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)

Intestinalized epithelium in traditional long-segment Barrett's esophagus (BE) shows increased proliferative activity, which is postulated to be an early step in the metaplasia-dysplasia-carcinoma sequence. The aim of this study was to evaluate the proliferative activity of intestinalized epithelium of the distal esophagus and gastroesophageal junction (IMEGEJ). Tissue sections from 78 consecutive patients (20 with IMEGEJ, 58 without IMEGEJ) who had elective upper gastrointestinal endoscopy over a 6-month period were immunohistochemically stained with MIB-1, the Ki-67 proliferation-antigen-associated marker, for evaluation of the crypt MIB-1 proliferation index (PI), size of the proliferative zone (PZ), and the presence of surface epithelial staining. Data from the IMEGEJ and non-IMEGEJ groups, and from 15 age-matched patients with traditional long-segment BE (>3.0 cm), were compared statistically. IMEGEJ patients showed a statistically significant increase in the mean crypt PI compared with non-IMEGEJ controls (21.9+/-19.5 v 14.3+/-9.3; P=.01). In addition, IMEGEJ cases showed an increase in the mean crypt PZ (52.3+/-16.4 v 45.2+/-17.2; P=.05), and a trend toward an increase in the percentage of cases with MIB-1-positive surface epithelial cells (50% v 33%, P=.18). Patients with IMEGEJ did not differ from patients without IMEGEJ with respect to any other clinical or histological feature, including signs or symptoms of gastroesophageal reflux disease and presence or absence of esophagitis or carditis. The MIB-1 results of the patients with long-segment BE (MIB-1 PI = 22.6+/-20.5, MIB-1 PZ = 51.8+/-19.6, proportion of cases with MIB-1-positive surface cells = 66%) were similar to those with IMEGEJ. Intestinalized epithelium in the distal esophagus or gastroesophageal junction shows increased proliferative activity in comparison with patients without intestinalized epithelium. This finding supports an increased risk of carcinogenesis in patients with IMEGEJ.
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PMID:Proliferative characteristics of intestinalized mucosa in the distal esophagus and gastroesophageal junction (short-segment Barrett's esophagus): a case control study. 1020 62

Cancer of the distal stomach, both of the intestinal and diffuse type, is strongly associated with Helicobacter pylori colonization. This bacterium causes chronic active inflammation of the gastric mucosa in the majority of colonized subjects. In a considerable number of them, this will eventually lead to a loss of gastric glands, and thus the establishment of atrophic gastritis, which is associated with the development of intestinal metaplasia and dysplasia. Development of atrophy and metaplasia of the gastric mucosa are thus strongly associated with H. pylori infection, instead of a direct and inevitable consequence of ageing. Approximately 40-50% of infected subjects develop these conditions, but they are rare in non-infected subjects. The presence of these consecutive disorders leads to a 5-90-fold increased risk for cancer of the distal stomach, in particular of the intestinal type. This sequence explains the increased risk for gastric cancer in H. pylori-infected subjects, as has been shown in various cross-sectional and longitudinal studies. In a combined analysis of three longitudinal studies, a significant trend was observed towards an increased odds ratio with longer intervals between (retrospective) serological diagnosis of H. pylori infection and observation of gastric cancer, this risk being more than eight-fold increased if the interval had been at least 15 years. This is thought to reflect development of atrophic gastritis and intestinal metaplasia with loss of H. pylori colonization in the years prior to development of cancer. Atrophic gastritis and gastric cancer thus appear closely associated with the presence of H. pylori, yet not all infected subjects will eventually develop atrophy and only a small minority develop gastric cancer. Factors that influence the risks for atrophy and cancer in the presence of infection may be related to the time that infection occurred and to characteristics of the bacterial strain and the host. Evidence for the role of these factors is now increasing. Recognition of the causal role of H. pylori in the induction of gastric cancer theoretically presents tools for cancer prevention. The efficacy of screening and bacterial eradication for prevention of distal gastric cancer is being studied in a number of large-scale intervention studies in different populations. It is hoped that these studies will also provide answers to the potential preventive role of H. pylori colonization in the development of gastro-oesophageal reflux disease and associated conditions, in particular development of cancer of the proximal stomach. Infection with H. pylori plays an important role in the aetiology of atrophic gastritis and gastric cancer. Studies suggest an eight-fold increased risk for both conditions in the presence of infection. Factors that influence the risk for both conditions in the presence of infection are the age at which infection occurred and the presence of cagA as a marker for more pathogenetic H. pylori strains. The efficacy and side-effects of intervention for the prevention of distal gastric cancer has yet to be established.
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PMID:Review article: exploring the link between Helicobacter pylori and gastric cancer. 1020 81

The last 2 decades have seen dramatic advances in Barrett's esophagus. The definition has evolved; the rising incidence of adenocarcinoma has been recognized; and effective therapy to control gastroesophageal reflux disease has been developed. Both proton pump inhibitor therapy and laparoscopic fundoplication represent major developments. Studies of patients with dysplasia have helped to clarify appropriate surveillance intervals and treatment strategies for these patients, although controversy still exists. The possibility of reversing Barrett's esophagus in selected high-risk patients offers major hope for the future prevention of adenocarcinoma of the esophagus.
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PMID:Barrett's esophagus: update on screening, surveillance, and treatment. 1039 92

Dysplasia in Barrett's esophagus (BE) is a precursor to adenocarcinoma and most commonly occurs as a flat, grossly undetectable lesion. Rarely, dysplasia in BE may grow as a polypoid lesion. Most BE-associated polypoid dysplastic lesions have been referred to as "adenomas" because of their histological similarity to a colonic adenoma. BE-associated polypoid dysplastic lesions have been less well characterized than the flat type. Therefore, our aim was to characterize the clinicopathologic and molecular features of five cases of BE-associated polypoid dysplasia and to review the literature on this entity. The cases were evaluated clinically, histologically, immunostained for MIB-1 and p53, and genotyped for loss of heterozygosity (LOH) at the adenomatous polyposis coli (APC) locus. Mucosal biopsy specimens of five BE patients without dysplasia, and five BE cases with high-grade flat dysplasia, were used as controls. The study patients were all male (average age, 71 years) who presented with symptoms of gastroesophageal reflux disease. Endoscopically, all five cases had a well-defined sessile or pedunculated polypoid lesion ranging from 0.4 to 1.5 cm in size in the mid (n = 1) or distal (n = 4) esophagus and were associated with specialized-type BE (four long segment, one short segment). Histologically, the polyps consisted of intestinalized epithelium with low- and high-grade dysplasia. All five cases contained adenocarcinoma (four within the polyp, one in adjacent BE). All polyps showed increased cell proliferation in the form of surface MiB-1 staining and showed positive p53 staining. Three of three (100%) informative cases showed LOH at the APC locus in the dysplastic epithelium and in areas of adenocarcinoma. All five flat dysplasia controls also showed surface MIB-1 staining and p53 positivity, and three of three informative controls showed LOH for APC. None of the nondysplastic BE controls showed any of these findings. Three patients were treated with esophagectomy and two with polypectomy. All were alive, without metastasis, from 2 months to 6 years later. A literature review of esophageal "adenomas" uncovered 12 cases. Four of these had no clinical or pathological information, two were, in fact, gastric heterotopic lesions, one was composed entirely of intestinal-type epithelium, and five were polypoid dysplastic lesions similar to the cases described here (three male, two female; mean age, 59 years). Four of these five cases were associated with adenocarcinoma in the polyp (two intramucosal, two submucosal). In summary, BE-associated polypoid dysplasia share similar clinical, pathological, and molecular features as flat dysplasia and are often associated with adenocarcinoma. Thus, we agree with other authors who recommend that the term adenoma, which usually carries a benign connotation, be abandoned in favor of a descriptive diagnostic term, such as "BE-associated polypoid dysplasia." BE patients with this lesion should be considered strong candidates for esophageal resection similar to lesions of this kind that occur in inflammatory bowel disease.
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PMID:Polypoid dysplasia in Barrett's esophagus: a clinicopathologic, immunohistochemical, and molecular study of five cases. 1041 92

Barrett's esophagus (BE), a complication of gastroesophageal reflux disease, is the replacement of squamous tissue with specialized intestinal metaplasia. Other noxious factor, as biliary acids, may contribute to the induction of BE. It is a premalignant condition, and adenocarcinoma arises in some cases. An endoscopic surveillance with multiple biopsies is mandatory to detect different grades of dysplasia or intramucosal cancer and allow effective therapy. Since its prevalence is high, current surveillance protocols become expensive and patient's compliance is difficult. The main medical goals are: 1) To stratify individuals without dysplasia as either lower or higher risk, to screen less often those at lower risk. 2) To obtain complete remission or eliminate the risk of cancer and the need for surveillance. Current treatments have not demonstrate complete regression of metaplasia. Recently, new endoscopic approaches to therapy have been developed. Although they remain experimental and larger series are required, initial results are encouraging.
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PMID:[Barrett's esophagus]. 1042 Sep 37

A metaplastic process, in which native squamous epithelium of the distal esophagus is replaced by columnar epithelium, is known as Barrett esophagus (BE). Over the past years, intestinal metaplasia was recognized as a marker for BE. The risk for the development of esophageal adenocarcinoma in a patients with BE is much higher when compared to the normal population. Duodeno-gastro-esophageal reflux is supposed to play a role in the pathogenesis of BE and rising incidence of adenocarcinoma of the esophagus. With current therapeutic options, when clinical manifestation of this cancer occurs, it is too late for cure in the majority of patients. Therefore, attention should be focused on early diagnosis, for which molecular genetic techniques might become available. Current data on genetic alterations involved in carcinogenesis of BE are discussed. Grading of dysplasia in BE carries important clinical consequences for the individual patient: intensification of endoscopic surveillance or 'prophylactic esophagectomy'. Several morpho- and/or cytometric parameters may be used for discrimination between different grades of dysplasia in BE. Therefore, a new and original algorythm for the potential application of quantitative pathology in grading of dysplasia in patients with BE has been proposed. Molecular biology together with image analysis of histological spectrum of BE enable better understanding of the mechanisms of malignant degeneration and might ultimately lead to targeted cancer prevention and/or therapeutic interventions.
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PMID:Barrett esophagus and cancer: pathogenesis, carcinogenesis, and diagnostic dilemmas. 1042 62

Studies in human beings and animals have shown that esophageal exposure to duodenal and gastric contents may be important for the development of Barrett's esophagus and its complications, including adenocarcinoma and epidermoid carcinoma. Diethylnitrosamine (DEN) is a carcinogen that stimulates the development of epidermoid carcinoma in the esophagus of mice. The aim of this study was to evaluate the effect of gastroduodenal and gastric content reflux on induction of esophageal carcinogenesis. Gastroesophageal reflux (GER) and gastroduodenoesophageal reflux (GDER) were produced by cardioplasty and esophagoduodenostomy. The chosen carcinogen was DEN, diluted in drinking water, given 3 days a week for 20 consecutive weeks. One hundred Wistar female rats were divided into six groups, as follows: group 1 (18 rats), cardioplasty without DEN; group 2 (18 rats), cardioplasty with DEN; group 3 (10 rats), only water; group 4 (17 rats), cardioplasty with DEN; group 5 (17 rats), esophagoduodenostomy with DEN; group 6 (20 rats), only DEN. GER in isolation induced papillomatosis or ulceration in 22.2% of rats and, when associated with DEN, induced papillomatosis in 61.1% of rats. GDER in isolation induced marked esophagitis in 61.1% of rats, Barrett's esophagus in 16.7% and esophageal adenocarcinoma in 16.7%; when associated with DEN, 23.5% of rats presented marked esophagitis, papillomatosis or ulceration, whereas 76.5% had esophageal carcinoma, with 70.6% epidermoid carcinoma and 5.9% adenocarcinoma. Rats treated with water alone did not show histologic abnormalities of the esophageal mucosa. Rats treated with DEN alone developed papillomas in 50.0% of the cases and remained histologically unchanged in 50.0%. There was no development of low- or high-grade dysplasia in any group. The conclusions are that (1) GDER is significantly more deleterious to esophageal mucosa than GER; (2) in this study, GER did not present carcinogenic potential in relation to the esophagus; (3) GDER in isolation is an esophageal carcinogen, producing Barrett's esophagus and esophageal adenocarcinoma; (4) esophageal oncogenesis caused by GDER is potentiated by DEN, inducing esophageal epidermoid carcinoma; (5) in this study, DEN in isolation did not generate tumors in the esophagus of rats.
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PMID:Influence of surgically induced gastric and gastroduodenal content reflux on esophageal carcinogenesis--experimental model in Wistar female rats. 1046 42

Barrett's metaplasia can develop in patients with gastroesophageal reflux disease (GERD), and metaplasia can evolve into dysplasia and adenocarcinoma. The optimal treatment for Barrett's metaplasia and dysplasia is still being debated. The study reported herein was designed to assess the following: (1) the incidence of Barrett's metaplasia among patients with GERD; (2) the ability of laparoscopic fundoplication to control symptoms in patients with Barrett's metaplasia; (3) the results of esophagectomy in patients with high-grade dysplasia; and (4) the character of endoscopic follow-up programs of patients with Barrett's disease being managed by physicians throughout a large geographic region (northern California). Five-hundred thirty-five patients evaluated between October 1989 and February 1997 at the University of California San Francisco Swallowing Center had a diagnosis of GERD established by upper gastrointestinal series, endoscopy, manometry, and pH monitoring. Thirty-eight symptomatic patients with GERD and Barrett's metaplasia underwent laparoscopic fundoplication. Eleven other consecutive patients with high-grade dysplasia underwent transhiatal esophagectomies. Barrett's metaplasia was present in 72 (13%) of the 535 patients with GERD. The following results were achieved in patients who underwent laparoscopic fundoplication (n = 38): Heartburn resolved in 95% of patients, regurgitation in 93% of patients, and cough in 100% of patients. With regard to transhiatal esophagectomy (n = 11), the average duration of the operation was 339 +/- 89 minutes. The only significant complications were two esophageal anastomotic leaks, both of which resolved without sequelae. Mean hospital stay was 14 +/- 5 days. There were no deaths. The specimens showed high-grade dysplasia in seven patients and invasive adenocarcinoma (undiagnosed preoperatively) in four (36%). These results can be summarized as follows: (1) Barrett's metaplasia was present in 13% of patients with GERD being evaluated at a busy diagnostic center; (2) laparoscopic fundoplication was highly successful in controlling symptoms of GERD in patients with Barrett's metaplasia; (3) in patients with high-grade dysplasia esophagectomy was performed safely (invasive cancer had eluded preoperative endoscopic biopsies in one third of these patients); and (4) even though periodic endoscopic examination of Barrett's disease is universally recommended, this was actually done in fewer than two thirds of patients being managed by a large number of independent physicians in this geographic area.
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PMID:Barrett's esophagus: a surgical disease. 1048 92

Since its description in the 1950s, the definition of Barrett's esophagus has evolved from the macroscopic visualization of gastric-appearing mucosa in the esophagus to the histologic identification of goblet cells confirming the presence of intestinal metaplasia within the esophagus. The length of intestinal metaplasia necessary to be classified as Barrett's, and the relationship between intestinal metaplasia of the esophagus and that limited to the cardia are all areas currently being evaluated. However, any segment of intestinal metaplasia is capable of undergoing dysplastic change and ultimately of becoming a focus of adenocarcinoma. It is logical to expect the degree of risk for developing cancer to be proportional to the amount of intestinal metaplasia present; however, within a population, the low risk to any individual is balanced by the relative frequency of the process. Thus, given the large numbers of people in America with CIM, even a small risk of progression to cancer will result in a large number of patients with adenocarcinoma of the cardia. This is exactly what is occurring today, with the incidence of adenocarcinoma of the cardia and esophagus currently rising faster than any other cancer in the United States. A major risk factor for adenocarcinoma of the esophagus is intestinal metaplasia, which occurs as a consequence of GERD. Patients with Barrett's esophagus usually have more severe reflux disease with significant impairment of LES function and esophageal body motility compared with patients without Barrett's. Furthermore, in patients with Barrett's, the composition of the refluxed juice is different. Patients who reflux both gastric and duodenal juice have a higher prevalence of Barrett's than do those who reflux gastric juice alone. Among patients with Barrett's, a significantly greater esophageal bilirubin exposure has been demonstrated in those with dysplasia. The mechanically defective sphincter and impaired esophageal body function in many patients with Barrett's makes their disease difficult to control medically. In addition, symptoms are unreliable as a guide to successful control of reflux. The hardest symptom to control is regurgitation, and there is concern that this and continued reflux of pharmacologically altered gastric contents, particularly bile acids in their nonpolar form, may contribute to progression of Barrett's. Both medical therapy and failed antireflux surgery are associated with progression of Barrett's to dysplasia and adenocarcinoma. On the other hand, a functioning fundoplication seems to be associated with protection from progression of Barrett's. Intestinal metaplasia of the esophagus is unlikely to regress after antireflux surgery; however, intestinal metaplasia limited to the cardia is perhaps more dynamic and able to regress. Furthermore, low-grade dysplasia frequently regresses after an antireflux procedure. Antireflux surgery is safe, effective, and durable, and often can be performed using minimally invasive techniques. Thus, antireflux surgery should be strongly considered in any patient with intestinal metaplasia of the esophagus or cardia. The possibility of mucosal ablation after an antireflux repair should be considered in patients with low-grade dysplasia. Patients with Barrett's and high-grade dysplasia are at high risk for having a focus of adenocarcinoma present. Even with multiple biopsies, a degree of sampling error exists. Also, adenocarcinoma can develop within the space of several months; and if the cancer is allowed to invade into the submucosa, 50% of these patients will have lymphatic metastases, thereby negating the purpose of surveillance. Although patients with high-grade dysplasia and intramucosal adenocarcinoma on biopsy who do not have an endoscopically visible lesion are unlikely to have lymphatic metastases, 7% do have submucosal invasion. Thus, even in these very early tumors, treatment directed only at the mucosa may be inadequate. (ABSTRACT
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PMID:The diagnosis and management of Barrett's esophagus. 1057 61

The incidence of adenocarcinoma of the distal esophagus is increasing at an alarming rate. Intestinal metaplasia in the distal esophagus, i.e. Barrett's esophagus, has been identified as the single most important risk factor for these tumors. Barrett's esophagus develops as a consequence of chronic mucosal injury in up to 10% of patients with long-lasting gastroesophageal reflux disease. Experimental and clinical data indicate that adenocarcinoma of the distal esophagus is a direct consequence of mixed (i.e., acid and bile) reflux into the esophagus. Interestingly, Helicobacter pylori infection of the stomach appears to exert a protective effect against the development of esophageal adenocarcinoma. Neither aggressive medical acid suppression nor antireflux surgery can induce a predictable regression of Barrett's esophagus or exert a protective effect against its malignant degeneration. Endoscopic ablation of Barrett's esophagus, although appealing, currently constitutes a potentially dangerous procedure without proven benefit for the patient. Since the development of Barrett's adenocarcinoma follows a multistep process from metaplasia through increasingly severe grades of dysplasia, close endoscopic surveillance with extensive biopsies currently remains the only means to identify patients at risk for malignant degeneration and detect esophageal adenocarcinoma at an early and curable stage.
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PMID:Malignant degeneration of Barrett's esophagus: clinical point of view. 1069 37


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