The designated area of the columnar-lined esophagus (CLE) is anatomically defined by the distal limit of the lower esophageal palisade vessels (LEPV) and the term 'Barrett's esophagus' is equally used along with the name CLE in Japan. The aim of this study was to investigate the actual prevalence of CLE based on the Japanese criteria and to evaluate the criteria per se. A total of 42 esophagi consecutively resected at this institute were included. All subjects underwent a surgical resection for squamous cell carcinoma of the esophagus. The position of the LEPV, squamocolumnar junction, the prevalence of CLE and intestinal metaplasia were investigated both pre- and postoperatively. Preoperative endoscopy revealed CLE based on the Japanese criteria in half of all patients. In the resected specimens the distal limit of LEPV was lower than the squamocolumnar junction in 95.2%. In other words, almost all cases had CLE (equivalent to Barrett's mucosa in Japanese criteria). However, most of the CLE areas were very short and their average maximum length was only about 5 mm. In addition, no intestinal metaplasia was observed in any of the CLE cases. Almost all individuals might therefore be diagnosed to have CLE or Barrett's mucosa based on precise endoscopic observations in Japan. The CLE located in a small area, e.g. less than 5 mm, defined according to the LEPV criteria without any other factor concerning typical Barrett's esophagus such as signs of gastroesophageal reflux should therefore be excluded from consideration as a high-risk mucosa.

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Norman Barrett originally described two special conditions, namely, a congenital short esophagus with an intrathoracic gastric columnar lining and congenital gastric heterotropia in the esophagus with ulceration. Thereafter, these conditions began to be known as "Barrett's esophagus." It is an acquired condition of esophageal columnar metaplasia following chronic gastroesophageal refl ux, and the classical Barrett's esophagus has been defi ned as having a circumferential columnar metaplasia spreading minimally 3 cm or more upward from the esophagogastric junction, because the esophagogastric junction still tends to be difficult to recognize precisely. Recently, from the point of view of adenocarcinogenesis of the esophagus, the term and concept of short-segment Barrett's esophagus (SSBE) as a developing condition of the classical Barrett's esophagus and the confi rmation of intestinal metaplasia has been required; however, the defi nition of Barrett's esophagus still remains controversial. In Japan, although the prevalence of shortsegment Barrett's esophagus has been reported to vary considerably, from 1% to 52%, the prevalence of long-segment Barrett's esophagus (LSBE) tends to range from 0% to 2%, which is a quite lower rate than that observed in Western countries. The great difference in the prevalence of SSBE is caused by the differences in the criteria of the esophagogastric junction and the defi nition concerning the necessity of intestinal metaplasia. A universally accepted defi nition of Barrett's esophagus is thus needed to accurately determine its actual prevalence.

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Previously, we demonstrated that CPT-11 is an effective agent against esophageal squamous cell cancers (ESCC), and that the protein level of DNA topoisomerase I can be a predictor for sensitivity to CPT-11 (Jpn J Cancer Res 2001; 92: 1335-41). Here, we describe our search for additional predictors of sensitivity to CPT-11, mainly among cell cycle-regulating proteins, because the cytotoxicity of CPT-11 is significantly correlated with the percentage of ESCC cells in S-phase. To this end, we selected and examined the expressions of 5 proteins involved in G 1 -S transition, i.e., p53, cyclin D1, p21, p27, and pRB, in 14 ESCC cell lines by western blot analysis. Among these proteins, the expression levels of p21 and pRB showed significant differences that were associated with the IC 50 values for CPT-11 (P = = = =0.0339 and P = = = =0.0109, respectively). Namely, the expression of p21 or pRB independently could be a good indicator of CPT-11 efficacy in ESCC. In addition, the cell proliferation activities examined by enzyme-linked immunosorbent assay (ELISA) using 5-bromo-2′ ′ ′ ′-deoxyuridine (BrdU) showed a significant correlation with the percentage of total S-phase cells (correlation coefficient = = = =0.568, P = = = =0.0324), and an inverse correlation with the IC 50 values for CPT-11 (correlation coefficient = = = = -0.601, P = = = =0.0213). Because, as in the case of DNA topoisomerase I, the cell proliferation activity determined using BrdU shows a close relationship with the MIB-1 labeling index, immunohistochemical studies of p21, pRB, and MIB-1 in resected ESCC specimens and/or biopsy samples could make it possible to predict more precisely the sensitivity of ESCC patients to CPT-11 prior to treatment. (Cancer Sci 2004; 95: 464-468) n recent years, many anti-cancer drugs have been developed that show potent anti-tumor activities against various experimental and clinical cancers. Moreover, combination chemotherapy using several anti-cancer drugs plays an important role in improving therapeutic efficacy. For esophageal squamous cell cancers (ESCC), cis-dichlorodiammineplatinum (II) (CDDP) is the key drug used for treatment, with 5-fluorouracil and/or leucovorin mainly used together as biochemical modulators.