Comparison of Efficacy of Self-Expandable Metallic Stent Placement in the Unresectable Esophageal Cancer Patients

This is a retrospective study to evaluate the prevention of complications of metallic stent placement in patients with unresectable advanced esophageal cancer. A total of 87 patients were treated with 4 types of metal stents in the esophagus over a period of 18 years. Stent placement was technically successful. The most common prior treatment was chemoradiotherapy. There were no significant differences in the rate of patients with no complications among the prior treatments. Approximately, 30% of patients had the most common chest pain in complications. Stent placement within one month after the completion of chemoradiotherapy should be avoided for the prevention of the chest pain. There was no significant difference in the rate of patients with no complications by lesion location. The rate of no complications was higher for the Niti-S stent than the Gianturco Z-stent or Ultraflex stent. Of note, no complications were noted for the Niti-S ultrathin stent at all. Among cases of stent-related death, the most common type of complication was respiratory disorder caused by the stent that seems to be thick and hard. Therefore, the stent with thin and flexible characteristics like the Niti-S ultrathin stent will solve the various problems of esophageal stent placement

Hyaluronan digestion controls DC migration from the skin

The breakdown and release of hyaluronan (HA) from the extracellular matrix has been hypothesized to act as an endogenous signal of injury. To test this hypothesis, we generated mice that conditionally overexpressed human hyaluronidase 1 (HYAL1). Mice expressing HYAL1 in skin either during early development or by inducible transient expression exhibited extensive HA degradation, yet displayed no evidence of spontaneous inflammation. Further, HYAL1 expression activated migration and promoted loss of DCs from the skin. We subsequently determined that induction of HYAL1 expression prior to topical antigen application resulted in a lack of an antigenic response due to the depletion of DCs from the skin. In contrast, induction of HYAL1 expression concurrent with antigen exposure accelerated allergic sensitization. Administration of HA tetrasaccharides, before or simultaneously with antigen application, recapitulated phenotypes observed in HYAL1-expressing animals, suggesting that the generation of small HA fragments, rather than the loss of large HA molecules, promotes DC migration and subsequent modification of allergic responses. Furthermore, mice lacking TLR4 did not exhibit HA-associated phenotypes, indicating that TLR4 mediates these responses. This study provides direct evidence that HA breakdown controls the capacity of the skin to present antigen. These events may influence DC function in injury or disease and have potential to be exploited therapeutically for modification of allergic responses

Discovery of a good responder subtype of esophageal squamous cell carcinoma with cytotoxic T-lymphocyte signatures activated by chemoradiotherapy

Definitive chemoradiotherapy (CRT) is a less invasive therapy for esophageal squamous cell carcinoma (ESCC). Five-year survival rate of locally advanced ESCC patients by definitive CRT were 37%. We previously reported that tumor-specific cytotoxic T-lymphocyte (CTL) activation signatures were preferentially found in long-Term survivors. However, it is unknown whether the CTL activation is actually driven by CRT. We compared gene expression profiles among pre-and post-Treatment biopsy specimens of 30 ESCC patients and 121 pre-Treatment ESCC biopsy specimens. In the complete response (CR) cases, 999 overexpressed genes including at least 234 tumor-specific CTL-Activation associated genes such as IFNG, PRF1, and GZMB, were found in post-Treatment biopsy specimens. Clustering analysis using expression profiles of these 234 genes allowed us to distinguish the immune-Activated cases, designating them as I-Type, from other cases. However, despite the better CR rate in the I-Type, overall survival was not significantly better in both these 30 cases and another 121 cases. Further comparative study identified a series of epithelial to mesenchymal transition-related genes overexpressed in the early relapse cases. Importantly, the clinical outcome of CDH2-negative cases in the I-Type was significantly better than that of the CDH2-positive cases in the I-Type. Furthermore, NK cells, which were activated by neutrophils-producing S100A8/S100A9, and CTLs were suggested tocooperatively enhance the effect of CRT in the CDH2-negative I-Type. These results suggested that CTL gene activation may provide a prognostic advantage in ESCCs with epithelial characteristics

Unsupervised clustering analysis with expression data of the processed 2,854 genes in the 60 ESCC samples treated with definitive CRT.

<p>Expression data in all of the 60 samples (A: 30 pre-treatment biopsy samples, B: 30 post-treatment biopsy samples) were analyzed by the Cluster and Treeview programs. Three patient clusters (box) were identified. Among them, one cluster (red) was a good responder with 73% CR.</p

Supervised clustering analysis with expression data of the 999 genes induced by CRT in a good responder cluster.

<p>(A) In accordance with the unsupervised clustering analysis with expression data of the processed 2,854 genes, the dendrograms reproducibly showed the presence of a good responder cluster (CR: 56% and 68%) in both pre- and post- treatment samples. (B) Comparison of immune-related gene expression levels between pre- and post- treatment samples. Key genes (<i>PRF1</i>, <i>GZMB</i>, <i>IFNG</i>, <i>CASPs</i>, <i>TNFs</i>) for the CTL activation, which were included in 234 immune-related genes of the above 999 genes, were upregulated in post-treatment samples especially with CR cases. Pre-treatment samples (blue), post-treatment samples (red). CR: cases with complete response, non CR: cases with non CR (partial response, PR). * <i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001.</p