standards for diagnosis gastrointestinal motility disorders. section: ultrasonography position...

R Portincasa A. Colecchial A. Di Ciaula A. Laroccal M. Muraca2 G. Palasciano E. Rodal D. Festi3

Ultrasonography is a non-invasive, relatively easy, validated and reproducible technique. We assessed the usefulness of functional ultrasonography to study disorders of gastro-oesophageal tract, gallbladder and pancreatic duct. Oesophagus Oesophagus and the gastro-oesophageal junction can be visualized in children up to 5 years old. Ultrasonography shows 100% sensitivity and 87.5% specificity compared to ambulatory pH-metry for gastro-oesophageal reflux disease diagnosis. Stom- ach Ultrasonography can be used to estimate whole gastric volume, antral area or diameters, antro-pyloric volume, transpyloric flow in fasting state and in response to test meal. Gallbladder UI- trasonography is reliable to estimate volume in fasting state and in response to test meal or exogenous stimulus. For both stomach and gallbladder: indications might include the study of healthy subjects and of pathophysiologically relevant conditions such as dysmotility-like dyspepsia, suspicion of delayed gastric emptying, diabetes mellitus, gallstone disease and effect of drugs either delaying or accelerating motility Common bile duct Ultrasonography can be used to estimate interprandial and postprandial common bile duct diameter in patients with clinical suspicion of common bile duct obstruction in fasting state and in response to test meal or exogenous stimuli. Although functional ultrasonography is used mainly for research purposes, its simplicity makes it appealing for clinical use to assess gastrointestinal motility in health and disease.

Digest Liver Dis 2000;32:160-72

Key words: gastrointestinal motility disorder; ultrasonography

Gastrointestinal motility disorders represent a frequent problem in clinical practice. The ultimate goal for assessing motor abnormalities of the gastrointestinal tract remains the need to improve the clinician’s ability to treat motility-related disorders in selected patients. Such disorders can now be better diagnosed choosing from a wide range of instrumentations and because more emphasis has been placed on the association between certain symptoms and dysmotility of the gastrointestinal tract. It must be stressed, however, that no single technique provides complete answers, so

P. Portincasa et al.

far, and that, in each clinical setting, the ultimate choice depends on availability, invasiveness, costs, and complexity of each technique. The more ad- vanced technology has expanded the use of ultrasound in clinical gastroenterology. By using “functional ultrasonography”, in fact, it is possible to mon- itor “real-time” changes of a distance, area or volume in the organ under investigation. Functional ultrasonographic studies can be performed for abdominal organs such as the oesophagus, the stomach, the gallbladder and the pancreatic duct. Although the technique is mainly used for research purposes, its simplicity makes it appealing for clinical use. In some cases, functional ultrasonography has a true clinical role when used either alone or associated with other investigations. In some other cases, the technique represents an important aid to the study of pathophysiological aspects. Although it has been suggested that ultrasonography can be highly operator-dependent this problem can, in our opinion, be overcome by standardizing the technique as much as possible and by appropriate training of the opera- tors. Instead, a major limitation of functional ultrasonography for the study of gastrointestinal motility disorders is that it can require prolonged observations. The aim of the present report is to focus on the role of functional ultrasonography in the assessment of gastrointestinal motility. The main technical aspects, interests and limitations of ultrasonography will be presented and discussed in comparison with other available techniques.

Ultrasonography is a non-invasive, relatively easy, validated and reproducible technique. No radiation is involved and, therefore, it can be used during pregnancy and in children. The compliance of the patient is optimal and standard equipment is widely available at a reasonable cost. Equipment and minimal require- ments for functional studies are similar to those used for morphological studies and can be applied to different organs.

Hardware and software - Ultrasound equipment with a linear or convex

probe at a frequency of 3.5 or 5.0 MHz. For the study of the oesophagus, in the inborn, a probe of 7.5 MHz for more superficial organs is used.

- “Built-in” software for automatic measurements of distances, areas and volumes.

- Printer for output reports, VHS tape recorder for prolonged recording (optional).

- Personal computer and appropriate software for automatic reports.

Room - Equipped with bed, comfortable chair, emergency

drugs, toilet facilities, etc.

Sta# - Medical personnel trained in abdominal and func-

tional ultrasonography. - Nurse.

Disposable material - Ultrasonographic gel. - Printer paper, videocassette. - Test meals and stimuli:

- Oesophagus: tea or milk. - Stomach: standard liquid or mixed (solid/liquid)

meal. - Gallbladder: standard liquid or mixed (solid/liq-

uid) meal. - Common bile duct: liquid test meal, iv caerulein,

cholecystokinin (CCK).

esupha~u§

Ultrasonography allows visualization of the oesophagus. Due to its anatomical characteristics, however, only two oesophageal tracts are visible by ultrasonography: the proximal (cervical) tract and the distal tract (gastro-oesophageal junction). Functionally, ultrasonographic study of the gastro-oesophageal junction has been proposed as an alternative method compared to more invasive examinations for the diagnosis of gastro-oesophageal reflux in children l 2. In a previous study, ultrasonography showed a 100% sensitivity and 87.5% specificity compared to outpa- tient pH-metry for the diagnosis of gastro-oesophageal reflux in children 3.

Technical aspects The oesophagus and the gastro-oesophageal junction can be easily visualized in children up to 5 years of age l 2. Both transverse and longitudinal scans are taken at the epigastrium in subjects having fasted for at least 4 hours. A longitudinal scan performed at the level of the left lobe of the liver, slightly rotating the probe, allows visualization of the oesophagus like a 3- layer canalicular structure posterior to the left lobe of the liver and anterior to the aorta, two important reference points. The three layers are: a) hypoechoic exter- nal muscular layer; b) hyperechoic middle mucosal layer; and c) hypo-anechoic internal lumen. Immedi- ately after ingestion of a liquid meal (usually 100-200

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Ultrasonography of intestinal motility

ml milk or detheinated tea), it is possible to observe the progression of the ingests in the lumen like hyperechoic micro-bubbles of gas. The protocol for the study of the oesophagus includes the following steps: 1) longitudinal scans in the upright position to detect

emptying of the distal oesophagus; 2) prolonged observation (at least 10 minutes) of the

oesophagus and the gastro-oesophageal junction with the patient in the supine position 3.

A gastro-oesophageal reflux, when present, is visible like a flow of hyperechoic material (gastric content with micro-bubbles of gas) moving from the gastric lumen to the distal oesophagus through the gastro-oesophageal junction.

Data analysis The test is considered positive (i.e., presence of gastro- oesophageal reflux) when at least two distinct episodes of retrograde filling of the distal oesophagus are recorded. The test provides the following information: - presence/absence of gastro-oesophageal reflux

episodes; - frequency of gastro-oesophageal reflux episodes (n.

episodes/time unit); - oesophageal clearance (mean time of permanence

of reflux within the distal oesophagus); - extent of gastro-oesophageal reflux (small/large

volume of refluxed material).

Indications Age ~5 years, clinical evidence of gastro-oesophageal reflux, gastro-oesophageal pH-metry not available or not possible (consent unavailable etc.), follow-up of patients with gastro-oesophageal reflux treated with prokinetic drugs.

Advantages The technique is non-invasive, relatively easy to per- form, validated and reproducible; no radiations are involved; compliance of the patient is usually good and standard equipment is widely available at a reasonable cost; simultaneous measurements are possible (e.g. gallbladder, stomach etc.).

Limitations The technique is useless in older children, adolescents and adults, for whom an expert operator and prolonged observations are necessary.

Stomach

Although several methods provide information on both pressure events and emptying of the stomach,

techniques such as perfused and ambulatory manometry, barostat, radiopaque markers, and gastric intubation are limited by their invasiveness and complexity or by radiation exposure (e.g. fluoroscopy). Thus, the ultimate application of such techniques in clinical practice can be very limited or restricted to a few re- ferral units. Other methods include magnetic reso- nance imaging, impedence epigastrography, applied tomography, drug pharmacokinetics or breath tests with stable isotopes (e.g. 13C-acetate and 13C-octanoic acid for liquid and gastric phases, respectively). These tests, however, are either expensive, have limited availability in only a few centres or need to be fully validated 4. Radionuclide scanning remains the gold standard for the study of gastric emptying both in research and clinical practice4. Markers can be employed to study liquid and solid phases, simultaneously. Relatively short scanning times (e.g. up to 90 min, postprandially) are chosen by many centres but might be inappro- priate in cases of severely delayed gastric emptying. To reliablyextrapolate the half-time of emptying, it is preferable to reduce the number of scans and to use data collected at 2, 4 and 6 hours 5. Albeit, scintigraphic gastric emptying may not always be available for routine purposes. Ultrasonography, thanks to its main features (i.e., non-invasive, radiation-free, widely available technique), can be repeated several times in the same patient. Another advantage is that the technique does not affect gastric physiology. At variance with scintigraphic methods functional ultrasonography allows the study of gastric areas, volumes, contractions, distension, co-ordination of movements, and transpyloric flow 6. There is a close correlation between the speed of gastric emptying calculated by radionuclide and ultrasonographic techniques 7 x. Validation studies have shown that day-to-day variations and intra- and inter- observer errors are generally low g. Finally, ultrasonography allows the simultaneous study of other organs such as gallbladder, liver, kidney, pancreas etc.

Technical aspects After a fasting of 6-8 hours (or 8-12 hours if the test is performed simultaneously with study of the gallbladder), the subject is asked to sit in a comfortable chair, leaning slightly backward. This position avoids interference from intragastric gases. The subject is not allowed to smoke or to drink either immediately before or during the exam. Attention should be paid to avoid the effect of medications that either inhibit or enhance motility (e.g., adrenergic agents, anticholinergics, calcium channel blockers, cisapride, erythromycin, etc.).

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Methods Several methods employed for the study of gastric emptying by two- or three-dimensional ultrasonography are described below: a) Whole gastric volume (antrum+body+fundus) This is achieved by adding together a series of parallel cross sections taken along the longitudinal axis. The first at- tempt at measuring gastric emptying, however, was rather complicated, time-consuming, and frequently problematic due to gas interference in the fundus. Overall, it required prolonged observations of the vis- cus and complicated calculations lo. More recently, a three-dimensional (3D) ultrasound imaging of the total stomach volume has been developed using a magnetic position sensor system for computer-assisted acquisi- tion of 3D ultrasonograms to determine gastric emptying rates and intragastric distribution of liquid meal ll. b) Gastric antrum Using both longitudinal and transverse views, the gastric antrum can be visualized at the epigastrium posterior to the left lobe of the liver and anterior to the pancreas. With a longitudinal scan, the antrum is cut transversally with the typical “bullseye” shape. During fasting, the lumen is virtual or very small (i.e., contains very little fluid), and the gastric wall is thick and hypoechogenic (musculature). On a transverse scan the antrum appears in longitudinal section as a tubular structure. During fasting, the lumen is nonechogenic, small, and defined by alternating layers of hypo- and hyperechogenicity. Prolonged observation of the antrum during fasting can show either absence of contractility, sporadic peristaltic movements, or frequent contractions (about 3 contractions/minute), depending on the phase of the interdigestive migrating motor complex of the intestine (phase I: no contractions; phase II: sporadic contractions; phase III: rhyth- mic high-frequency contractile activity with 2-3 contractions/minute) . l2 l3 During contractions, the gastric wall, in the longitudinal real-time scan, appears thicker with a rapid decrease of the antral area; in a transverse scan it appears as “rings” of thicker wall moving in an oro-caecal direction. After ingestion of a meal, the area of the antrum increases and the surrounding wall becomes thinner with a visible lumen. Peristaltic waves are also evident during the postprandial period. All measurements (area, distance and volume) must be taken between two peristaltic waves, to avoid underes- timation of the size of the stomach. An example of an ultrasonographic scan of the antrum in the healthy subject is given in Figures 1, 2. bl) antro-pyloric volume Three parallel longitudinal

scans are taken of the epigastric area, at the level of the antrum: angulus, anterior to the superior mesenteric vein and at the pre-pyloric portion. For each circular/elliptic scan, the antero-posteri- or and transverse diameters are calculated. By ro-

tating the probe, the length of the antrum is measured by transverse scan. A mathematical formula is then employed to calculate the antral volume 14-i6. Although a high interindividual variability has been reported, the volume which is obtained significantly correlates with the volume of fluids

Ultrasoaography of intestinal motility

administered 15. Another approach includes 3D ultrasonography of the antrum. This is obtained with a genuine 3D-probe or a two-dimensional probe connected to a tilting device, controlled by a computer. After interactive manual outlining of the gastric contour on a computer display, the stomach is reconstructed and visualized in 3D. The volume of the antrum is derived from lo- 15 planar contours 16.

,,b2)AntruZ area A single longitudinal scan is taken at the epigastrum to visualize the cross-section of the antrum anterior to the superior mesenteric vein and the aorta, both of which are important reference points 7 8 14. This method is simpler and quicker than method bl) and correlates well with intragastric volume7.

b3) Antral diameters Same scan as for the antral area. The mean from the antero-posterior and transverse diameters are then calculated 17.

b4) Observation of the antvopyloric region This is obtained from a transverse scan and allows a de- tailed study of antro-pyloric coordination, including episodes of duodenogastric reflux (i.e., transpyloric flow of hyperechoic material) 18. Flow across the pylorus can also be monitored by duplex sonography, and has been employed to study the effect of glyceryl trinitrate on gastric motility 19.

c) Proximal stomach This approach has been proposed to estimate the fundic response to meal ingestion 9, a function by which a high volume increase is associated with a minimal rise in intragastric pressure (i.e., receptive relaxation and accommodation in the fundus). The proximal stomach is visualized by positioning the probe at the left subcostal margin and tilting it cranially on a sagittal scan (landmark points: left renal pelvis, left liver lobe and the pancreatic tail) and then on a transverse scan (landmark points: left hemidiaphragm, top margin of the fundus and liver parenchyma). With these two scans, it is possible to estimate the sagittal area and a maximal diameter, respectively, from which the volume of the proximal stomach is estimated.

Data analysis As an example, the following steps are undertaken for the study of gastric emptying with the antral area technique 20; - start at 8.00-9.00 am. Fasting subject, relaxed and

seated, leaning slightly backward (+lOO”; interference from intragastric air is minimized). Subjects are not allowed to smoke or to drink immediately before or during the exam;

- equipment: probe of 3.5-5.0 MHz, longitudinal scans at epigastrium;

- duplicate measurements of basal (fasting) antral area (-5 and 0 min before test meal);

- liquid test meal (e.g. Nutridrink, Nutricia): volume 200 ml, 300 Kcal, 390 mOsm/l, containing: 13 g fat, 36 g carbohydrate, 10 g protein. The test meal is ingested in 1-2 min;

- measurement of maximal postprandial antral area (after maximal widening of the antrum has occurred, usually within 2 min, postprandially);

- measurement of postprandial antral areas at 5, 10, 15, 20, 25, 30, 35, 40,45, 60, 75, 90, 105 and 120 min after test meal. Antral areas are expressed as cm2 and as percentage of maximal areas after sub- tracting basal areas (i.e., Postprandial area (%) = 100 . (At-a)/(Amax-a); where A, = postprandial area at any given time; a=basal area; Amax = maximal postprandial area, all in cm2). Some patients (e.g. with functional dyspepsia) might present with a wide fasting antrum filled with fluid (e.g. increased salivary and/or gastric secretion and/or increased duodeno-gastric reflux) 21 22. It is, therefore, possible that emptying will be completed postprandially when the antral area becomes even smaller than the fasting area (i.e., resulting in a “negative” value in percent). It is safer, in this case, to confirm such a trend on at least two consecutive measurements;

- construction of the antral emptying curves is obtained by plotting antral areas vs time. The ultrasonographic emptying half-time (Tusl,z, min), i.e., the time when a 50% decrease of maximal antral area occurs is calculated by linear regression analysis from the linear part of the emptying curve and shows a good correlation with the scintigraphic emptying half-time (T,,1/2) *.

Further indices of gastric emptying are 8 23: - minimal postprandial antral area: the smallest area

measured at any time postprandially; after complete emptying has occurred this area is similar to the basal (fasting) area;

- integrated antral emptying: i.e., area under emptying time-curves after subtraction of basal values, expressed as percentage of basal antral area (AUC, percent* 120 min.‘);

- “Lag phase”: time required before gastric emptying starts; this is true when a mixed liquid/solid meal is given 23;

- frequency of phasic contractions of the antrum; usually expressed as n. of contractions/minute; can be measured in the interprandial as well as in the postprandial period.

The pattern of gastric emptying is influenced by several characteristics of the test meal: type (liquid or mixed), volume, fat content, energy, osmolarity, pH, palatability. A mixed test meal is more physiological

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in that all gastric functions are activated (mixing, grinding, secretion and emptying). However, the ex- amination requires more time (up to 6 hours) 14. Arti- facts due to gas in the intestine, moreover, can inter- fere with sonographic measurements. A liquid test meal, on the other hand, is usually rapidly emptied and thus requires a shorter observation time. Due to the initial fast emptying speed, the study of a liquid meal requires more frequent scans (at least initially every 5-10 min). It must be underlined, however, that there is a need for standardization of “normal values” in healthy in- dividuals. Table I shows that there is a wide variability between different groups in the literature as far as concerns type of test meal, technique, and reference values.

Indications Study of gastric emptying may be useful in at least three conditions: a) Evaluation of patients with “dysmotility-like”

dyspepsia. Impaired gastric motility, including antral hypomotility, has been reported in patients with functional dyspepsia previously studied by manometry and scintigraphy 5 24-26. A number of motility abnormalities have been found also at ultrasonography in patients with functional dyspepsia, including smaller size and more rapid emptying rates of the proximal stomach (i.e., impaired gastric accommodation), wide fasting and postprandial gastric antrum, early commencement of transpyloric flow 6 l6 l7 *l **. Postprandial dyspeptic symptoms can be associated with abnormalities such as prolonged antral distension, increased antral volume 27 and abnormal fundic function 2x which are detectable at ultrasonography 16. As op-

posed to more invasive techniques such as isobar- ic distension of the stomach 29, ultrasonographic studies of the proximal stomach can provide important information without altering gastric physiology 30.

b) Conditions frequently associated with delayed gastric emptying in patients with or without dyspeptic symptoms. Previous studies have focused on patients with diabetes mellitus (in which a large proximal stomach and large antrum are commonly found) 31-33, obesity 34, gallstone disease 20, liver cirrhosis 35.

c) Follow-up of the effect of drugs influencing gastric motility. This can include prokinetic drugs (e.g. cisapride, erythromycin, etc.) 22 36-41 or agents delaying gastric emptying 33 34 42.

Limitations The technique is mainly used for research purposes although several groups are attempting to introduce it into the clinical setting. The need for prolonged observations is a major limitation of ultrasonography. This is particularly true when estimating whole gastric volume, antral volume or the proximal stomach. For practical purposes, however, the problem can be overcome by using simplified gastric emptying tests (e.g. measuring antral areas instead of volumes or taking less frequent measurements at fixed time points, or using liquid instead of solid meals whenev- er possible). General limitations for the study are: concomitant treatment with drugs which can inhibit gastrointestinal motility, inadequate visualization of antrum or landmark points (high-grade obesity, gastric surgery, air bubbles), stomach underneath the ribs or very long stomach. Since there is no distinction between simultaneous emptying of solid and liquid

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phases, the test needs to be repeated on two separate days (should this information be needed). Although the 3D imaging method is less operator-dependent, it can be affected by air bubbles and antral contractions, causing potential errors in volume estimation l6 43.

Gallbladder

The gallbladder is a pear-shaped bag. The main motor functions of the gallbladder include emptying of its content in response to nutrients, filling during the interprandial period and mixing of its content. Gall- bladder motor function has previously been studied by various techniques including duodenal intubation 44, oral cholecystography 45, and radionuclide scanning . 46-48 Intrinsic limitations of such techniques are: invasiveness, indirect information on gallbladder function and morphology, and use of radiations. As a result, all the above-mentioned techniques (with the exception of radionuclide scanning - see below) have been abandoned. The development of ultrasonography has greatly im- proved the possibility to study gallbladder motor function 49. Due to its liquid (non-echoic) content, it can easily be visualized by ultrasonography below the right lobe of the liver. This feature allows a de- tailed study both of morphology and motor function of the gallbladder (Table II). Different ultrasonographic techniques have been employed to calculate the volume and the motor function of tbe gallbladder . 5o Previous mathematical formulas using two-dimensional measurements have been re-

placed by measurements of the three diameters of the organ, which allow a fair estimation of the volume and its time-dependent changes. For the study of gallbladder motility it is important to estimate: the fasting volume of the organ after at least a 12-hour fasting period and its time-related changes after appropriate stimulus (test meal or drugs) until a minimal residual volume is observed.


hfeasurement of gallbladder volume The subject is asked to lie in a supine position and to hold his/her breath for a few seconds during each measurement. Longitudinal, transverse, and oblique scans at the right hypochondrium are used to identify the longest diameter of the gallbladder. From this frozen image, the longitudinal diameter (length) is measured (Figs. 3, 4). By rotating the probe perpen- dicularly to the length, the anteroposterior diameter (depth) and the transverse diameter (width) is then calculated. All diameters are taken by positioning the calipers at the inner part of the gallbladder wall (i.e., mucosa) which delimits the lumen of the organ. The three diameters of the gallbladder are used to calculate the volume of the gallbladder. Two procedures are more commonly employed: the sum-of-cylinders method and the ellipsoid method. The former, first suggested by Everson et al. 49, assumes the gallbladder volume to be equal to the sum of cylinders of equal heights which are perpendicular to the length of the organ. The volume of each cylinder is calculated and then summated, according to the

Fig. 4. Measurement of gellbledder volume 30 min. after ingestion of

cm) and width 1.3 cm). The estimated volume

formula: Volume = 0.785-h.(C”i=o di2).E2 where 0.785 = constant value derived from n/4; h = height of each cylinder, n = number of cylinders, di = diameter of the i-th cylinder; E = correction factor applied for dis- placement of the sagittal scan from the central axis of the gallbladder = [(depth + width)/2d,,,] where width and depth are derived from the transverse scan; d,,, = maximal diameter of cylinder. The sum-of-cylinders method is generally considered the “gold standard” for calculating gallbladder volume. However, this method is tedious and time consuming, unless a computer programme is used. Thus, its use should be restricted to the study of dys- morphic gallbladders. For routine purposes, the ellipsoid method, originally described by Dodds et al. 51 is easier and assumes that the gallbladder volume approximates a solid, the sections of which are elliptic. In a small number of normal subjects, this method gave good results as compared to the sum-of- cylinders method 51. The formula is: Volume = length.depth.width.0.523 where 0.523 = 7c/6, depth = anteroposterior diameter, width = latero-lateral diameter. Volume is in ml (cm”) when diameters are taken in cm.

Evaluation of gallbladder motor function Gallbladder motor function can be studied by ultrasonography in the fasting state and after a stimulus which is administered exogenously (e.g. iv caerulein, CCK) or endogenously (e.g. a test meal which acti- vates the release of intestinal CCK). Thus, the time-

dependent decrease and subsequent increase of gallbladder volume are a function of the stimulus being used. Although physiological gallbladder emptying might be the result of rapid episodes of emptying-filling 52, the assessment of this activity requires very frequent measurements (i.e., every l-2 min) which can- not be easily done on a routine basis. Thus, an easier way is to measure fasting gallbladder volume by taking the mean of two consecutive measurements 10 min apart and at least two postprandial measurements at 30 and 4.5 min in order to document the smallest residual volume of the gallbladder 53 54. These few measurements are usually sufficient to provide a general estimate of postprandial gallbladder emptying. However, more accurate pathophysiological studies require frequent and prolonged measurements of the gallbladder volume (e.g. every lo-15 min, up to 120- 180 min, postprandially). Taken together, these measurements document the speed of gallbladder emptying and the refilling phase which usually reaches 80% of fasting volume within 180 min, postprandially. A standard meal (test meal) should contain an appropriate amount of fat in order to achieve a good CCK release and gallbladder contraction. Test meals com- mercially available include 200-250 ml liquid solu- tions of about 300 Kcal and about 40% carbohy- drates, 40% fat and 20% protein, with about 400 mOsm/l. An example of adequate test meals commer- cially available is shown in Table III. The most important feature of a good test meal should be its ability to discriminate between “normal” and “abnormal” gallbladder contractors 53 55-57. Indeed, a good correlation is found between iv caerulein- and test meal-induced gallbladder emptying.

Nutridrink [Nutriciel 200 10 Ensure plus (Abbott1 200 12.5

An appropriate stimulus of the gallbladder is also achieved by administering the CCK-analogue caerulein (Takus@, Pharmacia-Upjohn) which is given iv at the dose of 0.3 pg/kg body weight. Whereas both standardization and reproducibility might be better by this procedure, important pitfalls are the possibile side effects (e.g. abdominal cramps, nausea etc.) and difficult availability of the drug. The use of iv cholecystokinetic drugs is of interest during biliary

drainage to identify cholesterol monohydrate crystals (e.g. patients referred for episodes of acute pancreati- tis) or to study the biochemical composition of biles (e.g. before and after treatment for lithiasis in patients with gallstones).

Data analysis The following steps are given as an example for the study of gallbladder emptying. The volume can be calculated with the formula of Dodds et al. 51: - start at 8.00 am with the fasting subject (12

hours), supine or seated (if combined measurements with gastric emptying). The subj,ect is not allowed to smoke either immediately before or during the exam;

- measure basal (fasting) volume (FV): take duplicate measurements of gallbladder volume at -10 and 0 min before test meal;

- administer the test meal or infuse caerulein or CCK iv;

- measure residual volume (RV): minimal volume at 30 and 45 min after stimulus;

- calculate ejection volume (EV): difference between fasting and residual volume in ml;

- calculate ejection fraction (EF): emptying volume expressed as percent fasting volume, calculated as lOO.((FV-RV)/FV).

Further indices of gallbladder motor function are: - integrated gallbladder emptying: area under emp-

tying time-curves (AUC) obtained after subtraction of basal values and expressed as fasting volume (120 min.l; AUC is calculated when serial measurements of postprandial gallbladder volumes are carried out;

- half-time of emptying (Tr,z): time in minutes to observe 50% decrease of fasting gallbladder volume 57; the index is calculated by linear regression analysis from linear part of the emptying curve 58;

- emptying rate: the slope of regression analysis from the linear part of the emptying curve (-ml . min-l) 53.

As a general reference, Table IV shows the principal indices derived from motility studies in two large groups of adult healthy subjects living in Northern and Southern Italy.

Indications As a non-invasive, radiation-free technique, ultrasonography is well tolerated by patients, can be repeated several times, and can be performed during pregnancy and young age. For research purposes, combined ultrasonography and scintigraphy have been employed in gallstone patients and healthy subjects in order to calculate simultaneous episodes of emptying-filling of the gallbladder 59. This approach, however, is time-consuming and is not widely available, especially in a clinical setting. For many years, the study of gallbladder motor function by ultrasonography has been employed to evalu- ate pathophysiological aspects of gallbladder function, mainly in patients with gallstone disease. In a subgroup of gallstone patients, in fact, gallbladder motility is impaired 47 53 56 57 6o and this condition plays a key role in the pathogenesis of cholesterol gallstones 61. Gallbladder stasis also plays a role during experimental lithogenesis of cholesterol gallstones and in conditions associated with gallstone formation, namely vagotomy, pregnancy, use of oestroprog- estins, total parenteral nutrition, diabetes, obesity, rapid weight loss during very-low caloric diets ‘j2. The study of gallbladder motility by “functional” ultrasonography might play a role in the following cases: a>

b)

c)

selection of patients eligible for medical treatment of cholesterol gallstones (e.g. before oral litholysis alone or with extracorporeal shock wave lithotripsy): a good gallbladder response will confirm the presence of a patent cystic duct and a better chance of a good clearance of (small) gallstones or gallstone fragments during oral litholysis. Indeed, few studies have shown that gallbladder emptying is an important determinant both of early clearance 63-65 as well as recurrence of cholesterol gallstones after shock wave lithotripsy; diagnostic work-up of patients with functional diseases of the gastrointestinal tract. An abnormal gallbladder emptying has been shown in a subgroup of patients with acalculous biliary pain @j; study of the effect of prokinetic drugs on gallbladder motility l7 67-73. This might also be the case

Table Ill. indices of gallbladder motar function in two large studies carried out in healthy subjects studied by ultrasonography.

EV W EFW&FVl

2Q.4~1.2 5.@&5 14.5&l .I 69*2.0 Portincasa et al. 57 IQD 21.9ra.9 5.8AO.4 1 Eko.7 73kl.4

Da& are mean,& SE; fV = fa,%hg wulupw; RV = resjdual volume; EV = ejection volume; EF = eiectian fraction; Test meal: Fe&i: 375 Kc.& protein 113.4 g, fat 17 g, carbohydrate 45 g; Partincasa: 720 Kcal: protein 58 g, fat 1 I 5.

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in a series of patients at increased risk for gallstone formation, such as those with gallbladder sludge 73-76 and obese patients 77. The effect of other drugs potentially affecting gallbladder motility can also be assessed by ultrasonography 78-81.

Limitations The technique is not widely used in the clinical setting. General limitations include concomitant treatment with drugs which can inhibit gastrointestinal motility, high-grade obesity or intestinal gases which hinder the gallbladder, grossly abnormal gallbladder shape, acute cholecystitis or a shrunken gallbladder due to severe chronic cholecystitis or non-fasting subject, large gallstone burden occupying most of the gallbladder lumen, biliary obstruction.

Technical aspects The common bile duct (CBD) allows the flow of bile to the duodenum. From a functional point of view the CBD is very much dependent upon the motility pattern both of the gallbladder and the sphincter of Oddi which, in turn, are regulated by hormonal and neu- ronal factors. Two different motility patterns can be detected in the CBD: postprandial and interprandial (fasting) patterns. Several complementary techniques can be employed to study the CBD, some invasive (ERCP, PTC, echoendoscopy), others non-invasive [ultrasonography and cholangio-MR (magnetic reso- nance)]. Although ultrasonography is less sensitive compared to other techniques, it can be considered the first-choice test for the morphological study of the CBD, on account of its characteristics of safety, non- invasivity and low cost. Furthermore, ultrasonography allows functional studies of CBD after appropriate stimuli. a>

b)

Morphological evaluation The CBD is visible by oblique subcostal scan at the right hypochondrium anterior to the portal vein and close to the hepatic artery, from which it can be distinguished, when necessary, by Doppler flowmetry. Ultrasonograph- ic visualization of the CBD is optimal (up to 100% of cases) in the proximal and middle tract but de- creases markedly in the distal segment. In healthy subjects, the diameter of the CBD ranges from 1 to 7 mm; it may be greater (i.e., ~10 mm) in chole- cystectomized as well as in gallstone patients. Functional evaluation Functional study of the CBD by ultrasonography measures the time-dependent variations of CBD in response to exogenous (e.g. caerulein or CCK) or endogenous (standard liquid or solid meal) stimuli which activate

gallbladder contraction and simultaneous relaxation of the sphincter of Oddi. As the CBD has no spontaneous contractility, changes in its diameter occur mainly when the gallbladder bile is ejected from the gallbladder. CBD enlargement is tran- sient or prolonged in the absence or presence of anatomical or functional obstacles in biliary flow, respectively.

Methods The test is carried out after a 12-hour fasting period. The subject is asked to remain in a supine position and to hold his/her breath for few seconds during each measurement. The diameter of the CBD is recorded at regular intervals before and after ingestion of cholecystokinetic stimuli (either exogenous or endogenous). In healthy subjects, the diameter of the CBD returns to the basal value 30-45 minutes after the ingestion of a standard liquid meal (11 g fats) or lo-30 minutes after CCK or caerulein (0.3 yg/kg) in- fusion. When an obstacle is present, a progressive enlargement of the CBD occurs. A sensitivity of 67% and a specificity of 100% have been reported with this technique 82-84.

Indications Clinical suspicion of CBD obstruction.

Limitations Frequently needs confirmation by other tests.

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