Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Columnar epithelial metaplasia of the distal esophagus (i.e. barrett's esophagus) is an acquired condition showing a prevalence of 4%. It is probably due to abnormal reparative processes of the esophageal squamous epithelium after gastroesophageal reflux damage. "Mixed" (both acid and biliary) reflux seems more relevant for the pathogenesis of Barrett's esophagus than acid reflux alone, as shown by recent studies with Bilitec 2000. Its diagnosis is not easy for the "cardiac", "fundic" or "indeterminate" types of columnar metaplasia and needs a close cooperation between the endoscopist and the pathologist. On the contrary, it is less difficult for the "distinctive" type of metaplasia. Barrett's esophagus surveillance represents a major challenge in the perspective of its malignant degeneration (adenocarcinoma risk 350 times greater than in the general population). Therapy of Barrett's esophagus includes drugs and surgical treatment. Among the drugs proton pump inhibitors such as Omeprazole seem, at the moment, the most effective for reflux control, as well as the Nissen-Rossetti operation seems the most widely accepted among the anti-reflux surgical procedures. The novelty concerning Barrett's esophagus therapy is represented by laser photoablation associated with proton pump inhibiting therapy. But the experience with this treatment is still at a preliminary stage. For Barrett's esophagus with severe dysplasia and/or adenocarcinoma and/or squamous cell carcinoma esophagectomy is needed with a different extent and approach, according to the extent of Barrett's esophagus and to the stage and site of the neoplastic changes.
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PMID:[Barrett esophagus. Diagnosis and treatment]. 894

A novel pathophysiology of Barrett's esophagus and a new method of assessing biopsy specimens in patients with gastroesophageal reflux disease (GERD) are presented. This is based on the observation in autopsy studies of patients without GERD that the squamous epithelium of the esophagus transitions directly to fundic mucosa in many people and that the cardiac mucosa is of very short length in others. Available evidence suggests that what is termed gastric cardiac mucosa is in reality an abnormal mucosa resulting from metaplasia of the squamous epithelium of the esophagus as a result of GERD. The severity of GERD correlates with the length of metaplastic cardiac mucosa and further changes occurring in it, permitting development of a system that provides good correlation between biopsy histology and severity of GERD. Intestinal metaplasia ("Barrett's esophagus") always occurs in this metaplastic cardiac mucosa. The recognition of this new pathophysiology of Barrett's esophagus permits identification of the entire sequence whereby GERD leads to adenocarcinoma: GERD-->cardiac metaplasia of squamous epithelium-->reflux carditis-->intestinal metaplasia-->dysplasia-->adenocarcinoma. This article also attempts to develop a terminology that avoids use of the confusing term "Barrett's esophagus," which should be discarded.
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PMID:Pathophysiology of Barrett's esophagus. 926 45

Barrett's esophagus is a metaplastic change in the mucosal lining which represents a peculiar form of healing in response to the chronic injury due to gastroesophageal reflux. It has been recognized that this change is associated with an increased risk of developing esophageal adenocarcinoma. Several factors have been shown to identify the patients who are at particular risk for carcinoma, the most importance of which is the development of dysplasia. As a result, management of patients with Barrett's esophagus must include careful endoscopic surveillance with histological examination of the biopsies by two independent experienced pathologists. Patients with low-grade dysplasia require complete control of reflux and careful endoscopic surveillance. Because the majority of patients with high-grade dysplasia will have co-existent adenocarcinoma, and because of difficulties in differentiating high-grade dysplasia from invasive adenocarcinoma, esophagectomy is the treatment of choice for these individuals. This approach has been shown to result in a significant improvement in survival in patients with esophageal cancer identified under surveillance.
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PMID:Management of Barrett's esophagus with dysplasia. 926 47

The incidence of Barrett carcinoma has increased almost six-fold in the last 20 years. Barrett oesophagus is defined as the presence of metaplastic columnar epithelium in the oesophagus in continuity with the gastric mucosa. It is regarded as an acquired abnormality, developed as a result of chronic (duodenal) gastro-oesophageal reflux. It is especially the intestinal type of columnar epithelium that has a greatly enhanced risk of malignant degeneration. It is advisable that patients with a Barrett oesophagus should regularly be examined endoscopically, with extensive tissue biopsy. Presence of Barrett epithelium without dysplasia or with only moderate dysplasia does not in itself constitute an indication for supplementary treatment. Major dysplasia constitutes an indication for prophylactic resection. In the treatment with curative intention of Barrett carcinoma, surgery is the therapy of first choice.
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PMID:[Barrett esophagus and Barrett carcinoma]. 954 76

This article reviews the major changes that have occurred since the last Canadian consensus conference on gastroesophageal reflux disease (GERD), which was held four years ago. There were developments in the understanding of the pathophysiology of this disease and improvements in the methods of its investigation and management. Esophageal and extraesophageal complications have also been better defined. Since 1992 new knowledge on nitric oxide has been gained and several new inflammatory cytokines have been developed. Improved understanding of the mechanism of the hypersensitive esophagus helped to explain the presence of clinical symptoms with normal endoscopic findings. This also improved interpretation of the role of 24 h pH monitoring and 24 h pH with motility recording. There is better understanding of the role of H2 receptor antagonists and prokinetics and an increasing confidence in the long term safety of proton pump inhibitors (PPIs). The most important changes occurred in surgery with the introduction of laparoscopic fundoplication. Patients with Barrett's esophagus who are too ill for esophagectomy may now be enrolled in surveillance because it is possible to deal with dysplasia and small cancers with photodynamic therapy. As an introductory lecture to the consensus conference, this article also deals with the subject of health economics and discusses the necessity and the dangers involved in devising treatment guidelines. It indicates that guidelines change with advancing knowledge, and emphasizes that physicians' primary duty is toward their patients. Therefore, guidelines devised here should be adjusted to the individual needs of patients. Organizational aspects of the present conference are also described.
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PMID:Guidelines of the previous consensus conference and recent developments. 934 74

Barrett's esophagus is an acquired condition with columnar metaplasia of the distal esophagus. Gastroesophageal reflux is the main pathophysiological factor, although genetic predisposition may play a role. The significance of Barrett's esophagus is that it is the only recognized risk factor for adenocarcinoma of the esophagus, which is one of the most rapidly rising types of cancer in North America. Cancer develops in Barrett's esophagus through a series of steps including mucosal dysplasia. High grade dysplasia is clearly a premalignant lesion and has been the focus of endoscopic surveillance strategies. Because dysplasia and adenocarcinoma develop predominantly in patients with specialized intestinal columnar epithelium, they make up the group that would be considered for surveillance programs. Endoscopic surveillance for dysplasia is only indicated for patients in whom esophagectomy would be considered if high grade dysplasia or carcinoma was found, at least until other endoscopic ablative techniques are proven to be beneficial. It has been recommended that endoscopy be performed every other year and be increased to yearly if low grade dysplasia is found. High grade dysplasia should be confirmed by another expert pathologist, and the patient should then be considered for esophagectomy. Flow cytometry and genetic markers may improve the ability to select patients for surveillance programs in the near future.
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PMID:Pathophysiology and investigation of Barrett's esophagus. 934 77

Barrett's esophagus represents the most serious consequence of chronic gastroesophageal reflux disease (GERD), primarily because of its association with an increased incidence of esophageal adenocarcinoma. Specific therapy for Barrett's esophagus should lead to the complete regression of the metaplastic epithelium with adequate squamous reepithelialization. Ideally, this regression should be permanent and be associated with a reduction in the incidence of adenocarcinoma. Several reports in the literature have assessed the effects of H2-blocker treatment of Barrett's epithelium, but none has clearly documented a significant and consistent regression of the metaplastic epithelium. Proton pump inhibitors have been shown to be superior to H2 blockers in the treatment of patients with severe esophagitis. Despite initial enthusiasm, it does not appear that a significant regression of Barrett's epithelium can be achieved, even with high doses of proton pump inhibitors given for a prolonged period of time. Various groups have assessed the effects of antireflux surgery on the regression of columnar epithelium and dysplasia and its potential protective effect on the subsequent development of carcinoma. Overall, it appears from these reports that antireflux surgery, despite adequate symptomatic results, does not significantly and consistently lead to a reduction in length or disappearance of the Barrett's mucosa, and does not prevent the development of dysplasia and its progression to carcinoma. More recently, numerous authors have documented the regression of Barrett's mucosa by using various endoscopic thermal modalities. Technological advances including laser and photodynamic therapy have allowed for endoscopic mucosal ablation. Long term results are more encouraging when this mucosal ablation is associated with aggressive antireflux therapy (medical or surgical). Further studies are required before these exciting new therapies can be recommended. Currently, none of these approaches can obviate the need for continued endoscopic surveillance.
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PMID:Treatment of Barrett's esophagus. 934 88

We describe the clinical and pathologic features of a hitherto unreported finding in patients with esophagitis: the presence of multinucleated squamous epithelial giant cells simulating viral cytopathic effect and/or dysplasia. Routinely processed hematoxylin and eosin (H&E)-stained slides of esophageal mucosal biopsies from 14 patients with both active esophagitis and multinucleated epithelial giant cells were evaluated for a variety of inflammatory and epithelial features. Clinical, endoscopic, and follow-up data were collected and correlated with the histologic findings. Immunostaining (ABC method) for cytokeratin AE1/AE3, S-100, MIB-1, herpes simplex virus 1 and 2 (HSV), cytomegalovirus (CMV), as well as DNA in situ hybridization for human papilloma virus (HPV-ISH) was performed in all cases. Electron microscopic evaluation for viral particles was performed in three cases. The study group consisted of nine men and five women (mean age 59 years; range 23-87 years; 12 white, one black, one Hispanic). Patients presented with dysphagia or odynophagia (n = 5), upper gastrointestinal bleeding (n = 5), heartburn (n = 2), or abdominal pain (n = 2). The etiology of esophagitis was attributed to gastroesophageal reflux in 10, radiotherapy in one, Candida infection in one, drug-induced (alendronate) in one, and unknown in 1. Endoscopically, seven patients had an ulcer or erosion, four erythema, two stricture formation, and one white mucosal plaques. Microscopically, all cases showed multiple multinucleated (mean three nuclei per cell, range two to nine) squamous epithelial cells (range 2 to 11 cells per biopsy) confined to the basal zone in nine of 14 cases and involving the basal and superficial epithelium in the remainder. The nuclei contained a single or multiple eosinophilic nucleoli with a perinucleolar halo, but no inclusions, hyperchromaticity, or atypical mitoses. All cases showed associated nonspecific features of active esophagitis such as ulceration, neutrophilic and eosinophilic inflammation, basal cell hyperplasia, and elongation of the lamina propria papillae. The multinucleated giant cells, in all cases, were strongly positive for cytokeratin AE1/AE3 and were negative for S-100, HSV I and II, CMV, and HPV-ISH. MIB-1 positivity was observed in all basally located multinucleated giant cells, whereas those in the more superficial layers were negative. Electron microscopy failed to show viral particles in three of three cases. After treatment, all patients demonstrated clinical improvement. Three patients in whom follow-up biopsies were performed showed no evidence of esophagitis, epithelial cell multinucleation, or dysplasia. Multinucleated epithelial giant cell changes may rarely be seen in patients with esophagitis of varying etiology and probably represent a regenerative response to injury. This feature is important to distinguish from either viral cytopathic effect or dysplasia.
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PMID:Multinucleated epithelial giant cell changes in esophagitis: a clinicopathologic study of 14 cases. 942 21

Comparative value of esophagoscopy and biopsy in correlation with 24 hour esophageal pH metry parameters were assessed in 53 consecutive patients operated on due to GERD. The special attention was paid to the type and intensity of esophageal mucosa injury and the quantity of the pathological gastroesophageal reflux. The therapeutic effect of the Nissen Rossetti fundoplication on postoperative changes in esophageal mucosa was also estimated on the average 18 months after the antireflux procedure. Pre and postoperative efficiency of the antireflux mechanism and patients conditions were evaluated on the grounds of anamnesis, physical examination, x-ray examination, endoscopy with biopsy, 24 hours pH metry, LES and body of the esophagus manometry. The results were shown as mean and standard deviation. Statistical significance was determined using SPSS/PC-packet, Smirnow-Kolmogorow and Wilcoxon test, with p values < 0.05 considered as significant. After the operation complete and durable relief of reflux symptoms was obtained in 83% patients, with high significant decrease of DeMeester score from 21.15 +/- 12.19 to 3.43 +/- 5.22, p < 0.0002. Endoscopy following the operation confirmed significant regression of the GERD pathology, mainly in II and III degree according to Savary Miller classification, from 98.1% to 18.9%, p < 0.005. In comparison with other types of the pathology, Barrett's esophagus was always connected with significant higher quantity of the pathological gastroesophageal reflux before as well as after the operation. Biopsy following the operation revealed not significant regression of mucosal GERD lesions in 54.7%. The healing changes were observed first of all in the most severe esophageal injuries-chronic squamous esophagitis (64%), CLE except intestinal type of metaplasia (86.&%) and low grade dysplasia of squamous epithelium (100%). The absence of regression after the operation was always combined with unsatisfactory decrease of 24 hour pH metry parameters: DeMeester score, percentage of total time pH < 4.0 and time pH < 4.0 in supine position. Postoperative progression of GERD pathology was noticed in 12.6% patients. One third patients had the same biopsy outcome before and after the operation, even in those without any GERD complaints. Biopsy in correlation with 24 hour pH metry analysis similarly like endoscopy revealed in CLE twice higher DeMeester score than squamous esophagitis, hyperplasia or normal esophageal mucosa. The study proved that more advanced stages of GERD pathology were connected with higher quantity of the gastroesophageal reflux. The results presented in this study confirmed high efficacy of the Nissen Rossetti fundoplication in surgical treatment of GERD. We would to emphasize that with unsatisfactory biopsy results following the operation should be the reason for permanent follow up endoscopic and histopathologic verification.
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PMID:[Postoperative evaluation of esophageal mucosal change dynamics in patients with reflux diseases]. 944 69

Barrett's esophagus, or specialized intestinal metaplasia, is a common condition associated with gastroesophageal reflux and an increased risk for adenocarcinoma of the esophagus and gastric cardia. Currently, clinical surveillance for early detection of adenocarcinoma relies on the histopathological assessment of dysplasia. In this review we present data from the published literature, and combine this with results from our own research, to address what is currently known about the environmental factors and the molecular changes thought to be important in the pathogenesis of Barrett's esophagus. The most important and well-characterized molecular changes, preceding the development of dysplasia, are alterations in the p53 and erbB-2 genes and aneuploidy. These molecular changes, as well as environmental influences, such as the quality and quantity of gastroduodenal refluxate, may result in abnormal cell proliferation which in turn promotes further genetic abnormalities and deregulation of cell growth. The identification of molecular changes, in the context of predisposing environmental factors, will enhance our understanding of the malignant progression of Barrett's esophagus leading to more effective surveillance and treatment.
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PMID:Recent developments in the molecular characterization of Barrett's esophagus. 957 72


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