Older small- to medium-breed dogs seem to be predisposed (Norwich 2011). An average age of 9.1 years was found upon reviewing the current literature, but no sex predilection has been established (Aguirre et al. 2007; Besso et al. 2000; Choi et al. 2014; Crews et al. 2009; Malek et al. 2013; Mayhew, Mehler & Radhakrishnan 2008; Mealey et al. 2010; Mesich et al. 2009; Pike et al. 2004; Tsukagoshi et al. 2012; Uno et al. 2009; Walter et al. 2008; Worley et al. 2004). Shetland sheepdogs are predisposed to gallbladder disorders (comprising approximately 24.9% of reported cases), often with concurrent dyslipidaemia or gallbladder dysmotility (Aguirre et al. 2007; Crews et al. 2009). Cocker spaniels and miniature schnauzers are also over-represented (comprising 17.6% and 5% of reported cases, respectively) (Besso et al. 2000; Malek et al. 2013; Norwich 2011).

Clinical signs are often non-specific and include vomiting (approximately 69.3% of cases), lethargy (approximately 44.0% of cases), anorexia (approximately 42.2% of cases), abdominal pain (approximately 19.3% of cases), icterus (approximately 16.3% of cases) and polyuria-polydipsia (approximately 7.8% of cases) (Besso et al. 2000; Pike et al. 2004). The duration of signs is typically for 5 days prior to presentation, with only 71.3% of cases displaying clinical signs (Besso et al. 2000; Choi et al. 2014; Escobar & Neel 2011; Mayhew et al. 2008; Norwich 2011; Pike et al. 2004; Reed, Ramirez & American College of Veterinary Radiology 2007; Walter et al. 2008; Worley et al. 2004).

The results of a complete blood count are usually unremarkable with leukocytosis evident in 46.9% of cases. The leukocytosis can be characterised by a left shift neutrophilia (regenerative or degenerative) (Worley et al. 2004). Serum biochemistry reveals increased liver enzymes, including alkaline phosphatase (98.2% of cases), alanine aminotransferase (87.4% of cases), gamma-glutamyltransferase (85.7% of cases) and aspartate aminotransferase (62.2% of cases). Hyperbilirubinaemia is reported in 83.2% of the cases in the current literature (Center 2009; Malek et al. 2013). Amylase and lipase are also elevated in some cases: 29.5% and 33.3% of reported cases, where measured on serum biochemistry, respectively (Malek et al. 2013; Worley et al. 2004). Cholesterol is often elevated (55.6% of reported cases where measured) (Worley et al. 2004). However, the most significant biomarkers associated with outcome were found to be elevated mean serum lactate concentration and decreased packed cell volume (Malek et al. 2013).

The ultrasonographic appearance is diagnostic and well described in the literature. The classic GBM was described in earlier studies as a finely striated stellate pattern that differs from biliary sludge in that it is non-dependent (Besso et al. 2000). The most common abdominal ultrasonographic findings in dogs with clinically significant GBM include echogenic peritoneal fluid (more frequently confined to the gallbladder fossa), a thickened or laminated gallbladder wall, and an echogenic reaction in the gallbladder fossa (Crews et al. 2009). Ultrasonographic signs of gallbladder rupture were 100% specific and included discontinuity of the gallbladder wall, hyperechogenicity of the cranial abdominal fat, free peritoneal fluid, or a free, well-organised mucocoele within the peritoneal cavity (Center 2009; Crews et al. 2009; Gaschen 2009) (Figures 1 & 2).

A study of 11 dogs that underwent cholecystectomy for GBM examined the relationship between the morphological appearance of the gallbladder content and the ultrasonographic pattern (Uno et al. 2009). This study described three ultrasonographic patterns, namely: pattern one, hyperechoic content filling the entire gallbladder or precipitated immobile content; pattern two, a thin hypoechoic exterior layer separated by an indistinct border from an internal hyperechoic area containing moth-eaten to mosaic-form hypoechoic areas; and pattern three, a thick hypoechoic area in the exterior layer separated by a distinctive border from a prominent internal hyperechoic area. This study concluded that pattern two was a forerunner of the typical kiwi fruit pattern diagnostic for GBM and should indicate the gallbladder dysmotility and cholangiohepatitis that often accompany this disease.

A more recent study examined the ultrasonographic findings and attempted to correlate these with clinical signs (Choi et al. 2014). A larger group of dogs (n = 43) was divided into six groups based on the ultrasonographic pattern, namely: type 1, immobile echogenic bile (23%); type 2, incomplete stellate pattern (30%); type 3, typical stellate pattern (12%); type 4, kiwi-like pattern and stellate combination (26%); type 5, kiwi-like pattern with residual central echogenic bile (9%); and type 6, kiwi-like pattern (0%). The ultrasonographic pattern was not associated with the clinical signs and is thus not a valid diagnostic tool for grading disease.

Gallbladder motility can also be evaluated ultrasonographically. Tsukagoshi et al. (2012) developed a gallbladder ejection fraction index that could be used to estimate dysmotility. Gallbladder volume was estimated on a longitudinal image post-12 hour starve and then 60 and 120 min postprandial (Hills a/d at 10 g per kilogram body weight) in order to calculate this index. This study proposes that gallbladder dysmotility is important in the aetiopathogenesis of GBM due to the increased exposure time of epithelial cells to bile salts.

Hepatobiliary scintigraphy is helpful in determining bile duct patency (Head & Daniel 2005). Findings in animals with chronic, complete EHB obstruction include reduced hepatic extraction fraction (which represents the portion of the radiopharmaceutical that is removed from the plasma on each circulatory pass through the liver), prolonged clearance half-life, inability to view the biliary tree and absence of radioactivity in the intestine (Head & Daniel 2005).

Hepatobiliary scintigraphy was performed in three dogs in the diagnostic work-up of GBM (Worley et al. 2004). Dogs were given 2–3 mCi of technetium Tc 99m-mebrofenin intravenously. All the scintigraphic scans revealed complete obstruction of the extrahepatic biliary system. This diagnostic technique requires registered facilities and has a considerable health and safety risk with accuracies that do not compete favourably with ultrasound.

Approximately 13.5% of GBM have concurrent bacterial colonisation of the gallbladder (Amsellem et al. 2006; Malek et al. 2013; Mayhew et al. 2008; Pike et al. 2004; Uno et al. 2009; Worley et al. 2004). Ultrasound-guided cholecystocentesis is advised to collect a bile sample for bacterial culture and antibiogram testing in animals where medical management is pursued for cholecystitis. However, ultrasound-guided cholecystocentesis should be performed with caution if GBM is suspected as complication rates have not been determined (Center 2009). Complications associated with this procedure include bile leakage, bradycardia due to vagal stimulation, bacteraemia and local haemorrhage (Quinn & Cook 2009).

Cystic mucosal hyperplasia is often seen on microscopic examination of the affected gallbladder wall. Transmural ischaemic necrosis may be seen in the fundic region and precedes gallbladder rupture (Center 2009). The submission of all gallbladders post cholecystectomy is advised.

Large standardised prospective studies are still lacking for medical management of GBM and thus it cannot be recommended as the first line of treatment in dogs. It can be considered in asymptomatic animals and there are individual case reports supporting its use (Norwich 2011; Walter et al. 2008). However, all reported cases had concurrent hypothyroidism that needed to be addressed before resolution of GBM was possible.

Owners must be made aware that asymptomatic cases may develop into an acute clinical emergency should the disease progress to extrahepatic biliary obstruction or gallbladder rupture (Norwich 2011; Quinn & Cook 2009).

The foundation of medical management includes the use of choleretics and hepatoprotectants. Ursodeoxycholic acid is a naturally occurring hydrophilic bile acid that functions as a choleretic and hepatoprotectant at 10 mg/kg – 15 mg/kg PO, as a single dose or divided into two doses per day. S-adenosylmethionine is a naturally occurring precursor of cysteine that is essential in the production of the antioxidant glutathione, and therefore is hepatoprotectant at 18 mg/kg – 20 mg/kg PO, administered once daily on an empty stomach (tablets must not be split). A low-fat diet is encouraged, especially in animals with dyslipidaemias, as dietary management may stimulate biliary flow (Mitchell 2010; Norwich 2011). Concurrent endocrinopathies must be treated appropriately.

Regular monitoring of medically managed cases is recommended, with follow-up visits every 2–4 weeks for abdominal ultrasound, haematology and serum biochemistry. Any progression of the disease process warrants immediate surgical intervention (Center 2009; Quinn & Cook 2009).

Surgical intervention for the treatment of GBM remains the therapeutic gold standard. Pre-operative haematology, serum biochemistry, urinalysis and coagulation profiles are recommended in all cases. Supplementing animals with vitamin K₁ has been advocated pre-operatively, even in the light of normal coagulation profiles. This can be instituted by administering three doses of vitamin K₁ at 0.5 mg/kg SC every 12 hours prior to surgery (Mitchell 2010; Quinn & Cook 2009). However, there are no published studies that support this recommendation.

Cholecystectomy is the recommended surgical procedure for the treatment of GBM. Microscopic examination of the gallbladder wall in cases of GBM indicates that it is diseased and this warrants its removal. However, it is crucial that the patency of the common bile duct is confirmed prior to cholecystectomy, either via manual normograde expression of the gallbladder or retrograde catheterisation of the common bile duct via duodenal enterotomy. The biliary tree must be flushed prior to ligation of the cystic duct in order to remove residual thick, inspissated bile and/or small choleliths to minimise the risk of post-operative biliary obstruction. The resected gallbladder is submitted for microscopic examination and bacterial culture. Liver biopsy (for histopathology, copper, iron and zinc concentrations) is indicated in all cases.

Laproscopic cholecystectomy has been described for cases where biliary tract obstruction or rupture has been excluded (Mayhew et al. 2008).

Cholecystotomy is not recommended as microscopic mural necrosis may be present and could result in post-operative gallbladder rupture. There are also documented cases of recurrence of GBM formation in dogs where cholecystotomy was initially performed (Center 2009).

Cholecystoenterostomy is feasible for rare GBM cases in which the patency of the common bile duct cannot be established. This procedure is, however, associated with a higher complication rate.

Recommended peri-operative care includes feeding a low-fat diet and broad-spectrum antimicrobial and hepatoprotectant therapy as described for medical management (Quinn & Cook 2009).