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1.
Ann Surg ; 257(5): 886-93, 2013 May.
Article in English | MEDLINE | ID: mdl-23059500

ABSTRACT

OBJECTIVE: The aim of this study is to identify a set of microRNAs (miRNAs) as prognostic molecular biomarkers for the progression of Barrett esophagus (BE) to esophageal adenocarcinoma (EAC) to rationalize the surveillance programs in patients with BE. BACKGROUND: Histological dysplasia is currently used as the main biomarker to identify the BE patients at high risk for developing EAC. Although miRNA expression profiles in BE and EAC have been reported, it has not been established which set of miRNAs could constitute a robust diagnostic test to predict the progression of BE to EAC. METHODS: miRNAs associated with progression of BE to EAC were identified using miRNA sequencing analysis. Further validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in 2 groups of BE patients who either developed or did not develop adenocarcinoma after at least 5 years of follow-up. RESULTS: Twenty-three miRNAs were identified by miRNA sequencing analysis in the carcinogenesis process associated with BE. qRT-PCR analysis using independent tissue samples confirmed differential expression for 19 of them (miR-let-7c, 7, 146a, 149, 153, 192, 192*, 194, 194*, 196a, 196b, 200a, 203, 205, 215, 424, 625, 625*, and 944). However, only miR-192, 194, 196a, and 196b showed a significantly higher expression in BE samples from patients with progression to EAC compared with those who did not progress to EAC. CONCLUSIONS: These findings suggest that the expression pattern of a modest number of miRNAs in metaplasia biopsies could identify the BE patients at high risk for developing EAC. Therefore, it has potential use for the control and treatment of this malignancy.


Subject(s)
Adenocarcinoma/genetics , Barrett Esophagus/genetics , Biomarkers, Tumor/metabolism , Esophageal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/metabolism , Precancerous Conditions/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Barrett Esophagus/metabolism , Barrett Esophagus/pathology , Computational Biology , Disease Progression , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Follow-Up Studies , Humans , Logistic Models , Multivariate Analysis , Precancerous Conditions/metabolism , Precancerous Conditions/pathology , ROC Curve , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, RNA , Transcriptome
2.
Ann Surg ; 247(2): 258-64, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18216530

ABSTRACT

OBJECTIVE: To present the objectively assessed very long-term results of a prospective study of 149 patients with achalasia of the cardia who underwent Heller myotomy and posterior partial fundoplication. SUMMARY BACKGROUND DATA: Very few studies evaluate objectively the very long-term results to analyze whether the effectiveness of Heller myotomy is maintained with the passing of time. METHODS: The study group consisted of 149 patients who underwent a Heller myotomy plus a posterior partial fundoplication through a laparotomy. The median follow-up was 6 years (range, 1-27 years). Follow-up period was over 10 years in 53 patients and over 15 in 36. Clinical, radiologic, endoscopic, manometric, and pHmetric evaluations were performed postoperatively. RESULTS: Satisfactory results were higher than 90% up to 5 years. From that time on results gradually decreased to a 75% rate after 15 years (P < 0.001) due to either heartburn or dysphagia. Both the esophageal diameter and the mean resting pressure of the lower esophageal sphincter decreased postoperatively with no significant changes during follow-up. Esophagitis appeared in 11% of the patients (47% of them being asymptomatic) and 24-hour pH monitoring showed pathologic rates of acid reflux in 14% of patients, 58% of them being asymptomatic. Both esophagitis and pathologic rates of reflux appeared in >40% of the patients late in the follow-up. CONCLUSION: Results after Heller myotomy plus posterior partial fundoplication deteriorate with time, although we achieved a 75% of satisfactory results after >15 years of follow-up. Our study highlights the importance of life long follow-up and the objective assessment of the results.


Subject(s)
Cardia/surgery , Esophageal Achalasia/surgery , Fundoplication/methods , Adolescent , Adult , Aged , Aged, 80 and over , Child , Endoscopy, Gastrointestinal , Esophageal Achalasia/metabolism , Esophageal Achalasia/physiopathology , Esophagus/pathology , Esophagus/physiopathology , Esophagus/surgery , Female , Follow-Up Studies , Gastric Acid/metabolism , Gastric Acidity Determination , Humans , Hydrogen-Ion Concentration , Male , Manometry , Middle Aged , Patient Satisfaction , Postoperative Period , Pressure , Prospective Studies , Severity of Illness Index , Time Factors , Treatment Outcome
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