The impact of various surgical techniques on the molecular mechanisms of gynecological cancer metastasis.

The impact of minimally invasive surgical techniques, especially the influence of CO2 pneumoperitoneum and manipulator use in cervical cancer treatment is currently under investigation due to poor overall survival in comparison to open surgery for cervical cancer. Recent multi-centric research showed, that patients treated for cervical cancer with a laparoscopic approach had a higher risk of recurrence and worse overall survival than women treated with open surgery. The surprising outcome was unique for cervical cancer, as prior clinical research in endometrial cancer showed no such adverse events in comparing techniques. With no obvious explanation into the outcome difference, treatment options must be assessed through their mechanism of action. A possible route of tumor dissemination during surgery is therefore the use of CO2 pneumoperitoneum and use of a uterine manipulator. CO2 pneumoperitoneum has been assessed previously in studies with contradictory results. The preclinical understanding of tumor spillage by a uterine manipulator however has never even been attempted. Therefore this project aims to: i) identify alterations present in cancer cells exposed to CO2 by the use of cell culture gene expression analysis and RNA-seq; ii) understand the mechanistic background of immunological and pro-inflamatory events by means of identifying matrix components behavior and adhesion molecules (Western blot and RT-PCR); iii) develop a surgically-mechanistic in-vitro model by developing an in-vitro real time simulation of “shearstress ”and “mechanical stress”. Our model of exploration enables a comprehensive understanding of the factors involved, focusing on global gene expression in response to CO pneumoperitoneum, targeted molecular interactions, changes in cell-cell communication, as well as the development of a possibly more precise model of simulation with the use of a manipulator for adding pressure on the cancerous cells. Thus enabling us to assess the impact of laparoscopy on tumor dissemination and lead to evidence based decision making in clinical treatment of gynecological cancers.