A. J. P. M. Smout

The symptom-association probability: An improved method for symptom analysis of 24-hour esophageal pH data

BACKGROUND/AIMS All methods currently used to quantify the temporal relationships between symptoms and episodes of gastroesophageal reflux, as assessed by 24-hour pH monitoring, have major shortcomings. The aim of this study was to develop and validate a simple, all-comprising statistical method to calculate the probability that gastroesophageal reflux episodes and symptoms are associated. METHODS The 24-hour pH signal was divided into consecutive 2-minute periods. These periods and the 2-minute periods preceding the onset of symptoms were evaluated for the occurrence of reflux. Fishers Exact Test was then applied to calculate the probability (P value) that reflux and symptom episodes were unrelated. Finally, the symptom-association probability (SAP) was calculated as (1.0 - P) x 100%. The SAP values found in 184 24-hour esophageal pH tests were compared with the symptom index and the symptom sensitivity index. RESULTS Discordance between the SAP and the symptom index was found in 21 patients (11%) and discordance between the SAP and the symptom-sensitivity index in 28 (15%). False-positive and false-negative symptom index values occurred preferentially in patients with small and large numbers of symptom episodes during the test, respectively (P < 0.05). CONCLUSIONS The SAP is a single, simple, quantitative measure of the strength of the association between symptoms and reflux episodes that is devoid of the disadvantages inherent to previously used methods.

Responses to gastric distension in functional dyspepsia

Background—Studies have shown that an altered visceral perception threshold plays a role in the pathogenesis of upper gastrointestinal tract symptoms in dyspeptic patients. However, it is not clear whether the compliance and adaptive relaxation of the proximal stomach contribute to the symptoms. Aims—To investigate whether abnormal relaxation or adaptation of the proximal stomach during the interdigestive state and the postprandial phase could explain the symptoms of functional dyspepsia. Subjects—Twelve volunteers and 12 patients with dysmotility-like functional dyspepsia were included in the study. Methods—An electronic barostat was used to investigate adaptation to distension of the proximal stomach and accommodation in response to a liquid meal. Dyspeptic symptoms during distension and accommodation were assessed. Results—When the subjects were in the fasting state, the pressure-volume curve showed slightly higher compliance in the dyspeptic patients (p<0.05). Patients not only had a higher score for nausea, bloating, and pain but also the increase in nausea and pain scores with intragastric pressure was higher than in volunteers (p<0.05). The increase in intragastric bag volume in response to a meal was significantly lower in patients (p<0.05). Both bloating and pain significantly increased in the patients (p<0.05), but not in the healthy volunteers. Conclusions—Patients with functional dyspepsia show slightly higher compliance to mechanical distension. Their visceral perception of mechanical stress is enhanced. In contrast with the balloon distension, relaxation after a meal was less. Therefore the postprandial symptoms cannot be explained fully by greater global tension in the stomach wall, as assessed by the barostat technique. Visceral hypersensitivity plays a major role in the pathogenesis of the symptoms.

Disturbed Solid-Phase Gastric Emptying in Functional Dyspepsia (A Meta-Analysis)

Functional dyspepsia is a common disorder witha diverse pathophysiological background, but the role ofmotility disorders in functional dyspepsia remainsunclear. We aimed to quantify the relationship between disturbed gastric emptying andfunctional dyspepsia, using a meta-analytic approach.Through a structured literature search of Medline andEmbase from 1983 to 1996, we selected all studies inwhich scintigraphic solid-phase gastric emptying wasmeasured in both functional dyspeptic patients andcontrols. Seventeen studies involving 868 dyspepticpatients and 397 controls were pooled. Gastric emptying in patients with functional dyspepsia was 1.46(1.23-1.69) times slower than controls; the proportionof patients with abnormally slow emptying was either 37%(34-40%, simple numeric pooling) or 39% (29-49%,weighted pooling). We conclude that gastric emptying ofsolids in patients with functional dyspepsia is 1.5times slower than in healthy controls and that asignificant delay of emptying is present in almost 40% of patients with functionaldyspepsia.

Symptom association analysis in ambulatory gastro-oesophageal reflux monitoring

During the past three decades, prolonged monitoring of oesophageal pH has become increasingly popular among physicians. Most of the studies carried out with this technique focused on oesophageal acid exposure, defined as percentage of time with pH below 4. However, in most cases acid exposure variables are not very useful in the evaluation of patients with symptoms and signs of gastro-oesophageal reflux disease (GORD). An often neglected aspect of 24 hour pH recording is assessment of the temporal relation between reflux and symptoms. Various methods to quantify this relationship were developed. Here, we review these methods and the contribution of symptom association analysis to the evaluation of patients with symptoms suggestive of GORD.

What Is the Optimal Time Window in Symptom Analysis of 24-Hour Esophageal Pressure and pH Data?

Since noncardiac chest pain is the only well-established indication for 24-hr esophageal pH and pressure recording, the analysis of the association between chest pain episodes and esophageal motility abnormalities or reflux is the most important part of data analysis in 24-hr monitoring. Until now, different time windows have arbitrarily been used by various research groups. The aim of this study was to determine the optimal time window for symptom analysis in 24-hr esophageal pH and pressure monitoring. For this purpose repetitive symptom association analysis was carried out, using time windows of various onsets and durations. For each time window, the symptom indices for reflux and dysmotility were calculated. The symptom index for both reflux and dysmotility showed a gradual increase for windows with increasingly early onset, following a pattern that would be predicted on the basis of Poissons theory. However, both indices had a relatively sharp cutoff point at 2 min before the onset of pain. Both indices only showed a predictable gradual increase when the time window starting at −2 min was extended beyond the moment of pain onset. It is concluded that the optimal time window for symptom analysis in 24-hr esophageal pH and pressure recording begins at 2 min before the onset of pain and ends at the onset of pain.

Symptom perception in gastroesophageal reflux disease is dependent on spatiotemporal reflux characteristics

BACKGROUND/AIMS The mechanisms responsible for the development of symptoms in gastroesophageal reflux disease (GERD) are poorly understood. The aims of this study were to identify differences in spatiotemporal reflux characteristics (proximal extent and duration of reflux episodes, ascending velocity of the refluxate) between symptomatic and asymptomatic reflux episodes and to assess the influence of different pH sensor positions on the yield of symptom analysis. METHODS Esophageal pH was measured for 24 hours at 3, 6, 9, 12, and 15 cm above the lower esophageal sphincter (LES) in 18 symptomatic patients with GERD, and spatiotemporal reflux characteristics were assessed for symptomatic and asymptomatic reflux episodes. Additionally, the symptom-association probability (SAP) was calculated for each esophageal level. RESULTS The median episode duration (at 3 cm above the LES) was longer and the proximal extent was higher in symptomatic than in asymptomatic reflux episodes (P = 0.006 and P = 0.01). The ascending velocity of the refluxate was not significantly different. The SAP decreased significantly (P < 0.05) from distal to proximal, but no significant differences were found between distal and proximal esophageal levels for the proportion of patients with positive (> 95%) SAP values. CONCLUSIONS The perception of reflux symptoms depends on the duration of acid-exposure episodes and on the proximal extent of the refluxate. Small changes in pH-sensor position do not significantly influence the yield of symptom analysis.

Endoscopic gastroplication for the treatment of gastro-oesophageal reflux disease: a randomised, sham-controlled trial

Background: Endoscopic treatment for gastro-oesophageal reflux disease (GORD) is rapidly emerging, but there is a great need for randomised controlled trials to evaluate the efficacy. Design and setting: A single-centre, double-blind, randomised, sham-controlled trial of endoscopic gastroplication by the Endocinch suturing system. Patients and interventions: 60 patients with GORD were randomly assigned to three endoscopic gastroplications (n = 20), a sham procedure (n = 20) or observation (n = 20). The research nurse and patients in the active and sham groups were blinded to the procedure assignment. After 3 months, open-label active treatment was offered to all patients. Outcome measures: The primary outcome measures were proton pump inhibitor (PPI) use and GORD symptoms, and secondary measures were quality of life, 24-h oesophageal acid exposure, oesophageal manometry and adverse events. Follow-up assessments were performed at 3, 6 and 12 months. Results: At 3 months, the percentage of patients who had reduced drug use by ⩾50% was greater in the active treatment group (65%) than in the sham (25%) or observation groups (0%) (p<0.02). Symptoms (heartburn and to a lesser extent regurgitation) improved more in the active group than in the sham group. Three Short Form-20 quality of life subscales (role function, general health and bodily pain perception) improved in the active group versus sham. Oesophageal acid exposure was modestly decreased after active treatment (p<0.02), but not significantly greater than after the sham procedure (p = 0.61). The active treatment effects on PPI use, symptoms and quality of life persisted after 6 and 12 months of open-label follow-up (n = 41), but 29% of patients were retreated in this period. No serious adverse events occurred. Conclusions: Endoscopic gastroplication, using the Endocinch device, reduced acid-inhibitory drug use, improved GORD symptoms and improved the quality of life at 3 months compared with a sham procedure. The effects persisted up to 12 months. However, the reduction in oesophageal acid exposure was not greater after endoscopic treatment than after a sham procedure.

Hyperglycemia induces abnormalities of gastric myoelectrical activity in patients with type I diabetes mellitus.

BACKGROUND/AIMS Blood glucose concentration has been shown to be an important factor in gastric motility. However, the effect of hyperglycemia on gastric myoelectrical activity has not yet been studied in patients with diabetes. METHODS Surface electrogastrography was performed in eight patients with type I diabetes mellitus under normoglycemic and hyperglycemic conditions (glucose clamp technique) and in eight normoglycemic control subjects. RESULTS In the early postprandial state, the frequency of the normal pacemaker rhythm tended to be higher during hyperglycemia than during normoglycemia (3.10 +/- 0.27 vs. 2.92 +/- 0.19 cycle/min; P = 0.061). The frequency decrease that occurs immediately after a meal was found less frequently during hyperglycemia (in 25% vs. 75% of the patients; P = 0.046). Higher harmonics of the 3-cycle/min component, indicating an electrogastrographic waveform change, were found less often during hyperglycemia (in 13% vs. 63% of the patients; P = 0.039). Dysrhythmias (in particular, tachygastrias) were more prevalent during hyperglycemia (40.6% vs. 6.5% of the time; P = 0.028). No differences were found between normoglycemic patients and control subjects. CONCLUSIONS This study has shown that hyperglycemia is an important factor in the generation of gastric myoelectrical disturbances and tachygastrias in particular.

The effect of baclofen on gastro-oesophageal reflux, lower oesophageal sphincter function and reflux symptoms in patients with reflux disease.

Background : Baclofen decreases gastro‐oesophageal reflux episodes in healthy subjects by reducing the incidence of transient lower oesophageal sphincter relaxations.

Proximal gastric motor activity in response to a liquid meal in type I diabetes mellitus with autonomic neuropathy.

Disordered gastric emptying occurs in 30-50% ofpatients with diabetes mellitus. Although the rate ofgastric emptying is dependent on the integration ofmotor activity in different regions of the stomach, there is limited information about the functionof the proximal stomach in diabetes mellitus. In thepresent study the response of the proximal stomach to aliquid meal was examined in eight diabetic patients with autonomic neuropathy and gastrointestinalsymptoms and in 10 healthy volunteers, using anintragastric bag connected to an electronic barostat.Postprandial relaxation of the proximal stomach wasmeasured as an increase of intragastric bag volume at aconstant pressure level of 1 mm Hg above theintraabdominal pressure. During the experiment the bloodglucose levels were maintained within the euglycemic range. Before ingestion of the meal theintragastric bag volume was larger in the diabeticpatients than in the healthy volunteers, 234.4 ±29.1 ml vs 155.3 ± 15.3 ml (P = 0.06). Themaximum volume was not different in diabetics compared to the healthy controls(386.3 ± 45.2 ml versus 399.0 ± 35.2 ml).However, the maximum volume increase was significantlyless in diabetics (143.7 ± 38.6 ml) compared tothe controls (231.4 ± 30.5 ml, P < 0.04). Bloatingwas inversely correlated with the volume changes, whichsuggests that impaired relaxation of the proximalstomach may play a role in the genesis of thissensation. In conclusion, this study shows a lower fastingfundal tone and a decrease in volume change of thegastric fundus after a nutrient drink in patients withautonomic neuropathy due to type I diabetes mellitus. These abnormalities may play a role in theabnormal distribution of food, disordered liquid gastricemptying, and in the genesis of the sensation ofbloating observed in these patients.