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.

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.

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.

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.

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.

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.

Outcome of patients with esophageal carcinoma and suspicious celiac lymph nodes as determined by endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: The management of patients with esophageal cancer with malignant celiac lymph nodes (CLNs) is controversial. In this study we evaluated the management and survival of patients with positive CLN findings on endoscopic ultrasonography (EUS) and compared the outcome in surgically treated patients with that of nonsurgically treated patients. PATIENTS AND METHODS: The EUS database of the Academic Medical Center was retrospectively searched for patients with esophageal carcinoma and EUS-positive CLN. Follow-up comprised the review of medical charts and contact with general practitioners. RESULTS: From 1993 through 2000, 78 patients with esophageal carcinoma and suspicious CLN were eligible for inclusion in this study. The median survival of patients with CLN size < 2 cm was 13.5 months vs. 7.0 months for patients with CLN size >2 cm ( P = 0.01). In a multivariate model, CLN size was the only predictive factor for poor patient survival. Of the 78 study patients, 13 underwent a surgical resection and 65 received nonsurgical treatment. The surgical group was significantly younger and all patients in this group had CLN size < 2 cm. The median survival for the surgical group was 13.7 months vs. 13.5 months for the nonsurgical group with CLN size < 2 cm ( P = 0.63). CONCLUSIONS: In this retrospective study, CLN size was a significant predictor for poor survival. The surgically treated patients had a medium-term survival similar to that of nonsurgically treated patients with a CLN size < 2 cm. These findings underline the prognostic value of CLN size in patients with esophageal carcinoma.

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.

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.

[Barrett's esophagus: new developments in endoscopic surveillance]. / Barrett-slokdarm: nieuwe ontwikkelingen in endoscopische surveillance.

The current surveillance strategies for patients with a Barrett's oesophagus are hampered by the poor endoscopic visibility of early neoplastic lesions, the sampling error of random biopsies, the subjectivity of the histological evaluation, and the low incidence of carcinoma. New endoscopic techniques are available for a more reliable evaluation of a Barrett's oesophagus: high-resolution endoscopy, chromoendoscopy, fluorescence endoscopy and optical coherence tomography. The use of molecular markers will probably lead to a better risk stratification of patients. Detection of aneuploid cell populations and assessment of an increase of the number of cells in the S- and G2-phase are possible with DNA flow cytometry; flow cytometric abnormalities may be a more reliable predictor of carcinoma than histological assessment. A combined approach with the new endoscopic techniques and molecular markers may lead to a more efficient and cost-effective surveillance programme.

[Barrett's esophagus: endoscopic treatment of high-grade dysplasia and early cancer]. / Barrett-slokdarm: endoscopische behandeling van hooggradige dysplasie en vroegcarcinomen.

In a Barrett's oesophagus without dysplasia, endoscopic control every 3-5 years is sufficient. If low-grade dysplasia is encountered in the surveillance biopsies, then endoscopy should be repeated within 3-6 months and yearly thereafter if the low-grade dysplasia persists. Antacid medication must be prescribed in cases with extensive inflammation. The endoscopic treatment of patients with high-grade dysplasia and/or early cancer of the mucosa in a Barrett's oesophagus (tissue ablation and/or mucosa resection) seems a promising alternative to surgery in view of the combination of effectiveness, limited invasiveness compared to surgical resection, and the preservation of a functional oesophagus. Data from long-term follow-up are still limited. Strict endoscopic surveillance will probably detect metachronic abnormalities in an early and still curable stage, creating a new opportunity for endoscopic treatment.

Review article: management of mild and severe gastro-oesophageal reflux disease.

Treatment of endosocopy-negative gastro-oesophageal reflux disease (s-GERD) should be directed towards rapid relief of symptoms and then maintenance of relief using minimum yet effective therapy. Responses to proton pump inhibitors are somewhat lower in s-GERD patients compared to GERD with overt erosive damage (e-GERD). The reasons for a lower response rate are not clear but may relate to the inclusion of patients who do not have reflux disease or patients with a lower oesophageal sensory threshold. Also poorly understood is the lower yield of complete heartburn relief when the number of associated dyspeptic symptoms is high. Some form of long-term therapy is needed in the majority of patients. 'On demand' proton pump inhibitor therapy to control reflux symptoms is a new and attractive option. Time to study discontinuation due to insufficient control of heartburn, or any other reason resulting in unwillingness to continue with on-demand therapy, is a pragmatic outcome that is well suited to definition of the efficacy of on-demand therapy. The goals of treatment of e-GERD should be to relieve symptoms and to heal lesions. Symptom severity and much less endoscopic abnormalities drives the therapeutic choices. When symptoms are mild or intermittent and when oesophagitis is of limited degree, standard dose proton pump inhibitor is usually instituted. Fewer and fewer clinicians would still opt for an H2-receptor antagonist. If there is moderate or severe oesophagitis or if symptoms are particularly troublesome, then the patient should start with standard-dose proton pump inhibitor therapy once a day, but not uncommonly a b.d. dosage maybe necessary. Once the dose of the acid suppressant that relieves symptoms is found, this dose should be maintained for a period of 3 months. After this time, an attempt should be made to reduce the dose. If symptoms recur, then the patients should go back to the full-dose proton pump inhibitor and a plan should be formulated for long-term treatment. The long-term treatment options vary between ongoing acid and suppressant therapy, with occasional attempts to reduce the dose, or to go for 'on demand' therapy and (rarely) includes consideration for surgery or endoscopic anti-reflux therapy.