Resveratrol (3,5,4′-trihydroxy- trans -stilbene) is a natural product occurring in grapes and various other plants with medicinal properties associated with reduced cardiovascular disease and reduced cancer risk. To evaluate the possibility and potential mechanism(s) of which resveratrol inhibits N -nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis, 96 F344 male rats were divided into 10 groups and resveratrol (1 and 2 mg/kg) was administered orally or intraperitoneally (i.p.). In the groups in which resveratrol was administered at 2 mg/kg (orally, for 16 weeks), 1 and 2 mg/kg (i.p., for 16 weeks) and 1 mg/kg (i.p., for 20 weeks), the number of NMBA-induced esophageal tumors per rat was significantly reduced to 78, 62, 54 and 48, respectively ( P < 0.05), and the size of maximum tumors in each group with resveratrol treatment was also significantly smaller than that in NMBA alone group ( P < 0.05). Although the pathological examination did not indicate significantly decreased incidence of carcinomas by administering resveratrol, the tendency of carcinogensis suppression was observed ( P = 0.177). Semi-quantitative RT–PCR and ELISA analysis demonstrated that following NMBA treatment, the expression of COX-1 mRNA was strongly present in tumor tissues, while weakly present in non-tissues; the expression of COX-2 mRNA was induced in both tumor and non-tumor tissues. The production of prostaglandin E ₂ (PGE ₂ ) increased ∼6-fold, compared with the normal esophageal mucosa. The higher expression of COX-1, the up-regulated COX-2 expression and the increased levels of PGE ₂ synthesis were all significantly decreased by administering resveratrol. Our study suggests that resveratrol suppressed NMBA-induced rat esophageal tumorigenesis by targeting COXs and PGE ₂ , and therefore may be a promising natural anti-carcinogenesis agent for the prevention and treatment of human esophageal cancer.

Background Adequate blood supply for the reconstructed organ is important for safe esophagogastric anastomosis during esophagectomy. Recently, indocyanine green (ICG) has been used for visualization of the blood supply when anastomosis is performed in vascular surgery. To visualize the blood supply for reconstruction, we employed ICG fluorescence during esophagectomy. Methods From August 2008, 40 patients received cervical or thoracic esophagectomy. They consisted of 33 patients having esophagectomy for thoracic esophageal cancer, 3 being treated for cervical esophageal cancer, and 4 with double cancer of the thoracic and cervical regions. Before and after pulling up the reconstructed organ, 2.5 mg of ICG was injected as a bolus. Then ICG fluorescence was detected by a camera and recorded. Results ICG fluorescence was easily detected in all patients at 1 min after injection. The vascular network was well visualized in the gastric wall, colonic grafts, and free jejunal grafts. In five patients, we also performed anastomosis between the short gastric vein and the external cervical vein or superficial cervical vein. The intraoperative and postoperative course of all patients was uneventful apart from three anastomotic leakages. Conclusions ICG fluorescence can be employed to evaluate the blood supply to reconstructed organs and can be useful in selecting the patients who do not need additional vessel anastomosis. However, anastomotic leakage was not reduced, so the microcirculation detected by ICG fluorescence did not necessarily provide appropriate blood supply for a viable anastomosis.

Objective: Osteopontin (OPN) is a secreted integrin-binding glycophosphoprotein that may have a role in head and neck squamous cell carcinoma (SCC). To evaluate the clinical significance of OPN in esophageal squamous cell carcinoma (ESCC), we compared plasma OPN levels with those of common tumor markers. Methods: Preoperative plasma OPN levels were measured by enzyme immunoassay in 103 ESCC patients. Serum SCC antigen, Cyfra 21-1, and carcinoembryonic antigen (CEA) levels were also measured routinely at admission by radioimmunoassay. Results: Plasma OPN levels ranged from 82.8 to 1,980 ng/ml. High OPN level was associated with lymph node metastasis (p = 0.05), but not with tumor histology or depth of invasion. The overall survival of the patients with high OPN levels was worse than that of those with low OPN levels (p = 0.02). SCC antigen and Cyfra 21-1 levels were associated with the depth of tumor invasion, the tumor diameter, lymph node metastasis, and the overall survival, but CEA was not associated with these clinicopathological factors. Combined evaluation of OPN plus Cyfra 21-1 or OPN plus SCC antigen was useful as an independent prognostic indicator. Conclusion: Measurement of the plasma OPN level, as well as serum SCC antigen and Cyfra 21-1, may help to predict the progression of ESCC.

Purpose: Dysadherin, a cancer-associated cell membrane glycoprotein, has been reported to down-regulate E-cadherin expression and promote metastasis. To evaluate the role of dysadherin in gastric cancer, we examined dysadherin and E-cadherin expression in gastric cancer patients. Experimental Design: Dysadherin and E-cadherin expression were evaluated in 276 gastric cancer patients by immunohistochemistry, and the results were compared with the clinicopathological findings of the subjects. Results: Dysadherin was not expressed in normal gastric epithelium. Both dysadherin and E-cadherin were localized to the cell membrane. Dysadherin expression was sometimes largely localized to infiltrating tumor cells or cells dissociating. Ninety gastric cancer patients (32.6%) were positive for dysadherin, and 151 patients (54.7%) showed preservation of E-cadherin expression. Expression of dysadherin was associated with moderately differentiated carcinoma and hematogenous metastasis, whereas reduced expression of E-cadherin showed an association with poorly differentiated carcinoma and peritoneal dissemination. As a result, dysadherin positivity and reduced E-cadherin expression were associated with a poor prognosis. In addition, patients with both dysadherin positivity and reduced E-cadherin had the worst prognosis. Multivariate analysis revealed that reduced E-cadherin expression was an independent prognostic factor, but dysadherin expression was not. Conclusion: Combined analysis of dysadherin and E-cadherin expression may help to predict the prognosis and the mode of metastasis in gastric cancer patients. Patients with dysadherin positivity have a higher risk of hematogenous metastasis, whereas patients with reduced E-cadherin expression have an increased risk of peritoneal dissemination.

Background: Many studies have attempted to detect cancer cells using the reverse transcription–polymerase chain reaction (RT–PCR) for specific mRNAs. None has examined the correlation between the presence of circulating oesophageal cancer cells in peripheral blood and long-term outcome. Methods: Blood samples were obtained on admission, and before, during and after operation from 70 patients with squamous oesophageal cancer who had complete clinicopathological records and who underwent curative oesophagectomy between June 1997 and June 2000. RT–PCR for mRNA encoding squamous cell carcinoma antigen (SCCA mRNA) was used to detect oesophageal cancer cells in peripheral blood. Results: Twenty-three patients (33 per cent) were positive for SCCA mRNA on admission and 17 of these patients developed recurrent disease. SCCA mRNA on admission correlated with the depth of tumour invasion (P < 0·001) and with venous invasion (P < 0·001). Eleven of 24 patients with a positive intraoperative result were positive for SCCA mRNA only during operation, of whom seven also developed recurrence. Conclusion: RT–PCR for SCCA mRNA can detect oesophageal cancer cells in peripheral blood. The presence of such cells in blood samples obtained on admission or during operation is a useful predictor of outcome in patients with oesophageal squamous cell carcinoma.