Introduction: A positive surgical margin (R1 resection) is a relevant risk factor for local recurrence in patients with pancreatic ductal adenocarcinoma of the pancreas (PDAC). An intraoperative liquid biopsy (ILB) based on tumor cell mobilization could help to detect R1 resection intraoperatively. Objective: To evaluate the potential role of the intraoperative circulating tumor cells (CTCs) and cluster mobilization on the R0/R1 detection. Methods: Sixty-three patients with resectable PDAC of the head of the pancreas were prospective enrolled under the CETUPANC trial. Open pancreaticoduodenectomy (PD) was done in all patients. Intraoperative CTCs and clusters were determined during PD. Results: The overall rate of R1 resection was 34.9% (22/63 patients). Multivariate analysis showed that factors associated with R1 resection (AUC=0.920) were the presence of undifferentiated G3 tumor (P=0.017), microscopic vascular invasion (P=0.016), and the intraoperative increase of both free CTCs and clusters in portal vein determination from the beginning to the end of the surgery (P=0.002 and P=0.005, respectively). A specific logistic regression model, including delta end to baseline CTCs and cluster mobilization to achieve a combined cut-off to detect R1 detection was calculated (AUC=0.799). The obtained R1-index based on ILB had 84% of sensitivity and 68% of specificity to detect R1 resection. Conclusions: The ILB based on the intraoperative mobilization of CTCs and clusters from the beginning to the end of the PD was a predictive factor to detect R1 resection in patients with PDAC.

Background: Pancreatic ductal adenocarcinoma (PDAC) patients often present with early metastases after surgery, probably due to the mobilization of intraoperative circulating tumor cells (CTCs) and clusters. This exploratory study aimed to assess the potential association between the expression of substance P (SP) and neurokinin-1 receptor (NK-1R) in PDAC cells with CTC and cluster spread during pancreatoduodenectomy. Secondly, the potential impact on metastasis development and overall survival (OS) was also assessed. Methods: Twenty-one PDAC patients undergoing pancreatoduodenectomy were evaluated to analyze SP/NK-1R intra-tumor expression. Intraoperative portal vein samples were collected to quantify CTCs and clusters. Metastatic disease-free survival (MDFS) and OS were assessed during the 3-year follow-up. Results: High cytoplasmic expression of NK-1R in PDAC cells was associated with CTCs and cluster mobilization during surgery, between the beginning of the intervention and the resection of the pancreatic tumor ( P = 0.005 and P = 0.025, respectively). Cytoplasmic NK-1R expression in PDAC cells was also associated with lower MDFS 1 year after pancreatoduodenectomy ( P = 0.042). Similarly, the higher the cytoplasmic SP expression, the lower the OS ( P = 0.019). Conclusions: This exploratory study showed that higher NK-1R expression in PDAC cells’ cytoplasm was associated with higher intraoperative CTCs and cluster mobilization. A potential association between higher cytoplasmic expression of NK-1R and SP with lower MDFS and OS, respectively, was observed.