Outcome of patients with cancer of the esophagogastric junction in relation to histology and surgical strategy.

BACKGROUND/AIMS: The impact of histologic type and surgical strategy on survival of patients with cancer of the esophagogastric junction is debated. Thus, we evaluated the relationship between cancer histologic type (adenocarcinoma vs. squamous cell carcinoma) on long-term survival and the results of two different surgical techniques on outcome. METHODOLOGY: Two hundred and one patients with neoplasm of the esophagogastric junction were prospectively observed, and 133 patients (66%) underwent operation with curative intent. The results of two resective techniques, total gastrectomy with a thoraco-abdominal approach and total gastrectomy with a trans-hiatal approach were also compared in a subgroup with Siewert's type II and III cancer. RESULTS: Seventy-seven patients had an adenocarcinoma and 56 a squamous cell carcinoma. The 5-year proportion of survival was 35% in the adenocarcinoma group versus 40% in the squamous group (log-rank = 0.92), and the mean length of survival was 35 +/- 3 months and 34 +/- 5 months, respectively. The overall incidence of postoperative morbidity and the length of hospital stay were both significantly lower in the trans-hiatal group than in the thoraco-abdominal group (31% vs. 51%; p = 0.04; and 15.6 days vs. 23.2 days; p = 0.02 respectively), while the 5-year patient survival was 37% thoraco-abdominal approach and 42% in the trans-hiatal approach (log-rank = 0.62). CONCLUSIONS: In the present population, histologic type of the esophagogastric cancer was not a determinant factor for long-term survival. The transhiatal approach resulted in a better postoperative outcome without compromising surgical radicality and patient survival.

The CC chemokine MCP-1/CCL2 in pancreatic cancer progression: regulation of expression and potential mechanisms of antimalignant activity.

The aim of this study was to discover whether MCP-1/CCL2, a CC chemokine able to attract macrophages, is expressed in human pancreatic cancer and how it modulates cancer progression. All primary tumors were tested, and 6 of 14 pancreatic cancer cell lines were constitutively secreted CCL2. Analysis of the regulation demonstrated that the expression of CCL2 was significantly elevated and in a synergistic manner by IFN-gamma, tumor necrosis factor alpha, and interleukin 1beta. By immunohistochemistry and in situ hybridization, CCL2 production was confirmed in neoplastic ducts from surgical specimens. Serum levels of CCL2 in pancreatic cancer patients were significantly higher than in normal healthy subjects (P < 0.0001). Patients with high circulating levels of CCL2 had significantly higher survival rate than low CCL2 producers. Serum CCL2 levels positively correlated with tumor macrophage infiltration and inversely correlated with tumor proliferative activity (Ki67 expression). A direct effect of CCL2 on tumor cells is to be excluded, either because primary tumors as well as cell lines have no detectable CCL2 receptor (CCR2) and because addition of CCL2 on tumor cells in vitro did not modify cell cycle progression or apoptosis. In vitro, a model of tumor microenvironment showed a direct antiproliferative and proapoptotic activity of monocytes toward pancreatic cancer cell, which is mediated at least in part by interleukin 1beta. Moreover, other proinflammatory cytokines such as tumor necrosis factor alpha and IFN-gamma appeared able to induce apoptosis and to reduce the proliferative rate of pancreatic cancer. On the whole, the results presented in our investigation suggest that CCL2 could be a relevant negative regulator of pancreatic cancer progression.