Feasibility Analysis Of Endoscopic Treatment Expanded Indications And Risk Assessment Of Lymph Node Metastasis For Early Gastric Cancer

Objective: Endoscopic submucosal dissection(ESD)has been routinely performed in applicable early gastric cancer(EGC)patients as an alternative to conventional surgical operations that involve lymph node dissection.The indications for ESD have been recently expanded to include larger,ulcerated,and undifferentiated mucosal lesions,even some differentiated lesions with slight submucosal invasion.The risk of lymph node metastasis is the most important consideration when deciding on a treatment strategy for EGC.Despite the advantages over surgical procedures,lymph nodes cannot be removed by ESD.In addition,whether patients who meet the expanded indications for ESD can be managed safely remains controversial.This research aims to determine whether the ESD indications are applicable to Chinese patients and to investigate the predictors of lymph node metastasis in EGC.Methods: We retrospectively analyzed 12552 patients who underwent surgery for gastric cancer between June 2007 and December 2018 at the Affiliated Hospital of Qingdao University.A total of 1262(10.1%)EGC patients were eligible for inclusion in this study.We collected the clinical data,endoscopic features,and pathological characteristics of all enrolled patients.These data included age,sex,incidence of hypertension,heart disease and diabetes mellitus,drinking and smoking history,body mass index(BMI),family history,carcinoembryonic antigen(CEA)level,tumor location,lesion size,macroscopic type,depth of invasion,number of tumors,presence of ulcers,tumor differentiation,Lauren type,presence of lymphovascular invasion(LVI),perineural invasion,and lymph node metastasis.The absolute and expanded indications for ESD were validated by regrouping the enrolled patients and determining the positive lymph node metastasis results in each subgroup.Differences among categorical variables associated with predictors and lymph node metastasis were assessed using a chi-square test,and variables that were significant in the univariate analysis were subsequently entered into a multivariate logistic regression model for the analysis of independent risk factors for lymph node metastasis in EGC.Furthermore,we analyzed the respective risk factors of lymph node metastasis in the subgroups of differentiated and undifferentiated EGC patients seperately.Results: Lymph node metastasis was observed in 14.4%(182/1262)patients.No lymph node metastasis was detected in the patients who met the absolute indications(0/90).Lymph node metastasis occurred in 4/311(1.3%)patients who met the expanded indications.According to univariate analysis,lymph node metastasis was significantly associated with positive tumor marker status,large(>20 mm)lesion size,excavated macroscopic-type tumors,ulcer presence,submucosal invasion(SM1 and SM2),poor differentiation,LVI,perineural invasion,and diffuse and mixed Lauren's types.Multivariate analysis demonstrated SM1 invasion(odds ration [OR] = 2.285,P = 0.03),SM2 invasion(OR =3.230,P < 0.001),LVI(OR = 15.702,P< 0.001),mucinous adenocarcinoma(OR = 2.823,P= 0.015),and large lesion size(OR = 1.900,P = 0.006)to be independent risk factors.In the subgroup of differentiated EGC patients,lymph node metastasis occurred in 9.5%(43/455)patients,and 4 of the 201(2.0%)patients who met the expanded indications had lymph node metastasis.Positive tumor marker status,large(>20 mm)lesion size,the number of tumors,submucosal invasion(SM1 and SM2)and LVI were significantly associated with lymph node metastasis in univariate analysis.According to multivariate analysis,the independent risk factors of lymph node metastasis were the number of tumors(OR=6.157,P=0.008),SM2 invasion(OR=11.888,P<0.001)and LVI(OR=8.202,P<0.001).As for the undifferentiated EGC subgroup,17.2%(139/807)patients had lymph node metastasis,and none of the 110 patients who met the expanded indications had lymph node metastasis.Univariate analysis demonstrated that CEA level,large(>20 mm)lesion size,depressed macroscopic-type tumors,submucosal invasion(SM1 and SM2),ulcer presence,presence of LVI and perineural invasion were significantly associated with lymph node metastasis in undifferentiated EGC.The independent risk factors of lymph node metastasis in multivariate analysis were large(>20 mm)lesion size(OR=1.606,P=0.040),LVI(OR=16.835,P<0.01),SM1 invasion(OR=1.962,P=0.043)and SM2 invasion(OR=3.014,P<0.01).Conclusion: 1.The absolute indications for ESD are reasonable,the risk of lymph node metastasis is very low.2.The expanded indications for ESD in undifferentiated EGC are suitable for endoscopic treatment,while the feasibility of expanding the ESD indications for differentiated EGC requires further investigation.3.The predictors of lymph node metastasis in EGC include invasion depth,LVI,mucinous adenocarcinoma,and lesion size.The risk factors of lymph node metastasis are different between differentiated and undifferentiated subgroups of EGC patients.