magnetic resonance cholangiopancreatography ( mrcp ) is well recognised to have high sensitivity and specificity ( over 90% ) for the detection of common bile duct ( cbd ) calculi [ 15 ] . however , a significant proportion of physicians allow patients with suspected intra - cbd stones ( icss ) to proceed directly to endoscopic retrograde cholangiopancreatography ( ercp ) , a procedure not without risk . these may include post - ercp pancreatitis ( incidence rate 1.36.7% ) , haemorrhage ( 0.72% ) , and cholangitis ( 0.55% ) [ 610 ] . the risk for ercp - related complications is greatest in those with normal / marginal abnormalities in liver biochemistry and normal cbd diameter . in 2006 , cotton published a 10-year experience of being an expert witness in 59 cases that involved ercp where malpractice was alleged . the most common allegation ( 32 cases ) was that ercp ( with / without sphincterotomy ) was simply not indicated , with inadequate evidence for biliary ( or pancreatic ) pathology to necessitate said procedure . in over 30% of cases , there were no identifiable high risk factors which would arouse suspicion of ics , yet these patients , perhaps unjustifiably , proceeded directly to ercp , only to develop complications . a follow - up report from 2010 identified an ongoing trend whereby no less than 20 cases of ercp - related malpractice had taken place over the preceding 4 years , 45% of which related to patients having no high risk biochemical or transabdominal ultrasound ( taus ) features which supported the presence of ics . the american society for gastrointestinal endoscopy guidelines [ 13 , 14 ] , the national institutes of health ( nih ) state of the science conference on ercp , and the birtish society of gastroenterology   state clearly that ercp should be avoided if at all possible in such cases , with emphasis on noninvasive imaging , specifically mrcp as the diagnostic modalities of choice for confirming the presence of ics , whilst reserving ercp in cases where there is confidence an intervention will be required . although mrcp is an accurate and noninvasive tool for the diagnosis of cbd calculi , access is still limited in many hospitals . moreover , investigating all patients with gallstone disease for suspected ics with mrcp would not be practical or cost - effective . therefore , some form of patient selection or risk stratification based on the likelihood of cbd stone disease is required . clinical features at presentation ( jaundice , pancreatitis , ascending cholangitis ) , biochemical markers ( elevated bilirubin , alt / ast , and/or alp ) , and findings on taus ( dilated cbd , impression of cbd calculi ) have been previously investigated for the ability to predict the risk of ics . while findings such as a dilated cbd on taus or jaundice at presentation may increase the probability of cbd calculi , they suffer from low individual specificity . previous studies have demonstrated that models based on a combination of a patient 's age , biochemical , and ultrasound findings can be developed to predict the presence of cbd stones [ 1820 ] and therefore the need for further investigation or intervention . this has formed the basis of international guidelines [ 13 , 14 , 16 ] . the aims of this study were to identify factors which negatively predict the presence of ics thus preclude the need for ercp and devise a practicable algorithm for risk stratification in selecting patients with confirmed gallstone disease for mrcp versus proceeding directly to ercp or cholecystectomy . this is a single - centre study of all patients who underwent cholecystectomy in a north oxfordshire ( uk ) hospital between november 2007 and october 2008 . patients were identified from operating theatre records , intraoperative cholangiogram ( ioc ) reports , ercp reports , and in - patient case notes . patients ' medical records , including biochemical and radiological databases , were analysed for the presence of risk factors indicative of cbd calculi . for the clinical presentation , high - risk  factors based on findings from previous studies and meta - analysis [ 17 , 18 ] , while the absence of all three was classified as low risk . perioperative results of liver associated enzymes ( alp and alt ) and bilirubin were reviewed to assess biochemical risk factors , and the highest levels of each were recorded from time of first presentation to 30 days after cholecystectomy . any biochemical test value above our laboratory 's local upper limit of normal ( alt , 45  iu ; alp , 330  iu ; bilirubin 17 for the presence or absence of ultrasound indicators , the presence of a cbd diameter greater than 7  mm and/or an impression of ics on taus defined taus high risk . the presence or absence of cbd stones was confirmed by followup of the medical notes , review of ercp reports , and radiological databases , and when present , results of an intraoperative cholangiogram ( ioc ) . hospital admission records and further imaging performed in the 30 days following cholecystectomy were also analysed for evidence of ics presenting postoperatively . data was analysed using pasw statistics version 18.0 ( spss , chicago , il , usa ) . binomial logistic regression analysis for the prediction of cbd stones was performed using candidate factors of clinical risk , biochemical risk , and ultrasound risk . further binomial logistic regression analyses were performed using the level of each individual biochemical test as candidate factors in one analysis and a dilated cbd diameter ( > 7  mm ) and/or taus evidence of ics in the other . odds ratios ( ors ) , sensitivity , and specificity of each individual risk factor were subsequently calculated . the patient cohort included 231 patients ( 182 female ) with a mean age of 50 years ( 1877 ) . 10.4% ( n = 24 ) were diagnosed with cbd stones preoperatively ( n = 17 ) , intraoperatively ( n = 4 ) , or postoperatively ( n = 3 ) . a high biochemical risk , meaning high levels in one or more of the three tests of liver function , was associated with a significant odds ratio ( or ) of 23.9 for the presence of cbd stones ( table 1 ) . the three liver function tests studied ( alt , alp , and bilirubin ) were analysed as separate risk factors in a second logistic regression using only these factors . as shown in table 2 , both a high alt and a high alp were independently associated with a significantly high odds ratios of 13.7 and 7.2 , respectively . the or for a raised bilirubin in isolation , however , was only mildly raised at 1.10 and did not reach statistical significance . abnormal liver biochemistry predicted the presence of cbd stones with 96% sensitivity and 59% specificity . only 1 patient ( 0.85% ) with normal alt and normal alp was eventually diagnosed as having a cbd stone ( postoperatively ) . high taus risk was associated with a significant or of 3.03 ( tables 1 and 3 ) . when analysing these findings individually , a dilated cbd in isolation had a greater association with the eventual presence of cbd stones ( or 6.53 ) . only 13/197 ( 6% ) of patients with a normal cbd diameter were subsequently diagnosed as having ics . the impression of ics on taus in the absence of a dilated cbd did not give rise to a statistically significant or ( 0.97 ) . high clinical risk based on a history of jaundice , pancreatitis , or cholangitis demonstrated a slightly increased but nonsignificant or of 1.26 ( 95% confidence interval 0.463.45 ) . neither patient age nor sex influenced the odds of cbd calculi being present ( data not shown ) . we combined the biochemical and taus risk factors to define a group which included patients with either high biochemical risk and/or a high ultrasound risk , such that this group included all patients with one or more abnormalities in liver function tests and/or abnormalities on taus . this group contained 114 patients ( 49% of the total cohort ) in whom 23 ( 20.1% ) were subsequently confirmed to have cbd calculi . using this  and/or  method yielded a sensitivity of 96% and specificity of 56% for detecting ics disease ( table 1 ) . refining this combined risk group further , the presence of both abnormal taus and abnormal liver biochemistry yielded a higher specificity ( 92% ) , with an or of 8.88 on binominal logistic regression ( table 1 ) . out of 117 patients with normal liver function tests and normal cbd on ultrasound , only 1 patient ( 0.85% ) had a cbd stone subsequently detected ( identified postoperatively ) . the negative predictive value of a normal cbd diameter on taus and normal liver biochemistry in the perioperative cholecystectomy period was 99.5% for the eventual presence of ics . investigating individual liver function tests and the different cbd findings on ultrasound identified an increased alt , increased alp , or a cbd diameter greater than 7  mm as the most significant risk factors for ics . we have also shown that patients with both abnormal liver function tests and abnormal taus cbd appearances ( high - risk group ) are more likely to have cbd calculi compared to those with normal test results . thus , as this  combination  group bears the highest specificity , it may be reasonable for such patients to proceed directly to ercp for biliary intervention thereby circumventing the need for mrcp . however , mrcp provides clear additional benefits for the endoscopist by delineating the ductal anatomy , which is often not well demonstrated by taus alone and therefore anticipated that , where available , mrcp may still be a useful intermediate step prior to ercp . this decision should be made on a case - by - case basis . in those patients in whom neither liver - associated enzymes nor cbd dilatation is present ( low risk group ) , it is extremely unlikely that there are cbd calculi present . in this group , it is reasonable to proceed directly to cholecystectomy where indicated . the group in whom either ductal dilatation or abnormal biochemistry is present ( intermediate - risk group ) still have a 29-fold higher chance of having cbd calculi compared to those in the low - risk group . although this predicts the presence of ics with high sensitivity ( 96% ) , using this  either / or  approach still suffers from low specificity hence patients falling into this category are still advised to undergo mrcp prior to definitive biliary intervention due to the high false - positive rate . the low diagnostic accuracy of detecting ics by visualising cbd stones on taus ( in the presence of normal cbd diameter ) can be attributed to a number of factors . firstly , there isan acknowledged difficulty amongst radiologists that interrogate the biliary treein reliably identifying intraductal calculi in the extrahepatic biliary system . this is usually due to overlying bowel gasthat precludes identifying the calculus accurately despite manoeuvring the patient.in this situation , abdominal gas within a viscus dissipates the focussed ultrasound beam resulting in incoherent / nondiagnostic images beingproduced . secondly , the calculus depending on its size may not necessarily cast an acoustic shadow , and their location near the ampulla can bevery difficult to detect on ultrasound . conversely , the appearance of an acoustic shadow may be caused by refraction of the ultrasound beam or mucosal junctional folds which may falsely simulate the appearance of ics . finally , it is also important to note that , when intraductal calculi are detected , the delay between the ultrasound study and ercp / iocmay besubstantial , resulting in the passage of the calculus before the latter invasive studies are performed . it is worth noting that mrcp has a higher sensitivity particularly in detecting small cbd calculi , particularly if the fluid in the duodenum is suppressed ( e.g. , with pineapple juice within the duodenum ) . this is due to the magnesium content within the juice that suppresses the fluid signal . an alternative diagnostic modality for the evaluation of ics is endoscopic ultrasound ( eus ) , which in expert hands provides excellent images of the common bile duct . several studies have compared the diagnostic accuracy of eus to ercp in patients with moderate to high risk of having ics . taken collectively , the sensitivity of ercp for ics in these studies ranges from 79 to 100% compared to 84100% for eus , and the specificity from 87 to 100% for ercp compared to 96100% for eus . neither however , eus is not yet widely available and still requires the patient to undergo endoscopy without adequate visualisation of the intrahepatic ducts . the results of our study lead us to propose a pathway to select those at intermediate to high risk for further investigation with mrcp . if this pathway was applied to our sample group , a total of 114 patients ( 49% ) would have undergone mrcp with 23 out of 24 patients having cbd stones being correctly identified . compared to 84 patients ( 36% ) who actually received mrcp in our cohort , this is a significant but still practical increase in demand . while mrcp has benefits in being a noninvasive and accurate diagnostic test , it can however be viewed as an unnecessary step in the management of patients who will almost definitely have a cbd stone and require therapeutic ductal intervention . hence , as already discussed , it may be justified to proceed directly to ercp should the aforementioned high - risk indicators be present . this view is supported in the british society of gastroenterology ( bsg ) guidelines as a reasonable and cost - effective strategy , and , given variations in the accessibility to mrcp , this would also be relevant to many centres . therefore , in our proposed pathway ( figure 1 ) , we have suggested that a subgroup of patients in whom both liver - associated enzymes ( either alt or alp ) and cbd diameter are abnormal ( high specificity ) could be considered for direct referral to ercp . this may be especially useful in circumstances where difficult access to mrcp means that there would be undue delays for the diagnosis to be confirmed and definitive treatment offered to a high - risk patient . while other studies with larger sample sizes have developed similar predictive models based on patient age , clinical presentation , biochemistry , and ultrasound findings , they were developed such that the next step in the management pathway was either ercp or ioc , both invasive procedures with associated risks . because of the risks associated with ercp or ioc , these models required a high specificity and high positive predictive value in which those selected would have a high likelihood of requiring therapy . although only 20% of our intermediate - risk group and 38% of our high - risk group eventually had cbd stone disease , all - but - one patients with ics would have been included in these categories . thus , we have identified an accurate method of detecting those patients at low risk of needing invasive biliary intervention which may reduce the development of ercp - related complications . limitations to our study include the relatively small sample size from a single centre , which led to wide confidence intervals for our calculations of odds ratios . however , we hope that this study would provide a basis for larger scale studies to be carried out . secondly , it is likely , but not presumed in this study , that there is an association among abnormal individual liver function tests and cbd abnormalities on ultrasound ; therefore , the calculated odds ratios in the multivariate logistic regression analyses would not be simply multiplied in the case where more than one risk factor is positive . thirdly , there is a variable gap of time between liver function tests , taus , and verification of cbd stone disease . this raises the probability that cbd calculi could have developed or resolved in this time period . finally , a useful measure would be serial monitoring of liver associated enzymes and bilirubin over time rather than at one time point as in our study . this would enable us to trend whether normalisation in liver function tests equates to the successful ductal passage of calculi . we believe that , while this would influence the accurate predictive value of biochemistry and ultrasound , this more closely reflects what happens in routine clinical practice which is important given access pressures for investigations and procedures such as mrcp or ercp . in conclusion , patients with suspected ics can be risk stratified and appropriately selected for further investigation by mrcp or proceed straight to therapeutic ercp . individuals with either abnormal liver biochemistry or cbd appearances on taus may need further assessment with mrcp ; however , patients in whom both investigations are abnormal may proceed directly to ercp as mrcp may delay therapeutic intervention or be of limited availability . moreover , those with normal liver biochemistry and normal appearances of the cbd on taus are exceedingly unlikely to have cbd stone disease and thus ercp is not warranted in this setting . we have proposed an algorithm for patient selection that is practicable and useful at our centre .
background . magnetic resonance cholangiopancreatography ( mrcp ) is noninvasive and accurate for diagnosing intra common bile duct stones ( icss ) . however , given limited access , routine utilisation for investigating all patients with gallstone disease is neither practical nor cost - effective . 
 conversely , many individuals proceed directly to endoscopic retrograde cholangiopancreatography ( ercp ) , an invasive test with appreciable complications . aim . 
 identify factors associated with ics in order to improve risk - stratification for mrcp / ercp . 
 methods . 
 all patients having undergone cholecystectomy between november 2007 and october 2008 were reviewed . 
 high - risk features for ics were predefined , and their true presence confirmed by ercp or intraoperative cholangiogram . 
 multivariate logistic regression was performed on candidate risk features . 
 results . of 231 patients , 
 10.4% had ics . defining a high - risk group with 
 both  biochemical and ultrasound risk factors predicted ics with 92% specificity and also bore strong association ( or 8.88 ) . 
 however , isolated hyperbilirubinaemia , ultrasound impression of cbd stones , and clinical risk factors did not ( or 1.10 , 0.97 , and 1.26 ) . 
 normal liver biochemistry and normal ultrasound had a npv of 99.5% for ics . 
 conclusions . ultrasound impression of cbd calculi without ductal dilatation 
 is not predictive of ics . 
 patients with normal liver biochemistry and normal cbd diameter on ultrasound are unlikely to have ics and should not proceed to ercp .