Background: A phase II study to evaluate the efficacy and tolerability of weekly i.v. and i.p. paclitaxel (PTX) combined with S-1 was carried out in gastric cancer patients with peritoneal metastasis. Patients and methods: Gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered i.v. at 50 mg/m² and i.p. at 20 mg/m² on days 1 and 8. S-1 was administered at 80 mg/m²/day for 14 consecutive days, followed by 7 days rest. The primary end point was the 1-year overall survival (OS) rate. Secondary end points were the response rate, efficacy against malignant ascites and safety. Results: Forty patients were enrolled, including 21 with primary tumors with peritoneal dissemination, 13 with peritoneal recurrence and six with positive peritoneal cytology only. The median number of courses was 7 (range 1–23). The 1-year OS rate was 78% (95% confidence interval 65% to 90%). The overall response rate was 56% in 18 patients with target lesions. Malignant ascites disappeared or decreased in 13 of 21 (62%) patients. The frequent grade 3/4 toxic effects included neutropenia (38%), leukopenia (18%) and anemia (10%). Conclusion: Combination chemotherapy of i.v. and i.p. PTX with S-1 is well tolerated and active in gastric cancer patients with peritoneal metastasis.

Adiponectin, a circulating peptide hormone produced in adipose tissue, has been shown to be reduced in the plasma of patients with cancer, suggesting that this adipokine may be mechanically involved in the pathogenesis of adiposity‐related carcinogenesis. In this study, we examined the expression of adiponectin receptors (AdipoR1 and AdipoR2) and assessed the function of adiponectin in gastric cancer. All of the six gastric cancer cell lines significantly expressed mRNA and protein of both receptors with variable levels. Addition of 30 µg/mL adiponectin potently induced apoptosis and inhibited the proliferation of AZ521 and HCG27. Down‐regulation of either AdipoR1 or AdipoR2 by specific siRNA significantly suppressed the growth inhibitory effects of adiponectin in both cell lines. Moreover, a local injection of adiponectin markedly inhibited the growth of AZ521 inoculated subcutaneously in nude mice. Similarly, the continuous intraperitoneal infusion of adiponectin effectively suppressed the development of peritoneal metastasis of AZ521. Adiponectin negatively regulates the progression of gastric cancer cells possibly through both AdipoR1 and AdipoR2. Although adiponectin was already reported to have antiangiogenic effects, our results suggest that the antitumor effect of adiponectin was, at least partially, dependent on the direct effects on tumor cells. (Cancer Sci 2007; 98: 1120–1127)

Objective: To determine the optimal extent of lymph node dissection for carcinomas of the true cardia, otherwise called Siewert type II esophagogastric junction (EGJ) carcinomas. Background: In patients with cancer of the EGJ, comparable outcomes have been obtained with extended esophagectomy and total gastrectomy. The issue of the optimal surgical approach for EGJ tumors has been under debate. Nodal involvement is a strong predictor of survival, however, the optimal extent of prophylactic lymphadenectomy for Siewert type II tumors remains to be elucidated. Methods: We retrospectively evaluated the distributions of the metastatic nodes, the recurrence pattern, and the oncological outcomes in a single-center large cohort of 225 patients with Siewert type II tumors. To assess the therapeutic outcomes of respective node dissection, we applied an index calculated by multiplication of the incidence of metastasis by the 5-year survival rate of patients with metastasis in the respective node stations. Results: The incidence of nodal metastasis was high in the right paracardial (38.2%), lesser curve (35.1%) and left paracardial (23.1%) nodes, and also the nodes along the left gastric artery (20.9%). Involvement of the suprapancreatic nodes along the celiac artery, splenic artery and common hepatic artery was found in 23, 25, and 14 patients, respectively. According to the index of estimated benefit from lymph node dissection, dissection of the paracardial and lesser curve nodes yielded the highest therapeutic benefit. The number of metastatic nodes in these areas was as predictive of the disease-free and overall survivals as the TNM pN category. The 5-year overall survival rates in patients with no or 1–2 metastatic nodes were 76.6% and 62.3%, respectively, whereas the 5-year survival rate in those with 3 or more positive nodes was only 22.4%, comparable with the rate of 17.4% in patients with TNM pN3 tumors. Conclusions: Clear anatomic distinction of EGJ tumors is likely to provide insight into the appropriate extent of lymphadenectomy. Dissection of the paracardial and lesser curve nodes is essential for staging as well as for obtaining therapeutic benefit in surgery for in EGJ carcinomas (Siewert type II).