Diagnosis of choledocholithiasis: EUS or magnetic resonance cholangiography?

A prospective controlled study

Victor de Ldinghen, MD, Robin Lecesne, MD, Jean-Michel Raymond, MD, Vronique Gense, MD, Michel Amouretti, MD, Jacques Drouillard, MD, Patrice Couzigou, MD, Christine Silvain, MD
Pessac and Poitiers, France

Background: Endoscopic ultrasonography (EUS) appears to be the best imaging method for the diagnosis of choledocholithiasis. The aim of this preliminary, prospective, controlled study was to assess the accuracy of EUS and magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of common bile duct stones. Methods: From December 1995 through April 1997, all patients referred because of suspicion of the presence of common bile duct stones were included in the study. EUS and MRCP were performed. Each examination was performed by a different operator unaware of the result of the other procedure. The definitive diagnosis was established by means of endoscopic retrograde cholangiography with sphincterotomy or a surgical procedure. Results: Forty-three patients (18 men, 25 women) with a mean age of 60.9 14.5 years (range 25 to 81 years) were included in the study. Eleven patients were excluded because of unavailability of magnetic resonance imaging (n = 5) or EUS (n = 6). Ten patients (31.2%) had choledocholithiasis. For this diagnosis, the sensitivity of EUS was 100%, the specificity was 95.4%, the positive predictive value was 90.9%, and the negative predictive value was 100%. The corresponding values for MRCP were 100%, 72.7%, 62.5%, and 100%, not significantly different from EUS results. The accuracy of EUS was 96.9%, and that of MRCP was 82.2%. Conclusion: This preliminary study confirmed EUS as an accurate and noninvasive procedure for the diagnosis of common bile duct stones. MRCP, which had a high sensitivity and high negative predictive value, might be an accurate technique for patients with a contraindication to EUS. (Gastrointest Endosc 1999;49:26-31.)

Choledocholithiasis is a common complication of gallbladder stones, occurring among 15% to 20% of patients.1 Among patients who have undergone cholecystectomy, 1% to 5% have retained or recur-

Received September 18, 1997. For revision January 30, 1998. Accepted June 16, 1998. From the Departments of Hepatogastroenterology and Medical Imaging, Hpital du Haut-Lvque, and Department of Hepatogastroenterology, Hpital Jean Bernard, Pessac, France. Reprint requests: Docteur Victor de Ldinghen, Service dHpatoGastroentrologie, Hpital du Haut-Lvque, 33604 Pessac cedex, France. Copyright 1999 by the American Society for Gastrointestinal Endoscopy 0016-5107/99/$8.00 + 0 37/1/92453 26 GASTROINTESTINAL ENDOSCOPY

rent bile duct stones.1 Clinical and biochemical abnormalities associated with this condition are neither accurate nor specific enough for diagnosis. At present, two noninvasive procedures, abdominal US and CT, are the imaging methods of first choice for diagnosis, but they are not sufficiently sensitive.2-5 ERCP with or without sphincterotomy and intraoperative cholangiography with or without choledochoscopy are accurate procedures used as a second choice because of their invasive nature.6-9 There is need for a less invasive but highly accurate preoperative imaging method. EUS and magnetic resonance cholangiopancreatography (MRCP) are nonaggressive imaging procedures that are particularly useful for exploration of the biliopancreatic region.10-14 MRCP results in
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Diagnosis of choledocholithiasis: EUS or MRCP?

V de Ldinghen, R Lecesne, J-M Raymond, et al.

the diagnosis of choledocholithiasis have not been compared with those of EUS. The aims of this preliminary, prospective, controlled study were to evaluate and compare the diagnostic accuracy of EUS and MRCP in the care of patients with suspected choledocholithiasis.
PATIENTS AND METHODS Inclusion criteria From December 1995 through April 1997, patients were included if they had clinical or biochemical signs of choledocholithiasis according to the following criteria: combination of epigastric or right upper quadrant pain with fever or jaundice; one or two of the previous signs together with an elevation of serum alkaline phosphatase level or an elevation of serum -glutamyl transpeptidase or transaminase level more than the upper limit of normal; acute pancreatitis, defined as acute epigastric pain associated with an elevation of serum amylase, lipase, or urinary amylase level more than two times the upper limit of normal; and unexplained cholestasis defined by an elevation of serum alkaline phosphatase level and an elevation of serum -glutamyl transpeptidase level to more than two times the upper limit of normal. Exclusion criteria Patients were excluded if long-term daily alcohol intake exceeded 80 g, they were taking a hepatotoxic drug, or if serum hepatitis B or C antibodies were present. Radiologic methods All patients underwent EUS and MRCP. All examinations were performed by two different operators unaware of the results of the other investigation. EUS was performed with an Olympus GF EUM20 endoscope system (Scop, Rungis, France). The transducer was inserted to the distal portion of the second duodenum and gradually drawn back to the stomach. Acoustic coupling of the transducer to the digestive wall was achieved with a balloon filled with 5 to 20 mL of water. The procedures were performed with general anesthesia. Examination time was 15 to 30 minutes. The EUS diagnostic criterion for choledocholithiasis was a hyperechoic structure within the common bile duct sometimes associated with an acoustic shadow. The common hepatic duct was considered enlarged if the diameter was more than 7 mm (more than 10 mm for patients who had undergone cholecystectomy). All magnetic resonance examinations were performed after fasting for a minimum of 4 hours to promote filling of the gallbladder and gastric emptying. Magnetic resonance imaging was performed with a 1 T system (Siemens, Erlangen, Germany). The patients were examined in the supine position. A phase-array receiving coil strapped around the abdomen was used. Antiperistaltic drugs were injected intravenously. Before MRCP, a T1weighted ultrafast low-angle shot sequence was performed to localize the biliary tree. MRCP was performed with a half-fourier acquisition single shot Turbo spin echo
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Figure 1. Magnetic resonance cholangiogram shows choledocholithiasis. CBD, common bile duct; PD, pancreatic duct; S, stones.

(HASTE) sequence with an effective echo time of 87 ms, one excitation, and a 240 256 matrix.15 Because the HASTE sequence is a single-shot sequence, there is no repetition time. The fat-suppression technique was used when peritoneal fat resulted in artifact. Two acquisition techniques were used. First, sequential multisection imaging was performed to obtain eight 5-mm sections in a single breath hold of 14 seconds. The entire biliary tree was explored in 4 to 6 breath-hold periods in a coronal plane and in 6 to 8 periods in an axial plane. Maximum intensity projection reconstruction was not performed. Second, projection imaging was performed with a 20-mm thick section acquired in a coronal plane within a single breath hold of 2 seconds. The section position of projection imaging corresponded to the position of the 5-mm section that included the common bile duct. The MRCP results were focused on the common bile duct (size and number of common bile duct stones), and the entire biliary tract was explored. At the end of the examination, MRCP images were reviewed at the console jointly by two experienced radiologists to establish a real-time report. Common bile duct stones were diagnosed with MRCP when a round, oval, or multifaceted area of signal void (hypointensity) was present within the lumen of the hyperintense bile duct. The common hepatic duct was considered enlarged if the diameter was more than 7 mm (more than 10 mm for patients who had undergone cholecystectomy). Final diagnosis After EUS and MRCP were performed, patients underwent surgical treatment or endoscopic investigation. The choice between endoscopic investigation and surgical treatment depended on surgical risk and whether the patient had undergone cholecystectomy. All patients whose gallbladders had been removed underwent ERCP with general anesthesia. When ERCP was performed, endoscopic sphincterotomy was systematically conducted after opacification of the common bile duct. Bile duct stone clearance was attempted with stone baskets, balloon
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V de Ldinghen, R Lecesne, J-M Raymond, et al.

Diagnosis of choledocholithiasis: EUS or MRCP?

catheters, or both. In the surgical group, all patients underwent intraoperative cholangiography performed through the cystic duct or after choledochotomy. If intraoperative cholangiography did not demonstrate stones, a basket was passed through the common bile duct. When EUS, MRCP, or intraoperative cholangiography led to a suspicion of choledocholithiasis, intraoperative choledochoscopy was performed systematically. Choledochoscopy was performed after choledochotomy or through the cystic duct if the diameter was large enough. No complications were encountered. Statistical analysis The sensitivity, specificity, and accuracy of EUS and MRCP in the diagnosis of choledocholithiasis were calculated with a 95% confidence interval (CI).

RESULTS From December 1995 through April 1997, 43 patients (18 men, 25 women) with a mean age of 60.9 14.5 years (range 25 to 81 years) enrolled in the study. Eleven patients were excluded because magnetic resonance imaging (n = 5) or EUS (n = 6) was not available. Therefore 32 of 43 patients (74.4%) underwent EUS and MRCP. Median time between EUS and MRCP was 1 day (range 0 to 7 days). EUS was performed before MRCP in 12 instances and after MRCP in 20 instances. EUS and MRCP were successful in all instances. No inhospital morbidity or mortality was observed. Twenty-five patients underwent surgical treatment (including 5 with prior cholecystectomy). No clinical or biochemical difference was observed between patients who underwent operations and those who underwent endoscopic investigation. Twenty-three patients had gallbladder stones at the time of presentation. Median time between EUS or MRCP and operation or ERCP was 4.5 days (range 1 to 50 days). Patients were separated into three groups, as follows: those with stones at EUS and MRCP (group A, n = 11; Fig 1), those without stones at EUS and MRCP (group B, n = 16), and patients with no stones at EUS but with stones at MRCP (group C, n = 5). Results are shown in Tables 1 and 2. In group A, 10 of 11 patients (90.9%) were found to have stones at surgical intervention (n = 7) or ERCP (n = 3). Two of these patients had a stone 10 mm or more in diameter and 8 a stone less than 10 mm in diameter. No discrepancy was observed between EUS and MRCP findings concerning stone size. The single false-positive finding for EUS and MRCP in this group was that of a patient who had gallbladder and cystic duct stones found during an operation performed 24 hours after EUS. The stone diameter was 4 mm by EUS and MRCP in a normaldiameter common bile duct. This patient also had
28 GASTROINTESTINAL ENDOSCOPY

surgically proved swelling of the papilla caused by recent stone migration. All 16 patients (100%) in group B were found to be free of common bile duct stones at operation (n = 12) or ERCP (n = 4). In group C, all 5 patients (100%) were found to be free of common bile duct stones at operation (n = 5). For all of them, stone diameter was less than 10 mm at MRCP. Choledocholithiasis was found in 10 (31.2%) of the 32 consecutively treated patients. The mean age of patients with stones was 66.3 8.4 years. Two patients had previously undergone cholecystectomy, and 6 had gallbladder stones. In 2 patients the common bile duct was not enlarged. Twenty-two patients did not have choledocholithiasis. Their mean age was 54.3 17.1 years, and 2 of them had previously undergone cholecystectomy. Sensitivity, specificity, positive predictive value, and negative predictive value of EUS and MRCP are shown in Table 3. In the diagnosis of common bile duct stones, the accuracy of EUS was 96.87% (95% CI [83.78, 99.92]) and that of MRCP 81.25% (95% CI [63.56, 92.79]). DISCUSSION Diagnostic imaging of the biliary ductal system typically begins with noninvasive modalities such as ultrasonography or CT. However, information obtained with these techniques often is insufficient for diagnosis despite successive examinations that markedly increase the cost of diagnostic evaluation. In our study, 22 patients did not have choledocholithiasis. This ratio is high because patients were selected on few predictive features of choledocholithiasis. Ultrasonography is the easiest, fastest, and least expensive imaging procedure used for the diagnosis of choledocholithiasis. The diagnostic accuracy of this technique for extrahepatic cholestasis is high, the sensitivity reaching 94% and the specificity 100%.3,16,17 The level of biliary obstruction is identified more than 90% of the time, but the cause can be determined for only 71% of patients. Diagnostic failures are caused mainly by the location of stones within the intrapancreatic portion of the bile duct and the frequent absence of bile duct dilatation. With the use of real-time and high-definition ultrasonography, diagnostic sensitivity for choledocholithiasis is 55%.2-4 The overall diagnostic accuracy of CT for extrahepatic cholestasis is 87% to 98%.18-20 CT is more accurate than ultrasonography, especially in examinations of overweight patients and those with interposed digestive gas. CT has a sensitivity of 76% and a specificity of 98% for the diagnosis of choledocholithiasis.5
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Diagnosis of choledocholithiasis: EUS or MRCP?

V de Ldinghen, R Lecesne, J-M Raymond, et al.

Table 1. Detection of common bile duct stones by endoscopic ultrasonography (EUS) and magnetic resonance cholangiography (MRCP)
Final diagnosis Stones present Stones absent Total EUS + MRCP + 10 1 11 EUS + MRCP 0 0 0 EUS MRCP + 0 5 5 EUS MRCP 0 16 16 Total 10 22 32

+, stones detected with technique; , stones not detected with technique.

EUS is a valuable, noninvasive technique in the diagnosis of choledocholithiasis. In our study, no morbidity was encountered after EUS. Results are excellent in the diagnosis of extrahepatic cholestasis. 21 For choledocholithiasis, the sensitivity of EUS is 93% to 97%, and the specificity is 97% to 100%, better than for CT and ultrasonography.10,12,14 The results of EUS do depend on stone size and the diameter of the bile duct. EUS is particularly accurate for the diagnosis of small stones in the distal common bile duct, especially if the duct is not enlarged. Our study confirmed all previous reports concerning the accuracy of EUS in the diagnosis of choledocholithiasis (sensitivity 100%, specificity 95.4% regardless of stone or common bile duct diameter). The negative predictive value was 100%, so use of EUS may prevent unnecessary interventions. Use of MRCP has increased rapidly in recent years. Projectional images similar in appearance to direct cholangiograms produced with ERCP or percutaneous transhepatic cholangiography are obtained without oral or intravenous administration of a contrast agent. The noninvasive nature of MRCP makes it an appealing modality for the visualization of all segments of the biliary tract. MRCP is not a mature procedure, but in the detection of choledocholithiasis the sensitivity of HASTE MRCP is identical to that of other MRCP methods.22 In our study, no morbidity was observed. Several recent studies involving small numbers of patients have demonstrated the success of this technique in the diagnosis of choledocholithiasis.23-27 MRCP has a sensitivity of 71% to 100%, a specificity of 85%, and an accuracy of 89% to 94%,11,13,15,26 superior to those of ultrasonography and CT. Our study confirmed all previous results; MRCP in the diagnosis of choledocholithiasis had a sensitivity of 100% and a specificity of 72.7% regardless of the diameter of the stone or common bile duct. The negative predictive value was 100%, a factor that may prevent unnecessary intervention. ERCP and intraoperative cholangiography are considered to be the best imaging procedures for the diagnosis of choledocholithiasis. However,
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Table 2. Comparison of endoscopic ultrasonography (EUS) and magnetic resonance cholangiography (MRCP) in the detection of common bile duct enlargement for different subgroups of patients
Finding Group A (n = 11) Common bile duct Common bile duct Group B (n = 16) Common bile duct Common bile duct Group C (n = 5) Common bile duct Common bile duct enlarged not enlarged enlarged not enlarged enlarged not enlarged EUS (%) 8 (72.7) 3 (27.3) * 2 (12.5) 14 (87.5) 0 (0) 5 (100) MRCP (%) 8 (72.7) 3 (27.3)* 3 (18.7) 13 (81.3) 4 (80) 1 (20)

Group A, patients with stones at EUS, MRCP, and operation or endoscopic retrograde cholangiography (ERCP) except one patient; Group B, patients free of stones at EUS, MRCP, and operation or ERCP; Group C, patients with stones at MRCP and free of stones at EUS and operation. *The patient with stones at EUS and MRCP and without a stone at operation had a common bile duct that was not enlarged.

ERCP has a morbidity rate of 3% to 5%,6 8% to 10% if sphincterotomy is performed,28 and a procedure-related mortality rate of 1%.9 ERCP and intraoperative cholangiography may not help detect small stones (<3 mm in diameter) in a dilated common bile duct.8 There are no data on sensitivity, but the rate of false-negative results of intraoperative cholangiography has been estimated at 2% to 7%.29 The sensitivity of ERCP in the diagnosis of choledocholithiasis is 90%, and the specificity is 98%.7 There are many possible explanations for the six instances of false-positive findings of MRCP in the diagnosis of choledocholithiasis in our study. First, a false-positive result might be a false-negative diagnosis with ERCP or intraoperative cholangiography. Second, in 3 of the 6 instances of falsepositive findings swelling of the papilla found during surgical exploration might indicate recent stone migration. Thus our results concerning specificity and negative predictive value are probably underestimates. Third, stones could have migrated between MRCP and EUS or MRCP and surgical
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Diagnosis of choledocholithiasis: EUS or MRCP?

Table 3. Overall results of endoscopic ultrasonography (EUS) and magnetic resonance cholangiography (MRCP) for the diagnosis of choledocholithiasis
Value Sensitivity Specificity Positive predictive value Negative predictive value CI, Confidence interval. EUS (%) 100 95.4 90.9 100 95% CI 69.1100 77.299.9 58.799.8 83.9100 MRCP (%) 100 72.7 62.5 100 95% CI 69.1100 49.789.3 35.484.8 79.4100

exploration. Indeed, the intervals between MRCP and surgical intervention were 1, 3, and 9 days in the three cases. In all cases of conflicting results between EUS and MRCP, MRCP was performed before EUS (range 0 to 4 days). In our study, the median time between EUS or MRCP and ERCP or intraoperative cholangiography was 1 day. This time may not have precluded the possibility of spontaneous stone fragmentation or movement from the bile duct into the duodenum. The standard imaging methods for the diagnosis of choledocholithiasis (ERCP and intraoperative cholangiography) are not sensitive enough to completely reassure the surgeon or endoscopist that interventional manipulation of the common bile duct is not necessary. We have shown that EUS or MRCP may prevent some of these unnecessary interventions. These preliminary results show that EUS and MRCP appear to be the most reliable pretherapeutic diagnostic modalities for choledocholithiasis, but larger prospective studies are needed to confirm this conclusion. For patients with symptomatic choledocholithiasis, the strategy for diagnosis should include ultrasonography as the first choice of imaging followed by EUS or MRCP. MRCP might be more useful than EUS in the care of elderly patients at high surgical risk and patients for whom endoscopy has been unsuccessful, such as patients who have undergone surgical bypass procedures. ERCP with sphincterotomy and choledochoscopy can be reserved for therapeutic use.
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J, Takahashi J . MR cholangiopancreatography using HASTE (Half-Fourier Acquisition Single-shot Turbo Spin-Echo) sequences. AJR 1996;166:1297-303. 23. Macaulay SE, Schulte SJ, Sekijima JH, Obregon RG, Simon HE, Rohrmann CA, Freeny PC, Schmiedl UP. Evaluation of a non-breath-hold MR cholangiography technique. Radiology 1995;196:227-32. 24. Barish MA, Yucel EK, Soto JA, Chuttani R, Ferrucci JT. MR cholangiopancreatography: efficacy of three-dimensional turbo spin-echo technique. Am J Roentgenol 1995;165:295-300. 25. Guibaud L, Bret PM, Reinhold C, Atri M, Barkun ANG. Diagnosis of choledocholithiasis: value of MR cholangiography. Am J Roentgenol 1994;163:847-50.

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