Medicine

®

Observational Study

OPEN

Associations between body mass index and lymph node metastases of patients with papillary thyroid cancer A retrospective study ∗

Changhua Wu, MDa,b, Liang Wang, MDa,b, Wanjun Chen, PhDb, , Shujuan Zou, MDb, Aiju Yang, MDb Abstract

Epidemiological studies suggest that obesity is a risk of thyroid cancer, especially papillary thyroid cancer (PTC). However, the associations of obesity and clinic–pathological features, especially the association of body mass index (BMI) and lymph node metastasis of thyroid cancer are unclear. Seven hundred ninety-six primary patients with PTC were enrolled in this retrospective cohort study. The relationships between BMI and clinic-pathological features of PTC were evaluated by logistic regression models based on the 5-point increase in BMI and BMI quartiles (underweight, normal weight, overweight, and obesity). The 5-point increase in BMI was strongly associated with extra-thyroidal invasion [odds ratio (OR) 2.201, P < 0.001], primary tumor size larger than 1 cm (OR 1.267, P = 0.027), advanced tumor node metastasis (TNM) staging (OR 1.479, P = 0.004), and multifocality (OR 1.31, P = 0.01) in multivariable-adjusted models. The relationships between BMI and lymph node metastasis of PTC were evaluated by Mann–Whitney U test. The mean number of positive central lymph nodes and lateral nodes were increased with the increase of BMI when BMI ≥18.5 kg/m2. It was not shown in underweight group. The present study found that increased BMI was associated with the lymph node metastases (LNMs) of patients with PTC, and other invasive features, including large tumor size, extra-thyroidal invasion, advanced TNM staging, and multifocality. Further studies with long-term follow-up are needed to confirm this finding. Abbreviations: ATC = Anaplastic thyroid cancer, BMI = Body mass index, CI = Confidence intervals, CT = Computed tomography, DTC = Differentiated thyroid carcinoma, ER = Estrogen receptor, FNAC = Fine-needle aspiration cytology, FTC = Follicular thyroid carcinoma, HT = Hashimoto thyroiditis, LN = Lymph node, LNM = Lymph node metastases, OR = Odds ratios, PTC = Papillary thyroid cancer, SD = Standard deviation, TC = Thyroid cancer, TNM = Tumor node metastasis, TSH = Thyroidstimulating hormone, WHO = World Health Organization. Keywords: body mass index, prognosis, thyroid papillary carcinoma

significant increase of TC rates. Because the growing prevalence of TC has been began before the widespread use of diagnostic ultrasound.[7] In addition, an epidemiologic observation reported that half the overall increase in papillary carcinoma rates was due to increasing rates of very small (1.0 cm) cancers, 30% to cancers 1.1 to 2 cm, and 20% to cancers >2 cm since 1992 to 1995.[8] So, the alternative of a true rise in TC incidence should be considered. Obesity has become a mass phenomenon with a pronounced upward trend in most industrialized countries.[9,10] More and more epidemiological data support that obesity is a precipitating factor in cancer development, including TC.[11,12] World Health Organization (WHO) suggests that BMI is used as an index to evaluate the degree of obesity. In addition, clinically significant prognostic factors for patients with differentiated thyroid carcinoma (DTC) have also been associated with aggressive tumor pathological features and lymph node (LN) metastasis.[13] Some studies suggested that obesity was significantly associated with larger tumor size and marginally associated with advanced tumor stage.[14,15] At the same time, Kim et al[16] believed that the correlation between the 2 was found in a specific group of patients ≥45 years of age. In Chinese population, Liu et al[17] found that increased BMI might elevate the risks of aggressive clinicopathological features, such as extrathyroidal invasion and advanced TNM stage. In contrast, Paes et al[18] reported a negative association between obesity and aggressive histological tumor features, such as the absence of nodal metastasis and tumor invasion. However, the association of body mass index (BMI) and LN metastasis of TC is unclear.

1. Introduction Thyroid cancer (TC) incidence, specifically papillary TC (PTC), has increased rapidly over the world[1–5]; it is estimated that about 62,980 new cases of TC were diagnosed in the United States in 2014 and this disease accounted for about 1890 deaths.[6] Despite the fact that the majority of newly diagnosed TCs are small PTCs through the use of ultrasound and ultrasound-guided biopsy, it has been suggested that enhanced detection of early-stage tumors cannot completely explain the Editor: Qinhong Zhang. This work was supported by Shandong Cancer Hospital & Institute. The authors have no conflicts of interest to declare. a Department of School of Medical and Life Sciences, University of JinanShandong Academy of Medical Sciences, b Department of Head and Neck Surgery, Shandong Cancer Hospital affiliated to Shandong University, Jinan, China. ∗

Correspondence: Wanjun Chen, Room 440, Jiyan Road, Jinan City, Shandong prov. 250117, China (e-mail: [email protected]).

Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0, which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author. Medicine (2017) 96:9(e6202) Received: 28 March 2016 / Received in final form: 13 January 2017 / Accepted: 30 January 2017 http://dx.doi.org/10.1097/MD.0000000000006202

1

Wu et al. Medicine (2017) 96:9

Medicine

5 kg/m2 increase in BMI.[12] So, BMI with a 5 kg/m2 increase was used as a continuous variable in the initial models. At the same time, the other clinicopathological features were analyzed. All of the following clinicopathological features of PTC patients were used as binary variables such as primary tumor size (1 or >1 cm), advanced TNM stage (stage I/II or stage III/IV), extrathyroidal invasion (yes or no), age (1 Extra-thyroidal invasion nodular goiter or HT Cervical lymph node metastasis pN0/Nx pN1a pN1b Distant metastasis Multifocality Advanced TNM staging Vascular invasion

Total n = 796

Underweight N = 18

Normal-weight N = 403

Overweight N = 311

Obese N = 64

612 (76.9%) 46.17 (±11.5) 25 (±3.40) 2.9 (±1.6) 4.38 (±0.692) 5.4 (±2.0) 1.37 (±0.564) 1.37 (±1.11) 424 (53.3%) 372 (46.7%) 308 (38.7%) 239 (30%)

16 (88.9%) 40.94 (±19.3) 17.5 (±0.74) 2.6 (±1.97) 3.98 (±1.33) 4.7 (±0.32) 1.04 (±0.96) 1.38 (±1.09) 10 (55.6%) 8 (44.4%) 2 (11.1%) 12 (66.7%)

332 (79.9%) 45 (±12.1) 22.7 (±1.65) 3.7 (±2.37) 4.14 (±0.89) 5.2 (±1.02) 1.29 (±0.64) 1.29 (±1.1) 237 (58.8%) 166 (41.2%) 114 (28.3%) 121 (30%)

226 (72.7%) 47.9 (±10.5) 27.1 (±1.35) 3.3 (±2.2) 4.28 (±0.72) 5.7 (±2.94) 1.73 (±0.88) 1.42 (±1.09) 150 (48.2%) 161 (51.8%) 152 (48.9%) 85 (27.3%)

38 (59.4%) 44.9 (±10.1) 36.69 (±1.62) 2.5 (±0.96) 5.3 (±0.78) 5.6 (±1.04) 0.86 (±0.34) 1.63 (±1.21) 27 (42.2%) 37 (57.8%) 40 (62.5%) 21 (32.8%)

349 (43.8%) 408 (51.3%) 281 (35.3%) 12 (1.5%) 348 (43.7%) 255 (32%) 25 (3.1%)

5 (27.8%) 10 (55.6%) 8 (44.4%) 0 (0%) 3 (16.7%) 4 (22.2%) 1 (5.6%)

196 (48.6%) 188 (46.7%) 127 (31.5%) 8 (2.0%) 170 (42.2%) 105 (26.1%) 13 (3.2%)

125 (40.2%) 172 (55.3%) 119 (38.3%) 4 (1.3%) 144 (46.3%) 122 (39.2%) 10 (3.2%)

23 (35.3%) 38 (59.4%) 30 (46.9%) 0 (0%) 31 (48.4%) 24 (37.5%) 1 (1.6%)

P ∗

0.000 0.001† 0.000‡ 0.925† 0.726† 0.834† 0.235† ∗ 0.01 ∗

0.000 ∗ 0.005 ∗ 0.056



0.577 ∗ 0.067 ∗ 0.001 ∗ 0.829

Advanced TNM staging, Stage III + IV, BMI = body mass index, CI = confidence interval, HT = Hashimoto thyroiditis, OR = odds ratio, pN1a = central lymph node metastasis, pN1b = Lateral lymph node metastasis, TNM = tumor node metastasis, TSH = thyroid-stimulating hormone. ∗ Analysis using Chi-square test. † Analysis using ANOVA. ‡ Analysis using nonparametric test.

metastasis (OR = 1.09, CI: 0.78–1.53, P = 0.601 in overweight group, OR = 1.14, CI: 0.61–2.05, P = 0.605 in obese group) and lateral neck LN metastasis (OR = 1.35, CI: 0.98–1.84, P = 0.06 in overweight group, OR = 1.92, CI: 1.12–3.27, P = 0.017 in obese group) (Table 3). The sample size is quite small (only 18 patients) in underweight group, so we do not consider doing a statistical test. To further understand the unexpected relationship between BMI and LN metastases, the subjects were categorized into underweight, normal, overweight, and obese according to the WHO. The mean number of LNs removed was 4.09 in the central compartment and 10.88 in the lateral compartment. The mean number of positive nodes was 1.71 (range: 0–17) in the central compartment and 1.76 (range: 0–32) in the lateral compartment.

The incidence of central and lateral LN metastases was 55.3% and 37.9% in overweight group, 55.9% and 45.3% in obese group, respectively. The mean number of positive central LNs and lateral nodes also increased with the increase of BMI when BMI ≥18.5 kg/m2 (Table 4). It was not shown in underweight group. It is because the number of cases is too small in the underweight group. The incidence of central and lateral LN metastases was significantly higher in overweight group and obese group than in normal-weight group, but it was not significantly different between underweight group and normalweight group. Statistical analysis failed to show any significant difference in the number of removed lateral nodes among the groups. In addition, the 5-point increase in BMI was strongly associated with extra-thyroidal invasion (OR = 2.201, CI: 1.691–2.865, P < 0.001), primary tumor size larger than 1 cm (OR = 1.267, CI: 1.028–1.561, P = 0.027), advanced TNM staging (OR = 1.479, CI: 1.13–1.937, P = 0.004), and multifocality (OR = 1.31, CI: 1.066–1.61, P = 0.01) in multivariableadjusted models (Table 2). However, there were no statistically significant results between BMI and, distant metastasis, vascular invasion and nodular goiter and/or HT. In our study, the sample size is quite small (only 13 patients) for cancer recurrence, so we do not consider doing a statistical test.

Table 2 Adjusted odds ratios (ORs) (with 95% CI) of more severe disease at initial surgery with a 5-point increase in BMI. Adjusted OR (95%) Extra-thyroidal invasion Multifocality Central neck lymph node metastasis Lateral neck lymph node metastasis Nodular goiter or HT ∗ Advanced TNM staging Distant metastasis Vascular invasion Primary tumor size†

2.201 1.31 1.033 0.845 0.877 1.479 0.790 0.848 1.267

(1.691–2.865) (1.066–1.61) (0.817–1.308) (0.625–1.145) (0.703–1.096) (1.13–1.937) (0.341–1.828) (0.475–1.513) (1.028–1.561)

P 1 cm.

3

Wu et al. Medicine (2017) 96:9

Medicine

Table 3 Risk of more aggressive clinico-pathological features in patients with papillary thyroid carcinoma according to BMI group. BMI, kg/m2 2

Overweight OR (95% CI) Extra-thyroidal invasion Multifocality Central neck LNM Lateral neck LNM Nodular goiter and/or HT ∗ Advanced TNM staging Distant metastasis Vascular invasion Primary tumor size >1 cm

2.42 1.18 1.09 1.35 0.88 1.83 0.64 1 1.53

(25–29.9 kg/m ) P

Associations between body mass index and lymph node metastases of patients with papillary thyroid cancer: A retrospective study.

Epidemiological studies suggest that obesity is a risk of thyroid cancer, especially papillary thyroid cancer (PTC). However, the associations of obes...
192KB Sizes 0 Downloads 12 Views