparoscopic Cholecystectomy for Management of Uncomplicated Gall Bladder Mucocele in Six Dogs. Vet Surg, 2008; 37: 625-630. http://onlinelibrary.wiley.com/doi/10.1111/j.1532-950X.2008.00428.x/full http://www.bluegrassveterinaryspecialists.com/news/vetsurgerypaper.pdf
Comment: One of the dogs in the report was a Shetland Sheepdog.
Aguirre AL, Center SA, Randolph JF, et al. Gallbladder disease in Shetland Sheepdogs: 38 cases (1995-2005), J Am Vet Med Assoc, 2007; 231:79-88. http://www.ncbi.nlm.nih.gov/pubmed/17605668
Objective—To determine risk, clinical features, and treatment responses for gallbladder disorders in Shetland Sheepdogs.
Design—Retrospective case-control study.
Animals—38 Shetland Sheepdogs with gallbladder disease.
Procedures—Medical records were reviewed for signalment, history, physical findings, laboratory results, imaging features, coexistent illnesses, histologic findings, treatments, and survival rates.
Results—Mature dogs with gastrointestinal signs were predisposed (odds ratio, 7.2) to gallbladder disorders. Gallbladder mucocele was confirmed in 25 dogs. Concurrent problems included pancreatitis, hyperlipidemia, corticosteroid excess, hypothyroidism, protein-losing nephropathy, diabetes mellitus, cholelithiasis, and gallbladder dysmotility. Mortality rate was 68% with and 32% without bile peritonitis. Nonsurvivors had high WBC and neutrophil count and low potassium concentration. Although preprandial hypercholesterolemia, hypertriglyceridemia, and high serum liver enzyme activities were common, gallbladder disease was serendipitously discovered in 11 of 38 dogs. Histologic examination (n = 20 dogs) revealed gallbladder cystic mucosal hyperplasia in 20 dogs, cholecystitis in 16, periportal hepatitis in 9, and vacuolar hepatopathy in 7. Surgery included cholecystectomy (n = 17) and cholecystoenterostomy (4). In 1 hyperlipidemic dog without clinical signs, gallbladder mucocele resolved 6 months after beginning use of a fat-restricted diet and ursodeoxycholic acid.
Conclusions and Clinical Relevance—Shetland Sheepdogs are predisposed to gallbladder disorders, with mucoceles and concurrent dyslipidemia or dysmotility in many affected dogs. Most dogs were without clinical signs during mucocele development. Low survival rate after cholecystectomy in clinically affected dogs suggested that preemptive surgical interventions may be a more appropriate treatment strategy.
Departments of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY
Worley DR, Hottinger HA, Lawrence HJ. Surgical management of gallbladder mucoceles in dogs: 22 cases (1999–2003). J Am Vet Med Assoc, 2004; 225:1418–1422.
Animals—22 client-owned dogs. (Includes 4 Shetland Sheepdogs)
Procedures—Medical records of dogs with gallbladder mucoceles that were treated surgically were reviewed. History, clinical signs, results of selected clinicopathologic analyses and abdominal ultrasonography, surgical procedure performed, results of histologic examination of a liver biopsy specimen, and survival time were recorded. Followup information was obtained via telephone interview with owners and referring veterinarians.
Results—Dogs were 7 to 15 years of age and had nonspecific clinical signs (vomiting, anorexia, and lethargy). Physical examination findings included icterus, signs of depression, and signs of discomfort on palpation of the abdomen . Sixteen dogs had a definitive diagnosis and 6 dogs were strongly suspected of having a gallbladder mucocele on the basis of results of abdominal ultrasonography. Fifteen dogs survived after surgery; 3 of these dogs had bile-induced peritonitis, and 4 had pancreatitis. One dog was euthanatized as a result of severe pancreatitis, and 1 was euthanatized because of acute renal failure; 5 dogs died as a result of pancreatitis, cholecystitis, or bile-induced peritonitis. Hepatic abnormalities were detected histologically in all dogs.
Conclusions and Clinical Relevance—No predictors of survival were identified. No associations between outcome of surgical treatment (survival vs nonsurvival) and preoperative findings, biliary rupture, surgical procedure performed, results of histologic examination of the liver, or development of pancreatitis were found. Cholecystoduodenostomy and cholecystectomy appear to be acceptable treatments for gallbladder mucocele.
Gulf Coast Veterinary Surgery, Houston, TX
• Portosystemic shunts
Tobias KM, Rohrbach BW. Association of breed with the diagnosis of congenital portosystemic shunts in dogs: 2,400 cases (1980–2002). J Am Vet Med Assoc, 2003; 223:1636-1639.
Objective—To determine the annual and overall proportion of diagnoses of congenital portosystemic shunts (CPSS) in dogs and identify breeds at increased risk for CPSS.
Animals—2,400 dogs with CPSS from veterinary teaching hospitals that reported to the Veterinary Medical Database (VMDB) from January 1, 1980 to February 28, 2002.
Procedure—The proportion of diagnoses of CPSS was calculated for all dogs and each breed recorded in the VMDB annually and for the 22.2-year period. Odds ratios and adjusted confidence intervals were calculated for breeds with at least 100 accessions by comparing odds of each breed with a diagnosis of CPSS with that of mixed-breed dogs.
Results—Congenital portosystemic shunts were reported in 0.18% of all dogs and 0.05% of mixed breed dogs. The proportion of diagnoses of CPSS increased from 5 in 10,000 dogs in 1980 to 5 in 1,000 dogs in 2001. Yorkshire Terriers had the greatest total number of diagnoses of CPSS. Thirty-three breeds were significantly more likely to have a diagnosis of CPSS, compared with mixed-breed dogs. The greatest proportions of diagnoses were found in Havanese (3.2%), Yorkshire Terriers (2.9%), Maltese (1.6%), Dandie Dinmont Terriers (1.6%), and Pugs (1.3%).
Conclusions and Clinical Relevance—Certain breeds appear to be at increased risk for CPSS, compared with mixed-breed dogs. The increased odds ratios among specific breeds support the hypothesis of a genetic predisposition for CPSS. Clients and veterinarians should consider appropriate diagnostic tests for dogs with clinical signs and those used for breeding from breeds with increased risk of CPSS. (J Am Vet Med Assoc 2003;223:1636–1639)
Comment: 59 Shetland Sheepdogs were included in the report and represented 0.26% of affected dogs. They were one of the 33 breeds more likely to have a diagnosis of CPSS compared to mixed-breed dogs with an increased risk of 5.2. Havanese has the greatest increased risk of 64.9 times that of mixed breed dogs. Mixed-breed dogs with CPSS represented 0.05% of affected dogs.
Departments of Small Animal Clinical Sciences and Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
• Liver - other
Hall-Fonte DL, Center SA, McDonough SP, et al. Hepatocutaneous syndrome in Shih Tzus: 31 cases (1996–2014). J Am Vet Med Assoc, 2016; 248: 802-813.
Results suggested that HCS may have a heritable component in Shih Tzus, although the condition may also be identified in Shih Tzus without affected relatives. .. Previous reports have suggested that HCS is more common in male than female dogs, with a median age of onset of 10 years and a predilection for medium- and small-sized dogs. In a review, 4 of 110 cases, mixed-breed dogs were most common (28%), with breeds represented by ≥ 10 dogs including Shetland Sheepdog, Cocker Spaniel, and West Highland White Terrier. Reportedly, affected dogs are typically examined because of painful cutaneous lesions, lethargy, inappetence, and weight loss, and common clinicopathologic abnormalities include nonregenerative anemia and high hepatic enzyme activities (especially, high ALP activity).