Diagnostic yield of endoscopic ultrasonography in patients with intermediate or high likelihood of choledocholithiasis: a retrospective study from one university-based endoscopy center

Choledocholithiasis is a common condition, which occurs in 10–20% of patients with cholelithiasis, 7–14% of patients who have undergone cholecystectomy, and 18–33% of patients with acute biliary pancreatitis [1]. Management of patients with suspected choledocholithiasis requires confirmation of stones in the common bile duct (CBD).

Diagnosis of choledocholithiasis is based on clinical signs and symptoms, levels of serum markers of cholestasis, and imaging examination findings (transabdominal ultrasonography), but these factors are not highly sensitive or specific. Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard method for diagnosis and treatment of choledocholithiasis. However, as indiscriminate use of ERCP increases the risk of procedure-related complications [2], ERCP is almost exclusively reserved for therapeutic purposes, and choledocholithiasis is usually diagnosed using non-invasive methods.

The benefits of using endoscopic ultrasonography (EUS) for the detection of CBD stones were described by Amouyal et al. in 1989 [3]. EUS is less invasive than ERCP, and has excellent sensitivity and specificity for the detection of CBD stones [4, 5]. Considering the increasing availability of EUS in hospitals, and recent reports that EUS may have a higher diagnostic accuracy than magnetic resonance cholangiopancreatography for the detection of small CBD stones (<5 mm), EUS should be recommended for the detection of CBD stones instead of ERCP, to minimize the risk of procedure-related complications. According to the 2010 American Society for Gastrointestinal Endoscopy (ASGE) guidelines [6], which mainly cite the studies by Bakun et al. and Abboud et al. [7, 8], an EUS-guided management algorithm may be cost-effective for patients with an intermediate risk of choledocholithiasis, while an ERCP-guided approach may be more economic in patients with a high risk of choledocholithiasis. However, we experienced several patients at our institution who fulfilled the criteria for a high likelihood of choledocholithiasis and underwent ERCP, in whom no stones were detected. Ang et al. [9] reported that CBD stones were detected in only 29.6% of the 112 patients in their study who fulfilled the criteria for a high likelihood of CBD stones, which is lower than previously reported rates [9‐13]. We postulate that discrepancies between the likelihood of choledocholithiasis and the detection of CBD stones on EUS may be related to the length of time between the initial clinical presentation and the EUS examination, and that ERCP may not always be more appropriate than EUS in patients who fulfill the criteria for a high likelihood of choledocholithiasis. The aims of this study were to determine the diagnostic yield and optimal timing of EUS in patients with an intermediate or high likelihood of choledocholithiasis requiring therapeutic ERCP, and to identify the factors associated with detection of CBD stones in our endoscopy clinics.

Ninety-three patients were included in the study, out of a total of 914 patients who underwent ERCP for CBD stone removal between June 2009 and January 2012. The mean (±SD) age of the patients was 61.0 (±15.6) years (range, 26–85 years), and 47 (50.5%) were men. The mean (±SD) time between the initial clinical presentation and the EUS examination was 37.6 (±56.6) days (range, 1–420 days). The most common clinical manifestations were abdominal pain, jaundice, and fever, which occurred in 74.2%, 29.0%, and 23.7% of patients, respectively. Leukocytosis was found in 25.8% of patients. The bilirubin level was abnormal in 53.2% of patients, and the mean (±SD) total bilirubin level was 2.9 (±4.4) mg/dL (range, 0.2–34.8 mg/dL). Abnormal liver enzyme levels were found in 71.2% of patients. The mean (±SD) serum glutamic-oxaloacetic transaminase level was 169.9 (±206.9) U/L (range, 10–936 U/L), the mean (±SD) serum glutamic-pyruvic transaminase level was 158.3 (±203.2) U/L (range, 7–1376 U/L), and the mean (±SD) alkaline phosphatase level was 174.3 (±156.4) U/mL (range, 36–885 U/mL). According to the clinical classification criteria described previously [6], 52.7% of the patients had an intermediate likelihood of choledocholithiasis and 47.3% had a high likelihood choledocholithiasis.

EUS found CBD stones in 29 of the 93 patients (31.2%). Thirty-three patients underwent ERCP on the same day as their EUS examination, including 29 with CBD stones detected on EUS (28 truly positive) and 4 without CBD stones detected on EUS (all truly negative). EUS therefore had a sensitivity of 100% and specificity of 80% for detection of CBD stones, with a positive predictive value of 96.55% and a negative predictive value of 100%. Patients who did not have CBD stones detected on EUS were followed up. The mean (±SD) follow-up period was 10.2 (±7.9) months (range, 1–41 months). Thirty-four patients (36.6%) were lost to follow-up within 6 months. All the patients lost to follow-up were contacted by telephone, and none of them experienced any abdominal pain suspicious of biliary colic or underwent ERCP for stone removal at another hospital.

Table 1 shows the EUS and ERCP findings. CBD stones were detected in 22.44% of patients with an intermediate likelihood of choledocholithiasis and 38.63% of patients with a high likelihood of choledocholithiasis.

Univariate analyses of the factors potentially associated with choledocholithiasis are shown in Table 2. An elevated alkaline phosphatase level and EUS examination within 7 days of the initial clinical presentation were associated with detection of CBD stones.

Subgroup analysis was performed to compare patients who underwent EUS within 7 days of the initial clinical presentation and patients who underwent EUS more than 7 days after the initial clinical presentation. An alkaline phosphatase level of >133 mg/dL (area under the curve, 0.576) was the only factor associated with detection of CBD stones in patients who underwent EUS more than 7 days after the initial clinical presentation (odds ratio: 4.87, p = 0.01) (Table 3). Additional analyses of individual or combined choledocholithiasis predictors that are classified as “strong” or “very strong” in the ASGE guidelines [6] did not show significant associations between these factors and the detection of CBD stones (data not shown).

The reported sensitivity and specificity of non-invasive imaging examinations for the detection of CBD stones are 25–58% and 68–91%, respectively, for transabdominal ultrasonography; and 87% (95% CI: 84–90) and 97% (95% CI: 95–98), respectively, for computed tomography [14]. Magnetic resonance cholangiopancreatography has a sensitivity of approximately 91% (95% CI: 73–97) for detection of CBD stones, depending on the stone size as follows: 67–100% for stones >10 mm, 89–94% for stones 6–10 mm, and 33–71% for stones <6 mm [14]. The optimal initial non-operative investigation for the detection of CBD stones is therefore still unclear.

Although ERCP is the gold standard method for detection of CBD stones, with a reported sensitivity of 90% and specificity of 98%, indiscriminate use of ERCP results in an increased rate of associated complications. ERCP is therefore almost exclusively used for therapeutic purposes, with non-invasive tests used for the detection of CBD stones. EUS is a new, less invasive imaging technique that has shown very good sensitivity (95%) and specificity (98%) for the detection of CBD stones [4, 5]. In this study, EUS detected CBD stones in all the patients who were truly positive for CBD stones, with only one false-positive case. Retrospective review of the EUS images from the false-positive case showed a suspected echo artifact. EUS should be the imaging examination of choice for the detection of CBD stones, because of its high sensitivity and specificity. EUS is as effective as ERCP for detecting CBD stones, and has fewer procedural risks and complications. However, EUS also has some disadvantages, including the high cost, the need for expertise in the procedure, and the lack of availability in some hospitals.

The present study included almost equal numbers of patients with intermediate and high likelihood of choledocholithiasis. CBD stones were detected in 22.44% of patients in the intermediate likelihood group and 38.63% of patients in the high likelihood group. These results differ from previous studies, which reported detection of CBD stones in up to 40% of patients in the intermediate likelihood group and 60% of patients in the high likelihood group [10‐15]. We postulate that the lower rate detection of CBD stones in our study may reflect spontaneous passage of the stones, which is reported to occur at a rate of 20% per week [16], and would be affected by the time between the initial clinical presentation and the EUS examination. Our findings therefore support the potential cost-effectiveness of EUS for patients with an intermediate likelihood of choledocholithiasis suggested by the ASGE algorithm, and the performance of EUS-guided ERCP. However, routine ERCP may not be appropriate for all patients with a high likelihood of choledocholithiasis.

In the past decade, many studies have demonstrated that EUS is as accurate as ERCP for the detection of CBD stones, and that EUS is associated with fewer complications than ERCP [17‐22]. However, EUS is not available in all hospitals, especially in developing countries. Currently, EUS is only available in large tertiary hospitals, which may result in delay between the initial clinical presentation and the EUS examination. In the current study, patients who underwent EUS within 7 days of the initial presentation were more likely to have positive findings than patients who underwent EUS more than 7 days after the initial clinical presentation. Our analyses show that EUS more than 7 days after the initial clinical presentation and an elevated alkaline phosphatase level were associated with detection of CBD stones, especially when the alkaline phosphatase level was >133 mg/dL.

This study was limited by its retrospective design and the relatively small number of patients. The results are therefore only applicable to similar healthcare situations. Further prospective studies should be conducted to confirm the findings of this study.

EUS is an accurate diagnostic tool for the detection of CBD stones, and can reduce the unnecessary use of ERCP. This study demonstrated that use of clinical criteria alone might not provide good predictions regarding the presence of CBD stones in all patients, even those who fulfill the criteria for a high likelihood of choledocholithiasis. EUS examination should be considered for patients with a high likelihood of choledocholithiasis, especially those who cannot undergo ERCP within 7 days of the initial clinical presentation or who have a high risk of ERCP-related complications, to minimize unnecessary ERCP procedures.