Raf Bisschops

Radiofrequency Ablation vs Endoscopic Surveillance for Patients With Barrett Esophagus and Low-Grade Dysplasia: A Randomized Clinical Trial

IMPORTANCE Barrett esophagus containing low-grade dysplasia is associated with an increased risk of developing esophageal adenocarcinoma, a cancer with a rapidly increasing incidence in the western world. OBJECTIVE To investigate whether endoscopic radiofrequency ablation could decrease the rate of neoplastic progression. DESIGN, SETTING, AND PARTICIPANTS Multicenter randomized clinical trial that enrolled 136 patients with a confirmed diagnosis of Barrett esophagus containing low-grade dysplasia at 9 European sites between June 2007 and June 2011. Patient follow-up ended May 2013. INTERVENTIONS Eligible patients were randomly assigned in a 1:1 ratio to either endoscopic treatment with radiofrequency ablation (ablation) or endoscopic surveillance (control). Ablation was performed with the balloon device for circumferential ablation of the esophagus or the focal device for targeted ablation, with a maximum of 5 sessions allowed. MAIN OUTCOMES AND MEASURES The primary outcome was neoplastic progression to high-grade dysplasia or adenocarcinoma during a 3-year follow-up since randomization. Secondary outcomes were complete eradication of dysplasia and intestinal metaplasia and adverse events. RESULTS Sixty-eight patients were randomized to receive ablation and 68 to receive control. Ablation reduced the risk of progression to high-grade dysplasia or adenocarcinoma by 25.0% (1.5% for ablation vs 26.5% for control; 95% CI, 14.1%-35.9%; P < .001) and the risk of progression to adenocarcinoma by 7.4% (1.5% for ablation vs 8.8% for control; 95% CI, 0%-14.7%; P = .03). Among patients in the ablation group, complete eradication occurred in 92.6% for dysplasia and 88.2% for intestinal metaplasia compared with 27.9% for dysplasia and 0.0% for intestinal metaplasia among patients in the control group (P < .001). Treatment-related adverse events occurred in 19.1% of patients receiving ablation (P < .001). The most common adverse event was stricture, occurring in 8 patients receiving ablation (11.8%), all resolved by endoscopic dilation (median, 1 session). The data and safety monitoring board recommended early termination of the trial due to superiority of ablation for the primary outcome and the potential for patient safety issues if the trial continued. CONCLUSIONS AND RELEVANCE In this randomized trial of patients with Barrett esophagus and a confirmed diagnosis of low-grade dysplasia, radiofrequency ablation resulted in a reduced risk of neoplastic progression over 3 years of follow-up. TRIAL REGISTRATION trialregister.nl Identifier: NTR1198.

Influence of ghrelin on interdigestive gastrointestinal motility in humans

Background: Recent studies in animals have shown that ghrelin stimulates upper gastrointestinal motility through the vagus and enteric nervous system. The aim of the present study therefore was to simultaneously investigate the effect of administration of ghrelin on upper gastrointestinal motility and to elucidate its mode of action by measuring plasma levels of gastrointestinal hormones in humans. Materials and methods: Nine healthy volunteers (four males; aged 22–35 years) underwent combined antroduodenal manometry and proximal stomach barostat study on two separate occasions at least one week apart. Twenty minutes after the occurrence of phase III of the migrating motor complex (MMC), saline or ghrelin 40 μg was administered intravenously over 30 minutes in a double blind, randomised, crossover fashion. Ghrelin, motilin, pancreatic polypeptide, glucagon, and somatostatin were measured by radioimmunoassay in blood samples obtained at 15–30 minute intervals. The influence of ghrelin or saline on MMC phases, hormone levels, and intraballoon volume was compared using paired t test, ANOVA, and χ2 testing. Results: Spontaneous phase III occurred in all subjects, with a gastric origin in four. Administration of ghrelin induced a premature phase III (12 (3) minutes, p<0.001; gastric origin in nine, p<0.05), compared with saline (95 (13) minutes, gastric origin in two). Intraballoon volumes before infusion were similar (135 (13) v 119 (13) ml; NS) but ghrelin induced a longlasting decrease in intraballoon volume (184 (31) v 126 (21) ml in the first 60 minutes; p<0.05). Administration of ghrelin increased plasma levels of pancreatic polypeptide and ghrelin but motilin, somatostatin, and glucagon levels were not altered. Conclusions: In humans, administration of ghrelin induces a premature gastric phase III of the MMC, which is not mediated through release of motilin. This is accompanied by prolonged increased tone of the proximal stomach.

Influence of ghrelin on gastric emptying and meal-related symptoms in idiopathic gastroparesis.

Background : Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, is released from the stomach. Animal studies suggest that ghrelin stimulates gastrointestinal motor activity.

Pathophysiology, diagnosis and management of postoperative dumping syndrome

Dumping syndrome is a frequent complication of esophageal, gastric or bariatric surgery. Rapid gastric emptying, with the delivery to the small intestine of a significant proportion of solid food as large particles that are difficult to digest, is a key event in the pathogenesis of this syndrome. This occurrence causes a shift of fluid from the intravascular component to the intestinal lumen, which results in cardiovascular symptoms, release of several gastrointestinal and pancreatic hormones and late postprandial hypoglycemia. Early dumping symptoms comprise both gastrointestinal and vasomotor symptoms. Late dumping symptoms are the result of reactive hypoglycemia. Besides the assessment of clinical alertness and endoscopic or radiological imaging, a modified oral glucose tolerance test might help to establish a diagnosis. The first step in treating dumping syndrome is the introduction of dietary measures. Acarbose can be added to these measures for patients with hypoglycemia, whereas several studies advocate guar gum or pectin to slow gastric emptying. Somatostatin analogs are the most effective medical therapy for dumping syndrome, and a slow-release preparation is the treatment of choice. In patients with treatment-refractory dumping syndrome, surgical reintervention or continuous enteral feeding can be considered, but the outcomes of such approaches are variable.

Clinical trial: a randomized-controlled crossover study of intrapyloric injection of botulinum toxin in gastroparesis

Background  Uncontrolled studies suggest benefit of intrapyloric injection of botulinum toxin (botox) for the treatment of gastroparesis, but controlled data are lacking.

Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

MAIN RECOMMENDATIONS 1 ESGE suggests the routine use of high definition white-light endoscopy systems for detecting colorectal neoplasia in average risk populations (weak recommendation, moderate quality evidence). 2 ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (narrow band imaging [NBI], i-SCAN) chromoendoscopy in patients with known or suspected Lynch syndrome (strong recommendation, low quality evidence). 2b ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (NBI) chromoendoscopy in patients with known or suspected serrated polyposis syndrome (strong recommendation, low quality evidence). 3 ESGE recommends the routine use of 0.1 % methylene blue or 0.1 % - 0.5 % indigo carmine pancolonic chromoendoscopy with targeted biopsies for neoplasia surveillance in patients with long-standing colitis. In appropriately trained hands, in the situation of quiescent disease activity and adequate bowel preparation, nontargeted, four-quadrant biopsies can be abandoned (strong recommendation, high quality evidence). 4 ESGE suggests that virtual chromoendoscopy (NBI, FICE, i-SCAN) and conventional chromoendoscopy can be used, under strictly controlled conditions, for real-time optical diagnosis of diminutive (≤ 5 mm) colorectal polyps to replace histopathological diagnosis. The optical diagnosis has to be reported using validated scales, must be adequately photodocumented, and can be performed only by experienced endoscopists who are adequately trained and audited (weak recommendation, high quality evidence). 5 ESGE suggests the use of conventional or virtual (NBI) magnified chromoendoscopy to predict the risk of invasive cancer and deep submucosal invasion in lesions such as those with a depressed component (0-IIc according to the Paris classification) or nongranular or mixed-type laterally spreading tumors (weak recommendation, moderate quality evidence). CONCLUSION Advanced imaging techniques will need to be applied in specific patient groups in routine clinical practice and to be taught in endoscopic training programs.

Prognostic value of serologic and histologic markers on clinical relapse in ulcerative colitis patients with mucosal healing.

OBJECTIVES:Endoscopic mucosal healing is a key endpoint for the treatment of ulcerative colitis (UC). The role of microscopic activity in predicting disease relapse has not been fully assessed. We aimed to investigate the predictive role of serologic and histologic markers on disease relapse in UC patients with endoscopically inactive disease.METHODS:Adult UC patients with endoscopically inactive disease (Mayo 0) and a 12-month follow-up between 2008 and 2011 were retrospectively included. An expert pathologist evaluated all colonic biopsies for histologic activity (Geboes score) and the presence of basal plasmacytosis. Blood samples collected around the time of endoscopy were analyzed. Disease relapse, defined as a clinical Mayo score ≥3, was documented during follow-up.RESULTS:The study cohort consisted of 75 patients (53% men, median age 47 years). Despite normal endoscopy, histology showed inflammatory activity with a Geboes score ≥3.1 in 40% and basal plasmacytosis in 21% of patients. At 12 months, clinical relapse was observed in 20% (n=15) of patients. Presence of basal plasmacytosis (P=0.007) and a Geboes score ≥3.1 (P=0.007) were predictive of disease relapse. Using multivariate analysis, the presence of basal plasmacytosis was predictive of clinical relapse (odds ratio (OR) 5.13 (95% confidence interval (CI): 1.32–19.99), P=0.019), whereas the use of biologicals at endoscopy favored remission (OR 0.24 (95% CI: 0.05–1.01), P=0.052).CONCLUSIONS:We demonstrated that the presence of basal plasmacytosis predicts UC clinical relapse in patients with complete mucosal healing. We recommend closer follow-up and optimization of medical therapy in patients with basal plasmacytosis.

Acid and weakly acidic solutions impair mucosal integrity of distal exposed and proximal non-exposed human oesophagus

Background Oesophageal mucosa dilated intercellular spaces (DIS) may be important for symptom perception in non-erosive reflux disease (NERD). Patients with NERD might have DIS even in the proximal oesophagus. We aimed to assess the effect of oesophageal perfusions with acid and weakly acidic solutions on ‘exposed’ and ‘non-exposed’ oesophageal mucosa and its relationship to symptoms in healthy subjects. Methods 14 healthy volunteers underwent upper gastrointestinal endoscopy with biopsies at 3 and 13 cm proximal to the oesophagogastric junction (OGJ). In following sessions, subjects received 30 min perfusions with neutral, weakly acidic, acidic and acidic-bile acid solutions at 5 cm above the EGJ (separated 4 weeks). Biopsies were taken 20 min after perfusions. Electron microscopy was used to measure DIS. Subjects scored heartburn during perfusions using a visual analogue scale. Results (1) Oesophageal perfusion with acid solutions, with or without bile acids, provoked DIS in the ‘exposed’ oesophageal mucosa; (2) oesophageal perfusion with weakly acidic solutions provoked identical changes to those observed after perfusion with acid solutions; (3) distal oesophageal perfusions not only provoked changes in the ‘exposed’ but also in the more proximal ‘non-exposed’ mucosa; and (4) in spite of the presence of perfusion-induced DIS, most healthy subjects did not perceive heartburn during the experiments. Conclusions The human oesophageal mucosa is very sensitive to continuous exposure with acidic and weakly acidic solutions. In spite of the presence of intraluminal acid and DIS, healthy subjects did not experience heartburn, suggesting that NERD patients should have other critical factors underlying their symptoms.

Long Term outcome of endoscopic dilatation in patients with Crohn’s disease is not affected by disease activity or medical therapy

Background Endoscopic dilatation of Crohns disease-related strictures is an alternative to surgical resection in selected patients. The influence of disease activity and concomitant medical therapy on long-term outcomes is largely unknown. Aim and methods To study the long-term safety and efficacy of stricture dilatation in a single centre cohort. Results Between 1995 and 2006, 237 dilatations where performed in 138 patients (mean age 50.6±13.4, 56% female) for a clinically obstructive stricture (<5 cm, 84% anastomotic). Immediate success of a first dilatation was 97% with a 5% serious complication rate. After a median follow-up of 5.8 years (IQR 3.0–8.4), recurrent obstructive symptoms led to a new dilatation in 46% or surgery in 24%. Niether elevated levels of C-reactive protein nor endoscopic disease activity predicted the need for new intervention. None of the concomitant therapies influenced the outcome. Conclusion This largest series ever reported confirms that long term efficacy of endoscopic dilatation of Crohns disease outweighs the complication risk. Neither active disease at the time of dilatation nor medical therapy afterwards predict recurrent dilatation or surgery.

Relationship Between Symptoms And Ingestion Of A Meal In Functional Dyspepsia

Backgound and aims: A subset of functional dyspepsia (FD) patients report meal-related symptoms, possibly representing a pathophysiologically homogeneous subgroup. The aim of the present study was to establish the time-course of symptoms in relation to meal ingestion, and to assess the relationship between self-reported meal-related symptoms and pathophysiological mechanisms in FD. Methods: 218 FD patients (149 women, mean (SEM) age 39 (1) years) filled out a symptom questionnaire, including meal-induced aggravation. All patients underwent a gastric emptying breath test with severity (0–4) scoring of six symptoms (pain, fullness, bloating, nausea, burning and belching) at each sampling (15 min interval for 4 h). In 129 patients, gastric sensitivity and accommodation were assessed by barostat. Results: The intensity of each FD symptom was significantly increased 15 min after the meal, compared with the premeal score, and remained elevated until the end of the measurement period (all p<0.05). The time-course of individual symptoms varied, with early peaks for fullness and bloating, intermediate peaks for nausea and belching, and late peaks for pain and burning. Meal-induced aggravation was reported by 79% of patients, and in these patients postprandial fullness, which peaked early, was the most intense symptom. In patients without self-reported meal-induced aggravation, epigastric pain, which had a delayed peak, was the most intense symptom and they had a lower prevalence of gastric hypersensitivity (27.5% vs 7.7%). Conclusion: Meal ingestion aggravates FD symptoms in the vast majority of patients, with symptom-specific time-courses. Postprandial fullness is the most severe symptom in patients reporting aggravation by a meal, while it is pain in those not reporting meal-related symptoms.