Clinical Significance Of Preoperative Assessment Of Lymph Node Metastasis For Patients With Esophageal Squamous Cell Carcinoma(ESCC)

ObjectiveEsophageal squamous cell carcinoma(ESCC)is one of the most common gastrointestinal malignancies and China has the highest incidence and mortality around the world.ESCC shows a high incidence of lymph node metastasis as the lymphatic system is the major route for tumor spreading.Regional lymph nodes involvement is considered to be one of the most reliable prognostic factors for patients with ESCC.Surgical resection with lymphadenectomy is still the most curative treatment option,and preoperative staging is critical for selecting patients who will potentially benefit from surgical treatment.Accurate evaluation of regional lymph nodes status is an important part of preoperative assessment,and is also a difficult issue.Computed tomography(CT)and endoscopic ultrasonography(EUS)are both common imaging techniques for preoperative staging for ESCC,but the exact accuracy is still controversial.Therefore our retrospective study aimed to evaluate the validity of enhanced CT and EUS in the preoperative assessment of lymph node metastasis.Based on preoperative imaging and laboratory examinations,a prediction model for lymph node metastasis and a prognostic model was proposed.And a novel strategy of lymph nodes dissecton directed by CT scan was discussed.MethodsPatients who accepted radical esophagectomy and dignosed as ESCC at the Department of Thoracic Surgery during January,2009 to December,2016 were consecutively retrospected.The clinical and pathological information were collected using the electronic medical record system.Post-surgical follow-up was conducted by telephone and outpatient consultation.The validity of CT and EUS in preoperative assessment of lymph node metastasis was analyzed by compared with postoperative pathological tests.In order to improve the accuracy of lymph node metastasis detection,a prediction model was proposed based on clinical imaging and laboratory examinations.And a prognostic model based on clinical staging was also proposed by Cox survival analysis.Nomogram was used to show the results.Kaplan-Meier and Cox survival analysis were used to discuss the relationship between the number of harvested lymph nodes and prognosis.The appropriate number of harvested lymph nodes was confirmed by X-tile analysis and a novel strategy of lymph nodes dissecton directed by CT scan was proposed.ResultsA total of 400 patients pathologically diagnosed as ESCC were enrolled in this study,all patients accepted CT scan before the surgical treatment,241 of them accepted EUS examination at the same time.Among these patients,167 cases(41.8%)were pathologically confirmed with lymph node metastasis.Chest enhanced CT scan had an accuracy of 55.0%in evaluating lymph node metastasis,with a sensitivity of 51.5%and a specificity of 57.5%.The positive and negative predictive value was 46.5%and 62.3%.EUS examination had an accuracy of 53.5%with a sensitivity of 44.0%and a specificity of 60.2%.And the positive and negative predictive value was 44.0%and 60.3%.There was no significant difference between CT and EUS in preoperative detection of lymph node metastasis.Chest enhanced CT combined with EUS examination showed an increased sensitivity of 77.0%but reduced specificity of 36.9%,the overall accuracy,positive predictive value and negative predictive value was 53.5%,46.4%and 69.3%.Univariate analysis indicated some factors associated with lymph node metastasis,including serum ferritin level(P=0.065),tumor size(P=0.001),imaging signs of lymph node metastasis(P=0.022),tumor grade(P=0.086),and clinical and pathological T stage(P<0.001).However,only T stage was confirmed as independent risk factor of lymph node metastasis(P=0.003).A nomogram was proposed with ferritin level,clinical T and N stage as predictive factors.The AUC value of the model was 0.695,thus this model was supposed to improve the validity of preoperative lymph node assessment for patients with ESCC.We found that lymph nodal status evluated by CT and EUS was significantly related to the prognosis of patients with ESCC.Clinical lymph node metastasis detected by imaging examinations indicated a poor prognosis(P=0.001).And clinical T stage detected by EUS,was also a significant prognostic factor.We found that the preoperative levels of serum ferritin,CA19-9,and AFP were also realted to the prognosis of ESCC.And a prognostic nomogram model based on these imaging and laboratory tests was proposed,which showed satisfactory ability to reflect the prognosis of ESCC.Even for patients pathologically confirmed as stage pNO,positive lymph nodes detected by preoperative CT scan also indicated the poor prognosis(P=0.027).And the number of harvested lymph nodes was also associated with the prognosis of stage pN0 ESCC(P=0.010).We found that patients with positive lymph node metastasis detected by CT scan had better prognosis when the number of dissected lymph nodes was no less than 15(P=0.036).Patients with stage pT3-4N0 ESCC were supposed to obtain prognostic benefts with at least 17 lymph nodes dissected(P=0.037).On the other hand,for those with negative clinical lymph node metastasis,survival prognosis was improved when the number of harvested lymph nodes≥12(P=0.019),as for stage pT1-2N0 ESCC,the number of dissected lymph nodes should be no less than 7 for better prognosis(P=0.032).ConclusionsPreoperative valuation of lymph node status is important for patients who are supposed to accept surgical treatment.However,the accuracy of both CT and EUS might be unsatisfactory,accurate preoperative lymph node assessment is still a tough task.Combination of imaging techniques and laboratory tests was showed to improve the accuracy of metastatic lymph nodes detection and prognostic prediction for ESCC.And for patients with clinical lymph node metastasis detected by CT scan,lymph nodes dissection should be more careful and systematic to help confirm the pathological stage and improve the prognosis of patients with ESCC.