An Interactive Web-Based Educational Tool Improves Detection and Delineation of Barrett's Esophagus-Related Neoplasia.

BACKGROUND & AIMS: Endoscopic detection of early Barrett's esophagus-related neoplasia (BORN) is a challenge. We aimed to develop a web-based teaching tool for improving detection and delineation of BORN. METHODS: We made high-definition digital videos during endoscopies of patients with BORN and non-dysplastic Barrett's esophagus. Three experts superimposed their delineations of BORN lesions on the videos using special tools. In phase one, 68 general endoscopists from 4 countries assessed 4 batches of 20 videos. After each batch, mandatory feedback compared the assessors' interpretations with those from experts. These data informed the selection of 25 videos for the phase 2 module, which was completed by 121 new assessors from 5 countries. A 5-video test batch was completed before and after scoring of the four 5-video training batches. Mandatory feedback was as in phase 1. Outcome measures were scores for detection, delineation, agreement delineation, and relative delineation of BORN. RESULTS: A linear mixed-effect model showed significant sequential improvement for all 4 outcomes over successive training batches in both phases. In phase 2, median detection rates of BORN in the test batch increased by 30% (P < .001) after training. From baseline to the end of the study, there were relative increases in scores of 46% for detection, 129% for delineation, 105% for agreement delineation, and 106% for relative delineation (all, P < .001). Scores improved independent of assessors' country of origin or level of endoscopic experience. CONCLUSIONS: We developed a web-based teaching tool for endoscopic recognition of BORN that is easily accessible, efficient, and increases detection and delineation of neoplastic lesions. Widespread use of this tool might improve management of Barrett's esophagus by general endoscopists.

[Gastro-highlights 2012]. / Gastro-Highlights 2012.

The annual Gastro Highlights training event, held at the university Hospital Zurich last autumn, also celebrated the 60th birthday of prof.Dr.med. Michael Fried, who initiated this widely recognized event 17 years ago. Featured at the symposium was a round up of the most important new discoveries in the field of gastroenterology and hepatology to be published during the course of the previous year or represented at the Digestive Disease Week (DDW). To mark the birthday of Prf. Dr. med. Michael Fried, two international experts made a special report on the key developments in the gastroenterology to emerge over the past decades.

Etiopathogenetic principles and peptic ulcer disease classification.

Ulceration corresponds to tissue loss, breaching the muscularis mucosae. When ulcers develop in the acid-peptic environment of the gastroduodenum, they are traditionally called peptic ulcer (PUD). Ulcers never develop spontaneously in a healthy gastroduodenal mucosa. Ulceration is the ultimate consequence of a disequilibrium between aggressive injurious factors and defensive mucosa-protective factors. The dominant aggressors are strong acid and high proteolytic (pepsin) activity in gastric secretions. The dominant defensors are the phospholipid surfactant layer, covering the mucus bicarbonate gel, the mucus bicarbonate layer covering the epithelium, the tight junctional structures between the epithelial cells, restricting proton permeability, and the epithelial trefoil peptides, contributing to healing after injury. Initially, acid-peptic aggression was considered the overwhelming cause of PUD, supported by the pioneering work of Schwartz, launching the dictum 'no acid, no ulcer'. This led to the universal therapy directed against intragastric acidity, also interfering with peptic activity when the pH was >4. The therapeutic sequence went from large doses of antacids to H(2)-receptor antagonists and finally to proton pump inhibitors (PPIs). The longer the intragastric pH was >3, the quicker ulcer healing was seen. Unfortunately, ulcers often recurred after stopping therapy, demanding maintenance therapy to keep the ulcers healed and to prevent the need for surgery (vagotomy, partial gastric resection). Later on, the emphasis gradually shifted to weakening/failing of the defensive factors, raising the vulnerability of the gastroduodenal mucosa to luminal secretions. Leading injurious mechanisms jeopardizing the mucosal integrity are numerous: infections, especially Helicobacter pylori, drug-induced injury, particularly acetylsalicylic acid (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs), physicochemical and caustic injury, vascular disorders, interfering with perfusion, etc. Currently the leading cause of PUD is H. pylori infection. Standard triple eradication therapy is losing interest in favor of quadruple therapy (PPI, bismuth, tetracycline, metronidazole). H. pylori-induced PPI is rapidly disappearing in the Western world, in contrast to drug-induced ulcer disease and what is called idiopathic PUD. Partial prophylaxis of ASA/NSAID-induced ulceration is possible with PPI maintenance therapy, but novel ways to strengthen the mucosal defense are urgently awaited.

Diagnosis and management of non-erosive reflux disease--the Vevey NERD Consensus Group.

BACKGROUND/AIMS: Although considerable information exists regarding gastroesophageal reflux disease with erosions, much less is known of non-erosive reflux disease (NERD), the dominant form of reflux disease in the developed world. METHODS: An expert international group using the modified Delphi technique examined the quality of evidence and established levels of agreement relating to different aspects of NERD. Discussion focused on clinical presentation, assessment of clinical outcome, pathobiological mechanisms, and clinical strategies for diagnosis and management. RESULTS: Consensus was reached on 85 specific statements. NERD was defined as a condition with reflux symptoms in the absence of mucosal lesions or breaks detected by conventional endoscopy, and without prior effective acid-suppressive therapy. Evidence supporting this diagnosis included: responsiveness to acid suppression therapy, abnormal reflux monitoring or the identification of specific novel endoscopic and histological findings. Functional heartburn was considered a separate entity not related to acid reflux. Proton pump inhibitors are the definitive therapy for NERD, with efficacy best evaluated by validated quality-of-life instruments. Adjunctive antacids or H(2) receptor antagonists are ineffective, surgery seldom indicated. CONCLUSIONS: Little is known of the pathobiology of NERD. Further elucidation of the mechanisms of mucosal and visceral hypersensitivity is required to improve NERD management.

Gastric hypersensitivity induced by oesophageal acid infusion in healthy volunteers.

Distal oesophageal acid exposure has been shown to increase visceral sensitivity of the proximal oesophagus via central sensitization. Here we evaluated whether acidification of the distal oesophagus also affects the sensorimotor function of the proximal stomach. A gastric barostat study combined with a 30-min acid (HCl 0.15 mol L(-1)) or saline infusion in the distal oesophagus was performed in 18 healthy volunteers. Gastric and cutaneous sensitivity was assessed before and up to 2 h after the start of infusion. Directly after acid infusion, but not after saline, the threshold for discomfort decreased (-6.4 +/- 1.7 vs 0.4 +/- 0.4 mmHg; P = 0.028) and distension-induced symptoms increased significantly compared with the baseline (122 +/- 49% vs -3 +/- 9%). Cutaneous sensitivity remained unaffected by acid infusion. In contrast, when the infused liquid was aspirated 3 cm more distally, at the level of the lower oesophageal sphincter, the effect of acid infusion on gastric sensitivity was abolished and the increase in distension-induced symptoms was reduced (61 +/- 24%). Distal oesophageal acid infusion induces visceral hypersensitivity without affecting somatic sensitivity arguing against a similar mechanism of central sensitization as observed in non-cardiac chest pain. As reduction of the acid load to the stomach prevented this effect, our findings indicate that either gastric and/or duodenal acidification is involved. It should be emphasized though that aspiration from distal oesophagus may have attenuated the effect by reducing the acid-exposed area or by reducing the contact time.

New algorithm for the treatment of gastro-oesophageal reflux disease.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is associated with a variety of typical and atypical symptoms. Patients often present in the first instance to a pharmacist or primary care physician and are subsequently referred to secondary care if initial management fails. Guidelines usually do not provide a clear guidance for all healthcare professionals with whom the patient may consult. AIM: To update a 2002-treatment algorithm for GERD, making it more applicable to pharmacists as well as doctors. METHODS: A panel of international experts met to discuss the principles and practice of treating GERD. RESULTS: The updated algorithm for the management of GERD can be followed by pharmacists, for over-the-counter medications, primary care physicians, or secondary care gastroenterologists. The algorithm emphasizes the importance of life style changes to help control the triggers for heartburn and adjuvant therapies for rapid and adequate symptom relief. Proton pump inhibitors will remain a prominent treatment for GERD; however, the use of antacids and alginate-antacids (either alone or in combination with acid suppressants) is likely to increase. CONCLUSION: The newly developed algorithm takes into account latest clinical practice experience, offering healthcare professionals clear and effective treatment options for the management of GERD.

Impaired drinking capacity in patients with functional dyspepsia: intragastric distribution and distal stomach volume.

The water drink test is a good tool to evoke dyspeptic symptoms. To what extent these symptoms are related to altered gastric distribution is not clear. Therefore, we determined gastric volumes after a drink test using SPECT. After a baseline scan 20 healthy volunteers (HV) and 18 patients with functional dyspepsia (FD) underwent a drink test (100 mL min(-1)) followed by five scans up to 2 h. Dyspeptic symptoms were scored before every scan. A Wilcoxon signed rank test (P < 0.05) and a mixed effects model were used for statistical analyses. Fasting volumes were significantly higher in FD compared to HV for total, proximal and distal stomach (P < 0.001). Functional dyspeptic patients ingested significantly less water (P < 0.001) and had an impaired filling of the distal part of the stomach (P = 0.001) after the drink test. In FD, bloating (prox. 80%, dist. 56%), pain (prox. 87%, dist. 62%) and fullness (prox. 80%, dist. 59%) were determined more by proximal stomach volume rather than distal stomach volume. These data suggest that drinking capacity is mainly determined by antral volume, with a reduced antral filling in FD compared to HV. The persisting symptoms of bloating, pain and fullness in FD are predominantly associated with proximal stomach volume.

Potential impact of EUS-FNA staging of proximal lymph nodes in patients with distal esophageal carcinoma.

BACKGROUND AND STUDY AIMS: Distal esophageal carcinomas can be resected using transthoracic esophagectomy or transhiatal esophagectomy. Accurate diagnosis of subcarinal and supracarinal lymph-node metastases is important for selecting the surgical strategy. The impact of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) on the preoperative diagnosis of subcarinal and supracarinal lymph-node metastases in patients with distal esophageal carcinoma was therefore investigated. PATIENTS AND METHODS: Patients with a resectable distal esophageal carcinoma and subcarinal and/or supracarinal lymph nodes visualized on preoperative EUS were prospectively included. The lymph nodes were sampled using EUS-FNA, and if they were found to have metastases, transthoracic resection was offered; by contrast, patients without metastases were offered a transhiatal resection. RESULTS: Lymph-node metastases were found with EUS-FNA in 11 of the 48 patients included (23 %). Thirteen patients had suspicious nodes on EUS, in four of whom (31 %) the diagnosis was changed into nonmalignant nodes with FNA. Thirty-five patients had nonsuspicious nodes on EUS, in three of whom (9 %) the FNA procedure revealed malignant cells. CONCLUSIONS: EUS with the addition of the FNA procedure has a significant impact on decision-making in patients with esophageal carcinoma in whom transhiatal esophagectomy would otherwise be planned.

The influence of the novel 5-HT1A agonist R137696 on the proximal stomach function in healthy volunteers.

As fundic dysaccommodation represents one of the pathophysiological mechanisms underlying functional dyspepsia, gastric relaxant agents may serve as a new treatment of this disorder. Previous studies have suggested the involvement of 5HT1 receptors in the control of gastric tone. Our aim was to study the effect of R137696, a novel 5HT1A agonist, on fundus sensorimotor function in healthy volunteers. The effect of single oral doses (1-2 mg) R137696 was evaluated in a double-blind, placebo-controlled manner on fasting fundic volume, visceral perception, distension-evoked symptoms and fundic compliance in 21 healthy male subjects. R137696 increased the proximal stomach volumes in a dose-dependent manner. Distention-evoked symptoms or distention and discomfort threshold were not altered by R137696. A logistic regression model, characterizing the relationships between the volume and the visual analogue scale score for dyspeptic symptoms (nausea, fullness, discomfort, pain and satiety) as a sigmoidal curve, revealed that R137696 had no effect on distension-induced discomfort, fullness, pain and satiety compared to placebo. R137696 relaxes the gastric fundus in fasting conditions but has no effect on distension-evoked dyspeptic symptoms in healthy volunteers.

Placebo- and paracetamol-controlled study on the efficacy and tolerability of hyoscine butylbromide in the treatment of patients with recurrent crampy abdominal pain.

AIM: To compare the efficacy and tolerability of oral hyoscine butylbromide (hereafter hyoscine) 10 mg t.d.s., paracetamol 500 mg t.d.s. and their fixed combination against placebo in patients with recurrent crampy abdominal pain. METHODS: A total of 1637 patients were entered into a four-arm double-blind study. After a 1 week placebo run-in, they were randomized to 3 weeks of treatment with one of the four therapies with assessments after 1, 2 and 3 weeks. Pain intensity (Visual Analogue Scale) and pain frequency (Verbal Rating Scale) were self-assessed daily. RESULTS: Pain intensity on the Visual Analogue Scale decreased in all treatment groups; the adjusted mean changes from baseline were 2.3, 2.4 and 2.4 cm for the hyoscine, paracetamol and combination groups, respectively, compared with 1.9 cm for the placebo group (all P < 0.0001). The Verbal Rating Scale also showed a statistically significant decrease of 0.7, 0.7 and 0.7 in the hyoscine, paracetamol and combination groups compared with 0.5 in placebo (all P < 0.0001). All treatments were well tolerated: 16%, 14%, 17% and 11% of patients on hyoscine, paracetamol, combination and placebo reported at least one adverse event. CONCLUSIONS: Hyoscine, paracetamol and their fixed combination are effective in the treatment of recurrent crampy abdominal pain and well tolerated if used three times daily continuously for 3 weeks.

Prevalence and management of abdominal cramping and pain: a multinational survey.

BACKGROUND: Though functional gastrointestinal complaints are recognised as being common throughout the world, there have been few comparative studies of prevalence. AIM: To compare the prevalence and management of abdominal cramping/pain in nine countries. METHODS: In a two-stage community survey, approximately 1000 subjects were interviewed in each of nine countries to establish the demographics of individuals with abdominal cramping/pain (stage 1) followed by market research-driven interviews with >or=200 sufferers per country (stage 2). RESULTS: 9042 subjects were interviewed in stage 1. Mexico (46%) and Brazil (43%) had the highest prevalence of abdominal cramping/pain; Japan the lowest (10%). Abdominal cramping/pain was more common in women (12-55%) than in men (7-38%). About 1717 subjects participated in stage 2; 65% were women and the average age at symptom onset was 29 years. The frequency of episodes differed between countries, being highest in the US (61% suffered at least once in a week). Sufferers in the US and Latin America reported a higher usage of medications (around 90%) than those in Europe (around 72%). In most countries over-the-counter drugs were principally used. Antispasmodic drugs were most popular in Latin America and Italy, antacids in Germany and the UK. Drug therapy decreased the duration of episodes (by up to 81% in Brazil). CONCLUSIONS: The community prevalence, severity, healthcare seeking and medication usage related to abdominal cramping/pain are high overall, but vary considerably between countries.

Review article: from gastrin to gastro-oesophageal reflux disease--a century of acid suppression.

To commemorate Edkins' discovery of gastrin in 1905, we review a century of progress in the physiology and pathobiology of gastrin and acid secretion especially as it pertains to clinical aspects of gastro-oesophageal reflux disease. Although initially ignored, Edkins' observations eventually led to the enthusiastic investigation of gastrin and acid regulation in peptic ulcer disease, culminating in important therapeutic advances in the management of acid peptic disease. Following the improved understanding of gastric secretory physiology, and the development of acid suppressants with increasing efficacy, the use of surgical intervention for peptic ulcer disease was almost eliminated. Surgery became obsolete with the discovery of Helicobacter pylori. Three other advances are also influencing modern practice: the gastrotoxicity of aspirin and non-steroidal anti-inflammatory drugs is now increasingly appreciated, the role of endoscopy in the diagnosis and therapy of upper gastrointestinal bleeding, and the use of intravenous acid-suppressive agents. The major issue for the future resides within the epidemic of gastro-oesophageal reflux disease. How to diagnose, categorize and treat this condition and how to identify and prevent neoplasia, are the challenges of the new century.

Clinical and laboratory studies of the antacid and raft-forming properties of Rennie alginate suspension.

BACKGROUND: Acid pockets at the gastro-oesophageal junction escape buffering from meals in the stomach. Combining high-dose antacid with alginate may therefore be of benefit in gastro-oesophageal reflux disease. AIM: To characterize the antacid and raft-forming properties of Rennie alginate suspension (containing high-dose antacid and alginate; Bayer Consumer Care, Bladel, the Netherlands). METHODS: The in vitro acid-neutralizing capacity of Rennie algniate was compared with Gaviscon (Reckitt Benckiser, Slough, UK) by pH-recorded HCl titration. Alginate raft weight formed in vitro at different pH was used to evaluate the pH dependency of raft formation with each product. A double-blind, placebo-controlled, randomized crossover study also compared the antacid activity of Rennie alginate vs. placebo in vivo using continuous intragastric pH monitoring in 12 healthy fasting volunteers. RESULTS: Compared with Gaviscon, Rennie alginate had a higher acid-neutralizing capacity, greater maximum pH and longer duration of antacid activity in vitro. However, the two products produced comparable alginate rafts at each pH evaluated. In vivo, Rennie alginate provided rapid, effective and long-lasting acid neutralization, with an onset of action of <5 min, and duration of action of almost 90 min. CONCLUSIONS: The dual mode of action of Rennie alginate offers an effective treatment option for mild symptomatic gastro-oesophageal reflux disease particularly considering recent findings regarding 'acid pockets'.

Possible role of nitric oxide in visceral hypersensitivity in patients with irritable bowel syndrome.

BACKGROUND: Visceral hypersensitivity is a consistent finding in a considerable proportion of patients with irritable bowel syndrome (IBS), and may provide a physiological basis for the development of IBS symptoms. In this study, we aimed to confirm the hypothesis that nitric oxide (NO) is involved in maintaining visceral hypersensitivity in IBS. Ten healthy volunteers (HV) and 12 IBS patients with documented hypersensitivity to rectal distension underwent a rectal barostat study. The effect of placebo and the specific NO synthase inhibitor NG -monomethyl-L-arginine (L-NMMA) on resting volume, rectal sensitivity to distension and rectal compliance was evaluated in a double-blind, randomized, cross-over fashion. NG -monomethyl-L-arginine did not alter resting volumes in HV or IBS patients. In HV, l-NMMA did not alter rectal sensory thresholds compared to placebo (45 +/- 3 and 46 +/- 3 mmHg, respectively). In contrast, L-NMMA significantly increased the threshold for discomfort/pain in IBS patients (placebo: 18 +/- 2, l-NMMA: 21 +/- 3 mmHg, P < 0.05). Rectal compliance was not affected by L-NMMA. Although NO does not seem to play a major role in normal rectal sensation or tone, we provide evidence that NO may be involved in the pathophysiology of visceral hypersensitivity in IBS.

Differences and similarities of adenocarcinomas of the esophagus and esophagogastric junction.

During the last few decades there has been an alarming rise in the incidence of tumors originating at the esophagogastric junction (EGJ) [1]. The reason for this is unknown. Tumors of the EGJ can be categorized in two types of cancer divided according to their anatomical origin: distal esophageal adenocarcinoma and adenocarcinoma of the gastric cardia. However, due to their location, in the transitional zone of the esophagus and stomach, there is constant debate about the proper classification, staging, and management of these tumors. The etiology of distal esophageal adenocarcinoma is clearly related to gastroesophageal reflux disease (GERD) and the development of a Barrett's esophagus [2]. The etiology of adenocarcinoma of the gastric cardia is less well understood. In the present paper, we will discuss the clinical characteristics and clinical management of esophagogastric tumors. Special attention will be given to differences and similarities of adenocarcinomas of the gastric cardia and distal esophagus.

Gastrin (G) cells and somatostatin (D) cells in patients with dyspeptic symptoms: Helicobacter pylori associated and non-associated gastritis.

BACKGROUND: Gastrin G cells and somatostatin D cells are important regulators of gastric acid secretion and alterations in their relative numbers may play a key role in gastroduodenal disease. AIM: To investigate the effect of Helicobacter pylori infection on the density of immunoreactive G and D cells in gastric antral and corpus biopsies from patients with dyspeptic complaints. METHODS: One hundred and twenty two patients with dyspeptic complaints had two antrum and two corpus biopsies taken during upper endoscopy. The severity of inflammation and the density of H pylori were evaluated semiquantitatively. In addition, the density and distribution of neuroendocrine cells, especially G and D cells, were examined using immunohistochemistry. Patients were divided into three groups, those with H pylori positive gastritis, H pylori negative gastritis, and histologically normal gastric mucosa. RESULTS: The number of immunoreactive G cells was significantly higher and the number of immunoreactive D cells lower in patients with H pylori positive gastritis compared with H pylori negative gastritis or histological normal gastric mucosa. The percentage of G cells as a percentage of mucosal endocrine cells was also raised and that of D cells was decreased. CONCLUSIONS: Helicobacter pylori infection produces alterations in the number of endocrine cells responsible for regulating acid secretion in relation to intragastric pH and feeding. The alterations correlate best with the severity of inflammation and not with H pylori density.