State of the art lecture: Lithiasis and pancreatitis

Bile duct stones

Endoscopic retrograde cholangio-pancreaticography (ERCP) has long been used as the best diagnostic method for common bile duct stones (CBDS). Moreover, it was possible to combine stone removal with endoscopic sphincterotomy (ES) during the same endoscopic session. Nevertheless it remains an invasive method, associated with complications in 5 % of patients, and with a mortality rate of 0.1-0.2 % [1] [2] for ERCP, reaching 2.2 % for ES [3] [4] [5]. As transabdominal ultrasound (US) or computed tomography are not particularly sensitive for the diagnosis of choledocholithiasis [6] [7] an accurate diagnostic minimally invasive tool was awaited, to replace ERCP and to reserve ES for patients with CBDS.

In the past decade, helical computed tomodensitometry (hCT), endoscopic ultrasonography (EUS), and magnetic resonance cholangiopancreatography (MRCP) have improved the diagnosis of CBDS. More recently intraductal ultrasound (IDUS) has also been tested. Nevertheless ERCP is needed for this procedure and only ES should be avoided in patients without CBDS. Currently, what is the respective place of these modalities?

MRCP and hCT are non-invasive procedure. hCT is generally considered as inferior than MRCP, with a sensitivity of 85-88 %, specificity of 88-97 %, and diagnostic accuracy of 86-94 % [8] [9], for CBDS. Nevertheless in the first comparative study [10] the results were the same with an accuracy of 86 %, a sensitivity of 88 % and a specificity of 75 % for the two procedures. The main drawback of these two techniques is the limited spatial resolution. In the first series, stones not diagnosed by MRCP were always smaller than 10 mm [11] [12] [13]. Imaging improvements permit now the detection of calculi smaller than 5 mm [14] but the sensitivity remains low (67 %) for stones < 5 mm as for MRCP than for hCT [10]. Moreover, MRCP is contraindicated in patients with a permanent pacemaker or metallic clips, and claustrophobic patients cannot undergo the examination, when hCT is not applicable to patients allergic to contrast medium.

EUS offers higher resolution than MRCP or hCT (0.1 versus 1 mm). The accuracy of EUS is excellent with sensitivity, specificity and accuracy ranging from 81 to 98 %, 93 to 100 % and 93 to 99 % respectively [15] [16] [17] [18] [19] [20] [21] [22] [23]. It is a minimally invasive method [20] [24] with a lower failure rate than ERCP¹⁶. The specificity of EUS in ruling out the presence of CBDS is very high, until 98 % [25]. Detection of bile duct sludge as well as minilithiasis, often missed by the other imaging techniques [26], is possible with EUS. The type of echoendoscope seems of no importance. Results are as good with radial echoendoscopes as with linear scopes [21] or with extraductal catheter probe EUS [27].

The accuracy of IDUS for the diagnosis of CBDS is also very high, reaching 100 % [28] [29]. The size of the probe (2 mm) allows an insertion inside the bile duct during an ERCP. The high frequency (20MHz) provides higher resolution than conventional EUS. Moon et al in 2005 compared the sensitivity of IDUS and MRCP to the results of ERCP + ES and stone removal [28]. For the detection of CBDS the sensitivity of IDUS and ERCP was 95 % and 80 % respectively. The clinical utility of IDUS was evaluated by Catanzaro et al [29]. The performance was compared with results of ERCP. IDUS found CBDS in 8 out of 21 patients with normal cholangiogram. ES confirmed the diagnosis in 7 patients. IDUS also avoided unnecessary ES as no lithiasis was found in 36 % of patients with a positive finding on ERCP. The main drawback of IDUS remains the morbidity of ERCP which must be performed at the same time.

Very good comparative studies between these procedures are rare. In fact, to compare the performance of each technique, some parameters have to be considered. Spontaneous stone migration between the two examinations can lead to false-positive results. Stone migration has been found to have occurred in 21 % of patients within 1 month [30]. Ideally, the ‘gold standard’ examination should be performed as soon as possible (at least during the following 2 days) after the evaluated technique. Second, ERCP (or peroperative cholangiography) is not the best ‘gold standard’ as its sensitivity to diagnose CBDS is around 90 % [18]. Two different approaches should be considered as the most sensitive and specific : - systematic ERCP, ES and instrumental exploration of the CBD (with a Dormia basket or balloon) [18]; - depending of the result of the diagnostic tool : association of ERCP, ES, and bile duct exploration when a stone is evidenced or 6 months clinical follow-up when a stone has been excluded [20] [22] [23] [31]. More recently the excellent results of ERCP with IDUS [10] should also lead to a third ‘gold standard’.

In the first comparative studies, EUS was found to be superior to MRCP [10] [32] [33] or hCT [9] [10] [19] to detect CBDS. Improvements in imaging modalities may modify these findings: in the most recent series, the specificity of EUS and MRCP were found to be equal (97 %) when sensitivity was slightly greater with EUS than with MRCP (94 % versus 88 %, respectively) [14]. These good results need to be confirmed in largest series. At present, EUS can be considered to be more accurate than hCT or MRCP, especially for smaller stones.

A considerable reduction in the number of inappropriate ERCP is obtained with the use of alternative imaging procedures [22] [23]. Given that the accuracy of EUS is greater than that of MRCP or hCT, at least in patients with microlithiasis [13] [32] [33] EUS should replace diagnostic ERCP. Whenever EUS is contraindicated (total or Billroth II gastrectomy, digestive stenosis...), MRCP or hCT might be proposed. ERCP should be used in patients already known to have CBDS (shown by US, for example) or in patients with previous ES. IDUS cannot be proposed as a first step procedure because of the ERCP morbidity. It might be reserved to patients in whom CBDS have been found at EUS or MRCP, but not at ERCP.

Is it necessary to perform a systematic minimally invasive diagnostic procedure before ERCP?

Patients suspected of having CBDS on clinical and laboratory criteria and/or US findings can be ranged into risk classes from low to high [34] [35]. Less than 30 % of patients classified as being at moderate risk have CBDS [20] [31] whereas the proportion of high-risk patients that actually have CBDS is around 70 % [18] [19] [31] [36]. For moderate- and low-risk patients, the general consensus is to perform a first-line diagnostic (after US). Thus, EUS could be the ideal alternative, selecting only those patients with bile duct stones for ERCP/ES. In high-risk patients ERCP is generally proposed as the first-line approach [20] [22] [31] [35] [37]. Nevertheless, as it is impossible completely to avoid unnecessary ERCP investigations on clinical or biochemical criteria, some authors support EUS as a first-line approach [23] [38] [39]. In the recent series of Liu et al [38] 140 patients presenting acute pancreatitis suspected to be of biliary origin were prospectively randomized. In the first group, EUS was followed by ERCP when needed, and in the second group, ERCP was performed immediately. EUS had a higher successful examination rate and a higher sensitivity in the detection of cholelithiasis. The morbidity was higher in the ERCP group (14 % of complications) than in the EUS group (7 %) but it was not significant. Then the best choice, also in high risk patients, should be to perform EUS followed, during the same endoscopic procedure, with ERCP and ES when a stone is evidenced.

Regard to cost-effectiveness, first line EUS vs first line ERCP has been studied in two situations [23] [40]. In the context of laparoscopic cholecystectomy [23] EUS was performed for all patients with suspected CBDS followed by ERCP and ES when stone was evidenced. The cost of this approach was compared with the cost of a strategy proposing ERCP as first step. The mean cost for patients managed by the EUS-based strategy was significantly less than the theoretical mean cost for patients undergoing ERCP approach. In the context of acute biliary pancreatitis, Romagnuolo et al. [40] constructed a modeling standard care for non severe (selective ERCP) and severe pancreatitis (ERCP with sphincterotomy and balloon sweep). EUS was dominant in severe pancreatitis whereas it was slightly more costly in non severe (but associated with fewer ERCPs and ERCP-related complications). So, even if the estimation of cost is different depending of the countries and healthcare systems, EUS as first diagnostic tool seems to be the most effective not only for clinical impact but also for economic target. Further studies are necessary to confirm that the EUS-based strategy is also cost-effectiveness in the sub-group of high risk patients.

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