Impact of Gastric Ischemic Preconditioning Prior to Esophagectomy on Pathologic Response

Background Gastric ischemic preconditioning (GIP) prior to esophagectomy has been variably shown to reduce anastomotic complications, however it remains unknown whether delaying definitive surgical resection in favor of ischemic preconditioning has an impact on pathologic upstaging rates and overall survival. Furthermore, it is unclear if utilization of GIP has an additive or negative effect on pathologic response to preoperative therapy. Methods We performed a retrospective analysis of all patients undergoing esophagectomy for malignancy at a high-volume institution from 2017–2024. Patients were separated into those who underwent GIP and those who did not. Rates of overall and nodal pathologic upstaging, as well as overall survival (OS), were compared between groups using chi-square for binomial variables and log-rank test for survival data. Logistic regression was used to determine factors associated with upstaging, controlling for neoadjuvant treatment, clinical stage, sex, and age. Results Of 510 patients identified for analysis, 46 (9.0%) underwent GIP. 413 patients (81.0%) underwent neoadjuvant chemoradiotherapy. The cohorts were similar with regards to preoperative staging and treatment. Median time between GIP and esophagectomy was 36 days (IQR 29–96). Rate of overall pathologic upstaging was statistically similar between the groups (GIP 5.0% vs non-GIP 13.9%, p = 0.111); rate of nodal upstaging was significantly lower in the GIP group (GIP 2.4% vs non-GIP 18.7%, p = 0.007). Upon multivariable regression, GIP was associated with lower odds of nodal upstaging (aOR 0.08, 95% CI 0.01–0.59). OS was similar between the two groups by log-rank test (p = 0.273). Conclusion Performing GIP prior to definitive resection for esophageal malignancy does not result in higher pathologic stage or confer worse overall survival. Patients undergoing GIP prior to esophagectomy have lower rates of nodal upstaging, which may be secondary to physiologic alterations related to local ischemia. Further prospective, translational studies are needed to better elucidate the role of hypoxia-related factors as well as optimal timing of GIP before or after neoadjuvant therapy.