hERG1 channels in human esophagus: evidence for their aberrant expression in the malignant progression of Barrett's esophagus.

Ion channels regulate a broad range of cellular activities. Alteration in ion channel function has been reported in different human pathologies, such as cardiac, neuromuscular, autoimmune diseases, and cancer. We investigated the expression of hERG1 K+ channels in the human upper gastrointestinal tract, focusing our attention on the lower esophagus. In particular, we analyzed by both Reverse transcription and polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) endoscopic samples obtained from normal subjects, from patients suffering from gastroesophageal reflux, associated or not with esophagitis, and from patients affected by Barrett's esophagus (BE), that is, intestinal metaplasia. None of the normal samples, nor those from patients with gastro-esophageal reflux symptoms and reflux esophagitis expressed the hERG1 protein. On the other hand, 69% of patients with BE expressed hERG1. Since BE is a preneoplastic lesion, dysplasias (Ds) and adenocarcinomas (ADKs) arising on a previously diagnosed BE were also analyzed, and all the samples showed a high expression of the hERG1 protein. The surveillance of patients with BE showed that 89% of those who later developed ADKs displayed hERG1 expression. Data here reported, support the hypothesis that hERG1 expression marks an early step of the progression of normality to cancer in the human esophagus through a metaplastic and dysplastic stage.

Evaluation of Siewert classification in gastro-esophageal junction adenocarcinoma: What is the role of endoscopic ultrasonography?

BACKGROUND: Preoperative assessment of gastro-esophageal junction (GEJ) adenocarcinoma stage and its location according to Siewert are essential for planning the therapeutic approach. The present study was aimed at analyzing the utility of endoscopic ultrasonography (EUS) in evaluating GEJ adenocarcinoma stage and whether this modality added to EGD improves assessment of Siewert type. METHODS: The results of 51 patients studied by EGD plus EUS (EGD/EUS group) were compared with the results of 54 patients studied by EGD only (EGD group). RESULTS: A differentiation of pT1 tumors was attempted by measurement of the tumor length using 4 cm as a criterion. This goal was not achieved because of a high rate of advanced tumors less than 4 cm (sensitivity and specificity were 81.3% and 34.2%, respectively). Conversely EUS ability in pT1 assessment was very reliable (92%). The accuracy in defining the Siewert type was 72.5% and 64.8% for EGD/EUS and EGD groups, respectively (P = 0.394). Some difficulties in distinguishing between type II and III tumors were observed in both groups with an extremely low specificity (44%) in classifying type II tumors by EGD group. CONCLUSIONS: EUS seems to be essential in differentiating pT1 from advanced tumors. It shows an accuracy in defining the Siewert type of 72.5%, with some difficulties in distinguishing from type II and III tumors.

Endoscopic ablation of Barrett's esophagus using high power setting argon plasma coagulation: a prospective study.

AIM: This prospective study evaluated the effectiveness of 90 W argon plasma coagulation (APC) for the ablation of Barrett's esophagus (BE) that is considered to be the main risk factor for the development of esophageal adenocarcinoma. METHODS: The results from 25 patients, observed at the First Department of General Surgery, University of Verona, Italy, from October 2000 to October 2003, who underwent APC for histologically proven BE were prospectively analyzed. RESULTS: The ablation treatment was completed in all the patients but one (96%). The mean number of APC sessions needed to complete ablation was 1.6 (total number: 40). The eradication was obtained in the majority of cases by one session only (60%), two sessions were required in 24% of the cases and three or more in 16%. About 43% of the sessions were complicated. Retrosternal pain (22.5%) and fever (17.5%) were the most frequent symptoms. Only one major complication occurred, it was an hemorrhage due to ulcer formation on the treated esophagus that required urgent endoscopic sclerosis and admission. The follow-up was accomplished in all the patients with a mean period of 26.3 mo and 20 patients (84%) with a follow-up period longer than 24 mo. Only one patient showed a relapse of metaplastic mucosa 12 mo after the completion of ablation. The patient was hence re-treated and now is free from recurrence 33 mo later. CONCLUSION: High power setting (90 W) APC showed to be safe and effective. The effects persist at a mean follow-up period of two years with a comparable cost in term of complications with respect to standard power settings. Further studies with greater number of patients are required to confirm these results and to assess if ablation reduces the incidence of malignant progression.