Effects of intraoperative opioid use on recurrence-free and overall survival in patients with esophageal adenocarcinoma and squamous cell carcinoma

BACKGROUND: Perioperative opioid use is associated with poor survival in patients with esophageal squamous cell carcinoma. The most common histological type of esophageal cancer in western countries is adenocarcinoma. The objective of this study was to evaluate the association between intraoperative opioid consumption and survival in patients with adenocarcinoma and squamous cell carcinoma of the esophagus. METHODS: Records of patients who had undergone esophageal cancer surgery between January 2000 and January 2017 were reviewed. Comparisons were made between patients who received high versus low intraoperative doses of opioids. Groups were divided using the recursive partitioning method. Multicovariate Cox proportional hazards models were fitted to evaluate the impact of intraoperative opioid use on recurrence-free survival (RFS) and overall survival (OS). RESULTS: For patients with esophageal squamous cell carcinoma, the univariable analysis indicated that lower opioid dosages (<710 µg fentanyl equivalents) were significantly associated with worse RFS (P = .009) and OS (P = .002). With the adjustment of age, stage, and adjuvant chemotherapy, multivariable analysis confirmed significant associations between higher dosages of intraoperative fentanyl equivalents and better RFS (P = .002; hazard ratio [HR], 0.376; 95% confidence interval [CI], 0.201~0.704). Likewise, higher intraoperative fentanyl equivalents administered was associated with improved OS (P = .002; HR, 0.346; 95% CI, 0.177~0.676). In the adenocarcinoma population, the association between intraoperative opioid dosage and RFS (P = .15) or OS (P = .36) was not significant from univariable analysis. With the adjustment of age, body mass index, tumor staging, neoadjuvant chemotherapy, and adjuvant chemotherapy, multivariable analysis demonstrated marginal significant association between intraoperative fentanyl equivalents and RFS (P = .0866; HR, 0.806; 95% CI, 0.629~1.032). The association between intraoperative fentanyl equivalents and OS was not significant (P = .51). CONCLUSIONS: The results of this study indicate that the amounts of intraoperative opioids used are associated with recurrence and OS in patients with esophageal squamous cell carcinoma. The association between the dose of intraoperative opioids used and RFS was marginally significant in patients with adenocarcinoma. Until confirmation on our findings by future studies, opioids should continue to be a key component of balanced anesthesia in patients with esophageal cancer.