[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.

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.

New developments in the endoscopic surveillance of Barrett's oesophagus.

Patients with a Barrett's oesophagus are at risk for developing an adenocarcinoma of the distal oesophagus. Therefore, many patients undergo endoscopic surveillance to detect dysplasia and/or cancer at an early and curable stage. However, early neoplastic lesions are difficult to identify with standard endoscopy. In addition, the low incidence of these lesions, currently estimated at 0.5% per year, reduces the cost effectiveness of the surveillance strategy. New developments, aimed at improving the efficacy of Barrett's surveillance, focus on two areas: 1) improvement of the endoscopic detection of early neoplastic lesions; and 2) the use of alternative techniques for tissue sampling combined with molecular markers to identify patients at risk for malignant degeneration.

Are there unmet needs in acid suppression?

The development of proton-pump inhibitors (PPIs) caused impressive improvements in the control of gastric acid secretion. The clinically related consequences are most clearly expressed in the therapy of gastroesophageal reflux disease (GERD). Despite these glamorous outcomes, there still are unmet clinical needs. Ideally, full 24-h control of gastric acid secretion should be available to fine tune acid suppressant therapy to the individual clinical needs. Full control of acid secretion with oral PPI therapy in the presence of a healthy non-Helicobacter pylori-infected gastric mucosa is difficult, if not impossible, at present. However, there are circumstances in which full control is desirable if not essential (intensive care, esophageal columnar metaplasia, etc.). In particular, the so-called nocturnal acid breakthrough is difficult to control, particularly in patients with esophageal columnar metaplasia. But even for ordinary GERD, full symptom control and patient satisfaction is often lacking, necessating additional over-the-counter medication for control of remaining symptoms. A recent Gallup interview of 1000 symptomatic GERD patients stressed the frequency of nocturnal symptoms, insufficiently controlled with standard PPI therapy. Current PPIs are also suboptimal for 'on-demand' therapy in Non-Erosive Reflux Disease (NERD)/GERD. Moreover, rebound acid secretion after abrupt stopping of PPI therapy may favour early symptomatic relapse, necessating step-down therapy to prevent prolongation of the need of acid suppression.

[The effect of Helicobacter pylori eradication on chronic use of acid-suppressant medication by patients in general practice; a randomised, double-blind study]. / Het effect van Helicobacter pylori-eradicatie op chronisch gebruik van maagzuursecretieremmende medicatie door patiënten in de huisartsenpraktijk; een gerandomiseerd, dubbelblind onderzoek.

OBJECTIVE: To study the feasibility of tapering long-term acid-suppressant drugs (ASD) use in chronic dyspeptic patients in relation to Helicobacter pylori eradication. DESIGN: Prospective randomised double-blind study. METHOD: Patients from 54 general-practitioner practices in the Amsterdam area were studied in the period 1 April 1997 - 30 September 1999 after selection on the basis of their use of acid suppressants for a period of at least 8 weeks. After gastroscopy the patients with a peptic ulcer (PUD) and H. pylori were treated with eradication therapy and patients without an ulcer but with H. pylori were randomised for eradication or placebo treatment. After a gradual reduction of acid suppressants over a 3-week period following the intervention, the patients kept a diary for 24 weeks of the quantities of acid suppressants and antacids they used. RESULTS: Of the 1083 patients approached, 434 were prepared to undergo the gastroscopy. Data for the follow-up period were available for 186 of the 227 H. pylori-positive patients. Of them 61% stopped ASD use during follow-up. The mean daily ASD dosage per patient decreased by 85% from 1.85 to 0.27 units (p < 0.05), with minimal antacids use. Of the 75 patients with peptic-ulcer disease 86% stopped ASD use. In patients with functional dyspepsia no difference in ASD use was observed after successful H. pylori eradication or placebo. Patients with mild reflux disease (GERD) used more ASD after H. pylori eradication than after placebo (p < 0.05). CONCLUSION. After H. pylori eradication many patients with PUD stopped ADS use, while GERD patients used more ASD than after placebo. A gradual withdrawal of long-term ASD use, supported by antacids and on-demand use of low-dosage ASD, facilitated reduction of ASD use during 6 months.

Radial distribution of dilated intercellular spaces of the esophageal squamous epithelium in patients with reflux disease exhibiting discrete endoscopic lesions.

INTRODUCTION: Dilatation of intercellular spaces of the esophageal squamous epithelium has been suggested as a marker of early acid reflux-induced damage. This change is a potentially useful addition to histomorphological changes that represent so called minimal endoscopic lesions. We have assessed dilatation of intercellular spaces with regard to: (1) interobserver variability, and (2) whether the incidence of this varies between 'red streaks' and the adjacent normal looking squamous epithelium. METHODS: Esophageal biopsies from 44 patients with chronic gastro-esophageal reflux (GERD) were evaluated. At endoscopy, these patients had one or more red streaks on the tops of the mucosal folds in the distal esophagus. Biopsies were taken from the red streaks and from the normal-appearing mucosa 1 cm lateral to the red streaks. Biopsies were assessed in a blinded fashion by two independent pathologists (MV & RF). Criteria for assessing intercellular space dilatation were evaluated and agreed on prior to the study. RESULTS: Good interobserver agreement was recorded (kappa = 0.82 at the streaks and 0.77 for the control tissues) for absence/presence of intercellular space dilatation. Red streak and control biopsies differed significantly (p = 0.0001), with respect to presence of dilated intercellular spaces, with 90.5 % of the former demonstrating this as present compared to 56.1% in the controls. CONCLUSION: This study supports the concept that esophageal mucosal minimal changes due to reflux is localised and that dilatation of intercellular spaces is an early sign of reflux-induced epithelial damage. The low interobserver variability in the assessment of intercellular space dilatation suggests that this may be a useful variable for assessment of early signs of acid-reflux induced damage to the squamous epithelium of the esophagus by use of light microscopy.

Treatment of gastro-oesophageal reflux disease with rabeprazole in primary and secondary care: does Helicobacter pylori infection affect proton pump inhibitor effectiveness?

BACKGROUND: The presence of the gastric pathogen, Helicobacter pylori influences acid suppression by proton pump inhibitors and treatment outcome in patients with gastro-oesophageal reflux disease. AIM: To determine the influence of H. pylori infection on effectiveness of rabeprazole in primary and secondary care patients with gastro-oesophageal reflux disease. METHODS: Patients from primary and secondary care centres with uninvestigated gastro-oesophageal reflux disease (based on symptoms only) and investigated gastro-oesophageal reflux disease (endoscopically confirmed oesophagitis or endoscopy-negative reflux disease) were tested for H. pylori and treated with rabeprazole 20 mg once daily for 4-8 weeks in a non-randomized, multicentre, open-label study. Primary end-point for treatment effectiveness was complete resolution of both heartburn and acid regurgitation at 4-8 weeks; secondary end-point was quality of life as registered with the Psychological General Well-being Index. RESULTS: Data of 1787 patients could be analysed; mean duration of treatment was 36.3 days. At the evaluation visit 76.9% were heartburn-free, 77.7% regurgitation-free and 71% had complete symptom resolution. Overall Psychological General Well-being Index scores improved accordingly. Treatment was equally effective in patients with or without H. pylori infection, but more effective in patients with oesophagitis when compared with symptomatic gastro-oesophageal reflux disease. CONCLUSIONS: The effectiveness of rabeprazole in gastro-oesophageal reflux disease is not affected by the presence of H. pylori infection.

Cancer of the esophagus and gastric cardia: recent advances.

Esophageal cancer and cancer of the gastric cardia, in particular adenocarcinomas, have shown a rapid and largely unexplained increase in incidence in many developed countries around the world. These diseases have a poor prognosis and current therapies have a modest impact on survival. This review presents recent advances in the epidemiology, etiology, diagnosis, staging, prevention and treatment of resectable and advanced disease. Although significant progress has been made in these areas of research and patient management over the past years, prognosis for most patients diagnosed with esophageal cancer or cancer of the gastric cardia remains poor. New diagnostic procedures, improved surgical procedures, combined treatment modalities and new treatment modalities are being evaluated and may be expected to contribute to improved patient outcomes and better palliation of symptoms in the future.

Microorganisms and parasites in chronic infective diarrhea.

AIM: To reveal the pattern of microorganisms in chronic infective diarrhea cases. METHODS: We examined all patients suffering from chronic infective diarrhea over a six year period The patients were examined physically and at the same time laboratory tests,colon enema X-ray and colonoscopy, ileoscopy, upper GI endoscopy and small bowel X-ray were performed. RESULTS: We found 138 (66. 7%) chronic infective diarrhea from 207 chronic diarrhea patients. Parasitic causes were Candida albicans (48.55%), Blastocystis hominis (6.52%), Entamoeba histolytica (3.62%), and Giardia lamblia (3.62%) etc. Bacterial causes were Pathogenic E. coli(34.78%), Aerobacter aerogenes (3.62%), Mycobacterium tuberculosis (3.62%), Geotrichum (1.45%), Shigella sonnei(0. 72%), Salmonella paratyphi (2.89%)etc. CONCLUSION: The most frequent microorganisms and parasites found in chronic infective diarrhea were pathogenic E.coli and Candida albicans.

Fundic accommodation assessed by SPECT scanning: comparison with the gastric barostat.

BACKGROUND: Recently, single photon emission computed tomography (SPECT) scanning was described as a non-invasive technique to assess fundic accommodation. However, in contrast with the barostat, no intragastric distending force is applied during SPECT scanning. We hypothesised that in the absence of a barostat balloon, SPECT scanning largely detects the volume effect of the ingested meal and is a rather insensitive tool to detect fundic relaxation. METHODS: After an overnight fast, healthy volunteers underwent a barostat study and SPECT scanning on two separate days to assess: (1) meal induced fundic accommodation (Nutridrink, 200 ml, 300 kcal); and (2) gastric relaxation to 1 mg intravenous glucagon. RESULTS: Fasting fundic volumes (145 (8) v 280 (32) ml; p=0.001) and average postprandial volume (329 (10) v 571 (53) ml; p=0.001) were significantly lower measured with SPECT compared with the barostat study. Meal induced fundic relaxation (183 (10) v 289 (46) ml; p=0.050) and the postprandial/fasting volume ratio (2.32 (0.10) v 2.27 (0.29); p=0.892) did not differ significantly between SPECT scanning and the barostat. However, no correlation could be determined between accommodation volumes measured by both techniques. In contrast with meal induced relaxation, the glucagon induced increase in fundic volume (19 (5) v 406 (56) ml; p=0.007) and post/pre glucagon ratio (1.16 (0.03) v 3.02 (0.54); p=0.046) were significantly lower when measured by SPECT scanning compared with the barostat. CONCLUSION: SPECT scanning detects changes in postprandial volume but is less suitable than the gastric barostat in detecting changes in gastric tone. Our study therefore questions its role as a tool to detect impaired accommodation and warrants further validation of this technique.

Effect of prolonged gastric distention on lower esophageal sphincter function and gastroesophageal reflux.

OBJECTIVES: Morbidly obese patients treated with an intragastric balloon report a transient increase in gastroesophageal reflux (GER) symptoms. In the present study, we evaluated the underlying mechanisms of GER and examined the effect of prolonged gastric distention on lower esophageal sphincter function. METHODS: Fasting and postprandial manometric studies were performed in obese subjects (n = 15) before, immediately after, and 10 and 20 wk after placement of a 500-ml water-filled balloon. RESULTS: Residual lower esophageal sphincter (LES) pressure after water swallows was not affected after balloon placement, excluding mechanical interaction with sleeve function. Postprandial LES pressure was significantly increased after 10 and 20 wk. GER was increased in the right recumbent position until 10 wk after balloon placement, mainly because of an increased percentage of transient lower esophageal sphincter relaxations (TLESRs) accompanied by GER. TLESRs were the main mechanisms underlying reflux both before and after balloon placement. The rate of TLESRs was increased significantly immediately after introduction of the balloon, returning to baseline values after 20 wk. After balloon placement, reflux episodes were evoked by gastric contractions that were not inhibited by meals. CONCLUSIONS: Chronic distention by an intragastric balloon increased reflux up to 10 wk after placement because of an increase in the percentage of TLESRs accompanied by a reflux episode. In addition, prolonged balloon distention increased the rate of TLESRs and created a postprandial state even 10 wk after balloon placement. After 20 wk these effects largely resolved, illustrating adaptation to this artificial situation.