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)

Achalasia is characterized by failure of relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Few data are available regarding the morphologic features of achalasia, in particular its histologic progression. The esophagi of 42 patients with achalasia treated with total thoracic esophagectomy were examined histologically in order to systematically identify morphologic features of clinically unresponsive achalasia and to determine what could be learned about the disease's evolution. In all cases, myenteric ganglion cells within the esophageal body were markedly diminished, with 20 specimens having none. Twenty specimens had residual ganglion cells in the proximal esophagus, and 15 specimens had a few randomly distributed ganglion cells in the mid- and distal portions of the esophagus. Inflammation within myenteric nerves, present in all cases, generally consisted of a mixture of lymphocytes and eosinophils, occasionally with plasma and mast cells. Focal replacement of myenteric nerves by collagen occurred in all cases, and there was almost complete replacement in several cases. Actual destruction of the residual ganglion cells was not seen. The resected esophagi also shared extramyenteric morphologic features. Some features probably stemmed from physiologic obstruction, such as muscular hypertrophy, mainly of the muscularis propria (all cases), with secondary degeneration and fibrosis (29 cases), and eosinophilia of the muscularis propria (22 cases). Other changes, probably resulting from chronic stasis of ingested materials in the lumen, included diffuse squamous hyperplasia (all cases), lymphocytic mucosal esophagitis (28 cases), lymphocytic inflammation of the lamina propria and submucosa with prominent germinal centers (all cases), and submucosal periductal or glandular inflammation with complete loss of submucosal glands in half of the cases. One patient had high-grade squamous dysplasia, and another had superficially invasive squamous cell carcinoma. A third group of changes was probably due to previous esophagomyotomy, including abnormal gastroesophageal reflux, as shown by pH reflux testing (13 cases) and Barrett's mucosa (four cases). In one case of Barrett's there was low-grade dysplasia. Clinically unresponsive, surgically resected achalasia has almost total loss of ganglion cells, and widespread destruction of myenteric nerves has already occurred. The only active component is myenteric inflammation. However, it cannot be determined whether this inflammation is a manifestation of ongoing nerve destruction or whether it is a secondary phenomenon.
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PMID:Achalasia. A morphologic study of 42 resected specimens. 814 27

Barrett's carcinoma occurred in 66 of 331 patients with adenocarcinomas of the esophagus or gastroesophageal junction. Only 32 (46%) of these patients had a history of gastroesophageal reflux. A history of alcohol and tobacco abuse was absent in 50% and 47.5%, respectively. The mean length of Barrett's metaplasia was 7.37 cm. Operability was 98.5% and resectability 95.5%. No postoperative or hospital deaths occurred. Pathologic staging was as follows: stage 0 and I, 38.3%; stage II, 20.6%; stage III, 22.2%; and stage IV, 19%. Overall survivals were 80.5% at 1 year, 62.7% at 2 years, and 58.2% at 5 years. Five-year survival for patients with stage I disease was 100%; for stage II, 87.5%; for stage III, 22.2%; and for stage IV, 0%. Thirty-four (51.5%) patients were under surveillance for a related or unrelated condition before diagnosis of their carcinoma; only nine (26.5%) had diseased lymph nodes. In 32 the diagnosis was made at their first medical contact, and 78% of them had diseased lymph nodes. Five-year survival without nodal metastasis was 85.3% and significantly better than for patients with metastasis, 38.3% (p = 0.0033). Of the 66 patients, 19 (28.7%) had a biopsy-proved history of Barrett's metaplasia before malignancy developed. Mean time interval between diagnosis of metaplasia and degeneration was 3.8 years (89.5% > 1 year). Over the surveillance period, the length of metaplastic Barrett's esophagus remained unchanged in all patients. Barrett's ulceration was present from the beginning in 14 patients, and three patients never had an ulcer. Intestinal metaplasia was seen in 18 patients. Resected specimens revealed severe dysplasia in 16 patients. Of the 19 patients, 73.7% had stage I disease. Our data suggest that close endoscopic monitoring and systematic biopsies of the smallest irregularities in the metaplastic mucosa may result in early detection of carcinoma. In this respect, patients with an ulcer within a zone of intestinal metaplasia seem to be at risk. Early detection increases substantially the chances for cure by diminishing the risks of lymph node involvement. Resection remains the treatment of choice in Barrett's adenocarcinoma including high-grade dysplasia, because mortality can be kept low with excellent to very good functional results in the majority of the patients provided the intervention is performed by experienced teams.
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PMID:Surgical treatment of Barrett's carcinoma. Correlations between morphologic findings and prognosis. 815 27

Barrett esophagus was found in seven members of a single family. Two of these patients also had adenocarcinoma of the gastroesophageal junction. Among family members who did not have Barrett epithelium, one had esophageal ulcerations with dysplasia in squamous epithelium and another had an esophageal stricture. The pattern of involvement suggests autosomal dominant inheritance of Barrett esophagus and/or gastroesophageal reflux disease in this family, with a strong predisposition for adenocarcinoma of the esophagus.
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PMID:Familial Barrett esophagus and adenocarcinoma of the gastroesophageal junction. 834 64

Barrett's esophagus (i.e. columnar epithelial metaplasia in the distal esophagus) is an acquired condition that in most patients results from chronic gastroesophageal reflux. It is a disorder of the white male in the Western world with a prevalence of about 1/400 population. Due to the decreased sensitivity of the columnar epithelium to symptoms, Barrett's esophagus remains undiagnosed in the majority of patients. Gastroesophageal reflux disease in patients with Barrett's esophagus has a more severe character and is more frequently associated with complications as compared with reflux patients without columnar mucosa. This appears to be due to a combination of a mechanically defective lower esophageal sphincter, inefficient esophageal clearance function, and gastric acid hypersecretion. Excessive reflux of alkaline duodenal contents may be responsible for the development of complications (i.e., stricture, ulcer, and dysplasia). Therapy of benign Barrett's esophagus is directed towards treatment of the underlying reflux disease. Barrett's esophagus is associated with a 30- to 125-fold increased risk for adenocarcinoma of the esophagus. The reasons for the dramatic rise in the incidence of esophageal adenocarcinoma, which occurred during the past years, are unknown. High grade dysplasia in a patient with columnar mucosa is an ominous sign for malignant degeneration. Whether an esophagectomy should be performed in patients with high grade dysplasia remains controversial. Complete resection of the tumor and its lymphatic drainage is the procedure of choice in all patients with a resectable carcinoma who are fit for surgery. In patients with tumors located in the distal esophagus, this can be achieved by a transhiatal en-bloc esophagectomy and proximal gastrectomy. Early adenocarcinoma can be cured by this approach. The value of multimodality therapy in patients with advanced tumors needs to be shown in randomized prospective trials.
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PMID:Barrett's esophagus: pathogenesis, epidemiology, functional abnormalities, malignant degeneration, and surgical management. 835 51

Barrett's oesophagus is a pre-malignant condition with an increased risk of adenocarcinoma. The prevalence of adenocarcinoma in Barrett's oesophagus is about 10% but its true incidence in the general population is unknown. The development of adenocarcinoma in Barrett's oesophagus is a multi-step process. Gastro-oesophageal reflux symptoms are absent in many Barrett's patients and both Barrett's oesophagus and adenocarcinoma are usually but not always diagnosed simultaneously. When a carcinoma is identified, the treatment of choice is resection. Three-stage oesophagectomy is considered the most appropriate procedure. The prognosis of Barrett's carcinoma is dismal and the survival rate is related to stage of the tumour. However, encouraging results have been reported in the past 5 years. Endoscopic surveillance for Barrett's oesophagus is still a controversial topic but for some high-risk subgroups of patients regular surveillance is advocated. At the present time, dysplasia is the best available indicator of malignancy in Barrett's oesophagus.
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PMID:Malignant Barrett's oesophagus. 842 76

A 49-yr-old male was reviewed who had a 10-yr history of reflux esophagitis. He presented initially with frequent heartburn of moderate severity and, on subsequent endoscopy, was noted to have erosive esophagitis and, at that time, a high maximal gastric acid output. During the next 5 yr, his symptoms and acid output diminished. Eight years after presentation, he was noted to have developed a small area of Barrett's metaplasia, without dysplastic change. Ten years after the initial presentation he was completely asymptomatic, despite having extensive Barrett's metaplasia, now with high grade dysplasia. As a result, he was referred for esophagogastrectomy. At the time of surgery, he had alkaline reflux, with antacid gastric contents and, subsequently, hypochlorhydria was proven by a pentagastrin test. A second individual (male, 46 yr) who presented initially with reflux symptoms and gastric-type metaplasia, underwent gastric secretory studies that revealed a peak acid output of 16 mmol/L in 1986. During the period 1989 to 1991, his symptoms progressed despite H2 antagonist therapy. In this regard he was reinvestigated, and his peak acid output in 1991 was 0 mmol/L, and subsequent esophageal biopsies demonstrated intestinal metaplasia in four of six biopsies (two biopsies had high-grade dysplasia; the two others had gastric-type metaplasia). He has refused esophageal resection, and is being reviewed regularly at the endoscopy clinic. Flow cytometric analysis of the esophagus in both individuals revealed expression of epidermal growth factor receptor which was increased in the areas of high grade dysplasia, compared with Barrett's mucosa without dysplasia or normal cardiac mucosa. We conclude that alkaline reflux may accelerate the development of Barrett's esophagus (and intestinal type metaplasia) in patients with gastroesophageal reflux disease. The increased expressed of epidermal growth factor receptors in Barrett's mucosa with dysplasia compared with Barrett's mucosa without dysplasia may reflect the higher malignant potential of the former mucosa.
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PMID:Increased expression of epidermal growth factor receptors in Barrett's esophagus associated with alkaline reflux: a putative model for carcinogenesis. 843 48

The choice of surgery in patients with reflux-induced oesophageal stricture remains controversial. From 1976 to 1990, a total of 65 patients underwent fundoplication (36 patients), Collis gastroplasty plus fundoplication (ten), total duodenal diversion (four) and oesophageal resection (15). The postoperative mortality rate was 5 per cent (three patients): necrosis of the colon transplant in two patients and acute pancreatitis in one. The median follow-up was 25 (range 6-120) months. After conservative surgery, the median number of dilatations per patient per year significantly decreased (P < 0.001). Nine patients (25 per cent) complained of persistent or recurrent symptoms after standard fundoplication and six required reoperation. Clinical results were satisfactory in patients who underwent Collis fundoplication, total duodenal diversion and oesophageal resection. It is concluded that the causes of failed fundoplication are irreversible stricture or persistent gastro-oesophageal reflux; the latter may be caused by inefficacy or deterioration of the partial fundoplication wrap. A subtle degree of oesophageal shortening is probably underestimated in such patients and this may explain the better results obtained with the Collis fundoplication. Total duodenal diversion is a good therapeutic option in patients who have undergone previous oesophagogastric surgery. Oesophageal resection should be reserved for patients with tight strictures unresponsive to dilatation or those with scleroderma, multiple previous operations or severe dysplasia in Barrett's oesophagus.
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PMID:Surgical treatment of reflux stricture of the oesophagus. 847 38

Barrett's esophagus (BE) is a metaplastic change of the squamous esophageal epithelium to columnar gastric or intestinal-like epithelium. BE is associated with long-standing gastroesophageal reflux disease and carries an increased risk for dysplasia and adenocarcinoma. Little if any is known regarding the differentiation state of esophageal metaplasia and its relationship to carcinogenesis. In this study, we investigated the potential of villin, a cytoskeletal protein, and Ep-CAM, a glandular epithelial glycoprotein, to serve as markers for enterocytic differentiation in BE at the molecular level. Endoscopic mucosal biopsy samples of normal esophagus, BE, stomach and duodenum were collected from 23 patients with BE. Biopsies were analyzed for villin and Ep-CAM expression by immunoblotting, and in some cases for the presence of microvilli by electron microscopy. By mapping of BE segments in 6 patients, correlations were also made between the histologic evidence of metaplasia and villin expression. Villin was uniformly expressed in all duodenal samples but was not detected in normal esophagus and stomach. In BE biopsies, villin expression was limited to the subset of patients whose adjacent biopsies showed microvilli by electron microscopy. In several patients studied, however, the expression of villin and the epithelial glycoprotein Ep-CAM differed among various regions of esophageal metaplasia within the same patient. Mapping studies failed to reveal any correlation among histologic evidence of metaplasia, dysplasia and villin expression and confirmed the multifocal heterogeneity of villin expression in BE. Preliminary data of 4 adenocarcinoma patients studied showed that villin expression was absent in 3 and very low in 1 patient. Ep-CAM was highly expressed in all adenocarcinoma patients. Our results show that BE represents a complex epithelium with significant heterogeneity in antigen expression and ultrastructural morphologic features. This molecular heterogeneity supports the presence of different stages of differentiation within the same epithelium.
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PMID:Multifocal heterogeneity in villin and Ep-CAM expression in Barrett's esophagus. 860 65

A 66-yr-old white male with a long-standing history of gastroesophageal reflux and Barrett's esophagus developed squamous cell dysplasia proximal to the site of the metaplastic epithelium. Two months later, he presented with progressive dysphagia. Upper endoscopy revealed near obliteration of the lumen from a large friable mass in the distal esophagus. Repeat endoscopic biopsies revealed areas of focal dysplasia but were inconclusive for the presence of malignancy. At surgery, a large inflammatory fibrotic mass was resected that was confirmed histologically to be a verrucous squamous cell carcinoma. Twenty-two months after the resection, there is no evidence of tumor recurrence. The case and relevant literature is discussed.
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PMID:Long-term survival in a patient with verrucous carcinoma of the esophagus. 863 46

Barrett's esophagus is a premalignant metaplastic change in the lining of the distal esophagus. It represents a peculiar form of healing which occurs in response to chronic gastroesophageal reflux disease. The condition should be considered in all patients undergoing endoscopy for symptoms of reflux disease and is confirmed when any biopsy shows the presence of specialized intestinal metaplasia irrespective of the macroscopic appearance of the distal esophagus. Endoscopic surveillance with multiple biopsy sampling of the esophageal mucosa is indicated for all medically fit patients with Barrett's esophagus. The diagnosis of dysplastic change within this abnormal mucosa requires histological examination of the biopsies by 2 independent but experienced pathologists. Identification of high-grade dysplasia heralds the development of invasive cancer and offers the physician an opportunity to intervene. Despite extensive endoscopic sampling of the esophageal mucosa the differentiation between high-grade dysplasia and invasive adenocarcinoma is unreliable. Esophagectomy remains the treatment of choice for patients with high-grade dysplasia since adenocarcinoma of the esophagus carries such a poor prognosis.
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PMID:Dysplasia in Barrett's esophagus: diagnosis, surveillance and treatment. 884 77


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