Background Some tyrosine kinase receptors (RTKs) play critical roles in gastric cancer progression. Not only trastuzumab, but also several other agents targeting RTKs are being investigated for gastric cancer therapy. However, the simultaneous expression of multiple RTKs, which may interfere with the effectiveness of therapeutic agents, has not been evaluated in a large cohort with gastric adenocarcinoma (GAC). Methods We performed a tissue microarray analysis in 950 patients with GAC who underwent a gastrectomy without preoperative chemotherapy. The protein expressions of HER2, EGFR, MET and FGFR2 were evaluated using immunohistochemistry, and the gene amplifications of HER2, EGFR and MET were examined using dual-color in situ hybridization.Results The frequency of overexpression was 11.8 % for HER2, 23.5 % for EGFR, 24.9 % for MET and 31.1 % for FGFR2. Whereas strong staining for each of the RTKs was heterogeneous, tumors with homogeneously strong staining areas often exhibited gene amplification. Strong EGFR expression was significantly associated with a poor outcome, but no prognostic correlations were observed in other RTKs. The overexpression of single and multiple RTKs was observed in 40.4 and 22.7 % of the cases, respectively. HER2, EGFR, MET and FGFR2 predominance was observed in 10.1, 13.9, 16.1 and 22.9 % of the GACs, respectively. Conclusions Approximately two-thirds of patients with GAC exhibited the expression of at least one RTK and would be candidates for targeted therapies. Moreover, one-third of at least one RTK overexspressing cases showed multiple RTKs expression. Our results may be useful for selecting the most suitable patients for each targeted therapy.

Tumor-associated macrophages (TAMs) are candidate histological factors in invasive ductal carcinoma (IDC) of the pancreas. Tumorassociated macrophages can be affected by cancer-related inflammation and pancreatitis and interact with important invasive behavior in a recurrent manner in pancreatic IDC. These features may help elucidate the aggressiveness of pancreatic IDC. The aim of this study was to characterize TAMs in pancreatic IDC in comparison with chronic pancreatitis (CP) and to reveal TAM-related factors and the clinical impact of TAMs. CD68 (a pan-macrophage marker) and CD204 (an M2 macrophage marker) immunohistochemistry was carried out in pancreas head specimens from 107 IDC cases and 11 CP cases. Immunopositive cell areas were calculated at the periphery and center of the tumor. The distributions of macrophages in IDC and CP and the relationship between TAMs and histological tumor factors, survival, and recurrence were evaluated. Macrophages were more frequently observed in the lesion periphery than the center in IDC and CP. The density of macrophages was elevated in IDC compared to CP. Dense M2 macrophages at the tumor periphery were frequently seen in large tumors and showed an independent impact on overall survival and disease-free time. Early recurrence in the liver or the local manipulated area was associated with high accumulation of peripheral M2 macrophages. More M2 macrophages were seen in IDC than in CP in both the periphery and the center. High numbers of peripheral M2 macrophages were associated with large tumor size, early recurrence in the liver, local recurrence, and shortened survival time in patients with pancreatic IDC. (Cancer Sci 2012; 103: 2012-2020 T he prognosis of patients undergoing resection for pancreatic invasive ductal carcinoma (IDC) remains poor.(1-5) Histological studies have been carried out to elucidate the aggressiveness of pancreatic IDC and have revealed prognostic factors including tumor size, lymph node involvement, nerve plexus invasion, positive resected margin, and low tumor grade.(1-8)Tumor-associated macrophages (TAMs) have recently been reported as a candidate factor in poor prognosis. (9) Macrophages are the most abundant cancer stromal cells involved in the host immune system, (10) and TAMs have been found to play important roles in tumorigenesis, angiogenesis, matrix remodeling, and metastasis.(11-13) Tumor-associated macrophages have a prognostic impact in prostate, breast, and lung cancers, as well as pancreatic IDC.(9,14-16) The heterogeneity of macrophages has been discussed with regard to their different responses to various microenvironmental stimuli. Macrophages are classically activated towards the M1 phenotype by lipopolysaccharide and interferon-c. M1 macrophages are characterized by high expression of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-12, and tumor necrosis factor. Alternatively, macrophages are activated towards the M2 phenotype by IL-4, IL-13, and IL-10. M2 macrophages are characterized by high expression of ...

Background: Omentectomy is performed widely for locally advanced gastric cancer to prevent disease recurrence. However, its clinical benefit is unknown. Methods: This retrospective cohort study compared the outcome of gastrectomy with preservation of the omentum (GPO) and gastrectomy with resection of the omentum (GRO) among patients with cT3-T4 gastric cancer who underwent gastrectomy between 2006 and 2012 in one of five participating institutions. A consensus conference identified 28 variables potentially associated with outcome after gastrectomy for the estimation of propensity scores, and propensity score matching (PSM) was undertaken to control for possible confounders. Postoperative surgical outcomes, overall survival and disease recurrence were compared between GPO and GRO. Results: A total of 1758 patients were identified, of whom 526 remained after PSM, 263 in each group. Median follow-up was 4⋅9 (i.q.r. 3⋅1-5⋅9) years in the GRO group and 5⋅0 (2⋅5-6⋅8) years in the GPO group. The incidence of postoperative complications of Clavien-Dindo grade III or more was significantly higher in the GRO group (17⋅5 versus 10⋅3 per cent; P = 0⋅016). Five-year overall survival rates were 77⋅1 per cent in the GRO group and 79⋅4 per cent in the GPO group (P = 0⋅749). There were no significant differences in recurrence rate or pattern of recurrence between the groups. Conclusion: Overall survival and disease recurrence were comparable in patients with cT3-4 gastric cancer who underwent GPO or GRO.

Background:Clinical trials comparing laparoscopic gastrectomy (LG) versus traditional open gastrectomy (OG) have been planned, their surgical outcomes reported but their oncologic outcomes are still pending. Consequently, we have conducted this large-scale historical cohort study to provide relevant information rapidly to guide our current practice.Methods:Through a consensus meeting involving surgeons, biostatisticians, and epidemiologists, 30 variables of preoperative information possibly influencing surgeons’ choice between LG versus OG and potentially associating with outcomes were identified to enable rigorous estimation of propensity scores. A total of 4235 consecutive patients who underwent gastrectomy for gastric adenocarcinoma were identified and their relevant data were gathered from the participating hospitals. After propensity score matching, 1848 patients (924 each for LG and OG) were selected for comparison of long-term outcomes.Results:In the propensity-matched population, the 5-year overall survival was 96.3% [95% confidence interval (CI) 95.0–97.6] in the OG as compared with 97.1% (95% CI, 95.9–98.3) in LG. The number of all-cause death was 33/924 in the OG and 24/924 in the LG through the entire period, and the hazard ratio (LG/OG) for overall death was 0.75 (95% CI, 0.44–1.27; P = 0.290). The 3-year recurrence-free survival was 97.4% (95% CI, 96.4–98.5) in the OG and 97.7% (95% CI, 96.5–98.8) in the LG. The number of recurrence was 22/924 in the OG and 21/924 in the LG through the entire period, and the hazard ratio was 1.01 (95% CI, 0.55–1.84; P = 0.981).Conclusions:This observational study adjusted for all-known confounding factors seems to provide strong enough evidence to suggest that LG is oncologically comparable to OG for gastric cancer.