A systematic review and meta-analysis of the use of methylene blue to improve the lymph node harvest in rectal cancer surgery

Background Methylene blue staining of the resected specimen has been described as an alternative to the conventional palpation and visual inspection method to improve lymph node harvest. This meta-analysis evaluates the usefulness of this technique in surgery for rectal cancer, particularly after neoadjuvant therapy. Methods Randomized controlled trials (RCTs) comparing lymph node harvest in methylene blue-stained rectal specimens to those of unstained specimens were identified from the Medline, Embase, and Cochrane databases. Non-randomized studies and those with only colonic resections were excluded. The quality of RCTs was assessed using Cochrane’s risk of bias tool. A weighted mean difference (WMD) was calculated for overall harvest, harvest after neoadjuvant therapy, and metastatic nodal yield. In contrast, the risk difference (RD) was calculated to compare yields of less than 12 lymph nodes between the stained and unstained specimens. Results Study selection comprised seven RCTs with 343 patients in the unstained group and 337 in the stained group. Overall lymph node harvest and harvest after neoadjuvant therapy were significantly higher in stained specimens with a WMD of 13.4 and 10.6 and a 95% confidence interval (CI) of 9.5–17.2 and 4.8–16.3, respectively. Harvest of metastatic lymph nodes was significantly higher in the stained group (WMD 1.0, 95% CI 0.6–1.4). The yield of less than 12 lymph nodes was significantly higher in the unstained group with RD of 0.292 and 95% CI of 0.182–0.403. Conclusion Despite a small number of patients, this meta-analysis confirms improved lymph node harvest in surgical specimens stained with methylene blue compared with unstained specimens.