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Gastric acid secretion and emptying rates in children with duodenal ulcer
Gastric Acid Secretion and Emptying Rates in Children With Duodenal Ulcer By Paul K.H. Tam and Htut Saing Hong K o n g 9 Gastric acid secretion was studied in 30 children with duodenal ulcer and 33 normal children. Both basal (BAO) and maximal (MAO) acid outputs w e r e found to be significantly elevated in patients. In addition, among patients themselves, those with severe disease demonstrated significantly higher M A O than those with mild disease. A concomitant study on gastric emptying rates revealed no difference between patients and normal children. 9 1 9 8 6 by Grune & Stratton, Inc.
complications and those who presented with bleeding initially but which did not recur after institution of medical treatment. Comparisons were made between normal and the entire group of patients, and also between the two subgroups of patients. Student's t-test for unpaired comparison was used for analysis of results of gastric acid secretion. Wilcoxon's rank serum test was used for analysis of results of gastric emptying as the data appeared nonparametric. A P value < 0.05 was considered statistically significant.
INDEX W O R D S : Gastric acid secretion; childhood duodenal ulcer.
RESULTS
L T H O U G H D U O D E N A L U L C E R in children has become a well recognized entity, its pathophysiology has not been adequately studied. Data regarding gastric acid secretion are controversial, derived from small series, and have not been correlated with severity of disease? ~ Gastric emptying rate has been implicated in the pathogenesis of duodenal ulcer in adults 5 but such a possibility has not been investigated in children counterparts. A study was, therefore, conducted with a view to elucidating these points. Reference was also made to their possible values in management.
A
MATERIALS AND METHODS A total of 30 children with duodenal ulcer treated in the Department of Surgery, Queen Mary Hospital, in a 14-year period (1969 to 1982) entered the study. Age ranged from 6 to 16 years with a mean of 12.1 years. Acid study was performed on all 30 patients, gastric emptying test was done on 16 patients. A group of 33 children of comparable age with no gastrointestinal disease acted as control. All 33 children had acid study and 30 had gastric emptying test performed. The project was approved by the Ethical Committee. Informed consent was obtained from the parents in all instances. The method employed was similar to that previously described. 6 Briefly, both studies of gastric acid secretion and emptying rates were performed using a nasogastric-tube method. Basal acid output (BAO) was collected for an hour and maximal acid output (MAO) similarly measured after pentagastrin injection (0.06 m g / k g body weight intramuscularly). Gastric emptying rate was measured using the double sampling method, 7 which involved initial introduction of 250 mL of phenol red solution of known concentration followed by serial additions and withdrawals of small samples at 10 minute intervals. The rate of gastric emptying was expressed in Tl/2, the time required for the stomach to empty half of its liquid content. Results of gastric acid secretion were correlated to the clinical course of patients who had a follow-up ranging from 1 to 14 years with a mean of 3.7 years. Patients were divided into two subgroups: (1) Severe disease included all patients with perforations and bleeding, which either necessitated surgery or was recurrent despite medical treatment. (2) Mild disease included patients with no
Journal of PediatricSurgery, Vol 21, No 2 (February), 1986: pp 129-131
Gastric Acid Secretion Both the basal acid output (BAO) and the maximal acid output (MAO) were significantly higher in patients compared to normal (Figs 1 and 2, Table 1). BAO was greater than the normal mean plus 2 standard deviation in 8 out of 30 patients. MAO was greater than the normal mean plus 2 standard deviation in 18 out of 30 patients, and greater than the normal mean plus 3 standard deviation in 10 out of 30 patients.
Gastric Emptying Gastric emptying rates in patients appeared to scatter over a wider range than in normal children (Fig 3). The median Tl/2 for patients was 6.8 minutes and for normal was 7.0 minutes. The difference was not statistically significant. DISCUSSION
Duodenal ulcer in children appears to have features distinct from the disease in adults, being much less common, often presenting atypical clinical pictures and frequently running a virulent course) It is, therefore, interesting to see if they have a similar pathophysiology. Gastric acid secretion has been extensively studied in adult patients: four out of five gastroenterologists perform this routinely. 9 However, because of its low incidence, similar studies in children have been difficult. Occasional reports appeared with results ranging
From the Department of Surgery, Division of Paediatric Surgery, University of Hong Kong, Queen Mary Hospital, Hong Kong. Address reprint requests to Paul K.H. Tam, Department of Surgery, Division of Paediatric Surgery, University of Hong Kong, Queen Mary Hospital, Hong Kong. 9 1986 by Grune & Stratton, Inc. 0022-3468/86/2 102-0007503.00/0 129
130
T A M A N D SAING
! 0.9
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| 0.8
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0.8
0.7
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E E O
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E E
0.6
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O.
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9
9
9
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0.1
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L Severe duodenal ulcer
Mild
Normal
duodenal ulcer
Fig 1. Basal acid o u t p u t in n o r m a l c h i l d r e n and c h i l d r e n w i t h d u o d e n a l ulcers. Solid line i n d i c a t e s t h e m e a n o f n o r m a l subgroups o f d u o d e n a l ulcers. B r o k e n line indicates t h e m e a n o f w h o l e group of d u o d e n a l ulcers.
from hypoacidity, 1 normal acidity,2 to hyperacidity.3 Early publications often involved small numbers of patients with no valid control. A more recent and systematic study4 involving ten patients has apparently resolved the confusion, establishing that MAO was significantly higher in patients than in controls. The present study confirmed this finding and in addition, because of the larger number of subjects studied and a reasonable length of follow-up, several new conclusions could be drawn. First, whereas previous communications have failed to show a significantly high basal acid
Normal
Severe
Mild
duodenal
duodenal
ulcer
ulcer
Fig 2. M a x i m a l acid o u t p u t in n o r m a l c h i l d r e n and c h i l d r e n w i t h d u o d e n a l ulcers. Solid line indicates t h e m e a n o f n o r m a l subgroups o f d u o d e n a l ulcers. B r o k e n line indicates t h e m e a n o f w h o l e group o f d u o d e n a l ulcers.
secretion in children with duodenal ulcer, such a relationship has been established here. There were 8 out of 30 children with high basal secretion, conforming to the incidence observed in adults. It is tempting to attribute diagnostic implications to high basal and maximal acid levels especially when a third of patients had MAO completely above the normal range (mean plus 3 standard deviations). However, as overlap existed for the remaining two thirds, the yield would be limited and acid study should not be considered pri-
T a b l e 1. Gastric A c i d S e c r e t i o n in N o r m a l C h i l d r e n and C h i l d r e n W i t h D u o d e n a l Ulcer Duodenal Ulcer Severe No. = 15
Mild No. = 15
0 . 2 0 3 _+ 0 . 1 8 0
0 . 1 2 6 _+ 0 . 0 7 0
Statistical Significance
Duodenal Ulcer No. = 30
Normal No, = 33
not
O. 164 • O. 120
0 . 0 9 4 _+ 0 . 0 5 8
0.01 < P
0.551 _+ 0 . 1 5 8
0 . 3 0 4 _+ 0 . 1 0 5
0.001 < P
Statistical Significance
Basal acid output mmL/Kg/hr
significant
(mean + SD) Maximal acid output mmL/Kg/hr (mean _+ SD)
0 . 6 3 3 -+ 0 . 1 6 8
0 . 4 6 9 _+ 0 . 1 6 9
0.02 < P
ACID STUDY IN CHILDHOOD DUODENAL ULCER
131
children at least, it a p p e a r e d t h a t patients with higher acid o u t p u t were m o r e likely to be associated with complications such as perforations, severe or r e c u r r e n t bleeding and, therefore, they ought to be m a n a g e d more vigorously on a long-term basis. R a p i d gastric e m p t y i n g rates have been shown to be present in a d u l t patients with d u o d e n a l ulcer in some studies, 5'~5 although others have found no difference between patients and the general population 7"I6 It has been suggested t h a t defective acid inhibition on gastric e m p t y i n g rate could result in a g r e a t e r rate of acid delivery to the d u o d e n u m and be responsible p a r t l y for the pathogenesis of ulceration. Such an observation was not found in children with duodenal ulcer in the present study. This indicates t h a t up to now, only an increased gastric acid secretion has been established as a factor in the development of duodenal ulcer presenting in childhood.
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REFERENCES
Og 9
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8 7
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i
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3 2 1 0
Duodenal ulcer
Normal
Fig 3. Gastric emptying rate in normal children and children with duodenal ulcers. Solid line indicates the median.
m a r i l y as a diagnostic investigation, which in present d a y s is best achieved with endoscopy. 1~ In adults, a proportion of s y m p t o m a t i c hypersecretors with initially negative radiological and endoscopic findings subsequently developed positive evidence when followed long enough. H W e have no such experience in our children but the value of acid study in suggesting caution and repeat diagnostic studies in such cases r e m a i n s a distinct possibility. Finally, the present study suggests a possible prognostic value of acid study with hypersecretion associating with more severe disease in children. Such suggestions have been m a d e in studies with adults 12'13but denied in a n o t h e r s e r i e s ] 4 In
1. Rosenlund ML, Koop CE: Duodenal ulcer in childhood. Pediatrics 45:283-286, 1970 2. Robb JDA, Thomas JO, Olding-Smee GW: Duodenal ulcer in children. Arch Dis Child 47:688-696, 1972 3. Ghai OP, Singh M, Walia BNS, et al: An assessment of gastric acid secretory response with 'maximal' augmented histamine stimulation in children with peptic ulcer. Arch Dis Child 40:77-79, 1965 4. Christie DL, Ament ME: Gastric acid hypersecretion in children with duodenal ulcer. Gastroenterology 70:242-244, 1976 5. Lam SK, Isenberg JI, Grossman MI, et al: Rapid gastric emptying in duodenal ulcer patients. Dig Dis Sci 27:598-604, 1982 6. Tam PKH, Saing H, Koo J, et al: Pyloric function five to eleven years after Ramstedt's pyloromyotomy. J Pediatr Surg 20:236-239, 1985
7. George JD: New clinical method for measuring the rate of gastric emptying: The double sampling test meal. Gut 9:237-242, 1968 8. Seagram CGF, Stephens CA, Cumming WA: Peptic ulceration at the Hospital for Sick Children, Toronto, during the 20-year period 1949-1969. J Pediatr Surg 8:407-413, 1973 9. Baron JH: Williams JA: The use of gastric function tests by British gastroenterologists. Br Med J 1:196 199, 1971 10. Tam PKH, Saing H, Lau JTK: The diagnosis of peptic ulcer in children--the past and present. J Pediatr Surg (in press) 11. Baron JH: Clinical Tests of Gastric Secretion. History, Methodology and Interpretation. London, MacMillan Press Ltd, 1978, pp 120-122 12. Sun DCH, Ryan ML, Chang PL, et al: Augmented Histamine Test. Ann NY Acad Sci 140:875-881, 1967 13. Wormsley KG, Grossman MI: Maximal histolog test in control subjects and patients with peptic ulcer. Gut 6:427-438, 1965 14. Bonnevie O, Kallehange HE, Wulff HR, et al: Prognostic value of the augmented histamine test in ulcer disease and X-ray negative dyspepsia. Scand J Gastroenterol 6:727-729, 1971 15. Griffith GH, Owen GM, Campbell H, et al: Gastric emptying in health and in gastroduodenal disease. Gastroenterology 54:1-7, 1968 16. Hunt JN: Influence of hydrochloric acid on gastric secretion and emptying in patients with duodenal ulcer. Br Med J 1:681-684, 1957
complications and those who presented with bleeding initially but which did not recur after institution of medical treatment. Comparisons were made between normal and the entire group of patients, and also between the two subgroups of patients. Student's t-test for unpaired comparison was used for analysis of results of gastric acid secretion. Wilcoxon's rank serum test was used for analysis of results of gastric emptying as the data appeared nonparametric. A P value < 0.05 was considered statistically significant.
INDEX W O R D S : Gastric acid secretion; childhood duodenal ulcer.
RESULTS
L T H O U G H D U O D E N A L U L C E R in children has become a well recognized entity, its pathophysiology has not been adequately studied. Data regarding gastric acid secretion are controversial, derived from small series, and have not been correlated with severity of disease? ~ Gastric emptying rate has been implicated in the pathogenesis of duodenal ulcer in adults 5 but such a possibility has not been investigated in children counterparts. A study was, therefore, conducted with a view to elucidating these points. Reference was also made to their possible values in management.
A
MATERIALS AND METHODS A total of 30 children with duodenal ulcer treated in the Department of Surgery, Queen Mary Hospital, in a 14-year period (1969 to 1982) entered the study. Age ranged from 6 to 16 years with a mean of 12.1 years. Acid study was performed on all 30 patients, gastric emptying test was done on 16 patients. A group of 33 children of comparable age with no gastrointestinal disease acted as control. All 33 children had acid study and 30 had gastric emptying test performed. The project was approved by the Ethical Committee. Informed consent was obtained from the parents in all instances. The method employed was similar to that previously described. 6 Briefly, both studies of gastric acid secretion and emptying rates were performed using a nasogastric-tube method. Basal acid output (BAO) was collected for an hour and maximal acid output (MAO) similarly measured after pentagastrin injection (0.06 m g / k g body weight intramuscularly). Gastric emptying rate was measured using the double sampling method, 7 which involved initial introduction of 250 mL of phenol red solution of known concentration followed by serial additions and withdrawals of small samples at 10 minute intervals. The rate of gastric emptying was expressed in Tl/2, the time required for the stomach to empty half of its liquid content. Results of gastric acid secretion were correlated to the clinical course of patients who had a follow-up ranging from 1 to 14 years with a mean of 3.7 years. Patients were divided into two subgroups: (1) Severe disease included all patients with perforations and bleeding, which either necessitated surgery or was recurrent despite medical treatment. (2) Mild disease included patients with no
Journal of PediatricSurgery, Vol 21, No 2 (February), 1986: pp 129-131
Gastric Acid Secretion Both the basal acid output (BAO) and the maximal acid output (MAO) were significantly higher in patients compared to normal (Figs 1 and 2, Table 1). BAO was greater than the normal mean plus 2 standard deviation in 8 out of 30 patients. MAO was greater than the normal mean plus 2 standard deviation in 18 out of 30 patients, and greater than the normal mean plus 3 standard deviation in 10 out of 30 patients.
Gastric Emptying Gastric emptying rates in patients appeared to scatter over a wider range than in normal children (Fig 3). The median Tl/2 for patients was 6.8 minutes and for normal was 7.0 minutes. The difference was not statistically significant. DISCUSSION
Duodenal ulcer in children appears to have features distinct from the disease in adults, being much less common, often presenting atypical clinical pictures and frequently running a virulent course) It is, therefore, interesting to see if they have a similar pathophysiology. Gastric acid secretion has been extensively studied in adult patients: four out of five gastroenterologists perform this routinely. 9 However, because of its low incidence, similar studies in children have been difficult. Occasional reports appeared with results ranging
From the Department of Surgery, Division of Paediatric Surgery, University of Hong Kong, Queen Mary Hospital, Hong Kong. Address reprint requests to Paul K.H. Tam, Department of Surgery, Division of Paediatric Surgery, University of Hong Kong, Queen Mary Hospital, Hong Kong. 9 1986 by Grune & Stratton, Inc. 0022-3468/86/2 102-0007503.00/0 129
130
T A M A N D SAING
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X 9
ee
O.
lee
9 9
9
9
9
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0.1
eee
e l
L Severe duodenal ulcer
Mild
Normal
duodenal ulcer
Fig 1. Basal acid o u t p u t in n o r m a l c h i l d r e n and c h i l d r e n w i t h d u o d e n a l ulcers. Solid line i n d i c a t e s t h e m e a n o f n o r m a l subgroups o f d u o d e n a l ulcers. B r o k e n line indicates t h e m e a n o f w h o l e group of d u o d e n a l ulcers.
from hypoacidity, 1 normal acidity,2 to hyperacidity.3 Early publications often involved small numbers of patients with no valid control. A more recent and systematic study4 involving ten patients has apparently resolved the confusion, establishing that MAO was significantly higher in patients than in controls. The present study confirmed this finding and in addition, because of the larger number of subjects studied and a reasonable length of follow-up, several new conclusions could be drawn. First, whereas previous communications have failed to show a significantly high basal acid
Normal
Severe
Mild
duodenal
duodenal
ulcer
ulcer
Fig 2. M a x i m a l acid o u t p u t in n o r m a l c h i l d r e n and c h i l d r e n w i t h d u o d e n a l ulcers. Solid line indicates t h e m e a n o f n o r m a l subgroups o f d u o d e n a l ulcers. B r o k e n line indicates t h e m e a n o f w h o l e group o f d u o d e n a l ulcers.
secretion in children with duodenal ulcer, such a relationship has been established here. There were 8 out of 30 children with high basal secretion, conforming to the incidence observed in adults. It is tempting to attribute diagnostic implications to high basal and maximal acid levels especially when a third of patients had MAO completely above the normal range (mean plus 3 standard deviations). However, as overlap existed for the remaining two thirds, the yield would be limited and acid study should not be considered pri-
T a b l e 1. Gastric A c i d S e c r e t i o n in N o r m a l C h i l d r e n and C h i l d r e n W i t h D u o d e n a l Ulcer Duodenal Ulcer Severe No. = 15
Mild No. = 15
0 . 2 0 3 _+ 0 . 1 8 0
0 . 1 2 6 _+ 0 . 0 7 0
Statistical Significance
Duodenal Ulcer No. = 30
Normal No, = 33
not
O. 164 • O. 120
0 . 0 9 4 _+ 0 . 0 5 8
0.01 < P
0.551 _+ 0 . 1 5 8
0 . 3 0 4 _+ 0 . 1 0 5
0.001 < P
Statistical Significance
Basal acid output mmL/Kg/hr
significant
(mean + SD) Maximal acid output mmL/Kg/hr (mean _+ SD)
0 . 6 3 3 -+ 0 . 1 6 8
0 . 4 6 9 _+ 0 . 1 6 9
0.02 < P
ACID STUDY IN CHILDHOOD DUODENAL ULCER
131
children at least, it a p p e a r e d t h a t patients with higher acid o u t p u t were m o r e likely to be associated with complications such as perforations, severe or r e c u r r e n t bleeding and, therefore, they ought to be m a n a g e d more vigorously on a long-term basis. R a p i d gastric e m p t y i n g rates have been shown to be present in a d u l t patients with d u o d e n a l ulcer in some studies, 5'~5 although others have found no difference between patients and the general population 7"I6 It has been suggested t h a t defective acid inhibition on gastric e m p t y i n g rate could result in a g r e a t e r rate of acid delivery to the d u o d e n u m and be responsible p a r t l y for the pathogenesis of ulceration. Such an observation was not found in children with duodenal ulcer in the present study. This indicates t h a t up to now, only an increased gastric acid secretion has been established as a factor in the development of duodenal ulcer presenting in childhood.
22 21 20 19 18 17 OO
e-
16
r: A ~ttN
15
I-
14
o
13 12
e-
11
REFERENCES
Og 9
10 E
gO O
9 .i I,.
t~ r
8 7
oO
6 5
i
;.
4
.-
3 2 1 0
Duodenal ulcer
Normal
Fig 3. Gastric emptying rate in normal children and children with duodenal ulcers. Solid line indicates the median.
m a r i l y as a diagnostic investigation, which in present d a y s is best achieved with endoscopy. 1~ In adults, a proportion of s y m p t o m a t i c hypersecretors with initially negative radiological and endoscopic findings subsequently developed positive evidence when followed long enough. H W e have no such experience in our children but the value of acid study in suggesting caution and repeat diagnostic studies in such cases r e m a i n s a distinct possibility. Finally, the present study suggests a possible prognostic value of acid study with hypersecretion associating with more severe disease in children. Such suggestions have been m a d e in studies with adults 12'13but denied in a n o t h e r s e r i e s ] 4 In
1. Rosenlund ML, Koop CE: Duodenal ulcer in childhood. Pediatrics 45:283-286, 1970 2. Robb JDA, Thomas JO, Olding-Smee GW: Duodenal ulcer in children. Arch Dis Child 47:688-696, 1972 3. Ghai OP, Singh M, Walia BNS, et al: An assessment of gastric acid secretory response with 'maximal' augmented histamine stimulation in children with peptic ulcer. Arch Dis Child 40:77-79, 1965 4. Christie DL, Ament ME: Gastric acid hypersecretion in children with duodenal ulcer. Gastroenterology 70:242-244, 1976 5. Lam SK, Isenberg JI, Grossman MI, et al: Rapid gastric emptying in duodenal ulcer patients. Dig Dis Sci 27:598-604, 1982 6. Tam PKH, Saing H, Koo J, et al: Pyloric function five to eleven years after Ramstedt's pyloromyotomy. J Pediatr Surg 20:236-239, 1985
7. George JD: New clinical method for measuring the rate of gastric emptying: The double sampling test meal. Gut 9:237-242, 1968 8. Seagram CGF, Stephens CA, Cumming WA: Peptic ulceration at the Hospital for Sick Children, Toronto, during the 20-year period 1949-1969. J Pediatr Surg 8:407-413, 1973 9. Baron JH: Williams JA: The use of gastric function tests by British gastroenterologists. Br Med J 1:196 199, 1971 10. Tam PKH, Saing H, Lau JTK: The diagnosis of peptic ulcer in children--the past and present. J Pediatr Surg (in press) 11. Baron JH: Clinical Tests of Gastric Secretion. History, Methodology and Interpretation. London, MacMillan Press Ltd, 1978, pp 120-122 12. Sun DCH, Ryan ML, Chang PL, et al: Augmented Histamine Test. Ann NY Acad Sci 140:875-881, 1967 13. Wormsley KG, Grossman MI: Maximal histolog test in control subjects and patients with peptic ulcer. Gut 6:427-438, 1965 14. Bonnevie O, Kallehange HE, Wulff HR, et al: Prognostic value of the augmented histamine test in ulcer disease and X-ray negative dyspepsia. Scand J Gastroenterol 6:727-729, 1971 15. Griffith GH, Owen GM, Campbell H, et al: Gastric emptying in health and in gastroduodenal disease. Gastroenterology 54:1-7, 1968 16. Hunt JN: Influence of hydrochloric acid on gastric secretion and emptying in patients with duodenal ulcer. Br Med J 1:681-684, 1957