The effect of a controlled gluten challenge in a group of patients with suspected non-coeliac gluten sensitivity: A randomized, double-blind placebo-controlled challenge.

BACKGROUND: Non-coeliac gluten-sensitivity (NCGS) has been proposed as a new entity with unknown prevalence and mechanisms, and there is a need for a standardized procedure to confirm the diagnosis. The objective of this study was to characterize the response to an oral gluten-challenge in patients with a symptom-relief when following a gluten free-diet (GFD). METHODS: Twenty patients (14F/6M, age range: 21-62 years) with suspected NCGS, without coeliac disease and wheat-allergy, were included while on a gluten-free diet. All patients went through four periods of double-blinded provocation, two with gluten and two with placebo in randomized order. They consumed two muffins a day (11/0 g gluten) for 4 days, followed by a 3-day wash-out. Gastrointestinal symptoms were recorded with questionnaires at baseline and after each provocation. We also investigated whether patients were able to correctly identify periods with gluten-exposure. KEY RESULTS: Collectively the whole group reported the most severe symptoms after placebo (P = .012). Four out of twenty patients correctly identified the two periods when they received gluten, hence were diagnosed with NCGS. The diagnosed-group tended to show higher symptom scores than the not-diagnosed group both at baseline, after gluten exposure and after placebo, but no clear difference was seen between provocation with gluten and placebo. The not-diagnosed group showed more severe symptoms with placebo than with gluten (P = .029). CONCLUSIONS AND INFERENCES: The present study showed that the majority of patients with suspected NCGS are not able to identify when challenged with gluten in a double-blind placebo-controlled food challenge, indicating that gluten is not the cause of their symptoms.

Navigated retrograde endoscopic myotomy (REM) for the treatment of therapy-resistant achalasia.

BACKGROUND: In achalasia, muscle spasm may involve the proximal esophagus. When the muscle spasm is located in the proximal esophagus, conventional per oral endoscopic myotomy (POEM) may not be sufficient to relieve symptoms. In this paper, we describe retrograde endoscopic myotomy (REM) as a novel approach to perform myotomy of the proximal esophagus, with the application of a navigation tool for anatomical guidance during REM. We aim to evaluate the feasibility and safety of REM and usefulness of the navigation during REM. METHOD: A 42-year-old male with type III achalasia who was treated with laparoscopic myotomy with fundoplication, multiple pneumatic balloon dilations, Botox injections and anterior POEM of the middle and distal esophagus without symptomatic effect. Repeated high-resolution- manometry (HRM) revealed occluding contractions of high amplitude around and above the aortic arch. A probe-based real-time electromagnetic navigation platform was used to facilitate real-time anatomical orientation and to evaluate myotomy position and length during REM. RESULTS: The navigation system aided in identifying the major structures of the mediastinum, and position and length of the myotomy. Twelve weeks after REM, the Eckardt score fell from seven at baseline seven to two. We also observed improvement with reduction of the pressure at the level of previous spasms in the proximal esophagus from 124 mmHg to 8 mmHg on HRM. CONCLUSION: REM makes the proximal esophagus accessible for endoscopic myotomy. Potential indication for REM is motility disorders in the proximal esophagus and therapy failure after POEM.

Gastric accommodation in healthy subjects studied by ultrasound, manometry, and impedancemetry.

BACKGROUND: Gastric accommodation to a meal may be important in the pathogenesis of upper gastrointestinal disorders, but has been difficult to investigate in a minimally invasive fashion. METHODS: We studied gastric and lower esophageal physiology during food intake, combining transabdominal ultrasound, multichannel high-resolution impedance-manometry (HRIM) and a symptom questionnaire. A HRIM catheter was distally positioned at incisura angularis and 300 mL saline with 75 g glucose was ingested. Target variables were recorded for 30 min after fluid intake. KEY RESULTS: Fifteen healthy subjects' participated (11W/4M, median age 23.8 y) and all accepted the meal with few symptoms. At incisura angularis maximum change in pressure from pre-intake values was -7.4 mmHg after 60 s (P < .0001), rising to pre-intake values within 20 min. The corresponding area increased significantly from pre-intake values of 8.0 cm2 to 14.1 cm2 shortly after intake (P = .0012), peaked at 5 min and slowly decreased towards 30 min. The corresponding maximum change in stress from pre-intake pressure values was -59.2 mmHg shortly after (P < .0001), reaching pre-intake values within 20 min. Strain rose from 0 shortly before to 0.36 shortly after (P < .0001), peaking at 5 min. At incisura angularis, fullness was positively correlated with area and to strain, while fullness, area, and stress were negatively correlated with pressure. CONCLUSIONS & INFERENCES: The multimodal method enabled assessment of the gastric accommodation reflex, stress and strain in the stomach. It triggered few symptoms in healthy volunteers. We propose it to be a more physiological replacement of the barostat technique.

The dynamics of the oesophageal squamous epithelium 'normalisation' process in patients with gastro-oesophageal reflux disease treated with long-term acid suppression or anti-reflux surgery.

BACKGROUND: Proton pump inhibitors and laparoscopic anti-reflux surgery (LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease (GERD). AIM: To evaluate the process of 'normalisation' of the squamous epithelium morphology of the distal oesophagus on these therapies. METHODS: In the LOTUS trial, 554 patients with chronic GERD were randomised to receive either esomeprazole (20-40 mg daily) or LARS. After 5 years, 372 patients remained in the study (esomeprazole, 192; LARS, 180). Biopsies were taken at the Z-line and 2 cm above, at baseline, 1, 3 and 5 years. A severity score was calculated based on: papillae elongation, basal cell hyperplasia, intercellular space dilatations and eosinophilic infiltration. The epithelial proliferative activity was assessed by Ki-67 immunohistochemistry. RESULTS: A gradual improvement in all variables over 5 years was noted in both groups, at both the Z-line and 2 cm above. The severity score decreased from baseline at each subsequent time point in both groups (P < 0.001, all comparisons), attaining a normal level by 5 years. Corresponding decreases in Ki-67 expression were observed (P < 0.001, all comparisons). No significant differences were found between esomeprazole treatment and LARS. Neither baseline severity score nor Ki-67 expression predicted the risk of treatment failure. CONCLUSIONS: Five years of treatment is generally required before squamous epithelial cell morphology and proliferation are 'normalised' in patients with chronic GERD, despite endoscopic and symptomatic disease control. Control of the acid component of the refluxate seems to play the predominant role in restoring tissue morphology.

Gastro-oesophageal reflux in patients with chronic rhino-sinusitis investigated with multichannel impedance - pH monitoring.

INTRODUCTION: The pathophysiology of chronic rhinosinusitis (CRS) is unclear. It has been discussed for decades whether gastro-oesophageal reflux (GOR) may be a contributing factor for some patients. The aim of the present study was to evaluate the level of GOR in an unselected group of patients with CRS using multichannel impedance-pH monitoring. METHODS: Consecutive patients with CRS diagnosed using the EPOS2012 criteria, completed questionnaires on GOR symptoms and were offered 24-h multichannel intraluminal impedance (MII)-pH monitoring. The results were compared with a group of healthy controls. RESULTS: Forty-six patients completed MII-pH-monitoring and were compared with 45 control subjects, with comparable age and gender distributions. The median number of reflux episodes in the patients was 56.5 compared with 33 in controls, while, the numbers of proximal reflux episodes was 27.5 versus 3, respectively. Thirty nine patients had abnormal pH-impedance recordings compared with five controls. CONCLUSION: The CRS patients had significantly higher incidences of gastro-oesophageal reflux compared with asymptomatic controls. The results of this study suggest that GOR may be a causative or contributing factor of CRS.

Effects of varying dietary content of fermentable short-chain carbohydrates on symptoms, fecal microenvironment, and cytokine profiles in patients with irritable bowel syndrome.

BACKGROUND: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) is increasingly recommended for patients with irritable bowel syndrome (IBS). We aimed to investigate the effects of a blinded low-FODMAP vs high-fructo-oligosaccharides (FOS) diet on symptoms, immune activation, gut microbiota composition, and short-chain fatty acids (SCFAs). METHODS: Twenty patients with diarrhea-predominant or mixed IBS were instructed to follow a low-FODMAP diet (LFD) throughout a 9-week study period. After 3 weeks, they were randomized and double-blindly assigned to receive a supplement of either FOS (FODMAP) or maltodextrin (placebo) for the next 10 days, followed by a 3-week washout period before crossover. Irritable bowel syndrome severity scoring system (IBS-SSS) was used to evaluate symptoms. Cytokines (interleukin [IL]-6, IL-8, and tumor necrosis factor alpha) were analyzed in blood samples, and gut microbiota composition (16S rRNA) and SCFAs were analyzed in fecal samples. KEY RESULTS: Irritable bowel syndrome symptoms consistently improved after 3 weeks of LFD, and significantly more participants reported symptom relief in response to placebo (80%) than FOS (30%). Serum levels of proinflammatory IL-6 and IL-8, as well as levels of fecal bacteria (Actinobacteria, Bifidobacterium, and Faecalibacterium prausnitzii), total SCFAs, and n-butyric acid, decreased significantly on the LFD as compared to baseline. Ten days of FOS supplementation increased the level of these bacteria, whereas levels of cytokines and SCFAs remained unchanged. CONCLUSIONS AND INFERENCES: Our findings support the efficacy of a LFD in alleviating IBS symptoms, and show changes in inflammatory cytokines, microbiota profile, and SCFAs, which may have consequences for gut health.

Long-term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: data from the SOPRAN and LOTUS studies.

BACKGROUND: Control of chronic gastro-oesophageal reflux disease may be achieved either by anti-reflux surgery (ARS) or by long-term medical therapy with proton pump inhibitors (PPIs). The primary efficacy results of the SOPRAN study, comparing long-term omeprazole use with open ARS, and the LOTUS study, comparing long-term esomeprazole use with laparoscopic ARS, have been reported. A secondary objective of these studies was to address the long-term safety of these respective therapeutic strategies and thereby provide a valid scientific platform for assessing long-term PPI safety. AIM: To assess the safety of long-term PPI therapy with omeprazole and esomeprazole through analyses of data from the randomised SOPRAN and LOTUS studies. METHODS: Safety data were collected from patients during the 12-year period of the SOPRAN study (n = 298) and the 5-year period of the LOTUS study (n = 514). Reported serious adverse events (SAEs) and changes in laboratory variables were analysed. RESULTS: Across both studies, SAEs were reported at a similar frequency in the PPI and ARS treatment groups. Taking the time frames into consideration, the number of fatal SAEs in the two studies was low in both treatment groups. Laboratory results, including routine haematology and tests for liver enzymes, electrolytes, vitamin D, vitamin B12 , folate and homocysteine, showed no clinically relevant changes over time. As expected, gastrin and chromogranin A were elevated in the PPI groups, with the greatest increases observed in the first year. CONCLUSION: No major safety concerns arose during 5-12 years of continuous PPI therapy. (ClinicalTrials.gov: NCT00251927 and NCT00256737).

Central response to painful electrical esophageal stimulation in well-defined patients suffering from functional chest pain.

BACKGROUND: Functional chest pain (FCP) of presumed esophageal origin is considered a common cause for chest pain in which central nervous system hyperexcitability is thought to play an important role. We aimed to compare cerebral responses with painful esophageal stimuli between FCP patients and healthy subjects (HS). METHODS: Thirteen patients with FCP (seven females, mean age 50.4 ± 7.5 years) and 15 HS (eight females, mean age 49.1 ± 12.9 years) were enrolled. Inclusion criteria consisted of typical chest pain, normal coronary angiogram, and normal upper gastrointestinal evaluation. Electrical stimulations evoking the pain threshold were applied in the distal esophagus, while cortical evoked potentials were recorded from the scalp. Pain scores, resting electroencephalogram (EEG), evoked potential characteristics and brain electrical sources to pain stimulation were compared between groups. KEY RESULTS: No differences were seen between patients and HS regarding (i) pain thresholds (patients: 20.1 ± 7.4 mA vs HS: 22.4 ± 8.3 mA, all P > 0.05), (ii) resting-EEG (P > 0.05), (iii) evoked brain potential latencies (N2: patients 181.7 ± 25.7 mS vs HS 182.2 ± 25.8 mS, all P > 0.05) and amplitudes (N2P2: patients 8.2 ± 7.2 µV vs HS: 10.1 ± 3.4 µV, all P > 0.05), (iv) topography (P > 0.05), and (v) brain source location (P > 0.05). CONCLUSIONS & INFERENCES: No differences in activation of brain areas to painful esophageal stimulation were seen in this group of well characterized patients with FCP compared with sex- and age-matched HS. The mechanism of pain in FCP and whether it originates in the esophagus remains unsolved.

Validation of the GerdQ questionnaire for the diagnosis of gastro-oesophageal reflux disease.

BACKGROUND: The diagnosis of gastro-oesophageal reflux disease (GERD) remains a challenge as both invasive methods and symptom-based strategies have limitations. The symptom-based management of GERD in primary care may be further optimised with the use of a questionnaire. AIM: To assess the diagnostic validity of the GerdQ questionnaire in patients with symptoms suggestive of GERD. METHODS: Patients with symptoms suggestive of GERD without alarm features, underwent upper endoscopy, and if normal, pH-metry. Patients were followed for 4 weeks and GerdQ was completed blinded to the investigator at both visits. Reflux oesophagitis or pathological acid exposure was used as diagnostic references for GERD. The diagnostic accuracy for GERD on symptom response to proton pump inhibitor (PPI) was assessed. RESULTS: Among the 169 patients, a GerdQ cutoff ≥9 gave the best balance with regard to sensitivity, 66% (95% CI: 58-74), and specificity, 64% (95% CI: 41-83), for GERD. The high prevalence of reflux oesophagitis (81%) resulted in a high proportion of true positives, but at the same time a high proportion of false-negatives. Consequently, GerdQ had a high positive predictive value, 92% (95% CI: 86-97), but a low negative predictive value, 22% (95% CI: 13-34), for GERD. Symptom resolution on PPI therapy had high sensitivity, 76% (95% CI: 66-84), but low specificity, 33% (95% CI: 17-53), for GERD. CONCLUSIONS: GerdQ is a useful complementary tool for the diagnosis of gastro-oesophageal reflux disease in primary care. The implementation of GerdQ could reduce the need for upper endoscopy and improve resource utilisation. Symptom resolution on proton pump inhibitor did not predict gastro-oesophageal reflux disease.

Randomised clinical trial: a comparison between a GerdQ-based algorithm and an endoscopy-based approach for the diagnosis and initial treatment of GERD.

BACKGROUND: The diagnosis of gastro-oesophageal reflux disease (GERD) remains challenging. An algorithm, facilitated by a questionnaire, may provide a more structured and cost-effective care of patients. AIM: To compare symptom control achieved with empirical therapy for GERD, in an algorithm based on the GerdQ (new structured pathway, NSP), with that of current care after endoscopy (ordinary clinical pathway, OCP). METHODS: Patients with symptoms of GERD, but without alarm features, were randomised in an open, parallel-group study and followed for 4-8 weeks. In the NSP, GerdQ score was used as a basis for both diagnosis and a treatment algorithm. Patients with high likelihood of GERD were treated empirically with a PPI whereas patients with low likelihood of GERD received therapy chosen by the clinician. In the OCP, diagnosis and treatment were based on endoscopy or pH-metry findings. The statistical hypothesis was non-inferiority of NSP to OCP. RESULTS: A total of 147 patients (86.5%) in the NSP and 133 patients (80.1%) in the OCP arm were responders. Overall, NSP was non-inferior to OCP, but not superior (P = 0.14). Patients with high likelihood of GERD had significantly better symptom relief in the NSP (P = 0.03), whereas those with low likelihood of GERD showed a numerical difference in favour of an endoscopy-based approach (OCP). NSP saved 146 € per patient. CONCLUSIONS: A symptom-based approach using GerdQ reduced health care costs without loss in efficacy. Patients with high likelihood GERD benefited from empirical treatment. An algorithm based on GerdQ may provide physicians with a tool for a more structured care of patients (ClinicalTrials.gov NCT00842387).

The role of diet in the pathogenesis and management of irritable bowel syndrome (Review).

Most patients with irritable bowel syndrome (IBS) believe that diet plays a significant role in inducing IBS symptoms and desire to know what foods to avoid. It has been found that the intake of calories, carbohydrates, proteins and fat by IBS patients does not differ from that of the background population. IBS patients were found to avoid certain food items that are rich in fermentable oligo-, di- and monosacharides and polyols (FODMAPs), but they did have a high consumption of many other FODMAP-rich food items. The diet of IBS patients was found to consist of a low calcium, magnesium, phosphorus, vitamin B2 and vitamin A content. There is no consistent evidence that IBS patients suffer from food allergy, nor is there documented evidence that food intolerance plays a role in IBS symptoms. Abnormalities in gut hormones have been reported in IBS patients. As gut hormones control and regulate gastrointestinal motility and sensation, this may explain the abnormal gastrointestinal motility and visceral hypersensitivity reported in these patients. Guidance concerning food management which includes individually based restrictions of FODMAP-rich food items and individual evaluation of the effects of protein-, fat- and carbohydrate-rich/poor diets may reduce IBS symptoms.

Low densities of serotonin and peptide YY cells in the colon of patients with irritable bowel syndrome.

BACKGROUND: The gut hormones are important in regulating gastrointestinal motility. Disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). Reduced endocrine cell density, as revealed by chromogranin A, has been reported in the colon of IBS patients. AIMS: To investigate a possible abnormality in the colonic endocrine cells of IBS patients. METHODS: A total of 41 patients with IBS according to Rome Criteria III and 20 controls were included in the study. Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. The biopsies were immunostained for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), entroglucagon, and somatostatin cells. Cell densities were quantified by computerized image analysis. RESULTS: Serotonin and PYY cell densities were reduced in the colon of IBS patients. PP, entroglucagon, and somatostatin-immunoreactive cells were too few to enable reliable quantification. CONCLUSION: The cause of these observations could be primary genetic defect(s), secondary to altered serotonin and/or PYY signaling systems and/or subclinical inflammation. Serotonin activates the submucosal sensory branch of the enteric nervous system and controls gastrointestinal motility and chloride secretion via interneurons and motor neurons. PYY stimulates absorption of water and electrolytes, and inhibits prostaglandin (PG) E2, and vasoactive intestinal peptide, which stimulates intestinal fluid secretion and is a major regulator of the "ileal brake". Although the cause and effect relationship of these findings is difficult to elucidate, the abnormalities reported here might contribute to the symptoms associated with IBS.

Sensation evoked by esophageal distension in functional chest pain patients depends on mechanical stress rather than on ischemia.

BACKGROUND: Functional chest pain is commonly reproduced by bag distension in the esophageal body. It is unknown whether such pain is primarily associated with mechanical stress and strain (force-deformation) or with changes in mucosal perfusion. METHODS: Fourteen patients (6M, 8F, average age 55.9 years) underwent ramp bag distension before and after injection of 20 mg butylscopolamine bromide (BS) using a novel bag catheter incorporating endosonography and laser Doppler perfusion monitoring. Healthy subjects served as controls. Mucosal perfusion was evaluated and stress and strain were computed and related to the sensation. KEY RESULTS: The symptom score increased with bag volume (P < 0.001). Volume as a function of pressure was higher in patients than in controls (P < 0.001), both before and during BS. The stress-strain relationship was exponential and indicated a stiffer esophageal wall in patients especially before BS (P < 0.01). The stress-strain curves indicate increased muscle tone in the functional chest pain patients. The perfusion decreased with increasing symptom score from visual analog scale 1-7 during BS. The decrease was on average 18.9% in patients and 19.7% in controls (P = ns). Multiple regression analysis from distensions during BS showed that the discomfort/pain sensations depended on stress and strain (P < 0.001) and with stress as the largest contributor. Perfusion did not contribute. CONCLUSIONS & INFERENCES: Pain evoked by bag distension in patients with functional chest pain is stress-dependent rather than dependent on mucosal perfusion. Furthermore, the esophagus of the patients was characterized by more pronounced muscle tone during the distensions.

Medical or surgical management of GERD patients with Barrett's esophagus: the LOTUS trial 3-year experience.

INTRODUCTION: The long-term management of gastroesophageal reflux in patients with Barrett's esophagus (BE) is not well supported by an evidence-based consensus. We compare treatment outcome in patients with and without BE submitted to standardized laparoscopic antireflux surgery (LARS) or esomeprazole treatment. METHODS: In the Long-Term Usage of Acid Suppression Versus Antireflux Surgery trial (a European multicenter randomized study), LARS was compared with dose-adjusted esomeprazole (20-40 mg daily). Operative difficulty, complications, symptom outcomes [Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD)], and treatment failure at 3 years and pH testing (after 6 months) are reported. RESULTS: Of 554 patients with gastroesophageal reflux disease, 60 had BE-28 randomized to esomeprazole and 32 to LARS. Very few BE patients on either treatment strategy (four of 60) experienced treatment failure during the 3-year follow-up. Esophageal pH in BE patients was significantly better controlled after surgical treatment than after esomeprazole (p = 0.002), although mean GSRS and QOLRAD scores were similar for the two therapies at baseline and at 3 years. Although operative difficulty was slightly greater in patients with BE than those without, there was no difference in postoperative complications or level of symptomatic reflux control. CONCLUSION: In a well-controlled surgical environment, the success of LARS is similar in patients with or without BE and matches optimized medical therapy.

Seven-year follow-up of a randomized clinical trial comparing proton-pump inhibition with surgical therapy for reflux oesophagitis.

BACKGROUND: This randomized clinical trial compared long-term outcome after antireflux surgery with acid inhibition therapy in the treatment of chronic gastro-oesophageal reflux disease (GORD). METHODS: Patients with chronic GORD and oesophagitis verified at endoscopy were allocated to treatment with omeprazole (154 patients) or antireflux surgery (144). After 7 years of follow-up, 119 patients in the omeprazole arm and 99 who had antireflux surgery were available for evaluation. The primary outcome variable was the cumulative proportion of patients in whom treatment failed. Secondary objectives were evaluation of the treatment failure rate after dose adjustment of omeprazole, safety, and the frequency and severity of post-fundoplication complaints. RESULTS: The proportion of patients in whom treatment did not fail during the 7 years was significantly higher in the surgical than in the medical group (66.7 versus 46.7 per cent respectively; P=0.002). A smaller difference remained after dose adjustment in the omeprazole group (P=0.045). More patients in the surgical group complained of symptoms such as dysphagia, inability to belch or vomit, and rectal flatulence. These complaints were fairly stable throughout the study interval. The mean daily dose of omeprazole was 22.8, 24.1, 24.3 and 24.3 mg at 1, 3, 5 and 7 years respectively. CONCLUSION: Chronic GORD can be treated effectively by either antireflux surgery or omeprazole therapy. After 7 years, surgery was more effective in controlling overall disease symptoms, but specific post-fundoplication complaints remained a problem. There appeared to be no dose escalation of omeprazole with time.

Changes of gastric mucosal architecture during long-term omeprazole therapy: results of a randomized clinical trial.

BACKGROUND: The impact of long-term acid suppression on the gastric mucosa remains controversial. AIM: To report further observations on an established cohort of patients with gastro-oesophageal reflux disease, after 7 years of follow-up. METHODS: Of the original cohort randomized to either antireflux surgery or omeprazole, 117 and 98 patients remained in the medical and surgical arms, respectively. Gastric biopsies were taken at baseline and throughout the study. RESULTS: Fifty-three antireflux surgery and 39 omeprazole-treated patients had Helicobacter pylori infection at randomization. Eighty-three omeprazole-treated and 60 antireflux surgery patients remained H. pylori negative over the 7 years, and no change was observed in mucosal morphology except for a change in endocrine cell population (linear and diffuse hyperplasia, P = 0.03). During the 7-year study many patients, who were initially H. pylori infected, had the infection eradicated leaving only 13 omeprazole and 12 antireflux surgery patients still infected. In these patients, omeprazole induced a deterioration of the mucosal inflammation scores (P = 0.01) with a numerical increase of glandular atrophy. CONCLUSIONS: Long-term omeprazole therapy does not alter the exocrine oxyntic mucosal morphology in H. pylori-negative patients, but mucosal endocrine cells appear to be under proliferative stimulation; in H. pylori-positive patients there are changes in mucosal inflammation and atrophy.

A multimodal laser Doppler and endosonographic distension device for studying mechanosensation and mucosal blood flow in the oesophagus.

We describe the development of a multimodal device combining bag distension, manometry, high frequency intraluminal ultrasound, laser Doppler flowmetry and symptom registration. Bench tests showed that the different modalities did not influence each other. During bag distension we obtained high quality images of the oesophageal wall for computing biomechanical parameters, and laser Doppler signals showing variation in mucosal perfusion. We conclude that the principle of measurement is sound and that the device can provide a basis for further studies.

Diagnostic approach to suspected irritable bowel syndrome.

Diagnostic activity in patients with suspected irritable bowel syndrome (IBS) should be brief and focussed, limited to investigations that are likely to exclude serious alternative diagnoses and when negative support a positive diagnosis of IBS. The diagnosis of IBS is clinical, and is robust over time, although other symptoms may add to the clinical picture and other symptoms of functional disorders are common. The most important differential diagnoses are celiac disease, colorectal carcinoma and colitis. 'Red Flag' symptoms and signs should be considered indications for full colonoscopy, which should be performed with a low threshold in patients above 50 years of age. Serologic markers are useful to exclude celiac disease, but positive tests must be confirmed with duodenal biopsies.

Symptom-relieving effect of esomeprazole 40 mg daily in patients with heartburn.

BACKGROUND: To assess symptom relief in patients with heartburn following treatment with esomeprazole 40 mg daily. METHODS: Patients with heartburn (for > or = 6 months) were assessed in this double-blind, multicenter study. After a 3-day single-blind placebo run-in, 440 patients were randomized to esomeprazole 40 mg o.d., esomeprazole 20 mg b.i.d. or placebo for 14 days. Heartburn symptoms were recorded daily; as insufficient patients had data available from days 13 and 14, analyses included data up to day 12. Gastroesophageal reflux disease (GERD) was diagnosed by upper GI endoscopy and 24-h pH-monitoring. The primary end-point was total heartburn relief defined as no heartburn symptoms during the preceding 24-h period. RESULTS: 240 patients had erosive esophagitis (EO) and 114 patients had GERD defined by pH-monitoring. Proportions of patients with total heartburn relief increased during the first days of treatment and stabilized after Day 4. Total heartburn relief occurred in 67%-73%, 62%-70%, and 21%-32% of patients in the esomeprazole 40 mg o.d., esomeprazole 20 mg b.i.d., and placebo groups, respectively, between days 6 and 12. Proportions of patients with total heartburn relief were higher in patients with EO (71%-80% of patients from Day 4 onwards) compared to those without EO (52%-67% of patients from Day 4 onwards). Figures for patients diagnosed by pH-monitoring were 65%-73% of those with a positive diagnosis and 51%-58% with a negative diagnosis. CONCLUSION: Esomeprazole 40 mg o.d. treatment produces total heartburn relief in a high proportion of patients with GERD. Once-daily esomeprazole 40 mg dosing is recommended as no advantage was gained by splitting the dose.