This study aimed to compare the efficacy and safety of TLTG with the overlap technique to LATG in patients with advanced Siewert III Esophagogastric Junction Cancer and upper and middle third gastric cancer. This single-center RCT enrolled 292 patients with the mentioned cancers, randomly assigned to TLTG overlap (n=146) or LATG (n=146) groups. Data on demographics, pathology, intraoperative variables, postoperative complications, recovery parameters, and 3-year survival were collected. Main outcome: postoperative complications within 30 days. Secondary outcomes: 3-year disease-free and overall survival. TLTG versus LATG: TLTG had shorter incision, faster flatus/defecation, reduced analgesia, less opioid use, and shorter hospital stay. Similar operation time, anastomosis time, blood loss, and lymph node harvest. TLTG had lower overall post-op complication rate (P=0.047), no significant difference in serious complications (P=0.310). Variances in anastomotic stenosis occurrence at 3 months. No rehospitalization or mortality at 30 days. No significant differences in 3-month disease-free survival (P=0.058) or overall survival (P=0.236). Overlap method for anastomosis in TLTG is safe and feasible for advanced middle-upper-third gastric cancer, with positive short-term outcomes. This technique has potential as the preferred esophagojejunostomy approach in TLTG. This trial has been registered at Chinese Clinical Trial Registry: XXXXXXXX (registration date: September 4, 2019).
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