Impaired Gastric Emptying in Children With Repaired Esophageal Atresia: A Controlled Study

By Madeleine Montgomery, Ruby Escobar-Billing, Per M. Hellstrem, K. Anders Karlsson, and Bj6rn Frenckner Stockholm, Sweden

6ackground; Scintigraphy is considered the “gold standard” for investigating gastric emptying. The lack of standards regarding registration technique and meal composition has been a problem especially in pediatric patients.

Methods: In this study, gastric emptying of a solid meal was assessed by scintigraphy in 10 patients with repaired esopha- geal atresia (5 to 10 years old), and the results were com- pared with those in 11 healthy control children (5 to 11 years old). The meal consisted of pancakes with a fixed energy composition labeled with Tc-99m. Fractional meal retention values were plotted as a function of time.

/?esu/&; Half-emptying time and lag phase values were longer in the patient group, whereas the emptying rate was slower and the retention values at 60 and 90 minutes were higher than in the control group. Extremely long lag phase and slow emptying rates were seen in two patients with

reflux symptoms and abdominal complaints. Gastric empty- ing in healthy children has not previously been studied by scintigraphy. The results of this study show that values for gastric emptying of solids in healthy children correspond well to those reported in healthy adults.

Conclusion: Scintigraphy is an easy and reliable method for gastric emptying studies in children. The radioactive dose can be kept very low, which makes it a safe method even for pediatric patients. Delayed gastric emptying can occur in patients who have repaired esophageal atresia, and may be associated with reflux symptoms and abdominal complaints. J Pediatr Surg 33:476-480. Copyright 0 1998 by W.B. Saun- ders Company.

INDEX WORDS: Esophageal atresia, gastric emptying, healthy subject, scintigraphy.

T HERE IS A HIGH incidence of gastroesophageal reflux (GER) and motility disorders of the esopha-

gus in patients who have undergone surgical repair of esophageal atresia (EA).lW3 Esophageal dysmotility leads to an inability to clear the esophagus of acid gastric contents and can be associated with GER and slow gastric emptying4-6 consequently leading to aspiration, anasto- motic stricture, and esophagitis. Jolley et al1 showed a high incidence of slow gastric emptying of liquids in patients with repaired EA and GER. However, the emptying of solid foods was not studied in this group of patients. Because the emptying of solids is considered a more sensitive indicator of abnormal gastric emptying, we have performed a series of gastric emptying tests in children with repaired EA. and compared the results with those in age-matched healthy volunteers, using a scinti- graphic gastric emptying test for solids.

Radionuclide scintigraphy, first introduced by Griffith

From the Departments of Pediatric Surgery Pediatrzc Ra&ology, Hospital Physics, and Department of Medccme, St G&an’s/Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.

This study was supported by the Swedish Medical Council (7916), the Crown Princess Lovisa, the Ruth & Richard hthlin and “Mjtilkdrop- pen”foundations.

Address reprmt requests to Madeleine Montgomev, MD. Department of Pediatric Surgev, St G&an WKarolinska Hospztal, S-11281 Stock- holm, Sweden.

Copyright o 1998 by WB. Saunders Company 0022.3468/98/3303-0013$03.00/0

476

et al7 being noninvasive, quantitative, and physiologic, has emerged as the method of choice for evaluating gastric emptying. Scintigraphy can be used for solids as well as liquids. The test meal must be tasty, easy to prepare, and it should have a high affinity for the radioactive marker. However, the lack of standards regarding registration technique and meal composition has been a problem, especially in studies in children, because no reference data for healthy children are available.

A recent study has shown that Tc-99m-MAA (macroal- bumin aggregate)-labeled pancakes provide good marker stability and homogeneous distribution in the meal.* Such a meal is suitable for pediatric patients, because most children like pancakes.

The aim of this study was to evaluate gastric emptying of solids in children with repaired EA and to compare the results with those of gastric emptying in age- and sex-matched healthy controls, thereby obtaining normal values for pediatric subjects.

MATERIALS AND METHODS

Eleven patients who had undergone repair of esophageal atresia and tracheoesophageal fistula in the newborn period in Stockholm (St. G&an’s/Karolinska Hospital) were asked to participate in the study. All of the patients had undergone a primary esophageal anastomosls. In no case was the anastomosis performed under excessive tension, and none of the patients had undergone myotomy of the esophageal segments. Patients with mental retardation or other severe concomitant malforma- tions were excluded. Ten patients (age 5 to 10 years; median, 7.5 years)

Journal of Pecjiatric Surgery, Vol33, No 3 (March), 1998: pp 476-480

GASTRIC EMPTYING AFTER ESOPHAGEAL ATRESIA

agreed to enter the study. The control group consisted of 11 healthy children (age 5 to 11 years; median, 7 years), who had no symptoms of reflux, dyspha~la. or abdominal complaints.

The patients were asked to answer a questionnaire regarding dyspha- gia, reflux, abdominal, or respiratoq symptoms. Three patlen& who complained of GER underwent esophageal pH momtormg to determine the degree of reflux. The study was approved by the Ethics CommIttee at the hos@al. Written consent was obtained from the parents of all children.

Scintigraphy, Preparation of the Meal

Each subject had a light breakfast and then fasted for 4 hours before the examination at lunch time (12:OO). We used Swechsh pancake for the test meal, as described by Hermansson and Sivertson.7 A milk substitute (Prosobee. Mead Johnson, Nijmegen, The Netherlands) was used instead of milk, which thereby enabled children with milk allergy to tolerate the test meal. The pancake batter was labeled before frying with 0.5 MBq (children 5 5 years old) or 1 MBq (children > 5 yeas old) Tc-99m-macroalbumin aggregates (Tc-99m-MAA. Amerscan pulmo- nate II Amersham, UK). The size of the meal was 3 g pancake per bodyweight served with Jam, 0.5 g/kg bodyweight and water, 4 mL/kg bodyweight. The energy content of the admmistered meal was 8 kcaL’kg bodyweight with a fixed energy composition of 59% carbohydrate, 17% protein, and 24% fat. The pancake was cut into standardized pieces (1.5 X 1.5 cm) before it was given, and the meal was eaten v&in 10 min.

A separate in vitro test was carried out to determine the stab&y of the Tc-99m-labeling of the solid phase of the test meal (pancake). The pancake was cut into small pieces (4 X 4 mm), weighed, and mixed with an equal volume of gastric Juice. Seven &fferent specimens were prepared and shaken m a 37’C water bath for 2 hours. The liquid phase was then decanted and filtered through a gauze pad, permitting only particles smaller than 1 mm to pass through. Both solids and filtrates were counted in a well counter (Compucount. Beckman, Fullerton, CA).

Registration of activity started when the first lmagc was taken, within 10 minutes after intake of the meal. Static Images (128 X 128 word matrix) of 2 mim~te duration were obtained in the anterior and posterior supine projections with a gamma camera (General Electric 400 AT, Denmxk) fitted with a low-energy, all-puvose collimator. In the period between the images, the child was seated or was allowed to move freely about in the room. Images were recorded at: 0.10.20.30.45,60,75.90, and 120 minutes after the meal. The geometric mean value was calculated for each tlrne interval and corrected for radioactive decay.

A computer program (FORTRAN-77, gamma 11) was developed to estabhsh automatically a region of interest (ROI) sound the stomach, at a fixed isocount level relative to the maximum count inside each ROI, ROI included areas in whch the pixel count exceeded 15% of the maximal count. For the noise reduction of the image data, a 9.pcnnt smootlung filter was used.

Fractional meal retention values were plotted as a function of time. The emptying rate (% of initial value per hour) and half-emptying time values (T50) were calculated by hnear regression analysis of the emptying phase at the linea part of the retention curve. The hnear part was determined subjectively and in most cases included values recorded between 30 and 90 minutes. In a few cases with extremely long lag phases, the calculations were based on values recorded between 60 and 120 minutes. Lag phase was defined as the time-point when 90% of the

marker remamed in the stomach. Retention values were taken from the measured data points at 60 and 90 min after the start of data acqmsition. A “corrected’. half-emptying time value was calculated as the actual half-emptying time value derived from the Iinear regressIon analysis (T50) minus the time-pcnnt of 90% retention (lag phase value).

The results were expressed as median? and range. Nonparametric statistics (Mann-Whitney U test) was used for the statistical analysis. p < .05 was considered significant.

RESULTS

Symptoms

The symptoms of the 10 patients with repaired esopha- geal atresia are shown in Table 1. Dysphagia and symptoms of gastroesophageal reflux, such as regurgita- tion and heartburn, were common and occurred in five and six patients, respectively. Four patients complained of asthma as well as of reflux symptoms like regurgita- tion. Abdominal pain or abdominal distension after the meal occurred in four patients. Three of the patients with reflux symptoms underwent pH monitoring; two of these showed reflux.

Gastric Emptying

The pattern of the gastric emptying curve is seen as an initial delay (lag phase) followed by a phase of linear emptying (Fig 1). The number of counts within one ROI ranged between 7.000 and 10,000 in the first image (0 minutes). Figure 2 shows the A/P projections of the stomach in one of the healthy conuols. The results of the gastric emptying studies are presented in Table 2. T50 values, lag phase, and corrected T.50 values were signifi- cantly longer in the patient group than in the control group. The patient group also showed significantly higher retention values at 60 and 90 minutes and slower emptying rates than the control group. Retention values at 120 minutes were very low or close to zero in many of the healthy controls. This may have been because of the low amount of isotope used. The 120-minute values could not be further used in the analysis because of the difficulties of estimating correct values.

Table 1. Symptoms in 10 Patients With Repaired Esophageal Atresia

,%w F&flux Abdom!nal Patlent lvr) sex Dvsphaga Svmptoms Asthma Svmptoms

1 8 Male Mild Yes Yes Abdominal pain 2 7 Male Mild Yes No No

3 5 Female No No No No 4 10 Male Mild Yes Yes Abdominal pain

Abdominal 5* 5 Male Mild Yes Yes distension

Abdominal 6+ 10 Female Mild Yes No distension 7 8 Female No Yes Yes No

8 6 Male No No No No 9.x 6 Male No No No No

10 10 Female No No No No

*Patients 5< 6, and 9 showed delayed gastric emptying.

478 MONTGOMERY ET AL

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Fig 1. Fractional meal retention curve from one of the control subjects. Linear regression analysis was performed between 30 and 90 minutes (r = 0.99371. The curve through the measured values were obtained by a modified power exponential formula.

Figure 3 shows the retention curve from one of the patients with reflux symptoms (regurgitation and heart- burn) and abdominal complaints compared with the means (22 SD) of the controls. The curve for the means of the controls was calculated by a modified power exponential formula.9 Three of the patients had values of retention at 60 and 90 minutes outside 2 SD of the controls. Individual emptying rates, half-emptying time values and retention values at 90 minutes are shown in Fig 4. Individual values of T50 are also shown in Fig 5.

Fig 2. A/P projections of the stomach at the beginning of the data acquisition and at 30, 60, and 90 minutes. Note increasing activity in the intestine.

Table 2. Results of Scintigraphic Gastric Emptying of Solids in 11

Healthy Children and 10 Patients With Repaired Esophageal Atresia

Control Group Patient Group Vanable (n = II) h = IO)

T50 (min) 78 (62-l IO) 100 (78-173)

Lag phase (min) 21 (9-47) 34 (20-68)

Corr. T50 (T50-lag) 53 (44-76) 62 (48-105)

Emptying rate (%/hour) 46 G-55) 40 (23-50) Retention 60 min (%} 63 (47-82) 75 (63-97)

Retention 90 min (%t 40 (26-66) 56 (42-83)

NOTE. Control group patients were age 5 to 11 years; median, 7

years. Patient group was age 5 to 10 years; median, 7.5 years. Values are expressed as medians and ranges and are statistically significant.

Stability of Radioactive Labeling

Counting of the solids and filtrates from the in vitro experiments indicated firm binding of the radioactive marker to the solid phase of the test meal. with 97% (96 to 99) remaining after 2 hours in gastric juice (pH 1.4).

DISCUSSION

Radionuclide scintigraphy is an easy and reliable noninvasive method for gastric emptying studies. The Tc-99m-MAA-labeled pancake meal used in this study is easily prepared and suitable for gastric emptying studies in children. All children in our study found the meal tasty and cooperated well during the examination.

Gastric emptying in healthy children has not been studied by scintigraphy before. For ethical reasons, the activity of the isotope was kept very low (0.5 to 1.0 MBq). The effective dose and the mean dose absorbed by the intestinal mucosa was estimated at 0.06 to 0.13 mSv and 0.33 to 0.66 mGy, respectively.lO To achieve suffi- cient number of counts, the acquisition time for each recording was set at 2 minutes. Although an error is introduced in the geometric mean value at each time interval, because of a delay between the recordings of the

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Fig 3. A graphic presentation of the process of gastric emptying in one of the patients with slow gastric emptying and symptoms of GER and abdominal complaints, compared with the means of the control group (error bars correspond to 2 SD!.

GASTRIC EMPTYING AFTER ESOPHAGEAL ATRESIA 479

anterior and posterior images, this error was believed to be of no significance in the calculations. The computer program used automatically defines the stomach at a fixed isocount level, which provides repeatable results at each calculation of the retention data. This method is also less time consuming and less influenced by intraobserver error than a manual outlining technique.

The process of gastric emptying is affected by a number of factors like gastrointestinal electrical activity, hormones, and the composition of the meal. For example.

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Fig 4. individual emptying rates, half-emptying time values (T50) and retention values at 90 minutes in the control and in the patient groups.

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Fig 5 Kaplan-Meier diagram, which shows the individual T50 values in the control group compared with the group of patients.

a test meal with a high energy content delays gastric emptying compared with a low-energy mea1.l’ To reduce this source of error, the volume/energy content of the meal was adjusted to the body weight. The pancake was cut into standardized pieces, because the food particle size also affects the rate of gastric emptying.1z.13 Solid food particles are first processed into small particles in the stomach during the lag phase, before they pass out of the stomach. This means that the way one eats may affect the duration of the lag phase, because la.rger food particles remain in the stomach longer and prolong the lag phase.1zJ3 Because children operated on for EA usually chew their food thoroughly to prevent food getting stuck in the esophagus, this could not explain the long lag phase seen in some of the patients.

The values for gastric emptying in the control children in our study correspond well to those in healthy adults.13 A recent study published by Maes et all4 presents values for gastric emptying in healthy children obtained by the C-13 octanoic acid breath test. These values accord well with those for gastric emptying of solids in healthy adults. They also resemble the values of the healthy control children in this study.

The group of children with repaired EA showed slower gastric emptying than did the healthy controls. All parameters (T50, lag phase, and corrected T50) were significantly longer in the patient group. The retention values at 60 and 90 minutes were significantly higher and the emptying rates (percent per hour) were lower. Three of the patients were considered to have delayed gastric emptying, based on their results of retention at 60 and 90 minutes, that were outside 2 SD of the controls (Fig 3). However, as shown in Fig 4, there was a considerable overlap between the individual data. The lag phase was extremely long in a few cases reaching values of 60 to 68 minutes. Two of the patients with reflux symptoms and abdominal complaints showed long lag phases and slow

480 MONTGOMERY ET AL

gastric emptying. However, there was no difference in origin. Some data indicate that dysmotility in the esopha- gastric emptying rate between patients with symptoms gus exists preoperatively in patients with EA, and it is (reflux or abdominal) and patients without symptoms. therefore considered a congenital malfunction. ls

Delayed gastric emptying may be an important factor Gastric emptying studies can be easily and reliably contributing to the reflux symptoms seen in some patients carried out in children by the use of scintigraphy and a with repaired EA. The etiology of the impaired gastric Tc-99m-labeled pancake meal. The radioactive dose can emptying is not known; for instance it may be caused by be kept very low, which makes it a safe method for operative trauma or postoperative complications (vagal children. Delayed gastric emptying of solids can occur in injury, anastomotic leak, or infection). Another explana- patients with repaired EA, and may be associated with tion is that it is present at birth and has a congenital symptoms of reflux and abdominal complaints.

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15. Romeo G, Zuccarello B, Proietto F, et al: Disorders of the esophageal motor activity in atresia of the esophagus. J Pediatr Surg 22:120-124. 1987