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The aim of this study was to compare open esophagectomy (OE) with minimally invasive esophagectomy (MIE) in a population-based setting.Randomized controlled trials and cohort studies have shown that MIE is associated with reduced pulmonary complications and shorter hospital stay as compared to OE.Patients who underwent transthoracic esophagectomy for cancer between 2011 and 2015 were selected from the national Dutch Upper Gastrointestinal Cancer Audit. Hybrid, transhiatal, and emergency procedures were excluded. Patients who underwent OE were compared with those treated by MIE. Propensity score matching was used to correct for differences in baseline characteristics. The primary endpoint was postoperative pulmonary complications; secondary endpoints were morbidity, mortality, convalescence, and pathology.Some 1727 patients were included. After propensity score matching the percentage of patients with 1 or more complications was 62.6% after OE (N = 433) and 60.2% after MIE (N = 433) (P = 0.468). Pulmonary complication rate did not differ between groups: 34.2% (OE) versus 35.6% (MIE) (P = 0.669). Anastomotic leak (15.5% vs 21.2%, P = 0.028) and reintervention rates (21.1% vs 28.2%, P = 0.017) were higher after MIE. Mortality was 3.0% in the OE group and 4.7% in the MIE group (P = 0.209). Median hospital stay was shorter after MIE (14 vs 13 days, P = 0.001). Percentages of R0 resections (93%) did not differ between groups. The median (range) lymph node count was 18 (2–53) (OE) versus 20 (2–52) (MIE) (P < 0.001).This population-based study showed that mortality and pulmonary complications were similar for OE and MIE. Anastomotic leaks and reinterventions were more frequently observed after MIE. MIE was associated with a shorter hospital stay.