Previous literatures[2-4] have shown that LN involvement is relevant to local recurrence. Because of the increased risk of recurrence with focal “berry-pickin” techniques, compartmental surgery is recommended in accordance to the current American Thyroid Association (ATA) guidelines[11-12]. Our study was inspired by two cases where the PTC patients suffered hoarseness after a second operation addressin the presence of metastatic LN-epRLN, which may have been reserved in consideration of RLN injury and hypoparathyroidism during the primary operation.
The anatomic boundaries of CLND arefrom the hyoid bone to the innominate artery. An appropriate range of CLND should both reduce the local recurrence rate and the incidence of post-operative complications. In CLND, fear of RLN injury and hypoparathyroidism may lead to insufficient exposure where metastases are left at the laryngeal entry point. We refer to these as involved LN-epRLNs in our study. To this date, no studies have covered the significance of LN-epRLN, as part of central LNs[13-14] .
LN-epRLN was defined as lymph adipose tissue within 5mm from the outer edge of the lymph node to the RLN entrance point (Fig.1). In our study, there were variant nodes of 1 to 4 (1.51 on average), in diameter between 6 mm and 10 mm. In the present study, LN-epRLN was found in 73 of 878 patients (8.31%) and the metastasis rate was 3.76% (33/878). After the Carbon nanoparticles mapping, the non–black-stained parathyroid glands were easily discriminated from the lymph-fatty tissue[9-10]. Our findings indicated that CLND could be performed safely with the use of intraoperative CN mapping, Which has been reported in the previous study.
In terms of 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 left and right RLNs have slight differences in anatomical position, and the cervical part of the esophagus located closely next to the left. Therefore, there was a triangular space located posterior to the right RLN, which makes space for lymph adipose tissue[15-17]. In the literatures, the presence of Hashimoto’s thyroiditis leads to reactive lymphaden proliferation[18-19]. We preferred that the patients of Hashimoto’s thyroiditis would have positive LN-epRLNs. However, it showed no statistical significance between LN-epRLN metastasis and serum TgAb / TPOAb levels in our study, limited by small samples.
The univariate analysis showed that the factors influencing LN-epRLN involvement were the other central LN metastases, the upper third tumor location and tumor multifocality. Previous studies[20-24] have found that ipsilateral multifocal disease could be used to predict neck lymph node metastases, which may reflect the ability of clonal formation of cancer cells[25-27]. This result strengthens the argument for CLND (LN-epRLN included) in PTC as preoperative US and intra-operative frozen biopsy shows multifocality of the PTC nodules. In our study, the rate of other central LN metastasis in the presence of LN-epRLN metastasis was 93.9%. In line with multivariate analysis, central LN metastasis was stable parameters pointing toward positive LN-epRLN (Fig.2), which can be evaluated through preoperative US and frozen biopsy performed intra-operatively.
Usually, most patients with PTC obtain a 10-year survival rate of 80–90%, but the regional recurrence rate after surgery is 5-20%. Therefore, it’s important to improve the thoroughness of CLND. Our results mirror the data from previous literatures: reoperative CLND has been shown to have rates of RLN injury 21% transiently and postoperative hypocalcemia with a large range of 0-24%[29-36]. However, the incidence of complications varies according to the skill and experience of the surgeon [7,37].
PTC patients with clinically involved LNs in the central compartment should be managed with a LN-epRLN dissection during 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 observational study was limited by small samples, but we focus on acknowledgement of LN-epRLN. Moreover, patients with lateral neck lymph node metastases 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.