A Clinical Study On Prognostic Impact Of Lymph Node Skip Metastasis In Colorectal Cancer

Background:The prognostic impact and the related risk factors of lymph node skip metastasis(LNSM)has not been thoroughly evaluated in patients with advanced colorectal cancer(CRC).ObjectiveThe aim of this study was to evaluate the clinicopathological characteristics and prognostic impact of LNSM in patients with stage III colorectal cancer who underwent radical resection with D3 lymphadenectomy,and then explore the related risk factors for LNSM.Methods and materialsPatientsBetween April 2003 and December 2014,patients with CRC and final underwent radical D3 lymphadenectomy based on an existing collected colorectal database belong to Department of General Surgery of Nanfang Hospital of Southern Medical University were enrolled in this study.At last,a total of 184 patients were enrolled in this study.41 patients detected as lymph node skip metastasis(skip+ group)were compared to 86 patients detected as pericolic lymph node metastases(LND1 group)and 57 patients detected as complex with intermediate and/or main lymph node metastases(LND2+3 group).Data CollectionThe data collected for analysis included the age,gender,diagnosis,neoadjuvant therapy,preoperative serum level of carcinoembryonic antigen(CEA),the postoperative pathologic examination(including tumor differentiation,the infiltration of the tumor invasion,the number of the retrieved lymph nodes and the metastatic status of the lymph nodes harvested,et al.),and the survival data(including accumulative survival time,local recurrence and systemic metastasis or death,et al).Statistical AnalysisStatistical analysis was performed by the chi-square test or one-way ANOVA test,Games-Howell post-hoc tests for factorial ANOVA.Survival probability was estimated with the Kaplan-Meier method and compared by log-rank test.The Cox proportional hazard model to assess the independent predictors for DFS.The logistic regression model to assess the independent related risk factors for LNSM.Data analyses were performed using SPSS 19.0 and statistical program R(http://www.r-project.org/)for propensity matched score analyses.All tests were two-sided,and values of P<0.05 were considered significant.Results:1.Compared with the LND1 group,the skip+ group showed significant higher frequency of pTl-2 stage cancer(26.8 vs.5.8%,P=0.001).Compared with the LND2+3 group,the skip+ group was associated with lesser metastatic lymph nodes(1.9±1.5 vs.6.5± 6.0,P<0.001).2.The 3-year DFS of skip+ group,LND1 group,and LND2+3 group were 64.8%,69.7%,and 40.1%,respectively;(P=0.008).The 3-year systemic recurrence rates of skip+ group,LND1 group,and LND2+3 group were 30.2%,20.3%,and 48.1%,respectively;(P?0.002).After match,The 3-year DFS of skip+ group,LND1 group,and LND2+3 group were 64.8%,66.5%,42.8%,respectively;(P=0.049);The systemic recurrence of skip+ group,LND1 group,and LND2+3 group were 30.2%,25.9%,57.2%,respectively;(P=0.008).3.In multivariate analysis,preoperative CEA[hazard ratio(HR)=2.2,P=0.029],differentiation(HR=3.8,P=0.001),and skip+(HR=0.2,P=0.021)were retained in the final model.4.On the multivariate analysis,only the pTl-2[odds ratio(OR)=4.4,95%C.I.=1.6-11.7,P=0.003]and pNl(OR=5.9,95%C.I.=1.9-18.2,P=0.002)were found to still have significantly correlation with LNSM.Conclusion1.LNSM with LND1 negative metastasis can occur at the early stage of cancer progression.2.Positive lymph nodes with LNSM are often not more than 3.3.The prognosis of the skip+ group was better than that of the LND2+3 group and was similar to that of the LND1 group.4.The infiltration of T1-2 and the number of the positive lymph nodes no more than 3 were associated with LNSM.