Gallbladder mucocele in a 12-year-old cocker spaniel

Abstract

A 12-year-old, spayed cocker spaniel was presented for panting behavior which had increased over the past several months. A diagnosis of hyperadrenocorticism was made, and ultrasound imaging revealed the presence of a gallbladder mucocele. While often an incidental finding, gallbladder mucoceles can have consequences and require intervention. The etiology, diagnosis, and management of gallbladder mucoceles are discussed.

A 12-year-old, spayed cocker spaniel was presented with abnormal panting which had been increasing over the past several months. The dog had an extensive medical history including: glaucoma with bilateral enucleation, bilateral cruciate repair, hypothyroidism treated with levothyroxine sodium (Eltroxin; GlaxoSmithKline, Mississauga, Ontario), cognitive dysfunction treated with selegiline (Selegiline HCl; Summit Veterinary Pharmacy, Aurora, Ontario), chronic soft stools treated with FortiFlora (FortiFlora; Nestle Purina PetCare Company, St. Louis, Missouri, USA), and osteoarthritis treated with glucosamine (UBAVET Plus; Vet-Link, Toronto, Ontario).

The dog also had a history of consistently elevated alkaline phosphatase (ALP) levels over the past 5 y, for which she was prescribed S-adenosylmethionine (Denosyl, Nutramax Laboratories, Edgewood, Maryland, USA). Four years previously, she had been diagnosed with hyperadrenocorticism based on a low-dose dexamethasone suppression test and was treated with trilostane (Vetoryl; Vétoquinol N.-A., Georges, Lavaltrie, Quebec); this treatment was discontinued after 2 y, however, when she failed to respond appropriately to repeated ACTH stimulations. One year prior to presentation, her bloodwork revealed increased bile acid concentrations, and ursodeoxycholic acid (PMS-Ursodiol C; Pharmascience, Montreal, Quebec) was added to her treatment regime. Ultrasound and liver biopsy performed at that time demonstrated hepatomegaly and steroid hepatopathy, but the dog had shown no clinical signs of hyperadrenocorticism until the time of presentation. Bloodwork was evaluated routinely on this dog; the most recent complete blood (cell) count (CBC), serum biochemistry, and T4 levels were typical for her: platelets 691 × 10⁹/L [reference interval (RI)165 to 550 × 10⁹/L], ALP 2994 IU/L (RI: 23 to 212 IU/L), alanine transaminase (ALT) 107 IU/L (RI: 5 to 95 IU/L), urea 11.2 mmol/L (RI: 3 to 10 mmol/L), chloride 101 mmol/L (RI 107 to 123 mmol/L), T4 26 nmol/L (15 to 51 nmol/L). Physical examination revealed no new abnormal findings.

Given the complexity of this dog’s history, a number of differential diagnoses were considered to explain her recent panting behavior. Possibilities included a clinical manifestation of hyperadrenocorticism or cognitive dysfunction, pain from osteoarthritis, or a mass effect due to hepatomegaly. To better determine the cause, further bloodwork and diagnostic imaging were recommended.

A low-dose dexamethasone test was performed: 0 h: 166 nmol/L (RI: 15 to 120 nmol/L), 2 h: 137 nmol/L (RI: 0 to 10 nmol/L), 4 h: 155 nmol/L (RI: 0 to 10 nmol/L), 6 h: 184 nmol/L (RI: 0 to 10 nmol/L), 8 h: 245 nmol/L (RI: 0 to 10 nmol/L). Abdominal radiographs showed enlarged liver and spleen. Ultrasound revealed a diffusely enlarged liver and a distended gallbladder. The gallbladder contained non-mobile hyperechoic material located centrally, with stellate projections radiating towards the wall. Scalloped hypoechoic material lined the mucosal margin of the gallbladder wall (Figure 1). All other ultrasound findings were normal. The dog was diagnosed with hyperadrenocorticism and a gallbladder mucocele.

Figure 1.

Ultrasound image of the gallbladder mucocele. Note the stellate echogenic material located in the gallbladder lumen.

Given these findings, hyperadrenocorticism was considered to be the most likely reason for the dog’s panting behavior. She was restarted on trilostane to address this condition. The presence of a gallbladder mucocele was an incidental finding in this dog, but one that merited attention and intervention. Treatment options were discussed with the owners, including the inherent risks and benefits of each. Ultimately, the owners opted for medical management of the mucocele. This included S-adenosylmethionine (Zentonil Advanced, Vétoquinol N.-A.), 100 mg in the morning and 150 mg in the evening, PO, with instructions to continue ursodeoxycholic acid (PMS-Ursodiol C, Pharmascience) at her current dose (125mg, PO, twice daily). The dog was to return for abdominal ultrasounds every other week for monitoring of the mucocele, and for ACTH-stimulation tests to monitor her response to the trilostane. One month later, the dog’s gallbladder mucocele appeared unchanged. Her owners reported that her panting seemed to have decreased.

Discussion

A gallbladder mucocele (GBM) is an inappropriate accumulation of mucus or inspissated bile in the gallbladder lumen (1). Once considered a rare condition, GBMs are becoming an increasingly common diagnosis, especially in older, small- to medium-sized dogs (1–3). Cocker spaniels appear to be the most commonly afflicted breed (2–6), while the Shetland sheepdog and miniature schnauzer also tend to be overrepresented (1,4).

While the exact etiology and pathogenesis of GBMs are unknown, histologic findings have consistently demonstrated a dysfunction and proliferation of the mucus-secreting glands in the gallbladder wall (2,4,5). The secreted mucus causes distension, obstruction, and in some cases, eventual rupture of the gallbladder (4–6). It is unclear whether or not the cystic hyperplasia is a primary cause of mucocele formation or secondary to an underlying gallbladder dysfunction or dysmotility (4). Previous research suggesting an inflammatory or bacterial etiology have not been consistently supported (5). Most likely, the etiology is complex and multifactorial (7).

It has been suggested that biliary stasis or an increased concentration of bile salts in the gallbladder lumen encourage the formation of GBMs (5–7). Additionally, alterations in phospholipid concentration seem to be a precipitating factor (5). An association has been found between dyslipidemias (hypertriglyceridemias and hypercholesterolemias) and mucocele formation (4); this includes idiopathic hyperlipidemia of certain breeds, such as the Shetland sheepdog and miniature schnauzer, as well as endocrinopathies known to aggravate lipid metabolism. Dogs receiving glucocorticoid supplementation also appear over-represented (4). A recent study corroborated these findings, reporting that the odds of mucocele formation in dogs with hyperadrenocorticsm were 29 times those of dogs without the condition. Hypothyroidism has also been implicated, but to a lesser extent (1).

Diagnosing a GBM is best done via ultrasound imaging (3). The characteristic appearance is that of an echogenic organized structure in the gallbladder lumen, which is not gravity dependent. This can be distinguished from other biliary sludge by ballottement of the abdomen or repositioning of the patient; the mucocele will be completely immobile (6). The echogenic material tends to be fine and granular, and takes on a stellate appearance. A prominent hypoechoic rim is seen between the mucocele and the gallbladder wall (5,7). The wall itself appears laminated with variable hyperechogenicity and thickness (7).

Initial detection of a GBM on ultrasound sometimes occurs incidentally while evaluating for another disease process, but most often it is found alongside an array of non-specific clinical signs. The most common of these include vomiting, anorexia, and lethargy (2,5). On physical examinaton, more specific findings may include abdominal pain, icterus, fever, tachypnea, and tachycardia (5). A CBC in these dogs is usually unremarkable, but serum biochemistry panels may reveal elevated activities of ALP, ALT, aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT), as well as increased concentrations of blood urea nitrogen (BUN) and total bilirubin (3,5). In some cases which lack clinical signs, an unexplained increase in ALP activity may be the only finding (2).

Surgical treatment via cholecystectomy is recommended for dogs diagnosed with a GBM. This recommendation is based on a number of factors. First, the histologic evidence of mucosal hyperplasia in these dogs indicates that the gallbladder itself is diseased. Also, the semisolid mass of bile-laden mucus that forms in GBMs seems unlikely to pass through the use of choleretics alone. Finally, the risk of rupture and secondary bacterial infections puts the dog at risk until the mucocele has been removed (5). In dogs without clinical signs, surgery can be scheduled on an elective basis. More serious cases, and particularly those with evidence of rupture, should be treated as a surgical emergency (5).

Survival following surgery of this kind tends to be guarded, which reflects the compromised state of the gallbladder at the time of surgery (3,4,8). The perioperative mortality rate ranges from 21% to 32% (3). The most significant pre-operative risk factors are increased ALP and GGT activities and increased bilirubin concentrations, which indicate the extent of cholestasis, and a positive culture of bacteria in the gallbladder, which increases its potential for necrosis and rupture (7,8). The most common adverse event associated with this surgery is bile peritonitis; however, if there is no infection or cholangiohepatitis present, this tends to be a localized problem and is not associated with a poor prognosis for survival (8). Other causes of death within the first week after surgery include sepsis, disseminated intravascular coagulation, and surgical site dehiscence (7). One study documented pancreatitis as a serious complication following surgery for GBMs (6). The highest level of risk is associated with the early post-operative period, and dogs that survive this period are considered to have a good prognosis (8).

Less is known about medical management of GBMs. Medical treatment is generally reserved for animals lacking clinical signs or for those whose owners are unable or unwilling to pursue surgery (4). The mainstay of medical management for a GBM includes ursodeoxycholic acid (10 to 15 mg/kg, PO, divided into 2 doses per day), and s-adenosylmethionine (20 mg/kg, PO, on an empty stomach). It is also recommended that these patients return once or twice a month for ultrasonographic monitoring of their GBM (4). If concurrent hypothyroidism is diagnosed, management with levothyroxine may help to improve gallbladder emptying (3). Low fat diets may also improve biliary flow, especially in patients with confirmed hypertriglyceridemia (3,4). It has also been suggested that impaired enteric bile flow increases the risk of bacterial translocation and complicating infections in these patients; therefore, bile culture or prophylactic treatment with antimicrobials may be indicated (4,6).

Medical resolution of GBMs has been documented; however, the success rate is not encouraging (3). In some cases, the GBM does not resolve, but remains static for long periods of time. Even in subclinical cases, GBMs have been known to transform into an acute clinical condition (4). Clients should be told about the risks associated with medical management. It is also important to educate clients to detect the signs of gallbladder rupture which always requires immediate surgical intervention (3).

In this case, given the dog’s complex medical condition, lack of typical clinical signs, and the inherent risks of anesthesia and surgery, the owners opted for medical management of the GBM. While surgical intervention remains the treatment of choice, cases such as this suggest that further research into the medical management of GBMs will be of great benefit to patients and their owners.