Strong Association of Lymph Node Metastasis with Intraperitoneal Free Cancer Cell (IFCC) in Advanced Gastric Cancer

Background/Aims: Advanced gastric cancer is a disease with dismal prognosis, which is mainly characterized by the emerging intraperitoneal free gastric cancer cells (IFCC). Our interest is to elucidate a causative phenotype linking to IFCC. Methodology: Two hundred and sixty-nine resected gastric cancer patients examined for IFCC were enrolled at the Kitasato University Hospital to evaluate the clinical significance of the interaction between IFCC and other tumor phenotypes. Results: IFCC was not found in the 22 early gastric cancers. and we were thus restricted to evaluate the remaining gastric cancers beyond the muscuralis propria (MP). Among the 247 advanced gastric cancer patients. IFCC was a potent univariate prognostic factor (p < 0.0001) as well as lymph node metastasis (P < 0.0001), depth of invasion (P=0.0015), and age (P=0.009). IFCC affects poor prognosis more strongly in the modest node disease (n0/n1) than in the severe node disease (n2/n3/M), even after considering D2 dissection. In the modest node disease, multivariate prognostic analysis revealed IFCC as all independent prognostic factor, and lymph node metastasis (n1 against n0 disease) is the only independent predictive tumor factor of IFCC in the logistic regression analysis. As a result, we finally noticed that lymph node metastasis exists in almost advanced gastric cancer with IFCC, while IFCC was hardly detected unless lymph node metastasis exists. Conclusions: IFCC could be rather strongly associated with lymph node metastasis than depth of invasion in advanced gastric cancer, and transition from the node disease to the peritoneal disease plays a critical role in gastric cancer progression affecting dismal prognosis. Its regulation may be art optimal therapeutic target of advanced gastric cancer.