Gastric Accommodation and Emptying in Evaluation of Patients With Upper Gastrointestinal Symptoms

Transcription

1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2003;1: Gastric Accommodation and Emptying in Evaluation of Patients With Upper Gastrointestinal Symptoms ALBERT J. BREDENOORD,* HEATHER J. CHIAL,* MICHAEL CAMILLERI,* BRIAN P. MULLAN, and JOSEPH A. MURRAY* *Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) Program; and the Section of Nuclear Medicine, Mayo Clinic, Rochester, Minnesota Background & Aims: Endoscopy-negative dyspepsia is a common symptom that often is difficult to define in pathophysiologic terms. The aim of this study was to assess the frequency of disordered gastric accommodation and emptying in patients referred with unexplained upper gastrointestinal symptoms. Methods: A computerized diagnostic index was used to identify all patients, years old, who underwent single-photon emission computed tomography (SPECT) to assess gastric accommodation at Mayo Clinic Rochester over a 3-year period. Demographics, clinical features, and results of diagnostic testing, including scintigraphic gastric emptying, were extracted from the electronic record. Results: A total of 214 patients were identified; the primary clinical diagnoses were functional dyspepsia, postfundoplication syndromes, rumination syndrome, and diabetic dyspepsia. Gastric accommodation was impaired in 43% of the whole group: 47% of functional dyspepsia, 44% of postfundoplication syndromes, and 33% of diabetic dyspepsia. Delayed gastric emptying was most prevalent in diabetic dyspepsia, and was accelerated in postfundoplication syndromes groups. Thirty-seven percent of patients had abnormal gastric emptying. The highest prevalence of delayed gastric emptying was in the diabetic dyspepsia and accelerated gastric emptying in postfundoplication syndromes groups. Twenty-five percent of patients with normal gastric emptying had impaired accommodation. Upper-gastrointestinal symptoms were not different in groups based on gastric accommodation or emptying results. Conclusions: Impaired gastric accommodation is common in patients with unexplained dyspepsia. Symptoms alone cannot predict physiologic disturbances. These noninvasive tests identify single or combined pathophysiologic disturbances and may help to identify subgroups of patients as candidates for more selective pharmacotherapy in the future. Gastric accommodation is a vagally mediated reflex that results in reduced gastric tone, increased compliance, and increased gastric volume. Accommodation allows the ingestion of large volumes of solids or liquids without inducing postprandial symptoms. Impaired gastric accommodation has been associated with upper gastrointestinal symptoms including early satiety, bloating, epigastric pain, weight loss, and nausea. Impaired accommodation has been identified in patients with functional dyspepsia, 1 7 diabetes mellitus, 2 rumination syndrome, 8 and prior surgeries including Nissen fundoplication, 9,10 vagotomy, and gastrectomy. 11 However, the relationship between symptoms and gastric accommodation in these conditions remains unclear. 3,4,12 Gastric emptying is delayed in 15% 50% of patients with functional dyspepsia, 13 but the relationship with upper gastrointestinal/abdominal symptoms is unclear. 13,14 It is generally acknowledged that prokinetics are ineffective in the treatment of patients with functional dyspepsia unless they have delayed gastric emptying. On the other hand, 2 studies showed benefit among patients with delayed gastric emptying, 15,16 and the relationship of vomiting and early satiety has been documented in patients with delayed gastric emptying. 17 However, measurement of gastric emptying alone may not predict therapeutic responses to prokinetic agents in dyspepsia. 18 A critical question therefore arises: Are there clinically applicable approaches to permit identification of subgroups of patients according to pathophysiology to enhance clinical trials and patient management? Does measurement of accommodation identify a frequent pathophysiologic mechanism in dyspeptic patients seen in clinical practice? A variety of techniques 19 have been used to evaluate gastric accommodation including the gastric barostat, abdominal ultrasonography, and magnetic resonance imaging. More recently, single-photon emission computed tomography (SPECT) has been introduced as a noninva- Abbreviation used in this paper: SPECT, single-photon emission computed tomography by the American Gastroenterological Association /03/$30.00 doi: /s (03)

2 July 2003 SPECT AND SCINTIGRAPHY IN DYSPEPSIA 265 sive alternative to study gastric accommodation and its perturbations by medications. 4,10,20,21 At the Mayo Medical Center, the SPECT technique has been available to assess gastric accommodation in clinical practice since The aim of this study was to ascertain whether SPECT assessment of gastric accommodation and scintigraphic assessment of gastric emptying can provide additional information that is clinically relevant to patients with upper gastrointestinal symptoms and negative upper endoscopy in a tertiary care setting. Materials and Methods Study Participants The study was approved by the Mayo Institutional Review Board, and patient authorization for use of the medical records for research purposes was confirmed before access to the medical records was provided. A computerized diagnostic index was used to identify all patients who had a prior negative upper gastrointestinal endoscopy between the ages of and subsequently underwent SPECT imaging to assess gastric accommodation at the Mayo Medical Center in Rochester, MN, between September 1999 and July Data extracted from the medical records included demographics, clinical features, past medical history, results of diagnostic testing, and treatment recommendations. A total of 214 patients were identified, all of whom had been referred to the Gastroenterology Motility Clinic at Mayo Clinic Rochester for the evaluation of upper gastrointestinal symptoms. Functional dyspepsia was defined as upper gastrointestinal symptoms after meals in the absence of organic abnormalities on routine diagnostic testing. 22 Rumination syndrome was identified by effortless, early postprandial regurgitation Patients who were taking medications with potential effects on gastrointestinal sensorimotor function were weaned off these medications for at least 48 hours before physiologic testing. Control data from healthy controls previously studied using identical imaging techniques in the same clinical nuclear medicine laboratory were used for comparison. Measurement of Gastric Accommodation A noninvasive method that was developed in our laboratory 20 and validated 10 by comparison with gastric barostat measurements was used to measure fasting and postprandial gastric volumes using an intravenous injection of 99m Tc-pertechnetate ( 99m TcO 4 ) and imaging with SPECT. Tomographic images were acquired using a large field-of-view, dual-headed gamma camera system. Gastric volumes were measured using the SPECT-ANALYZE PC 2.5 (Biomedical Imaging Resource, Mayo Foundation, Rochester, MN) software system. 20 The gastric mucosa is able to take up intravenously administered 99m Tc-pertechnetate from the circulating blood pool. Starting 10 minutes after the intravenous injection of 10 mci 99m Tc-pertechnetate, SPECT imaging was performed during fasting and for a total of 32 minutes after ingestion of a 300 ml nutrient drink (Ensure, 1 kcal/ml) through a straw. Gastric volumes were assessed during 2 postprandial periods: 0 10 minutes and minutes after the meal. Transaxial images of the stomach were rendered with ANALYZE to reconstruct 3-dimensional images of the stomach and to measure gastric volumes during the fasting and postprandial periods. Volume changes and ratios between the fasting and postprandial periods were calculated. Measurement of Gastric Emptying Scintigraphic techniques were used to evaluate gastric emptying, as described in prior studies conducted in our laboratory. 26,27 After an overnight fast, a 99m Tc-sulfur colloidlabeled egg meal was used to assess gastric emptying. The eggs were served with one slice of buttered bread and an 8-oz glass of 1% milk (total calories: 296 kcal, 32% protein, 35% fat, 33% carbohydrates). Anterior and posterior gamma camera images were obtained 0, 1, 2, and 4 hours after the test meal ingestion to assess gastric emptying. Although we were the first 26 to show that this abbreviated approach can identify accelerated or delayed gastric emptying effectively, this has been confirmed in multicenter and international studies. 28,29 Data and Statistical Analysis Gastric accommodation data from the patients were compared with data from 28 healthy volunteers, acquired on the same SPECT camera and using the same analysis program. The data from healthy volunteers have been reported previously in the literature. 20,21 Data for gastric emptying were compared with data from a second group of 37 healthy volunteers. 27 The primary measurement for reduced gastric accommodation was a postprandial change in gastric volume of less than 428 ml (10th percentile for 28 healthy volunteers evaluated in the same laboratory). Accelerated gastric emptying was defined as more than 39% emptied at 1 hour, whereas delayed gastric emptying was defined as less than 84% emptied at 4 hours. Data are displayed as mean SEM for demographic data, and as medians and interquartile ranges and percentages for clinical data. The Mann-Whitney test and the 2 test were used for comparisons of medians and proportions between patients and healthy controls, respectively. Subgroup analyses were performed using one-way analysis of variance (ANOVA) and the Kruskal- Wallis test (ANOVA on ranks) for parametric and nonparametric data, respectively. When the overall comparisons on ANOVA or the Kruskal-Wallis test were significant (P 0.05), pairwise comparisons between each subgroup of patients and healthy controls were performed using Dunnett s test. Results Patients and Subgroups A total of 214 patients underwent SPECT assessment of gastric accommodation at Mayo Clinic Rochester

3 266 BREDENOORD ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 1, No. 4 Table 1. Demographics and Symptoms of Patients All patients Functional dyspepsia Postfundoplication Rumination syndrome Diabetes mellitus N Age (yr) % Women Height (cm) Weight (kg) BMI (kg/m 2 ) Abdominal pain (%) Weight loss (%) Nausea (%) Vomiting (%) Bloating (%) Early satiety (%) Constipation (%) Diarrhea (%) Heartburn (%) NOTE. Data are presented as mean SEM or percentages. BMI, body mass index. between September 1999 and July These patients were categorized into 4 subgroups: (1) patients with upper abdominal symptoms without a prior history of fundoplication, diabetes mellitus, or rumination syndrome categorized as having functional dyspepsia; (2) patients with upper abdominal symptoms postfundoplication; (3) patients with upper abdominal symptoms and a history of diabetes mellitus; and (4) patients with upper abdominal symptoms and clinical features of rumination syndrome. Demographics and Clinical Features Demographic data and symptoms for the 214 patients with upper abdominal symptoms and for the 4 patient subgroups are shown in Table 1. The 4 patient subgroups were exclusive. Patient classification was based on the diagnosis entered by the gastroenterologist in the medical record. One hundred fifty-one patients were classified as having functional dyspepsia. Thirtyseven had upper dyspepsia like abdominal symptoms and a prior history of fundoplication; 32 had undergone a standard Nissen fundoplication procedure, 1 a Toupet procedure, 1 a repeat Nissen fundoplication, and 2 had pyloroplasty in addition to Nissen fundoplication. Fifteen patients described effortless postprandial regurgitation and met criteria for rumination syndrome. Eleven patients had diabetes mellitus; 6 were treated with insulin and 5 with oral hypoglycemic agents. Past medical history, psychiatric history, and medications are summarized in Table 2. All of the patients had undergone extensive diagnostic testing, including at least one upper gastrointestinal endoscopy, before and during their referral to our tertiary care center. During their evaluation at our medical center, 87.4% underwent laboratory testing, 48.6% upper gastrointestinal barium studies with small bowel examination, 38.3% abdominal computed tomography scanning, 27.6% abdominal ultrasound, 23.4% 24-hour ambulatory ph testing, and Table 2. Commonly Encountered Past Medical Illnesses, Psychiatric History, and Medications Used at Time of Presentation All patients Functional dyspepsia Postfundoplication Rumination syndrome Diabetes mellitus Peptic ulcer IBS Psychiatric disorder PPIs H 2 RAs TCAs SSRIs Other antidepressants NSAIDs Antiemetics Prokinetics NOTE. Data are presented as percentages. IBS, irritable bowel syndrome; PPIs, proton pump inhibitors; H 2 RAs, histamine-2 receptor antagonists; TCAs, tricyclic antidepressants; SSRIs, serotonin selective reuptake inhibitors; NSAIDs, nonsteroidal anti-inflammatory drugs.

4 July 2003 SPECT AND SCINTIGRAPHY IN DYSPEPSIA % esophageal manometry testing; the results of these tests were either normal or noncontributory. Assessment of Gastric Volumes An example of fasting and postprandial volumes in a patient with functional dyspepsia is shown in Figure 1. The fasting and postprandial gastric volumes for all patients are shown in Table 3 and Figure 2. The postprandial gastric volume response or gastric accommodation was considered abnormal if the postprandial change in gastric volume was less than 428 ml, the 10th percentile for the healthy control group. Gastric Volumes: Whole Patient Group The postprandial increase in gastric volume on SPECT imaging for the whole patient group (n 214) was less than 428 ml after the standard 300 ml (300 kcal) Ensure meal in 43%. As shown in Table 3, the fasting gastric volume was significantly larger for patients vs. controls (both P 0.05). The average postprandial change in gastric volume and the average postprandial to fasting gastric volume ratio were significantly lower in the patient group compared with the control group (both P 0.05). In the whole patient group and in the patient subgroups, no differences in the prevalence of symptoms were detected between patients with normal or reduced gastric accommodation (Figure 3). Gastric Volumes in Patient Subgroups An abnormal postprandial gastric volume response was observed in 46.7% of the 151 patients in the Table 3. Gastric Volumes in Patients With Upper Gastrointestinal Symptoms and Healthy Controls All patients Functional dyspepsia Figure 1. Examples of SPECT measurement of gastric volume during fasting (left) and postprandially (right) in 2 patients. Postfundoplication Rumination syndrome Diabetes mellitus Healthy controls Fasting volume (ml) 245 (195, 295) a 246 (194, 297) 232 (171, 309) 228 (203, 280) 258 (233, 288) 190 (165, 250) Postprandial volume (ml) 695 (608, 805) 677 (594, 803) 673 (590, 806) 744 (697, 767) 820 (596, 885) 710 (657, 827) Ratio c 2.78 (2.36, 3.34) a 2.78 (2.41, 3.35) a 2.71 (2.07, 3.24) a 3.25 (2.7, 3.64) 2.67 (2.05, 3.07) a 3.52 (2.84, 4.19) Volume change (ml) b 446 (372, 529) a 439 (378, 524) a 440 (309, 515) a 494 (458, 562) 479 (342, 590) 494 (462, 591) NOTE. Data are presented as median (interquartile range). a P 0.05 vs. healthy controls. b Normal 428 ml. c Ratio: postprandial/fasting volume.

5 268 BREDENOORD ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 1, No. 4 Figure 3. Prevalence of symptoms in patients with impaired gastric accommodation compared with patients with normal gastric accommodation. Figure 2. (A) Postprandial to fasting volume change in the different subgroups and healthy controls. (B) Postprandial to fasting volume ratio in the different subgroups and healthy controls. functional dyspepsia subgroup (Table 3). Fasting and postprandial gastric volumes did not differ between patients with functional dyspepsia and healthy controls. Forty-four percent of the 37 patients in the postfundoplication subgroup had an abnormal postprandial gastric volume response (i.e., less than 428 ml). Fasting and postprandial gastric volumes were not different between the postfundoplication patients and healthy volunteers (Table 3). The postprandial to fasting gastric volume ratio and the postprandial change in gastric volume for patients with rumination syndrome were not significantly different from healthy controls (Table 3). The postprandial to fasting gastric volume ratio was significantly lower (P 0.05) in patients with diabetes mellitus compared with healthy controls. However, no difference in the postprandial change in gastric volume was noted between the patients with diabetes mellitus and healthy controls (Table 3). Assessment of Gastric Emptying A total of 173 (81%) of the 214 patients underwent a scintigraphic assessment of gastric emptying of solids. Results are shown in Table 4. Overall, accelerated gastric emptying was slightly more common than delayed gastric emptying; this likely reflects the greater proportion of postfundoplication than diabetic patients in the cohort studied. Table 5 shows the distribution of gastric emptying rates in patients with reduced gastric accommodation. Overall, 25% of patients with normal emptying had evidence of impaired gastric accommodation. No significant differences in the symptoms reported by patients with normal, accelerated, or delayed gastric Table 4. Distribution (%) of Gastric Emptying Results Relative to Normal Values All patients Functional dyspepsia Postfundoplication Rumination syndrome Diabetes mellitus Delayed Accelerated Normal

6 July 2003 SPECT AND SCINTIGRAPHY IN DYSPEPSIA 269 Table 5. Distribution (%) of Reduced Gastric Accommodation and Range of Gastric Emptying Emptying Accommodation All patients Functional dyspepsia Postfundoplication Rumination syndrome Diabetes mellitus Delayed Low Accelerated Low Normal Low emptying (Figure 4) were noted. Although the frequency of vomiting was 20% higher in the diabetics with delayed gastric emptying, this difference was not statistically significant (Figure 4). A total of 126 of the 151 (83%) patients in the functional dyspepsia subgroup underwent assessment of gastric emptying. Only 13.3% had evidence of delayed gastric emptying, whereas 21% had accelerated gastric emptying. Of the patients with functional dyspepsia who had normal gastric emptying, 27% had impaired gastric accommodation on SPECT imaging. Twenty-three of the 37 patients with upper abdominal symptoms postfundoplication underwent assessment of gastric emptying of solids. Thirty-six percent of patients in this subgroup had accelerated gastric emptying, and 4% had delayed gastric emptying. Overall, 70% of patients in this group had abnormal gastric emptying and/or impaired gastric accommodation (Figure 5). Abnormal gastric accommodation in this patient subgroup tended to occur in patients with normal gastric emptying. Fourteen of the 15 patients in the rumination subgroup underwent assessment of gastric emptying. Gastric emptying was delayed in 15.4% and accelerated in 23.1%. The significance of this finding is unclear in the setting of recurrent regurgitation during the measurement of gastric emptying. Gastric emptying was delayed in 45% of the 9 patients with diabetes mellitus who underwent assessment of gastric emptying. Eleven percent of diabetic patients with normal gastric emptying had evidence of impaired gastric accommodation. Overall, 67% of the diabetic patients had delayed gastric emptying and/or impaired gastric accommodation (Figure 5). Impaired gastric accommodation was more common in diabetic patients with delayed gastric emptying. Discussion This study evaluated the clinical application of SPECT and scintigraphic imaging to assess gastric accommodation and emptying, respectively, in patients with endoscopy-negative upper abdominal symptoms in a tertiary referral setting. Our aim was to assess whether SPECT and scintigraphy provide clinically useful information beyond what is provided from more standard clinical testing. The majority (174 of the 214 patients) underwent assessment of both gastric accommodation and gastric emptying, and 60.6% of these patients had evidence of impaired gastric motor function (i.e., either abnormal gastric emptying or reduced gastric accommodation). As shown in Figure 5, this applied to all groups except rumination, with the proportion of abnormal test results reaching 70% among symptomatic diabetics and post- Figure 4. Prevalence of symptoms in patients with normal, accelerated, and delayed gastric emptying. Figure 5. Gastric motor dysfunction in the different subgroups.

7 270 BREDENOORD ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 1, No. 4 fundoplication patients. Gastric emptying frequently is accelerated postfundoplication. 30 Overall, 44% of patients in the postfundoplication subgroup had evidence of impaired gastric accommodation, consistent with previous reports in the literature. 9,10,31 Vagal dysfunction is potentially relevant in patients postfundoplication, and it has been documented in a minority of patients with functional dyspepsia. 1,32,33 It is interesting to contrast the findings among the patients with diabetes and patients postfundoplication who are susceptible to vagal injury by different mechanisms. In diabetic patients, reduced accommodation was associated more often with delayed gastric emptying, in contrast to the postfundoplication group. The differences between potential vagal injury owing to fundoplication and diabetes may reflect the different mechanisms of injury. Vagal neural supply to the stomach originates from the anterior and posterior vagal trunks at the level of the diaphragmatic hiatus. Thus, the posterior vagal trunk divides into a small gastric and a large celiac branch. The gastric branch supplies the posteroinferior aspect of the stomach with the exception of the pyloric canal. This branch sends twigs along the short gastric vessels. The anterior vagal trunk divides into right and left branches, and a separate definable branch courses to the antrum as the nerve of Latarjet. The left branches follow the lesser curve and supply the anterosuperior surface of the stomach. Thus, it is conceivable that fundoplication results in neural injury to branches of the vagus to the proximal stomach (thereby reducing vagal control of accommodation) without injury to the nerve of Latarjet. Another nonvagal component of the innervation of the stomach could be altered or injured in disease state or postsurgery. Christensen and Rick 34 performed an anatomic study in several species and showed abundant shunt fascicles entering the stomach at the cardia and radiating toward the greater curvature in the myenteric plexus layer. These shunt fascicles are either extensions of the esophageal myenteric plexus or of the vagal branches to the distal esophagus. Injury to the branches of the vagus nerve may be more likely to occur when the short gastric vessels are divided as part of the Nissen fundoplication. 35 Conversely, diabetic neuropathy is a length-dependent demyelination and may preferentially affect the more distal branches supplying the gastric antrum, reducing the ability of the stomach to activate trituration, sieving, and emptying of solid food 36 ; 5 of 11 diabetic patients had delayed gastric emptying. In contrast to some studies, 37,38 accommodation in symptomatic diabetes was normal in two thirds of the 11 patients with diabetes, confirming the overall normal accommodation noted in previous studies from our laboratory in different cohorts of diabetic patients without 39 or with 40 vagal neuropathy. We found delayed or accelerated gastric emptying in 35% of the entire group of patients with dyspeptic symptoms. The observation that gastric emptying was delayed in 14% is within the wide range (11% to 83%) in the literature concerning scintigraphic gastric emptying tests of solids in functional dyspepsia. 13 On the other hand, 21.1% of patients with functional dyspepsia had accelerated gastric emptying, two thirds of whom had reduced gastric accommodation. This suggests either that the 2 functions may be linked etiologically (e.g., by a common mechanism such as vagal dysfunction) or that one function influences the other. Thus, it is conceivable that impaired gastric accommodation resulted in acceleration of gastric emptying in this cohort of patients with functional dyspepsia. This also was observed in 10% of postfundoplication patients. Our data in 151 patients with functional dyspepsia (i.e., abnormal gastric accommodation in 46.7%) confirmed 3 smaller previous studies documenting that gastric accommodation was impaired in approximately 45% of patients evaluated using barostat 3,12 or SPECT imaging. 4 SPECT assisted the identification of a motor abnormality potentially contributing to symptoms in 26% of the functional dyspepsia patients who had normal gastric emptying. Thus, our data suggested that SPECT may provide additional insight into the pathophysiology of symptoms in this patient population. If more specific therapies are identified to correct the variety of pathophysiologic disturbances contributing to dyspepsia, these data suggest that the tests would help identify patients for selective and potentially more effective therapy. Although there was a large variety of symptoms in all groups, we were not able to link symptoms, including early satiety or weight loss, in any group to impaired gastric accommodation. This is consistent with the observation of Boeckxstaens et al. 7,12 that impaired gastric accommodation is not predicted by any specific symptom, and the concept that the relationship between symptoms and motor dysfunction of the stomach requires further study. Stanghellini et al. 17 showed an association between delayed gastric emptying and severe vomiting. In our study, vomiting was 20% more prevalent in patients with delayed gastric emptying, but this difference was not statistically significant. Other groups have reported lack of an association between symptoms and

8 July 2003 SPECT AND SCINTIGRAPHY IN DYSPEPSIA 271 impaired gastric emptying. 14 Nevertheless, few reports document that treatment with cisapride of dyspeptic patients with delayed gastric emptying improved upper gastrointestinal symptoms. 15,16 This suggests that it still may be possible to enhance the success of prokinetic or other therapies by careful selection of appropriate subgroups of patients to maximize the potential efficacy of the drug. This hypothesis can now be tested, given the availability of valid, accurate, noninvasive tests of the different gastric motor functions. The retrospective nature of this project and the tertiary care setting are limitations of our study. However, our study used electronic records; standard questionnaires assessing personal, social, and family history; and standardized, validated physiologic measurements. These data are representative of patients who present with upper gastrointestinal symptoms and negative upper endoscopy in the tertiary care setting. A potential weakness is that gastric accommodation and emptying were not measured simultaneously. Alternative approaches such as ultrasonography and magnetic resonance imaging 41 are reputed to allow such simultaneous measurements. However, unlike SPECT, these techniques still require validation, specifically, comparison with simultaneous barostat measurement of gastric accommodation, as in our previous work 10 with SPECT. In summary, our study showed that formal testing of a large proportion of patients with upper abdominal symptoms shows either reduced gastric accommodation and/or delayed or accelerated gastric emptying of solids. A considerable proportion (26%) of patients with reduced gastric accommodation had normal gastric emptying. Evaluation of gastric accommodation may prove more useful in the future when its role in the etiology of symptoms is clarified and when better fundic-relaxing medications become available. Our study suggested that gastric accommodation and emptying may be involved in the pathophysiology of functional dyspepsia and could help to subclassify patients with functional dyspepsia in addition to symptoms for clinical trials or treatment selection. References 1. Thumshirn M, Camilleri M, Saslow SB, Williams DE, Burton DD, Hanson RB. Gastric accommodation in non-ulcer dyspepsia and the roles of Helicobacter pylori infection and vagal function. Gut 1999;44: Salet GA, Samsom M, Roelofs JM, van Berge Henegouwen GP, Smout AJ, Akkermans LM. Responses to gastric distension in functional dyspepsia. Gut 1998;42: Tack J, Piessevaux H, Coulie B, Caenepeel P, Janssens J. Role of impaired gastric accommodation to a meal in functional dyspepsia. 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