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Digestive Diseases and Sciences, Vol. 51, No. 3 (March 2006), pp. 517526 (
DOI: 10.1007/s10620-006-3164-5
We investigated the relationships between intragastric food maldistribution and antral dysmotility in
functional dyspepsia, and whether these abnormalities relate to meal-induced symptoms. Intragastric
distribution of food throughout gastric emptying was determined in patients (n = 24) and controls
(n = 38) after a liquid nutrient meal labeled with 99m technetium phytate. Antral contractility was
also periodically assessed by dynamic scintigraphy and postprandial symptoms were monitored
with visual analog scales. Residence of food in the proximal stomach was decreased in 8 (33%) and
antral contractility was increased in 9 (37.5%) and decreased in 2 (8%) patients. Proximal and distal
stomach motor abnormalities were neither significantly correlated nor associated. Increased antral
contractility was significantly correlated (Rs = 0.54; P < .01) with postprandial nausea. We conclude
that diminished residence of food in the proximal stomach and disturbed antral contractility occur
independently in different subsets of functional dyspepsia patients. Increased antral contractility
seems to play a role in postprandial nausea in functional dyspepsia.
KEY WORDS: antral contractility; functional dyspepsia; gastric accommodation; gastric emptying; gastric motility;
symptoms.
Functional dyspepsia is a common clinical syndrome characterized by chronic upper abdominal symptoms, such as
epigastric pain or discomfort, fullness, early satiety, and
nausea, without any underlying organic abnormality identifiable by conventional diagnostic tests, including upper
gastrointestinal (GI) endoscopy (1). Functional dyspepsia
is a heterogeneous condition, which is indicated by the fact
Manuscript received December 15, 2004; accepted July 1, 2005.
From the *Division of Gastroenterology, Department of Medicine,
Ribeirao Preto Faculty of Medicine and Department of Physics and
Mathematics, Ribeirao Preto School of Sciences (FFCLRP-USP), University of Sao Paulo, Campus of Ribeirao Preto, Sao Paulo, Brazil.
Address for reprint requests: Professor Luiz E. A. Troncon, Depto.
Clnica Medica, Hospital das Clnicas, Campus da USP, CEP: 14048900, Ribeirao Preto, State of Sao Paulo, Brazil; ledatron@fmrp.usp.br
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518
Because the relationships between proximal and distal stomach motor abnormalities are still unclear and the
reports on antral contractility in functional dyspepsia patients are somewhat conflicting, we designed this study to
assess whether decreased retention of food in the proximal stomach and disturbed antral contractility might be
related in this common clinical condition. We also aimed
at determining possible associations between intragastric
maldistribution of food or abnormalities of antral contractility to specific symptoms actually elicited by ingestion
of a standard test meal in functional dyspepsia patients.
MATERIAL AND METHODS
Subjects. Twenty-four patients with functional dyspepsia
(9 men and 15 women of median age 33 years; range, 17
57 years, median body mass index [BMI]: 21.6 kg/m2 , range,
19.727.7 kg/m2 ) and 38 healthy asymptomatic volunteers
(20 men and 18 women of median age 29 years; range, 18
49 years; median BMI, 24.6 kg/m2 ; range, 19.630.3 kg/m2 ;
P > .20 versus patients) selected from the local hospital medical and staff population were included in the study, after giving
written informed consent. The investigation was carried out according to the Declaration of Helsinki and the local Ethics Committee previously approved the protocol for the study (Statement 4685/99). All patients presented with upper abdominal
pain and/or discomfort, which were not explained by any organic abnormality found in conventional tests, including upper
GI endoscopy and abdominal ultrasonography. The diagnosis of
functional dyspepsia was then carried out according to Rome II
criteria (1), which included pain or discomfort centered in the
upper abdomen, occurring for at least 12 weeks in the last year, in
the absence of evidence of organic or metabolic disease and not
fulfilling criteria for irritable bowel syndrome. According to the
results of a structured questionnaire administered on inclusion
in the study, all patients had typical dyspeptic symptoms, such
as epigastric pain, postprandial fullness, early satiety, nausea,
and vomiting. In all patients, a definite relationship of symptom appearance or worsening with meal ingestion was found.
In 20 (83.3%) patients, symptoms were regarded to be relevant
enough, so as to interfere with daily activities.
None of the subjects included in the study was a smoker,
had other diseases (including peptic ulcer), or had previous abdominal operations, except for appendectomy. The presence of
diabetes mellitus, renal insufficiency, Chagas disease, and gallstones was ruled out by the appropriate tests. All drugs in use
were discontinued at least 1 week before the test. Women were
studied in the first half of the menstrual cycle, so as to avoid undesirable hormonal influences on the results of gastric motility
tests (21).
Symptom Questionnaire. Upon inclusion in the study, each
selected patient was asked to answer to a structured questionnaire
aimed at detecting and quantifying the intensity of 6 dyspeptic symptoms: heartburn, epigastric pain, postprandial fullness,
early satiety, nausea, and vomiting. Patients were required to
quantify the intensity of each specific symptom using a 4-point
scale as follows: 0, absent; 1, mild; 2, relevant but not interfering
with daily activities; and 3, severe enough to interfere with daily
activities. Patients were also asked to estimate the frequency of
each reported symptom using another scale, as follows: 1, only
Digestive Diseases and Sciences, Vol. 51, No. 3 (March 2006)
number of pixels enclosed in each segmental ROI (22). Assessment of intragastric distribution was done by calculating overall
residence of food in the proximal stomach throughout gastric
emptying, which corresponded to the ratio between the areas
under the curves (AUC) representing the proximal (AUCprox )
and the total (AUCtot ) stomach.
Antral Contractility. In all functional dyspepsia patients
and in 14 control subjects, antral contractility was assessed by
dynamic antral scintigraphy using the technique described by
Urbain et al. (7). Immediately following the acquisition of the
static images corresponding to the time points 15, 30, 60, and 90
minutes after test meal ingestion, a dynamic set of 240 frames
(1 frame/sec) from the anterior aspect of the abdomen was acquired for 4 minutes (1 frame/sec). Subjects stood still in the
upright position and were specifically instructed not to talk or
move during image acquisition. Each set of images was stored
for further analysis.
Data Analysis for Antral Contractility. The 240 1-second
images of each set of dynamic images were summed up, so as
to form a single 4-minute composite image, which yield a clear
visual resolution of the stomach shape. Over this image, a rectangular ROI measuring 1 812 pixels was then delineated in
the most horizontal part of the gastric antrum, at a mid-distance
between the pylorus and the incisura angularis (7, 21). The activity in this ROI in each of the 240 frames was counted and the
values were plotted in an activity-versus-time curve. Data for
this curve were exported to a personal computer and processed
(24) using programs written in the Mathlab 5.2 environment and
toolboxes (The MathWorks Inc., Natick, MA, USA). Data were
first submitted to digital filtering using a second-order Butterworth filter, with a low-pass cutoff adjusted for 12 oscillations
per minute. Spectral analysis was then performed using the Fast
Fourier Transform, which allowed assessment of antral contractility in the frequency domain. This was expressed as dominant
frequency (DF), defined as the frequency at which the highest Fourier power spectrum was observed. Amplitude of antral
contractions was determined as a regional ejection fraction according to the technique described by Knight et al. (21). Filtered
data corresponding to each set of 240 frames were normalized
so as to correspond to percent variation around the mean of all
counts. An automated analysis routine calculated the average
of the values for the difference between the maximum and the
minimum of each contraction cycle, expressed in percentage of
the maximum (21). For each subject and time interval, an antral
motility index was calculated by multiplying the values for the
DF and those for the average amplitude of contractions (7, 21).
Because preliminary inspection of curves corresponding to the
first (15 minutes) and last (90 minutes) acquisitions showed a
pattern of hardly discernible contractions cycles and further processing indicated highly variable values for either frequency and
amplitude in both control and patients groups, antral contractility
analysis was restricted to the intermediate time intervals (30 and
60 minutes). The individual values for the antral motility index
were then expressed as the arithmetic mean of data obtained at
these 2 time intervals.
Assessment of Meal-Induced Symptoms. All functional
dyspepsia patients and 12 control subjects were evaluated regarding symptoms occurring after test meal ingestion. Preliminary
studies indicated that 3 main symptoms could be elicited by
ingestion of our test meal: epigastric pain, fullness, and nausea. Immediately after meal, and thereafter at 5, 15, 30, 60, and
90 minutes, subjects were required to score eventual symptoms
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TRONCON ET AL.
on 10-cm visual analog scales (VAS) specific for each sensation.
To help subjects to score their symptoms, each scale was complemented with written descriptors set at the following standard
points: 0, I dont feel anything; 3, I feel a little, but it doesnt
bother me; 5, I feel a bothersome sensation of . . . ; and 10,
I feel an unbearable sensation of . . . .
Data Analysis for Symptom Assessment. Patients and controls were regarded as having had any meal-induced symptom
(pain, fullness, nausea) when scoring at least 5 for that particular
sensation, at any moment after test meal ingestion. The sum of
all scores, as well as the highest score attributed for each of the
3 symptoms investigated, were also recorded for each subject.
Statistical Analysis. Data were presented as median and
range, because a normal distribution of individual values for the
variables studied could not be ascertained. Individual values for
gastric emptying t1/2 , overall intragastric distribution (AUCprox
to AUCtot ratio) and antral motility index were regarded as abnormal when falling outside the range obtained in the control group.
Differences between groups and subgroups were analyzed by the
Mann-Whitney U test. Association analysis was performed using
Fishers exact probability test. The Spearman rank correlation
coefficient (Rs) was employed for the assessment of the relationships between the several variables. Differences were taken
as statistically significant for values of P of less than .05.
RESULTS
Gastric Emptying
In the functional dyspepsia group, t1/2 values
(84 minutes; range, 67147 minutes) were significantly
greater (P = .006) than those obtained in the control
group (67 minutes; range, 30105 minutes). Six (25%)
out of the 24 functional dyspepsia patients studied were
found to have delayed gastric emptying.
Intragastric Meal Distribution
The distribution of individual values for residence of
food in the proximal stomach in patients and controls
is shown in Figure 1. In the functional dyspepsia group,
values for the AUCprox to AUCtot ratio (47%; range, 17
520
Control group
(n = 14)
FD patients
(n = 24)
P-Value
.78
.42
.08
63%) were significantly lower (P = .04) than in the control group (56%; range, 4569%). Among dyspepsia patients, 8 (33.3%) were found to have abnormally diminished retention of the food in the proximal stomach.
Antral Contractility
Data for the antral motility variables in both functional
dyspepsia and control groups are shown in Table 1.
The distribution of individual values for the antral motility index in functional dyspepsia patients and controls is
shown in Figure 2. There were no significant differences
between patients and controls regarding either the mean
DF of antral contractions or the amplitude of antral contractions. The values for the antral motility index tended
to be increased in the dyspepsia group, but this difference did not quite reach statistical significance (P = .08).
However, 9 (37.5%) patients in the functional dyspepsia
group had antral hypercontractility, whereas only 2 (8.3%)
patients had antral hypomotility (see Figure 2).
Relationships Between Intragastric Meal
Distribution and Antral Contractility
Values for the antral motility index in the subgroup of
dyspepsia patients with diminished values for the AUCprox
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522
Fig 5. Correlation between values for the antral motility index (AMI)
(average of values for frequency times amplitude of antral contractions
observed at 30 and 60 minutes after meal ingestion) and the cumulative
scores in a VAS for meal-induced nausea in functional dyspepsia patients.
tion. Also, there were no significant differences concerning postprandial residence of food in the proximal stomach, between the subgroups of dyspepsia patients with
or without pain (47%; 1762% versus 52%; 3260%),
fullness (50%; 1762% versus 54%; 3762%) or nausea
(51%; 1755% versus 51%; 3262%). On the other hand,
values for the antral motility index were significantly increased (P < .05) in the subgroup with postprandial pain
(77 %var.min; 31127%var.min versus 52 %var.min; 32
60 %var.min), as well in those functional dyspepsia patients with nausea (77 %var.min; 39109 %var.min versus
51 %var.min; 3160 %var.min).
There were no significant associations between delayed
gastric emptying or diminished residence of food in the
proximal stomach and the presence of any specific symptom. Also, there were no significant correlations between
values for gastric emptying t1/2 or residence of food in the
proximal stomach and either cumulative or peak scores
for postprandial pain, fullness, and nausea. On the other
hand, increased antral contractility was found to be significantly associated with nausea (P < .05), but not with
pain or fullness. Also, a significant positive correlation
was found between values for the antral motility index
and the cumulative VAS scores for nausea (Figure 5).
DISCUSSION
Our study shows that substantial proportions of patients
with functional dyspepsia may have decreased residence
of food in the proximal stomach throughout gastric emptying or abnormal antral contractility, and that these regional
disturbances of gastric motility do not seem to be interrelated. Also, delayed gastric emptying, which was found
in one quarter of our dyspepsia patients, as reported by
Digestive Diseases and Sciences, Vol. 51, No. 3 (March 2006)
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that stomach evacuation is a complex process, which depends on a number of different factors, such as fundal pressure, propagated and nonpropagated antral contractions,
isolated pyloric pressure waves, and duodenal resistance
(9). On the other hand, the present finding of a significant,
negative correlation between antral motility index values
and gastric emptying time in our patients might indicate
a more preponderant role of antral contractions in gastric emptying control in functional dyspepsia. One might
then speculate that increased contractility in dyspepsia patients might occur as a compensatory mechanism against
putative pyloric or postpyloric abnormalities, such as increased intestinal tone and contractility (8), which were
not addressed in our study and might otherwise induce
delayed gastric emptying.
In contrast to other findings (5, 18, 19), we were not
able to show any relationship between specific presenting
symptoms recorded with a questionnaire at inclusion in
the study and gastric motor disturbances. However, the
hypothesis of association cannot be rejected by our data,
because there was a considerable overlapping between different dyspeptic symptoms and we studied a relatively
small number of patients, which precluded multivariate
analysis from being carried out.
As far as the relationships between gastric motor
disturbances and meal-induced symptoms are concerned,
the most striking finding in our study was a definite
association between increased antral contractility and the
occurrence of nausea in functional dyspepsia patients,
with a significant, positive correlation between the
intensity of this symptom and the magnitude of the
antral contractility index. This is rather puzzling, because
earlier studies have consistently shown that this particular
symptom is more commonly associated with antral
hypocontractility and delayed gastric emptying (1, 2).
On the other hand, nausea may be provoked by a variety
of stimuli (35), which may favor the speculation that
either antral distention associated with hypocontractility
and delayed gastric emptying or abnormally increased
excursion of antral walls could elicit nausea in different
subsets of functional dyspepsia patients.
Because postprandial symptoms in our patients occurred soon after meal ingestion, it could be argued that increased antral contractility might have caused early transfer of meal up to the duodenum, which could lead to excessive stimulation of mucosal receptors sensitive to meal
composition (9) and be able to induce nausea in hypersensitive patients, as shown by different authors (36, 37).
Indeed, it was reported in a recent paper (38) that a substantial proportion of functional dyspepsia patients may
have rapid initial gastric emptying, which was associated
with a higher symptom score, and was also a determi-
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