D~wstivc Di.~cases and Sci,'nccs, 1 )d. 41. N+,. 4 (..lpril 19qr pp. t~,~,'O-gJgr

Impaired Accommodation of Proximal Stomach to a Meal in Functional Dyspepsia

O.H. GILJA, MD, T. HAUSKEN, MD, PhD, I. WILHELMSEN, MD, PhD, and A. BERSTAD, MD, PhD

In patients with functional dyspepsia, scanning by a novel ultrasonographic method was carried out to investigate postprandial accommodation of the proximal stomach. Twenty patients with ftmctional dyspepsia and 20 controls were scanned fasting in a sitting position after drinking 5(10 ml meat soup. Images were recorded up to 25 min after the ingestion period using an ultrasound sector scanner with a 3.25-MHz transducer. The area in a sagittal section and the maximal diameter in an oblique frontal section were chosen as the main wtriables for calculating the emptying fraction of the proximal stomach, defined its: (aP).~,,i. , - - a V u c t u a l / a l / 2 . 5 m m. All subjects were asked to score total symptoms (1-9) provoked by the meal. From 7.5 to 25 rain after the ingestion period the patients exhibited both smaller area in the sagittal section (P < 0.018) and shorter diameter in the frontal section (P < 0.046) compared with healthy controls, and they suffered more symptoms in response to the meal (P = 0.002). Dyspeptic patients revealed higher emptying fractions (P = (/.(11_105, ANOVA), and H. pylori status did not influence the emptying fractions. Diagnostic sensitivity of the method at 20 min postprandially was 70"% and the specificity wits 65(;~. Patients with functional dyspepsia have impaired accommodation of the proximal stomach to a meal, temporarily related to symptom induction.

KEY WORDS: accommodation: adaptive relaxation: stomach: gustric emptying: ultrasonography: gastric physiok~gy: functional dyspepsia.

Accommodation of the human stomach to a meal is a specialized motor function of the gastric corpus- fundus enabling high volume increase with minimal rise in intragastric pressure (1, 2). After an initial receptive relaxation of the proximal stomach induced by swallowing and bohts passage through the esoph- agus (3), an ongoing adaptive relaxation (4, 5) occurs providing the meal with a reservoir in the proximal stomach from which it is delivered to the antrum for grinding and final emptying through the pylorus.

The reservoir function of the proximal stomach has been studied both scintigraphically and by use of

Manuscript received July 16, 1995; revised manuscript received December 19, 19t)5: accepted January 2, 1996.

From the Medical Department A and Department of PsychiatD'. Haukeland Hospital, University of Bergen. Bergen, Norway.

Address for reprint requests: Dr. Odd Helge Gilja, Medical Department A, Haukeland Hospital, University of Bergen, N-5021 Bergen, Nop, vay.

different balloon devices in patients with functional dyspepsia. Radionuclide methods have disclosed a delayed total gastric emptying (6) of both liquids (7) and solids (8, 9) in a subset of these patients. Fur- thermore, intragastric maldistribution of the meal, observed as a relatively higher portion of the meal residing in the antrum rather than in the proximal stomach, seems to be evident in these patients (10) and when total gastric emptying is normal (11).

Isobaric distension of the stomach (12) has shown that patients with functional dyspepsia exhibit a lower threshold to perception of visceral pain (13-15). These studies also advocate, although it has not been tested during meal ingestion, that the compliance of the proximal stomach is not altered in dyspeptic pa- tients. The presence of an artificial balloon in the proximal stomach is known to influence the normal gastric physiology (16-18); thus a noninvasive

Digestive Dise,~sc.~ and Scivnc,'.~. I hi. 41. No. 4 t.-Ipril l')',u

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GILJA ET AL

TAI:ILE 1. CIIARA(~FEI?,ISTI(S OF 20 PATIENTS wrr l l FUNLqI(INAI. DYSPEPSIA AND 2[1 111(,.\1.111"( CON'I-ROI S AT ENrl.t'~ 1() STLtD', :~

Pat ien ts ()mtrol,s"

IVlale./female ra t io 6/14 6114 M e d i a n age ( r a n g e ) . yea r s 38 ( I S - f 1 ) 27 (22-51)) M e a n we igh t +_ SD, kg ~6 ~_ 7 t~4 = Ill M e a n he igh t ~ s ix cm 171 z 8 171 _" I I)

Smokers ~ 5

*None of the diflerenccs between the groups tire slalislically sig- nificant.

m e t h o d to evalua te the size of the proximal s tomach dur ing a c c o m m o d a t i o n to a meal may yield significant in format ion .

T r a n s a b d o m i n a l u l t r a sonography is a noninvasive and rad ia t ion- f ree m e t h o d that has proven appl icab le in the study of antral moti l i ty in pa t ien ts with func- t ional dyspeps ia (19, 20), par t ly due to the fact that it leaves gastr ic moti l i ty undis tu rbed . We have devel- oped and eva lua ted a sonograph ic m e t h o d to esti- mate pos tp rand ia l size and empty ing fract ion of the proximal s tomach (21). The objec t ive of the p resen t stud), was to invest igate the a c c o m m o d a t i o n of the proximal s tomach and its re la t ion to symptoms in pa t ien ts with funct ional dyspeps ia by using a soup meal , previously shown to induce symptoms in these patients (22, 23).

MATERIALS AND METHODS

Subjects. Consecutive patients referred for tipper gastro- intestinal endoscopy were recruited to participatc in the trial. A history of dyspeptic complaints for a minimum of three months and at least seven of thc last 14 days were required to enter the study. All patients reported epigastric pain or discomfort as their main symptom, and one or more of the following symptoms were present: bloating, nausea. vorniting, early satiety and postprandial fullness. Symptoms of irritable bowel syndrome could be present, but upper dyspepsia had to be the dominating comphlint. No organic explanation for their symptoms was found during endos- copy or ultrasonography of the upper abdomen.

Twenty patients with functional dyspepsia, ~ men and 14 women, median age 38 years (range 18-61 years) were included in the study (Table 1). Six patients were H. pylori positive, as evaluated by rapid urease test or [14Ciurca breath test. Patients with functional dyspepsia had a mean symptom duration of 64 months, and the mean duration of symptoms in tile 14 preceding days just prior to the inves- tigation was 12.4 days. Twelve patients (60C~) reported early satie .ty, 13 patients (65r complained of nausea, and 14 (70%) patients stated that their symptoms were meal- related.

Criteria of exclusion from the study were serious systemic disease or possible malignant disease: clinical evidence of myalgia of the abdominal muscles; past surgery of the upper gastrointestinal tract: previous peptic ulcer discase: alcohol-

ism; diseases of tile liver, pancreas, ~r bile ducts: pregnancy or hictation: or drugs known to influence gastrointcstinal motility.

Twenty healthy controls, 6 nlen and 14 worneu, nlcdiun age 27 years (range 22-50 years) were recruited from med- ical students and staff at Haukcland 1 lospital (Table 1 ). The differences betwecn patients and healthy controls with rc- spect to age, height, weight, and smoking habits were not statistically significant.

Psychological Assessment. In oMer to characterize the patients and healthy controls regarding personality and possible psychopatholoD,, both groups received two self- rating instruments on the day of exanlinalion. Thc Evsenck Personality Questionnairc, Ncuroticism scale (EPQ-N), was applied to indicate a general lifc-stylc of hyl~erresl)on- sivcncss or emotional over.'cactiveness (24. 25). The Gen- eral Health Questionnaire (GHQ-28+) was used to detect psychiatric morbidity in a somatic setting and to evaluate qualit)' of lifc (26). Both test instrumcnls were available in vaIMated versions in Norwc,,ian translation (27).

Test Meal. Five hundred millilitcrs of commercial naettt soup (Tore clear mcat soup, Rieber & Son A/S, Bcrgcn, Norwav). containin~ l.,g ~,, proicin, 0.9 g fat. and 1.1 g carbohydrate (20 kcal) was ingested during a pcriod of 4 rain. The soup was boiled ~lnd then cooled to 37~ thus improving image quality by reducing the anaount of air bubbles after ingestion. The pH of the soup varied bctwccn 5.4 and 5.7, and the osmolarity was 350 nlosm/kg H~O. Fat, protein, and carbohydrate were all sohible in water. In addition, the soup ct:.ntaincd nonsolublc scasoning (0.4 g/liter). In previous studics, this soup rncal induccd antral contractions at a frcqucncy of 3!rain (fcd state) hi over 85 c}

_8). of patients and controls (20, ~ ' Fifteen ~rams of bovine fat (150 kcal) were addcd to the soup to increase the adaptive response of the stomach (29).

Symptom Scores. All participants wcrc asked to cwlluate their global dyspeptic synlptoms both before and after the soup meal on a L iker t scale fronl l) to 9. :also uscd in a previous stud)' (23). Zero denotes :,ibsellcc of synlptonls and 9 denotes excruciating symptoms.

Experimental Procedure. All participants werc examined between {i8:0[);.lnd [{i:31)AM after an overnight fast. Snlok- ers were not allowed to smoke on the morning of the examination. The individuals were scanned while sitting in a chair, leaning back slightly at :,In angle of 12{I ~ The transducer was positioncd in the epigastrium by the left subcostal rnargin and tilted cranially (Figurc 1). Ultrasound inaa,,es were obtained usine, a mechanical sector scanner (CFM 750, Vingmcd Sound, Herren, Norway) with a 3.25- MHz annular array, enabling smooth rotation subcostally. The maximal angle of view (911 ~ obtained with this scanner was chosen to visualize as nluch of the proximal stomach as possible. The maximal depth of scanning in this study was 22 cm. Two standardized sonographic image sections were chosen to monitor thc size e l the proximal stomach. First, a sagittal section with thc Icft renal pelvis in a longitudinal projection, the left lobe of the liver and the tail of the pancreas as internal landmarks, was rccordcd. Then the transducer was rotated 9(I ~ clockwise to obtain an obliquc frontal section where the left henfidiaphragm, the top nlar- gin of t i le fundus, and the l iver parenchynla served ;.is landmarks. A l l selected ul t rasound images were scanned at

690 Di,q, estin' l)i~c,t~c.~ and 3;cictwc,. 17,1. 41..V,,. 4 f.-Ip,41 /t,'qt,/

IMPAIRED ACCOMMODATION IN FUNCTIONAL DYSPEPSIA

J

oo #~ ..... ~ i ' ,

Transpyloric ~plane

Fig I. Drawing showing the position of the ultrasound transducer that enabled scanning of the proximal stomach in patients with functional dyspepsia and healthy controls.

tile end of normal expiration and each standardized image was frozen before recording on a video tape.

Measuremenls, All measures of the size of the proximal stomach were obtained after replaying the tapes and by utilizing the manual tracing facilities on the CFM scanner. A proximal gastric area in a sagittal section (SA) was

outlined by tracing from the top margin of the fundus and 7 cm downwards along the axis of the stomach (Figure 2). The maximal diameter in an oblique frontal section (OFD), kept within 7 cm along the long axis of the proximal stomach, was chosen as the second measure (Figure 3). By combining these two measures, an approximate volume (aV) of the proximal stomach was estimated (aV = Sit • OFD). The aV values were used to compute the individual's emptying fraction of the proximal stomach, defined as (aV2.smi n - a ~ ....... i)/aV~.Smin. Time zero was defined as the end of the ingestion period of 4 rain. All measures were traced twice and the average results recorded. The ultra- sound examinations and the measurements were performed by O.H.G., who was blinded with respect to diagnosis when measuring the scans.

Definitions. In order to address the problem of air pock- ets in the gastric fundus, tile visible amount of air was graded from 0 to 3. Grade (I denoted absence of visible air in the fundus, grade I small amounts of air, grade 2 mod- erate amounts, and grade 3 such great amounts of air that exclusion from tile study was necessary.

Ethical Approval. The study was approved by the Re- gional Ethics Committee and was conducted in accordance with the revised Declaration of Helsinki. All participants gave a written, informed consent to participate in the trial.

Fig 2. Ultrasonogram of the sagitlal section applied for scanning of the proximal stomach with the area measurement denoted. The area was outlined by tracing from tile top margin of the fundus and 7 cm downwards along the axis of the stomach. The right side of the image corresponds to the posterior part of the subject. S: stomach: L: liver: P: pancreas: K: kidney: D: diaphragm.

/.~,c.,#,.c /~i.,ea.,<., am/Scie, wes. l ~,/. 4/ . ,V<,. 4 IApr i l /<ram 69 ]

GILJA ET AL

Fig 3. Ullrasonogram of the oblique frontal section applied lor scanning of the proximal stomach including diamctcr measurement. The maximal diameter in this section, kept within 7 cm along the long axis of the proximal stomach, was traccd. Thc right side of the image corresponds to the riglu side of the subject S: stomach: D: diaplmigm.

Statistical Analysis. In the patient and control group mean values _+ SD of variables are eiven, if not othcnvise stated. The distribution of data was evaluated by inspecting a histogram and a probability plot and by utilising Kohnog- orov-Smirnov test with Lillefors subanalysis. If the data were approximately normally distributed, Student's t test with two-sided probabilities was used to compare results between the groups. Separate variances were selected in the analysis, and P < 0.05 was chosen as the level of statistical significance. If the data did not follow an approximate normal distribution, the Mann-Whitney U test was applied to estinaate group differences. Analysis of variance with repeated measurements was utilized to evaluate trends during the emptying time from the proximal stomach. All statistic calculations and graphic designs were performed using commercially available software (Systat, Systat Inc., Ewmston, Illinois, USA).

RESULTS

Patients with functional dyspepsia revealed smaller sagittal area measurements and shor ter frontal diam- eter measurements of the proximal s tomach post- prandially than healthy controls. However , only 7.5, 15, 20, and 25 min after the ingestion period the

differences in the sagittal sections (P < 0.018) and frontal sections (P < 0.046) were signiticantly differ- eat from healthy controls (Figures 4 and 5). Further- more, when calculating emptying fiactions of the proximal s tomach and applying A N O V A , a highly significant difference (P = 0.0005; G r e e n h o u s e - Geisser: P = 0.002) between the two groups were

detected (Figure 6). Nei ther patients nor healthy controls had to be

excluded from the study due to air (grade 3) in the gastric fundus impairing sonographic image quality. The number of subjects with grade 0 (absence of visible air) were 14 and 11, with grade 1 were 4 and 5, with grade 2 were 2 and 4, for patients with functional dyspepsia and healthy controls, respectively. None of these differences between the two groups were statis- tically significant (P > 0.5).

Pat ients with funct ional dyspepsia exper ienced more symptoms (P = 0.002), scored as global dyspep- sia in response to the soup meal, than healthy controls (Figure 7). Sixteen of 20 patients ( 7 5 ( , ~ ) experienced

692 l ) (wsmc l)ise,t.ws ,rod Scicmc.~. I 7,1. 41. No. 4 IApril l?9,'~J

25

8

20 * ,.9o

Contro ls 1 5 n=20

P a t i e n t s n=20

1 0 I I L .J 0 1 0 2 0 3 0 4 0

T i m e (min)

Fig 4. Graph showing the dillerenccs in area measurements in a sagittaI section hctv,'cen patients with functitmal dyspepsia and healthy ctmlrols. SEM bars arc shov,'n. 1' -4 0.05.

worsening of symptoms or induction of symptoms during or within 10 min after the ingestion of the meal. The emptying fractions were not correlated with symptoms induced by the soup. However, the duration of the disease was associated with the degree of symptom induction (r = 0.58, P = 0.{}{}9).

In the patient group, H. pylori status did not influ- ence (P = 0.44, NS) the emptying fraction rate of the

&

* g 7

~6

c 5 8

U_

C o n t r o l s n = 2 0

P a t i e n t s

n = 2 0

3 I I I I

0 10 20 30 40

Time (mln)

Fig 5. Graph demonstrat ing the dill'crcnccs in gastric diameter measured in an oblique frontal section between patients with functional dyspepsia and healthy controls. SEM bars are denoted. ~' P -< ().{15.

g

E w

0.8

0.6

0,4

0.2

0.0

IMPAIRED ACCOMMODATION IN FUNCTIONAL DYSPEPSIA

P a t i e n t s

n=20

Controls n=20

-0.2 i i OO 10.0 20.0 3 0 0

Time (rain)

Fig 6. Plot revealing tile differences in emptying fractions of tile proximal s tumach between healthy controls and patients with func- tional dyspepsia. Bars denoting SEXl are drawn. ~ P < ().(15.

proximal stomach, nor did gender (P = 0.23, NS) or smoking habits (P = 0.18, NS). Patients with func- tional dyspepsia had higher scores on the G H Q - 2 8 + registration (P < 0.0005), and neuroticism was a more dominant feature (P < 0.0005) compared with healthy controls (Figure 8).

With the present soup meal, the proximal gastric emptying fraction discriminating best between pa- tients and healthy controls, was seen 20 min post-

10 I I

CD 0 C) 69

E o c t E

- 5

p=O.O02

I [

:x~

Controls Patients

Fig 7. Combination of box and dot plot showing tile differences in s.vnlptOWI SCOreS between patients with functional dyspepsia and ctmtrols. The median of the batch is marked by the center hori- ztmtal line with a quartile on each side comprising tile box.

I) igc,f i , ' , ' /) iwa.,, ' , ,rod );cic, u'c,. I M. 41..V,,. 4 (..l l,ri l lg'R,J 6 9 3

10,00

o o Z

I

2 UJ

5.00

0.00

-5.00

p<O.O005

I J

Controis Patients

Fig 8. Conlbination of box and clot plot depicting the ditfcrcnccs in EPQ-N scorc between functional dyspepsia paticnts and Ilcalthv controls. The median of the batch is markcd bv the cenler hori- zontal linc with a quartile on each sidc embracing the box.

cibally. The diagnostic sensitivity of the method at 20 rain postprandially was 70% and the specificity 65%. The positive predictive value using this method was 67%, and the negative predictive value was 68C~.

DISCUSSION

The present ultrasonographic method disclosed that patients with functional dyspepsia, in response to a soup meal, had smaller sizes and higher emptying fractions of the proximal stomach than healthy con- trois. This population of patients was also character- ized by general hyperresponsiveness, lower quality of life, and higher susceptibility to psychiatric morbidity. Furthermore, ingestion of our soup meal induced significantly more symptoms in these patients than in healthy controls. Thus, this novel noninvasive method for measuring postprandial size and initial emptying fraction of the proximal stomach, previously shown to be applicable and to contribute to low intra- and interobserver error in healthy volunteers (21), seemed useful also in the evaluation of patients with functional dyspepsia.

Interestingly, there was no significant difference in the size of the proximal stomach between dyspeptics and controls immediately after the meal ingestion. This finding is consistent with other observations sug- gesting a normal compliance during pressure incre- ments of the proximal stomach in fasting patients with functional dyspepsia ( 13. 15). Accordingly, in the time

GILJA ET AL

period before a substantial portion of the meal has reached the intestines, the proximal stomach seemed to relax adequately. However, after this initial, near- normal receptive relaxation, accommodation of the proximal stomach appeared to be impaired with ab- normally high emptying fractions. It is documented that tile proximal stomach receives reflex signals that induce gastric relaxation, both after volume expan- sion (30, 31) and nutrient infusion (32) into the duo- denum. When the duodenum is properly exposed to nutrients or sufficiently dilated by the volume of the soup, feedback signals to the proximal stomach start to moderate the reservoir flmction of the corpus- fundus, interfering with normal adaptive relaxation. It is not possible from the present study to deduce which mechanism underlies the impaired accommodation in patients with functional dyspepsia, but our finding is supported by the previous detection of an impaired duodenogastric reflex in this patient group (33). Fur- thermore, intragastric maldistribution of a meal with a relatively lower proportion of the meal residing in the proximal stomach has been encountered in pa- tients with functional dyspepsia (10, 11), substantiat- ing our finding of impaired accommodation to a meal in these patients.

In patients with functional dyspepsia, it has been a constant challenge to establish valid associations be- tween reported symptoms and actual physiological abnormalities. Evidence of altered gastric functions, like antral hypomotility (22, 34), delayed gastric emp- tying (6, 8, 9), and a wide antrum (20) have been found in subgroups of patients, but the diagnostic sensitivity and specificity of these findings are too low to allow conclusive diagnosis. We found a relatively high predictive value of the emptying fraction indi- cating that insufficient accommodation of the proxi- mal stomach may constitute a significant sign in this patient population. Although no significant correla- tions between symptoms and emptying fraction were detected in this study, the patients experienced sig- nificantly more dyspepsia than controls following the meal at the same time as impaired adaptive relaxation of the proximal stomach was seen. Hence, as impaired accommodation and symptoms were temporarily re- lated, a causal relationship is possible.

In accordance with previous studies (27, 35, 36), the present patients with functional dyspepsia were prone to a general lifestyle of hyperresponsiveness and emo- tional overreactiveness, as ewfluated by EPQ-N score. In recent studies, a low vagal tone (22), and a signif- icant negative correlation between EPQ-N score and vagal tone (37) was observed in patients with func-

694 i ,~ , , . , i , , , i)i.wasc.~ and Science.s. I ~L 41. No. 4 L.Ipri/ l~U61

IMPAIRED ACCOMMODATION IN FUNCTIONAL DYSPEPSIA

tional dyspepsia. In fact, low vagal activity may con- stitute a mediating mechanism for the relationship between personal factors and gastric symptoms in functional dyspepsia (37). Both receptive and adap- tive relaxation of the proximal stomach are facilitated by vagal nerves (38). In vagotomized patients, expe- riencing postcibal discomfort and fullness, increased intragastric pressure (16) and impairment of gastric adaptive relaxation (4, 39) have been discovered. Taken together with previous results, our study sug- gests a relation between impaired accommodation of the proximal stomach, low vagal tone, and induction of symptoms in patients with functional dyspepsia.

Limitations of the Study. In general, ultrasono- graphic methods require sonographic skills and a certain level of experience to fully decipher the infor- mation of the images. The present method is vulner- able with respect to the presence of gas pockets in the proximal stomach, and this problem was discussed in a previous paper (21). However, no patients or con- trois had to be excluded due to this phenomenon, and the amount of gas present was not statistically differ- ent in the two groups. In the validation study on healthy controls, we found a moderate day-to-day variation and low intra- and interobserver error of both the scanning procedure and the applied mea- surements.

The emptying fractions of the proximal stomach would be easier to interpret if total gastric emptying and intragastric distribution were known parameters. Unfortunately, it was practically impossible to mea- sure gastric emptying by radionuclide methods in this study. Several studies have found that patients with functional dyspepsia exhibit delayed gastric emptying, including when ingesting liquid meals (6, 7, 40-42). Accordingly, it seems unlikely that our results are due to a rapid total gastric emptying in patients with functional dyspepsia. However, further studies are needed to elucidate the interplay and the coordina- tion between the different parts of the stomach to facilitate accommodation of a meal.

The present ultrasonographic method is rather time consuming, but our results indicate that the ideal point of measurement, with respect to discriminating power, was at 20 min postprandially. Hence, to use this method in the clinical evaluation of patients with functional dyspepsia, it seems sufficient to measure postprandial sizes of the proximal stomach immedi- ately after the meal and 2(I rain postprandially.

In conclusion, this novel noninvasive method to monitor the size and emptying fraction of the proxi- mal stomach by ultrasonic scanning was also useful in

evaluating the accommodation in a patient popula- tion. Patients with functional dyspepsia referred to a gastroenterologic unit for upper endoscopy exhibited greater symptom induction and impaired accommo- dation of the proximal stomach to a soup meal com- pared with healthy controls, suggesting a relationship between symptoms and impaired accommodation in these patients.

ACKNOWLEDGMENTS

We want to express our thanks to Christen Bang, MD, PhD, for his kind st.pporl in recruiting patients to the study.

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