A Randomized, Single-blind, Controlled Trial of Electroacupuncture for the Treatment of Symptomatic Gallstone Diseases

Introduction:

Gallstone disease is a significant health problem affecting 10%-15% of the adult population. Gallstone diseases include cholelithiasis, choledocholithiasis or intrahepatic gallstones. In Hong Kong, gallstones are found in 2-3% of the population and 20% of the gallstones are symptomatic. To date, cholecystectomy is the gold standard treatment for acute cholecystitis. Laparoscopic cholecystectomy is the preferred modality for elective cholecystectomy and is advised mainly for symptomatic gallstones such as acute cholecystitis or biliary pancreatitis. It is recommended that the cholecystectomy should be performed within weeks after resolution of any episode of complications. However, in Hong Kong, the average waiting time for cholecystectomy ranged from 9 months to years. The prolonged waiting time increases the risk of severe complications such as high conversion rate of acute inflammation, pancreatitis, cholecystitis; obstructive jaundice or gallbladder cancer.

Acupuncture has been extensively applied in clinical practice to treat symptomatic gallstone diseases in the ancient Traditional Chinese Medicine (TCM) diagnoses of hypochondrite pain , jaundice or pyretic thoracic retention. The mechanism of acupuncture had been studied with (1) increasing of the excretory function of gall bladder; (2) increasing the relaxation of the sphincter of Oddi and (3) increasing the secretion of bile. All the above actions aim at promoting the spontaneous clearance of gallstones from the biliary system to the gut. In fact, gallstone clinic are commonly available in acupuncture department of Chinese Medicine Hospitals in China for daily practice. Owing to the poor clinical trial methodology, the evidence of effectiveness of acupuncture were not well established yet.

As a highly recognized traditional therapy, acupuncture has been increasingly used for the treatment of pain. Early studies in both animals and human subjects found that electroacupuncture (EA) stimulation on certain acupoints could induce the release of endogenous opioid peptides and modulate the activities of related receptors in the brain. These opioid peptides mainly include endomorphin, β-endorphin, enkephalins, and dynorphin. Furthermore, EA stimulation also could modulate central neurotransmitters, including serotonin and dopamine, which play important roles in pain signal processing. In addition, it was found that EA can help antagonize smooth muscle relaxation. Based on these findings, EA may be useful in fostering the expelling effect of the smooth muscle of the gallbladder.

There had been case reports and case series supporting the use of EA in the treatment of symptomatic gallstones. However, only one controlled trial has reported EA in treating gallstone diseases on 120 patients with total excretion of gallstones with confirmed with ultrasonography (Treatment group 30% vs control group 16.7%, p<0.05) with stone size smaller than 1cm. However, this study did not report any adverse event during the course of treatment. Apart from absence of adverse events reporting, the reference study did use the percentage of patients with total excretion of gallstone confirmed by ultrasound scanning as the primary outcome. Bearing in mind safety as the first priority, the study did not adopt any blinding in the clinical trial and could overestimate the effectiveness of acupuncture in treating gallstone diseases. With our proposed rigorous conduction of clinical trial in terms of objective assessment of primary outcome and the blinding of assessor, the investigators hope to confirm the effectiveness of acupuncture in gallstone diseases despite of the results published in China. In fact, many patients in Hong Kong are waiting for cholecystectomy with average time of 9 months to years owing to the less urgency of the operation. The investigators hope this study could confirm the effectiveness of acupuncture on gallstone diseases so as to develop more evidence. To substantiate the effectiveness and safety of EA as an alternative intervention for symptomatic gallstones in clinical practice, this study aims at pioneering a well-designed, long-term, large-scale controlled trial for further evaluation of the effectiveness of EA in treating gallstone diseases.