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Lymph node micrometastasis (LNM) can now be detected thanks to the development of various biological methods such as immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR). Although several reports have examined LNM in various carcinomas, including gastrointestinal (GI) cancer, the clinical significance of LNM remains controversial. Clinically, the presence of LNM is particularly important in patients without nodal metastasis on routine histological examination (pN0), because patients with pN0 but with LNM already in fact have metastatic potential. However, at present, several technical obstacles are impeding the detection of LNM using methods such as IHC or RT-PCR. Accurate evaluation should be carried out using the same antibody or primer and the same technique in a large number of patients. The clinical importance of the difference between LNM and isolated tumor cells (≤0.2 mm in diameter) will also be gradually clarified. It is important that the results of basic studies on LNM are prospectively introduced into the clinical field. Rapid diagnosis of LNM using IHC and RT-PCR during surgery would be clinically useful. Currently, minimally invasive treatments such as endoscopic submucosal dissection and laparoscopic surgery with individualized lymphadenectomy are increasingly being performed. Accurate diagnosis of LNM would clarify issues of curability and safety when performing such treatments. In the near future, individualized lymphadenectomy will develop based on the establishment of rapid, accurate diagnosis of LNM. [ABSTRACT FROM AUTHOR]

Abstract: Background: Recently, neoadjuvant chemoradiation therapy (CRT) has been introduced for treatment of esophageal squamous cell carcinoma (ESCC). This study was performed to investigate the usefulness of endoscopic ultrasonography (EUS) in comparison with EUS findings before and after CRT, and histologic findings. Methods: There were 33 patients with potentially resectable ESCC who underwent neoadjuvant CRT. Preoperative EUS and histologic findings were compared. EUS criteria were established on the basis of low and high echoic regions. Resected specimens were examined by hematoxylin-eosin, azan, and cytokeratin immunohistochemical staining. Results: Azan and cytokeratin staining clearly delineated fibrous changes and residual tumor. Low echoic regions corresponded to residual tumor and high echoic spots corresponded to fibrosis. All 12 patients classified as grade 1 on EUS diagnosis had histologic grade 1 tumors. Nineteen of 21 cases that presented with high echo were grade 2 or 3. The prognosis according to EUS diagnosis was similar to the histologic effect. Conclusions: Preoperative EUS findings reflected the histologic effect after neoadjuvant CRT. EUS is a useful tool to assess the effect for CRT and to predict the prognosis in ESCC patients. [Copyright &y& Elsevier]

Background: The expression of E-cadherin correlates with the progression and metastasis of gastric cancer. Slug, a member of the snail family of transcriptional factors, is a newly identified factor that represses transcription of the E- cadherin gene. The purpose of the present study was to evaluate the clinical significance of E-cadherin and Slug expression in gastric cancer. Methods: Immunohistochemistry was used to investigate the expression of E-cadherin and Slug proteins in 164 patients with gastric cancer. The relationships between the expression of these proteins and clinicopathological factors, including prognosis, were analyzed. Results: Positive expression of E-cadherin and Slug was observed in 43.9 and 29.9% of cases, respectively. Tumors with reduced E-cadherin or positive Slug expression had greater extent of lymph node metastasis, lymphatic invasion, and venous invasion, and were at a worse stage than the tumors with preserved E-cadherin or negative Slug expression. Slug expression was significantly correlated with reduced E-cadherin expression; 37 of the 49 (75.5%) tumors with positive Slug expression had reduced E-cadherin expression ( P = 0.0008). Patients with reduced E-cadherin expression or positive Slug expression had poor clinical outcomes. In the group with preserved E-cadherin expression, the 5-year survival rate was better for patients who were negative for Slug expression than for those who were positive for Slug expression ( P = 0.0001). However, multivariate analysis indicated that E-cadherin expression and Slug expression were not independent prognostic factors. Conclusions: Evaluation of not only the expression of E-cadherin, but also the coexpression of E-cadherin and Slug in patients with preserved E-cadherin expression would be useful for predicting malignant properties of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Interactions of stromal hyaluronic acid (HA) with its binding protein RHAMM (receptor for HAmediated motility) (CD168) have been reported to affect tumor extension and the migration of crucial molecules to promote tumor progression and metastases. Cancerous CD168 expression is correlated with aggressive biological features in several cancers. However, the clinical implications of CD168 positivity in gastric cancer have remained unclear. Methods: We examined the CD168 expression of 196 consecutive gastric cancer patients by immunohistochemistry. According to CD168 positivity, the 196 gastric cancer patients were divided into two groups (57 CD168-positive and 139 CD168-negative patients). The correlation between CD168 expression and clinicopathological factors (age, sex, histology, tumor depth, lymph node status, and vessel invasion) was evaluated according to the Japanese Classification of Gastric Carcinoma. Results: Cancerous CD168 expression was detectable in 57 of the 196 tumors (29%). CD168 positivity was significantly correlated with the depth of invasion, nodal involvement, and vessel invasion (p < 0.01). Survival analysis of the 196 gastric cancer patients showed that the CD168-positive group had a significantly higher mortality than the CD168-negative group (p < 0.01). In terms of a correlation with CD168 positivity at separate clinical stages, a significance difference was only found in stages II and III. Multivariate analysis revealed that CD168 expression was a significant independent prognostic marker (p = 0.013) after depth of invasion (p < 0.005) and nodal involvement (p < 0.01). Conclusion: Our results suggest that cancerous CD168 positivity is strongly related to the invasion and metastasis of gastric cancer tumors. These results suggest that cancerous CD168 expression can be used as a prognostic marker of gastric cancer owing to its interactions with stromal hyaluronic acid. [ABSTRACT FROM AUTHOR]

A new marker, CD208, was recently explored as a mature interdigitating dendritic cell (DC), and the correlation between the infiltration of CD208-positive cells and clinical factors has been reported in various types of cancers. In this study, we tried to clarify the clinical implication of CD208-positive cell infiltration in gastric cancer immunohistochemically. A total of 128 gastric cancer patients who underwent a curative operation were enrolled. DCs in tumor nests were identified with two DC markers, CD208 and S-100 protein (S100), by immunohistochemistry. The correlation between clinicopathological features and the CD208- or S100-positive cell infiltration degree was analyzed. Infiltration of S100-positive cells did not correlate with the degree of CD208-positive cell infiltration. Patients with high CD208-positive cell infiltration in the peritumor had a poorer surgical outcome than those with low CD208 infiltration ( p < 0.05). Multivariate analysis revealed that CD208-positive cell infiltration was not an independent prognostic factor. We showed that intratumoral CD208-positive cells, as mature DCs, had an inverse correlation to patients’ postoperative outcome in gastric cancer, unlike a conventional DC marker. Evaluation of CD208-positive cell infiltration with S100-positive cell infiltration in gastric cancer is useful to predict antitumor immunological conditions in gastric cancer. [ABSTRACT FROM AUTHOR]

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]

Background. Paraaortic lymph node dissection in advanced gastric carcinoma is controversial. The purpose of this study was to investigate the incidence and significance of micrometastasis (MM) or tumor cell microinvolvement (TCM) in these critical lymph nodes. Methods. A total of 2339 lymph nodes, including 390 paraaortic nodes, obtained from 47 patients with advanced gastric carcinoma were examined immunohistochemically, using cytokeratin antibody. Results. Lymph node metastasis was found in 95 of the 390 paraaortic nodes of 14 patients by routine histological examination. MM or TCM was immunohistochemically detected in 45 of the 295 negative paraaortic lymph nodes from 15 of 33 patients (MM, n = 5; TCM, n = 10). The 5-year-survival rate in the paraaortic node-negative group and cytokeratin-positive group was significantly higher that that of the hematoxilin and eosin-positive group. The total number of lymph node metastases by hematoxylin and eosin staining and the pathological lymph node compartments, by cytokeratin-positive nodes, were prognostic factors by multivariate analysis. Conclusions. We demonstrated a high rate of MM or TCM in the paraaortic lymph nodes and suggest that such harbored metastases are related to the prognosis of patients with advanced gastric carcinoma. On the basis of this study, a multi-institutional study should be considered. [ABSTRACT FROM AUTHOR]