Genetic and epigenetic alterations during development of pancreatic ductal adenocarcinomas (PDACs) are well known. This study investigates genetic and epigenetic data together with tumor biology to find specific alterations responsible for metastasis formation. Using 16 human PDAC cell lines in a murine orthotopic PDAC model, local infiltration and metastatic spread were assessed by standardized dissemination scores. The cell lines were further classified into 3 hierarchical groups according to their metastatic potential. Their mRNA and microRNA (miRNA) expression was profiledviamRNA‐microarray as well as Taqman Low Density Array, and validated by single quantitative RT‐PCR and Western blotting. In the highly metastatic group, a significant induction of EP300 targeting miRNAs miR‐194 (fold change: 26.88), miR‐200b (fold change: 61.65), miR‐200c (fold change: 19.44) and miR‐429 (fold change: 21.67) (p< 0.05) was detected. Corresponding to this, decreased expression of EP300 mRNA (p< 0.0001) and protein (p< 0.05) were detected in the highly metastatic PDAC cell lines with liver metastases compared to the nonmetastatic or marginally metastatic cell lines, while no correlation with local tumor growth was found. In conclusion, epigenetic alterations with upregulated EP300 targeting miRNAs miR‐194, miR‐200b, miR‐200c and miR‐429 are related to reduced EP300 mRNA and protein in PDAC. These results demonstrate that miRNAs might be able to modulate the expression of metastasis‐specific suppressor genes and metastatic behavior in PDAC, suggesting diagnostic and therapeutic opportunities for EP300 and its targeting miRNAs in PDAC.

Anastomotic insufficiency in patients with colorectal anastomosis is a major complication with high morbidity and mortality. Local treatment with transrectal lavage and drainage can be considered in patient without peritonitis. In order to prevent prolonged wound closure and secondary complications during conservative treatment we investigated the vacuum assisted closure (VAC) in this setting. Ten patients with anastomotic insufficiency after colorectal resections, who did not require transabdominal interventions, were treated with an Endo-vacuum assisted closure dressing (Group A; n = 5) or by transrectal lavage (Group B; n = 5). Time for wound healing, duration of hospitalization and pain assessment were compared in both groups. The Endo-vacuum assisted closure treatment was performed for a median time of 27 days without any vacuum assisted closure associated complications. Wound healing was significantly accelerated in Group A compared to Group B. Time in hospital was slightly shortened in patients with Endo-vacuum assisted closure. Pain assessment in both groups did not show any significant differences. Endo-vacuum assisted closure therapy is a novel approach that can be considered in diverted patients with failed colorectal anastomoses. Larger randomized trials that include complete cost-benefit analyses are needed to establish its role in this setting.

Metastasis formation is the leading cause of death among colon cancer patients. We established a new in-situ model of in vivo microscopy of the lung to analyse initiating events of metastatic tumor cell adhesion within this typical metastatic target of colon cancer.

Early metastasis and infiltration are survival limiting characteristics of pancreatic ductal adenocarcinoma (PDAC). Thus, PDAC is likely to harbor alterations in metastasis suppressor genes that may provide novel diagnostic and therapeutic opportunities. This study investigates a panel of metastasis suppressor genes in correlation to PDAC phenotype and examines promoter methylation for regulatory influence on metastasis suppressor gene expression and for its potential as a diagnostic tool.