| 1.BackgroundEsophageal cancer is one of the most common malignant tumors in the world.The morbidity and mortality rate of esophageal cancer in China were above the world average.In terms of histological types,adenocarcinoma was the dominant type in European and American countries,while squamous cell carcinoma was the dominant type in China,accounting for more than 95%.The initial treatment for esophageal cancer is mainly based on the clinical stage of esophageal cancer,while the state of the lymph nodes of esophageal cancer directly determines the N stage.Currently,the methods to evaluate whether the lymph nodes of esophageal cancer are invaded including enhanced CT,PET,MRI,PET/CT and EUS,but they can not evaluate the clinical N stage very well.In clinical practice,regional lymph nodes are round and/or short diameter>10mm are often used as the clinical diagnostic criteria for malignant lymph nodes.Previous literature suggested that there were differences in the size of lymph nodes in different regions of the mediastinum,and there were also differences in the metastasis rate of lymph nodes in different regions of esophageal cancer.Taking 10mm as the standard may be an important reason for the poor accuracy of clinical N staging of esophageal cancer.Setting the diagnostic criteria for metastatic lymph nodes of esophageal cancer in different regions may become a breakthrough to improve the accuracy of clinical N stage.Operation is still the most important method in the comprehensive treatment of esophageal cancer,and lymph node dissection is very important in the operation.The accuracy of the diagnosis of recurrent laryngeal nerve lymph nodes is very important in balancing the high rate of metastasis and high rate of recurrent laryngeal nerve damage.Whether tumor markers can assist the clinical diagnosis of recurrent laryngeal nerve lymph node metastasis in esophageal cancer is still unknown.The formation of new lymphatic vessels is a necessary condition for lymph node metastasis of cancer cells.Vascular endothelial growth factor C(VEGF-C)plays an important role in the formation of angiogenesis and lymphangiogenesis in cancer tissues.At present,a number of studies have shown that VEGF-C is a good predictor of lymph node metastasis and prognosis of esophageal cancer,but no study has suggested the relationship between VEGF-C and recurrent laryngeal nerve lymph node metastasis of esophageal cancer.Whether VEGF-C combined with imaging can improve the accuracy of clinical diagnosis of recurrent laryngeal nerve lymph nodes in esophageal squamous cell carcinoma is a problem that needs to be explored.2.Materials and methodsA retrospective analysis was performed on 477 patients with thoracic esophageal squamous cell carcinoma who underwent radical resection of esophageal carcinoma through right thoracic approach in the department of thoracic surgery,Affiliated Cancer Hospital of Zhengzhou University from January 2013 to December 2017.Inclusion criteria:(1)primary thoracic esophageal squamous cell carcinoma without distant organ metastasis;(2)preoperative enhanced CT of chest and upper abdomen was performed in our hospital,which could be reviewed by PACS system(3)Mckeown esophagogastrectomy(esophagogastric partial resection via right chest and upper abdomen+esophagogastric neck anastomosis)+complete two-field lymph node dissection/three-field lymph node dissection were performed.(4)Clinical and pathological data were complete.Exclusion criteria:(1)combined malignant tumors at other sites;(2)preoperative neoadjuvant therapy such as radiotherapy and chemotherapy;(3)salvage surgery;(4)palliative surgery(R2 resection).Preoperative enhanced CT images of patients were collected on the PACS system,and the short diameters of the largest lymph nodes in each region were observed and measured.The differences of the short diameters of lymph nodes in different regions were found,and the effectiveness of the short diameters of lymph nodes in diagnosing lymph node metastasis was observed by ROC curve referring to postoperative pathological results.Immunohistochemistry was used to detect the relationship between VEGF-C and recurrent laryngeal nerve lymph node metastasis after the removal of lymph node short diameter factor in 106 postoperative tumor tissues.The chi-square test and Logistic regressive were used to analyze the differences between the qualitative data.The diagnostic test used a receiver operating characteristic(ROC)curve.Kaplan-meier method was used for survival analysis,and bilateral tests were used for all statistical tests.P<0.05 was considered as statistically significant difference.3.Results3.1 Difference of lymph node metastasis rate in esophageal squamous cell carcinomaIn this study,The total lymph node metastasis rate of the patients was 32.7%,among which the right recurrent laryngeal nerve lymph node metastasis rate was the highest(14.9%),and the regions with high metastasis rate also included the paraesophageal lymph nodes(9.0%),the left gastric artery nodes(8.6%),the paracardial nodes(8.0%),the left recurrent laryngeal nerve lymph node(7.1%)and the subcarinal node(6.5%)3.2 Difference of lymph node ratio in esophageal squamous cell carcinomaIn this study,the overall lymph node ratio of the patients was 3.0%,among which the lymph node ratio of the right recurrent laryngeal nerve nodes was the highest,reaching 7.9%.Other areas with higher metastasis were the paracardial nodes(4.0%),the left gastric nodes(3.3%),and the left recurrent laryngeal nerve nodes(3.2%).3.3 Differences in lymph node size and diagnostic criteria of esophageal squamous cell carcinoma3.3.1 Differences in the short diameter of lymph nodes in major regions of esophageal squamous cell carcinomaAmong the 321 patients with esophageal squamous cell carcinoma without lymph node metastasis,the subcarinal lymph node was the largest,with the largest lymph node shorter diameter≥5mm accounting for 83.5%.The right recurrent laryngeal nerve nodes,left recurrent laryngeal nerve nodes,paraesophageal lymph nodes,paracardial nodes and left gastric nodes were relatively small,and the largest lymph node shorter diameter≥5mm accounting for 24.9%,3.7%,4.4%,15.0%and 9.0%,respectively.3.3.2 Diagnostic criteria for regional lymph node metastasis in esophageal squamous cell carcinomaWhen evaluating lymph node metastasis in all regions of esophageal squamous cell carcinoma with short diameter length of lymph node,the AUC was only 0.776,and regional diagnosis showed good diagnostic efficacy.The short diameter length of lymph nodes can effectively evaluate the right recurrent laryngeal nerve nodes,left recurrent laryngeal nerve nodes,paraesophageal lymph nodes,paracardial nodes and left gastric nodes of esophageal squamous cell carcinoma,and the AUC values are 0.931,0.915,0.845,0.958 and 0.937,respectively.The corresponding optimal cut-off points are 5.5mm,4.8mm,5.2mm,5.7mm and 5.7mm,respectively.The sensitivity was 88.7%,79.4%,72.1%,94.7%and 85.4%,respectively.The specificity was 86.2%,95.0%,95.4%,93.8%,96.3%,respectively.The accuracy was 86.6%,93.9%,93.3%,93.9%and 95.4%,respectively.If the traditional cut-off value of 1cm is taken as the cut-off value,the omission diagnostic rate will reach 90.1%,94.1%,83.7%,76.3%and 82.9%,respectively.The short diameter length of the lymph node is not effective in predicting the subcarinal nodes of esophageal squamous cell carcinoma.Its corresponding AUC value is only 0.688.3.4 Related factors of regional lymph node metastasis in esophageal squamous cell carcinomaThe related factors of lymph node metastasis of esophageal squamous cell carcinoma are the short diameter of the largest lymph node,vascular tumor embolism and tumor invasion depth.The strongest correlation factor for right recurrent laryngeal node,left recurrent laryngeal node,paraesophageal lymph node,paracardial lymph node and left gastric node of esophageal squamous cell carcinoma metastasis was the length of lymph node short diameter(OR values were 47.4,77.2,56.1,468.0,98.6),and the strongest correlation factor for the subcarinal nodes of esophageal squamous cell carcinoma was the depth of tumor invasion(OR=6.3).3.5 Survival differences of lymph node metastasis in different regions of esophageal squamous cell carcinomaPatients with right recurrent laryngeal node metastasis(χ2=5.92,P<0.001),paraesophageal lymph node metastasis(χ2=14.01,P<0.001)or subcarinal node metastasis(χ2=13.68,P<0.001)had a worse prognosis than those with lymph node metastasis in other areas of esophageal squamous cell carcinoma.3.6 Value of VEGF-C in the diagnosis of recurrent laryngeal nerve nodesOn the premise of the consistent short diameter of recurrent laryngeal nerve lymph nodes in esophageal squamous cell carcinoma,VEGF-C positive tumor cells were not found to be related to the metastasis of the lymph nodes(χ2=0.44,P=0.507),and VEGF-C positive lymphocytes were not found to be related to the metastasis of the lymph nodes(χ2=1.751,P=0.186).4.Conclusion4.1 Lymph node metastasis of thoracic esophageal squamous cell carcinoma is mainly concentrated in the recurrent laryngeal nerve lymph nodes,paracardial nodes and left gastric nodes,paraesophageal lymph node metastasis and subcarinal node metastasis followed.4.2 The size of short diameter of lymph nodes in different regions of thoracic esophageal squamous cell carcinoma was significantly different,and setting criteria for lymph node metastasis by region could obtain higher diagnostic efficiency.After removing the factor of recurrent laryngeal nerve lymph node short diameter,VEGF-C could not effectively predict recurrent laryngeal nerve lymph node metastasis.4.3 Patients with thoracic esophageal squamous cell carcinoma with right recurrent laryngeal nerve lymph node metastasis,paraesophageal lymph node metastasis or subcarinal node metastasis have a poor prognosis. |
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