The hunt for microlithiasis in idiopathic acute recurrent pancreatitis: Should we abandon the search or intensify our efforts?
2002; Elsevier BV; Volume: 55; Issue: 2 Linguagem: Inglês
10.1067/mge.2002.121224
ISSN1097-6779
Autores Tópico(s)Gastrointestinal disorders and treatments
ResumoAcute pancreatitis results most commonly from alcohol abuse or gallstone disease. When patients have more than one clinical episode of acute pancreatitis they are given the diagnosis of acute recurrent pancreatitis (ARP). The etiology of ARP is identified in 70% to 90% of patients after an initial evaluation that includes a thorough history, physical examination, routine laboratory tests, and transabdominal ultrasound (TUS) or CT.1Venu RP Geenen JE Hogan W Stone J Johnson GK Soergel K Idiopathic recurrent pancreatitis. An approach to diagnosis and treatment.Dig Dis Sci. 1989; 34: 56-60Crossref PubMed Scopus (164) Google Scholar, 2Ballinger AB Barnes E Alstead EM Fairclough PD Is intervention necessary after a first episode of acute idiopathic pancreatitis?.Gut. 1996; 38: 293-295Crossref PubMed Scopus (63) Google Scholar, 3Thomson SR Hendry WS McFarlane GA Davidson AI Epidemiology and outcome of acute pancreatitis.Br J Surg. 1987; 74: 398-401Crossref PubMed Scopus (125) Google Scholar, 4Lee SP Nicholls JF Park HZ Biliary sludge as a cause of acute pancreatitis.N Engl J Med. 1992; 326: 589-593Crossref PubMed Scopus (463) Google Scholar, 5Levy MJ Geenen J Idiopathic acute recurrent pancreatitis.Am J Gastroenterol. 2001; 96: 2540-2555Crossref PubMed Google Scholar For the 10% to 30% of patients in whom the initial evaluation fails to reveal an etiology, the diagnosis of “idiopathic” acute recurrent pancreatitis (IARP) is often applied.1Venu RP Geenen JE Hogan W Stone J Johnson GK Soergel K Idiopathic recurrent pancreatitis. An approach to diagnosis and treatment.Dig Dis Sci. 1989; 34: 56-60Crossref PubMed Scopus (164) Google Scholar, 2Ballinger AB Barnes E Alstead EM Fairclough PD Is intervention necessary after a first episode of acute idiopathic pancreatitis?.Gut. 1996; 38: 293-295Crossref PubMed Scopus (63) Google Scholar, 3Thomson SR Hendry WS McFarlane GA Davidson AI Epidemiology and outcome of acute pancreatitis.Br J Surg. 1987; 74: 398-401Crossref PubMed Scopus (125) Google Scholar, 4Lee SP Nicholls JF Park HZ Biliary sludge as a cause of acute pancreatitis.N Engl J Med. 1992; 326: 589-593Crossref PubMed Scopus (463) Google Scholar, 5Levy MJ Geenen J Idiopathic acute recurrent pancreatitis.Am J Gastroenterol. 2001; 96: 2540-2555Crossref PubMed Google Scholar The extent of the evaluation impacts the frequency with which an etiology can be found and how often the diagnosis of IARP is used.2Ballinger AB Barnes E Alstead EM Fairclough PD Is intervention necessary after a first episode of acute idiopathic pancreatitis?.Gut. 1996; 38: 293-295Crossref PubMed Scopus (63) Google Scholar, 6Geenen JE Nash JA The role of sphincter of Oddi manometry and biliary microscopy in evaluating idiopathic recurrent pancreatitis.Endoscopy. 1998; 30: A237-A241PubMed Google Scholar This diagnosis is most often used when a more limited evaluation, as detailed above, fails to reveal an etiology. A more extensive evaluation may include specialized laboratory tests, ERCP, EUS, and magnetic resonance cholangiopancreatography (MRCP). Inclusion of these additional tests usually leads to the diagnosis of microlithiasis, sphincter of Oddi dysfunction, or pancreas divisum.1Venu RP Geenen JE Hogan W Stone J Johnson GK Soergel K Idiopathic recurrent pancreatitis. An approach to diagnosis and treatment.Dig Dis Sci. 1989; 34: 56-60Crossref PubMed Scopus (164) Google Scholar, 3Thomson SR Hendry WS McFarlane GA Davidson AI Epidemiology and outcome of acute pancreatitis.Br J Surg. 1987; 74: 398-401Crossref PubMed Scopus (125) Google Scholar, 7Steinberg W Tenner S Acute pancreatitis.N Engl J Med. 1994; 330: 1198-1210Crossref PubMed Scopus (875) Google Scholar If this more extensive evaluation fails to reveal an etiology, then the diagnosis of “true” IARP may be assigned. Determining the etiology is important because it helps to direct therapy, limits further unnecessary tests, and may improve a patient's long-term prognosis. Although some investigators have detected microlithiasis in fewer than 10% of patients evaluated for ARP,1Venu RP Geenen JE Hogan W Stone J Johnson GK Soergel K Idiopathic recurrent pancreatitis. An approach to diagnosis and treatment.Dig Dis Sci. 1989; 34: 56-60Crossref PubMed Scopus (164) Google Scholar, 8Nash JA Geenen JE Hogan WJ Geenen DJ Catalano MF Johnson GK et al.The role of sphincter of Oddi manometry (SOM) and biliary microscopy in evaluating idiopathic recurrent pancreatitis (IRP) [abstract].Gastroenterology. 1996; 110: 31AGoogle Scholar most have found evidence of microlithiasis in approximately two thirds of these patients (Table 1).4Lee SP Nicholls JF Park HZ Biliary sludge as a cause of acute pancreatitis.N Engl J Med. 1992; 326: 589-593Crossref PubMed Scopus (463) Google Scholar, 9Ros E Navarro S Bru C Garcia-Puges A Valderrama R Occult microlithiasis in ‘idiopathic’ acute pancreatitis: prevention of relapses by cholecystectomy or ursodeoxycholic acid therapy.Gastroenterology. 1991; 101: 1701-1709Abstract PubMed Google Scholar, 10Kaw M Verma R Brodmerkel GJ ERCP, biliary analysis, sphincter of Oddi manometry (SOM) in idiopathic pancreatitis (IP) and response to endoscopic sphincterotomy (ES) [abstract].Am J Gastroenterol. 1996; 91: 1935AGoogle Scholar, 11Sherman S Jamidar P Reber H Idiopathic acute pancreatitis (IAP): endoscopic approach to diagnosis and therapy [abstract].Am J Gastroenterol. 1993; 88: 1541AGoogle ScholarTable 1Frequency of microlithiasis in patients with idiopathic acute recurrent pancreatitisFrequencyPercentStudies with low frequency Venu 19898/1167 Nash 19965/88613/2046Studies with high frequency Ros 199137/5173 Lee 199221/2972 Sherman 19937/1354 Kaw 199615/256080/11868 Open table in a new tab In the study by Kaw and Brodmerkel in this issue of Gastrointestinal Endoscopy,12Kaw M Brodmerkel GJ ERCP, biliary crystal analysis and sphincter of Oddi manometry in idiopathic recurrent pancreatitis.Gastrointest Endosc. 2002; 55: 157-162Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar 50% of patients were found to have microlithiasis. Most investigators believe that in the absence of another identifiable risk factor, the presence of microlithiasis in a patient with pancreatitis is evidence enough for causality. Although some routinely search for microlithiasis,4Lee SP Nicholls JF Park HZ Biliary sludge as a cause of acute pancreatitis.N Engl J Med. 1992; 326: 589-593Crossref PubMed Scopus (463) Google Scholar, 9Ros E Navarro S Bru C Garcia-Puges A Valderrama R Occult microlithiasis in ‘idiopathic’ acute pancreatitis: prevention of relapses by cholecystectomy or ursodeoxycholic acid therapy.Gastroenterology. 1991; 101: 1701-1709Abstract PubMed Google Scholar, 10Kaw M Verma R Brodmerkel GJ ERCP, biliary analysis, sphincter of Oddi manometry (SOM) in idiopathic pancreatitis (IP) and response to endoscopic sphincterotomy (ES) [abstract].Am J Gastroenterol. 1996; 91: 1935AGoogle Scholar, 11Sherman S Jamidar P Reber H Idiopathic acute pancreatitis (IAP): endoscopic approach to diagnosis and therapy [abstract].Am J Gastroenterol. 1993; 88: 1541AGoogle Scholar others question this practice.13Janowitz P Kratzer W Zemmler T Tudyka J Wechsler JG Gallbladder sludge: spontaneous course and incidence of complications in patients without stones.Hepatology. 1994; 20: 291-294Crossref PubMed Scopus (61) Google Scholar, 14Andersen IB Hojgaard L Whither biliary sludge—do you exist? [letter; comment].Gastroenterology. 1991; 101: 1758-1759PubMed Google Scholar The differing views stem in part from uncertainty regarding the pathogenesis, clinical significance, natural history, ideal means of diagnosis, and optimum therapy. Microlithiasis is also referred to as sludge, biliary sand, biliary sediment, microcrystalline disease, pseudolithiasis, and reversible cholelithiasis. Most use the term microlithiasis or sludge, and although they are technically different, the terms are often used interchangeably. This may be the case because many consider sludge to be a precursor to microlithiasis with both having the same clinical significance. The interpretation and applicability of data obtained from prior studies are limited by the lack of a uniformly accepted definition.15Lee SP Hayashi A Kim YS Biliary sludge: curiosity or culprit?.Hepatology. 1994; 20: 523-525Crossref PubMed Scopus (40) Google Scholar, 16Cetta F Biliary sludge: necessity for a better distinction between crushable and noncrushable microconcrements. Sludge is responsible for symptoms not by itself, but also in relationship to the variability of the container, i.e., the bile tract wall.Hepatology. 1996; 23: 191-192Crossref PubMed Scopus (1) Google Scholar, 17Houssin D Castaing D Lemoine J Bismuth H Microlithiasis of the gallbladder.Surg Gyn Obstet. 1983; 157: 20-24PubMed Google Scholar, 18Block MA Priest RJ Acute pancreatitis related to grossly minute stones in a radiographically normal gallbladder.Am J Dig Dis. 1967; 12: 934-938Crossref PubMed Scopus (20) Google Scholar, 19Pfefferman R Luttwak EM Gallstone pancreatitis. Exploration of the biliary system in pancreatitis of undetermined origin.Arch Surg. 1971; 103: 484-486Crossref PubMed Scopus (6) Google Scholar Although the definition varies among investigators, most refer to microlithiasis as stones less than 3 mm in diameter,17Houssin D Castaing D Lemoine J Bismuth H Microlithiasis of the gallbladder.Surg Gyn Obstet. 1983; 157: 20-24PubMed Google Scholar, 20Sarva RP Farivar S Fromm H Poller W Study of the sensitivity and specificity of computerized tomography in the detection of calcified gallstones which appears radiolucent by conventional roentgenography.Gastrointest Radiol. 1981; 6: 165-167Crossref PubMed Scopus (24) Google Scholar, 21Sharma BC Agarwal DK Dhiman RK Baijal SS Choudhuri G Saraswat VA Bile lithogenicity and gallbladder emptying in patients with microlithiasis: effect of bile acid therapy.Gastroenterology. 1998; 115: 124-128Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar and biliary sludge is considered to be a suspension of crystals, mucin, glycoproteins, cellular debris, and proteinaceous material within bile.4Lee SP Nicholls JF Park HZ Biliary sludge as a cause of acute pancreatitis.N Engl J Med. 1992; 326: 589-593Crossref PubMed Scopus (463) Google Scholar, 22Ko CW Sekijima JH Lee SP Biliary sludge.Ann Intern Med. 1999; 130: 301-311Crossref PubMed Scopus (170) Google Scholar, 23Filly RA Allen B Minton MJ Bernhoft R Way LW In vitro investigation of the origin of echoes with biliary sludge.J Clin Ultrasound. 1980; 8: 193-200Crossref PubMed Scopus (75) Google Scholar, 24Allen B Bernhoft R Blanckaert N Svanvik J Filly R Gooding G et al.Sludge is calcium bilirubinate associated with bile stasis.Am J Surg. 1981; 141: 51-56Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 25Lee SP Nicholls JF Nature and composition of biliary sludge.Gastroenterology. 1986; 90: 677-686Abstract Full Text PDF PubMed Scopus (183) Google Scholar The various types of crystals include cholesterol monohydrate, calcium bilirubinate, and other calcium salts (carbonate, phosphate and fatty acid complexes). To what extent microlithiasis develops in persons who have no identifiable risk factor is controversial.13Janowitz P Kratzer W Zemmler T Tudyka J Wechsler JG Gallbladder sludge: spontaneous course and incidence of complications in patients without stones.Hepatology. 1994; 20: 291-294Crossref PubMed Scopus (61) Google Scholar, 14Andersen IB Hojgaard L Whither biliary sludge—do you exist? [letter; comment].Gastroenterology. 1991; 101: 1758-1759PubMed Google Scholar, 26Jorgensen T Prevalence of gallstones in a Danish population.Am J Epidemiol. 1987; 126: 912-921Crossref PubMed Scopus (260) Google Scholar, 27Ros E Navarro S Fernandez I Reixach M Ribo JM Rodes J Utility of biliary microscopy for the prediction of the chemical composition of gallstones and the outcome of dissolution therapy with ursodeoxycholic acid.Gastroenterology. 1986; 91: 703-712PubMed Google Scholar, 28Sedaghat A Grundy SM Cholesterol crystals and the formation of cholesterol gallstones.N Engl J Med. 1980; 302: 1274-1277Crossref PubMed Scopus (182) Google Scholar, 29Delchier JC Benfredj P Preaux AM Metreau JM Dhumeaux D The usefulness of microscopic bile examination in patients with suspected microlithiasis: a prospective evaluation.Hepatology. 1986; 6: 118-122Crossref PubMed Scopus (49) Google Scholar However, there are a number of clinical conditions that are clearly associated with the formation of sludge and microlithiasis (Table 2).Table 2Clinical conditions associated with the formation of microlithiasisNo identifiable risk factorNutrition/weight related Prolonged fasting Total parenteral nutrition (long-term) Rapid weight lossPregnancyChronic illness Acquired immunodeficiency syndrome Cirrhosis Sickle cell anemiaAcute illness Intensive care unit Spinal cord injury SurgeryTransplantation Bone marrow Solid organMedications Cefriaxone Cyclosporine Octreotide Open table in a new tab These include parenteral supplementation,30Gafa M Sarli L Miselli A Pietra N Carreras F Peracchia A Sludge and microlithiasis of the biliary tract after total gastrectomy and postoperative total parenteral nutrition.Surg Gyn Obstet. 1987; 165: 413-418PubMed Google Scholar, 31Pitt HA King III, W Mann LL Roslyn JJ Berquist WE Ament ME et al.Increased risk of cholelithiasis with prolonged total parenteral nutrition.Am J Surg. 1983; 145: 106-112Abstract Full Text PDF PubMed Scopus (150) Google Scholar, 32Muller EL Grace PA Pitt HA The effect of parenteral nutrition on biliary calcium and bilirubin.J Surg Res. 1986; 40: 55-62Abstract Full Text PDF PubMed Scopus (41) Google Scholar conditions associated with weight loss,33Rahmani MR Tumefactive biliary sludge.AJR Am J Roentgenol. 1985; 145: 860-861Crossref PubMed Scopus (2) Google Scholar, 34Schlierf G Schellenberg B Stiehl A Czygan P Oster P Biliary cholesterol saturation and weight reduction—effects of fasting and low calorie diet.Digestion. 1981; 21: 44-49Crossref PubMed Scopus (16) Google Scholar, 35Shiffman ML Sugerman HJ Kellum JM Moore EW Changes in gallbladder bile composition following gallstone formation and weight reduction.Gastroenterology. 1992; 103: 214-221Abstract PubMed Google Scholar, 36Wise L Stein T The effect of jejunoileal bypass on bile composition and the formation of billiary calculi.Ann Surg. 1978; 187: 57-62Crossref PubMed Scopus (14) Google Scholar pregnancy,37Maringhini A Ciambra M Baccelliere P Raimondo M Orlando A Tine F et al.Biliary sludge and gallstones in pregnancy: incidence, risk factors, and natural history.Ann Intern Med. 1993; 119: 116-120Crossref PubMed Scopus (196) Google Scholar, 38Everson GT Fennessey P Kern Jr, F Contraceptive steroids alter the steady-state kinetics of bile acids.J Lipid Res. 1988; 29: 68-76PubMed Google Scholar, 39Everson GT McKinley C Kern Jr, F Mechanisms of gallstone formation in women. 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The optimal method for detecting microlithiasis and the extent to which a diagnosis is sought largely depend on the clinical setting and prior evaluation. The two most widely used techniques are TUS and bile microscopy. Although CT and magnetic resonance imaging may detect microlithiasis, their cost and unproven utility should preclude their use solely for this purpose unless otherwise indicated. The evaluation usually begins with TUS because it is noninvasive and relatively inexpensive. The combination of mucus and crystals greater than 50 μm in size produce low-amplitude echoes without a postacoustic shadow that layer in the dependent portion of the gallbladder and shift with positional changes (Fig. 1).23Filly RA Allen B Minton MJ Bernhoft R Way LW In vitro investigation of the origin of echoes with biliary sludge.J Clin Ultrasound. 1980; 8: 193-200Crossref PubMed Scopus (75) Google Scholar, 59Lee SP Maher K Nicholls JF Origin and fate of biliary sludge.Gastroenterology. 1988; 94: 170-176Abstract PubMed Scopus (0) Google Scholar, 60Conrad MR Janes JO Dietchy J Significance of low level echoes within the gallbladder.AJR Am J Roentgenol. 1979; 132: 967-972Crossref PubMed Scopus (73) Google ScholarLarger stones produce high-amplitude echoes and a postacoustic shadow. The use of TUS is limited by its low sensitivity (~50%-60%)4Lee SP Nicholls JF Park HZ Biliary sludge as a cause of acute pancreatitis.N Engl J Med. 1992; 326: 589-593Crossref PubMed Scopus (463) Google Scholar, 22Ko CW Sekijima JH Lee SP Biliary sludge.Ann Intern Med. 1999; 130: 301-311Crossref PubMed Scopus (170) Google Scholar, 61Venu RP Geenen JE Toouli J Stewart E Hogan WJ Endoscopic retrograde cholangiopancreatography. Diagnosis of cholelithiasis in patients with normal gallbladder x-ray and ultrasound studies.JAMA. 1983; 249: 758-761Crossref PubMed Scopus (40) Google Scholar and inability to determine the chemical composition of bile or its microprecipitates. The low sensitivity may be due to the operator-dependent nature of this procedure, the tendency for cholesterol crystals but not calcium bilirubinate crystals to be imaged, and the intermittent presence of sludge or microlithiasis.4Lee SP Nicholls JF Park HZ Biliary sludge as a cause of acute pancreatitis.N Engl J Med. 1992; 326: 589-593Crossref PubMed Scopus (463) Google Scholar, 22Ko CW Sekijima JH Lee SP Biliary sludge.Ann Intern Med. 1999; 130: 301-311Crossref PubMed Scopus (170) Google Scholar Repeat examination may improve the diagnostic yield. EUS operates at a higher frequency than TUS and minimizes the influence of bowel gas or subcutaneous tissue on image quality. EUS produces higher image resolution and greater diagnostic sensitivity (~95%) (Fig. 2A-C).62Dahan P Andant C Levy P Amouyal P Amouyal G Dumont M et al.Prospective evaluation of endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis in 45 patients with normal conventional ultrasonography.Gut. 1996; 38: 277-281Crossref PubMed Scopus (175) Google Scholar, 63Dill JE Hill S Callis J Berkhouse L Evans P Martin D et al.Combined endoscopic ultrasound and stimulated biliary drainage in cholecystitis and microlithiasis—diagnoses and outcomes.Endoscopy. 1995; 27: 424-427Crossref PubMed Google ScholarStimulated biliary drainage can be performed at the time of EUS and has been shown to further enhance diagnostic capability.63Dill JE Hill S Callis J Berkhouse L Evans P Martin D et al.Combined endoscopic ultrasound and stimulated biliary drainage in cholecystitis and microlithiasis—diagnoses and outcomes.Endoscopy. 1995; 27: 424-427Crossref PubMed Google Scholar Bile microscopy is the standard for the diagnosis of microlithiasis with an overall sensitivity of about 65% to 90%.29Delchier JC Benfredj P Preaux AM Metreau JM Dhumeaux D The usefulness of microscopic bile examination in patients with suspected microlithiasis: a prospective evaluation.Hepatology. 1986; 6: 118-122Crossref PubMed Scopus (49) Google Scholar, 61Venu RP Geenen JE Toouli J Stewart E Hogan WJ Endoscopic retrograde cholangiopancreatography. Diagnosis of cholelithiasis in patients with normal gallbladder x-ray and ultrasound studies.JAMA. 1983; 249: 758-761Crossref PubMed Scopus (40) Google Scholar, 64Moskovitz M Min TC Gavaler JS The microscopic examination of bile in patients with biliary pain and negative imaging tests.Am J Gastroenterol. 1986; 81: 329-333PubMed Google Scholar, 65Neoptolemos JP Davidson BR Winder AF Vallance D Role of duodenal bile crystal analysis in the investigation of ‘idiopathic’ pancreatitis.Br J Surg. 1988; 75: 450-453Crossref PubMed Scopus (90) Google Scholar, 66Buscail L Escourrou J Delvaux M Guimbard R Nicolet T Frexinos J et al.Microscopic examination of bile directly collected during endoscopic cannulation of the papilla. Utility in patients with suspected microlithiasis.Dig Dis Sci. 1992; 37: 116-120Crossref PubMed Scopus (55) Google Scholar, 67Agarwal DK Choudhuri G Saraswat VA Negi TS Utility of biliary microcrystal analysis in predicting composition of common bile duct stones.Scand J Gastroenterol. 1994; 29: 352-354Crossref PubMed Scopus (7) Google Scholar Bile sampling should be performed only if less invasive studies are negative, the clinical suspicion of microlithiasis is high, and the results will be used to guide management. Techniques vary with respect to the site of bile aspiration, use of cholecystokinin, processing of samples, and criteria for a positive test. Bile may be collected from the duodenum (during or separate from endoscopy), bile duct (during ERCP), or the gallbladder itself (by percutaneous aspiration). The diagnostic yield of microscopy is greatest when bile is collected from the gallbladder, lower when collected from the bile duct, and lowest from the duodenum. Although the reported sensitivity of microscopy varies according to the site of bile aspiration, there is likely minimal difference between sampling techniques when “gallbladder” bile is collected.29Delchier JC Benfredj P Preaux AM Metreau JM Dhumeaux D The usefulness of microscopic bile examination in patients with suspected microlithiasis: a prospective evaluation.Hepatology. 1986; 6: 118-122Crossref PubMed Scopus (49) Google Scholar, 62Dahan P Andant C Levy P Amouyal P Amouyal G Dumont M et al.Prospective evaluation of endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis in 45 patients with normal conventional ultrasonography.Gut. 1996; 38: 277-281Crossref PubMed Scopus (175) Google Scholar Cholecystokinin is typically administered before bile aspiration to enhance gallbladder contractility, improve the collection of “gallbladder” bile, and increase the diagnostic yield.4Lee SP Nicholls JF Park HZ Biliary sludge as a cause of acute pancreatitis.N Engl J Med. 1992; 326: 589-593Crossref PubMed Scopus (463) Google Scholar, 68Negro P Flati G Flati D Porowska B Tuscano D Carboni M Occult gallbladder microlithiasis causing acute recurrent pancreatitis. A report of three cases.Acta Chir Scand. 1984; 150: 503-506PubMed Google Scholar, 69Dill JE Hill S Callis J Berkhouse L Evans P Martin D Combined endoscopic ultrasound and stimulated biliary drainage in the diagnosis of cholecystitis and microlithiasis.Endoscopy. 1995; 27: 424-427Crossref PubMed Scopus (103) Google Scholar The need to control the temperature of the bile sample and equipment is controversial.22Ko CW Sekijima JH Lee SP Biliary sludge.Ann Intern Med. 1999; 130: 301-311Crossref PubMed Scopus (170) Google Scholar Most investigators favor maintaining the temperature at 37°C because of the risk of precipitating cholesterol from the micellar form to crystalline phase that occurs with a drop in temperature.9Ros E Navarro S Bru C Garcia-Puges A Valderrama R Occult microlithiasis in ‘idiopathic’ acute pancreatitis: prevention of relapses by cholecystectomy or ursodeoxycholic acid therapy.Gastroenterology. 1991; 101: 1701-1709Abstract PubMed Google Scholar, 21Sharma BC Agarwal DK Dhiman RK Baijal SS Choudhuri G Saraswat VA Bile lithogenicity and gallbladder emptying in patients with microlithiasis: effect of bile acid therapy.Gastroenterology. 1998; 115: 124-128Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 25Lee SP Nicholls JF Nature and composition of biliary sludge.Gastroenterology. 1986; 90: 677-686Abstract Full Text PDF PubMed Scopus (183) Google Scholar, 29Delchier JC Benfredj P Preaux AM Metreau JM Dhumeaux D The usefulness of microscopic bile examination in patients with suspected microlithiasis: a prospective evaluation.Hepatology. 1986; 6: 118-122Crossref PubMed Scopus (49) Google Scholar, 66Buscail L Escourrou J Delvaux M Guimbard R Nicolet T Frexinos J et al.Microscopic examination of bile directly collected during endoscopic cannulation of the papilla. Utility in patients with suspected microlithiasis.Dig Dis Sci. 1992; 37: 116-120Crossref PubMed Scopus (55) Google Scholar The bile is usually centrifuged at 2000g for 10 minutes.21Sharma BC Agarwal DK Dhiman RK Baijal SS Choudhuri G Saraswat VA Bile lithogenicity and gallbladder emptying in patients with microlithiasis: effect of bile acid therapy.Gastroenterology. 1998; 115: 124-128Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 62Dahan P Andant C Levy P Amouyal P Amouyal G Dumont M et al.Prospective evaluation of endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis in 45 patients with normal conventional ultrasonography.Gut. 1996; 38: 277-281Crossref PubMed Scopus (175) Google Scholar, 67Agarwal DK Choudhuri G Saraswat VA Negi TS Utility of biliary mic
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