Clinical Study On Patterns Of Lymph Node Metastases In Patients With Synchronous Multiple Primary Esophageal Squamous Cell Carcinoma

ObjectiveWe aimed to study the the pattern and prognostic factors of lymph node metastasis in synchronous multiple primary esophageal squamous cell carcinoma(S-MPESCC).And the other purpose was to compare the clinical features and prognostic differences between S-MPESCC and single esophageal squamous cell carcinoma(SESCC).MethodsGeneral information A total of 567 patients with esophageal squamous cell carcinoma who underwent surgery in Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2018 were screened by computer medical record system.We recorded these patients’ clinical data for retrospective analysis.The patients with S-MPESCC(50 cases)identified by preoperative auxiliary examination or postoperative pathological examination were divided into a group and the other patients with SESCC(517 cases)were divided into another group.Follow-up Patients’ follow-up were conducted by outpatient or telephone until December 2019.The patients followed up for 3 or 5 years were included in the survival analysis.Statistical methods Statistical analyses was performed using SPSS version 25.0.The optimal cut-off point of the relevant variables,that is,the value corresponding to the maximum Youden index,was determined by using the receiver operating characteristic(ROC)curve.Univariate analyses between groups were performed using Wilcoxon rank sum test for non-normal distribution numerical variables and chi-square test or Fisher exact test for categorical variables.Binary logistic regression analyses were performed to investigate univariable and multivariable relationships of variable with the presence of LNM.Survival analyses were performed using Kaplan–Meier curves and compared using log rank tests for significance.Cox proportional hazard regression model was established to identify independent factors associated with prognosis by forward LR method.The difference was considered statistically significant if P value less than 0.05.Results1.Tumor foci distribution of patients A total 106 tumor foci were counted in 50 cases of S-MPESCC group,and the incidence rates of upper,middle and lower thoracic esophagus were 6.6%,63.2% and 30.2%,respectively.2.Characteristics of lymph node metastasis In the 50 patients with S-MPESCC,62.0% developed the metastatic lymph nodes,and the lymph node metastasis rates of cervical,upper mediastinal,lower mediastinal and celiac were 2.0%,32.0%,32.0% and 38.0%,respectively.The lymph node metastasis rate of M-m group was 56.3%,and the lymph node metastasis rates of cervical,upper mediastinal,lower mediastinal and celiac were 6.3%,37.5%,31.3% and 37.5%,respectively.The lymph node metastasis rate of M-l group was 46.2%,and the lymph node metastasis rates of cervical,upper mediastinal,lower mediastinal and celiac were 0.0%,23.1%,15.4% and 30.8%,respectively.The lymph node metastasis rate of L-m group was 83.3%,and the lymph node metastasis rates of cervical,upper mediastinal,lower mediastinal and celiac were 0.0%,41.7%,41.7% and 50.0%,respectively.The results from multivariate analysis showed that the depth of tumor infiltration of the primary tumor site was significantly related to the lymph node metastasis(OR=5.613,P<0.05),as well as the group of harvested lymph node numbers more than 24(OR=9.156,P<0.05).Compared with the lymph node metastasis rate of 44.1% in the SESCC group,the patients of SMPESCC group were more likely to suffer lymph node metastasis(P< 0.05),in which the upper mediastinal lymph node metastasis rate was 32.0% and 18.6%,and the celiac lymph node metastasis rate was 38.0% and 22.8%,respectively(P < 0.05).For the subgroup with primary tumor site located in middle thoracic esophagus,patients with S-MPESCC were more likely to happen lymph node metastasis compared to those with SESCC,especially in celiac region(P < 0.05),which reflected in the total,cervical,upper mediastinal,lower mediastinal and celiac lymph node metastasis rates were 56.3%,3.1%,31.3%,31.3%,37.5% in S-MPESCC group and 41.7%,3.0%,20.5%,21.1%,19.3% in SESCC group,respectively.For the subgroup with primary tumor site located in lower thoracic esophagus,patients with S-MPESCC were also more likely to happen lymph node metastasis compared to those with SESCC,especially in upper mediastinal region(P < 0.05),which reflected in the total,cervical,upper mediastinal,lower mediastinal and celiac lymph node metastasis rates were 80.0%,0.0%,33.3%,40.0%,46.7% in S-MPESCC group and 52.1%,2.5%,9.1%,27.3%,38.0% in SESCC group,respectively.3.Univariate and multivariate survival analyses for all patients The cumulative 3-,and 5-year survival rates for the patients with S-MPESCC were 60.7% and 38.9%,respectively.Multivariate analysis of prognostic factors identified that compared with the T1-2 patients,the T3-4 patients held a 6.351 increased risk of death(95%CI = 1.349-29.901,P<0.05).The cumulative 3-,and 5-year survival rates of SMPESCC group were 60.7% and 38.9%,whereas the SESCC group showed 60.1% and 49.4%,respectively.There was no significant statistical difference between the above comparisons.However,in the T3-4 subgroup,the 5-year cumulative survival rate of patients with S-MPESCC was significantly lesser than those with SESCC(10.0% and 48.0%,respectively;P<0.05).ConclusionThe lymph node metastasis patterns with S-MPESCC varied according to different cancer sites.But lymph node metastasis was always observed in the areas of cervical,mediastinal,and along with the celiac.Compared with SESCC,S-MPESCC showed a higher lymph node metastasis rate.But there was no significant difference in prognosis between S-MPESCC and SESCC.However,it can be concluded that with the increase of the depth of primary tumor site infiltration in S-MPESCC group,the long-term prognosis is even worse.