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Methods of measuring gallbladder motor functions—the need for standardization: scintigraphy
Digestive and Liver Disease 35 (Suppl. 3) (2003) S62–S66 www.elsevier.com / locate / dld
Methods of measuring gallbladder motor functions— the need for standardization: scintigraphy N. Prandini* Nuclear Medicine Department, Azienda Ospedaliera-Universitaria, Corso Giovecca 203, Ferrara 44100, Italy
Abstract Emptying the gallbladder is part of the complex process of food digestion. The gallbladder interacts with other gastrointestinal organs and its movements are coordinated and modified by functions of the stomach, intestine and pancreas. Many factors can modify gallbladder motility, for example, sex and age of the subject, their body mass, the kinds of food ingested and stimulus used. The assumption that the gallbladder progressively empties during meals and refills during fasting is incorrect. Using a combination of ultrasonography and cholescintigraphy, it is possible to measure absolute and net gallbladder emptying. In this way we demonstrated that the gallbladder begins to refill immediately after emptying begins, and the difference between net and absolute emptying of the gallbladder indicates the refilling of bile and provides a measure of bile turnover rate, an accurate index to assess gallbladder motility. 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Cholescintigraphy; Gallbladder emptying; Radionuclide imaging; Ultrasonography
1. Background The gallbladder (GB) normally stores bile during fasting and releases it into the duodenum with ingestion of a meal in a complex process involving most gastrointestinal organs: these organs work together and influence each other by their actions. GB motor function can be modified by the duodenogastric emptying rate and by food composition (quantity and caloric content and percentage of fat, carbohydrates and proteins). Primary gallstones and other diseases of the GB impair the emptying of bile, and in the same way, alterations in stomach and intestine motility, and in exocrine secretion of pancreas effect GB contraction [1]. To standardise a method to measure GB emptying we must consider patient characteristics, the kind of stimulus and the method used to assess GB emptying. A wide spectrum of normal values have been proposed to measure gallbladder motility, but the results are often conflicting in similar patients using different techniques (cholecystography, ultrasonography or cholescintigraphy) [2–4].
*Tel.: 139-0532-825317; fax: 139-0532-237553. E-mail address: [email protected] (N. Prandini).
Therefore, the aim of this study is to propose a standardisation of techniques to assess GB motor function with an excursus on all factors that can modify these measures.
2. Subjects Sex and female hormones are important factors that affect GB motility: fertile women have impaired GB emptying compared to men and postmenopausal women. Similarly, the negative influence of oestroprogestinics during pregnancy on GB motility has been demonstrated, as has administration of female sex hormones in women: both these groups of women more frequently developed gallstones with reduced GB emptying [5,6]. GB volume is correlated with weight and body surface of subjects, but the incidence of gallstone disease is not correlated with GB volume or body weight [7]. Significant impairment of GB emptying was found in obese diabetic patients versus diabetics of normal weight [8]. This effect is mainly due to hyperglycaemia which causes reduced GB emptying in diabetics [9]. Other pathologic conditions that can impair GB motility are acromegaly and gastrointestinal diseases such as
1590-8658 / 03 / $30 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016 / S1590-8658(03)00097-5
N. Prandini / Digestive and Liver Disease 35 ( Suppl. 3) (2003) S62 –S66
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cholelithiasis, gastric ulcers, pancreatitis and Crohn’s disease [10]. Previous surgery on the upper gastrointestinal tract impairs GB motility reducing the velocity and the percentage of emptying [11]. Excluding all drugs influencing GB motility such as sincalide, morphine, cholecystokinin (CCK), and biliary acids, most treatment that acts on gastrointestinal motility can also modify GB motility. For example, a significant increase in gallstone disease was found in subjects treated with octreotide [12].
3. Stimulus The stimulus used to obtain a GB response should be natural (meal) or exogenous (mostly CCK). Fatty meals are widely used because of their availability: the response of GB to a stimulus depends on the amount of food and its composition (fat, carbohydrates and proteins). However, there is no universal standard meal because of different habits and tastes, and in most papers the number of normal subjects studied is insufficient to provide normal values. One of the most widely used meals to stimulate GB contraction is milk (250–300 ml), but many patients are lactose intolerant and so this cannot be proposed as a standard choleretic stimulus. Exogenous stimulus with CCK should be a reliable and standard method to stimulate the GB. Sincalide (Kinevac , Bracco Diagnostics) is the only CCK analogue approved by the FDA: however, it is not available in most European countries or, because of manufacturing and regulatory problems, in the USA [13]. A commercially available liquid food supplement containing adequate fat to stimulate GB contraction would be the correct choice in all countries because of the absence of clinical contraindications and because, unlike sincalide, i.v. injection or infusion is not required. Ensure plus (Abbott Laboratories, Columbus, OH) or Fortimel are two examples of fatty meals which are easily sourced and can be used in all ultrasonographic and scintigraphic laboratories. We advise consumption of a semisolid fatty meal with 370 kcal, 55% fat, 25% carbohydrates, and 20% proteins using a standard supplement (2 Fortimel). The use of CCK-8 (bolus of 0.04 mg / kg or infusion of 0.3 ng / kg for 60 min) i.v. 30 min before injection of imino diacetic acid (IDA) compounds is questionable.
4. Techniques GB motor function studies often produce conflicting results because different techniques are used (cholecystography, ultrasonography, and cholescintigraphy) [14]. Cholangiography calculates GB contraction by measuring the diameter of the area on film using a bidimensional
Fig. 1. Mean values of GB emptying measured in 12 normal subjects: the percentage of ultrasonographic emptying (black triangle) is always lower than absolute, cholescintigraphic emptying (black circle).
method which is less precise than ultrasonography, which measures the volume with a three-dimensional method, or scintigraphy, which measures the global activity of GB independent of area or volume. Scintigraphic measurement is more reproducible and independent of the operator: filling and emptying of GB can be followed continuously during all phases. Furthermore, scintigraphy measures cessation of GB activity (absolute emptying) whereas ultrasonography measures GB volume and is thus influenced by refilling. This explains the conflicting results of these two widely used methods: they measure two different functions, absolute emptying of GB (scintigraphy) and volume (ultrasonography). In our experience, by combining the two methods it is possible to measure GB refilling and the turnover rate of bile after stimulation with a fatty meal. This provides a real and complete assessment of GB motor function [15] (Fig. 1).
5. Patient preparation The ideal patient preparation is to maximize bile entry into the GB by allowing maximum relaxation of the GB and maximum contraction of the sphincter of Oddi. An overnight fast accomplishes this, but longer hours of fasting or total parental nutrition are suggested in order to obtain no GB visualisation [16]. A fasting state of 8 h is adequate for a 99m Tc-HIDA study to ensure complete GB filling, but most prefer a minimum of 4 h. In all patients, personal data concerning weight, height, age, drug intake, gastrointestinal and metabolic diseases should be collected to avoid mistakes in data interpretation.
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N. Prandini / Digestive and Liver Disease 35 ( Suppl. 3) (2003) S62 –S66
Fig. 2. Comparison of blood clearance (left graphics) and time activity curves (right graphics) obtained in a subject after simultaneous injection of 75 SeHCAT (empty circle, triangle and box) and 99m Tc-Bromida (filled circle, triangle and box): curves of biliary acids and of IDA derivatives are analogues.
6. Radiopharmaceuticals Derivatives of HIDA (iminodiacetic acid) labelled with technetium are widely used to obtain biliary tract visualisation. After i.v. injection, they are taken up, conjugated and eliminated by hepatocytes in the biliary ducts thus visualizing the biliary tree, choledoc and GB. They are excreted into bile ducts both by active transport and passive diffusion. The radiopharmaceutical is not conjugated by the liver and so remains almost identical to its originally administered form. Several HIDA derivatives are proposed which differ in their liver uptake and elimination in different levels of blood bilirubin. The IDA derivatives mainly used for hepatobiliary scintigraphy are mebrofenin and DISIDA: mebrofenin has 98% hepatic uptake with a hepatic excretion of 1761.3 min and 1.5% urinary excretion. Kinetics of these HIDA derivatives are similar to kinetics of biliary acids (Fig. 2): the most important difference is that biliary acid (SEHCAT for example) is re-adsorbed by the small bowel and slowly returns to the liver by the portal system, whereas HIDA derivatives are not reabsorbed and are eliminated by the intestine. 99m
intestine, kidneys and bladder is sufficient for complete study of GB function. In our experience, study of GB motility begins 90 min after i.v. injection of 40–60 MBq of 99m Tc-Br-HIDA to obtain a liver elimination of bile .95%, avoiding any new GB activity which could influence the calculation of absolute GB emptying. We perform two basic acquisitions of GB parameters (volume and activity). After stimulus with a standard fatty meal, a series of nine acquisitions (ultrasonography and cholescintigraphy), with one every 10 min, is performed.
8. Analysis All scintigraphic methods to assess GB motility require computerized analysis of the data with ROIs (regions of interest) drawn on the GB, liver, intestine, background and bladder. The counts obtained must be corrected for physical decay of technetium (6 h) and for activity of the liver, background and intestine close to the GB. This type of study is reproducible: Xynos et al. showed that, when repeating the same GB study in 30 patients stimulated with 250 ml of fresh milk, the lag phase duration and the ejection fraction were reproduced with a high degree of correlation (r50.87 and r50.84, respectively) [17].
7. Acquisition A dynamic sequence of 60-min computed assisted scintigraphy is mandatory for the study of liver and GB kinetics (1283128 matrix, one image every minute). An anterior view of the abdomen including whole liver,
9. Clinical applications The major advantage of cholescintigraphic assessment of GB motility versus ultrasonographic assessment is the
N. Prandini / Digestive and Liver Disease 35 ( Suppl. 3) (2003) S62 –S66
Fig. 3. Combination of ultrasonography and cholescintigraphy in an acromegalic patient in basic conditions (fill triangle and circle) and after s.c. administration of 100 ng of octreotide (empty triangle and box). Octreotide significantly impairs GB emptying measured by both ultrasonography and cholescintigraphy.
S65
sex, age, weight, BMI), pathological condition of the patient (diseases or their treatments), the kind of stimulus used (fatty meal, CCK, etc.), and methods used to assess GB motility (ultrasonography, scintigraphy, etc.). A good standardized method requires collection of all data that can modify GB motor function, but the technique necessary for complete assessment of GB motor function is the combination of the two most widely used procedures: ultrasonography and scintigraphy. Using our combination of procedures it is possible to carry out a complete study of GB parameters, including volume, GB absolute emptying, GB relative emptying, GB refilling, bile turnover rate, and bile turnover index. Scintigraphy still plays a role in functional studies: its use in combination with ultrasonography is essential to assess refilling in the study of GB motor function.
Conflict of interest statement None declared.
reproducibility of the studies and independence from the operator. However, quantitative assessment of scintigraphic emptying is incomplete if volume and relative emptying of the GB is not measured. Turnover rate and turnover index of bile assessed with our proposed method can correctly differentiate the GB motor functions of gallstone patients from normal subjects. Furthermore, measurement of bile turnover rate is a standardized and controlled method that can be very useful in research, for example, to study the effects of treatments on GB motor function. Pazzi et al. showed that there is significant difference between two groups of patients after dissolution of gallstones with bile acid treatment: the patients with recurrence of gallstones have a lower bile turnover index than patients without recurrence. Motility of gallstone patients without recurrence was very similar to normal controls, with a small and insignificant reduction in emptying and no reduction in postprandial refilling or turnover [18]. More recent study on the effects of drug treatments can benefit this standard technique: for example in a group of acromegalic patients treated with octreotide we found a fasting GB volume higher than normal. Acute s.c. and long-acting release (Sandostatin LAR ) i.m. administration of octreotide produces impaired gallbladder emptying as measured both by ultrasonography and cholescintigraphy, with a significant reduction in postprandial refilling, bile turnover and turnover index (Fig. 3).
10. Conclusions Many parameters can affect the response of the GB to a stimulus, including characteristics of the patient (fasting,
List of abbreviations CCK, cholecystokinin; GB, gallbladder; ROI, region of interest.
References [1] Shaffer EA. Control of gallbladder motor function. Aliment Pharmacol Ther 2000;14(Suppl 2):2–8. [2] Pomeranz IS, Shaffer EA. Abnormal gallbladder emptying in a subgroup of patients with gallstones. Gastroenterology 1985;88:787–91. [3] Sylvestrowics TA, Shaffer EA. Gallbladder function during gallstone dissolution. Effect of bile acid therapy in patients with gallstones. Gastroenterology 1988;95:740–8. [4] Masclee AAM, Jansen JBMJ, Dressen WMM, Geuskens LM, Lamers CBHW. Plasma cholecystokinin and gallbladder responses to intraduodenal fat in gallstone patients. Dig Dis Sci 1989;34:353– 9. [5] Everson GT. Gastrointestinal motility in pregnancy. Gastroenterol Clin North Am 1992;21:751–76. [6] Messa C, Maselli MA, Cavallini A, Caruso ML, Pezzolla F, Di Leo A. Sex steroid hormone receptors and human gallbladder motility in vitro. Digestion 1990;46:214–9. [7] Caroli-Bosc FX, Pugliese P, Peten EP, Demarquay JF, Montet JC, Hastier P, et al. Gallbladder volume in adults and its relationship to age, sex, body mass index, body surface area and gallstones. An epidemiologic study in a non-selected population in France. Digestion 1999;60:344–8. [8] Shreiner DP, Sarva RP, Van Thiel D, Yingvorantpant N. Gallbladder function in diabetic patients. J Nucl Med 1986;27:357–60. [9] Kao CH, Tsou CT, Wang SJ, Yeh SH. The evaluation of gallbladder functions by quantitative radionuclide cholescintigraphy in patients
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[10]
[11]
[12]
[13]
N. Prandini / Digestive and Liver Disease 35 ( Suppl. 3) (2003) S62 –S66 with non-insulin-dependent diabetes mellitus. Nucl Med Commun 1993;14:868–72. Gielkens HA, Eddes EH, Vecht J, van Oostayen JA, Lamers CB, Masclee AA. Gallbladder motility and cholecystokinin secretion in chronic pancreatitis: relationship with exocrine pancreatic function. J Hepatol 1997;27:306–12. Vu MK, Gielkens HA, van Hogezand RA, van Oostayen JA, Lamers CB, Masclee AA. Gallbladder motility in Crohn’s disease: influence of disease localization and bowel resection. Scand J Gastroenterol 2000;35:1157–62. Hussaini SH, Pereira SP, Veysey MJ, Kennedy C, Jenkins P, Murphy GM, et al. Roles of gall bladder emptying and intestinal transit in the pathogenesis of octreotide induced gall bladder stones. Gut 1996;38:775–83. Ziessman HA, Muenz LR, Agardwal AK, Zaza AA. Normal values for sincalide cholescintigraphy: comparison of two methods. Radiology 2001;221:404–10.
[14] Mackie CR, Baxter JN, Grime JS, Cuschieri A. Gallbladder emptying in normal subjects—a data base for clinical cholescintigraphy. Gut 1987;28:137–41. [15] 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. [16] Larson MJ, Klingen-Smith III WC, Kuni CC. Radionuclide hepatobiliary imaging: non-visualization of the gallbladder secondary to prolonged fasting. J Nucl Med 1982;23:1003–5. [17] Xynos E, Pechlivanides G, Zoras OJ, Chrysos E, Tzovaras G, Fountos A, et al. Reproducibility of gallbladder emptying in scintigraphic studies. J Nucl Med 1994;35:835–8. [18] Pazzi P, Petroni ML, Prandini N, Adam JA, Gullini S, Northfield TC, et al. Postprandial refilling and turnover: specific gall bladder motor function in patients with gallstone recurrence. Eur J Gastroenterol Hepatol 2000;12:787–94.
Methods of measuring gallbladder motor functions— the need for standardization: scintigraphy N. Prandini* Nuclear Medicine Department, Azienda Ospedaliera-Universitaria, Corso Giovecca 203, Ferrara 44100, Italy
Abstract Emptying the gallbladder is part of the complex process of food digestion. The gallbladder interacts with other gastrointestinal organs and its movements are coordinated and modified by functions of the stomach, intestine and pancreas. Many factors can modify gallbladder motility, for example, sex and age of the subject, their body mass, the kinds of food ingested and stimulus used. The assumption that the gallbladder progressively empties during meals and refills during fasting is incorrect. Using a combination of ultrasonography and cholescintigraphy, it is possible to measure absolute and net gallbladder emptying. In this way we demonstrated that the gallbladder begins to refill immediately after emptying begins, and the difference between net and absolute emptying of the gallbladder indicates the refilling of bile and provides a measure of bile turnover rate, an accurate index to assess gallbladder motility. 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Cholescintigraphy; Gallbladder emptying; Radionuclide imaging; Ultrasonography
1. Background The gallbladder (GB) normally stores bile during fasting and releases it into the duodenum with ingestion of a meal in a complex process involving most gastrointestinal organs: these organs work together and influence each other by their actions. GB motor function can be modified by the duodenogastric emptying rate and by food composition (quantity and caloric content and percentage of fat, carbohydrates and proteins). Primary gallstones and other diseases of the GB impair the emptying of bile, and in the same way, alterations in stomach and intestine motility, and in exocrine secretion of pancreas effect GB contraction [1]. To standardise a method to measure GB emptying we must consider patient characteristics, the kind of stimulus and the method used to assess GB emptying. A wide spectrum of normal values have been proposed to measure gallbladder motility, but the results are often conflicting in similar patients using different techniques (cholecystography, ultrasonography or cholescintigraphy) [2–4].
*Tel.: 139-0532-825317; fax: 139-0532-237553. E-mail address: [email protected] (N. Prandini).
Therefore, the aim of this study is to propose a standardisation of techniques to assess GB motor function with an excursus on all factors that can modify these measures.
2. Subjects Sex and female hormones are important factors that affect GB motility: fertile women have impaired GB emptying compared to men and postmenopausal women. Similarly, the negative influence of oestroprogestinics during pregnancy on GB motility has been demonstrated, as has administration of female sex hormones in women: both these groups of women more frequently developed gallstones with reduced GB emptying [5,6]. GB volume is correlated with weight and body surface of subjects, but the incidence of gallstone disease is not correlated with GB volume or body weight [7]. Significant impairment of GB emptying was found in obese diabetic patients versus diabetics of normal weight [8]. This effect is mainly due to hyperglycaemia which causes reduced GB emptying in diabetics [9]. Other pathologic conditions that can impair GB motility are acromegaly and gastrointestinal diseases such as
1590-8658 / 03 / $30 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016 / S1590-8658(03)00097-5
N. Prandini / Digestive and Liver Disease 35 ( Suppl. 3) (2003) S62 –S66
S63
cholelithiasis, gastric ulcers, pancreatitis and Crohn’s disease [10]. Previous surgery on the upper gastrointestinal tract impairs GB motility reducing the velocity and the percentage of emptying [11]. Excluding all drugs influencing GB motility such as sincalide, morphine, cholecystokinin (CCK), and biliary acids, most treatment that acts on gastrointestinal motility can also modify GB motility. For example, a significant increase in gallstone disease was found in subjects treated with octreotide [12].
3. Stimulus The stimulus used to obtain a GB response should be natural (meal) or exogenous (mostly CCK). Fatty meals are widely used because of their availability: the response of GB to a stimulus depends on the amount of food and its composition (fat, carbohydrates and proteins). However, there is no universal standard meal because of different habits and tastes, and in most papers the number of normal subjects studied is insufficient to provide normal values. One of the most widely used meals to stimulate GB contraction is milk (250–300 ml), but many patients are lactose intolerant and so this cannot be proposed as a standard choleretic stimulus. Exogenous stimulus with CCK should be a reliable and standard method to stimulate the GB. Sincalide (Kinevac , Bracco Diagnostics) is the only CCK analogue approved by the FDA: however, it is not available in most European countries or, because of manufacturing and regulatory problems, in the USA [13]. A commercially available liquid food supplement containing adequate fat to stimulate GB contraction would be the correct choice in all countries because of the absence of clinical contraindications and because, unlike sincalide, i.v. injection or infusion is not required. Ensure plus (Abbott Laboratories, Columbus, OH) or Fortimel are two examples of fatty meals which are easily sourced and can be used in all ultrasonographic and scintigraphic laboratories. We advise consumption of a semisolid fatty meal with 370 kcal, 55% fat, 25% carbohydrates, and 20% proteins using a standard supplement (2 Fortimel). The use of CCK-8 (bolus of 0.04 mg / kg or infusion of 0.3 ng / kg for 60 min) i.v. 30 min before injection of imino diacetic acid (IDA) compounds is questionable.
4. Techniques GB motor function studies often produce conflicting results because different techniques are used (cholecystography, ultrasonography, and cholescintigraphy) [14]. Cholangiography calculates GB contraction by measuring the diameter of the area on film using a bidimensional
Fig. 1. Mean values of GB emptying measured in 12 normal subjects: the percentage of ultrasonographic emptying (black triangle) is always lower than absolute, cholescintigraphic emptying (black circle).
method which is less precise than ultrasonography, which measures the volume with a three-dimensional method, or scintigraphy, which measures the global activity of GB independent of area or volume. Scintigraphic measurement is more reproducible and independent of the operator: filling and emptying of GB can be followed continuously during all phases. Furthermore, scintigraphy measures cessation of GB activity (absolute emptying) whereas ultrasonography measures GB volume and is thus influenced by refilling. This explains the conflicting results of these two widely used methods: they measure two different functions, absolute emptying of GB (scintigraphy) and volume (ultrasonography). In our experience, by combining the two methods it is possible to measure GB refilling and the turnover rate of bile after stimulation with a fatty meal. This provides a real and complete assessment of GB motor function [15] (Fig. 1).
5. Patient preparation The ideal patient preparation is to maximize bile entry into the GB by allowing maximum relaxation of the GB and maximum contraction of the sphincter of Oddi. An overnight fast accomplishes this, but longer hours of fasting or total parental nutrition are suggested in order to obtain no GB visualisation [16]. A fasting state of 8 h is adequate for a 99m Tc-HIDA study to ensure complete GB filling, but most prefer a minimum of 4 h. In all patients, personal data concerning weight, height, age, drug intake, gastrointestinal and metabolic diseases should be collected to avoid mistakes in data interpretation.
S64
N. Prandini / Digestive and Liver Disease 35 ( Suppl. 3) (2003) S62 –S66
Fig. 2. Comparison of blood clearance (left graphics) and time activity curves (right graphics) obtained in a subject after simultaneous injection of 75 SeHCAT (empty circle, triangle and box) and 99m Tc-Bromida (filled circle, triangle and box): curves of biliary acids and of IDA derivatives are analogues.
6. Radiopharmaceuticals Derivatives of HIDA (iminodiacetic acid) labelled with technetium are widely used to obtain biliary tract visualisation. After i.v. injection, they are taken up, conjugated and eliminated by hepatocytes in the biliary ducts thus visualizing the biliary tree, choledoc and GB. They are excreted into bile ducts both by active transport and passive diffusion. The radiopharmaceutical is not conjugated by the liver and so remains almost identical to its originally administered form. Several HIDA derivatives are proposed which differ in their liver uptake and elimination in different levels of blood bilirubin. The IDA derivatives mainly used for hepatobiliary scintigraphy are mebrofenin and DISIDA: mebrofenin has 98% hepatic uptake with a hepatic excretion of 1761.3 min and 1.5% urinary excretion. Kinetics of these HIDA derivatives are similar to kinetics of biliary acids (Fig. 2): the most important difference is that biliary acid (SEHCAT for example) is re-adsorbed by the small bowel and slowly returns to the liver by the portal system, whereas HIDA derivatives are not reabsorbed and are eliminated by the intestine. 99m
intestine, kidneys and bladder is sufficient for complete study of GB function. In our experience, study of GB motility begins 90 min after i.v. injection of 40–60 MBq of 99m Tc-Br-HIDA to obtain a liver elimination of bile .95%, avoiding any new GB activity which could influence the calculation of absolute GB emptying. We perform two basic acquisitions of GB parameters (volume and activity). After stimulus with a standard fatty meal, a series of nine acquisitions (ultrasonography and cholescintigraphy), with one every 10 min, is performed.
8. Analysis All scintigraphic methods to assess GB motility require computerized analysis of the data with ROIs (regions of interest) drawn on the GB, liver, intestine, background and bladder. The counts obtained must be corrected for physical decay of technetium (6 h) and for activity of the liver, background and intestine close to the GB. This type of study is reproducible: Xynos et al. showed that, when repeating the same GB study in 30 patients stimulated with 250 ml of fresh milk, the lag phase duration and the ejection fraction were reproduced with a high degree of correlation (r50.87 and r50.84, respectively) [17].
7. Acquisition A dynamic sequence of 60-min computed assisted scintigraphy is mandatory for the study of liver and GB kinetics (1283128 matrix, one image every minute). An anterior view of the abdomen including whole liver,
9. Clinical applications The major advantage of cholescintigraphic assessment of GB motility versus ultrasonographic assessment is the
N. Prandini / Digestive and Liver Disease 35 ( Suppl. 3) (2003) S62 –S66
Fig. 3. Combination of ultrasonography and cholescintigraphy in an acromegalic patient in basic conditions (fill triangle and circle) and after s.c. administration of 100 ng of octreotide (empty triangle and box). Octreotide significantly impairs GB emptying measured by both ultrasonography and cholescintigraphy.
S65
sex, age, weight, BMI), pathological condition of the patient (diseases or their treatments), the kind of stimulus used (fatty meal, CCK, etc.), and methods used to assess GB motility (ultrasonography, scintigraphy, etc.). A good standardized method requires collection of all data that can modify GB motor function, but the technique necessary for complete assessment of GB motor function is the combination of the two most widely used procedures: ultrasonography and scintigraphy. Using our combination of procedures it is possible to carry out a complete study of GB parameters, including volume, GB absolute emptying, GB relative emptying, GB refilling, bile turnover rate, and bile turnover index. Scintigraphy still plays a role in functional studies: its use in combination with ultrasonography is essential to assess refilling in the study of GB motor function.
Conflict of interest statement None declared.
reproducibility of the studies and independence from the operator. However, quantitative assessment of scintigraphic emptying is incomplete if volume and relative emptying of the GB is not measured. Turnover rate and turnover index of bile assessed with our proposed method can correctly differentiate the GB motor functions of gallstone patients from normal subjects. Furthermore, measurement of bile turnover rate is a standardized and controlled method that can be very useful in research, for example, to study the effects of treatments on GB motor function. Pazzi et al. showed that there is significant difference between two groups of patients after dissolution of gallstones with bile acid treatment: the patients with recurrence of gallstones have a lower bile turnover index than patients without recurrence. Motility of gallstone patients without recurrence was very similar to normal controls, with a small and insignificant reduction in emptying and no reduction in postprandial refilling or turnover [18]. More recent study on the effects of drug treatments can benefit this standard technique: for example in a group of acromegalic patients treated with octreotide we found a fasting GB volume higher than normal. Acute s.c. and long-acting release (Sandostatin LAR ) i.m. administration of octreotide produces impaired gallbladder emptying as measured both by ultrasonography and cholescintigraphy, with a significant reduction in postprandial refilling, bile turnover and turnover index (Fig. 3).
10. Conclusions Many parameters can affect the response of the GB to a stimulus, including characteristics of the patient (fasting,
List of abbreviations CCK, cholecystokinin; GB, gallbladder; ROI, region of interest.
References [1] Shaffer EA. Control of gallbladder motor function. Aliment Pharmacol Ther 2000;14(Suppl 2):2–8. [2] Pomeranz IS, Shaffer EA. Abnormal gallbladder emptying in a subgroup of patients with gallstones. Gastroenterology 1985;88:787–91. [3] Sylvestrowics TA, Shaffer EA. Gallbladder function during gallstone dissolution. Effect of bile acid therapy in patients with gallstones. Gastroenterology 1988;95:740–8. [4] Masclee AAM, Jansen JBMJ, Dressen WMM, Geuskens LM, Lamers CBHW. Plasma cholecystokinin and gallbladder responses to intraduodenal fat in gallstone patients. Dig Dis Sci 1989;34:353– 9. [5] Everson GT. Gastrointestinal motility in pregnancy. Gastroenterol Clin North Am 1992;21:751–76. [6] Messa C, Maselli MA, Cavallini A, Caruso ML, Pezzolla F, Di Leo A. Sex steroid hormone receptors and human gallbladder motility in vitro. Digestion 1990;46:214–9. [7] Caroli-Bosc FX, Pugliese P, Peten EP, Demarquay JF, Montet JC, Hastier P, et al. Gallbladder volume in adults and its relationship to age, sex, body mass index, body surface area and gallstones. An epidemiologic study in a non-selected population in France. Digestion 1999;60:344–8. [8] Shreiner DP, Sarva RP, Van Thiel D, Yingvorantpant N. Gallbladder function in diabetic patients. J Nucl Med 1986;27:357–60. [9] Kao CH, Tsou CT, Wang SJ, Yeh SH. The evaluation of gallbladder functions by quantitative radionuclide cholescintigraphy in patients
S66
[10]
[11]
[12]
[13]
N. Prandini / Digestive and Liver Disease 35 ( Suppl. 3) (2003) S62 –S66 with non-insulin-dependent diabetes mellitus. Nucl Med Commun 1993;14:868–72. Gielkens HA, Eddes EH, Vecht J, van Oostayen JA, Lamers CB, Masclee AA. Gallbladder motility and cholecystokinin secretion in chronic pancreatitis: relationship with exocrine pancreatic function. J Hepatol 1997;27:306–12. Vu MK, Gielkens HA, van Hogezand RA, van Oostayen JA, Lamers CB, Masclee AA. Gallbladder motility in Crohn’s disease: influence of disease localization and bowel resection. Scand J Gastroenterol 2000;35:1157–62. Hussaini SH, Pereira SP, Veysey MJ, Kennedy C, Jenkins P, Murphy GM, et al. Roles of gall bladder emptying and intestinal transit in the pathogenesis of octreotide induced gall bladder stones. Gut 1996;38:775–83. Ziessman HA, Muenz LR, Agardwal AK, Zaza AA. Normal values for sincalide cholescintigraphy: comparison of two methods. Radiology 2001;221:404–10.
[14] Mackie CR, Baxter JN, Grime JS, Cuschieri A. Gallbladder emptying in normal subjects—a data base for clinical cholescintigraphy. Gut 1987;28:137–41. [15] 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. [16] Larson MJ, Klingen-Smith III WC, Kuni CC. Radionuclide hepatobiliary imaging: non-visualization of the gallbladder secondary to prolonged fasting. J Nucl Med 1982;23:1003–5. [17] Xynos E, Pechlivanides G, Zoras OJ, Chrysos E, Tzovaras G, Fountos A, et al. Reproducibility of gallbladder emptying in scintigraphic studies. J Nucl Med 1994;35:835–8. [18] Pazzi P, Petroni ML, Prandini N, Adam JA, Gullini S, Northfield TC, et al. Postprandial refilling and turnover: specific gall bladder motor function in patients with gallstone recurrence. Eur J Gastroenterol Hepatol 2000;12:787–94.