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甲状腺癌的发病率在全球范围内呈现逐年上升趋势,最常见的类型是甲状腺乳头状癌(papillary thyroid carcinoma,PTC)。其中病灶最大直径≤10 mm的PTC被定义为甲状腺微小乳头状癌(papillary thyroid microcarcinoma,PTMC)。目前超过一半的PTC病人为PTMC。由于PTMC生长缓慢,恶性程度较低,预后较好,有指南推荐对于无腺体外侵袭且淋巴结术前评估为阴性(clinically negative lymph node,cN0)的PTMC病人,可以仅行单侧甲状腺叶+峡部切除术或甲状腺全切除术,无需进行颈部淋巴结清扫[1]。但研究[2]发现,PTMC早期便会发生颈部淋巴结转移,有相关研究表明初诊为PTMC的病人中央区淋巴结转移发生率在30%左右。且几乎均集中在中央区淋巴结,而更为重要的是淋巴结转移是甲状腺癌病人复发的重要危险因素。同时临床依赖的术前超声检查对中央区淋巴结转移与否的诊断具有一定的主观性和漏诊概率,更甚者可能一半以上的淋巴结转移PTMC病人术前存在漏诊[2-3]。因此,关于cN0的PTMC是否需要预防性行颈中央区淋巴结清扫术,一直存在临床争议。有专家认为cN0的PTMC预后较好,诊疗应遵照指南无需行淋巴结清扫,且清扫淋巴结会增加喉返神经损伤和甲状旁腺功能减低等并发症的风险[4]。但另一部分学者认为如果忽略潜在转移的中央区淋巴结,会增加复发风险,进而增加二次手术难度及并发症的发生率[5-6]。故如何术前更加精确地识别那些存在淋巴结转移的病人就显得尤为重要,本研究通过回顾性收集本临床中心术前评估为cN0的PTMC病人临床资料,分析中央区淋巴结转移的高危因素,为cN0 PTMC病人的手术范围提供参考。
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年龄、肿瘤直径、多灶、侵犯包膜、腺体外侵犯、BRAF基因突变与PTMC病人发生中央区淋巴结转移具有相关性(P <0.05~P <0.01);而病人性别、肿瘤单/双侧、是否合并桥本氏甲状腺炎、术前TSH与病人是否发生中央区淋巴结转移无明显相关性(P>0.05)(见表 1)。
指标 淋巴结阳性组
(n=63)淋巴结阴性组
(n=137)χ2 P 年龄/岁 42.94±11.68 47.36±11.56 2.50△ < 0.05 性别 男
女11(42.3)
52(29.9)15(57.7)
122(70.1)1.62 > 0.05 单/双侧 单侧
双侧38(27.3)
25(41.0)101(72.7)
36(59.0)3.66 > 0.05 直径/mm 6.49±1.87 5.15±2.25 4.12△ < 0.01 单/多灶 单灶
多灶22(19.8)
41(46.1)89(80.2)
48(53.9)15.77 < 0.01 侵犯包膜 是
否26(70.3)
37(22.7)11(29.7)
126(77.3)31.63 < 0.01 腺体外侵犯 是
否4(100.0)
59(30.1)0(0.0)
137(69.9)5.93▲ < 0.05 BRAF基因突变 阴性
阳性5(13.5)
58(35.6)32(86.5)
105(64.4)6.81 < 0.01 合并桥本氏甲状腺炎 有
无39(37.1)
24(25.3)66(62.9)
71(74.7)3.26 > 0.05 TSH/(mIU/L) 2.73±1.56 3.12±2.84 1.02△ > 0.05 △示t值;▲示校正χ2值 表 1 PTMC中央区淋巴结转移的单因素分析[n;百分率(%)]
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将单因素分析结果中有统计学意义的临床特征纳入logistic回归分析,以中央区淋巴结是否转移作为因变量(是=1,否=0),以单因素分析中差异有统计学意义的因素作为自变量,分类变量中多灶、侵犯包膜、腺体外侵犯、BRAF突变阳性赋值为1;单灶、未侵犯包膜、无腺体外侵犯、BRAF突变阴性赋值为0。连续变量中年龄原值、肿瘤直径录入。多因素logistic回归分析结果显示,年龄、肿瘤直径、多灶、侵犯包膜、BRAF基因突变阳性是中央区淋巴结转移的独立危险因素(P <0.05~P <0.01)(见表 2)。
变量 B SE Wald χ2 P OR(95% CI) 年龄 -0.044 0.017 6.61 < 0.01 0.926~0.990 直径 0.212 0.09 5.61 < 0.05 1.037~1.474 单/多灶 1.082 0.374 8.38 < 0.01 0.418~6.140 是否侵犯包膜 1.901 0.463 16.88 < 0.01 2.702~16.575 腺体外侵犯 18.824 10 669.9 0 > 0.05 — BRAF基因 -1.29 0.546 5.57 < 0.05 0.094~0.803 表 2 PTMC中央区淋巴结转移风险的多因素logistic回归分析
cN0甲状腺微小乳头状癌中央区淋巴结转移风险分析及对手术的指导意义
Risk analysis of lymph node metastasis of cN0 papillary thyroid microcarcinoma in region VI and its guiding significance for surgery
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摘要:
目的分析cN0甲状腺微小乳头状癌(PTMC)发生中央区淋巴结转移的危险因素。 方法收集200例cN0 PTMC病人的临床资料,包括性别、年龄、术前促甲状腺激素、BRAF基因突变与否、肿瘤直径、多灶性、单/双侧、是否合并慢性淋巴细胞性甲状腺炎、是否侵犯包膜,是否腺体外侵犯及术后病理。根据中央区淋巴结是否转移将病人分为淋巴结阳性组和淋巴结阴性组,分析cN0 PTMC发生中央区淋巴结转移的危险因素。 结果单因素分析显示,年龄、肿瘤直径、多灶、侵犯包膜、腺体外侵犯、BRAF基因突变与PTMC病人发生中央区淋巴结转移具有相关性(P < 0.05~P < 0.01)。多因素logistic回归分析显示,年龄、肿瘤直径、多灶、侵犯包膜、BRAF基因突变阳性是中央区淋巴结转移的独立危险因素(P < 0.05~P < 0.01)。 结论针对PTMC病人,如有年龄较小、肿瘤直径较大、多病灶、侵犯包膜、BRAF基因突变阳性的临床特征,中央区淋巴结转移的风险较高,即使术前评估中央区淋巴结为阴性,手术范围也应包含中央区淋巴结的清扫,减少癌症残留及复发的风险。 Abstract:ObjectiveTo analyze the risk factors of central lymph node metastasis in cN0 papillary thyroid microcarcinoma (PTMC). MethodsThe clinical data of 200 patients with cN0 PTMC were collected, which included gender, age, preoperative TSH, BRAF gene mutation or not, tumor diameter, multiple lesions, unilateral/bilateral, combining chronic lymphocytic thyroiditis or not, envelope invasion or not, extragland invasion or not, and postoperative pathology.The patients were divided into lymph node positive group and lymph node negative group according to the central lymph node metastasis or not, and the risk factors of central lymph node metastasis of cN0 PTMC were analyzed. ResultsUnivariate analysis showed that age, tumor diameter, multiple lesions, envelope invasion, extragland invasion, BRAF gene mutation were associated with central lymph node metastasis in patients with PTMC(P < 0.05 to P < 0.01).Multivariate logistic regression analysis showed that age, tumor diameter, multiple lesions, envelope invasion, and BRAF gene mutation were the independent risk factors for central lymph node metastasis(P < 0.05 to P < 0.01). ConclusionsFor PTMC patients, if there are clinical features of younger age, larger tumor diameter, multiple lesions, envelope invasion, and positive BRAF gene mutation, the risk of central lymph node metastasis is higher.Even if the preoperative assessment of central lymph node is negative, the scope of surgery should also include the dissection of central lymph nodes to reduce the risk of residual cancer and recurrence. -
表 1 PTMC中央区淋巴结转移的单因素分析[n;百分率(%)]
指标 淋巴结阳性组
(n=63)淋巴结阴性组
(n=137)χ2 P 年龄/岁 42.94±11.68 47.36±11.56 2.50△ < 0.05 性别 男
女11(42.3)
52(29.9)15(57.7)
122(70.1)1.62 > 0.05 单/双侧 单侧
双侧38(27.3)
25(41.0)101(72.7)
36(59.0)3.66 > 0.05 直径/mm 6.49±1.87 5.15±2.25 4.12△ < 0.01 单/多灶 单灶
多灶22(19.8)
41(46.1)89(80.2)
48(53.9)15.77 < 0.01 侵犯包膜 是
否26(70.3)
37(22.7)11(29.7)
126(77.3)31.63 < 0.01 腺体外侵犯 是
否4(100.0)
59(30.1)0(0.0)
137(69.9)5.93▲ < 0.05 BRAF基因突变 阴性
阳性5(13.5)
58(35.6)32(86.5)
105(64.4)6.81 < 0.01 合并桥本氏甲状腺炎 有
无39(37.1)
24(25.3)66(62.9)
71(74.7)3.26 > 0.05 TSH/(mIU/L) 2.73±1.56 3.12±2.84 1.02△ > 0.05 △示t值;▲示校正χ2值 表 2 PTMC中央区淋巴结转移风险的多因素logistic回归分析
变量 B SE Wald χ2 P OR(95% CI) 年龄 -0.044 0.017 6.61 < 0.01 0.926~0.990 直径 0.212 0.09 5.61 < 0.05 1.037~1.474 单/多灶 1.082 0.374 8.38 < 0.01 0.418~6.140 是否侵犯包膜 1.901 0.463 16.88 < 0.01 2.702~16.575 腺体外侵犯 18.824 10 669.9 0 > 0.05 — BRAF基因 -1.29 0.546 5.57 < 0.05 0.094~0.803 -
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