The goal of this clinical trial is to learn if selective plasma adsorption of extracellular DNA works to prevent formation of metastases of pancreatic cancer during surgical removal of the tumor. It will also help researchers to learn about the safety of selective plasma adsorption of extracellular DNA during the surgery. The main questions it aims to answer are:

• Does selective plasma adsorption of extracellular DNA improve the survival of participants after surgical removal of pancreatic cancer?
• Does selective plasma adsorption of extracellular DNA reduce the risk of the recurrence of pancreatic cancer?
• What medical problems do participants have when they receive selective plasma adsorption of extracellular DNA during surgical removal of pancreatic cancer? Researchers will compare clinical data of participants who had selective plasma adsorption of extracellular DNA and those who did not to see if there are any differences in their health.

Participants who are scheduled for surgical removal of pancreatic cancer by their doctor according to medical indications will:

• Either receive selective plasma adsorption of extracellular DNA during surgical removal of pancreatic cancer and on the next day after the surgery, or not.
• Do blood tests prior to surgery, during the surgery, on the next day after the surgery, one week after the surgery, 3, 6, 9, and 12 months after the surgery.
• Do computed tomography scans 3, 6, 9, and 12 months after the surgery. Participants will receive selective plasma adsorption of extracellular DNA, blood tests, and computed tomography scans for free.

Rationale for the study Tumor metastasis is the leading cause of cancer-associated mortality. In pancreatic cancer, metastases develop in more than 80% of patients (in 40-50% of cases in the first year after tumor removal surgery). All the details of the metastasis formation process are still unknown to science, but the key stages have been identified and are actively studied: tumor cell dissemination, intravasation, epithelial-mesenchymal and mesenchymal-epithelial transition, extravasation of circulating tumor cells, formation of remote pro-tumor niches, as well as evasion from immune surveillance.

The tumor microenvironment plays a key role in the formation of metastases and in modulating the response to therapy in patients with cancer. It is represented by cancer-associated fibroblasts, as well as a number of infiltrating immune cells, including cancer-associated neutrophils (CAN). CAN make up a significant proportion of all cells surrounding the tumor. It has been shown that an increase in their number is associated with metastases and, in general, a worse prognosis in a number of cancer diseases. Moreover, the neutrophil-to-lymphocyte ratio has found wide clinical application as a predictor of overall and cancer progression-related mortality.

The most studied mechanism of the positive effect of CAN on metastasis and evasion of the immune response is the production of neutrophil extracellular traps (NETs). NETs are web-like structures whose main purpose is to immobilize pathogens (bacteria, fungi, etc.). They consist of chromatin, histones, a number of signaling molecules and antimicrobial peptides. However, in cancer, the ability of NETs to entangle targets, on the contrary, promotes tumor metastasis. It has been shown that NETs surrounding a tumor cell can serve as an adhesive substrate, which mediates the anchoring of metastasis in a new niche. NETs promote the transition of naïve CD4 cells to immunosuppressive regulatory T cells, allowing metastases to further evade immune surveillance. Also, for example, NETs components such as myeloperoxidase promote tumor cell extravasation and metastasis by degrading the extracellular matrix. Co-culture of cancer cells with NETs has been shown to increase the expression of E-cadherin and vimentin, which enhances their migratory capacity.

There is a wealth of data, both in animal models and in patient biomaterial, indicating that elevated NETs levels are associated not only with cancer in general, but also with the presence of metastases. A number of studies have shown that administration of DNase, which cleaves NETs, to animals stops the spread of metastases. Moreover, clinical trials are currently underway on the use of DNase in chemotherapy (NCT00536952, NCT02462265, etc.). It is worth noting that NETs are not the only DNA-containing structures that promote metastasis. There are also cancer extracellular chromatin networks (CECN); In animal models, it has been shown that the introduction of DNase, which affects NETs and CECN, significantly reduces the likelihood of metastasis, while no decrease in the level of circulating tumor cells is observed, indicating a significant modulating role of these DNA structures in the metastasis process. At the same time, it is known that long-term use of DNase leads to a decrease in the overall survival of laboratory animals, which raises the question of when metastasis prevention should be carried out, given the ambiguous safety of this approach.

The dynamics of metastasis formation throughout a patient's life are not completely clear. There is evidence that metastasis can begin almost in parallel with the development of the primary tumor, and in such cases (the frequency of which, unfortunately, cannot be estimated) it is very difficult to influence the development of metastases. At the same time, many researchers note that the most significant (and potentially controllable) moment at which metastases can form is the invasive intervention (biopsy, perhaps to a greater extent - resection). According to the results of dozens of studies in various types of oncological diseases in patients and in animal models, it is noted that invasive intervention is significantly associated with both an increase in the level of circulating tumor cells and the development of metastases (dissemination of cells along the needle or when tumor tissue is damaged; the occurrence of a proinflammatory background that promotes the breakdown of the extracellular matrix and extravasation, etc.).

Thus, there is a need to develop a technology for intraoperative prevention of metastasis formation based on the removal of DNA-containing structures (NETs and CECN) from the bloodstream of patients with pancreatic cancer, for which the use of selective plasma adsorption using the NucleoCor® sorption column might be of great value.

Inclusion Criteria:

- Histologically and/or radiologically proven diagnosis of "Non-metastatic pancreatic ductal adenocarcinoma" of any localization, with ECOG physical status 0-1, who are scheduled for surgery for radical removal of the tumor, without previous chemotherapy (stage cT0-4 N0-2 M0) or after neoadjuvant chemotherapy (stage ycT0-4 N0-2 M0).

Exclusion Criteria:

• Presence of other known oncological diseases.
• General contraindication to plasma adsorption (hypoproteinemia; acute cardiovascular failure; intolerance to foreign protein; decreased (less than 90/60 mm Hg) arterial pressure; gastrointestinal bleeding; acute cerebrovascular accidents; acute anemia; severe hypoxia).

All IPD collected throughout the trial

Beginning 3 months and ending 3 years after the publication of results

IPD will be shared upon a reasonable request containing the analysis plan. Request must be submitted to the principal investigator Dr. Egorov by email (v.egorov@ihospital.ru).