Heterogeneous expression of DNA-dependent protein kinase in esophageal cancer and normal epithelium.

Esophageal cancer tissues and adjacent normal mucosae in 13 patients with primary esophageal cancer were examined for quantitative differences in DNA-dependent protein kinase (DNA-PK) activity and for expressions of Ku70, Ku80 and DNA-PKcs proteins by Western blotting and immunohistochemistry. The tumor tissues showed higher DNA-PK activity than the normal mucosae. Protein levels of Ku70, Ku80 and DNA-PKcs correlated with DNA-PK activities in the tumor tissues. Immunohistochemical analysis revealed that Ku70, Ku80 and DNA-PKcs located predominantly in the nuclei in both the tumor tissues and normal mucosae. In the normal epithelium, Ku70, Ku80 and DNA-PKcs were expressed only in the nuclei of the basal cell layers and not in those of the lumenal cell layers. In the tumor tissues, the expressions of DNA-PK proteins showed intratumoral heterogeneity. The different portions in the same tumor showed different expression levels of DNA-PK proteins, and even each tumor cell showed different expression levels. These results suggest that cell differentiation and tumor progression affect cellular DNA-PK protein levels and its activity. Furthermore, the intratumoral heterogeneity of DNA-PK protein expression in esophageal cancer cells/ tissues also suggests the difficulty in prediction of radio- or chemo-sensitivity of the tumor through estimation of DNA-PK activity/protein levels in tumor specimens.

High incidence of reflux esophagitis observed by routine endoscopic examination after gastric pull-up esophagectomy.

A gastric tube has been widely used for reconstruction of the esophagus after esophagectomy for esophageal cancer. Reflux esophagitis after esophagectomy is frequently observed. Therefore we retrospectively investigated the risk factors for reflux esophagitis after gastric pull-up esophagectomy in 74 outpatients with thoracic esophageal cancer. Reflux esophagitis was diagnosed endoscopically. Esophagitis was classified according to the Los Angeles classification. Reflux symptoms, medications, and the surgical procedure were reviewed. The relation between reflux symptoms and reflux esophagitis and the influence of the anastomotic site were evaluated. Reflux esophagitis was observed in 53 patients. Severe esophagitis (grade C or D) was found in 75.6% of these patients. Although all patients with esophagitis took antacid agents, histamine receptor-2 blocker was effective in only 35% of them. The correlation between reflux symptoms and reflux esophagitis was not significant. Reflux esophagitis was present in 56.4% of patients with neck anastomosis and in 88.6% of patients with intrathoracic anastomosis ( p = 0.0039). We concluded that routine endoscopic examination is necessary after gastric pull-up esophagectomy because reflux esophagitis is not diagnosed based on reflux symptoms. When a gastric tube is used for reconstruction after esophagectomy, neck anastomosis is recommended to lower the risk of reflux esophagitis.