Esophageal cancer is a common malignant tumor that poses a serious threat to human health, accounting for the fifth place of male cancer incidence and mortality [1]. China is a high incidence country of esophageal cancer and there is an obvious geographical distribution of esophageal cancer, and the incidence rate of high incidence areas can reach more than 100/100,000, and more than 90%-95% of the tissue types are squamous cell carcinoma. Surgery is the first choice and the only possible cure for esophageal cancer, but by the time a patient presents to the doctor with dysphagia, most of the cases have already progressed to the advanced stage, losing the chance of surgical radical treatment. In recent years, the overall 5-year survival rate of esophageal cancer is still hovering around 10% despite the continuous progress of surgery and other treatments. Numerous studies have shown that the depth of infiltration and lymph node metastasis of esophageal cancer are the most important factors influencing the prognosis of esophageal cancer [2,3], therefore, for the surgical treatment of esophageal cancer, the thoroughness of surgical resection and the quality of lymph node dissection are the key factors influencing the survival of patients after surgery. In this paper, we will have a preliminary discussion on the standardization of lymph node dissection of esophageal cancer by combining with the newest staging criteria of esophageal cancer TNM. Staging progress of esophageal cancer The esophagus passes through the three major anatomical regions of cervical, thoracic and abdominal regions, adjacent to many important organs, and there is abundant lymphatic traffic in the submucosal layer of the esophagus, which makes esophageal cancer present more jumping metastasis and extensive regional lymph node metastasis [4], therefore, the surgical treatment of esophageal cancer is characterized by a variety of methods, changing surgical paths, and inconsistent scope of lymph node dissection, which is different from that of other solid tumors. Therefore, the surgical treatment of esophageal cancer is characterized by a wide variety of methods and variable surgical routes, and the scope of lymph node dissection is not uniform. The TNM staging criteria for esophageal cancer formulated by the International Union Against Cancer (UICC) based on the depth of tumor infiltration (T), lymph node invasion (N) and distant metastasis (M) are the most widely used international staging criteria for tumors to standardize clinicopathological staging, guide treatment decisions, judge patient prognosis and compare efficacy, and the 6th edition of tumor TNM staging criteria launched by the UICC together with the American Joint Cancer Consortium (AJCC) in 2002 is the most widely used staging criteria for esophageal cancer in the international arena. In 2002, the UICC and the American Cancer Consortium (AJCC) launched the 6th edition of the TNM staging criteria [5,6], which classified esophageal cancer lymph node metastasis into two grades: N0 (without regional lymph node metastasis) and N1 (with regional lymph node metastasis). When this criterion was first published, it attracted a lot of questions. Firstly, it was recently found that lymph node metastasis of esophageal cancer is the most important factor affecting patients’ postoperative long-term survival, and it has a close relationship with the degree of metastasis, i.e., the number of lymph nodes, so the staging of esophageal cancer according to the presence or absence of lymph node metastasis alone cannot accurately reflect the pathological and prognostic characteristics of esophageal cancer. Secondly, the criteria formulated by European and American scholars are mainly based on the data of esophageal cancer patients in the West, whereas adenocarcinoma predominates in Western esophageal cancer, which is different from the proportion of esophageal cancer cell types in Asian countries (esophageal squamous cancer accounts for more than 90%~95%), and therefore cannot satisfy the needs of staging and treatment of patients with esophageal cancer in Asian countries, which is mainly squamous cancer. In view of this, the AJCC began to include Asian cases of squamous esophageal cancer and invited Asian scholars to participate in the staging development when revising the TNM staging criteria for esophageal cancer [7,8], and the new TNM staging criteria for esophageal cancer were published in 2009 and have been implemented globally since 2010 [9]. The most obvious changes in the new TNM staging criteria are the unified naming and grouping of regional lymph nodes in esophageal cancer and the change of the N classification of lymph node metastasis to N0-3 according to the number of lymph node metastases, which corresponds to 0, 1-2, 3-6, and more than 6 lymph node metastases, respectively [10], which better reflects the role of this most important prognostic factor in the staging of esophageal cancer, and will bring far-reaching implications to the standardization and recording of lymph node dissection in esophageal cancer [11]. This will bring far-reaching influence on the standardization and recording method of esophageal cancer. The new TNM staging standard does not require the number of radical lymph node dissection for esophageal cancer, and in principle, it requires the dissection of as many regional lymph nodes as possible, but the surgical complications must be controlled. Obviously, the greater the number of lymph nodes cleared, the less likely to miss metastatic lymph nodes, therefore, the judgment of lymph node negative (N0) must be based on a certain number of resected lymph nodes to be reliable. The 6th edition of TNM staging of esophageal cancer stipulates that at least 6 lymph nodes should be cleared, and studies have shown that this threshold is more accurate for making N staging than clearing less than 6 lymph nodes [11-13]. However, as the importance of understanding the pattern of lymph node metastasis and the impact of the number of metastatic lymph nodes on the prognosis of esophageal cancer has been gradually recognized [14,15], the minimum number of lymph nodes required for radical lymph node dissection has also increased, and different authors have proposed different lymph node clearance thresholds based on their own findings, e.g., Ikimura suggested 10 lymph nodes, Yang suggested 18 lymph nodes, Peyre suggested 23 [16-18], Groth observed the treatment and follow-up results of 4882 progressive esophageal cancers and categorized the number of lymph node dissection into four groups, including 0, 1-11, 12-29 and 330, and found that only 312 lymph nodes were cleared to have a significant survival improvement, and the improvement was even more significant for 330 lymph nodes [19], In addition, one of the leaders of the development of this TNM standard Rice et al. analyzed the collected data of 4627 esophageal cancer cases and found that the depth of invasion T of esophageal cancer is closely related to the degree of lymph node metastasis in its region, so the number of lymph node dissection should be adjusted according to the depth of invasion of the lesion: at least 10 lymph nodes were removed for T1 tumors, 20 for T2 tumors, and at least 30 for T3/4 tumors [20]. In addition to the above considerations, the current new TNM staging of esophageal cancer suggests a minimum of 12 regional lymph nodes to be cleared, mainly based on the results of a detailed study of a large number of cases by Dutkowski, who found that the diagnostic sensitivity of lymph node metastasis in esophageal cancer started to increase drastically with increasing the number of lymph nodes cleared, and the sensitivity reached more than 90% after 12 nodes were cleared, and then continued to increase the number of lymph nodes removed had limited improvement in the sensitivity. After that, increasing the number of lymph node dissection will only improve the sensitivity to a limited extent, but the increase of complications will be more obvious [21]. Therefore, in addition to the requirement of removing at least 12 lymph nodes, the new version of TNM staging criteria also pointed out that “the regional lymph nodes of the esophagus should be cleared as thoroughly as possible, but the control of the surgical complications arising from this procedure must be taken into account” [9]. Technical problems of lymph node dissection in esophageal cancer: scope, counting and surgical route In addition to the requirement of the number of lymph nodes, the regional problem of lymph node dissection in esophageal cancer should also be emphasized. As mentioned earlier, the anatomical route of esophagus is extensive, and lymphatic drainage is also extensive, so the identification of regional lymph nodes of esophagus is very necessary. The new version of TNM staging of esophageal cancer clearly stipulates that 20 groups of lymph nodes from the peri-esophageal lymph nodes in the neck to the lymph nodes in the abdominal cavity (except for 11-14 groups of lymph nodes in the lungs) belong to the regional lymph nodes of the esophagus [9, 10], which should be the target of surgical dissection, and ignoring this, the lymph node dissection techniques should be considered. It is not sufficient to remove only one or several groups of lymph nodes just to fulfill the minimum number requirement. The TNM staging criteria for stage 7 esophageal cancer have modified the N classification, and the staging according to the number of lymph node metastases has obvious progress compared with the previous one, but ignoring the site or range distribution of the metastatic lymph nodes is still a major shortcoming of it, because the prognosis significance of a fixed number of positive lymph nodes concentrating in a certain region is different from that of scattering them in several regions [22,23]. The radical lymph node dissection should target all lymph nodes in the esophagus, rather than only meeting the number requirement. It was found that the lymph node metastasis of esophageal cancer is along the parietal esophagusà cardia-gastric curvatureà left gastric arteryà abdominal artery and along the laryngeal recurrent nerve chain to the cervical lymph nodes on both sides of the parietal esophagus, and it is difficult to completely clear lymph nodes of the above areas due to the obstruction of the aortic arch and the limitation of the field of view of the abdominal cavity exposed by the trans-thoracic and diaphragmatic apertures, so the traditional Ivac route through the upper abdomen and right thorax is used to clear lymph nodes of these areas in recent years. Therefore, in recent years, the Ivor-Lewis procedure via epigastric and right thoracic approach has increasingly become an excellent choice for the treatment of lower and middle esophageal cancer, especially gastroesophageal junction cancer, which is also recommended in China’s new version of Standardized Diagnostic and Treatment Guidelines for Esophageal Cancer [24]. Despite the great technological progress in recent years, the removal of upper mediastinal and cervical lymph nodes along the retropharyngeal nerve chain and its subsequent cervical anastomosis are still accompanied by high complications and obviously affect the quality of life of patients, thus, there is always a controversy on whether or not every patient and patients with upper esophageal cancers should be subjected to three-field lymph node dissection. For example, for early-stage or superficial esophageal cancer with few lymph node metastases, it is difficult for patients to benefit from three-field lymph node dissection [25], and for advanced esophageal cancer with extensive lymph node metastases, which is considered to be a systemic disease in the West, the superiority of radical lymph node dissection versus limited resection + radiochemotherapy is controversial, and lack of large-scale comparative prospective study data is lacking. It can be said that the procedure with high postoperative complications in esophageal cancer is esophageal neck anastomosis + radical three-field dissection. In order to balance the radicality and complications, the selective three-field lymph node dissection recently proposed by some scholars is not a better solution, i.e., the use of ultrasonography of the neck is used to guide the dissection, and if there are enlarged cervical lymph nodes, the three-field dissection is carried out, whereas if there is no enlargement of cervical lymph nodes, the necessity of performing the radical three-field clearance [24,26], but this recommendation is yet to be supported by prospective studies with large sample sizes. The issue of lymph node counting has also become important after N staging was changed to be based on the number of lymph node metastases. In clinical practice, the problem of multiple metastatic lymph nodes becoming enlarged and fused is often encountered, in which it is not a big problem to determine the presence of lymph node metastasis, but it becomes difficult to distinguish how many lymph nodes have metastasized [27], and in this case, according to the principle of the new staging, which stipulates that the indeterminate grading is up to the next level (less severe) and relies on the principle of the new staging [9], the counting of lymph nodes is limited to only 1 lymph node. Another common situation is the fragmentation of lymph nodes during the clearance process, if not indicated with the specimen sent for examination, the number of lymph nodes will be overestimated, making the TNM incremental stage, therefore, the fragmented lymph nodes in this case should be bagged separately, indicating that it is a single lymph node and then sent for examination. The author’s unit tried to realize printing the lymph nodes and number of each group on self-adhesive labels, and labeling with bagging during surgery, which is not only less prone to errors, but also conducive to the supervision of bystanders to remind attention to the examination of the lymph nodes in the region without omitting the possibility, which can be used as a reference. 4. Scope of lymph node dissection and surgical complications in esophageal cancer Radical lymph node dissection in esophageal cancer is a large and traumatic operation, which requires fine dissection to expose many important organs such as the trachea, aorta, pulmonary blood vessels, laryngeal reentry nerves, thyroid peritoneum, nerves of large vessels of the cervical region, thoracic ducts, abdominal arteries and their genitourinary branches etc., and since a lot of patients have coexisting preoperative cardiac or pulmonary pathologies, postoperative complications are very common [28 ], with the progress of surgical techniques, surgical instruments and anesthesia techniques, the rate of postoperative complications in esophageal cancer is decreasing but ultimately cannot be completely avoided. Chen et al. found, based on their larger data, that the postoperative complication rate of esophageal cancer was not associated with an increase in the number of lymph node dissection within a certain number (10-50), and that the site of esophageal anastomosis and the surgeon’s personal skill were independent prognostic factors [29]. The anastomosis site is determined according to the location of the esophagus where the tumor is located and the anastomosis site cannot be changed arbitrarily, but one can improve surgical technique and the use of innovative machinery such as ultrasonic knives so that radical lymph node dissection can be obtained without increasing the incidence of surgical complications. 5.Prospect With the deepening understanding of the law of lymph node metastasis of esophageal cancer and the rapid progress of surgical and anesthesia techniques, radical lymph node dissection of esophageal cancer has now been standardized [24]. Meanwhile, the application of various preoperative assessment measures and the use of lymphatic tracers during lymph node dissection are all conducive to the thorough clearance of regional lymph nodes in the esophagus. Meanwhile, the effects of surgical removal of negative lymph nodes in patients are not known if the patient does not have lymph node metastases. It has been suggested that retaining these negative lymph nodes can form a trap for tumor cells during later recurrence of esophageal cancer, which is conducive to the early detection of recurrent metastasis of tumor cells and active pursuit of the next step of treatment [30]. On the other hand, modern lymphatic imaging technology is developing rapidly, if the contrast agent that can specifically show metastasis of esophageal cancer and thus carry out targeted lymphatic dissection will be helpful to maintain radicality and reduce the incidence of postoperative complications of esophageal cancer, which will make lymph node dissection of esophageal cancer more targeted.