Fibrin sealant for prophylaxis of cervical anastomotic leakage after McKeown esophagectomy for esophageal or esophagogastric junction cancer (PLACE030): a Phase III multicenter randomized clinical trial

PURPOSE: Anastomotic leakage (AL) is one of the most serious complications after esophagectomy, and previous studies have suggested that fibrin sealant (FS) might be beneficial in preventing AL. This study aimed to evaluate the efficacy and safety of FS in preventing AL. METHODS: This randomized controlled trial included 360 patients aged 18-75 years with resectable esophageal or esophagogastric junction cancer, clinically staged as T1-4aN0-3M0, from six centers in China. Surgery was performed using McKeown esophagectomy with circular stapled anastomosis combined with two-field lymphadenectomy. In the FS group, 2.5 ml of FS was applied circumferentially to the cervical anastomotic site. The primary endpoint was the incidence of AL within the first 3 months postoperatively. RESULTS: A total of 360 patients were recruited from February 2019 to May 2023, with 179 in the FS group and 181 in the control group. The incidence of AL was 7.3% in the FS group and 13.3% in the control group (P = 0.061). According to the subgroup analysis of patients who underwent upfront surgery without neoadjuvant treatment, the incidence of AL in the FS group was numerically lower without statistical significance [FS group: 5.8% vs. control group: 15.1%; P = 0.046, RR = 0.385 (95% CI, 0.143-1.032)]. The incidence of postoperative complications was similar between the two groups (FS group: 41.6% vs. control group: 48.9%; P = 0.163). CONCLUSIONS: Intraoperative sealing with porcine FS did not significantly reduce the incidence of cervical AL. For patients who undergo upfront esophagectomy, the potential protective effect of FS needs further studies.