- Email: [email protected]
Ultrasonography in the assessment of gallbladder motor activity
Digestive and Liver Disease 35 (Suppl. 3) (2003) S67–S69 www.elsevier.com / locate / dld
Ultrasonography in the assessment of gallbladder motor activity N. Pallotta* Department of Clinical Science, University of Rome, Rome, Italy
Abstract Ultrasonography is an accurate and useful method for studying gallbladder volume variations and thus indirectly gallbladder emptying and refilling in humans. It has been shown that gallbladder main motor function is the result of a bellows-like mechanism with outflow and inflow of bile occurring during continuously alternating phases of gallbladder emptying and filling, that in turn lead to bile recycling within the gallbladder. Therefore, bile flux through the gallbladder cannot be properly expressed by time and rate of gallbladder emptying and gallbladder ejection fraction. In an attempt to analyse the gallbladder volume–hepatic bile flux relationship, simultaneous assessment of the gallbladder volume variations at ultrasonography and of the labelled bile in the gallbladder at cholescintigraphy during continuous infusion of an hydroxy iminodiacetic acid compound has been carried out. By applying a mathematical model to the analysis of gallbladder volume ultrasonography measurements, it is possible to measure the flux of bile through the gallbladder. By validating ultrasonography assessment of gallbladder volume variations with quantitative cholescintigraphy, it has been shown that the single non-invasive ultrasonography technique with serial frequent measurements of the gallbladder volume enables separate estimation of the flux of bile through the gallbladder in humans and in physiological conditions. In the postprandial state, hepatic bile was mainly: (1) stored in the gallbladder in a first phase; (2) emptied from the gallbladder in a second phase; and (3) stored in the gallbladder in a third phase. The amount of bile flowing bidirectionally through the cystic duct was about fivefold greater than that estimated with the usually employed variables, such as gallbladder ejection fraction or emptying and refilling delta volume. The mathematical analysis of minute-by-minute ultrasonography measurements of gallbladder volume variations yields both physiological and pathological insights. In healthy volunteers, it has been shown that: (1) caloric content of meals affects the total amount of bile recycled by the gallbladder; and (2) fat content of meals affects the modality of gallbladder emptying and refilling but does not affect the total amount of bile recycled by the gallbladder. In gallstone patients, a decreased turnover of bile has been shown which may contribute to cholesterol crystal precipitation and stone growth. In conclusion, unlike conventional variables used to assess gallbladder motor function such as gallbladder ejection fraction and rate of gallbladder emptying, mathematical analysis of frequent ultrasonography measurements of gallbladder volume variations enables non-invasive estimation of bile flow through the gallbladder in normal and abnormal physiological conditions. 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Bile flux, Gallbladder; Ultrasonography
Several studies have demonstrated that ultrasonography is an accurate and useful method for studying gallbladder (GB) volume variations and thus indirectly GB emptying and refilling in humans [1–4]. However, the assessment of the GB volume variations after a cholecystokinetic stimulus offers information concerning only the net bile emptying and net bile refilling of the GB. The first ultrasonographic studies carried out over long time intervals reinforced the widely accepted interpretation that GB emptying and refilling are, respectively, the result of a progressive sustained tonic contraction and relaxation of the viscus. In contrast, various authors, using different *Tel.: 139-06-4997-2308; fax: 139-06-4938-2437. E-mail address: [email protected] (N. Pallotta).
techniques and in different animal species, reported evidence of continuous rapid alternating phases of GB emptying and filling [3–9]. These observations led to the interpretation of the GB main motor function as the result of a bellows-like mechanism with outflow and inflow of bile occurring, respectively, during continuously alternating phases of GB contraction and decontraction. Continuous rapid alternating phases of emptying and filling inevitably lead to a continuous alternating one-way traffic of bile through the cystic duct and bile recycling within the GB. This alternating pattern of GB motor activity and thus bile flux through the GB, however, cannot be properly expressed by the usual radiological, ultrasonographic and scintigraphic variables, such as time and rate of GB emptying and GB ejection fraction.
1590-8658 / 03 / $30 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016 / S1590-8658(03)00098-7
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N. Pallotta / Digestive and Liver Disease 35 ( Suppl. 3) (2003) S67 –S69
The demonstration of the bellows-like mechanism and measurement of bile fluxes through the GB could only be carried out with invasive non-physiological methods in experimental animals [6–8,10–12] and, only indirectly, with invasive [5] and non-invasive [3,4] techniques in humans. In an attempt to analyse the GB volume–hepatic bile flux relationship, simultaneous assessment of GB volume variations by ultrasonography (US) and of the labelled bile in the GB by cholescintigraphy has been carried out [13–15]. This approach has also been used to express the amount of bile flux through the GB [13]. However, these studies have not provided a correct assessment of the hepatic bile entering into the gallbladder except for the late gallbladder refilling phase, since cholescintigraphy was carried out after a single i.v. bolus injection of an IDA compound. This technique can only express linear emptying of the labelled bile already stored in the GB, offering no indication on the non-labelled hepatic bile which would enter into, and exit from, the GB after a cholecystokinetic stimulus. Furthermore, the combined use of two methods is too cumbersome to be employed in large populations and to be applied in different groups of patients. The GB is a hollow viscus connected to the common bile duct by the cystic duct, which represents a one-way duct for the flow of bile in and out of the GB. Assuming that GB volume variation expresses the amount of bile flowing through the cystic duct, serial measurements of GB volumes can be used to estimate the amount of bile flowing through the GB. Starting from this assumption and applying a mathematical model, it is possible to quantify the amount of bile handled by the GB by frequent measurement of GB volumes [16]. Due to the lack of any ‘gold standard’ to measure bile displacement within the GB in physiological conditions, the cholescintigraphic time–activity curve has been used as an independent estimate of the hepatic bile handled by the GB, to assess whether the mathematical model applied to the analysis of the GB volume US measurements is reliable to measure the flux of hepatic bile through the GB. The results of the study indicate that the net scintigraphic time–activity curve of the GB ROI and US-estimated hepatic bile curve were not statistically different, were highly correlated, and were visually superimposable. Validating US assessment of GB volume variations with quantitative cholescintigraphy, it was demonstrated in healthy volunteers, that the single noninvasive US technique by serial frequent measurements of the GB volume enables one to estimate separately the flux of the hepatic and cholecystic bile through the GB in humans and in physiological conditions [16]. It has thus been possible to show that the GB motor function has three different phases in the postprandial state. Patterns and amount of hepatic bile handled by the GB are remarkably different during these three successive
phases. Postprandially, hepatic bile was mainly: (1) stored in the GB in the first phase; (2) emptied from the GB in the second phase; and (3) stored in the GB in the third phase. The amount of bile flowing bidirectionally through the cystic duct was about fivefold greater than that estimated by the usually employed variables, such as GB ejection fraction or emptying and refilling delta volume.
1. Caloric and nutrient content of meal and GB motor function The GB motor response to a test meal is usually expressed as the GB ejection fraction (GBEF) and GB refilling volume (GBRE). The effect of meal caloric content on GB motor activity in healthy volunteers was evaluated comparatively. The subjects consumed, on different days and in random order, two meals equivalent in nutrient composition (25% lipid, 25% protein, 50% carbohydrate), consistency (solid) and volume (750 ml) but differing in caloric content, 1050 versus 525 kcal. GB volume was assessed in fasting conditions and at frequent intervals after meal ingestion for 7 h. GB showed volume fluctuations during the entire postprandial period after both meals. According to the conventional variables evaluated, there was no difference between the meals in GBEF whereas GBRE was greater after the meal with half the caloric content. Applying the mathematical analysis to frequent US GB volume measurements, it appears that the entire amount of bile recycled by the GB was significantly ( p,0.02) greater after a 1050 kcal meal compared with a 525 kcal meal (personal observations). The effect of fat content of meals on the modality of GB recycling of bile was then assessed. In this attempt, it was evaluated on two different days and in random order, 10 healthy volunteers in fasting conditions and after the ingestion of equicaloric (525 kcal), equivolumetric (500 ml) liquid meals with low fat (lipids 4%) and normal fat (lipids 25%). Serial US measurements of GB volume were carried out at 5-min intervals after meal ingestion for 3 h. According to the conventional variables evaluated, GBEF was greater whereas GBRE was lower after a normal fat meal compared with a low fat meal. Applying the mathematical analysis to US GB volume assessments, it appears that the total amount of bile recycled by the GB was not different between the low and normal fat meals [17]. The results of these studies indicate that:
1. Caloric content of meals affects the total amount of bile recycled by the GB. 2. Fat content of meal affects the modality of GB emptying and refilling but does not affect the total amount of bile recycled by the GB.
N. Pallotta / Digestive and Liver Disease 35 ( Suppl. 3) (2003) S67 –S69
2. GB motor function in gallstone disease In the pathogenesis of cholesterol gallstone, impaired GB motility may play a role facilitating cholesterol crystal precipitation and stone growth. So far, however, several studies have shown conflicting results and defective GB motility has been found only in subgroups of patients [18,19]. Combining US with scintigraphy, Jazrawi et al. [13] showed that compared with healthy controls, turnover of bile is impaired during the refilling phase in gallstone patients. More recently, Cicala et al. [20], applying mathematical analysis to minute-by-minute US measurements of GB volume variations, demonstrated that in gallstone patients there is a decreased turnover of bile that may contribute to cholesterol crystal precipitation and stone growth. In conclusion, the conventional variables used to assess GB motor function such as GBEF and GBRE do not allow evaluation of the recycling of bile by the GB. In contrast, mathematical analysis applied to frequent US measurement of GB volume variations enables us to estimate noninvasively the bile flux through the GB in normal and abnormal physiological conditions, within the limits of acceptable approximation of the technique used.
[4] [5]
[6]
[7]
[8]
[9]
[10] [11] [12]
[13]
[14]
Conflict of interest statement None declared. [15]
List of abbreviations [16]
GB, gallbladder; GBEF, gallbladder ejection fraction; GBER, gallbladder refilling volume; US, ultrasonography.
[17]
[18]
References [1] Everson GT, Braverman DZ, Johnson ML, Kern F. A critical evaluation of real-time ultrasonography for the study of gallbladder volume and contraction. Gastroenterology 1980;79:40–6. [2] Dodds WJ, Groh WJ, Darweesh RMA, Lawson TL, Kishk SMA, Kern MK. Sonographic measurement of gallbladder volume. Am J Roentgenol 1985;145:1009–11. [3] Howard PJ, Murphy GM, Dowling RH. Gallbladder emptying
[19]
[20]
S69
patterns in response to a normal meal in healthy subjects and patients with gallstones: ultrasound study. Gut 1991;32:1406–11. Pallotta N, Corazziari E, Biliotti D, Torsoli A. Gallbladder volume variations after meal ingestion. Am J Gastroenterol 1994;89:2212–6. Lanzini A, Jazrawi RP, Northfield TC. Simultaneous quantitative measurements of absolute gallbladder storage and emptying during fasting and eating in humans. Gastroenterology 1987;92:852–61. Takahashi I, Nakaya M, Suzuky T, Itoh Z. Postprandial changes in contractile activity and bile concentration in the gallbladder of the dog. Am J Physiol 1982;243:G365–71. Scott RB, Diamant SC. Biliary motility associated with gallbladder storage and duodenal delivery of canine hepatic biliary output. Gastroenterology 1988;95:1069–80. Abiru H, Sarna SK, Condon RE. Contractile mechanism of gallbladder filling and emptying in dogs. Gastroenterology 1994;106:1652–61. Jazrawi RP, Kupfer RM, Bridges C, Joseph A, Northfield TC. Assessment of gallbladder storage function in man. Clin Sci 1983;65:185–91. Peustow CB. The discharge of bile into the duodenum, an experimental study. Arch Surg 1931;23:1013–29. Snape W J. Studies on the gallbladder in unanesthetized dogs before and after vagotomy. Gastroenterology 1948;10:129–34. Gilsdorf R B. The effect of simulated gallstone on gallbladder pressures and bile flow response to eating. Surg Gynecol Obstet 1974;138:161–8. Jazrawi RP, Pazzi P, Petroni ML, Prandini N, Paul C, Adam JA, et al. Postprandial gallbladder motor function: refilling and turnover of bile in health and in cholelithiasis. Gastroenterology 1995;109:582– 91. Masclee AM, Hopman PM, Corsterns FHM, Rosenbusch G, Jansen BMJJ, Lamers BHW. Simultaneous measurement of gallbladder emptying with cholescintigraphy and US during infusion of physiologic doses of cholecystokinin: a comparison. Radiology 1989;173:407–10. Kronert K, Gotz V, Reuland P, Luft D, Eggstein M. Gallbladder emptying in diabetic patients and control subjects assessed by real-time ultrasonography and cholescintigraphy: a methodological comparison. Ultrasound Med Biol 1989;15:535–9. Pallotta N, Corazziari E, Scopinaro F, Bonino R, Schillaci O, Vignoni A, et al. Noninvasive estimate of bile flux through the gallbladder in humans. Am J Gastroenterol 1998;93:1877–85. Pallotta N, Cicala M, Costa E, Corazziari E, Torsoli A. Gallbladder motor response to meals with different nutrient composition. Neurogastroenterol Motil 1995;7:A278. Pomeranz IS, Shaffer EA. Abnormal gallbladder emptying in a subgroup of patients with gallstone. Gastroenterology 1985;88:787– 91. Sharma 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;115:124–8. Cicala M, Guarino MPL, Vavassori P, Alloni R, Emerengiani S, Arullani A, et al. Ultrasonographic assessment of gallbladder bile exchange in healthy subjects and in gallstone patients. Ultrasound Med Biol 2001;27:1445–50.
Ultrasonography in the assessment of gallbladder motor activity N. Pallotta* Department of Clinical Science, University of Rome, Rome, Italy
Abstract Ultrasonography is an accurate and useful method for studying gallbladder volume variations and thus indirectly gallbladder emptying and refilling in humans. It has been shown that gallbladder main motor function is the result of a bellows-like mechanism with outflow and inflow of bile occurring during continuously alternating phases of gallbladder emptying and filling, that in turn lead to bile recycling within the gallbladder. Therefore, bile flux through the gallbladder cannot be properly expressed by time and rate of gallbladder emptying and gallbladder ejection fraction. In an attempt to analyse the gallbladder volume–hepatic bile flux relationship, simultaneous assessment of the gallbladder volume variations at ultrasonography and of the labelled bile in the gallbladder at cholescintigraphy during continuous infusion of an hydroxy iminodiacetic acid compound has been carried out. By applying a mathematical model to the analysis of gallbladder volume ultrasonography measurements, it is possible to measure the flux of bile through the gallbladder. By validating ultrasonography assessment of gallbladder volume variations with quantitative cholescintigraphy, it has been shown that the single non-invasive ultrasonography technique with serial frequent measurements of the gallbladder volume enables separate estimation of the flux of bile through the gallbladder in humans and in physiological conditions. In the postprandial state, hepatic bile was mainly: (1) stored in the gallbladder in a first phase; (2) emptied from the gallbladder in a second phase; and (3) stored in the gallbladder in a third phase. The amount of bile flowing bidirectionally through the cystic duct was about fivefold greater than that estimated with the usually employed variables, such as gallbladder ejection fraction or emptying and refilling delta volume. The mathematical analysis of minute-by-minute ultrasonography measurements of gallbladder volume variations yields both physiological and pathological insights. In healthy volunteers, it has been shown that: (1) caloric content of meals affects the total amount of bile recycled by the gallbladder; and (2) fat content of meals affects the modality of gallbladder emptying and refilling but does not affect the total amount of bile recycled by the gallbladder. In gallstone patients, a decreased turnover of bile has been shown which may contribute to cholesterol crystal precipitation and stone growth. In conclusion, unlike conventional variables used to assess gallbladder motor function such as gallbladder ejection fraction and rate of gallbladder emptying, mathematical analysis of frequent ultrasonography measurements of gallbladder volume variations enables non-invasive estimation of bile flow through the gallbladder in normal and abnormal physiological conditions. 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Bile flux, Gallbladder; Ultrasonography
Several studies have demonstrated that ultrasonography is an accurate and useful method for studying gallbladder (GB) volume variations and thus indirectly GB emptying and refilling in humans [1–4]. However, the assessment of the GB volume variations after a cholecystokinetic stimulus offers information concerning only the net bile emptying and net bile refilling of the GB. The first ultrasonographic studies carried out over long time intervals reinforced the widely accepted interpretation that GB emptying and refilling are, respectively, the result of a progressive sustained tonic contraction and relaxation of the viscus. In contrast, various authors, using different *Tel.: 139-06-4997-2308; fax: 139-06-4938-2437. E-mail address: [email protected] (N. Pallotta).
techniques and in different animal species, reported evidence of continuous rapid alternating phases of GB emptying and filling [3–9]. These observations led to the interpretation of the GB main motor function as the result of a bellows-like mechanism with outflow and inflow of bile occurring, respectively, during continuously alternating phases of GB contraction and decontraction. Continuous rapid alternating phases of emptying and filling inevitably lead to a continuous alternating one-way traffic of bile through the cystic duct and bile recycling within the GB. This alternating pattern of GB motor activity and thus bile flux through the GB, however, cannot be properly expressed by the usual radiological, ultrasonographic and scintigraphic variables, such as time and rate of GB emptying and GB ejection fraction.
1590-8658 / 03 / $30 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016 / S1590-8658(03)00098-7
S68
N. Pallotta / Digestive and Liver Disease 35 ( Suppl. 3) (2003) S67 –S69
The demonstration of the bellows-like mechanism and measurement of bile fluxes through the GB could only be carried out with invasive non-physiological methods in experimental animals [6–8,10–12] and, only indirectly, with invasive [5] and non-invasive [3,4] techniques in humans. In an attempt to analyse the GB volume–hepatic bile flux relationship, simultaneous assessment of GB volume variations by ultrasonography (US) and of the labelled bile in the GB by cholescintigraphy has been carried out [13–15]. This approach has also been used to express the amount of bile flux through the GB [13]. However, these studies have not provided a correct assessment of the hepatic bile entering into the gallbladder except for the late gallbladder refilling phase, since cholescintigraphy was carried out after a single i.v. bolus injection of an IDA compound. This technique can only express linear emptying of the labelled bile already stored in the GB, offering no indication on the non-labelled hepatic bile which would enter into, and exit from, the GB after a cholecystokinetic stimulus. Furthermore, the combined use of two methods is too cumbersome to be employed in large populations and to be applied in different groups of patients. The GB is a hollow viscus connected to the common bile duct by the cystic duct, which represents a one-way duct for the flow of bile in and out of the GB. Assuming that GB volume variation expresses the amount of bile flowing through the cystic duct, serial measurements of GB volumes can be used to estimate the amount of bile flowing through the GB. Starting from this assumption and applying a mathematical model, it is possible to quantify the amount of bile handled by the GB by frequent measurement of GB volumes [16]. Due to the lack of any ‘gold standard’ to measure bile displacement within the GB in physiological conditions, the cholescintigraphic time–activity curve has been used as an independent estimate of the hepatic bile handled by the GB, to assess whether the mathematical model applied to the analysis of the GB volume US measurements is reliable to measure the flux of hepatic bile through the GB. The results of the study indicate that the net scintigraphic time–activity curve of the GB ROI and US-estimated hepatic bile curve were not statistically different, were highly correlated, and were visually superimposable. Validating US assessment of GB volume variations with quantitative cholescintigraphy, it was demonstrated in healthy volunteers, that the single noninvasive US technique by serial frequent measurements of the GB volume enables one to estimate separately the flux of the hepatic and cholecystic bile through the GB in humans and in physiological conditions [16]. It has thus been possible to show that the GB motor function has three different phases in the postprandial state. Patterns and amount of hepatic bile handled by the GB are remarkably different during these three successive
phases. Postprandially, hepatic bile was mainly: (1) stored in the GB in the first phase; (2) emptied from the GB in the second phase; and (3) stored in the GB in the third phase. The amount of bile flowing bidirectionally through the cystic duct was about fivefold greater than that estimated by the usually employed variables, such as GB ejection fraction or emptying and refilling delta volume.
1. Caloric and nutrient content of meal and GB motor function The GB motor response to a test meal is usually expressed as the GB ejection fraction (GBEF) and GB refilling volume (GBRE). The effect of meal caloric content on GB motor activity in healthy volunteers was evaluated comparatively. The subjects consumed, on different days and in random order, two meals equivalent in nutrient composition (25% lipid, 25% protein, 50% carbohydrate), consistency (solid) and volume (750 ml) but differing in caloric content, 1050 versus 525 kcal. GB volume was assessed in fasting conditions and at frequent intervals after meal ingestion for 7 h. GB showed volume fluctuations during the entire postprandial period after both meals. According to the conventional variables evaluated, there was no difference between the meals in GBEF whereas GBRE was greater after the meal with half the caloric content. Applying the mathematical analysis to frequent US GB volume measurements, it appears that the entire amount of bile recycled by the GB was significantly ( p,0.02) greater after a 1050 kcal meal compared with a 525 kcal meal (personal observations). The effect of fat content of meals on the modality of GB recycling of bile was then assessed. In this attempt, it was evaluated on two different days and in random order, 10 healthy volunteers in fasting conditions and after the ingestion of equicaloric (525 kcal), equivolumetric (500 ml) liquid meals with low fat (lipids 4%) and normal fat (lipids 25%). Serial US measurements of GB volume were carried out at 5-min intervals after meal ingestion for 3 h. According to the conventional variables evaluated, GBEF was greater whereas GBRE was lower after a normal fat meal compared with a low fat meal. Applying the mathematical analysis to US GB volume assessments, it appears that the total amount of bile recycled by the GB was not different between the low and normal fat meals [17]. The results of these studies indicate that:
1. Caloric content of meals affects the total amount of bile recycled by the GB. 2. Fat content of meal affects the modality of GB emptying and refilling but does not affect the total amount of bile recycled by the GB.
N. Pallotta / Digestive and Liver Disease 35 ( Suppl. 3) (2003) S67 –S69
2. GB motor function in gallstone disease In the pathogenesis of cholesterol gallstone, impaired GB motility may play a role facilitating cholesterol crystal precipitation and stone growth. So far, however, several studies have shown conflicting results and defective GB motility has been found only in subgroups of patients [18,19]. Combining US with scintigraphy, Jazrawi et al. [13] showed that compared with healthy controls, turnover of bile is impaired during the refilling phase in gallstone patients. More recently, Cicala et al. [20], applying mathematical analysis to minute-by-minute US measurements of GB volume variations, demonstrated that in gallstone patients there is a decreased turnover of bile that may contribute to cholesterol crystal precipitation and stone growth. In conclusion, the conventional variables used to assess GB motor function such as GBEF and GBRE do not allow evaluation of the recycling of bile by the GB. In contrast, mathematical analysis applied to frequent US measurement of GB volume variations enables us to estimate noninvasively the bile flux through the GB in normal and abnormal physiological conditions, within the limits of acceptable approximation of the technique used.
[4] [5]
[6]
[7]
[8]
[9]
[10] [11] [12]
[13]
[14]
Conflict of interest statement None declared. [15]
List of abbreviations [16]
GB, gallbladder; GBEF, gallbladder ejection fraction; GBER, gallbladder refilling volume; US, ultrasonography.
[17]
[18]
References [1] Everson GT, Braverman DZ, Johnson ML, Kern F. A critical evaluation of real-time ultrasonography for the study of gallbladder volume and contraction. Gastroenterology 1980;79:40–6. [2] Dodds WJ, Groh WJ, Darweesh RMA, Lawson TL, Kishk SMA, Kern MK. Sonographic measurement of gallbladder volume. Am J Roentgenol 1985;145:1009–11. [3] Howard PJ, Murphy GM, Dowling RH. Gallbladder emptying
[19]
[20]
S69
patterns in response to a normal meal in healthy subjects and patients with gallstones: ultrasound study. Gut 1991;32:1406–11. Pallotta N, Corazziari E, Biliotti D, Torsoli A. Gallbladder volume variations after meal ingestion. Am J Gastroenterol 1994;89:2212–6. Lanzini A, Jazrawi RP, Northfield TC. Simultaneous quantitative measurements of absolute gallbladder storage and emptying during fasting and eating in humans. Gastroenterology 1987;92:852–61. Takahashi I, Nakaya M, Suzuky T, Itoh Z. Postprandial changes in contractile activity and bile concentration in the gallbladder of the dog. Am J Physiol 1982;243:G365–71. Scott RB, Diamant SC. Biliary motility associated with gallbladder storage and duodenal delivery of canine hepatic biliary output. Gastroenterology 1988;95:1069–80. Abiru H, Sarna SK, Condon RE. Contractile mechanism of gallbladder filling and emptying in dogs. Gastroenterology 1994;106:1652–61. Jazrawi RP, Kupfer RM, Bridges C, Joseph A, Northfield TC. Assessment of gallbladder storage function in man. Clin Sci 1983;65:185–91. Peustow CB. The discharge of bile into the duodenum, an experimental study. Arch Surg 1931;23:1013–29. Snape W J. Studies on the gallbladder in unanesthetized dogs before and after vagotomy. Gastroenterology 1948;10:129–34. Gilsdorf R B. The effect of simulated gallstone on gallbladder pressures and bile flow response to eating. Surg Gynecol Obstet 1974;138:161–8. Jazrawi RP, Pazzi P, Petroni ML, Prandini N, Paul C, Adam JA, et al. Postprandial gallbladder motor function: refilling and turnover of bile in health and in cholelithiasis. Gastroenterology 1995;109:582– 91. Masclee AM, Hopman PM, Corsterns FHM, Rosenbusch G, Jansen BMJJ, Lamers BHW. Simultaneous measurement of gallbladder emptying with cholescintigraphy and US during infusion of physiologic doses of cholecystokinin: a comparison. Radiology 1989;173:407–10. Kronert K, Gotz V, Reuland P, Luft D, Eggstein M. Gallbladder emptying in diabetic patients and control subjects assessed by real-time ultrasonography and cholescintigraphy: a methodological comparison. Ultrasound Med Biol 1989;15:535–9. Pallotta N, Corazziari E, Scopinaro F, Bonino R, Schillaci O, Vignoni A, et al. Noninvasive estimate of bile flux through the gallbladder in humans. Am J Gastroenterol 1998;93:1877–85. Pallotta N, Cicala M, Costa E, Corazziari E, Torsoli A. Gallbladder motor response to meals with different nutrient composition. Neurogastroenterol Motil 1995;7:A278. Pomeranz IS, Shaffer EA. Abnormal gallbladder emptying in a subgroup of patients with gallstone. Gastroenterology 1985;88:787– 91. Sharma 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;115:124–8. Cicala M, Guarino MPL, Vavassori P, Alloni R, Emerengiani S, Arullani A, et al. Ultrasonographic assessment of gallbladder bile exchange in healthy subjects and in gallstone patients. Ultrasound Med Biol 2001;27:1445–50.