P1.170. Circulating Biomarkers of Angiogenesis in Esophageal Cancer Patients Undergoing Laparoscopic Gastric Ischemic Preconditioning: A Pilot Study

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Abstract Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer Background Laparoscopic gastric ischemic preconditioning (LGIP = ligation of the left gastric and short gastric vessels) aims to promote gastric conduit neovascularization and reduce anastomotic leak, a major complication following esophagectomy for esophageal cancer. The feasibility of measuring systemic peri-LGIP angiogenic biomarkers as a potential signal of preconditioning response was evaluated. Methods Twenty-three patients with resectable esophageal cancer were prospectively enrolled at a single institution between January and December 2024. Final analysis included 17 patients who consented to biomarker analysis and underwent LGIP prior to planned esophagectomy. Reconstruction with a gastric conduit was performed in all cases. Peripheral blood was collected at two timepoints: immediately before LGIP and immediately before esophagectomy. Serum concentrations of angiogenesis-related biomarkers were quantified using electrochemiluminescence-based V-PLEX assays (Meso Scale Discovery), including basic fibroblast growth factor (bFGF), vascular endothelial growth factor receptor-1 (VEGFR-1), placental growth factor (PIGF), Tie-2, VEGF-A, VEGF-C, and VEGF-D. CD34 expression, a marker of endothelial activity, was measured using enzyme-linked immunosorbent assay (ELISA). All assays were performed in duplicate and averaged for analysis. For each biomarker, within-patient changes were calculated as the log2 fold-change before and after LGIP. Paired fold-changes were assessed using the Wilcoxon signed-rank test, with two-sided p-values <0.05 considered significant. Results Seventeen patients meeting study criteria were included in the final analysis; baseline oncologic and treatment characteristics are shown in Table 1. At diagnosis, clinical stage distribution was I (12%), IIB (18%), III (41%), IVA (18%), unknown (12%). Fifteen patients (88%) received neoadjuvant therapy, including chemotherapy alone (12%), chemoradiation alone (29%), or sequential chemotherapy and chemoradiation (47%). The median interval between LGIP and esophagectomy was 5.1 weeks. Ivor-Lewis esophagectomy was performed in 82% of cases and three-field esophagectomy was performed in 18%; a stapled anastomosis was performed in all cases. Anastomotic leak was diagnosed in 3 patients (18%); all were managed endoscopically. Following LGIP, significant reductions in circulating VEGFR-1 and VEGF-C were observed, while other angiogenic biomarkers showed no significant change (Figure 1). This study was not powered to formally assess associations between peri-LGIP angiogenic biomarkers and anastomotic leak. Conclusion In this pilot study demonstrating the feasibility of systemic biomarker assessment in response to gastric preconditioning, LGIP was associated with measurable changes in circulating angiogenic biomarkers, including significant reductions in VEGFR-1 and VEGF-C. Lower levels of the soluble receptor VEGFR-1 after LGIP may allow for more unbound angiogenic growth factors to act on the endothelium. Larger, prospective studies are needed to determine whether peri-LGIP angiogenic biomarkers can inform risk stratification and optimize perioperative management.

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