Gut 1996; 38: 277-281

Prospective evaluation of endoscopicultrasonography and microscopic examinationof duodenal bile in the diagnosis ofcholecystolithiasis in 45 patients with normalconventional ultrasonography

P Dahan, C Andant, P Levy, P Amouyal, G Amouyal, M Dumont, S Erlinger,A Sauvanet, J Belghiti, M Zins, V Vilgrain, P Bemades

AbstractThe aim of this study was to prospectivelyevaluate endoscopic ultrasonography andmicroscopic examination of duodenal bilein the diagnosis of cholecystolithiasis notdetected by conventional ultrasono-graphy. Forty five consecutive patients (26females, 19 males, mean age: 50 years)with suspected cholecystolithiasis and atleast two normal transcutaneous ultra-sonography examinations were included.Endoscopic ultrasonographic criteria forthe diagnosis of cholecystolithiasis werethe presence of stones with or withoutacoustic shadowing or sludge. Criteria ofmicroscopic examination of bile werecholesterol or bilirubinate crystals orspheroliths. Thirty three patients under-went cholecystectomy and lithiasis wasfound in gall bladder bile in 24. Twelvepatients who were not operated on andwere followed up (median: 17 months),had no evidence of cholecystolithiasis.Endoscopic ultrasonography and duo-denal bile examination were 96% and 67%sensitive, respectively (p<0.03). Thespecificity was not different (86 and 91%/respectively). None of the 16 patients withnegative results in both procedures hadevidence of cholecystolithiasis. It wasfound that for the diagnosis of cholecys-tolithiasis in patients with normal conven-tional ultrasonography, the sensitivity ofendoscopic ultrasonography is higherthan that of microscopic examination ofduodenal bile. If endoscopic ultrasono-graphy and microscopic examination ofduodenal bile are negative, the risk ofunderdiagnosing cholecystolithiasis isnegligible.(Gut 1996; 38: 277-281)

Keywords: gall bladder, lithiasis, bile, endoscopicultrasonography, microscopic bile examination.

The diagnosis of cholecystolithiasis is mainlybased on conventional transcutaneous ultra-sonography (TUS).1 2 TUS fails to detectcholecystolithiasis in some cases; it has beensuggested that the detection of cholesterol orbilirubinate crystals in gall bladder or duodenalbile could identify patients with and those

without cholecystolithiasis.3-6 The sensitivityof microscopic bile examination (MBE) isprobably lower when duodenal bile is studiedbecause of dilution with gastric, pancreatic,and intestinal secretions and possible incom-plete contraction of gall bladder even afterinjection of caeruleine.5 7

Endoscopic ultrasonography (EUS), a newimaging procedure, is particularly useful forexploring the biliopancreatic region and has ahigh sensitivity for the diagnosis of choledo-cholitiasis.8 9 The usefulness of EUS for thediagnosis of cholecystolithiasis has not beenassessed. The aim of this study was to prospec-tively evaluate and compare the accuracy ofEUS and MBE of gall bladder bile collected inthe duodenum in consecutive patients sus-pected of having a cholecystolithiasis but withnegative TUS.

Methods

Selection ofpatientsFrom January 1992 to July 1993, all patientswho fulfilled the inclusion criteria were prospec-tively studied. Inclusion criteria were either (a)transient epigastric or right upper quadrant painwith fever and jaundice associated with raisedserum alkaline phosphatase activities or raisedserum -y-glutamyltransferase or transaminaseactivities, or both over two times the upper limitof normal (n=20), or (b) acute pancreatitisdefined by acute epigastric pain requiring hos-pitalisation associated with increased serumamylase or lipase activities over three times theupper limit of normal (n= 25). Alcoholicpatients and patients suspected of having acutepancreatitis from other causes (drugs, hypercal-caemia, hypertriglyceridaemia) were excluded.Patients must also have had at least two normalTUS examinations (mean 2.3, range: 2-4) withat least one performed in our institution by anexperienced radiologist. Patients with abnormalgall bladder (stones, sludge, thickened wall) orwith abnormal common bile duct (stones,sludge, diameter enlargement, thickened wall)were excluded.

InterventionsIn our institution, TUS was performed withreal time, Siemens Sonoline (SL2) or

Service deGastroenterologieP DahanC AndantP LevyP AmouyalG AmouyalP Bemades

Service d'Hepatologieand INSERM U24M DumontS Erlinger

Service de ChirurgieVisceraleA SauvanetJ Belghiti

and Service deRadiologieM ZinsV Vilgrain

Hopital Beaujon,Clichy, France

Correspondence to:Dr P Levy, Service deGastroenterologie, H6pitalBeaujon, 92118 ClichyCedex, France.

Accepted for publication12 July 1995

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Komtron Signa 1 (frequency: 3.5 and 5MHz). To increase TUS sensitivity, patientposition was changed during the examination(to mobilise gall bladder lithiasis) andpatients were given water to reduce intestinalgas. TUS diagnostic criterion for gall bladderlithiasis was a hyperechoic structure withinthe gall bladder sometimes associated with anacoustic shadow.

All patients included underwent EUS andMBE of gall bladder bile collected from theduodenum. EUS was performed within 72hours after the last TUS with an OlympusGFUM 3/EUM 3 or GFUM 20/EUM 20. Thetransducer was inserted into the inferiorportion of the second duodenum and graduallydrawn back to the stomach. The acoustic liai-son between the transducer and the digestivewall was achieved by a balloon filled with5-20 ml water. The gall bladder was examinedthrough the duodenum and the stomachdepending on anatomical variations using7.5 MHz transducer frequency. The examina-tion lasted 10-30 minutes. Patients weresedated with intravenous propofol (ICIPharma, Cergy, France). The gall bladder wasexamined in all cases. Images were interpretedby four skilled operators (PD, PL, GA, PA)unaware of the MBE results.EUS diagnostic criteria for gall bladder

lithiasis was the presence within the gallbladder of: (a) a hyperechoic semicirculararch or circular shape associated with anacoustic shadow (Fig 1); (b) a hyperechoicfoci without associated acoustic shadowing(Fig 2); (c) gall bladder sludge defined bymobile, low amplitude echoes seen in thelumen that layered the most dependent partof the gall bladder without associated acousticshadowing10 (Fig 3).

Collection of duodenal bile was performedunder endoscopic control. A polyvinyl singleholed catheter (2.2 mm diameter; Olympus)was introduced into the operating channel ofthe echoendoscope or endoscope (OlympusGIF XQ 20) and placed in the second duode-num near the papilla of Vater, 10 to 15minutes after intramuscular injection of 30 ,ugof caerulein (Cerulex, Farmitalia Carlo Erba,Rueil Malmaison, France). Two to four twomillilitre aliquots of bile were aspirated fromthe catheter by gentle suction through a sterilesyringe and the darkest aliquot was used formicroscopic examination. Bile samples werekept at 37°C for at least one hour and thencentrifuged at 12 000 rpm for five minutes. Adrop of bile was examined under direct andpolarised light microscopy. All manipulationswere performed in sterile glass tubes pre-warmed to 37°C. MBE was performed imme-diately, 24 hours, and 48 hours after collectionwhile bile samples were kept at 37°C. Thediagnosis of cholecystolithiasis was consideredif at least one typical cholesterol crystal orbilirubinate granule were present according tocriteria established by Juniper and Burson3or in the presence of a large amount ofspheroliths.11 Duodenal MBE was alwaysperformed after EUS without knowledge ofEUS results.

Figure 1: 1 ransduodenal endoscopic ultrasonography:hyperechoic circular shape (thin black arrow) with a 3 mmdiameter associated with an acoustic shadow (thick blackarrow) suggesting a stone in the gall bladder infundibulum.

iiil::

Figure 2: Transduodenal endoscopic ultrasonography:hyperechoic foci with a diameter <2 mm without associatedacoustic shadowing suggesting stones (white arrows).

Figure 3: 1 ransduodenal endoscopic ultrasonography:mobile, low amplitude echoes seen in the lumen, whichlayered in the most dependent part of the gall bladderwithout associated acoustic shadowing suggesting gallbladder sludge.

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Endoscopic ultrasonography and cholecystolithiasis

TABLE I Patient characteristics

Women! Age (y)Clinical symptoms Number men (median (range))

Acute pancreatitis 25 14/11 49 (28-66)Symptoms of

cholecystolithiasis 20 12/8 52 (24-78)Total 45 26/19 50 (24-78)

Therapeutic decisionA laparoscopic or traditional cholecystectomywas performed: (a) if EUS or MBE suggestedthe presence of lithiasis, (b) in patients withoutradiological, duodenal MBE and EUS abnor-malities but with clinical and biochemical datastrongly suggesting lithiasis without any otherobvious causes; in these patients, the decisionof a cholecystectomy was made by the clinicianresponsible for the patient.

In patients who were operated on, gallbladder bile was collected operatively by needlepuncture and then immediately filtered througha pad to look for macroscopically visible stones.A MBE was performed with the same methodsas above. The gall bladder was then opened andmacroscopically visible stones were searchedfor. Gall bladder lithiasis was diagnosed ifmacroscopically visible stones or typical choles-terol crystals or bilirubinate granules were pre-sent according to criteria established by Juniperand Burson3 or if there were many spheroliths.'1

Patients who did not undergo cholecystec-tomy were followed up for at least six monthsand serum transaminase, alkaline phosphatase,and amylase activities were measured every sixmonths. These patients were interviewed forclinical signs of biliary disease. The decision torepeat TUS was made by the clinician respon-sible for the patient. All non-operated patientswere contacted in June 1994.

Statistical methodsBoth procedures (EUS and duodenal MBE)were compared using conventional x2 test withYates's correction to study variations in pre-dictability. A p value <005 was consideredsignificant. Sensitivity and specificity as well aspositive and negative predictive values werecalculated within the selected patient groups.

ResultsTable I gives the main characteristics of 45

TABLE II Correlation between EUS findings, duodenal MBE, and operative gall bladderbile examination in the 26 patients with positive EUS

Operative gall bladderEUSfindings Duodenal MBE bile examination

Hyperechoic foci with Cholesterol crystals (n= 1) Macroscopically visible stones (n= 3)acoustic shadowing No lithiasis (n=2)(n=3)*

Sludge (n= 5) Bilirubinate granules (n= 1) Bilirubinate granules (n= 1)Cholesterol crystals (n=2) Macroscopically visible stones (n=4)No lithiasis (n=2)

Hyperechoic foci without Cholesterol crystals (n= 6) Macroscopically visible stonesacoustic shadowing No lithiasis (n=4) (n= 10)(n= 18) Cholesterol crystals (n= 3) Cholesterol crystals (n= 3)

Bilirubinate granules (n= 1) Spheroliths (n= 1)Bilirubinate granules (n= 1) Bilirubinate granules (n= 1)No lithiasis (n=3) No lithiasis (n=3)

*Diameter <2 mm in all cases.

patients (26 women, 19 men; median age: 50(range 24-78) years). The mean time betweenEUS and bile sampling was 2.7 days (range0-32). There were no procedure related com-plications.

EUS resultsResults of EUS suggested cholecystolithiasis in26 patients (Table II). None of the patients haddirect or indirect signs of stones in the commonbile duct. The 26 patients with positive EUSwere operated on and the presence of lithiasismarkers was confirmed at cholecystectomy in23 including 17 patients with macroscopicallyvisible stone. Table II shows the correlationbetween EUS results, duodenal MBE, and thatof the examination of operatively obtained bile.The diagnosis was not confirmed by the exami-nation of operatively obtained bile in threepatients. In these, EUS only showed hypere-choic foci without acoustic shadowing aftertranscutaneous manual mobilisation of the gallbladder and the duodenal MBE was negative.

In 19 patients in whom EUS did not suggestcholecystolithiasis, seven underwent cholecys-tectomy (four based on the choice of the clini-cian, three because pre-operative duodenalMBE was positive). Lithiasis markers werefound in only one of these patients (Table III).Table IV summarises the results of EUS.

DuodenalMBE resultsDuodenal MBE was positive in 18 patients andshowed cholesterol crystals in 14, bilirubinategranules in three, and spheroliths in one. Allthese patients were operated on and the pres-ence of lithiasis markers was confirmed atcholecystectomy in 16 including nine withmacroscopically visible stone. In two patients(one with spheroliths, one with cholesterolcrystals), the diagnosis was not confirmed byexamination of the operatively obtained bile.

In 27 patients in whom duodenal MBE wasnegative, 15 underwent cholecystectomy (11because pre-operative EUS was positive, fourbased on the choice of the clinician).Macroscopically visible stones were found ineight patients and no lithiasis markers werefound in the remaining patients. Tables II andIII show the correlation between duodenal andoperative MBE. Table IV summarises theresults of duodenal MBE.

Diagnostic and therapeutic procedureThirty three patients underwent cholecystec-tomy, 29 because lithiasis criteria were present atEUS or duodenal MBE (EUS alone: n= 11,

TABLE iII Correlation between duodenal MBE andoperative gall bladder bile examination in seven patientswith negative EUS who were operated on

DuodenalMBE Operative gall bladder bileexamination

Cholesterol crystals (n= 1) Cholesterol crystals (n= 1)Cholesterol crystals (n= 1) No lithiasis (n= 1)Spheroliths (n= 1) No lithiasis (n= 1)No lithiasis (n=4) No lithiasis (n=4)

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TABLE IV Summary of the results ofEUS and duodenal MBEfor the diagnosis ofcholecystolithiasis in 45 patients suspected of having gall bladder stones undetectable byconventional TUS

EUS DuodenalMBE

Positive Negative Positive Negative

Number 26 19 18 27Lithiasis markers (n=24)* 23 1 16 8Patients with macroscopically visible stones 17 0 9 8No lithiasis markers (n=21) 3 18 2 19

*Patients with either macroscopically visible stones, cholesterol crystals, bilirubinate granules orspheroliths in operatively obtained bile.

TABLE V Sensitivity, specificity, positive and negative predictive values ofEUS andduodenal MBEfor the diagnosis of cholecystolithiasis in 45 patients suspected of havinggall bladder stones undetectable by conventional TUS

EUS MBE p Value

Sensitivity 96 (88 to 100) 67 (48 to 85) 0.0394* 82* NS*

Specificity 86 (71 to 100) 91 (79 to 100) NSPositive predictive value 89 (77 to 100) 89 (74 to 100) NSNegative predictive value 95 (85 to 100) 70 (53 to 87) NS

(95% confidence intervals).*Sensitivity of EUS and MBE for detecting patients with macroscopically visible stones.

TABLE VI Summary of the results ofEUS and duodenal MBEfor the diagnosis ofcholecystolithiasis in 25 patients suspected of having biliary pancreatitis without gallbladder stones detectable by conventional TUS

EUS DuodenalMBE

Positive Negative Positive Negative

Number 15 10 9 16Lithiasis markers (n= 14)* 14 0 7 7Patients with macroscopically visible stones 11 0 6 5No lithiasis (n= 11) 1 10 2 9

*Patients with either macroscopically visible stones, cholesterol crystals, bilirubinate granules orspheroliths in operatively obtained bile.

duodenal MBE alone: n=3, both procedures:n=15) and four patients with negative EUSand duodenal MBE because of the clinician'schoice. Bile obtained during the operationshowed lithiasis markers in 24 patients: macro-scopically visible stones: n= 17, cholesterolcrystals; n=4, bilirubinate granules: n=2,spheroliths: n= 1. No lithiasis markers werefound at cholecystectomy in nine patientsincluding the four with negative EUS andMBE findings. No patient had choledocholiti-asis. Twelve patients were not operated on andwere followed up (median: 17 (range: 12-21)months). All these patients were free of clinicaland biochemical symptoms. Four of them alsohad a normal TUS during follow up period,12-21 months after EUS and MBE.

Comparison ofEUS and duodenal MBETable V shows the sensitivity and specificity, aswell as positive and negative predictive valuesof the two procedures for the detection ofcholecystolithiasis in the group of selectedpatients. EUS was more sensitive but asspecific as duodenal MBE for the detection ofcholecystolithiasis. In 16 cases, both BUS andduodenal MBE were negative. None of these16 patients had evidence of cholecystolithiasisas shown by MBE of bile obtained at cholecys-tectomy in four patients and during follow upin 12 patients (four had a normal TUS duringfollow up). If the 12 patients who did not havea cholecystecomy are considered as false

negatives, EUS and duodenal MBE sensitivityreaches 64% and 44%, respectively.

Results ofEUS and MBE in the subgroup ofpatients with acute pancreatitis (n= 25)Table VI gives the EUS results. None of thepatients with negative EUS had evidence ofcholecystolithiasis based on examination ofbile obtained at cholecystectomy in four andfollow up in six. In this group of patients withsuspected acute biliary pancreatitis, the sensi-tivity and specificity of EUS were 100% and91%, respectively.

Table VI gives the duodenal MBE results.Seven patients with negative duodenal MBEhad evidence of lithiasis markers in the bileobtained at cholecystectomy (false negative)including five patients with macroscopically vis-ible stones. In nine patients with negative MBE,there was no evidence of cholecystolithiasisbased on examination of bile obtained at chole-cystectomy in three and follow up in six.

In the group of patients with suspected acutebiliary pancreatitis, the sensitivity of EUS andduodenal MBE were 100% and 500% (9/5% con-fidence intervals: 24 to 76%), respectively(p<0.01). The specificity ofthe two procedureswas 91% (95% confidence intervals: 76 to100%) and 82% (95% confidence intervals: 59to 1 00%), respectively (not significant).

DiscussionThe aim of this study was to prospectivelyevaluate the accuracy of EUS in diagnosingcholecystolithiasis when conventional TUS isnegative and to compare EUS to duodenalMBE. The diagnosis of cholecystolithiasis wasconsidered highly probable if lithiasis markers- that is, macroscopically visible stones,cholesterol crystals, bilirubinate granules,spheroliths - were present in bile collectedoperatively.6 The sensitivity of EUS (96%) wassignificantly higher than duodenal MBE (67%)but the specificity of both techniques wassimilar (86% and 91%, respectively). If weonly considered macroscopically visible stonesas the gold standard for the positive diagnosisof lithiasis, the sensitivity of EUS and MBEwere 94 and 82%, respectively.The accuracy of TUS in detecting chole-

cystolithiasis is high. The sensitivity of TUShas ranged from 92 to 96% in previousstudies.1 2 12 13 TUS false negatives mainlyresult from (a) stones <3 mm diameter thatare below TUS resolution, (b) stones locatedin the gall bladder infudibulum that are diffi-cult to visualise. In these cases, TUS sensitivityis about 65%.14 The specificity is about 100%if a hyperechoic image with acoustic shadow-ing is found in the gall bladder.1 2 New toolsthat are now available to explore the biliary treemay improve the detection rate of cholecys-tolithiasis in patients with symptoms suggest-ing gall stone disease.

Patients with negative EUS and duodenalMBE either had a cholecystectomy (n=4) orwere followed up (n= 12). A cholecystectomywas not justified for all patients in the study,

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Endoscopic ultrasonography and cholecystolithiasis 281

particularly for those with clinical and bio-chemical data that did not sufficiently suggestgall stone disease. In these patients, theabsence of gall stone disease was suggested bythe absence of symptoms during follow up. Asa result, we cannot be completely sure thatthese patients were free of gall stones.Nevertheless, lithiasis was not a clinicalproblem in these patients at least during theduration of follow up.EUS was only shown to be falsely negative in

one patient. This patient had a cholecystectomybecause of positive duodenal MBE and micro-scopic cholesterol crystals were found at opera-tion. EUS was falsely positive in three patients,but hyperechoic foci were only identified aftermanual transcutaneous mobilisation of the gallbladder. Perhaps the images seen in these caseswere acoustic reverberation artefacts caused bygall bladder wall movement and thus, only'spontaneously observed' hyperechoic foci -that is, those seen without manual transcu-taneous mobilisation - should be considered.Many authors have shown that cholesterol

crystals in bile are markers of the presence ofstones.5-7 15-17 Although the specificity of duo-denal MBE was similar to that of previousreports, the sensitivity (67%) was lower than inthe studies by Ros et al (86%),l5 Buscail et al(85%),16 and Delchier et al (880/o).17 In thesestudies, bile collection was performed withdirect cannulation of the papilla of Vater orwith a catheter in the duodenum for 12 hours.The many duodenal MBE false negatives inthis study were also found by other investiga-tors4 5 and may have many causes: (a) biledilution by gastric, duodenal and pancreaticsecretions: cholesterol crystals are lesscommon in duodenal than in gall bladderbile'8; (b) the intermittent presence of choles-terol crystals in duodenal bile.7 Althoughseveral bile collections would certainly improvethe sensitivity of this method, this would beless acceptable to patients. Two patients hadfalse positive duodenal MBE. In one, MBEshowed spheroliths. Spheroliths are only con-sidered markers of gall stone disease when theyare found in high numbers,'5 a quantitativeinterpretation that may increase the variabilityof the results. There is no clear explanation forthe other patient with false positive MBEshowing cholesterol crystals.

In the 25 patients with suspected acutebiliary pancreatitis, lithiasis markers werefound in 14 (56%). EUS sensitivity and speci-ficity were 100% and 91%, and those of duo-denal MBE were 50% and 82%, respectively.The diagnosis of cholecystolithiasis is particu-larly important and urgent as cholecystectomyor endoscopic sphincterotomy are required. Ina study that included patients with acute pan-creatitis, TUS sensitivity was 87%.11 In thestudy by Lee et al'19 that included 31 patientswith acute pancreatitis considered as idio-pathic (no gall stones at TUS and no othercauses), duodenal MBE showed bilirubinategranules or cholesterol crystals in 23 (86%) butbiliary sludge was shown by TUS in only 48%/.Our study showed that gall bladder sludgeidentified by EUS but not by TUS was also

closely related to the presence of lithiasismarkers. A previous study from our groupshowed that EUS was the most sensitive pro-cedure for the diagnosis of choledocholithia-sis.9 Thus, EUS may be performed in casesof acute pancreatitis of unknown aetiologyespecially if gall stones are suspected.

It is noteworthy that 16 patients with nega-tive results for both EUS and MBE had nocholecystolithiasis as shown by cholecystec-tomy in four and follow up in 12. Therefore,the negative predictive value of both tech-niques may be 100%. Associating these twoprocedures - which can be performed at thesame time - may be a highly accurate methodfor diagnosing or excluding cholecystolithiasis.The clinical significance of this result is of par-ticular importance in patients with pancreatitisof unknown aetiology and the drawbacks ofundergoing EUS should be counterbalancedby the seriousness of failing to diagnosecholelithiasis.The authors wish to thank Ms Dale Roche, editorial assistant ofthe 3'ournal of Hepatology, for her help in preparing the manu-script.

1 Hessler PC, Hill DS, Defoirie FM, Rocco AA. Highaccuracy sonographic recognition of gallstones. Am JRoentgenol 1981; 136: 517-20.

2 Cooperberg PL, Burhenne HJ. Real-time ultrasonography.Diagnostic technique of choice in calculous gallbladderdisease. NEngl3Med 1980; 302: 1277-9.

3 Juniper K Jr, Burson EN Jr. Biliary tract studies. II. Thesignificance of biliary crystals. Gastroenterology 1957; 32:175-211.

4 Neoptolemos JP, Davidson BR, Winder AF, Vallance D.Role of duodenal crystal analysis in the investigation ofidiopathic pancreatitis. BrJ Surg 1988; 75: 450-3.

5 Abbas A, Baumann R, Schutz JF, Maillard D, Sondag D,Weil JP. Cristaux de cholesterol et lithiase biliaire. Interetde l'etude de la bile recueillie par tubage duodenal.Gastroenterol Clin Biol 1984; 8: 454-7.

6 Ramond MJ, Dumont M, Belghiti J, Erlinger S. Sensitivityand specificity of microscopic examination of gallbladderbile for gallstone recognition and identification.Gastroenterology 1988; 95: 1339-43.

7 Marks JW, Bonorris G. Intermittency of cholesterol crystalsin duodenal bile from gallstone patients. Gastroenterology1984; 87: 622-7.

8 Amouyal P, Palazzo L, Amouyal G, Ponsot P, MompointD, Vilgrain V, et al. Endosonography: promising methodfor diagnosis of extrahepatic cholestasis. Lancet 1989; ii:1195-8.

9 Amouyal P, Amouyal G, Levy P, Tuzet S, Palazzo L,Vilgrain V, et al. Diagnosis of choledocolithiasis by endo-scopic ultrasonography. Gastroenterology 1994; 106:1062-7.

10 Conrad RR, Janes JO, Dietchy J. Significance of low levelechoes within the gallbladder. Am J Roentgenol 1979; 132:967-72.

11 Goodman AJ, Neoptolemos JP, Carr-Locke DL, FinlayDB, Fossard DP. Detection of gallstones after acute pan-creatitis. Gut 1985; 26: 125-32.

12 Lee CL, Wu CH, Chen TK, Yang SS, Huang CS.Prospective study of abdominal ultrasonography beforelaparoscopic cholecystectomy. _J Clin Gastroenterol 1993;1: 113-6.

13 McIntosch DMF, Pennay HF. Gray scale ultrasonographyas a screening procedure in the detection of gallbladderdisease. Radiology 1980; 136: 725-7.

14 Kurol M, Forsberg L. Ultrasonography in the diagnosis ofcholecystitis. Acta Radiol 1984; 25: 379-83.

15 Ros E, Navarro S, Bru C, Garcia-Puges A, Valderrama R.Occult microlithiasis in 'idiopathic' acute pancreatitis:prevention of relapses by cholecystectomy or ursode-oxycholic acid therapy. Gastroenterology 1991; 101:1701-9.

16 Buscail L, Escourrou J, Delvaux M, Guimbaud R, NicoletT, Frexinos J, et al. Microscopic examination of biledirectly collected during endoscopic cannulation of thepapilla. Utility in patients with suspected microlithiasis.Dig Ths Sci 1992; 37: 116-20.

17 Delchier JC, Benfredj P, Preaux AM, Metreau JM,Dhumeaux D. The usefulness of microscopic bile exami-nation in patients with suspected microlithiasis.Hepatology 1986; 6: 118-22.

18 Jonowitz P, Swobodnik W, Weschler JG, Zoller A, Kuhn K,Ditschuneit H. Comparison of gallbladder bile and endo-scopically obtained duodenal bile. Gut 1990; 31:1407-10.

19 Lee SP, Nicholls JF, Park HZ. Biliary sludge as a cause ofacute pancreatitis. NEngl3'Med 1992; 326: 589-93.

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