Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines.

There is an ongoing need for patient-specific chemotherapy for pancreatic cancer. Tumour cells isolated from human tissues can be used to predict patients' response to chemotherapy. However, the isolation and maintenance of pancreatic cancer cells is challenging because these cells become highly vulnerable after losing the tumour microenvironment. Therefore, we investigated whether the cells retained their original characteristics after lentiviral transfection and expansion. Three human primary pancreatic cancer cell lines were lentivirally transduced to create expandable (Ex) cells which were then compared with primary (Pri) cells. No obvious differences in the morphology or epithelial-mesenchymal transition (EMT) were observed between the primary and expandable cell lines. The two expandable cell lines showed higher proliferation rates in the 2D and 3D models. All three expandable cell lines showed attenuated migratory ability. Differences in gene expression between primary and expandable cell lines were then compared using RNA-Seq data. Potential target drugs were predicted by differentially expressed genes (DEGs), and differentially expressed pathways (DEPs) related to tumour-specific characteristics such as proliferation, migration, EMT, drug resistance, and reactive oxygen species (ROS) were investigated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We found that the two expandable cell lines expressed similar chemosensitivity and redox-regulatory capability to gemcitabine and oxaliplatin in the 2D model as compared to their counterparts. In conclusion, we successfully generated expandable primary pancreatic cancer cell lines using lentiviral transduction. These expandable cells not only retain some tumour-specific biological traits of primary cells but also show an ongoing proliferative capacity, thereby yielding sufficient material for drug response assays, which may provide a patient-specific platform for chemotherapy drug screening.

Evaluation of POSSUM for patients undergoing pancreatoduodenectomy.

BACKGROUND: The POSSUM score is a predictive scoring system for postoperative morbidity. Although numerous studies have validated its application in major abdominal surgery, few have exclusively considered pancreatic resections, which have unique complications that are costly and problematic. We examined whether POSSUM could accurately reflect the clinical outcomes in pancreatic resection. METHODS: A total of 694 consecutive resections of the pancreatic head were performed between 1993 and 2010 at the Department of General, Thoracic, and Vascular Surgery at the University Hospital Dresden. The POSSUM score calculated for each case was compared with the observed morbidity. Relevance and predictive performance of the score were assessed; in particular, because of the poor calibration of the POSSUM predictions on the Dresden data, a new score was created that was externally validated on patient cohorts from two different centers for pancreatic surgery. RESULTS: The goodness-of-fit analysis revealed that the POSSUM score was not well calibrated because the POSSUM-predicted morbidity rate was 58.9% on average whereas the observed morbidity rate was 43.4%. Discrepancies occurred particularly among the predicted high-risk patients, for whom the score actually overestimated the morbidity risk. Therefore, we adapted the score and complemented it with additional prognostic parameters. The new score was validated in a patient cohort from two other German centers and fitted better to the data. CONCLUSION: The new score, named PS-POSSUM (POSSUM in pancreatic surgery), fits the data better. However, the prediction ability remains rather poor. PS-POSSUM may still be helpful, as it draws attention to additional risk and protective factors in addition to those in the original POSSUM score.