This is a prospective observational study. 30 patients (arbitrarily chosen) were recruited to determine the sensitivity, specificity, positive and negative predicted values of linear EUS for the diagnosis of occult bile duct stone, as well as, possible related adverse events.
Patients
This prospective study was approved by the Institutional Review Board of Kaohsiung Veterans General Hospital, and written informed consent was obtained from all the participating patients beforehand.
Between February 2009 and December 2011, 30 patients with intermediate risk (<67%) for CBD stones [2] were enrolled in our study. Inclusion criteria involved a manifestation of the following set of symptoms/signs at presentation or within six months prior to admission [14] biliary colic, unexplained derangement of liver function tests (such as total bilirubin, alkaline-phosphatase, GOT (glutamic oxaloacetic transaminase)/GPT (glutamic pyruvic transaminase), and γ-GT (Gamma-glutamyl transferase)), enlarged CBD ≧ 8 mm with an intact gallbladder (GB) (≧ 10 mm in patients who had received cholecystectomy) under conventional ultrasound (US) without an identifiable cause, or any combination of the above symptoms/signs such as biliary pancreatitis.
Exclusion criteria included patients with acute cholangitis, history of gastrectomy, sphincterotomy, or sphincteroplasty, possible drug- or alcohol-related liver function impairment, history of CBD stones that had already been found by means of conventional ultrasound/CT scan, tumor of the bile duct that had already been identified, impaired consciousness, and severe cardiovascular or psychiatric diseases.
Diagnostic and therapeutic procedures
Local anesthesia of the pharynx was performed using 10% xylocaine, and an intramuscular injection of 40 mg hyoscine-N-butylbromide and 25–50 mg meperidine were administered as premedication. EUS was performed using a linear-array echoendoscope (GF-C2000, Olympus Optical, Tokyo, Japan) at 7.5 MHz frequency and ERCP was performed with a side-view endoscope (JF-240; Olympus Optical Corporation, Tokyo, Japan) by the same experienced operator (Chan HH). A CBD stone was diagnosed by EUS if a persistent hyperechoic lesion was noted, with or without an acoustic shadow. Once the stone was disclosed by EUS imagery, ERCP with stone extraction was subsequently performed in the same section. This procedure was in compliance with the recently published guidelines by the American Society for Gastrointestinal Endoscopy emphasizing that CBD stones should be removed if detected unless significant mitigating clinical circumstances are present [15].
After selective cannulation of the CBD using a catheter, cholangiography was performed to confirm the diagnosis of a CBD stone. A 0.035-inch guide-wire (Boston Scientific, Corp, MA, USA) was then inserted into the bile duct through the catheter. A dilating balloon (CRE balloon, 5.5 cm in length, 0.8-1.2 cm in diameter; Boston Scientific, Corp, Ireland) was passed via the pre-positioned guide-wire into the bile duct. Using fluoroscopic and endoscopic guidance, the balloon was inflated with sterile saline solution up to the optimal size and duration (usually 3–5 min) according to the stone size and each patient’s tolerance. In order to minimize the risk of perforation, the size of the balloon must not exceed the size of the CBD. After removal of the balloon and guide-wire, the stones were removed using a Dormia basket or balloon-tipped catheter. Each patient was observed in the hospital for at least 24 hours after endoscopic treatment. Procedure-related adverse events were recorded according to the definitions and grading systems of the recent workshop held by the American Society of Gastrointestinal Endoscopy [16]. Clinical evaluation of each patient’s symptoms and serum amylase was performed the following day.
The patients with positive CBD stones found by EUS who subsequently failed ERCP procedures were referred for surgical intervention. If no stone was found by EUS, ERCP would not be performed and patients were followed-up in the outpatient clinic or via telephone for detection of any possible biliary symptoms for up to three months. In the case of recurrence of biliary symptoms that necessitated further treatment during the follow-up period, patients were admitted for ERCP on an in-patient basis or referred for surgical treatment. Figure 1 shows a flow-chart summarizing our study plan.
Patients with stones correctly identified by EUS who were subsequently proved by ERCP or surgery were considered true positive. Patients who had no stones, but were incorrectly diagnosed by EUS and subsequently disclosed by ERCP (with bile analysis) or surgery were considered false positive. Patients who had no stones, but were correctly diagnosed by EUS and found to have no biliary symptoms during the follow-up period, were considered true negative. Patients who had stones in their bile ducts, but were missed by EUS and finally found to be symptomatic during the period of follow-up, were considered false negative.