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)

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

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

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

MIB-1, a proliferation marker may be useful in the assessment of esophageal biopsy specimens for gastroesophageal reflux disease (GERD). Forty-five hematoxylin and eosin-stained esophageal biopsy specimens were histologically assessed for basal zone height, papillary length, and inflammatory cell infiltrate and classified as 10 normal and 35 esophagitis. The percentage of MIB-1-positive area (MIB-1% area) was measured on immunostained sections using image analysis (CAS 200) in the basal half of well-oriented areas and adjacent to five cross-sectioned papillae (c-pap) in poorly oriented areas. The cell layer of the MIB-1-positive cell furthest from the basal layer of the c-pap was also noted. MIB-1% area was significantly greater in both well- and poorly oriented areas of esophagitis biopsy specimens compared with normal biopsy specimens. MIB-1 positivity in the basal half and c-pap were correlated (r = 0.43, p = 0.017). MIB-1 expression correlated with basal zone height and eosinophil infiltrate (r = 0.61, p < 0.001; r = 0.32, p = 0.03, respectively). The cell layer with positive cells furthest from c-pap in normal and esophagitis biopsy specimens was two and six layers, respectively. Using 31% as a threshold to detect abnormal findings, the MIB-1 sensitivity/specificity and positive predictive value in the basal half and c-pap were 86, 70, 91% and 80, 80, 94%, respectively. In summary, MIB-1 staining correlates with basal zone hyperplasia and eosinophil infiltrate seen in GERD. MIB-1 staining can be assessed both in well- and poorly oriented areas as MIB-1% areas. Alternatively simply finding MIB-1 positive cells more than three cell layers from the basal layer is abnormal and consistent with GERD.
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PMID:Use of MIB-1 in the assessment of esophageal biopsy specimens from patients with gastroesophageal reflux disease in well- and poorly oriented areas. 1205 30

Eosinophilic esophagitis (EoE) has been recognized as a chronic disease of the esophagus with significant involvement of the mucosal immune system. Similar conditions in other gastrointestinal diseases have led to a malignant transformation (ie, inflammatory bowel disease, celiac disease, etc). MIB-1 (Ki-67) and p53 are monoclonal antibodies that are used to detect early markers for dysplastic changes, possibly leading to cancer development in adult patients with chronic gastroesophageal reflux disease (GERD), Barrett's esophagus, and/or the adenocarcinoma sequence of the esophagus. Only limited studies of these cell markers have been published in children with EoE. The aim of this study is to examine p53 and Ki-67 cell markers in children with EoE before and after medical therapy. The immunohistochemical staining of cell markers p53 and Ki-67 was examined in esophageal biopsies of children diagnosed with EoE, GERD, and normal esophagus. In addition, biopsies from adults with EoE and adenocarcinoma were used as positive controls. In 10 children who were successfully treated for EoE, immunohistochemical staining was compared before and after medical therapy. The immunohistochemical staining of p53 and Ki-67 was increased in children with EoE compared with children with a normal esophagus but not in children with GERD. Children with EoE posttherapy had significantly lower immunohistochemical staining for both markers compared to pretreatment staining. p53 and Ki-67 markers are associated with cell proliferation in children with EoE but do not represent a premalignant (dysplastic) condition of the esophagus.
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PMID:Immunoreactivity of p53 and Ki-67 for dysplastic changes in children with eosinophilic esophagitis. 2371 21