OncoTargets and Therapy Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Individualized Prediction Of Metastatic Involvement Of Lymph Nodes Posterior To The Right Recurrent Laryngeal Nerve In Papillary Thyroid Carcinoma This article was published in the following Dove Press journal: OncoTargets and Therapy Jiang Zhu1 Purpose: We aimed to establish a prediction model based on preoperative clinicopathologic Rui Huang2 features and intraoperative frozen section examination for precise prediction of metastatic DaiXing Hu1 involvement of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) in Yi Dou1 patients with papillary thyroid carcinoma (PTC). HaoYu Ren1 Methods: Clinicopathologic data pertaining to patients with PTC who underwent initial thyroid surgery between July 2015 and December 2017 were collected from electronic ZhiXin Yang1 medical records. Multivariate logistic regression analysis was performed to identify inde- Chang Deng1 1 pendent predictors of LN-prRLN metastasis for incorporation in the nomogram. The perfor- Wei Xiong mance of the model was assessed using discriminative ability, calibration, and clinical 1 Denghui Wang application. 1 Yu Mao Results: A total of 592 patients were enrolled in this study. The LN-prRLN metastatic 1 Xuesong Li positivity was 19% (95% confidence interval [CI], 15.61–21.89%). On multivariate analysis, 1 XinLiang Su ultrasonography-reported LN status, extrathyroid extension, Delphian lymph node metastasis, 1Department of Endocrine and Breast and number of metastatic pretracheal and paratracheal lymph nodes were independent pre- Surgery, The First Affiliated Hospital of dictors of LN-prRLN metastasis. The nomogram showed good discriminative ability (C-index: Chongqing Medical University, Chongqing 0.87; [95% CI, 0.84–0.91]; bias-corrected C-index: 0.86 [through bootstrapping validation]) 400016, People’s Republic of China; 2Department of Anesthesiology, The and was well calibrated. The decision curve analysis indicated potential clinical usefulness of First Affiliated Hospital of Chongqing the nomogram. Medical University, Chongqing 400016, Conclusion: This study demonstrates that the risk of LN-prRLN metastasis in individual People’s Republic of China patients can be robustly predicted by a nomogram that integrates readily available preopera- tive clinicopathologic features and intraoperative frozen section examination. The nomogram may facilitate intraoperative decision-making for patients with PTC. Keywords: papillary thyroid carcinoma, lymph node metastasis, lymph nodes posterior to the right recurrent laryngeal nerve, predict model, nomogram Introduction Correspondence: XinLiang Su Globally, an estimated 567,000 incident cases of thyroid cancer were reported in 2018. Department of Endocrine and Breast Surgery, The First Affiliated Hospital of The number of new cases of thyroid cancer increased by 50% in the period Chongqing Medical University, 1 Youyi 2006–2016.1,2 Papillary thyroid cancer (PTC) accounts for approximately 95% of all Road, Chongqing 400016, People’s Republic of China thyroid cancers. PTC is characterized by a propensity for dissemination to cervical Tel +86 135 0830 9161 lymph nodes at an early stage; the reported rates of cervical lymph node metastasis at Fax +86 23 8901 1463 3 Email [email protected] the time of diagnosis range from 30% to 90%, even in patients with small tumors. submit your manuscript | www.dovepress.com OncoTargets and Therapy 2019:12 9077–9084 9077 DovePress © 2019 Zhu et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php – http://doi.org/10.2147/OTT.S220926 and incorporate the Creative Commons Attribution Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Zhu et al Dovepress Lymph node metastasis is associated with locoregional recur- University, were retrieved from the electronic medical rence and distant metastasis.4–6 Despite its excellent prog- records. The inclusion criteria were: intraoperative frozen nosis because of good surgical outcomes, disease recurrence biopsy and postoperatively proven PTC; and patients with rates may approach 30%, typically in the central compart- right-sided or bilateral lesions. The exclusion criteria were: ment, and this is largely attributed to incomplete initial patients who underwent reoperation; solitary lesions located surgical resection.7 It is worth mentioning that the left recur- in the isthmus; vocal cord paralysis examined by preopera- rent laryngeal nerve courses along the esophagus and trachea tive laryngoscopy; distant metastasis; and incomplete clinical while the right recurrent laryngeal nerve ascends through the information. right central compartment due to anatomical differences. Data pertaining to the following clinicopathologic vari- Therefore, the paratracheal lymph nodes in the right central ables were collected: sex, age, tumor size, tumor location, compartment are divided into two parts: lymph nodes located extrathyroidal extension, multifocality, Hashimoto thyroi- posterior to the right recurrent laryngeal nerve (LN-prRLN) ditis, and lymph node metastasis. Tumor location, size, and lymph nodes located anterior to the right recurrent lar- and presence of lymph node metastasis were described in yngeal nerve.8 The LN-prRLN are distributed deep in a long, the preoperative ultrasonography report. Presence of extra- narrow, confined space; this special and complex anatomical thyroidal extension was recorded in preoperative ultraso- position contains important nerves, vessels, and other impor- nography report or intraoperative findings. tant structures, which makes it challenging to perform surgi- cal exposure and dissection. Therefore, dissection of Surgical Procedures LN-prRLN remains contentious. The arguments against At our center, for patients with right PTC with tumor size LN-prRLN dissection cite this as the most difficult and <4 cm, we routinely perform at least unilateral lobectomy risky procedure with an increased risk of devascularization and isthmus resection with ipsilateral central compartment of parathyroid gland and recurrent laryngeal nerve injury neck dissection; total thyroidectomy is performed if intrao- than other subgroups; these adverse events have a long- perative frozen section examination reveals metastatic term effect on the quality of life of patients.9 The proponents involvement of lymph nodes. For patients with bilateral argue that the LN-prRLN dissection during the initial opera- PTC, we perform total thyroidectomy with bilateral central tion would eliminate the cancer. Failure to remove the compartment neck dissection. In addition, lateral lymph involved lymph nodes will result in recurrent disease. node dissection is considered in patients with suspected Furthermore, reoperation in this region is a surgical challenge lateral lymph node metastasis based on preoperative ultra- and may cause much more adverse effects than ever before.10 sonography or intraoperative exploration. Therefore, precise assessment of LN-prRLN metastasis The boundaries of right central neck compartment were is crucial for personalized treatment to optimally balance defined by the hyoid bone superiorly, the innominate the dissection-related benefits and risks in patients with artery inferiorly, the trachea medially, and the right carotid PTC. Accuracy of preoperative ultrasound in the central arteries laterally. In the right paratracheal basins, the neck compartment is unsatisfactory.11 Several studies have superficial nodes anterior to the right recurrent laryngeal preliminarily explored the risk factors for LN-prRLN nerve were labeled as paratracheal lymph nodes in order to – metastasis.12 15 Thus, it is important to develop an evalua- distinguish these from LN-prRLN12 The right central tion tool adapted to the profile of an individual patient in lymph nodes (rCLN) excluding the LN-prRLN refer to order to accurately estimate the risk of LN-prRLN metas- the group of Delphian, pretracheal, and paratracheal tasis. This study aimed to develop an intraoperative deci- lymph nodes collectively. The surgical procedure was sion-making predictive model based on preoperative described in our previous study.16 After thyroid lobectomy, clinicopathologic features and intraoperative frozen section we subdivided the right central compartment into examination to predict the individual risk of LN-prRLN Delphian, pretracheal, paratracheal, and LN-prRLN groups metastasis and to improve treatment decision-making. depending on the anatomical position12 Four subgroups were removed and labeled sequentially, and then immedi- Methods ately sent for intraoperative frozen section examination. Data pertaining to 1258 consecutive patients with PTC who Postoperative histopathologic examination of all resected underwent thyroid surgery between July 2015 and December specimens was conducted independently by three patholo- 2017 at the First Affiliated Hospital, Chongqing Medical gists. Pathologic features including tumor size, lymph 9078 submit your manuscript | www.dovepress.com OncoTargets