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Gallbladder dyskinesia (GD) is controversial. We sought to determine the success rate of cholecystectomy or observation in treating patients with GD with intervention decisions based upon clearly defined symptoms.Ninety-three consecutive patients with documented GD were enrolled into a 2-year prospective study. Based upon the presenting symptoms categorized as either classic for gallbladder pathology or atypical, patients underwent cholecystectomy (classic) or observation (atypical). We defined dyskinesia as a cholecystokinin (CCK)-stimulated ejection fraction (EF) <35% on nuclear cholescintigraphy and a negative gallbladder ultrasound.Classic gallbladder symptoms were identified in 61 patients and an atypical presentation occurred in 32 patients. The EF with CCK stimulation was not significantly different between the groups (19±9% vs. 16±7%, P=0.12). Of those with atypical symptoms, 28% (9 out of 32) had resolution of their symptoms without surgery. About 72% (23 out of 32) had worsening or progressive symptoms that did not resolve during observation, and later underwent surgery. Of these, 57% (13 out of 23) had resolution of their symptoms after surgery, but 43% (10 out of 23) had no improvement. Of those with classic symptoms, 60 patients underwent laparoscopic cholecystectomy with resolution of symptoms in 58 (97%). Patients with classic symptoms were 22 times more likely to have relief after cholecystectomy (odds ratio 22.3, P=0.0002). Eight patients had their symptoms recur more than 1 year after surgery (3 atypical and 5 classic) such that at long-term follow-up, cholecystectomy had helped only 43% of the atypical patients and 88% of the classic patients.Classic biliary symptoms are more predictive of success after cholecystectomy in patients with GD than is EF. The symptoms that are most predictive of success after surgery are right upper quadrant pain, pain after meals, and reproduction of the pain after CCK administration. Patients with atypical symptoms are much less likely to have improvement after surgery and should be observed; however, recurrent or progressive symptoms should prompt intervention if all additional testing is negative.