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Evaluation of Body Surface Area as a Determinant of Cholecystodynamics Due to Orally Administered Standardized Skimmed Milk
A. C. UGWU, BSc, MSc, PGC-CT

The author studied the relationship between body surface area and both the gallbladder contraction index and gallbladder emptying rate. Using the ellipsoid formula, gallbladder volumes were sonographically measured in the preprandial state and 20 minutes after a standardized fatty meal in 62 subjects. Gallbladder contraction indices and emptying rates were calculated. The body surface area of 61 subjects who followed the study design was computed from their height and weight measurements. Parametric tests also were carried out, revealing that there were no significant correlations between body surface area and gallbladder contraction index and gallbladder emptying rate. Dosing in cholecystodynamic studies may be limited by lack of correlation between gallbladder emptying rate and body surface area. Key words: body surface area, cholecystodynamics, milk, sonography

From the Federal Medical Centre, Abakaliki, Nigeria. Correspondence: A. C. Ugwu, BSc, MSc, PGC-CT Federal Medical Centre, Nigeria, F.M.B. 102, Abakaliki, Nigeria. E-mail: tonybullng@yahoo.ca. The author acknowledges with deep appreciation Mr Otu Emerson, director of the Jeomedics Ultrasound Centre, for his material assistance and Mrs Ngozi Ugwu for her financial assistance. DOI: 10.1177/8756479307311912

Cholecystodynamics refers to gallbladder contraction as substances induce contraction on the gallbladder wall.1 Gallbladder motility (contractility) is important to assess because impairment of motility has been demonstrated in some gallbladder diseases. Gallbladder motility has been studied in a Nigerian population using the gallbladder contraction index (GBCI)2 and the gallbladder emptying rate (GBER).1,2 A conventional cholecystosonography technique is to use a standardized fatty meal (SFM) to assess and compare gallbladder functions. Some anthropometric and pharmacologic factors have been noted to affect gallbladder motility. Body mass index was noted to negatively correlate with GBCI.2 Opiates contribute to gallbladder stasis by

BODY SURFACE AREA AS A DETERMINANT OF CHOLECYSTODYNAMICS / Ugwu

inhibiting ganglionic activity and neurogenic contractions.3 One study has indicated that motilin may play a physiological role in the regulation of gallbladder emptying in a fasted state.4 The traditional method of individualizing cytotoxic drug dose is to use body surface area (BSA), which is equivalent to the 2D surface area of the skin of an individual.5 Estimation of BSA is most commonly done with a formula that was derived in 1916 by Du Bois and Du Bois,6 who examined nine individuals of various ages, shapes, and sizes and measured their body surface area directly with molds. By trial and error, they derived a formula to estimate body surface area. This formula was useful because it correlates with the basal metabolic rate. Body surface area is also proportional to blood volume. The Du Bois formula was challenged in 1970 by Gehan and George,7 who directly measured the skin surface area of 410 individuals. They found that the Du Bois formula overestimated body surface area by 15% in 15% of cases, but otherwise, the original formula was surprisingly accurate, considering the small sample size used in its derivation, and remains the most popular way to measure BSA. Body surface area has a rational use for interspecies scaling and for calculating an initial starting dose for a human phase I trial, based on prior experience in laboratory animals.8 However, in the sonographic assessment of gallbladder motility, a standardized quantity of milk (usually a tin: 165 mL) has been adopted. Little data are available relating to BSA on the gallbladder, so this study aimed at evaluating the effect of body surface area on gallbladder motility.

included in the study. The subjects had to be aware of the nature of the study and willingly provide informed consent before entering the study. Institutional review board or ethics board review and approval of the protocol at the center was required.
EVALUATIONS

Materials and Methods

PATIENT ELIGIBILITY

Subjects with a positive history of hepatobiliary disease were not eligible for the study, as well as people with a history of diabetes, which has been reported to have an effect on gallbladder motility.9 Volunteers younger than 18 years or with a history of lactose intolerance were also excluded from the study. Only healthy adults of Nigerian descent with no history of diabetes or hepatobiliary disease were

Each subject was scanned in the morning after an overnight fast. Subjects had their weight (kg) measured on a bathroom scale (Model H 89 LT Blue), and height was measured on a calibrated vertical wall. Two serial sonograms were carried out on each subject in supine position using a Sonoline SL-1 machine with a 3.5-MHz sector transducer (Siemens Medical Systems, USA Inc, Ultrasound Group, Issaquah, Washington) as follows: before ingesting a tin (165 mL) of evaporated skimmed cows milk (trade name: Three Crowns) and 20 minutes postprandial. The subjects sat down while ingesting milk and were supine throughout the procedure. Milk was standardized in this way because the fat content of a meal in healthy volunteers affects the modality of gallbladder emptying.10 These procedures enabled variations of gallbladder volumes with bile emptying to be obtained. The transducer was used to scan the right upper quadrant of the abdomen after applying ultrasound gel to the skin. After visualization of the maximal gallbladder longitudinal outline, the length and maximal antero-posterior diameter (height) measurements were taken on arrested respiration with calipers crossing each other at 90 degrees, and then the transducer was rotated 90 degrees to obtain the maximal transverse dimension. This resulted in three orthogonal (perpendicular) measurements (Figure 1a,b). Length, width, and height measurements were taken from outerto-outer hyperechoic walls. Fasting gallbladder measurements were taken in triplicate and the mean values obtained by an imaging scientist who is a sonographer. Body surface area (m2) was obtained using the following formula derived by Du Bois and Du Bois6: BSA = (weight 0.425 height 0.725) 0.007184, where weight is in kilograms and height is in centimeters.

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TABLE 1. Characteristics of Subjects A Variable

Height

n 61 61 61

Minimum 1.35 15.79 0.04

Maximum 2.17 85.53 2.03

Mean 1.7642 52.4207 0.7338

SD 0.17723 17.64387 0.44111

BSA GBCI GBER

Length

BSA, body surface area; GBCI, gallbladder contraction index; GBER, gallbladder emptying rate.

was generated, the degree of linear relationship between cholecystodynamic parameters and BSA was investigated using Pearsons correlation coefficient (r). Tests were two-tailed, with P < 0.05 indicating statistical significance.
Width

Results
Fifty-two subjects volunteered in this study between January 2005 and June 2006. Of the subjects, 30 were men and 22 were women. Subjects ages ranged from 18 to 63 years. The characteristics of the 51 subjects are shown in Table 1 (1 subject moved off the couch to make a phone call downstairs after milk ingestion and so was not included). Data approximated a normal distribution (using values of skewness and kurtosis), and hence a parametric test (Pearsons correlation) was carried out. BSA ranged from 1.35 to 2.17, with a mean value of 1.7642; GBCI ranged from 15.79 to 85.53, with a mean value of 52.4207; and GBER ranged from 0.04 to 2.03, with a mean value of 0.7338.
BODY SURFACE AREA AND CHOLECYSTODYNAMICS

FIGURE 1. Line drawings showing (A) a longitudinal section of the gallbladder and (B) a transverse section of the gallbladder. CHOLECYSTODYNAMICS

Gallbladder volumes were obtained using the formula for volume calculation (approximation) for the prolate ellipsoid. GBCI was computed as the percentage decrement of postprandial size (volume) from the initial size. GBER was obtained as the change in volume divided by 20 minutes (cm3/min).
STATISTICS

There was no significant relationship between BSA and GBER, as well as between BSA and GBCI. Figure 2 shows the relationship between GBER and body surface area.

Data were not categorized to sex because previous studies in this population have not shown any significant (P > .05) difference in GBER1 and GBCI11 for men and women. SPSS 11.0 software was used for summary statistics and correlation analysis. The graph was plotted and regression equation developed in Microsoft Excel Office 2000. After summary statistics of cholecystodynamic parameters (GBCI and GBER) and BSA

Discussion
The development of radiology of the biliary tract has been punctuated at intervals by technological advances that affect medical imaging. The first of these was the development of oral cholecystography, which depends on adequate absorption of the oral contrast medium from the small

BODY SURFACE AREA AS A DETERMINANT OF CHOLECYSTODYNAMICS / Ugwu

2.5

1.5 GBER

y = 0.614x - 0.3423

0.5

0.5

1.5

2.5

-0.5 BSA

FIGURE 2.

A scattergram of gallbladder emptying rate on body surface area.

intestine, its excretion from the liver with bile, the patency of the cystic duct, and adequate concentration by the gallbladder. This requires about 11 hours for completion. According to Lamb,12 sonography is the modality of choice in assessing gallbladder changes. Dynamic cholescintigraphy (DCS) has presently been adopted as the gold standard to assess gallbladder function. A study13 has shown that dynamic ultrasonography (DUS), performed using simple technique, lacks diagnostic value in gallbladder dysfunction when dynamic cholescintigraphy is taken as a reference test. When gallbladders that were ellipsoidal were subselected, the correlation between DUS and DCS was noted to have improved.14 Another research study by Cay et al15 showed that sonographic evaluation of gallbladder contraction stimulated by a fatty meal provides relatively reliable and reproducible results. Therefore, this can be used for assessing patients with biliary symptoms as a prior modality to cholecystokinin scintigraphy (CCKs-HBS) because it is a relatively easier, safer, and available method with which to make a definitive diagnosis in biliary dyskinesia. The differences in the results of the sonographic assessment of biliary functions could possibly result from using one formula (in this study, only the ellipsoid formula was used) to assess gallbladders of various shapes, which obviously would create a mathematical trade-off.

As demonstrated in this study, there is no significant correlation between body surface area and gallbladder motility indices. This relates to previous studies that did not establish any significant correlation between gallbladder motility and some anthropometric factors such as age,11 body mass index,11 height, and weight,1 which implies that BSA can be used for dosing in some therapeutic procedures5,8 but cannot be used to determine the quantity of milk to be taken by subjects in cholecystodynamic studies. A research study10 noted that by applying a mathematical model to the analysis of gallbladder volume sonography measurements, it is possible to measure the flux of bile through the gallbladder. Hence, further studies in this area are required to investigate the relationship between body surface area and influx of bile into the gallbladder, which could be a factor in cholesterol crystal precipitation and stone growth. An obvious limitation of this study is the use of 2D sonography; 3D studies have obvious advantages over 2D studies. Volume sonography is becoming highly used in the sonography laboratory and may well prove to be an appropriate technology to apply in future studies.16 In this study, one imaging scientist (AC) took the measurements. This was done to avoid possible interobserver variations. Further studies on interobserver reproducibility in the sonographic measurements of gallbladder dimensions are recommended to

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enable many imaging scientists to collect data in a wide range of settings in future studies. Evaluation of only subjects who volunteered for the study is another nonrandom factor that may have contorted the study population in this pilot study.

Conclusion
This study indicates that BSA does not correlate with GBER. Dosing in cholecystodynamic studies may be limited by lack of correlation between GBER and BSA.

References
1. Ugwu AC: Cholecystodynamics: a new regression formula. Pak J Med Res 2006;45:1721. 2. Ugwu AC, Ovuoba KN, Udo B, et al: Sonographic assessment of gallbladder motility in the Ibo population of Nigeria: a feasibility study. J Diagn Med Sonography 2007;23:410. 3. Guarraci FA, Pozo MJ, Palomeres SM, et al: Opioid agonists inhibit excitatory neuromuscular junction in guinea pig gallbladder. Available at: www.handheldmed.cn. Accessed December 9, 2007. 4. Luiking YC, Pecters TL, Stolk MF, et al: Motilin induces gallbladder emptying and anthral contractions in the fasted state in humans. Gut 1998;42:830835. 5. Miller AA, Rosner GL, Egorin MJ, et al: Prospective evaluation of body surface area as a determinant of paclitaxel pharmacokinetics and pharmacodynamics in women with solid tumors. Clin Cancer Res 2004;10:83258331.

6. Du Bois D, Du Bois EF: A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 1916;17:863871. 7. Gehan EA, George SL: Estimation of human body surface area from height and weight. Cancer Chemother Rep 1970;54:225235. 8. Freireich EJ, Gehan EA, Rall DP, et al: Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man. Cancer Chemother Rep 1996;50:219231. 9. Guliter S, Tlmaz S, Karakan T: Evaluation of gallbladder volume and motility in non-insulin-dependent diabetes mellitus. J Clin Gastroenterol 1990;98:10011007. 10. Pallota N: Ultrasonography in the assessment of gallbladder motor activity. Dig Liver Dis 2003;3:6769. 11. Ugwu AC: Sonographic assessment of gallbladder sizes and contraction index in an adult Nigerian population. Completed MSC research work, 2006. 12. Lamb CR: Ultrasonography of the liver and biliary tract, in Kay WJ, Brown NO (eds): Problems in Tertiary Medicine. Philadelphia, J. B. Lippincott, 1991, pp 111121. 13. Pons V, Ballesta A, Pouce M, et al: Dynamic ultrasonography in the diagnosis of gallbladder dysfunction: reliability of a simple method with easy clinical application. Gastroenterol Hepatol 2003;26:812. 14. Siegel A, Kuhn JC, Crow H, et al: Gallbladder ejection fraction: correlation of scintigraphic and ultrasonographic techniques. Clin Nucl Med 2000;25:16. 15. Cay A, Imamoglu M, Sarihan H, et al: Ultrasonographic evaluation of fatty meal stimulated gallbladder contraction in the diagnosis of biliary dyskinesia in children. Acta Paediatr 2006;95:838842. 16. Hashimoto S, Goto H, Hirooka Y, et al: An evaluation of threedimensional ultrasonography for the measurement of gallbladder volume. Am J Gastroenterol 1999;94:3492.

JDMS

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January/February 2008

SDMS-JDMS CME TEST

Article: Evaluation of Body Surface Area as a Determinant of Cholecystodynamics Due to Orally Administered Standardized Skimmed Milk Author: A. C. Ugwu, BSc, MSc, PGC-CT Category: Abdomen (AB) Credit: 0.5 CME Objectives: After studying the article titled Evaluation of Body Surface Area as a Determinant of Cholecystodynamics Due to Orally Administered Standardized Skimmed Milk, you will be able to: 1. Discuss factors involved with gallbladder motility. 2. Explain the method for calculating body surface area. 3. Describe the gallbladder contraction index and emptying rate. 5. Which two measurements were performed in this study to calculate the gallbladder motility? a. The length and maximal antero-posterior diameter b. Maximum dimensions before and after c. The maximum length in the supine and right lateral decubitus positions d. Area of the gallbladder in two planes 6. What method of evaluation can be used prior to cholecystokinin scintigraphy for diagnosis of biliary dyskinesia? a. Gallbladder contraction b. Gallbladder concentration c. Gallbladder volume d. Gallbladder area 7. Which of the following can be used to aid in dosing for gallbladder motility? a. Age b. Height c. Weight d. None of the above 8. Which of the following was not a limitation of this study? a. 3D was used to calculate volumes b. One observer performed the measurements c. Sample size was small d. Generalizability limited those similar to the population studied 9. Figure 1 demonstrates the measurements performed for which results? a. Gallbladder fractional change b. Gallbladder filling rate c. Gallbladder length times width d. Gallbladder contraction index 10. Which of the following was used to simulate a meal? a. Evaporated ice cream b. Evaporated skimmed cows milk c. Dairy shake d. Condensed milk

1. Cholecystodynamics is studied with which of the following methods? a. Gallbladder contraction index b. Gallbladder fractional change c. Gallbladder filling rate d. Gallbladder length times width 2. The body surface area formula used in this study most closely correlates with which of the following? a. Exercise-induced functional change b. Circulating blood index c. Change in rate over time d. Basal metabolic rate 3. This study indicated which of the following relationships between body surface area (BSA) and gallbladder motility (GM)? a. As BSA increases, GM decreases b. As BSA increases, GM increases c. As BSA decreases, GM decreases d. There was no relationship 4. Which of the following best describes cholecystodynamics? a. Gallbladder relaxation b. Gallbladder contraction c. Gallbladder location d. Gallbladder sludge