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Lymph node metastasis, including lymph node micrometastasis (LMM), is one of the most important prognostic factors in esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor C (VEGF-C) plays a key role in the process of lymphangiogenesis. We examined VEGF-C expression and tumor microvessel density of the primary tumors in ESCC and analyzed relationships between VEGF-C expression and clinicopathologic findings including LMM in submucosal ESCC. The subjects were 87 patients with submucosal ESCC. Immunohistochemical staining of VEGF-C and CD34 was performed with primary tumors, and staining of cytokeratin was performed with dissected lymph nodes. Microvessel density was calculated from CD34 expression, and LMM was detected by cytokeratin staining. VEGF-C overexpression significantly correlated with depth of tumor invasion, lymphatic invasion, and lymph node metastasis (P < 0.05, P < 0.0001, and P < 0.0001, respectively). High microvessel density also correlated with lymphatic invasion and lymph node metastasis (P < 0.005 and P < 0.05, respectively). LMM was detected in 8 cases and 14 lymph nodes by cytokeratin staining. VEGF-C overexpression and high microvessel density were found in tumors with lymph node metastasis and/or LMM, compared with tumors without nodal metastasis or LMM (P < 0.0001 and P < 0.01, respectively). The present findings indicate that in ESCC with submucosal invasion, VEGF-C overexpression of the primary tumor is a strong high risk factor for lymph node metastasis, including LMM. [Copyright &y& Elsevier]

The detection rate of early-stage esophageal cancer has increased recently. Various types of treatment including endoscopic mucosal resection, blunt dissection, and esophagectomy with extended lymphadenectomy are employed in patients with submucosal esophageal cancer. The purpose of the present study was to analyze prognostic factors in patients with submucosal esophageal cancer. Univariate analysis showed that lymph node metastasis, subdivision of tumor depth, and lymphatic invasion were correlated with prognosis, whereas sex, age, tumor location, surgical procedure, adjuvant therapy, histologic findings, and venous invasion did not affect prognosis. Multivariate analysis demonstrated lymph node metastasis to be the only significant prognostic factor in submucosal esophageal cancer. Although subdivisions of tumor depth did not reach significance as prognostic factors, lymph node metastasis was strongly related to tumor depth. To select the individualized treatment in patients with submucosal esophageal cancer, accurate diagnosis of lymph node metastasis necessitates a combination of imaging methods such as endoscopic ultrasound–guided fine-needle aspiration, computed tomography, and positron emission tomography. [Copyright &y& Elsevier]

The sentinel node (SN) is regarded as the first drainage lymph node, and tumor cells are considered likely to directly affect the SN. However, few reports have identified differences between SNs and non-SNs in cancer patients. Subjects in this study included 27 patients with gastric cancer who underwent curative operation and intraoperative detection of SNs by radioisotope methods. The mean number of SNs was 3.2 (range 1 to 5). Degree of infiltration of natural killer cells, dendritic cells, MIB-1 labeling index, and CD3-ζ expression of lymphocytes in SNs and non-SNs were examined by means of immunohistochemical methods. Degree of infiltration was compared according to depth of invasion and between SNs and non-SNs. Patients with early-stage cancer displayed a greater degree of infiltration of MIB-1 labeling index and CD3-ζ expression than patients with pT2 or pT3 lesions (P<0.05). The MIB-1 labeling index in SNs was significantly lower than that in non-SNs (P<0.05). However, no significant difference was observed in infiltration of natural killer cells, dendritic cells, or CD3-ζ. Morphologic changes of dendritic cells in SNs were not definite. Our results suggest that SNs in gastric cancer might not be suppressed, unlike in breast cancer and melanoma. SN paralysis may depend on tumor- and organ-specific characteristics or exogenous stimulation from the gastric mucosa. Studies in progress will help to identify immunologic paralysis of the SN in various types of cancer. Attention must therefore be paid to organ specificity. [Copyright &y& Elsevier]