33rd Annual Scientific Meeting proceedings

Gallbladder mucocele (GBM) is defined a distension of the gallbladder due to cystic mucosal hyperplasia with hypersecretion of a thick, gelatinous mucus leading to obstruction of the extrahepatic biliary tree. It has been associated with hypokinesia causing cholestasis, cholecystitis with or without necrotic foci and bactibilia. It can also lead to rupture of the gallbladder and bile peritonitis. GBM development is a life-threatening disease. Death can result with or without surgery and has been reported to be due pancreatitis, cholecystitis, pre-existing peritonitis, biliary leakage causing bile peritonitis, renal failure, biliary (re)obstruction, sepsis, hypotension, aspiration events, multiple organ dysfunction.

Predispositions have been reported with breed (Shetland sheep dog, miniature schnauzer, cocker spaniel), age, gene mutations (ABCB4), underlying hpokinesia & cholestasis, endocrinopathies (hyperadrenocorticism, hypothyroidism), and hyperlipidemia.

Medical management
holecystectomy, although not without risk, is associated with the best long-term outcome in patients with GBM. Medical management can be successful, but it is difficult to predict which patients will respond to treatment, and there are no clear prognostic factors that will predict medical failure. In some studies serum ALP elevation, serum creatinine elevation and hyperphosphatemia are associated with poor prognosis in both surgically and medically managed cases. Medical management typically consists of ursodiol, S-adenosylmethionine, antacids (H2 antagonists, proton pump inhibitors), maropitant, antibiotics and opioids.

Indications for medical over surgical management, or a therapeutic trial attempt before surgery include owner reluctance for surgery, patient that is early in the course of the disease, or if the patient is a poor anesthesia candidate. However, increasing severity of GBM (based on ultrasound and laboratory assessment) is clearly associated with decreased survival for both medically and surgically managed cases, so earlier surgical intervention is considered to be a safer option.

Surgical management – if, when and what
Cholecystectomy is probably the most common procedure performed on the extrahepatic biliary tree and is considered the standard-of-care intervention for sick animals with GBM. Mortality rates in the post-operative period have been high – historically between 22-40% for animals presenting with clinical disease consistent with extrahepatic biliary obstruction or presenting on an urgent basis (such as ruptured gallbladder). More recently, these mortality rates have decreased, as it is now widespread practice to operate on incidentally diagnosed GBM. Studies appear to support that cholecystectomy is associated with improved short- and long-term outcomes for early GBM or “pre-mucoceles”.

The presence of biliary rupture does not necessarily associate with a poor outcome, although this statement may be inaccurate due to the propensity for retrospective studies where biliary rupture was diagnosed ultrasonographically, which can be overestimated. There are some studies which do show increased mortality with biliary rupture. A positive bacterial culture is associated with decreased survival, but this is not often useful information as culture results may not be reported until after surgical intervention.

Complications following surgery include biliary leakage and peritonitis, pancreatitis, re-obstruction, so it is important to minimize these risks with meticulous and gentle surgical technique.

Timing of surgery
If cholecystectomy is considered the standard-of-care, one question is when to go to surgery. Clearly, an overall less clinically affected animal will have a lower ASA score and will be more likely to have an improved outcome. There are a number of institutions where the patient is managed medically to improve clinical condition and stability and then taken to surgery. Others will stabilize or resuscitate as rapidly as possible but not delay surgical intervention. There are no prospective studies to show which option results in lower mortality on non-elective cholecystectomies.

Elective cholecystectomy on the incidentally found GBM is supported by most surgeons today. The patient is stable, with no signs of biliary obstruction, and outcomes have shown to be better compared to clinically ill patients. Many of these patients are candidates for laparoscopic cholecystectomy. The decision to operate laparoscopically or open on patients without evidence of extrahepatic biliary obstruction depends on surgeon familiarity with minimally invasive surgery and patient size.

Intraoperative decisions
Once the decision to operate is made (laparoscopically or open), several considerations still face the surgeon. Firstly, confirm that removal of the gallbladder is the appropriate intervention – once removed, a cholecystoenterostomy cannot be performed. Visual assessment of the extrahepatic biliary tree should be thorough. Obviously, attention should be paid to operative technique. Gentle manipulation of tissues (especially pancreas and biliary tree), keeping viscera warm and moist, avoiding bile leakage and contamination, lavage and suction of the fossa, hemostasis, secure ligatures and suturing are especially important with this surgery, as access does require a degree of liver retraction, mobilization and traction on various viscera such as intestines and pancreas.

Other decisions that need to be considered

Flushing the extrahepatic biliary tree consists of catheterizing and flushing the extrahepatic biliary tree with a red rubber catheter (5-8Fr) and gently instilling warm sterile saline. Over 30% of GBM cases can be considered to have concurrent extrahepatic biliary obstruction, either anatomic or functional, and in these cases flushing is considered critical to ensure post-cholecystectomy patency of the biliary tree by flushing out mucoid debris and inspissated bile remaining in the tract. It is difficult to compare outcomes between flushing or no flushing, as patients that undergo flushing are typically sicker (clinically, ASA score, imaging and laboratory values) than those patients that are not flushed. However, if there is evidence of obstruction on laboratory values or imaging studies, then flushing of the extrahepatic biliary tree should be undertaken. Early or incidental mucoceles that are cut on “healthy” animals do not appear to benefit from flushing. The flushing procedure is not completely benign – it increases surgical time, can cause rupture of the cystic, hepatic or bile ducts, and increases risk of post-operative pancreatitis.

Flushing can be performed in a retrograde or normograde direction. Retrograde flushing involves catheterizing the bile duct through the major duodenal papilla via an antimesenteric duodenotomy. Normograde flushing involves catheterizing the cystic duct. Either way does not impact short- or long-term survival, but it appears that normograde flushing results in fewer complications, and we recommend that this be attempted initially. It also makes intuitive sense to flush components in a normograde direction towards the bowel lumen. Normograde catheterization can be challenging to advance the catheter past the sharp angle from the cystic duct into the bile duct, but flushing can also be performed without fully advancing the catheter into the bile duct and duodenum, as long as one can visualize flow through the bile duct.

Histopathology – both the gallbladder and a liver biopsy should be submitted for histopathology. Some pathologists prefer several biopsies from multiple lobes.

Culture (bile and gallbladder wall) – Some studies report decreased survival with positive biliary culture, which occurs in about 20% of cases. Most common isolates are E. coli, Enterococcus spp, Clostridium spp, alpha-hemolytic Streptococcus, Acinetobacter spp, Staphylococcus epidermidis. Because of the more guarded outcome with bactibilia, all dogs undergoing cholecystectomy should receive empiric antimicrobial therapy, and a sample of bile and gallbladder wall should be submitted for aerobic and anaerobic cultures.

Choledochal stenting – the most common indication for temporary biliary stenting for GBM is when there is functional obstruction to the bile duct from pancreatitis. As cholecystoenterostomy should not be performed with GBM due to intrinsic pathology of the gallbladder, stenting may be the best way (cf cholecystostomy tube) of ensuring patency of the extrahepatic biliary tree until the obstruction has resolved. The stent is placed via an antimesenteric duodenotomy and can be a human choledochal stent with flange, pigtail catheter, or less ideally a shortened red rubber catheter sutured in place. A guidewire can be used to facilitate placement.

Abdominal drainage – Placement of a closed-suction abdominal drain should be considered in the face of bile peritonitis. Alternatives are planned relaparotomy, abdominal negative pressure therapy or open abdominal management.

The surgeon needs to be competent and prepared to perform multiple procedures when performing cholecystectomy for GBM. Surgical plans may alter in surgery and being able to make prudent and rational intra-operative decisions and carry them out in a timely fashion, logical order and with meticulous technique will impact short-term morbidity and mortality. The importance of long-term follow up is not to be underestimated.