Pilot Randomized Controlled Trial of Laparoscopic Cholecystectomy vs Active Nonoperative Therapy for the Treatment of Biliary Dyskinesia

Abstract

Introduction Despite widespread adoption by the surgical community, high-quality prospective data supporting the practice of laparoscopic cholecystectomy (LC) for the treatment of biliary dyskinesia (BD) is lacking. Methods Adult patients meeting criteria for diagnosis of BD (Rome III symptoms, normal ultrasound, gallbladder ejection fraction<38%) were randomized to either LC or a trial of non-operative (NO) therapy with a low-dose neuromodulator (amitriptyline 25mg/day). Patients in the NO arm were allowed to cross over to the surgical arm and remain in the study for any reason. Besides collection of basic demographics and medical/surgical history, patients were administered a standardized quality of life (QOL) assessment (SF-8) and a symptom-specific questionnaire (Rome III criteria) at enrollment and monthly through the study to assess the effect of treatment on biliary symptoms and overall QOL. Results Thirty patients were enrolled over 12 months (15LC, 15NO). In the LC group, 13 underwent LC, 1 refused surgery, 1 withdrew. In the NO group, 14 crossed over to the LC group (of which 13 had LC), yielding 26 patients who underwent LC. SF-8 physical scores (PCS-8) were significantly improved at both the first and last follow-up visits (p<0.0001, p=0.0003 respectively). SF-8 mental scores (MCS-8) were also significantly improved at both the first and last follow-up visits (p=0.0187, p=0.0017 respectively). With median follow-up of 12 months [range 3–14], all 26 reported relief of pain. Conclusions This pilot study raises doubts regarding the feasibility of a randomized trial, presumably due to both clinician and patient bias toward LC and the lack of “gold-standard” non-operative treatments. However, these prospective data indicate that, with careful patient selection (standardized symptom criteria/imaging methodology), LC results in pain relief and significant improvement in QOL in BD patients. Further prospective study of these findings is warranted.

Systematic review with meta‐analysis: cholecystectomy for biliary dyskinesia—what can the gallbladder ejection fraction tell us?

“…One hundred four studies were further excluded on initial review with reasons for exclusion noted. Forty‐six studies were included; a further 17 were excluded due to lack of a matching comparator group; 29 were included in the final quantitative analysis (Table and Figure ) …”

“…Retrospective case series carry inherent high risk of bias therefore they were not separately analysed. The RCT by Richmond was considered to be at a high bias risk in the domains of performance and detection bias, due to a lack of study blinding. Additionally, it had an unclear bias risk in both the domains of selection bias.…”

“…Fifteen studies reported using a laparoscopic approach to cholecystectomy, the first of which was published in 1997 by Khosla et al Although a formal comparative subgroup analysis of patients undergoing laparoscopic vs conventional cholecystectomy was not performed by us, two prospective studies in low GBEF patients seemed to indicate that careful patient selection based on symptoms and imaging methods was more predictive of successful outcomes than GBEF value, even when using a laparoscopic approach …”

“…To address this variability, the Society of Nuclear Medicine recommends using a dose of 0.02 µg/kg infused at a constant rate via an infusion pump or slow drip over 60 minutes, with imaging and quantification over the entire 60‐minute period as the method of choice . In the studies included in this analysis, only one study (Richmond et al) used the now recommended 60 minute infusion protocol. Yap used a 45‐minute infusion; nine studies did not report this information and most of the remaining studies used a much shorter duration of infusion of CCK ranging from 2 to 30 minutes; an approach that has been associated with false‐positive results (falsely‐low GBEF) and a higher rate of adverse effects .…”

“…Statistical comparisons which had a “0” value attributed to its both arms were excluded (eg Watson et al had zero patients in both low vs normal GBEF arms, and Nusrat et al had zero patients with “improvement/cure” post‐cholecystectomy in the low versus normal GBEF arms (Figure ). Similarly, Richmond et al had zero patients classified as “persistent/worse” in both‐operative and non‐operative arms (Figure ) thus excluding these comparisons; see references below).…”