Background
Selection routines for preoperative endoscopic retrograde cholangiopancreatography (ERCP) in patients with symptomatic gallstone disease should give a low frequency of both false-negative ERCP results and residual common bile duct stones (CBDS).
Objective
To validate a discriminant function (DF) based on retrospectively collected data, for characterization of patients with symptomatic gallstone disease as regards presence of CBDS, and to compare clinical, ultrasonographic, and DF characterization.
Design
Prospective registration of CBDS criteria in consecutive patients with symptomatic gallstone disease.
Setting
A department of surgical gastroenterology in a Norwegian central hospital.
Patients
One hundred ninety-two patients with gallbladder stones.
Intervention
Laparoscopic cholecystectomy or ERCP with or without endoscopic sphincterotomy.
Main Outcome Measurements
Sensitivity and specificity of the clinical, ultrasonographic, and DF characterizations, and test of the validity of the DF.
Results
Thirty-two patients had CBDS. The clinical criteria of CBDS were present in 152 patients (79.2%): 21.1% of these patients had CBDS and there were no false-negative results (sensitivity, 100%; specificity, 25%). The risk of CBDS in patients with normal bile ducts at ultrasonographic examination was 8 of 124, and in patients with dilated ducts or suspected CBDS, 17 of 47 (sensitivity, 68%; specificity, 80%). The DF was positive in 50 patients (26%): 60% of these had CBDS, and there were 2 false-negative results (sensitivity, 94%; specificity, 88%). A discriminant analysis of the prospectively registered data selected the same set of CBDS criteria, and a new DF did not alter the characterization of any patient.
Conclusions
Clinical characterization had a higher sensitivity for CBDS detection than ultrasonography alone, but a lower specificity. The DF analysis was both more sensitive and specific than ultrasonography, and seemed efficient in selecting symptomatic gallstone patients for ERCP. It was reproducible and simple to use.
ABOUT 10% to 20% of patients presenting with symptomatic gallstone disease have common bile duct stones (CBDS).1-5 The symptoms of CBDS may be difficult to distinguish from those of gallbladder stones.1
The clinical implications of residual stones are debatable1,6,7 but may be serious,6-8 and detection of CBDS is therefore important in cholecystectomy patients. Laparoscopic CBDS removal is not feasible in many centers. Furthermore, 85% of patients, in whom an endoscopic sphincterotomy (EST) has been performed, will not need a cholecystectomy.9 Thus, preoperative detection of CBDS is justified.
In a previous study,6 a discriminant functon (DF)
to select patients for preoperative ERCP was shown to reduce the rate of unnecessary ERCP without an increase in the number of missed CBDS as compared with selection by clinical criteria.6,10,11 The DF was based on a discriminant analysis of retrospectively collected CBDS criteria.6 The disciminant analysis selected the combination of the age of the patient and the levels of serum bilirubin, alanine aminotransferase, and γ-glutamyltransferase as the best criteria to predict the risk of CBDS.
The aim of our study was to prospectively compare the sensitivity and specificity of the clinical and ultrasonographic characterizations with the DF characterization for the presence of CBDS in patients with symptomatic gallstone disease. We also wanted to validate the DF.
From October 1993 to August 1994, 192 patients with gallbladder stones were included in the study. There were 140 women and 52 men, with a mean age of 52.8 years (range, 9-99 years). Patients who had a previous EST, chronic or acute hepatitis, inflammatory bowel disease, or a history of alcohol abuse were excluded.
The CBDS parameters (liver function test results and previous or current clinical or ultrasonographic signs of biliary obstruction)6 were recorded for all the patients. Blood samples were obtained no more than 2 weeks before surgery or endoscopy; this was also the maximum interval for ultrasonography. The presence of 1 or more positive clinical criteria was defined as a positive clinical characterization. A diameter larger than 6 mm or suspected CBDS was considered a positive ultrasonographic indication. The DF characterization included the most recent liver function test results. A positive value indicated CBDS.6 Patients with gallstone pancreatitis underwent ERCP independently of their DF value.
The measurement of the bile duct diameter was performed during routine ultrasonography and the part of the measured bile duct was not specified. During ERCP the diameters of the hepatic duct, the bile duct at the cysticohepatic confluence, and the CBD were measured, using the diameter of the endoscope as a reference.
The patients who underwent cholecystectomy had primary follow-up by a telephone interview after 1 month, followed by a written questionnaire after 1 year. The slightest symptoms of residual stones were used as indications for examination at the outpatient clinic with liver function tests and ultrasonography. If stones could not be ruled out, ERCP was performed.
The definite CBDS classification of the patients was based on ERCP or a postoperative follow-up period of at least 1 year without indication of residual stones.
Continuously distributed variables and factors were expressed by mean values with SDs and categorized variables in contingency tables. Univariate comparisons between groups were carried out by using 2-tailed tests with a significance level of 5%. A 1-way analysis of variance (ANOVA) model was used for analysis of the assumed continuously distributed variables, and categorical variables were analyzed with the Fisher exact test and paired binomial test.12 The Pearson correlation coefficient was also used.12
To characterize patients with gallstone disease, the Fisher linear discriminant model13 was used. The discriminant analysis procedure14 has been described previously.6
Seventy-two patients had ERCP as the primary procedure. Fifty-seven of them had either a positive DF value (n=35), a positive DF value and pancreatitis (n=16), or a negative DF value and pancreatitis (n=6). Forty-four (79%) of these patients were treated with EST, 30 because of CBDS and 14 prophylactically. Fifteen patients had a negative DF value and no pancreatitis; none of them had CBDS.
One hundred thirty-seven patients underwent surgery with laparoscopic cholecystectomy and no preoperative ERCP (n=120) or after a negative ERCP (n=17). One patient underwent intraoperative cholangiography, and 3 had early postoperative ERCP. One of them, with an unrecognized positive DF value, had a residual stone, as did 1 of 2 others with a negative DF value. One patient died of myocardial infarcation postoperatively; autopsy results revealed no CBDS.
There were no dropouts in the follow-up program. At the primary follow-up (n=132), 4 to 12 weeks postoperatively, 27 patients were examined in the outpatient department and 7 of them had an ERCP examination; the results were negative for all. At the second follow-up (n=125), 11 to 32 months (mean, 17.5 months) postoperatively, 1 patient had had symptoms that suggested the spontaneous passage of a stone 2 months postoperatively. Twenty-five patients were examined at the outpatient department and 7 of them underwent ERCP: 6 had normal results and in 1 patient the ERCP results were uncertain and an EST was done, but no stone was found. Thus, no late residual stones were found.
According to our definitions, 32 of 192 patients had CBDS. The mean age of the patients with CBDS was 61.5 years (range, 22-99 years), while the mean age of the patients without CBDS was 50.8 years (range, 9-87 years) (P=.02).
The interval between blood sampling and surgery or ERCP was 1.7 days (range, 0-14 days, SD, 2.13). Four patients with positive DF values were, for various reasons, observed for 5 to 15 days. Blood sampling and DF analysis immediately before ERCP revealed a negative DF value, and ERCP was negative in all these patients.
Ultrasonographic evaluation of the bile ducts was successful in 171 patients (95.5%); 25 had CBDS. In patients with CBDS, the mean diameter of the duct was 8.4 mm (range, 3-18 mm; SD, 3.72); in patients without CBDS it was 4.8 mm (range, 1-12 mm; SD, 2.02) (P<.001). The frequency of CBDS was strongly correlated with the diameter of the duct. In 3 patients, CBDS were correctly diagnosed by ultrasonography, and 2 of the 3 with suspected CBDS proved to have CBDS.
Two patients with CBDS had a negative DF value. In 1 patient with gallstone pancreatitis, the diameter of the bile duct was 4 mm as measured by ultrasonography. In the other patient with an otherwise negative clinical characterization, bile duct diameter by ultrasonography was 9 mm.
At univariate analysis of the clinical variables, only actual jaundice, the findings of dark urine or light stools, and abnormal results of biochemical tests differed significantly (P<.01) between patients with and without CBDS.
Clinical characterization was positive in 152 patients (79.2%), but only 32 of them had CBDS (Table 1). None were false-negative results (sensitivity, 100%; specificity, 25%).
Ultrasonography was correct in 93.6% of the patients with a bile duct diameter of 6 mm or less, and 35% of the patients with a diameter larger than 6 mm had CBDS. The sensitivity of ultrasonography was 68% and the specificity was 79.5%.
The DF value was positive in 50 patients (26%); 30 (60%) of these had CBDS. Two were false-negative results (sensitivity, 93.8%) and there were 20 false-positive results (specificity, 87.5%).
In 52 patients, both ERCP and ultrasonography had been done within a mean period of 2.7 days (SD, 4.1 days). In many of the patients, the bile duct diameter measured at ultrasonography differed substantially from the diameter measured at ERCP (Table 2). The correlation between measurements at ultrasonography and ERCP was significant (P<.001), but the correlation coefficient was only 0.52. With ERCP as the standard, the sensitivity of detection of bile duct dilation by ultrasonography was 71% and the specificity was 57%.
The discriminant analysis of the CBDS indicators in the present series selected the same combination as in the previous series.6 The previous DF formula based on these prospective data (y= −3.40801 + 0.02666 × age + 0.02949 × bilirubin level + 0.00693 × alanine aminotransferase level + 0.00245 × γ-glutamyltransferase level) did not change the CBDS characterization in any patient in the prospective series. However, applied to the retrospective series6 it was more sensitive than the retrospectively based formula, detecting 1 more patient with CBDS (10 vs 11 false-negative characterizations; sensitivity, 95.6% vs 95.2%), and also less specific, with 8 more false-positive results (30 vs 22; specificity, 91.9% vs 94.1%). The new formula produced a y value slightly shifted in the positive direction compared with the retrospectively based formula. The probability of CBDS related to the various y values was identical in both series.6
If strict selection criteria according to the DF had been followed in all the patients, 8 (5.8%) would have had preoperative ERCP results that were negative for CBDS.
The frequency of unsuspected CBDS is reported to be 0% to 3.4%,1,6,10,15 and a routine stone detection procedure does not seem necessary.4,15,16 On the other hand, only half of the patients with positive clinical criteria6,15 (in the present study, 1 of 5) have CBDS, and it is important to identify the group of patients in whom the yield of a detection procedure is sufficient to warrant it. Relevant diagnostic criteria are debated in the literature, without general agreement.2,3,5,17-22
The DF6 is an alternate method to ensure a clinically acceptable detection rate and a low rate of unnecessary ERCP. The reduced frequency of ERCP outweighs the risks related to the slight increase in residual stones. The DF program is computerized and is simple to use, as it only requires entering the values of 4 parameters.
The variables we selected for the DF function do not differ much from other studies,18,20,23,24 although alkaline phosphatase levels were not included.5,17 The use of a combination of CBDS indicators is well recognized. The discriminant analysis by Taylor et al19 selected the combination of intraoperatively measured bile duct diameter and number of gallbladder stones greater than 10, with an accuracy of 92.5% and false-negative results in fewer than 1% of patients. Onken et al25 selected the patient age, alkaline phosphatase level, bilirubin level, aspartate aminotransferase level, and CBD diameter by a logistic regression technique and made a diagram from which the probability of CBDS could be read directly. The logistic regression analysis of Houdart et al4 selected no jaundice, normal transaminase levels, CBD diameter less than 8 mm, and no intrahepatic bile duct enlargement at ultrasonography as the best parameters to predict low risk of CBDS. Two thirds of his patients were at low risk, and CBDS occurred unexpectedly in 1% of them. Barkun et al22 selected age older than 55 years, bilirubin level greater than 30 µmol/L (1.8 mg/dL), and CBD diameter greater than 6 mm assessed by ultrasonography as the best model for CBDS prediction. The probability of CBDS in that study was 19% when no predictor was present and 72% with 3 predictors present. Suspected or detected CBDS at ultrasonography increased the probability to up to 94%. Robertson et al17 selected age, jaundice, alkaline phosphatase level, albumin level, and ultrasonography criteria, producing a sensitivity of 89% and a specificity of 75% for the presence of CBDS.
Ultrasonographic bile duct diameter is considered valuable in CBDS prediction.1,3,15-17,19,25 Our use of 6 mm as the upper normal limit is in accordance with others,20,22,26,27 but 4 mm,28,29 5 mm,15,30 7 mm5,17 and 8 mm31 are also used. Sensitivity and specificity of bile duct diameter as a CBDS indicator are 94% and 99% and 79% and 85% for 4 mm,28,29 76% and 49% for 5 mm,30 53% and 73% for 6 mm,22 and 80% and 70% for 7 mm,17 respectively; the last 2 sets of value concur with our results.
Ultrasonography has been reported by some authors26,30 to be less precise than ERCP in bile duct diameter measurement. However, good to excellent correlation (r=0.73-0.94) between ultrasonography and radiographic methods has been described by others.27,29,31-33 The results of ultrasonography may be improved by special techniques29,31,33 or especially dedicated examiners.34
In our series, 60% of the patients with positive DF values and 1.4% with negative values had CBDS, indicating a acceptable yield for patients selected for ERCP with a low risk of residual stones and comparing well with other methods.4,19
Many CBDS pass spontaneously over the sphincter of Oddi.22,28,35,36 Repeated biochemical tests and a recharacterization of the patient may therefore be worthwhile if some days pass before the ERCP procedure.
The DF characterization we used was dependent on only a few variables that can be precisely determined, and not on clinical signs and technical procedures that may be difficult to interpret. The results of the DF characterization were reproducible. The new formula was slightly more sensitive and less specific, but both formulas have proved efficient in clinical practice. Which one of them should be preferred should be an objective for future studies on large patient series.
In our study, 36.4% of the patients with pancreatitis had CBDS at ERCP; 7 of 16 patients with positive DF values and 1 of 6 with negative values. We think that the dramatic improvement often observed after EST in these patients37 justifies the low detection rates. We have adopted a liberal practice of prophylactic EST in patients with gallstone pancreatitis, with a recurrence rate of 0%.38 Only a few patients have later required a cholecystectomy for gallbladder stone disease.38
In conclusion, the clinical characterization of patients with symptomatic gallstones with regard to the presence of CBDS was highly sensitive, but the specificity was too low for practical application. The sensitivity of ultrasonography was too low in our study to concur with that of other selection procedures. The DF was both more sensitive and specific than ultrasonography, and ensured a clinically acceptable detection rate and a low rate of unnecessary ERCP. The DF program was simple to use and dependent on only a few precisely determined variables. The DF formula as well as the DF characterization were reproducible in 2 independent patient series.
Presented as a scientific exhibit at the Fifth Annual United European Gastroenterology Week, Paris, France, November 5, 1996.
Corresponding author: Arne R. Rosseland, PhD, Department of Surgical Gastroenterology, Central Hospital of Akershus, N-1474 Nordbyhagen, Norway.
1.Neuhaus
HFeussner
HUngeheuer
AHoffmann
WSiewert
JRClassen
M Prospective evaluation of the use of endoscopic retrograde cholangiography prior to laparoscopic cholecystography.
Endoscopy. 1992;24745- 749
Google ScholarCrossref 2.Saltzstein
ECPeacock
JBThomas
MD Preoperative bilirubin, alkaline phosphatase and amylase levels as predictors of common duct stones.
Surg Gynecol Obstet. 1982;154381- 384
Google Scholar 3.Lacaine
FCorlette
MBBismuth
H Preoperative evaluation of the risk of common bile duct stones.
Arch Surg. 1980;1151114- 1116
Google ScholarCrossref 4.Houdart
RPerniceni
TDarne
BSalmeron
MSimon
JF Predicting common bile duct lithiasis: determination and prospective validation of a model predicting low risk.
Am J Surg. 1995;17038- 43
Google ScholarCrossref 5.Welbourn
CRBMehta
DArmstrong
CPGear
MWLEyre-Brook
IA Selective preoperative endoscopic retrograde cholangiography with sphincterotomy avoids bile duct exploration during laparoscopic cholecystectomy.
Gut. 1995;37576- 579
Google ScholarCrossref 6.Trondsen
EEdwin
BReiertsen
OFagertun
HRosseland
AR Selection criteria for endoscopic retrograde cholangiography (ERCP) in patients with gallstone disease.
World J Surg. 1995;19852- 857
Google ScholarCrossref 7.Stiegman
GVGoff
JSMansour
APearlman
NReveille
RMNorton
L Precholecystectomy endoscopic cholangiography and stone removal is not superior to cholecystectomy, cholangiography, and common bile duct exploration.
Am J Surg. 1992;163227- 230
Google ScholarCrossref 8.Mjåaland
ORaeder
JAaseboe
VTrondsen
EBuanes
T Outpatient laparoscopic cholecystectomy, patient satisfaction and safety: prospective study of 200 patients.
Br J Surg. In press
Google Scholar 10.Hauer-Jensen
MKåresen
RNygaard
K
et al. Predictive ability of choledocholithiasis indicators: a prospective evaluation.
Ann Surg. 1985;20264- 68
Google ScholarCrossref 11.Hauer-Jensen
MKåresen
RNygaard
K
et al. Consequences of routine preoperative cholangiography during cholecystectomy for gallstone disease: a prospective, randomized study.
World J Surg. 1986;10996- 1002
Google ScholarCrossref 12.Altman
DG Practical Statistics for Medical Research. London, England Chapman & Hall1992;
13.Hand
DJ Discrimination and Classification. New York, NY John Wiley & Sons1976;
14.Jennrich
RIEnslein
KedRalston
AedWilf
Hed Stepwise discriminant analysis.
Statistical Methods for Digital Computers. New York, NY John Wiley & Sons1979;
Google Scholar 15.Voyles
CRPetro
ABMeena
ALHaick
AJKoury
AM A practical approach to laparoscopic cholecystectomy.
Am J Surg. 1991;161365- 370
Google ScholarCrossref 16.Cotton
PB Endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy.
Am J Surg. 1993;165474- 478
Google ScholarCrossref 17.Robertson
GSMJagger
CJohnson
PRV
et al. Selection criteria for preoperative endoscopic retrograde cholangiography in the laparoscopic era.
Arch Surg. 1996;13189- 94
Google ScholarCrossref 18.Anciaux
MLPelletier
GAttali
PMeduri
BLiguory
CEtienne
JP Prospective study of clinical and biochemical features of symptomatic choledocholithiasis.
Dig Dis Sci. 1986;31449- 453
Google ScholarCrossref 19.Taylor
TVArmstrong
CPRimmer
SLucas
SBJeacock
JGunn
AA Prediction of choledocholithiasis using a pocket microcomputer.
Br J Surg. 1988;75138- 140
Google ScholarCrossref 20.Reiss
RDeutsch
AANudelman
IKott
I Statistical value of various clinical parameters in predicting the presence of choledochal stones.
Surg Gynecol Obstet. 1984;159273- 276
Google Scholar 21.Santo
PDKazarian
KKRogers
JFBevins
PAHall
JR Prediction of operative cholangiography in patients undergoing elective cholecystectomy with routine liver function chemistry.
Surgery. 1985;987- 11
Google Scholar 22.Barkun
ANBarkun
JSFried
GM
et al. Useful predictors of bile duct stones in patients undergoing laparoscopic cholecystectomy.
Ann Surg. 1994;22032- 39
Google ScholarCrossref 23.Patwardhan
RVSmith
OJFarmelant
MH Serum transaminase levels and cholescintigraphic anomalies in acute biliary tract obstruction.
Arch Intern Med. 1987;1471249- 1253
Google ScholarCrossref 24.Clemets
DAslan
SWilkins
WE Common bile duct gallstones, anicteric presentation in the elderly: under-recognized but important.
Postgrad Med J. 1990;66878- 879
Google ScholarCrossref 25.Onken
JBrazer
SEisen
G
et al. Accurate prediction of choledocholithiasis. Program and abstracts of the American Association for the Study of Liver Disease, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, and Society for Surgery of the Alimentary Tract group conference May 15-18, 1994 New Orleans, LaAbstract 699
26.Bhargava
SVashisht
SKakaria
ATandon
RKBerry
M Choledocholithiasis: an ultrasonic study with comparative evaluation with ERCP/PTC.
Australas Radiol. 1988;32220- 226
Google ScholarCrossref 27.O'Connor
HJBartlett
RJHamilton
I
et al. Bile duct calibre: the value of ultrasonic and cholangiographic measurement in the postcholecystectomy patient.
Gut. 1984;25(suppl)A576
Google Scholar 28.Cooperberg
PLLi
DWong
PCohen
MMBurhenne
HJ Accuracy of common hepatic duct size in the evaluation of extrahepatic biliary obstruction.
Radiology. 1980;135141- 144
Google Scholar 29.Hunt
DRScott
AJ Changes in bile duct diameter after cholecystectomy: a 5-year prospective study.
Gastroenterology. 1989;971485- 1488
Google Scholar 30.Gross
BHHarter
LPGore
RM
et al. Ultrasonic evaluation of common bile duct stones: prospective comparison with endoscopic retrograde cholangiography.
Radiology. 1983;146471- 474
Google Scholar 31.Behan
MKazam
E Sonography of the common bile duct: value of the right anterior oblique view.
AJR Am J Roentgenol. 1978;130701- 709
Google ScholarCrossref 32.Niederau
CSonnenberg
AMueller
J Comparison of the extrahepatic bile duct size measured by ultrasound and by different radiographic methods.
Gastroenterology. 1984;87615- 621
Google Scholar 33.Sauerbrei
EECooperberg
PLGordon
PLi
DCohen
MMBurhenne
HJ The discrepancy between radiographic and sonographic bile duct measurements.
Radiology. 1980;137751- 755
Google Scholar 34.Hunt
DRReiter
LScott
AJ Preoperative ultrasound measurement of bile duct diameter: basis for selective cholangiography.
Aust N Z J Surg. 1990;60189- 192
Google Scholar 35.Pasanen
PPartanen
KPikkarainen
PAlhava
EPirinen
AJanatuinen
E Ultrasonography, CT, and ERCP in the diagnosis of choledochal stones.
Acta Radiol. 1992;3353- 56
Google ScholarCrossref 36.Kelly
TR Gallstone pancreatitis: the timing of surgery.
Surgery. 1980;88345- 350
Google Scholar 37.Rosseland
ARSolhaug
JH Early or delayed endoscopic papillotomy (EPT) in gallstone pancreatitis.
Ann Surg. 1984;199165- 167
Google ScholarCrossref 38.Edwin
BRosseland
ARRTrondsen
E Prophylactic endoscopic sphincterotomy as treatment for gallstone pancreatitis.
Scand J Gastroenterol. 1993;28(suppl 197)58
Google Scholar