The “Excitable” Gallbladder: Cholecystectomy for symptomatic acalculous hyperkinesia in adults

Introduction: In addition to biliary colic from gallstones (calculous biliary colic), cholecystectomy for acalculous biliary colic associated with gallbladder hypokinesia is the Standard of Care and has shown good outcomes. The opposite of hypokinesia or the "lazy" gallbladder [HIDA scan Ejection Fraction (EF) < 38%], is hyperkinesia (the "excitable" gallbladder; HIDA EF > 80%). Although recognized in children, cholecystectomy is not the Standard of Care for acalculous biliary colic from gallbladder hyperkinesia in adults. The primary objective of the study was to test the hypothesis that gallbladder hyperkinesia is involved in the pathogenesis of biliary colic in the absence of gallstones in adults, and that symptomatic acalculous gallbladder hyperkinesia should be a new indication for cholecystectomy in adults. Although there are occasional publications supporting cholecystectomy for gallbladder hyperkinesia, ours is the first study that compares outcomes in patients that did not have cholecystectomy.

Methods: We performed a retrospective, case-control series, comparing outcomes of adults with symptomatic acalculous gallbladder hyperkinesia that had cholecystectomy (Study Group) or did not have cholecystectomy (Control Group). Institutional electronic medical records were analyzed of all patients that had HIDA scan between January 2013 and September 2018, and clinical progress was followed up in the records until December 2019. Eligibility criteria included absence of gallstones on ultrasound, clinical presentation compatible with biliary colic, and evidence of adequate clinical or diagnostic workup to exclude other common causes of upper abdominal pain.

Results: Out of a total of 1477 consecutive HIDA scans done during the 5.75 years studied, we identified a cohort of 46 adults with symptomatic acalculous gallbladder hyperkinesia that met the eligibility criteria out of 327 HIDA scans with ejection fraction >80%. Out of these 46 patients, 21 had cholecystectomy (Study Group) and 25 did not (Control Group). Demographics of the cohort (mean+standard deviation) in Study and Control Groups, respectively, were age 39+14 and 40+6, BMI 29.1+7.1 kg/m² and 28.9+5.2 kg/m², and HIDA EF 91+6% and 93+6%, with 18 (86%) and 15 (60%) females in each group. In the Study Group, 18/21 patients (86%) had amelioration of biliary colic soon after cholecystectomy. In contrast, the vast majority of controls (20/25 or 80%) continued to suffer with biliary colic even after a mean follow-up of nearly three years (Wilcoxon rank sum test, p<0.01), with odds of success 19.7 times with cholecystectomy that was independent of demographic variables (univariate Firth penalized logistic regression, p<0.01). Histopathological examination (H- & E-stain) of gallbladder specimens from all 21 cholecystectomy cases showed chronic cholecystitis as evidenced by mild to moderate lymphocytic infiltration (21/21, 100%), transmural fibrosis (21/21, 100%), tunica muscularis thickening (16/21, 76%), and epithelial pyloric metaplasia (3/21, 14%), compared to historical normal gallbladder specimens that only showed occasional patchy lymphocytic infiltration.

Conclusions: Symptomatic acalculous gallbladder hyperkinesia could be a new indication for cholecystectomy in adults and prospective trials are needed to confirm or refute our preliminary observation. The histopathological findings support our central hypothesis. By using the strict Firth logistic regression analysis we have addressed the small sample size limitation of our study. If the need for cholecystectomy to reduce pain in acalculous biliary colic from the “excitable” gallbladder is confirmed, it will have healthcare relevance across several disciplines including primary care clinicians, emergency department practitioners, specialists such as gastroenterologists and cardiologists, nuclear medicine radiologists, and surgeons.