单侧甲状腺乳头状癌对侧淋巴结转移高危因素的临床研究

doi:10.19401/j.cnki.1007-3639.2023.06.010

摘要/Abstract

摘要：

背景与目的：甲状腺乳头状癌（papillary thyroid carcinoma，PTC）发生淋巴结转移时会对患者预后产生不良影响，本研究旨在讨论单侧PTC发生对侧中央区淋巴结转移（central lymph node metastases，CLNM）及影像学怀疑同侧颈侧区淋巴结转移（lateral lymph node metastases，LLNM）时发生对侧LLNM的相关高危因素。方法：回顾性分析2011年1月—2021年12月于江苏省肿瘤医院头颈外科同一治疗组行手术治疗的526例初治的行甲状腺全切及双侧中央区±颈侧区淋巴结清扫，术后病理学检查确诊为单侧PTC的患者的临床资料，分析发生对侧淋巴结转移的相关高危因素。结果：526例患者中，295例为CLNM，其中272例存在同侧CLNM（含同侧和双侧），129例存在对侧CLNM（含对侧和双侧）；165例存在LLNM，其中同侧129例，对侧和双侧转移均为18例。行预防性中央区淋巴结清扫（central lymph node dissection，CLND）的365例中65例（17.8%）出现对侧CLNM；治疗性CLND的161例中68例（42.2%）出现对侧CLNM。单因素及多因素回归分析结果显示，年龄<55岁、肿瘤最大径≥2 cm、CLNM数量≥6枚、多灶、无桥本甲状腺炎及肿瘤外侵与对侧CLNM有关（P均<0.05）；肿瘤最大径≥2 cm与对侧LLNM有关（P<0.05），而淋巴结外侵及癌灶侧淋巴结转移是发生对侧CLNM与对侧LLNM的独立危险因素（P均<0.05）。随访显示5年总生存（overall survival，OS）率为97.9%，无病生存（disease-free survival，DFS）率为97.5%。结论：单侧PTC患者存在多灶、无桥本甲状腺炎、肿瘤及淋巴结外侵、癌灶侧CLNM、年龄<55岁、肿瘤最大径≥2 cm、CLNM数量≥6枚等高危因素时更易出现对侧CLNM，临床上对出现上述高危因素的患者，应考虑行双侧CLND以降低肿瘤的残留复发。

关键词: 甲状腺乳头状癌, 中央区淋巴结清扫, 对侧中央区淋巴结转移

Abstract:

Background and purpose: The occurrence of lymph node metastasis in papillary thyroid cancer (PTC) can have adverse effects on the prognosis of patients. This study aimed to investigate risk factors related to the occurrence of contralateral central lymph node metastases (CLNM) and contralateral lateral lymph node metastases (LLNM) when imaging suspected ipsilateral LLNM in unilateral PTC. Methods: We retrospectively analyzed the clinical data of 526 patients who received surgical treatment in the same treatment group of Jiangsu Cancer Hospital Head and Neck Surgery Department from January 2011 to December 2021. They were initially treated with total thyroidectomy and bilateral central lymph node dissection (CLND) ± lateral lymph node dissection, and their postoperative pathology was uni-PTC. This study analyzed the relevant high-risk factors of contralateral lymph node metastasis. Results: Among the 526 patients, 295 had CLNM, including 272 ipsilateral CLNM, 129 contralateral CLNM and 106 of both sides CLNM; 165 patients had LLNM including 129 ipsilateral LLNM, 18 contralateral LLNM, and 18 of both ipsilateral and contralateral LLNM. Contralateral CLNM occurred in 65 (17.8%) of 365 patients who underwent preventive CLND, and contralateral CLNM was found in 68 (42.2%) of 161 patients with therapeutic CLND. Univariate and multivariate regression analyses showed that contralateral CLNM was associated with maximum diameter of tumor ≥2 cm, multiple foci, no Hashimoto's thyroiditis, tumor invasion, number of CLNM≥6 and age <55 years (P<0.05). Maximum diameter of tumor ≥2 cm was related to contralateral LLNM (P<0.05), while lymph extracapsular extension and lymph node metastasis at tumor side were independent risk factors for contralateral CLNM and contralateral LLNM (P<0.05). Follow-up showed that 5-year overall survival (OS) rate was 97.9% and 5-year disease-free survival (DFS) rate was 97.5%. Conclusion: Contralateral CLNM is more likely to occur in patients with maximum diameter of tumor ≥2 cm, multiple foci, no Hashimoto's thyroiditis, number of CLNM ≥6, age <55 years, tumor and lymph extracapsular extension and lymph node metastasis at the cancer side. In clinical practice, bilateral CLND should be considered for patients with high-risk factors to reduce the residual recurrence of the tumor. Since metastatic rate of contralateral LLNM is relatively low, preventive contralateral lateral lymph node dissection should not be performed routinely when there are no high-risk factors mentioned above.

Key words: Papillary thyroid cancer, Central lymph node dissection, Contralateral central lymph node metastasis

中图分类号:

R736.1

袁欣越, 姚瑶, 程帅, 郑鑫, 张园. 单侧甲状腺乳头状癌对侧淋巴结转移高危因素的临床研究[J]. 中国癌症杂志, 2023, 33(6): 619-628.

YUAN Xinyue, YAO Yao, CHENG Shuai, ZHENG Xin, ZHANG Yuan. Clinical study on high-risk factors for contralateral lymph node metastasis in unilateral papillary thyroid carcinoma[J]. China Oncology, 2023, 33(6): 619-628.

图/表 6

表1

表2

表3

表4

表5

表6

参考文献 19

[1]	SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.v71.3
[2]	CAO W, CHEN H D, YU Y W, et al. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020[J]. Chin Med J (Engl), 2021, 134(7): 783-791.
[3]	HIGASHINO M, AYANI Y, TERADA T, et al. Clinical features of poorly differentiated thyroid papillary carcinoma[J]. Auris Nasus Larynx, 2019, 46(3): 437-442. doi: S0385-8146(18)30526-1 pmid: 30466760
[4]	中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)分化型甲状腺癌诊疗指南2021[J]. 肿瘤预防与治疗, 2021, 34(12): 1164-1201.
	Guidelines Working Committee of the Chinese Clinical Oncology Society. Chinese society of clinical oncology (CSCO) guidelines for diagnosis and treatment of differentiated thyroid cancer 2021[J]. J Cancer Control Treat, 2021, 34(12): 1164-1201.
[5]	ZHOU L, LI Q Q, CHEN S C, et al. Synergic effects of histology subtype, lymph node metastasis, and distant metastasis on prognosis in differentiated thyroid carcinoma using the SEER database[J]. Gland Surg, 2020, 9(4): 907-918. doi: 10.21037/gs-20-273 pmid: 32953600
[6]	KIM D H, KIM G J, KIM S W, et al. Predictive value of ipsilateral central lymph node metastasis for contralateral central lymph node metastasis in patients with thyroid cancer: systematic review and meta-analysis[J]. Head Neck, 2021, 43(10): 3177-3184. doi: 10.1002/hed.v43.10
[7]	AMIN M B, GREENE F L, EDGE S B, 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[J]. CA Cancer J Clin, 2017, 67(2): 93-99. doi: 10.3322/caac.21388
[8]	HAUGEN B R, ALEXANDER E K, BIBLE K C, 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[J]. Thyroid, 2016, 26(1): 1-133. doi: 10.1089/thy.2015.0020
[9]	中国医疗保健国际交流促进会营养与代谢管理分会中国营养学会临床营养分会中华医学会糖尿病学分会, 等. 中国超重/肥胖医学营养治疗指南(2021)[J]. 中国医学前沿杂志(电子版), 2021, 13(11): 1-55.
	Nutrition and Metabolism Management Branch of China Health Care International Exchange Promotion Association Clinical Nutrition Branch of China Nutrition Society Diabetes Branch of Chinese Medical Association, et al. Guidelines for medical nutrition treatment of overweight/obesity in China (2021)[J] Chin J Med Frontiers (Electronic Edition), 2021, 13(11): 1-55.
[10]	MIN Y, HUANG Y Z, WEI M J, et al. Preoperatively predicting the central lymph node metastasis for papillary thyroid cancer patients with Hashimoto’s thyroiditis[J]. Front Endocrinol (Lausanne), 2021, 12: 713475. doi: 10.3389/fendo.2021.713475
[11]	MEDAS F, CANU G L, CAPPELLACCI F, et al. Prophylactic central lymph node dissection improves disease-free survival in patients with intermediate and high risk differentiated thyroid carcinoma: a retrospective analysis on 399 patients[J]. Cancers (Basel), 2020, 12(6): 1658. doi: 10.3390/cancers12061658
[12]	GRŠIĆ K, BUMBER B, CURIĆ RADIVOJEVIĆ R, et al. Prophylactic central neck dissection in well-differentiated thyroid cancer[J]. Acta Clin Croat, 2020, 59(Suppl 1): 87-95. doi: 10.20471/acc.2020.59.s1.11 pmid: 34219889
[13]	CABANILLAS M E, MCFADDEN D G, DURANTE C. Thyroid cancer[J]. Lancet, 2016, 388(10061): 2783-2795. doi: S0140-6736(16)30172-6 pmid: 27240885
[14]	TAN H L, HUANG B Q, LI G Y, et al. A prediction model for contralateral central neck lymph node metastases in unilateral papillary thyroid cancer[J]. Int J Endocrinol, 2021, 2021: 6621067.
[15]	ROBINSON T J, THOMAS S, DINAN M A, et al. How many lymph nodes are enough? Assessing the adequacy of lymph node yield for papillary thyroid cancer[J]. J Clin Oncol, 2016, 34(28): 3434-3439. doi: 10.1200/JCO.2016.67.6437 pmid: 27528716
[16]	YANG Z Y, HENG Y, ZHAO Q W, et al. A specific predicting model for screening skip metastasis from patients with negative central lymph nodes metastasis in papillary thyroid cancer[J]. Front Endocrinol (Lausanne), 2021, 12: 743900. doi: 10.3389/fendo.2021.743900
[17]	SHI R L, QU N, YANG S W, et al. Tumor size interpretation for predicting cervical lymph node metastasis using a differentiated thyroid cancer risk model[J]. Onco Targets Ther, 2016, 9: 5015-5022. doi: 10.2147/OTT
[18]	CUI N, SUN Q, CHEN L. A meta-analysis of the influence of body mass index on the clinicopathologic progression of papillary thyroid carcinoma[J]. Medicine (Baltimore), 2021, 100(32): e26882. doi: 10.1097/MD.0000000000026882
[19]	TAM A A, ÖZDEMIR D, FAKI S, et al. ABO blood groups, Rh factor, and thyroid cancer risk: to ‘B’ or not to ‘B’[J]. Endocr Res, 2020, 45(2): 137-146. doi: 10.1080/07435800.2019.1695261

Characteristics	Case n (%)	Characteristics	Case n (%)
Age/year		Esophagus	10 (1.9)
<55	405 (76.7)	Larynx	3 (0.1)
≥55	121 (23.0)	Nerve	12 (2.3)
Gender		Muscle	97 (18.4)
Male	113 (29.1)	No	389 (73.9)
Female	373 (70.9)	Lymph ECE
Position		Yes	38 (7.2)
Upper	141 (26.8)	No	488 (92.7)
Middle	286 (54.3)	Obesity (BMI≥28 kg/m²)
Lower	99 (18.8)	Yes	67 (12.7)
Maximum diameter of tumor D/cm		No	459 (87.3)
<1	200 (38.0)	Blood type
1-2	194 (36.8)	A	195 (37.0)
2-4	88 (16.7)	B	150 (28.4)
>4	44 (8.3)	AB	35 (6.7)
Multifocal		O	146 (27.7)
No	157 (29.8)	CN₀	161 (30.6)
Yes	369 (70.1)	CN₁	365 (69.4)
Tumor side metastasis and contralateral metastasis		CN_1a	200 (38.0)
Yes	98 (18.6)	CN_1b	165 (31.4)
No	215 (40.8)	BRAF mutation
Tumor side no metastasis	213 (40.4)	Yes	200 (77.5)
HT		No	58 (22.4)
Yes	173 (32.8)	Distant metastasis
No	353 (67.1)	Yes	9 (1.7)
Tumor invasion		No	517 (98.3)
Trachea	15 (2.9)

Treatment results	Case n (%)
Injury of recurrent laryngeal nerve
Permanent	9 (1.7)
Temporary	37 (7.0)
Injury of parathyroid
Permanent	8 (1.5)
Temporary	320 (0.8)
¹³¹I treatment
Yes	63 (12.0)
No	463 (88.0)
Local radiotherapy
Yes	6 (1.2)
No	520 (98.9)
Target therapy
Yes	2 (0.4)
No	524 (99.6)
Recurrence of ipsilateral LLNM after treatment
Yes	9 (1.7)
No	517 (98.3)

Clinical feature	Contralateral CLNM (n=129)	Contralateral non-CLNM (n=166)	F value	P value
Age/year			3.263	0.032
<55	116 (89.9)	137 (82.5)
≥55	13 (10.0)	29 (17.5)
Gender			0.532	0.466
Male	52 (40.3)	60 (36.1)
Female	77 (59.6)	106 (63.9)
Maximum diameter of tumor D/cm			3.994	0.047
<1	32 (24.8)	53 (31.9)
1-2	48 (37.2)	67 (40.4)
2-4	34 (26.4)	34 (20.5)
>4	15 (11.6)	12 (7.2)
Position			0.546	0.460
Upper	33 (25.5)	40 (24.1)
Middle	64 (49.6)	97 (58.4)
Lower	32 (24.8)	29 (17.5)
Multifocal			0.297	0.586
No	53 (41.0)	63 (38.0)
Yes	76 (58.9)	103 (62.0)
Tumor side CLNM			479.635	0.000
Yes	96 (74.4)	166 (100.0)
No	33 (25.5)	0 (0.0)
HT			1.018	0.314
Yes	32 (24.8)	50 (30.1)
No	97 (75.1)	116 (69.9)
Tumor invasion			0.726	0.395
Yes	39 (30.3)	58 (34.9)
No	90 (69.7)	108 (65.1)
Lymph ECE			7.697	0.006
Yes	17 (13.2)	15 (9.0)
No	112 (86.8)	151 (91.0)
Obesity (BMI≥28 kg/m²)			0.046	0.830
Yes	16 (12.4)	22 (13.3)
No	113 (87.5)	144 (86.7)
Blood type			1.656	0.177
A	53 (41.1)	55 (33.1)
B	35 (27.1)	51 (30.7)
AB	5 (3.8)	14 (8.4)
O	36 (27.8)	46 (27.7)
Number of CLNM			7.065	0.008
<6	27 (20.9)	58 (34.9)
≥6	102 (79.0)	108 (65.0)
BRAF mutation (n=75)			0.042	0.839
Yes	22 (88.0)	46 (92.0)
No	3 (12.0)	4 (8.0)

Clinical feature	OR	95% CI	P value
Multifocal	0.346	0.126-0.954	0.029
HT	0.251	0.077-0.821	0.012
Tumor side CLNM	-	-	0.000
Tumor invasion	0.162	0.043-0.605	0.002
Lymph ECE	5.287	1.325-21.090	0.021
Maximum diameter of tumor	1.269	0.422-3.817	0.668
Position	0.803	0.264-2.441	0.425
Age	1.427	0.476-4.277	0.519
Number of CLNM	0.567	0.225-1.431	0.219

Clinical features	Contralateral LLNM (n=18)	Contralateral non-LLNM (n=147)	F value	P value
Age/year			0.192	0.662
<55	15 (83.3)	128 (87.1)
≥55	3 (16.6)	19 (12.9)
Gender			0.044	0.883
Male	7 (38.8)	61 (41.5)
Female	11 (61.1)	86 (58.5)
Maximum diameter of tumor D/cm			1.663	0.045
<1	2 (11.1)	37 (25.2)
1-2	4 (22.2)	52 (35.4)
2-4	8 (44.4)	39 (26.5)
>4	4 (22.2)	19 (12.9)
Position			0.438	0.646
Upper	3 (16.6)	35 (23.8)
Middle	12 (66.6)	81 (55.1)
Lower	3 (16.6)	31 (21.1)
Multifocal			0.513	0.475
No	9 (50.0)	62 (42.2)
Yes	9 (50.0)	85 (57.8)
Tumor side CLNM			463.273	0.000
Yes	17 (94.4)	147 (100.0)
No	1 (5.6)	0 (0.0)
Tumor side LLNM			479.635	0.000
Yes	18 (100.0)	147 (100.0)
No	0 (0.0)	0 (0.0)
HT			0.174	0.677
Yes	6 (33.3)	42 (28.6)
No	12 (66.6)	105 (71.4)
Tumor invasion			0.480	0.489
Yes	8 (44.5)	53 (36.1)
No	10 (55.5)	94 (63.9)
Lymph ECE			12.058	0.001
Yes	8 (44.5)	24 (16.3)
No	10 (55.5)	123 (83.7)
Obesity (BMI≥28 kg/m²)			2.617	0.104
Yes	4 (22.2)	14 (9.5)
No	14 (77.7)	133 (90.5)
Number of CLNM			1.156	0.097
<6	5 (27.8)	42 (28.6)
≥6	13 (72.2)	105 (71.4)
BRAF mutation (n=32)			0.139	0.712
Yes	1 (100.0)	27 (87.1)
No	0 (0.0)	4 (12.9)