Demographic and clinicopathologic characteristics. A total of 1828 eligible adult female patients were included. The mean age was 45.53 ± 11.8 (mean ± SD). The average tumor size was about 1.13 ± 0.84, of which 621 (34.0%) were multifocal, 424 (23.2%) were bilateral, 385 (21%) had ETE, and a total of 903 (49.4%) patients developed lymph node metastasis at the first operation. Table 1 describes the details of the included patients.
Table 1
Female patients’ demographics features and clinicopathological characteristics
Variables
|
Number of patients
|
%
|
Total
|
1828
|
--
|
Age (mean ± SD, years)
|
45.53 ± 11.8
|
--
|
BMI (≤ 25 vs > 25 Kg/m 2 )
|
1050/778
|
57.4/42.6
|
Hypertension (yes/no)
|
318/1510
|
17.4/82.6
|
Type 2 Diabetes Mellitus(yes/no)
|
103/1725
|
5.6/94.4
|
Malignant tumor history(yes/no)
|
58/1770
|
3.2/96.8
|
Hashimoto’s thyroiditis (yes/no)
|
149/1679
|
8.2/91.8
|
TSH level (mIU/L, mean ± SD)
|
2.26 ± 1.92
|
--
|
Tumor size (≤ 10 mm vs > 10 mm)
|
1183/645
|
64.7/35.3
|
Tumors size (mean ± SD, cm)
|
1.13 ± 0.84
|
--
|
Multifocality (yes/no)
|
621/1207
|
34.0/66.0
|
Bilaterality (yes/no)
|
424/1404
|
23.2/76.8
|
Extrathyroid extension (yes/no)
|
385/1443
|
21.1/78.9
|
Lymph node metastasis
|
|
CLNM
|
572
|
31.3
|
LLNM
|
52
|
2.9
|
CLNM + LLNM
|
279
|
15.3
|
Post-menopause (yes/no)
|
708/1120
|
38.7/61.3
|
Post-menopause Age(mean ± SD, years)
|
48.82 ± 4.5
|
--
|
Reproductive history (yes/no)
|
1691/137
|
92.5/7.5
|
BMI: body-mass index; TSH:Thyroid Stimulating Hormone.CLNM: central lymph nodes metastasis. LLNM: lateral lymph nodes metastasis. |
Univariate analysis and Multivariate logistic regression analysis regarding CLNM only in adult women. Univariate analysis showed that there was no significant difference in CLNM positivity among women in terms of BMI, hypertension, history of malignancy, and Hashimoto 's thyroiditis. The positive rate of CLNM metastasis was significantly increased in patients aged ≥ 45 years (χ2 = 60.857, P < 0.001), > 1 cm in diameter (χ2 = 71.005, P < 0.001), and multifocal cancer (χ2 = 5.862, P = 0.015), bilateral cancer (χ2 = 134.402, P < 0.001), and those who developed ETE (χ2 = 17.337, P < 0.001), but decreased significantly in patients with T2DM (χ2 = 4.415, P = 0.036), fertile women (χ2 = 36.139, P < 0.001), and postmenopausal women (χ2 = 21.824, P < 0.001). Multivariate logistic regression analysis revealed that all of the above significant variables, except T2DM, multifocalilty and menopausal history, were independent factors for both, with a lower incidence of CLNM in those with reproductive history than in those without reproductive history (OR = 0.414, 95% CI: 0.266–0.645) (Table 2).
Table 2
Univariate and multivariate analysis for Female only CLNM with the statistically significant variables.
Variables
|
Univariate analysis
|
Multivariate analysis
|
|
CLNM(+, 572)(n,%)
|
χ2 value
|
P-value
|
OR
|
95%CI
|
P-value
|
Age (years)
|
|
60.857
|
< 0.001a
|
0.442 0.350–0.557 <0.001a
|
< 45
|
325(56.8%)
|
|
|
|
≥ 45
|
247(43.2%)
|
|
|
|
BMI(kg/m2)
|
|
1.161
|
0.281
|
|
< 25
|
339(59.3%)
|
|
≥ 25
|
233(40.8%)
|
Hypertension
|
87(15.2%)
|
2.180
|
0.140
|
|
T2DM
|
24(4.2%)
|
4.415
|
0.036a
|
|
Malignant tumor history
|
18(3.1)
|
0.295
|
0.587
|
|
HT
|
39(6.8%)
|
1.278
|
0.258
|
|
Post-menopause history
|
183(32.0%)
|
23.236
|
< 0.001a
|
|
Reproductive history
|
502(87.8%)
|
36.139
|
< 0.001a
|
0.414 0.266–0.645 <0.001a
|
Tumor size
|
|
71.005
|
< 0.001a
|
2.388 1.872–3.045 <0.001a
|
≤1
|
333(58.2%)
|
|
> 1
|
239(41.8%)
|
Multifocality
|
194(33.9%)
|
5.862
|
0.015a
|
|
Bilaterality
|
135(23.6%)
|
9.890
|
0.002a
|
1.507 1.143–1.987 0.004a
|
ETE
|
129(22.6%)
|
17.337
|
< 0.001a
|
1.602 1.194–20151 0.002a
|
a Statistically significant (P < 0.05).All Calculated using two-tailed student t test. |
CLNM(+): central lymph nodes metastasis positive.CLNM: central lymph nodes metastasis positive. HT:Hashimoto’s thyroiditis; T2DM: Type 2 Diabetes Mellitus. ETE: Extrathyroidal extension. tumor extends into any of the strap muscles, including the omohyoid, sternohyoid, sternothyroid, or thyrohyoid or tumor extends to soft tissues or other anatomy beyond the strap muscles.OR: odds ratio; CI: confidence interva. |
Univariate analysis and Multivariate logistic regression analysis regarding CLNM + LLNM in adult females. Univariate analysis showed that there was no significant difference in BMI, hypertension, history of malignant tumor, and Hashimoto 's thyroiditis between women with positive CLNM + LLNM. The CLNM + LLNM metastasis rate was significantly increased in patients aged ≥ 45 years (χ2 = 24.266, P < 0.001), > 1 cm in diameter (χ2 = 205.084, P < 0.001), and multifocal cancer (χ2 = 65.129, P < 0.001), bilateral cancer (χ2 = 134.40286.184, P < 0.001), and those who developed ETE (χ2 = 83.309, P < 0.001), but showed a decreasing trend in fertile women (χ2 = 16.915, P < 0.001) and postmenopausal women (χ2 = 14.097, P < 0.001). Multivariate logistic regression analysis revealed that all of the above significant variables were independent factors except menopausal history, and the incidence of CLNM + LLNM was lower in those with reproductive history than in those without reproductive history (OR = 0.346, 95% CI: 0.187–0.642) (Table 3).
Table 3
Univariate and multivariate analysis for Female CLNM + LLNM with the statistically significant variables.
Variables
|
Univariate analysis
|
Multivariate analysis
|
|
CLNM + LLNM(+, 279) (n,%)
|
χ2 value
|
P-value
|
OR
|
95%CI
|
P-value
|
Age (years)
|
|
24.266
|
< 0.001a
|
0.429 0.306–0.603 <0.001a
|
< 45
|
147(52.7%)
|
|
|
|
≥ 45
|
132(47.3%)
|
|
|
|
BMI(kg/m2)
|
|
0.073
|
0.787
|
|
< 25
|
160(57.3%)
|
|
≥ 25
|
119(42.7%)
|
Hypertension
|
55(24.7%)
|
0.342
|
0.559
|
|
T2DM
|
12(4.3%)
|
2.311
|
0.128
|
|
Malignant tumor history
|
5(1.8%)
|
2.426
|
0.119
|
|
HT
|
23(8.2%)
|
0.010
|
0.921
|
|
Post-menopause history
|
89(31.9)
|
14.097
|
< 0.001a
|
|
Reproductive history
|
250(89.6%)
|
16.915
|
< 0.001a
|
0.346 0.187–0.642 0.001a
|
Tumor size(cm)
|
|
205.084
|
0.001a
|
5.756 4.172–7.941 <0.001a
|
≤1
|
92(33.0%)
|
|
> 1
|
187(67.0%)
|
Multifocality
|
151(54.1%)
|
65.129
|
< 0.001a
|
1.808 1.083–3.017 0.023a
|
Bilaterality
|
122(43.7%)
|
86.184
|
< 0.001a
|
2.155 1.254–3.702 0.005a
|
ETE
|
109(39.1%)
|
83.309
|
< 0.001a
|
2.765 1.923–3.975 <0.001a
|
a Statistically significant (P < 0.05).All Calculated using two-tailed student t test. |
CLNM + LLNM(+): central lymph nodes and lateral lymph nodes metastasis positive. LLNM:lateral lymph nodes metastasis. CLNM:central lymph nodes metastasis. HT:Hashimoto’s thyroiditis. T2DM: Type 2 Diabetes Mellitus. ETE: Extrathyroidal extension. ETE Mini: tumor extends through capsule only; ETE Macro: tumor extends into any of the strap muscles, including the omohyoid, sternohyoid, sternothyroid, or thyrohyoid or tumor extends to soft tissues or other anatomy beyond the strap muscles.OR: odds ratio; CI: confidence interva. |
Regarding Univariate and Multivariate analysis of LLNM in adult females. Univariate analysis of LLNM in the overall sample showed no significant differences in BMI, T2DM, history of malignancy, Hashimoto, reproductive history, history of menopause, or TSH values. However, LLNM was more likely to occur with a diameter > 1 cm (χ2 = 134.402, P < 0.001), multifocality (χ2 = 50.759, P < 0.001), bilateralilty (χ2 = 63.157, P < 0.001) and ETE (χ2 = 67.827, P < 0.001), and CLNM (χ2 = 231.330, P < 0.001). Multivariate analysis showed that only diameter (OR = 2.316, 95% CI: 1.756–3.054), bilateral cancer (OR = 1.903, 95% CI: 1.434–2.525), ETE (OR = 1.678, 95% CI: 1.248–2.255) and CLNM (OR = 6.318, 95% CI: 4.571–8.734) were independent factors for the development of LLNM after adjusting for all the above variables (Table 4).
Univariate analysis regarding fertility in 1828 adult female patients. Compared with nulliparous women, fertile women were older (P < 0.001), had a higher portion in BMI (P < 0.001), and hypertension (P < 0.001) and T2DM (P < 0.001). At the same time, thyroid primary tumors showed bilaterality cancer (P = 0.023) and multifocality (P = 0.030), which were more likely to have ETE (P = 0.010), but the lymph node metastasis rate was significantly lower (P < 0.001), and the differences were statistically significant. Potential confounding factors at baseline, including age, BMI, history of hypertension, history of T2DM, history of malignancy, maximum tumor diameter, multifocality, bilaterality, ETE, combined HT, and TSH, were also matched to remove heterogeneity using propensity score matching, and a total of 274 women were matched, including 137 women with and 137 women without reproductive history, and each matching factor was balanced and comparable between the two groups, and the only observation index was LNM. The results showed that the incidence of LNM was still lower in those with reproductive history than in those without reproductive history, and the positive rate in CLNM was mainly affected (P = 0.018), except for each confounding factor. (Table 5A) Combined with the results, further grouping analysis revealed that the rate of CLNM was significantly lower in term births or pregnancies with one or more births (P < 0.001), while the rate of LLNM was significantly lower in women who were more than three pregnancies than in women who were less than three pregnancies (P = 0.028) (Table 5B).
Table 4
Univariate and multivariate analysis for Female LLNM with the statistically significant variables.
Variables
|
Univariate analysis
|
Multivariate analysis
|
LLNM(+, 331) (n,%)
|
χ2 value
|
P-value
|
OR
|
95%CI
|
P-value
|
Age(years)
|
|
3.633
|
0.057
|
|
|
|
< 45
|
165(20.0%)
|
|
|
|
|
|
≥ 45
|
166(16.6%)
|
|
|
|
|
|
BMI(kg/m2)
|
|
0.019
|
0.890
|
|
|
|
< 24
|
189(57.1%)
|
|
≥ 24
|
142(42.9%)
|
Hypertension
|
63(19.0%)
|
0.754
|
0.385
|
|
T2DM
|
16(4.8%)
|
0.487
|
0.485
|
|
Malignant tumor history
|
6(1.8%)
|
2.434
|
0.119
|
|
HT
|
32(9.7%)
|
1.242
|
0.265
|
|
Post-menopause history
|
113(34.1%)
|
3.591
|
0.058
|
|
Reproductive history
|
301(90.9%)
|
1.435
|
0.231
|
|
Tumor size(cm)
|
|
134.402
|
< 0.001a
|
2.316 1.756–3.054 <0.001a
|
≤1
|
123(37.2%)
|
|
> 1
|
208(62.8)
|
Multifocality
|
168(50.8%)
|
50.759
|
< 0.001a
|
|
Bilaterality
|
132(39.9%)
|
63.157
|
< 0.001a
|
1.903 1.434–2.525 <0.001a
|
ETE
|
125(37.8%)
|
67.827
|
< 0.001a
|
1.678 1.248–2.255 0.001a
|
CLNM
|
279(84..3%)
|
231.330
|
< 0.001a
|
6.318 4.571–8.734 <0.001a
|
a Statistically significant (P < 0.05).All Calculated using two-tailed student t test. |
LLNM(+): lateral lymph nodes metastasis positive. LLNM:lateral lymph nodes metastasis. CLNM:central lymph nodes metastasis. HT:Hashimoto’s thyroiditis. T2DM: Type 2 Diabetes Mellitus. ETE: Extrathyroidal extension. ETE Mini: tumor extends through capsule only; ETE Macro: tumor extends into any of the strap muscles, including the omohyoid, sternohyoid, sternothyroid, or thyrohyoid or tumor extends to soft tissues or other anatomy beyond the strap muscles.OR: odds ratio; CI: confidence interva. |
Table 5
Reproductive history in 1828 female patients with PTC.
A. Demographics features and clinicopathologic characteristics of 1828 female patients with PTC by Reproductive history.
Variables
|
Reproductive history (Original cohort)
|
Reproductive history(Matched cohort)
|
Yes(n=1691)
|
No(n=137)
|
χ2 value
|
P-value
|
Yes(n=137)
|
No(n=137)
|
χ2 value
|
P-value
|
Age(years)
|
<45
|
694
|
131
|
152.407
|
<0.001a
|
130(94.9%)
|
131(95.6%)
|
0.081
|
0.766
|
|
≥45
|
997
|
6
|
|
|
7(5.1%)
|
6(4.4%)
|
|
|
BMI(kg/m2)
|
≤25
|
944(55.8%)
|
106(77.4%)
|
24.069
|
<0.001a
|
26(19.0%)
|
31(22.6%)
|
0.554
|
0.457
|
>25
|
747(44.2%)
|
31(22.6%)
|
111(81.0%)
|
106(77.4%)
|
|
|
Hypertension
|
Yes
|
317(18.7%)
|
1(0.7%)
|
28.627
|
<0.001a
|
1(0.7%)
|
1(0.7%)
|
0.000
|
1.000
|
No
|
1374(81.3%)
|
136(99.3%)
|
136(99.3%)
|
136(99.3%)
|
|
|
T2DM
|
Yes
|
100(5.9%)
|
2(1.5%)
|
4.772
|
0.029a
|
6(4.4%)
|
2(1.5%)
|
2.060
|
0.151
|
No
|
1591(94.1%)
|
135(98.5%)
|
131(95.6%)
|
135(98.5%)
|
|
|
Malignant tumor history
|
Yes
|
55(3.3%)
|
3(2.2%)
|
0.466
|
0.495
|
3(2.2%)
|
3(2.2%)
|
0.000
|
1.000
|
No
|
1636(96.7%)
|
134(97.8%)
|
134(97.8%)
|
134(97.8%)
|
|
|
HT
|
Yes
|
138(8.2%)
|
11(8.0%)
|
0.003
|
0.957
|
17(12.4%)
|
11(8.0%)
|
1.432
|
0.231
|
No
|
1553(91.8%)
|
126(92.8%)
|
120(87.6%)
|
126(92.0%)
|
|
|
TSH level(uIU/mL)
|
≤2.26
|
1071(63.3%)
|
80(58.4%)
|
1.327
|
0.249
|
90(65.7%)
|
80(58.4%)
|
1.550
|
0.213
|
>2.26
|
620(36.7%)
|
57(41.6%)
|
47(34.3%)
|
57(41.6%)
|
|
|
Tumor size(cm)
|
≤1
|
1100(65.1%)
|
83(60.6%)
|
1.107
|
0.293
|
90(65.7%)
|
83(60.6%)
|
0.768
|
0.381
|
>1
|
591(34.9%)
|
54(39.4%)
|
47(34.3%)
|
54(39.4%)
|
|
|
Multifocality
|
Yes
|
586(34.7%)
|
35(25.5%)
|
4.685
|
0.030a
|
37(27.0%)
|
35(25.5%)
|
0.075
|
0.784
|
No
|
1105(65.3%)
|
102(74.5%)
|
100(73.0%)
|
102(74.5%)
|
|
|
Bilaterality
|
Yes
|
403(23.8%)
|
21(15.3%)
|
5.144
|
0.023a
|
26(19.0%)
|
21(15.3%)
|
0.642
|
0.423
|
No
|
1288(76.2%)
|
116(84.7%)
|
111(81.0%)
|
116(84.7%)
|
|
|
ETE
|
Yes
|
368(21.8%)
|
17(12.4%)
|
6.69
|
0.010a
|
13(9.5%)
|
17(12.4%)
|
0.599
|
0.439
|
No
|
1323(78.2%)
|
120(87.6%)
|
124(90.5%)
|
120(87.6%)
|
|
|
LNM
|
CLNMA
|
502(29.7%)
|
70(51.1%)
|
40.568
|
<0.001a
|
54(39.4%)
|
70(51.1%)
|
7.858
|
0.049a
|
LLNMB
|
51(3.0%)
|
1(0.7%)
|
4(2.9%)
|
1(0.7%)
|
5.568AD
|
0.018a,AD
|
CLNM+LLNMC
|
250(14.8%)
|
29(21.2%)
|
24(17.5%)
|
29(21.2%)
|
--
|
0.645BD
|
NoneD
|
888(52.5%)
|
37(27.0%)
|
55(40.1%)
|
37(27.0%)
|
2.851CD
|
0.091CD
|
a Statistically significant (P<0.05). All Calculated using two-tailed student t test.
All calculated using chi-square test.
ADNumber of CLNM (Matched cohort) vs Number of None(Matched cohort); BDNumber of LLNM (Matched cohort) vs Number of None(Matched cohort);CDNumber of CLNM+LLNM (Matched cohort) vs Number of None(Matched cohort);
LNM: lymph nodes metastasis positive; CLNM: central lymph nodes metastasis; LLNM: lateral lymph nodes metastasis; BMI: body-mass index; TSH: Thyroid Stimulating Hormone; HT:Hashimoto’s thyroiditis; T2DM:Type 2 Diabetes Mellitus;ETE:Extrathyroidal extension. ETE None: tumor confined to the thyroid; ETE Minimal: tumor extends through capsule only; ETE Macro: tumor extends into any of the strap muscles, including the omohyoid, sternohyoid, sternothyroid, or thyrohyoid or tumor extends to soft tissues or other anatomy beyond the strap muscles.
B. Analysis reproductive factors associated with CLNM, CLNM+LLNM or LLNM of female PTC.
Variables |
CLNM(+)
(n,%)
|
CLNM(-)
(n,%)
|
t/χ2 value
|
P-Value
|
CLNM+LLNM(+) (n,%)
|
CLNM+LLNM(-) (n,%)
|
t/χ2 value
|
P-Value
|
LLNM(+) (n,%)
|
LLNM(-) (n,%)
|
t/χ2 value
|
P-Value
|
Total patients
|
572
|
925
|
|
|
279
|
925
|
--
|
--
|
331
|
925
|
--
|
--
|
Number of full-term pregnancies 31.402 <0.001A
|
|
|
13.239
|
0.004A
|
|
|
9.351
|
0.025A
|
|
0a
|
72(62.1%)
|
44(37.9%)
|
25.704ab
0.286bc
0.452cd
|
<0.001ab,A
0.593bc
0.502cd
|
29(39.7%)
|
44(60.3%)
|
9.881ab
|
0.002ab,A
|
30(40.5%)
|
44(59.5%)
|
6.875ab
|
0.009ab,A
|
1b
|
273(37.2%)
|
461(62.8%)
|
137(22.9%)
|
461(77.1%)
|
0.955bc
|
0.328bc
|
163(26.1%)
|
461(73.9%)
|
0.737bc
|
0.391bc
|
2c
|
185(35.7%)
|
333(64.3%)
|
85(20.3%)
|
333(79.7%)
|
0.869cd
|
0.351cd
|
104(23.8%)
|
333(76.2%)
|
0.941cd
|
0.332cd
|
≥3d
|
42(32.6%)
|
87(67.4%)
|
28(24.3)
|
87(75.7%)
|
|
|
34(28.1%)
|
87(71.9%)
|
|
|
Number of Pregnancies 39.557 <0.001A
|
|
|
24.499
|
<0.001A
|
|
|
20.310
|
<0.001A
|
|
0e
|
70(65.4%)
|
37(34.6%)
|
27.675ef
0.163fg
1.956gh
|
<0.001ef,A
0.686fg
0.162gh
|
29(43.9%)
|
37(56.1%)
|
10.329ef
|
0.001ef,A
|
30(44.8%)
|
37(55.2%)
|
7.759ef
|
0.005ef,A
|
1f
|
218(38.0%)
|
355(62.0%)
|
119(25.1%)
|
355(74.9%)
|
0.936fg
|
0.333fg
|
139(28.1%)
|
355(71.9%)
|
0.335fg
|
0.563fg
|
2g
|
169(36.8%)
|
290(63.2%)
|
83(22.3%)
|
290(77.7%)
|
3.421gh
|
0.064gh
|
104(26.4%)
|
290(73.6%)
|
4.848gh
|
0.028gh,A
|
≥3h
|
115(32.1%)
|
243(67.9%)
|
48(16.5%)
|
243(83.5%)
|
|
|
58(19.3%)
|
243(80.7%)
|
|
|
Abortion History 41.184 <0.001A
|
|
|
26.033
|
<0.001A
|
|
|
20.289
|
<0.001A
|
|
YESI
|
114(31.8%)
|
245(68.2%)
|
3.908
|
0.048IG,A
|
47(16.1%)
|
245(83.9%)
|
7.738
|
0.005IG,A
|
60(19.7%)
|
245(80.3%)
|
6.770
|
0.009IG,A
|
NOG
|
387(37.6%)
|
643(62.4%)
|
202(23.9%)
|
643(76.1%)
|
|
|
240(27.2%)
|
643(72.8%)
|
|
|
Unpregnancy
|
71(65.7%)
|
37(34.3%)
|
30(44.8%)
|
37(55.2%)
|
|
|
31(45.6%)
|
37(54.4%)
|
|
|
All Calculated using two-tailed student t test.
A Statistically significant (P<0.05).
B Calculated using t- test, others calculated using chi-square test.
abNumber of full-term Pregnancies 0 time vs Number of full-term Pregnancies 1 time; bcNumber of full-term Pregnancies 1 time vs Number of full-term Pregnancies 2 times; cdNumber of full-term Pregnancies 2 times vs Number of full-term Pregnancies ≥3 times.
efNumber of Pregnancies 0 time vs Number of Pregnancies 1 time; fgNumber of Pregnancies 1 time vs Number of Pregnancies 2 times; ghNumber of Pregnancies 2 times vs Number of Pregnancies ≥3 times.
IG With the abortion history vs without the abortion history.
CLNM+:central lymph nodes metastasis positive, CLNM-:central lymph nodes metastasis negative.
LNM+:lymph nodes metastasis positive, LNM-: lymph nodes metastasis negative.
Table 6 Post-menopause history in 1828 female patients with PTC.
A.Demographics features and clinicopathologic characteristics of 1828 female patients with PTC by Post-menopause history
Variables
|
Post-menopause history (Original cohort)
|
Post-menopause history(Matched cohort)
|
Yes(n,%)
|
|
|
Yes(n,%)
|
|
|
≤48years(249)
|
>48years(459)
|
χ2 value
|
P-value
|
≤48years(188)
|
>48years(335)
|
χ2 value
|
P-value
|
BMI(kg/m2)
|
≤25
|
128(51.4%)
|
224(48.8%)
|
28.636
|
<0.001a
|
97(51.6%)
|
163(48.7%)
|
2.811
|
0.245
|
>25
|
121(48.6%)
|
235(51.2%)
|
|
|
91(48.4%)
|
172(51.3%)
|
|
|
Hypertension
|
Yes
|
77(30.9%)
|
164(35.7%)
|
225.350
|
<0.001a
|
22(11.7%)
|
51(15.2%)
|
1.340
|
0.512
|
No
|
172(69.1%)
|
295(64.3%)
|
|
|
166(88.3%)
|
284(84.8%)
|
|
|
T2DM
|
Yes
|
27(10.8%)
|
51(11.1%)
|
62.982
|
<0.001a
|
10(5.3%)
|
16(4.8%)
|
0.097
|
0.953
|
No
|
222(89.2%)
|
408(88.9%)
|
|
|
178(94.7%)
|
319(95.2%)
|
|
|
Malignant tumor history
|
Yes
|
11(4.4%)
|
25(5.4%)
|
14.305
|
0.001a
|
11(5.9%)
|
16(4.8%)
|
0.847
|
0.655
|
No
|
238(95.6%)
|
434(94.6%)
|
|
|
177(94.1%)
|
319(95.2%)
|
|
|
HT
|
Yes
|
14(5.6%)
|
35(7.6%)
|
3.200
|
0.202
|
13(6.9%)
|
27(8.1%)
|
0.271
|
0.873
|
No
|
235(94.4%)
|
424(92.4%)
|
|
|
175(93.1%)
|
308(91.9%)
|
|
|
TSH level(uIU/mL)
|
≤2.26
|
160(64.3%)
|
280(61.0%)
|
1.065
|
0.587
|
120(63.8%)
|
212(63.3%)
|
0.703
|
0.704
|
>2.26
|
89(35.7%)
|
179(39.0%)
|
|
|
68(36.2%)
|
123(36.7%)
|
|
|
Tumor size(cm)
|
≤1
|
168(67.5%)
|
291(63.4%)
|
1.178
|
0.555
|
127(67.6%)
|
217(64.8%)
|
5.964
|
0.051
|
>1
|
81(32.5%)
|
168(36.6%)
|
|
|
61(32.4%)
|
118(35.2%)
|
|
|
Multifocality
|
Yes
|
94(37.8%)
|
178(38.8%)
|
10.262
|
0.006a
|
63(33.5%)
|
109(32.5%)
|
3.554
|
0.169
|
No
|
155(62.2%)
|
281(61.2%)
|
|
|
125(66.5%)
|
226(67.5%)
|
|
|
Bilaterality
|
Yes
|
67(26.9%)
|
121(26.4%)
|
7.345
|
0.025a
|
41(21.8%)
|
72(21.5%)
|
3.283
|
0.194
|
No
|
182(73.1%)
|
338(73.6%)
|
|
|
147(78.2%)
|
263(78.5%)
|
|
|
ETE
|
Yes
|
64(25.7%)
|
122(26.5%)
|
18.791
|
<0.001a
|
44(23.4%)
|
88(26.3%)
|
0.547
|
0.761
|
No
|
185(74.3%)
|
337(73.5%)
|
|
|
144
|
247
|
|
|
LNM
|
CLNMA,E
|
79(31.7%)
|
104(22.7%)
|
37.280
|
<0.001a
|
57(30.3%)
|
77(23.0%)
|
39.884
|
<0.001a
|
LLNMB,F
|
9(3.6%)
|
15(3.3%)
|
6.550AD
|
0.010a,AD
|
7(3.7%)
|
12(3.6%)
|
3.608EH
|
0.058EH
|
CLNM+LLNMC,G
|
28(11.2%)
|
61(13.3%)
|
0.281BD
|
0.596BD
|
21(11.2%)
|
38(11.3%)
|
0.112FH
|
0.738FH
|
NoneD,H
|
133(53.4%)
|
279(60.8%)
|
0.023CD
|
0.880CD
|
103(54.8%)
|
208(62.1%)
|
0.136GH
|
0.712GH
|
a Statistically significant (P<0.05). All Calculated using two-tailed student t test.
All calculated using chi-square test.
ADNumber of CLNM vs Number of none in female with Post-menopause history (Original cohort) between years ≤48 and years > 48; BDNumbr of LLNM vs Number of None in female with Post-menopause history (Original cohort) between years ≤48 and years > 48; CDNumber of CLNM+LLNM vs Number of None in female with Post-menopause history (Original cohort) between years ≤48 and years > 48;
EHNumber of CLNM vs Number of none in female with Post-menopause history(Matched cohort) between years ≤48 and years > 48; BDNumbr of LLNM vs Number of None in female with Post-menopause history (Matched cohort) between years ≤48 and years > 48; CDNumber of CLNM+LLNM vs Number of None in female with Post-menopause history(Matched cohort) between years ≤48 and years > 48;
LNM: lymph nodes metastasis positive; CLNM: central lymph nodes metastasis; LLNM: lateral lymph nodes metastasis; BMI: body-mass index; TSH: Thyroid Stimulating Hormone; HT:Hashimoto’s thyroiditis; T2DM:Type 2 Diabetes Mellitus;ETE:Extrathyroidal extension.ETE None: tumor confined to the thyroid; ETE Minimal: tumor extends through capsule only; ETE Macro: tumor extends into any of the strap muscles, including the omohyoid, sternohyoid, sternothyroid, or thyrohyoid or tumor extends to soft tissues or other anatomy beyond the strap muscles.
B.Analysis menopausal factors associated with CLNM, CLNM+LLNM or LLNM of female PTC.
Variables
|
CLNM(+)
(n,%)
|
CLNM(-)
(n,%)
|
t/χ2 value
|
P-Value
|
CLNM+LLNM(+) (n,%)
|
CLNM+LLNM(-) (n,%)
|
t/χ2 value
|
P-Value
|
LLNM
(+) (n,%)
|
LLNM
(-) (n,%)
|
t/χ2 value
|
P-Value
|
Total patients
|
572
|
925
|
|
|
279
|
925
|
--
|
--
|
331
|
925
|
--
|
--
|
Menopausal
|
|
|
23.901
|
<0.001A
|
|
|
14.097
|
<0.001A
|
|
|
10.841
|
<0.001A
|
|
Premenopausal
|
390(68.2%)
|
513(55.5%)
|
|
|
190
(27.0%)
|
513
(73.0%)
|
|
|
218
(29.8%)
|
513
(70.2%)
|
|
|
|
Postmenopausal
|
182(31.8%)
|
412(44.5%)
|
|
|
89
(17.8%)
|
412
(82.2%)
|
|
|
113
(21.5%)
|
412
(78.5%)
|
|
|
Menopausal age (years)
|
|
|
26.427
|
<0.001A
|
|
|
16.372
|
0.001A
|
|
|
13.595
|
0.004A
|
|
<45a
|
28(37.8%)
|
46(62.6%)
|
2.220ab
|
0.136ab
|
9
(16.4%)
|
46
(83.6%)
|
0.023ab
|
0.879ab
|
13
(22.0%)
|
46
(78.0%)
|
0.045ab
|
0.833ab
|
|
45-55b
|
148(29.3%)
|
357(70.7%)
|
0.325bc
|
0.568bc
|
75
(17.2%)
|
357
(82.8%)
|
2.669bc
|
0.102bc
|
94
(20.8%)
|
357
(79.2%)
|
3.161bc
|
0.075bc
|
|
>55c
|
6(24.0%)
|
19(76.0%)
|
|
|
5
(29.6%)
|
9
(70.4%)
|
|
|
6
(40.0%)
|
9
(60.0%)
|
|
|
|
None
|
390(43.2%)
|
513(56.8)
|
|
|
190
(27.0%)
|
513
(73.0%)
|
|
|
218
(29.8%)
|
513
(70.2%)
|
|
|
All Calculated using two-tailed student t test.
A Statistically significant (P<0.05).
B Calculated using t- test, others calculated using chi-square test.C Calculated using Fisher exact test.
abMenopausal age <45 vs Menopausal age 45-55; bcMenopausal age 45-55 vs Menopausal age >55.
CLNM+:central lymph nodes metastasis positive, CLNM-:central lymph nodes metastasis negative.
LNM+:lymph nodes metastasis positive, LNM-: lymph nodes metastasis negative.
Univariate analysis regarding menopause status in 1828 adult female patients. Postmenopausal women had a higher BMI (P < 0.001), a higher proportion of hypertension (P < 0.001) and diabetes (P < 0.001), and a higher proportion of patients with a history of malignant tumors (P < 0.001) than premenopausal women. At the same time, tumors were more likely to present with multifocal (P = 0.001), bilateral cancer (P = 0.007), and thyroid gland invasion (P < 0.001), but the lymph node metastasis rate also showed a lower status, and the difference was statistically significant (P < 0.001). After grouping according to the mean age of menopause, the positive rate of CLNM was higher in women aged ≤ 48 years than in women aged > 48 years. Potential confounding factors at baseline, including BMI, history of hypertension, history of T2DM, history of malignancy, maximum tumor diameter, multifocality, bilaterality, ETE and other significant factors, were again matched to remove heterogeneity using propensity score matching, and a total of 1046 women were matched, including 523 postmenopausal and 523 premenopausal women, and each matching factor was balanced and comparable between the two groups, and the only outcome measure was age at menopause and LNM. The results showed that age at menopause was still associated with lymph node metastasis after excluding each confounding factor (P < 0.001), but the size of age at menopause was no longer specifically affected, but in CLNM, the percentage trend was the same as that before matching data. (Table 6A) Combined with the age of menopause, it was found that the metastasis rate of PTC was significantly lower after menopause, but if the age of menopause was 55 years higher than the age of normal menopause, the trend of LLNM rate was significantly higher in postmenopausal women (40%), although there was no statistical significance (P = 0.075).