01/27/2023
CASE OF THE MONTH: Impending Mucocele in an 11 year old FS Dog
This patient was referred for ultrasound due to a persistent and progressive ALP elevation. She had no clinical signs at the time of the ultrasound. Her gall bladder had echogenic, non-mineralized, non-dependent sludge with a hypoechoic to anechoic rim in between the sludge and inner GB wall (suspected entrapped mucus). No inflammatory changes in the GB wall or surrounding tissue. This patient was managed medically with a plan to recheck lab work and ultrasound in 4 weeks.
TAKE HOME TIPS ON MANAGING MUCOCELES:
1) Not all dogs have clinical signs.
2) The most common signs are vomiting, abdominal pain, and anorexia. Lab work changes can include elevated liver values (one or several) and leukocytosis.
3) Dogs with a mature or impending mucocele should be screened for diseases that cause hypercholesterolemia/hyperlipidemia (adrenal hyperplasia diseases, diabetes mellitus, hypothyroidism)
4) Dogs that have sonographic evidence of a mucocele and also have clinical signs and associated lab abnormalities should be treated surgically
5) Ursodiol should not be used if sonographic evidence of gall bladder wall inflammation or impending rupture exist
Below is a detailed article about the management of mucoceles in dogs.
GALLBLADDER MUCOCELES
Description:
A gallbladder mucocele occurs when the gallbladder becomes overly distended with an excessive accumulation of mucus secondary to cystic mucosal hyperplasia. Previously, pathologists noted this finding at necropsy and considered it an incidental or age-related lesion. In the last decade, however, it has become evident that not all gallbladder mucoceles remain clinically silent and that they can in fact be associated with extrahepatic bile duct obstruction (EHBDO), cholecystitis, and gallbladder wall rupture. Approximately 50% of mucoceles may result in necrosis and rupture, typically at the neck or fundic region of the gallbladder. The etiology of these mucoceles remains unknown, but researchers suspect that it is related to disordered cholestasis and/or lipid metabolism. Suggested causes include: primary or secondary gallbladder motility disorder; dyslipidemia/hypercholesterolemia; extrahepatic bile duct obstruction; and primary or secondary disorders of mucus-producing cells, such as cystic mucosal hyperplasia of the gallbladder wall. Clinical correlation is also seen with cholangitis, cholecystitis, cholelithiasis, biliary obstruction from cholelithiasis or neoplasia, and pancreatitis. Abnormal adrenal hormones may also play a causal role in altering gallbladder mucus secretion. Hypothyroid dogs are three times more likely to develop a mucocele, and Cushinoid dogs are twenty-nine times more likely to do so. Vacuolar hepatopathy frequently co-occurs with mucoceles; practitioners are therefore advised to investigate underlying disorders associated with vacuolar hepatopathy. Bacterial infection of the gallbladder has been associated with increased mucin production in dogs; this condition may also become pathological and lead to excessive mucus accumulation. In humans, hypercortisolism is related to chronic cholecystitis and changes the biochemical composition of bile. The latter, however, was not substantiated by two studies evaluating bile composition, bacterial infection, and sludge formation during a three-month period of exogenous administration of hydrocortisone administration in dogs. There is a marked increase in the prevalence of mucocele formation in dogs with naturally occurring hyperadrenocorticism, but a definitive correlational mechanism has yet not been ascertained. Mucoceles are most commonly seen in middle-aged to older dogs (median age of 10 years); however, researchers have reported mucocele development in dogs as young as 3 years old. Certain breeds—Miniature Schnauzers, Shetland Sheepdogs, Cocker Spaniels, Shih-tzus, Pugs, Bichon Frisés, Schipperkes, West Highland White Terriers, and Scottish Terriers—appear to be overrepresented among canine patients. Significant predisposition to mucocele formation in Shelties prompted an investigation that uncovered a specific genetic mutation in the ABCB4 gene, which functions in the translocation of phosphatidylcholine across hepatocyte cell membranes. In the future, we may be able to screen young Shelties for this mutation, which would allow us to monitor gallbladder mucocele development with ultrasound over time and thereby offer early dietary and medical management, or even surgical intervention as needed. Felines are less commonly affected.
Clinical Signs:
According to several retrospective studies, the most common clinical signs include vomiting (87%), abdominal pain (87%), anorexia (78%), lethargy, icterus (57%), and fever (26%). The average duration of illness is 5 days. Focal pain upon examining the gallbladder is common and referred to as a positive Murphy sign. Patients may also be asymptomatic, despite biochemical abnormalities, even in the face of ultrasonographic evidence of a mucocele. Patients with fully formed mucoceles are at risk of further complications, such as gallbladder rupture, peritonitis, sepsis, and related coagulopathies, and should be considered for surgical intervention.
Diagnostics:
Biochemical analyses may indicate leukocytosis, with or without a left shift, and most commonly reveal elevated hepatic enzymes (SAP 100%, GGT 86%, ALT 77%, AST 60%) and bilirubin (63%). Ultrasonographic findings may include: a distended gallbladder with centrally suspended luminal content and a hypoechoic intraluminal rim; a thickened gallbladder wall; intraluminal stellate; echogenic striations (the “kiwi fruit sign”); and/or the presence of non dependent intraluminal contents or sludge. (Note: The presence of the “kiwi fuit sign” is not essential for the diagnosis of a gall bladder mucocele, as many mucocele variations do not demonstrate a complete stellate pattern.) A hypoechoic ring seen around the gallbladder may indicate wall edema or early rupture. Presence of free fluid, as well as localized, echogenic hepatic parenchyma and intra-abdominal fat, are also consistent with bile leakage and peritonitis. Pain is often noted upon interrogation of the area. Dilation of the common bile duct may also be present.
Since there exists an association between hypercholesterolemia/hyperlipidemia and gallbladder mucoceles, patients that exhibit both should be screened for hypothyroidism, adrenal hyperplasia syndromes (Cushing’s disease and s*x hormone dysregulation), diabetes mellitus, pancreatitis, exogenous exposure to glucocorticoids, and necroinflammatory liver disease.
Treatment:
Surgical intervention is recommended due to the significant risk of peritonitis and sepsis associated with rupture, and since medical management on its own may not be effective. Candidates for surgery must be adequately stabilized prior to surgery, and a coagulation panel should be assessed beforehand. Use of ursodeoxycholic acid (Actigall) is not recommended if any sonographic aspects of wall inflammation or emergent perforation are present. Percutaneous centesis of the gallbladder is also not advised in the presence of a mucocele. Some studies that have investigated a relatively small number of dogs have found medical therapy with Actigall and SAMe to be somewhat effective at a very early subclinical stage. Yet, there are no definitive guidelines for ascertaining whether certain sonographic or laboratory findings permit the differentiation of a clinically significant mucocele versus a non-clinical, stable mucocele that may become clinically significant in the future. For this reason, each patient must be assessed individually. It may be the case that very dramatic mucoceles do not cause any overt clinical signs, whereas other patients may have minor mucoceles that lead to significant clinical signs and necessitate urgent cholecystectomy to avoid the onset of bile peritonitis due to rupture. It is generally advised that dogs with clinical signs, elevated liver enzymes, elevated WBC counts, and sonographic evidence of a mucocele be treated surgically. However, if a clinically silent mucocele is found incidentally on ultrasound, careful observation and monitoring is reasonable, provided there are no underlying diseases that may promote degradation (e.g., hyperadrenocorticism). Owners should be instructed to carefully monitor their pets for the development of clinical signs that may signal progression of the disease. Antibiotic therapy directed towards gram-negative, enteric bacteria (i.e., E. coli, Klebsiella, Enterobacter, etc.) and anaerobic bacteria is indicated, and will likely be necessary for several weeks following surgery. Culture and sensitivity results should guide long-term treatment. Cholecystectomy with a possible bile duct transposition is the procedure of choice. The bile duct is often flushed to remove sludge and debris to help avoid post-surgical obstruction. Cholecystotomy for removing gallbladder contents is not advised as studies have shown that mucocele concretions have reformed in several dogs treated in this manner. At the time of surgery, one should obtain liver biopsies as well as submit cultures and sensitivity of the gallbladder contents. Liver biopsies may show normal tissue, cholangiohepatitis, biliary hyperplasia, vacuolar hepatopathy, or mild to moderate portal hepatitis/fibrosis with bile duct proliferation. Ultrasound guided cholecystocentesis is not recommended in dogs with mature mucoceles due to the risk of gallbladder rupture and seeding the abdomen with bacteria. Rupture of the gallbladder constitutes a surgical emergency and carries a worse prognosis for survival. Several investigators have noted that, upon surgical exploration of asymptomatic mucocele patients, there is evidence of prior localized peritonitis and fibrosis, likely resulting from tears in the gallbladder’s neck, which lead to minute amounts of bile leakage.
Conclusion:
Possible etiological explanations for gallbladder mucoceles are quite varied, and underlying diseases must be treated. The treatment of choice is cholecystectomy, with surgical intervention especially recommended for patients with clinical signs or significantly elevated liver enzymes so as to avoid gallbladder rupture and subsequent peritonitis.
