Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0154059 (Esophagus)
 2,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5), a recently discovered intestinal stem cell marker, is expressed in premalignant lesions including Barrett's esophagus (BE) and cancers including colon cancer, ovarian cancer, and hepatocellular carcinoma. It was also recently found to be expressed in tumor spheres prepared from colon cancer, suggesting that it will likely serve as a cancer stem cell marker. We sought to examine Lgr5 as a biomarker in BE-associated neoplasia. Using standard immunohistochemistry, we performed immunostaining on 81 esophageal specimens (53 biopsy specimens and 28 surgical resections) representing BE, BE-associated dysplasia, and esophageal adenocarcinoma (EAC). Each immunostain was scored based on intensity of immunostaining and percentage of positive cells. For 24 EAC cases, survival analysis was performed with expression scores and other clinicopathological variables. We found that Lgr5 expression was detected in 70% of BE cases and between 90 and 100% of advanced dysplastic lesions and EAC. The intensity of expression was significantly higher in high-grade dysplasia and EAC than BE. In EAC, high Lgr5 expression scores (> or = 5) were associated with worse survival, independent of stage, age, and neoadjuvant/adjuvant therapy (P = 0.03). Our findings suggest that Lgr5 has potential utility as a biomarker for BE-associated dysplasia and EAC.
Dis Esophagus 2010 Feb
PMID:Lgr5, an intestinal stem cell marker, is abnormally expressed in Barrett's esophagus and esophageal adenocarcinoma. 1954 12

Barrett's columnar-lined oesophagus is the precursor lesion for oesophageal adenocarcinoma. The overall rate of progression to adenocarcinoma is 0.59% per annum. A large prospective multicentre trial is recruiting to assess the role of aspirin as a chemoprotective agent in prevention of development of cancer as well as cardiovascular protection in patients with Barrett's oesophagus. This retrospective analysis of the large UK National Barrett's Oesophagus Registry database seeks to analyse this question from within its large natural history study cohort. Multicentre UK retrospective cohort compared patients known to have been taking aspirin with those who did not take aspirin during the course of surveillance for columnar-lined oesophagus. End point was development of dysplasia or oesophageal adenocarcinoma. Analysis was undertaken using Cox's proportional hazard ratio. Total follow-up was 3683 patient-years. Eighty-six patients were taking aspirin, 650 were not taking aspirin (reference group). Numbers of patients developing all grades of dysplasia and adenocarcinoma were: 13 aspirin (15.1%) and 97 no aspirin (14.9%) (hazard ratio 0.723, 95% confidence interval 0.410-1.310, P = 0.294), high-grade dysplasia and adenocarcinoma: five aspirin (5.8%) and 25 no aspirin (3.8%) (hazard ratio 0.898, 95% confidence interval 0.340-2.368, P = 0.827) and adenocarcinoma: four aspirin (4.7%) and 16 no aspirin (2.5%) (hazard ratio 1.092, 95% confidence interval 0.358-3.335, P = 0.877). No significant difference was observed in hazard of developing dysplasia or adenocarcinoma between patients taking aspirin and those not taking aspirin during the course of follow-up of surveillance for columnar-lined oesophagus. In conclusion, no difference in risk of development of dysplasia or adenocarcinoma was observed between patients taking aspirin and those not taking aspirin in this large cohort.
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PMID:Aspirin is not chemoprotective for Barrett's adenocarcinoma of the oesophagus in multicentre cohort. 1962 Aug 73

The discrepancy between Eastern and Western countries exists regarding the time trends of Barrett's esophagus (BE)/adenocarcinoma. We aimed to elucidate this issue through a retrospective review of the endoscopic and pathological diagnoses of gastroesophageal reflux disease (GERD) over time in a Chinese population. All records were analyzed from 2000 to 2007. Records included demographic data, clinical indication for endoscopy, and endoscopic findings. The total number of endoscopic procedures increased over time. The indications for referral endoscopy secondary to GERD increased from 366 cases (4.9%) in the beginning of the study to 1439 cases (14.1%) at the end. Concomitant GERD symptoms did not significantly change (range, 13-15.1%) in screening endoscopic studies. Endoscopic detection of erosive esophagitis increased in referral populations from 1546 (20.7%) to 5207 cases (51%) and by screening endoscopy from 791 (14.5%) to 1983 cases (23.5%). The prevalence of nonerosive reflux disease and BE did not change over time. BE-associated dysplasia and adenocarcinoma were rare. The detection of Los Angeles class A disease increased with time in referral endoscopy cases with a focus on erosive esophagitis composition. The endoscopic demand for GERD investigation and the GERD endoscopic diagnosis increased in our population. The results were related to a higher prevalence of low-grade erosive disease diagnosed. The incidence of BE-associated dysplasia and adenocarcinoma has been the same and the increased screening did not detect more cancers.
Dis Esophagus 2010 Apr
PMID:Time trends of endoscopic and pathological diagnoses related to gastroesophageal reflux disease in a Chinese population: eight years single institution experience. 1978 38

There are 5 to 6 levels of biomarker validation. Those for Barrett's esophagus are currently at level 3, despite small prospective studies. What is ideally required is a very large prospective assessment of biopsies in large cohorts, such as the ASPirin Esomeprazole Chemoprevention Trial (AspECT) and Barrett's Oesophagus Surveillance Study (BOSS) trials, so that unbiased and random selection of cases can be subjected to rigorous pathology and biomarker assessment (level 4). Only then can the predictive power of the data be exploited in a randomized intervention trial (level 5) whereby a series of biomarkers would trigger therapy. The real trouble is that this spot is currently occupied, satisfactorily according to some researchers, by conventional histological identification of high-grade dysplasia (HGD) as used in a recent randomized study of ablation in Barrett's esophagus (BE).
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PMID:Editorial: One small step for metaplasia, but one giant leap for biomarkers is needed. 1963 63

Patients with longstanding achalasia have an increased risk of developing esophageal cancer. Surveillance is hampered by chronic stasis. We investigated whether aberrant expressions of tumor suppressor gene p53 and proliferation marker ki67 are early predictors for progression to malignancy. In 399 achalasia patients, 4% died of esophageal cancer despite surveillance. We performed a cohort study, using surveillance biopsies from 18 patients (11 carcinoma, one high-grade dysplasia [HGD], and six low-grade dysplasia [LGD]) and 10 controls (achalasia patients without cancer or dysplasia development). One hundred sixty-four biopsies were re-evaluated and studied for p53 and ki67 expression using immunohistochemistry. Eighty-two percent of patients with cancer/HGD showed p53 overexpression in surveillance biopsies at a mean of 6 (1-11) years prior to cancer development. In 67% of patients with LGD and only in 10% of the controls p53 overexpression was present. The proportion of samples with p53 overexpression increased with increasing grades of dysplasia. We found no difference for ki67 overexpression. p53 overexpression may identify achalasia patients at increased risk of developing esophageal carcinoma. Further study is needed to determine if patients with p53 overexpression would benefit from intensive surveillance to detect esophageal neoplasia at a potential curable stage.
Dis Esophagus 2010 Aug
PMID:Expression of p53 as predictor for the development of esophageal cancer in achalasia patients. 2011 24

The cancer stem cell theory states that cancers contain tumor-forming cells that have the ability to self-renew as well as give rise to cells that differentiate. Cancer stem cells have been identified in several solid tumors, but stem cells in normal human esophagus or in Barrett's esophagus or adenocarcinoma have not been reported. Musashi-1 is expressed by the crypt base columnar cells identified as intestinal stem cells. In other diseases of the gastrointestinal tract, local inflammation of the tunica mucosa may be an initiating factor of alteration of focal tissue 'niches,' where dormant stem cells locate. The present study investigated whether Musashi-1 is expressed in the esophagus and its relation to immune inflammation of the mucosa in Barrett's esophagus and esophageal adenocarcinoma. A total of 41 esophageal tissue specimens from 41 patients were studied. Of these, 15 were esophageal adenocarcinoma, 17 were Barrett's esophagus (10 intestinal metaplasia and 7 dysplasia), and 9 were normal squamous esophagus tissue specimens from patients without esophageal pathology. Immunohistochemistry was performed using antibodies to Musashi-1 and to a set of cell type-specific markers. A multiplexed tandem polymerase chain reaction method was used to measure the relative mRNA expression levels of Musashi-1 and the specific dendritic cell marker dendritic cell-specific intercellular molecule-3 (ICAM-3)-grabbing nonintegrin. Immunohistochemistry demonstrated the presence of small numbers of Musashi-1+ cells scattered in the connective tissue stroma and within the epithelium in cardiac-type glands in biopsies from patients without Barrett's esophagus. Musashi-1 expression was present in Barrett's intestinal metaplasia and in dysplastic Barrett's in which the majority of epithelial cells in individual glands expressed this antigen. Expression of Musashi-1 was highest in esophageal adenocarcinoma, where it was most intense in glands that displayed features of early stages of adenocarcinoma formation. In contrast, Musashi-1 staining level was weaker in glands that displayed features of advanced adenocarcinoma. Double immunostaining with proliferating cell nuclear antigen showed low proliferation in the vast majority of Musashi-1+ cells. Musashi-1 mRNA expression levels were significantly higher in esophageal adenocarcinoma than in normal esophagus or Barrett's esophagus tissues. Dendritic cell-specific intercellular molecule-3 (ICAM-3)-grabbing nonintegrin (DC-SIGN) mRNA expression levels were significantly increased in both Barrett's tissues and adenocarcinoma tissues. Expression of the putative stem cell marker Musashi-1 is absent in normal squamous epithelium, weak in esophageal cardiac-type glands and Barrett's esophagus, and markedly increased in adenocarcinoma, especially in glands displaying features of early cancer development. Musashi-1 expressing cells may be significant in the etiology of Barrett's esophagus and adenocarcinoma, and perhaps even a cell of origin for this disease. We speculate that immune inflammation occurring in Barrett's esophagus alters the mucosal microenvironment in a manner which is favorable to the activation of dormant stem cells.
Dis Esophagus 2010 Sep
PMID:Expression of the putative stem cell marker Musashi-1 in Barrett's esophagus and esophageal adenocarcinoma. 2045 40

Barrett's esophagus, the management of which remains controversial, is the precursor condition to esophageal adenocarcinoma. A number of endoscopic treatments have been designed as an alternative to surgical resection for patients with high-grade dysplasia. One of these, photodynamic therapy, involves the light activation of a photosensitizer that causes local tissue destruction via oxidation reactions. The present work reviews the effectiveness, safety, and cost-effectiveness of this treatment. A systematic review of the literature recorded in the Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database, and the National Health Service Economic Evaluation Database was undertaken. Articles reporting randomized clinical trials of photodynamic therapy for the treatment of Barrett's esophagus, and economic assessments of the procedure, were selected. The quality of the articles was checked. Twelve articles were included in this review: eight randomized, controlled clinical trials and four economic assessments. The clinical trials suffered from methodological limitations, but the economic assessments were considered to be good quality. Photodynamic therapy is effective for the ablation of dysplasia in Barrett's esophagus, although the frequency of adverse events is quite high. The procedure is presented as a cost-effective alternative to intense endoscopic monitoring and esophagectomy. However, the evidence regarding its effectiveness in reducing the number of patients who go on to develop cancer is only incipient. Rigorous, controlled studies with longer follow-up times, in which photodynamic therapy is compared with surgical resection and other endoscopic techniques, are needed.
Dis Esophagus 2010 Nov
PMID:Effectiveness, safety, and cost-effectiveness of photodynamic therapy in Barrett's esophagus: a systematic review. 2054 70

Confocal laser endomicroscopy (CLE) can serve as a useful adjunct imaging modality for targeted endoscopic biopsies during surveillance of Barrett's esophagus (BE). In addition, CLE may also have potential roles during therapeutic procedures that include localization of pathology, targeting of resections, guiding which therapy to use, and determining adequacy of treatment. This case series illustrates a range of cases in which endomicroscopy was performed during the procedure and offers possibilities of real-time decision-making to select specific therapies in patients with known high-grade dysplasia (HGD) and intramucosal carcinoma in the setting of BE presented for endoscopic treatment or follow-up. Patients with BE with HGD and intramucosal carcinoma presented for management for initial treatment or follow-up. Examinations were performed sequentially with detailed white light endoscopy, narrow band imaging (NBI), acetic acid, and CLE. This is a retrospective case series describing the characteristics of the exam findings and illustrating the role of endomicroscopy on real-time case management. Seven patients with Barrett-associated neoplasia underwent endomicroscopy as part of their endoscopic examination. CLE confirmed findings of neoplasia seen with red flag techniques such as NBI, and in one case independently suggested findings of neoplasia. In the majority of cases, these findings were incorporated into the decision of which modality of treatment was used. Future prospective studies should be done to validate the role of endomicroscopy in BE.
Dis Esophagus 2010 Jul
PMID:Confocal laser endomicroscopy: potential in the management of Barrett's esophagus. 2062 48

Dysplasia and esophageal adenocarcinoma may arise in patients with Barrett's esophagus after fundoplication esophageal pH monitoring showing no acid in esophagus. This suggests the need to develop methodology to evaluate the occurrence of ultra-distal reflux (1cm above the LES). The objective of the study was to compare acid exposition in three different levels: 5cm above the upper border of the LES, 1cm above the LES and in the intrasphincteric region. Eleven patients with Barrett's esophagus after Nissen fundoplication with no clinical, endoscopic and radiologic evidence of reflux were selected. Four-channel pH monitoring took place: channel A, 5cm above the upper border of the LES; channel B, 1cm above the LES; channel C, intrasphincteric; channel D, intragastric. The results of channels A, B and C were compared. There was significant increase in number of reflux episodes and a higher fraction of time with pH <4.0 in channel B compared to channel A. There was significant decrease in fraction of time with pH <4.0 in channel B compared to channel C. Two cases of esophageal adenocarcinoma were diagnosed in the studied patients. The region 1cm above the upper border of the LES is more exposed to acid than the region 5cm above the upper border of the LES, although this exposure occurred in reduced levels. The region 1cm above the upper border of the LES is less exposed to acid than the intrasphincteric region.
Dis Esophagus 2011 Aug
PMID:Use of multiple channel pH monitoring for evaluation of ultra-distal reflux in patients after fundoplication for treatment of Barrett's esophagus. 2130 10

To date, Lugol chromo-endoscopy is the reference technique to detect an esophageal neoplasia in patients with prior esophageal squamous-cell carcinoma (ESCC), but is not easy to perform without general anesthesia, which can limit its use in routine practice. The objective of this study were to compare the accuracy of white light, narrow band imaging (NBI), and Lugol to detect esophageal neoplasia in patients with a history of cured ESCC, in a prospective study. Thirty patients were prospectively included between June 2006 and June 2009. They all had a history of cured ESCC. Esophageal mucosa was examined first using white light, second NBI, and third after Lugol staining. Histology was obtained in all abnormalities detected by white light, NBI, and/or Lugol. Five neoplastic lesions in five different patients were identified at histology, four cancers, and one high-grade dysplasia. NBI and Lugol both detected all esophageal neoplastic lesions, whereas white light detected the four cancers but missed the high-grade dysplasia. In this feasibility study, NBI and Lugol both detected all identified esophageal neoplasia in very high-risk patients of ESCC. This result suggests that NBI could be used instead of Lugol to detect an esophageal neoplasia in patients with high risk of ESCC, but needs to be confirmed in a larger study.
Dis Esophagus 2011 Aug
PMID:Lugol chromo-endoscopy versus narrow band imaging for endoscopic screening of esophageal squamous-cell carcinoma in patients with a history of cured esophageal cancer: a feasibility study. 2130 14


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