Uncomplicated gallbladder mucoceles – is it better for prognosis to perform cholecystectomy or medically manage?

PICO question 
In dogs with an uncomplicated gallbladder mucocele, is the long-term survival when surgically managed superior, inferior, or equal to those medically managed? 
  
Clinical bottom line 
Category of research question 
Treatment and prognosis 
The number and type of study designs reviewed 
Three papers were critically reviewed. All of the studies were retrospective analyses of medical records, two of which were cohort studies, and one which was a case control study 
Strength of evidence 
Weak 
Outcomes reported 
There is some evidence that surgical management of gallbladder mucoceles is associated with longer survival times than medically managed cases, although there is no direct analysis of uncomplicated vs complicated cases 
Conclusion 
We cannot clearly make a conclusion based on the available evidence. To date, there is only one retrospective analysis that directly compares the long-term survival of cases medically vs surgically managed, but this study does not separate uncomplicated vs complicated cases of gallbladder mucocele. In order to more accurately determine which type of treatment should be recommended for uncomplicated cases of gallbladder mucoceles, a prospective study comparing long-term survival with each treatment should be performed. These studies should also standardise medical management in order to more accurately compare survival time to surgical treatment 
  
How to apply this evidence in practice 
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. 
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care. 
  



The evidence
The evidence consists of retrospective analyses of medical records from various veterinary hospitals, primarily cohort studies with one case control study performed in the UK. Retrospective studies have inherent biases, and therefore provide weaker evidence than prospective analyses. To date, only one study directly compares long-term survival between surgically and medically managed cases (Parkanzky et al. 2018). Other studies included in this Knowledge Summary did not primarily aim to determine mean survival time between the two treatment types, but did provide some survival data. None of these studies directly compared medical and surgical treatment in uncomplicated cases of gallbladder mucoceles, and instead included both uncomplicated and complicated cases. As a result, it is difficult to establish a meaningful clinical difference in mean survival time between medically and surgically managed cases of uncomplicated gallbladder mucoceles in dogs. In order to better answer this question, more prospective analyses of medically and surgically managed cases of uncomplicated gallbladder mucoceles should be performed.  year and there was no statistically significant difference in survival time according to breed status • There was not a statistically significant difference in 7 days, 6 months, or 1 year survival between medically managed and surgically managed groups • MST could not be calculated for any group (<50% case fatality rate)

Limitations:
• This is a retrospective study, and therefore has more bias than a prospective study • This study focused on a single breed, and thus may not be applicable to the canine species as a whole • It is unclear how many dogs from the medically and surgically managed groups had uncomplicated cases of GBM vs complicated cases of GBM • While the researchers did provide some survival data for the GBM cases, over 50% of the population were still alive at the time of census thus they could not calculate an MST

Limitations:
• This is a retrospective study, and therefore has more bias than a prospective study. Specifically, diagnostic approach, recommended treatments, and case follow-up varied between case and attending clinician • Many cases were censored by researchers due to lack of follow-up data -more in the medically managed group than the surgically managed group • Survival analysis also excluded patients that died before 14 days, and it is unclear which of these patients were uncomplicated vs. complicated cases of GBM (second Kaplan-Meier analysis was included to remove death in the postoperative period) • Does not discuss or separate cases of uncomplicated GBM from complicated cases (gallbladder rupture, peritonitis, extrahepatic biliary tract rupture) • Unable to determine if the group that was both medically and surgically managed received surgical treatment because they were complicated cases vs uncomplicated • Medical management was not standardised • Unequal treatment group sizes • Groups varied significantly in sex and in spay/neuter status  • All dogs that survived the postoperative period were alive at follow-up (18/23 that had surgery), and owners described the clinical outcome after surgery as excellent (complete resolution of clinical signs). Mean follow-up time was 13.9 months with a range of 1.0-34.0 months • Cholecystectomy for dogs with GBM is associated with substantial perioperative mortality rate of 21.7% (5/23)

Limitations:
• This is a retrospective study, and therefore has more bias than a prospective study • Patients were included in the study if they had ultrasonographic evidence of GBM, but it is unknown if these records were reviewed in a consistent manner before patient inclusion • Follow-up information was only collected for patients that underwent cholecystectomy, which is applicable to the purpose of this study but does not evaluate long-term survival outcomes for patients that either underwent medical management or those that did not receive surgical treatment • Mean follow-up period was 13.9 months (range 1-34 months), and was only collected from a total of six dogs, although researchers attempted to reach all surviving patients' owners; survival analysis was performed • Does not discuss or separate cases of uncomplicated GBM from complicated cases (gallbladder rupture, peritonitis, extrahepatic biliary tract rupture) • Outcome of the patient's clinical signs was owner reported, although there was some standardization in how they were classified as either excellent, fair, or poor based on researcher definition

Appraisal, application and reflection
Traditionally, GBM cases are presented on an emergent basis due to gallbladder rupture or other complications (peritonitis, extrahepatic biliary tract rupture, etc.), but more cases are presenting with incidental ultrasonographic findings of uncomplicated GBM (Smalle et al. 2015). Usually these emergent cases are treated surgically with a cholecystectomy, but little is known about treatment recommendations for incidental and uncomplicated cases. Parkanzky et al. (2019) showed a significantly longer difference in long-term survival for surgically managed cases over those medically managed cases of canine GBM, but this was a retrospective analysis of medical records and did not separate uncomplicated cases from complicated cases. The method of medical management was also not standardised between patients. There were also more patients lost to follow-up in the medically managed group than the surgically managed group, which may lead to bias in the analysis of long-term survival. The retrospective nature of this study also creates implicit bias due to differences in diagnostic approach, recommended treatments, and case follow-up that may vary between case and attending clinician.
Other studies included in this Knowledge Summary did not primarily aim to compare MST between the two treatment types, but did provide some survival data. Allerton et al. (2018) reported survival in Border Terrier and non-Border Terrier cases with GBM. There was data provided at 7 days, 6 months, and 1 year survival between medically and surgically managed cases, but with no significant difference between the groups at any of the follow-up periods. There were significantly more dogs in the surgically managed group than the medically managed group (77 and 12 respectively). However, the aim of this study was to determine if there was a breed disposition for GBM in Border Terriers, and comparison of medical and surgical management was not the primary outcome measure. Pike et al. (2004) does not provide long-term survival analysis, but does provide some survival data in which all of the patients that survived 14 days post-surgery were still alive after an average follow-up of 13.9 months (range 1.0-34.0 months). This data was only provided on six of the patients in total, further limiting conclusions that can be drawn from the study as it relates to the PICO question.
The application of the included studies is still debatable. There are currently no prospective studies comparing medical and surgical management of uncomplicated GBM in dogs. In order to more accurately recommend which type of treatment will offer better long-term survival in uncomplicated cases of gallbladder mucoceles, a prospective study comparing MST between surgically and medically managed cases would be ideal, but would likely not obtain ethical approval.

Search Strategy
Databases searched and dates covered: