Mesenteric approach during pancreaticoduodenectomy as modulator of CTC DNA dynamics in pancreatic cancer.

Abstract

e16464 Background: In pancreatic ductal adenocarcinoma (PDAC), surgical manipulation may facilitate the intraoperative release of circulating tumor cells (CTCs) into the portal venous circulation. The mesenteric approach has been advocated as a strategy to reduce tumor handling and potential tumor cell dissemination; however, its effect on perioperative CTC-related biomarkers has not been fully elucidated. We evaluated perioperative changes in portal venous circulating tumor cell–derived DNA (CTC DNA) to assess the biological impact of surgical approach. Methods: Portal venous blood samples were collected intraoperatively at two time points—immediately after laparotomy and just before specimen removal—in patients undergoing pancreatectomy for PDAC. A total of 107 patients were included: 52 patients underwent the conventional approach and 55 patients underwent the mesenteric-first approach. CTC DNA copy numbers were quantified, and perioperative changes were compared between surgical approaches. Overall survival (OS) was analyzed according to surgical approach and perioperative CTC DNA dynamics. Results: Baseline clinicopathological characteristics and pathological diagnoses were well balanced between the two groups. The mean CTC DNA copy number immediately after laparotomy was 16.0 ± 16.2 copies in the conventional group and 23.7 ± 28.9 copies in the mesenteric-first group. Just before specimen removal, the mean CTC DNA copy number increased to 26.1 ± 29.3 copies in the conventional group, whereas it decreased to 16.3 ± 17.8 copies in the mesenteric-first group. The mean perioperative change in CTC DNA copy number was significantly different between groups, with an increase of +10.1 ± 2.6 copies in the conventional group and a decrease of –7.3 ± 2.6 copies in the mesenteric-first group (p < 0.0001). Despite these marked biological differences, no significant difference in OS was observed between the conventional and mesenteric-first approaches (HR 0.67, 95% CI 0.39–1.13; p = 0.127). Similarly, OS did not differ significantly between patients with increased versus decreased intraoperative CTC DNA copy numbers (HR 0.77, 95% CI 0.45–1.31; p = 0.331). Conclusions: The mesenteric approach was associated with a significant intraoperative reduction in portal venous CTC DNA copy number, suggesting suppression of CTC release during tumor manipulation. Although these perioperative CTC-related changes did not translate into a survival benefit, CTC DNA dynamics may serve as a sensitive biomarker reflecting the biological impact of surgical handling in pancreatic cancer resection. Clinical trial information: NCT03317886 .