Kazuo Ogiya

Prevalence of Barrett's esophagus in Japan

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 “Barretts esophagus.” It is an acquired condition of esophageal columnar metaplasia following chronic gastroesophageal reflux, and the classical Barretts esophagus has been defined 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 Barretts esophagus (SSBE) as a developing condition of the classical Barretts esophagus and the confirmation of intestinal metaplasia has been required; however, the definition of Barretts esophagus still remains controversial. In Japan, although the prevalence of short-segment Barretts esophagus has been reported to vary considerably, from 1% to 52%, the prevalence of long-segment Barretts 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 definition concerning the necessity of intestinal metaplasia. A universally accepted definition of Barretts esophagus is thus needed to accurately determine its actual prevalence.

NEW ARGON PLASMA COAGULATION METHOD FOR SUPERFICIAL ESOPHAGEAL CARCINOMAS: ARGON PLASMA COAGULATION‐SUBEPITHELIAL ABLATION

Argon plasma coagulation (APC) has been introduced to the field of therapeutic endoscopy and is now widely used. A new ablation technique is herein proposed for the treatment of superficial esophageal carcinomas. According to this technique, after the initial ablation, we exfoliate the epithelium and then perform a second ablation (APC‐subepithelial ablation). APC is applied at a power/gas setting of 60 W and 2l min in the esophagus. The APC applicator is inserted through the working channel of the endoscope, and a transparent hood is then set at the tip of the endoscope. At first, lines are traced around the tumor. Next, the initial ablation is made in a uniform manner. A transparent hood is then attached to the ablated tumor and, thereafter, the epithelium is easily exfoliated. The muscularis mucosae are preserved. We next identify any remaining non‐uniform ablation areas and then a second ablation is made on those areas. To obtain a complete eradication of the mucosal and submucosal tissue, the endoscopic appearance of brownish subepithelial tissue following the secondary argon plasma irradiation after epithelial exfoliation with initial argon plasma irradiation is needed. The secondary ablation could thus safely ablate at the esophageal gland level. The procedure is minimally invasive and easy to apply. A total of 48 patients with superficial esophageal squamous cell carcinoma were treated between February 2000 and April 2006 (median follow up 46 months). One hundred and sixty one sessions were performed with no major complications (no bleeding, no perforation, and no stenosis). The technique is thus considered to be safe.

The expressions of p21 and pRB may be good indicators for the sensitivity of esophageal squamous cell cancers to CPT-11: Cell proliferation activity correlates with the effect of CPT-11

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 G1‐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 IC50 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 IC50 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.

Argon plasma coagulation for local recurrence of squamous cell carcinoma of the esophagus after endoscopic mucosal resection: technique and outcome

BackgroundIt is difficult to undergo a second endoscopic mucosal resection (EMR) for local cancer recurrence because ulcer scars caused by the previous EMR are frequently located near the tumor. The main objective of this study was to evaluate whether argon plasma coagulation (APC) is an effective and safe modality for treating early esophageal cancer recurrence untreatable by EMR.MethodsWe reviewed the experience of this clinic in the administration of EMR for the treatment of mucosal esophageal cancer in 249 patients with 276 lesions (142, m1; 98, m2; 36, m3) between December 1989 and March 2005. A local recurrence of the disease after the EMR was detected in 24 cases (9.6%). Seventeen patients were treated with APC. An argon gas flow of 2 l/min was used at a power setting of 60 W. The follow-up period of the 17 patients ranged from 13 to 87 months (median, 68 months).ResultsThe depth of tumor invasion, estimated by endoscopy, was mucosal in all patients. Seventy-three sessions (mean, 4.3 sessions/person; range, 1–12 sessions) were performed. All lesions were easily irradiated. No serious complications such as bleeding, perforation, or stenosis occurred. Complete local control was achieved in 16 of the 17 patients, but the remaining patient required further surgery. Death occurred in 3 cases. Two patients died as a result of other disease, and 1 patient died of other carcinomas, but no patient died of esophageal carcinoma.ConclusionAPC is a safe and effective method for the treatment of local recurrence of squamous cell carcinoma of the esophagus after an EMR.

P69 A pilot trial of Docetaxel plus Pedaplatin in Cisplatin-pretreated esophageal cancer

patients. The aim of the study was the assessment of the impact of therapeutic strategy with a combined modality treatment on the status of regional lymph nodes in patients with squamous cell carcinoma (SSC) of the esophagus. Methods: Between 2001 and 2004, in a prospective randomized controlled multicenter (4 institutions) trial (SCSR 6PO5C01320), 84 stage II and III patients (75M/9K; median age 56, range 42–76) with SCC of the thoracic esophagus were randomly assigned to one of the following therapeutic arms: surgery alone (SURG) – 30 pts, chemotherapy followed by surgery (CHTH+SURG) – 23 pts and chemoradiotherapy followed by surgery (CHRTH+SURG) – 31 pts. The 21-day combination chemotherapy regimen consisted of a continuous infusion of cisplatin (20mg/m/day) and 5-fluorouracil (300mg/m/day). The patients who underwent chemoradiotherapy received concomitant fractionated radiation to a total dose of 30Gy. After 3 week interval transthoracic esophagectomy with 2-field extended lymph node dissection was carried out in all the patients. Lymph node involvment rate, number of metastatic nodes and positive nodes ratio (positive/harvested) were analysed in particular therapeutic arms. A statistical analysis was conducted with the computer statistical package STATISTICA v. 6.0 (StatSoft). A P value lower than 0.05 was considered as significant. Results: The median number of harvested lymph nodes was 23.7±9.6 for all patients and 27.8±11, 22.5±10.1 and 22.5±8.5, for particular therapeutic arms CHTH+SURG, CHRTH+SURG and SURG, respectively (P=0.2283). Metastatic nodes were found in 63.9% of all patients and in 46.7, 41.2 and 86.2% of patients treated with CHTH+SURG, CHRTH+SURG and SURG, respectively (P=0.0027). The median number of metastatic nodes was 2.6±3.1 for all patients and 1.3±2.6, 1.3±2.4 and 3.8±3.3 for CHTH+SURG, CHRTH+SURG and SURG, respectively (P=0.0013). The median positive nodes ratio was 0.12±0.06 for all patients and 0.05±0.10, 0.05±0.09 and 0.18±0.17 for CHTH+SURG, CHRTH+SURG and SURG, respectively (P=0.0018). Conclusion: Neoadiuvant treatment in patients with SCC of the esophagus significantly decreases the number and ratio of positive lymph nodes and thus it might result in potentially better local clearance of resection surgery.