Relationship between histological mixed-type early gastric cancer and lymph node metastasis: A systematic review and meta-analysis

The clinicopathological features of early gastric cancer (EGC) with mixed-type histology (differentiated and undifferentiated) are incompletely understood, and the capacity of endoscopic submucosal dissection (ESD) to treat mixed-type cancer remains controversial. This systematic review analyzed the rate of lymph node metastasis (LNM) in mixed-type EGC. We gathered articles published up to February 21, 2021, that analyzed the relationship between LNM and mixed-type EGC from Embase, PubMed, and Web of Science. The primary outcome was the LNM rate associated with different histological types of EGC, and the secondary outcomes were the odds ratios (ORs) for LNM risk factors among EGC patients. From the 24 studies included in this meta-analysis, the overall rate of LNM in predominantly differentiated mixed-type (MD) EGC was 12%, whereas the LNM rate in predominantly undifferentiated mixed-type (MU) EGC was 22%. We further divided these studies into 2 groups according to the depth of invasion. In mixed-type mucosal EGC, the pooled LNM rate was 15%; in submucosal EGC, the rate was 33% for MU, which was higher than the rates for pure types (pure differentiated type, 13%; pure undifferentiated type, 21%; p<0.05). The LNM rate of MD was 20%, it was higher than those of the pure differentiated type and nearly the same as pure undifferentiated type. Other pooled statistics showed that submucosal invasion, pure undifferentiated EGC, and mixed-type EGC were independent risk factors for LNM. This meta-analysis showed that MD submucosal EGC has a high rate of LNM and is highly correlated with LNM; thus, the management of MD EGC as purely differentiated EGC according to the indications for ESD is inappropriate, and the mixed type should be added as a parameter in these indications.