GERD is associated with shortened telomeres in the squamous epithelium of the distal esophagus.

Telomeres are repetitive DNA sequences located at the ends of chromosomes. Telomeres are shortened by repeated cell divisions and by oxidative DNA damage, and cells with critically shortened telomeres cannot divide. We hypothesized that chronic gastroesophageal reflux disease (GERD)-induced injury of the esophageal squamous epithelium results in progressive telomeric shortening that eventually might interfere with mucosal healing. To address our hypothesis, we compared telomere length and telomerase activity in biopsy specimens of esophageal squamous epithelium from GERD patients and control patients. Endoscopic biopsies were taken from the esophageal squamous epithelium of 38 patients with GERD [10 long-segment Barrett's esophagus (LSBE), 15 short-segment (SSBE), 13 GERD without Barrett's esophagus] and 16 control patients without GERD. Telomere length was assessed using the terminal restriction fragment assay, and telomerase activity was studied by the PCR-based telomeric repeat amplification protocol assay. Patients with GERD had significantly shorter telomeres in the distal esophagus than controls [8.3 +/- 0.5 vs. 10.9 +/- 1.5 (SE) Kbp, P = 0.043]. Among the patients with GERD, telomere length in the distal esophagus did not differ significantly in those with and without Barrett's esophagus (LSBE 7.9 +/- 0.8, SSBE 8.6 +/- 0.9, GERD without BE 8.7 +/- 1.0 Kbp). No significant differences in telomerase activity in the distal esophagus were noted between patients with GERD and controls (4.0 +/- 0.39 vs. 5.2 +/- 0.53 RIUs). Telomeres in the squamous epithelium of the distal esophagus of patients who have GERD, with and without Barrett's esophagus, are significantly shorter than those of patients without GERD despite similar levels of telomerase activity.

Liposarcoma of the tongue: case report and review of the literature.

Liposarcoma is the most common soft-tissue malignancy in adults, but the appearance of a liposarcoma in the head and neck region is distinctly unusual. Intraoral liposarcomas represent a particularly interesting subset of this tumor in that (1) they are exceedingly rare and (2) affected patients tend to have a better prognosis than do patients with a similar lesion located elsewhere in the head and neck. An understanding of the histologic subtypes and corresponding clinical behavior of liposarcomas will assist physicians in appropriately managing these patients. Most of these tumors can be effectively treated with conservative surgery. We report the rare case of a well-differentiated liposarcoma arising in the tongue of a 55-year-old man. We also discuss the typical pathologic findings in these malignancies and review the diagnosis, associated controversies, management, and prognosis.

Differences in ERK activation in squamous mucosa in patients who have gastroesophageal reflux disease with and without Barrett's esophagus.

OBJECTIVES: In some patients with gastroesophageal reflux disease (GERD), the reflux-damaged esophageal squamous epithelium heals through the process of intestinal metaplasia (resulting in Barrett's esophagus) rather than through the regeneration of more squamous cells. We hypothesized that squamous epithelium in Barrett's esophagus might have abnormalities in activation of the extracellular-regulated kinases 1 and 2 (ERK1/2) signaling pathway that may facilitate esophageal repair through metaplasia in response to acid-induced injury. METHODS: Endoscopic biopsies were taken from distal esophageal squamous mucosa in patients who had GERD with and without Barrett's esophagus and in controls, before and after esophageal perfusion with 0.1 N HCl acid. Basal ERK1/2 phosphorylation, acid-induced ERK1/2 activity and phosphorylation, and localization of phosphorylated ERK1/2 were determined using immunoblotting, Western blotting, and immunohistochemistry. RESULTS: Compared to patients with Barrett's esophagus, patients with GERD exhibited significantly lower baseline levels of phosphorylated ERK1/2 expression (35 +/- 4%vs 90 +/- 21% control, p= 0.01) Acid exposure significantly increased ERK1/2 activity (346.6 +/- 51.90 to 446.8 +/- 62.44 RIU, p= 0.02) and phosphorylation (3.55 +/- 1.26 to 4.49 +/- 1.25 [ratio phospho/total ERK], p= 0.01) in the squamous mucosa of GERD patients, but not in those with Barrett's esophagus or in controls. CONCLUSIONS: Between patients with Barrett's esophagus and patients with uncomplicated GERD, there are significant differences in baseline levels and in acid-induced activation of ERK1/2 in esophageal squamous epithelium. To our knowledge, this is the first description of a molecular, phenotypic feature that distinguishes the esophageal squamous mucosa of GERD patients with and without Barrett's esophagus.