Introduction 1 2 3 1 4 5 6 7 8 6 9 10 We conducted a study to assess the relationship between gastric function and upper abdominal sensations. Gastric emptying rate, proximal gastric relaxation, and maximum drinking capacity were assessed in FD patients. The symptoms experienced in daily life (chronic upper abdominal symptoms) were assessed and related to the primary outcome parameters of the gastric function tests. We hypothesised that chronic upper abdominal symptoms and specific pathophysiologic mechanisms have no correlation in functional dyspepsia. Materials and methods Patients 1 The inclusion criteria were (a) the presence of dyspeptic symptoms, assessed using the questionnaire described below; (b) no evidence of macroscopic inflammation of the esophageal mucosa or focal lesions of the esophagogastroduodenal mucosa at upper gastrointestinal endoscopy (performed within 1-year prior to inclusion); (c) no abnormalities seen during upper abdominal ultrasonography (performed within 1 year prior to inclusion); (d) absence of serious concomitant illness; and (e) the absence of major gastrointestinal surgery (excluding appendectomy). The protocol was approved by the ethics committee of the University Medical Center Utrecht. All patients gave written informed consent for inclusion in the trial. Chronic dyspeptic symptoms questionnaire 5 6 11 Study protocol All patients underwent three functional tests of the stomach on three separate days; the ¹³C-octanoic breath test, three-dimensional ultrasonography of the stomach, and a nutrient drink test. The order of the three study days was arbitrary. Each of the study days started at 08:00 h after an overnight fast of at least 10 h. The time interval between the tests was three days to 2 weeks. Patients were asked to discontinue any medication known to influence gastrointestinal motility or sensitivity for at least 7 days prior to the study, including PPI therapy. The use of narcotics, anticholinergic medication, serotonergic medication (including selective serotonin reuptake inhibitors), and antidepressants was considered an exclusion criterion. None of the patients were on NSAID therapy. 13 13 12 13 Three-dimensional ultrasonography 13 16 17 14 18 7 Nutrient drink test 19 20 19 Statistical analysis 13 t 2 We have analysed the effect of age, height, weight, BMI, and sex on the outcome of the gastric function tests and the chronic symptoms using a regression analysis. All variables were tested in single models and using multivariable analysis. P 2 t 21 Results 13 1 Table 1 Frequency of severity grading for each of six dyspeptic symptoms in 60 dyspeptic patients (chronic symptoms)  0 (None) 1–2 (Very mild–mild) 3 (Moderate) 4–5 (Severe–very severe) Upper abdominal pain 1 (2) 11 (18) 18 (30) 30 (50) Early satiety 7 (12) 18 (30) 19 (32) 16 (27) Bloating 4 (7) 10 (17) 27 (45) 19 (32) Fullness 2 (3) 15 (25) 26 (43) 17 (28) Nausea 10 (17) 19 (32) 14 (23) 17 (28) Vomiting 46 (77) 6 (10) 2 (3) 6 (10) Numbers in parentheses represent row percentages Gastric emptying and proximal gastric relaxation 1 7 5 6 Fig. 1 Gastric emptying and proximal gastric relaxation in 60 FD patients: 33% of patients have a delayed gastric emptying and normal proximal gastric relaxation (black), 23% of patients have impaired proximal gastric relaxation and a normal gastric emptying rate (striped), 38% of patients have none of the pathophysiologic disorders (white), and 5% of patients have both disorders (grey)  Nutrient drink test 2 P P Table 2 The effect of age, BMI, and sex on maximum tolerated volume (MTV) and the change in upper abdominal sensations after the nutrient drink test  Age BMI Sex 0 1 0 1 Female Male MTV 329 (160–499) 1.7 (−2.2–5.6) 363 (3–725) 1.6 (−14 –18) 359 (301–417) 500 (381–618) Delta symptoms      Pain 11 (0–35) 0.02 (−0.5–0.6) 24 (0–74) -0.5 (−3–2) 10 (0–20) 14 (0–28)     Fullness 49 (23–76) -0.1 (−0.7–0.5) 49 (0–100) -0.1 (−2–2) 48 (37–59) 42 (29–55)     Nausea 46 (20–72) -0.5 (−1–0.1) 28 (0–85) -0.2 (−3–2) 21 (11–31) 31 (12–50)     Hunger −28 (−50–0) 0.09 (−0.4–0.6) −7 (−52–40) −0.8 (−3–1.2) −24 (−33  to  −15) −25 (−37 to −14) 0 1 I P Relationship between gastric emptying, total and partial gastric volume, and drinking capacity 3 P = P = Table 3 n  Proximal gastric relaxation Gastric emptying n n n n Age 41 (36–45) 42 (35–49) 40.9 (36–45) 41 (35–48) BMI 22 (21–23) 23 (21–25) 22 (21–23) 22 (21–23) MTV (ml) 404 (346–461) 384 (237–530) 439 (359–519) 334 (279–389) Fasting gastric volume (ml) 50 (41–59) 34 (24–44) 44 (33–55) 47 (37–56) Data are presented as mean (95% confidence interval for mean). No effect of age and BMI on proximal gastric relaxation or gastric emptying was observed P = r P r P 13 Relationship between chronic symptoms and gastric function P 2 P P Fig. 2 A B  2 P 3 Fig. 3 P  Discussion The following were the most important findings of this study: (1) no relationship was found between chronic upper abdominal symptoms and gastric function (proximal gastric relaxation, gastric emptying rate, or drinking capacity), (2) a third of all FD patients had a normal gastric emptying rate and a normal proximal gastric relaxation, and only a small overlap existed between the two pathophysiologic disorders (7%), and (3) there was an absence of any relationship between maximum drinking capacity and proximal gastric relaxation or gastric emptying rate. 5 6 22 23 For assessment of partial gastric volumes we used 3D-US as a noninvasive alternative for the barostat technique. Recently, a head-to-head comparison between the barostat and 3D-US was performed, in which it was shown that 3D-US was able to identify almost all patients with impaired accommodation assessed by barostat. It was, however, emphasized that the two techniques are not interchangeable, which is likely to be due to the difference in invasiveness of both techniques. Since there is no absolute concordance between the two techniques, we must preserve some reservations in generalizing the results of the current study. 6 19 24 25 26 27 9 19 P 20 27 28 P In summary, the maximum drinking capacity of FD patients, seen at a tertiary referral practice, is not influenced by gastric emptying rate or proximal gastric relaxation. The question is raised what usefulness this test has, in terms of diagnosis or treatment options, in FD patients and as a tool to analyze gastric function or upper abdominal sensations. Since we did not find any relationship between upper abdominal symptoms and MTV, the nutrient drink test cannot be regarded as an alternative for measuring visceral perception, as can be done by gastric barostat. In our opinion, many subjective factors, like motivation, probably play an important disturbing factor in the outcome of the test. In conclusion, in spite of a high prevalence of impaired proximal accommodation and delayed gastric emptying in FD patients, the lack of correlation between chronic upper abdominal sensations and gastric function questions the role of these pathophysiologic mechanisms in the generation of symptoms. Consequently, gastric function does not serve as a clear marker for the symptoms experienced by FD patients in daily life, and limited effect on symptoms may be expected when targeting these specific mechanisms. Finally, despite many efforts, no (measurable) motoric disorder can be appointed as a possible pathophysiologic mechanism underlying the presence of upper abdominal symptoms. Most likely, other factors like visceral perception play a vital role in functional dyspepsia.