Background: Tumor sorrounding stroma and cancer associated fibroblast (CAFs) in particular play a major role in ductal adenocarcinoma of the pancreas (PDAC). The aim of our study was to r investigate the interaction between CAFs and PDAC cells in vitro using patient derived CAF cultures. Methods: CAFs were isolated from tumor tissue, transferred to in vitro setting and phenotypically characterized. Migration capacity and chemo-sensitivity was evaluated in a modified two-well system with established PDAC cell lines. Non-malignant fibroblast from foreskin served as controls. Paracrine interaction via chemokines was measured using elisa. Results: CAFs resemble activated pancreatic stellate cells. A strong negative effect on the therapeutic response of PDAC cells to Gemcitabine, Notch inhibition (DAPT) and nab-paclitaxel could be observed in direct co-cultures. Indirect co-culturing showed no significant effect on the chemo-sensitivity of PDAC cells but nevertheless resulted in a significant increase of IL-6 levels. PDAC cells showed a higher migration capacity when cocultured with CAFs. CAFs themselves showed a significantly higher migration capacity compared to non-malignant fibroblasts. This was further boosted in presence of PDAC cells. Conclusion: We elucidated a strong interaction between PDAC cells and CAFs, which may have a high impact on therapeutic efficiency. Paracrine inflammation response could play a pivotal role in this modification process. Further evaluation is needed to clarify this observations.

Background: Many techniques have been used for liver parenchymal transection. It remains unknown which technique is superior with regards to perioperative outcomes. Vascular staplers have been used to perform liver parenchymal transection; however, evidence of their performance is still lacking. Methods: This is a single center, retrospective, comparative analysis of surgical outcomes of utilizing the stapler technique versus the harmonic scalpel for parenchymal transection during major hepatectomy. Results: Between 2011 and 2016, 176 patients with an otherwise healthy liver underwent right hepatectomy. A vascular stapler was used for parenchymal transection in 82 patients and the harmonic scalpel in 94 patients (control group). Morbidity, relaparotomy rate, and mortality were similar between groups. Median parenchymal transection time was shorter for patients undergoing stapled hepatectomy (7 vs 39 minutes, p<0.001). Median total operative time was also shorter (205 vs 255 minutes, p<0.001). Conclusion: Stapled parenchymal transection during major hepatectomy is feasible and safe. Transection and total operative times are significantly shorter when the stapler technique is employed. Morbidity and mortality rate are comparable between the two group. The stapler technique should be considered a standard method for liver parenchymal transection.