Effect of anastomotic leaks on long-term survival after oesophagectomy for oesophageal cancer: systematic review and meta-analysis

Introduction: Long-term survival after curative surgery for oesophageal cancer surgery remains poor, and the prognostic impact of anastomotic leak (AL) remains unknown. A meta-analysis was conducted to investigate the impact of AL on long-term survival. Methods: A systematic electronic search for articles was performed for studies published between 2001 and 2020 evaluating the long-term oncological impact of AL. Meta-analysis was performed using the DerSimonian-Laird random-effects model to compute hazard ratios and 95% confidence intervals. Results: Nineteen studies met the inclusion criteria, yielding a total of 9885 patients. Long-term survival was significantly reduced after AL (HR: 1.79, 95% CI: 1.33-2.43). AL was associated with significantly reduced overall survival in studies within hospital volume Quintile 1 (HR: 1.35, 95% CI: 1.12-1.63) and Quintile 2 (HR: 1.83, 95% CI: 1.35-2.47). However, no significant association was found for studies within Quintile 3 (HR: 2.24, 95% CI: 0.85-5.88), Quintile 4 (HR: 2.59, 95% CI: 0.67-10.07), and Quintile 5 (HR: 1.29, 95% CI: 0.92-1.81). AL was significantly associated with poor long-term survival in patients with associated overall Clavien Dindo Grades 1-5 (HR: 2.17, 95% CI: 1.31-3.59) and severe Clavien Dindo Grades 3-5 (HR: 1.42, 95% CI: 1.14-1.78) complications. Conclusions: AL has a negative prognostic impact on long-term survival after restorative resection of oesophageal cancers, particularly in low-volume centers. Future efforts must be focused on strategies to minimize the septic and immunological response to AL with early recognition and treatment thus reducing the impact on long-term survival.