The esophageal submucosa is rich in vertical and horizontal lymphatic vessels, which communicates with each other in the esophagus and in the mediastinal lymph network. Once tumor invades the submucosal layer, the tumor cells can spread along the longitudinal lymphatic vessels in the esophageal submucosa to the remote LNs, which result in distant or skip metastasis . LN metastasis in the upper mediastinum and cervical region is the main cause of local recurrence of esophageal cancer in the thoracic esophageal cancer . LN metastasis along bilateral RLN was reported to account for a major proportion of the mediastina LNs. Fujita et al. reported that the LN metastasis rate along right recurrent laryngeal nerve was the highest among all LN stations around the esophagus . Ye et al. reported that the LN metastasis rate along the bilateral recurrent laryngeal nerves was 34.2% in total, 15.8% for the left RLN and 20.8% for the right RLN [8–9]. In our study, the LN metastasis rate along bilateral RLNs was 28.3%, which was much higher than that in the other mediastinal lymph node stations. Our result is consistent with what has been reported in the literatures [10–13]. Furthermore, it was 22.4% for the nodes along the right RLN and 13.9% along the left RLN, with a significant difference between the right and left RLN (P=0.004). This suggests esophageal cancer has a predilection of metastasis to the nodes along bilateral RLNs, while the LNs along right RLN are the most common metastasis station. Therefore, LNs dissection along bilateral RLN is a necessary procedure in the patients with thoracic ESCC, which not only increase accuracy of tumor staging, but also improve R0 resection.
In this study, it was found that LN metastasis rate along bilateral RLNs was significantly correlated with primary tumor sites, tumor differentiation and depth of tumor invasion in the patients with thoracic ESCC, this is consistent with the results reported in the literatures [9–11]. Upper third thoracic esophageal tumors, T3/T4 tumors and poorly differentiated tumors have much higher risk of LN metastasis along RLNs, and deserve more extensive LN dissection. It was reported that lower third thoracic ESCC mainly metastasize downward to the LNs around paracardia and left gastric artery. However, our study showed that the lower third thoracic ESCC also had a high LN metastasis rate along RLNs. This implies that complete LN dissection near bilateral RLNs should also be emphasized as a necessary procedure in those patients. Our study also found that the LN metastasis rate along RLNs was significantly higher in the patients with the positive LNs of other stations such as subcarinal, left tracheobronchial and upper abdominal stations than those with negative LNs in the other stations. This suggest that more advanced stage tumors have much higher risk of LNs metastasis along RLNs.
It has been reported that LN metastasis was one of the most important factors affecting the prognosis of patients with esophageal cancer. Not only the number of metastatic LNs, but also the site of LN metastasis, particularly the RLN-LNs, was an important prognostic indicator . Our study demonstrated that the OS and DFS of the patients with LN metastasis along RLNs were significantly poorer than that of those without and those with LN metastasis in other stations. Therefore, the LN metastasis along RLNs usually indicated an advanced stage. Another interesting finding was that the prognosis of the patients with single RLN nodal metastasis was much better than the patients with ≥2 nodal metastasis. All the above findings suggested that LN metastasis along RLNs was an important prognostic factor for the patients with thoracic ESCC, and neoadjuvant therapy may be necessary for those patients with preoperative suspicious nodal metastasis along RLNs.
Besides, RLNP occurred in 38 patients (11.2%). The incidence of RLNP was related to the degree of lymph node dissection (3FL 24.0% versus 2FL 7.6%, P<0.001), and was not related to operation method, tumor T stage, and degree of tumor differentiation (P>0.05).
The limitation of this study is that this was a retrospective study, and all included patients were from a single center and operated by a group of surgeons with difference in surgical skills and experience, which may produce bias in the results. And this study lacks data on postoperative treatment of the included patients and the impact of postoperative treatment on survival was missing. Besides, factors cause the higher metastasis rate of the right RLN chain lymph node were also not explained in our study.
In conclusion, for the patients with thoracic ESCC, RLN-LNs are the most frequent metastatic sites; the metastasis in the RLN-LNs significantly correlated with tumor invasion depth, tumor locations and differentiation, and usually indicate an advanced stage and poor prognosis. Complete LN dissection of bilateral RLNs is strongly recommend for the patients with thoracic ESCC.