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

Barrett's esophagus is a condition in which the normal stratified squamous epithelium is replaced by a specialized metaplastic columnar epithelium. It develops as a consequence of chronic gastroesophageal reflux and predisposes to the development of esophageal adenocarcinoma. Adenocarcinoma develops in Barrett's esophagus by a multistep process in which specialized metaplasia progresses to dysplasia, then to early adenocarcinoma, and eventually to deeply invasive and metastatic disease. This neoplastic progression is associated with a process of genomic instability that generates abnormal clones of cells, some of which have aneuploid or increased G2/tetraploid DNA content. A systematic protocol of endoscopic biopsy can detect Barrett's adenocarcinomas at an early stage, when they may be curable.
 ...
PMID:Barrett's esophagus and esophageal adenocarcinoma. 178 15

Barrett's esophagus develops as a complication of chronic gastroesophageal reflux and predisposes patients to the development of dysplasia and adenocarcinoma of the esophagus. Because light microscopy of dysplasia in Barrett's esophagus shows diminished or absent mucus, we used transmission electron microscopy to compare cytoplasmic organelles required for mucus production in dysplastic and nondysplastic esophageal columnar epithelium. These observations of the rough endoplasmic reticulum, Golgi apparatus, and secretory granules were correlated with histologic interpretations and flow cytometric measurements of abnormalities of DNA content. Ultrastructural abnormalities included depletion and alteration of organelles required for mucus biosynthesis. These abnormalities often were accompanied by cells with markedly distended rough endoplasmic reticulum and massive accumulation of cytoplasmic glycogen aggregates. All 9 patients who had Barrett's dysplasia with or without early adenocarcinoma had ultrastructural abnormalities, as did 3 of 8 patients whose biopsy histology was indefinite for dysplasia. Abnormalities measured by flow cytometry correlated well with the presence of these ultrastructural aberrations. All 9 patients with Barrett's dysplasia with or without early adenocarcinoma had abnormalities observed by electron microscopy and aneuploidy or increased G2/tetraploid fractions measured by flow cytometry. Two of the 3 patients whose biopsies were indefinite for dysplasia and who had ultrastructural abnormalities also had aneuploidy or increased G2/tetraploid fractions. Neither ultrastructural nor flow cytometric abnormalities were found in the remaining 5 patients whose biopsies were indefinite for dysplasia, in 19 of 22 patients with Barrett's specialized metaplasia, or in any of the 7 patients with gastroesophageal reflux disease without Barrett's specialized metaplasia. Two of the 22 patients with Barrett's specialized metaplasia had distended rough endoplasmic reticulum in rare cells, and one other had an aneuploid cell population. We conclude that neoplastic progression in Barrett's esophagus is associated with abnormalities of cytoplasmic organelles required for mucus production. With few exceptions, these ultrastructural aberrations correspond to the presence of dysplasia or of aneuploidy or increased G2/tetraploid fractions. Electron microscopy and flow cytometery detect abnormalities associated with the development of dysplasia and cancer in Barrett's esophagus that may be biologically significant.
 ...
PMID:Correlation of ultrastructural aberrations with dysplasia and flow cytometric abnormalities in Barrett's epithelium. 291 Jul 57

Barrett's esophagus is a condition in which metaplastic columnar epithelium replaces squamous esophageal epithelium as a consequence of chronic gastroesophageal reflux. Patients with this condition are at increased risk for the development of adenocarcinoma. To better understand the progression to adenocarcinoma in this disease, we studied abnormalities in DNA content of epithelial cells in Barrett's esophagus. Using flow cytometry, we examined the spatial distribution of abnormal nuclear DNA contents (aneuploidy) in the esophagi of 14 patients with Barrett's adenocarcinoma. Multiple (2 to 14) populations of aneuploid cells were seen in 12 of the 14 cases. Some early carcinomas appeared to be associated with a single aneuploid population of cells. Surrounding dysplastic epithelium often contained multiple, different overlapping aneuploid populations. These data suggest that neoplastic progression in Barret's esophagus is associated with a process of genomic instability which leads to evolution of multiple aneuploid populations, with the ultimate development of a clone of cells capable of malignant invasion. Thus, detection of multiple aneuploid populations of cells in Barrett's esophagus may indicate a high risk of cancer. Barrett's esophagus provides a unique and readily accessible model for the study of neoplastic progression in human epithelial malignancy.
 ...
PMID:Progression to cancer in Barrett's esophagus is associated with genomic instability. 291 Nov 84

Gastroesophageal reflux is a very common disorder. Typical symptoms are heartburn, regurgitation and chest pain. Recently, it has been demonstrated that gastroesophageal reflux may generate or worse extraesophageal symptoms such as asthma, chronic bronchitis, posterior laryngitis, and chronic cough. The diagnosis of gastroesophageal reflux is suggested by typical symptoms which improve under a therapy with proton pump inhibitors. pH-monitoring over 24 hours is able to establish directly the diagnosis by measuring acid reflux into the esophagus. Manometry detects the two most common causes of gastroesophageal reflux: insufficiency of the lower esophageal sphincter or esophageal motility abnormalities. Gastroesophageal reflux can lead to reflux esophagitis, which is diagnosed endoscopically. An endoscopy should routinely be performed in case of dysphagia, anemia, or loss of weight. A long-term sequela of gastroesophageal reflux is the development of Barrett's-esophagus, a condition which has to be verified by endoscopy and biopsy. This premalignant lesion is defined by a metaplastic change from the normal squamous mucosa to a specialized intestinal epithelium characterized by goblet cells. Because dysplasia in these metaplastic areas can lead to esophageal adenocarcinoma, regular endoscopic surveillance with biopsies is recommended. Gastroesophageal reflux can significantly impair the quality of life and can cause complications that include the neoplastic progression from Barrett's esophagus to carcinoma. Therefore, appropriate diagnostic procedures and adequate therapy are required. This article summarizes the diagnostic approach to patients with gastroesophageal reflux, reflux esophagitis and Barrett's-esophagus. The impact of endoscopy, pH-monitoring, esophageal manometry, radiology and scintigraphy are reviewed.
 ...
PMID:[Diagnosis of gastroesophageal reflux and Barrett esophagus]. 1092 25

A dramatic increase in the incidence of esophageal adenocarcinoma has occurred among men in the United States over the last two decades. The underlying reasons remain largely unknown, although the increasing prevalence of obesity likely plays a role. Most adenocarcinomas arise in a metaplastic epithelium termed Barrett's esophagus (BE) that develops in approximately 10% of persons who have chronic gastroesophageal reflux. Persons with BE are at high risk (0.5-1.0%/year) of progressing to cancer. In a cross-sectional study of 429 persons with BE, we evaluated the associations between increased body mass index, anthropometric measures, cigarette smoking, use of nonsteroidal anti-inflammatory drugs (NSAIDs) and markers of increased risk, including aneuploidy, increased 4N fraction, loss of heterozygosity (LOH) of 17p and 9p alleles, and high-grade dysplasia (HGD). In logistic regression models adjusting for age, gender, NSAID use, and cigarette smoking, increasing waist:hip ratio was related to increasing risk of aneuploidy (trend P = 0.01), 17p LOH (trend P = 0.005), and 9p LOH (trend P = 0.007). The odds ratios comparing highest to lowest quartiles were 4.3 [95% confidence interval (CI), 1.2-15.6] for aneuploidy, 3.9 (95% CI, 1.3-11.4) for 17p LOH, and 2.7 (95% CI, 1.2-6.3) for 9p LOH. A nonsignificant trend was also observed for increased 4N fraction, whereas little association was found for HGD. Similar patterns of risk were noted for other anthropometric measures such as waist:thigh and abdomen:thigh ratios. There was no evidence that elevated body mass index increased risk of any of the biomarkers. Suggestive evidence also was found for a protective effect of NSAID use. The odds ratios for current users, compared with those who never used NSAIDs regularly, were 0.6 (95% CI, 0.3-1.4) for increased 4N, 0.6 (95% CI, 0.3-1.3) for aneuploidy, 0.3 (95% CI, 0.1-0.7) for 17p LOH, and 0.7 (95% CI, 0.4-1.2) for HGD. There was no association between NSAID use and risk of 9p LOH. We conclude that an abdominal distribution of body fat, which is more common in men and is termed male-pattern obesity, may be a strong predictor of risk of neoplastic progression among persons with BE and may account in part for the male predominance of BE and esophageal adenocarcinoma. We also conclude that NSAID use may reduce the risk of progression to cancer in this population. Prospective studies are needed to confirm these results.
 ...
PMID:Nonsteroidal anti-inflammatory drug use, body mass index, and anthropometry in relation to genetic and flow cytometric abnormalities in Barrett's esophagus. 1216 28

Barrett's oesophagus is a change in the lining of the distal oesophagus recognised at endoscopy and documented to have intestinal metaplasia by biopsy. It is thought that it is an acquired condition resulting from chronic gastro-oesophageal reflux disease (GORD). Barrett's oesophagus has the potential to progress to adenocarcinoma of the oesophagus. Evidence to support the association between Barrett's oesophagus and GORD appears to be strong but circumstantial. The intermediate steps that lead from GORD to Barrett's oesophagus are speculative and the timeline for the development of this condition remains obscure. It has yet to be demonstrated that erosive oesophagitis is a necessary intermediate step for the development of Barrett's oesophagus. In spite of effective therapy, documentation that medical or surgical therapy prevents Barrett's oesophagus is lacking. The goal of screening for Barrett's oesophagus is ultimately to improve the survival of patients with adenocarcinoma of the oesophagus. This goal has not been achieved and the evidence-based criteria for screening remain to be defined. Medical and surgical therapy of Barrett's oesophagus is effective in controlling reflux, although not proven to prevent neoplastic progression of the at risk mucosa. Endoscopic techniques of mucosal injury have been applied as alternatives to oesophagectomy in efforts to prevent progression to cancer. Surveillance endoscopy and biopsy is the currently accepted method aimed at early intervention and improved survival for oesophageal adenocarcinoma. A working surveillance protocol to accomplish this is proposed based on dysplasia grade. If no dysplasia is found and confirmed with subsequent endoscopy and biopsy, a 3-year interval is recommended. If only low grade dysplasia is confirmed, then annual endoscopy until no dysplasia is recognised is recommended. On the basis of defined risk factors, high grade dysplasia can lead to intense surveillance every 3 months or an intervention. Future developments in understanding the biology of Barrett's oesophagus and in therapeutic interventions will provide an opportunity for more effective screening, surveillance and prevention of neoplastic progression.
 ...
PMID:Barrett's oesophagus: optimal strategies for prevention and treatment. 1265 53

Gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma are related diseases with environmental and genetic determinants. The genetic changes are relevant in 2 distinct ways. First, there are heritable variations in germline DNA that may influence the individual susceptibility to cancer. Second, there is an accumulation of somatic-cell genetic and epigenetic changes within the epithelium during the metaplasia-dysplasia-carcinoma sequence, which may be an important determinant for the likelihood for cancer progression. Esophageal cancer occurring in the context of a familial syndrome is rare and most cases are sporadic. The sporadic cases still may have heritable germline influences, but these are likely to involve multiple, low-penetrance susceptibility genes. To date, the relative contribution and identity of such genes are unknown. However, in the future the identification of susceptibility genes could have important public health implications for patient management. With regard to the epithelium, a map gradually is being created of the frequently occurring alterations. Some of these changes are critical whereas others are bystanders. As well as the identification of abnormalities in target genes, it also is possible to determine the global gene expression profile of these diseases and to correlate this profile with clinical outcome. It is hoped that these complementary approaches will enable patients to be stratified in terms of their cancer risk so that prevention, surveillance, and treatment strategies can be targeted appropriately. At the current time, genetics does not influence routine clinical management of patients with gastroesophageal reflux disease, Barrett's esophagus, or esophageal adenocarcinoma.
 ...
PMID:Complex diseases in gastroenterology and hepatology: GERD, Barrett's, and esophageal adenocarcinoma. 1595 94

SUMMARY. Esophageal cancer is one of the most deadly forms of gastrointestinal cancer with a mortality rate exceeding 90%. The major risk factors for esophageal adenocarcinoma are gastroesophageal reflux disease (GERD) and its sequela, Barrett's esophagus. GERD commonly leads to esophagitis. In a minority of patients however, ongoing GERD leads to replacement of esophageal squamous mucosa with metaplastic, intestinal-type Barrett's mucosa. In the setting of continued peptic injury, Barrett's mucosa can give rise to esophageal adenocarcinoma. Despite the widespread use of potent acid suppressive therapies for patients with GERD, the incidence of esophageal adenocarcinoma, among white men in the USA, the UK and Europe has continued to rise. Cancers in Barrett's esophagus arise through a sequence of genetic events that endow the cells with six essential physiologic hallmarks of cancer as described by Hanahan and Weinberg in 2000. These cancer hallmarks include the ability to proliferate without exogenous stimulation, to resist growth-inhibitory signals, to avoid triggering the programmed death mechanism (apoptosis), to resist cell senescence, to develop new vascular supplies (angiogenesis), and to invade and metastasize. While the acquisition of these essential attributes is not specific to the neoplastic progression of Barrett's esophagus, this review will focus on the genetic alterations that occur in Barrett's cells that contribute to the acquisition of each of the hallmarks. Moreover, potential diagnostic and therapeutic strategies for Barrett's patients aimed at each of these cancer hallmarks will be reviewed.
 ...
PMID:Molecular targets for treatment of Barrett's esophagus. 1605 81

Barrett's esophagus (BE) is a metaplastic disorder in which specialized columnar epithelium replaces healthy squamous epithelium (intestinal metaplasia). Even though its pathophysiology and the steps of its neoplastic progression are not completely understood, BE can be considered as a complication of gastroesophageal reflux disease (GERD). Given that esophageal adenocarcinoma, which is continually increasing in the Western world, still has a poor prognosis and suffers from late diagnosis, and because BE is a precancerous lesion, there is a strong need for good molecular markers of malignant progression in Barrett's metaplasia (BM). The aim of this review is to examine the published data regarding the role that assessment of p53 may play in the management of BE, trying to understand if it may be a useful marker to early diagnose BE malignant transformation.
 ...
PMID:p53 and the malignant progression of Barrett's esophagus. 1611 Apr 81

The pathogenesis of cancer in Barrett's esophagus is multifactorial. Gastroesophageal reflux seems to be important in the initiation of Barrett's esophagus, but its role in promoting carcinogenesis has yet to be established. Diet, lifestyle and carcinogens, especially the nitrates, may be important in the development of carcinogenesis, and require further investigation. Inhibition of reflux-stimulated inflammatory changes, for example by inhibiting cyclooxygenase, holds promise for decreasing cancer progression. Similarly, dietary and lifestyle modification used in the management of reflux may also help to prevent the development of esophageal cancer. The molecular changes that are associated with the development of cancer in Barrett's esophagus offer several potential areas of intervention to prevent and manage esophageal cancer. Limiting cell growth, increasing apoptosis of damaged cells, limiting cell invasion and angiogenesis factors could be useful to accomplish this goal. Having a greater understanding of the pathogenesis of this condition can only help to develop more management options in the future.
 ...
PMID:Mechanisms of disease: Carcinogenesis in Barrett's esophagus. 1626 72


1 2 3 4 Next >>