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Risk factors of skip lateral cervical lymph node metastasis in papillary thyroid carcinoma: a systematic review and meta-analysis

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Abstract

Objective

To analyze and explore the risk factors of skip lateral cervical lymph node metastasis (SLLNM) in papillary thyroid carcinoma (PTC).

Methods

PubMed, Web of Science, Embase, Cochrane, Wanfang, China National Knowledge Infrastructure, and China Science and Technology Journal databases, updated to April 4, 2021, were systematically searched for literature on the risk factors of SLLNM in PTC. The meta-analysis was completed using Stata 15.0 software after quality evaluation. The odds ratio (OR) and 95% confidence interval (CI) of each variable were calculated using fixed or random-effects models, and the publication bias was evaluated by the Egger’s test.

Results

A total of 28 studies with 10,682 cases were included in our meta-analysis; 1592 (14.90%) cases were positive for SLLNM. The meta-analysis showed that female sex (OR = 1.16, 95% CI = 1.02–1.31, P = 0.021), age ≥45 (OR = 1.60, 95% CI = 1.19–2.15, P = 0.002), tumor diameter ≤10 mm (OR = 2.23, 95% CI = 1.62–3.06, P < 0.001), and upper location of tumor (OR = 3.60, 95% CI = 2.65–4.89, P < 0.001) were risk factors for SLLNM in PTC patients. Hashimoto’s thyroiditis (OR = 1.02, 95% CI = 0.88–1.19, P = 0.777), multifocality (OR = 0.98, 95% CI = 0.75–1.28, P = 0.873), bilateral tumors (OR = 0.92, 95% CI = 0.70–1.19, P = 0.515), extrathyroidal extensions (OR = 1.07, 95% CI = 0.83–1.39, P = 0.598), and capsular invasion (OR = 0.93, 95% CI = 0.65–1.31, P = 0.660) were not closely related to SLLNM risk.

Conclusion

This study confirmed significant associations between SLLNM and female sex, age ≥45, tumor diameter ≤10 mm, and upper location of the tumor.

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Data availability

The data sets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Y.J. Jo, H.R. Choi, S.H. Park, Y.J. Jeong, Extent of thyroid surgery for clinically node-negative papillary thyroid carcinoma with confirmed nodal metastases after prophylactic central neck dissection: a 15-year experience in a single center. Ann. Surg. Treat. Res. 99, 197–204 (2020)

    Article  Google Scholar 

  2. Y.K. So, M.J. Kim, S. Kim, Y.I. Son, Lateral lymph node metastasis in papillary thyroid carcinoma: a systematic review and meta-analysis for prevalence, risk factors, and location. Int J. Surg. 50, 94–103 (2018)

    Article  Google Scholar 

  3. H. Kim, T.H. Kim, J.H. Choe, J.H. Kim, J.S. Kim et al. Patterns of initial recurrence in completely resected papillary thyroid carcinoma. Thyroid 27, 908–914 (2017)

    Article  CAS  Google Scholar 

  4. S. Noguchi, A. Noguchi, N. Murakami, Papillary carcinoma of the thyroid. I. Developing pattern of metastasis. Cancer 26, 1053–1060 (1970)

    Article  CAS  Google Scholar 

  5. B.R. Haugen, E.K. Alexander, K.C. Bible, G.M. Doherty, S.J. Mandel et al. 2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 26, 1–133 (2016)

    Article  Google Scholar 

  6. F. Pacini, M.G. Castagna, L. Brilli, G. Pentheroudakis, E.G.W. Group, Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 21(Suppl 5), S214–S219 (2010)

    Article  Google Scholar 

  7. M. Song, Z. Huang, S. Wang, J. Huang, H. Shi et al. Predictive factors of lateral lymph node metastasis in conventional papillary thyroid carcinoma. Gland Surg. 9, 1000–1007 (2020)

    Article  Google Scholar 

  8. Y. Huang, Y. Yin, W. Zhou, Risk factors for central and lateral lymph node metastases in patients with papillary thyroid micro-carcinoma: retrospective analysis on 484 cases. Front Endocrinol. 12, 640565 (2021)

    Article  Google Scholar 

  9. M.A. Adam, J. Pura, P. Goffredo, M.A. Dinan, S.D. Reed et al. Presence and number of lymph node metastases are associated with compromised survival for patients younger than age 45 years with papillary thyroid cancer. J. Clin. Oncol. 33, 2370–2375 (2015)

    Article  Google Scholar 

  10. J. Hou, Y. Zhang, Y. Fan, B. Wu, Risk factors of skip lateral lymph node metastasis in papillary thyroid carcinoma. Eur. Arch. Otorhinolaryngol. 278, 493–498 (2021)

    Article  Google Scholar 

  11. D. Hu, H. Lin, X. Zeng, T. Wang, J. Deng et al. Risk factors for and prediction model of skip metastasis to lateral lymph nodes in papillary thyroid carcinoma. World J. Surg. 44, 1498–1505 (2020)

    Article  Google Scholar 

  12. A. Attard, N.C. Paladino, A.I. Lo Monte, N. Falco, G. Melfa et al. Skip metastases to lateral cervical lymph nodes in differentiated thyroid cancer: a systematic review. BMC Surg. 18, 112 (2019)

    Article  Google Scholar 

  13. A. Machens, H.J. Holzhausen, H. Dralle, Skip metastases in thyroid cancer leaping the central lymph node compartment. Arch. Surg. 139, 43–45 (2004)

    Article  Google Scholar 

  14. T. Li, Z. Jiang, M. Lu, S. Zou, M. Wu et al. Computer-aided diagnosis system of thyroid nodules ultrasonography: Diagnostic performance difference between computer-aided diagnosis and 111 radiologists. Medicines 99, e20634 (2020)

    Google Scholar 

  15. J. Liang, X. Huang, H. Hu, Y. Liu, Q. Zhou et al. Predicting malignancy in thyroid nodules: radiomics score versus 2017 American College of Radiology Thyroid Imaging, Reporting and Data System. Thyroid 28, 1024–1033 (2018)

    Article  CAS  Google Scholar 

  16. J. Ding, W. Wu, J. Fang, J. Zhao, L. Jiang, Male sex is associated with aggressive behaviour and poor prognosis in Chinese papillary thyroid carcinoma. Sci. Rep. 10, 4141 (2020)

    Article  CAS  Google Scholar 

  17. C. Sui, Q. He, R. Du, D. Zhang, F. Li et al. Lymph node characteristics of 6279 N1 differentiated thyroid cancer patients. Endocr. Connect. 9, 201–210 (2020)

    Article  CAS  Google Scholar 

  18. M. Kim, H.K. Kim, H.I. Kim, E.H. Kim, M.J. Jeon et al. Modification of the eight-edition tumor-node-metastasis staging system with N1b for papillary thyroid carcinoma: a multi-institutional cohort study. Oral. Oncol. 86, 48–52 (2018)

    Article  Google Scholar 

  19. P.E. Voutilainen, M.M. Multanen, A.K. Leppaniemi, C.H. Haglund, R.K. Haapiainen et al. Prognosis after lymph node recurrence in papillary thyroid carcinoma depends on age. Thyroid 11, 953–957 (2001)

    Article  CAS  Google Scholar 

  20. Z. Xin, X. Shuai, Y. Yue, C. Guang, Related factors on skip metastasis of neck lymph node in papillary thyroid carcinoma. Chin. J. Surg. 55, 599–602 (2017)

    Google Scholar 

  21. R. Sun, H. Zhang, K. Liu, J. Fan, G. Li et al. Clinicopathologic predictive factors of cervical lymph node metastasis in differentiated thyroid cancer. Acta Otorrinolaringol. Esp. 69, 149–155 (2018)

    Article  Google Scholar 

  22. H. Zhao, T. Huang, H. Li, Risk factors for skip metastasis and lateral lymph node metastasis of papillary thyroid cancer. Surgery 166, 55–60 (2019)

    Article  Google Scholar 

  23. S. Ozden, B. Comcali, H. Atas, S. Er, M. Tez et al. A diagnostic dilemma: skip metastasis in papillary thyroid cancer. Am. Surg. 86, 245–249 (2020)

    Article  Google Scholar 

  24. J.-W. Feng, A.-C. Qin, J. Ye, H. Pan, Y. Jiang et al. Predictive factors for lateral lymph node metastasis and skip metastasis in papillary thyroid carcinoma. Endocr. Pathol. 31, 67–76 (2020)

    Article  CAS  Google Scholar 

  25. C.I. Lee, O. Kutlu, Z.F. Khan, O. Picado, J.I. Lew, Margin positivity and survival in papillary thyroid microcarcinoma: a national cancer database analysis. J. Am. Coll. Surg. 233, 537–544 (2021)

    Article  Google Scholar 

  26. K. Back, J.S. Kim, J.H. Kim, J.H. Choe, Superior located papillary thyroid microcarcinoma is a risk factor for lateral lymph node metastasis. Ann. Surg. Oncol. 26, 3992–4001 (2019)

    Article  Google Scholar 

  27. D. Xiang, L. Xie, Y. Xu, Z. Li, Y. Hong et al. Papillary thyroid microcarcinomas located at the middle part of the middle third of the thyroid gland correlates with the presence of neck metastasis. Surgery 157, 526–533 (2015)

    Article  Google Scholar 

  28. Y. Dou, D. Hu, Y. Chen, W. Xiong, Q. Xiao et al. PTC located in the upper pole is more prone to lateral lymph node metastasis and skip metastasis. World J. Surg. Oncol. 18, 188 (2020)

    Article  Google Scholar 

  29. I. Likhterov, L.L. Reis, M.L. Urken, Central compartment management in patients with papillary thyroid cancer presenting with metastatic disease to the lateral neck: Anatomic pathways of lymphatic spread. Head. Neck 39, 853–859 (2017)

    Article  Google Scholar 

  30. F.I. Moulana, A.A.H. Priyani, M.V.C. de Silva, R.S. Dassanayake, BRAF-oncogene-induced senescence and the role of thyroid-stimulating hormone signaling in the progression of papillary thyroid carcinoma. Horm. Cancer 9, 1–11 (2018)

    Article  CAS  Google Scholar 

  31. J. Mao, Q. Zhang, H. Zhang, K. Zheng, R. Wang et al. Risk factors for lymph node metastasis in papillary thyroid carcinoma: a systematic review and meta-analysis. Front Endocrinol. 11, 265 (2020)

    Article  Google Scholar 

  32. W.X. Jin, Y.X. Jin, D.R. Ye, Z.C. Zheng, Y.H. Sun et al. Predictive factors of skip metastasis in papillary thyroid cancer. Med. Sci. Monit. 24, 2744–2749 (2018)

    Article  Google Scholar 

  33. S. Jingjing, D. Jinwang, P. You, Z. Yu, P. Gang, Clinical risk factors analysis and model prediction of skip lateral cervical lymph node metastasis in papillary thyroid microcarcinoma. Chin. J. Exp. Surg. 37, 2289–2291 (2020)

    Google Scholar 

  34. J.H. Park, Y.S. Lee, B.W. Kim, H.S. Chang, C.S. Park, Skip lateral neck node metastases in papillary thyroid carcinoma. World J. Surg. 36, 743–747 (2012)

    Article  Google Scholar 

  35. W. Wendong, G. Jialei, Z. Weihui, W. Peng, Clinical study of lymphatic drainage pathways in central and lateral neck of patients with papillary thyroid carcinoma. Chin. J. Crit. Care Med. (Electron. Ed.) 12, 158–162 (2019)

    Google Scholar 

  36. Z. Huang, M. Song, S. Wang, J. Huang, H. Shi et al. Preoperative serum thyroglobulin is a risk factor of skip metastasis in papillary thyroid carcinoma. Ann. Transl. Med. 8, 389 (2020)

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China

    Lingqian Zhao, Fan Wu, Tianhan Zhou & Kecheng Jiang

  2. Department of Surgical Oncology, Affiliated Hangzhou First People’s Hospital Zhejiang University School of Medicine, Hangzhou, 310006, China

    Kaining Lu, Yu Zhang & Dingcun Luo

Authors
  1. Lingqian Zhao
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  2. Fan Wu
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  3. Tianhan Zhou
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  4. Kaining Lu
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  5. Kecheng Jiang
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  6. Yu Zhang
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  7. Dingcun Luo
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Contributions

Lingqian Zhao and Fan Wu contributed equally to this work. Dingcun Luo had full access to all of the data in the manuscript and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript. Concept and design: all authors. Acquisition, analysis, or interpretation of data: all authors. Drafting of the manuscript: Lingqian Zhao and Fan Wu. Critical revision of the manuscript for important intellectual content: Lingqian Zhao, Fan Wu and Dingcun Luo. Statistical analysis: Lingqian Zhao and Fan Wu. Supervision: Yu Zhang and Dingcun Luo.

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Correspondence to Dingcun Luo.

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Zhao, L., Wu, F., Zhou, T. et al. Risk factors of skip lateral cervical lymph node metastasis in papillary thyroid carcinoma: a systematic review and meta-analysis. Endocrine 75, 351–359 (2022). https://doi.org/10.1007/s12020-021-02967-9

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  • DOI: https://doi.org/10.1007/s12020-021-02967-9

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