Predictors of central lymph node metastasis in papillary thyroid carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Wen ,  CHENG Ruochuan

Diagnosis and Treatment Center of Thyroid Disease, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, P. R. China;

Corresponding?author：

CHENG Ruochuan, Email: cruochuan@foxmail.com

Keywords：

papillary thyroid carcinoma; central lymph node metastasis; prophylactic central lymph node dissection; review

DOI：

10.7507/1007-9424.201706093

Video：

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Objective To summarize the influencing factors of central lymph node metastasis in thyroid papillary carcinoma. Method Relevant literature about papillary thyroid carcinoma were reviewed and predictive factors of central lymph node metastasis were summarized. Results Studies had shown that, male, younger age, larger tumor size, multifocal, and BRAF mutations were risk factors for central lymph node metastasis in thyroid papillary carcinoma, while tumors located in the upper pole and combined with Hashimoto disease (HT) were the protective factors for central lymph node metastasis. Conclusions The central lymph node metastasis detection rate is low, so it is unable to meet with the preoperative diagnosis in papillary thyroid carcinoma. A large number of studies have confirmed that clinical pathological features have predictive value for preoperative lymph node diagnosis, and can provide a reference for the selection of surgical methods in thyroid papillary carcinoma.

Citation： LIU Wen, CHENG Ruochuan. Predictors of central lymph node metastasis in papillary thyroid carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(1): 99-103. doi: 10.7507/1007-9424.201706093 Copy

1.	WHO, IARC. International agency for research on cancer. World Cancer Report 2014. Lyon: IARC Press, 2014: 738-750.
2.	Dal Maso L, Lise M, Zambon P, et al. Incidence of thyroid cancer in Italy, 1991-2005: time trends and age-period-cohort effects. Ann Oncol, 2011, 22(4): 957-963.
3.	Mao LN, Wang P, Li ZY, et al. Risk factor analysis for central nodal metastasis in papillary thyroid carcinoma. Oncol Lett, 2015, 9(1): 103-107.
4.	劉文, 程若川, 蘇艷軍, 等. 2015 版美國甲狀腺協會指南 cN0 甲狀腺乳頭狀癌手術方案合理性分析. 中國實用外科雜志, 2017, 37(5): 568-571.
5.	Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more " personalized” approach to cancer staging. CA Cancer J Clin, 2017, 67(2): 93-99.
6.	Chéreau N, Buffet C, Trésallet C, et al. Recurrence of papillary thyroid carcinoma with lateral cervical node metastases: Predictive factors and operative management. Surgery, 2016, 159(3): 755-762.
7.	劉文, 程若川, 蘇艷軍, 等. 甲狀腺微小乳頭狀癌 rⅥb 區轉移預測因素及 rⅥa 區、rⅥb 區轉移相關性研究. 中國實用外科雜志, 2017, 37(9): 1007-1012.
8.	NCCN. The NCCN Thyroid Carcinoma Clinical Practice Guidelines in Oncology (Version 2.2017). 2017-05-17. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
9.	Haugen BR, Alexander EK, Bible KC, 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, 2016, 26(1): 1-133.
10.	Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, American College of Endocrinology and Associazione Medici Endocrinologi Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules-2016 update executive summary of recommendations. Endocr Pract, 2016, 22(5): 622-639.
11.	中華醫學會內分泌學分會, 中華醫學會外科學分會, 中國抗癌協會頭頸腫瘤專業委員會, 等. 甲狀腺結節和分化型甲狀腺癌診治指南. 中國腫瘤臨床, 2012, 39(17): 1249-1272.
12.	Lee DW, Ji YB, Sung ES, et al. Roles of ultrasonography and computed tomography in the surgical management of cervical lymph node metastases in papillary thyroid carcinoma. Eur J Surg Oncol, 2013, 39(2): 191-196.
13.	Khokhar MT, Day KM, Sangal RB, et al. Preoperative high-resolution ultrasound for the assessment of malignant central compartment lymph nodes in papillary thyroid cancer. Thyroid, 2015, 25(12): 1351-1354.
14.	劉文, 閆雪晶, 程若川, 等. 甲狀腺術后低鈣血癥早期預測研究進展. 中國實用外科雜志, 2016, 36(11): 1234-1237.
15.	Zhang L, Wei WJ, Ji QH, et al. Risk factors for neck nodal metastasis in papillary thyroid microcarcinoma: a study of 1 066 patients. J Clin Endocrinol Metab, 2012, 97(4): 1250-1257.
16.	Nam IC, Park JO, Joo YH, et al. Pattern and predictive factors of regional lymph node metastasis in papillary thyroid carcinoma: a prospective study. Head Neck, 2013, 35(1): 40-45.
17.	Ito Y, Miyauchi A, Kihara M, et al. Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation. Thyroid, 2014, 24(1): 27-34.
18.	Ma B, Wang Y, Yang S, et al. Predictive factors for central lymph node metastasis in patients with cN0 papillary thyroid carcinoma: a systematic review and meta-analysis. Int J Surg, 2016, 28: 153-161.
19.	Ito Y, Fukushima M, Higashiyama T, et al. Tumor size is the strongest predictor of microscopic lymph node metastasis and lymph node recurrence of N0 papillary thyroid carcinoma. Endocr J, 2013, 60(1): 113-117.
20.	Liang K, He L, Dong W, et al. Risk factors of central lymph node metastasis in cN0 papillary thyroid carcinoma: a study of 529 patients. Med Sci Monit, 2014, 20: 807-811.
21.	Jiang LH, Chen C, Tan Z, et al. Clinical characteristics related to central lymph node metastasis in cN0 papillary thyroid carcinoma: a retrospective study of 916 patients. Int J Endocrinol, 2014, 2014: 385787.
22.	Lang BH, Chai YJ, Cowling BJ, et al. Is BRAF^V600E mutation a marker for central nodal metastasis in small papillary thyroid carcinoma? Endocr Relat Cancer, 2014, 21(2): 285-295.
23.	Xue S, Wang P, Liu J, et al. Prophylactic central lymph node dissection in cN0 patients with papillary thyroid carcinoma: A retrospective study in China. Asian J Surg, 2016, 39(3): 131-136.
24.	Kim E, Choi JY, Koo do H, et al. Differences in the characteristics of papillary thyroid microcarcinoma ≤5 mm and >5 mm in diameter. Head Neck, 2015, 37(5): 694-697.
25.	Vasileiadis I, Karakostas E, Charitoudis G, et al. Papillary thyroid microcarcinoma: clinicopathological characteristics and implications for treatment in 276 patients. Eur J Clin Invest, 2012, 42(6): 657-664.
26.	Zhang LY, Liu ZW, Liu YW, et al. Risk factors for nodal metastasis in cN0 papillary thyroid microcarcinoma. Asian Pac J Cancer Prev, 2015, 16(8): 3361-3363.
27.	Lee KJ, Cho YJ, Kim SJ, et al. Analysis of the clinicopathologic features of papillary thyroid microcarcinoma based on 7-mm tumor size. World J Surg, 2011, 35(2): 318-323.
28.	Sugitani I, Toda K, Yamada K, et al. Three distinctly different kinds of papillary thyroid microcarcinoma should be recognized: our treatment strategies and outcomes. World J Surg, 2010, 34(6): 1222-1231.
29.	Lundgren CI, Hall P, Dickman PW, et al. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study. Cancer, 2006, 106(3): 524-531.
30.	程若川. 2015 年版較 2009 年版 ATA 指南對甲狀腺乳頭狀癌的手術治療變化及解讀. 中國普外基礎與臨床雜志, 2016, 23(10): 1166-1168.
31.	Park JP, Roh JL, Lee JH, et al. Risk factors for central neck lymph node metastasis of clinically noninvasive, node-negative papillary thyroid microcarcinoma. Am J Surg, 2014, 208(3): 412-418.
32.	Ji YB, Yoo HS, Song CM, et al. Predictive factors and pattern of central lymph node metastasis in unilateral papillary thyroid carcinoma. Auris Nasus Larynx, 2016, 43(1): 79-83.
33.	Viola D, Materazzi G, Valerio L, et al. Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study. J Clin Endocrinol Metab, 2015, 100(4): 1316-1324.
34.	Kim BY, Jung CH, Kim JW, et al. Impact of clinicopathologic factors on subclinical central lymph node metastasis in papillary thyroid microcarcinoma. Yonsei Med J, 2012, 53(5): 924-930.
35.	Mitchell AL, Gandhi A, Scott-Coombes D, et al. Management of thyroid cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol, 2016, 130(S2): S150-S160.
36.	Xiang D, Xie L, Xu Y, 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, 2015, 157(3): 526-533.
37.	Wada N, Duh QY, Sugino K, et al. Lymph node metastasis from 259 papillary thyroid microcarcinomas: frequency, pattern of occurrence and recurrence, and optimal strategy for neck dissection. Ann Surg, 2003, 237(3): 399-407.
38.	Lee YS, Shin SC, Lim YS, et al. Tumor location-dependent skip lateral cervical lymph node metastasis in papillary thyroid cancer. Head Neck, 2014, 36(6): 887-891.
39.	Liu Z, Wang L, Yi P, et al. Risk factors for central lymph node metastasis of patients with papillary thyroid microcarcinoma: a meta-analysis. Int J Clin Exp Pathol, 2014, 7(3): 932-937.
40.	彭琛, 魏松鋒, 鄭向前, 等. 1 401 例甲狀腺微小乳頭狀癌臨床病理特征及中央區淋巴結轉移危險因素分析. 中國腫瘤臨床, 2016, 43(3): 95-99.
41.	Randolph GW著; 田文, 姜可偉, 譯. 甲狀腺和甲狀旁腺外科學. 第 2 版. 北京: 北京大學醫學出版社, 2016: 49-51.
42.	Shan Z, Chen L, Lian X, et al. Iodine status and prevalence of thyroid disorders after introduction of mandatory universal salt iodization for 16 years in China: a cross-sectional study in 10 cities. Thyroid, 2016, 26(8): 1125-1130.
43.	Lee JH, Kim Y, Choi JW, et al. The association between papillary thyroid carcinoma and histologically proven Hashimoto’s thyroiditis: a meta-analysis. Eur J Endocrinol, 2013, 168(3): 343-349.
44.	Zhu Y, Zheng K, Zhang H, et al. The clinicopathologic differences of central lymph node metastasis in predicting lateral lymph node metastasis and prognosis in papillary thyroid cancer associated with or without Hashimoto's thyroiditis. Tumour Biol, 2016, 37(6): 8037-8045.
45.	Kim KW, Park YJ, Kim EH, et al. Elevated risk of papillary thyroid cancer in Korean patients with Hashimoto’s thyroiditis. Head Neck, 2011, 33(5): 691-695.
46.	Zhang L, Li H, Ji QH, et al. The clinical features of papillary thyroid cancer in Hashimoto's thyroiditis patients from an area with a high prevalence of Hashimoto’s disease. BMC Cancer, 2012, 12(1): 610-617.
47.	Liotti F, Visciano C, Melillo RM. Inflammation in thyroid oncogenesis. Am J Cancer Res, 2012, 2(3): 286-297.
48.	Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell, 2011, 144(5): 646-674.
49.	Fugazzola L, Puxeddu E, Avenia N, et al. Correlation between B-RAF^V600E mutation and clinico-pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature. Endocr Relat Cancer, 2006, 13(2): 455-464.
50.	Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA, 2013, 309(14): 1493-1501.
51.	Kim TH, Park YJ, Lim JA, et al. The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer, 2012, 118(7): 1764-1773.
52.	石臣磊, 丁超, 秦華東, 等. BRAF^V600E 突變與乳頭狀甲狀腺癌中央區淋巴結轉移的關系. 中國普通外科雜志, 2014, 23(11): 1522-1526.
53.	高慶軍, 張偉, 王南鵬, 等. BRAFV600E 突變和 cN0 期甲狀腺乳頭狀癌淋巴結轉移相關性研究. 臨床耳鼻咽喉頭頸外科雜志, 2015, 29(23): 2048-2052.
54.	Schneider DF, Chen H. New developments in the diagnosis and treatment of thyroid cancer. CA Cancer J Clin, 2013, 63(6): 374-394.

1. WHO, IARC. International agency for research on cancer. World Cancer Report 2014. Lyon: IARC Press, 2014: 738-750.
2. Dal Maso L, Lise M, Zambon P, et al. Incidence of thyroid cancer in Italy, 1991-2005: time trends and age-period-cohort effects. Ann Oncol, 2011, 22(4): 957-963.
3. Mao LN, Wang P, Li ZY, et al. Risk factor analysis for central nodal metastasis in papillary thyroid carcinoma. Oncol Lett, 2015, 9(1): 103-107.
4. 劉文, 程若川, 蘇艷軍, 等. 2015 版美國甲狀腺協會指南 cN0 甲狀腺乳頭狀癌手術方案合理性分析. 中國實用外科雜志, 2017, 37(5): 568-571.
5. Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more " personalized” approach to cancer staging. CA Cancer J Clin, 2017, 67(2): 93-99.
6. Chéreau N, Buffet C, Trésallet C, et al. Recurrence of papillary thyroid carcinoma with lateral cervical node metastases: Predictive factors and operative management. Surgery, 2016, 159(3): 755-762.
7. 劉文, 程若川, 蘇艷軍, 等. 甲狀腺微小乳頭狀癌 rⅥb 區轉移預測因素及 rⅥa 區、rⅥb 區轉移相關性研究. 中國實用外科雜志, 2017, 37(9): 1007-1012.
8. NCCN. The NCCN Thyroid Carcinoma Clinical Practice Guidelines in Oncology (Version 2.2017). 2017-05-17. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
9. Haugen BR, Alexander EK, Bible KC, 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, 2016, 26(1): 1-133.
10. Gharib H, Papini E, Garber JR, et al. American Association of Clinical Endocrinologists, American College of Endocrinology and Associazione Medici Endocrinologi Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules-2016 update executive summary of recommendations. Endocr Pract, 2016, 22(5): 622-639.
11. 中華醫學會內分泌學分會, 中華醫學會外科學分會, 中國抗癌協會頭頸腫瘤專業委員會, 等. 甲狀腺結節和分化型甲狀腺癌診治指南. 中國腫瘤臨床, 2012, 39(17): 1249-1272.
12. Lee DW, Ji YB, Sung ES, et al. Roles of ultrasonography and computed tomography in the surgical management of cervical lymph node metastases in papillary thyroid carcinoma. Eur J Surg Oncol, 2013, 39(2): 191-196.
13. Khokhar MT, Day KM, Sangal RB, et al. Preoperative high-resolution ultrasound for the assessment of malignant central compartment lymph nodes in papillary thyroid cancer. Thyroid, 2015, 25(12): 1351-1354.
14. 劉文, 閆雪晶, 程若川, 等. 甲狀腺術后低鈣血癥早期預測研究進展. 中國實用外科雜志, 2016, 36(11): 1234-1237.
15. Zhang L, Wei WJ, Ji QH, et al. Risk factors for neck nodal metastasis in papillary thyroid microcarcinoma: a study of 1 066 patients. J Clin Endocrinol Metab, 2012, 97(4): 1250-1257.
16. Nam IC, Park JO, Joo YH, et al. Pattern and predictive factors of regional lymph node metastasis in papillary thyroid carcinoma: a prospective study. Head Neck, 2013, 35(1): 40-45.
17. Ito Y, Miyauchi A, Kihara M, et al. Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation. Thyroid, 2014, 24(1): 27-34.
18. Ma B, Wang Y, Yang S, et al. Predictive factors for central lymph node metastasis in patients with cN0 papillary thyroid carcinoma: a systematic review and meta-analysis. Int J Surg, 2016, 28: 153-161.
19. Ito Y, Fukushima M, Higashiyama T, et al. Tumor size is the strongest predictor of microscopic lymph node metastasis and lymph node recurrence of N0 papillary thyroid carcinoma. Endocr J, 2013, 60(1): 113-117.
20. Liang K, He L, Dong W, et al. Risk factors of central lymph node metastasis in cN0 papillary thyroid carcinoma: a study of 529 patients. Med Sci Monit, 2014, 20: 807-811.
21. Jiang LH, Chen C, Tan Z, et al. Clinical characteristics related to central lymph node metastasis in cN0 papillary thyroid carcinoma: a retrospective study of 916 patients. Int J Endocrinol, 2014, 2014: 385787.
22. Lang BH, Chai YJ, Cowling BJ, et al. Is BRAF^V600E mutation a marker for central nodal metastasis in small papillary thyroid carcinoma? Endocr Relat Cancer, 2014, 21(2): 285-295.
23. Xue S, Wang P, Liu J, et al. Prophylactic central lymph node dissection in cN0 patients with papillary thyroid carcinoma: A retrospective study in China. Asian J Surg, 2016, 39(3): 131-136.
24. Kim E, Choi JY, Koo do H, et al. Differences in the characteristics of papillary thyroid microcarcinoma ≤5 mm and >5 mm in diameter. Head Neck, 2015, 37(5): 694-697.
25. Vasileiadis I, Karakostas E, Charitoudis G, et al. Papillary thyroid microcarcinoma: clinicopathological characteristics and implications for treatment in 276 patients. Eur J Clin Invest, 2012, 42(6): 657-664.
26. Zhang LY, Liu ZW, Liu YW, et al. Risk factors for nodal metastasis in cN0 papillary thyroid microcarcinoma. Asian Pac J Cancer Prev, 2015, 16(8): 3361-3363.
27. Lee KJ, Cho YJ, Kim SJ, et al. Analysis of the clinicopathologic features of papillary thyroid microcarcinoma based on 7-mm tumor size. World J Surg, 2011, 35(2): 318-323.
28. Sugitani I, Toda K, Yamada K, et al. Three distinctly different kinds of papillary thyroid microcarcinoma should be recognized: our treatment strategies and outcomes. World J Surg, 2010, 34(6): 1222-1231.
29. Lundgren CI, Hall P, Dickman PW, et al. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study. Cancer, 2006, 106(3): 524-531.
30. 程若川. 2015 年版較 2009 年版 ATA 指南對甲狀腺乳頭狀癌的手術治療變化及解讀. 中國普外基礎與臨床雜志, 2016, 23(10): 1166-1168.
31. Park JP, Roh JL, Lee JH, et al. Risk factors for central neck lymph node metastasis of clinically noninvasive, node-negative papillary thyroid microcarcinoma. Am J Surg, 2014, 208(3): 412-418.
32. Ji YB, Yoo HS, Song CM, et al. Predictive factors and pattern of central lymph node metastasis in unilateral papillary thyroid carcinoma. Auris Nasus Larynx, 2016, 43(1): 79-83.
33. Viola D, Materazzi G, Valerio L, et al. Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study. J Clin Endocrinol Metab, 2015, 100(4): 1316-1324.
34. Kim BY, Jung CH, Kim JW, et al. Impact of clinicopathologic factors on subclinical central lymph node metastasis in papillary thyroid microcarcinoma. Yonsei Med J, 2012, 53(5): 924-930.
35. Mitchell AL, Gandhi A, Scott-Coombes D, et al. Management of thyroid cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol, 2016, 130(S2): S150-S160.
36. Xiang D, Xie L, Xu Y, 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, 2015, 157(3): 526-533.
37. Wada N, Duh QY, Sugino K, et al. Lymph node metastasis from 259 papillary thyroid microcarcinomas: frequency, pattern of occurrence and recurrence, and optimal strategy for neck dissection. Ann Surg, 2003, 237(3): 399-407.
38. Lee YS, Shin SC, Lim YS, et al. Tumor location-dependent skip lateral cervical lymph node metastasis in papillary thyroid cancer. Head Neck, 2014, 36(6): 887-891.
39. Liu Z, Wang L, Yi P, et al. Risk factors for central lymph node metastasis of patients with papillary thyroid microcarcinoma: a meta-analysis. Int J Clin Exp Pathol, 2014, 7(3): 932-937.
40. 彭琛, 魏松鋒, 鄭向前, 等. 1 401 例甲狀腺微小乳頭狀癌臨床病理特征及中央區淋巴結轉移危險因素分析. 中國腫瘤臨床, 2016, 43(3): 95-99.
41. Randolph GW著; 田文, 姜可偉, 譯. 甲狀腺和甲狀旁腺外科學. 第 2 版. 北京: 北京大學醫學出版社, 2016: 49-51.
42. Shan Z, Chen L, Lian X, et al. Iodine status and prevalence of thyroid disorders after introduction of mandatory universal salt iodization for 16 years in China: a cross-sectional study in 10 cities. Thyroid, 2016, 26(8): 1125-1130.
43. Lee JH, Kim Y, Choi JW, et al. The association between papillary thyroid carcinoma and histologically proven Hashimoto’s thyroiditis: a meta-analysis. Eur J Endocrinol, 2013, 168(3): 343-349.
44. Zhu Y, Zheng K, Zhang H, et al. The clinicopathologic differences of central lymph node metastasis in predicting lateral lymph node metastasis and prognosis in papillary thyroid cancer associated with or without Hashimoto's thyroiditis. Tumour Biol, 2016, 37(6): 8037-8045.
45. Kim KW, Park YJ, Kim EH, et al. Elevated risk of papillary thyroid cancer in Korean patients with Hashimoto’s thyroiditis. Head Neck, 2011, 33(5): 691-695.
46. Zhang L, Li H, Ji QH, et al. The clinical features of papillary thyroid cancer in Hashimoto's thyroiditis patients from an area with a high prevalence of Hashimoto’s disease. BMC Cancer, 2012, 12(1): 610-617.
47. Liotti F, Visciano C, Melillo RM. Inflammation in thyroid oncogenesis. Am J Cancer Res, 2012, 2(3): 286-297.
48. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell, 2011, 144(5): 646-674.
49. Fugazzola L, Puxeddu E, Avenia N, et al. Correlation between B-RAF^V600E mutation and clinico-pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature. Endocr Relat Cancer, 2006, 13(2): 455-464.
50. Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA, 2013, 309(14): 1493-1501.
51. Kim TH, Park YJ, Lim JA, et al. The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer, 2012, 118(7): 1764-1773.
52. 石臣磊, 丁超, 秦華東, 等. BRAF^V600E 突變與乳頭狀甲狀腺癌中央區淋巴結轉移的關系. 中國普通外科雜志, 2014, 23(11): 1522-1526.
53. 高慶軍, 張偉, 王南鵬, 等. BRAFV600E 突變和 cN0 期甲狀腺乳頭狀癌淋巴結轉移相關性研究. 臨床耳鼻咽喉頭頸外科雜志, 2015, 29(23): 2048-2052.
54. Schneider DF, Chen H. New developments in the diagnosis and treatment of thyroid cancer. CA Cancer J Clin, 2013, 63(6): 374-394.

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Predictors of central lymph node metastasis in papillary thyroid carcinoma

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