Previous literatures[3-5] have shown that lymph node involvement is relevant to local recurrence, in fact. This is controversial according to the current American Thyroid Association (ATA) guidelines for a routine prophylactic or therapeutic CLND in patients with PTC[9-10]. The guideline recommended that prophylactic CLND (ipsilateral or bilateral) should be considered only in PTC patients with cT3-4N0 (clinically uninvolved central neck lymph nodes who have advanced primary tumors) or clinically involved lateral neck nodes (cN1b) [10]. For less aggressive PTC (like cN0-1a), routine CLND was argued. In clinics, two PTC patients suffered second operation for the presence of metastatic LN-epRLN, which may be reserved in consideration of RLN injury and hypoparathyroidism during the primary operation. After the second operation, the two patients both had transient hoarseness. In that case, we started this study.
The anatomic boundaries of CLND include the carotid arteries from the hyoid bone superiorly to the innominate artery inferiorly. An appropriate range of CLND should both reduce the local recurrence rate and the incidence of post-operative complications. There have been none articles written on the significance of the LN-epRLN, as part of paratracheal LNs. In the current study[11-12], therefore, LN-epRLN did not fall under the normal subdivisions of the central compartment. In the CLND, however, LN-epRLN is easy to overlook when the parathyroid glands and RLN are preserved, thus resulting in insufficient exposure.
The LN-epRLN was defined as the lymph node located within the distance from outer edge of the lymph node to the RLN entrance point less than 5 mm (Fig.1). In our study, there were inconstant nodes, 1 to 4 (1 in average), in diameter between 6 mm and 10 mm. In the present study, LN-epRLN was found in 73 of 878 patients and the metastasis rate was 3.76% (33/878). After the Carbon nanoparticles mapping, the RLNs and parathyroid glands could be protected by meticulously dissecting around the thyroid gland. The yellow and pink tissues were preserved as much as possible during the procedure. The lymph-fatty tissue in the central compartment was dissected en bloc after retraction and protection of the RLN. Since parathyroid glands were not stained black by the Carbon nanoparticles like the LNs were, the non–black-stained parathyroid glands were easily discriminated from the lymph-fatty tissue. In this way, we could identify the dissected area of the RLN entrance point, as well as ensuring RLN and parathyroid glands function. Our findings indicate that CLND can be performed safely with the use of intraoperative CN mapping, by surgeons that have a thorough understanding of the jugular anatomy and take care to achieve excellent haemostasis while performing careful manipulations of the tissues.
Thinking about involved thyroid lobes, the positive LN-epRLN rate was 46.84% (37/79), and the incidence of the right lobe was slightly higher than that on the left side. The univariate analysis showed that the factors affecting LN-epRLN involvement were the other central LN metastases, the upper third tumor location and tumor multifocality. The LN-epRLN receives afferent lymphatic drainage from the thyroid gland[13]. Considering the anatomical location of the LN-epRLN, it may be expected that tumors located in the upper third will spread to the LN-epRLN more frequently than other.
Previous studies[14-18] have found that ipsilateral multifocal disease could be used to predict neck lymph node matastases, which may reflect the ability of clonal formation of cancer cells[19-20]. On the other hand, multifocality of the thyroid nodules suggested occult PTC[21]. This result may tell us that when preoperative US and intra-operative frozen biopsy shows multifocality of the PTC nodules, the argument for CLND (LN-epRLN included) was strengthened.
In our study, the rate of other central neck node metastasis in the presence of LN-epRLN metastasis was 93.9%. Supporting our results, the positive LN-epRLN was highly predictive of other central nodal metastasis. In our study, we found that less than 50% of PTC patients those not presenting LN-epRLN had central LN metastases, which was significantly different from that (65.8%) in PTC patients with LN-epRLN, and we suspect it was an independent predictor. However, this tendency merits further investigation. On the other hand, the exploration and removal of LN-epRLN should be included in CLND for cN1a PTC.
Usually, most patients with PTC obtain a 10-year survival rate of 80–90%, but the regional recurrence rate after surgery is 5-20%[22]. Therefore, it’s important to improve the thoroughness of CLND. Our results mirror the data from literature: Reoperative CLND has been shown to have rates of RLN injury 21% transiently and postoperative hypocalcemia with a large range of 0-24%[23-30]. However, the incidence of complications varies according to the skill and experience of the surgeon [7,31].
PTC patients with clinically involved lymph nodes in the central compartment should be managed with a LN-epRLN dissection procedure as the time of CLND, taking into consideration RLN and parathyroid glands which are closely related to the nodal basins. The standard exploration and resection procedures are key factors that impact the relative difficulty of performing secondary surgery.
Our prospective study was limited by small samples, but we focus on acknowledgement of LN-epRLN. Moreover, patients with lateral neck lymph node matastases were excluded due to inclusion criteria. These patients may have experienced worse outcomes than patients enrolled in our study. However, to our knowledge, this is the first article in English to progress our understanding of LN-epRLN metastases in PTC patients.