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)

Esophageal adenocarcinoma is increasing in incidence; it relates to chronic gastroesophageal reflux, it is difficult to cure, and treatment modalities increasingly use chemotherapy and radiation therapy prior to resectional surgery. Nuclear factor-kappa B (NF-kappaB) is a pleiotropic transcription factor that regulates several genes for cytokines and enzymes involved in inflammation and immunity, and we have previously described sequential expression of NF-kappaB from the normal esophagus through Barrett's metaplasia to adenocarcinoma. The aim of this exploratory study was to assess the NF-kappaB status and cytokine profiles pre- and post-chemoradiotherapy for esophageal adenocarcinoma. Fresh biopsy specimens obtained from 20 patients with esophageal adenocarcinoma and normal adjacent squamous epithelium were obtained pre-, during and post-chemoradiotherapy, and NF-kappaB expression was analyzed by electrophoretic mobility shift assay. The cytokine protein content of interleukin-1 beta (IL-1beta) and interleukin-8 (IL-8) of tissue homogenates was measured using the ELISA technique. NF-kappaB was constitutively activated in tumor tissues from esophageal adenocarcinoma but was not detected in adjacent normal esophageal mucosa. Elevated levels of IL-1beta and IL-8 were significantly (P < 0.05) higher in tumor tissues compared to control tissues. Patients with a major or complete pathological response (responders) were associated with absence of activated NF-kappaB from nuclear extracts after treatment. Moreover, IL-1beta and IL-8 levels were significantly (P < 0.05) down-regulated in tumor tissues from patients who demonstrated a complete pathological response. No differences in NF-kappaB, IL-1beta and IL-8 levels were detected pre- and post-treatment in patients who did not have a major or complete pathological response (non-responders). The study suggests that monitoring of molecular and cytokine patterns in patients undergoing this neoadjuvant regimen may help subselect the cohort that derives most benefit from the multimodal approach.
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PMID:Activated nuclear factor-kappa B and cytokine profiles in the esophagus parallel tumor regression following neoadjuvant chemoradiotherapy. 1612 81

Chronic gastroesophageal reflux disease is a known risk factor for Barrett's esophagus (BE), which induces oxidative mucosal damage. Glutathione peroxidase-3 (GPx3) is a secretory protein with potent extracellular antioxidant activity. In this study, we have investigated the mRNA and protein expression of GPx3, and explored promoter hypermethylation as an epigenetic mechanism for GPx3 gene inactivation during Barrett's carcinogenesis. Quantitative real-time reverse transcription polymerase chain reaction on 42 Barrett's adenocarcinomas (BAs) revealed consistently reduced levels of GPx3 mRNA in 91% of tumor samples. GPx3 promoter hypermethylation was detected in 62% of Barrett's metaplasia, 82% of dysplasia, and 88% of BA samples. Hypermethylation of both alleles of GPx3 was most frequently seen in BAs (P = .001). Immunohistochemical staining of GPx3 in matching tissue sections (normal, BE, Barrett's dysplasia, and BA) revealed strong immunostaining for GPx3 in normal esophageal and gastric tissues. However, weak to absent GPx3 staining was observed in Barrett's dysplasia and adenocarcinoma samples where the promoter was hypermethylated. The degree of loss of immunohistochemistry correlated with the hypermethylation pattern (monoallelic versus biallelic). The observed high frequency of promoter hypermethylation and progressive loss of GPx3 expression in BA and its associated lesions, together with its known function as a potent antioxidant, suggest that epigenetic inactivation and regulation of glutathione pathway may be critical in the development and progression of BE.
Neoplasia 2005 Sep
PMID:Hypermethylation and loss of expression of glutathione peroxidase-3 in Barrett's tumorigenesis. 1622 8

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.
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PMID:Differences and similarities of adenocarcinomas of the esophagus and esophagogastric junction. 1629 81

There are a wide variety of palliative treatments for esophageal cancer. The aim of most treatments is to maintain oral food intake, which should stabilize or even improve quality of life. Stent placement is currently the most widely used treatment modality for palliation of dysphagia from esophageal cancer. Stent placement offers a rapid relief of dysphagia, however, the rate of complications (late hemorrhage) and recurrent dysphagia (stent migration, tumor overgrowth) is relatively high. The scientific evidence to advocate the use of anti-reflux stents for the prevention of gastro-esophageal reflux is currently too low. Photodynamic therapy is mostly used in North America; however, due to the high costs of the treatment, the long-lasting side effects and the necessity of repeated treatments, it is not an ideal treatment for palliation of malignant dysphagia. Nd:YAG laser is a relatively effective and safe treatment modality, although laser treatment is also expensive, technically difficult and requiring repeated treatment sessions at 4-6 weeks intervals. Single dose brachytherapy compares favorably to stent placement in long-term effectiveness and safety. Effective treatment strategies are probably 12 Gy given in one fraction or 16 Gy given in two fractions. Palliative chemotherapy offers response rates in recent trials (including partial and complete responses) ranging from 35% to 50%. Whether palliative chemotherapy also results in a survival benefit is not established yet. For clinical trials on palliation of esophageal cancer, the measurement of quality of life is an important outcome measure. The cancer-specific EORTC QLQ-C30 and the esophageal cancer-specific EORTC-OES-18 are validated measures for establishing quality of life status. For the future, a multimodality approach with stent placement or brachytherapy in combination with chemotherapy may be indicated.
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PMID:Palliative therapy. 1629 91

The development of endoscopic techniques for the treatment of gastroesophageal reflux disease has come to an abrupt halt after some of the most widely disseminated and best evaluated techniques were withdrawn from the market. This underlines the importance of conducting high-quality endoscopic research before techniques are adopted in routine practice. The endoscopic surveillance of patients with Barrett's esophagus needs to be improved in order to be cost-effective. Alternative techniques for tissue sampling are being explored (e. g., brush cytology, imaging cytometry), as well as the use of molecular markers, to select patients who are at risk and to improve compliance by patients. New endoscopic imaging techniques (such as autofluorescence endoscopy) may improve the detection of early neoplasia in those Barrett's patients who are at risk for malignant degeneration. Subsequent endoscopic treatment should primarily consist of an endoscopic resection technique with restricted use of ablative therapies. Future studies should focus on the development of endoscopic resection techniques that allow en-bloc resection of Barrett's lesions, stepwise complete resection of the whole Barrett's segment, and/or easier and safer tissue ablation. Finally, histopathological studies are needed in order to detect risk factors for an adverse outcome after endoscopic treatment for early neoplasia in Barrett's patients.
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PMID:Latest developments in the endoscopic management of gastroesophageal reflux disease and Barrett's esophagus: an overview of the year's literature. 1647 18

Barrett's esophagus (BE), a complication of chronic gastroesophageal reflux disease (GORD), is a condition that is premalignant for adenocarcinoma of the esophagus and esophagogastric junction. Esophageal adenocarcinoma, once an uncommon entity, has been growing rapidly in incidence over the last two decades in several parts of the world. Barrett's esophagus is a change in the esophageal epithelium of any length that can be recognized at endoscopy and is confirmed to have intestinal metaplasia by biopsy (American College of Gastroenterology guidelines). Because of its premalignant nature, it is recommended that patients with BE undergo regular endoscopic surveillance. The recommendation for endoscopic surveillance is based on unproved and controversial assumptions including: 1) the assumption that Barrett's esophagus adversely influences survival; 2) the assumption that endoscopic surveillance can reliably detect early, curable neoplasia in the columnar lined esophagus. Moreover, the low incidence of adenocarcinoma (reported cancer incidence rates in prospective studies on BE range between 0.5% and 1.9%) is used to support an approach of not surveying patients with Barrett's esophagus. Despite these not convincing data, endoscopic surveillance is considered ''reasonable'' and ''desirable'' by the gastroenterological associations and consensus meetings. Endoscopic surveillance for cancer in Barrett's esophagus (BE) is performed primarily to seek dysplasia, to prevent the progression to invasive malignancy; however, one of the limitations of using dysplasia is a lack of understanding of its natural history. The efficacy of endoscopic surveillance for Barrett's esophagus is likely to remain unclear for a long time. The American College of Gastroenterology has recommended the following practice guidelines: a) for patients with no dysplasia, surveillance endoscopy is recommended at an interval of every 2 to 3 years; b) for patients with low grade dysplasia, surveillance endoscopy every 6 months for the first year is recommended, followed by yearly endoscopy if the dysplasia has not progressed in severity; c) for patients with high grade dysplasia, two alternatives are proposed after the diagnosis has been confirmed by an expert gastrointestinal pathologist. One alternative is intensive endoscopic surveillance until intramucosal cancer is detected at an interval of every 3-6 months. The other alternative is esophageal resection. In the situation of indeterminate dysplasia, whereas the pathologist can not come to definite diagnosis, control biopsies are proposed after 2 months of adequate acid suppression by means of proton pump inhibition. In all cases, the technique of random, four quadrant biopsies taken every 2 cm in the columnar-lined esophagus for standard histologic evaluation is recommended. Any grossly abnormal areas may be biopsied too. One can expect however that during the next future these protocol will change considering new data on dysplasia detection (biochemical markers, flow cytometry), new techniques to identify dysplasia (chromoendoscopy, endosonography, coherence optical tomography, fluorescence techniques) and development of better ablative techniques. At present a marker other than dysplasia identifying a high risk group for cancer on which to focus endoscopic surveillance has not yet been established.
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PMID:Endoscopic surveillance in Barrett's esophagus. 1648 97

The incidence and mortality of gastric cancer have fallen dramatically in US and elsewhere over the past several decades. Nonetheless, gastric cancer remains a major public health issue as the fourth most common cancer and the second leading cause of cancer death worldwide. Demographic trends differ by tumor location and histology. While there has been a marked decline in distal, intestinal type gastric cancers, the incidence of proximal, diffuse type adenocarcinomas of the gastric cardia has been increasing, particularly in the Western countries. Incidence by tumor sub-site also varies widely based on geographic location, race, and socio-economic status. Distal gastric cancer predominates in developing countries, among blacks, and in lower socio-economic groups, whereas proximal tumors are more common in developed countries, among whites, and in higher socio-economic classes. Diverging trends in the incidence of gastric cancer by tumor location suggest that they may represent two diseases with different etiologies. The main risk factors for distal gastric cancer include Helicobacter pylori (H pylori) infection and dietary factors, whereas gastroesophageal reflux disease and obesity play important roles in the development of proximal stomach cancer. The purpose of this review is to examine the epidemiology and risk factors of gastric cancer, and to discuss strategies for primary prevention.
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PMID:Epidemiology of gastric cancer. 1648 33

The incidence of esophageal adenocarcinoma is rapidly rising in Western populations. Gastroesophageal reflux disease (GERD) is thought to be one of the most important risk factors. However, the mechanisms by which GERD enhances tumor formation at the gastroesophageal junction are not well understood. Myosmine is a tobacco alkaloid which has also a wide spread occurrence in human diet. It is readily activated by nitrosation and peroxidation giving rise to the same hydroxypyridylbutanone-releasing DNA adducts as the esophageal carcinogen N'-nitrosonornicotine. Therefore, the genotoxicity of myosmine was tested in a human esophageal adenocarcinoma cell line (OE33). DNA damage was assessed by single-cell gel electrophoresis (Comet assay). DNA strand breaks, alkali labile sites and incomplete excision repair were expressed using the Olive tail moment (OTM). The Fapy glycosylase (Fpg) enzyme was incorporated into the assay to reveal additional oxidative DNA damage. DNA migration was determined after incubation of the cells for 1-24h. Under neutral conditions high myosmine concentrations of 25-50mM were necessary to elicit a weak genotoxic effect. At pH 6 genotoxicity was clearly enhanced giving a significant increase of OTM values at 5mM myosmine. Lower pH values could not be tested because of massive cytotoxicity even in the absence of myosmine. Co-incubation of 25 mM myosmine with 1mM H(2)O(2) for 1h significantly enhanced the genotoxicity of H(2)O(2) but not the oxidative lesions additionally detected with the Fpg enzyme. In the presence of the peroxynitrite donor 3-morpholinosydnonimine (SIN-1) a dose-dependent significant genotoxic effect was obtained with 1-10mM myosmine after 4h incubation. NS-398, a selective inhibitor of cyclooxygenase 2, did not affect the SIN-1 stimulated genotoxicity of myosmine. Finally, the 23 h repair of N-methyl-N'-nitro-N-nitrosoguanidine-induced DNA lesions was significantly inhibited in the presence of 10mM myosmine. In conclusion, myosmine exerts significant genotoxic effects in esophageal cells under conditions which may prevail in GERD such as increased oxidative and nitrosative stress resulting from chronic inflammation.
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PMID:Genotoxic effects of myosmine in a human esophageal adenocarcinoma cell line. 1650 64

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.
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PMID:Review article: from gastrin to gastro-oesophageal reflux disease--a century of acid suppression. 1655 70

Surgery for cancer carries concerns of tumor dissemination related to tumor manipulation, tumor violation, and wound seeding. Minimally invasive surgery is now standard for several benign conditions, such as symptomatic cholelithiasis and surgical therapy of gastroesophageal reflux. With the minimally invasive surgery explosion of the 1990s, virtually every procedure traditionally performed via laparotomy has been performed successfully with laparoscopic methods, including pancreaticoduodenectomy for cancer. Shortly after the first descriptions of laparoscopic-assisted colectomy, reports of port-site tumor recurrences surfaced, raising concerns of usingpneumoperitoneum-based surgery for malignancy. This review covers the development of laparoscopic surgery for cancer. Historical perspectives elucidate factors that helped shape the current state of the art. Theoretical concerns are discussed regarding surgery-induced immune suppression and its potential effects on tumor recurrence with both open and laparoscopic approaches. The concerns of laparoscopic port-site wound metastases are addressed, with a critical evaluation of the literature. Finally, a technical discussion of laparoscopic-assisted resections of hepatic and pancreatic tumors details patient selection, operative approach, and existing data for these operations.
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PMID:Laparoscopic surgery for cancer: historical, theoretical, and technical considerations. 1692 61


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