Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus.

BACKGROUND & AIMS: Barrett's esophagus-associated high-grade dysplasia is commonly treated by endoscopy. However, most guidelines offer no recommendations for endoscopic treatment of mucosal adenocarcinoma of the esophagus (mAC). We investigated the efficacy and safety of endoscopic resection in a large series of patients with mAC. METHODS: We collected data from 1000 consecutive patients (mean age, 69.1 ± 10.7 years; 861 men) with mAC (481 with short-segment and 519 with long-segment Barrett's esophagus) who presented at a tertiary care center from October 1996 to September 2010. Patients with low-grade and high-grade dysplasia and submucosal or more advanced cancer were excluded. All patients underwent endoscopic resection of mACs. Patients found to have submucosal cancer at their first endoscopy examination were excluded from the analysis. RESULTS: After a mean follow-up period of 56.6 ± 33.4 months, 963 patients (96.3%) had achieved a complete response; surgery was necessary in 12 patients (3.7%) after endoscopic therapy failed. Metachronous lesions or recurrence of cancer developed during the follow-up period in 140 patients (14.5%) but endoscopic re-treatment was successful in 115, resulting in a long-term complete remission rate of 93.8%; 111 died of concomitant disease and 2 of Barrett's esophagus-associated cancer. The calculated 10-year survival rate of patients who underwent endoscopic resection of mACs was 75%. Major complications developed in 15 patients (1.5%) but could be managed conservatively. CONCLUSIONS: Endoscopic therapy is highly effective and safe for patients with mAC, with excellent long-term results. In an almost 5-year follow-up of 1000 patients treated with endoscopic resection, there was no mortality and less than 2% had major complications. Endoscopic therapy should become the standard of care for patients with mAC.

Cloning and characterization of the promoter of Hugl-2, the human homologue of Drosophila lethal giant larvae (lgl) polarity gene.

The human lgl gene, Hugl-2 (llgl2, Lgl2), codes for a cytoskeletal protein involved in regulating cell polarity. Here, we report the identification and functional characterization of the promoter region ( approximately 1.2kb) of the Hugl-2 gene. Luciferase expression assays show a high basal Hugl-2 promoter activity in different cell lines and primary human hepatocytes. Truncations of the promoter identified a GC-rich region important for this activity. Alignment of human and mouse genomic sequences demonstrate that this is an evolutionary conserved region fcontaining putative binding sites for several transcription factors including Elk-1 and Sp-1. Mithramycin A reduces Hugl-2 expression indicating Sp-1 transcription factors activate Hugl-2. Treatment of primary hepatocytes with epidermal growth factor (EGF) suppresses Hugl-2, suggesting regulation by the EGF-signaling pathway. Downregulation of Hugl-2 by EGF may contribute to loss of cell polarity and tumour progression, therefore supporting a tumour suppressor role for Hugl-2.