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Keywords:

  • functional dyspepsia;
  • gastric accommodation;
  • gastric emptying;
  • scintigraphy;
  • stomach physiology

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

Abstract  In functional dyspepsia, abnormal intragastric distribution of a test meal has been identified but has never been correlated to any symptom pattern. The aim of this study was to compare the intragastric distribution of a meal between functional dyspepsia patients and controls, and to correlate distribution with symptom patterns, using scintigraphic gastric emptying studies. In forty patients with functional dyspepsia and 29 healthy volunteers, scintigraphic planar images were obtained immediately after ingestion of a mixed radiolabelled test meal and every 20 min for 2 h. The images of the stomach were divided into proximal and distal compartments. The mean intragastric distribution was similar in patients and controls. Over the whole test, 18 (45%) and 20 (50%) patients had a distal redistribution of the solid and liquid phase of the meal, respectively, while proximal retention of these phases was found in 13 (33%) and 9 (23%) patients. Early satiety was associated with early distal redistribution of the liquid phase and fullness was associated with late proximal retention. This study shows similar intragastric distribution of a test meal in health and functional dyspepsia. Within the patient group, an association between abnormal intragastric distribution patterns and symptom profiles was found, which might be related to different pathophysiological mechanisms.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

Functional dyspepsia is a clinical syndrome defined by chronic or recurrent upper abdominal symptoms without any identifiable cause by conventional diagnostic means.1 The symptoms are related to ingestion of a meal in 62% of the patients.2 The symptom complex includes epigastric pain, fullness, bloating, early satiety, belching, nausea and vomiting.

Several pathophysiological mechanisms have been proposed such as delayed gastric emptying, Helicobacter pylori infection, abnormal duodenojejunal motility, hyper-sensitivity to lipids or acid in the duodenum, or central nervous system dysfunction.3–8 Recent research has focused on an important role for defective accommodation and visceral hypersensitivity in symptom production of functional gastrointestinal disorders.9–11 It is increasingly clear that functional dyspepsia is a heterogeneous disorder, but several associations between pathophysiological mechanisms and symptom profiles have been found. Delayed gastric emptying has been associated with the presence of postprandial fullness, nausea and vomiting.3,12 Hypersensitivity to gastric distension, which is present in 34% of dyspeptic patients, is associated to postprandial pain, belching and weight loss.13 Impaired gastric accommodation to a meal is found in 40% of these patients and is associated with the symptom of early satiety.9,14

While gastric emptying can be assessed non-invasively,15–17 evaluation of gastric accommodation and hypersensitivity to distension still needs poorly tolerated gastric barostat studies.10,18 There have been attempts to develop non-invasive techniques to assess gastric accommodation. Gastric single-photon emission computed tomography (SPECT) is still not widely available and requires administration of considerable doses of radioactivity.19 Gastric ultrasonography is limited by its operator dependency and the need for sophisticated devices to reconstruct volumetric data.20 These difficulties limit the assessment of gastric accommodation in functional dyspepsia patients in daily practice.

Abnormal intragastric distribution of the radiolabelled meal during scintigraphic gastric emptying studies has been reported in patients with functional dyspepsia.21 In this study, functional dyspepsia patients were taken as a group and correlations between specific symptom profiles and distribution patterns were not looked for.

The aim of the present study was to compare how, using conventional scintigraphic gastric emptying study, the intragastric distribution of meal occurs in healthy volunteers and in functional dyspepsia patients. An additional aim was to link a symptom pattern to the intragastric distribution profile in patients.

Study subjects

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

Forty patients with functional dyspepsia (14 men, 26 women; mean age 50.9 ± 2.6 years) participated in this prospective study. Twenty-nine healthy controls (20 men, 9 women; mean age 25.3 ± 3.0) had participated previously in a validation study of the scintigraphic evaluation of gastric emptying at our institution. None of the healthy subjects reported symptoms or a history of gastrointestinal disease or drug allergies, nor were taking any medication.

The patients presented to the outpatient clinic because of meal-related epigastric symptoms, and all underwent careful history taking and clinical examination, upper gastrointestinal endoscopy, routine biochemistry and upper abdominal ultrasound. Inclusion criteria were the presence of functional dyspepsia according to the Rome II criteria, i.e. the presence of dyspeptic symptoms for at least 12 weeks in the last 12 months, in the absence of organic, systemic, or metabolic disease. Dyspeptic symptoms had to be present at least 3 days per week, with two or more symptoms scored as moderate or severe on the symptom questionnaire. Exclusion criteria were the presence of oesophagitis, gastric atrophy, or erosive gastro-duodenal lesions on endoscopy; heartburn as a predominant symptom; a history of peptic ulcer, major abdominal surgery, or underlying psychiatric illness; and the use of non-steroidal anti-inflammatory drugs, steroids, or drugs affecting gastric acid secretion. During upper gastrointestinal endoscopy, biopsy specimens were taken from the antrum and the corpus to perform immunohistochemistry for the presence of H. pylori. In patients with moderate or severe epigastric burning on the symptom questionnaire (n = 5), a 24-h oesophageal pH monitoring was performed and found to be normal (< 4% of time pH < 4). A psychiatrist ruled out anorexia nervosa in patients with weight loss in excess of 5% of the initial body weight. All drugs potentially affecting gastrointestinal motility were discontinued at least 1 week before the gastric emptying studies.

Symptom questionnaire

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

Before the studies, each patient completed a dyspepsia questionnaire as reported previously.9 The patient was asked to grade the intensity (0–3; 0 = absent, 1 = mild, 2 = moderate, and 3 = severe and interfering with daily activities) of eight different symptoms (epigastric pain, bloating, postprandial fullness, early satiety, nausea, vomiting, belching and epigastric burning) over the last 3 months. Also, the amount of weight lost as the onset of the symptoms was noted.

Test procedure

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

Scintigraphic assessment of gastric emptying of both the solid and the liquid phase of a mixed meal was performed in all subjects. All studies were performed in the morning after an overnight fast. Patients or volunteers did not take any medication known to affect gastrointestinal motility 48 h prior to assessment of gastric emptying. The test meal consisted of two scrambled eggs (50 g each) to which had been added 22 MBq 99mTc sulphur colloid (600 μCi), two slices of white bread (35 g each) and 10 g of butter. After ingestion of this solid phase, patients were asked to drink 170 ml of water labelled with 3.7 MBq 111In DTPA (100 μCi). This test meal had a caloric content of 413 kcal (carbohydrate 36%, protein 18% and fat 46%). The in vitro stability of this test meal had been confirmed previously. Anteroposterior (AP) and posteroanterior (PA) images were acquired during 1 min in upright position using a gamma camera Diacam (Siemens Gammasonics Inc., IL, USA) equipped with a medium-energy all-purpose collimator. Scintigraphic planar images were obtained immediately after intake of the meal and every 20 min for the next 2 h. The images were transferred to a computer for further analysis.

Image analysis

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

A summation of all Tc images was used to draw a region of interest around the stomach. Matching this region of interest to all images, fine alignment was performed if necessary. Afterwards a summation of all images was computed. The final region of interest of the stomach was determined by the software using a preset threshold activity. All images were corrected for the difference of the tissue attenuation between the proximal and distal area of the stomach by computing geometric means of AP and PA images. The longitudinal axis of the stomach was indicated by the operator to the computer. The region of interest of the stomach was then separated in a proximal and distal compartment using a mid-length separation (Fig. 1). The computer-generated tables with total counts of both regions corrected for the isotopes’ physical decay at each time point. Finally, the counts were plotted as a residual fraction of the initial image (taken immediately after meal intake) and for the delay between initiation of the meal and the first image. The data points were fitted using the Siegel gastric emptying model f(t) = (1 − (1 − ekt)β) and t1/2 (t1/2 = − log (1 − 0.51/β)/k) and tlag (for solids; tlag =  log (β)/k) were calculated.22

image

Figure 1. Representative image analysis of the solid phase of a meal in a healthy subject: all images at different time intervals have been summated. The white contour of the stomach has been computed automatically. The longitudinal axis of the stomach was indicated to the computer by the investigator. The stomach was divided in two parts based on the midlength of this axis.

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The ratio of proximal over distal counts was computed at all time intervals for both phases.

Statistical analysis

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

Continuous variables (age, body weight, amount of weight loss, t1/2, tlag, ratio of proximal over distal counts at each time point) were tested for normality and compared using Student's t-test. Proportions between two groups (H. pylori status, prevalence of symptoms) were compared using chi-square analysis. Time series of continuous variables (intragastric distribution ratio) were compared using anova and Student's t-test on the area under the curve. The influence of categorical variables (e.g. symptom grading) on continuous variables (e.g. distribution ratio) was assessed using multiple linear regression. The correlation between two continuous variables (age and t1/2) was evaluated using linear regression analysis. The association between dichotomous independent (presence or absence of symptoms) and dependent variables (intragastric distribution ratio at specific time points, gastric emptying parameters, H. pylori status, age, gender) was assessed using multiple logistic regression analysis with backward Wald's elimination procedure. In the stepwise procedure, the probability for entry was 0.05 and for removal 0.10. Odds ratios and the 95% CI were computed and differences were considered significant at the 0.05 level.

Gastric emptying and intragastric distribution of a meal in healthy volunteers

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

The total gastric emptying characteristics of normal subjects were as follows: t1/2 for solids, 91.8 ± 21.6 min; tlag for solids, 61.2 ± 16.9 min; t1/2 for liquids, 55.9 ± 20.9 min.

The intragastric distribution of the test meal could be assessed in all healthy volunteers. Table 1 represents the characteristics of this group. The distribution of the solid phase was initially more proximal, whereas for the liquid phase the distribution is more constant over time. There was, however, no significant correlation between time points and proximal/distal counts ratio for the solid phase (slope = −0.02; r = 0.21). The 95% confidence interval determining the range of normal values was computed for both phases and for the different time points (see Table 1). Over the whole test, the area under the curve of the intragastric distribution ratio over time was 247 ± 155 (mean ± SD, 95% CI 189–305) for solids and 210 ± 108 (mean ± SD, 95% CI 170–251) for liquids.

Table 1.  Ratio of radioactivity counts from the proximal over the distal stomach in 29 healthy subjects after ingestion of a radiolabelled mixed solid/liquid meal
Time (min)Solid phaseLiquid phase
prox/dist ratio (mean)SEM95% CIProx/dist ratio (mean)SEM95% CI
Postprandial3.840.852.9–4.82.130.301.8–2.5
202.690.502.1–3.32.050.311.7–2.4
402.480.501.9–3.12.030.311.7–2.4
602.210.571.6–2.91.780.301.4–2.1
801.730.451.2–2.21.600.321.2–2.0
1001.280.330.9–1.71.470.341.1–1.9
1201.070.260.8–1.41.240.260.9–1.5

Symptom patterns of functional dyspepsia patients

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

Table 2 summarizes the grading of dyspeptic symptoms in the patient group. Moderate to severe nausea and epigastric pain were the most prevalent symptoms, present in, respectively, 28 (70%) and 27 (68%) patients. Bloating 24 patients, (60%), fullness 21 patients, (53%) and early satiety 15 patients, (38%) were also frequently reported. Vomiting, belching and epigastric burning sensation were present in, respectively, eight (20%), 10 (25%) and 12 (30%) patients. Weight loss in excess of 5% was present in eight patients (20%).

Table 2.  Frequency of severity grading for each of eight dyspepsia symptoms in 40 patients with functional dyspepsia
 0 (absent)1 (mild)2 (relevant)3 (severe)
Fullness154912
Bloating151915
Epigastric pain1021117
Early satiety223213
Nausea1121215
Vomiting29353
Belching22855
Heartburn181066

Total gastric emptying parameters

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

The total gastric emptying characteristics of the patients were as follows: (mean ± SD) t1/2 for solids: 121 ± 49 min; tlag for solids: 70 ± 38; t1/2 for liquids: 53 ± 21. These characteristics, although slightly outside normal ranges, were not significantly different when compared with the healthy controls. Twelve patients (30%) had a significantly delayed gastric emptying for the solid phase, i.e. having a t1/2 above the mean + 2 SD in the healthy volunteers of their gender, and eight patients (20%) for the liquid phase. In this patients group, we found no correlation between age and any of the total gastric emptying parameters.

Intragastric distribution compared with volunteers

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

The intragastric distribution as evaluated by the proximal/distal counts ratio was not different for patients as a group when compared with the healthy volunteers (Fig. 2) nor was the area under the curve of the intragastric distribution ratio over time (mean ± SD) (256 ± 160 in patients vs 247 ± 155 in volunteers and 187 ± 95 in patients vs 210 ± 109 in volunteers, for solids and liquids, respectively, not significant). Comparison of distribution ratios at the different time points was also not significantly different.

image

Figure 2. Mean ratio of counts of the proximal over the distal compartment of the stomach for the solid phase, in patients (open squares), compared with healthy volunteers (full diamonds).

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Integrated intragastric distribution comparison between patients

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

Using the 95% confidence interval of the area under the curve of the distribution ratio over time for solids as a cut-off, 18 patients (45%) had a distal redistribution of the solid phase of the meal and 13 patients (33%) had a proximal retention. Similarly, for the liquid phase, 20 patients (50%) had a distal redistribution of the liquid phase of the meal and nine patients (23%) had a proximal retention. Patients with proximal retention for solids were older (58 ± 14 years vs 47 ± 15 years, P < 0.05) and had a higher t1/2 for total gastric emptying (143 ± 51 min vs 109 ± 43 min; P < 0.05). Patients with distal redistribution of the solid phase were younger (42 ± 13 years vs 59 ± 13 years, P < 0.01), had a lower t1/2 for total gastric emptying (101 ± 28 min vs 136 ± 56 min, P < 0.05) and were more likely to be H. pylori positive (11/18 vs 6/32, P < 0.05). Patients with proximal retention of liquids were older (63 ± 14 years vs 48 ± 14 years, P < 0.05). Finally, patients with distal redistribution of the liquid phase were younger (44 ± 14 years vs 59 ± 13 years, P < 0.05). All other demographic correlates were not significant.

Univariate analysis

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

When the patient population was divided, based on the presence of an abnormal integrated intragastric distribution pattern, no symptom appeared to be associated to any pattern.

Early satiety was significantly more prevalent in patients with distal redistribution of the liquid phase immediately after intake of the meal (12/20 vs 3/20, P < 0.01;Table 3A). The proportion of patients with an intragastric distribution ratio below the normal values (95% CI) at this time point was significantly higher in patients with early satiety (12/15 vs 8/25, P < 0.01). Conversely, when patients were grouped based on the presence or absence of moderate or severe early satiety, the intragastric distribution ratio was lower in the presence of early satiety (Table 3B). This difference reached statistical significance for the liquid phase immediately after intake of the meal and at 20 min. Fullness was significantly more prevalent in patients with proximal retention of the solid phase at 80 min (12/16 vs 9/24, P < 0.01; Table 4A). The proportion of patients with an intragastric distribution ratio above the normal values (95% CI) at this time point was significantly higher in patients with fullness (12/21 vs 4/19, P < 0.01). Similarly when patients were divided on the presence or absence of fullness, the intragastric distribution ratios at 80 and 100 min was significantly higher in the presence of moderate to severe fullness (Table 4B). Representative studies are shown in Fig. 3.

Table 3.  Prevalence of relevant or severe early satiety in functional dyspepsia patients with distal redistribution of the meal immediately after intake (panel A) and mean (±SD) intragastric distribution ratio in the presence or absence of relevant to severe early satiety (panel B) Panel A:
Proximal/distal ratio of liquids immediately after the mealNumber of patients
Early satiety presentEarly satiety absent
< 1.8128
≥ 1.8317
Table Panel B: . 
 Proximal/distal ratio immediately after the meal
Solid phaseLiquid phase
Early satiety present3.6 ± 0.51.5 ± 0.2
Early satiety absent6.9 ± 1.52.9 ± 0.5
Table 4.  Prevalence of relevant or severe fullness in functional dyspepsia patients with proximal retention of the meal 80 min after intake (panel A) and mean (±SD) intragastric distribution ratio in the presence or absence of relevant to severe fullness (panel B) Panel A:
Proximal/distal ratio of liquids at 80 min after the mealNumber of patients
Fullness presentFullness absent
> 1.5124
≤ 1.5915
Table Panel B: . 
 Proximal/distal ratio immediately after the meal
Solid phaseLiquid phase
Fullness present2.0 ± 0.31.6 ± 0.2
Fullness absent1.0 ± 0.11.0 ± 0.1
image

Figure 3. Panel A: Scintigraphic images of the liquid phase in representative patients with functional dyspepsia. The top series depicts the intragastric distribution in the absence (top series) or presence (bottom series) of moderate or severe early satiety at 0, 20, 40, 60, 80, 100 and 120 min after intake of the meal. Panel B: Scintigraphic images of the solid phase in representative patients with functional dyspepsia. The top series depicts the intragastric distribution in the absence (top series) or presence (bottom series) of moderate or severe fullness at 0, 20, 40, 60, 80, 100 and 120 min after intake of the meal.

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Multivariate analysis

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

Linear regression analysis was used to identify an association between the presence of distal distribution or proximal retention (evaluated by the area under the curve of the distribution ratio over time) and the grading of specific symptoms. None of these predictor variables (symptoms) was associated with one of both distribution patterns. Using multiple logistic regression analysis with backward Wald's elimination procedure, the association between the risk of early distal redistribution of liquids and the presence of moderate or severe specific symptoms was studied. The presence of moderate or severe early satiety was significantly associated with the risk of early distal redistribution of liquids (odds ratio 5.04, 95% CI 1.05–28.00; P = 0.05). The presence of moderate or severe fullness was significantly associated with the risk of late (100 min) proximal retention of solids (odds ratio 0.067, 95% CI 0.003–0.429; P < 0.05). When the cut-off value for the presence or absence of a symptom was changed to mild or severe, similar associations were identified, but these did not reach statistical significance.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References

In these studies we have shown that the evaluation of the intragastric distribution of the solid and liquid phase of a standard test meal can be assessed using a conventional scintigraphic emptying test.

From a methodological point of view, we have elaborated an image analysis protocol, which lead to reproducible analyses and which minimized the intervention of the operator, leading to more objective compartmentalization of the stomach. Indeed, in previous studies,19,21 the gastric area was divided in two parts on visual appreciation of the incisura. We believe however, that this subjective division may lead to false and subjective results, mainly in view of the poor spatial resolution of these scintigraphic studies, which hampers correct identification of the anatomical landmarks. Kuiken et al. reported that in a significant proportion of subjects the incisura is not clearly visible.19 In some studies the stomach was divided in two parts of equal surface on AP or PA projections.21 This method seemed inappropriate, as the outcome measure, namely the distribution of the meal within the area of the stomach, may strongly influence the way the stomach is subdivided. We experienced that the least subjective parameter of the morphology of the stomach was the identification of its longitudinal axis. Using powerful computer algorithms, it might even be possible to reconstruct this axis mathematically. In our hands, our method to divide the stomach in a proximal and a distal part was very reproducible. Moreover, when visually comparing the calculated region of interests to the actual images, we found excellent agreement, even in individuals with unusual stomach shape.

As we wanted to evaluate the intragastric distribution of a test meal without interference of gastric emptying we used the intragastric distribution ratio [activity of the proximal stomach (counts)/activity of the distal stomach (counts)] as an objective measurement. Our primary aim was to thoroughly evaluate and compare the intragastric distribution pattern of a meal in health and functional dyspepsia.

First, in our healthy volunteers’ studies, we carefully documented the characteristics of the normal intragastric distribution pattern of a meal. Analysis of distribution curves over time confirmed the role of the proximal stomach as an early postprandial reservoir. Confirming the data obtained by Collins et al. we found a more diffuse distribution of the liquid phase of the meal, when compared with the solid phase.23 Based on our findings, however, we cannot infer whether the proximal stomach has a driving force in the emptying of the solid or liquid phases of a meal or only a storage function.24,25 The age range in our healthy volunteers was insufficient to identify the age-related modifications of the total gastric emptying parameters which have been previously described,26–30 nor of the intragastric distribution patterns. Similarly, we did not find significant gender-related differences of the total gastric emptying parameters nor of the intragastric distribution patterns. Because of the set-up of our studies we did not evaluate the symptoms in healthy volunteers using the patient's questionnaire. However, healthy controls were required to report absence of abdominal symptoms to be eligible for the studies. In a combined scintigraphic and ultrasound study in healthy volunteers, postprandial satiation was correlated to the antral area.31

In patients, we found a proportion of patients with delayed total gastric emptying but we did not find a different intragastric distribution pattern compared with volunteers. This last observation is in contrast with Troncon's scintigraphic21 and to Gilja's ultrasonographic studies.14 In an earlier study, Scott et al. did find abnormal intragastric distribution of a radiolabelled mixed meal only in a small subset of functional dyspepsia patients (13% for solids and 9% for liquids).32 Our findings might be explained by methodological differences in the image analysis, which we already alluded to. Also, our patients and volunteers were not age- and gender matched, and this might have influenced our observations. But, although we cannot rule out an influence of group differences such as the older age and higher prevalence of women in our patients’ group, the use of a distribution ratio corrects our distribution data for differences in gastric emptying, bearing in mind that functional dyspepsia patients may have delayed gastric emptying in one-third of the cases and that the gastric emptying rate for solids is significantly lower in functional dyspepsia patients as compared with controls.3 Like in Stanghellini's et al. study, in patients there was no correlation between age and gastric emptying parameters. Finally, Troncon et al. did not observe any influence of gender on intragastric distribution of food in patients or volunteers.21 In our patients, we found a larger dispersion of intragastric distribution patterns, both for the solid and the liquid phase, indicating the disease might interfere with this parameter in opposite directions.

Interestingly, in contrast with volunteers’ data, in our study, age was a significant determinant of intragastric distribution within the patients’ group. In these, proximal retention of both phases was associated with delayed gastric emptying and ageing. Both observations might be linked, because, at least during the earlier phases of the gastric emptying process, the antral filling is known to be less variable over time. The filling of the proximal stomach is then correlated with the total gastric emptying. As mentioned higher, our control group has an insufficiently large age range to evaluate whether the variations of intragastric distribution with age is a phenomenon related to the disease or if this phenomenon is also observed in health. A gastric barostat study has found a decreased postprandial gastric tone in older healthy volunteers.33 In line with these findings, in our previous studies, we observed that the age of patients with impaired gastric accommodation tended to be lower than those with normal accommodation, although this difference was statistically not significant (34 ± 4 years vs 41 ± 2 years).9

Another interesting finding is the higher prevalence of H. pylori in patients with distal redistribution of solids. An association between H. pylori infection and impaired accommodation was reported in healthy volunteers,34 but we did not find any correlation between defective accommodation and H. pylori status in previous gastric barostat studies in patients.9,13,35

Our secondary aim was to link different intragastric distribution patterns to symptoms. When studying the integrated intragastric distribution patterns over a whole 2-h postprandial period we found no correlation to symptoms. The reason for this might be that initial small differences in intragastric distribution might be corrected during the later phases of the gastric meal processing or that the process of emptying dominates later phases. However, when we looked at the distribution ratios at specific time points, we found early satiety being associated with early (immediately after intake of the meal) distal redistribution and fullness being associated with late (at 80 and 100 min after the meal) proximal retention.

Early satiety is a symptom that has been linked to defective gastric accommodation.9 It is therefore likely that patients presenting with early satiety have more frequently defective accommodation. In turn, defective accommodation may lead to disturbed intragastric distribution of the meal, particularly at the start of the postprandial period when early satiety is most prominent. Our previous studies indicated that increased gastric wall tension might lead to symptoms.36 In our hypothesis, patients with defective accommodation would have increased wall tension both in the proximal stomach, because of the absence of the normal relaxation, and/or in the antrum because of a driving force to distend the antrum. In these scintigraphic assessments, it is impossible to distinguish between both potential origins of symptoms. Data in healthy volunteers tend to indicate that the increased wall tension in the proximal stomach may be predominant.36

In conclusion, using conventional scintigraphic emptying studies, we characterized the intragastric distribution patterns for solids and liquids following a standardized meal in health and in functional dyspepsia. These findings allowed us to reveal an association between specific intragastric distribution patterns and symptom profiles. Early distal redistribution of the liquid phase and late proximal retention of the solid phase might be related to different pathophysiological mechanisms.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Study subjects
  6. Symptom questionnaire
  7. Test procedure
  8. Image analysis
  9. Statistical analysis
  10. Results
  11. Gastric emptying and intragastric distribution of a meal in healthy volunteers
  12. Patient characteristics
  13. Symptom patterns of functional dyspepsia patients
  14. H. pylori status 
  15. Total gastric emptying parameters
  16. Intragastric distribution of a meal in functional dyspepsia patients
  17. Intragastric distribution compared with volunteers
  18. Integrated intragastric distribution comparison between patients
  19. Intragastric distribution at specific time points: comparison between patients
  20. Correlation between intragastric distribution and symptoms in functional dyspepsia patients
  21. Univariate analysis
  22. Multivariate analysis
  23. Discussion
  24. References
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