Meta-analysis and Trial Sequential Analysis of Randomized Controlled Trials Comparing High and Low Ligation of the Inferior Mesenteric Artery in Rectal Cancer Surgery

BACKGROUND: Despite ongoing debates, there is still no consensus regarding where to divide the inferior mesenteric artery for oncological reasons in rectal cancer: at its origin from the aorta (high ligation) or distal to the origin of the left colic artery (low ligation). OBJECTIVES: The purpose of this study was to compare the outcomes of high and low ligation of the inferior mesenteric artery in rectal cancer surgery. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry, , and ISRCTN Register were searched. STUDY SELECTION: andomized controlled trials investigating outcomes of curative anterior resection in patients with cancer of the rectum were included. INTERVENTIONS: High ligation of the inferior mesenteric artery was compared with low ligation technique. MAIN OUTCOME MEASURES: We measured the total number of lymph nodes harvested, anastomotic leak, postoperative complications, postoperative mortality, operative time, intraoperative blood loss, conversion to open surgery, overall survival, and disease-free survival. RESULTS: Analysis of 1102 patients from 8 trials suggested no difference between high and low ligation of the inferior mesenteric artery in terms of total number of lymph nodes harvested (mean difference = -0.87; p = 0.26), anastomotic leak (OR = 1.39; p = 0.15), postoperative complications (OR = 1.39; p = 0.78), postoperative mortality (risk difference = -0.00; p = 0.48), operative time (mean difference = -1.99; p = 0.79), intraoperative blood loss (mean difference = -2.28; p = 0.77), conversion to open surgery (risk difference = 0.01; p = 0.48), 5-year overall survival (OR = 0.76; p = 0.32), 5-year disease-free survival (OR = 0.88; p = 0.58), overall survival at maximum follow up (OR = 0.80; p = 0.43), and disease-free survival at maximum follow-up (OR = 0.83; p = 0.35). LIMITATIONS: Limited data were available on functional and long-term survival outcomes. CONCLUSIONS: There is no difference between high and low ligation of the inferior mesenteric artery in terms of oncological outcomes or postoperative morbidity and mortality. The available evidence is subject to potential confounding by the use of neoadjuvant therapy, adjuvant therapy, disease stage, location of tumor, and use of protective stoma. Functional outcomes including postoperative bowel, urinary and sexual function, and long-term survival outcomes should be the outcome of study in future trials. PROSPERO registration number: CRD42019148626