ERCP: Targeting the Stone

The risks of complications of endoscopic retrograde cholangiopancreatoscopy (ERCP), including fatalities, increases with a decreasing probability of bile duct stones [1] [2]. A useful phrase to bear in mind is that ERCP is most dangerous for people who need it least [3]. This is the most important reason why the goal of patient selection for ERCP is to ensure that an absolute minimum of patients are subjected to a futile and risky procedure without a need for therapeutic intervention. On the other hand, a necessary ERCP must not be delayed, since this exposes the patient to the risks of complications such as cholangitis and pancreatitis.

Patients with gallbladder stones have concurrent bile duct stones in 8 - 18 % of cases, depending on the population. The probability ranges from less than 1 % in patients without symptoms or signs suggestive of bile duct stones [4] [5] to 100 % in patients with cholangitis in whom ultrasonography or magnetic resonance imaging documents a stone [4] [6]. Overlooked bile duct stones are found in less than 4 % of patients after cholecystectomy in Western populations [7] [8] [9].

With gallstone prevalences of 8 - 22 % [10] and cholecystectomy rates in Europe and the USA of 69 - 200 per 100 000 [10] [11] [12], the quantitative problem is significant. The endoscopic method is unchallenged as the cornerstone for bile duct stone removal, since laparoscopic bile duct stone removal has not gained widespread general use even though it was first introduced 15 years ago [13] and several groups have published series including more than 200 successful cases [5]. Laparoscopic bile duct clearance adds 1 h to the procedure time in laparoscopic cholecystectomy [5] - but so does intraoperative ERCP, without prolonging or complicating the postoperative course [5]. Randomized studies comparing preoperative [14] [15] or postoperative [16] endoscopic duct clearance with a single-stage laparoscopic procedure have found comparable clearance rates in the ERCP and laparoscopy groups.

Recently, a randomized study comparing a wait-and-see approach with cholecystectomy after sphincterotomy and stone removal, including all patients regardless of age (which ranged from 18 to 80 years) found that 37 % needed cholecystectomy, although those needing surgery were younger than those who did not [17]. In the middle-aged and elderly (who are at greater risk for complications after laparoscopic cholecystectomy than younger patients [18]), it appears that no more that one-fifth will have symptoms from the gallbladder stones later, and almost 90 % of these patients have symptoms leading to cholecystectomy within 2 years of ERCP [19]. This makes endoscopic treatment with clinical follow-up, rather than cholecystectomy with concurrent bile duct intervention, the preferred primary choice for these patients.

Several groups have taken up the challenge of developing and evaluating methods of calculating the probability that the patient may have bile duct stones, in order to fine-tune the selection of patients for ERCP, and have applied these methods clinically. The methods range from relatively simple risk-factor identification [7] [20] to mathematical models made simple to use as nomograms [21] or formulas leading to a discriminant factor [22], and multivariate analysis using logistic regression to identify independent predictors of stones [23] or a need for therapy [24].

When only a single criterion is used for selection, the number of negative ERCPs increases, as shown by Katz et al. in the present issue of Endoscopy [7]. Methods using combined criteria will result in higher predictive values. Everyday use of mathematical formulas is relatively simple, since it can be integrated into the laboratory’s computers, with a numerical value being printed out, or can be used in personal digital assistant-based calculators. The use of a neural network for prediction has been evaluated and found useful in a small series [25].

With selection tests resulting in a probability figure [21] [24], the clinician needs to decide on which cut-off levels to use. In this context, the classification levels usually applied are a low probability (< 10 %), intermediate probability (11 - 55 %), and high probability (> 55 %) of common bile duct stones [26], but 75 - 80 % is probably a more appropriate level for high probability if nontherapeutic ERCP is to be avoided [24].

How good are the methods of detecting those patients who harbor bile duct stones and correctly identifying those who do not? This issue has been analyzed both by the originators of such methods themselves [21] [23] [24] [25] [27] [28] and by other groups, thus independently validating the proposed models [29]. For a selection method to be a useful tool for the clinician, its positive and negative predictive values should be high - ideally 100 %, indicating that all patients with a positive selection test have bile duct stones, and none of those with a negative selection test have stones. This is, of course, never the case, but the task is to get as close to this ideal as possible.

What is a dilated common bile duct? In patients without disorders affecting the bile ducts, the diameters of normal common bile ducts range up to 10 mm, depending on where the duct is measured [30]. The diameter increases somewhat with age [30] [31] [32], and slightly, but significantly, after cholecystectomy [33] [34]. There is a discrepancy between ultrasound measurement and measurement on endoscopic cholangiograms, depending on the way in which the ultrasonography is performed (transverse or anteroposterior scanning), since the duct may be oval in shape, especially when dilated [35]. In addition, there is significant interobserver variation between trainees and trained ultrasonographers in measuring the bile duct diameter [36]. These limitations imply that a high cut-off level should be applied, in order to minimize the number of patients subjected to further investigations. Suggested levels are 8.5 mm in patients older than 50 [30], or, probably better, 10 mm for the extrahepatic ducts on transverse measurement [31] [32] and 5 mm for the intrahepatic ducts. Future studies should include the use of transverse scanning, and observer variation must be taken into account.

A thorough meta-analysis of studies describing predictive factors for common bile duct stones, ranked these [20]. Predictors with likelihood ratios above 10 were cholangitis, preoperative jaundice, and ultrasound visualization of common bile duct stones. Positive likelihood ratios for a dilated common bile duct on ultrasound, hyperbilirubinemia, and jaundice, ranged from almost 4 to almost 7. Elevated levels of alkaline phosphatase, pancreatitis, cholecystitis, and hyperamylasemia showed positive likelihood ratios of less than 3.

The diagnostic methods for visualizing the ducts and bile duct stones, including endoscopic ultrasonography (EUS), magnetic resonance cholangiopancreatography (MRCP), helical computed tomographic cholangiography, intraoperative ultrasonography, and intraoperative cholangiography have been extensively reviewed in a recent technology review [37]. The present evidence supports the view that abdominal ultrasonography is the most cost-effective initial imaging test in the initial work-up of patients with suspected common bile duct stones (level of evidence 2A, grade of recommendation B [38]), and that predictive models are useful in stratifying the risks of patients who have common bile duct stones (1B, A), in order to identify those with a low risk who may proceed to laparoscopic cholecystectomy (2B, B), with preoperative ERCP being reserved for those with a high probability of common bile duct stones (2B, B), while patients with an intermediate risk may be further evaluated with MRCP, EUS, or intraoperative cholangiography (2B, B) [37].

Thus, patients with suspected common bile duct stones who have cholangitis, persistent jaundice, or stones visualized on ultrasonography, MRCP, or CT and patients with a calculated probability of common bile duct stones higher than 75 - 80 %, or a positive discriminant factor, can proceed directly to ERCP [20] [29] [37]. It should be borne in mind that a negative discriminant factor does not exclude the possibility that endoscopic therapy may be needed [29]. This strategy will ensure that the number of patients exposed to unnecessary ERCPs is kept as low as possible.

References

• 1 Freeman M L, DiSario J A, Nelson D B. et al . Risk factors for post-ERCP pancreatitis: a prospective, multicenter study.  Gastrointest Endosc. 2001;  54 425-434
• 2 Trap R, Adamsen S, Hart-Hansen O, Henriksen M. Severe and fatal complications after diagnostic and therapeutic ERCP: a prospective series of claims to insurance covering public hospitals.  Endoscopy. 1999;  31 125-130
• 3 Cotton P B. ERCP is most dangerous for people who need it least.  Gastrointest Endosc. 2001;  54 535-536
• 4 Jendresen M B, Thorboll J E, Adamsen S. et al . Preoperative routine magnetic resonance cholangiopancreatography before laparoscopic cholecystectomy: a prospective study.  Eur J Surg. 2002;  168 690-694
• 5 NIH state-of-the-science statement on endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and therapy . .  NIH Consens State Sci Statements. 2002;  19 1-26
• 6 Tranter S E, Thompson M H. Spontaneous passage of bile duct stones: frequency of occurrence and relation to clinical presentation.  Ann R Coll Surg Engl. 2003;  85 174-177
• 7 Katz D, Nikfarjam M, Sfakiotaki A, Christophi C. Selective endoscopic cholangiography for the detection of common bile duct stones in patients with cholelithiasis.  Endoscopy. 2004;  36 1045-1049
• 8 Kejriwal R, Liang J, Anderson G, Hill A. Magnetic resonance imaging of the common bile duct to exclude choledocholithiasis.  ANZ J Surg. 2004;  74 619-621
• 9 Bentzon N, Adamsen S. Impact of laparoscopic technique on the quality of cholecystectomy.  J Laparoendosc Surg. 1995;  5 279-287
• 10 Aerts R, Penninckx F. The burden of gallstone disease in Europe.  Aliment Pharmacol Ther. 2003;  18 (Suppl 3) 49-53
• 11 Kozak L J, Owings M F, Hall M J. National Hospital Discharge Survey: 2001 annual summary with detailed diagnosis and procedure data.  Vital Health Stat. 2004;  13 1-198
• 12 Mjaland O, Adamsen S, Hjelmquist B. et al . Cholecystectomy rates, gallstone prevalence, and handling of bile duct injuries in Scandinavia: a comparative audit.  Surg Endosc. 1998;  12 1386-1389
• 13 Bagnato J. Laparoscopic common bile duct exploration.  J Miss State Med Assoc. 1990;  31 361-362
• 14 Sgourakis G, Karaliotas K. Laparoscopic common bile duct exploration and cholecystectomy versus endoscopic stone extraction and laparoscopic cholecystectomy for choledocholithiasis: a prospective randomized study.  Minerva Chir. 2002;  57 467-474
• 15 Cuschieri A, Lezoche E, Morino M. et al . E.A.E.S. multicenter prospective randomized trial comparing two-stage vs single-stage management of patients with gallstone disease and ductal calculi.  Surg Endosc. 1999;  13 952-957
• 16 Rhodes M, Sussman L, Cohen L, Lewis M P. Randomised trial of laparoscopic exploration of common bile duct versus postoperative endoscopic retrograde cholangiography for common bile duct stones.  Lancet. 1998;  351 159-161
• 17 Boerma D, Rauws E A, Keulemans Y C. et al . Wait-and-see policy or laparoscopic cholecystectomy after endoscopic sphincterotomy for bile-duct stones: a randomised trial.  Lancet. 2002;  360 761-765
• 18 Adamsen S, Hansen O H, Jensen P M. et al . Laparoscopic cholecystectomy in Denmark: a prospective registration.  Ugeskr Laeger. 1995;  157 4449-4454
• 19 Hammarstrom L E, Holmin T, Stridbeck H. Endoscopic treatment of bile duct calculi in patients with gallbladder in situ: long-term outcome and factors.  Scand J Gastroenterol. 1996;  31 294-301
• 20 Abboud P A, Malet P F, Berlin J A. et al . Predictors of common bile duct stones prior to cholecystectomy: a meta-analysis.  Gastrointest Endosc. 1996;  44 450-455
• 21 Onken J E, Brazer S R, Eisen G M. et al . Predicting the presence of choledocholithiasis in patients with symptomatic cholelithiasis.  Am J Gastroenterol. 1996;  91 762-767
• 22 Trondsen E, Edwin B, Reiertsen O. et al . Selection criteria for endoscopic retrograde cholangiopancreatography (ERCP) in patients with gallstone disease.  World J Surg. 1995;  19 852-856
• 23 Barkun A N, Barkun J S, Fried G M. et al . Useful predictors of bile duct stones in patients undergoing laparoscopic cholecystectomy. McGill Gallstone Treatment Group.  Ann Surg. 1994;  220 32-39
• 24 Nathan T, Kjeldsen J, Schaffalitzky de Muckadell O B. Prediction of therapy in primary endoscopic retrograde cholangiopancreatography.  Endoscopy. 2004;  36 527-534
• 25 Golub R, Cantu R Jr, Tan M. The prediction of common bile duct stones using a neural network.  J Am Coll Surg. 1998;  187 584-590
• 26 Jakribettuu V S, Gilliam J H, Pineau B C. Comparisons of five algorithms used to predict common bile duct stones.  Am J Gastroenterol. 2001;  96 588
• 27 Menezes N, Marson L P, Debeaux A C. et al . Prospective analysis of a scoring system to predict choledocholithiasis.  Br J Surg. 2000;  87 1176-1181
• 28 Trondsen E, Edwin B, Reiertsen O. et al . Prediction of common bile duct stones prior to cholecystectomy: a prospective validation of a discriminant analysis function.  Arch Surg. 1998;  133 162-166
• 29 Ainsworth A P, Pless T, Mortensen M B, Wamberg P A. Is the ”Trondsen Discriminant Function” useful in patients referred for endoscopic retrograde cholangiopancreatography?.  Scand J Gastroenterol. 2003;  38 1068-1071
• 30 Bachar G N, Cohen M, Belenky A. et al . Effect of aging on the adult extrahepatic bile duct: a sonographic study.  J Ultrasound Med. 2003;  22 879-882
• 31 Deitch E A. The reliability and clinical limitations of sonographic scanning of the biliary ducts.  Ann Surg. 1981;  194 167-170
• 32 Wu C C, Ho Y H, Chen C Y. Effect of aging on common bile duct diameter: a real-time ultrasonographic study.  J Clin Ultrasound. 1984;  12 473-478
• 33 Feng B, Song Q. Does the common bile duct dilate after cholecystectomy? Sonographic evaluation in 234 patients.  Am J Roentgenol. 1995;  165 859-861
• 34 Chung S C, Leung J W, Li A K. Bile duct size after cholecystectomy: an endoscopic retrograde cholangiopancreatographic study.  Br J Surg. 1990;  77 534-535
• 35 Wachsberg R H, Kim K H, Sundaram K. Sonographic versus endoscopic retrograde cholangiographic measurements of the bile duct revisited: importance of the transverse diameter.  Am J Roentgenol. 1998;  170 669-674
• 36 Grantcharov T P, Rasti Z, Rossen B. et al . Interobserver agreement in ultrasound examination of the biliary tract.  Acta Radiol. 2002;  43 77-79
• 37 Tse F, Barkun J S, Barkun A N. The elective evaluation of patients with suspected choledocholithiasis undergoing laparoscopic cholecystectomy.  Gastrointest Endosc. 2004;  60 437-448
• 38 Guyatt G H, Sackett D L, Sinclair J C. et al . Users’ guides to the medical literature, 9: a method for grading health care recommendations. Evidence-Based Medicine Working Group.  JAMA. 1995;  274 1800-1804